Prenatal and postnatal exposure to NO2 and rapid infant weight gain - A population-based cohort study.

BACKGROUND: Childhood overweight and obesity is a global public health problem. Rapid infant weight gain is predictive of childhood overweight. Studies found that exposure to ambient air pollution is associated with childhood overweight, and have linked prenatal exposure to air pollution with rapid infant weight gain. OBJECTIVES: To examine the association between prenatal and postnatal ambient NO2 exposure, a traffic-related marker, with rapid weight gain in infants. METHODS: We carried out a population-based historical cohort study using data from the Israeli national network of maternal and child health clinics. The study included 474,136 infants born at term with birthweight ≥2500 g in 2011-2019 in central Israel. Weekly averages of NO2 concentration throughout pregnancy (prenatal) and the first 4 weeks of life (postnatal) were assessed using an optimized dispersion model and were linked to geocoded home addresses. We modelled weight gain velocity throughout infancy using the SuperImposition by Translation and Rotation (SITAR) method, a mixed-effects nonlinear model specialized for modelling growth curves, and defined rapid weight gain as the highest velocity tertile. Distributed-lag models were used to assess critical periods of risk and to measure relative risks for rapid weight gain. Adjustments were made for socioeconomic status, population group, subdistrict, month and year of birth, and the alternate exposure period - prenatal or postnatal. RESULTS: The cumulative adjusted relative risk for rapid weight gain of NO2 exposure was 1.02 (95% confidence intereval [CI] 1.00, 1.04) for exposure throughout pregnancy and 1.02 (95% CI 1.01, 1.04) for exposure during the first four postnatal weeks per NO2 interquartile range increase (7.3 ppb). An examination of weekly associations revealed that the critical period of risk for the prenatal exposure was from mid-pregnancy to birth. CONCLUSIONS: Prenatal and postnatal exposures to higher concentrations of traffic-related air pollution are each independently associated with rapid infant weight gain, a risk factor for childhood overweight and obesity.

Gestational age at birth and academic attainment in primary and secondary school in England: Evidence from a national cohort study.

Preterm birth (<37 weeks' gestation) is a risk factor for poor educational outcomes. A dose-response effect of earlier gestational age at birth on poor primary school attainment has been observed, but evidence for secondary school attainment is limited and focused predominantly on the very preterm (<32 weeks) population. We examined the association between gestational age at birth and academic attainment at the end of primary and secondary schooling in England. Data for children born in England from 2000-2001 were drawn from the population-based UK Millennium Cohort Study. Information about the child's birth, sociodemographic factors and health was collected from parents. Attainment on national tests at the end of primary (age 11) and secondary school (age 16) was derived from linked education records. Data on attainment in primary school was available for 6,950 pupils and that of secondary school was available for 7,131 pupils. Adjusted relative risks (aRRs) for these outcomes were estimated at each stage separately using modified Poisson regression. At the end of primary school, 17.7% of children had not achieved the expected level in both English and Mathematics and this proportion increased with increasing prematurity. Compared to full term (39-41 weeks) children, the strongest associations were among children born moderately (32-33 weeks; aRR = 2.13 (95% CI 1.44-3.13)) and very preterm (aRR = 2.06 (95% CI 1.46-2.92)). Children born late preterm (34-36 weeks) and early term (37-38 weeks) were also at higher risk with aRR = 1.18 (95% CI 0.94-1.49) and aRR = 1.21 (95% CI 1.05-1.38), respectively. At the end of secondary school, 45.2% had not passed at least five General Certificate of Secondary Education examinations including English and Mathematics. Following adjustment, only children born very preterm were at significantly higher risk (aRR = 1.26 (95% CI 1.03-1.54)). All children born before full term are at risk of poorer attainment during primary school compared with term-born children, but only children born very preterm remain at risk at the end of secondary schooling. Children born very preterm may require additional educational support throughout compulsory schooling.

Postnatal exposure to ambient temperature and rapid weight gain among infants delivered at term gestations: a population-based cohort study.

BACKGROUND: The global prevalence of childhood obesity has risen dramatically recently. Previous studies found an association between rapid infant weight gain and childhood overweight. Evidence suggests that exposure to high ambient air temperatures during prenatal life and during adulthood is associated with birthweight and obesity respectively. OBJECTIVE: The objective of this study was to examine whether exposure to high ambient temperatures during infancy is associated with rapid infant weight gain in Israel. METHODS: This is a population-based historical cohort study using data from the Israeli national public network of maternal and child health clinics between 2008 and 2013. We assessed exposure to ambient temperature in the first year of life using a high-resolution hybrid spatio-temporal model and calculated annual mean and minimum temperatures for each infant based on daily mean and minimum temperatures at the community clinic location. We defined rapid infant weight gain as a World Health Organization weight z-score difference >0.67 between birthweight and weight at age one year. We estimated these associations using log-linear and general additive models and adjusted for population group, district, maternal age, parental education, parity, sex, gestational age, birthweight, calendar year and calendar month of birth. RESULTS: The study population included 217,310 singleton-term infants. Adjusted models demonstrated a positive association between ambient temperature exposure and rapid infant weight gain. Compared to the third quintile of minimum temperature, infants exposed to the first and second quintile had an adjusted relative risk of 0.98 (95% CI 0.96, 1.00) and 0.97 (95% CI 0.95, 0.98), respectively, while those exposed to the fourth and fifth quintiles had an adjusted relative risk of 1.06 (95% CI 1.04, 1.07) and 1.02 (95% CI 1.00, 1.04) respectively. The associations with mean temperature were similar but slightly weaker. CONCLUSIONS: Exposure to higher ambient temperatures, of emerging importance in the climate change era, is associated with rapid infant weight gain in Israel. Future studies should use additional exposure, covariate, and outcome data to analyse the nature and the source of this association in more detail.

Caesarean section and severe upper and lower respiratory tract infections during infancy: Evidence from two UK cohorts.

BACKGROUND: Several studies have reported that birth by caesarean section is associated with increased risk of lower respiratory tract infections in the child, but it is unclear whether this applies to any caesarean section or specifically to planned caesareans. Furthermore, although infections of the upper respiratory tract are very common during childhood, there is a scarcity of studies examining whether caesarean is also a risk factor for this site of infection. METHODS: We obtained data from two UK cohorts: the Millennium Cohort Study (MCS) and linked administrative datasets of the population of Wales through the Secure Anonymised Information Linkage (SAIL) databank. The study focused on term-born singleton infants and included 15,580 infants born 2000-2002 (MCS) and 392,145 infants born 2002-2016 (SAIL). We used information about mode of birth (vaginal delivery, assisted vaginal delivery, planned caesarean and emergency caesarean) from maternal report in the MCS and from hospital birth records in SAIL. Unplanned hospital admission for lower respiratory tract infection (LRTI) was ascertained from maternal report in the MCS and from hospital record ICD codes in SAIL. Information about admissions for upper respiratory tract infection (URTI) was available from SAIL only. Cox regression was used to estimate hazard ratios for each outcome and cohort separately while accounting for a wide range of confounders. Gestational age at birth was further examined as a potential added, indirect risk of planned caesarean birth due to the early delivery. FINDINGS: The rate of hospital admission for LRTI was 4.6 per 100 child years in the MCS and 5.9 per 100 child years in SAIL. Emergency caesarean was not associated with LRTI admission during infancy in either cohort. In the MCS, planned caesarean was associated with a hazard ratio of 1.39 (95% CI 1.03, 1.87) which further increased to 1.65 (95% CI 1.24, 2.19) when gestational age was not adjusted for. In SAIL, the adjusted hazard ratio was 1.10 (95% CI 1.05, 1.15), which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for. The rate of hospital admission for URTI was 5.9 per 100 child years in SAIL. Following adjustments, emergency caesarean was found to have a hazard ratio of 1.09 (95% CI 1.05, 1.14) for hospital admission for URTI. Planned caesarean was associated with a hazard ratio of 1.11 (95% CI 1.06, 1.16) which increased to 1.17 (95% CI 1.12, 1.22) when gestational age was not adjusted for. CONCLUSIONS: The risk of severe LRTIs during infancy is moderately elevated in infants born by planned caesarean compared to those born vaginally. Infants born by any type of caesarean may also be at a small increased risk of severe URTIs. The estimated effect sizes are stronger if including the indirect effect arising from planning the caesarean birth for an earlier gestation than would have occurred spontaneously. Further studies are needed to confirm these results.

Gestational age at birth and child special educational needs: a UK representative birth cohort study.

OBJECTIVE: To examine the association between gestational age at birth across the entire gestational age spectrum and special educational needs (SENs) in UK children at 11 years of age. METHODS: The Millennium Cohort Study is a nationally representative longitudinal sample of children born in the UK during 2000-2002. Information about the child's birth, health and sociodemographic factors was collected when children were 9 months old. Information about presence and reasons for SEN was collected from parents at age 11. Adjusted relative risks (aRRs) were estimated using modified Poisson regression, accounting for confounders. RESULTS: The sample included 12 081 children with data at both time points. The overall prevalence of SEN was 11.2%, and it was inversely associated with gestational age. Among children born <32 weeks of gestation, the prevalence of SEN was 27.4%, three times higher than among those born at 40 weeks (aRR=2.89; 95% CI 2.02 to 4.13). Children born early term (37-38 weeks) were also at increased risk for SEN (aRR=1.33; 95% CI 1.11 to 1.59); this was the same when the analysis was restricted to births after labour with spontaneous onset. Birth before full term was more strongly associated with having a formal statement of SEN or SEN for multiple reasons. CONCLUSION: Children born at earlier gestational ages are more likely to experience SEN, have more complex SEN and require support in multiple facets of learning. This association was observed even among children born early-term and when labour began spontaneously.

Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurodegeneration, immunodeficiency, susceptibility to cancer, genomic instability, and sensitivity to ionizing radiation. A-T is caused by mutations that eliminate or inactivate the nuclear protein kinase ATM, the chief activator of the cellular response to double strand breaks (DSBs) in the DNA. Mild A-T is usually caused by ATM mutations that leave residual amounts of active ATM. We studied two siblings with mild A-T, as defined by clinical examination and a quantitative A-T neurological index. Surprisingly, no ATM was detected in the patients' cells, and sequence analysis revealed that they were homozygous for a truncating ATM mutation (5653delA) that is expected to lead to the classical, severe neurological presentation. Moreover, the cellular phenotype of these patients was indistinguishable from that of classical A-T: all the tested parameters of the DSB response were severely defective as in typical A-T. This analysis shows that the severity of the neurological component of A-T is determined not only by ATM mutations but also by other influences yet to be found.