Smoking in Pregnancy and Child ADHD.

BACKGROUND AND OBJECTIVE: There is a well-documented association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD). The degree to which this reflects causal intrauterine effects or is due to unmeasured confounding is not clear. We sought to compare the association between maternal smoking during pregnancy and offspring ADHD with the associations with paternal smoking, grandmother's smoking when pregnant with mother, and maternal smoking in previous pregnancies. Each of these exposures is expected to be influenced by much of the same confounding factors as maternal smoking during pregnancy, but cannot have direct intrauterine effects. A sibling control design was also used. METHODS: The current study used data from the Norwegian Mother and Child Cohort Study (n > 100 000 children). Mothers and fathers reported on smoking during pregnancy, and mothers reported on smoking in previous pregnancies and their mother's smoking when pregnant with them. Mothers reported on child ADHD symptoms at 5 years of age. Information about child ADHD diagnosis was obtained from the Norwegian Patient Registry. RESULTS: Maternal smoking during pregnancy was not more strongly associated with offspring ADHD diagnosis than was paternal smoking, grandmother's smoking when pregnant with mother, or maternal smoking in previous pregnancies. Sibling control analyses showed no association between maternal smoking in pregnancy and child ADHD symptoms among siblings discordant for maternal smoking. CONCLUSIONS: These results suggest that the association between maternal smoking during pregnancy and offspring ADHD is not due to causal intrauterine effects, but reflects unmeasured confounding.

Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring.

OBJECTIVES: To investigate the association between maternal pre-pregnancy BMI and risk of cerebral palsy (CP) in offspring. METHODS: The study population consisted of 188 788 children in the Mothers and Babies in Norway and Denmark CP study, using data from 2 population-based, prospective birth cohorts: the Norwegian Mother and Child Cohort Study and the Danish National Birth Cohort. Prepregnancy BMI was classified as underweight (BMI <18.5), lower normal weight (BMI 18.5-22.9), upper normal weight (BMI 23.0-24.9), overweight (BMI 25.0-29.9), and obese (BMI ≥30). CP diagnoses were obtained from the national CP registries. Associations between maternal prepregnancy BMI and CP in offspring were investigated by using log-binomial regression models. RESULTS: The 2 cohorts had 390 eligible cases of CP (2.1 per 1000 live-born children). Compared with mothers in the lower normal weight group, mothers in the upper normal group had a 40% excess risk of having a child with CP (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.78). Excess risk was 60% (RR, 1.56; 95% CI, 1.21-2.01) for overweight mothers and 60% (RR, 1.55; 95% CI 1.11-2.18) for obese mothers. The risk of CP increased ∼4% for each unit increase in BMI (RR, 1.04; 95% CI, 1.02-1.06). Estimates changed little with adjustment for mother's occupational status, age, and smoking habits. CONCLUSIONS: Higher prepregnancy maternal BMI was associated with increased risk of CP in offspring.

Identifying children with autism spectrum disorder at 18 months in a general population sample.

BACKGROUND: Previous research on clinical and high-risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 months in a population-based sample and the association with later ASD diagnosis. METHODS: The study sample includes 52,026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population-based longitudinal study, and the Autism Birth Cohort (ABC), a sub-study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months. RESULTS: The M-CHAT 6-critical-item criterion and the 23-item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut-off on either of the screening criteria. The items with the highest likelihood ratios were 'interest in other children', 'show objects to others' and 'response to name'. CONCLUSION: Even though one-third of the children who later received an ASD diagnosis were identified through M-CHAT items, the majority scored below cut-off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age.

Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders.

BACKGROUND: This study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs). METHODS: The cohort sample (n = 89 836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n = 507 856). The children were born in 1999­2007, and seven prenatal and perinatal exposures were selected for analyses. RESULTS: ASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500 g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04. CONCLUSIONS: Associations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study.

Folic acid supplements in pregnancy and severe language delay in children.

CONTEXT: Prenatal folic acid supplements reduce the risk of neural tube defects and may have beneficial effects on other aspects of neurodevelopment. OBJECTIVE: To examine associations between mothers' use of prenatal folic acid supplements and risk of severe language delay in their children at age 3 years. DESIGN, SETTING, AND PATIENTS: The prospective observational Norwegian Mother and Child Cohort Study recruited pregnant women between 1999 and December 2008. Data on children born before 2008 whose mothers returned the 3-year follow-up questionnaire by June 16, 2010, were used. Maternal use of folic acid supplements within the interval from 4 weeks before to 8 weeks after conception was the exposure. Relative risks were approximated by estimating odds ratios (ORs) with 95% CIs in a logistic regression analysis. MAIN OUTCOME MEASURE: Children's language competency at age 3 years measured by maternal report on a 6-point ordinal language grammar scale. Children with minimal expressive language (only 1-word or unintelligible utterances) were rated as having severe language delay. RESULTS: Among 38,954 children, 204 (0.5%) had severe language delay. Children whose mothers took no dietary supplements in the specified exposure interval were the reference group (n = 9052 [24.0%], with severe language delay in 81 children [0.9%]). Adjusted ORs for 3 patterns of exposure to maternal dietary supplements were (1) other supplements, but no folic acid (n = 2480 [6.6%], with severe language delay in 22 children [0.9%]; OR, 1.04; 95% CI, 0.62-1.74); (2) folic acid only (n = 7127 [18.9%], with severe language delay in 28 children [0.4%]; OR, 0.55; 95% CI, 0.35-0.86); and (3) folic acid in combination with other supplements (n = 19,005 [50.5%], with severe language delay in 73 children [0.4%]; OR, 0.55; 95% CI, 0.39-0.78). CONCLUSION: Among this Norwegian cohort of mothers and children, maternal use of folic acid supplements in early pregnancy was associated with a reduced risk of severe language delay in children at age 3 years.