Ultrasound Measures Of Fetal Growth Research Articles

Organophosphate Ester Flame Retardants and Plasticizers in Relation to Fetal Growth in the LIFECODES Fetal Growth Study.

Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity. Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z-score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth. In the LIFECODES Fetal Growth Study (2008-2018), an enriched case-cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models. Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; ) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z-scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: , 0.17). At delivery, an IQR () increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94). In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647.

An application of group-based trajectory modeling to define fetal growth phenotypes among small-for-gestational-age births in the LIFECODES Fetal Growth Study

Reductions in fetal growth are associated with adverse outcomes at birth and later in life. However, identifying fetuses with pathologically small growth remains challenging. Definitions of small-for-gestational age are often used as a proxy to identify those experiencing pathologic growth (ie, fetal growth restriction). However, this approach is subject to limitation as most newborns labeled small-for-gestational age are constitutionally, not pathologically, small. Incorporating repeated ultrasound measures to examine fetal growth trajectories may help distinguish pathologic deviations in growth from normal variability, beyond a simple definition of small-for-gestational age. This study aimed to characterize phenotypes of growth using ultrasound trajectories of fetal growth among small-for-gestational-age births. This study identified and described trajectories of fetal growth among small-for-gestational-age births (<10th percentile weight for gestational age; n=245) in the LIFECODES Fetal Growth Study using univariate and multivariate trajectory modeling approaches. Available ultrasound measures of fetal growth (estimated fetal weight, head circumference, abdominal circumference, and femur length) from health records were abstracted. First, univariate group-based trajectory modeling was used to define trajectories of estimated fetal weight z scores during gestation. Second, group-based multi-trajectory modeling was used to identify trajectories based on concurrent measures of head circumference, abdominal circumference, and femur length z scores. Last, how these trajectories were related to patient demographics, pregnancy characteristics, and birth outcomes compared with those observed among appropriate-for-gestational-age controls was described. Of note, 3 univariate trajectories of estimated fetal weight and 4 multivariate trajectories of fetal growth among small-for-gestational-age births were identified. In our univariate approach, infants with the smallest estimated fetal weight trajectory throughout pregnancy had poorer outcomes, including the highest risk of neonatal intensive care unit admission. The remaining univariate trajectory groups did not have an elevated risk of adverse birth outcomes relative to appropriate-for-gestational-age controls. In our multivariate approach, 2 groups at increased or moderately increased risk of neonatal intensive care unit admission were identified, including infants that remained extremely small for all parameters throughout pregnancy and those who had disproportionately smaller femur length and abdominal circumference compared with head circumference. The remaining multivariate trajectory groups did not have an elevated risk of adverse birth outcome relative to appropriate-for-gestational-age controls. Latent class group-based trajectory modeling applied to ultrasound measures of fetal growth may help distinguish pathologic vs constitutional growth profiles among newborns born small-for-gestational age. Although trajectories cannot be fully characterized until delivery, limiting the direct clinical application of these methods, they may still contribute to the development of approaches for separating growth restriction from constitutional smallness.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China

BackgroundDisinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. ObjectiveTo investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. MethodsWe included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. ResultsWe found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: −0.35, −0.07; P for trend = 0.003), 0.46 cm (95% CI: −0.81, −0.10; P for trend = 0.01) and 0.17 cm (95% CI: −0.30, −0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. ConclusionThe results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Effects of trimester-specific exposure to vanadium on ultrasound measures of fetal growth and birth size: a longitudinal prospective prenatal cohort study

Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort. The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth. As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown-rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (-4·2%, -8·2 to -0·1), head circumference (-6·0%, -10·1 to -1·9), occipitofrontal diameter (-5·7%, -9·9 to -1·5), and abdominal circumference (-5·3%, -9·4 to -1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (-7·2%, -14·1 to -0·3) and abdominal circumference (-6·9%, -13·8 to -0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 μg/L) in the first trimester, when compared with the lowest quartile (≤0·60 μg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5-22·8; ptrend=0·0055) and a mean decrease in ponderal index of 0·07 kg/m3 (0·01-0·12; ptrend=0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters. Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations. National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology.

Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy.

Perturbations in normal fetal growth during pregnancy are associated with poor child and adult health outcomes. Inflammation and oxidative stress are recognized as important mechanisms in preeclampsia and preterm birth but have been examined less in relation to fetal growth. We hypothesized that maternal inflammation and oxidative stress in pregnancy would be associated with reduced fetal growth and sought to identify windows of vulnerability. In a secondary analysis of 482 women from the LIFECODES birth cohort study, we measured inflammation (C-reactive protein [CRP] and the cytokines IL-1β, IL-6, IL-10, and TNF-α) and oxidative stress (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) biomarkers in plasma and urine, respectively, at four time points during pregnancy. We examined associations between repeated measures of each marker and ultrasound (head and abdominal circumference, femur length, and a summary measure of estimated fetal weight) as well as delivery (birthweight) metrics of growth. In adjusted repeated-measures models, an interquartile range (IQR) increase in CRP was associated with a 0.12 standard deviation decrease in fetal weight z-score (95% confidence interval, CI, -0.21, -0.02), which corresponds to approximately 50g at 40-week gestation. The association was greatest in magnitude (ie, most negative) with CRP measured later in pregnancy. Oxidative stress markers were not associated with fetal weight, although both were inversely associated with head circumference and femur length. Inflammation and oxidative stress markers measured later in pregnancy were associated with reduced fetal growth as measured by repeated ultrasound scans.

Green Space Exposure and Ultrasound Measures of Fetal Growth: A Spanish Birth Cohort Study

Background/Aim: In recent years, the effect of greenness on birth weight has been studied in different analyses across multiple countries; however, the available evidence on such an effect on measu...

Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP).

Improving micronutrient intakes of under‐nourished mothers in low‐ and middle‐income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food‐based supplement affected fetal growth. Non‐pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient‐rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower‐micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First‐trimester (median: 10 weeks, interquartile range: 9–12 weeks) fetal crown‐rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19–20 weeks) and third trimesters (29, 28–30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient‐rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative.

Prenatal exposure to mercury and ultrasound measures of fetal growth in a Spanish birth cohort study

Introduction: Levels of mercury (Hg) has been reported as relatively high in Spanish population, including vulnerable groups such as pregnant women, fetuses, and children. There is little but sugge...

Air pollution and fetal growth- a study on ultrasound measures of Swedish children

Background: Air pollution has been suggested to affect fetal growth. Most studies have relied on birth weight from birth records. Recent studies have been using ultrasound measures of fetal growth to assess air pollution effects. All of these studies have, however, been conducted in smaller study populations. Here, we have the opportunity to further advance our knowledge regarding the influence of air pollution exposures on fetal growth in a population based cohort of more than 48 000 pregnancies in women from Southern Sweden. The large study population allows us to perform sensitivity analyses. Methods: In this study we used outcome data from Swedish medical birth registers and an ultrasound database for around 55 000 pregnancies with two ultrasound measurements (one early in pregnancy and one late in pregnancy). We estimated exposures during different parts of pregnancies for all the pregnancies in the ultrasound database using geocoded residential adresses. The measures of air pollution exposure were obtained through dispersion modelling with input data from an emissions database (NOx) with high resolution (100m grids). We had knowledge from registers on potential confounders/interfering factors and effect modifiers (e.g.parity, sex, smoking, age and education of the mother). Results: In this large cohort of Swedish born children, we consistently estimated negative effects for NOx on most measures of fetal growth late in pregnancy. As an example, we show that our modelled NOx-exposures exhibit an effect on birth weight reducing birth weight by approximately 10g per 10 µg/m3 increment of NOx. This work was supported by FORMAS, The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning.

Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort.

Background:Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies.Objectives:We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother–child pairs.Methods:We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12–20 and 20–34), and for birth weight, birth length, head circumference at birth, and placental weight.Results:Overall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20–34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (–27 g; 95% CI: –79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12–20 pregnancy weeks [–4.88% of HC average (95% CI: –8.36, –1.36%)].Conclusions:This study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication.Citation:Casas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J, Vrijheid M. 2016. Exposure to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect 124:521–528; http://dx.doi.org/10.1289/ehp.1409190

Prenatal Exposure to NO2 and Ultrasound Measures of Fetal Growth in the Spanish INMA Cohort.

BackgroundAir pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability.ObjectiveThe aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study.MethodsBiparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis.ResultsA 10-μg/m3 increase in average exposure to NO2 during weeks 0–12 was associated with reduced growth at weeks 0–12 in AC (–2.1%; 95% CI: –3.7, –0.6) and EFW (–1.6%; 95% CI: –3.0, –0.3). The same exposure was inversely associated with reduced growth at weeks 20–34 in BPD (–2.6%; 95% CI: –3.9, –1.2), AC (–1.8%; 95% CI: –3.3, –0.2), and EFW (–2.1%; 95% CI: –3.7, –0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers.ConclusionsMaternal exposure to NO2 in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth.CitationIñiguez C, Esplugues A, Sunyer J, Basterrechea M, Fernández-Somoano A, Costa O, Estarlich M, Aguilera I, Lertxundi A, Tardón A, Guxens M, Murcia M, Lopez-Espinosa MJ, Ballester F, on behalf of the INMA Project. 2016. Prenatal exposure to NO2 and ultrasound measures of fetal growth in the Spanish INMA Cohort. Environ Health Perspect 124:235–242; http://dx.doi.org/10.1289/ehp.1409423

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project

In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Bill & Melinda Gates Foundation.

Prenatal air pollution exposure and ultrasound measures of fetal growth in Los Angeles, California

BackgroundFew previous studies examined the impact of prenatal air pollution exposures on fetal development based on ultrasound measures during pregnancy. MethodsIn a prospective birth cohort of more than 500 women followed during 1993–1996 in Los Angeles, California, we examined how air pollution impacts fetal growth during pregnancy. Exposure to traffic related air pollution was estimated using CALINE4 air dispersion modeling for nitrogen oxides (NOx) and a land use regression (LUR) model for nitrogen monoxide (NO), nitrogen dioxide (NO2) and NOx. Exposures to carbon monoxide (CO), NO2, ozone (O3) and particles <10μm in aerodynamic diameter (PM10) were estimated using government monitoring data. We employed a linear mixed effects model to estimate changes in fetal size at approximately 19, 29 and 37 weeks gestation based on ultrasound. ResultsExposure to traffic-derived air pollution during 29 to 37 weeks was negatively associated with biparietal diameter at 37 weeks gestation. For each interquartile range (IQR) increase in LUR-based estimates of NO, NO2 and NOx, or freeway CALINE4 NOx we estimated a reduction in biparietal diameter of 0.2–0.3mm. For women residing within 5km of a monitoring station, we estimated biparietal diameter reductions of 0.9–1.0mm per IQR increase in CO and NO2. Effect estimates were robust to adjustment for a number of potential confounders. We did not observe consistent patterns for other growth endpoints we examined. ConclusionsPrenatal exposure to traffic-derived pollution was negatively associated with fetal head size measured as biparietal diameter in late pregnancy.

Fetal programming in 2-year-old calving heifers: peri-conception and first trimester protein restriction alters fetal growth in a gender-specific manner

Protein restriction in early bovine gestation affects post-natal reproduction and production traits in progeny. This experiment evaluated the effects of dietary protein restriction during the peri-conception period and first trimester in yearling heifers on conceptus growth and development; this period of dietary intervention being earlier than any previous bovine fetal programming studies. Three-hundred and sixty primiparous 12-month-old Santa Gertrudis heifers were individually fed high [14% crude protein (CP)] or low (7% CP) diets for 60 days before conception. At 23 days post-conception (dpc), each high (HPERI) or low (LPERI) group was again split into high (HPOST) or low (LPOST) protein groups yielding four treatment groups in a 2 × 2 factorial design. From the end of the first trimester of gestation (98dpc), the pregnant heifers were individually fed a 12% CP diet until parturition. Forty-six fetuses were excised at 98dpc. Sixty-four heifers went on to calve. Conceptus development was assessed via transrectal ultrasound from 36dpc, fetal necropsy at 98dpc and live calf measures at term. At 36dpc, HPERI diet increased fetal crown–rump length (CRL) (P &lt; 0.05) and at the 60dpc scan, biparietal diameter (BPD) tended to be increased by HPOST diet (P &lt; 0.1) though the greater effect upon BPD was still the HPERI diet (P &lt; 0.05). At 60dpc, BPD in the male fetus was affected by the peri-conception diet (P &lt; 0.05), while in females, BPD was not different among nutritional groups. These ultrasound measures of fetal growth were validated by measures of the excised fetus at 98dpc. Fetal weight was heavier (P &lt; 0.01) in those whose mothers were fed the HPOST diet than their LPOST counterparts. Males fetuses were heavier than female fetuses (P &lt; 0.001). Fetal CRL was increased by HPERI diet (P &lt; 0.05) and tended to be increased by HPOST diet (P &lt; 0.1). Fetal BPD tended to be increased by HPERI diet (P &lt; 0.1). In males, BPD tended to be increased in those fetuses whose mothers were fed HPERI (P &lt; 0.1). For females, maternal nutrition during PERI or POST did not affect BPD at 98dpc (P &gt; 0.1). At term, no dietary effect on birthweight was observed (P &gt; 0.1) and males were not heavier than females (P &gt; 0.1). These results suggest that maternal protein intake during the peri-conception (–60 to 23dpc) and first trimester (24–98dpc) may influence early conceptus growth and development in the bovine. The long-term effects on offspring metabolism and post-natal development of this dietary intervention are yet to be determined.

The Impact of Umbilical Blood Flow Regulation on Fetal Development Differs in Diabetic and Non-Diabetic Pregnancy

Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 ±16.29 of gestation) and late (day 268.12 ±13.04 of gestation) pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies.

Small for Gestational Age and Intrauterine Growth Restriction Decreases Cognitive Function in Young Adults

To examine the effect on adult cognitive function of being born small for gestational age (SGA), and to evaluate whether cognitive function is related to intrauterine growth restriction (IUGR). Fifty-nine SGA subjects (birth weight <10th percentile) and 81 controls (birth weight ≥10th percentile) born at term underwent cognitive assessment with the Wechsler Adult Intelligence Scale-Third Edition at age 19-20 years. Repeated ultrasound measures of fetal growth were available for weeks 25, 33, and 37 in a subgroup of 29 SGA subjects and 75 control subjects, and these were data used to dichotomize the 29 SGA subjects into those with IUGR and those without IUGR. IUGR was defined as growth deviating more than -2 SD from the mean value of the control group. The effect of maternal smoking during pregnancy was considered as well. Group differences were analyzed using a general linear model, controlling for sex and socioeconomic status. The SGA group had lower full IQ scores than the control group (mean difference, -6.3; 95% CI, -2.8 to -9.7; P = .001), including lower scores on 6 of the Wechsler Adult Intelligence Scale-Third Edition subtests. In the SGA subgroup with repeated ultrasound measures, 6 of 29 subjects (21%) had IUGR, and these subjects also had a lower IQ compared with controls (mean difference, -14.0; 95% CI: -4.8 to -23.3; P = .003). Maternal smoking during pregnancy was related to lower IQ in the control group but not in the SGA group, independent of IUGR or non-IUGR status. IQ scores were lower in young adults born SGA compared with controls. Our analysis suggest that this outcome is related to IUGR.

Air Pollution Exposure During Pregnancy, Ultrasound Measures of Fetal Growth, and Adverse Birth Outcomes: A Prospective Cohort Study

Background: Air pollution exposure during pregnancy might have trimester-specific effects on fetal growth.Objective: We prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands.Methods: Particulate matter with an aerodynamic diameter < 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records.Results: In cross-sectional analyses, NO2 levels were inversely associated with fetal femur length in the second and third trimester, and PM10 and NO2 levels both were associated with smaller fetal head circumference in the third trimester [–0.18 mm, 95% confidence interval (CI): –0.24, –0.12 mm; and –0.12 mm, 95% CI: –0.17, –0.06 mm per 1-μg/m3 increase in PM10 and NO2, respectively]. Average PM10 and NO2 levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (–3.6 g, 95% CI: –6.7, –0.4 g; and –3.4 g, 95% CI: –6.2, –0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM10 exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM10 exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO2 levels and adverse birth outcomes.Conclusions: Results suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with weight at birth. PM10 exposure was positively associated with preterm birth and SGA.

Active and passive smoking during pregnancy and ultrasound measures of fetal growth in a cohort of pregnant women

BackgroundIn utero tobacco exposure has been associated with adverse pregnancy outcomes but few studies have used longitudinal ultrasound measurements to asses the effects on fetal growth. The aim of this...

In Utero Exposure to Air Pollution and Ultrasound Measures of Fetal Growth in Los Angeles, California

In Utero Exposure to Air Pollution and Ultrasound Measures of Fetal Growth in Los Angeles, California

Different indices of fetal growth predict bone size and volumetric density at 4 years of age

We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks' gestation from ultrasound measurements in participants in the Southampton Women's Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks' gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.