BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.
OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable.
METHODS: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks\' using linear mixed models for repeated measures with cubic splines.
RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver.
CONCLUSIONS: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

There\'s a paucity of robust normal fractional limb and organ volume standards from a large and diverse ethnic population. The Fetal 3D Study was designed to develop research and clinical applications for fetal soft tissue and organ volume assessment. The NICHD Fetal Growth Studies (2009-2013) collected 2D and 3D fetal volumes. In the Fetal 3D Study (2015-2019), sonographers performed longitudinal 2D and 3D measurements for specific fetal anatomical structures in research ultrasounds of singletons and dichorionic twins. The primary aim was to establish standards for fetal body composition and organ volumes, overall and by maternal race/ethnicity, and determine whether these standards vary for twins versus singletons. We describe the study design, methods, and details about reviewer training. Basic characteristics of this cohort, with their corresponding distributions of fetal 3D measurements by anatomical structure, are summarized. This investigation is responsive to critical data gaps in understanding serial changes in fetal subcutaneous fat, lean body mass, and organ volume in association with pregnancy complications. In the future, this cohort can answer critical questions regarding the potential influence of maternal characteristics, lifestyle factors, nutrition, and biomarker and chemical data on longitudinal measures of fetal subcutaneous fat, lean body mass, and organ volumes.

UNASSIGNED: Imprinted genes are important for the offspring development. To assess the relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression and offspring growth and body composition.
UNASSIGNED: Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the \"Araraquara Cohort Study\" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of H19DMR in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and H19 and IGF2 expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters.
UNASSIGNED: H19DMR was less methylated in maternal blood of the overweight/obese group. There were associations of H19DMR methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); H19DMR methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; H19DMR methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. H19 expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. IGF2 expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD.
UNASSIGNED: To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition.

Newborns exhibit substantial variation in fat mass accretion over gestation. These individual differences in newborn adiposity extend into infancy and childhood and relate to subsequent risk of obesity and metabolic dysregulation. Maternal glucose homeostasis in pregnancy has been proposed as an underlying mechanism; however, the timing in gestation when maternal glucose regulation influences the progression of fetal fat deposition remain unclear.
This study aimed to investigate the cross-sectional and longitudinal association of maternal insulin resistance in early, mid, and late pregnancy with fetal fat deposition in uncomplicated pregnancies. We hypothesized that maternal insulin resistance at early, mid, and late gestation is positively associated with fetal fat deposition, and that the magnitude of the association is greater for the mid and late gestation measures than for the early gestation measure.
In a longitudinal study of 137 low-risk pregnancies, a fasting maternal blood sample was obtained and fetal ultrasonography was performed at ≈ 12, 20, and 30 weeks\' gestation. Maternal insulin resistance was quantified using the homeostasis model assessment of insulin resistance (fasting insulin×fasting glucose/405). Estimated fetal adiposity was calculated by integrating measurements of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness. The associations between maternal homeostasis model assessment of insulin resistance and estimated fetal adiposity and estimated fetal weight were determined by multiple linear regression adjusted for potential confounding factors including maternal age, parity, race and ethnicity, prepregnancy body mass index, gestational weight gain per week, fetal sex, and gestational age at assessments.
Maternal homeostasis model assessment of insulin resistance at ≈ 12, 20, and 30 weeks was 2.79±1.79 (±standard deviation), 2.78±1.54, and 3.76±2.30, respectively. Homeostasis model assessment of insulin resistance at 20 weeks was positively associated with estimated fetal adiposity at 20 weeks (r=0.261; P=.005). Homeostasis model assessment of insulin resistance at 20 weeks (r=0.215; P=.011) and 30 weeks (r=0.285; P=.001) were also positively associated with estimated fetal adiposity at 30 weeks. These relationships remained significant after adjustment for confounding factors. There was no significant correlation between homeostasis model assessment of insulin resistance and estimated fetal weight at 20 and 30 weeks\' gestation.
In low-risk pregnancies, maternal insulin resistance at mid and late but not early pregnancy is significantly associated with fetal adiposity but not with fetal weight. Maternal insulin resistance in mid-gestation could provide a basis for risk identification and interventions that target child adiposity.

Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.

BACKGROUND: To determine the association between maternal cardiometabolic and inflammatory markers with measures of fetal biometry and adiposity.
METHODS: Women included in this exploratory analysis were randomised to the \'Standard Care\' group (N = 911) from the LIMIT randomised trial involving a total of 2212 pregnant women who were overweight or obese (ACTRN12607000161426, Date of registration 9/03/2007, prospectively registered). Fetal biometry including abdominal circumference (AC), estimated fetal weight (EFW), and adiposity measurements (mid-thigh fat mass, subscapular fat mass, abdominal fat mass) were obtained from ultrasound assessments at 28 and 36 weeks\' gestation. Maternal markers included C reactive protein (CRP), leptin and adiponectin concentrations, measured at 28 and 36 weeks\' gestation and fasting triglycerides and glucose concentrations measured at 28 weeks\' gestation.
RESULTS: There were negative associations identified between maternal serum adiponectin and fetal ultrasound markers of biometry and adiposity. After adjusting for confounders, a 1-unit increase in log Adiponectin was associated with a reduction in the mean AC z score [- 0.21 (- 0.35, - 0.07), P = 0.004] and EFW [- 0.23 (- 0.37, - 0.10), P < 0.001] at 28 weeks gestation. Similarly, a 1-unit increase in log Adiponectin was association with a reduction in the mean AC z score [- 0.30 (- 0.46, - 0.13), P < 0.001] and EFW [- 0.24 (- 0.38, - 0.10), P < 0.001] at 36 weeks gestation. There were no consistent associations between maternal cardiometabolic and inflammatory markers with measurements of fetal adiposity.
CONCLUSIONS: Adiponectin concentrations are associated with measures of fetal growth. Our findings contribute to further understanding of fetal growth in the setting of women who are overweight or obesity.

The aim of this study was to evaluate the association between fetal ultrasound and newborn biometry and adiposity measures in the setting of maternal obesity.
The study population involved 845 overweight or obese pregnant women, who participated in the Standard Care Group of the LIMIT randomised trial (ACTRN12607000161426, 9/03/2007). At 36 weeks gestation, fetal biometry, estimated fetal weight (EFW) and adiposity measures including mid-thigh fat mass (MTFM), subscapular fat mass (SSFM), and abdominal fat mass (AFM) were undertaken using ultrasound. Neonatal anthropometric measurements obtained after birth included birthweight, head circumference (HC), abdominal circumference (AC) and skinfold thickness measurements (SFTM) of the subscapular region and abdomen.
At 36 weeks gestation, every 1 g increase in EFW was associated with a 0.94 g increase in birthweight (95% CI 0.88-0.99; P < 0.001). For every 1 mm increase in the fetal ultrasound measure, there was a 0.69 mm increase in birth HC (95% CI 0.63-0.75, P < 0.001) and 0.69 mm increase in birth AC (95% CI 0.60-0.79, P < 0.001). Subscapular fat mass in the fetus and the newborn (0.29 mm, 95% CI 0.20-0.39, P < 0.001) were moderately associated, but AFM measurements were not (0.06 mm, -0.03 to 0.15, P = 0.203). There is no evidence that these relationships differed by maternal body mass index.
In women who are overweight or obese, fetal ultrasound accurately predicts neonatal HC and AC along with birthweight.

BACKGROUND: Over fifty percent of women entering pregnancy are overweight or obese. This has a significant impact on short and long term maternal and infant health outcomes, and the intergenerational effects of obesity are now a major public health problem globally. Areas covered: There are two major pathways contributing to fetal growth. Glucose and insulin directly affect growth, while other substrates such as leptin, adiponectin and insulin-like growth factors indirectly influence growth through structural and morphological effects on the placenta, uteroplacental blood flow, and regulation of placental transporters. Advances in ultrasonography over the past decade have led to interest in the prediction of the fetus at risk of overgrowth and adiposity utilizing both standard ultrasound biometry and fetal body composition measurements. However, to date there is no consensus regarding the definition of fetal overgrowth, its reporting, and clinical management. Expert commentary: Maternal dietary intervention targeting the antenatal period appear to be too late to sufficiently affect fetal growth. The peri-conceptual period and early pregnancy are being evaluated to determine if the intergenerational effects of maternal obesity can be altered to improve newborn, infant and child health.

OBJECTIVE: To determine the correlation between pre-pregnancy body mass index (BMI) and maternal visceral adiposity with fetal biometry during the second trimester.
METHODS: A cross-sectional observational study was conducted among pregnant women who received prenatal care at a center in Recife, Brazil, between October 3, 2011, and September 27, 2013. Pre-pregnancy BMI was determined at the first prenatal care visit. Maternal visceral adiposity and fetal biometry were measured at the same ultrasonography session. The associations between maternal and fetal variables were evaluated using the Pearson correlation coefficient (R). The Student t test was used to test the null hypothesis of adjusted correlation coefficients.
RESULTS: Overall, 740 women were included. No correlation was found between pre-pregnancy BMI and any of the fetal biometric variables assessed. By contrast, maternal visceral adiposity positively correlated with fetal abdominal circumference (R=0.529), estimated fetal weight (R=0.524), head circumference (R=0.521), femur length (R=0.521), and biparietal diameter (R=0.524; P<0.001 for all fetal variables). These findings remained statistically significant after controlling for pregnancy length.
CONCLUSIONS: Maternal visceral adiposity, but not pre-pregnancy BMI, positively correlated with fetal biometry during the second trimester.

Newborns exhibit substantial variation in gestational age-adjusted and sex-adjusted fat mass proportion. The antecedent characteristics of fetal body composition that are associated with newborn fat mass proportion are poorly understood.
The aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity.
In a longitudinal study of 109 low-risk pregnancies, fetal ultrasonography was performed at approximately 12, 20 and 30 weeks gestation. Estimated fetal adiposity (EFA) was derived by integrating cross-sectional arm and thigh per cent fat area and anterior abdominal wall thickness. Newborn per cent body fat was quantified by Dual Energy X-Ray Absorptiometry. The association between EFA and newborn per cent body fat was determined by multiple linear regression.
After controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent body fat (standardized β = 0.41, p < 0.001) and explained 24.0% of its variance, which was substantially higher than that explained by estimated fetal weight (8.1%). The observed effect was driven primarily by arm per cent fat area.
A composite measure of fetal adiposity at 30 weeks gestation may constitute a better predictor of newborn per cent body fat than estimated fetal weight by conventional fetal biometry. Fetal arm fat deposition may represent an early indicator of newborn adiposity. After replication, these findings may provide a basis for an improved understanding of the ontogeny of fetal fat deposition, thereby contributing to a better understanding of its intrauterine determinants and the development of potential interventions.