Pauline Mendola

Elevated Blood Pressure in Pregnancy and Subsequent Chronic Disease Risk

Background— Preeclampsia, a new-onset hypertensive disorder of pregnancy, is associated with lifetime cardiovascular disease risk, but less is known about risk after other pregnancy-related hypertension. Methods and Results— The Northern Finland Birth Cohort 1966 included all expected births from 1 year (N=12 055 women). Blood pressure measurements and other prospective data were determined from prenatal care records and questionnaires for 10 314 women. Subsequent diagnoses were ascertained from Finnish registries (average follow-up, 39.4 years). Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) estimate risks in hypertensive women compared with normotensive women. Hypertension during pregnancy was associated with increased risk of subsequent cardiovascular disease and arterial hypertension. Women with chronic hypertension and superimposed preeclampsia/eclampsia had high risk for future diseases. Gestational hypertension was associated with increased risk of ischemic heart disease (HR, 1.44 [95% CI, 1.24–1.68]), myocardial infarcts (HR, 1.75 [95% CI, 1.40–2.19]), myocardial infarct death (HR, 3.00 [95% CI, 1.98–4.55]), heart failure (HR, 1.78 [95% CI, 1.43–2.21]), ischemic stroke (HR, 1.59 [95% CI, 1.24–2.04]), kidney disease (HR, 1.91 [95% CI, 1.18–3.09]), and diabetes mellitus (HR, 1.52 [95% CI, 1.21–1.89]). Isolated systolic hypertension was associated with increased risk of myocardial infarct death (HR, 2.15 [95% CI, 1.35–3.41]), heart failure (HR, 1.43 [95% CI, 1.13–1.82]), and diabetes mellitus (HR, 1.42 [95% CI, 1.13–1.78]), whereas isolated diastolic hypertension was associated with increased risk of ischemic heart disease (HR, 1.26 [95% CI, 1.05–1.50]). Results were similar in nonsmoking women aged <35 years with normal weight and no diabetes mellitus during pregnancy. Conclusions— Elevated blood pressure during pregnancy, regardless of type and even without known risk factors, signals high risk of later cardiovascular disease, chronic kidney disease, and diabetes mellitus. Clinical monitoring, risk factor evaluation, and early intervention could benefit women with hypertension in pregnancy.

A Time Series Analysis of Air Pollution and Preterm Birth in Pennsylvania, 1997--2001

Preterm delivery can lead to serious infant health outcomes, including death and lifelong disability. Small increases in preterm delivery risk in relation to spatial gradients of air pollution have been reported, but previous studies may have controlled inadequately for individual factors. Using a time-series analysis, which eliminates potential confounding by individual risk factors that do not change over short periods of time, we investigated the effect of ambient outdoor particulate matter with diameter ≤10 μm (PM10) and sulfur dioxide on risk for preterm delivery. Daily counts of preterm births were obtained from birth records in four Pennsylvania counties from 1997 through 2001. We observed increased risk for preterm delivery with exposure to average PM10 and SO2 in the 6 weeks before birth [respectively, relative risk (RR) = 1.07; 95% confidence interval (CI), 0.98–1.18 per 50 μg/m3 increase; RR = 1.15; 95% CI, 1.00–1. 32 per 15 ppb increase], adjusting for long-term preterm delivery trends, co-pollutants, and offsetting by the number of gestations at risk. We also examined lags up to 7 days before the birth and found an acute effect of exposure to PM10 2 days and 5 days before birth (respectively, RR = 1.10; 95% CI, 1.00–1.21; RR = 1.07; 95% CI, 0.98–1.18) and SO2 3 days before birth (RR = 1.07; 95% CI, 0.99–1.15), adjusting for covariates, including temperature, dew point temperature, and day of the week. The results from this time-series analysis, which provides evidence of an increase in preterm birth risk with exposure to PM10 and SO2, are consistent with prior investigations of spatial contrasts.

Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult female.

STUDY OBJECTIVE To broadly review the recent literature linking environmental factors and adult female reproductive health for the UCSF-CHE Summit on Environmental Challenges to Reproductive Health and Fertility. DESIGN Reviewed articles indexed in PubMed from 1999-2007 addressing environment and puberty, menstrual and ovarian function, fertility, and menopause. RESULT(S) The strongest evidence of environmental contaminant exposures interfering with healthy reproductive function in adult females is for heavy metals, particularly lead. Compounds that can influence hormone function, including pesticides and persistent pollutants, are also associated with risk. The pattern of effects for these endocrine-active compounds is often complex, with no clear dose response, but alterations in function and poor reproductive health outcomes are observed. From a clinical perspective, most modifiable risk appears to be associated with exposures in unique populations (contaminated fish consumers) or occupational groups (farmworkers). Many compounds have demonstrated increased risks for reproductive health impairment in women, but the literature is largely cross-sectional in nature and too sparse or inconclusive to support causal inference. CONCLUSION(S) Reproductive function in adult females is impaired by lead exposure. Pesticides and persistent pollutants can alter hormone function resulting in adverse reproductive health effects. Coordinated research is needed to address contaminant effects across the life span.

Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women

Background Phthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated. Objectives The objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women. Methods We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters. Results We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations. Conclusions Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.

Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability.

Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.

Comparison of gestational age at birth based on last menstrual period and ultrasound during the first trimester

Reported last menstrual period (LMP) is commonly used to estimate gestational age (GA) but may be unreliable. Ultrasound in the first trimester is generally considered a highly accurate method of pregnancy dating. The authors compared first trimester report of LMP and first trimester ultrasound for estimating GA at birth and examined whether disagreement between estimates varied by maternal and infant characteristics. Analyses included 1867 singleton livebirths to women enrolled in a prospective pregnancy cohort. The authors computed the difference between LMP and ultrasound GA estimates (GA difference) and examined the proportion of births within categories of GA difference stratified by maternal and infant characteristics. The proportion of births classified as preterm, term and post-term by pregnancy dating methods was also examined. LMP-based estimates were 0.8 days (standard deviation = 8.0, median = 0) longer on average than ultrasound estimates. LMP classified more births as post-term than ultrasound (4.0% vs. 0.7%). GA difference was greater among young women, non-Hispanic Black and Hispanic women, women of non-optimal body weight and mothers of low-birthweight infants. Results indicate first trimester report of LMP reasonably approximates gestational age obtained from first trimester ultrasound, but the degree of discrepancy between estimates varies by important maternal characteristics.

Thyroid Diseases and Adverse Pregnancy Outcomes in a Contemporary US Cohort

CONTEXT Thyroid diseases are inconsistently reported to increase risk for pregnancy complications. OBJECTIVE The objective of this study was to study pregnancy complications associated with common and uncommon thyroid diseases. DESIGN, SETTING, AND PARTICIPANTS We analyzed singleton pregnancies (N = 223 512) from a retrospective US cohort, the Consortium on Safe Labor (2002-2008). Thyroid diseases and outcomes were derived from electronic medical records. Multivariable logistic regression with generalized estimating equations estimated adjusted odds ratios (ORs) with 99% confidence intervals (99% CI). MAIN OUTCOME MEASURES Hypertensive diseases, diabetes, preterm birth, cesarean sections, inductions, and intensive care unit (ICU) admissions were analyzed. RESULTS Primary hypothyroidism was associated with increased odds of preeclampsia (OR = 1.47, 99% CI = 1.20-1.81), superimposed preeclampsia (OR = 2.25, 99% CI = 1.53-3.29), gestational diabetes (OR = 1.57, 99% CI = 1.33-1.86), preterm birth (OR = 1.34, 99% CI = 1.17-1.53), induction (OR = 1.15, 99% CI = 1.04-1.28), cesarean section (prelabor, OR = 1.31, 99% CI = 1.11-1.54; after spontaneous labor OR = 1.38, 99% CI = 1.14-1.66), and ICU admission (OR = 2.08, 99% CI = 1.04-4.15). Iatrogenic hypothyroidism was associated with increased odds of placental abruption (OR = 2.89, 99% CI = 1.14-7.36), breech presentation (OR = 2.09, 99% CI = 1.07-4.07), and cesarean section after spontaneous labor (OR = 2.05, 99% CI = 1.01-4.16). Hyperthyroidism was associated with increased odds of preeclampsia (OR = 1.78, 99% CI = 1.08-2.94), superimposed preeclampsia (OR = 3.64, 99% CI = 1.82-7.29), preterm birth (OR = 1.81, 99% CI = 1.32-2.49), induction (OR = 1.40, 99% CI = 1.06-1.86), and ICU admission (OR = 3.70, 99% CI = 1.16-11.80). CONCLUSIONS Thyroid diseases were associated with obstetrical, labor, and delivery complications. Although we lacked information on treatment during pregnancy, these nationwide data suggest either that there is a need for better thyroid disease management during pregnancy or that there may be an intrinsic aspect of thyroid disease that causes poor pregnancy outcomes.

Drinking water disinfection by-product exposure and fetal growth.

Background: Previous studies suggest that elevated exposure to drinking water disinfection by-products (DBPs)—in particular, total trihalomethanes (TTHMs)—may lead to fetal growth restriction. We examined the effects of exposure to TTHMs, haloacetic acids, and total organic halide on the probability of delivering a small-for-gestational-age (SGA) infant and on birth weight at term. Methods: Women early in pregnancy (≤12 weeks’ gestation) or planning a pregnancy were enrolled in a prospective pregnancy study conducted in 3 US communities from 2000 through 2004. Weekly (or biweekly) water samples were collected at each site as well as individual-level participant data. Associations between DBP exposures (TTHMs, haloacetic acids, total organic halide) and fetal growth were assessed using log-binomial regression for SGA (n = 1958) and linear regression for term birth weight (n = 1854). We conducted a Bayesian analysis to examine associations between individual DBP species and fetal growth. Results: Haloacetic acids and total organic halide were not associated with SGA or term birth weight. The probability of delivering an SGA infant was elevated when comparing women with an average third-trimester residential TTHM concentration ≥80 &mgr;g/L to women with exposure <80 &mgr;g/L (risk ratio = 2.0 [95% confidence interval = 1.1–3.6]), but not when examining other exposure contrasts. Bayesian analyses did not support a consistent association between any DBP species and fetal growth, although these analyses were based on small sample sizes. Conclusions: Our results do not suggest an adverse effect of haloacetic acid or total organic halide exposure on fetal growth. An association of TTHM with SGA was seen only for average residential concentrations above the current regulatory standard.

Prenatal smoking cessation and the risk of delivering preterm and small-for-gestational-age newborns.

OBJECTIVE: To examine the association between prenatal smoking cessation and delivery of a preterm or small-for-gestational-age (SGA) newborn in a large U.S. subpopulation using the revised (2003) birth certificate, which now assesses maternal smoking status by trimester. METHODS: We analyzed a cohort of U.S.-resident, singleton births in the 11 states that used the revised birth certificate in 2005 (n=915,441). Self-reported maternal smoking status was categorized as “never smoked,” “quit in the first trimester,” “quit in the second trimester,” and “smoked throughout” pregnancy (referent). Multinomial logistic regression was used to estimate adjusted odds ratios (aORs) for three outcomes (preterm non-SGA, term SGA, or preterm SGA newborns) by maternal smoking status. Analyses stratified by maternal age were also conducted. RESULTS: Compared with women who smoked throughout pregnancy, first-trimester quitters reduced their odds of delivering a preterm non-SGA newborn by 31% (aOR 0.69, 95% confidence interval [CI] 0.65–0.74), a term SGA newborn by 55% (aOR 0.45, 95% CI 0.42–0.48), and a preterm SGA newborn by 53% (aOR 0.47, 95% CI 0.40–0.55), similar to nonsmokers. Second-trimester quitters also reduced their odds of delivering preterm non-SGA and term SGA newborns but to a lesser magnitude. When comparing first-trimester quitters with smokers in each age group, older mothers had generally lower odds of these outcomes than younger mothers. CONCLUSION: Pregnant smokers who quit in the first trimester lowered their risk of delivering preterm and SGA newborns to a level similar to that of pregnant nonsmokers, and this benefit appeared to increase with maternal age. These findings reinforce current clinical guidance to encourage smoking cessation among pregnant smokers and serve as an additional incentive to quit. LEVEL OF EVIDENCE: II

Segregation and preterm birth: the effects of neighborhood racial composition in North Carolina.

Epidemiologic research suggests that racial segregation is associated with poor health among blacks in the United States (US). We used geocoded birth records and US census data to investigate whether neighborhood-level percent black is associated with preterm birth (PTB) for black and white women in two counties in the southern US, whether area-level deprivation modifies this association, and whether the association is influenced by the choice of geographic unit used to approximate a neighborhood. A 20%-point increase in tract-level percent black was found to be associated with increased PTB odds in white (OR=1.09, 95% CI: 1.01, 1.18) and black (OR=1.05, 95% CI: 0.99, 1.11) women. These small associations were similar to those observed in other US regions. Effects were robust to choice of neighborhood proxy and were not modified by area-level deprivation.