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Fetal macrosomia

Fetal macrosomia
Literature review current through: Jan 2024.
This topic last updated: Jul 12, 2022.

INTRODUCTION — A fetus larger than 4000 to 4500 grams (or 9 to 10 pounds) is considered macrosomic. Macrosomia is associated with an increased risk of several complications, particularly maternal and/or fetal trauma during birth and neonatal hypoglycemia and respiratory problems. Long-term adverse effects in these offspring include obesity and insulin resistance.

This topic will review the definition, prevalence, significance, risk factors, etiology, and diagnosis of macrosomia. Obstetric and pediatric management are discussed separately. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies" and "Large for gestational age (LGA) newborn".)

DEFINITION — Macrosomia refers to growth beyond a specific threshold, regardless of gestational age. In high income countries, the most commonly used threshold is weight above 4500 g (9 lb 15 oz), but weight above 4000 g (8 lb 13 oz) is also commonly used [1-5]. A grading system has been suggested: grade 1 for infants 4000 to 4499 g, grade 2 for 4500 to 4999 g, and grade 3 for over 5000 g [6]. This system may be useful at term for decision making regarding operative delivery. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies" and "Assisted (operative) vaginal birth".)

Limitations and controversies — Absolute weight thresholds are not useful for identifying the preterm macrosomic fetus since they are not based upon population statistics, where normal weight is typically defined as between the 10th and 90th percentile for gestational age (assuming a normal population distribution). Using a statistical approach, any fetus/infant weighing >90th percentile for gestational age is considered large for gestational age. The following table shows the 5th, 10th, 50th, 90th, and 95th percentile birth weights for gestational ages 24 to 42 weeks in the United States (table 1). Some researchers prefer to use the 95th percentile as the threshold for macrosomia as it corresponds to 1.90 standard deviations (SD) above the mean and defines 90 percent of the population as normal weight. Others use the 97.75th percentile, which corresponds to 1.96 SD above the mean and defines 95 percent of the population as normal weight.

Generating local tables, when possible, should be considered if the population involved is constitutionally more uniform but different from published tables. The use of contemporary country-specific percentile tables is advisable when interpreting estimated fetal and newborn weight, particularly in low and middle income countries. Newborn weights have increased over the past few decades, thus making older tables obsolete [7,8]. In addition, some older tables (eg, Lubchenco) excluded, by choice, infants of African American, Asian, and Native American ancestry [9]. Racial and ethnic differences influence birth weight and also should be considered when interpreting estimated fetal and newborn weight [10-12]. Most relatively recent research has shown that White mothers tend to have the largest fetuses, followed by Hispanic mothers, then Black mothers. This may involve both biologic and social determinants of health [13].

The World Health Organization (WHO), the National Institute of Child Health and Diseases (NICHD), and the International Fetal and Newborn Growth Consortium for the 21st Century have published tables that should be adoptable virtually worldwide [14-16].

PREVALENCE — The birth prevalence of infants ≥4000 g is approximately 9 percent worldwide and approximately 0.1 percent for ≥5000 g, with wide variations among countries [17].

In the United States, approximately 7 percent of live born infants weigh ≥4000 g and 1 percent weigh >4500 g [18]. The prevalence of birth weight ≥4000 g in low income countries is typically 1 to 5 percent but ranges from 0.5 to 14.9 percent [19].

SIGNIFICANCE — The risk of adverse outcome increases along a continuum based on the degree of macrosomia between 4000 and 4999 g [5,20]. At ≥5000 g, the risk of stillbirth/neonatal death increases. For this reason, the presence of macrosomia is an important factor to consider in decision making during birth (eg, whether to use forceps or vacuum versus whether to proceed to cesarean birth). (See "Assisted (operative) vaginal birth" and "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies".)

Specific risks include [20-28]:

Maternal:

Protracted or arrested labor

Assisted vaginal birth

Cesarean birth

Genital tract lacerations (vaginal, anal sphincter, rectum)

Postpartum hemorrhage

Uterine rupture

Macrosomia can be a greater obstetric hazard for patients in low-income countries where undernutrition during childhood can inhibit growth of the pelvis to its full potential, pregnancy before the pelvis is fully developed is common, and facilities for cesarean birth are not consistently available [29].

Fetal [30]:

Shoulder dystocia leading to birth trauma (brachial plexus injury, fracture) or asphyxia. This is the most common serious intrapartum concern, and is discussed in detail separately [30]. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies" and "Shoulder dystocia: Intrapartum diagnosis, management, and outcome".)

Stillbirth. Fetuses ≥5000 grams appear to be at particularly high risk.

Neonatal (see "Large for gestational age (LGA) newborn", section on 'Complications'):

Hypoglycemia

Respiratory problems

Polycythemia

Minor congenital anomalies

Increased frequency of admission and prolonged admission (greater than three days) to a neonatal intensive care unit

Childhood and beyond (see "Large for gestational age (LGA) newborn", section on 'Potential long-term effects'):

Obesity

Impaired glucose tolerance

Metabolic syndrome

Cardiac remodeling (increase in aorta intima-media thickness and left ventricular mass)

A meta-analysis of 17 studies reporting data on maternal and/or neonatal complications in pregnancies complicated by macrosomia calculated the risk for and pooled frequencies of several of these outcomes, as shown in the table (table 2) [31].

It should be noted that the consequences of macrosomia also vary depending on its etiology [32]. (See 'Syndromes associated with macrosomia' below.)

PATHOGENESIS — A major pathway to macrosomia is thought to be intermittent maternal and, in turn, fetal hyperglycemia. Fetal release of insulin, insulin-like growth factors, and growth hormone leads to increased fetal fat deposition and, in turn, enhanced fetal size [33]. Abnormalities in maternal lipids levels also may be an important factor [34].

Although it is clear that a relationship exists between maternal metabolic conditions, such as diabetes (see 'Risk factors' below), and large for gestational age infants, macronutrient metabolism cannot completely explain the phenomenon since lifestyle modification (eg, changing the macronutrient composition of the maternal diet) does not reduce the incidence of either [35]. Other maternal and placental factors can affect the supply of nutrients to the fetus and can contribute to fetal overgrowth [36]. These factors include decreased physical activity, increased uteroplacental blood flow, increased placental size, increased transplacental concentration gradient, and increased placental transfer capabilities [37,38]. Such factors may be particularly important in pregnant patients without diabetes [39].

RISK FACTORS — Risk factors for macrosomia are listed in the table (table 3) [40]. In a correctly dated pregnancy, macrosomia is usually related to constitutional factors, maternal diabetes (gestational or pregestational), and/or maternal obesity/excessive gestational weight gain. With the increasing prevalence of pregnant patients who are overweight or obese (60 percent in one large study [41]), maternal obesity and excessive gestational weight gain now appear to have a greater impact on the prevalence of macrosomia than maternal diabetes (prevalence 19 percent in the same study [41]) [41-45].

In a retrospective study of the relative contribution of prepregnancy weight and gestational diabetes to the prevalence of large for gestational age (LGA) infants, the prevalence of LGA among patients without gestational diabetes who had a normal versus obese body mass index was 7.7 versus 12.7 percent [41]. For those with gestational diabetes, the prevalence of LGA was 13.6 and 22.3 percent, respectively. These differences were statistically significant.

SYNDROMES ASSOCIATED WITH MACROSOMIA — If constitutional factors, maternal diabetes, and/or maternal obesity/excessive gestational weight gain have been excluded or seem unlikely, then the possibility of one of the rare syndromes associated with accelerated fetal growth should be considered, particularly in the presence of one or more fetal structural anomalies [46].

A large number of genetic conditions has been associated with overgrowth [47]. Therefore, consultation with a geneticist can be useful to help with differential diagnosis, prenatal diagnostic evaluation (eg, selection and interpretation of molecular testing), and patient counseling. Some of the major syndromes associated with fetal overgrowth include:

Pallister-Killian (see "Congenital cytogenetic abnormalities", section on '47,+i(12p)')

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

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

Perlman (see "Presentation, diagnosis, and staging of Wilms tumor", section on 'Other congenital anomalies')

Simpson-Golabi-Behmel (see "Renal hypodysplasia", section on 'Genetic disorders')

Costello [48]

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

Macrocephaly-cutis marmorata telangiectasia congenita (M-CMTC) (see "Vascular lesions in the newborn", section on 'Cutis marmorata telangiectatica congenita')

DIAGNOSIS — Two-dimensional ultrasound examination is the standard modality used for diagnosis of fetal macrosomia and large for gestational age. In the general obstetric population, Hadlock's formula (which incorporates head circumference, abdominal circumference, and femur length measurements) is more informative than other methods. (See 'Estimating fetal weight' below.)

Macrosomia is best identified by an ultrasound scan at the gestational age when a decision regarding the clinical management has to be made. Performing a single estimate at 29 to 34 weeks of gestation has very poor predictive value for birth weight at term; estimated fetal weight at this time can significantly underestimate birth weight, probably because of accelerated fetal growth in the later part of the third trimester [49,50]. As discussed below, the estimation of fetal weight is not precise at any gestational age, and accurately identifying clinically important deviations of fetal growth, whether excessively large or excessively small, is particularly difficult. (See 'Diagnostic performance' below.)

SONOGRAPHY

Diagnostic performance — Fetal weight is calculated by integrating biometric measurements into a formula, given that weight cannot be measured directly. Since the fetus is an irregular, three-dimensional (3D) structure of varying density, the ability of any formula to predict fetal density or weight is limited. Approximately three dozen formulas for sonographic estimation of fetal weight have been proposed, attesting to the inadequacy of all methods (table 4) [51,52]. These formulas use measurements of fetal body parts with regression analysis of the dimension of one or multiple fetal biometric parameters against gestational age and actual birth weight [53]. Available formulas perform better for fetuses that are an appropriate size for gestational age than for macrosomic ones [17,54-60], and no formula is clearly superior [51,52]. Unfortunately, small measurement errors can cause serious misdiagnosis regarding who is a large for gestational age (LGA) fetus (and a small for gestational age fetus) [61]. (See 'Estimating fetal weight' below.)

In a meta-analysis of studies of universal third-trimester ultrasound screening for macrosomia (41 studies, >100,000 pregnancies), estimated fetal weight >4000 g (or 90th centile for the gestational age) and abdominal circumference >36 cm (or 90th centile) had summary sensitivities of 53 and 58 percent, respectively, for predicting macrosomia at birth (birth weight above 4000 g or 90th centile); positive likelihood ratios of 8.74 (95% CI 6.84-11.17) and 7.56 (95% CI 5.85-9.77), respectively; and summary specificities of 94 and 92 percent, respectively [62]. Sensitivity for diagnosis of birth weight >4500 g was higher (68 percent) and specificity lower (90 percent). Importantly, an estimated fetal weight >4000 g (or 90th centile) had only 22 percent sensitivity and 90 percent specificity for subsequent shoulder dystocia, with a positive likelihood ratio of 2.12 (95% CI 1.34-3.35). There was significant heterogeneity, likely related to differences in study design, characteristics of the included populations, and formulas used.

There are minimal data on the ability of ultrasound to identify fetuses >5000 g [17].

Comparison of diagnostic methods is complicated because investigators have used different methodologies to obtain and analyze their data (eg, mean error, mean percent error, standard deviation, and proportion of estimated fetal weight within 10 percent of actual birth weight). For diagnosing macrosomia, the accuracy of the testing method depends upon how well the test distinguishes macrosomic fetuses from those with a weight within the normal range for gestational age. Thus, a receiver-operator characteristic curve is the ideal way to compare methods of fetal weight estimation, but it has not been used consistently in diagnostic studies. (See "Evaluating diagnostic tests", section on 'Receiver operating characteristic curves'.)

Another consideration is that sonographic measurement does not permit accurate differentiation between fetuses who are large because of intrinsic fetal (genetic) versus extrinsic (environmental) factors [63], similar to the scenario with the "constitutionally small" versus "growth-restricted" fetus.

Adding to the confusion, the American College of Obstetricians and Gynecologists concluded that ultrasound is better at ruling out macrosomia than ruling it in, since ultrasound tends to overestimate fetal weight [5], while others have concluded that a positive ultrasound result is more accurate for ruling in macrosomia than a negative result for ruling it out [64].

Estimating fetal weight — Ultrasound examination typically involves measurement of multiple biometric parameters that are incorporated into a formula for calculating estimated fetal weight (EFW). Most commonly, a combination of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) is used. The most popular formulas are Hadlock's [65,66] and Warsof's [67] with Shepard's modification [68]. These formulas are included in most ultrasound equipment packages:

Hadlock formulas:

Log10 BW = 1.3598 + 0.051 (AC) + 0.1844 (FL) – 0.0037 (AC X FL), or

Log10 BW = 1.4787 + 0.001837 (BPD)2 + 0.0458 (AC) + 0.158 (FL) – 0.003343 (AC X FL)

Shepard formula:

Log10 BW = -1.7492 + 0.166 (BPD) + 0.046 (AC) -(2.646 [AC X BPD] /100)

Comparisons of these formulas concluded that the formula using BPD, FL, and AC (second Hadlock's formula) resulted in the best estimate of fetal weight, while the formula using only BPD and AC (Shepard's formula) had the least accurate estimate [69,70].

Adjusting EFW for maternal weight, maternal height, and presence of diabetes yields better sensitivity and specificity than traditional unadjusted formulas, particularly in macrosomic fetuses [71,72]. Some investigators have combined ultrasonography with pregnancy-specific data (eg, parity, ethnicity, body mass index, maternal height, weight, and weight gain) to create nomograms for detecting fetal macrosomia, but these methods have not performed well consistently [73-75].

Abdominal circumference — The AC is the most important parameter for assessment of risk of macrosomia [76,77]: An AC of 35 to 38 cm alone is predictive of macrosomia [64]. AC is measured on a defined plane incorporating the liver since growth abnormalities are often reflected by changes in liver size [53]. The AC measurement is equally accurate whether determined in two dimensions (image 1) or by an elliptical estimate (image 2). Manually tracing the abdominal circumference is less accurate and should be avoided [78]. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Abdominal circumference'.)

An AC >90th percentile or two to three weeks ahead of gestational age may be an early marker for development of macrosomia despite normal EFW. Assessment of an enlarged AC on ultrasound should prompt fetal re-evaluation in three to four weeks, especially in patients with diabetes. Predictions for absence or presence of macrosomia can generally be made after two successive scans that show an increased AC. If the AC remains <90th percentile, then performing more ultrasound examinations does not increase predictive value [79]. The rate of growth of the AC over time, starting around 21 to 22 weeks, has also been shown to be helpful in predicting macrosomia [80].

Adjunctive techniques

Serial measurements – Serial measurements can be taken over time to create an individual growth curve specific to an individual fetus. This makes it possible to extrapolate from multiple points to predict birth weight, theoretically enhancing diagnostic accuracy. However, the superiority and cost-effectiveness of this approach have not been proven [81-83].

Soft tissue measurements – The majority of sonographic EFW formulas do not take body composition into account. Because body composition can vary greatly, even in the fetus, significant variation in birth weight can occur among fetuses with similar biometric parameters.

Ultrasound measurement of subcutaneous fat may improve assessment of normal versus accelerated growth [84,85]. Body fat accounts for 14 percent of the birth weight in neonates, but 46 percent of birth weight variance [84], and is subject to major changes when conditions associated with accelerated growth are present. As an example, patients with poorly controlled diabetes are at increased risk of having a macrosomic infant with a large volume of subcutaneous fat [86]. (See 'Patients with diabetes' below.)

Subcutaneous fat has been measured at the midhumerus [87,88], shoulder [89], abdominal wall [90-92], thigh [91-95], and peribuccal area [96-100]. Prenatal sonographic evaluation of adipose tissue appears to have good correlation with postnatal skinfold measurements, although data are limited [98,101]. An analysis of three studies with a total of 287 fetuses reported a high degree of accuracy in predicting macrosomia, based on measurements of the abdominal or thigh fetal soft tissue, with a pooled detection rate of 80 percent [102].

However, a study comparing measurement of various soft tissues with traditional estimated fetal weight obtained from HC, AC, and FL found that no subcutaneous tissue measurement performed better than estimated fetal weight for detection of macrosomia [98]. Combinations of soft tissue measurements or other parameters (umbilical cord cross section, amniotic fluid volume) with estimated fetal weight may be more useful for predicting macrosomia than any method alone [99,100,103,104].

Fetal volume measurement – The sonographic measurements described above estimate weight using two-dimensional (2D) principles on a 3D subject. Improvements in imaging technologies have helped alleviate this problem, leading to better weight estimation.

Volumetric measurement by 2D ultrasound can be calculated using the following formula [51]:

EFW = (0.23718 X AC2 X FL) + (0.03312 X HC3)

When compared with the traditional calculation of EFW using Shepard or Hadlock formulas described above, this method had fewer systematic and absolute errors (mean percent error was 6.2).

Three-dimensional ultrasound examination can improve sonographic estimates of fetal weight by providing more accurate assessment of fetal volume. In addition, better qualitative analysis of fetal soft tissue may be possible with 3D ultrasound, allowing for improved estimation of actual birth weight [105]. Studies using 3D ultrasound for birth weight prediction have validated the technique, with most predictions within 10 percent of birth weight [106-109]. However, 2D ultrasound remains the main method of sonographic weight estimation because 3D ultrasound is not always practical and, in a comparative study, was not superior to 2D ultrasound [110].

The best approach for predicting macrosomia may be to combine 3D volumetric measurements (volume of upper arms, thigh, and abdomen) with 2D measurements [111,112]:

Formula = -1478.557 + 7.242 X thigh vol + 13.309 X upper arm vol + 852.998 X log10 AC vol + 0.526 X BPD3

With combined measurements, the mean absolute percentage of error was 6.5 percent versus 10 to 15 percent with 2D ultrasound alone.

Another study showed improved sensitivity (87.5 percent) and specificity (91.7 percent) using 3D limb volume ultrasound and abdominal circumference [113]. The formula the authors utilized was:

EFW = -481.965 + 12.194 X thigh vol + 15.358 upper arm vol + 67.998 AC

Neural network and artificial intelligence (AI) – A neural network is a computerized model of a biologic neural system that can be "trained" by establishing connections between basic data (input: BPD, occipitofrontal diameter, AC, FL, gestational age, fetal position) and results (output: EFW) and constantly rectifying the relations. It is still investigational but appears to be promising in this and other "automated" calculations.

Two studies have been performed analyzing the value of artificial neural networks in the estimation of fetal weight [114,115].

In one study, assuming a 10 percent error in macrosomia, the neural network method was applied to 100 presumed macrosomic fetuses and yielded an error of 4.7 percent, significantly better than conventional methods [114].

In the other analysis, 991 singleton fetuses within three days of delivery were used to train the system, and then 362 additional fetuses were examined to validate the method [115]. The absolute percent error was 6.15 percent and the absolute error was 179.91 g, both better than traditional methods [115]. However, the method was less accurate at <2500 g or >4000 g and therefore would not offer an advantage in diagnosis of macrosomia.

AI can be defined as "a system's ability to correctly interpret external data, to learn from such data, and to use those learnings to achieve specific goals and tasks through flexible adaptation" [116]. This definition would seem to fit perfectly in an objective extraction of biometric measurements by a process called segmentation and calculation of an EFW [117]. Although this has been attempted [118], specifically in cases of diabetes [119], it has not been proven to offer better fetal assessment.

HC/AC – The HC/AC ratio is of no proven value in predicting macrosomia since the constitutionally large fetus maintains a normal HC/AC ratio. However, in one study, a difference in HC/AC ≥50 mm predicted shoulder dystocia regardless of EFW, with an odds ratio of 7.3 (95% CI 1.6-33.3) [120].

Doppler – Doppler velocimetry of the umbilical artery in fetuses suspected of being LGA does not have prognostic value, in contrast to fetuses with growth restriction. In one study of 964 pregnancies (241 complicated by fetal macrosomia), Doppler velocimetry of the umbilical vein at the 11+0 to 13+6 weeks ultrasound examination ("NT scan") was independently associated with and predictive of fetal macrosomia and birth weight >4000 g when combined with maternal and biochemical factors [121].

NONSONOGRAPHIC METHODS

Maternal estimation — In several studies, a mother's estimate of their newborn's birth weight has been reported to be as, or more, accurate than clinical or sonographic estimates (table 4) [122-127]. Most of these studies have been in parous patients, in whom an increased risk of repeat macrosomic birth in subsequent pregnancies has been well documented [6,128]. Maternal estimation has been used primarily to predict macrosomia during labor in patients without a recent ultrasound examination.

Physical examination — Fetal weight can be estimated clinically by simple palpation of the fetus through the maternal abdomen (eg, Leopold maneuvers) and/or by measurement of fundal height (the distance between the superior aspect of the symphysis pubis and the upper border of the uterine fundus). These assessments are performed with the patient supine and bladder empty.

Major factors that affect estimation of fetal weight by palpation include maternal habitus [129], fetal position, amniotic fluid volume, and the examiner's experience [56]. For fundal height measurement, the fundal endpoint is more a matter of judgment than a well-defined point. Some clinicians prefer starting the measurement at the fundus, which tends to prevent "adjustments" to selection of a specific endpoint, which may occur when measuring from the symphysis.

Although inexpensive, convenient, and easy to learn, prospective studies of symphysis-fundal measurements combined with Leopold maneuvers showed sensitivities of only 10 to 43 percent and positive predictive values of 28 to 53 percent for detecting macrosomia (table 4) [130]. A 2020 meta-analysis on the value of symphysis-pubis measurement to identify large for gestational age (LGA; >90th percentile) and macrosomia (>4000 g) at birth yielded a low sensitivity (76 and 30 percent, respectively), specificity (67 and 80 percent, respectively), and diagnostic odds ratio (6 and 4, respectively) [131]. A review of a variety of clinical methodologies used to diagnose macrosomia reported that these methods detected 34 to 68 percent of infants ≥4000 g, and the posttest probability of macrosomia after a positive test was similar to positive predictive values reported by others [17]. As would be expected, clinical diagnosis was more accurate (posttest probability of macrosomia after a positive test: 61 to 86 percent) in populations with a higher prevalence of macrosomia, such as postterm and diabetic pregnancies. Thus, the capacity for antepartum diagnosis of fetal macrosomia in the general obstetric population by clinical means is limited but is somewhat better in patients at higher risk.

Magnetic resonance imaging — In theory, magnetic resonance imaging (MRI) should be a superior technique for evaluation of macrosomia because it evaluates adipose tissue better than ultrasound [132]. A few studies have evaluated MRI for EFW and found that this technique, which is based on measurement of total fetal body volume, performs better than two-dimensional (2D) ultrasound.

A meta-analysis of studies comparing MRI versus two-dimensional ultrasound for predicting birth weight >4000 g or >90th percentile found that MRI estimated fetal weight (EFW) had higher sensitivity that 2D ultrasound EFW (93 versus 56 percent), but MRI EFW was not significantly more sensitive than 2D ultrasound abdominal circumference >35 cm (93 versus 80 percent) [133].

In a prospective study comparing EFW based on 2D ultrasound and MRI at 360/7 to 366/7 weeks with actual birthweights in over 2000 routine pregnancies, for a fixed false-positive rate of 5 percent, MRI detected 80 percent of infants with birth weight ≥95th percentile (positive and negative predictive value 42 and 99 percent, respectively), whereas ultrasound detected 59.1 percent (positive and negative predictive value 35.4 and 98 percent, respectively) [134].

Three-dimensional (3D) ultrasound may perform better than 2D ultrasound because it incorporates thigh volume in the EFW calculation, but 3D ultrasound has not been compared with MRI for this indication.

Barriers to routine clinical use of MRI for EFW at this time include cost, availability, and discomfort for some patients. Also, an improvement in pregnancy outcome needs to be established before adopting a new approach to fetal weight assessment.

Novel biomarkers — MicroRNAs (miRNAs) have been shown to be involved in placental growth and development, and thus may affect fetal growth and size. In one study, the expression levels of several miRNAs were significantly elevated in placentas of macrosomic newborns [135]. Other biomarkers with promise for assisting in the prediction of macrosomia include maternal glycemic markers (eg, 1,5-anhydroglucitol) and hormones thought to be involved in placental nutrient transfer (eg, adiponectin, insulin-like growth factor-1) [136]. However, the markers for macrosomia in particular are more predictive of gestational diabetes mellitus rather than macrosomia alone [137]. Currently, measurement of these markers has no clinical role but warrants further investigation.

SCREENING — There are no guidelines that recommend screening for macrosomia in the general obstetric population. It is has not been proven to be beneficial and was not cost-effective in a study of nulliparous patients [138]. However, selective screening in the third trimester is often performed in the following clinical scenarios since the information affects delivery planning (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies", section on 'Planning birth in high-risk pregnancies'.):

Maternal diabetes (particularly if glucose levels are poorly controlled)

Previous macrosomic newborn (particularly if labor and delivery were complicated)

Previous shoulder dystocia.

To be effective, a macrosomia screening program should have a reliable method for predicting macrosomia (ultrasound, arguably, is such a test [139,140]) and a means of improving outcome when macrosomia is identified (eg, an intervention that safely reduces the rate of growth acceleration, reliable prediction of risk of neonatal injury from shoulder dystocia at vaginal birth so a cesarean delivery can be scheduled). These prerequisites for screening cannot be met. Moreover, a (false) positive diagnosis of macrosomia based on ultrasound will likely be followed by an unnecessary increase in inductions of labor or cesarean delivery with the potential for iatrogenic harm [141].

In a meta-analysis of 41 studies involving over 112,000 patients (29 retrospective cohort studies, 11 prospective cohort studies, one randomized trial), both EFW >4000 g (or 90th centile for the gestational age) and AC >36 cm (or 90th centile for the gestational age) had >50 percent sensitivity for predicting macrosomia (birthweight >4000 g or 90th centile) at birth [62]. However, EFW >4000 g (or 90th centile) only had 22 percent sensitivity for predicting shoulder dystocia with a positive likelihood ratio of 2.12 (95% CI 1.34-3.35); there were insufficient data to analyze other markers of neonatal morbidity.

DIAGNOSIS IN SPECIAL SITUATIONS — The methods for detection of macrosomia described above are standardized for singleton, cephalic presenting, nondiabetic pregnancies. When special situations prevail, limitations in these formulas should be recognized [130]. Overestimations and underestimations are more common in estimating weight in infants of diabetic mothers, multiple gestations, and breech fetuses.

Patients with diabetes — The growth pattern of fetuses of patients with diabetes, especially when glycemic control has been poor, is different from that in fetuses of those without diabetes [63,142,143]. Macrosomic infants of patients with diabetes have larger shoulders and greater amounts of body fat, decreased head-to-shoulder ratio, and increased skinfolds in the upper extremities [144,145]. Several studies have used this information in an attempt to predict the risk of shoulder dystocia in pregnancies complicated by diabetes, but no method has proven to be reliable [146-150].

Since infants of patients with diabetes are at greatest relative risk of shoulder dystocia, this population has been targeted for prenatal diagnosis of macrosomia. An analysis of 22 estimated fetal weight formulas in patients with diabetes showed that, although some appear more accurate than others in estimating fetal weight, none perform well in fetuses who had macrosomia at birth [151].

Ultrasound prediction of estimated fetal weight in fetuses of diabetic mothers tends to overestimate fetal weight since the formula is very sensitive to measurement of abdominal circumference (AC), and AC in particular is increased in these fetuses [152-157]. As an example, approximately 50 percent of infants of diabetic mothers delivered by scheduled cesarean for sonographic estimated fetal weight ≥4250 g had a birth weight <4000 g in one study [158]. Customized formulas for use in patients with diabetes have generally not been proven to be more accurate.

The AC, measured in the second and, particularly, the third trimester, is an independent predictor of birthweight and macrosomia/large for gestational age (LGA) irrespective of the severity of maternal glucose intolerance [159]. A study comparing three estimated fetal weight formulas using multiple parameters versus prediction of birth weight by formulas using AC alone concluded that measurement of AC was quicker and similarly accurate; all of the formulas were associated with an error of ±20 to 25 percent [160]. Another study reported that AC >70th percentile is predictive of poor glycemic control and increased risk of macrosomia [161]. Based on these findings, the American Diabetes Association recommended the use of AC >75th percentile as a measure of glycemic control and risk for macrosomia in patients with diabetes, as discussed at the Fifth International Workshop-Conference on Gestational Diabetes [162]. They suggested less intensified management (eg, less frequent self-blood glucose monitoring, medical nutritional therapy alone [without insulin]) was reasonable in pregnancies with normal fetal growth (defined as fetal AC <75th percentile for gestational age).

Breech presentation — The mean biparietal diameter measurement in breech fetuses measured at 33, 35, and 38 weeks is 2 to 3 mm less than that of cephalic fetuses of the same gestational age. This disparity has been attributed to the dolichocephalic (long and narrow) head shape of the breech fetus. Nevertheless, ultrasound weight estimations of breech fetuses are reasonably consistent with actual birth weight since AC and femur length have greater impact in the formula; therefore, the usual formulas may be used. Furthermore, the risk for macrosomia is lower in the breech fetus; infants delivered from breech presentation are 4.9 percent lighter than cephalic infants, suggesting a true deviation in growth [163].

Multiple gestation — Singleton estimated fetal weight formulas used with multiple gestations tend to overestimate estimated fetal weight, particularly at weights less than 2500 g [164], possibly due to distortion of the AC from overcrowding [53]. This is not clinically important for macrosomia screening since macrosomia is rare in multiple gestations.

MANAGEMENT — Obstetric and pediatric management are discussed separately. (See "Shoulder dystocia: Risk factors and planning birth of high-risk pregnancies" and "Assisted (operative) vaginal birth" and "Large for gestational age (LGA) newborn".)

PREVENTION

Patients with diabetes mellitus – In patients with gestational diabetes mellitus (GDM), the combination of nutritional therapy, self-blood glucose monitoring, administration of insulin when target blood glucose concentrations are not met with diet alone) resulted in a reduction in macrosomia in a meta-analysis of randomized trials [165,166].

In patients with pregestational diabetes, studies have noted that mean blood glucose levels need to be less than approximately 100 mg/dL (5.6 mmol/L) to achieve a macrosomia rate comparable to general obstetric population without diabetes [167,168]. (See "Pregestational (preexisting) diabetes mellitus: Antenatal glycemic control" and "Gestational diabetes mellitus: Glucose management and maternal prognosis".)

Patients with obesity – Prepregnancy weight loss in patients with obesity can reduce the risk of delivering a macrosomic infant. Prepregnancy intervention (eg, bariatric surgery for severe obesity) is important because substantial weight loss is probably not safe during pregnancy and fetal growth acceleration is sometimes noted as early as the first or early to mid-second trimester [169]. (See "Fertility and pregnancy after bariatric surgery", section on 'Birth weight' and "Obesity in pregnancy: Complications and maternal management".)

Other patient groups

Normal BMI – Patients with a normal body mass index (BMI) can reduce the risk of macrosomia by avoiding excessive gestational weight gain by diet and exercise. (See "Gestational weight gain", section on 'Relationship between gestational weight gain and pregnancy outcome' and "Exercise during pregnancy and the postpartum period".)

Hyperglycemia without meeting criteria for diabetes – Some authors have suggested medical nutritional therapy for patients who do not meet standard glucose tolerance test (GTT) criteria for gestational diabetes but have fasting blood glucose concentrations >90 mg/dL [5 mmol/L] [170], an abnormal 50 gram one hour GTT [171,172], or one abnormal value on the 100 g three-hour GTT. The rationale for this approach is that there appears to be a continuous relationship between glucose concentration and fetal growth/adverse fetal outcome, even in pregnant people who did not meet formal criteria for diagnosis of diabetes [170-176]. In a meta-analysis of four randomized trials (543 participants) of pregnant people with one or more elevated glucose levels on a three-hour 100 g GTT who did not meet standard criteria for GDM, glucose monitoring and medical nutritional therapy (with or without insulin) resulted in a reduction in delivery of large for gestational age newborns compared with usual care [177].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Labor" and "Society guideline links: Shoulder dystocia and macrosomia".)

SUMMARY AND RECOMMENDATIONS

Definition – An estimated weight of 4500 g (9 lb 15 oz) is a widely used threshold for diagnosis of macrosomia, but formulae for deriving this number have a significant error rate. Weight above 4000 g (8 lb 13 oz) is also commonly used. Using a statistical approach, any fetus/infant weighing >90th percentile for gestational age can be considered large for gestational age (LGA). (See 'Definition' above.)

Clinical significance – The risk of adverse outcome increases along a continuum based on the degree of macrosomia (eg, 4000 to 4499 g, 4500 to 4999 g, ≥5000 g). Fetal macrosomia is an important risk factor for operative delivery, as well as poor birth outcomes, particularly maternal and infant traumatic injury. For this reason, it is an important factor in decision-making during delivery. (See 'Significance' above.)

Risk factors – Macrosomia may be related to constitutional factors, environmental factors, or genetic variants, as shown in the table (table 3). (See 'Risk factors' above and 'Syndromes associated with macrosomia' above.)

Diagnosis – Two-dimensional ultrasound examination is the standard modality used for diagnosis of macrosomia and LGA. Hadlock's formula (encompassing head circumference, abdominal circumference, and femur length measurements) has the highest predictive value in the nondiabetic population. An abdominal circumference >35 cm is also predictive of macrosomia, but no test is highly sensitive and specific (table 4). (See 'Sonography' above.)

Prevention – Some approaches that individuals can use to reduce their risk of having a macrosomic infant are (see 'Prevention' above):

Patients with diabetes mellitus should manage blood glucoses to avoid hyperglycemia

Patients with obesity should try to lose weight before pregnancy and avoid excessive gestational weight gain

Patients of normal weight body mass index should avoid excessive gestational weight gain

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Topic 4443 Version 41.0

References

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