Yeyi Zhu

Growth and obesity through the first 7 y of life in association with levels of maternal glycemia during pregnancy: a prospective cohort study

BACKGROUND Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. OBJECTIVE We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. DESIGN FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offsprings ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. RESULTS At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. CONCLUSION Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI.

Obstetric and Neonatal Risks Among Obese Women Without Chronic Disease.

OBJECTIVE: To investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease. METHODS: Singleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race–ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site. RESULTS: Obstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose–response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86–2.13], 2.94 [2.73–3.18], 3.97 [3.61–4.36], and 5.47 [4.96–6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose–response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45–1.58), 1.74 (1.65–1.83), 1.93 (1.79–2.07), and 2.32 (2.14–2.52) as BMI category increased. CONCLUSION: Prepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases.

Racial/ethnic differences in preterm perinatal outcomes.

Background: Racial disparities in preterm birth and infant death have been well documented. Less is known about racial disparities in neonatal morbidities among infants who are born at <37 weeks of gestation. Objective: The purpose of this study was to determine whether the risk for morbidity and death among infants who are born preterm differs by maternal race. Study Design: A retrospective cohort design included medical records from preterm deliveries of 19,325 black, Hispanic, and white women in the Consortium on Safe Labor. Sequentially adjusted Poisson models with generalized estimating equations estimated racial differences in the risk for neonatal morbidities and death, controlling for maternal demographics, health behaviors, and medical history. Sex differences between and within race were examined. Results: Black preterm infants had an elevated risk for perinatal death, but there was no difference in risk for neonatal death across racial groups. Relative to white infants, black infants were significantly more likely to experience sepsis (9.1% vs 13.6%), peri‐ or intraventricular hemorrhage (2.6% vs 3.3%), intracranial hemorrhage (0.6% vs 1.8%), and retinopathy of prematurity (1.0% vs 2.6%). Hispanic and white preterm neonates had similar risk profiles. In general, female infants had lower risk relative to male infants, with white female infants having the lowest prevalence of a composite indicator of perinatal death or any morbidity across all races (30.9%). Differences in maternal demographics, health behaviors, and medical history did little to influence these associations, which were robust to sensitivity analyses of pregnancy complications as potential underlying mechanisms. Conclusion: Preterm infants were at similar risk for neonatal death, regardless of race; however, there were notable racial disparities and sex differences in rare, but serious, adverse neonatal morbidities.

Insulin-Like Growth Factor Axis and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort

The insulin-like growth factor (IGF) axis may be implicated in glucose homeostasis, but its longitudinal profile across gestation in relation to the development of gestational diabetes mellitus (GDM) is largely unknown. We prospectively investigated IGF axis biomarkers in early-to-midpregnancy in relation to subsequent GDM risk in a case-control study of 107 case subjects with GDM and 214 control subjects without GDM, with blood sample collection at gestational weeks 10–14, 15–26, 23–31, and 33–39. Conditional logistic regression was used, adjusting for major risk factors including prepregnancy BMI. Plasma IGF-I and IGF binding protein 3 (IGFBP-3) concentrations and molar ratio of IGF-I to IGFBP-3 increased, whereas IGFBP-2 decreased throughout pregnancy. At gestational weeks 10–14, both IGF-I and IGF-I/IGFBP-3 were positively associated with GDM risk; adjusted odds ratio (OR) comparing the highest versus lowest quartile (ORQ4-Q1) was 2.93 (95% CI 1.18, 7.30) for IGF-I and 3.31 (1.10, 9.98) for IGF-I/IGFBP-3. In contrast, higher IGFBP-2 levels were related to a substantially lower risk of GDM (ORQ4-Q1 0.04 [0.01, 0.06]). Similar results were observed at gestational weeks 15–26. In sum, the IGF axis, IGFBP-2 in particular, may be implicated in the pathogenesis of GDM, with significant associations and incremental predictive value detected as early as gestational weeks 10–14, ∼10–18 weeks earlier before GDM is typically screened for.

Exposure to Ambient Air Pollution and Premature Rupture of Membranes

Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 µm or less than 2.5 µm in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR = 1.15, 95% CI: 1.06, 1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 µm in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM.

Maternal consumption of artificially sweetened beverages during pregnancy, and offspring growth through 7 years of age: a prospective cohort study

Background Artificial sweeteners are widely replacing caloric sweeteners. Data on long-term impact of artificially sweetened beverage (ASB) consumption during pregnancy on offspring obesity risk are lacking. We prospectively investigated intake of ASBs and sugar-sweetened beverages (SSBs) during pregnancy in relation to offspring growth through age 7 years among high-risk children born to women with gestational diabetes. Methods In a prospective study of 918 mother-singleton child dyads from the Danish National Birth Cohort, maternal dietary intake was assessed by a food frequency questionnaire during pregnancy. Offspring body mass index z-scores (BMIZ) and overweight/obesity status were derived using weight and length/height at birth, 5 and 12 months and 7 years. Linear regression and Poisson regression with robust standard errors were used, adjusting for major risk factors. Results Approximately half of women reported consuming ASBs during pregnancy and 9% consumed daily. Compared to never consumption, daily ASB intake during pregnancy was positively associated with offspring large-for-gestational age [adjusted relative risk (aRR) 1.57; 95% CI: 1.05, 2.35 at birth], BMIZ (adjusted β 0.59; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years. Per-serving-per-day substitution of ASBs with water during pregnancy was related to a lower overweight/obesity risk at 7 years (aRR 0.83; 95% CI: 0.76, 0.91), whereas SSB substitution with ASBs was not related to a lower risk (aRR 1.14; 95% CI: 1.00, 1.31). Conclusions Our findings illustrated positive associations between intrauterine exposure to ASBs and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted.

Ambient temperature and air quality in relation to small for gestational age and term low birthweight

Background: Exposures to extreme ambient temperature and air pollution are linked to adverse birth outcomes, but the associations with small for gestational age (SGA) and term low birthweight (tLBW) are unclear. We aimed to investigate exposures to site‐specific temperature extremes and selected criteria air pollutants in relation to SGA and tLBW. Methods: We linked medical records of 220,572 singleton births (2002–2008) from 12 US sites to local temperature estimated by the Weather Research and Forecasting model, and air pollution estimated by modified Community Multiscale Air Quality models. Exposures to hot (>95th percentile) and cold (<5th percentile) were defined using site‐specific distributions of daily temperature over three‐month preconception, each trimester, and whole‐pregnancy. Average concentrations of five criteria air pollutants and six fine particulate matter constituents were also calculated for these pregnancy windows. Poisson regression with generalized estimating equations calculated the relative risks (RR) and 95% confidence intervals for SGA (weight <10th percentile conditional on gestational age and sex) and tLBW (≥37 weeks and <2500 g) associated with an interquartile range increment of air pollutants, and cold or hot compared to mild (5–95th percentile) temperature. Models were adjusted for maternal demographics, lifestyle, and clinical factors, season, and site. Results: Compared to mild temperature, cold exposure during trimester 2 [RR: 1.21 (1.05–1.38)], trimester 3 [RR: 1.18 (1.03–1.36)], and whole‐pregnancy [RR: 2.57 (2.27–2.91)]; and hot exposure during trimester 3 [RR: 1.31 (1.15–1.50)] and whole‐pregnancy [RR: 2.49 (2.20–2.83)] increased tLBW risk. No consistent association was observed between temperature and SGA. Air pollutant analyses were generally null but preconception elemental carbon was associated with a 4% increase in SGA while dust particles increased tLBW by 10%. Particulate matter ≤10 &mgr;m in the second trimester and whole pregnancy also appeared related to tLBW. Conclusions: Our findings suggest prenatal exposures to extreme ambient temperature relative to usual environment may increase tLBW risk. Given concerns related to climate change, these findings merit further investigation. HighlightsWhole‐pregnancy cold or hot temperature increased term low birthweight (tLBW) risk.Cold exposures during trimesters 2 and 3 & hot during trimester 3 increased tLBW risk.There was no association between temperature and small for gestational age (SGA).Most associations between air pollution and SGA or tLBW were null.

Age at Menarche and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study Among 27,482 Women

OBJECTIVE To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses’ Health Study II. RESULTS The adjusted risk ratios for GDM across the age at menarche categories (≤11, 12, 13, and ≥14 years) were 1.34 (95% CI 1.14–1.58), 1.13 (0.97–1.31), 1.11 (0.95–1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI. CONCLUSIONS These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity.

Ambient Temperature and Early Delivery of Singleton Pregnancies.

Background: Extreme temperature is associated with adverse birth outcomes but it is unclear whether it increases early delivery risk. Objectives: We aimed to determine the association between ambient temperature and early delivery. Methods: Medical records from 223,375 singleton deliveries from 12 U.S. sites were linked to local ambient temperature. Exposure to hot (> 90th percentile) or cold (< 10th percentile) using site-specific and window-specific temperature distributions were defined for 3-months preconception, 7-week periods during the first two trimesters, 1 week preceding delivery, and whole pregnancy. Poisson regression with generalized estimating equations calculated the relative risk (RR) and 95% confidence interval for early deliveries associated with hot/cold exposures, adjusting for conception month, humidity, site, sex, maternal demographics, parity, insurance, prepregnancy body mass index, pregnancy complications, and smoking or drinking during pregnancy. Acute temperature associations were estimated separately for warm (May–September) and cold season (October–April) in a case-crossover analysis using conditional logistic regression. Results: Compared with mild temperature (10–90th percentile), exposure to hot or cold during weeks 1–7 increased risk for early preterm (< 34 weeks) [RRhot: 1.11 (95% CI: 1.01, 1.21); RRcold: 1.20 (95% CI: 1.11, 1.30)], late preterm (34–36 weeks) [RRcold: 1.09 (95% CI: 1.04, 1.15)], and early term (37–38 weeks) [RRhot: 1.04 (95% CI: 1.02, 1.07); RRcold: 1.03 (95% CI: 1.00, 1.05)] delivery. Findings were similar for hot exposures during weeks 15–21. Examining deliveries at each week from 23 through 38, whole-pregnancy hot exposures increased delivery risk by 6–21% at weeks 34 and 36–38. In the case-crossover analysis, a 5°F increase during the week preceding delivery was associated with 12–16% higher and 4–5% lower early delivery risk during warm and cold season, respectively. Conclusions: Both acute and chronic ambient temperature extremes may affect early delivery risk. Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453–459; http://dx.doi.org/10.1289/EHP97

Maternal ambient air pollution exposure preconception and during early gestation and offspring congenital orofacial defects

BACKGROUND Maternal air pollution exposure has been related to orofacial clefts but the literature is equivocal. Potential chronic preconception effects have not been studied. OBJECTIVES Criteria air pollutant exposure during three months preconception and gestational weeks 3-8 was studied in relation to orofacial defects. METHODS Among 188,102 live births and fetal deaths from the Consortium on Safe Labor (2002-2008), 63 had isolated cleft palate (CP) and 159 had isolated cleft lip with or without cleft palate (CL ±CP). Exposures were estimated using a modified Community Multiscale Air Quality model. Logistic regression with generalized estimating equations adjusted for site/region and maternal demographic, lifestyle and clinical factors calculated the odds ratio (OR) and 95% CI per interquartile increase in each pollutant. RESULTS Preconception, carbon monoxide (CO; OR=2.24; CI: 1.21, 4.16) and particulate matter (PM) ≤10 µm (OR=1.72; CI: 1.12, 2.66) were significantly associated with CP, while sulfur dioxide (SO2) was associated with CL ±CP (OR=1.93; CI: 1.16, 3.21). During gestational weeks 3-8, CO remained a significant risk for CP (OR=2.74; CI: 1.62, 4.62) and nitrogen oxides (NOx; OR=3.64; CI: 1.73, 7.66) and PM ≤2.5 µm (PM2.5; OR=1.74; CI: 1.15, 2.64) were also related to the risk. Analyses by individual week revealed that positive associations of NOx and PM2.5 with CP were most prominent from weeks 3-6 and 3-5, respectively. CONCLUSIONS Exposure to several criteria air pollutants preconception and during early gestation was associated with elevated odds for CP, while CL ±CP was only associated with preconception SO2 exposure.