DOI: 10.1111/tog.
12475 2018;20:109–17
The Obstetrician & Gynaecologist
http://onlinetog.org
Extreme prematurity and perinatal management
a,
Anna L David PhD MRCOG, * Aung Soe FRCPCH MRCP
a
Professor and Consultant in Obstetrics and Maternal Fetal Medicine, Institute for Women’s Health, University College London, London,
WC1E 6HX, UK
b
Consultant Neonatologist, Medway Maritime Hospital, Gillingham, Kent, ME7 5NY, UK
*Correspondence: Anna L. David. Email: a.david@ucl.ac.uk
Accepted on 3 May 2017
Key content
 Perinatal management of pregnant women delivering at the
threshold of viability has medical and ethical considerations. It
should be preceded by the best advice from a multidisciplinary
neonatal and obstetric team to fully inform parents and
achieve a consensus on the optimal care for the
mother and neonate.
 Obstetric interventions can affect maternal and neonatal outcomes
after birth at the threshold of viability. These include
administration of steroids, magnesium sulphate and tocolysis, fetal
monitoring in labour and mode of delivery.
 Obstetric complications such as malpresentation are common and
can affect delivery choices at extreme preterm gestational ages. This
requires obstetricians to plan carefully with parents before
labour starts.
Please cite this paper as: David AL, Soe A. Extreme prematurity and perinatal management. The Obstetrician & Gynaecologist 2018;20:109–17. https://doi.org/10.
1111/tog.12475
Introduction
Perinatal management of pregnant women who deliver at the
threshold of viability (22+0 weeks to 25+6 weeks of gestation)
is a major medical and ethical issue. It can also be an
extremely stressful experience for parents, medical and
midwifery staff alike, since birth can be rapid, and
complications catastrophic and unexpected. Parents need
the best possible information from a multidisciplinary
neonatal and obstetric team to be able to consider all their
options, and for all to reach a consensus on the best way to
optimally care for the mother and neonate.
In 2006, the Nuffield Council on Bioethics considered the
ethical, social, economic and legal issues of birth around
‘borderline viability’ and made several recommendations.1
Internationally, there is currently a consensus that there is no
hope of neonate survival at 22 weeks of gestation, and that
up to 22+6 weeks is the cut-off for human viability. For
gestation of 25+0 weeks onwards, there is also a general
agreement that active management should be offered.2
Delivery between 22+6 and 24+6 weeks is the most
challenging since decision making may be fluid as the
situation rapidly changes.
ª 2018 Royal College of Obstetricians and Gynaecologists
Review
b
Learning objectives
 To understand how obstetric decisions and interventions can affect
maternal and neonatal outcomes when women are at risk of
delivery at extreme premature gestational ages.
 To enable trainee obstetricians to better counsel women and their
partners about possible complications before and during labour at
extreme preterm gestations.
Ethical issues
 Should we monitor the fetal heart during labour, deliver by
caesarean section and resuscitate a baby born at extreme
prematurity when short-term and long-term neonatal outcomes
are likely to be poor?
Keywords: caesarean section / counselling / extreme prematurity /
in utero transfer / labour management
Given the morbidity associated with extreme prematurity,
obstetricians should strive to optimise all aspects of the
peridelivery period at the threshold of viability. Parents
should receive accurate counselling about likely outcomes
and a prediction of impending preterm delivery. Other
strategies to improve neonatal outcome include transferring
the woman to an appropriate perinatal unit, promoting fetal
maturation and optimising the timing, site and mode of
delivery, while at the same time minimising the risk of
infection and neurological injury and preventing cerebral
palsy. There is evidence to guide obstetric perinatal
management of extremely preterm infants for some issues
such as the use of steroids and in utero transfer. For other
important aspects of care, however, there is little to guide the
clinician. Two documents from the Royal College of
Obstetricians and Gynaecologists (RCOG) and the
American College of Obstetricians and Gynecologists
(ACOG)/Society for Maternal–Fetal Medicine (SMFM)
summarise the evidence and provide consensus on
periviable delivery.3,4 A framework for clinical practice at
the time of birth for babies born extremely preterm
(<26 weeks of gestation) is also available from the British
Association of Perinatal Medicine (BAPM).5
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 Extreme prematurity and perinatal management
Neonatal outcomes after extreme
preterm birth
The first question that parents often ask when faced with
the possibility that their baby will be born extremely
prematurely is, ‘will my baby be ok?’ At present, in the UK,
active resuscitation is attempted for the 84% of infants born
alive at 23+0 to 23+6 weeks of gestation (Table 1).6
Although largely related to long-term survival, the 5-
minute Apgar score is associated with short-term
outcomes for infants born at 23–24 weeks of gestation,
with this association being stronger for infants born at
24 weeks.7 Survival rates for extremely preterm infants after
birth vary between countries. Differences in the availability
of neonatal intensive care, and in attitudes towards end-of-
life decisions such as removal of care, can – in part –
explain these differences. A 1995 study comparing practices
of care and outcomes for infants born between 23 and
25 weeks of gestation in the British Isles (EPICure), and a
1997–8 French study (EPIPAGE)8 found that, despite
apparent differences in the modalities of groups with
limited intensive care, the longer-term outcomes for
infants were not significantly different.
A review of studies published over the past three decades
around the world reveals a progressive increase in the survival
rate for infants born at 23, 24, and 25 weeks of gestation
(Figure 1).3 Admissions and survival of babies born at
extreme preterm gestations were studied in the two EPICure
cohorts of 1995 and 2006.6 Between 1995 and 2006, the
number of babies born at fewer than 26 completed weeks of
gestation and admitted to neonatal units in England
increased by 30% (Table 1). Survival for babies born at
22–25 weeks of gestation and admitted for intensive care
increased by 13%; the proportion of babies admitted with
severe disability did not change significantly, whereas the
proportion surviving without disability rose by 11%
(P < 0.001).6 The proportion of admitted babies surviving
rose significantly only for those born at 24 and 25 completed
weeks of gestation (Table 1).
Predicting delivery and birth outcome
At the threshold of viability, delivery at as few as 5 extra days
further along in gestation can double the chance of survival
and greatly increase neurologically intact survival. In many
cases, however, there is little choice about the timing of
delivery and, more importantly, leaving a fetus in a hostile
environment such as in the presence of infection or bleeding
can mean that prolonging gestation may worsen the
outcome. As gestational age is the primary determinant of
almost all perinatal outcomes, it is therefore essential to
accurately estimate gestational age by ultrasound as early as
possible; national guidelines recommend first trimester
110
ultrasound.9 Birthweight and female sex are independently
positively associated with survival after extremely preterm
birth, with greatest survival in infants born weighing
between the 50th and 85th centile.10 The accuracy of
estimated fetal weight (EFW) measurement at extreme
preterm gestations is compromised by large intra-observer
and inter-observer variability; no specific EFW formula is
recommended.5 It can be particularly difficult to measure the
EFW accurately when the membranes have ruptured and the
presenting part, head or breech, is low in the pelvis. A variety
of Doppler indices are frequently used to assess fetal
wellbeing, but their ability to predict long-term outcomes
at extremely preterm gestations is limited. Therefore, it is
sensible to decide to resuscitate a baby born at
extreme prematurity based not solely on EFW, but also on
the true birthweight measured immediately after birth
and neonatal vigour.
Neonatal survival is improved when extreme preterm
infants are delivered in an appropriate level neonatal unit.
Transfer probably optimises management, but may not
necessarily aim to do everything possible to achieve
neonatal survival when faced with imminent delivery at the
limits of viability. Diagnosis of preterm labour in
symptomatic women at extremes of prematurity can be
challenging. As well as vaginal examination, several
techniques are available to aid diagnosis, such as
transvaginal ultrasound measurement of cervical length,
vaginal fetal fibronectin, cervical phosphorylated insulin-
like growth factor binding protein-1 and placental alpha
microglobulin-1.12,13 Translabial cervical length assessment
achieves similar measurements of cervical length to those
obtained by transvaginal sonography at 22–24 weeks of
gestation.14 Although there is no evidence for its preferred
use in preterm labour at extremes of viability, translabial
ultrasound can be a useful alternative to transvaginal
ultrasound if there are concerns that introducing the probe
into the vagina might cause rupture of bulging membranes.
Once the membranes have ruptured, however, there is no
correlation between cervical length as measured by translabial
ultrasound and latency to delivery interval.15
Based on cost-effectiveness, the recent National Institute
for Health and Care Excellence (NICE) pathway on preterm
birth and labour proposes that these tests are not used in
women with pregnancies below 29+6 weeks of gestation, but
that these women should be offered steroids and tocolysis
instead.16 At the low gestational ages at the threshold of
viability that are considered in this article (22+0 weeks to
25+6 weeks of gestation), the absolute benefits for the baby of
treatments such as steroids and tocolysis are much higher
than at later gestational ages (for example, >29+6 weeks).
Thus, there are greater implications for failing to treat a
woman who is truly in threatened preterm labour but is
misdiagnosed to be at low risk of delivery (false negative).16
ª 2018 Royal College of Obstetricians and Gynaecologists
 Table 1. Perinatal characteristics of births between 22 and 26 weeks of gestation in 2006 and survival to discharge from hospital.6 Figures are numbers (percentages, as shown), unless stated
otherwise.

Gestational age (weeks) 22 23 24 25 26 22–26 P value*

Births (including all stillbirths)

Total 478 594 636 692 733 3133 —
Antepartum stillbirths 158 153 133 140 131 715 —
Alive at onset of labour† (% total births) 272 (57) 416 (70) 494 (78) 550 (80) 594 (81) 2326 (74) —
Intrapartum stillbirths 120 77 52 29 14 292 —
Time of intrauterine death unknown 48 25 9 2 8 92 —
Live births
Total (% alive at onset of labour) 152 (56) 339 (81) 442 (89) 521 (95) 580 (98) 2034 (87) <0.001
Birth in hospital with designated tertiary 69 (45) 163 (48) 254 (58) 343 (66) 350 (60%) 1179 (58%) <0.001

ª 2018 Royal College of Obstetricians and Gynaecologists

neonatal intensive care unit (% live births)
Active stabilisation withheld (% live births) 111/152 (73) 55/338 (16) 16/441 (4) 4/520 (1) 3/574 (1) 189/2031 (9) <0.001
Admissions for palliative care 0 1 2 0 0 3 —
Admissions for intensive care
Total (% live births) 19 (13) 217 (64) 381 (86) 498 (96) 571 (98) 1686 (83) <0.001
Any antenatal steroid (% of admissions) 8 (42) 140 (65) 326 (86) 437 (88) 486 (86) 1397 (83) <0.001
Caesarean section (% of admissions) 1 (5) 12 (6) 55 (14) 153 (31) 250 (44) 471 (28) <0.001
Median (IQR) birth weight (g)‡ 540 (509–574) 600 (548–649) 671 (610–730) 779 (699–850) 879 (787–970) 750 (639–870) <0.001
Surfactant given at any time (% 18/19 (95) 215/217 (99) 379/381 (81) 490/498 (98) 567/571 (99) 1669/1686 (99) 0.66
admissions)
Admission temperature <35°C (% 5/16 (31) 60/206 (29) 64/374 (17) 58/495 (12) 37/562 (7) 224/1653 (14) <0.001
admissions)
Total transferred§ within 24 hours (% 3/19 (16) 53/217 (24) 84/381 (22) 85/498 (17) 74/571 (13) 299/1686 (18) <0.001
admissions)
Survival to 28 days
Total 5 88 226 378 472 1169 —
% of live births (95% CI) 3 (1 to 8) 26 (21 to 31) 51 (46 to 56) 73 (68 to 76) 81 (78 to 85) 57 (55 to 60) <0.001
% of admissions (95% CI) 26 (9 to 51) 41 (34 to 47) 59 (54 to 64) 76 (72 to 80) 83 (79 to 86) 69 (67 to 72) <0.001
Survival to discharge
Total 3 66 178 346 448 1041 —
% of live births (95% CI) 2 (0 to 6) 19 (15 to 24) 40 (36 to 45) 66 (62 to 71) 77 (73 to 81) 51 (49 to 53) <0.001
% of admissions (95% CI) 16 (3 to 40) 30 (24 to 37) 47 (41 to 52) 69 (65 to 74) 78 (75 to 82) 62 (59 to 64) <0.001
Median age (days) at discharge (IQR) 124 (119–252) 134 (115–171) 116 (98–141) 102 (87–1221) 91 (80–113) 102 (86 to 113) <0.001

*P value for association of gestational age using either logistic regression or regression with gestational age in days.
†
Includes all births by caesarean section when fetus was known to be alive at beginning of procedure.
‡
Missing for one baby born at 23 weeks’ gestation.
§
Transferred to another hospital for ongoing care within 24 hours of birth.
Key: IQR = interquartile range; CI = confidence interval.
David and Soe

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 Extreme prematurity and perinatal management
Figure 1. A review of studies published over the past three decades around the world revealed progressive increase in the survival rate for infants
born at 23, 24, and 25 weeks of gestation.3 Figure reproduced with permission of Elsevier/American Journal of Obstetrics & Gynecology.
Copyright© 2015 American College of Obstetricians and Gynecologists.
Antenatal maternal and fetal interventions
Given that increasing gestational age clearly improves overall
survival at extreme prematurity, much attention has focused
on methods to prevent or delay preterm birth in women who
present in threatened preterm labour at extremely preterm
gestations. However, prolonging the pregnancy may be
inappropriate for some women because of intrauterine
infection or placental abruption. Thus, the decision to
prolong pregnancy should be based on the balance between
maternal and fetal risks.
Evidence for the use of tocolysis in preterm labour is
summarised in the RCOG’s Green-top Guideline17 and more
recently by NICE.16 Systematic reviews have not
distinguished between tocolytic use at the threshold of
viability (≤26 weeks of gestation) and later preterm
gestations. One systematic review concluded that tocolytics
were not associated with a significant reduction in births
before 30 weeks of gestation18 and another concluded that
oxytocin receptor antagonists such as atosiban did not
prevent preterm birth at <28 weeks of gestation.19 The recent
Swedish EXPRESS (Early Use of Existing Preventive
Strategies for Stroke) study,20 which assessed the impact of
obstetric factors on the outcome of babies born before
27 weeks of gestation, found that tocolysis decreased the risk
of infant death within the first year of life.
Evidence on the best type of tocolytic to use is unclear. In
extreme preterm gestations, a randomised controlled trial
(RCT) of atosiban found a higher incidence of perinatal and
neonatal death in women with pregnancies at <26 weeks of
gestation who were randomised to atosiban compared to
placebo. This difference may be explained by the fact that
patients randomised to the atosiban intervention arm had a
lower gestational age than those in the control placebo arm.21
A second study comparing glyceryl trinitrate skin patches
with placebo conducted a priori sub-analysis according to
112
gestational age and showed a non-significant decreased risk
of delivery before 28 weeks of gestation (relative risk [RR]
0.50; 95% confidence interval [CI] 0.23–1.09).22 For women
already in threatened or established labour with intact
membranes, there is insufficient evidence to advocate the
use of progesterone as a tocolytic agent.23 A systematic review
and meta-analysis of nifedipine as a tocolytic agent in women
with preterm labour did not stratify for gestational age, and
no conclusions could be drawn.24 NICE recommends that for
women with intact membranes in suspected preterm labour,
obstetricians should consider nifedipine for women with
pregnancies between 24+0 and 25+6 weeks of gestation, and
offer it to women over 26+0 weeks.16 In the UK, patients
should be advised that nifedipine has no market
authorisation licence for this indication; the prescriber
should follow relevant professional guidance and take full
responsibility for their decision to administer this drug.
Cervical cerclage can be performed as a salvage measure in
cases of premature cervical dilatation with exposed fetal
membranes in the vagina. However, this is not recommended
for women in established preterm labour, who have uterine
contractions, infection or active vaginal bleeding.16,25 Some
women who already have a cervical cerclage in place will
present with labour symptoms at extreme preterm gestations.
The decision to remove a vaginal cervical cerclage, such as a
Macdonald (low vaginal) or Shirodkar (high vaginal)
cerclage, must be carefully timed to avoid unnecessary
trauma to the cervix if the woman labours with the
cerclage in situ. Once preterm prelabour rupture of the
membranes (PPROM) has occurred, the cerclage is usually
removed to avoid infection with a foreign body. However,
the best time to remove a vaginal cervical cerclage remains
unclear; a recent RCT on retention versus immediate removal
of vaginal cervical cerclage after PPROM was terminated
before the sample size was reached, and showed no
significant differences in neonatal outcomes.26 Pooling of
ª 2018 Royal College of Obstetricians and Gynaecologists

amniotic fluid is commonly seen following PPROM but if it
is not seen, NICE recommends testing the vaginal fluid for
insulin-like growth factor binding protein-1 or placental
alpha-microglobulin-1.16
The many neonatal benefits of antenatal corticosteroids are
well established. All women requiring, or at high risk of,
impending preterm delivery between 24+0 and 34+6 weeks of
gestation should receive antenatal corticosteroids.27 This
should also be considered for women at the threshold of
viability who are at risk of preterm birth. In prospective
cohort studies of women delivering at extreme preterm
gestations, antenatal corticosteroid use reduces the rate of
infant death or neurodevelopmental impairment.20,28 The
question of whether to repeat a course of steroids may arise
in women at the threshold of viability. The short-term
benefits for babies, including less respiratory distress and
fewer serious health problems in the first few weeks after
birth, support the use of repeat doses of prenatal
corticosteroids for women who remain at risk of preterm
birth 7 days or more after an initial course. These benefits
were associated with a small reduction in head size at birth.
Reassuringly, however, despite no benefit, the current
available evidence shows no significant harm
in early childhood.29
Prematurity is a risk factor for early onset group B
streptococcus (GBS) disease for neonates. NICE
evaluation of the evidence for antibiotics to prevent
early onset neonatal sepsis found that a few studies had
focused on extreme preterm gestations.30–33 Indicators of
suspected or confirmed clinical chorioamnionitis, such as
intrapartum fever >38°C, foul-smelling amniotic fluid,
leukocytes or bacteria in amniotic fluid, fetal tachycardia
or meconium-stained amniotic fluid, were identified as
risk factors for early onset neonatal infection. NICE and a
more recent RCOG guideline recommend that
intrapartum antibiotic prophylaxis using intravenous
benzyl penicillin should be given to prevent early-onset
neonatal infection in women in preterm labour with or
without prelabour rupture of membranes.30,34 However,
intrapartum antibiotic prophylaxis is not recommended
for women having preterm planned caesarean section
with intact membranes.34
In gestations at the threshold of viability, evidence for the
administration of peripartum magnesium sulphate infusion
to prevent cerebral palsy is lacking.35,36 If a decision is made
for active intervention, then it would seem sensible to
consider the use of peripartum magnesium infusion, in
discussion with the parents. Peripartum magnesium infusion
is recommended after 24 weeks of gestation.16,35
It is occasionally necessary to expedite delivery at the
threshold of viability for maternal benefit, for example, when
severe chorioamnionitis has developed. However, guidelines
on induction of labour in women with PPROM have only
ª 2018 Royal College of Obstetricians and Gynaecologists
David and Soe
identified studies conducted in women with pregnancies at
greater than 29 weeks of gestation and the best
method to induce labour at extreme prematurity
is currently unknown.37,38
Decision making for births at extreme
prematurity
Advances in perinatal and neonatal medicine have lowered
the gestational age at which viability, defined as the ability to
live independently, grow and develop, is considered possible.
The greatest uncertainty surrounding survival and outcome is
for those infants born between 23+0 and 24+6 weeks of
gestation with a birthweight of 500–599 g,6 where the line
between patient (parent) autonomy and medical futility is
blurred. At birthweights <500 g, resuscitation should be
performed only after very careful consideration. Infants born
at ≥25 weeks of gestation and with a birthweight of ≥600 g
are mature enough to warrant initiation of intensive care
because most of these babies survive and at least 50% do so
without long-term disabilities.
Medical decision making must carefully consider several
factors, especially the best interests of the child, while at the
same time maintaining a dialogue with the parents. These
factors include prenatal data such as EFW, sonographic signs
of fetal wellbeing and evaluation of the gestational age,
parental wishes regarding resuscitation and continuing care,
the birthweight and clinical condition at delivery, continuing
assessment of the baby’s response to resuscitation and
intensive care, and continued involvement of the parents in
the decision-making process after delivery. The General
Medical Council (GMC) advises clinicians to work with
parents when considering their child’s treatment, sharing
with them the information they want or need about their
child’s condition and options for care in a way that they can
understand. Parental views should be accounted for when
identifying clinically appropriate options that are likely to be
in the child’s best interests. Parents’ preferences should be
considered and discussion carefully documented.
Having a consistent obstetric and neonatal approach is
important when managing the birth of an infant in this ‘grey
zone’ of viability. There must be discussion with the woman
and her partner in advance of the labour so that they are
aware of the risk of obstetric emergencies such as cord
prolapse and, if possible, to agree the mode of delivery in
these circumstances. Obstetric management is partly driven
by plans for neonatal resuscitation that are agreed with the
parents. For example, if agreed that the neonatologists will
not plan to resuscitate the baby then there is little point in
monitoring fetal wellbeing during labour, or in performing a
caesarean section to improve outcome.
Three scenarios are therefore available. The first is ‘active’
management with recourse to caesarean section if
113
 Extreme prematurity and perinatal management
cardiotocography reveals signs of fetal hypoxia, and full
resuscitation. The second, which might be considered
‘passive’ management, involves no caesarean delivery but
resuscitation is attempted. The third scenario, ‘palliative’
management, provides comfort care if a live birth ensues.
For each scenario, discussion is needed regarding other
obstetric interventions such as steroids, magnesium
sulphate and tocolysis. A few days can make a huge
difference to neonatal survival and outcome, thus it is worth
revisiting decisions of ‘passive’ or ‘palliative’ management if
gestational age advances.
Most extremely preterm births result from spontaneous
preterm labour with limited options to intervene. Elective
delivery at the limits of viability is less common, but occurs
when the mother’s life is in imminent danger; for example, in
cases of severe pre-eclampsia or even chorioamnionitis.
Uncommonly, elective delivery is required because of
imminent danger to the life of the fetus; for example, in
cases of severe early onset fetal growth restriction. The
decision to undertake elective delivery must include
discussion of the risks of the delivery procedure for the
mother, since it will almost certainly be surgical, and a
classical caesarean section.
Discussion with the parents, in consultation with the
multidisciplinary team, should centre on the chance of
survival for the baby and the risks of significant disability at
this gestational age/EFW, using the best available data.
Maternal risks of early delivery should be discussed,
including that of future fertility – particularly when
caesarean section is considered. Discussions must be
conducted with kindness and sensitivity, conveying that
fetal death may not be the worst outcome, and that severe
neonatal morbidity and maternal and fertility morbidity are
also important things for the woman and her
partner to consider.
Interventions in labour
Currently there is no evidence to suggest that continuous or
intermittent fetal heart rate monitoring is of benefit in infants
at the threshold of viability during labour. Cardiotocography
can also be difficult to interpret at low gestational ages
because the autonomic nervous system may be immature.
Intrapartum continuous fetal heart rate monitoring during
labour would seem appropriate for pregnancies in which
active obstetric intervention, such as emergency caesarean
section in the presence of an abnormal cardiotocograph, and
full neonatal support is planned.
Analgesia in labour is an important consideration. Though
labour at the threshold of viability can occasionally progress
rapidly with minimal painful uterine contractions and no
requirement for analgesia, it is more frequently lengthy and
painful. There is no evidence that the choice of analgesia
114
(e.g., transcutaneous electrical nerve stimulation, gas and air,
opiates or epidural analgesia) influences infant outcome.
Currently there is no evidence to support the use of
ultrasound in preterm labour at the threshold of viability.
Intermittent abdominal ultrasound can be helpful for the
parents and the neonatal team to monitor fetal viability
during labour and to confirm fetal presentation, which can
rapidly change when the fetus is so small. It can also be
useful to monitor progress in the second stage of labour,
such as descent of the presenting part, when the practitioner
wishes to avoid vaginal examination that could
rupture the membranes.
Keeping the membranes intact during labour and delivery
may prevent fetal trauma when the fetus is very small.
Uterine contractions can diminish during labour; this is
sometimes associated with the use of peripartum magnesium
sulphate, which as well as providing neuroprotection, is used
in some countries as a short-term tocolytic.39 There appears
to be no contraindication to the use of oxytocin to augment
labour at extremely preterm gestations, but evidence is
lacking on the risk of amniotic fluid embolism and induction
of labour with intact membranes at the threshold of viability.
Cord prolapse is more common in preterm deliveries,40
particularly in non-cephalic presentations, and should be
managed in accordance with current guidelines.41 In breech
deliveries, entrapment of the fetal head affects approximately
9.3% of vaginally delivered neonates and 5.6% of neonates
delivered by caesarean section at 24–27 weeks of gestation.42
Manoeuvres such as intravenous maternal administration of
nitro-glycerine (150–250 lg)43 or lateral cervical incisions
are reported as immediate therapies.44 There are no data on
the role of episiotomy at the threshold of viability, but it may
be useful to widen the introitus to aid delivery of the
presenting part in non-cephalic presentations.
Immediate cord clamping, defined as clamping the
umbilical cord within the first 30 seconds of birth, reduces
placental transfusion and thus lowers neonatal
haemoglobin.45 For very preterm infants, delayed cord
clamping reduces the need for short-term blood
transfusion.46 Milking the cord four times appears to have
similar outcomes to delayed cord clamping in the delivery of
very preterm infants.47 The evidence on delayed cord
clamping is summarised in a Scientific Advisory Committee
opinion paper published by the RCOG.48
Mode of delivery
When immediate delivery is required, because of massive
antepartum haemorrhage or fulminating preeclampsia, for
example, then caesarean section delivery may be the only
option. Given a choice of delivery modes, caesarean section
might intuitively appear less traumatic for the infant, but
studies fail to show a significant advantage to the infant in
ª 2018 Royal College of Obstetricians and Gynaecologists

unselected cases and systematic reviews have not stratified
preterm births according to their gestation.49 Even less data
exist on the mode of delivery at the threshold of viability, and
no RCTs comparing vaginal with caesarean birth have
yet been conducted.
For singleton pregnancies with a cephalic presentation
at very preterm gestations, retrospective studies in the
USA reveal a high success rate of attempted vaginal
delivery, with no difference in neonatal mortality.50,51 In
Israel, there was no benefit of caesarean section on
survival for preterm infants <1500 g, except in a sub-
group of women with chorioamnionitis.52
Limited retrospective data support caesarean delivery in
the presence of malpresentation. In the EXPRESS study,20
vaginal breech delivery was associated with increased risk of
infant mortality and neurodevelopmental delay at 2.5 years
of age. However, another US study53 found no benefit of
caesarean section to long-term neonatal survival at 6 months
of age in breech presentation.53 Second-born twins delivered
by caesarean section before 34 weeks of gestation had a lower
risk of neonatal death than those delivered vaginally
(2.1 versus 9.0%; adjusted odds ration [OR] 0.40; 95% CI
0.17–0.95), but this study included only low numbers of
extremely preterm infants (1.2–1.4% were born at
<28 weeks of gestation).
The rate of classical caesarean section is inversely related to
gestation. A large cohort study of caesarean deliveries54 found
that 20% of incisions were classical at 24 weeks of gestation,
reducing to 12–13% by 28 weeks and <5% at 30 weeks of
gestation. Delivery of the fetus within the intact gestation sac
(‘en caul’) is well described to reduce trauma during
caesarean delivery, particularly when a classical incision is
made, although substantive evidence for this approach is
lacking. The complications of classical caesarean section are
increased risk of scar rupture, future subfertility and higher
maternal morbidity (bleeding, paralytic ileus). Hence,
women require counselling on these issues when classical
caesarean section is anticipated. Existing evidence suggests
that the delivery method in extreme prematurity should be
based on obstetric or maternal indications rather than
perceived outcome of the baby. Caesarean delivery cannot
be recommended routinely.
Maternal morbidity should not be underestimated in
delivery at extreme preterm gestations. A large retrospective
cohort study from the USA,55 which examined morbidity in
early preterm delivery (23–33 weeks of gestation), found
serious outcomes such as haemorrhage (blood loss <1500 ml,
blood transfusion, or hysterectomy for haemorrhage),
infection (endometritis, wound dehiscence, or wound
infection requiring antibiotics), intensive care unit
admission, or death were most common (11.5%) in women
delivering at 23–27 weeks. Overall, the frequency of
complications was associated with route of delivery, with
ª 2018 Royal College of Obstetricians and Gynaecologists
David and Soe
serious maternal complications found in 23.0% of those
undergoing classical caesarean delivery, compared with 12.0%
of those undergoing lower transverse or vertical incision
caesarean section and 3.5% of women delivering vaginally.55
After the birth
After delivery, the cause of spontaneous preterm birth should
be investigated using techniques such as placental histology,
microbiology, urine culture and (if abruption is suspected)
the Kleihauer test on maternal blood. It is also important to
take a careful history of possible social factors that may be
amenable to intervention, such as smoking, drug use and
domestic violence. There is no available evidence or
recommendation on obstetric postnatal management in
terms of investigations or the optimum arrangements for
postnatal counselling appointments.16 Couples have many
questions after the birth, particularly about why the mother
went into extremely preterm labour, the risk of recurrence
and how to manage a future pregnancy. Therefore, it is good
practice to offer a follow-up appointment to discuss the
results of placental histological analysis, any adverse events at
the delivery and to plan best management of the next
pregnancy. If women have a failed cervical cerclage or a very
deficient cervix, referral for a pre-conceptual abdominal
cerclage may be considered.56 Mothers of very preterm
infants score highly on measures of post-traumatic stress,
anxiety and depression57 and may benefit from counselling.
Conclusion
Labour and delivery at the threshold of viability can pose a
great dilemma to the obstetrician. Almost all studies in the
current literature are either underpowered or do not stratify
for extreme preterm gestations, and therefore there is little
evidence available to guide best practice. In many cases there
is little elective decision making and clinicians must
commonly react to events quickly using their experience.
Planning ahead and involving parents in decision-making
discussions is likely to result in the most satisfactory outcome
for all.
Disclosure of interests
There are no conflicts of interest.
Contribution to authorship
ALD instigated, wrote and edited the article. AS researched,
wrote and edited the article. Both authors approved the
final version.
Acknowledgements
ALD receives funding from the University College London
Hospital/University College London via the Department of
115
 Extreme prematurity and perinatal management
Health’s National Institute for Health Research Biomedical
Research Centres funding scheme.
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