<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>

<p><strong>BACKGROUND: </strong>Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water.</p>

<p><strong>OBJECTIVE: </strong>Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study.</p>

<p><strong>DESIGN/METHODS: </strong>We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression. models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (&lt;10th percentile, SGA) and large-for-gestational age (&gt;90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic.</p>

<p><strong>RESULTS: </strong>Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) μg/L, maternal third trimester 0.75 (0.41) μg/L, maternal at delivery 0.85 (0.70) μg/L, and infant cord 0.78 (0.65) μg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r = 0.65, p &lt; 0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR = 1.44, 95% CI: 1.08-1.93) and LGA (adj. OR = 2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR = 1.46, 95% CI: 0.67-3.12).</p>

<p><strong>CONCLUSION: </strong>We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.</p>

<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>