Fetal growth trajectories of small/large for gestational age infants in twin pregnancies.

BACKGROUND: Birthweight is the most common and accessible parameter in assessing neonatal perinatal outcomes and in evaluating the intrauterine environment globally. Infants born too large or too small not only may alter the maternal mode of delivery but also may face other long-term disorders, such as metabolic diseases and neurodevelopmental delay. Studies have revealed different growth profiles of large-for-gestational-age and small-for-gestational-age fetuses in singleton pregnancies. However, currently, no research is focused on the growth trajectories of these infants during twin pregnancies, even though they are at a much higher risk of being small for gestational age. OBJECTIVE: This study aimed to explore fetal growth trajectories of large-for-gestational-age and small-for-gestational-age infants in twin pregnancies to provide strategies for fetal growth management. STUDY DESIGN: This was a case-control study of all noncomplicated twin pregnancies delivered after 36 weeks of gestation at the Peking University First Hospital between 2012 and 2021. Ultrasound data were recorded every 2 to 4 weeks until delivery. All the infants were divided into large-for-gestational-age, small-for-gestational-age, and appropriate-for-gestational-age groups. Longitudinal fetal growth (estimated fetal weight, abdominal circumference, etc.) was compared among the 3 groups using a linear mixed model, and other maternal and neonatal perinatal outcomes were compared. Receiver operating characteristic curves were used to explore optimal biometric parameters and gestational weeks for predicting small-for-gestational-age infants. RESULTS: Here, 797 pregnant patients with 1494 infants were recruited, with 59 small-for-gestational-age infants, 1335 appropriate-for-gestational-age infants, and 200 large-for-gestational-age infants. The mean birthweights were 1985.34±28.34 g in small-for-gestational-age infants, 2662.08±6.60 g in appropriate-for-gestational-age infants, and 3231.24±11.04 g in large-for-gestational-age infants. The estimated fetal weight of the 3 groups differed from each other from week 26, with the small-for-gestational-age fetuses weighing 51.946 g less and the large-for-gestational-age fetuses weighing 35.233 g more than the appropriate-for-gestational-age fetuses. This difference increased with gestation; at 39 weeks, the small-for-gestational-age fetuses weighed 707.438 g less and the large-for-gestational-age fetuses weighed 614.182 g more than the appropriate-for-gestational-age fetuses (all P<.05). The small-for-gestational-age group had a significantly higher rate of hospitalization (89.9 %) and jaundice (40.7 %) than the appropriate-for-gestational-age group, whereas the hospitalization rate in the large-for-gestational-age group was significantly lower than the appropriate-for-gestational-age group (7.5% and 2.5%; all P<.05). The fetal weight of the small-for-gestational-age infants with adverse outcomes remained near the 10th percentile of the reference and fell below the 3rd percentile at 34 weeks of gestation. The estimated fetal weight after 30 weeks of gestation had a satisfactory diagnostic value in predicting small-for-gestational-age infants. At 30, 32, 34, and 36 weeks of gestation, the areas under the curve were 0.829, 0.840, 0.929, and 0.889 respectively. CONCLUSION: The growth patterns of small-for-gestational-age, appropriate-for-gestational-age, and large-for-gestational-age twin fetuses diverged from 26 weeks of gestation and continued to increase until delivery; therefore, closer monitoring is suggested from 26 weeks of gestation for those carrying small fetuses.

Fetal growth trajectories of babies born large-for-gestational age in the LIFECODES Fetal Growth Study.

BACKGROUND: Babies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups. OBJECTIVE: This study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups. STUDY DESIGN: This study identified and described trajectories of fetal growth among large-for-gestational age births (n=235) in the LIFECODES Fetal Growth Study. Ultrasound measurements of fetal growth in middle to late pregnancy were abstracted from health records. Group-based multi-trajectory modeling was applied to measurements of head circumference, abdominal circumference, and femur length z-scores to identify multivariate trajectories of fetal growth. Moreover, sociodemographic variables, pregnancy characteristics, and birth outcomes based on trajectory membership were summarized. RESULTS: This study identified 4 multivariate trajectories of fetal growth among large-for-gestational age births: catch-up growth (n=28), proportional abdominal circumference-to-femur length growth (n=67), disproportional abdominal circumference-to-femur length growth (n=96), and consistently large (n=44). Fetuses in the "catch-up growth" group exhibited small relative sizes in midpregnancy (ie, below average head circumference, abdominal circumference, and femur length z-scores) and large relative sizes in late pregnancy. Growth among these births was driven by increases in relative abdominal circumference and head circumference sizes. Participants who delivered births assigned to this group were less likely to have normal glucose control (40% vs 65%-75%) and more likely to have pregestational diabetes mellitus (36% vs 10%-17%) than other large-for-gestational age subgroups. In addition, the babies in this trajectory group were more likely to have macrosomia (86% vs 67%-73%) and to be admitted to the neonatal intensive care unit (32% vs 14%-21%) than other large-for-gestational age subgroups. In contrast, babies in the "consistently large" group had the largest relative size for all growth parameters throughout gestation and experienced a lower risk of adverse birth outcomes than other large-for-gestational age subgroups. CONCLUSION: This study characterized several trajectories of fetal growth among large-for-gestational age births, which were related to different pregnancy characteristics and the distribution of adverse birth outcomes. Although the number of individuals within some trajectories was small, a subgroup that exhibited a catch-up growth phenotype during gestation was identified, which may be uniquely associated with exposure to pregestational diabetes mellitus and a higher risk of admission to the neonatal intensive care unit. These results have highlighted that the risk of adverse outcomes may not be evenly distributed across all large-for-gestational age births.

The association between first-trimester omega-3 fatty acid supplementation and fetal growth trajectories.

BACKGROUND: Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown. OBJECTIVE: This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery. STUDY DESIGN: In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation. Fetal ultrasonographic measurements, including abdominal circumference, biparietal diameter, femur length, head circumference, and humerus length, were measured at enrollment (8-13 weeks) and up to 5 follow-up visits. Estimated fetal weight and head circumference-to-abdominal circumference ratio (a measure of growth symmetry) were calculated. Fetal growth trajectories were modeled for each measure using a linear mixed model with cubic splines. If significant differences in fetal growth trajectories between groups were observed (global P<.05), weekly comparisons were performed to determine when in gestation these differences emerged. Analyses were adjusted for maternal sociodemographics, parity, infant sex, total energy consumption, and diet quality score. All analyses were repeated using dietary docosahexaenoic acid and eicosapentaenoic acid intake, dichotomized at the recommended cutoff for pregnant and lactating women (≥0.25 vs <0.25 g/d), among women who did not report supplement intake in the first trimester of pregnancy were repeated. RESULTS: Among 1535 women, 143 (9%) reported docosahexaenoic acid and eicosapentaenoic acid supplementation in the first trimester of pregnancy. Overall, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with statistically significant differences (P-value <.05) in fetal growth trajectories during pregnancy. Specifically, estimated fetal weight was larger among women with docosahexaenoic acid and eicosapentaenoic acid supplementation than among those without supplementation (global P=.028) with significant weekly differences in median estimated fetal weight most apparent between 38 to 41 weeks of gestation (median estimated fetal weight difference at 40 weeks of gestation, 114 g). Differences in fetal growth trajectories for abdominal circumference (P=.003), head circumference (P=.003), and head circumference-to-abdominal circumference ratio (P=.0004) were also identified by supplementation status. In weekly comparisons, docosahexaenoic acid and eicosapentaenoic acid supplement use was associated with larger median abdominal circumference (changed from 2 to 9 mm) in midpregnancy onward (19 to 41 weeks), larger median head circumference between 30 to 33 weeks of gestation, and smaller median head circumference-to-abdominal circumference ratio in the second and third trimesters of pregnancy. There was no specific weekly difference in fetal femur length or humerus length by docosahexaenoic acid and eicosapentaenoic acid supplementation. First-trimester dietary sources of docosahexaenoic acid and eicosapentaenoic acid among women with no first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation (n=1392) were associated with differences in fetal biparietal diameter (P=.043), but not other metrics of fetal growth. At the recommended dietary docosahexaenoic acid and eicosapentaenoic acid levels compared with below-recommended levels, biparietal diameter was larger between 38 to 41 weeks of gestation. CONCLUSION: In this racially diverse pregnancy cohort, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with significant increases in fetal growth, specifically greater estimated fetal abdominal circumference in the second and third trimesters of pregnancy.

Comparing fetal biometric growth velocity versus estimated fetal weight for prediction of neonatal small for gestational age.

OBJECTIVE: Growth velocities derived from fetal biometrics have been proposed to improve prediction of small for gestational age (SGA) neonates. We sought to determine if ultrasound growth velocities for abdominal circumference (AC) and estimated fetal weight (EFW) improve the prediction of SGA infants when compared to using EFW alone. STUDY DESIGN: This is a secondary analysis from a prospective study of women referred for growth ultrasounds during the third trimester. Growth velocities for AC and EFW were derived from the difference in Z-scores between measurements at the anatomy survey (18-22 weeks gestation) and later growth ultrasound (26-36 weeks gestation). Change in AC and EFW growth velocities <10th percentile were compared with prenatally suspected SGA from Hadlock EFW <10th percentile for prediction of SGA neonates. The primary outcome was defined as the sensitivity and specificity of the growth velocities and Hadlock EFW in predicting SGA neonates. Logistic regression modeling was used to determine if the growth velocities improved prediction of neonatal SGA. Area under the ROC curves (AUC) were determined and compared. RESULTS: Of 612 singleton pregnancies meeting inclusion criteria, 68 (11.1%) resulted in SGA neonates. Hadlock EFW <10th percentile had higher sensitivity and specificity when compared to AC growth velocity and EFW growth velocity. Only AC growth velocity and Hadlock EFW had significant odds ratios for association with neonatal SGA. The AUC were 0.54, 0.53, and 0.61 using AC growth velocity, EFW growth velocity, and Hadlock EFW, respectively. The AUC did not significantly improve when the growth velocities were combined with Hadlock EFW (0.63). Adjustment of Z-scores for gestational age at anatomy scan or third trimester growth scan did not significantly change these results (AUC = 0.69). CONCLUSION: EFW determined by Hadlock formula has the highest predictive value in detecting SGA neonates when compared to both AC and EFW growth velocities.

The value of fetal growth biometry velocities to predict large for gestational age (LGA) infants.

OBJECTIVE: The use of growth velocities derived from fetal biometrics have been suggested to improve prediction of large for gestational age (LGA). Our objective was to determine if ultrasonographic growth velocities (GV) for abdominal circumference (AC) and estimated fetal weight (EFW) improve the prediction of LGA infants when compared to Hadlock EFW. METHODS: This was a secondary analysis of data from a prospective study of women referred for growth ultrasounds during the 3rd trimester. Growth velocities (GV) for AC (AC - GV) and EFW (EFW - GV) were derived from the difference in Z-scores between measurements at the time of anatomy survey (18-24 week) and third trimester ultrasound (26-36 weeks). Change in AC - GV and EFW - GV >90th %ile alone or in combination with Hadlock EFW >90th%ile were compared for prediction of a LGA neonate. The primary outcome was the sensitivity and specificity of the (1) Hadlock EFW >90%ile, (2) AC - GV, (3) EFW - GV, (4) Hadlock EFW + AC - GV, and (5) Hadlock EFW + EFW - GV for the prediction of neonatal LGA. Test characteristics and area under the ROC curve (AUC) were determined. The association between the ultrasound predicted growth and adverse neonatal outcome was assessed using logistic regression. RESULTS: Of 630 women meeting inclusion criteria, 85 (13.5%) had LGA neonates. Hadlock EFW showed a better NPV (98.0%) and sensitivity (71.1%) when compared to AC - GV (NPV 87.5%, sensitivity 17.7%) and EFW - GV (NPV 88.0%, sensitivity 22.6%). Combining Hadlock EFW and AC-GV or EFW - GV did little to improve the test characteristics for the prediction of LGA (AUC 0.65 and 0.64, respectively). All five measurements were unable to predict a composite of adverse neonatal outcome or need for maternal cesarean delivery. Adjustment of the growth velocities for gestational age at anatomy scan or 3rd trimester growth scan did not change these results. CONCLUSION: AC and EFW growth velocities do not appear to improve the prediction of LGA infants when compared to using the third trimester Hadlock EFW.

Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey.

INTRODUCTION: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. METHODS: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. RESULTS: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002-0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DISCUSSION: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.