Macrosomia

Factors associated with fetal macrosomia include genetics; duration of gestation; presence of gestational diabetes; high pre-pregnancy body mass index (BMI); excessive gestational weight gain; and class A, B, and C diabetes mellitus.[3] Genetic, sex, racial, and ethnic factors influence birth weight and the risk of macrosomia.[4] Male newborns typically weigh more than female newborns and thus comprise a greater proportion of infants with birth weights exceeding 4500 g. The risk of macrosomia also varies with ethnicity. Even when controlled for diabetes, studies have demonstrated that Hispanic women have a higher risk of fetal macrosomia compared with white, African American, or Asian women. Genetic factors, such as parental height and weight, may also play a role in determining newborn birth weight.

Despite the identification and characterization of risk factors, no combination of these risk factors can predict macrosomia accurately enough to be used clinically. Much of the birth weight variation remains unexplained, and most macrosomic infants do not have identifiable risk factors. Finally, macrosomia is reportedly associated with neonatal morbidity, neonatal injury, maternal injury, and cesarean delivery.[5, 6]  Risks associated with macrosomia increase on a continuum. Macrosomia is often divided into three categories with different levels of risk: (1) 4000-4499 g, (2) 4500-4999 g, and (3) more than 5000 g.[1]

The pathophysiology of macrosomia is related to the associated maternal or fetal condition that accounts for its development. In general, poorly controlled diabetes, maternal obesity, and excessive maternal weight gain are all associated with macrosomia and have intermittent periods of hyperglycemia in common. Hyperglycemia in the fetus results in the stimulation of insulin, insulin-like growth factors, growth hormone, and other growth factors, which, in turn, stimulate fetal growth and deposition of fat and glycogen. Advanced gestational age results in a larger birth weight at delivery by allowing the growth process to continue in utero.

Various studies have examined the in utero development of macrosomic fetuses. In a secondary analysis of data from a randomized control trial on treatment versus non-treatment of mild gestational diabetics, Stuebe et al assessed the link between maternal BMI, glucose intolerance, and fetal and maternal risk factors. Stuebe et al found pre-gravid maternal BMI is linked with macrosomia and with increased neonatal fat mass independent of oral glucose challenge test values.[7] Another study performed by Catalano et al further elucidates this link in their analysis of >400 infants born to women with and without glucose intolerance. They found that infants born to women with glucose intolerance have increased fat mass when compared to infants born to women with normal glucose tolerance. This was independent of maternal BMI.[8]  Geraghty et al collected blood samples on 331 mother-child pairs in a prospective cohort. They found that maternal serum triglycerides correlated positively with birth weight.[9]   These studies highlight the complexity of the pathophysiology leading to macrosomia and also demonstrate that both maternal obesity and maternal glucose intolerance not only increase birth weight but also lead to increased neonatal adiposity or percent body fat, in turn putting them at increased risk of macrosomia and its complications, including shoulder dystocia, birth injury, neonatal intensive care unit admission, and even fetal death.[7, 8, 10, 11]

Macrosomia may be associated with birth trauma for the neonate and birth canal lacerations, eg, perineal, vaginal, and cervical,[12]  or cesarean delivery for the mother. A large for gestational age fetus in a diabetic mother may indicate poor glucose control. These infants are at increased risk of intrauterine death[13] and thus require close monitoring and antepartum fetal testing.

Causes for macrosomia include factors that contribute to excessive fetal growth and weight gain.

There are numerous contributors to macrosomia, many of which are assessed in a case-control study by Okun et al, which list factors including: prior macrosomic infant, maternal prepregnancy weight, excessive gestational weight gain, multiparity, male fetus, gestational age >40 weeks, ethnicity, maternal birth weight, maternal height, maternal age younger than 17 years, and a positive 50g glucose screen with a normal 100g glucose tolerance test, in descending order of effect according to their analysis of data from 1000 deliveries of macrosomic and non-macrosomic infants in Edmonton, Alberta.[4]

A study done by Kim et al reviewed vital records between 2004 and 2008 in the state of Florida to assess the association between maternal BMI, maternal weight gain, and gestational diabetes mellitus with fetal macrosomia. They found that excessive maternal weight gain had the strongest association for a large for gestational age infant of the examined variables. BMI of greater than 25 and gestational diabetes were also associated with having a large-for-gestational-age (LGA) infant. Initial BMI and gestational weight gain are also both modifiable risk factors and provide potential interventions to decrease a patient’s risk of having a macrosomic infant.[3]

Poor glycemic control in pregnancy is a major risk factor for fetal macrosomia. Maternal glucose passes through the placenta, leading to fetal hyperglycemia and hyperinsulinemia as well as an increase in levels of insulin-like growth factors and growth hormone. This leads to increased fetal fat deposition, glycogen synthesis, and larger fetal size. Elevated fasting glucose levels may be more strongly associated with macrosomia.[14]

Genetic factors also contribute to fetal size. Taller (80th percentile or more) and heavier parents typically produce larger offspring. Women with short stature and obesity are at almost threefold higher risk for macrosomia compared with those of short stature with normal/overweight BMI.[15]

United States data

Of U.S. births in 2017, approximately 7.8% of infants had birth weight >4000 g, 1% had birth weight greater than 4500 g, and 0.1% had birth weight greater than 5000 g.[2]  Rates of large-for-gestational-age (LGA) newborns are increased in women with gestational diabetes mellitus (GDM), with 13.6% of fetuses being macrosomic in normal-weight women and 22.3% in obese women.[16]

Race- and sex-related demographics

Macrosomia occurs with higher frequency in newborns of Hispanic origin. Part of the preponderance of macrosomia in this ethnic group may be due to the higher incidence of diabetes in pregnancy. However, even when corrected for diabetes, Hispanic mothers tend to have larger newborns.

Male infants are more likely to be macrosomic than female infants. Male infants are generally approximately 150-200 g larger than female infants of the same gestational age near term.[17, 18]

Gestational age

Macrosomia, as defined by birth weight greater than 4000-4500 g, occurs with higher frequency in prolonged pregnancies that continue beyond the expected delivery date. This is to be expected as infants gain approximately 150-200 g weekly near term.[17]

There is some evidence that link may exist between macrosomia and longstanding health issues that develop later in life, such as insulin resistance, hypertension, and obesity. A study of macrosomic mice found that males with macrosomia had increased likelihood of heavier body weight, insulin resistance, and impaired glucose tolerance compared to non-macrosomic males. In females, there was a link with macrosomia and higher blood pressures, rather than body weight or glycemic control issues.[19] A cross-sectional study of adults with type 2 diabetes in China found an associations between macrosomia and  increased abdominal obesity as well as  increased rates of  hypertension.[20] Furthermore, a  meta-analysis performed by Harder et al, found a “U-shaped” relationship between birth weight and risk of type 2 diabetes mellitus later in life, meaning infants born at both extremes of birth weight, both SGA and LGA, are at increased risk of developing type 2 diabetes in adulthood.[21]

Morbidity/mortality

Morbidity and mortality associated with macrosomia can be divided into maternal, fetal, and neonatal categories. A study investigating the effects of birth weight on fetal mortality shows that higher fetal mortality rates are associated with a birth weight of greater than 4250 g in nondiabetic mothers and a birth weight of 4000 g in diabetic mothers.[13]

Maternal morbidity

Macrosomia is associated with a higher incidence of cesarean delivery (double that of control subjects) and with birth canal lacerations associated with vaginal delivery. Labor protraction and arrest disorders are more common with fetal macrosomia. The preponderance of cesarean deliveries related to macrosomia are due to abnormal labor.[1]  There is a twofold to threefold increased risk of third-degree and fourth-degree lacerations associated with macrosomia.[22]  The risks of postpartum hemorrhage and chorioamnionitis are also increased.[23]

Mulik et al reviewed the outcomes of 8617 deliveries over a period of 11 years.[24]  In that population, 666 neonates were born with a birth weight of 4000-4499 g and 97 neonates were larger than 4500 g. In their study, Mulik et al found maternal morbidity to be associated with a birth weight of 4500 g or higher compared with a birth weight of less than 4000 g. Postpartum hemorrhage occurred in 3.1% of mothers with newborns weighing 4500 g or more compared with 1.5% in mothers with newborns weighing less than 4000 g. Blood transfusions occurred in 15.4% of mothers with newborns weighing 4500 g or more compared with 3.1% in mothers with newborns weighing less than 4000 g.

Neonatal morbidity

Macrosomic neonates are at risk for shoulder dystocia and birth trauma. The common injuries are clavicular fracture and brachial plexus injury, specifically C5-C6 leading to Erb-Duchenne paralysis.[25]  This risk is directly related to neonatal birth weight and begins to increase substantially when birth weight exceeds 4500 g and particularly when it exceeds 5000 g. Brachial plexus injury is rare, with an incidence of fewer than 2 cases per 1000 vaginal deliveries. This risk is approximately 20 times higher when the birth weight is more than 4500 g.[12]  Risk of fracture of the clavicle is approximately 0.4-0.6% of all births, increasing 10-fold for macrosomic newborns.[25]  Mulik et al reported a higher incidence of NICU admissions for neonates with a birth weight higher than 4500 g compared with newborns with a birth weight of less than 4000 g (9.3% vs 2.7%). Risk of shoulder dystocia was 10 times higher in the larger babies (4.1% vs 0.4%).

Fetal morbidity/mortality

When associated with diabetes, fetal macrosomia indicates poor maternal glucose control, and these infants are at risk of stillbirth. Stillbirth rates in macrosomic infants are twice as high as those in control subjects, irrespective of diabetes. However, for a birth weight of 4500-5000 g, the fetal death rate is fewer than 2 deaths per 1000 births for nondiabetic women and is approximately 8 deaths per 1000 births for diabetic women. For a birth weight of 5000-5500 g, this rate is 5-18 deaths per 1000 births for nondiabetic women and is approximately 40 deaths per 1000 births for diabetic women.[13]

Fetal macrosomia has been defined to include birth weight greater than 4000 g or greater than 4500 g.[1]  Macrosomia may place the mother and fetus or neonate at risk for adverse outcomes. Identification of pregnancies with antenatal risk factors for macrosomia may allow intervention to reduce the risk, to provide appropriate counseling, and to implement appropriate plans for monitoring and follow-up care during pregnancy and after delivery.

Note the following:

• Maternal diabetes is a strong risk factor associated with giving birth to an infant that is considered large for gestational age. Pregestational and gestational diabetes result in fetal macrosomia in as many as 50% of pregnancies complicated by gestational diabetes and in 40% of those complicated by type 1 diabetes mellitus. Studies of macrosomic infants of diabetic mothers reveal a greater amount of total body fat, thicker upper-extremity skin fold measurements, and smaller ratios of head to abdominal circumference than macrosomic infants of nondiabetic mothers.[10]

• Maternal weight prior to pregnancy can affect the weight of the fetus. Women who are obese are more likely to have larger infants.[26, 27, 3]

• Excessive weight gain in pregnancy is a risk factor for macrosomia. The risk is greater for women with obesity than for women without obesity.[26, 3]  Maternal obesity is linked to a 4- to 12-fold increase in the risk of macrosomia.[28]

• Gestational age is associated with macrosomia. Birth weight increases as gestational age increases. Prolonged pregnancies (>41 wk) are associated with an increased incidence of macrosomia. Macrosomic infants account for about 1% of term deliveries and 3-10% of postterm deliveries.[5] See the Gestational Age from Estimated Date of Delivery (EDD) calculator.

• Multiparity and grand multiparity increase the risk of macrosomia.[29] Parity has been reported to be associated with 100-150 grams of weight gain at birth.[30]  The risk increases with women with parity greater than three. Multiparity is not a major maternal risk factor, but it contributes to the risk of diabetes and obesity.[28]

• A history of macrosomia can influence future pregnancies. Women who previously delivered a macrosomic fetus are 5-10 times more likely than women without such a history to deliver a baby considered large for gestational age the next time they become pregnant.[31]  In a large study that controlled for BMI, excess weight gain, diabetes, race, parity, and age, a history of macrosomia was a strong individual risk factor for macrosomia.[32]

• Fetal sex influences macrosomic potential. Male infants weigh more than female infants at any gestational age. Recent studies have confirmed this association.[33, 17]

• Excessive amniotic fluid defined as greater than or equal to 60th percentile for gestational age has recently been associated with macrosomia.[34]

• Despite these so-called risk factors for macrosomia, much of the variation in birth weights remains unexplained. Most infants who weigh more than 4500 g have no identifiable risk factors. Kim et al found that 46.8-61.0% of the mothers with macrosomic infants assessed in their study had none of the three primary risk factors studied, which included maternal overweight, excessive gestational weight gain and GDM.[3]

• Certain genetic and congenital disorders are associated with an increased risk of macrosomia, including Beckwith-Weidemann syndrome, Sotos syndrome, fragile X syndrome, and Weaver syndrome.[35]

Many physical examination findings help identify a pregnancy at risk for macrosomia.

Maternal obesity

Maternal obesity is associated with fetal macrosomia.[27]  Maternal body mass index (BMI) is a good way of diagnosing obesity prior to pregnancy. The most widely accepted definition for obesity is based on the World Health Organization (WHO) criteria, which uses the BMI. Under this convention for adults, grade 1 overweight (commonly and simply called overweight) is a BMI of 25-29.9 kg/m2. Grade 2 overweight (commonly called obesity) is a BMI of 30-39.9 kg/m2. Grade 3 overweight (commonly called severe or morbid obesity) is a BMI greater than or equal to 40 kg/m2. A BMI greater than 30 kg/m2 is associated with larger infants at delivery.

Maternal obesity is associated with an increased risk of diabetes. Increased concentration of glucose in diabetic mothers leads to fetal hyperinsulinemia, which contributes to increased fetal growth.[35]

Pregnancy weight gain

The recommendations for weight gain in pregnancy have been based on the Institute of Medicine (IOM) guidelines which were updated in 2009. The suggested weight gain is 28-40 lbs for BMI < 18.5, 25-35 lbs for BMI 18.5 – 24.9, 15-25 lbs for BMI 25.0-29.9, and 11-20 lbs for BMI ≥ 30.0.[19]  The slowest weight gain occurs in the first trimester and the fastest in the second trimester. Most of the weight gained in the first trimester is fat. Later in pregnancy, the weight is from fetal weight, extravascular fluid, and maternal fat stores. Women with obesity require less weight gain in pregnancy owing to increased fat deposits; therefore, the energy expenditure associated with pregnancy is much less than in normal-weight women.[36]

Half of the weight gained in pregnancy is from the fetus, placenta, amniotic fluid, and gravid uterus. A quarter is from increased blood volume, extravascular volume, and breast tissue. The rest is associated with increased maternal accumulation of cellular water, fat, and protein. Other weight gain is attributable to maternal fat deposition. Increased weight gain in pregnancy is associated with an elevated risk of increased fetal growth, preterm delivery, cesarean delivery, gestational diabetes, hypertensive disorders, and infant mortality.[36]

Fundal height measurements and Leopold maneuvers

Fundal height measurements are an inaccurate way of estimating fetal size. A large retrospective cohort study, which used the perinatal database at Washington University Medical Center from 1990 to 2009, reviewed patients referred for a third-trimester ultrasound scan for “size unequal to dates” (both size less than dates and size greater than dates). These patients were further compared across various maternal BMI categories. There was a low detection rate of fetal growth abnormalities for those referred for an ultrasound scan based on clinical examination (ie, fundal height measurements). Only 15.8% of patients referred for size greater than dates actually had an estimated fetal weight of >90th percentile for gestational age. The sensitivity and specificity for detecting birth weight of  >90th percentile were 9.7% and 96.6%, respectively. As maternal BMI increased, the sensitivity increased and the specificity and negative predictive value decreased. Interestingly, about 11.1% of patients in the study who had a normal fundal height delivered a neonate weighing >90th percentile for gestational age.[37]  

Another retrospective cohort study, by Sparks et al, had similar findings, with a sensitivity and specificity of 16.6% and 95.4%, respectively, for detection with fundal heights of birth weight of >90th percentile for gestational age.[38]  Fundal heights are influenced by maternal size, the amount of amniotic fluid, the status of the bladder, the presence of pelvic masses (eg, fibroids), fetal position, and many other factors. 

Leopold maneuvers are techniques developed to determine fetal presentation, lie, and size. They are also limited by many factors, as mentioned previously for fundal height measurements. However, these maneuvers provide the clinician with a general appreciation of fetal size and other important information. Prospective studies designed to evaluate Leopold maneuvers with fundal height measurement for the prenatal diagnosis of possible macrosomia report sensitivities of 10-43%, specificities of 99-99.8%, and positive predictive values of 28-53%.[39, 40]  However, discrepancy between fundal height and estimated gestation age is often used to screen women for referral for evaluation of possible large for gestational age fetus by growth ultrasound.

Morbidity/mortality

Morbidity and mortality associated with macrosomia can be divided into maternal, fetal, and neonatal categories.

Maternal morbidity

Macrosomia is associated with a higher incidence of cesarean delivery (double that of control subjects) and with birth canal lacerations associated with vaginal delivery. Mulik et al reviewed the outcomes of 8617 deliveries over a period of 11 years.[24] In that population, 666 neonates were born with a birth weight of 4000-4499 g and 97 neonates were larger than 4500 g. In their study, Mulik et al found maternal morbidity to be associated with a birthweight of 4500 g or higher compared with a birth weight of less than 4000 g. Postpartum hemorrhage occurred in 3.1% of mothers with newborns weighing 4500 g or more compared with 1.5% in mothers with newborns weighing less than 4000 g. Blood transfusions occurred in 15.4% of mothers with newborns weighing 4500 g or more compared with 3.1% in mothers with newborns weighing less than 4000 g.

Neonatal morbidity

Macrosomic neonates are at risk for shoulder dystocia and birth trauma. This risk is directly related to neonatal birth weight and begins to increase substantially when birth weight exceeds 4500 g and particularly when it exceeds 5000 g.[6] Brachial plexus injury is rare, with an incidence of fewer than two cases per 1000 vaginal deliveries. This risk is approximately 20 times higher when the birth weight is more than 4500 g.[12] Mulik et al reported a higher incidence of NICU admissions for neonates with a birth weight higher than 4500 g compared with newborns with a birth weight of less than 4000 g (9.3% vs 2.7%). Risk of shoulder dystocia was 10 times higher in the larger babies (4.1% vs 0.4%).

In a large study by Raio et al, 3356 newborns who weighed more than 4500 g at birth were studied. Shoulder dystocia occurred in 310 of the newborns, and brachial plexus injuries occurred in 94 of the newborns (about 10% and 3%, respectively). In this population, gestational diabetes increased the risk of shoulder dystocia by a factor of two, while preexisting diabetes increased the risk four-fold.[41]

Fetal morbidity/mortality

Mondestin et al investigated the effects of birth weight on fetal mortality and demonstrated that higher fetal mortality rates are associated with a birth weight of greater than 4250 g in nondiabetic mothers and a birth weight of 4000 g in diabetic mothers.[13] Stillbirth rates in macrosomic infants are twice as high as those in control subjects, irrespective of diabetes. However, for a birth weight of 4500-5000 g, the fetal death rate is fewer than two deaths per 1000 births for nondiabetic women and is approximately eight deaths per 1000 births for diabetic women. For a birth weight of 5000-5500 g, this rate is five to 18 deaths per 1000 births for nondiabetic women and is approximately 40 deaths per 1000 births for diabetic women.[13]

A retrospective cohort analysis designed to demonstrate the link between SGA and perinatal demise showed a “reverse J-shaped relationship” between birth weight percentile and risk of fetal and neonatal death. This means that the greatest risk of perinatal death is at birth weights ≤3rd percentile and ≥98th percentile. A great deal of research and management guidance has gone into surveillance for SGA infants, and this study would suggest that more investigation is warranted to examine the perinatal risks and optimal surveillance of the fetus with accelerated growth.[42]

This is supported by a study by Boulet et al that showed increased risk of neonatal death with increasing birth weight, most notable and statistically significant for infants with birth weights greater than 5000 g, or “grade 3 macrosomia” according to the model in their study.[6]

A large retrospective cohort study by Linder et al included singleton, full-term newborns with a birth weight of ≥4000 g at a tertiary care center, who were matched with healthy newborns with a birth weight of 3000-4000 g. The results showed that macrosomic infants had higher rates of hypoglycemia, transient tachypnea of the newborn, hyperthermia, and birth trauma. There were no differences between the two groups in low 5-minute Apgar scores, metabolic acidosis, infection, loss of >10% of body weight, meconium aspiration syndrome, or cyanotic episodes. Two additional studies that examined infants of diabetic mothers suggested that in utero exposure to hyperglycemia leads to disproportionate growth and higher rates of neonatal complications, such as hypoglycemia, hyperbilirubinemia, polycythemia, and metabolic acidosis.[43]

A glucose tolerance test at 24-28 weeks of gestation screens for gestational diabetes, a known risk factor for macrosomia. Identification and treatment of gestational diabetes has been shown in randomized controlled trials to decrease fetal birth weight, thereby reducing risk of macrosomia.[44, 45]

Early glucose screening is necessary for women with risk factors for the development of diabetes (eg, obesity, strong family history of diabetes, prior pregnancy affected by macrosomia or gestational diabetes).

According to an ACOG Practice Bulletin regarding gestational diabetes mellitus (GDM), antenatal testing should be performed when the mother has pregestational diabetes mellitus or poor glycemic control with GDM. However, the exact timing and the specific testing are based on local practice, rather than on an official recommendation.[46]

Neonatal evaluation for hypoglycemia, polycythemia, hyperbilirubinemia, and electrolyte abnormalities is indicated in all macrosomic newborns because maternal hyperglycemia is the most common cause and sometimes this diagnosis is not made in the mother prior to delivery of her child.

Long-term follow-up care of these infants is needed because they are at risk for obesity and perhaps diabetes in later life.[20]

Ultrasound measurements to obtain estimated fetal weights are indicated when clinical assessments indicate a uterine size greater than that expected for the gestational age. An examination within 1-2 weeks of delivery showing an abdominal circumference of 35 cm or larger should alert the clinician to anticipate a fetus with a birthweight of 4000 g or more. The definitive diagnosis can only be made after delivery of the neonate.[47, 48] It has been established that at higher fetal weights there is reduced accuracy of ultrasound in estimating fetal weight, most notable for birth weights over 4500g, thereby providing a greater challenge in care decisions and prediction of birth weight in suspected macrosomic infants.[49]

Jazayeri et al showed in a retrospective study that abdominal circumference measurements made within 2 weeks of delivery can be predictive of a birth weight greater than 4000 g.[50] Note the following:

• A measurement of 35 cm or more identified more than 90% of newborns with a birth weight greater than 4000 g and occurred in only 18% of the population.

• An abdominal circumference measurement within 2 weeks of delivery had sensitivity, specificity, and positive and negative predictive values of approximately 90%.

• Abdominal circumference measurements in patients at risk for macrosomia can provide some clues to the size of the fetus and thus allow appropriate preparations for delivery (see Surgical Care).

Ben-Haroush et al[51] reported ultrasonography to be an accurate way of estimating birth weight as a screening measure. In patients suspected to have macrosomic fetuses, sensitivity was 75% and specificity was 65% resulting in a positive predictive value of 57% and a negative predictive value of 81%. In patients where macrosomia is not suspected, sensitivity was 32% and specificity was 92% resulting in a positive predictive value of 33% and a negative predictive value of 90%. In the overall population of 298 newborns, sensitivity was 56% and specificity was 88% resulting in a positive predictive value of 48% and a negative predictive value of 91%.

Most ultrasound machines have one or more estimated fetal weight equations in the software. Most of these equations are associated with significant errors. The Hadlock formula is commonly used, and it has a mean absolute percent error of 13% for birth weight of ≥4500g compared with 8% for non-macrosomic newborns. No single formula has been proven to be superior to another for detection of macrosomia of more than 4500 g.[49, 52, 53]

More recent studies have confirmed that appropriately performed abdominal circumference measurements by ultrasonography in the third trimester is the best way of predicting neonatal weight. Without doubt, the usefulness of this technique depends on the quality of image obtained in late third trimester and the cut off used to define the at-risk neonate. Studies using different cut-offs have come with a variety of positive and negative predictive values as well as sensitivities and specificities.[54, 55, 56]

Bicocca et al performed a multicenter, retrospective cohort study of all non-anomalous singletons with an estimated fetal weight of ≥4000 g by ultrasound scanning within 14 days of delivery. Cohorts were then divided into two groups based on time interval between the ultrasound scan and delivery (0-7 days and 8-14 days). The rate of detection and false-positive rate for the detection of birth weight of ≥4500 g were compared between the two groups. No significant difference in false-positive rate was found; however, the detection of birth weight of ≥4500 g was higher when the ultrasound scan was performed within 7 days of delivery, irrespective of maternal diabetes.[57]

Induction of labor for presumed fetal macrosomia has in recent history been discouraged due to unclear benefit. However, in a randomized controlled trial (RCT) by Boulvain et al, 822 women with estimated fetal weight > 95th percentile at term were randomized to induction versus expectant management. Induction of labor was associated with reduced risk of shoulder dystocia; however, the study was underpowered to detect a difference in brachial plexus injury and none occurred in either group. In addition, induction of labor did not increase cesarean section rate as had been feared. A Cochrane systematic review of four RCTs that included 1190 patients examined outcomes with induction of labor for large for gestational age.[58] The Boulvain RCT contributed 800 of the 1190 patients and dominated the findings of the review. The review concluded that induction of labor in suspected fetal macrosomia does not reduce the risk of brachial plexus injury but does reduce birth weight, or the risk of skeletal injury and shoulder dystocia.[59]

Macrosomia is related to perinatal complications and the term fetus increases its body mass approximately 150-200g per week.  Early term or 39-week induction of labor can reduce rates of macrosomia compared with expectant management, and therefore may decrease the complications of macrosomia.

A large retrospective cohort study using the U.S. Vital Statistics data that included singleton, non-anomalous deliveries at 37-39 weeks of gestation from 2011 to 2013 compared maternal and neonatal outcomes of appropriate weight for gestational age (AGA) infants versus large for gestational age (LGA) but non-macrosomic infants (< 4000 g). The study showed that LGA non-macrosomic birth weights were associated with increased composite maternal and neonatal morbidity compared with infants born with AGA growth. Maternal morbidity included maternal transfusion, ruptured uterus, unplanned hysterectomy, admission to intensive care unit, or unplanned procedure. Neonatal morbidity included Apgar score less than 5 at 5 minutes, assisted ventilation for more than 6 hours, seizure or serious neurologic dysfunction, significant birth injury, or neonatal mortality.[60]

Even though the risk of fetal and maternal morbidity increases with macrosomia, most deliveries of macrosomic infants are uncomplicated. The American College of Obstetricians and Gynecologists (ACOG) continues to recommend against delivery before 39 0/7 weeks unless medically indicated. Data remain inconclusive whether intervention is better than expectant management for suspected LGA fetuses. Therefore, induction of labor for suspected macrosomia before 39 0/7 weeks of gestation is not recommended by ACOG owing to insufficient evidence that reducing the risk of shoulder dystocia outweighs the risks associated with early delivery.[1]  

Cesarean delivery to reduce the risk associated with macrosomia may place the mother at risk, and subsequent pregnancies are at risk of uterine dehiscence before or during the onset of labor. Not all cases of nerve injuries can be prevented by cesarean delivery because some occur in utero. Estimates indicate that as many as 3,695 cesarean deliveries in non-diabetic women and 443 cesarean deliveries in diabetic women must be performed to prevent a single permanent brachial plexus nerve injury in infants of estimated fetal weight greater than 4,500 g.[61]  Expert opinion suggests that there may be some benefit to offering scheduled cesarean section to mothers with suspected macrosomia (>5000 g in non-diabetic mothers and >4500 g in diabetic mothers); however, the decision to perform cesarean section for macrosomia is left to the provider and patient.[1]

Decision making regarding delivery should be individualized to the patient, taking into account risks and benefits of both macrosomia and other delivery factors such as surgical risks, including implications for future childbearing, and the neonatal risks of early term delivery.

The obstetrician involved in the care of a macrosomic infant must be familiar with procedures that release a shoulder dystocia at delivery. See the Medscape topic Shoulder Dystocia for more information.

Because macrosomic infants are at increased risk of cesarean delivery the provider must be capable of performing a cesarean delivery or must have backup help available in case cesarean delivery is necessary.

Operative vaginal deliveries (eg, forceps, vacuum) must be performed with caution in infants with risk factors for macrosomia. Midpelvic procedures are associated with a much greater risk of significant shoulder dystocia (50%) in macrosomic infants than non-macrosomic infants.[62]

In patients with poorly controlled diabetes resulting in macrosomia, consultation with a maternal fetal medicine specialist to obtain better control may be useful.

In cases of significant macrosomia (estimated fetal weight >99th percentile), a careful evaluation of the dates and a sonographic evaluation of fetal anatomy can be helpful to investigate potential causes of the macrosomia. Incorrect gestational age is frequently encountered and may result in estimated fetal weights that are greater than the 90th percentile but usually should not result in estimations greater than 4000 or 4500 grams. Intra-abdominal and intracranial masses may result in larger abdomen and head measurements resulting in a large estimated fetal weight. Such causes should be diagnosed prior to delivery if at all possible.

Pre-gestational obesity and excessive gestational weight gain in pregnancy are two of the strongest predictors of macrosomia at birth; therefore, a possible intervention to prevent macrosomia may be nutrition education and an exercise program. Excessive maternal weight gain can double the risk of macrosomia; thus, a reasonable suggestion is careful weight control for women who exceed the recommended weight gain in pregnancy.[10, 36, 43]  Gestational weight gain is a modifiable risk factor.[36]  Intuitively, this type of intervention, if successful, may reduce the risks of macrosomia in those women who are obese prior to pregnancy or who may gain excessive weight in pregnancy. In diabetic patients, maternal diet alone, without the use of insulin, did not alter rates of macrosomia.[63, 64]

A systematic review that included 18 RCTs with 1151 women revealed that dietary changes/interventions resulted in a greater decrease in fasting and postprandial glucose values and a lower need for medication treatment for gestational diabetes. Dietary interventions were also shown to be associated with lower birth weight and lower rates of macrosomia (relative risk, 0.49 [95% CI, 0.27-0.88]; P =.02).[65]

A multi-center RCT by Landon et al assessed 958 women with mild gestational diabetes and randomized them to usual prenatal care vs diet and lifestyle intervention with treatment as medically indicated for glycemic control. The study found a statistically significant difference in the control group vs treatment group in the frequency of large-for-gestational-age infants, 14.5% vs 7.1%, as well as reduced frequency of shoulder dystocia (4.0% vs 1.5%) and birth weight over 4000 g (14.3% v 5.9%).[44]

One study randomized 98 women with gestational diabetes mellitus and fetal abdominal circumference of >75% for gestational age to either diet alone or diet and twice-daily insulin. Insulin along with diet decreased the risk of birth weight > 90th percentile from 45% in those treated with diet alone to 13% in those treated with diet and insulin (P< .01).[63]

Dietary and weight gain guideline education should be provided for obese patients of patients experiencing excessive gestational weight gain as these are associated with macrosomia, gestational diabetes, cesarean delivery, and preeclampsia. Such intervention may potentially reduce maternal and neonatal risks. At the present time, clinical trials are lacking support of the effectiveness of such intervention.[66]

ACOG recommends that women without any contraindications should be encouraged to participate in aerobic and strength conditioning exercises during pregnancy to reduce the risk of macrosomia.[1]  The U.S. Department of Health and Human Services Physical Activity Guidelines for Americans recommends at least 150 minutes of moderate intensity aerobic exercise per week during pregnancy and postpartum.[67]  Despite these recommendations, only 9-15% of pregnant women meet this guidelines.[68]

A systematic review that included 135 studies revealed that prenatal exercise is safe and beneficial for the fetus, with decreased rates of macrosomia without an increase in neonatal complications or adverse childhood outcomes.[68]  Another meta-analysis that included RCTs comparing standard care with standard care plus supervised prenatal exercise revealed that prenatal exercise reduced the risk of having a LGA infant (greater than 4000 g or greater than 90th percentile for gestational age) without increasing the risk of having a small for gestational age (SGA) infant (odds ratio, 0.69; 95% CI, 0.55-0.86). Maternal gestational weight gain and odds of cesarean delivery were also decreased in the group that had supervised prenatal exercise.[69]

Diabetes is the major risk associated with macrosomia, and this risk is for both the mother and the neonate. Once a mother gives birth to a macrosomic child, early maternal glucose screening should be considered in subsequent pregnancies.

The macrosomic infant may be at risk of developing diabetes and obesity later in life and deserves careful long-term follow-up care. This risk of developing a metabolic syndrome in adolescents was recently addressed by Boney et al in a study of appropriate for gestational age (AGA) and large for gestational age (LGA) infants of women with normal glucose tolerance and gestational diabetes mellitus (GDM).[70] Metabolic syndrome was defined as two or more of the following being present: obesity, hypertension, glucose intolerance, and dyslipidemia. Children who were LGA at birth had an increased risk of metabolic syndrome (2.19, 95% CI, 1.25–3.82, P=.01) by 11 years of age, as did children of obese women (1.81, 95% CI, 1.03–3.19, P=.04). The presence of maternal GDM was not independently significant, but the risk of metabolic syndrome was significantly different between LGA and AGA children of women with GDM by age 11 (relative risk 3.6).

Several potentially useful strategies may be helpful in prevention of macrosomia. Note the following:

• In both diabetic mothers and in those with gestational diabetes, tight control during pregnancy with the use of diet and insulin can reduce the frequency of macrosomia. The association between post-meal glucose levels and fetal macrosomia has been studied and illustrated.[71]

• Prevention of maternal obesity before pregnancy may reduce the frequency of macrosomia. However, no clinical randomized trials have validated this hypothesis. Obesity is also associated with other morbidities in pregnancy, including higher rates of preeclampsia and cesarean delivery.

• Maggard et al published data on pregnancy outcome from obese women after bariatric surgery. These results showed improvements in pregnancy outcome, including macrosomia, which was reduced by almost 50%.[72] These findings were confirmed by Karmon et al, indicating a reduction in maternal morbidity related to obesity after bariatric surgery.[73]  The rate of LGA infants was decreased in those who had bariatric surgery in a large study that included 627,693 women with a history of bariatric surgery from the Swedish birth registry. The risk of gestational diabetes was also reduced. However, the rate of small for gestational age (SGA) infants was also higher in this group. The risk of preterm birth was not different.[74]  Nonetheless, ACOG recommends counseling patients with class 2 or class 3 obesity regarding the risks and benefits of bariatric surgery prior to pregnancy.[1]

As with obesity, excessive maternal weight gain can be prevented by appropriate education of expecting mothers regarding weight gain in pregnancy. Such interventions may reduce the risk of macrosomia in specific pregnancies that may have been placed at risk because of excessive maternal weight gain. However, although excessive maternal weight or weight gain in pregnancy has been associated with fetal macrosomia, the effectiveness of reducing prepregnancy weight or curtailing excessive weight gain in pregnancy has not been tested to determine whether these measures will reduce rates of fetal macrosomia. Furthermore, one must consider the risk of insufficient gestational weight gain including increased risk of growth restriction.[75]

For patient education resources, see Pregnancy Center, as well as Pregnancy.