Macrosomia

Etiology

The etiology of fetal macrosomia can be categorized under two major classes:

Maternal Causes

1. Maternal diabetes: diabetes in pregnancy could be gestational diabetes, insulin-dependent, or drug-induced/chemical diabetes. Jordan Pederson in 1920 hypothesized that maternal hyperglycemia is associated with fetal hyperinsulinemia and fetal hyperglycemia, which ultimately leads to the overutilization of glucose by the fetus and hence the abnormal increase in growth.[3]
2. Obesity: globally, there is a current epidemic of obesity. Obesity constitutes a significant risk for diabetes mellitus in all demographics. Precisely, maternal obesity is linked to a 4 to 12 folds increase in the prospect of fetal macrosomia. The standard metabolic basis of macrosomia is believed to be increased insulin resistance and hyperinsulinemia.
3.  Multiparity: when compared to other maternal risk factors, multiparity is not a major risk factor for macrosomia. Still, it can contribute to maternal diabetes mellitus and obesity, which are more important causes. Women with parity greater than three are prone to have macrosomic babies.[4] An associated 100 to 150-gram weight gain can be observed with each pregnancy, thus increasing the risk of macrosomia in the long-term in this group of patients.
4. Previous LGA (large for gestational age) infants: women who have had previous macrocosmic babies are at five to ten folds at an increased risk of another macrosomic baby.
5. Post date pregnancy: prolonged gestation of more than 42 weeks is more likely linked with an increased chance of macrosomia due to the continuous supply of nutrients and oxygen-rich blood to the developing fetus.

 Fetal Causes 

1.  Fetal gender: macrosomia is more commonly observed in the male gender over the female gender. This can be partly attributed to the fact that male fetuses are usually about 150 grams heavier than female fetuses.
2.  Genetic and congenital disorders: a couple of congenital disorders that have been shown to have associations with macrosomia and LGA fetuses are:

•  Beckwith – Weiderman syndrome
•  Sotos syndrome
•  Fragile X syndrome
•  Weaver syndrome

Epidemiology

The U.S. vital statistics report of the year 2015 indicates that seven percent of infants had a birth weight greater than 4000 grams, while one percent had a birth weight greater than 4500 grams. Other factors, such as age, race, genetics, ethnic groups are noted to also contribute to macrosomia. Hispanic pregnant women are observed to have a higher risk of fetal macrosomia compared to other races.

Pathophysiology

An interplay of physiologic and endocrine changes occurs in pregnancy, aiming at adequate nurturing of the developing fetus. The primary underlying pathophysiology of macrosomia could be broadly divided into maternal and fetal risk factors. However, maternal hyperglycemia appears to be the most significant factor in the pathogenesis of macrosomia. In the second trimester of pregnancy, an increase in the levels of the stress hormones such as cortisone, human placenta lactogen (HPL), and prolactin leads to modest degrees of maternal insulin resistance. This, however, is countered by physiologic postprandial hyperinsulinemia. Patients with metabolic syndrome or other existing risk factors may be unable to mount an adequate hyperinsulinemic response leading to the development of hyperglycemia. Glucose transfer through the placenta occurs through facilitated diffusion that results in fetal hyperglycemia. This, in turn, brings about the hyperplasia of the beta islet cells of the fetal pancreas leading to overutilization of glucose by the fetus and hence an abnormal increase in fetal growth.

Findings from the Hyperglycemia and Adverse Pregnancy Outcomes study show a strong linear relationship between maternal glucose concentration and large for gestational age (LGA) fetuses, fetal adiposity, and fetal hyperinsulinemia.[5] A subsequent meta-analysis of the relationship between macrosomia (weight more than 4,000 g) and maternal glucose levels in women without diabetes demonstrates that a fasting blood glucose level or any abnormal value on oral glucose tolerance testing is associated with macrosomia. However, the fasting glucose level is more strongly associated with macrosomia. In women with gestational diabetes mellitus (GDM), the risk of macrosomia increases two-fold to three-fold, even with treatment. In a cohort of nearly 13,000 women, LGA newborns occurred in 29 percent of women with GDM type A1, 30 percent of women with GDM type A2, and 38 percent of women with preexisting diabetes.[2] N.B. Type A1 GDM: Patients typically have an abnormal glucose tolerance test but can keep blood glucose levels in the normal range with dietary changes alone. Type A2 GDM: Patients usually have an abnormal glucose tolerance test and abnormal glucose levels during fasting and after meals.

History and Physical

Pregnancy is a physiologic state that requires close monitoring and evaluation from the time of initial diagnosis to the expulsion of the full products of conception. Patients with high-risk pregnancies should be observed and monitored more closely.

History

 A detailed history should be taken at the initial visit as well as in subsequent prenatal follow-up visits. The obstetric provider should obtain a comprehensive history. The essential components of the medical history should include:

•  The first day of the last menstrual period (LMP)
•  Gestational age
•  Parity
•  Prepregnancy weight
•  Immunization history
•  Previous/existing medical conditions including diabetes mellitus, obesity, polyhydramnios, RH incompatibility
•  Past pregnancies, including previous macrosomic infants’ mode of delivery, associated complications, child gender

Physical Examination

 A detailed physical examination should include monitoring of patient weight at each prenatal visit that should be correlated with suggested U.S. institute of medicine guidelines (IOM) as follows:

•  A weight gain of 28-40 lbs (12-18 kg) for patients with a body mass index (BMI) of less than 18 kg/m^2 
•  A weight gain of 25-35 lbs (11.5-16 kg) for patients with body mass index (BMI) between 18.5 to 24.9 kg/m^2
•  A weight gain of 15-25 lbs (7-11.5 kg)  for patients with body mass index (BMI) between 25.0 to 29.9 kg/m^2
•  A weight gain of 11-20 lbs (5-9 kg) for patients with a body mass index (BMI) greater than 30 kg/m^2

Any aberrations of the patient’s weight should prompt a repeat abdominal examination with measurement of fundal height correlated with the patient’s gestational age and the subsequent performance of Leopold maneuver by the obstetric provider. According to Tthe (ACOG) Ameican college of obstetrics and gynecology, weighting the newborn after delivery is the most accurate way to diagnose macrosomia, and no singular modality such as Leupold maneuver, fundal height measurement, or an ultrasound scan can effectively diagnose macrosomia. A combination of these factors, on the other hand, should warrant a very high suspicion index.[2]

Evaluation

Maternal Evaluation

 Maternal hyperglycemia has been a significant cause of fetal macrosomia and should be screened for by the following:

•  One-hour 50-gram glucose challenge test at 24 to 28 weeks of gestation-values higher than 140 mg/dL is considered abnormal.
•  Confirmatory testing is with the 3-hour 100 gram glucose tolerance test.

 Gestational diabetes is confirmed when any two readings shown below are abnormal.

 Fasting glucose greater than 95 mg/dL

•  Glucose level after one hour greater than 180 mg/dL
•  Glucose level after two hours greater than 155 mg/dL
•  Glucose level after three hours greater than 140 mg/dL

 Other maternal evaluations should include:

•  Blood pressure monitoring to rule out pre-eclampsia
•  Complete blood count (CBC)
•  Urinalysis
•  BUN
•  Creatinine
•  Lipid profile
•  Liver function tests (LFT)
•  Routine fetal imagine studies with abdominal ultrasound

Fetal Evaluation 

Macrosomic fetuses are at risk of various metabolic derangements and should be monitored closely. Laboratory measurements of the following electrolytes should be taken immediately after delivery.

• Glucose levels: with the sudden withdrawal of the glucose-rich in utero environment, neonates born to diabetic mothers are prone to hypoglycemia.
• Calcium levels: hypocalcemia and tetany can occur.
• Magnesium levels: hypomagnesemia can also occur
• Bilirubin levels: this may occur as a result of inefficient enterohepatic circulation and increased hemolysis if polycythemia also exists.
• Complete blood count: it is necessary to check for polycythemia.

Clinical evaluation of the neonate’s respiratory effort after birth is also essential as meconium aspiration due to fetal distress and transient tachypnea of the newborn (TTN) are common and tend to occur two to three times more frequently in macrocosmic babies, especially if secondary to gestational diabetes.

Treatment / Management

The management of macrosomia is not clearly defined and should be multifaceted.

Medical Management

Induction of labor (IOL), which was widely recommended until recently, has been discouraged due to the lack of clear evidence on its significance in the management of macrosomia. Pregnancies complicated by fetal macrosomia in patients with pre-existing or gestational diabetes and improved glycemic control via recommended pharmacologic and other interventions will lead to a reduction in the risk of perinatal complications. Pregnancies with macrosomia and no underlying diabetes pose a different challenge to the obstetric provider and other health care providers when appropriate treatment and intervention are needed. The American College of Obstetrics and Gynecology (ACOG) recommends an elective caesarian delivery to women with pregnancies complicated by macrosomia if the estimated fetal weight is above 5000 g and no underlying glucose intolerance or 4500 g with underlying glucose intolerance.[6] Assisted vaginal delivery, such as forceps or vacuum-assisted deliveries, should be performed with significant caution in women with macrosomic pregnancies.

Diet and Exercise Program

As previously stated, the two most important determinants of fetal macrosomia are uncontrolled maternal diabetes and excessive weight gain. The combination of a modified dietary regimen with adequate insulin therapy in pregnant women with diabetes might lead to a significant reduction in the likelihood of developing macrosomia. Graduated and tolerable exercise programs may decrease the risk of unnecessary weight gain during pregnancy and, in the long-term, reduce the risk of macrosomia if the patient has no other risk factors.[2]

Differential Diagnosis

1.  Polyhydramnios
2.  Inaccurate estimation of gestational age
3.  Multiple gestations
4.  Uterine anatomic lesions such as uterine myoma, adenomyosis
5.  Pelvic masses such as ovarian masses
6.  Morbid obesity
7.  Post date pregnancies

Treatment Planning

The ACOG recommends against delivery before 39 0/7 weeks of gestation unless it is medically indicated. At this time, and until additional studies are reported, suspected macrosomia or LGA fetus is not an indication for induction of labor before 39 0/7 weeks of gestation because there is insufficient evidence that benefits of reducing shoulder dystocia risk would outweigh the harms of early delivery.[5]

Prognosis

A patient who delivers a macrosomic infant should be screened very carefully for previously undiagnosed diabetes. If such screening is negative, they should be monitored carefully in their following pregnancies. The goal of scheduled cesarean birth for suspected macrosomia is to reduce fetal morbidity or maternal morbidity, or both. Although fetal and maternal morbidity increase with birth weights more than 4,000 g, most births of macrosomic newborns are uncomplicated.[5]

Complications

Macrosomia and its complications and its risk factors can be subdivided under two broad categories:

 Maternal Complications

• Postpartum hemorrhage (PPH): postpartum hemorrhage typically refers to excessive blood loss (greater than 500 mL) with vaginal delivery or loss of 1000 mL of blood or greater with the cesarian section. PPH is the leading cause of maternal mortality worldwide as well as in industrialized nations; it is one of the top three causes of maternal mortality. One of the most significant contributors to postpartum hemorrhage is uterine atony, which arises from the over-distention of the pregnant uterus and can be further complicated by macrosomic pregnancies.
• Perineal trauma of various degrees: this arises from the prolongation of the second phase of labor and operative vaginal deliveries, both of which are associated with the delivery of macrosomic babies.
• Prolongation of the second phase of labor[7][8]

 Fetal Complications

• Shoulder dystocia: this refers to the mechanical inability to deliver the anterior fetal shoulder after delivery of the fetal head and is also associated with injury to the clavicle and brachial plexus. The occurrence of shoulder dystocia after vaginal deliveries varies with the weight of the newborn. There is a 1 percent chance of shoulder dystocia in newborns with birth weight less than 4000 g and about a 5 to 10 percent chance for the newborn with a birth weight of 4000 to 4500 grams[9]
• Fetal distress
• Congenital anomalies: most of which are associated with infants of diabetic mother includes congenital heart diseases, caudal regression syndrome, small left colon syndrome, spinal bifida, etc.
• Metabolic and electrolyte imbalance, e.g., hypocalcemia, hypomagnesemia, hyperinsulinemia, hypoglycemia
• Polycythemia
• Hyperbilirubinemia