Maternal Urinary Concentrations Research Articles

TSH Mediated the Effect of Iodized Salt on Child Cognition in a Randomized Clinical Trial.

Objectives:This study examines the hormonal mediators of the effect of iodized salt in pregnancy on child cognition.Methods:Sixty districts across 6 zones in the Amhara region of Ethiopia were randomly allocated to a control or intervention arm of early market access to iodized salt. Twenty-two villages per arm were randomly selected for this sub-study. A total of 1220 pregnant women who conceived after the intervention began were enrolled and assessed for their iodine and iron status. Data were collected once on the household socio-demographic status and iodized salt use, and maternal urinary iodine during pregnancy. Then, infants’ diet, urinary iodine level, cognitive development (Bayley III), serum hormonal levels, iron status, and inflammation markers were measured between 2 and 13 months of age.Results:The median maternal urinary iodine concentration was adequate and significantly higher in the intervention mothers than that of the controls (163 vs 121 µg/L, P < .0001). Intervention children compared to the control children had lower thyroid-stimulating hormone (TSH) (mean: 2.4 ± 1.0 µIU/mL vs 2.7 ± 1.0 µIU/mL, effect size = 0.18, P < .01) and thyroglobulin (Tg) (41.6 ± 1.0 ng/mL vs 45.1 ± 1.0 ng/mL, effect size = 0.14, P < .05). There was an interaction between the intervention and iron stores such that cognition was higher with iron (effect size = 0.28, 100 vs 94 IQ points). TSH was a partial mediator (12%) of the effect of the intervention on child cognition (Sobel z-score = 2.1 ± 0.06, P < .05).Conclusion:TSH partially mediated the effect of the iodized salt intervention on child cognition.

Prenatal phthalate exposures and autism spectrum disorder symptoms in low-risk children

BackgroundPrenatal exposure to environmental chemicals has been associated with Autism Spectrum Disorder (ASD) symptoms in some, but not all, studies, but most research has not accounted for other childhood behavior problems. ObjectivesTo evaluate the specific associations of prenatal phthalate exposures with ASD symptoms in children (ages 3–6) accounting for other behavior problems, and to assess sex differences in these associations. MethodsWe measured phthalate metabolites in prenatal urine samples. Mothers completed the Social Responsiveness Scale-2nd edition (SRS-2) to assess child ASD symptoms and the Child Behavior Checklist (CBCL) to assess general behavior problems. We assessed associations of the sum of di-(2-ethylhexyl) phthalate metabolites, monobutyl phthalate, mono-isobutyl phthalate, and monoethyl phthalate (mEP) with ASD symptoms, adjusting for other behavior problems, using linear regression models (n=77). ResultsMost associations were null, and the sample size limited power to detect associations, particularly in the stratified analyses. After adjusting for internalizing and externalizing problems from the CBCL, ASD symptoms increased for each doubling of prenatal mEP concentration among boys only. ConclusionsFurther investigation of maternal prenatal urinary phthalate metabolite concentrations and ASD symptoms while adjusting for other behavioral problems is warranted.

Associations between prenatal and postnatal lead exposure and preschool children humoral and cellular immune responses

Studies have shown that lead exposure affected the immune function, but few studies have examined the relationships between in utero lead exposure, a sensitive period that is important for immune development, and later immune responses. To investigate the effects of prenatal and childhood lead exposure on the preschool-aged children’s immune responses, a prospective birth cohort study was established in Wuhan, China, in which lead concentrations were analyzed in maternal urine during the third trimester and in plasma samples from children aged about 3 years. We assessed immune responses by measuring immune cytokines in the children's plasma (n = 326) and peripheral blood T lymphocyte subsets (n = 394) at 3 years of age. Each unit increase in maternal urinary lead concentration (μg/g creatinine) was associated with reduced IL-10 (β = −5.93%, 95%CI: −11.82%, −0.03%) and reduced IL-4 levels (β = −5.62%, 95%CI: −10.44%, −0.80%). Lead in children’s plasma (μg/L) was associated with significant increase in TNF-α (β = 10.78%, 95%CI: 3.97%, 17.59%). No statistically significant relationship of childhood lead exposure with T lymphocyte subsets was observed. The study suggested prenatal and childhood lead exposure was associated with changes in preschool children’s plasma cytokine levels.

Maternal Cadmium Exposure and Neurobehavior in Children up to Age 8 Years: The HOME Study

Background: It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior. This study examined the potential associations between Cd exposure during pregnancy and neurobehavior among children. Methods: We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior. Results: We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: &lt; limit of detection (LOD), Group 2: 0.06-0.22 μg/g creatinine, Group 3: &gt;0.22-1.73 μg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years. Conclusions: No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1 to 8 years of age in this study.

Prenatal phthalate exposures and anthropometryduring adolescence: The HOME Study

Background/Aim: Phthalate exposures are ubiquitous in pregnant women and may be obesogenic. Although excess adolescent adiposity predicts obesity and cardiometabolic diseases during adulthood, few studies have examined associations between prenatal phthalate exposures and anthropometric outcomes during adolescence. We investigated the relationships between prenatal phthalate exposures and anthropometry at age 12 years.Methods: We used data from 219 mother-child pairs enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003-2006. We measured monobutyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and four metabolites of di-2-ethylhexyl phthalate (DEHP) in maternal urine samples collected at 16 and 26 weeks of pregnancy. At age 12 years, we measured child weight and height. We used multivariable linear regression to estimate covariate-adjusted associations of a 10-fold increase in average maternal urinary phthalate metabolite concentrations with age- and sex- standardized height, weight, and BMI z-scores. We assessed effect measure modification (EMM) by child sex using stratified models.Results: In adjusted analyses, maternal urinary phthalate metabolite concentrations were not associated with height, weight, or BMI z-scores in the overall sample. However, associations of MBzP concentrations with all anthropometry z-scores were modified by child sex, with lower z-scores among girls, but not boys. For example, a 10-fold increase in MBzP concentrations was associated with lower BMI z-scores in girls (β=-0.4; 95% CI: -0.9, 0.0) but not boys (β=0.2; 95% CI: -0.3, 0.7; EMM p-value=0.09). Additionally, a 10-fold increase in MiBP was associated with increased height z-scores among boys (β=0.7; 95% CI: 0.1, 1.3), but not girls (β=0.0; 95% CI: -0.6, 0.5; EMM p-value=0.09).Conclusions: In this prospective cohort study, higher prenatal phthalate exposures were not associated with adolescent anthropometry, but there may be sex-specific effects.

Maternal Urinary Benzophenone-3 Concentrations During Pregnancy and Duration of Breastfeeding

Background: Benzophenone-3, an ultraviolet-protectant used in some sunscreens and personal care products, is detectable in the urine of virtually all Americans. In animal models, gestational benzophenone-3 exposure leads to alterations in mammary gland morphology and function. However, it is unknown if benzophenone-3 exposure affects mammary gland function in humans. We estimated the association between maternal urinary benzophenone-3 concentrations during gestation and subsequent breastfeeding duration. Methods: We used data from 302 mother-child pairs in the HOME Study (Cincinnati, Ohio, enrolled: 2003-2006). We calculated average benzophenone-3 concentrations in two urine samples collected from women at 16- and 26-weeks gestation. After delivery, participants completed standardized interviewer-administered surveys on their breastfeeding practices every 3 months until discontinuation of breastfeeding or when children were age 3 years. We used a multivariable Poisson regression model with robust standard errors adjusted for relevant demographic and perinatal potential confounders to estimate the relative risk (RR) of discontinuing breastfeeding by age 3 months or 6 months with increasing benzophenone-3 concentrations.Results: Median urinary benzophenone-3 concentrations were 35 ng/mL (25th-75th percentile: 11-107). Approximately 57% and 44% of women fed their infants some breastmilk until 3 and 6 months, respectively. Increasing urinary benzophenone-3 concentrations were not associated with a higher risk of breastfeeding cessation at 3 months (RR for 3rd vs. 1st tercile=1.09; 95% CI: 0.75-1.58) or at 6 months (RR for 3rd vs. 1st tercile=1.13; 95% CI: 0.86-1.21).Conclusion: In this cohort, gestational urinary benzophenone-3 concentrations were not associated with duration of breastfeeding.

Gestational Triclosan Exposure and Infant Birth Weight: A Systematic Review and Meta-analysis

Background/Aim: Exposure to triclosan, an antimicrobial chemical used in personal care and cleaning products, has been associated with reduced birth weight in some, but not all studies. Thus, we conducted a systematic review and meta-analysis to characterize the relation of gestational triclosan exposure with infant birth weight, and identify potential sources of heterogeneity between studies. Methods: We identified original studies that measured maternal urinary triclosan concentrations during pregnancy and reported their association with infant birth weight. We considered birth weight, which we further characterized based on adjustment for gestational age or gestational age standardized birth weight z-scores. Using a random effects model, we estimated differences in these outcomes per 10-fold increase in triclosan concentrations. Results: Among thirteen identified studies, the range of median triclosan concentrations varied by approximately 2 orders of magnitude (0.6 to 29 ng/mL), with higher concentrations in North American and most European studies compared to Asian ones. Associations between triclosan and birth weight (β: -41g; 95% CI: -110, -28; n=4) were stronger than those when birth weight was adjusted for gestational age (β: -16g; 95% CI: -24, -8; n=8). Similarly, increasing triclosan was associated with modest decreases in birth weight z-scores (β: -0.08; 95% CI: -0.22, 0.07; n=4). The association between triclosan and gestational age adjusted birth weight was stronger in studies with higher median triclosan values &gt;10ng/mL compared to studies with median values &lt;10 ng/mL (β: -27g; 95% CI: -61, 7; n=3 vs. β: 6g; 95% CI: -20, 31; n=5). Conclusion: We observed that the association of urinary triclosan concentrations with birth weight varied by adjustment for gestational age and study-specific urinary triclosan concentrations. Our results suggest that urinary triclosan concentrations are associated with lower infant birth weight in populations with higher degrees of exposure prevalence.

Gestational exposure to organophosphate esters (OPEs) and maternal blood pressure during pregnancy: The HOME Study

Background: After the phase-out of polybrominated diphenyl ethers, exposure to organophosphate esters (OPEs), which are potential endocrine disruptors, is ubiquitous. No study has examined the associations between gestational exposure to OPEs and blood pressure and the risk of pregnancy-induced hypertensive diseases.Methods: We used data from 333 women who had liveborn singletons without congenital abnormalities in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort. We quantified maternal urinary OPE metabolites at 16 weeks of gestation. Outcomes included the highest maternal blood pressure measurement at ≥20 weeks of gestation and pregnancy-induced hypertensive diseases (gestational hypertension, preeclampsia, and eclampsia) from medical chart review. We used linear regression and modified Poisson regression with covariate adjustment to estimate the associations of exposure with blood pressure and the risk of pregnancy-induced hypertensive diseases, respectively.Results: Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.65 µg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.76 µg/g creatinine), bis(2-chloroethyl) phosphate (BCEP; 0.70 µg/g creatinine), and dibutyl phosphate (DBUP; 0.25 µg/g creatinine). There were 29 (8.7%) women diagnosed with pregnancy-induced hypertensive diseases. Average systolic and diastolic blood pressure, measured at an average of 31 weeks gestation (range: 20-41), were 117±13 and 72±9 mmHg, respectively. None of the urinary OPE metabolites were significantly associated with the highest maternal blood pressure at ≥20 weeks of gestation, nor were they strongly associated with an increased risk of pregnancy-induced hypertensive diseases. The relative risk (RR; 95% confidence interval) of pregnancy-induced hypertensive diseases by a 10-fold increase in exposure was 1.31 (0.66, 2.59) for DPHP, 1.36 (0.51, 3.67) for BDCIPP, 0.63 (0.16, 2.39) for BCEP and 2.13 (0.78, 5.77) for DBUP.Conclusion: This study suggests no associations between maternal urinary OPE metabolite concentrations and blood pressure or an increased risk of pregnancy-induced hypertensive diseases during pregnancy.

Urinary BPA Concentrations and Postpartum Depressive Symptoms: The HOME Study

Background/Aim: Bisphenol-A (BPA) is a suspected endocrine disrupting compound (EDC) that may adversely affect human health. In rodent studies, prenatal BPA exposure alters maternal behavior, including reduced caregiving behavior towards their pups. These rodent behaviors may be correlates of maternal postpartum depressive symptoms that include feeling withdrawn, numb/disconnected from their offspring, or in doubt of their caregiving ability.Methods: We analyzed data from the Health Outcomes and Measures of the Environment (HOME) Study (n=346), a cohort of pregnant women and their children in Cincinnati, Ohio, enrolled between March 2003 and January 2006. We measured BPA concentrations in urine samples collected at ~16 and 26 weeks gestation. Mothers self-reported depressive symptoms at approximately four weeks post-partum using the Beck Depression Inventory-II (BDI-II). Using linear and logistic regression, we estimated changes in continuous and categorical (&gt;mild vs. minimal symptoms) BDI-II scores, respectively, per interquartile range (IQR) increase in log10-transformed urinary BPA concentrations, adjusting for sociodemographic and perinatal factors.Results: The mean BDI-II score was 8.3 (25th and 75th percentiles: 5, 11). A total of 25 (7.2%), 13 (3.8%), and 6 (1.7%) women reported mild (scores: 14-19), moderate (scores: 20-28), and severe (scores: 29-63) depressive symptoms, respectively. Each IQR increase in log10-transformed urinary BPA concentration was associated with a 0.85-point increase in BDI-II score (95% CI: 0.2, 1.6). In addition, each IQR increase in BPA concentrations was associated with a 50% increased odds of having &gt; minimal depressive symptoms (95% CI: 1.0, 2.2).Conclusion: Higher maternal urinary BPA concentrations during pregnancy were associated with more postpartum depressive symptoms at four weeks among mothers in this study.

Exposure to heavy metals in utero and autism spectrum disorder at age 3

Background: Autism spectrum disorder is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an enriched-risk pregnancy cohort, maternal urinary metals concentrations at two time points during pregnancy were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed autism spectrum disorder with DSM-5 criteria. Using multivariable logistic regression, we tested each metal for association with autism spectrum disorder status, adjusting for gestational age, child sex, and maternal education.Results: In this enriched-risk study sample (n=167), 18.6% of children were diagnosed with autism spectrum disorder, 31.1% were non-neurotypical, and 50.9% were males. Mothers averaged 34 years old and 57.5% had greater than high school education. Median urinary metals concentrations were 0.04 ppb antimony, 6.8 ppb arsenic, 1.8 ppb barium, 0.12 ppb cadmium, 3.9 ppb cesium, 0.66 ppb cobalt, 8.5 ppb copper, 0.26 ppb lead, 0.26 ppb manganese, 0.22 ppb mercury, 51.8 ppb molybdenum, 3.5 ppb nickel, 39 ppb selenium, 0.14 ppb thallium, 0.37 ppb tin, and 245 ppb zinc. In early pregnancy, an interquartile range increase in barium concentration was associated with 2.33 (1.13, 4.82) higher odds of autism spectrum disorder, an interquartile range increase of cesium with 2.65 (1.37,5.13) higher odds, and an interquartile range increase in zinc with 2.11 (1.21, 3.69) higher odds. Having cadmium concentration over the level of detection was associated with 2.78 (1.02, 7.59) higher odds of autism spectrum disorder. Longitudinal analyses and mixtures analyses will be presented.Conclusion: Exposure in utero to elevated metals levels (barium, cesium, cadmium, zinc), as measured via maternal urine, was associated with increased odds of developing autism spectrum disorder. Prenatal timing of exposure and longitudinal clinical evaluations are critical.

Gestational phthalate exposures and bone mineral density in early adolescence: the HOME Study

Background/Aim: Phthalate exposures have been associated with lower areal bone mineral density (aBMD) and osteoporosis in adults. Although early life may be a period of heightened susceptibility to environmental osteotoxicants, we are unaware of any studies of phthalate exposures in utero and aBMD in children. Thus, we examined gestational phthalate exposures and early adolescent aBMD in a prospective birth cohort study. Methods: We used data from 225 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003-2006. We measured monobutyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and four metabolites of di-2-ethylhexyl phthalate (DEHP) in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We measured children’s femoral neck, distal forearm (1/3 radius), spine, total hip, and total body (excluding head) aBMD with dual x-ray absorptiometry at 12 years of age and calculated height-, age-, sex-, and race-specific aBMD z-scores. We estimated covariate-adjusted associations per 2-fold increase in maternal urinary phthalate concentrations and assessed effect measure modification (EMM) by child’s sex using sex-stratified models. Results: In adjusted analyses, higher MCPP and MEP concentrations were associated with greater aBMD at all sites with estimates generally stronger for MCPP. For example, associations of MCPP and MEP concentrations with total hip aBMD z-score were 0.16 (95% CI: 0.01, 0.32) and 0.09 (95% CI: 0.01, 0.17), respectively. Sex modified urinary MEP and MiBP concentration’s associations with spine aBMD. Higher MEP concentrations were associated with greater spine aBMD z-score in males (β = 0.19, 95% CI: 0.09, 0.30; EMM p-value 0.06) while higher MiBP concentrations were associated with greater spine aBMD z-score in females (β = 0.24, 95% CI: 0.07, 0.41; EMM p-value 0.07). Conclusions: Gestational phthalate exposures may increase bone mineral density in early adolescence.

Association of urinary bisphenols during pregnancy with maternal, cord blood and childhood thyroid function

BackgroundMost pregnant women are exposed to bisphenols, a group of chemicals that can interfere with various components of the thyroid system. ObjectivesTo investigate the association of maternal urinary bisphenol concentrations during pregnancy with maternal, newborn and early childhood thyroid function. MethodsThis study was embedded in Generation R, a prospective, population-based birth cohort (Rotterdam, the Netherlands). Maternal urine samples were analyzed for eight bisphenols at early (<18), mid (18–25) and late (>25 weeks) pregnancy. Maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and total thyroxine (TT4) were measured in early pregnancy and child TSH and FT4 were measured in cord blood and childhood. ResultsThe final study population comprised 1,267 mothers, 853 newborns and 882 children. Of the eight bisphenols measured, only bisphenol A (BPA) was detected in >50% of samples at all three time-points and bisphenol S (BPS) at the first time-point. There was no association of BPA or the bisphenol molar sum with maternal thyroid function. Higher BPS concentrations were associated with a higher maternal TT4 (β [95% CI] per 1 (natural-log) unit increase: 0.97 [0.03 to 1.91]) but there was no association with TSH or FT4. Furthermore, higher BPS was associated with an attenuation of the association between maternal FT4 and TSH (Pinteraction = 0.001). There was no association of early or mid-pregnancy BPA or early pregnancy BPS with cord blood or childhood TSH and FT4. A higher late pregnancy maternal BPA exposure was associated with a higher TSH in female newborns (Pinteraction = 0.06) and a higher FT4 during childhood in males (Pinteraction = 0.08). DiscussionOur findings show that exposure to bisphenols may interfere with the thyroid system during pregnancy. Furthermore, the potential developmental toxicity of exposure to bisphenols during pregnancy could affect the thyroid system in the offspring in a sex-specific manner.

Associations of maternal soy product consumption and urinary isoflavone concentrations with neonatal anthropometry: A prospective cohort study.

Isoflavones (ISOs) are naturally occurring endocrine-disrupting compounds. Few human studies have evaluated the effects of ISO exposure on neonatal anthropometry. This study aimed to examine the associations of maternal soy product consumption and urinary ISO concentrations, including genistein, daidzein, glycitein, and equol, with neonatal anthropometry, based on a Chinese cohort study. In Shanghai-Minhang Birth Cohort Study, pregnant women at 12-16 weeks of gestation were recruited, and they completed a structured questionnaire to assess soy product consumption during pregnancy. They also provided a single spot urine sample for the ISO assay. Neonatal anthropometric indices (birth weight; arm, waist, and head circumference; and triceps, back, and abdominal skinfold thickness) were measured at birth. Multivariable linear regression analysis was performed among the 1188 mother-infant pairs to examine the associations between maternal soy product consumption and neonatal anthropometry. The same statistical model was applied to examine the associations between maternal ISO exposure and neonatal anthropometry among 480 mother-infant pairs. Neonate girls born to mothers who "sometimes" and "frequent" consumed soy products had 169.1g (95% confidence interval [CI],-68.9-407.1) and 256.5g (95% CI, 17.1-495.8) higher birth weight, respectively, than those born to mothers who "never" consumed soy products during pregnancy. We observed consistent associations between higher maternal urine ISO concentrations and increased anthropometric indices (birth weight, arm and waist circumference, and triceps and abdominal skinfold thickness) in neonate girls, while no association was observed among boys. The findings suggested that maternal dietary ISO intake during pregnancy is associated with fetal development in a sex-specific pattern. In addition, follow-up studies are required to evaluate whether the observed changes in anthropometric indices at birth are associated with health conditions later in life.

Fetal exposure to phthalates and bisphenols and childhood general and organ fat. A population-based prospective cohort study.

Fetal exposure to phthalates and bisphenols might have long-lasting effects on growth and fat development. Not much is known about the effects on general and organ fat development in childhood. We assessed the associations of fetal exposure to phthalates and bisphenols with general and organ fat measures in school-aged children. In a population-based, prospective cohort study among 1128 mother-child pairs, we measured maternal urinary phthalate metabolites and bisphenol concentrations in first, second, and third trimester. Offspring body mass index, fat mass index by dual-energy X-ray absorptiometry, and visceral and pericardial fat indices and liver fat fraction were measured by magnetic resonance imaging at 10 years. After adjustment for confounders and correction for multiple testing, an interquartile range increase in first trimester phthalic acid concentrations remained associated with a 0.14 (95% confidence interval: 0.05, 0.22) standard deviation score increase in pericardial fat index. We also observed tendencies for associations of higher maternal low molecular weight phthalate urinary concentrations in second trimester with childhood pericardial fat index, but these were not significant after adjustment for multiple testing. High molecular weight phthalate, di-2-ethylhexyl phthalate, and di-n-octyl phthalate concentrations were not associated with childhood outcomes. Maternal urinary bisphenol concentrations were not associated with childhood adiposity. Maternal first trimester phthalic acid concentrations are associated with increased childhood pericardial fat index at 10 years of age, whereas maternal bisphenol concentrations are not associated with childhood adiposity. We did not find significant sex-specific effects. These findings should be considered as hypothesis generating and need further replication and identification of underlying mechanisms.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island

BackgroundOrganophosphate esters (OPEs)—used as flame retardants and plasticizers—are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors.MethodsWe quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks’ gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex.ResultsWe observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = − 0.50 cm, 95%CI = − 0.86, − 0.14) and female weight (β = − 0.19 kg, 95%CI = − 0.36, − 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28).ConclusionsCollectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Effects of an Iodine-Containing Prenatal Multiple Micronutrient on Maternal and Infant Iodine Status and Thyroid Function: A Randomized Trial in The Gambia.

Background: Iodine supplementation is recommended to pregnant women in iodine-deficient populations, but the impact in moderate iodine deficiency is uncertain. We assessed the effect of an iodine-containing prenatal multiple micronutrient (MMN) supplement in a rural Gambian population at risk of moderate iodine deficiency.Materials and Methods: This study uses data and samples collected as a part of the randomized controlled trial Early Nutrition and Immune Development (ENID; ISRCTN49285450) conducted in Keneba, The Gambia. Pregnant women (<20 weeks gestation) were randomized to either a daily supplement of MMNs containing 300 μg of iodine or an iron and folic acid (FeFol) supplement. Randomization was double blinded (participants and investigators). The coprimary outcomes were maternal urinary iodine concentration (UIC) and serum thyroglobulin (Tg), assessed at baseline and at 30 weeks' gestation. Secondary outcomes were maternal serum thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) (assessed at baseline and at 30 weeks' gestation), breast milk iodine concentration (BMIC) (assessed at 8, 12, and 24 weeks postpartum), infant serum Tg (assessed at birth [cord], 12, and 24 weeks postpartum), and serum TSH (assessed at birth [cord]). The effect of supplementation was evaluated using mixed effects models.Results: A total of 875 pregnant women were enrolled between April 2010 and February 2015. In this secondary analysis, we included women from the MMN (n = 219) and FeFol (n = 219) arm of the ENID trial. At baseline, median (interquartile range or IQR) maternal UIC and Tg was 51 μg/L (33–82) and 22 μg/L (12–39), respectively, indicating moderate iodine deficiency. Maternal MMN supplement increased maternal UIC (p < 0.001), decreased maternal Tg (p < 0.001), and cord blood Tg (p < 0.001) compared with FeFol. Maternal thyroid function tests (TSH, TT3, TT4, and TT3/TT4 ratio) and BMIC did not differ according to maternal supplement group over the course of the study. Median (IQR) BMIC, maternal UIC, and infant Tg in the MMN group were 51 μg/L (35–72), 39 μg/L (25–64), and 87 μg/L (59–127), respectively, at 12 weeks postpartum, and did not differ between supplement groups.Conclusions: Supplementing moderately iodine-deficient women during pregnancy improved maternal iodine status and reduced Tg concentration. However, the effects were not attained postpartum and maternal and infant iodine nutrition remained inadequate during the first six months after birth. Consideration should be given to ensuring adequate maternal status through pregnancy and lactation in populations with moderate deficiency.

Prenatal exposure to organophosphate pesticides and brain morphology and white matter microstructure in preadolescents

BackgroundPrenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9–12 years. MethodData came from 518 mother–child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9–12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and cortical surface area, and diffusion tensor imaging was used to measure white matter microstructure through fractional anisotropy (FA) and mean diffusivity (MD). Linear regression models were fit for the averaged prenatal exposure across pregnancy. ResultsDM and DE metabolite concentrations were not associated with brain volumes, cortical thickness, and cortical surface area. However, a 10-fold increase in averaged DM metabolite concentrations across pregnancy was associated with lower FA (B = −1.00, 95%CI = −1.80, −0.20) and higher MD (B = 0.13, 95%CI = 0.04, 0.21). Similar associations were observed for DE concentrations. ConclusionsThis study provides the first evidence that OP pesticides may alter normal white matter microstructure in children, which could have consequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area.

Maternal phthalate exposure associated with decreased testosterone/LH ratio in male offspring during mini-puberty. Odense Child Cohort

BackgroundPhthalates are plastic softeners with anti-androgenic properties. Prenatal exposure has led to lower testosterone (T) levels and smaller testicles in adult rats. To our knowledge, no studies have examined associations between prenatal phthalate exposure and sex hormone concentrations in infants. ObjectiveTo study associations between phthalate exposure in Danish pregnant women and T, luteinizing hormone (LH), follicle stimulating hormone (FSH), Δ4-androstenedione (adion), 17α-hydroxyprogesterone (17-OHP) dehydroepiandrosterone sulfate (DHEAS) concentrations in their infants (N = 479) during mini-puberty. MethodsConcentrations of 12 phthalate metabolites from six phthalate diesters were measured in urine samples collected from 2010 to 2012 from 479 pregnant women participating in the Odense Child Cohort at gestational week 28 (range 20.4–30.4). Serum T, LH, FSH, adion, 17-OHP, DHEAS, weight and height were measured approximately three months after expected date of birth. Associations between prenatal phthalate exposure and gonadotropin and androgen metabolite concentrations were estimated in boys and girls separately in adjusted linear regression models. ResultsT concentration was lower in boys prenatally exposed to phthalates. Maternal urinary concentrations of summed mono-iso-butyl and mono-n-butyl phthalate (∑MBPi+n) and summed metabolites of di-iso-nonyl phthalate (∑DiNPm) were associated with lower T/LH ratio in male offspring and a dose-response association was found. FSH was 14% (95% CI: 1; 25) lower among male offspring from mothers exposed to ∑DiNPm in the highest compared to the lowest tertile. No association was found for girls. ConclusionEven in these low exposed children, we found a significant decrease in T/LH ratio during mini-puberty in boys prenatally exposed to phthalates, which may suggest impairment of Leydig cells. The children will be followed as they approach adrenarche and pubarche in order to assess if long-term adverse effects persist.

Exposure to uranium and co-occurring metals among pregnant Navajo women

Navajo Nation residents are at risk for exposure to uranium and other co-occurring metals found in abandoned mine waste. The Navajo Birth Cohort Study (NBCS) was initiated in 2010 to address community concerns regarding the impact of chronic environmental exposure to metals on pregnancy and birth outcomes. The objectives of this paper were to 1) evaluate maternal urine concentrations of key metals at enrollment and delivery from a pregnancy cohort; and 2) compare the NBCS to the US general population by comparing representative summary statistical values. Pregnant Navajo women (N = 783, age range 14–45 years) were recruited from hospital facilities on the Navajo Nation during prenatal visits and urine samples were collected by trained staff in pre-screened containers. The U.S. Centers for Disease Control and Prevention (CDC), National Center for Environmental Health's (NCEH) Division of Laboratory Sciences (DLS) analyzed urine samples for metals. Creatinine-corrected urine concentrations of cadmium decreased between enrollment (1st or 2nd trimester) and delivery (3rd trimester) while urine uranium concentrations were not observed to change. Median and 95th percentile values of maternal NBCS urine concentrations of uranium, manganese, cadmium, and lead exceeded respective percentiles for National Health and Nutrition Evaluation Survey (NHANES) percentiles for women (ages 14–45 either pregnant or not pregnant.) Median NBCS maternal urine uranium concentrations were 2.67 (enrollment) and 2.8 (delivery) times greater than the NHANES median concentration, indicating that pregnant Navajo women are exposed to metal mixtures and have higher uranium exposure compared to NHANES data for women. This demonstrates support for community concerns about uranium exposure and suggests a need for additional analyses to evaluate the impact of maternal metal mixtures exposure on birth outcomes.

Weight and head circumference at birth in function of placental paraben load in Belgium: an ENVIRONAGE birth cohort study

BackgroundParabens are a group of esters of para-hydroxybenzoic acid utilized as antimicrobial preservatives in many personal care products. Epidemiological studies regarding the adverse effects of parabens on fetuses are limited. The aim of this study was to determine the association between placental paraben exposure and birth outcomes. We assessed paraben concentrations in placental tissue, which potentially gives a better understanding of fetal exposure than the maternal urinary concentrations which are the current golden standard.MethodsPlacental tissue was collected immediately after birth from 142 mother-child pairs from the ENVIRONAGE birth cohort. The placental concentrations of four parabens (methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)) were determined by ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Generalized linear regression models were used to determine the association between paraben exposure levels and birth outcomes.ResultsThe geometric means of placental MeP, EtP, PrP, and BuP were 1.84, 2.16, 1.68 and 0.05 ng/g tissue, respectively. The sum of parabens (∑ parabens, including MeP, EtP and PrP) was negatively associated with birth weight in newborn girls (− 166 g, 95% CI: − 322, − 8.6, p = 0.04) after adjustment for a priori selected covariates. The sum of parabens was negatively associated with head circumference (− 0.6 cm, 95% CI: − 1.1, − 0.2, p = 0.008) and borderline associated with birth length (− 0.6 cm, 95% CI:-1.3, 0.1, p = 0.08). In newborn girls the placental concentration of EtP was negatively associated with head circumference (− 0.6 cm, 95% CI:-1.1, − 0.1, p = 0.01) and borderline significantly associated with birth weight and birth length. Lastly, placental EtP and ∑parabens were negatively associated with placental weight in newborn girls but not in newborn boys (− 45.3 g, 95% CI:-86.2, − 4.4, p = 0.03).ConclusionThe negative association between maternal paraben exposure and birth outcomes warrants further research and follow-up over time to determine long term effects of gestational exposure to parabens.