Block VI Module 1 Case 2

“Two Peas in a Pod”

PRETERM LABOR

1. Define preterm labor.

Preterm birth — delivery before 37 completed weeks but beyond 20 weeks gestation
Premature — neonate that has the function expected of a newborn with AOG < 37 weeks. Problems of underdevelopment of
organ functions are present.
Premature rupture of membranes (PROM) — rupture of membranes at any time before the onset of labor irrespective of the
duration of pregnancy at the time of rupture.
Preterm premature rupture of membranes (PPROM) — rupture of membranes remote from term

Diagnostic Criteria
• 4 contractions in 20 minutes or 8 in 60 mins, plus progressive change in cervix
• Cervical dilatation > 1 cm
• Cervical effacement of 80% or more

Differential Diagnosis: Braxton Hicks contractions

2. Identify the causes of preterm birth.

INDICATED — 28%
Preeclampsia - 43%
Fetal Distress - 27%
Fetal Growth Restriction - 10%
Abruptio Placenta - 7%
Intrauterine Fetal Death - 7%

SPONTANEOUS — 72%
Medical/Obstetrical Complications
Placenta Previa or Abruption - 50%
Amniotic Fluid Infection - 38%
Immunological — APAS - 30%
Cervical Incompetence - 16%
Uterine — anomaly, fibroid - 14%
Maternal — PIH, drug abuse - 10%
Trauma or surgery - 8%
Fetal Anomalies - 6%

ANTECEDENTS AND CONTRIBUTING FACTORS

• Threatened Abortion — bleeding early in pregnancy associated with
pregnancy loss, preterm labor, and placental abruption.
• Lifestyle Factors
‣ Cigarette smoking
‣ Inadequate maternal weight gain
‣ Young or advanced maternal age
‣ Illicit drug use
‣ Occupational factors
‣ Stress
• Genetic Factors
• Chorioamnionitis
‣ Intrauterine infections are believed to trigger preterm labor by
activation of the innate immune system. Prostaglandins stimulate
FIGURE 27-8. !1
Proposed schematic mechanism of action for bacteria to inc
(Compiled from Berry, 1995; Gravett, 1994; Molnar, 1993; N
 uterine contractions, whereas degradation of extracellular matrix in the fetal membranes lead to preterm rupture of
membranes.

3. Identify the risk factors for spontaneous preterm labor.

• Prior Preterm Birth

TABLE 27-7. Recurrent Spontaneous Preterm Births According to
Prior Outcome in 6072 Scottish Women
First Birth Second Birth Next Birth Preterm (%)
Term — 5
Preterm — 15
Term Preterm 24
Preterm Preterm 32
From Carr-Hill and Hall (1985), with permission.

• Incompetent Cervix — recurrent, painless cervical dilatation and spontaneous midtrimester birth in the absence of spontaneous
membrane rupture, bleeding, or infection.
Document Bibliographic Information:
• Cervical dilatation
Date Accessed:
11:23:00 AM PST (GMT -08:00)
28-34 weeks: dilatation
Electronic Address: 1cm or >
559effacement >30%
Location
Ultrasonic In Book: of cervical length: <35 mm — high risk for preterm birth
measurement
WILLIAMS OBSTETRICS - 21st Ed. (2001)
Routine cervical ultrasonography
SECTION VII - COMMON — has no role inOF
COMPLICATIONS screening of normal-risk pregnant women
PREGNANCY
27. Preterm Birth
TABLES
• Signs and symptoms TABLE 27-7. Recurrent Spontaneous Preterm Births According to Prior Outcome in 6072 Scottish Women
‣ Pelvic Date
pressure
Posted:
1/10/2002 3:06:36 PM PST (GMT -08:00)
‣ Menstrual-like cramps
‣ Watery vaginal discharge
‣ Lower back pain

• Fetal Fibronectin
‣ Glycoprotein produced by cell types like hepatocytes, fibroblasts and endothelial cells and fetal amnion.
‣ Present in high concentration in maternal blood and amniotic fluid.
‣ Through to play a role in intercellular adhesion during implantation and in maintenance of placental adhesion to the
deciduas.
‣ Detected in cervicovaginal secretions prior to membrane rupture.
‣ > 50 ng/mL — possible marker for impending labor
‣ Positive value at 8-22 weeks — powerful predictor of preterm birth

• Bacterial Vaginosis
‣ In this condition, normal, hydrogen peroxide-producing, lactobacillus-predominant vaginal flora is replaced with anaerobes
that include Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis.
‣ Bacterial vaginosis has been associated with spontaneous abortion, preterm labor, PPROM, chorioamnionitis, and amniotic
fluid infection.

• Lower genital tract infection

‣ Trichomonas, Candida, Chlamydia — role in preterm birth controversial

• Salivary estriol — under investigation

• Priodontal disease — seven-fold risk of preterm birth

4. Discuss the management of preterm labor.

WITH INTACT FETAL MEMBRANES

• Amniocentesis to detect infection
‣ Negative gram stain — most reliable test to exclude amnionic fluid bacteria

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 ‣ High interleukin-6 level — most sensitive test for detection of amnionic fluids containing bacteria
‣ No studies to show that amniocentesis to diagnose infections is associated with improved pregnancy outcome

• Glucocorticoid Therapy — to enhance fetal lung maturation

‣ to accelerate lung maturation
‣ decrease the incidence of hyaline membrane disease if birth is delayed for 24 hours after completion of Rx and up to 7
days
‣ decrease the incidence of necrotizing enterocolitis and intraventricular hemorrhage
‣ given between 24-34 weeks gestations
‣ Adverse Effects:
- Pulmonary edema
- Infections
- More difficult glucose control in diabetics
‣ Further studies needed to evaluate:
- its effectiveness in pregnancies complicated by HPN, diabetes, multiple gestation, FGR, fetal hydrops
- risks/benefits of repeated courses
‣ Side effects of multiple doses
- early-onset neonatal sepsis
- chorioamnionitis
- neonatal death
‣ “Insufficient data to support routine use of repeat or rescue doses. Repeat or rescue doses should be reserved for
patients enrolled in clinical trials.” — 2000 NIH Consensus Development Conference
‣ Doses: Betamethasone 12 mg IM OD x 2 doses
Dexamethason 6 mg IM q 12 hours x 4

• Interventions to delay preterm birth

‣ Antimicrobials — antimicrobial treatment of women with preterm labor for the sole purpose of preventing delivery is
generally not recommended
‣ Bed rest — no evidence that this is helpful; associated with increased thromboembolic complications
‣ Hydration and sedation — no benefit
‣ Tocolytics:
➡Beta-adrenergic Receptor Agonists
- Ritodrine — approved by FDA for Rx of preterm labor
- Terbutaline
- Can delay delivery for not >48 hours
- Oral preparations — ineffective
- Side effects:
✓Maternal tachycardia
✓Hypotension
✓Pulmonary edema
✓Hyperglycemia
✓Hypokalemia
✓Lactic and ketoacidosis

➡Magnesium sulfate
- calcium antagonist
- Elliot (1983), Spisso and co-workers (1982): “effective, inexpensive, non-toxic”
- Cox, et. al. (1990) “no benefits”
- Cochrane Library (2006): “There is not enough evidence to show any difference between magnesium
maintenance therapy and either placebo or no treatment, or alternative therapies (ritodrine or terbutaline) in
preventing preterm birth after an episode of threatened preterm labor.”
- Dose: 4g IV loading then 2g/hr infusion
- Side effects:
✓Pulmonary edema
✓Respiratory depression
✓Maternal tetany
✓Cardiac arrest

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 ➡Prostaglandin Inhibitors
- Indomethacin
- Side effects:
✓Oligohydramnios
✓Intraventricular hemorrhage in newborn
✓Patent Ductus Arteriosus

➡Calcium Channel Blockers

- Nifedipine
- Side effects:
✓Maternal hypotension
✓Decreased uteroplacental perfusion
✓Enhanced toxicity when combined with MgSO4

Cochrane Library, 2006: “When tocolysis is indicated for women in preterm labor, calcium channel blockers are
preferable to other tocolytic agents compared, mainly betamimetics.”

• Prevention of neonatal Group B Streptococcal Infection

‣ Important cause of perinatal morbidity and mortality (sepsis, pneumonia, meningitis)
‣ Ampicillin 2 grams IV every 6 hours until delivery

WITH RUPTURED FETAL MEMBRANES

• Sterile speculum exam
‣ To verify membrane rupture
‣ to rule out cord prolapse
• Ultrasound
‣ to confirm gestational age
‣ to identify presenting part
‣ to assess amniotic fluid volume
• If >34 weeks and in labor — allow to progress
• If >34 weeks and not in labor — oxytocin induction of labor
• If 34 weeks or < and no maternal or fetal indications for delivery
‣ Close observation with continuous electronic fetal monitoring to look for evidence of cord compression, especially if in
labor
• Corticosteroids
‣ If <34 weeks; to prevent RDS
• Antibiotics
‣ If in labor
‣ To prevent neonatal Group B Streptococcal infection

Reference: Williams Obstetrics, 24th ed., Chapter 42

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MULTIFETAL PREGNANCY

1. Describe the etiology of multifetal gestation.

Dizygotic or Fraternal twins — result from fertilization of two separate ova

Monozygotic or Identical twins — arise from a single fertilized ovum that subsequently divides into two similar structures, each
with the potential for developing into a separate individual
Multifetal Pregnancy 893

2-cell stage

CHAPTER 45
A B C D 0–4 days

4–8 days

Amnionic Shared
8–12 days
cavity amnion
on

Chorionic
i
cavity or
Shared > 13 days
chorion
chor ion

Separate Fused
placenta placenta
Dichorionic Monochorionic Monochorionic Monochorionic
diamnionic diamnionic monoamnionic monoamnionic
conjoined twins
FIGURE 45-1 Mechanism of monozygotic twinning. Black boxing and blue arrows in columns A, B, and C indicate timing of division.
A. At 0 to 4 days postfertilization, an early conceptus may divide into two. Division at this early stage creates two chorions and two
amnions (dichorionic, diamnionic). Placentas may be separate or fused. B. Division between 4 and 8 days leads to formation of a
blastocyst with two separate embryoblasts (inner cell masses). Each embryoblast will form its own amnion within a shared chorion
(monochorionic, diamnionic). C. Between 8 and 12 days, the amnion and amnionic cavity form above the germinal disc. Embryonic
division leads to two embryos with a shared amnion and shared chorion (monochorionic, monoamnionic). D. Differing theories explain
conjoined twin development. One describes an incomplete splitting of one embryo into two. The other describes fusion of a portion of
one embryo from a monozygotic pair onto the other.

2. Identify the factors

evaluated with that affectin the
sonography incidence
the first trimester of
havemultifetal
shown gestation
tation. It has been estimated that 1 in 80 birthss are multifetal,
that one twin is lost or “vanishes” before the second trimester whereas 1 in 8 pregnanciess begin multifetal followed by sponta-
• Race —inmore common
up to 10 in blacks
to 40 percent thanpregnancies
of all twin in whites (Brady, 2013). neous reduction of one or more embryos or fetuses (Corsello,
The incidence is higher in the setting of ART.
• Heredity — maternal history of twinning more important than paternal 2010).
Monochorionic twins have a significantly greater risk of Dickey and associates (2002) described spontaneous reduction
‣ mother one of dizygotic twins — 1:58 births
abortion than dichorionic twins (Sperling, 2006). In some in 709 women with a multifetal pregnancy. Before 12 weeks, one
‣ father one of dizygotic twins — 1:116
cases, the entire pregnancy aborts. In many cases, however, only or more embryos died in 36 percent of twin pregnancies, 53 per-
one fetus dies, and the remaining fetus delivers as a singleton. cent of triplet pregnancies, and 65 percent of quadruplet preg-
Undoubtedly, some threatened abortions have resulted in death nancies. Interestingly, pregnancy duration and birthweight were
and resorption of one embryo from an unrecognized twin ges- inversely related to the initial gestational sac number regardless !5
 • Maternal Age and Parity
‣ >35 years
‣ Dizygotic twinning frequency increases almost fourfold between the ages 15 and 37 years. It is in this age range that
maximal FSH stimulation increased the rate of multiple follicles developing.
‣ The rate of twinning also increases dramatically with advancing maternal age because the use of artificial reproductive
technology is more likely in older women.
‣ > G3 — threefold increase
‣ 24th ed.: eightfold in G4 or less, 20-fold in G5 or more
• Maternal size and nutrition — more common in taller, heavier women; 40% increase in prevalence of twinning among women
who have taken supplementary folic acid.
• Pituitary Gonadotropin — higher rate of twinning in women who conceive within 1 month after stopping oral contraceptives —
may be due to sudden release of pituitary gonadotropin in amounts greater than usual during the first spontaneous cycle after
stopping OCP.
• Infertility Therapy (Ovulation Induction Drugs) — i.e., FSH + hCG; Clomiphene citrate increases both dizygotic and
monozygotic twinning
‣ In general with IVF, the greater the number of embryos that are transferred, the greater the risk of twins and multiple
fetuses.

3. Differentiate zygosity (monozygotic from dizygotic).

Periods of fertilized ovum division and consequent outcome

• Diamnionic, Dichorionic
‣ Division occurs within 1st 72 hours after fertilization
‣ Before inner cell mass is formed and outer layer of blastocyst in not yet committed to become the chorion
• Diamnionic, Monochorionic
‣ Division occurs between day 4-8
‣ After inner cell mass is formed and cells destined to become chorion have differentiated but those of the amnion not
• Monoamnionic, Monochorionic
‣ Division occurs 8 days after fertilization
‣ When amnion has been established
• Conjoined Twins
‣ Division occurs later
‣ After embryonic disk is formed

Types of multifetal gestation based on placentation and amnionicity

• Dichorionic-diamnionic
• Monochorionic-diamnionic
• Monochorionic-monoamnionic
• Monochrorionic-monoamnionic

Methods of determination of zygosity

The main reason to determine zygosity antenatally is that it can aid obstetrical risk assessment and guide management of
multifetal gestation. Monochorionic twin gestations are at increased risk for a variety of pregnancy complications, some of
which may be minimized by early antepartum recognition.

• Ultrasound — easier and more accurate in first half of pregnancy because fetuses are smaller, therefore easy to evaluate
the dividing membranes
‣ Indicators of Dichorionicity
- Presence of two separate placentas
- Thick (generally 2 mm or >) dividing membrane
- Fetuses of opposite gender
- Twin Peak Sign — triangular projection of placental tissue extending beyond the chorionic surface between the
layers of the dividing membrane
- T Sign — seen in monochorionic pregnancies; the right-angle relationship between the membranes and placenta
with no apparent extension of placenta between the dividing membranes

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 • Placental Examination
‣ If one common amnionic sac, not separated by chorion — fetuses are monozygotic
‣ If adjacent amnions are separated by chorion — fetuses could either be dizygotic or monozygotic (but more commonly
dizygotic)
‣ If same sex, blood typing of cord blood samples may be done (if different — dizygotic; if same — may be mono or di)
‣ Definitive diagnosis — DNA fingerprinting (only if with pressing medical condition)

• Infant gender — opposite sex — almost always dizygotic

4. Describe the diagnostic tools for identification of multifetal gestation.

• History
‣ Maternal family history of twins
‣ Advanced maternal age
‣ High parity
‣ Large maternal size
‣ Personal history of twins
‣ Use of ovulation induction drugs

• Physical Examination
‣ Uterine size larger than expected for gestational age
➡Ddx: distended bladder, inaccurate menstrual history, hydramnios, hydatidiform mole, uterine myoma, closely attached
adnexal mass, fetal macrosomia
‣ Multiplicity of fetal parts by palpation
‣ 2 fetal heart tones with difference in rate of at least 10 beats/minute in 2 widely separated areas

• Ultrasonography — earlier diagnosis, safer, more accurate

• Other aids
‣ Radiography — fetal skeletons sufficiently radioopaque after 18 weeks
‣ Biochemical tests — high hCG and AFP but not definitive
‣ MRI — delineate complications in monochorionic twins; provides a more detailed assessment of pathology in twins and is
particularly helpful in cases of conjoined twins.

5. Enumerate the differences in maternal adaptations in multifetal compared to singleton pregnancy.

• Nausea and vomiting — more pronounced

• Maternal blood volume expansion — greater, 50-60%
• Red cell mass increase — proportionately less than in singletons resulting in more pronounced physiological anemia
• Iron and folate requirements — higher
• Cardiac funciton — cardiac output increased by 20% compared to singletons due to greater stroke volume and increased heart
rate
• Blood pressure changes — lower diastolic BP at 20 weeks compared to singleton but higher by delivery by at least 15 mmHg
• Uterine growth — increased
• Maternal renal function — impaired especially in those complicated by hydramnios, most likely due to obstructive uropathy

6. Discuss obstetric complications that accompany multifetal gestation.

• Maternal complications
‣ Symptoms from marked abdominal enlargement
‣ Increased incidence of PIH
‣ Increased incidence of Iron deficiency anemia
‣ Placenta previa
‣ Abruptio placenta
‣ Postpartum hemorrhage
‣ Fetal malpresentation

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 • Fetal/Neonatal complications
• Abortion
• Malformations
‣ Defects from twinning itself — conjoined, acardiac, sirenomelia, neural tube defects, holoprosencephaly
‣ Defects from vascular interchange between monochorionic twins — microcephaly, hydrancencephaly, intestinal atresia,
aplasia cutis, limb amputation
‣ Defects from overcrowding — Talipes, congenital hip dislocation
• Low birthweight
• Preterm birth — mean gestational age for twins in 35 weeks and for triplets, 32 weeks.

7. Describe various unique complications of multifetal gestation

• Monoamniotic twinning: Intertwining of umbilical cords — common cause of death

• Conjoined fetal twins: thoracopagus (anterior), pygopagus (posterior), craniopagus (cephalic), ischiopagus (caudal)
• Acardiac twin – Twin Reversed-Arterial Perfusion (TRAP) sequence
‣ Caused by large artery-to-artery placental shunt, often also accompanied by a vein-to-vein shunt
‣ The used arterial blood reaching recipient twin preferentially goes to iliac vessels and thus perfuses only the lower part of
the body, leading to disruption or deterioration of growth and development of upper body
‣ What results is the other twin manifesting failure or disrupted growth of head (acardius acephalus) or a partially developed
head with identifiable limbs (acardius myelacephalus) or failure of any recognizable structure to form (acardius amorphous)
• Vascular anatomoses – most are hemodynamically balanced and of little fetal consequence but in others, this can cause
hemodynamically significant shunts between fetuses leading to acardiac twinning or twin-to-twin transfusion syndrome.
‣ Twin-to-Twin Transfusion Syndrome (TTTS) — blood is transfused from donor twin to recipient sibling such that donor
becomes anemic and growth restricted and recipient becomes polycythemic and may develop circulatory overload
manifesting as hydrops and heart failure.
‣ Postnatal diagnosis:
✓ Weight difference 15-20%
✓ Hydramnios in larger twin
✓ Oligohydramnios or stuck twin in smaller twin
✓ Hemoglobin difference 5g/dL or >
• Discordant twins – size inequality. Accumulated data suggest that weight discordancy greater than 25-30% most accurately
predicts perinatal outcome
Etiology:
‣ in monochorionic – due to placental vascular anastomoses that cause hemodynamic imbalance between twins
‣ in dichorionic – may be due to suboptimal implantation site of one twin or in utero crowding
• Death of one fetus – cerebral pathology in survivor most likely from acute hypotension at the time of death of another twin or
less likely from emboli or thromboplastic material originating from dead fetus
• Complete H mole and coexisting fetus

8. Enumerate and state the management of multifetal gestation

ANTEPARTUM
• Goals of antepartum care
‣ Prevent the delivery of markedly preterm infants
‣ Identify failure of one or both fetuses to thrive and deliver fetuses so afflicted before they become moribund
‣ Eliminate fetal trauma during labor and delivery
‣ Provide expert neonatal care
• Maternal diet
‣ Increased requirements
‣ Weight gain based on prepregnancy weight
‣ Iron and folic acid supplementation
• Maternal medical problems — BP monitoring
• Fetal Surveillance
‣ Serial sonography –3rd trimester
- monitor fetal size
- assess amniotic fluid volume

!8
 ‣ Tests of fetal health
- Non-stress test
- Biophysical profile
- Doppler velocimetry
• Management of complications
‣ Hydramnios – amniocentesis
‣ Preterm Labor
‣ Bed rest
‣ Tocolytics – risky
‣ Corticosteroids

INTRAPARTUM
• Recommendations for intrapartum management
‣ Continuous electronic fetal monitoring
‣ Blood available for transfusion
‣ Intravenous fluid
‣ Prophylactic antibiotics in preterm labor
‣ Ampicillin – 2 g every 6 hours IV
• Vaginal delivery
‣ cephalic-cephalic
‣ labor induction – not contraindicated; warrants special attention
‣ collision
• Caesarean Delivery
‣ noncephalic 1st twin
‣ interlocking twins (breech – cephalic)
‣ high order multifetal pregnancy

Reference: Williams Obstetrics, 24th ed., Chapter 45

FETAL GROWTH RESTRICTION

1. Define fetal growth restriction.

Birthweight
• Below the 5th percentile (Seeds, 1984)
• Below the 10th percentile small for gestational age (SGA). Such infants were shown to be at increased risk for neonatal
death (Lubchenco, 1967).
• Usher and McLean (1969) proposed that fetal growth standards should be based on mean values with normal limits defined
by + 2 standard deviations because this definition would limit small-for-gestational-age infants to 3 percent of births
compared with the 10th percentile.
• From a clinical standpoint, the latter definition appears to be most meaningful, most poor outcomes are in those infants
with birth weights below the 3rd percentile. Moreover, not all infants with birth weights less than the 10th percentile are
pathologically growth restricted; some are small simply because of constitutional factors. Indeed, Manning and Hohler
(1991) and Gardosi and colleagues (1992) concluded that 25 to 60% of infants conventionally diagnosed to be small for
gestational age were in fact appropriately grown when determinants of birthweight such as maternal ethnic group, parity,
weight and height were considered.

Normal Infant Birthweight

Varies with different cultures, ethnic groups, regions; babies born in high altitudes are often smaller than those in low altitudes.

2. Identify theories on pathophysiology of Fetal Growth Restriction. Differentiate between symmetrical versus
asymmetrical FGR.

Symmetrical versus asymmetrical fetal growth restriction

Campbell/Thomas (1977) described the use of ultrasonographically determined head-to-abdomen circumference ratio (HC/
AC) to differentiate growth restricted fetuses.

!9
 Theories as to Pathophysiology:
1. Symmetrical: proportionally small
- Early insult could theoretically result in relative decrease in cell number as well as cell size (such as chemical exposure,
viral infection, congenital or chromosomal problems) —> proportionate reduction in head and body size.
2. Asymmetrical: disproportionately lagging abdominal growth in overgrown neonates of mothers with well-controlled diabe- affect m
- Late pregnancy insult, such as placental insufficiency, theoretically could primarily
tes in affect
pregnancy. cell size.
Garcia-Flores (2011) also reported increased causes s
fetal cardiac
- Placental insufficiency —> diminished glucose transfer and hepatic storage —>intraventricular
Fetal abdominal septal thickness using sonography
circumference, which In cont
in women with well-controlled diabetes. Large-for-gestational signific
reflects liver size, would be reduced.
age infants delivered of women without impaired glucose tol- Malaria
- Recognition of symmetrical and asymmetrical patterns of impaired fetal erancegrowth has prompted
show higher insulin levelsconsiderable interest in
in childhood (Evagelidou, dysfunc
the antepartum diagnosis of these two forms of compromised growth because
2006). the pattern
Not surprisingly, fetalmay potentially
overgrowth reveal
has been the
associated diminis
cause. with development of the metabolic syndrome even in child- tors, be
hood (Boney, 2005). affected
This has been particularly true in the ultrasonic evaluation of fetal growth restriction, where several dimensions of the fetus are Consti
■ Accelerated Lung Maturation
now measured and can be related to each other in an attempt to evaluate proportionality of fetal structures. It is axi
Numerous reports describe accelerated fetal pulmonary matura-
• In practice, however, accurate identification of the symmetrical versus asymmetrical fetus has proved difficult. This is borns.
tion in complicated pregnancies associated with growth restric-
probably because the concept of brain sparing in asymmetrical growth restriction is difficult pounds
tion (Perelman, 1985).toOne
document in all but isthe
possible explanation most
that the
least tw
extreme cases. fetus responds to a stressed environment by increasing adrenal
both pr
• Crane and Kopta (1980) analyzed several anthropometric measurements in glucocorticoid secretion, newborns
growth-restricted which leads to accelerated
and concluded fetal lung
that late this
maturation (Laatikainen, 1988). Although
the concept of brain sparing was erroneous and could not be used to diagnose the cause of individual fetal growth this concept per-
of deliv
vades modern perinatal thinking, there is negligible evidence
restriction. to support it.
women
• Campbell: asymmetric GR: more likely were associated with pregnancies complicated Institut
To examineby thissevere preeclampsia,
hypothesis, fetal distress,
Owen and associates (1990)
and pat
operative intervention, lower APGAR scores. analyzed perinatal outcomes in 178 women delivered because
of 137,5
• Dashe (2000) growth restricted fetuses with sonographic HC/AC asymmetry of hypertension. They compared
were at increased risk these with outcomesand
for intrapartum in
ers esti
infants of 159 women delivered because of spontaneous pre-
perinatal complications while symmetrically growth restricted fetuses were not. explaine
term labor or ruptured membranes. They concluded that a
tively (M
“stressed” pregnancy did not confer an appreciable survival
Conclusion: Asymmetric fetal growth restriction represented significantly disordered growth,
advantage. Similar whereas
findings symmetrical
were reported by Friedmangrowth
and Gestat
restriction more likely represented normal, genetically-determined small stature. colleagues (1995) in women with severe preeclampsia. Two In the w
studies from Parkland Hospital also substantiate that the pre-
out pre
term infant accrues no apparent advantages from fetal-growth
(Rode,
3. Identify the risk factors that predispose to FGR. restriction (McIntire, 1999; Tyson, 1995).
weight
than th
Risk Factors and
• Many causes of poor fetal growth are a result of early viral insults, or genetic■developmental EtiologiesIn such cases, the
abnormalities. ciated w
Risk factors
long-term prognosis is clearly related to the nature and severity of the underlying problem. for impaired fetal growth include potential except c
abnormalities in the mother, fetus, and placenta. These three weight
• In other cases, however, fetal growth restriction is due to placental failure in an otherwise normal fetus, and timely diagnosis and
“compartments” are depicted in Figure 44-4. Some of these weight
appropriate obstetrical and neonatal management may reduce the risks of adverse factorsoutcome.
are known causes of fetal-growth restriction and may As p
significa
Risk factors for fetal growth restriction birth (P
(p. 121
Woman Fetus should
1. Constitutionally small mothers p. 177).
- Small women typically have smaller babies. If a woman begins Fetal day adv
Poor gestational weight gain Drugs and
pregnancy weighing less than 100 pounds, the risk of developing Constitutionally small teratogens malformations The bes
Poor nutrition the Hu
a small-for-gestational age infant is increased by at least two. Social deprivation
Infection German
(Simpson and colleagues, 1975). Eating disorders
Genetic
kcal/day
Maternal medical
abnormalities or in an av
2. Poor maternal weight gain and nutrition conditions
multifetal gestation It is
- In the woman of average or low BMI, poor weight gain efit from
throughout pregnancy may be associated with fetal-growth Supplem
Placental or cord abnormalities Trial (
restriction (Rode, 2007). Indones
- Lack of weight gain in the second trimester is especially strongly Placenta supplem
correlated with decreased birthweight. If the mother is large and receivin
otherwise healthy, however, below-average maternal weight gain FIGURE 44-4 Risk factors and causes of impaired fetal growth ity and
centering on the mother, her fetus, and the placenta. cognitiv
without maternal disease is unlikely to be associated with
appreciable fetal growth restriction.
- Marked restriction of weight gain during pregnancy should not be encouraged during the last half of pregnancy.

3. Social Deprivation
- The effects of social deprivation on birthweight is interconnected to the effects of associated lifestyle factors such as
smoking, alcohol or other substance abuse and poor nutrition.
!10
4. Fetal Infections
- Viral, bacterial, protozoan, and spirochetal infections have been implicated In up to 10% of cases of fetal growth
restriction (Knox, 1978). The best known of these are infections caused by rubella and CMV.
‣ CMV is associated with direct cytolysis and loss of functional cells.
‣ Rubella infection causes vascular insufficiency by damaging the endothelium of small vessels. Cell division rate is
also reduced in congenital rubella infections.
‣ Hepatitis A and B are associated with preterm delivery but may also adversely affect fetal growth (Waterson, 1979).
‣ Listeriosis, tuberculosis, and syphilis have been reported to cause fetal growth restriction. Paradoxically, in cases of
syphilis, the placenta is almost always increased in weight and size due to edema and perivascular inflammation.
‣ Toxoplasmosis is the protozoan infection most often associated with compromised fetal growth, but congenital
malaria may produce the same result.

5. Congenital malformations
- In general, the more severe the malformation, the more likely the fetus is to be small for gestational age. This is
especially evident in fetuses with chromosomal abnormalities or those with serious cardiovascular malformations.

6. Chromosomal abnormalities
- Placentas of fetuses with autosomal trisomies have a reduced number of small muscular arteries in the tertiary stem villi.
Thus, both placental insufficiency and primary abnormal cellular growth and differentiation may contribute to the
significant degree of fetal growth restriction often associated with karyotype abnormalities.
- Although postnatal growth failure is prominent in children with trisomy 21, fetal growth restriction is generally mild.
- Fetuses with trisomy 18 are virtually always significantly affected. Growth failure has been noted as early as the 1st
trimester. By the second trimester, long bone measurements typically fall below the 3rd percentile for age and the
upper extremity is more severely affected than the lower. Visceral organ growth is also abnormal in this condition.
- Significant fetal growth restriction is not seen with Turner syndrome (45, X or gonadal dysgenesis) or Klinefelter
syndrome (47, XXY).

7. Primary disorders of cartilage and bone

- Numerous inherited syndromes such as osteogenesis imperfecta and various chondrodystrophies are associated with
fetal growth restriction.

8. Chemical teratogens
- Any agent that causes a teratogenic injury is capable of adversely affecting fetal growth.
- Some anticonvulsants, such as phenytoin and trimethadione, may produce specific and characteristic syndromes that
include fetal growth restriction.
- Tobacco is a well-documented cause of fetal hypoxia and ischemia. The ensuing fetal damage may involve growth
restriction, and appears to impair fetal growth in a direct relationship with the number of cigarettes smoked.
- Narcotics and related drugs act by decreasing maternal food intake and fetal cell number.
- Alcohol is a potent teratogen that acts in a linear dose-related fashion. There is a 10% incidence of the fetal alcohol
syndrome in fetuses whose mothers are moderate drinkers (2-3 drinks per day), and up to a 30% incidence in fetuses
whose mothers are heavy drinkers (5 or more drinks per day).

9. Vascular Diseases
- Chronic vascular disease, especially when further complicated by superimposed preeclampsia, commonly causes
growth restriction.
- Preeclampsia itself may cause fetal growth failure. Abnormal vascular response is often seen in women with
preeclampsia even before the manifestations of overt hypertension, and occasionally an already growth-restricted fetus
is associated with recent-onset preeclampsia. As discussed in Chapter 31, fetal growth restriction with preeclampsia is a
marker of severity.

10.Chronic Renal Disease

- Renal insufficiency may be accompanied by restricted fetal growth.

11.Chronic Hypoxia
- When exposed to a chronically hypoxic environment, some fetuses have significant reduction in birthweight. Fetuses of
women who reside at high altitude usually weigh less than those born to women who live at a lower altitude.
- Fetuses of women with cyanotic heart disease are also frequently growth restricted.

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 12.Maternal Anemia
- Maternal anemia generally does not cause growth restriction except in those with sickle cell disease or with other
inherited anemias associated with serious maternal disease/
- Conversely, deficient in maternal total blood volume early in pregnancy has been linked to fetal growth restriction.

13.Placental and Cord Abnormalities

- Chronic partial placental separation, extensive infarction or chorioangioma are likely to cause restricted fetal growth. A
circumvallate placenta or a placenta previa may impair growth, but usually the fetus is not markedly smaller than
normal.
- Marginal insertion of the cord and especially velamentous insertions are more likely to be accompanied by a growth-
restricted fetus.
- Many cases of fetal growth restriction are in pregnancies with apparently normal fetuses whose placentas are grossly
normal. The cause of growth failure in these cases is often presumed to be uteroplacental insufficiency.
‣ Women with otherwise unexplained fetal growth restriction demonstrated a fourfold reduction in uteroplacental
blood flow compared with normally grown fetuses.
- Similar reductions are also seen in growth-restricted fetuses with congenital malformations, suggesting that maternal
blood flow may in part be regulated by the fetus.

14.Multiple Fetuses
- Pregnancy with 2 or more fetuses is more likely to be complicated by abnormal growth of one or both fetuses
compared with normal singletons. Fetal growth restrictions has been reported in 10 – 50% of twins

15.Antiphospholipid Antibody Syndrome

- Adverse obstetrical outcomes including feta-growth restriction have been associated with 3 species of antiphospholipid
antibodies: anticariolipin antibodies, lupus anticoagulant, and antibodies against beta-2-glycoprotein-I
- Pregnancy outcome in women with these antibodies is often poor, and may also involve early-onset preeclampsia and
2nd or 3rd trimester fetal demise.
- Maternal morbidity due to vascular thrombotic evens is not uncommon. Pathophysiological mechanisms in the fetus
appear to be caused by maternal platelet aggregation and placental thrombosis. These antibodies may also be
suspected in women demonstrating repetitive second-trimester fetal loss or early-onset fetal growth restriction,
especially when accompanied by early, severe hypertensive disease.

16.Extrauterine Pregnancy
- The fetus gestated outside the uterus is usually growth restricted. Also, some uterine malformations have been linked
to impaired fetal growth.

4. Identify complications associated with FGR.

Mortality and Morbidity

• Fetal growth restriction is associated with substantive perinatal morbidity and mortality
• Increased incidence of:
‣ Fetal demise
‣ Birth asphyxia
‣ Meconium aspiration
‣ Neonatal hypoglycemia
‣ Hypothermia
‣ Prevalence of abnormal neurologic development

5. Identify screening methods employed to identify FGR.

• Identification of risk factors, including a previously growth-restricted fetus, should raise the possibility of growth restriction
during the current pregnancy. In women with significant risk factors

• Early establishment of gestational age

‣ One of the most important parameters in prenatal care
‣ Based on LMP in women with regular cycles, early UTZ if cycles are not regular

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 • Attention to maternal weight gain — pregnant women should gain an average of 25–30 lbs throughout pregnancy; failure to
gain weight may be due to failure of fetal growth and/or lack of amniotic fluid.

• Fundic height measurements

‣ Carefully performed serial fundal height measurements throughout gestation are a simple, safe, inexpensive, and
reasonably accurate screening method that may be used to detect many small-for-gestational-age fetuses
‣ The method used in most clinics in the United States was reported by Jimenez and colleagues. Briefly, this consists of a
tape calibrated in centimeters being applied over the abdominal curvature from the top of the symphysis to the top of the
uterine fundus which is identified by palpation or percussion
‣ The tape is applied with the markings away from the examiner to avoid prejudice. Between 18 and 30 weeks, the uterine
fundal height in centimeters coincides with weeks of gestation. If the measurement is more than 2-3cm from the expected
height, inappropriate fetal growth may be suspected

• Ultrasonic measurements
‣ In women with significant risk factors, consideration should be given to serial sonography to detect abnormal fetal growth
‣ The frequency of such examinations will vary depending upon clinical circumstances
- An initial dating examination
- Followed by a second examination 32 – 34 weeks, should serve to identify many cases of fetal growth restriction. If
clinical findings suggest inadequate fetal growth prior to this time, earlier sonography is necessary. Definitive diagnosis,
however, usually cannot be made until delivery

‣ The optimal ultrasonographic method of estimating fetal size, and therefore fetal growth restriction, has been reviewed by
Manning (1995). Abdominal circumference measurements have been accepted by experienced ultrasonographers as
the most reliable index of fetal size.
- The estimated fetal weight using sonographic abdominal circumference measurements was almost always within 10%
of the actual birthweight
- Abdominal circumference, measured directly in the newborn infant, was also shown to be an important anatomical
marker of growth restriction

‣ An association between oligohydramnios and pathological fetal growth restriction has long been recognized. The smaller
the vertical dimension of sonographically measured pocket of amniotic fluid, the greater the perinatal mortality. The likely
explanation for oligohydramnios is diminished urine production due to hypoxia.

• Doppler Velocimetry in Fetal Growth Restriction

• Abdominal umbilical artery Doppler velocimetry — characterized by absent or reversed end-diastolic flow — has been
uniquely associated with fetal growth restriction.
- The use of Doppler velocimetry in management of fetal growth restriction has been recommended as a possible
adjunct to techniques such as nonstress testing or biophysical profile (ACOG, 2000).

6. Discuss management options for FGR

• Near term vs remote from term

• Method of choice for labor and delivery

Management of Fetal Growth Restriction

Once a small-for-gestational-age fetus is suspected, intensive efforts should be made to determine if growth restriction is
present and, if so, its type and the etiology. In the presence of sonographically detectable anomalies, cordocentesis may be
performed for rapid karyotyping. The detection of a lethal aneuploidy may obviate cesarean section for fetal indications.
Efforts are made to ensure delivery, when possible, of an infant who will subsequently thrive and achieve normal potential.

Growth Restriction Near Term

• Prompt delivery is likely to afford the best outcome for the fetus who is considered growth restricted at or near term.
• In the presence of significant oligohydramnios, most fetuses will be delivered if gestational age has reached 34 weeks or
beyond.
• With reassuring fetal heart rate pattern, vaginal delivery may be attempted.
‣ Unfortunately, such fetuses often tolerate labor less well than appropriately grown counterparts, and cesarean section is
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 indicated for intrapartum fetal compromise
• Uncertainty about the diagnosis of fetal growth restriction should preclude intervention until fetal lung maturity is assured.
• Expectant management can be guided using antepartum fetal surveillance techniques. Fetal-Growth Disorders 883

Suspected fetal-growth restriction < 38 weeks

CHAPTER 44
< 24 weeks ≥ 24 weeks but < 34 weeks ≥ 34 weeks but < 38 weeks

Deliver if maternal - Evaluate maternal status and - Evaluate maternal status and
status indicates; comorbidities comorbidities
otherwise repeat - Umbilical artery Doppler velocimetry - Umbilical artery Doppler velocimetry
sonography every - Fetal testing—NST,T BPPP, etc. - Fetal testing—NST,T BPPP, etc.
3–4 weeks - Consider corticosteroids for lung
maturation
Consider delivery if:
- Absent or reversed end-diastolic flow
Consider delivery if:
- Oligohydramnios
- Reversed end-diastolic flow
- Nonreassuring fetal tracing
- Nonreassuring fetal tracing
- Maternal status or obstetrical
- Maternal or obstetrical indications
indications necessitate delivery
necessitate delivery

If no indications for immediate delivery, If no indications for immediate delivery:

begin antepartum fetal surveillance:
- Regular fetal testing
- Weekly umbilical artery Doppler velocimetry
- Weekly evaluation of amnionic fluid
- Antepartum fetal surveillance—BPP, P NST
T, etc.
- Umbilical artery Doppler velocimetry weekly
- Amnionic fluid evaluation weekly

Repeat sonography for fetal growth Repeat sonography for fetal growth
every 3–4 weeks every 3–4 weeks

Fetal growth—continue None or poor Fetal growth—continue None or poor

antepartum fetal growth—consider fetal surveillance until growth—consider
surveillance until delivery 38 weeks, then deliver delivery
34 weeks, then begin
protocol for after
34 weeks (above)

FIGURE 44-9 Algorithm for management of fetal-growth restriction at Parkland Hospital. BPP = biophysical profile; NST = nonstress test.

Growth Restriction
involved 548Remote from Term
women between 24 and 36 weeks’ gestation with opmental and behavioral outcomes that did not differ at age
• When growth
clinical restriction
uncertainty is diagnosed
regarding in an Women
delivery timing. anatomically
were normal
2 years fetus prior2012).
(Van Wyk, to 34 weeks, and amniotic fluid volume and
randomly fetal
antepartum assigned to immediate
surveillance delivery orobservation
is normal, to delayed delivery
is recommended.
until the situation Management of the Near-Term Fetus
• As long as there is worsened.
continued The primaryand
growth outcome
fetalwas perina- remains
evaluation normal, the pregnancy is allowed to continue until fetal
tal death or disability after reaching age 2 years. There were no As shown in Figure 44-9, delivery of a suspected growth-
maturity is achieved; otherwise, delivery is effected.
differences in mortality rates through 2 years of age. Moreover, restricted fetus with normal umbilical artery Doppler velocim-
• At times,
childrenamniocentesis
aged 6 to 13 years for assessment
did not show of pulmonary
clinically maturity
significant may
etry, be helpful
normal amnionic in fluid
clinical decision
volume, making. fetal heart
and reassuring
• Sonography
differencesisbetween
repeated at intervals
the two of 2 to2011).
groups (Walker, 3 weeks. rate testing can likely be deferred until 38 weeks’ gestation.
• In fetalThe
growth restriction remote from Intrauterine
DIGITAT—Disproportionate term, no specific
Growthtreatment will ameliorate
Said another the condition.
way, uncertainty regarding the diagnosis should
‣ Intervention
No evidence Trial
thatat bed
Term—was designed
rest actually to study
results delivery
in accelerated preclude
fetal growthintervention until fetal
or improved lung maturity
outcome is assured. fetuses
in growth-restricted
timing of growth-restricted fetuses who were 36 weeks’ gesta- Expectant management can
➡Despite this, many clinicians advise a program of modified rest in the lateral recumbent position in which be guided using antepartum fetal maternal
tion or older. There were no differences in composite neona- surveillance techniques described in Chapter 17. Most clini-
cardiac output — and presumably placental perfusion — is maximized.
tal morbidity in 321 women with fetal-growth restriction and cians, however, recommend delivery at 34 weeks or beyond if
a gestational agesupplementation,
➡Nutrient of at least 360/7 weeks plasma volume
who were expansion,
randomly thereantihypertensive drugs,
is clinically significant heparin, and
oligohydramnios. aspirinstate-
Consensus have all been
shown
assigned to be ineffective
to induction (ACOG,
or to expectant 2000). (Boers,
management ments by the Society of Maternal-Fetal Medicine (Spong, 2011)
• In most
2010).cases
Secondaryof fetal growth
analyses restriction
included assessmentdiagnosed
of neurodevel-prior and
to term, neitherCollege
the American a precise etiology and
of Obstetricians norGynecologists
a specific therapy is
apparent. Management decisions in such cases hinge upon an assessment of the relative risks of fetal damage or death with
continued prenatal evaluation versus the risks due to preterm delivery.

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 • Although reassuring tests of fetal well-being will in many cases allow safe observation and continued maturation of
significantly preterm growth-restricted fetuses, concern exists for their long-term neurological outcome.
• Although it is generally believed that various tests of fetal well-being appear to be effective in reducing the risks of fetal
death, some investigators challenge this belief. Winer and colleagues (1996) performed nonstress tests, biophysical profiles,
and umbilical artery velocimetry within 3 days of delivery in 135 fetuses who, at birth, were confirmed to have growth
restriction.
‣ Other than metabolic acidosis at birth, which was predicted by absent or reversed end-diastolic umbilical artery
velocimetry, morbidity and mortality in the growth restricted fetuses were determined primarily by gestational age and
birthweight and not by abnormal fetal testing
‣ Moreover, there is no convincing evidence that any such testing scheme reduces the risk of survival with long-term
neurological deficit
‣ Thus, the optimal management of the preterm growth-restricted fetus remains problematic

Labor and Delivery

• Throughout labor, spontaneous or induced, those fetuses who are suspected of being growth restricted should be
monitored for evidence of compromise, most commonly manifested by abnormalities of fetal heart rate.
• Fetal growth restriction is commonly the result of insufficient placental function as a consequence of faulty maternal
perfusion, ablation of functional placenta, or both. These conditions are likely aggravated by labor. Importantly, diminished
amniotic fluid also predisposes to cord compression and its dangers.
• A woman with suspected growth-restricted fetus should undergo “high-risk” intrapartum monitoring
• Cesarean delivery is increased in fetal growth restriction
‣ The infant may need expert assistance in making a successful transition to air breathing
‣ Increased risk of being born hypoxic and of having aspirated meconium
‣ It is essential that care for the newborn be provided immediately by someone, who can skillfully clear the airway below
the vocal cords, especially of meconium, and ventilate the infant as needed
‣ The severely growth-restricted newborn is particularly susceptible to hypothermia and may also develop other
metabolic derangements such as serious hypoglycemia, polycythemia and hyperviscosity.
‣ Low-birth weight infants are at increased risk for motor and other neurological disabilities.

Reference: Williams Obstetrics, 24th ed., Chapter 44

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