Pre-natal exposure to NO2 and PM2.5 and newborn lung function: An approach based on repeated personal exposure measurements.

CONTEXT: While strong evidence supports adverse effects of pre-natal air pollution on child's lung function, previous studies rarely considered fine particulate matter (PM2.5) or the potential role of offspring sex and no study examined the effects of pre-natal PM2.5 on the lung function of the newborn. AIM: We examined overall and sex-specific associations of personal pre-natal exposure to PM2.5 and nitrogen (NO2) with newborn lung function measurements. METHODS: This study relied on 391 mother-child pairs from the French SEPAGES cohort. PM2.5 and NO2 exposure was estimated by the average concentration of pollutants measured by sensors carried by the pregnant women during repeated periods of one week. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple breath washout (N2MBW) test, performed at 7 weeks. Associations between pre-natal exposure to air pollutants and lung function indicators were estimated by linear regression models adjusted for potential confounders, and then stratified by sex. RESULTS: Mean exposure to NO2 and PM2.5 during pregnancy was 20.2 µg/m3 and 14.3 µg/m3, respectively. A 10 µg/m3 increase in PM2.5 maternal personal exposure during pregnancy was associated with an adjusted 2.5 ml (2.3%) decrease in the functional residual capacity of the newborn (p-value = 0.11). In females, functional residual capacity was decreased by 5.2 ml (5.0%) (p = 0.02) and tidal volume by 1.6 ml (p = 0.08) for each 10 µg/m3 increase in PM2.5. No association was found between maternal NO2 exposure and newborns lung function. CONCLUSIONS: Personal pre-natal PM2.5 exposure was associated with lower lung volumes in female newborns, but not in males. Our results provide evidence that pulmonary effects of air pollution exposure can be initiated in utero. These findings have long term implications for respiratory health and may provide insights into the underlying mechanisms of PM2.5 effects.

Comparison of a Barcode-Based Smartphone Application to a Questionnaire to Assess the Use of Cleaning Products at Home and Their Association with Asthma Symptoms.

Household disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00-1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors.

Deciphering the Impact of Early-Life Exposures to Highly Variable Environmental Factors on Foetal and Child Health: Design of SEPAGES Couple-Child Cohort.

In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathways whereby exposures affect health, this design is expected to provide deeper understanding of the interplay between the Exposome and child development and health.

Prevalence and associated factors of minor neuromotor dysfunctions at age 5 years in prematurely born children: the EPIPAGE Study.

OBJECTIVES: To assess the frequency of minor neuromotor dysfunctions (MNDs) at age 5 years according to gestational age, to test their association with behavioral and learning difficulties, and to find determining neonatal factors. DESIGN: Prospective population-based cohort study of children born in 1997 and followed up from birth to age 5 years. SETTING: All maternity wards in 9 regions of France. PARTICIPANTS: A total of 1662 children born before 33 completed weeks of gestation and 2 control groups including 245 children born at 33 to 34 weeks and 332 children born at 39 to 40 weeks. Main Exposure Birth before 33 weeks. Main Outcome Measure Short version of the Touwen neurological examination classifying children as healthy, having mild MND (MND-1), or having moderate MND (MND-2) depending on the number of abnormal neuromotor signs found. RESULTS: Of children born before 33 weeks, 41.4% had MND-1 and 3.0% had MND-2. These proportions were 30.8% and 0.5%, respectively, for children born at 33 to 34 weeks and 22.0% and 0.7%, respectively, for children born at 39 to 40 weeks. Minor neuromotor dysfunction was independently associated with learning difficulties at age 5 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). In very preterm children, factors associated with MND-1 were postnatal corticotherapy (OR, 1.8; 95% CI, 1.3-2.6), multiple births (OR, 0.7; 95% CI, 0.6-0.9), and, in singletons, breastfeeding (OR, 0.8; 95% CI, 0.6-0.99). Being a boy (OR, 3.1; 95% CI, 1.5-6.4), having had acute fetal distress (OR, 2.8; 95% CI, 1.4-5.5) or severe abnormalities on early cranial ultrasonography (OR, 2.7; 95% CI, 1.2-6.2), and having had postnatal corticotherapy (OR, 2.7; 95% CI, 1.2-6.1) increased the risk of MND-2. CONCLUSIONS: The high rate of MNDs and their association with an increased risk for learning difficulties justify their screening in case of (even moderate) prematurity.

White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study.

OBJECTIVE: To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge. STUDY DESIGN: A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available. RESULTS: The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL. CONCLUSION: The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

Sex-specific impact of congenital hypothyroidism due to thyroid dysgenesis on skeletal maturation in term newborns.

Newborns with severe congenital hypothyroidism (often defined by the absence of knee epiphyses at diagnosis) are still at risk of loss of intellectual potential despite early treatment. Although there is no significant sexual dimorphism in the age at appearance and size of the knee epiphyses in normal newborns, it was our clinical impression that these epiphyses were more often absent in hypothyroid newborn males than in affected females. Using the large French database of congenital hypothyroidism, we studied the presence or absence of knee epiphyses at diagnosis, as well as the length of gestation and the birth weight of 1827 term newborns with athyreosis or ectopic thyroid. Boys were twice as likely as girls to have absent epiphyses [odds ratio, 2.1 (95% confidence interval, 1.6-2.7), P < 0.001, after adjustment for etiology, plasma free T(4) concentration, and presence or absence of clinical signs at diagnosis, gestational age and birth weight]. Compared with the general population of French newborns, those with congenital hypothyroidism were more often born after a prolonged gestation (> or =42 wk) and with a high birth weight (9% were above the 95th centile, as opposed to the expected 5%), regardless of sex. We conclude that the impact of congenital hypothyroidism on fetal skeletal maturation is sexually dimorphic. This may result from less efficient conversion of T(4) to T(3) by growth plate chondrocytes in males.