Birth Size Measures Research Articles

The Association of Infant Birth Sizes and Anemia under Five Years Old: A Population-Based Prospective Cohort Study in China.

Infant birth sizes are vital clinical parameters to predict poor growth and micronutrient deficiency in early life. However, their effects on childhood anemia remain unclear. We aimed to explore the associations between birth weight, crown-heel length, and head circumference with anemia in early childhood, as well as potential modification factors. This population-based prospective cohort study included 204,556 participants with singleton live births delivered at gestational ages of 28-42 weeks. A logistic regression model was used to estimate the associations of the measures of infant birth size and their Z-score with anemia under five years old. There were 26,802 (13.10%) children under five years old who were diagnosed has having anemia. Compared with children who did not have anemia, children who had anemia had a lower birth weight and smaller head circumference and a longer crown-heel length (all p-values < 0.05). After adjusting for confounders, not only birth weight (β coefficient, -0.008; 95% CI, -0.011--0.004; p < 0.001) and head circumference (β coefficient, -0.004; 95% CI, -0.007--0.001; p = 0.009), but also the related Z-scores were negatively associated with childhood anemia, while the trends for crown-heel length were the opposite. We further found significant interactions of folic acid use and maternal occupation with infant birth sizes. In conclusion, infants having abnormal sizes at birth are significantly associated with the risk for childhood anemia, which can be modified by folic acid use during pregnancy and maternal occupation.

Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica.

To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants' Environmental Health (ISA) birth cohort, Costa Rica. We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10-90 = 1.90-6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10-90 = 0.97-4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10-90 = 0.18-1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., β per 10-fold-increase) during the second half of pregnancy = -129.6 (95% confidence interval [CI] = -255.8, -3.5) grams, and -0.61 (95% CI = -1.05, -0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight (β per 10-fold-increase = -125.1; 95% CI = -228.8, -21.5), smaller head circumference (β = -0.41; 95% CI = -0.78, -0.03), and, during the second half of pregnancy, with shorter body length (β = -0.58; 95% CI = -1.09, -0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.

Association between maternal plasma total antioxidant capacity and dietary antioxidants intake with birth size outcomes.

Maternal antioxidants intake and plasma total antioxidant capacity (TAC) concentration during pregnancy might influence on birth outcomes. This study was conducted to determine the association between dietary antioxidants intake and plasma TAC during pregnancy with birth outcomes. Overall, 220 mother-infant pairs were recruited in the first trimester of pregnancy. Maternal whole blood was collected and TAC was determined by the ELISA kit. Food frequency questionnaire was used to collect information regarding usual dietary intake. Birth size measurements including birth weight, length and head circumference were measured according to standardized protocols. Energy-adjusted intake of beta-carotene in the first trimester of gestation [beta (SE) = 0.0002 (0.00008); p = 0.016] and energy-adjusted intake of vitamin E in third trimester of pregnancy [beta (SE) = -0.31 (0.15); p = 0.046] had significantly positive and negative associations with birth length, respectively. The maternal plasma TAC was positively correlated with birth weight in both unadjusted and adjusted models [beta (SE) = 2.75 (1.35); p = 0.043 and beta (SE) = 3.43 (1.50); p = 0.023, respectively]. In addition, the adjusted model showed a significant positive relationship between the maternal plasma TAC and birth length [beta (SE) = 0.023 (0.009); p = 0.01]. This study showed the positive association of maternal plasma TAC with birth weight and length. Moreover, maternal dietary intake of beta-carotene in the first trimester and vitamin E in the third trimester of pregnancy had significant positive and negative correlations with birth length, respectively.

Individual and mixed metal maternal blood concentrations in relation to birth size: An analysis of the Japan Environment and Children’s Study (JECS)

Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Birth Size Outcomes in Relation to Maternal Blood Levels of Some Essential and Toxic Elements.

Exposures to toxic trace elements and deficiencies of essential trace elements during pregnancy may impact fetal growth. This study was conducted to determine the association between maternal blood levels of essential elements including manganese (Mn), copper (Cu), and zinc (Zn) and toxic elements including arsenic (As), cadmium (Cd), and lead (Pb) at the first trimester with neonatal anthropometric parameters. This cross-sectional study was conducted in 2019-2020 in Isfahan, Iran. Overall, 263 mother-infant pairs were recruited in the first trimester of pregnancy. Maternal whole blood was collected, and essential and toxic elements were determined by mass spectrometry (ICP-MS)-based method. Birth size measurements were performed according to standardized protocols. Geometric means and standard deviations of maternal blood concentrations of Mn, Cu, Zn, As, Cd, and Pb were 3.94 ± 0.82, 5.22 ± 0.57, 7.67 ± 0.58, 2.21 ± 0.77, - 0.59 ± 0.98, and 3.23 ± 0.72 µg/l, respectively. Mean age of mothers was 29.94 ± 5.22 years. Thirty-one (12.1%) neonates were preterm. Maternal blood Pb levels were negatively correlated with birth weight (β = - 0.22 (CI 95%: - 0.38, - 0.05) p = 0.010) and marginally with birth head circumference (β = - 0.14(CI 95%: - 0.29, 0.02), P = 0.094) after adjustment for potential confounder variables. There was no significant association between Mn, Cu, Zn, As, Cd, and birth size measurements. Reverse association was found between maternal blood Pb levels and birth weight and birth head circumference. There is limited evidence related to the association between essential and toxic elements during pregnancy with birth size measurements and pregnancy disorders. More studies are suggested to assess of the effect of the trace elements and birth outcomes.

Placental cadmium, placental genetic variations, and birth size

Background Maternal cadmium (Cd) burden has been associated with offspring birth size measures, yet associations of placental Cd with birth size are less clear. Further, the role of genetics in these associations has not been examined. We investigated associations of placental Cd with birth size and placental genotypes. We also examined the potential role of placental genotypes as modifiers of placental Cd and birth size associations. Methods Participants were 490 mother-child pairs from the Omega and Placenta Microarray studies based in Seattle, WA. Placental Cd was measured using Agilent 7500 ICP-MS. The birth size was characterized using birth weight (BW), ponderal index (PI), and head circumference (HC). Eleven placental single nucleotide polymorphisms (SNPs) related to metal transport, growth regulation, endocrine response, and cell signaling were genotyped. Adjusted multivariable linear regression models were used to examine overall and sex-specific associations of placental Cd with birth size (BW, PI and HC), as well as associations of placental genotypes with placental Cd. Effect modification of placenta Cd and birth size associations by placental SNPs was examined using interaction terms and stratified analyses. Results Mean maternal age was 33.6 years (SD = 4.4). Mean and median placental Cd levels were 4.0 ng/g tissue (SD = 2.7 ng/g tissue) and 3.6 ng/g (IQR 2.5 − 5.2 ng/g), respectively. Overall, compared with infants in the lowest quartile for placental Cd, infants in the second (ß = −102.8 g, 95% CI: −220.7, 15.1), third (ß = –83.2 g, 95% CI: −199.3, 32.9) and fourth (ß = −109.2 g, 95% CI: −225.4, 7.1) quartiles had lower BW, though associations were not statistically significant (all p-values > .05, trend p-value = .11). Among male infants, infants in the second (ß = −203.3 g, 95% CI: −379.7, −27.0) and fourth quartiles (ß = −198.3 g, 95% CI: −364.2, −32.5) had lower BW compared with those in the first quartiles (p-values < .05, trend p-value = .08). Similar relationships were not observed among female infants, though infant sex-placental Cd interaction terms were not significant. Similarly, male, but not female, infants had marginally significant positive associations between placental Cd and ponderal index (trend p-value = .06). The minor rs3811647 allele of the placental transferrin gene (NCBI Gene ID: 7018) was associated with an increase in Cd among all infants (p-value = .04). We did not find differences in associations of placental Cd with birth size markers among infants stratified by rs3811647 genotype. Conclusions Placental Cd was inversely associated with BW among male infants. The rs3811647 SNP of the transferrin gene was associated with placental Cd.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01–2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844–868) at birth in terms of weight (β’ = 0.078 (0.024–0.133); p = 0.005), head circumference (β’ = 0.060 (0.012–0.107); p = 0.02), body mass index (β’ = 0.067 (0.014–0.119); p = 0.01), and various skinfold thicknesses (β’ = 0.067–0.094; p = 0.03–0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children.

Background:Studies have evaluated environmental exposure to toxic metals such as arsenic (As), cadmium (Cd), manganese (Mn), or lead (Pb) on birth size; however, information on potential effects of exposures to metal mixtures is limited.Objectives:We assessed the association between metal mixtures (As, Cd, Mn, Pb) in umbilical cord blood and neonate size in Bangladeshi children.Methods:In this birth cohort study, pregnant women who were of age with an ultrasound-confirmed singleton pregnancy of gestation were recruited from two Bangladesh clinics between 2008 and 2011. Neonate size metrics were measured at the time of delivery. Metals in cord blood were measured using inductively coupled plasma mass spectrometry. We employed multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations of individual metals and metal mixtures with birth size parameters.Results:Data from 1,088 participants was assessed. We found a significant negative association between metal mixture and birth length and head circumference when all metal concentrations were above the 60th and 55th percentiles, respectively, compared with the median. An interquartile range (IQR) increase in log Cd concentration {log[Cd (in micrograms per deciliter)] } was associated with a 0.13-standard deviation (SD) decrease in mean birth length (95% CI: , ) and a 0.17-SD decrease in mean head circumference (95% CI: , ), based on linear regression models adjusted for covariates and the other metals. An IQR increase in log Mn concentration {log[Mn (in micrograms per deciliter)] } was associated with a 0.07-SD decrease in mean birth weight (95% CI: , 0.002).Discussion:Metal mixtures in cord blood were associated with reduced birth size in Bangladeshi children. Results from linear regression models adjusted and the BKMR mixtures analyses suggest adverse effects of Cd and Mn, as individual metal exposures, on birth size outcomes. https://doi.org/10.1289/EHP7502

Proposing a new approach to measuring birth size asymmetry.

Existing methods of measuring birth size asymmetry based on ratios of growth parameters are clinically useful but simplistic, and as such may have limited usefulness in studies of aetiology. We aimed to develop a novel method of measuring asymmetric fetal growth at birth and demonstrate its utility in characterising the perturbed growth associated with a number of prenatal exposures and neonatal outcomes. Data were drawn from the Queensland (QLD) Perinatal Data Collection, which included all livebirths in the Australian state of QLD between July 2010 and December 2015, with analyses restricted to babies born between 32 and 42weeks of gestation (n=280084). Novel measures of asymmetric birthweight, length, and head circumference were developed using a weighted average, representing "how far" an individual's given birth size measure deviated from the sample average and their other birth size measures. Associations among prenatal exposures and neonatal outcomes with the new asymmetry measures and traditional ratio measures (ie ponderal index, brain-to-body weight ratio, and birth length divided by head circumference) were then compared using log-binomial and multinomial regressions. The new asymmetry measures clearly indicated that prenatal smoking was linked to a disproportionate decrease in all birth size measures and that low birthweight asymmetry and low birth head circumference asymmetry were specifically associated with neonatal respiratory distress and chromosomal abnormalities, respectively. When these same associations were tested using the traditional ratios, the estimates were weak, imprecise, and non-specific. We developed a new approach to measuring fetal growth asymmetry which provides complimentary insights against the existing ratios approach. Associations with the new asymmetry measures were more precise and easier to interpret than the associations obtained using the ratios, and may better reflect the underlying pathological processes, providing an advantage when investigating the aetiologies of perturbed fetal growth.

Different Birth Size Measures are Not Equivalent in Predicting Health Outcomes in Young Women

Different Birth Size Measures are Not Equivalent in Predicting Health Outcomes in Young Women

A 2017 US Reference for Singleton Birth Weight Percentiles Using Obstetric Estimates of Gestation.

To provide an updated birth weight-for-gestational age (BW-for-GA) reference in the United States by using the most recent, nationally representative birth data with obstetric estimates of gestational age (GA). We abstracted 3 285 552 singleton births between 22 and 42 weeks' gestation with nonmissing race and/or ethnicity, infant sex, parity, birth weight, and obstetric estimate of GA from the 2017 US natality files. We used 2 techniques (nonlinear, resistant smoothing [4253H] and lambda-mu-sigma) to derive smoothed BW-for-GA curves and compared resulting BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles with US references from 1999 to 2009. The smoothed BW-for-GA curves from both techniques overlapped considerably with each other, with strong agreements seen between the 2 techniques (>99% agreement; κ-statistic >0.9) for BW-for-GA cut-points at the third, 10th, 90th, and 97th percentiles across all GAs. Cut-points from 2017 using the lambda-mu-sigma method captured 9.8% to 10.2% of births <10th and >90th percentiles and 2.6% to 3.3% of births below the third and above the 97th percentile across all GAs. However, cut-points from US references in 1999 and 2009 (when GA was based on last menstrual period) captured a much larger range of proportions of 2017 births at these thresholds, especially among preterm and postterm GA categories. We have provided an updated BW-for-GA reference in the United States using the most recent births with obstetric estimates of GA and information to calculate continuous measures of birth size that are sex or parity specific.

Fetal size and eating behaviour in childhood: a prospective cohort study.

Although studies showed that an adverse intrauterine environment increases the obesity risk in adulthood, little is known about consequences of fetal growth and birth size for eating behaviour. We examined whether fetal and birth size are associated with childhood eating behaviour. Participants were 4350 mother-child dyads of the prospective cohort study Generation R. We assessed the relation between fetal and birth size measurements with child eating behaviour at age 4 years by maternal report on the Child Eating Behaviour Questionnaire. Child body mass index (BMI) was measured at age 2 years. Per one standard deviation (SD) larger birthweight, children scored lower on Satiety Responsiveness [-0.29 points; 95% confidence interval (CI): -0.39; -0.18], higher on Food Responsiveness (0.28 points; 95% CI: 0.17; 0.39) and on Enjoyment of Food (0.21 points; 95% CI: 0.12; 0.31) at age 4 years. Similar associations were found in late pregnancy. Per one SD increase in fetal growth from late pregnancy to birth, children scored lower on Satiety Responsiveness (-0.15 points; 95% CI: -0.26; -0.04). Children within the 10% highest birthweight scored higher on food approach and lower on food avoidant scales, whereas associations in children within the 10% lowest birthweights were absent. Although child BMI partly mediated the association, direct effects of birthweight on appetitive traits remained. This study indicates that fetal size, especially being large in utero, is associated with obesity-inducing eating behaviour. Our findings point to intrauterine influences on appetite and satiety, and contribute to understanding the complex aetiology of obesity.

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.

Effects of prenatal oxidative stress levels on fetal programming: Results from the NELA birth cohort

Introduction The Developmental Origins of Health and Diseases (DOHaD) hypothesis states that both the pre- and postnatal environments shape health and disease later in life. Prenatal oxidative stress can have long term health consequences in the offspring through developmental programming, including an increased risk of adiposity; however studies in humans are limited. We aim to investigate the effects of prenatal oxidative stress levels on birth size measures used as proxies of fetal adiposity development. Methods Data come from the Nutrition and Early Life Asthma (NELA) study, a population-based birth cohort set up in 2015 in Spain. Maternal fasting blood samples were drawn at 24 weeks of gestation and newborn cord blood samples were collected at birth to analyze for oxidative stress markers, including protein carbonyl (protein oxidation), hydroperoxides (lipid oxidation), and 8-hydroxy-2’ -deoxyguanosine (DNA oxidation). Maternal and newborn antioxidant status was assessed by glutathione peroxidase, catalase, the trolox equivalent antioxidant capacity (TEAC), and the ferric reducing ability of plasma (FRAP). In addition, vitamin A and E levels were assessed as a measured of exogenous antioxidant markers. In multivariable regression models we assessed the association between maternal and newborn biomarkers with birth size measures including weight and length-derived anthropometric indicators: weight-for-age z score, weight-for-length z score, and BMI-for age z score as proxies of body composition; skinfold thickness as a proxy for subcutaneous adiposity; and length z score, which is considered as a proxy for lean mass. Results Maternal and newborn FRAP, TEAC and protein carbonyl levels were positively correlated (correlation coefficients range 0.45–0.63, P-values Conclusions Fetal antioxidant capacity and exogenous antioxidant levels (i.e. vitamin A) may influence body composition at birth. These results could help to unravel the link between prenatal oxidative stress with fetal programming and long term health consequences for the offspring. In addition, the results will shed new light on prenatal factors that may perturb maternal and fetal oxidative stress status providing new insights of the biological pathways central to fetal programming.

Gestational diabetes and offspring birth size at elevated environmental pollutant exposures

BackgroundGestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. ObjectiveWe examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. MethodsWe analyzed 604 Faroese pregnant women and their offsprings born in 1997–2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. ResultsSerum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: −169g; 95% CI: −359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. ConclusionsWe found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.

Spontaneous intrauterine growth restriction due to increased litter size in the guinea pig programmes postnatal growth, appetite and adult body composition.

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in the programming of increased appetite, adiposity and cardiometabolic diseases. Guinea pigs provide an alternate small animal model to rodents to investigate mechanisms underlying prenatal programming, being relatively precocial at birth, with smaller litter sizes and undergoing neonatal catch-up growth after IUGR. The current study, therefore, investigated postnatal consequences of spontaneous IUGR due to varying litter size in this species. Size at birth, neonatal, juvenile (post-weaning, 30-60 days) and adolescent (60-90 days) growth, juvenile and adolescent food intake, and body composition of young adults (120 days) were measured in 158 male and female guinea pigs from litter sizes of one to five pups. Compared with singleton pups, birth weight of pups from litters of five was reduced by 38%. Other birth size measures were reduced to lesser degrees with head dimensions being relatively conserved. Pups from larger litters had faster fractional neonatal growth and faster absolute and fractional juvenile growth rates (P<0.005 for all). Relationships of post-weaning growth, feed intakes and adult body composition with size at birth and neonatal growth rate were sex specific, with neonatal growth rates strongly and positively correlated with adiposity in males only. In conclusion, spontaneous IUGR due to large litter sizes in the guinea pig causes many of the programmed sequelae of IUGR reported in other species, including human. This may therefore be a useful model to investigate the mechanisms underpinning perinatal programming of hyperphagia, obesity and longer-term metabolic consequences.

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.Trial RegistrationClinicalTrials.gov NCT00860470

Cord IGF-I concentrations in Indian newborns: associations with neonatal body composition and maternal determinants.

Indian newborns have been described as 'thin-fat' compared with European babies, but little is known about how this phenotype relates to the foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein IGFBP-3. To assess cord IGF-I and IGFBP-3 concentrations in a sample of Indian newborns and evaluate their associations with neonatal adiposity and maternal factors. A prospective cohort study of 146 pregnant mothers with dietary, anthropometric and biochemical measurements at 28 and 34 weeks gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood IGF-I and IGFBP-3 concentrations were measured at birth. Average cord IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) , respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively correlated with all birth size measures except length, and most strongly with neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21, 0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric characteristics, only parity was correlated with cord IGF-I (r = 0.27, P < 0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1) vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics, placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds. Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold quartile, P < 0.001). IGFBP-3 did not show significant relationships with these covariates. In this Indian study, cord IGF-I concentration was associated with greater adiposity among newborns. Maternal milk intake may play a role in this relationship.

Birth outcomes and background exposures to select elements, the Longitudinal Investigation of Fertility and the Environment (LIFE)

Evidence suggests that trace exposures to select elements may increase the risk for adverse birth outcomes. To investigate further, we used multiple regression to assess associations between preconception parental exposures to Pb, Cd, and total Hg in blood, and 21 elements in urine, with n=235 singleton birth outcomes, adjusted for confounders and partner's exposure. Earlier gestational age at delivery (GA) was associated with higher tertiles of urine maternal W (−1.22 days) and paternal U (−1.07 days), but GA was later for higher tertiles of maternal (+1.11 days) and paternal (+1.30 days) blood Hg. Additional analysis indicated shorter GA associated with higher paternal urine Ba, W, and U, and with higher maternal blood Pb for boys, but GA was longer in association with higher maternal urine Cr. Birth weight (BW) was lower for higher tertiles of paternal urine Cs (−237.85g), U (−187.34g), and Zn (−209.08g), and for higher continuous Cr (P=0.021). In contrast, BW was higher for higher tertiles of paternal urine As (+194.71g) and counterintuitively for maternal blood Cd (+178.52g). Birth length (BL) was shorter for higher tertiles of urine maternal W (−1.22cm) and paternal U (−1.10cm). Yet, higher tertiles of maternal (+1.11cm) and paternal (+1.30) blood Hg were associated with longer BL. Head circumference at delivery was lower for higher tertiles of paternal urine U (−0.83cm), and for higher continuous Mo in boys (−0.57cm). Overall, associations were most consistently indicated for GA and measures of birth size with urine W and U, and paternal exposures were more frequently associated than maternal. Though limited by several factors, ours is the largest multi-element investigation of prospective couple-level trace exposures and birth outcomes to date; the novel observations for W and U merit further investigation.

Association between dietary patterns during pregnancy and birth size measures in a diverse population in Southern US.

Despite increased interest in promoting nutrition during pregnancy, the association between maternal dietary patterns and birth outcomes has been equivocal. We examined maternal dietary patterns during pregnancy as a determinant of offspring’s birth weight-for-length (WLZ), weight-for-age (WAZ), length-for-age (LAZ), and head circumference (HCZ) Z-scores in Southern United States (n = 1151). Maternal diet during pregnancy was assessed by seven dietary patterns. Multivariable linear regression models described the association of WLZ, WAZ, LAZ, and HCZ with diet patterns controlling for other maternal and child characteristics. In bivariate analyses, WAZ and HCZ were significantly lower for processed and processed-Southern compared to healthy dietary patterns, whereas LAZ was significantly higher for these patterns. In the multivariate models, mothers who consumed a healthy-processed dietary pattern had children with significantly higher HCZ compared to the ones who consumed a healthy dietary pattern (HCZ β: 0.36; p = 0.019). No other dietary pattern was significantly associated with any of the birth outcomes. Instead, the major outcome determinants were: African American race, pre-pregnancy BMI, and gestational weight gain. These findings justify further investigation about socio-environmental and genetic factors related to race and birth outcomes in this population.