Toward more predictable birthdays: Low-cost methods for monitoring fetal development could improve prenatal care, especially in low-resource settings. By measuring the levels of certain placental RNA transcripts in maternal blood, Ngo et al. developed two noninvasive blood tests that provide a window into the progression of individual pregnancies. In a small proof-of-concept study, the first blood test predicted fetal age and delivery date with an accuracy comparable to that of ultrasound. The second blood test, also examined in a small pilot study, discriminated women at risk of preterm delivery from those who delivered at full term. The next step will be to assess the reliability of the tests in large, blinded clinical trials. Science , this issue p. 1133

We examined whether early gestational exposures to pesticides were associated with an increased risk of anencephaly, spina bifida, cleft lip with or without cleft palate (CLP), or cleft palate only. We used population-based data along with detailed information from maternal interviews. Exposure estimates were based on residential proximity to agricultural pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley, California (1997–2006). Analyses included 73 cases with anencephaly, 123 with spina bifida, 277 with CLP, and 117 with cleft palate only in addition to 785 controls. A total of 38% of the subjects were exposed to 52 chemical groups and 257 specific chemicals. There were relatively few elevated odds ratios with 95% confidence intervals that excluded 1 after adjustment for relevant covariates. Those chemical groups included petroleum derivatives for anencephaly, hydroxybenzonitrile herbicides for spina bifida, and 2,6-dinitroaniline herbicides and dithiocarbamates-methyl isothiocyanate for CLP. The specific chemicals included 2,4-D dimethylamine salt, methomyl, imidacloprid, and α-(para-nonylphenyl)-ω-hydroxypoly(oxyethylene) phosphate ester for anencephaly; the herbicide bromoxynil octanoate for spina bifida; and trifluralin and maneb for CLP. Adjusted odds ratios ranged from 1.6 to 5.1. Given that such odds ratios might have arisen by chance because of the number of comparisons, our study showed a general lack of association between a range of agricultural pesticide exposures and risks of selected birth defects.

Peripheral blood dynamics in the 100 days before delivery reveal a transition from pregnancy maintenance to prelabor biology.

Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism. Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs) associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes. Few odds ratios (ORs) revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous) relative to the reference genotype: BHMT (rs3733890) OR = 1.8 (1.1–3.1), CBS (rs2851391) OR = 2.0 (1.2–3.1); CBS (rs234713) OR = 2.9 (1.3–6.7); MTHFD1 (rs2236224) OR = 1.7 (1.1–2.7); MTHFD1 (hcv11462908) OR = 0.2 (0–0.9); MTHFD2 (rs702465) OR = 0.6 (0.4–0.9); MTHFD2 (rs7571842) OR = 0.6 (0.4–0.9); MTHFR (rs1801133) OR = 2.0 (1.2–3.1); MTRR (rs162036) OR = 3.0 (1.5–5.9); MTRR (rs10380) OR = 3.4 (1.6–7.1); MTRR (rs1801394) OR = 0.7 (0.5–0.9); MTRR (rs9332) OR = 2.7 (1.3–5.3); TYMS (rs2847149) OR = 2.2 (1.4–3.5); TYMS (rs1001761) OR = 2.4 (1.5–3.8); and TYMS (rs502396) OR = 2.1 (1.3–3.3). However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating that the observed SNPs were not individually contributing to risk. We did not observe any ORs with confidence intervals that did not include 1.0 for any of the studied SNPs with conotruncal heart defects. Haplotype reconstruction showed statistical evidence of nonrandom associations with TYMS, MTHFR, BHMT and MTR for spina bifida. Our observations do not implicate a particular folate transport or metabolism gene to be strongly associated with risks for spina bifida or conotruncal defects.

Folic acid is known to reduce risk of neural tube defects (NTDs). Even so, NTDs continue to occur despite individual supplementation or population fortification with folic acid. We investigated other nutrients related to one-carbon metabolism that may affect NTD risk. This prospective study included data from more than 180,000 pregnant women in California from 2003 through 2005. Midpregnancy serum specimens were linked with delivery information regarding the presence of a NTD, another structural malformation, or no malformation in the fetus. We identified 80 NTD-affected pregnancies (cases) and we randomly selected 409 pregnancy controls. Serum specimens were tested for methylmalonic acid, homocysteine, cysteine, methionine, total choline, betaine, cystathionine, vitamin B6, folate, vitamin B12, riboflavin, and creatinine. We observed elevated NTD risks associated with lower levels of total choline, and reduced risks with higher levels of choline. Specifically, we observed an odds ratio of 2.4 (95% confidence interval = 1.3–4.7) associated with the lowest decile and an odds ratio of 0.14 (0.02–1.0) associated with the highest decile, both relative to the 25th–74th percentiles of the control distribution. These data did not show meaningful differences between cases and controls for any other analytes. This is the first study to investigate total choline in NTD-affected pregnancies. Our findings for choline, for which low levels were a risk factor and higher levels were a protective factor for NTDs, may offer a useful clue toward understanding the complex etiologies of NTDs in an era of folic acid fortification of the food supply.

Background: Findings from studies examining risk of preterm birth associated with elevated prepregnancy body mass index (BMI) have been inconsistent.Methods: Within a large population‐based cohort, we explored associations between prepregnancy BMI and spontaneous preterm birth across a spectrum of BMI, gestational age, and racial/ethnic categories. We analysed data for 989 687 singleton births in California, 2007–09. Preterm birth was grouped as 20–23, 24–27, 28–31, or 32–36 weeks gestation (compared with 37–41 weeks). BMI was categorised as <18.5 (underweight); 18.5–24.9 (normal); 25.0–29.9 (overweight); 30.0–34.9 (obese I); 35.0–39.9 (obese II); and ≥40.0 (obese III). We assessed associations between BMI and spontaneous preterm birth of varying severity among non‐Hispanic White, Hispanic, and non‐Hispanic Black women.Results: Analyses of mothers without hypertension and diabetes, adjusted for age, education, height, and prenatal care initiation, showed obesity categories I–III to be associated with increased risk of spontaneous preterm birth at 20–23 and 24–27 weeks among those of parity 1 in each race/ethnic group. Relative risks for obese III and preterm birth at 20–23 weeks were 6.29 [95% confidence interval (CI) 3.06, 12.9], 4.34 [95% CI 2.30, 8.16], and 4.45 [95% CI 2.53, 7.82] for non‐Hispanic Whites, non‐Hispanic Blacks, and Hispanics, respectively. A similar, but lower risk, pattern was observed for women of parity ≥2 and preterm birth at 20–23 weeks. Underweight was associated with modest risks for preterm birth at ≥24 weeks among women in each racial/ethnic group regardless of parity.Conclusions: The association between women's prepregnancy BMI and risk of spontaneous preterm birth is complex and is influenced by race/ethnicity, gestational age, and parity.