Review: Management of Large-For-Gestational-Age Pregnancy in Non-Diabetic Women

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Review 2010;12:250–256 10.1576/toag.12.4.250.27617 http://onlinetog.org The Obstetrician & Gynaecologist

Review Management of large-for-


gestational-age pregnancy in
non-diabetic women
Authors San San Aye / Veronica Miller / Saloni Saxena / Mohamad Farhan

Key content:
• Over the last two to three decades there has been a 15–25% increase in many countries
in the number of women giving birth to large infants.
• Rates of shoulder dystocia and caesarean birth rise substantially at 4000 g and again
at 4500 g.
• There is an increase in maternal and neonatal morbidity associated with fetal macrosomia.
• Serial measurement of fundal height adjusted for maternal physiological variables
substantially improves antenatal detection.
• Sonographic assessment of fetal weight is frequently inaccurate.
• Induction of labour for suspected macrosomia in non-diabetic women has not been shown
to reduce the risk of caesarean section, instrumental delivery or perinatal morbidity.

Learning objectives:
• To identify the risks associated with fetal macrosomia and to be aware of the long-term
implications.
• To understand the limitations of predictive tools.
• To be able to take an informed approach to managing the macrosomic fetus.

Ethical issues:
• To what extent should the fear of medico-legal action influence obstetricians’
management of suspected fetal macrosomia?
• What advice should clinicians give women regarding modes of delivery?

Keywords birth weight / estimated fetal weight / induction of labour / macrosomia /


shoulder dystocia
Please cite this article as: Aye SS, MillerV, Saxena S, Farhan M. Management of large-for-gestational-age pregnancy in non-diabetic women. The Obstetrician & Gynaecologist 2010;12:250–256.

Author details
San San Aye MMedSc MRCOG Veronica Miller MRCOG Saloni Saxena MBBS Dr Mohamad Farhan MBBS
Consultant Obstetrician and Gynaecologist Consultant Obstetrician and Gynaecologist Senior House Officer in Obstetrics Senior House Officer in Obstetrics
North Devon District Hospital, Raleigh Park, Stoke Mandeville Hospital, Mandeville Road, and Gynaecology and Gynaecology
Barnstaple, Devon EX31 4JB, UK Aylesbury, Buckinghamshire HP21 8AL, UK University Hospital Lewisham, Lewisham Wycombe General Hospital, Queen
Email: sansanaye@hotmail.com High Street, London SE13 6LH, UK Alexandra Road, High Wycombe,
(corresponding author) Bucks HP112TT, UK

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The Obstetrician & Gynaecologist 2010;12:250–256 Review

Introduction with information about body proportions,


There has been a rise in the prevalence of large composition and metabolic characteristics,
newborns in many parts of the world. Over the last which are determinants of short-term obstetric
two to three decades, an overall 15–25% increase in complications and long-term health problems.
the proportion of women giving birth to large In this article, we will define LGA fetuses as those
infants has been documented in the USA, Canada, with an (estimated) birth weight 4500 g.9–12
Germany, Scotland and Denmark.1–5 This trend has
been attributed to increases in maternal height, Risk factors and obstetric
body mass, gestational weight gain and diabetes; complications associated
reduced maternal cigarette smoking; and changes
in sociodemographic factors.2,4 The prevalence of with macrosomia
liveborn infants weighing 4000 g was 11.65% in In an American cohort study, Stotland et al.9
our institution (Wycombe Hospital, UK) in 2008. identified the risk factors associated with neonatal
It is known that there is an increase in maternal birth weight 4500 g. Male infant sex, multiparity,
and neonatal morbidity associated with fetal maternal age 30–40 years, white race, diabetes and
macrosomia. However, there is no universal gestational age 41 weeks appeared to be
consensus on the definition, diagnosis and associated risk factors (P  0.001). Adverse
antenatal management of fetal macrosomia. In this obstetric outcomes were also studied in this cohort.
review, we try to provide a sensible approach to Women who delivered a macrosomic infant were
management of large-for-gestational-age (LGA) more likely to undergo caesarean birth and to suffer
pregnancies in non-diabetic women based on the shoulder dystocia, chorioamnionitis, fourth-degree
available evidence. perineal lacerations, postpartum haemorrhage and
longer hospital stay. Adjusted odds ratios (ORs) for
caesarean birth of birth weight groups 4000–4499 g,
Search strategy 4500–4999 g and 5000 g were 1.69, 2.99 and 5.46;
Electronic searches of literature published between and for shoulder dystocia were 6.29, 13.05 and
1980 and 2009 were undertaken using MEDLINE, 17.52, respectively.9 Limitations of this study are
Embase, CINHAL, the Cochrane Database of secondary data analysis, lack of data on
Systematic Reviews and the National Institute for confounding factors and the study group being
Health and Clinical Excellence (NICE) website. a cohort of privately insured patients.
Search items included: pregnancy, fetal
macrosomia, foetal macrosomia, macrosomic On the other hand, the evidence showed no
fetus, large for dates, large for gestational age and differences in adverse birth outcomes between birth
macrosomia, combined with the terms non- weights of 3500–3999 g and those of 4000–4499 g.10
diabetic, brachial plexus injury, shoulder dystocia, High birth weight (4500–4999 g) and very high birth
antenatal care, perinatal care and management. weight (5000 g) were found to be associated with
Terms were connected by the Boolean operator early neonatal death; the leading cause of death was
‘OR’. This retrieved a total of 312 references and, asphyxia. The majority of post-neonatal deaths were
after exclusion of duplicate and obviously caused by sudden infant death syndrome.Very high
irrelevant papers, 60 studies published in the birth weight infants were twice as likely to die of
English language or with an English language sudden infant death syndrome as normosomic
abstract were identified. infants, whereas high birth weight infants were not at
increased risk.10 The risk of shoulder dystocia rises
Terminology from 1.4% for all vaginal deliveries to 9.2–24% for
The term large-for-gestational-age has mainly been birth weights 4500 g.11
used for fetuses or newborns with an (estimated)
weight 90th percentile or 2 standard deviations The American College of Obstetricians and
from the mean for the gestational age.6–8 The Gynecologists defines macrosomia as birth weight
Ponderal Index is an indicator of body proportions 4500 g, irrespective of gestational age, as both
of infants, defined as body weight divided by the maternal complications and perinatal morbidity
third power of length (g/cm3). Macrosomia is a term and mortality begin to rise from that birth weight.12
mostly used for newborns with a birth weight above
a certain limit. However, there is no consensus as to Long-term health risks
what this limit should be. Birth weights 4000 g, Meta-analysis of the 14 studies that examined the
4200 g and 4500 g are used as definitions of association between birth weight and risk of type 2
newborn macrosomia.6–8 Generally, it seems diabetes in later life showed a U-shaped association.
appropriate to consider a fetus or newborn with an Low birth weight (2500 g) and high birth weight
estimated or actual birth weight 4000 g as (4000 g) were associated with increased risk of
macrosomic,6,9 especially in cases of insulin- type 2 diabetes.13 Size at birth, particularly length
dependent diabetes mellitus.6 However, it is more and head circumference, is associated with
important to supplement the term fetal macrosomia increased risk of breast cancer in premenopausal

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women after adjustment for adult risk factors and of the bladder, pelvic masses (e.g. fibroids), fetal
birth weight.14 A population-based cohort study by position and many other factors.
Sin et al.15 determined the relationship between
birth weight and risk of emergency visits for asthma Serial measurements of fundal height adjusted
during childhood. Those with a high birth weight for maternal physiological variables such as age,
had a significantly increased number of visits and weight, height, ethnicity, parity and birth weight
the relationship was linear if birth weight was in previous pregnancies, significantly increase
4500 g, such that every increment of 100 g in the antenatal detection of LGA babies (the
birth weight was associated with an additional 10% detection rate was 46% in the study group
increase in the risk of emergency visits. A number compared with 24% in the control group; OR
of very large, well-conducted studies have shown an 2.6; confidence interval [CI] 1.3–5.5). This is
association between birth weight and subsequent followed by fewer investigations and, hence, is a
body mass index (BMI) (kg/m2) or overweight, at cost-effective screening tool for fetal growth in
least for young white adults and children. By the community. To improve assessment of fetal
contrast, several studies have shown no association growth it is critical that the measurements are
in middle-aged subjects, although these were fairly taken serially rather than done as a one-off
small studies. Genetic factors were predominant in measurement.17
this association, especially with BMI in adulthood.16
Ultrasonographic prediction
Diagnosis of fetal macrosomia of fetal macrosomia
(See Figure 1.) Clinical estimations are based on Ultrasound measures used for predicting a
palpation of the uterus and measurement of the macrosomic fetus are either single parameters
height of the fundus of the uterus; both are subject (such as abdominal circumference or subcutaneous
to considerable variation. tissue thickness) or combinations of measurements
to estimate fetal weight. Ultrasound biometry used
Fundal height measurements are an inaccurate way to detect fetal weight 4000 g is characterised by
of estimating fetal size. They are influenced by the low sensitivity, low positive predictive value and
maternal size, amount of amniotic fluid, status high negative predictive value.18,19

Figure 1 Clinically LGA at 36 weeks of gestation by


Algorithm for the diagnosis of LGA
palpation
pregnancy in non-diabetic women.
At all stages of management, it is
crucial to obtain the woman’s
agreement SFH >90th centile confirmed on personalised
growth chart

Ultrasound biometry, including AFI

EFW >90th centile and increased AFI

Check glucose in urine, GTT at booking visit,


previous history of gestational diabetes mellitus

Increased AFI or glucose in urine

Arrange GTT34,35

Normal GTT Abnormal GTT

Follow primiparous or Refer to diabetes team


multiparous pathway (Figure 2
and Figure 3)

AFI = amniotic fluid index; EFW = estimated fetal weight; GTT = glucose tolerance test;
SFH = symphysio–fundal height

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A systematic quantitative review of 63 accuracy imaging (MRI) are expected to be additional tools in
studies21 (which included 51 evaluating the future to estimate fetal weight and even body
accuracy of estimated fetal weight [EFW] and composition, but their usefulness needs to
12 evaluating the accuracy of fetal abdominal be further investigated.19,27,28 A software program
circumference, including a total of 19 117 women) (a customised fetal growth chart) that calculates on
assessed ultrasonographically-estimated fetal the basis of pregnancy variables entered at the first
weight and abdominal circumference in the visit provides an adjusted normal range for that
prediction of macrosomia. The summary receiver particular fetal size and is, thus, more specific.
operating characteristic curve (sROC) area for Using the program, 22% of those designated large
EFW was not different from the area for fetal (90th centile) on the standard population growth
abdominal circumference (0.87 versus 0.85, chart were within normal limits for the pregnancy.
P  0.91), suggesting that there was no difference in Conversely, 26% of babies identified as large, with
accuracy between ultrasonographically-estimated adjusted centiles, were ‘missed’ by conventional
fetal weight and abdominal circumference in the unadjusted centile assessment. Adjustment for
prediction of a macrosomic baby at birth. For physiological variables makes assessment of fetal
predicting a birth weight of 4000 g, the summary growth more precise and reduces unnecessary
likelihood ratios (LRs) were 5.7 (95% CI 4.3–7.6) interventions and parental anxiety.29,30 Similarly,
for a positive test and 0.48 (95% CI 0.38–0.60) for a computerised combinations of a number of risk
negative test, using Hadlock et al.’s formula of factors such as diabetes and twin pregnancy may
estimating fetal weight ultrasonographically.20 also improve identification of macrosomia.31
For ultrasound fetal abdominal circumference of
36 cm, the respective LRs for predicting birth Other predictors of macrosomia
weight 4000 g were 6.9 (95% CI 5.2–9.0) and 0.37 A change in maternal BMI during pregnancy has an
(95% CI 0.30–0.45). A positive test result is more independent positive predictive value for fetal
accurate at ruling in macrosomia than a negative macrosomia. An increase in BMI 25% during
test result at ruling it out.21 pregnancy has a sensitivity of 86.2%, specificity of
93.6%, positive predictive value of 71.4% and
Similarly, ROC curves indicated that measurements negative predictive value of 97.45% for
of soft tissue are not superior to clinical or other macrosomia.32
sonographic predictions in identifying fetuses with
weights of 4000 g, although the study had limited Women with a history of one macrosomic infant
power.22 are at significantly increased risk of another
macrosomic infant in a subsequent pregnancy. For
Combinations of amniotic fluid index and EFW women with two or more macrosomic infants, the
measurements during the middle of the third risk is even greater.33
trimester are useful predictors of macrosomia at
birth. Combined analysis of amniotic fluid index
60th percentile and EFW 71st percentile Management
resulted in a positive predictive value of 85%.23 Management of pregnancies with suspected fetal
macrosomia (Figure 2, Figure 3 and Box 1) is
Several studies24,25 have compared clinical with challenging for clinicians. Elective caesarean
ultrasound estimation of birth weight and none of section is intended to prevent several of the
these have demonstrated ultrasound to be superior complications associated with fetal macrosomia,
to clinical estimation. Both clinical and especially brachial plexus injuries and maternal
sonographic predictions of macrosomia include perineal lacerations. However, it has been
areas of the ROC curve between 0.81 and 0.95, estimated that 3600 caesarean deliveries need
which is defined as useful from a statistical point to be performed in non-diabetic women with
of view. However, predictions of macrosomia by suspected fetal macrosomia (4500 g) to
these techniques are limited by the substantial prevent a single permanent brachial plexus
false-positive and false-negative rates inherent in injury.36 Thus, elective caesarean section for the
these tests.26 sole indication of macrosomia cannot be
justified.
There are some studies that suggest ways to
improve the predictive accuracy of fetal Clinical research, in conjunction with cost-
macrosomia. Serial sonographic measurements can effectiveness analyses, has led to the consensus that
increase the positive predictive value.19 However, elective caesarean delivery is only beneficial for
serial biometry is time consuming and the cost non-diabetic women whose fetus is suspected to be
effectiveness is questionable. Regardless of the 5000 g.37,38
formula used, the accuracy of sonographic estimates
decrease with increasing birth weight.19 Three- Before caesarean section became reasonably safe,
dimensional ultrasound and magnetic resonance induction of labour for suspected macrosomia was

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Figure 2
Algorithm for antenatal management No further scans after 36 weeks
of LGA pregnancy in non-diabetic Maternal BMI, cervical
primiparous women. At all stages
of management, it is crucial to obtain assessment at 41 weeks
the woman’s agreement

BMI <30, BMI >30,


favourable cervix unfavourable cervix

Induction of labour Consider elective


at 41+4 weeks lower segment caesarean
section or induction of labour

Figure 3
Algorithm for antenatal management No further scans after 36 weeks
of LGA pregnancy in non-diabetic
multiparous women. At all stages
of management, it is crucial to obtain
the woman’s agreement
Previous history of Previous Previous history
macrosomia,vaginal delivery, caesarean section of shoulder dystocia
no birth injuries

Induction of labour Previous vaginal No previous vaginal Mild (no Severe (brachial
at 41+4 weeks delivery or indication delivery; or previous brachial plexus injury)
for caesarean section caesarean section plexus injury)
not failure to indicated by failure to
advance; and/or advance; and/or BMI
BMI <30 >30 Induction of Elective lower
labour at 41+4 segment
weeks and short caesarean
Vaginal birth Consider elective trial of labour section
after caesarean lower segment
section caesarean
section

Box 1 First stage


expectant management with labour induction in
Management in labour of women
Intravenous line, group and save
women with suspected fetal macrosomia.Based
with LGA pregnancy
Continuous cardiotocograph monitoring
on data from nine observational studies,labour
Adequate pain relief
induction for suspected fetal macrosomia results
Regular cervical assessment, especially of descent of the
in an increased caesarean delivery rate without
presenting part improving perinatal outcomes.However,two
Timely augmentation with oxytocin if delay in the first stage randomised controlled trials have not confirmed these
is diagnosed
findings,although their statistical power is limited.
Second stage
Early recourse to caesarean section if there is no descent
of the presenting part
Similarly, according to Irion and Boulvain,40
Delivery by a senior midwife
compared with expectant management, induction
Obstetric registrar or consultant in attendance
of labour for suspected macrosomia in non-
Third stage
diabetic women has not been shown to reduce the
Active management of third stage and administration of
risk of caesarean section or instrumental delivery.
Syntometrine® (Alliance) (ergometrine and oxytocin) by Perinatal morbidity (shoulder dystocia) was not
injection
significantly different between groups.

performed because it was thought to prevent Thus, current evidence shows no benefit of a policy
problems from severe cephalopelvic disproportion of routine induction of labour at the mere indication
and its associated maternal mortality and severe of suspected fetal macrosomia (4000 g).
morbidity. Nowadays, many obstetricians induce
labour at term when the fetus is estimated to be From the retrospective case-controlled study by
either LGA or macrosomic. Ben-Haroush et al.,41 induction of labour for
suspected LGA fetuses increases the risk of
A meta-analysis of systematic review on 11 studies by caesarean section, confirming the results of
Sanchez-Ramos et al.39 compared the outcomes of previous studies. However, within the subgroup of

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multiparous women, caesarean section rates were with a birth weight of 4000 g. One in four non-
not increased, with no major maternal or fetal diabetic pregnant women with a birth weight
complications, showing that nulliparity was 4000 g underwent elective caesarean section with
significantly and independently associated with the indication of ‘one previous caesarean section
increased risk of caesarean section. with large for date’ in our institution (unpublished
retrospective audit from 1 January 2008 to 30 June
A holistic approach should be taken in the 2009).
management of pregnant women. Important
variables such as women’s age, height, BMI, parity, Strong predictors of success of vaginal delivery are:
birth weights of previous babies and obstetric previous vaginal birth, indication for previous
history, including previous shoulder dystocia and caesarean delivery and maternal BMI. Previous
cervical score, should be considered in the decision- vaginal birth predicted the success of trial of vaginal
making process. births in women with macrosomic fetuses.43–46
'Failure to advance’ as an indication for previous
Based on an analysis of treatment of suspected fetal caesarean section seems to be associated with lower
macrosomia,37 expectant treatment is the most success rates of trial of labour.46 Maternal obesity is
cost-effective approach. In a large cohort studied an independent risk factor for failed trial of labour
by Walsh et al.,33 88% of women who laboured with in women with previous caesarean sections.47
a macrosomic infant achieved vaginal delivery. If
expectant management is decided upon, the Previous shoulder dystocia
woman should be fully informed about the benefits Women (with or without diabetes) with previous
and possible consequences, including care during shoulder dystocia have an increased risk of
labour. recurrence, ranging from 1.1–16.7%.48,49 In
non-diabetic women, there is insufficient
An observational study carried out by Draycott evidence to support routine elective delivery;
et al.42 demonstrated that the introduction of however, the contrary applies to those cases
shoulder dystocia training for all maternity staff complicated by permanent brachial plexus
was associated with improved management and injury.50 A thorough review of previous delivery
neonatal outcomes of births complicated by records is necessary.
shoulder dystocia.
Shoulder dystocia seldom results in brachial plexus
During labour, regular assessment of progress is injury. Most injuries are transient; half the cases of
required, especially of engagement, descent and shoulder dystocia occur in infants with birth
rotation of the fetal head. Continuous electronic weights 4000 g and approximately one-third of
monitoring of the fetal heart rate should also be brachial plexus injuries are not even associated with
performed because of the increased oxygen a clinical diagnosis of shoulder dystocia. As many as
requirement of the macrosomic fetus and the 50% of all brachial plexus injuries are attributable
association with prolonged labour. Thorough to unavoidable intrapartum or antepartum
second stage assessment is crucial if it is prolonged, events.51 They can, therefore, occur through
in order to avoid forceful extraction by mechanisms other than the efforts exerted to
instrumental delivery. A competent obstetrician reduce an impacted shoulder. This implies that the
must be in attendance to handle shoulder dystocia mode of delivery does not have a major impact on
promptly and effectively. Moreover, a paediatrician the incidence of injuries in about 40% of women
should be present at the time of delivery, since experiencing brachial plexus injury.52 In fact,
hypoxia and other injuries may be expected. Active brachial plexus injury has been reported even after
management of the third stage of labour should be caesarean delivery. Thus, caesarean delivery reduces
exercised to avoid postpartum haemorrhage. but does not eliminate the risk of birth trauma
associated with macrosomia.51
Management of fetal
Conclusion
macrosomia in special The widespread availability of obstetric ultrasound
circumstances and the fear of medico-legal action due to shoulder
Previous caesarean section dystocia have led obstetricians to consider
The medical literature does not support elective interventions for ultrasonographically diagnosed
caesarean section for suspected fetal macrosomia macrosomia. We have found no evidence to
in non-diabetic women and there appears to be support a policy of induction of labour or routine
no reason for treating mothers with previous elective caesarean section of non-diabetic women
caesarean sections differently.43 with ultrasonographically diagnosed LGA
pregnancies if the EFW is 5000 g. However, there
There is still a very low threshold for elective is evidence to support elective caesarean section
caesarean section in non-diabetic pregnant women for women with EFW 5000 g.

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