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Large for gestational age newborn

Author: George T Mandy, MD
Section Editor: Leonard E Weisman, MD
Deputy Editor: Laurie Wilkie, MD, MS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2022. | This topic last updated: Aug 10, 2021.

INTRODUCTION

Infants who are born large for gestational age (LGA), especially full-term or post-term
infants, are at risk for perinatal morbidity and potentially long-term metabolic complications.

The pathogenesis, epidemiology, risk factors, complications, and management of infants

born LGA will be reviewed here.

DEFINITION

In general, LGA is defined as a birth weight (BW) greater than the 90th percentile for age.
However, it has been suggested that the definition be restricted to infants with BW greater
than the 97th percentile (2 standard deviations above the mean), as this more accurately
describes infants who are at greatest risk for perinatal morbidity and mortality ( figure 1)
[1,2]. Using a national reference based on single live births in the United States, infants born
at 40 weeks gestation at the 90th percentile had BW greater than 4000 g, and those at the
97th percentile had BW greater than 4400 g [3].

Macrosomia refers to excessive intrauterine growth beyond a specific threshold regardless

of gestational age (GA). This condition is usually defined as a BW greater than 4000 or 4500
g. The American College of Obstetricians and Gynecologists (ACOG) supports use of the 4500
g threshold for diagnosis of macrosomia because morbidity increases sharply beyond this
weight.

A grading system for macrosomia has been proposed based on BW (see "Fetal macrosomia",
section on 'Definition'):

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● Grade 1 – 4000 to 4499 g

● Grade 2 – 4500 to 4999 g
● Grade 3 – >5000 g

Term infants who are appropriate for gestational age have BW between 2500 and 3999 g.

INCIDENCE

Among term liveborn infants in the United States born in 2008, the incidence of LGA based
on the above grades of macrosomia is 6.6, 0.9, and 0.1 percent for BW of 4000 to 4499 g,
4500 to 4999 g, and >5000 g, respectively [4]. The birth rates for all three grades of LGA have
declined in the United States from 1990 to 2008 [4]. However, in other countries (eg, Sweden
and Australia), the reported incidence of LGA births has increased [5,6]. In these countries,
the rise in proportion of neonates born LGA was thought to be due to a decreased exposure
to prenatal smoking, increases in maternal age and weight, and gestational diabetes.

RISK FACTORS AND ETIOLOGY

Although the mechanisms that control fetal weight gain and growth are poorly understood,
excessive fetal growth appears to be due to increased delivery of nutrients to the fetus,
which is influenced/caused by genetic factors and intrauterine environmental factors, or a
combination of the two.

● Genetic factors – In a number of genetic syndromes, macrosomia is a characteristic

feature [2].

• There is ethnic variability in the incidence of LGA infants.

• Familial trait – Mothers who were LGA are more likely to deliver an LGA infant than
mothers who were appropriate for gestational age.

● Intrauterine environmental factors – LGA infants are more likely to be delivered to

mothers who are obese, who have diabetes, and those with excessive gestational
weight gain [7]. These maternal conditions result in excessive delivery of nutrients to
the fetus, which contributes to increased fetal growth.

● Epigenetic factors – Limited data suggest that placental epigenetic alterations may
contribute to increased fetal growth [8-11].

Genetic factors

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Genetic syndromes — Several genetic disorders are characterized by early excessive

growth resulting in an LGA infant. They include Beckwith-Wiedemann syndrome, Simpson-
Golabi-Behmel syndrome, Sotos syndrome, Weaver syndrome, and Berardinelli
lipodystrophy ( table 1).

Race and ethnicity — Racial and ethnic factors influence birth weight (BW). In a study from
the United States that included all term, singleton live births from 1995 to 1997, mothers
who were White, American Indian, or Samoan were disproportionately overrepresented in
the group with LGA offspring [2]. In another report of mothers with gestational diabetes,
macrosomia occurred significantly more often in Latino than in Black infants (50 versus 19
percent) [12].

Maternal factors

Maternal diabetes — Macrosomia is common in infants of diabetic mothers (IDMs),

especially when maternal diabetes is poorly controlled. Excessive delivery of nutrients to the
fetus results in fetal hyperglycemia, hyperinsulinemia, and increased growth. In IDMs,
macrosomia is also associated with disproportionate growth with an increased ponderal
index that results in higher chest-to-head and shoulder-to-head ratios, higher body fat, and
thicker upper extremity skinfolds compared with LGA offspring of nondiabetic mothers
( picture 1). This disproportionate macrosomia increases the risk of birth injuries,
especially shoulder dystocia. (See "Infants of women with diabetes", section on 'Macrosomia'
and "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and
management".)

Maternal prepregnancy weight — The risk of an LGA offspring increases in a linear

fashion as the prepregnancy maternal weight rises. As a result, the highest risk of delivering
an LGA infant occurs in obese mothers. This relationship is independent of the increased
prevalence of gestational diabetes in obese women. The evidence for the effect of maternal
prepregnancy weight on BW is presented separately. (See "Obesity in pregnancy:
Complications and maternal management", section on 'Large for gestational age'.)

Excessive maternal weight gain — Excessive maternal weight gain during pregnancy is

associated with macrosomia. Women with normal prepregnancy body mass index who
gained more than 35 lbs (15.9 kg) had an almost 2.5 times greater risk of delivering an LGA
infant compared with mothers who gained between 25 and 35 lbs (11.3 and 15.9 kg) [13].
The amount of weight gain associated with an LGA birth is lower in women who are
overweight or obese, as discussed separately. (See "Obesity in pregnancy: Complications and
maternal management", section on 'Large for gestational age' and "Gestational weight
gain", section on 'Recommendations for gestational weight gain' and "Gestational weight
gain", section on 'Overweight and obese pregnant people'.)

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Other factors — Other factors that are associated with the birth of LGA infants include
multiparity, advanced maternal age, post-term pregnancy, male infant, birth of a previous
LGA infant, and maternal BW greater than 4000 g.

NEONATAL MORBIDITY

Overview — Neonatal morbidity for term infants is greater in LGA infants (birth weights
[BWs] above 4000 g) compared with appropriate for gestational age (AGA) infants (BW
between 2500 and 3999 g) [2,14]. In addition, morbidity increases as the BW increases above
4000 g.

This was best illustrated in a study that analyzed data that included all singleton live births in
the United States from 1995 to 1997 with a gestational age between 37 and 44 weeks of
gestation [2]. Logistic regression analysis demonstrated that the risk of several neonatal
complications was greater in LGA infants compared with infants who were AGA (BW 3000 to
3999 g), and the frequency increased with increasing severity of macrosomia as follows:

● Compared with AGA infants, the risk of birth injuries was twofold, threefold, and
fourfold greater for infants with grade 1 (BW between 4000 and 4499 g), grade 2 (BW
between 4500 and 4999 g), and grade 3 (BW >5000 g) macrosomia, respectively.

● Mechanical ventilation for more than 30 minutes duration was 1.19 (95% CI 1.14-1.23),
1.85 (95% CI 1.73-1.99), and 3.96 (95% CI 3.45-4.55) times greater for infants with
grades 1, 2, and 3 macrosomia, respectively.

● The risk of a five-minute Apgar score lower than 3 was 1.3 (95% CI 1.21-1.39), 2 (95% CI
1.76-2.29), and 5.2 (95% CI 4.09-6.62) times greater for infants with grades 1, 2, and 3
macrosomia, respectively.

● The risk of respiratory distress syndrome (RDS; referred to as hyaline membrane

disease) was 1.15 (95% CI 1.1-1.22), 1.84 (95% CI 1.68-2.01), and 3.7 (95% CI 3.11-4.4)
times greater for infants with grades 1, 2, and 3 macrosomia, respectively.

● The risk of meconium aspiration was 1.28 (95% CI 1.23-1.34), 1.65 (95% CI 1.52-1.79),
and 2.61 (95% CI 2.15-3.16) times greater for infants with grades 1, 2, and 3
macrosomia, respectively.

● Neonatal mortality was only increased in infants with grade 3 macrosomia and was
2.69 (95% CI 1.91-3.8) times greater than the mortality rate in AGA infants.

Macrosomia is also associated with significant maternal morbidity, including an increased

likelihood of cesarean delivery, severe postpartum hemorrhage, and vaginal lacerations.

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(See "Fetal macrosomia" and "Shoulder dystocia: Intrapartum diagnosis, management, and
outcome", section on 'Maternal'.)

The increased morbidity seen in LGA infants results in a higher utilization of neonatal
intensive care compared with AGA infants, as illustrated by a study from the Arizona
Neonatal Intensive Care Program (NICP) of infants born between 1994 and 1998 [15]. In this
study, LGA infants with BW >4000 g were more likely to be enrolled in the NICP (criteria
included admission to a neonatal intensive care unit [NICU] for a prolonged stay [>72 hours],
readmission to a NICU, or transport to a NICU) compared with AGA infants with BWs
between 2500 and 3999 g (2.7 versus 2.1 percent). The four most common diagnoses in LGA
infants, which accounted for 53 percent of the admission diagnoses, were respiratory
distress (19 percent), transient tachypnea of the newborn infant (16 percent), hypoglycemia
(9 percent), and meconium aspiration (9 percent).

Birth injury — Macrosomia predisposes to shoulder dystocia and birth injury, including

brachial plexus injury and clavicular fracture [2,16,17]. As previously noted, the risk of birth
injury increases with the severity of macrosomia [2]. In addition, the rate of birth injury for
LGA infants is greater in vaginal compared with cesarean deliveries. In one large case series,
birth injury was three times more likely when LGA infants (BW 4500 to 5000 g) were the
product of vaginal compared with cesarean delivery (9.3 versus 2.6 percent) [16].

The neonatal complications of shoulder dystocia are discussed in greater detail separately.
(See "Shoulder dystocia: Intrapartum diagnosis, management, and outcome", section on
'Infant'.)

Respiratory distress — As noted above, LGA infants are more likely to develop respiratory
distress than AGA infants [2,15]. This is primarily due to the increased risk of RDS, especially
in infants of diabetic mothers (IDMs), who are more likely to be delivered prematurely. The
higher incidence of cesarean deliveries in LGA infants appears to increase the risk of
transient tachypnea of the newborn. In addition, meconium aspiration is a common
respiratory complication in LGA infants, perhaps due to the increased risk of perinatal
depression. (See "Infants of women with diabetes", section on 'Respiratory distress' and
"Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis"
and "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and
diagnosis", section on 'Pathophysiology' and "Transient tachypnea of the newborn".)

Preterm birth — There may be an increased risk of preterm birth, as illustrated in a study

from the Dutch perinatal registry of singleton birth in nulliparous women from 1999 to 2010
[18]. In this large cohort, the risk of preterm birth between 25 and <37 weeks gestation was
greater in LGA (BW >97th percentile for age) compared with those born AGA (11.3 versus 7.3
percent, odds ratio [OR] 1.8, 85% CI 1.7-1.9).

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Other abnormalities — LGA infants have increased intrauterine exposure to excessive

nutrients, especially glucose, which may result in hyperinsulinemia, increased utilization of
oxygen and glucose, and oxidative stress [19,20]. These abnormalities may lead to perinatal
complications, including hypoglycemia, polycythemia, and asphyxia.

Hypoglycemia — LGA infants can develop hypoglycemia when the placental supply of

glucose is interrupted at birth. In a report based upon data from the Netherlands Perinatal
Registry from 1997 to 2002, the incidence of hypoglycemia was approximately 19 and 15
percent in all LGA infants and in LGA infants of nondiabetic mothers, respectively [21].
Seizures due to hypoglycemia occurred in 0.3 percent of all LGA infants and in 0.2 percent of
LGA infants without maternal diabetes. In another large case series of 887 German LGA
infants (defined as a BW >90th percentile) who were tested for hypoglycemia, 16 percent had
hypoglycemia (blood glucose level <40 mg/dL) during the first 24 hours of life [22]. (See
"Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Increased
glucose utilization' and "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia",
section on 'Who should be screened?'.)

Polycythemia — Polycythemia occurs more frequently in LGA infants of both diabetic and

nondiabetic mothers compared with AGA infants [23]. The mechanism of polycythemia is
thought to be due to an increased production of erythropoietin, which results from fetal
hypoxia caused by the increased oxidative demands associated with hyperglycemia and
hyperinsulinemia. (See "Neonatal polycythemia".)

Perinatal asphyxia — Macrosomic infants are at increased risk for perinatal asphyxia,

especially IDMs. Indirect evidence of the increased risk of perinatal asphyxia in LGA infants is
the higher frequency of low Apgar scores in LGA compared with AGA infants [1,2,16,24].
Contributing factors are thought to be increased intrauterine oxygen utilization due to fetal
hyperglycemia and hyperinsulinemia, especially in IDMs, and complications of delivery
related to shoulder dystocia. (See "Infants of women with diabetes", section on 'Perinatal
asphyxia' and "Shoulder dystocia: Intrapartum diagnosis, management, and outcome",
section on 'Infant'.)

Congenital anomalies — Minor congenital anomalies are more common in LGA than AGA
infants. This was evaluated in a retrospective case-control study of more than two million
births in Latin America, of which 1800, out of 31,897 infants with congenital anomalies, were
LGA [25]. The most common anomalies associated with macrosomia included:

● Talipes calcaneovalgus and hip subluxation caused by intrauterine deformation

● Hydrocephaly and combined angiomatoses reflect increased body mass and fluid, and
thus increased BW
● Non-brown pigmented nevi

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NEONATAL MORTALITY

Increased mortality is associated with LGA and may only occur in the most severe grade of
macrosomia. As noted above, in a study of all singleton, term live births between 1995 and
1997, the neonatal mortality rate was only higher in infants born with grade 3 macrosomia
(BW >5000 g) compared with AGA infants (adjusted odds ratio [aOR] 2.69, 95% CI 1.91-3.8)
[2]. Similar results were noted in a Canadian study that reported more than a twofold
increased risk of deaths in term infants with BW greater than the 97th percentile compared
with AGA term infants [24].

Neonatal mortality is also higher in LGA preterm infants compared with AGA infants born at
the same gestation. In a retrospective cohort study of preterm infants (gestational age <29
weeks) from the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network
databases, LGA infants compared with AGA infants had a higher risk of death (26 versus 18
percent, aOR, 1.6, 95% CI 1.0-2.54) [26].

PRETERM INFANTS

Unlike term infants, preterm infants who are LGA may have lower mortality and morbidity
than appropriate for gestational age (AGA) infants with the same gestational age (GA). This
was illustrated by a retrospective review of data from the Vermont Oxford Network of
preterm infants (GA 22 to 29 weeks) born between 2006 and 2014 [27]. Compared with AGA
infants, LGA preterm infants had decreased risks of mortality, respiratory distress syndrome,
patent ductus arteriosus, necrotizing enterocolitis, late-onset sepsis, severe retinopathy of
prematurity, and chronic lung disease. However, LGA infants were more likely to have early-
onset sepsis and severe intraventricular hemorrhage, but these findings were not consistent
across GA range. These data suggest that for preterm infants, large birth weight may be a
protective factor resulting in better outcomes. These findings are limited, as they were based
on a review of the medical record without validation of GA and need to be confirmed in other
cohorts, preferably in a prospective study with validation of GA.

NEONATAL MANAGEMENT

Neonatal management of LGA infants includes screening and treating complications

associated with macrosomia; determining, if possible, the etiology of increased growth; and
providing routine newborn care.

● Prior to delivery, an assessment of the need for neonatal resuscitation is made based
on the gestational age, anticipated birth weight, presence of a congenital anomaly or

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labor complications, mode of delivery (eg, cesarean delivery), and maternal history.
(See "Neonatal resuscitation in the delivery room", section on 'Anticipation of
resuscitation need'.)

● Immediately after delivery, routine neonatal care is provided that includes drying,
clearing the airway of secretions, maintaining warmth, and a rapid assessment of the
infant's clinical status based on respiratory effort, tone, heart rate, and an examination
to identify any major congenital anomaly or genetic syndrome. The need for further
intervention is based on this initial evaluation. If the infant does not require additional
resuscitation, the infant should be given to the mother for skin-to-skin care and
initiation of breastfeeding in the delivery room. LGA infants should be fed as quickly as
possible after delivery to avoid hypoglycemia. (See "Neonatal resuscitation in the
delivery room", section on 'Resuscitation' and "Overview of the routine management of
the healthy newborn infant", section on 'Delivery room care'.)

● Further evaluation following transition from the delivery room includes a

comprehensive examination to identify any underlying genetic syndrome ( table 1),
any evidence of birth trauma (eg, perinatal depression, brachial plexus injury, or
clavicular fracture), or congenital defects. (See 'Genetic syndromes' above and 'Birth
injury' above and 'Congenital anomalies' above.)

● Laboratory screening for hypoglycemia and polycythemia should be performed within

the first hours following birth. (See 'Hypoglycemia' above and 'Polycythemia' above and
"Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on
'Screening' and "Neonatal polycythemia", section on 'Diagnosis'.)

● If there are no significant complications that require further intervention, routine

newborn care should be provided. (See "Overview of the routine management of the
healthy newborn infant".)

POTENTIAL LONG-TERM EFFECTS

Individuals of both diabetic and nondiabetic mothers who were born LGA may have long-
term metabolic effects that increase the risk of obesity [28,29] and insulin resistance [30-33].
Ongoing studies will be needed to see whether effects increase the incidence of adult
diseases, such as obesity, diabetes, and cardiovascular disease.

Limited data suggest neurodevelopmental outcome is similar for LGA and AGA infants.

● In a study of 2930 children from the Early Childhood Longitudinal Study, Birth Cohort
(ECLS-B), the cognitive function of 271 children with birth weights (BWs) ≥90th
percentile did not differ from that of children with normal BW (defined as between the
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5th and 89th percentile) at 9 months, and 2, 3.5, and 5.5 years of age [34]. By contrast,
there are small observational studies that suggest infants born to mothers with poorly
controlled diabetes may be at risk for developmental abnormalities, but the quality of
evidence is poor. (See "Infants of women with diabetes", section on
'Neurodevelopmental outcome'.)

● In the previously described Canadian retrospective cohort study of preterm survivors

born (gestational age <29 weeks), the risk of significant neurodevelopmental outcome
(defined as severe cerebral palsy; Bayley III cognitive, language, and motor scores of
<70; need for hearing aids or cochlear implant; and bilateral visual impairment) at 18 to
21 months corrected age were similar for those born LGA compared with those born
AGA (15.3 versus 16.7 percent, adjusted odds ratio 0.97, 95% CI 0.55-1.72) [26].

SUMMARY AND RECOMMENDATIONS

Infants who are born large for gestational age (LGA), especially full-term or post-term
infants, are at risk for perinatal morbidity and potentially long-term metabolic complications.

● Although LGA has been defined as a birth weight (BW) greater than the 90th percentile,
it has been proposed that a higher threshold of at least the 97th percentile be used
because this more accurately describes infants who are at greatest risk for perinatal
morbidity and mortality ( figure 1). At 40 weeks gestation, infants at the 90th and 97th
percentile weigh more than 4000 or 4400 g. The American College of Obstetricians and
Gynecologists (ACOG) uses a 4500 g threshold for the diagnosis of macrosomia (ie,
excessive fetal growth). (See 'Definition' above.)

● In the United States, the incidence of LGA for infants born at 40 weeks gestation is 6.6,
0.9, and 0.1 percent based on BWs of 4000 to 4499 g, 4500 to 4999 g, and >5000 g,
respectively. Although the incidence of LGA has declined in the United States, it
appears to be increasing in other countries due to increases in maternal age and
weight, gestational diabetes, and decreases in maternal smoking. (See 'Incidence'
above.)

● Excessive fetal growth (macrosomia) resulting in LGA is associated with genetic factors
(eg, syndromes such as Beckwith-Wiedemann ( table 1)), intrauterine environmental
factors (eg, maternal diabetes and obesity, excessive maternal weight gain), and other
maternal factors, such as advanced maternal age and multiparity. (See 'Risk factors and
etiology' above.)

● Neonatal complications are more frequent in infants who are LGA compared with those
who are born appropriate for gestational age (AGA). Complications associated with LGA

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include:

• Birth injuries (eg, brachial plexus injury, perinatal asphyxia, and clavicular injury)
primarily due to shoulder dystocia (see 'Birth injury' above)

• Respiratory distress generally due to respiratory distress syndrome, transient

tachypnea of the newborn, or meconium aspiration (see 'Respiratory distress'
above)

• Hypoglycemia (see 'Hypoglycemia' above)

• Polycythemia (see 'Polycythemia' above)

● Neonatal mortality appears to be increased only in LGA term infants with BWs >5000 g
compared with AGA term infants. (See 'Neonatal mortality' above.)

● The management of an LGA infant includes screening and treating any complication
associated with macrosomia; determining, if possible, the etiology of macrosomia; and
providing routine newborn care. We recommend that in the first few hours following
delivery, laboratory evaluation includes measurement of blood glucose and hematocrit
(Grade 1B).

● Individuals of both diabetic and nondiabetic mothers who were born LGA may have
long-term metabolic effects that increase the risk of obesity and insulin resistance. (See
'Potential long-term effects' above.)

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REFERENCES

1. Xu H, Simonet F, Luo ZC. Optimal birth weight percentile cut-offs in defining small- or
large-for-gestational-age. Acta Paediatr 2010; 99:550.

2. Boulet SL, Alexander GR, Salihu HM, Pass M. Macrosomic births in the united states:
determinants, outcomes, and proposed grades of risk. Am J Obstet Gynecol 2003;
188:1372.
3. Alexander GR, Himes JH, Kaufman RB, et al. A United States national reference for fetal
growth. Obstet Gynecol 1996; 87:163.
4. Martin JA, Hamilton BE, Sutton PD, et al. Births: Final Data for 2006. Natl Vital Stat Rep 20
10; 59:1. http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_01.pdf (Accessed on Octobe
r 26, 2011).
5. Surkan PJ, Hsieh CC, Johansson AL, et al. Reasons for increasing trends in large for
gestational age births. Obstet Gynecol 2004; 104:720.
https://www.uptodate.com/contents/large-for-gestational-age-newborn/print?source=bookmarks_widget 10/17
27/9/22, 20:25 Large for gestational age newborn - UpToDate

6. Hadfield RM, Lain SJ, Simpson JM, et al. Are babies getting bigger? An analysis of
birthweight trends in New South Wales, 1990-2005. Med J Aust 2009; 190:312.
7. Kim SY, Sharma AJ, Sappenfield W, et al. Association of maternal body mass index,
excessive weight gain, and gestational diabetes mellitus with large-for-gestational-age
births. Obstet Gynecol 2014; 123:737.
8. Männik J, Vaas P, Rull K, et al. Differential expression profile of growth
hormone/chorionic somatomammotropin genes in placenta of small- and large-for-
gestational-age newborns. J Clin Endocrinol Metab 2010; 95:2433.
9. Freemark M. Placental hormones and the control of fetal growth. J Clin Endocrinol
Metab 2010; 95:2054.
10. Filiberto AC, Maccani MA, Koestler D, et al. Birthweight is associated with DNA promoter
methylation of the glucocorticoid receptor in human placenta. Epigenetics 2011; 6:566.

11. Haworth KE, Farrell WE, Emes RD, et al. Methylation of the FGFR2 gene is associated
with high birth weight centile in humans. Epigenomics 2014; 6:477.
12. Homko CJ, Sivan E, Nyirjesy P, Reece EA. The interrelationship between ethnicity and
gestational diabetes in fetal macrosomia. Diabetes Care 1995; 18:1442.

13. DeVader SR, Neeley HL, Myles TD, Leet TL. Evaluation of gestational weight gain
guidelines for women with normal prepregnancy body mass index. Obstet Gynecol
2007; 110:745.

14. Linder N, Lahat Y, Kogan A, et al. Macrosomic newborns of non-diabetic mothers:

anthropometric measurements and neonatal complications. Arch Dis Child Fetal
Neonatal Ed 2014; 99:F353.
15. Gillean JR, Coonrod DV, Russ R, Bay RC. Big infants in the neonatal intensive care unit.
Am J Obstet Gynecol 2005; 192:1948.

16. Spellacy WN, Miller S, Winegar A, Peterson PQ. Macrosomia--maternal characteristics

and infant complications. Obstet Gynecol 1985; 66:158.

17. Ju H, Chadha Y, Donovan T, O'Rourke P. Fetal macrosomia and pregnancy outcomes.

Aust N Z J Obstet Gynaecol 2009; 49:504.
18. van Zijl MD, Oudijk MA, Ravelli ACJ, et al. Large-for-gestational-age fetuses have an
increased risk for spontaneous preterm birth. J Perinatol 2019; 39:1050.

19. Akinbi HT, Gerdes JS. Macrosomic infants of nondiabetic mothers and elevated C-
peptide levels in cord blood. J Pediatr 1995; 127:481.

20. Ahlsson FS, Diderholm B, Ewald U, Gustafsson J. Lipolysis and insulin sensitivity at birth
in infants who are large for gestational age. Pediatrics 2007; 120:958.

21. Groenendaal F, Elferink-Stinkens PM, Netherlands Perinatal Registry . Hypoglycaemia

and seizures in large-for-gestational-age (LGA) full-term neonates. Acta Paediatr 2006;

https://www.uptodate.com/contents/large-for-gestational-age-newborn/print?source=bookmarks_widget 11/17
27/9/22, 20:25 Large for gestational age newborn - UpToDate

95:874.

22. Schaefer-Graf UM, Rossi R, Bührer C, et al. Rate and risk factors of hypoglycemia in
large-for-gestational-age newborn infants of nondiabetic mothers. Am J Obstet Gynecol
2002; 187:913.
23. Dollberg S, Marom R, Mimouni FB, Yeruchimovich M. Normoblasts in large for
gestational age infants. Arch Dis Child Fetal Neonatal Ed 2000; 83:F148.

24. Lackman F, Capewell V, Richardson B, et al. The risks of spontaneous preterm delivery
and perinatal mortality in relation to size at birth according to fetal versus neonatal
growth standards. Am J Obstet Gynecol 2001; 184:946.

25. Lapunzina P, Camelo JS, Rittler M, Castilla EE. Risks of congenital anomalies in large for
gestational age infants. J Pediatr 2002; 140:200.
26. Rustogi D, Synnes A, Alshaikh B, et al. Neurodevelopmental outcomes of singleton large
for gestational age infants <29 weeks' gestation: a retrospective cohort study. J Perinatol
2021; 41:1313.

27. Boghossian NS, Geraci M, Edwards EM, Horbar JD. In-Hospital Outcomes in Large for
Gestational Age Infants at 22-29 Weeks of Gestation. J Pediatr 2018; 198:174.

28. Sørensen HT, Sabroe S, Rothman KJ, et al. Relation between weight and length at birth
and body mass index in young adulthood: cohort study. BMJ 1997; 315:1137.
29. Seidman DS, Laor A, Gale R, et al. A longitudinal study of birth weight and being
overweight in late adolescence. Am J Dis Child 1991; 145:782.

30. Chiavaroli V, Giannini C, D'Adamo E, et al. Insulin resistance and oxidative stress in
children born small and large for gestational age. Pediatrics 2009; 124:695.
31. Darendeliler F, Poyrazoglu S, Sancakli O, et al. Adiponectin is an indicator of insulin
resistance in non-obese prepubertal children born large for gestational age (LGA) and is
affected by birth weight. Clin Endocrinol (Oxf) 2009; 70:710.
32. Giapros V, Evagelidou E, Challa A, et al. Serum adiponectin and leptin levels and insulin
resistance in children born large for gestational age are affected by the degree of
overweight. Clin Endocrinol (Oxf) 2007; 66:353.

33. Evagelidou EN, Kiortsis DN, Bairaktari ET, et al. Lipid profile, glucose homeostasis, blood
pressure, and obesity-anthropometric markers in macrosomic offspring of nondiabetic
mothers. Diabetes Care 2006; 29:1197.

34. Paulson JF, Mehta SH, Sokol RJ, Chauhan SP. Large for gestational age and long-term
cognitive function. Am J Obstet Gynecol 2014; 210:343.e1.
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GRAPHICS

Singleton United States birth weight percentile curves for boys and girls
born in 2017

Comparison of smoothed BW-for-GA percentile curves for infants born in the United States in
2017 using two smoothing techniques (lambda-mu-sigma [LMS] and 4235H, a nonlinear
resistant method).

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BW: birth weight; GA: gestational age.

Reproduced with permission from Pediatrics, Vol. 144, e20190076, Copyright © 2019 by the AAP.

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Genetic syndromes frequently associated with macrosomia

Syndrome Main characteristics

Beckwith- Macroglossia, omphalocele, macrosomia, ear creases

Wiedemann

Marshall- Accelerated growth and maturation, shallow orbits, broad middle phalanges
Smith

Simpson- Macrocephaly, coarse face, ocular hypertelorism, broad flat nose, macrostomia,
Golabi-Behmel macroglossia, nail hypoplasia, skeletal abnormalities

Sotos (cerebral Large size, large hands and feet, poor coordination
gigantism)

Berardinelli Lipoatrophy, phallic hypertrophy, hepatomegaly, hyperlipemia

lipodystrophy

Weaver Macrosomia, accelerated skeletal maturation, camptodactyly, unusual facies

Data from: Jones KL. Smith's Recognizable Patterns of Human Malformation. WB Saunders, Philadelphia 2006.

Graphic 62116 Version 3.0

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Macrosomic infant of diabetic mother

A newborn macrosomic infant of a diabetic mother. The main abnormalities

are disproportionate growth with a plethoric appearance and excessive fat
accumulation.

Courtesy of G Cabrera- Mesa, MD.

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Contributor Disclosures
George T Mandy, MD No relevant financial relationship(s) with ineligible companies to
disclose. Leonard E Weisman, MD Equity Ownership/Stock Options: Vax-Immune [Ureaplasma
diagnosis, vaccines, antibodies, other medical diagnostics and pre-analytical devices].
Patent Holder:
Baylor College of Medicine [Ureaplasma diagnosis, vaccines, antibodies, process for preparing
biological samples].
All of the relevant financial relationships listed have been mitigated. Laurie
Wilkie, MD, MS No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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