Effect of prenatal exposure to organophosphates and pyrethroid pesticides on neonatal anthropometric measures and gestational age.

Several studies have examined the association between prenatal exposure to organophosphate and pyrethroid pesticides and their impact on foetal growth and newborn anthropometry; however, the available evidence is limited and inconclusive. This study examined whether prenatal organophosphate and pyrethroid pesticide exposure was associated with anthropometric measures at birth (weight, length, head circumference), ponderal index, gestational age, and prematurity in 537 mother-child pairs. These were randomly selected from the 800 pairs participating in the prospective birth cohort GENEIDA (Genetics, early life environmental exposures and infant development in Andalusia). Six non-specific organophosphate metabolites (dialkylphosphates, DAPs), one metabolite relatively specific to chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy) and a common metabolite to several pyrethroids (3-phenoxybenzoic acid, 3-PBA) were measured in maternal urine from the 1st and 3rd pregnancy trimesters. Information on anthropometric measures at birth, gestational age and prematurity was retrieved from medical records. The sum on a molar basis of DAPs with methyl (Æ©DMs) and ethyl (Æ©DEs) moieties and the sum of the 6 DAPs metabolites (Æ©DAPs) was calculated for both trimesters of pregnancy. High urinary levels of dimethyl phosphate (DMP) during the 3rd trimester were associated with a decrease in birth weight (ß = -0.24; 95% CI: 0.41; -0.06) and birth length (ß = -0.20; 95% CI: 0.41; 0.02). Likewise, ΣDMs during 3rd trimester were near-significantly associated with decreased birth weight (ß = -0.18; 95% CI: 0.37; 0.01). In turn, increased urinary TCPy during 1st trimester was associated with a decreased head circumference (ß = -0.31; 95% CI: 0.57; -0.06). Finally, an increase in 3-PBA in the 1st trimester was associated with a decreased gestational age (ß = -0.36 95% CI: 0.65-0.08), whereas increased 3-PBA at 1st and 3rd trimester was associated with prematurity. These results indicate that prenatal exposure to organophosphate and pyrethroid insecticides could affect normal foetal growth, shorten gestational age and alter anthropometric measures at birth.

The Effect of Size and Asymmetry at Birth on Brain Injury and Neurodevelopmental Outcomes in Congenital Heart Disease.

Poor and asymmetric fetal growth have been associated with neonatal brain injury (BI) and worse neurodevelopmental outcomes (NDO) in the growth-restricted population due to placental insufficiency. We tested the hypothesis that postnatal markers of fetal growth (birthweight (BW), head circumference (HC), and head to body symmetry) are associated with preoperative white matter injury (WMI) and NDO in infants with single ventricle physiology (SVP) and d-transposition of great arteries (TGA). 173 term newborns (106 TGA; 67 SVP) at two sites had pre-operative brain MRI to assess for WMI and measures of microstructural brain development. NDO was assessed at 30 months with the Bayley Scale of Infant Development-II (n = 69). We tested the association between growth parameters at birth with the primary outcome of WMI on the pre-operative brain MRI. Secondary outcomes included measures of NDO. Newborns with TGA were more likely to have growth asymmetry with smaller heads relative to weight while SVP newborns were symmetrically small. There was no association between BW, HC or asymmetry and WMI on preoperative brain MRI or with measures of microstructural brain development. Similarly, growth parameters at birth were not associated with NDO at 30 months. In a multivariable model only cardiac lesion and site were associated with NDO. Unlike other high-risk infant populations, postnatal markers of fetal growth including head to body asymmetry that is common in TGA is not associated with brain injury or NDO. Lesion type appears to play a more important role in NDO in CHD.

Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain).

We assessed whether prenatal selenium (Se) exposure is associated with anthropometry at birth, placental weight and gestational age. Study subjects were 1249 mother-child pairs from the Valencia and Gipuzkoa cohorts of the Spanish Childhood and Environment Project (INMA, 2003-2008). Se was determined in serum samples taken at the first trimester of pregnancy. Socio-demographic and dietary characteristics were also collected by questionnaires. Mean (SD) serum Se concentration was 79.57 (9.64) µg/L. Se showed weak associations with both head circumference and gestational age. The association between serum Se concentration and birth weight and length was negative, and direct for placental weight and probability of preterm birth, although the coefficients did not reach statistical significance. Individuals with total mercury (THg) levels >15 µg/L reversed the serum Se concentration effect on head circumference. Significant interactions were found between sex and both gestational age and prematurity. Spontaneous birth gestational ages were estimated to be lower for males and their probability of prematurity was higher. In conclusion, prenatal Se exposure may be associated with lower head circumference and lower gestational ages at spontaneous birth. Interactions with THg exposure and gender should be considered when assessing these relationships.

Impact of gestational weight gain on fetal growth in obese normoglycemic mothers: a comparative study.

OBJECTIVE: To assess the pattern of gestational weight gain (GWG) and its effect on fetal growth among normogylycemic obese and lean mothers. DESIGN: Prospective longitudinal study. SETTING: Teaching hospitals, Sheffield, UK. POPULATION: Forty-six euglycemic obese and 30 lean mothers and their offspring. METHOD: The contrast slope of GWG was calculated and its impact on fetal growth trajectory and birth anthropometry examined in both groups. RESULTS: The GWG contrast slope trended significantly upward in both groups but it was steeper among lean mothers (p = 0.003), particularly in second trimester. Lean mothers had a biphasic GWG pattern with a higher early weight gain (p = 0.02), whereas obese mothers had a monophasic GWG. Both groups had similar third trimester GWG. The GWG contrast slope was influenced by early pregnancy maternal anthropometry in the obese group only. Nonetheless, the obese mothers' glucose and insulin indices had no significant relationship to GWG. GWG had a significant positive relationship with intrauterine femur length (r = 0.32, p = 0.04) and abdominal circumference (r = 0.42, p = 0.006) growth trajectories, as well as birthweight standard deviation scores (r = 0.32, p = 0.036) and the ponderal index (r = 0.45, p = 0.003) in the obese mothers. CONCLUSIONS: Gestational weight gain among lean mothers is biphasic and significantly higher than their obese counterparts, but without effect on fetal growth. The obese mothers' monophasic weight gain was influenced by their anthropometry, but not by their insulin or glucose indices, and impacted on the growth of their babies.

Maternal and Neonatal Vitamin D Binding Protein Polymorphisms and 25-Hydroxyvitamin D Cutoffs as Determinants of Neonatal Birth Anthropometry.

BACKGROUND: Vitamin D-binding protein (VDBP) is a vital regulator of optimal vitamin D homeostasis and bioavailability. Apart from its well-documented role as a key component in vitamin D dynamic transfer and circulation, it has a myriad of immunoregulatory functions related to innate immunity, which becomes particularly critical in states of increased immunological tolerance including pregnancy. In this regard, VDBP dyshomeostasis is considered to contribute to the development of several fetal, maternal, and neonatal adverse outcomes. However, precise physiological pathways, including the contribution of specific VDBP polymorphisms behind such phenomena, are yet to be fully deciphered. Our aim was to assess the combined effect of maternal and neonatal VDBP polymorphism heterogeneity in conjunction with different maternal and neonatal 25(OH)D cutoffs on the neonatal anthropometric profile at birth. METHODS: The study included data and samples from a cohort of 66 mother-child pairs at birth. The inclusion criterion was full-term pregnancy (gestational weeks 37-42). Neonatal and maternal 25(OH)D cutoffs were included according to vitamin D status at birth and delivery. Concentrations of 25(OH)D2 and 25(OH)D3 were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The upper arm length of neonates with 25(OH)D ≤ 25 nmol/L was higher in neonate CC carriers for rs2298850. The upper thigh neonatal circumference was also higher in the ones with either 25(OH)D ≤ 50 or ≤75 nmol/L in rs2298850 CG + GG or rs4588 GT + TT carriers. We did not observe any significant effect for maternal VDBP polymorphisms nor for birth maternal 25(OH)D concentrations, on birth neonatal anthropometry. CONCLUSIONS: Our findings emphasize a potential role for neonatal VDBP genotypes rs2298850 and rs4588, in conjunction with specific neonatal 25(OH)D cutoffs, in the range of sufficiency on neonatal growth and development.

Birth anthropometry predicts neonatal and infant mortality in rural Bangladesh: a focus on circumferential measurements.

BACKGROUND: Low birth weight predicts risk of infant death. However, several birth measurements may be equally predictive, for which cutoffs and associated risks are less explored. OBJECTIVES: We assessed and optimized population cutoffs of birth length, weight, and midupper arm circumference (MUAC), head circumference (HC), and chest circumference (CC) for predicting neonatal (≤28 d) and infant (≤365 d) mortality in northwest Bangladesh. METHODS: Among 28,026 singletons born in an antenatal micronutrient supplement trial, 21,174 received anthropometry ≤72 h after birth, among whom 583 died in infancy. Optimization for predicting mortality for each measurement was guided by the Youden Index (sensitivity + specificity - 1). Relative risk ratios (RRRs) and positive predictive values (PPVs) were calculated across cutoff ranges for individual and any pair of measurements. RESULTS: Optimal cutoffs, harmonized to 100-g or 0.5-cm readings, for neonatal and infant mortality were 44.5 cm for length, 2200 g for weight, 9.0 cm for MUAC, 31.0 cm for HC, and 28.5 cm for CC, below which all predicted mortality. However, a CC <28.5 cm, alone and combined with HC <31.0 cm, yielded the highest RRR [9.68 (95% CI: 7.84, 11.94) and 15.74 (95% CI: 12.54, 19.75), respectively] and PPV (11.3% and 10.7%) for neonatal mortality and highest RRR [6.02 (95% CI: 5.15, 7.02) and 9.19 (95% CI: 7.72, 10.95)] and PPV (16.3% and 14.5%) for infant mortality. Pairs of measurements revealed a higher RRR for neonatal and infant mortality than individual measurements of any one pair, although the ranges of PPV remained comparable. CONCLUSIONS: In Bangladesh, multiple birth measurements alone or in combination, particularly chest circumference, predict neonatal and infant mortality.

Diverse Effects of Combinations of Maternal-Neonatal VDR Polymorphisms and 25-Hydroxyvitamin D Concentrations on Neonatal Birth Anthropometry: Functional Phenocopy Variability Dependence, Highlights the Need for Targeted Maternal 25-Hydroxyvitamin D Cut-Offs during Pregnancy.

Vitamin D receptor (VDR) polymorphisms have been associated with a plethora of adverse pregnancy and offspring outcomes. The aim of this study was to evaluate the combined effect of maternal and neonatal VDR polymorphisms (ApaI, TaqI, BsmI, FokI, Tru9I) and different maternal and neonatal 25(OH)D cut-offs on neonatal birth anthropometry. This cross-sectional study included data and samples from a cohort of mother-child pairs at birth. A detailed neonatal anthropometry analysis at birth was also conducted. Different 25(OH)D cut-offs for neonates and mothers were included, according to their vitamin D status at birth: for neonates, cut-offs of [25(OH)D ≤ 25 and > 25 nmol/L] and [25(OH)D ≤ 50 nmol/L] were adopted, whereas for mothers, a 25(OH)D cut-off of [25(OH)D ≤ 50 and > 50 nmol/L)] was investigated. Following this classification, maternal and neonatal VDR polymorphisms were evaluated to investigate the potential different effects of different neonatal and maternal 25(OH)D cut-offs on neonatal birth anthropometry. A total of 69 maternal-neonatal dyads were included in final analysis. Weight, neck rump length, chest circumference, abdominal circumference, abdominal circumference (iliac), high thigh circumference, middle thigh circumference, lower arm radial circumference, and lower leg calf circumference of neonates who had the TAQl SNP TT genotype and maternal 25(OH)D < 50 nmol/L were significantly higher than that of neonates who had the Tt or tt genotypes (p = 0.001, Hg = 1.341, p = 0.036, Hg = 0.976, p = 0.004, Hg = 1.381, p = 0.001, Hg = 1.554, p = 0.001, Hg = 1.351, p = 0.028, Hg = 0.918, p = 0.008, Hg = 1.090, p = 0.002, Hg = 1.217, and p = 0.020, Hg = 1.263, respectively). Skin fold high anterior was significantly lower in neonates who had the BSMI SNP BB genotype compared to that of neonates with Bb or bb genotypes (p = 0.041, Hg = 0.950), whereas neck rump length was significantly higher in neonates who had the FOKI SNP FF genotype compared to that of neonates who had Ff or ff genotypes (p = 0.042, Hg = 1.228). Regarding neonatal VDR polymorphisms and cut-offs, the abdominal circumference (cm) of neonates who had the TAQI SNP TT genotype and 25(OH)D < 25 nmol/L were significantly higher than that of neonates who had the Tt or tt genotypes (p = 0.038, Hg = 1.138). In conclusion, these results indicate that the maternal TAQI VDR polymorphism significantly affected neonatal birth anthropometry when maternal 25(OH) concentrations were <50 nmol/L, but not for a higher cut-off of >50 nmol/L, whereas this effect is minimally evident in the presence of neonatal TAQI polymorphism with neonatal 25(OH)D values <25 nmol/L. The implication of these findings could be incorporated in daily clinical practice by targeting a maternal 25(OH)D cut-off >50 nmol/L, which could be protective against any effect of genetic VDR variance polymorphism on birth anthropometry.

Impact of opioid maintenance treatment during pregnancy on neonatal birth weight and head circumference.

BACKGROUND: Pregnant mothers with opioid dependency commonly receive maintenance treatment of opioid (OMT), either as buprenorphine (BMT) or methadone maintenance treatment (MMT). We investigated, whether OMT adversely affects standardized neonatal anthropometric outcomes and whether BMT is potentially safer than MMT in this regard. METHODS: Retrospective chart review of mother infant dyad, with and without OMT. Infant's absolute and standardized (z-score) anthropometric outcomes at birth were first compared, between OMT and control group (negative meconium drug screen), and then between BMT and MMT group. These outcomes were also compared between infants who did or did not require treatment after birth for neonatal abstinence syndrome (NAS). RESULT: A total of 1479 participants with MDS were included [Control = 1251; OMT = 228 (MMT = 181; BMT = 47)]. Both the z-scores of birth weight (BW) and head circumference (HC) was lower in OMT group (p < 0.001). Among the OMT group, GA at delivery was slightly higher in the BMT group (p = 0.05). There was an inverse correlation between maternal dose at the time of delivery and anthropometric z-scores in the BMT group, mainly in female infants (BW: p = 0.006; HC: p = 0.003). Furthermore, In BMT group, infants with lower HC were more likely to require treatment for NAS (p = 0.01). CONCLUSION: HC and BW when comparing Z-scores were not different between MMT and BMT. High maternal dosing of buprenorphine is associated with lower BW and HC Z-scores but dose effect is not seen with methadone. In addition, there seems to be an association between NAS severity and HC, especially in the BMT group.

Birth anthropometry and cord blood leptin in Korean appropriate-for-gestational-age infants born at ≥ 28 weeks' gestation: a cross sectional study.

BACKGROUND: We investigated whether leptin during the third trimester was associated with fetal growth compared to IGF-1. METHODS: One hundred five appropriate-for-gestational-age (AGA) infants born at ≥28 weeks' gestation were enrolled. Cord blood leptin and insulin like growth factor 1 (IGF-1) were collected simultaneously during delivery. Enrolled infants were stratified into three groups according to GA as follows: 28 to < 34 weeks' gestation, very preterm (VP); 34 to < 37 weeks' gestation, late preterm (LP); and 37 to < 41 weeks' gestation, term. Birth weight (BW), birth length (BL), head circumference (HC), and body mass index (BMI) were measured. Leptin and IGF-1 were logarithmically transformed to normalize their distributions in multivariable regression analysis. RESULTS: Sixty-eight infants out of 105 infants were preterm (32.5 ± 2.5 weeks), and 37 infants were term (37.8 ± 1.2 weeks). BW, BL, HC, and BMI were higher with increasing gestational age among the three gestational age-specific groups. With regard to hormones, leptin and IGF-1 were higher with increasing gestational age. Log cord serum leptin was independently associated with BW and BL in multivariable linear regression analysis, after adjustment for confounding factors including gestational age, delivery mode, multiple pregnancy, pregnancy induced hypertension, gestational diabetes mellitus, infant's BMI, and log cord blood IGF-1 levels. CONCLUSIONS: During the third trimester, cord serum leptin was independently associated with fetal growth.