Correction to: Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico.

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Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico.

The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women's metabolism of As as indicated by greater proportions of MMAs and smaller proportions of  DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 µmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.

Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico.

BACKGROUND: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. OBJECTIVES: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. METHODS: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. RESULTS: DW-iAs for the study subjects ranged from < 0.5 to 236 µg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 µg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. CONCLUSIONS: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.

Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants.

OBJECTIVE: To examine the effect of early initiation of caffeine therapy on neonatal outcomes and characterize the use of caffeine therapy in very low birth weight (VLBW) infants. STUDY DESIGN: We analyzed a cohort of 62 056 VLBW infants discharged between 1997 and 2010 who received caffeine therapy. We compared outcomes in infants receiving early caffeine therapy (initial dose before 3 days of life) and those receiving late caffeine therapy (initial dose at or after 3 days of life) through propensity scoring using baseline and early clinical variables. The primary outcome was the association between the timing of caffeine initiation and the incidence of bronchopulmonary dysplasia (BPD) or death. RESULTS: We propensity score-matched 29 070 VLBW infants at a 1:1. Of infants receiving early caffeine therapy, 3681 (27.6%) died or developed BPD, compared with 4591 infants (34.0%) receiving late caffeine therapy (OR, 0.74; 99% CI, 0.69-0.80). Infants receiving early caffeine had a lower incidence of BPD (23.1% vs 30.7%; OR, 0.68; 95% CI, 0.63-0.73) and a higher incidence of death (4.5% vs 3.7%; OR, 1.23; 95% CI, 1.05-1.43). Infants receiving early caffeine therapy had less treatment of patent ductus arteriosus (OR, 0.60; 95% CI, 0.55-0.65) and a shorter duration of mechanical ventilation (mean difference, 6 days; P < .001). CONCLUSION: Early caffeine initiation is associated with a decreased incidence of BPD. Randomized trials are needed to determine the efficacy and safety of early caffeine prophylaxis in VLBW infants.

Effects of pre-pregnancy body mass index and gestational weight gain on infant anthropometric outcomes.

OBJECTIVE: To determine whether pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) influence infant postnatal growth. STUDY DESIGN: Participants were from the Pregnancy, Infection, and Nutrition study, a prospective pregnancy cohort. Term infants with weight or length measurements at approximately 6 months were included (n = 363). Multivariable regression estimated associations for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length z-scores (WLZ) and rapid infant weight gain with categorical maternal exposures defined with the 2009 Institute of Medicine recommendations. RESULTS: Pre-pregnancy overweight and obesity were associated with higher WAZ (linear regression coefficient [ß], 0.32; 95% CI, 0.04-0.61) and WLZ (ß, 0.39; 95% CI, 0.02-0.76), respectively. Pre-pregnancy BMI was not associated with LAZ. Excessive GWG was associated with higher WAZ (ß, 0.39; 95% CI, 0.15-0.62) and LAZ (ß, 0.34; 95% CI, 0.12-0.56). Excessive GWG ≥ 200% of recommended amount was associated with higher WAZ (ß, 0.68; 95% CI, 0.28-1.07), LAZ (ß, 0.45; 95% CI, 0.06-0.83), and WLZ (ß, 0.43; 95% CI, 0.04-0.82). Risk of rapid weight gain increased across maternal exposure categories; however, none of the estimates were significant. CONCLUSIONS: Pre-pregnancy BMI and GWG are modifiable intrauterine exposures that influence infant postnatal anthropometric outcomes. Further investigation with infant body composition measurements is warranted.