Sgavpeerreview 1

CONSULTATION APRIL–MAY 2022
1 Green-top Guideline No. 31

2 Peer Review Draft – April 2022
3
4 This is the third edition of this guideline. It replaces the previous editions published in February 2013
5 and November 2002 under the same title.
6
7 1. Purpose and scope
8
9 The purpose of this guideline is to provide advice that is based on the best evidence where available
10 in order to guide clinicians, regarding the investigation and care of the small–for–gestational age
11 (SGA) fetus, fetal growth restricted (FGR) fetus and determining sub optimal fetal growth. The
12 guideline reviews the risk factors for these conditions and provides recommendations regarding
13 surveillance, diagnosis and management, including recommendations for fetal monitoring and birth.
14
15 Population and setting
16
17 Women at low risk of fetal growth problems in community settings.
18
19 Women at moderate or high risk of fetal growth problems (determined based on past obstetric
20 history, current medical disorders or ultrasound diagnosis) in the hospital setting.
21
22 The guideline does not address multiple pregnancies or pregnancies with fetal anomalies
23 (chromosomal or structural).
24
25 Interventions to be studied
26
27 Comparison of modalities for surveillance and diagnosis of an SGA fetus/FGR fetus and those fetuses
28 with sub optimal fetal growth. Comparison of modalities to monitor fetuses with concerns regarding
29 growth.
30
31 2. Definitions
32
33 SGA refers to an infant born with a birth weight less than the 10th centile. This may be determined
34 from birth weight charts that are specific to the sex of the baby with centiles that are either
35 population based or adjusted for maternal characteristics (e.g. maternal height, weight, parity and
36 ethnic group).
37 Antenatally, SGA fetuses can be identified by either an estimated fetal weight (EFW) or abdominal
38 circumference (AC) less than the 10th centile.
39
40 Fetal growth restriction (FGR) implies a pathological restriction of the genetic growth potential.1
41 Some, but not all, growth restricted fetuses/infants are SGA. The likelihood of FGR is higher in fetuses
42 that are smaller.2,3 Growth restricted fetuses may manifest evidence of fetal compromise (abnormal
43 Doppler studies, reduced liquor volume).
44
45 FGR can be sub-divided clinically into early and late depending on the gestational age, with variation
46 in gestational thresholds between 32 and 37 weeks. A Delphi consensus based definition of FGR has
47 been suggested for use in research for both early (defined in the Delphi consensus as before 32
48 weeks) and late onset FGR.4,5
49
50 Low birth weight (LBW) refers to an infant with a birth weight less than 2500 g regardless of
51 gestation.
Green-top Guideline No. 31 Page 1 of 58 ©2022 Royal College of Obstetricians and Gynaecologists
52
53 Table 1 Consensus Based definitions for early and late fetal growth restriction (FGR) in absence of
54 congenital anomalies6
Early FGR: Gestational age < 32 weeks, in absence Late FGR: Gestational age ≥ 32 weeks, in absence
of congenital anomalies of congenital anomalies
AC/EFW < 3rd centile or UA-AEDF AC/EFW < 3rd centile
Or Or at least two out of three of the following:
AC/EFW <10th centile combined with either: 1. AC/EFW <10th centile
1. UtA-PI > 95th centile and/or 2. AC/EFW crossing centiles > 2 quartiles on
growth centiles*
2. UA-PI > 95th centile 3. CPR<5th centile or UA-PI > 95th centile
55 * Growth centiles are non-customised centiles. AC, fetal abdominal circumference; AEDF, absent end-diastolic
56 flow; CPR, cerebroplacental ratio; EFW, estimated fetal weight; PI, pulsatility index; UA, umbilical artery; UtA,
57 uterine artery
58
59 Diagnosing FGR in a current pregnancy and risk assessing whether FGR existed in a previous
60 pregnancy also presents different challenges. Thus, the following definitions are suggested within
61 the Saving Babies Lives Care Bundle Version 2 (SBLCBv2) to address these challenges and remain
62 practical for the majority of providers.7 It highlights that absent or reversed end diastolic flow in the
63 umbilical artery is a feature of early onset FGR, but importantly that absence of this feature (for
64 example, a normal umbilical artery Doppler) after 32 weeks of gestation does not mean that the
65 fetus is not growth restricted nor that there is no evidence of fetal compromise.
66
67 Definition of FGR in a previous pregnancy as a risk factor, defined as any of the following:
68  birthweight below 3rd centile
69  early onset placental dysfunction necessitating birth before 34 weeks
70  birthweight below 10th centile with evidence of placental dysfunction, (defined as below for
71 current pregnancy).
72
73 Definition of FGR in a current pregnancy: defined as either of the following:
74  EFW or abdominal circumference (AC) below the 3rd centile
75  EFW or AC below the 10th centile with evidence of placental dysfunction (either):
76 o Abnormal uterine artery Doppler (mean pulsatility index above 95th centile8 earlier
77 in pregnancy (20–24 weeks) and/or
78 o Abnormal umbilical artery Doppler (absent or reversed end diastolic flow or
79 pulsatility index above 95th centile).
80
81 These definitions all relate to an assessment of fetal size at one point in time. Assessment of fetal
82 wellbeing for all fetuses, independent of size, requires assessment of growth velocity i.e. the change
83 in fetal growth across at least two time points. Sub optimal fetal growth may be diagnosed when a
84 previously well-grown fetus (i.e. size 10th centile or above) fails to maintain adequate fetal growth
85 during pregnancy.
86
87 Suboptimal fetal growth:
88  Increase in EFW below 280g over 14 days (20g per day) from 34 weeks6,8
89
90 In order to ensure that pregnancies are being surveyed, and management is appropriate, all
91 pregnancies need to be assessed for their risk of a fetal growth disorder (i.e. SGA, FGR, sub-optimal
92 fetal growth) and based on the results of investigations (i.e. ultrasound biometry, Doppler
93 velocimetry) classified as either SGA (i.e. below 10th centile but no evidence of placental
94 dysfunction), FGR (as described above) or sub-optimal fetal growth.
95
96 Fetal growth disorder refers to a concern regarding fetal growth which encompasses SGA, FGR and
97 suboptimal growth.
98
99 3. Introduction and epidemiology
100
101 Small fetuses are divided into normal (constitutionally small), non–placenta mediated growth
102 restriction, (e.g. structural or chromosomal anomaly, inborn errors of metabolism and fetal infection)
103 and placenta mediated growth restriction. Maternal factors such as low pre–pregnancy weight,
104 under nutrition, substance abuse or severe anaemia can affect placental transfer of nutrients.
105 Medical conditions can also affect placental implantation and vasculature and hence transfer (pre-
106 eclampsia, autoimmune disease, thrombophilias, renal disease, diabetes and essential
107 hypertension).
108
109 The underlying aetiology as well as timing of onset is important when considering the risk of adverse
110 outcome in pregnancy. Early onset fetal growth restriction is associated with significant and
111 abnormal placentation that results in increased hypoxia and cardiovascular adaptions9 and therefore
112 carries an increased risk of adverse perinatal mortality and morbidity. In late onset fetal growth
113 restriction the deficit in placentation is milder, with less cardiovascular adaption and a lower risk of
114 adverse events. SGA fetuses are at increased risk of perinatal mortality and morbidity but most
115 adverse outcomes occur in the early onset growth restricted group.10
116
117 Serial symphysio-fundal height measurement (SFH) is a method of surveillance for fetal size, however
118 has a low sensitivity for detecting SGA/FGR fetuses.11 Diagnosis of a fetal growth disorder usually
119 relies on ultrasound measurement of fetal abdominal circumference or estimation of fetal weight.
120 Care of the SGA/FGR fetus is directed at timely birth. A number of surveillance tests are available,
121 including cardiotocography (CTG), Doppler and ultrasound (USS) to assess biophysical activity but
122 there is controversy about which test or combination of tests should be used to time birth in late
123 onset FGR and SGA.
124
125 The SpiRE evaluation of the Saving Babies Lives Care Bundle (SBLCB) demonstrated a measurable
126 difference in antenatal detection of SGA babies across England.12,13 The evaluation also
127 demonstrated an increase in ultrasound scans and inductions of labour at early term (37–39 weeks).
128 Thus, by seeking to capture all babies at risk, interventions have increased in women who are only
129 marginally at increased risk of FGR related stillbirth with risks to the babies of early term induction,
130 namely increased risk of admission to the neonatal unit and potential long term adverse effects e.g.
131 increased risk of special educational needs.14,15 SBLCB v2, and this guideline, addresses this with a
132 focus on detecting FGR and targeting intervention (i.e. birth) for those at increased risk of perinatal
133 death.
134
135 4. Identification and assessment of evidence
136
137 The Cochrane Library and electronic databases (DARE, EMBASE, Trip, MEDLINE and PubMed) were
138 searched using the relevant Medical Subject Headings (MeSH) terms, including all subheadings and
139 synonyms, and this was combined with a keyword search and was limited to humans and English
140 language; search terms included ‘fetal growth retardation’, ‘fetal growth restriction’ and ‘infant,
141 small for gestational age’. The search was restricted to articles published from 2011 until May 2020.
142 The full search strategy is available to view online as supporting information (Appendix S1 and S2).
143
144 This guideline was developed using the standard methodology for Green-top Guidelines.16 Where
145 possible, recommendations are based on available evidence. In the absence of published evidence,
146 these have been annotated as ‘good practice points’. Further information about the assessment of
147 evidence and the grading of recommendations may be found in Appendix 1.
148
149 5. What are the risk factors for fetal growth disorders in pregnancy?
150
151 Many analyses of risk factors for fetal growth disorders use babies less than the 10th percentile as a
152 proxy for FGR with the majority of these births occurring at term and thus including a significant
153 proportion of heathy SGA babies. Hence, studies using SGA as a proxy for FGR may underestimate
154 the risk of adverse outcomes associated with FGR.
155
156 The pathophysiology of preterm FGR is associated with pre-eclampsia and placental insufficiency.
157 Both entities are associated with high-risk patterns of flow in the maternal uterine arteries at 18–24
158 weeks’ gestation, and the utility of this measurement as a tool to further triage for risk of FGR is
159 discussed in section 7.
160
161 5.1 Booking history
162
Evidence Rationale for the
Recommendation quality Strength recommendation
All women should be assessed at 3 GPP Risk assessment at the
booking for risk factors for fetal growth beginning of pregnancy allows
restriction to identify those who require women to make informed
increased surveillance (appendix 1). choices about their care and for
planning of antenatal care.
The birthweight, gestation and 3 GPP This allows accurate risk

birthweight centiles of all previous assessment.
pregnancies should be recorded at the
booking appointment.
An individualised plan of assessment 3 GPP An individualised plan allows

should be made based on the specific care to be made in the
combination of risk factors and this will presence of multiple risk
inform further targeted tests (such as factors.
uterine artery Doppler when available)
and/or serial ultrasonic surveillance
(see section 7).
163
164 All women should be assessed at booking for risk factors associated with fetal growth disorders and
165 assessed as low, moderate or high risk for FGR, (Appendix 1). Risk assessment must always be
166 individualised taking into account previous medical, obstetric history and current pregnancy history.
167
168 Women should also be assessed at booking for conditions where SFH measurements are not
169 appropriate (e.g. raised BMI of 35 kg/m2 or above at booking; presence of fibroids in uterus [based
170 on clinical judgement], uterine anomalies, multiple pregnancy).
171
172 Previous SGA neonate
173
174 Women who have previously had an SGA neonate have an increased risk of a subsequent SGA
175 neonate.17-19 The risk is increased further after each additional SGA birth.18 [Evidence level 2+]
176
177 Individualised assessment must include calculation of previous birthweight centiles and not simply
178 rely on a previous history of low birth weight. [Evidence level 4]
179
180 There is consistent evidence that a previous pregnancy with the birth of an SGA neonate is a risk
181 factor for recurrence in a subsequent pregnancy (SGA below 10th centile OR 3.9, 95% CI 3.7–4.0).20
182 In a large cohort study evaluating the risk of recurrence of an SGA pregnancy (defined in this study
183 as a neonate below 5th centile) there was an increased risk of a subsequent SGA neonate (AOR 8.1,
184 95% CI 7.8–8.5).21 [Evidence level 2+]
185
186 Previous stillbirth
187
188 A systematic review summarises the evidence evaluating the risk of adverse pregnancy outcomes
189 following exposure to one of stillbirth, preterm birth (PTB) and SGA in a previous pregnancy. 22
190 Previous stillbirth is associated with an increased risk of SGA in a subsequent pregnancy, with the
191 association greater when there was evidence of FGR in association with the stillbirth.22 This
192 observation is supported by other studies23,24 with an increased risk of a SGA infant following a
193 previous pregnancy with a placentally related stillbirth (OR 2.3, 95% CI 1.2–4.2).24 [Evidence level 2+]
194
195 Previous preterm birth
196
197 Women with a previous PTB (before 37 weeks) have an increased risk of SGA; this effect is greater
198 after extreme PTB (20–27 weeks). Most studies did not differentiate between iatrogenic or
199 spontaneous PTB, thus it is possible that this association is secondary to birth for maternal medical
200 conditions such as pre-eclampsia or indeed placental dysfunction leading to FGR, rather than an
201 independent association with spontaneous PTB and subsequent SGA.22 No evidence was identified
202 that evaluated the risk of fetal growth disorders following a history of second trimester pregnancy
203 loss. It is recommended in any women with a history of preterm birth or second trimester pregnancy
204 loss that a detailed history is undertaken to determine whether placental dysfunction was
205 implicated. [Evidence level 2++]
206
207 Previous Pregnancy Loss
208
209 The evidence regarding recurrent miscarriage (RM) is conflicting and comes mainly from
210 retrospective cohort studies. The largest study to date demonstrated no increased risk of SGA (aOR
211 1.07 [95% CI 0.93–1.23)].25 As RM can be caused by a heterogenous group of conditions and some of
212 these are associated with pregnancy complications themselves, it is important to look at the group
213 with unexplained RM as these women may have underlying abnormal placentation.26 Another
214 retrospective study found an increased risk of SGA below 10th centile but this was not adjusted for
215 other confounders (OR 2.82 [95% CI 1.32–6.04]).27 There is thus a need for further prospective
216 research, to evaluate the relationship between unexplained RM and SGA/FGR. [Evidence level 2–]
217
218 Second trimester medical termination of pregnancy (MTOP) is not a risk factor for an SGA infant,
219 with this being explored in a large cohort study comparing the outcomes of preterm birth, low birth
220 weight, SGA and placental complications in women undergoing first trimester versus second
221 trimester MTOP.28 [Evidence level 2+]
222
223 Previous pregnancy with placenta-mediated complications
224
225 Women who have had a previous pregnancy affected by a placenta-mediated complication (e.g.
226 hypertensive disorders of pregnancy, placental abruption or abnormal fetal growth) are at greater
227 risk of recurrence of these complications in subsequent pregnancies with the risk increasing with
228 each pregnancy affected.29 [Evidence level 2–]
229
230 NICE recommends aspirin to reduce the risk of pregnancy complications related to placental
231 dysfunction, particularly preeclampsia.30 [Evidence level 1++]
232
233 In women with previous FGR (including those born preterm), clinicians should determine whether
234 placental dysfunction was a contributory factor and, if so, advise low dose aspirin 150mg from 12
235 weeks’ gestation. [Evidence level 4]
236
237 Maternal characteristics and medical history
238
239 Maternal medical conditions associated with an increased risk of a fetal growth disorder include
240 diabetes with vascular disease,31 moderate and severe renal impairment (especially when associated
241 with hypertension),32 antiphospholipid syndrome,33 chronic hypertension34 and systemic lupus
242 erythematosus (SLE).35 [Evidence level 2– to 2++]
243
244 Maternal congenital heart disease (CHD) has a varying association with SGA, and the largest
245 prospective series to date demonstrated that SGA was mainly seen in women with complex CHD (OR
246 2.29, 95% CI 1.49–3.51) and symptomatic patients (New York Heart Association class III-IV) (OR 2.39,
247 95% CI 0.72–7.95). Multivariable analysis revealed that in women with valvular disease, stenotic
248 lesions (OR 2.31, 95% CI 1.33–4.03) and anticoagulant use (OR 2.16, 95% CI 1.24–3.78) there was an
249 association with SGA. Thus, women with complex CHD and/or ventricular dysfunction should be
250 offered fetal monitoring by ultrasound.36 [Evidence level 2+]
251
252 The associations with asthma, anaemia, inflammatory bowel disease (IBD) and depression are less
253 strong. Meta-analyses of observational studies have demonstrated weak or no associations with SGA
254 (less than 50% increase in risk) for asthma, IBD,37 anaemia38 and depression.37,39 Therefore, if
255 uncomplicated and adequately treated, these are not considered important risk factors for an SGA
256 fetus.40,41 [Evidence level 2++]
257
258 Advanced maternal age of 40 years or more is associated with increased risk of SGA and FGR although
259 this is smaller than previously thought (SGA OR 1.20, 95% CI 1.07–1.33; FGR BW below 5th centile OR
260 1.53, 95% CI 1.07–2.20).42 [Evidence level 1–]
261
262 Maternal pre-pregnancy body mass index (BMI) and gestational weight gain have been evaluated in
263 an IPD meta-analysis of 265 270 singleton pregnancies.43 Maternal pre-pregnancy BMI of 20–30 was
264 associated with a lower risk of SGA (P < 0.05) (reference group 20.0–22.4 kg/m2). Women with
265 excessive weight gain had a lower risk for SGA (OR 0.62, 95% CI 0.60–0.65). Women with a BMI lower
266 than 18.5kg/m2 and low gestational weight gain (Z scores of –1.1SD or less Institute of Medicine
267 Guidelines) had the highest risk for SGA birth (OR 3.12, 95% CI 2.75–3.54).43 NICE guidance
268 recommends that women are not routinely weighed during pregnancy and thus women with a low
269 BMI at booking (below 18.5) who are likely to have a low gestational weight gain e.g. those with
270 eating disorders or medical disorders affecting nutrition, should be considered at increased risk and
271 serial USS performed.44 [Evidence level 2++]
272
273 Bariatric surgery appears to increase the risk of SGA independent of BMI associated risks, with gastric
274 bypass (malabsorptive) associated with a higher risk compared to gastric bands (restrictive) (gastric
275 bypass [OR 2.39, 95% CI 1.94–2.94]; gastric bands [OR 1.38 95% CI 0.90–2.10]).45-47 Thus, in women
276 with a gastric band there is no evidence of increased risk. However, women who have undergone
277 gastric bypass surgery should be considered at moderate risk of fetal growth disorders regardless of
278 their BMI. [Evidence level 2++]
279
280 Ethnicity, specifically Pakistani, African and Black African Caribbean ethnicity, have been reported to
281 be associated with an increased risk of SGA.48-50 The relationship between ethnicity and adverse
282 pregnancy outcomes is complex and multifaceted. The evidence base is limited due to its
283 observational nature, lack of relevant classification, and lack of adjustment for confounders e.g.
284 geographical location, healthcare system, co-existing disease, malnutrition, inequality etc. More
285 importantly health inequality, racial bias and the lack of high quality research into ethnic disparities
286 needs to be addressed. Maternity services and healthcare providers have an important role to play
287 in ensuring that all women are provided with a risk assessment at booking for fetal growth disorders
288 and all modifiable contributory factors are addressed. [Evidence level 2+]
289
290 Nulliparity, social deprivation, unmarried status, maternal SGA, a short (less than 6 months) or long
291 (over 60 months) inter–pregnancy interval have all been shown to have minor associations with
292 SGA.51-55 The effect of some of these risk factors is reduced once adjusted for other factors. [Evidence
293 level 2++]
294
295 An individual patient level meta-analysis did not support an association between moderate to
296 vigorous physical activity and the risk of SGA.56 [Evidence level 2++]
297
298 The interaction of multiple maternal risk factors is unknown and is an important area for further
299 research.
300
301 Antenatal risk factors
302
303 Several maternal exposures have a seemingly causative relationship with fetal growth disorders. A
304 systematic review from 2011 reported a dose response relationship with maternal alcohol
305 consumption and SGA with no association with low levels of alcohol consumption, a small association
306 with one drink per day and a doubling of risk at approximately 4 drinks per day.57 A more recent
307 systematic review concluded that there is limited evidence on the effects of drinking 32 g/week or
308 less (two UK units up to twice per week). There was some evidence that light prenatal alcohol
309 consumption was associated with the risk of having an SGA infant (OR 1.08, 95% CI 1.02–1.14) but
310 there is a lack of evidence about the effect of alcohol consumption at different stages of conception
311 and pregnancy. They concluded that guidance could advise abstention as a precautionary principle,
312 but clinicians should explain this is based on limited evidence.58 [Evidence level 2++]
313
314 Drug misuse is associated with being born SGA, specifically cocaine use (OR 3.23; 95% CI 2.43–4.30)
315 with crack cocaine use increasing the risk further (OR 4.00; 95% CI 1.74–9.18).59,60 Data regarding
316 fetal growth with marijuana exposure are mixed, with some studies demonstrating a decrease in
317 birthweight and/or growth and others demonstrating no association. It must be noted that often
318 studies of marijuana use are hampered by inadequate reporting of usage and concomitant tobacco
319 use.61 [Evidence level 2++]
320
321 Smoking increases the risk of SGA and the effects of smoking are dose dependent and stronger in
322 older women.62 Multiple cohort studies have demonstrated that smoking throughout pregnancy
323 approximately doubles the risk of SGA.63-65 The risk of preterm SGA which is more strongly associated
324 with FGR is also increased (OR 1.39; 95% CI 1.35–1.42).65 Women who are able to stop smoking can
325 reduce their risk of SGA. If able to stop by 15 weeks of gestation, they can return to the pregnancy
326 risk status of similar non-smoking women of preterm and term SGA. Less is known about the impact
327 of second hand smoke on SGA rates.63,66 [Evidence level 2+]
328
329 Maternal caffeine consumption of 300 mg per day or more in the third trimester has been associated
330 with SGA, with evidence suggesting that even lower consumption has an association with SGA (OR
331 1.9; 95% CI 1.3–2.8).67,68 A high green leafy vegetable intake pre–pregnancy has been reported to be
332 protective (aOR 0.44; 95% CI 0.24–0.81).69 The current recommended daily maximum caffeine intake
333 in pregnancy is 200mg per day (two mugs of instant coffee).70 [Evidence level 2+]
334
335 A systematic review assessing in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI)
336 has shown an association with these techniques and SGA (RR 1.39; 95% CI 1.27–1.53).71 However,
337 there does not appear to be an association between ovum donation and the risk of SGA.72 [Evidence
338 level 2++]
339
340 There is increasing interest on the paternal influence on adverse pregnancy outcomes.73 A systematic
341 review of 36 studies on paternal factors and birth outcomes concluded that extreme paternal ages
342 (below 20 and above 40 years), height and paternal birth weight had no association with SGA.73,74
343 Changing paternity has been associated with an increased risk of a SGA infant (aOR 2.25; 95% CI
344 1.13–1.47) and pre-eclampsia even after taking into account confounders related to changing
345 paternity such as social and behavioural changes.75 Further research is needed to evaluate the
346 potential mechanism between paternity change and SGA/pre-eclampsia.75 [Evidence level 2++]
347
348 There is insufficient evidence to determine how risk factors relate to each other in the individual
349 woman and consequently how these risk factors should be managed. This guideline has therefore
350 categorized women into low, moderate and high risk reflecting the risk of fetal growth restriction
351 (Appendix 1). Further guidance regarding surveillance and assessment of fetal wellbeing, determined
352 by risk category, is summarised in Appendix 2.
353
354 5.2 Current pregnancy risk factors
355
356 5.2.1 Biochemical markers used for aneuploidy screening
357
When low Pregnancy‐associated 2+ B Low PAPP-A, raised AFP and
plasma protein A (PAPP–A) levels or raised inhibin are independent
raised AFP levels and/or raised Inhibin risk factors for SGA and FGR.
A are incidentally detected following
first or second trimester screening for
aneuploidy, women should undergo
additional ultrasound surveillance for
SGA/FGR.
358
359 Low (below 5th centile or below 0.415 Multiples of Median [MoM] if local data reference data
360 unavailable) PAPP-A levels are an independent risk factor for SGA, with the odds of SGA decreasing
361 as PAPP-A increases.76 Low PAPP-A levels are also strongly associated with stillbirth due to placental
362 dysfunction, defined as abruption or unexplained stillbirth associated with growth restriction
363 (incidence rate: 11.7 versus 0.3 per 10 000 women per week, respectively; Hazard Ratio 46.0 [95%
364 CI, 11.9–178.0]).77 A large meta-analysis of 32 studies (175 240 pregnancies) demonstrated that low
365 PAPP-A is associated with SGA below 10th centile (OR 2.08 [95% CI 1.8–2.29]), SGA below 5th centile
366 (OR 2.83 [95%CI 2.52–3.18]).78 Raised alpha fetoprotein (AFP)(above 2 MoM) and raised Inhibin A
367 (above 2 MoM) are also associated with SGA/FGR.79 A recent large UK observational study of 1079
368 women which included women with low PAPP-A or raised AFP and/or raised Inhibin A confirmed the
369 increased risk of SGA (24.5%) and FGR (10.3%) and demonstrated that most of the increased risk is
370 FGR after 34 weeks’ gestation with only 2.3% (27/1079) requiring birth before this gestation.80 90.6%
371 of cases of early FGR were identified by performing uterine artery Doppler assessment and
372 ultrasound EFW in the early third trimester (LR-0.14; 0.06–0.35) supporting earlier studies.81 Risks of
373 SGA and FGR were similar in low PAPP-A, raised AFP and raised Inhibin A populations and risks
374 increased as levels deviated further from the median. This finding is supported by other recent
375 observational studies and as a result additional surveillance for FGR should be offered if abnormal
376 levels of any of these biochemical markers are detected.80,82 Information on low Estriol levels (below
377 0.5 MoM) is too limited to draw firm conclusions due rarity in chromosomally normal fetuses. Raised
378 hCG (above 4 MoM) is not reliably associated with SGA/FGR and does not need to precipitate
379 additional monitoring in isolation, though if it occurs in association with other raised mid trimester
380 markers (AFP and/or Inhibin A) then may indicate even higher risk of SGA and FGR.83 [Evidence level
381 2++]
382
383 Although when incidentally detected, low PAPP-A or raised AFP and/or raised Inhibin A are strongly
384 associated with SGA and FGR, systematic reviews and observational studies have not supported their
385 use in isolation as primary detection tools for FGR due to their low sensitivity.79,80,84,85 Thus their use
386 as a screening tool is not recommended. [Evidence level 2++]
387
388 There are no prospective studies demonstrating the effectiveness of the use of aspirin in women
389 with an isolated low PAPP-A or raised hCG and thus aspirin should not be prescribed to women for
390 this reason alone.86,87 However, abnormal screening results can be used to contribute to risk
391 assessment for that pregnancy and help determine surveillance pathways for fetal growth.87
392 [Evidence level 2+]
393
394 5.2.2 Findings at routine mid trimester anomaly scan
395
Women should be reassessed for their 4 GPP The review following the anomaly
risk of a fetal growth disorder scan appointment presents an
following the mid-trimester anomaly opportunity to review maternal
scan. medical conditions, fetal condition
and size and thus reassess risk for
a fetal growth disorder.
Personalised care plans should be
revised or confirmed at this
appointment.
396
397 At the time of the mid-trimester fetal anomaly scan, certain normal variants and incidental findings
398 may be observed as well as fetal anomalies detected. The Fetal Anomaly Screening Programme
399 (FASP) provides guidance as to how these findings should be classified and whether referral for
400 further assessment as for other suspected fetal anomalies should occur.88 The guidance below
401 discusses the association of these with fetal growth disorders and stillbirth and thus consideration
402 as to whether the surveillance pathway for fetal growth should be amended.
403
404 Fetal echogenic bowel
405
406 Fetal echogenic bowel has been shown to be independently associated with a SGA neonate (aOR 2.1;
407 95% CI 1.5–2.9) and intrauterine fetal death (aOR 9.6; 95% CI 5.8–15.9).89 A prospective study of
408 22 000 women with ultrasound findings of unknown significance at the 20-week anomaly scan
409 included 50 cases of isolated echogenic bowel. There was an association with an increased risk of
410 stillbirth but when restricted to livebirths with BW below3rd centile no conclusion could be made.90
412
413 Single umbilical artery
414
415 A meta-analysis of 11 observational studies including 1731 pregnancies demonstrated an almost 3-
416 fold risk of SGA associated with isolated single umbilical artery.91 Further studies have also
417 demonstrated an association between single umbilical artery and the risk of growth restricted
418 stillbirths.92,93 Finally, a retrospective analysis of over 200 000 pregnancies, excluding those with
419 structural or chromosomal anomalies, reported an odds ratio of 8.1 for stillbirth with isolated single
420 umbilical artery.94 [Evidence level 2–]
421
422
423 Fetal biometry less than the 5th centile
424
425 The FASP guidance suggests that fetuses with measurements significantly less than the 5th centile at
426 the mid-trimester anomaly scan should be referred for further assessment. This may include fetal
427 medicine assessment for fetal anomaly or medical assessment for review of risk of fetal growth
428 disorders and change of surveillance pathway (see Section 8).
429
430 5.2.3 Risk factors developing in pregnancy
431
Women should be reassessed for their 4 GPP The 28-week appointment
risk of a fetal growth disorder at 28 presents a universal opportunity
weeks and after any antenatal to review the pregnancy (and
admission. thus risk assessment) at the start
of the third trimester. Antenatal
admissions will be prompted by a
change in maternal or fetal
condition and thus should
prompt a reassessment of the
fetal growth monitoring plan.
Women with hypertensive disorders of 2+ C Women with hypertensive

pregnancy need to be assessed for the disorders of pregnancy can be at
need for growth scans. increased risk of fetal growth
disorders. The nature and
severity of the hypertensive
disorder determines the risk.
432
433 Bleeding in the first trimester is common and a systematic review demonstrated an association with
434 threatened miscarriage and growth restriction (OR 1.54; 95% CI 1.18–2.0) but with no consistent
435 definition of the outcome and significant heterogeneity in results.95 [Evidence level 2++]
436
437 Previous evidence regarding association between bleeding in the second half of pregnancy and fetal
438 growth disorders has been conflicting with heterogeneity in definitions of bleeding and outcomes
439 with the need for large, prospective studies able to adjust for confounders.96 [Evidence level 2–]
440
441 Current RCOG guidance for care of women following an antepartum haemorrhage recommends
442 serial scans for fetal growth. Placenta praevia not complicated by antepartum haemorrhage is not a
443 significant risk factor for SGA.97
444
445 A large population based study assessed the risk of SGA in women with hypertensive disorders of
446 pregnancy. Women who develop hypertensive disorders of pregnancy had an increased risk of an
447 SGA neonate compared to normotensive women (gestational hypertension no proteinuria RR 1.5
448 [95% CI 1.47–1.6, P < 0.001]; gestational hypertension with proteinuria RR 3.3 [95% CI 3.0–3.9, P <
449 0.001]; pre-existing hypertension were RR 2.5 [95% CI 2.1–2.9, P < 0.001]).98 There is a dose response
450 relationship between SGA and hypertension with increases in diastolic blood pressure in women with
451 non-proteinuric hypertension in pregnancy associated with an increased risk of SGA (severe
452 Pregnancy Induced Hypertension (PIH) diastolic ≥110mHg RR 2.5 95% CI 2.3–2.8).98-100 NICE guidance
453 recommends that women with chronic hypertension, severe gestational hypertension (BP≥ 160/110
454 mmHg) and pre-eclampsia have ultrasound assessment for fetal growth and for women with mild
455 hypertension if clinically indicated.30 [Evidence level 2+]
456
457 5.2.4 Risk stratification for FGR and Prediction models
458
Evidence Strength Rationale for the
Recommendation quality recommendation
Prediction models should not be used 2+ C Despite moderate predictive
in routine clinical practice. ability, these models have not
been shown to have sufficient
clinical utility to determine which
women should have ultrasound
surveillance.
459
460 There are several published prediction models for SGA based on combinations of maternal
461 characteristics, biomarkers and ultrasound features.101-106 However further analysis has
462 demonstrated that while the models have moderate predictive value for SGA below the 5th centile,
463 the clinical utility is limited due to the heterogeneous aetiology of fetal growth disorders. 107 Thus at
464 present these models are not sufficient to determine which women should have ultrasound
465 surveillance. [Evidence level 2+]
466
467 6. How can the risk of fetal growth disorders in pregnancy be reduced?
468
469 6.1 General population
470
All pregnant women should be offered 4 GPP Smoking increases the risk of SGA
carbon monoxide (CO) testing at the and women who are able to stop
antenatal booking appointment, as smoking can reduce their risk of
appropriate throughout pregnancy SGA.
and at 36 weeks. Women with
elevated levels (4ppm or above)
should be referred to a trained stop
smoking specialist with efforts for the
pregnancy to be smoke free before 16
weeks.
1– B The benefit of vitamin D and folic

All women should continue to take acid supplementation in
the 10 micrograms/day pregnancy to reduce the risk of
recommended of vitamin D preeclampsia, SGA or FGR remains
(throughout pregnancy) and 400 uncertain and thus all women
micrograms/day of folic acid should follow general pregnancy
(preconception and for the first three guidance to prevent other
months of pregnancy). pregnancy complications.
471
472 Dietary modification
473
474 Balanced energy/protein supplementation has been associated with a reduction of SGA (RR 0.79;
475 95% CI 0.69–0.90) and an increase in mean birthweight (+40.96g, 95% CI 4.66–77.26, 11 trials, 5385
476 women).108 The same meta-analysis examined whether high protein supplementation alone was
477 beneficial. Only one study of 1051 women was included and appeared to show an increase in SGA
478 (RR 1.58; 95% CI 1.03–2.41), however, the evidence was of low quality, therefore high protein
479 supplementation is not recommended.108 [Evidence level 1–]
480
481 Dietary supplements, minerals, micronutrients and vitamins
482
483 Supplementation with omega‐3 long chain polyunsaturated fatty acids has not been shown to reduce
484 small-for-gestational age or intrauterine growth restriction (RR 1.01; 95% CI 0.90–1.13; eight RCTs,
485 6907 participants).109 Multiple–micronutrient supplementation in pregnancy has been addressed in
486 a recent Cochrane review of 21 trials involving 142 496 women. Micronutrient supplementation
487 appeared to reduce the risk of SGA (RR 0.92; 95% CI 0.88–0.97).110 However, all but one of these
488 studies was conducted in low or middle income countries and the only UK study failed to
489 demonstrate any significant effect.111 [Evidence level 1–]
490
491 High dose folic acid supplementation has been previously suggested to reduce the risk of SGA, but
492 the recently completed FACT study did not demonstrate any reduction in SGA or FGR rates over the
493 standard pre-conceptual dose (400microgram/day).112 Calcium supplementation has been suggested
494 to reduce the incidence of pre-eclampsia although the most recent Cochrane review shows this to
495 be a modest 8% reduction at best and the latest high quality RCT did not demonstrate an effect.113-
115
496 The Cochrane review did not re-consider the effect of calcium on reducing the prevalence of
497 SGA.113 An NIHR funded RCT in the UK will commence in 2021 (CaPE NIHR27325) and consider
498 maternal and fetal outcomes. Magnesium supplementation to reduce the incidence of SGA has been
499 extensively investigated, but a recent Cochrane review (10 trials 9090 women) concluded there was
500 no effect.116 [Evidence level 1–]
501
502 Vitamin D supplementation
503
504 The benefit of vitamin D supplementation to reduce the risk preeclampsia, SGA or FGR in pregnancy
505 remains uncertain. Several recent systematic reviews have not found evidence of a reduced
506 preeclampsia or stillbirth risk, but have found some evidence of a reduced risk of low birthweight
507 (LBW, below 2500g) and/or SGA,117-119 a more recent systematic review suggested that vitamin D
508 supplementation may be useful in preventing preeclampsia.120 At present therefore, there is
509 insufficient evidence to recommend high dose supplementation for pregnant women at risk of FGR
510 and women should continue to take the 10 microgram/day recommended for all UK pregnant
511 women,44 unless there are other reasons to increase daily dose independent of pregnancy e.g.
512 cultural skin coverage, in which case dose should be determined by local prescribing policy. [Evidence
513 level 1-]
514
515 Smoking cessation
516
517 Smoking increases the risk of SGA and women who are able to stop smoking can reduce their risk of
518 SGA. If able to quit by 15 weeks of gestation they can return to the pregnancy risk status of similar
519 non-smoking women of preterm and term SGA.63,121 [Evidence level 1–]
520
521 Reduction in SGA or FGR are not often reported as outcomes from smoking cessation programmes
522 although there is evidence of an association with increased mean birthweight (55.60g higher 95% CI
523 29.82–81.38; 26 RCTs, 11 338 women) and reduced risk of low birthweight (RR 0.83 95% CI 0.72–
524 0.94; 18 RCTs, 9402 women) in women who stop smoking.122 [Evidence level 1–]
525
526 Evidence for use of E-cigarettes/vaping, nicotine replacement therapies (NRTs) and other
527 pharmacological agents in pregnancy for smoking cessation is either sparse or inconsistent.122,123
528 SBLCBv2 element 1 provides a practical approach to reducing smoking in pregnancy by following
529 NICE guidance which recommends that all pregnant women who smoke are referred to a specialist
530 service.122 The aim is for the home to be smoke free (maternal or passive smoking) by the 16th week
531 of pregnancy.7 [Evidence level 3]
532
533 6.2 Women at risk of fetal growth disorders
534
Taking folic acid and vitamin D doses 1– B Dietary modification/supplement
above the recommended does not interventions for the prevention of
appear to provide any additional FGR in an at risk population have
benefit to women at risk of FGR. yielded conflicting results, but
have consistently failed to show
benefit when tested with
adequately powered randomised
controlled trials.
Women at risk of preeclampsia and/or 1++ A There is good evidence of aspirin

placental dysfunction should take safety and efficacy at 150mg and
aspirin 150mg once daily at night from doses below 100mg should only be
12–36 weeks of pregnancy to reduce considered in the presence of
their risk of SGA and FGR. other relative contraindications to
prescription.
LMWH should not be prescribed to 1+ A Randomised controlled trial

reduce the risk of SGA or FGR in at risk evidence has failed to
women. demonstrate a reduction in FGR in
any at risk group including those
with inherited thrombophilias.
535
536 Maternal micronutrients
537
538 A Cochrane review published in 2003 and updated in 2010 reported four studies of 165 women and
539 did not find evidence of improved outcomes or enhanced fetal growth.124 [Evidence level 1–]
540
541 Antiplatelet agents
542
543 Antiplatelet agents have been extensively investigated in women at varying levels of risk for pre-
544 eclampsia, with SGA and/or FGR as outcomes, in multiple meta-analyses.125,126 These studies have
545 suggested a reduction in SGA and FGR birth with the use of aspirin in women at risk of preeclampsia,
546 driven by a reduction in the incidence of preeclampsia in treated women.127 Aspirin seems more
547 effective if given before 16 weeks’ gestation. A recent meta-analysis demonstrated administration
548 before 16 weeks was associated with a reduction in SGA (RR 0.76; 95% CI 0.61–0.94; 13 trials, 6393
549 women), where after 16 weeks there was no significant effect (RR 0.95; 95% CI 0.84–1.08; 18 trials,
550 14 996 women).128 Meta-analysis supported the concept of a dose response relationship for SGA
551 prevention favouring a dose of 100–150mg per day.129 There is good evidence of aspirin safety and
552 efficacy at 150mg.130 Thus, doses below 100mg should only be considered in the presence of other
553 relative contraindications. Two RCTs have demonstrated that administration of aspirin in the evening
554 or night is more effective at lowering ambulatory blood pressure and reducing the risk of
555 preeclampsia, than in the morning or day.131,132 [Evidence level 1++]
556
557 Antithrombotic therapy
558
559 Antithrombotic therapy using low molecular weight heparin (LMWH) has been trialled repeatedly in
560 women at risk of FGR, usually in association with preeclampsia, with or without co-existent
561 thrombophilias. Previous systematic reviews have suggested a potential benefit in reducing the risk
562 of SGA with the use of LMWH and aspirin (RR 0.41; 95% CI 0.27–0.61; seven studies, 710 women; RR
563 0.41; 95% CI 0.20–0.93).133,134 However, more recent prospective studies have failed to identify any
564 benefit in reducing placental mediated disease. In the HEPEPE trial, 257 women with a previous
565 history of early onset (before 34 weeks) severe preeclampsia were randomised to aspirin 100mg with
566 or without enoxaparin 4000iu/day from early pregnancy.135 There was no difference in the rate of
567 SGA (RR 0.78; 95% CI 0.50–1.22) or FGR (defined below the5th centile; RR 0.65; 95% CI 0.36–1.18).
568 The EPPI study randomised 156 women with a history of either early onset preeclampsia (before 36
569 weeks) or early onset SGA (before 36 weeks) to aspirin 100mg with or without enoxaparin
570 4000iu/day.136 There was no difference in the rate of SGA (aOR 1.17; 95%CI 0.56–2.47) or FGR
571 (defined <3rd centile; aOR 1.19; 95% CI 0.40–3.52). Similarly Martinelli et al randomised 135 women
572 with a previous history of preeclampsia and showed no difference in the incidence of FGR (16%,
573 P=0.3).137 A secondary analysis of the FRUIT-RCT which examined the risk of SGA in women with a
574 history of previous preeclampsia and an inherited thrombophilia, treated with or without
575 enoxaparin, could also find no reduction in risks.138 Finally, an IPD meta-analysis of 963 women from
576 eight eligible studies (published prior to HEPEPE and EPPI and therefore not including their
577 participants) failed to find any reduction in any placentally mediated outcome (RR 0.64; 95% CI 0.36–
578 1.11).139 [Evidence level 1+]
579
580 In summary present evidence does not support the use of LMWH as an effective treatment to
581 prevent SGA or FGR, even in the presence of heritable thrombophilia.
582
583 Progesterone
584
585 Secondary outcome analyses of studies on progesterone to prevent preterm birth have shown no
586 effect on the risk of preeclampsia or FGR.140-142 [Evidence level 1+]
587
588 Hydroxychloroquine
589
590 Studies examining the effects of hydroxychloroquine on risk of FGR are small and of low quality and
591 recent meta-analysis failed to show significant benefit.143 Hydroxychloroquine has also been
592 suggested as treatment for women with previous placental Chronic Histiocytic Intervillositis, but no
593 prospective RCT data are currently available and therefore is not recommended outside a research
594 setting.144,145 [Evidence level 1–]
595
596 Antihypertensive use
597
598 Antihypertensive drug therapy for hypertension in pregnancy does not seem to increase the risk of
599 having an SGA neonate (aRR 0.96; 95% CI 0.78–1.18; 21 trials, 2686 women).146 Long standing
600 concerns regarding atenolol are based on one small study and should be interpreted with caution.147
601 [Evidence level 1–]
602
603 7. What is the optimum surveillance pathway for women according to their risk for FGR and how
604 to diagnose fetal growth disorders?
605
606 The risks of a pregnant woman developing early or late onset FGR are strongly linked to concurrent
607 pregnancy risk factors. As a result of this, the prevalence of FGR varies dramatically in different
608 pregnant populations directly influencing the performance of prediction and detection methods.
609 Early onset FGR is a relatively uncommon condition (~0.3 %). Late onset FGR is more common, but
610 by its very nature does not require intervention before term.
611
612 7.1 Low risk of FGR
613
614 Women who are assessed as being at a low risk for FGR should have serial assessment of fetal growth
615 using antenatal symphysis fundal height (SFH) charts by health care professionals trained in their
616 use. All staff performing these measurements should be competent in measuring, plotting,
617 interpreting appropriately and referring when indicated and measurements should be performed as
618 per NICE guidelines.44 [Evidence level 1–]
619
620 7.1.1 Clinical examination and symphysio-fundal height measurement
621
Abdominal palpation has limited 2+ C Studies in both low and high risk
accuracy for the prediction of an SGA populations have consistently
neonate and thus should not be shown abdominal palpation to be
routinely performed in this context. of limited accuracy in the
detection of a SGA neonate.
Serial measurement of symphysis 1– B SFH remains a valuable, although

fundal height (SFH) is recommended limited tool for the detection of
at each antenatal appointment from SGA. Serial measurement may
24 weeks of pregnancy as this improve predictive accuracy.
improves prediction of an SGA
neonate.
Women with a single SFH which plots 4 GPP Due to the limited accuracy of SFH,
below the 10th centile or serial abnormal SFH measurements
measurements which demonstrate should prompt assessment of the
suboptimal fetal growth (no apparent fetus with ultrasound.
fetal growth over two weeks) should
be referred for ultrasound
measurement of fetal size.
Women in whom measurement of 4 GPP Maternal obesity, abnormal fetal

SFH is less accurate (e.g. BMI of 35 or lie, large fibroids, hydramnios and
above, large fibroids, the extent of fetal head
polyhydramnios) should be referred engagement contribute to the
for serial assessment of fetal size using limited predictive accuracy of SFH
ultrasound. measurement
622
623 Studies in low risk populations have consistently shown abdominal palpation to be of limited
624 accuracy in the detection of a SGA neonate (sensitivity 19–21%, specificity 98%) and severely SGA
625 neonate (less than 2.3rd centile, sensitivity 28%).148,149 In mixed risk populations, the sensitivity
626 increases to 32–44%.150,151 In high risk populations sensitivity is reported as 37% for a SGA neonate
627 and 53% for severe SGA.147 A Cochrane meta-analysis in 2015 did not find evidence that
628 measurement of SFH was superior to abdominal palpation, but only included one study of 1639
629 women.152 A large retrospective cohort study of 42 018 women in Sweden found improved overall
630 sensitivity (47%) for SGA.153 Thus, SFH measurement would seem superior to palpation in detecting
631 fetuses at risk, although both methods have significant limitations. The Swedish study also
632 demonstrated that SFH performs best nearer term Combining these findings with the most recent
633 meta-analysis of SFH for detection of SGA studies (eight studies, 10 018 women) confirms that SFH
634 remains a valuable, although limited tool for the detection of SGA (sensitivity 27%–76%).11 [Evidence
635 level 1–]
636
637 Maternal BMI greater than 35, abnormal fetal lie, large fibroids, hydramnios and fetal head
638 engagement contribute to the limited predictive accuracy of SFH measurement. SFH is associated
639 with significant intra– and inter–observer variation and serial measurement may improve predictive
640 accuracy.154-156 SFH should be measured from the fundus (variable point) to the symphysis pubis
641 (fixed point) with the measurement hidden from the examiner.151 Women with a single SFH which
642 plots below the 10th centile should be referred for further investigation with ultrasound assessment
643 (Appendix 2). There are no high quality data that enables recommendations on how reducing SFH
644 velocity should be defined, but if measurements more than 2 weeks apart do show not any increase
645 in SFH then women should be referred for single ultrasound assessment of fetal growth. [Evidence
646 level 4]
647
648 Evidence to support which chart to plot measurements is currently only provided by observational
649 studies. Population and customised charts to plot SFH are available (adjusted for maternal
650 characteristics). No trials were identified that compared customised with non–customised SFH charts
651 and thus evidence for their effectiveness on outcomes such as perinatal morbidity/mortality is
652 lacking.157 Whilst there have been concerns raised about the use of the Intergrowth estimated fetal
653 weight and biometry charts,158 the Intergrowth SFH chart159 is the most recent methodologically
654 robust chart available and is therefore recommended for use for plotting of SFH measurements.
655 Providers should determine which charts they are going to use antenatally to record SFH and staff
656 should be trained in the use of these. [Evidence level 2+]
657
658 7.1.2 Universal ultrasound
659
Routine measurement of fetal AC or 1+ A While studies have demonstrated
EFW in the third trimester does not and increase in detection of SGA
reduce the incidence of an SGA with universal rather than
selective ultrasound, this has not
neonate nor does it improve perinatal been demonstrated in clinical

outcome. trials to translate into improved
outcome. Routine fetal biometry is
thus not justified.
660
661 A meta-analysis of thirteen trials assessing universal late pregnancy ultrasonography in low risk or
662 unselected women demonstrated no beneficial effect, with the recommendation that it should not
663 be offered routinely in the third trimester.160 More recent studies suggest increased detection of SGA
664 with routine third trimester ultrasound assessment of growth, but no improvement in perinatal
665 outcome.161 [Evidence level 1+]
666
667 7.2 Moderate risk
668
669 7.2.1 Ultrasound biometry
670
Women in the moderate risk category are 2++ B Early onset FGR is uncommon.
at risk of late onset FGR and so require Ultrasounds can thus commence
serial assessment of fetal growth at 32 weeks but should continue
commencing at 32 weeks. For the until birth due to the risk of late
majority of women a scan interval of four onset FGR. An interval of four
weeks is appropriate. weeks between scans has a low
false positive rate.
When assessing fetal size the Hadlock 2+ C The Hadlock formula performed
formula should be used with HC (±BPD), the best in evaluation of optimal
AC and FL. formula for predicting EFW.
Assessment of the fetal AC may help in 2+ C Practical advice on the value of AC.
determining the fetus that is FGR.
671
672 Serial scanning is recommended for women at increased risk of fetal growth disorders. Early onset
673 FGR is uncommon (~0.5%) with the vast majority of cases associated with abnormal uterine artery
674 Doppler indices or already present estimated fetal weight (EFW) below the 10th centile in the early
675 third trimester (see section 7.3).162 Women at moderate risk of FGR do not require uterine artery
676 Doppler assessment but are still at risk of later onset FGR so require serial ultrasound assessment of
677 fetal growth from 32 weeks. [Evidence level 2++]
678
679 Although a scan at 32 weeks can identify 90% of SGA below the5th centile being born preterm, it only
680 identifies 60% of SGA births near term (for a 10% false positive rate). An ultrasound scan at 36 weeks
681 improves the detection of term SGA (SGA below the 5th centile at 37 weeks or more) from 58 to 70%
682 but this is at the expense of missing preterm SGA.163 Thus, the recommendation for surveillance for
683 late FGR and SGA is to commence at 32 weeks. The interval between scans should be no more
684 frequently than 14 days, with optimum assessment for growth velocity being 21–28 days. Mongelli
685 et al. used a mathematical model to estimate the impact of time interval between examinations on
686 the false positive rates for FGR (defined as no apparent growth in fetal AC between two consecutive
687 examinations).164 When the initial scan was performed at 32 weeks of gestation, the false positive
688 rates were 30.8%, 16.9%, 8.1% and 3.2% for intervals of 1, 2, 3 and 4 weeks respectively. False
689 positive rates were higher when the first scan was performed at 36 weeks of gestation (34.4%, 22.1%,
690 12.7% and 6.9% respectively). These findings suggest that if two measurements are to be used to
691 estimate velocity, they should be a minimum of 3 weeks apart to minimise false–positive rates for
692 diagnosing FGR. This recommendation does not preclude more frequent ultrasound measurements
693 of AC/EFW to predict fetal size at birth but rather indicates which measurements should be used to
694 interpret growth. For many pregnancies in the moderate risk category or in those unsuitable for SFH
695 measurements, an interval of four weeks is appropriate and reducing scan interval has not been
696 demonstrated to improve pregnancy outcome.165 [Evidence level 2++]
697
698 Three systematic reviews have assessed the accuracy of ultrasound biometric measures, both as
699 individual measures, as ratios, and combined (as the EFW).166-168 The most recent study
700 demonstrated that abdominal circumference (AC) is comparable to EFW in predicting SGA.168 The
701 largest prospective study within the systematic review demonstrated that prediction of SGA
702 provided by the fetal AC is better than head circumference (HC) or femur length (FL), but inferior to
703 the three measurements combined as EFW.169 Within the prospective POP study, the addition of AC
704 growth velocity was the only biometric measure that identified babies at increased risk of neonatal
705 morbidity.161 [Evidence level 2+]
706
707 The largest study to assess formulae for calculation of EFW suggested that 170 the most accurate
708 model was that of Hadlock et al incorporating HC, FL and AC with or without the addition of biparietal
709 diameter (BPD).171 Comparative studies have indicated that the Hadlock equation may more
710 accurately estimate fetal size than the Intergrowth 21 equation, including both analysis of routinely
711 collected un-blinded ultrasound scans and a prospective cohort study of blinded ultrasound scans at
712 28 and 36 weeks of gestational age.158 Given this and the much greater experience of its use, the
713 Hadlock equation is recommended for the estimation of fetal weight. [Evidence level 2+]
714
715 There is some contradictory evidence for whether the precision of EFW can be improved by three‐
716 dimensional (3D) ultrasound volumetry.172-174 Recent evidence suggests that EFW using magnetic
717 resonance imaging (MRI) may be more accurate than ultrasound in the prediction of both SGA and
718 LGA neonates.175,176 [Evidence level 2–]
719
720 There is no evidence to recommend one specific method of measuring AC (directly or derived from
721 abdominal diameters) nor which centile chart to use. The centile charts produced by Chitty et al.
722 were optimally constructed and are widely used.177 [Evidence level 2+]
723
724 Previous recommendations for the use of customised centile charts for EFW were based on
725 observational studies comparing units within England and Wales that had adopted a customisation
726 programme compared to those that did not.178 Recent analyses of the use of partially customised
727 versus non-customised centiles using population-based linkage studies from Scotland have
728 demonstrated that customisation of fetal size did not improve prediction of stillbirth.179 Similar
729 population based studies have not confirmed any benefit of customised charts compared to standard
730 assessment.20,180 Further analysis of the POP cohort demonstrated that previous findings of the
731 beneficial effects of customisation are likely to relate to more preterm infants being classified as SGA
732 by customised standards and the mothers of these infants more likely to have a higher BMI.181 Thus
733 raising concerns that customisation may “account” for apparent physiologic determinants of growth
734 that actually are causal and associated with risk of adverse outcome.181 [Evidence level 2+]
735
736 The Design study, which prospectively examined the use of customised antenatal SFH and ultrasound
737 EFW against non-customised measurements is due to be published in 2021 and will provide more
738 definitive evidence on the value of customisation, but at present the use of customisation for either
739 estimated fetal weight or symphysis fundal height measurement cannot be recommended.
740
741 Until further evidence is obtained the recommendation is to use the World Health Organization Fetal
742 Growth Charts to plot EFW.182 [Evidence level 2+]
743
744 7.3 High risk
745
746 7.3.1 Uterine artery Doppler waveform
747
In high risk populations uterine artery 2++ B In high risk populations uterine
Doppler should be performed at the artery Doppler at 20–24 weeks of
time of the routine anomaly scan to pregnancy has a moderate
determine when ultrasound predictive value for early onset
surveillance of fetal growth should SGA. In women with an
commence. Subsequently repeating abnormal uterine artery Doppler
uterine artery Doppler is of limited at 20–24 weeks of pregnancy,
value in this situation. subsequent normalisation of
flow velocity indices is still
associated with an increased risk
of an SGA neonate.
2++ B For women with a normal
Woman who are at a high risk with a uterine artery Doppler pulsatility
normal uterine artery Doppler index (mean ≤95th centile) the
midtrimester and normal fetal biometry risk of these disorders is low and
serial scanning for fetal biometry can thus serial scanning for fetal
commence at 32 weeks. biometry can be commenced in
the third trimester (from 32
weeks).
748
749 FGR particularly when severe (birth weight below the 3rd centile) or necessitating birth before 36
750 weeks of gestation, is characterised by lack of adequate trophoblast invasion of the myometrial
751 uterine spiral arteries and reduced uteroplacental blood flow resulting in persistent notching or
752 abnormal flow velocity ratios after 24 weeks of gestation.183 However, reduced endovascular
753 trophoblast invasion of decidual spiral arteries has been associated with the same waveform
754 abnormalities as early as 10–14 weeks of pregnancy.184 [Evidence level 2+]
755
756 Uterine artery Doppler has been incorporated into first trimester screening algorithms and combined
757 with maternal risk factors/characteristics and biomarkers to predict adverse pregnant outcomes
758 related to SGA births.185 However, studies where aspirin is administered to test positive women while
759 demonstrating a reduction in preterm preeclampsia did not demonstrate any effect on birthweight.
760 Thus highlighting that much of the benefit of uterine artery Doppler risk assessment for FGR is
761 identifying women at risk for early-onset preeclampsia.185 [Evidence level 2+]
762
763 In women with a low risk/who were unselected, uterine artery Doppler has insufficient predictive
764 ability as a test,186 in either the first or second trimester, to be clinically useful as shown in
765 randomised controlled trials and large cohort studies.187,188 [Evidence level 1+]
766
767 Using uterine artery Doppler alongside maternal factors and fetal biometry at a mid-trimester scan
768 (19–24 weeks) has been shown to be able to detect 89% of very preterm SGA below the 5th centile
769 (10% false-positive rate before 32 weeks) with 77% detected with uterine artery Doppler alone.189,190
770 Thus, although the predictive value of abnormal uterine Doppler is limited, it can be used in the
771 second trimester (18–24 weeks alongside the routine fetal anomaly scan) to further determine the
772 risk of placental dysfunction and therefore risk of hypertensive disorders or early onset FGR for
773 women at high risk, including those with abnormal serum analytes.191 While there are no effective
774 interventions to reduce this risk, the uterine artery Doppler can help determine further growth
775 surveillance pathways.192 For women with a normal uterine artery Doppler pulsatility index (mean
776 95th centile or below) the risk of these disorders is low and thus serial scanning for fetal biometry can
777 be commenced in the third trimester (from 32 weeks).8 [Evidence level 2++]
778
779 Abnormal uterine artery Doppler may normalize later in the second trimester, while normalisation
780 is associated with improved outcomes compared to women with persistently abnormal waveforms,
781 there is still an increased risk in those women in whom there is normalisation.193-195 Thus at present
782 the evidence suggests that repeating uterine artery Doppler later in the second trimester appears
783 to be of limited value. [Evidence level 2–]
784
785 It should be noted that there are reference ranges available for uterine artery Doppler PI throughout
786 pregnancy and thus while offering alongside the fetal anomaly scan is appropriate (for resource use
787 and convenience), the measurement may be performed at any time during pregnancy.8 [Evidence
788 level 2+]
789
790 Third-trimester uterine artery Doppler is not an effective risk assessment tool in unselected
791 pregnancies,196 but has been used to help identify where cases of FGR are due to placental
792 insufficiency when diagnosed later in pregnancy and moderately useful in predicting adverse
793 outcome in pregnancies with suspected SGA in the third trimester but not as a standalone test. 197
794 [Evidence level 2++]
795
796 For women at high risk with a normal uterine artery Doppler, serial scans are recommended to
797 commence at 32 weeks and for women with an abnormal uterine artery Doppler these can
798 commence at 28 weeks. Scans should be performed every 2–4 weeks with the scan interval
799 confirmed following the first assessment for fetal growth. SBLCBv2 gives guidance on
800 implementation of uterine artery Doppler assessment. For women in the high-risk group, in whom
801 uterine artery Doppler assessment has not been performed, serial scans should be commenced from
802 28 weeks, but this should only be used if uterine artery Doppler scanning has not been performed
803 by 24 weeks and not as an alternative routine surveillance pathway.
804
805 7.3.2 Ultrasound biometry
806
Fetal size alone is not sufficient to 2– C Many fetuses with growth below
identify FGR, unless AC or EFW is the 10th centile are healthy and
below the 3rd percentile. constitutionally small.
If two measurements are to be used to 2– C

estimate velocity, they should ideally
be a minimum of 3–4 weeks apart to
minimise false–positive rates for
diagnosing FGR.
Fetal growth disorders are suspected 4 GPP While suggested definitions can be
when there is sub-optimal, reduced given for changes in fetal growth
growth velocity and static growth. e.g. static, drop in velocity or
suboptimal; these should prompt

further assessment of maternal
and fetal wellbeing and re-
evaluation of fetal monitoring
plans rather than intervention due
to a lack of evidence.
Doppler velocimetry of uteroplacental 4 GPP For fetal growth disorders

circulation may be used to help diagnosed in the third trimester,
distinguish between SGA and FGR in uterine artery Dopplers can be
the third trimester used to assess for placental
insufficiency and are moderately
useful in predicting adverse
outcome in pregnancies with
suspected SGA in the third
trimester but not as a standalone
test.
When a fetal growth disorder is 4 GPP Management of a fetal growth

diagnosed an assessment of fetal disorder needs to be individualised
wellbeing should be made to include a but it is important to make an
discussion regarding fetal movements initial assessment of fetal
and a computerised CTG (cCTG) where wellbeing and maternal wellbeing,
there are concerns. A maternal due to association with
assessment should be made to include hypertensive disorders of
a blood pressure and proteinuria pregnancy
assessment.
807
808 It is intuitive to consider that assessment of growth would improve the diagnosis of FGR and of those
809 at greater risk of adverse outcome and there is some evidence that this is true in high risk women,
810 particularly in the SGA group.161,198,199 However, the optimal approach to interpret the information
811 from serial measurements of the same fetus remains unclear and is hampered by the non-linear
812 growth across pregnancy. Several approaches are available including fetal growth velocity (change
813 in fetal size between two time points), conditional percentiles (calculation of EFW percentile
814 expected at time point is determined by previous weight estimation of same fetus earlier in
815 pregnancy), projection based methods (models to predict EFW at a later point in gestation are based
816 on 2 or more observations of EFW combining size and velocity information).200-202 All of these
817 approaches require information on the mean and standard deviations of fetal growth at different
818 gestations and have methodological limitations including the spacing of the USS and inherent error
819 in measurements. Further research is required to quantify the predictive accuracy of different
820 methods, to determine the optimal timing of the first ultrasound, the optimal interval between scans
821 and the cost-effectiveness of a screening programme with appropriate neonatal outcomes.29
822 [Evidence level 2–]
823
824 Until this research has been conducted SBLCBv2 took a pragmatic approach, giving a definition for
825 suboptimal (rather than abnormal) growth, to help clinicians determine when there might be a
826 change in fetal growth that should prompt extra surveillance. This was based on assessment of fetal
827 growth standards in a low risk and general population and the observation of quasi-linear growth in
828 the third trimester.162,200 A figure of 280g every 2 weeks (20g per day) equates to the mean observed
829 weight gain minus one standard deviation from the mean across these two studies (abnormal growth
830 would be defined as the 3rd centile or approximately two standard deviations) from 32 weeks. Prior
831 to this gestation weight gain is less pronounced and less linear, thus making it difficult to provide a
832 single figure for assessment. [Evidence level 4]
833
834 Thus the following are advised and is based on the fact that fetal size alone is not sufficient to identify
835 FGR, unless AC or EFW is below the third percentile:
836
837  Define suboptimal growth as increase in EFW below 280g over 14 days (20g per day) from
838 32 weeks. A diagnosis of suboptimal growth should prompt a repeat ultrasound for biometry
839 in 2 weeks but not should not be used in isolation to make decisions regarding birth.
840  Static growth is defined as minimal change in fetal biometry over at least two weeks and
841 should be managed as suspected FGR until a further assessment of growth can be made.
842  Where there is a single measurement of EFW in the third trimester and an assessment of
843 fetal growth is required, the abdominal circumference can be compared to the measurement
844 obtained at the midtrimester anomaly scan. A subjective assessment of whether growth is
845 following the same trajectory can be made.160
846  A drop in fetal growth velocity, i.e. drop in AC or EFW of more than 2 quartiles or more than
847 50 percentiles (e.g. from 70th percentile to or below 20th percentile), should be considered as
848 suspicions of FGR until a further assessment of fetal growth can be made.
849  When a fetal growth disorder is diagnosed an assessment of fetal wellbeing should be made
850 to include a discussion regarding fetal movements and a cCTG where there are concerns. A
851 maternal assessment should be made to include a blood pressure and proteinuria
852 assessment.
853  For fetal growth disorders diagnosed in the third trimester, uterine artery Dopplers can be
854 used to assess for placental insufficiency and are moderately useful in predicting adverse
855 outcome in pregnancies with suspected SGA in the third trimester but not as a standalone
856 test.197
857
858 When a fetal growth disorder is suspected or diagnosed an assessment of fetal wellbeing should be
859 made to include a discussion regarding fetal movements and a cCTG where there are concerns. A
860 maternal assessment should be made to include a blood pressure and proteinuria assessment.
861 Further guidance regarding management of SGA and FGR is given in section 10.
862
863 7.4 Other methods
864
Clinical tests that measure PlGF, s-flt1 2++ B In the absence of features of
or the ratio between the two are now maternal hypertensive disease
clinically available and recommended there is limited data to support
for the diagnosis of preeclampsia. performing angiogenic marker
Although SGA/FGR are strongly testing unless there is diagnostic
associated with preeclampsia and uncertainty regarding the presence
placental dysfunction, the use of or absence of placental
PlGF/s-flt1 testing for the prediction insufficiency as a cause of FGR.
and diagnosis in non-hypertensive (e.g. in circumstances where fetal
women is not routinely growth is suggestive of genetically
recommended. small fetuses in conjunction with
uterine artery Doppler features of
placenta dysfunction).
865
866 7.4.1 Placental morphology and biometry
867
868 FGR that results from placental dysfunction is known to be associated with placentas that have
869 smaller diameters and increased depth,203 lower volumes204 and irregular shapes.205 As a result of
870 these findings there have been multiple studies examining whether antenatal assessment of
871 placental morphometry using either ultrasound or MRI can predict early and late FGR.77,203,204,206,207
873
874 In low risk populations the addition of placental biometry has not been shown to be effective at
875 predicting SGA or FGR as there are relatively weak association between placental size and
876 birthweight.208 In high-risk women with abnormal uterine artery doppler PI between 20–24 weeks,
877 abnormal placental morphometry is associated with an increased risk of birth before 32 weeks
878 (OR 4.7, CI 1.4–15.1).209 However, concerns have been raised around the reliability and
879 reproducibility of 2D ultrasound techniques,210 and it remains unclear what role the measurement
880 of 2D placental biometry should have in current clinical models used to predict FGR. [Evidence level
881 2–]
882
883 MRI can overcome some of the potential accuracy difficulties in assessing placental volume/shape
884 with ultrasound211 and can provide placental functional data that further delineate FGR from non-
885 FGR babies and SGA pregnancies,212 but at present the high cost and time required for each
886 examination limits its clinical applicability outside of research studies. [Evidence level 2–]
887
888 7.4.2 Biomarkers
889
890 Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family produced
891 in pregnancy by the placenta, in the circulation it binds to soluble fms-like tyrosine kinase-1 (s-flt1).213
892 The observation that women with preeclampsia have high circulating levels of s-flt1 has been
893 extensively investigated and it is recognised that low levels of PlGF and/or high levels of s-flt1 are
894 strongly associated with placental dysfunction and preeclampsia.85,214,215 Clinical tests that measure
895 PlGF, s-flt1 or the ratio between the two are now clinically available and recommended for the
896 diagnosis of preeclampsia.215 Although SGA/FGR are strongly associated with preeclampsia and
897 placental dysfunction, the use of PlGF/s-flt1 testing for the prediction and diagnosis of FGR in non-
898 hypertensive women remains uncertain. [Evidence level 2++]
899
900 Meta-analysis of first trimester measurement in women destined to give birth to SGA babies shows
901 low sensitivity (27% CI–20-36) and specificity (90% CI 83–94).85 Measurement of PlGF/s-flt1 in the
902 second trimester is similarly hampered by low sensitivity when distant from disease.216 However, if
903 measured near disease in the third trimester, PlGF/s-flt1 levels maybe more clinically useful
904 particularly when used in combination with EFW or uterine artery Doppler or other indicators of
905 FGR.217,218 A study of 9360 women who had PlGF combined with EFW measurement at 30–34 weeks
906 demonstrated 85% sensitivity for SGA and 92% sensitivity for FGR (at a fixed 10% false positive rate)
907 for infants born within 5 weeks of the test.219 More recently a large study in a low risk population of
908 3737 women demonstrated that the combination of EFW below the 10th centile with PlGF/s-flt1
909 resulted in drastically improved specificity in SGA infant with complicating features suggestive of FGR
910 compared with EFW below the 10th centile alone (97.8% [CI 97.3–98.3] versus 86.9% [CI 85.8–88.0])
911 though at the expense of sensitivity.220 It may therefore be that PlGF/s-flt1 testing enables the
912 antenatal identification of early and late onset FGR within SGA and even within non-SGA cohorts,
913 however this requires confirmation with prospective randomised controlled trials. [Evidence level
914 2++]
915
916 8. Which pregnancies complicated by fetal growth disorders should be further investigated?
917

Offer referral to fetal medicine if EFW 4 GPP To assess the risk of aneuploidy a
below the 3rd centile or below the 10th detailed anatomical survey and
centile with abnormal uterine artery assessment for uteroplacental
Doppler at the midtrimester anomaly insufficiency is performed.
scan.
Karyotyping should be offered in 2++ B Invasive testing for aneuploidy

severely SGA fetuses with structural would generally be reserved for
anomalies and considered in non- those with other structural
anomalous fetuses detected before 23 anomalies following a detailed
weeks of gestation, especially if anatomical survey.
uterine artery Doppler is normal.
Analysis should include a microarray
to detect microdeletions and micro-
insertions.
Serological screening for congenital 2– B Fetal infections are responsible for

cytomegalovirus (CMV) and up to 5% of SGA fetuses.
toxoplasmosis infection should be
offered in severe SGA.
Testing for malaria and Zika should be 4 GPP Fetal infections are responsible for
considered in high risk populations. up to 5% of SGA fetuses, of which
the commonest causes are CMV
and toxoplasmosis. For those that
have had recent travel to relevant
areas Zika and malaria should be
considered.
Following hospitalisation for 4 GPP For women who have been acutely
confirmed COVID-19 women should unwell with COVID-19 there is a
be referred for a fetal growth scan 14 risk that the severity of the illness
days after resolution of the acute may affect fetal growth.
illness.
918
919 Historically, identification of severe SGA (either EFW below the 3rd or 5th centile) was used as a marker
920 for aneuploidy and studies which predated widespread population based screening for aneuploidy
921 reported aneuploidy rates of up to 20%.221-223 These data are less applicable in modern practice, due
922 to the widespread use of population based screening for aneuploidy. However, invasive testing
923 should be considered in the context of severe SGA due to the possibility of other chromosomal
924 abnormalities which can be detected using DNA microarrays. A systematic review and meta-analysis
925 demonstrated that in fetuses undergoing invasive testing for FGR with no other structural anomalies
926 there was a 4% incremental yield of chromosomal microarray analysis (CMA) over karyotyping and a
927 10% incremental yield in FGR with associated fetal malformations.224 [Evidence level 2++]
928
929 A large population based study from Israel reported a 3% detection rate of pathological
930 abnormalities using microarray in the context of fetal growth restriction, and only a single case out
931 of 13 was an aneuploidy, underlining the transformative effect of population screening for
932 aneuploidy on this association.225 Therefore, when invasive testing is done in the context of SGA fetal
933 biometry, analysis of specimens should include CMA for the detection of micro-deletions and micro-
934 insertions. In early onset FGR CMA demonstrated an incremental yield over karyotyping of 4.8% in
935 isolated FGR, 10% in FGR with non-structural anomalies and 10.5% in FGR with structural
936 anomalies.226 [Evidence level 2+]
937
938 A retrospective cohort study from Denmark reported the associations with a below the 5th percentile
939 femur length (FL) at the time of a 17–22-week anomaly scan (with or without other features).227 The
940 positive likelihood ratio for trisomy 21 was 8.8, for 13/18 it was 6.5 and for other unbalanced
941 structural chromosomal abnormalities it was 17.4, with an absolute risk of 1 in 339. There was an
942 approximate 4-fold subsequent risk of both preterm birth and birth of an SGA infant. This has been
943 confirmed in a systematic review, which demonstrated that an isolated short FL is significantly
944 associated with SGA (OR 4.04, 95% CI 3.63–4.50) and preterm birth (OR 3.09, 95% CI 1.57–6.08).228
946
947 A case series from the Netherlands of 158 fetuses with an AC of the 5th percentile or below during a
948 detailed scan at 18–24 weeks (isolated feature) demonstrated two cases of trisomy 21 and a single
949 case of an unbalanced structural chromosomal abnormality (detected by SNP array).229 [Evidence
950 level 2–]
951
952 Hence, karyotyping should be offered in severely SGA fetuses with structural anomalies and
953 considered in non-anomalous fetuses detected before 23 weeks of gestation, especially if uterine
954 artery Doppler is normal.
955
956 Follow up scans should also be arranged given the association with subsequent birth of an SGA infant
957 and the timing of commencement and frequency individualised following the additional
958 investigations.
959
960 Fetal infections are responsible for up to 5% of SGA fetuses.230 The most common pathogens are
961 reported to be cytomegalovirus (CMV), toxoplasmosis, malaria and syphilis, although a recent
962 multicentre study found no association between congenital toxoplasmosis and incidence of a SGA
963 infant.230,231 A full maternal TORCH screen is unnecessary and testing should be based on history and
964 presentation.232 Malaria is a significant cause of preterm birth and LBW worldwide and it should be
965 considered in those from, or who have travelled in, endemic areas. 233 In congenital Zika virus
966 infection, fetal growth restriction is seen in 10% of affected pregnancies, and a femur-sparing pattern
967 of fetal growth restriction is commonly seen.234 [Evidence level 2–]
968
969 There are still limited data about coronavirus infection and COVID-19 illness in pregnancy and fetal
970 growth.235,236 Extrapolating data from other coronavirus infections (e.g. SARS and MERS) has led to
971 recommendations that women who required hospital admission for confirmed COVID-19 have a fetal
972 growth scan, 14 days following resolution of the acute illness.237 [Evidence level 2–]
973
974 9. What interventions should be considered when a fetal growth disorder has been diagnosed?
975
LMWH should not be prescribed to 1++ A Prospective trial evidence has
reduce the risk of SGA or FGR in failed to demonstrate a reduction
women at risk of FGR. in FGR in any at risk group
including those with heritable
clotting disposition.
Women should not be prescribed 1+ A There is no evidence in human

Phosphodiesterase 5 (PDE5) inhibitors studies with a low risk of bias, of
to treat FGR outside of randomised benefit from PDE5 inhibitors
controlled trials. prescription.
976
977 There are no proven interventions in SGA and FGR other than birth of the baby. Experimental
978 treatments under investigation in early phase clinical trials/studies include maternal VEGF (vascular
979 endothelial growth factor) gene therapy, melatonin and for pre-eclampsia with the potential to
980 impact on fetal growth; statins, nitric oxide donors, proton pump inhibitors and N-acetycysteine. Pre-
981 clinical investigations are underway in nanoparticles, microRNAs, hydrogen sulphide and
982 creatinine.238
983
984 PDE5 inhibitors
985
986 PDE5 inhibitors have been tested in women with early onset placental disease, including FGR
987 pregnancies to determine if they can improve outcomes. Most studies have focused on sildenafil
988 (Viagra) which was shown to improve Doppler parameters in animal models and suggested in case
989 series to be effective in increasing human fetal growth velocity.239,240 A small RCT of sildenafil (50mg
990 TDS) in women with early onset preeclampsia reported a prolongation of pregnancy by four days,
991 although only 60% of participants had recorded SGA and there was no effect of treatment on BW.241
992 However, prospective RCTs focusing on FGR have failed to show any benefit. Results from the
993 international STRIDER collaboration did not show any prolongation in pregnancy or improvement in
994 outcome from sildenafil (25mg TDS) treatment.242,243 The Dutch arm of STRIDER study was stopped
995 early due to safety concerns, although meta-analysis of outcomes from the three studies has failed
996 to show a conclusively detrimental effect.244 Tadalafil, a longer acting PDE5 inhibitor has also been
997 tested in case reports with reported improved neonatal outcome and no adverse effects, but no RCT
998 evidence is currently available.245,246 Therefore although some studies have suggested benefit using
999 PDE5 inhibitors to improve outcomes in FGR pregnancies, the negative results from STRIDER do not
1000 support the use of these drugs outside of clinical trials for the treatment or prevention of FGR.
1002
1003 Anti-thrombotic therapy
1004
1005 Randomised controlled trial evidence does not support the use of LMWH as an effective treatment
1006 to prevent SGA or FGR, even in the presence of heritable thrombophilia, and should only be used in
1007 women at risk of thromboembolic disease.135,136,138,139 There is insufficient evidence that
1008 administration of LMWH to pregnancies with FGR prolongs or improves pregnancy outcome.247
1010
1011 10. What is the optimal method and frequency of fetal surveillance when a fetal growth disorder
1012 has been diagnosed and when should birth occur?
1013
1014 10.1 SGA fetuses
1015
Ultrasound biometry should be 2– C More frequent measurements
performed every 2 weeks in fetuses increase the false-positive rate
identified to be SGA. for diagnosing FGR.
Umbilical artery Doppler is the primary 2+ B Use of umbilical artery Doppler

surveillance tool and should be in high risk pregnancy has been
performed at the point of diagnosis of shown to reduce perinatal
SGA and during follow-up as a minimum morbidity and mortality, reduce
every 2 weeks. antenatal admissions and
inductions of labour.
In fetuses with an EFW between the 3rd 2– C Timing of birth should be

and 10th centile, other features must be optimised to ensure balance of
present for birth to be recommended risks. The risks to be considered
prior to 39 weeks either maternal include those for mother and
(maternal medical conditions or baby (fetal and neonatal).
concerns regarding fetal movements) or
fetal compromise (a diagnosis of FGR
based on Doppler assessment or a
concern on CTG).
For all fetuses with an EFW or AC less 1+ B

than the 10th centile where FGR has
been excluded, birth or the initiation of
induction of labour should be
considered at 39+0 weeks after
discussion with the woman and her
partner. Birth should be achieved by
39+6 weeks.
For women who are recommended for 4 GPP There is no evidence to

induction of labour or planned birth determine how fetuses with
after 39+0 weeks for SGA but who wish SGA/FGR should be monitored if
to continue the pregnancy, counselling pregnancy continues, in this
must include a discussion regarding context.
evidence that there is no additional risk
for the baby or for the woman from
planned birth/induction at this
gestation when compared to expectant
care. An individual plan for the
continuation of the pregnancy must be
made.
After 37 weeks, an abnormal middle 2+ C In the term SGA fetus with

cerebral artery (MCA), CPR or UCR can normal umbilical artery Doppler,
be used to guide timing of birth. A an abnormal middle cerebral
normal MCA, cerebroplacental ratio artery Doppler (PI< 5th centile)
(CPR) or UCR does not provide has moderate predictive value
reassurance that the fetus is not for acidosis at birth and should
compromised and in all cases birth is be used to time delivery.
recommended prior to 39+6 weeks.
Induction of labour is not 2– C Compared to appropriately

contraindicated in the SGA fetus. . grown babies, SGA fetuses are at
greater risk of fetal heart rate
abnormalities in labour and thus

emergency caesarean section.
Continuous fetal heart rate monitoring 4 GPP

in labour is recommended.
1016
1017 SGA fetuses (see section 2) are those whose AC or EFW is below the 10th percentile but do not exhibit
1018 Doppler changes, where there are normal fetal movements and normal amniotic fluid. For these
1019 pregnancies where there are no additional maternal risk factors (for example maternal hypertension)
1020 ultrasound surveillance every 2 weeks is appropriate.248 Some cases of SGA progress to FGR-
1021 depending on gestation at diagnosis, this risk being greater with SGA detected early on. [Evidence
1022 level 2–]
1023
1024 Umbilical artery Doppler is the primary surveillance tool. Its use in high risk pregnancy has been
1025 shown to reduce perinatal morbidity and mortality, reduce antenatal admissions and inductions of
1026 labour.249 [Evidence level 2+]
1027
1028 Amniotic fluid can be assessed by the single deepest vertical pocket (SDVP) or amniotic fluid index
1029 (AFI) methods; although both correlate poorly with actual amniotic fluid volume.250 A Cochrane
1030 systematic review compared the two methods and concluded that there was no evidence that one
1031 method was superior in the prevention of adverse perinatal outcomes. However, compared to a
1032 SDVP less than 2 cm, when an AFI of 5 cm or less was used more cases of oligohydramnios were
1033 diagnosed and more women had induction of labour without an improvement in perinatal
1034 outcome.251 In a prospective study of pregnancies with FGR and oligohydramnios monitored for 8
1035 weeks after the initial diagnosis of oligohydramnios, mean EFW centile did not change significantly
1036 (remaining on 3rd centile in SGA fetuses) suggesting that oligohydramnios in this context is not
1037 associated with an increased risk of progression.252 Systematic reviews of observational and RCT data
1038 have demonstrated that while there is an association with oligohydramnios and SGA and adverse
1039 pregnancy outcome, it is not significant as a predictive test and in RCTs was only shown to be
1040 associated with an abnormal 5 minute Apgar but not acidosis or perinatal death in SGA.253,254 Thus
1041 while ultrasound assessment of amniotic fluid volume can be used as a form of monitoring to inform
1042 overall assessment of fetal wellbeing, it should not be used to determine management in isolation.
1044
1045 For SGA fetuses the recommendations for birth are based on the findings of the Disproportionate
1046 Intrauterine Growth Intervention Trial at Term Study (DIGITAT) and consideration of data related to
1047 morbidity related to “early term” (37–38 week) birth.255 In DIGITAT 650 women with suspected FGR
1048 above 36 weeks were randomised to induction or expectant management with twice weekly
1049 surveillance. There was no difference between the groups in severe neonatal morbidity or in
1050 caesarean birth but there was an increase in neonatal unit admission with induction before 38 weeks.
1051 The trial was not powered to assess perinatal mortality. Longer term childhood adverse outcomes
1052 were related to severe FGR (birth weight less than 2.3 centile).256 A health economics analysis
1053 demonstrated lower costs with induction at 38 weeks compared to earlier.257 It is noted that in the
1054 expectant management group more babies were likely to be born with a birthweight less than 3rd
1055 centile, reflecting the difficulty in distinguishing between FGR and SGA at term, and these were the
1056 babies at greatest risk of adverse neonatal outcome. [Evidence level 1+]
1057
1058 A Cochrane Review of the management of ‘compromised babies’ at term showed no difference in
1059 perinatal or long-term outcome with a policy of early birth versus expectant management.258 Only
1060 three trials were included: two included small babies, both part of the DIGITAT study.255,259 The third
1061 included babies with reduced amniotic fluid.260 [Evidence level 1+]
1062
1063 Stock et al compared the risk of neonatal unit admission with induction of labour at each given week
1064 (compared to the previous week) and demonstrated that at 37 weeks the risk was aOR 2.01 (95% CI
1065 1.80–2.25) and at 38 weeks aOR 1.53 (95% CI 1.41–1.67).15 While, there was a decreased odds of
1066 perinatal mortality with planned induction (37 weeks aOR 0.05 [0.03–0.68] and 38 weeks 0.23 [0.09–
1067 0.58]) 10 inductions would lead to one additional baby being admitted for neonatal care and it would
1068 require more than 700 inductions to prevent each perinatal death.15 There is also an association with
1069 early term birth and risk of subsequent special educational needs (SEN). After adjusting for maternal
1070 and obstetric characteristics and expressed relative to birth at 40 weeks, the risk of SEN was
1071 increased by 36% at 37 weeks, by 19% at 38 weeks and by 9% at 39 weeks.14 The ARRIVE trial
1072 randomised low risk nulliparous women to induction of labour at 39 weeks or expectant
1073 management and while it did not result in a significantly lower frequency of a composite perinatal
1074 outcome, there was a lower frequency of caesarean birth in the induction group.261 [Evidence level
1075 2+]
1076
1077 Thus, induction of labour between 37 and 38 weeks must only be considered as an intervention for
1078 fetuses at significantly increased risk of perinatal mortality (maternal or fetal compromise) with SGA
1079 babies offered induction of labour from 39 weeks with birth achieved by 39+6 weeks.262
1080
1081 10.2 FGR fetuses
1082
1083 FGR fetuses defined as those whose AC or EFW below the 10th percentile with Doppler changes (as
1084 described in the definitions of FGR) or AC/EFW less than the 3rd percentile- are a higher risk category,
1085 and in contrast to SGA, FGR is more frequently associated with maternal hypertension (occurring in
1086 70% of early onset pre 32 week FGR cases).263 While early and late FGR are in reality a continuum
1087 there are important differences with respect to the sequencing of Doppler, CTG and amniotic fluid
1088 changes and thus it is important to differentiate between them with respect to surveillance for fetal
1089 wellbeing.264,265 Most experts differentiate early from late FGR at 32–34 weeks of gestation. Prior to
1090 32 weeks the care of the FGR fetus is informed by randomised controlled trial evidence.263 Between
1091 32 and 34 weeks the evidence for monitoring of the FGR fetus is inconclusive. The high variability in
1092 Doppler reference ranges and indices used has a major clinical impact on prenatal diagnosis,
1093 monitoring, timing of birth decision, reproducibility and comparison of findings between research
1094 studies, efficacy of clinical policies and protocols, and many other aspects.266
1095
1096 10.2.1 Early FGR
1097
Pregnancies with early FGR should be 4 GPP When considering birth of a
monitored and managed with input from preterm fetus with FGR,
tertiary level units with the highest level particularly when very preterm
neonatal care. Care should be before 28 weeks and severe,
multidisciplinary by neonatology and counselling of the parents by
obstetricians with fetal medicine an experience obstetrician and
expertise, particularly when very neonatologist should occur.
preterm (before 28 weeks). Decisions for birth should take
into account predictors of
survival and morbidity (i.e.
weight, gestation).
Biometry in FGR should be repeated 1– C More frequent measurements

every 2 weeks.267 increase the false-positive rate
for diagnosing FGR.
In early FGR, the frequency of assessment 1– C The frequency of monitoring in

of fetal wellbeing will be based on the early FGR has not been
severity of FGR and UA Doppler subjected to any prospective
assessment with a minimum of weekly, randomized studies.
when there are no other concerns and 2– Nevertheless, analysis of
3 times weekly when there are UA TRUFFLE and other early FGR
abnormalities. Assessment of fetal cohorts suggests that sudden
wellbeing can include multiple modalities deterioration can occur.
but must include cCTG and/or ductus
venosus.
A large prospective
Computerised CTG analysis using the 2– C observational study of early
Dawes-Redman CTG system is FGR compared monitoring
recommended with the short term parameters and found that the
variation (STV) being the key parameter. ductus venosus and cCTG)
changes were most
discriminatory in relation to the
timing of birth. Of all
parameters measured, the
most marked changes
immediately prior to birth were
of raised ductus venosus
pulsatility index for veins (PIV)
and low cCTG STV.
MCA CPR/UCR can inform monitoring 4 GPP A weak relationship between

strategy and frequency. MCA CPR/UCR cerebral redistribution and
should not be used to determine birth adverse perinatal and 2 year
decisions prior to 37+0 weeks. outcome was found with MCA
pulsatility index and, for the
latter, umbilical-cerebral ratio
but not cerebroplacental ratio
(CPR).
Birth should be based on fetal wellbeing

assessment or maternal indication (e.g.
severe preeclampsia), as follows:
 Due to a lack of RCT evidence care of
fetuses before 26 weeks needs to be 4 GPP
personalised.
 From 26+0 weeks, birth if any of the 1+ B A comparative analysis of the
following is present: GRIT and TRUFFLE studies
- Spontaneous repeated suggested that long term (2
persistent unprovoked fetal year) outcomes were best in
heart rate decelerations; those women who were cared
- 26+0 to 28+6 weeks: birth if for based on cCTG and ductus
ductus venosus a-wave is at or venosus Doppler changes and
below baseline or STV is below thus timing of delivery should

2.6ms; be based on these parameters
- 29+0 to 31+6 weeks: birth if prior to 32 weeks.
ductus venosus a-wave is at or Consensus management of late
below baseline or STV is below preterm FGR following TRUFFLE
3.0ms; suggests birth if the umbilical
- 32+0 to 33+6 weeks (consider artery EDF is reversed at 32
after 30+0 weeks): birth if UA- weeks and absent at 34 weeks.
EDF is reversed or STV is below Birth can be considered from
3.5ms; 30 weeks and 32 weeks
- From 34+0 weeks (consider respectively and if continuing
after 32+0 weeks): deliver if UA- to the later gestation
EDF is absent or STV is below monitoring should be
4.5ms. performed with DV and cCTG.
Abnormal umbilical vein Doppler with 4 GPP

pulsations may be seen in early FGR and
should prompt assessment of the ductus
venosus waveform.
4 GPP
In early FGR a woman’s subjective
assessment of reduced fetal movements
or reduced or absent movements on
ultrasound should prompt an assessment
with cCTG.
1098
1099 A large prospective observational study of early FGR compared monitoring parameters and found
1100 that the ductus venosus and computerised CTG (cCTG) changes were most discriminatory in relation
1101 to the timing of birth.268 Of all parameters measured, the most marked changes immediately prior
1102 to birth were of raised ductus venosus pulsatility index for veins (PIV) and low cCTG short term
1103 variability (STV); these were of a greater magnitude than changes in the umbilical and MCA Dopplers,
1104 and amniotic fluid. In a later study relating these findings to adverse outcome, only ductus venosus
1105 contributed in a multivariable model.269 [Evidence level 2+]
1106
1107 Assessment of fetal heart rate variability is an important parameter in assessment of fetal wellbeing.
1108 However, visual inspection of conventional CTG is subjective and associated with low intra and
1109 interobserver reproducibility. The fetal heart rate STV is a biophysical parameter obtained by
1110 computerized CTG (cCTG). It reflects autonomic nervous system function and in the context of
1111 fetuses with FGR can reflect changes in autonomic activity induced by hypoxia, this has been
1112 validated with invasive testing demonstrating fetal hypoxaemia and acidaemia.270 [Evidence level XX]
1113
1114 The optimum management of early FGR has largely been defined by the TRUFFLE (trial of umbilical
1115 and fetal flow in Europe) study.263,271 In this study of growth restriction diagnosed between 26-32
1116 weeks, abnormal umbilical artery Doppler defined entry to the study (to confirm diagnosis of FGR),
1117 but did not play a part in management until after 32 weeks. Women whose pregnancies were
1118 randomized to fetal monitoring and birth based on late (critical) changes of the ductus venosus
1119 and/or cCTG had the lowest incidence of neurodevelopmentally poor outcome amongst survivors at
1120 2 years (5%) versus those managed by CTG alone (15%). The overall perinatal death rate was 8% and
1121 cerebral palsy rate 1%.85 The earlier GRIT randomized controlled study did not give a clear answer on
1122 whether compromised babies are best born immediately or managed expectantly.272 A comparative
1123 analysis of the two studies suggested that long term (2 year) outcomes were best in those women
1124 who were cared for based on cCTG and ductus venosus Doppler.273 A weak relationship between
1125 cerebral redistribution and adverse perinatal and 2 year outcome was found with MCA pulsatility
1126 index and, for the latter, umbilical-cerebral ratio but not cerebro-placental ratio (CPR).274 [Evidence
1127 level 1+]
1128
1129 The frequency of monitoring in early FGR has not been subjected to any prospective randomized
1130 studies. Nevertheless, analysis of TRUFFLE and other early FGR cohorts suggests that sudden
1131 deterioration can occur.275 [Evidence level 1–]
1132
1133 Umbilical artery Doppler changes are defined as: pulsatility index (PI) above the 95th centile
1134 (borderline), absent end diastolic flow (EDF) (pre-critical), reversed EDF (critical).
1135
1136 Ductus venosus Doppler changes are defined as: raised pulsatility index for veins (PIV) above the
1137 95th centile (borderline), or absent ‘a’ wave to baseline (pre-critical) or reversed ‘a’ wave (critical).
1138
1139 Depending on the severity of FGR repeat ultrasound scans (umbilical and ductus venosus Doppler)
1140 and CTG monitoring is normally undertaken every week where the umbilical Doppler changes are
1141 borderline, to alternate daily in the case of early onset FGR with pre-critical umbilical Doppler
1142 changes. Where the umbilical Doppler changes are critical, daily cCTG and/or Ductus venosus
1143 Doppler are indicated as sudden deterioration of the fetal condition may occur.
1144
1145 Birth should be planned when the Ductus venosus ‘a’ wave is at (absent) or below baseline (reversed)
1146 or there are CTG abnormalities; STV less than 2.6ms 26+0–28+6 weeks or less than 3.0ms at 29+0–31+6
1147 weeks.
1148
1149 When considering birth of a preterm fetus with FGR, particularly when very preterm before 28 weeks
1150 and severe, counselling of the parents by an experienced obstetrician and neonatologist should
1151 occur. Decisions for birth should take into account predictors of survival and morbidity (i.e. weight,
1152 gestation).276,277 [Evidence level 4]
1153
1154 10.2.2 Late FGR
1155
In late and term FGR, assessing the 4 GPP
ductus venosus waveform is unlikely to
be informative as it is very unlikely to
show severe abnormalities.
In pregnancies with late FGR, birth should 4 GPP In this group, a normal
be based on fetal wellbeing assessments umbilical artery Doppler cannot
or maternal indication (e.g. severe pre- exclude placental insufficiency
eclampsia) For fetal assessment, birth and thus it is important that
should occur if any of the following are other methods of surveillance
present: are used.
 Spontaneous repeated persistent

unprovoked fetal heart rate
decelerations;
 cCTG STV less than 3.5ms at 32+0
to 33+6 weeks and less than 4.5ms
at 34+0 weeks or above;
 Or abnormal UA Doppler as
follows:
- Absent end diastolic flow,
considered at 32 weeks and
absolute by 34 weeks;
- raised umbilical PI above the
95th percentile, 36+0 to 36+6
weeks.
In pregnancies with AC/EFW below the Fetuses at term with birth

3rd centile, birth should be initiated from weight below the 3rd
37+0 weeks to be completed by 37+6 percentile have the highest risk
weeks. of stillbirth, hence these
pregnancies should not exceed
37+6 weeks of gestation,
independent of Doppler
findings
Cerebral Doppler: abnormal MCA 2++ D It is likely that an association

CPR/UCR can inform monitoring strategy exists between cerebral
and frequency but should not be used to redistribution and adverse
determine birth decisions prior to 37 perinatal outcome, it is not
weeks. After 37 weeks, an abnormal established that birth based on
MCA, CPR or UCR can be used to guide MCA Doppler changes would
timing of birth. A normal MCA, CPR or improve outcome and there is
umbilicocerebral ratio (UCR) does not the potential that actually it
provide reassurance that the fetus is not might be harmful. urthermore,
compromised and in all cases birth is it is not clear that cerebral
recommended prior to 37+6 weeks. Doppler changes are
independently associated with
adverse neurodevelopmental
outcome.
In late FGR a woman’s subjective 4 GPP

assessment of reduced fetal movements
or reduced or absent movements on
ultrasound should prompt an assessment
with cCTG.
1156
1157 In this group, a normal umbilical artery Doppler cannot exclude placental insufficiency and thus it is
1158 important that other methods of surveillance are used.199,277,278 An abnormal umbilical artery Doppler
1159 should also prompt further assessment. There has been renewed recent interest in cerebral Doppler
1160 changes in FGR.279-282 While it is likely that an association exists between cerebral redistribution and
1161 adverse perinatal outcome, it is not established that birth based on MCA Doppler changes would
1162 improve outcome and there is the potential that actually it might be harmful. Furthermore, it is not
1163 clear that cerebral Doppler changes are independently associated with adverse neurodevelopmental
1164 outcome.283 Uterine artery Doppler has also been assessed in this group and an abnormal uterine
1165 artery Doppler is associated with an increased risk of intrapartum fetal distress, emergency
1166 caesarean birth and admission to neonatal intensive care unit.284-286 [Evidence level 2++]
1167
1168 There is no Cochrane Review on the optimal time of birth in late preterm babies and there has only
1169 been one trial of late preterm timed birth. The Growth Restriction Intervention Trial included 210
1170 babies at risk of late preterm growth restriction or compromise between 33+0 and 36+6 weeks, of
1171 whom 107 were randomised to early birth and 103 to delayed.272 Mortality and a range of
1172 neurodevelopmental measures were similarly distributed between the groups. Limitations of this
1173 study are the use of only one Doppler measure (umbilical artery Doppler), visual inspection of the
1174 CTG, and management prior to birth was not standardised, but left to the clinician’s discretion.
1175 Consensus management of late preterm FGR suggests birth if the umbilical artery EDF is reversed at
1176 32 weeks, absent at 34 weeks and raised PI at 36 weeks. For all babies with FGR, birth should be
1177 planned for and initiated by 37 weeks with birth achieved by 37+6 weeks.287 [Evidence level 1+]
1178
1179 Recent data from those women that declined randomization in the DIGITAT study of term fetal
1180 growth restriction, showed a significantly higher perinatal mortality. In these women, three of four
1181 pregnancies proceeded beyond 40 weeks.262 [Evidence level 1+]
1182
1183 11. How should fetuses with fetal growth disorders be born and prepared for birth?
1184
1185 The birth of a preterm or early term neonate on the basis of concerns regarding fetal growth should
1186 be optimised.
1187
1188 11.1 Antenatal corticosteroids
1189
Antenatal corticosteroids should be 1++ A High quality evidence, need
offered to women between 24+0–34+6 to ensure optimal timing.
weeks, ideally 48 hours before an
anticipated birth.
1190
1191 Antenatal corticosteroids should be offered to women between 24+0 and 34+6 weeks’ gestation who
1192 are at high risk of imminent preterm birth (for example, having a planned preterm birth). Clinicians
1193 and women should consider the balance of risks and benefits of corticosteroids in women at risk of
1194 imminent preterm birth beyond 35+0 weeks’ gestation.288 The optimal timing of steroids is key to
1195 ensure their effectiveness, and a steroid to birth interval of greater than 7 days should be avoided if
1196 possible.289 [Evidence level 1++]
1197
1198 11.2 Intrauterine transfer
1199
All women undergoing a preterm birth 1– B Babies less than 27 weeks or
should be offered transfer to a unit with with EFW < 800g should be
appropriate and available neonatal cot born in a unit with a neonatal
facilities when safe to do so. intensive care unit.
1200
1201 All women undergoing a preterm birth should be offered transfer to a unit with appropriate and
1202 available neonatal cot facilities when safe to do so and as agreed by the relevant neonatal
1203 Operational Delivery Network (ODN). Ensure the neonatal team are involved when a preterm birth
1204 is anticipated, so that they have time to discuss options with the woman and whoever may be
1205 supporting her prior to birth and to be present at the time of birth.290,291 [Evidence level 1–]
1206
1207 11.3 Magnesium sulphate for neuroprotection
1208
Magnesium sulphate for neuroprotection 1– B Magnesium sulphate
should be offered between 23+6 and 29+6 administration to the woman
weeks and considered up to 33+6 weeks. before the birth of a preterm
neonate is neuroprotective
reducing the risk of cerebral
palsy.
1209
1210 Magnesium sulphate administration to the woman before the birth of a preterm neonate is
1211 neuroprotective reducing the risk of cerebral palsy. As standard practice within the UK it should be
1212 offered to all women between 23+1–29+6 weeks.289 In a growth restricted fetus there is evidence of
1213 neurological developmental abnormalities persisting at least into the later preterm period.274 Hence,
1214 in the absence of robust evidence, the gestational window for administration should be extended to
1215 33+6 weeks. [Evidence level 1–]
1216
1217 11.4 Mode of birth
1218
In the FGR fetus with abnormal cCTG 4 GPP The risk of emergency
STV, ductus venosus alteration, caesarean section in this group
umbilical artery absent or reversed end will be very high.
diastolic flow velocities (AREDV)
caesarean birth is recommended and
should occur after administration of
steroids and magnesium sulphate.
In the SGA fetus or late FGR fetus with 4 GPP Compared to appropriately
normal umbilical artery Doppler or with grown babies, SGA fetuses are
abnormal umbilical artery PI but end– at greater risk of fetal heart
diastolic velocities present, induction of rate abnormalities in labour
labour can be offered but rates of and thus emergency caesarean
emergency caesarean birth are section.
increased and continuous fetal heart
rate monitoring is recommended from
the onset of uterine contractions.
Early admission is recommended in 4 GPP

women in spontaneous labour with a
SGA/FGR fetus in order to instigate
continuous fetal heart rate monitoring.
1219
1220 Compared to appropriate-for-gestational age fetuses, term and near term SGA fetuses are at
1221 increased risk of fetal heart rate (FHR) decelerations in labour, emergency caesarean birth for
1222 suspected fetal compromise and metabolic acidaemia at birth. This reflects a lower prelabour pO2
1223 and pH, greater cord compression and a greater fall in pH and higher lactate levels when FHR
1224 decelerations are present.274,292 Reported rates of emergency caesarean birth for suspected fetal
1225 compromise vary from 6-45% but a rate of ~15% is probably reasonable for fetuses with an AC or
1226 EFW less than 10th centile, with higher rates in those with serial AC or EFW measurements suggestive
1227 of FGR.202,293,294 No RCTs of mode of birth in the SGA fetus were identified. [Evidence level 2–]
1228
1229 In all recent studies reporting outcome of viable SGA fetuses with UA AREDV birth has been by
1230 caesarean birth and thus it is not possible to determine the likelihood of adverse outcome (including
1231 emergency caesarean birth for suspected fetal compromise) associated with induced / spontaneous
1232 labour.271,295 Older series report rates of intrapartum fetal heart decelerations necessitating CS of
1233 75–95%.296,297 More recent prospective data on the outcome of labour in SGA fetsuses with an
1234 abnormal UA Doppler but end-diastolic velocities is also extremely limited; suspected fetal
1235 compromise (necessitating emergency caesarean birth) has been reported in 17–32% of such cases,
1236 compared to 6-9% in SGA fetuses with normal UA Doppler, although it is acknowledged that
1237 knowledge of Doppler may lower obstetricians’ threshold for emergency caesarean birth.293,294,298,299
1238 The offer of induction of labour with continuous FHR monitoring is therefore reasonable in term and
1239 near term SGA/FGR fetuses without UA AREDV. The procedures for induction of labour should follow
1240 existing guidance.300 A systematic review concluded that mechanical methods of labour induction
1241 reduced uterine hyperstimulation with fetal heart rate changes compared to prostaglandins (RR 0.14
1242 [95% CI 0.04–0.53]) although there was no difference in caesarean birth rates and a recent study
1243 supported mechanical methods compared to dinoprostone in late FGR.301,302 [Evidence level 4]
1244
1245 12. Postnatal Investigations and Pre-pregnancy Counselling
1246
Histopathological examination of the 3 D To confirm placental disease
placenta maybe useful where FGR is and guide future pregnancy
diagnosed prenatally or at birth to management.
understand the underlying causes and
guide management in a subsequent
pregnancy.
Women who have given birth to a 4 GPP Important to confirm pathology

growth restricted infant should be and optimise future pregnancy
offered an appointment for postnatal management and modify the
counselling, review of placental women’s health to improve
histology and consideration of future pregnancy outcomes.
investigations of underlying causes such
as thrombophilia screening.
A plan for future pregnancies and 4 GPP

preventative strategies (in particular
smoking cessation, aspirin treatment)
should be recorded in the notes and
discussed with the woman.
1247
1248 As discussed in section 4, the birth of a baby with FGR is a major risk factor for FGR in a subsequent
1249 pregnancy. Thus following the birth of a baby with FGR investigations should be offered to try to
1250 determine the underlying cause and help provide an opportunity to discuss risk of recurrence and
1251 possible interventions to reduce risk at a pre-pregnancy appointment. These investigations should
1252 consider placental histopathology which may be useful303 (as recommended by the Royal College of
1253 Pathologists defined as birthweight below the 10th centile with an abnormal fetal growth curve) and
1254 investigation for thrombophilias. Modifiable risk factors should be addressed such as lifestyle factors
1255 (e.g. smoking, BMI) and medical conditions optimised. Plans for prevention (i.e. aspirin) and
1256 monitoring in future pregnancies should be discussed.
1257
1258 13. Recommendations for future research
1259
1260 - The interaction of multiple maternal risk factors is unknown and is an important area for
1261 further research.
1262 - Further research is required to quantify the predictive accuracy of different methods, to
1263 determine the optimal timing of the first ultrasound, the optimal interval between scans the
1264 benefits of universal growth scans. This should include cost-effectiveness of a screening
1265 programme with appropriate longer term neonatal outcomes.
1266 - Randomised controlled trials are required to determine whether biomarkers enables further
1267 delineation of early and late onset FGR and whether their use can help further determine
1268 management when combined with other tests.
1269 - Longitudinal studies of fetuses, whose birth weight falls within the normal range but who
1270 are suspected of abnormal fetal growth, should address whether additional measures of
1271 fetal growth e.g. ultrasound biometry and velocity, Doppler assessment and biomarkers can
1272 help determine those at risk of adverse outcome.
1273 - The role of middle cerebral artery Doppler in timing of birth in late preterm and term FGR
1274 - Use of maternal and fetal Doppler in the management of FGR needs to be supported by
1275 research to homogenize the Doppler indices, thresholds and reference ranges used.
1276 - Research into functional imaging of the placenta and its potential use in predicting adverse
1277 outcome.
1278 - Research into discovering novel biomarkers of fetal growth restriction.
1279
1280 14. Auditable topics
1281
1282 - Audit to report percentage of babies born <3rd centile and >37+6 weeks and case note audit
1283 of those babies <3rd centile not detected antenatally to identify areas of improvement.
1284 - Audit of babies born >39+6 weeks and <10th centile to provide an indication of detection rates
1285 (%) and management of SGA babies.
1286 - Use the PMRT to calculate the percentage of perinatal mortality cases annually where the
1287 risk assessment and management of FGR was a relevant issue.
1288 - Appropriate risk assessment during pregnancy, assessed as percentage of pregnancies
1289 where a risk status for FGR is identified and recorded at booking, and prescribing of aspirin
1290 to those at risk of placental dysfunction.
1291
1292 15. Useful links and support groups
1293
1294 - Tommy’s Charity [https://www.tommys.org]
1295 - Sands Stillbirth and Neonatal Death Charity [https://www.sands.org.uk/]
1296
1297 References
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2196 33. doi:10.1034/j.1600-0412.2003.00213.x
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2199 doi:10.1159/000491784
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2201 London: The Royal College of Pathologists; 2019.
2202
2203 Appendix 1: Surveillance pathway following risk assessment for Fetal growth
2204
2205
2206 Fetal medicine refers to a clinician with fetal medicine expertise.
2207 Appendix 2: Management of fetal growth restriction (FGR)
2208
2209
2210 *Consider after 30+0 weeks; **Consider after 32+0 weeks; EFW, estimated fetal weight; UA, umbilical artery; DV, ductus venosus; cCTG, computerised cardiotocograph; STV,
2211 short term variation; ms, milliseconds; AC, abdominal circumference; PI, pulsatility index; AREDF, absent reversed end-diastolic flow.
2212 This guideline was produced on behalf of the Royal College of Obstetricians and Gynaecologists by:
2213 Professor R K Morris MRCOG, Birmingham; Professor E Johnstone MRCOG, Manchester; Professor
2214 C Lees FRCOG, London; Dr V Hodgetts Morton MRCOG, Birmingham; Professor G Smith FRCOG,
2215 Cambridge
2216
2217 and peer reviewed by: XXX
2218
2219 Committee lead reviewers were: Dr M Madhra MRCOG, Edinburgh and Dr S Karavolos MRCOG,
2220 Manchester;1 and Dr R Bahl MRCOG, Bristol.2
1
2221 until September 2020; 2from September 2020.
2222
2223 The chair of the Guidelines Committee were: Dr MA Ledingham FRCOG, Glasgow and Dr B Magowan
2224 FRCOG, Melrose.
2225
2226 All RCOG guidance developers are asked to declare any conflicts of interest. A statement
2227 summarising any conflicts of interest for this guideline is available from:
2228 https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg51/.
2229
2230 The final version is the responsibility of the Guidelines Committee of the RCOG.
2231
2232 The guideline will be considered for update 3 years after publication, with an intermediate
2233 assessment of the need to update 2 years after publication.
2234
2235
2236
2237 DISCLAIMER
2238
2239 The Royal College of Obstetricians and Gynaecologists produces guidelines as an educational aid to
2240 good clinical practice. They present recognised methods and techniques of clinical practice, based on
2241 published evidence, for consideration by obstetricians and gynaecologists and other relevant health
2242 professionals. The ultimate judgement regarding a particular clinical procedure or treatment plan
2243 must be made by the doctor or other attendant in the light of clinical data presented by the patient
2244 and the diagnostic and treatment options available.
2245
2246 This means that RCOG Guidelines are unlike protocols or guidelines issued by employers, as they are
2247 not intended to be prescriptive directions defining a single course of management. Departure from
2248 the local prescriptive protocols or guidelines should be fully documented in the patient’s case notes
2249 at the time the relevant decision is taken.
2250

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CONSULTATION APRIL–MAY 2022

1 Green-top Guideline No. 31

The birthweight, gestation and 3 GPP This allows accurate risk

An individualised plan of assessment 3 GPP An individualised plan allows

Women with hypertensive disorders of 2+ C Women with hypertensive

1– B The benefit of vitamin D and folic

Women at risk of preeclampsia and/or 1++ A There is good evidence of aspirin

LMWH should not be prescribed to 1+ A Randomised controlled trial

Serial measurement of symphysis 1– B SFH remains a valuable, although

Women in whom measurement of 4 GPP Maternal obesity, abnormal fetal

neonate nor does it improve perinatal been demonstrated in clinical

If two measurements are to be used to 2– C

suboptimal; these should prompt

Doppler velocimetry of uteroplacental 4 GPP For fetal growth disorders

When a fetal growth disorder is 4 GPP Management of a fetal growth

Evidence Rationale for the

Karyotyping should be offered in 2++ B Invasive testing for aneuploidy

Serological screening for congenital 2– B Fetal infections are responsible for

Women should not be prescribed 1+ A There is no evidence in human

Umbilical artery Doppler is the primary 2+ B Use of umbilical artery Doppler

In fetuses with an EFW between the 3rd 2– C Timing of birth should be

For all fetuses with an EFW or AC less 1+ B

For women who are recommended for 4 GPP There is no evidence to

After 37 weeks, an abnormal middle 2+ C In the term SGA fetus with

Induction of labour is not 2– C Compared to appropriately

abnormalities in labour and thus

Continuous fetal heart rate monitoring 4 GPP

Biometry in FGR should be repeated 1– C More frequent measurements

In early FGR, the frequency of assessment 1– C The frequency of monitoring in

MCA CPR/UCR can inform monitoring 4 GPP A weak relationship between

Birth should be based on fetal wellbeing

below baseline or STV is below thus timing of delivery should

Abnormal umbilical vein Doppler with 4 GPP

 Spontaneous repeated persistent

In pregnancies with AC/EFW below the Fetuses at term with birth

Cerebral Doppler: abnormal MCA 2++ D It is likely that an association

In late FGR a woman’s subjective 4 GPP

Early admission is recommended in 4 GPP

Women who have given birth to a 4 GPP Important to confirm pathology

A plan for future pregnancies and 4 GPP

2207 Appendix 2: Management of fetal growth restriction (FGR)

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