Background

Using ICD-9 codes underestimates the prevalence of obesity in adults; however, the validity of these codes in studies of pregnancy-related outcomes is not known.

Objectives

To compare classification of maternal obesity based on ICD-9 codes in hospital discharge records versus data from birth certificates in the same women, examine predictors of agreement, and assess how associations between obesity and two birth outcomes differ by source of weight data.

Methods

This population-based study included 2 329 145 California births between 2007 and 2012. We compared data on obesity from childbirth hospital discharge records (ICD-9 codes for obesity) and birth certificates (pre-pregnancy body mass index (BMI) calculated from weight and height) and identified predictors of agreement between the two sources. Logistic regression models assessed whether the two definitions of obesity resulted in different estimates of the associations of obesity with caesarean birth and large-for-gestational age.

Results

Overall, 464 754 women (20.0%) had obesity based on their pre-pregnancy BMI while only 100 002 (4.3%) had an obesity-related ICD-9 code. The sensitivity of ICD-9-based obesity was low at 16.2%; however, obesity codes were highly specific at 98.7%, with a negative predictive value of 82.5% and a positive predictive value of 75.2%. Among women with obesity identified by the birth certificate, those with pre-pregnancy and pregnancy-related complications (eg diabetes and hypertension) were more likely to have an obesity-related diagnosis in their delivery hospital discharge record. Using ICD-9 codes overestimated the association of obesity with caesarean birth and newborn large-for-gestational age.

Conclusions

ICD-9 codes in childbirth discharge records captured only one in five women with pre-pregnancy obesity. Sensitivity varied by maternal characteristics and conditions. This misclassification resulted in bias when examining the association of obesity and pregnancy-related outcomes.

Purpose

Folate, vitamins B12 and B6, riboflavin, and methionine are critical nutrients for the one-carbon metabolism cycle involved in DNA synthesis and epigenetic processes. We examined the association between maternal intake of these nutrients before pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in a matched case-control study.

Methods

Maternal dietary intake and vitamin supplement use in the year before pregnancy was assessed by food frequency questionnaire for 681 ALL cases, 103 AML cases, and 1076 controls. Principal component analysis was used to construct a variable representing combined nutrient intake, and conditional logistic regression estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ALL and AML with the principal component and each nutrient.

Results

Higher maternal intake of one-carbon metabolism nutrients from food and supplements combined was associated with reduced risk of ALL (OR for one-unit change in the principal component = 0.91, CI 0.84-0.99) and possibly AML (OR for the principal component = 0.83, CI 0.66-1.04). When analyzed separately, intake of supplements high in these nutrients was associated with a reduced risk of ALL in children of Hispanic women only.

Conclusions

In conclusion, these data suggest that higher maternal intake of one-carbon metabolism nutrients may reduce risk of childhood leukemia.

Environmental pollutants have been associated with hypertensive disorders in pregnancy including gestational hypertension, preeclampsia, and eclampsia, though few have focused on drinking water contamination. Water pollution can be an important source of exposures that may contribute to adverse pregnancy outcomes.

Methods

We linked water quality data on 13 contaminants and two violations from the California Communities Environmental Health Screening Tool to birth records from vital statistics and hospital discharge records (2007-2012) to examine the relationship between drinking water contamination and hypertensive disorders in pregnancy. We examined contaminants in single- and multipollutant models. Additionally, we examined if the relationship between water contamination and hypertensive disorders in pregnancy differed by neighborhood poverty, individual socioeconomic status, and race/ethnicity.

Results

Arsenic, nitrate, trihalomethane, hexavalent chromium, and uranium were detected in a majority of water systems. Increased risk of hypertensive disorders in pregnancy was modestly associated with exposure to cadmium, lead, trihalomethane, and hexavalent chromium in drinking water after adjusting for covariates in single pollutant models with odds ratios ranging from 1.01 to 1.08. In multipollutant models, cadmium was consistent, lead and trihalomethane were stronger, and additional contaminants were associated with hypertensive disorders in pregnancy including trichloroethylene, 1,2-Dibromo-3-chloropropane, nitrate, and tetrachloroethylene. Other contaminants either showed null results or modest inverse associations. The relationship between water contaminants and hypertensive disorders in pregnancy did not differ by neighborhood poverty.

Conclusions

We found increased risk of hypertensive disorders in pregnancy associated with exposure to several contaminants in drinking water in California. Results for cadmium, lead, trihalomethane, and hexavalent chromium were robust in multipollutant models.

Purpose

We determined whether variants in genes associated with genital tubercle (the anlage for the penis) and early urethral development were associated with hypospadias in humans.

Materials and methods

We examined 293 relatively common tag single nucleotide polymorphisms in BMP4, BMP7, FGF8, FGF10, FGFR2, HOXA13, HOXD13, HOXA4, HOXB6, SRY, WT1, WTAP, SHH, GLI1, GLI2 and GLI3. The analysis included 624 cases (81 mild, 319 moderate, 209 severe, 15 undetermined severity) and 844 population based nonmalformed male controls born in California from 1990 to 2003.

Results

There were 28 single nucleotide polymorphisms for which any of the comparisons (ie overall or for a specific severity) had a p value of less than 0.01. The homozygous variant genotypes for 4 single nucleotide polymorphisms in BMP7 were associated with at least a twofold increased risk of hypospadias regardless of severity. Five single nucleotide polymorphisms for FGF10 were associated with threefold to fourfold increased risks, regardless of severity. For 4 of them the results were restricted to whites. For GLI1, GLI2 and GLI3 there were 12 associated single nucleotide polymorphisms but results were inconsistent by severity and race/ethnicity. For SHH 1 single nucleotide polymorphism was associated with a 2.4-fold increased risk of moderate hypospadias. For WT1 6 single nucleotide polymorphisms were associated with approximately a twofold increased risk, primarily for severe hypospadias.

Conclusions

This study provides evidence that single nucleotide polymorphisms in several genes that contribute to genital tubercle and early urethral development are associated with hypospadias risk.

Background

To generate new leads about risk factors for gastroschisis, a birth defect that has been increasing in prevalence over time, we performed an untargeted data mining statistical approach.

Methods

Using data exclusively from the California Center of the National Birth Defects Prevention Study, we compared 286 cases of gastroschisis and 1,263 non-malformed, live-born controls. All infants had delivery dates between October 1997 and December 2011 and were stratified by maternal age at birth (<20 and ≥ 20 years). Cases and controls were compared by maternal responses to 183 questions (219 variables) using random forest, a data mining procedure. Variables deemed important by random forest were included in logistic regression models to estimate odds ratios and 95% confidence intervals.

Results

Among women younger than 20, of variables deemed important, there were higher odds observed for higher consumption of chocolate, low intake of iron, acetaminophen use, and urinary tract infections during the beginning of pregnancy. After adjustment, the higher odds remained for low iron intake and a urinary tract infection in the first month of pregnancy. Among women aged 20 or older, of variables deemed important, higher odds were observed for US-born women of Hispanic ethnicity and for parental substance abuse. There were lower odds observed for obese women, women who ate any cereal the month before pregnancy, and those with higher parity.

Conclusions

We did not discover many previously unreported associations, despite our novel approach to generate new hypotheses. However, our results do add evidence to some previously proposed risk factors.

Purpose

In Scandinavia, delivery of a first-born son elevates the risk of preterm delivery and intrauterine growth restriction of the next-born infant. External validity of these results remains unclear. We test this hypothesis for preterm delivery and growth restriction using the linked California birth cohort file. We examined the hypothesis separately by race and/or ethnicity.

Methods

We retrieved data on 2,852,976 births to 1,426,488 mothers with at least two live births. Our within-mother tests applied Cox proportional hazards (preterm delivery, defined as less than 37 weeks gestation) and linear regression models (birth weight for gestational age percentiles).

Results

For non-Hispanic whites, Hispanics, Asians, and American Indian and/or Alaska Natives, analyses indicate heightened risk of preterm delivery and growth restriction after a first-born male. The race-specific hazard ratios for preterm delivery range from 1.07 to 1.18. Regression coefficients for birth weight for gestational age percentile range from -0.73 to -1.49. The 95% confidence intervals for all these estimates do not contain the null. By contrast, we could not reject the null for non-Hispanic black mothers.

Conclusions

Whereas California findings generally support those from Scandinavia, the null results among non-Hispanic black mothers suggest that we do not detect adverse outcomes after a first-born male in all racial and/or ethnic groups.

Objective

The aim of this study is to evaluate the contribution of pre-pregnancy obesity and overweight to peripartum cardiomyopathy.

Study design

This population-based study used linked birth record and maternal hospital discharge data from live births in California during 2007 to 2012 (n = 2,548,380). All women who had a diagnosis of peripartum cardiomyopathy during the childbirth hospitalization or who were diagnosed with peripartum cardiomyopathy during a postpartum hospital readmission within 5 months of birth were identified as cases. Pre-pregnancy body mass index (BMI, kg/m²) was classified as normal weight (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40). Because of small numbers, we excluded women with underweight BMI, and in some analyses, we combined obesity classes into one group. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) expressing associations between BMI and peripartum cardiomyopathy, adjusted for maternal age, race/ethnicity, education, health care payer, parity, plurality, and comorbidities.

Results

The overall prevalence of peripartum cardiomyopathy during hospital admissions was 1.3 per 10,000 live births (n = 320). Unadjusted ORs were 1.32 (95% CI: 1.01-1.74) for women with overweight BMI and 2.03 (95% CI: 1.57-2.62) for women with obesity, compared with women with normal pre-pregnancy BMI. Adjusted ORs were 1.26 (95% CI: 0.95-1.66) for overweight women and 1.38 (95% CI: 1.04-1.84) for women with obesity. The ORs suggested a dose-response relationship with increasing levels of obesity, but the 95% CIs for the specific classes of obesity included 1.00.

Conclusion

Pre-pregnancy obesity was associated with an increased risk of peripartum cardiomyopathy. These findings underscore the importance of BMI during pregnancy. There is a need to recognize the increased risk of peripartum cardiomyopathy in women with high BMI, especially in the late postpartum period.

Key points

· Pre-pregnancy obesity affects maternal health.. · Effects may extend to peripartum cardiomyopathy.. · The risk includes peripartum cardiomyopathy that emerges postpartum..

Background

Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood.

Methods

We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use.

Results

We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods.

Conclusions

Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California.

In a population-based case-control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (OR_h ) or homozygous variants (OR_v ) genotypes. These included NOS3 (rs1036145) OR_h  = 0.4 (95% CI: 0.2-0.7); NOS3 (rs10277237) OR_v  = 2.7 (95% CI: 1.3-6.0); ADD1 (rs12503220) OR_h  = 2.9 (95% CI: 1.6-5.4), GNB3 (rs5443) OR_h  = 0.2 (95% CI: 0.1-0.5), OR_v  = 0.4 (95% CI: 0.2-0.9); ICAM1 (rs281428) OR_v  = 6.9 (95% CI: 2.1-22.9), ICAM1 (rs3093030) OR_v  = 2.6 (95% CI: 1.2-5.6); ICAM4 (rs281438) OR_v  = 4.9 (95% CI: 1.4-16.6), ICAM5 (rs281417) OR_h  = 2.1 (95% CI: 1.1-4.1), OR_v  = 4.8 (95% CI: 1.7-13.6); ICAM5 (rs281440) OR_h  = 23.7 (95% CI: 5.5-102.5), OR_v  = 20.6 (95% CI: 3.4-124.3); ICAM5 (rs2075741) OR_v  = 2.2 (95% CI: 1.1-4.4); NAT1 OR_v  = 0.3 (95% CI: 0.1-0.9). There were additional associations between several gene variants and gastroschisis among women aged 20-24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc.

Background

Birth defects are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some structural anomalies, although evidence is limited and several anomalies have not been investigated previously.

Methods

We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 26 congenital birth defect phenotypes with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and 849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity, education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases.

Results

Few odds ratios had confidence intervals that did not include 1.0. Odds of esophageal atresia were increased for the highest versus lowest of traffic density (aOR = 2.8, 95% confidence interval [CI], 1.1-7.4) and PM10 exposure (aOR 4.9; 95% CI, 1.4-17.2). PM₁₀ was associated with a decreased risk of hydrocephaly (aOR= 0.3; 95% CI, 0.1-0.9) and CO with decreased risk of anotia/microtia (aOR = 0.4; 95% CI, 0.2-0.8) and transverse limb deficiency (aOR = 0.4; 95% CI, 0.2-0.9), again reflecting highest versus lowest quartile comparisons.

Conclusion

Most analyses showed no substantive association between air pollution and the selected birth defects with few exceptions of mixed results.