Maternal Ambient Exposure to Atmospheric Pollutants during Pregnancy and Offspring Term Birth Weight in the Nationwide ELFE Cohort.

BACKGROUND: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study. METHODS: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM2.5, PM10 (particles < 2.5 µm and <10 µm) and NO2 (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW. RESULTS: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, -26.8, -7.3) and by 18.0 g (-26.6, -9.4) for each 5 µg/m3 increase in PM2.5 and PM10, respectively, and by 15.9 g (-27.6, -4.2) for each 10 µg/m3 increase in NO2. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (-58.1, -38.0) for PM2.5, 38.1 g (-46.7, -29.6) for PM10 and 14.7 g (-25.3, -4.0) for NO2. Effects of pollutants on TBW were larger in rural areas. CONCLUSIONS: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.

Pregnancy outcomes in women with preexisting thyroid diseases: a French cohort study.

Women with thyroid diseases at the beginning of pregnancy may have suboptimal thyroid hormone levels because of potential difficulties in compensating for the physiological thyroid hormone changes occurring in pregnancy. Our objective was to study the association between preexisting thyroid diseases, pregnancy complications, and neonatal anthropometry. In total, 16,395 women from the ELFE French longitudinal birth cohort were included, and 273 declared pre-pregnancy thyroid diseases. Associations were investigated with multivariable regression models, with adjustment for relevant potential confounders. Body mass index (BMI) was additionally adjusted for in a second stage. As compared with other women, women with pre-pregnancy thyroid diseases were more frequently obese (19.6% vs. 9.8%) and had greater odds of gestational diabetes development (odds ratio [OR] = 1.58 [95% confidence interval [CI] 1.08, 2.30]) or had undergone treatment for infertility (OR = 1.57 [95% CI 1.07, 2.31]). After adjustment for BMI, the association with gestational diabetes was no longer significant (OR = 1.27 [95% CI 0.86, 1.88]). After excluding women with another medical history, those with pre-pregnancy thyroid diseases had increased odds of premature rupture of membranes (OR = 1.51 [95% CI 1.01, 2.25]). Children born from mothers with hypothyroidism before conception due to a disease or as a potential side effect of treatment had a smaller head circumference at birth than other children (ß = -0.23 [95% CI -0.44, -0.01] cm). In conclusion, pre-pregnancy thyroid diseases were associated with risk of infertility treatment, gestational diabetes, and premature rupture of membranes. The association between history of hypothyroidism and moderate adverse effects on fetal head circumference growth needs replication.

Maternal cumulative exposure to extremely low frequency electromagnetic fields, prematurity and small for gestational age: a pooled analysis of two birth cohorts.

BACKGROUND: Data on the effects of extremely low frequency electromagnetic fields (ELF-EMF) on pregnancy outcomes are inconclusive. OBJECTIVE: To study the relation between maternal cumulative exposure to ELF-EMF during pregnancy and the risk of prematurity or small for gestational age (SGA) in a pooled analysis of two French birth cohorts. METHODS: Elfe and Epipage2 are both population-based birth cohorts initiated in 2011 and included 18 329 and 8400 births, respectively. Health data and household, mother and child characteristics were obtained from medical records and questionnaires at maternity and during follow-up. A job exposure matrix was used to assess cumulative exposure to ELF-EMF during three periods: (1) until 15 weeks of gestation, (2) until 28 weeks of gestation and (3) until 32 weeks of gestation. Analyses were restricted to single live births in mainland France and to mothers with documented jobs (N=19 894). Adjusted logistic regression models were used. RESULTS: According to the period studied, 3.2%-4% of mothers were classified as highly exposed. Results were heterogeneous. Increased risks of prematurity were found among low exposed mothers for the three periods, and no association was observed among the most exposed (OR1=0.92 (95% CI 0.74 to 1.15); OR2=0.98 (95% CI 0.80 to 1.21); OR3=1.14 (95% CI 0.92 to 1.41)). For SGA, no association was observed with the exception of increased risk among the low exposed mothers in period 2 and the most exposed in period 3 (OR=1.25 (95% CI 1.02 to 1.53)). CONCLUSION: Some heterogeneous associations between ELF-EMF exposure and prematurity and SGA were observed. However, due to heterogeneity (ie, their independence regarding the level of exposure), associations cannot be definitely explained by ELF-EMF exposure.

An association between maternal weight change in the year before pregnancy and infant birth weight: ELFE, a French national birth cohort study.

BACKGROUND: Weight-control interventions in pregnant women with overweight or obesity have limited effectiveness for fetal growth and birth outcomes. Interventions or prevention programs aiming at the pre-pregnancy period should be considered. However, how the woman's weight change before pregnancy affects fetal growth is not known. We investigated the association between weight change over the year before pregnancy and birth weight. METHODS AND FINDINGS: We used the inclusion data of 16,395 women from the ELFE French national birth cohort, a nationally representative cohort in which infants were enrolled at birth with their families in 2011. Maternal weight change was self-reported and classified into 3 groups: moderate weight variation or stable weight, weight loss > 5 kg, and weight gain > 5 kg or both weight loss and gain > 5 kg. Multiple linear regression models were used to investigate the association between pre-pregnancy weight change and a birth weight z-score calculated according to the French Audipog reference, adjusted for a large set of maternal characteristics. The analyses were stratified by maternal body mass index (BMI) at conception (<25 versus ≥25 kg/m2) and adjusted for BMI within these categories. We used the MacKinnon method to test the mediating effect of gestational weight gain (GWG) on these associations. Mother's mean age was 30.5 years, 87% were born in France, and 26% had overweight or obesity. For women in either BMI category at conception, GWG was more than 2 kg higher, on average, for women with weight loss before pregnancy than for women with stable weight or moderate weight variation. For women with BMI < 25 kg/m2 at conception, birth weight was significantly higher with weight loss than stable weight before pregnancy (ß = 0.08 [95% CI 0.02; 0.14], p = 0.01), and this total effect was explained by a significant mediating effect through GWG. For women with BMI ≥ 25 kg/m2 at conception, birth weight was not associated with pre-pregnancy weight loss during the year before pregnancy. Mediation analysis revealed that in these women, the direct effect of pre-pregnancy weight loss that would have resulted in a smaller birth weight z-score (ß = -0.11 [95% CI -0.19; -0.03], p = 0.01) was cancelled out by the GWG. The mediating effect of GWG was even higher when weight loss resulted from a restrictive diet in the year before pregnancy. Weight gain before pregnancy was not associated with birth weight. Although we included a large number of women and had extensive data, the only potential cause of pre-pregnancy weight loss that was investigated was dieting for intentional weight loss. We have no information on other potential causes but did however exclude women with a history of pre-pregnancy chronic disease. Another limitation is declaration bias due to self-reported data. CONCLUSIONS: Health professionals should be aware that GWG may offset the expected effect of weight loss before conception on fetal growth in overweight and obese women. Further studies are required to understand the underlying mechanisms in order to develop weight-control interventions and improve maternal periconceptional health and developmental conditions for the fetus.

Breastfeeding Status and Duration and Infections, Hospitalizations for Infections, and Antibiotic Use in the First Two Years of Life in the ELFE Cohort.

In low- and middle-income countries, the protective effect of breastfeeding against infections is well established, but in high-income countries, the effect could be weakened by higher hygienic conditions. We aimed to examine the association between breastfeeding and infections in the first 2 years of life, in a high-income country with relatively short breastfeeding duration. Among 10,349 young children from the nationwide Etude Longitudinale Française depuis l'Enfance (ELFE) birth cohort, breastfeeding and parent-reported hospitalizations, bronchiolitis and otitis events, and antibiotic use were prospectively collected up to 2 years. Never-breastfed infants were used as reference group. Any breastfeeding for <3 months was associated with higher risks of hospitalizations from gastrointestinal infections or fever. Predominant breastfeeding for <1 month was associated with higher risk of a single hospital admission while predominant breastfeeding for ≥3 months was associated with a lower risk of long duration (≥4 nights) of hospitalization. Ever breastfeeding was associated with lower risk of antibiotic use. This study confirmed the well-known associations between breastfeeding and hospitalizations but also highlighted a strong inverse association between breastfeeding and antibiotic use. Although we cannot infer causality from this observational study, this finding is worth highlighting in a context of rising concern regarding antibiotic resistance.

Social Inequalities in Prenatal Folic Acid Supplementation: Results from the ELFE Cohort.

Most professional and international organizations recommend folic acid supplementation for women planning pregnancy. Various studies have shown high levels of non-compliance with this recommendation. This study aimed to identify sociodemographic characteristics related to this compliance. The analyses were based on 16,809 women from the French nationwide ELFE cohort (Etude Longitudinale Française depuis l'Enfance). Folic acid supplementation was assessed at delivery, and sociodemographic characteristics were collected at two months postpartum. The association between sociodemographic characteristics and compliance with recommendations on folic acid supplementation (no supplementation, periconceptional supplementation, and supplementation only after the periconceptional period) was examined using multivariate multinomial logistic regression. Only 26% of French women received folic acid supplementation during the periconceptional period, 10% of women received supplementation after the periconceptional period, and 64% received no supplementation. Young maternal age, low education level, low family income, multiparity, single parenthood, maternal unemployment, maternal overweight, and smoking during pregnancy were related to lower likelihood of folic acid supplementation during the periconceptional period compared to no supplementation. These associations were not explained by unplanned pregnancy. Immigrant and underweight women were more likely to receive folic acid supplementation after the periconceptional period. Our study confirms great social disparities in France regarding the compliance with the recommendations on folic acid supplementation.

Are selection criteria for healthy pregnancies responsible for the gap between fetal growth in the French national Elfe birth cohort and the Intergrowth-21st fetal growth standards?

BACKGROUND: The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies. METHOD: We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14 607 singleton pregnancies from the Elfe national birth cohort. We compared concordance of centile thresholds using the IG standards and current French references and used restricted cubic splines to plot z-scores by gestational age. A "healthy pregnancy" sub-sample was created based on maternal and pregnancy selection criteria, as specified by IG. RESULTS: Mean gestational age-specific z-scores for femur length and abdominal circumference using French references fluctuated around 0 (-0.2 to 0.1), while those based on IG standards were higher (0.3-0.8). Using IG standards, 2.5% and 5.2% of fetuses at the third ultrasound were <10th centile for femur length and abdominal circumference, respectively, and 31.5% and 16.7% were >90th. Only 34% of pregnancies fulfilled IG low-risk criteria, but sub-analyses yielded very similar results. CONCLUSION: Intergrowth standards differed from fetal biometric measures in France, including among low-risk pregnancies selected to replicate IG's healthy pregnancy sample. These results challenge the project's assumption that careful constitution of a low-risk population makes it possible to describe normative fetal growth across populations.

Is atmospheric pollution exposure during pregnancy associated with individual and contextual characteristics? A nationwide study in France.

BACKGROUND: Exposure to atmospheric pollutants is a danger for the health of pregnant mother and children. Our objective was to identify individual (socioeconomic and behavioural) and contextual factors associated with atmospheric pollution pregnancy exposure at the nationwide level. METHOD: Among 14 921 women from the French nationwide ELFE (French Longitudinal Study of Children) mother-child cohort recruited in 2011, outdoor exposure levels of PM2.5, PM10 (particulate matter <2.5 µm and <10 µm in diameter) and NO2 (nitrogen dioxide) were estimated at the pregnancy home address from a dispersion model with 1 km resolution. We used classification and regression trees (CART) and linear regression to characterise the association of atmospheric pollutants with individual (maternal age, body mass index, parity, education level, relationship status, smoking status) and contextual (European Deprivation Index, urbanisation level) factors. RESULTS: Patterns of associations were globally similar across pollutants. For the CART approach, the highest tertile of exposure included mainly women not in a relationship living in urban and socially deprived areas, with lower education level. Linear regression models identified different determinants of atmospheric pollutants exposure according to the residential urbanisation level. In urban areas, atmospheric pollutants exposure increased with social deprivation, while in rural areas a U-shaped relationship was observed. CONCLUSION: We highlighted social inequalities in atmospheric pollutants exposure according to contextual characteristics such as urbanisation level and social deprivation and also according to individual characteristics such as education, being in a relationship and smoking status. In French urban areas, pregnant women from the most deprived neighbourhoods were those most exposed to health-threatening atmospheric pollutants.