Prenatal lead exposure and fetal growth: Smaller infants have heightened susceptibility.

2017

228-233

2017 Feb

1873-6750

<p><strong>BACKGROUND: </strong>As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth.</p>

<p><strong>OBJECTIVES: </strong>To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth.</p>

<p><strong>METHODS: </strong>We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders.</p>

<p><strong>RESULTS: </strong>While linear regression showed a negative association between maternal BLL and BWGA z-score (β=-0.06 z-score units per log BLL increase; 95% CI: -0.13, 0.003; P=0.06), quantile regression revealed larger magnitudes of this association in the &lt;30th percentiles of BWGA z-score (β range [-0.08, -0.13] z-score units per log BLL increase; all P values&lt;0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99-2.65) for having a SGA infant compared to the lowest BLL quartile.</p>

<p><strong>CONCLUSIONS: </strong>While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation.</p>

10.1016/j.envint.2016.11.023

Environ Int

27923585

Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study.

2018

34-41

2018 01

1534-7796

<p><strong>OBJECTIVE: </strong>Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico.</p>

<p><strong>METHODS: </strong>A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing.</p>

<p><strong>RESULTS: </strong>An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference.</p>

<p><strong>CONCLUSIONS: </strong>Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.</p>

10.1097/PSY.0000000000000517

Psychosom Med

28787364

Prenatal lead exposure modifies the effect of shorter gestation on increased blood pressure in children.

2018

464-471

2018 Aug 23

1873-6750

<p><strong>BACKGROUND: </strong>High blood pressure (BP) in childhood is frequently renal in origin and a risk factor for adult hypertension and cardiovascular disease. Shorter gestations are a known risk factor for increased BP in adults and children, due in part to a nephron deficit in children born preterm. As nephrogenesis is incomplete until 36 weeks gestation, prenatal lead exposure occurring during a susceptible period of renal development may contribute to programming for later life renal disease. The relationship between shorter gestation and children's BP has not yet been explored to identify i) critical windows using nonlinear piecewise models or ii) combined with other early life risk factors such as prenatal lead exposure.</p>

<p><strong>OBJECTIVES: </strong>(1) To evaluate the nonlinear relationship between lower gestational age and childhood BP measured at 4-6 years of age, and (2) to investigate modification by prenatal lead exposure.</p>

<p><strong>METHODS: </strong>In a prospective longitudinal birth cohort, we assessed 565 children between 4 and 6 years of age (mean: 4.8 years) in the PROGRESS cohort in Mexico City, Mexico. Gestational age at delivery was calculated using maternal report of last menstrual period (LMP) and confirmed with Capurro physical examination at birth. We measured pregnant women's blood lead levels (BLLs) in the second trimester via inductively coupled plasma-mass spectrometry and children's BP using an automated device. We performed both linear and nonlinear piecewise regression analyses to examine associations of gestational age with children's BP adjusting for children's age, sex, height, prenatal exposure to smoke, and maternal socioeconomic status. We stratified to assess modification by prenatal lead exposure, and used a data-adaptive approach to identify a lead cutpoint.</p>

<p><strong>RESULTS: </strong>Maternal second trimester BLLs ranged from 0.7 to 17.8 μg/dL with 112 (20%) women above the CDC guideline level of 5 μg/dL. In adjusted linear regression models, a one week reduction in gestational age was associated with a 0.5 mm Hg (95%CI: 0.2, 0.8) increase in SBP and a 0.4 mm Hg (95%CI 0.1, 0.6) increase in DBP. Our nonlinear models suggested evidence for different magnitude estimates on either side of an estimated join-point at 35.9 weeks' gestation, but did not reach statistical significance. However, when stratified by prenatal lead exposure, we identified a cutpoint lead level of concern of 2.5 μg/dL that suggested an interaction between gestational age and blood lead. Specifically, for BLLs ≥ 2.5 μg/dL, SBP was 1.6 (95%CI: 0.3, 2.9) mm Hg higher per each week reduction in gestational age among children born before 37.0 weeks; and among children born after 37.0 weeks, this relationship was attenuated yet remained significant [β: 0.9, 95%CI (0.2, 1.6)]. At BLLs below 2.5 μg/dL, there was no appreciable association between lower gestational age and SBP.</p>

<p><strong>CONCLUSIONS: </strong>Our findings suggest that shorter gestation combined with higher prenatal lead exposure contributes to a higher risk of increased SBP at 4-6 years of age, particularly among infants born &lt;37 weeks gestation. Our results underscore the importance of preventing prenatal lead exposure - even levels as low as 2.5 μg/dL - especially among pregnant women at risk for preterm birth. Given that high BP in childhood is a risk factor for adult hypertension and cardiovascular disease later in life, these results may have implications that extend across the life span.</p>

10.1016/j.envint.2018.08.038

Environ Int

30145310