Large for gestational age (LGA) newborn

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 definition, prevalence, risk factors, complications, evaluation, and management of infants born LGA will be reviewed here. Other related topics include:

●(See "Infants of mothers with diabetes (IMD)".)

●(See "Fetal macrosomia".)

●(See "Postterm infant".)

DEFINITIONS

●LGA – LGA is generally defined as a birth weight (BW) >90^th percentile for gestational age (GA) (figure 1). However, it has been suggested that the definition be restricted to infants with BW ≥97^th percentile (2 standard deviations above the mean), since infants in this category are at greatest risk for perinatal morbidity and mortality [1,2]. Using normative data based upon all singleton live births in the United States in 2017, the 90^th percentile for BW among infants born at 40 weeks gestation corresponds to approximately 4000 g, and the 97^th percentile corresponds to approximately 4400 g [3].

●Macrosomia – Macrosomia is a related term that refers to excessive intrauterine growth based upon an absolute BW threshold, regardless of GA. Macrosomia is usually defined as BW >4000 or >4500 g. The American College of Obstetricians and Gynecologists (ACOG) uses the 4500 g threshold because morbidity increases sharply beyond this BW.

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

•Grade 1 – 4000 to 4499 g

•Grade 2 – 4500 to 4999 g

•Grade 3 – >5000 g

●Appropriate for gestational age (AGA) – AGA is defined as BW between the 10^th and 90^th percentile for GA (figure 1). For term infants, this corresponds to BW between approximately 2500 and 4000 g.

●Small for gestational age (SGA) – SGA is typically defined as BW <10th percentile for GA (figure 1). (See "Infants with fetal (intrauterine) growth restriction", section on 'Small for gestational age'.)

PREVALENCE — The prevalence of LGA varies depending on the definition used. When defining LGA as birth weight (BW) >90^th percentile for gestational age (GA), approximately 10 percent of newborns will be classified as LGA. When using the BW >97^th percentile definition, approximately 3 percent of newborns will be classified as LGA.

The prevalence of macrosomia also varies depending on the definition. Approximately 7 percent of all live births in the United States have BW ≥4000 g and approximately 1 percent have BW ≥4500 g [4].

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 – Macrosomia is a characteristic feature of certain genetic syndromes (eg, Beckwith-Wiedemann syndrome). In addition, mothers who were born LGA are more likely to deliver LGA infants compared with those who were appropriate for gestational age. (See 'Genetic factors' below.)

Limited data suggest that placental epigenetic alterations may contribute to increased fetal growth [5-8].

●Antenatal maternal factors – These include (see 'Maternal factors' below):

•Maternal diabetes (pregestational or gestational) (see 'Maternal diabetes' below)

•Maternal obesity (see 'Maternal prepregnancy weight' below)

•Excessive gestational weight gain (see 'Excessive maternal weight gain' below)

Genetic factors — Certain genetic disorders are characterized by early excessive growth resulting in macrosomia/LGA. Some examples include (table 1):

●Beckwith-Wiedemann syndrome (see "Beckwith-Wiedemann syndrome")

●Simpson-Golabi-Behmel syndrome (OMIM #312870)

●Sotos syndrome (see "Microdeletion syndromes (chromosomes 1 to 11)", section on '5q35 deletion syndrome (Sotos syndrome)')

●Weaver syndrome (OMIM #277590)

●Berardinelli lipodystrophy (see "Lipodystrophic syndromes", section on 'Congenital generalized lipodystrophy')

In addition, macrosomia/LGA is more common in newborns whose mother and/or older sibling(s) were born LGA.

Race and ethnicity — Birth weight (BW) is influenced by race and ethnicity. In a report from the United States that included all singleton live births in 2017, macrosomia (BW ≥4000 g) was more common among White newborns compared with Black or Hispanic newborns (9.1 versus 4.1 and 6.7 percent, respectively) [4].

Maternal factors

Maternal diabetes — Macrosomia is common in infants of mothers with diabetes (IMD), especially when maternal diabetes is poorly controlled. Excessive delivery of nutrients to the fetus results in fetal hyperglycemia, hyperinsulinemia, and increased growth. In IMDs, 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 mothers with diabetes (IMD)", 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) [9]. 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'.)

Other factors — Other factors associated with increased risk of macrosomia/LGA include:

●Multiparity

●Advanced maternal age

●Post-term pregnancy (see "Postterm infant", section on 'Macrosomia')

COMPLICATIONS

Term LGA infants — Term newborns with macrosomia/LGA are at increased risk for neonatal complications and mortality compared with appropriate for gestational age (AGA) infants [2,10]. The risk of morbidity increases sharply as the BW increases above 4500 g.

Macrosomia is also associated with increased risk of peripartum maternal complications, including cesarean delivery, severe postpartum hemorrhage, and vaginal lacerations. These risks are discussed separately. (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 unit (NICU) resources compared with AGA newborns [11]. The most common diagnoses seen in LGA infants, which account for approximately half of NICU admissions in this population, include respiratory distress (particularly transient tachypnea of the newborn [TTN]), hypoglycemia, and meconium aspiration [11].

Mortality — Infants who are born extremely LGA (ie, birth weight [BW] >97^th percentile) or with severe macrosomia (ie, BW >5000 g) have a more than twofold increased risk of neonatal mortality compared with AGA infants (adjusted odds ratio [aOR] 2.69, 95% CI 1.91-3.8) [2,12].

Birth injury — Macrosomia predisposes to shoulder dystocia and birth injury, including brachial plexus injury and clavicular fracture [2,13,14]. The risk of birth injury depends upon the severity of macrosomia (the risk is highest among newborns >4500 g) and route of delivery (risk is greater in vaginal compared with cesarean delivery) [13]. (See "Neonatal birth injuries".)

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

Perinatal asphyxia — Macrosomic infants, especially infants of mothers with diabetes (IMD), are at increased risk for perinatal asphyxia. Several studies have reported that LGA infants more commonly have low five-minute Apgar scores compared with AGA infants [1,2,12,13]. Contributing factors are thought to be increased intrauterine oxygen utilization due to fetal hyperglycemia and hyperinsulinemia, especially in IMDs, and complications of delivery related to shoulder dystocia. (See "Infants of mothers with diabetes (IMD)", section on 'Perinatal asphyxia' and "Shoulder dystocia: Intrapartum diagnosis, management, and outcome", section on 'Infant'.)

Respiratory distress — LGA infants are more likely to develop respiratory distress than AGA infants [2,11]. Respiratory distress in this population may be due to:

●TTN, likely related to the increased incidence of cesarean delivery in LGA infants. (See "Transient tachypnea of the newborn".)

●Meconium aspiration. (See "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis".)

●Preterm birth and associated risk of respiratory distress syndrome (RDS). Preterm birth is more likely in IMDs. (See "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis".)

Hypoglycemia — LGA infants can develop hypoglycemia when the placental supply of glucose is interrupted at birth. In two large European studies, reported rates of hypoglycemia among LGA newborns ranged from 16 to 19 percent [15,16]. Hypoglycemia can occur in LGA newborns born to mothers with or without diabetes. In one study, hypoglycemia occurred in 15 percent of LGA newborns born to mothers without diabetes [15]. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)

Polycythemia — Polycythemia is a common complication seen in LGA newborns born to mothers with or without diabetes [17]. 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".)

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 [18]. Of the nearly 32,000 infants with congenital anomalies, 5 percent were LGA [18]. The most common abnormalities associated with macrosomia included:

●Talipes calcaneovalgus (see "Lower extremity positional deformations")

●Hip subluxation (see "Developmental dysplasia of the hip: Clinical features and diagnosis")

●Hydrocephalus (see "Hydrocephalus in children: Clinical features and diagnosis")

Hospital readmissions — Compared with AGA infants, LGA infants are more likely to be readmitted to the hospital within the first month after discharge from the birth hospitalization. In a population-based study from France that included data on >65,000 term singleton births, 28-day readmission rates were higher for LGA compared with AGA infants (4.3 versus 3.5 percent, respectively; adjusted odds ratio 1.21, 95% CI 1.06-1.39) [19]. The most common reasons for readmission were infections (58 percent), feeding and digestive disorders (22 percent), and jaundice or other metabolic disorder (5 percent).

Potential long-term effects — Individuals who were born LGA, whether born to a mother with or without diabetes, may have long-term metabolic effects that increase the risk of obesity and insulin resistance in adulthood [20-25]. The impact on cardiovascular health is less clear, but there appears to be an increased risk of cardiovascular disease (CVD) among individuals born LGA [26]. Studies have generally found that the relationship between BW and adult CVD is U-shaped, with increased risk at both extremes (ie, BW <2500 g and >4000 g) [26]. The type of CVD appears to vary between individuals with low versus high BW; low BW is linked to greater risk of coronary heart disease, whereas high BW may be associated with increased risk of arterial fibrillation and stroke.

Macrosomia/LGA does not appear to be an independent predictor of long-term neurodevelopmental impairment (NDI) as outcomes appear to be generally similar for LGA and AGA infants [27-29]. However, LGA infants who were exposed to poorly controlled diabetes during pregnancy may be at risk for NDI, as discussed separately. (See "Infants of mothers with diabetes (IMD)", section on 'Neurodevelopmental outcome'.)

Preterm LGA infants — It is unclear whether preterm infants who are LGA have a higher or lower risk of mortality and morbidity compared with AGA infants with the same gestational age (GA). Some studies suggest that higher BW may be a protective factor for preterm neonates [30,31], others studies suggest that preterm LGA infants may be at higher risk for mortality [27], and some studies have concluded that being LGA does not impact risk of morbidity and mortality in preterm neonates [32].

In a study from the Vermont Oxford Network of >150,000 preterm infants (GA 22 to 29 weeks), LGA preterm infants compared with AGA preterm infants had lower mortality and reduced rates of respiratory distress syndrome, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late-onset sepsis, severe retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). Rates of early-onset sepsis and severe intraventricular hemorrhage were slightly higher in LGA infants, though these findings were not consistent across the GA range.

By contrast, a retrospective cohort study of preterm infants (GA <29 weeks) from the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases, in-hospital mortality was higher for LGA infants compared with AGA infants (25 versus 18 percent) [27]. This study did not detect any differences in rates of neonatal morbidities (eg, PDA requiring treatment, NEC, BPD, ROP, severe IVH, late-onset sepsis) between LGA and AGA infants.

EVALUATION AND MANAGEMENT OF THE LGA NEWBORN — Management of LGA newborns includes screening for and treating complications associated with macrosomia (eg, hypoglycemia, respiratory distress); evaluating for the underlying etiology of increased growth, if not readily apparent from the history and physical examination; and providing routine newborn care.

●Prior to delivery, an assessment of the need for neonatal resuscitation is made based on the gestational age, estimated birth weight, maternal history (including complications during pregnancy), prenatally diagnosed congenital abnormalities, and mode of delivery (cesarean versus vaginal). (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 clinical assessment. 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 "Overview of the routine management of the healthy newborn infant", section on 'Assessment and disposition' and "Management and outcome of neonatal hypoglycemia", section on 'Oral feeds'.)

●Further evaluation following transition from the delivery room includes a comprehensive clinical assessment to identify any abnormalities that might suggest an underlying genetic syndrome (table 1) or evidence of birth trauma (eg, brachial plexus injury or clavicular fracture). (See 'Genetic factors' above and 'Birth injury' above and 'Congenital anomalies' above.)

●All LGA infants should undergo screening for hypoglycemia within the first hours following birth, as described separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening'.)

●If the newborn has any signs or symptoms that may be due to polycythemia (eg, cyanosis, tachypnea, poor feeding), the hematocrit should be measured. (See "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".)

SUMMARY AND RECOMMENDATIONS

●Definitions – Large for gestational age (LGA) is generally defined as a birth weight (BW) >90^th percentile (figure 1). A higher threshold (BW ≥97^th percentile) has been proposed since infants in this category are at greatest risk for perinatal morbidity and mortality. Macrosomia is a related term that refers to excessive intrauterine growth based upon an absolute BW threshold, regardless of GA. Macrosomia is usually defined as BW >4000 or >4500 g. The risk of morbidity increases sharply if the BW exceeds 4500 g. (See 'Definitions' above.)

●Prevalence – The prevalence of LGA/macrosomia varies depending on the definition used. When defining LGA as BW >90^th percentile for GA, approximately 10 percent of newborns will be classified as LGA. When using the >97^th percentile definition, approximately 3 percent of newborns will be classified as LGA. In the United States, approximately 7 percent of all live births have BW ≥4000 g and approximately 1 percent have BW ≥4500 g. (See 'Prevalence' above.)

●Risk factors and etiology – Macrosomia/LGA is associated with genetic factors (eg, syndromes such as Beckwith-Wiedemann (table 1)), prenatal maternal factors (eg, maternal diabetes, obesity, excessive maternal weight gain), and other maternal factors, such as advanced maternal age and multiparity. (See 'Risk factors and etiology' above.)

●Complications – Infants who are LGA compared with those who are born appropriate for gestational age (AGA) are at increased risk for short- and long-term complications, which may include (see 'Complications' above):

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

•Perinatal asphyxia and low five-minute Apgar scores. (See 'Perinatal asphyxia' above.)

•Birth injuries (eg, brachial plexus injury, perinatal asphyxia, and clavicular injury) primarily due to shoulder dystocia. (See 'Birth injury' above and "Neonatal birth injuries" and "Shoulder dystocia: Intrapartum diagnosis, management, and outcome".)

•Respiratory distress, which may be due to transient tachypnea of the newborn, meconium aspiration, or respiratory distress syndrome. (See 'Respiratory distress' above and "Overview of neonatal respiratory distress and disorders of transition".)

•Hypoglycemia. (See 'Hypoglycemia' above and "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)

•Polycythemia. (See 'Polycythemia' above and "Neonatal polycythemia".)

•Congenital abnormalities such as talipes calcaneovalgus, hip subluxation, and hydrocephalus. (See 'Congenital anomalies' above.)

•Hospital readmission after discharge from the birth hospitalization. (See 'Hospital readmissions' above.)

•Increased risk of obesity, insulin resistance, and cardiovascular disease in adulthood. (See 'Potential long-term effects' above.)

●Evaluation and management of LGA newborns – Management of LGA newborns includes assessing for and treating complications associated with macrosomia (eg, hypoglycemia, respiratory distress); evaluating for the underlying etiology of increased growth, if not readily apparent from the history and physical examination; and providing routine newborn care. (See 'Evaluation and management of the LGA newborn' above and "Overview of the routine management of the healthy newborn infant".)

All LGA infants should undergo screening for hypoglycemia within the first hours following birth, as described separately. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening'.)

If the newborn has any signs or symptoms that may be due to polycythemia (eg, cyanosis, tachypnea, poor feeding), the hematocrit should be measured. (See "Neonatal polycythemia", section on 'Diagnosis'.)