Prediction and prevention of the macrosomic fetus

Abstract

Fetal macrosomia is associated with significant maternal and neonatal morbidity. In the long term, infants who are large for gestational age are more likely than other infants to be obese in childhood, adolescence and early adulthood, and are inherently at higher risk of cardiovascular and metabolic complications in adulthood. With over one billion adults in the world now overweight and more than 600 million clinically obese, preventing the vicious cycle effect of fetal macrosomia and childhood obesity is an increasingly pertinent issue.

Fetal growth is determined by a complex interplay of various genetic and environmental influences. Consequently the prediction of pregnancies at risk of pathological overgrowth is difficult. Many risk factors for fetal macrosomia, such as maternal obesity and advanced maternal age, are also conversely associated with intrauterine growth restriction. Sonographic detection of fetal macrosomia is notoriously fraught with difficulties, with dozens of formulas for estimated fetal weight proposed but few with sufficient sensitivity to alter clinical practice. This calls into question policies of elective delivery based on projected estimated fetal weight cut-offs alone. More recently the identification of markers of fetal adiposity and maternal serum biomarkers are being investigated to improve the antenatal detection of the large for gestational age fetus.

Prevention of fetal macrosomia is entirely dependent upon correct identification of those at risk. Maternal weight, gestational weight gain and glycaemic control are the risk factors for fetal macrosomia that are most amenable to intervention, and have potential maternal health benefits beyond pregnancy and childbirth. The ideal method of optimising maternal weight and glucose homeostasis is yet to be elucidated, though a number of promising advances are recently being reported.

In this review we outline the contemporary evidence for the prediction and prevention of fetal macrosomia, which is indeed a contemporary dilemma.

Introduction

The large for gestational age fetus is predisposed to a variety of adverse obstetric and neonatal outcomes, largely accounted for by the excess risks associated with labour and delivery, including shoulder dystocia and brachial plexus injury [1], [2]. Delivery of a large infant also significantly increases the risk of birth complications for the mother [3], [4]. In the neonatal period, macrosomic infants are predisposed to electrolyte and metabolic disturbances, such as hypoglycaemia, hyperbilirubinaemia and hypomagnesaemia [5]. In the long term, infants that are at the highest end of the distribution for weight or body mass index (BMI) are more likely than other infants to be obese in childhood, adolescence, and early adulthood [6], and are at risk of cardiovascular and metabolic complications later in life [7], [8].

Fetal macrosomia is varyingly defined as either an absolute birthweight greater than 4000 g, 4500 g or 5000 g, or as a customised birth weight centile of greater than the 90th, 95th or 97th percentile for the infant's gestational age. None of these terms discriminates the fetus of abnormal body composition from normal. Customised centiles based on individual fetal growth potential are recognised to increase the likelihood of differentiating between physiological and pathological growth [9]. Birth trauma rates for the macrosomic fetus appear to be more closely related to absolute birthweight rather than birth weight centile, though there is evidence for a strong correlation between fetal macrosomia with a short maternal stature and the likelihood of birth injury [10]. The metabolic consequences of macrosomia, however, are more likely to be secondary to pathological overgrowth and abnormal fat deposition in utero [11] than to either absolute birthweight or birthweight centile.

With over one billion adults in the world now overweight and more than 600 million clinically obese [12], methods to accurately predict and ultimately prevent fetal macrosomia are now essential to reduce this potential global health burden.