Maternal Caffeine Consumption during Pregnancy and Behavioral Disorders in 11-Year-Old Offspring: A Danish National Birth Cohort Study.

OBJECTIVE: To examine the association between maternal caffeine consumption from coffee and tea during pregnancy and offspring behavioral disorders. STUDY DESIGN: We studied 47 491 children enrolled in the Danish National Birth Cohort between 1996 and 2002. Data on maternal coffee and tea consumption was collected at 15 and 30 weeks of gestation. When the child was 11 years old, the Strength and Difficulties Questionnaire was filled in by children, parents, and teachers. We estimated risk ratios (RRs) for offspring behavioral disorders. RESULTS: At 15 weeks of gestation 3% and 4% of the pregnant women consumed ≥8 cups/d of coffee or tea, respectively. Maternal coffee consumption ≥8 cups/d at 15 weeks of gestation was associated with increased risk of hyperactivity-inattention disorder (RR 1.47; 95% CI 1.18-1.83), conduct-oppositional disorders (RR 1.22; 95% CI 1.01-1.48), and any psychiatric disorder (RR 1.23; 95% CI 1.08-1.40). Maternal tea consumption ≥8 cups/d at 15 weeks of gestation was associated with increased risk of anxiety-depressive disorders (RR 1.28; 95% CI 1.09-1.52) and any psychiatric disorder (RR 1.24; 95% CI 1.11-1.40). An increased risk of hyperactivity-inattention disorder was observed with increasing daily caffeine consumption at 15 weeks of gestation. CONCLUSION: High maternal caffeine consumption from coffee and tea at 15 weeks of gestation was associated with behavioral disorders in 11-year-old offspring. We hypothesize that caffeine exposure may affect the fetal brain and program for behavioral disorders later in life. The fetal brain seems to be more sensitive to caffeine exposure at 15 weeks of pregnancy compared with 30 weeks of gestation.

Developmental Coordination Disorder in Children with a History of Infantile Colic.

OBJECTIVE: To investigate whether children with a history of infantile colic showed impaired motor development at age 7 years compared with unaffected peers. STUDY DESIGN: We studied 27,940 children from the Danish National Birth Cohort (1997-2002), including 1879 (6.8%) with a history of infantile colic. Infantile colic was defined according to the modified Wessel criteria as crying for more than 3 hours per day and more than 3 days per week. We compared the parental Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) scores in children with and without infantile colic after adjustment for intrauterine exposures, feeding type, parity, maternal age, socioeconomic status, Apgar score, gestational age, and birth weight. RESULTS: Children with a history of infantile colic had an elevated risk of scoring above the predefined cutoff limit of possible or suspected developmental coordination disorder (OR, 1.3; 95% CI, 1.0-1.7; P = .034). The mean total DCDQ'07 score was -0.4 point (95% CI, -0.8 to 0) lower in children with a history of infantile colic. Moreover, they were at higher risk for a low total score (OR for a 10-point decrease, 1.1; 95% CI, 1.0-1.1; P = .006) and a low general coordination score (OR, 1.3; 95% CI, 1.1-1.5, P = .000) in the DCDQ'07. All associations appeared to be stronger among boys, but no statistically significant effect measure modification between infantile colic and sex was found. CONCLUSION: We found no evidence of a strong association between infantile colic and developmental coordination disorder in this large Danish cohort.

Prenatal Chlamydia trachomatis infection increases the risk of preeclampsia.

The relationship between Chlamydia trachomatis (CT) and preeclampsia was examined longitudinally among 205 cases and 423 normotensive controls nested within the Collaborative Perinatal Project. Antibodies were analyzed at a first prenatal visit (mean 14.2 weeks) and at delivery. Prenatal infections were identified as IgG/IgM seroconversion or a four-fold rise in IgG antibody titers. Although serological evidence of incident prenatal CT infection was uncommon (n=9, 1.4%) in this general pregnant population, infected women were more likely to develop preeclampsia, after adjustment for maternal age, body mass index, smoking status, race and time between blood draws (ORadj 7.2, 95% CI 1.3 - 39.7).

Second trimester anti-angiogenic proteins and preeclampsia.

OBJECTIVE: To measure the relationships between soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and preeclampsia. STUDY DESIGN: We utilized a nested case-control study comprised of 211 preeclamptic women and 213 normotensive women with primiparous singleton pregnancies enrolled from ≥13 and <27 gestational weeks among the Danish National Birth Cohort of 100,000 women. Relationships between sFlt1, sEng and preeclampsia were estimated using smoothing splines in generalized linear models, adjusting for maternal age, body mass index, pre-existing hypertension, smoking, and gestational age. MAIN OUTCOME MEASURES: Preeclampsia was confirmed by an International Classification of Diseases (ICD) discharge diagnosis of 637.03, 637.04 637.09, 637.19 (ICD-8) or DO14 to DO15 (ICD-10) in the National Hospital Discharge Registry. In this sample, few cases delivered small for gestational age infants (8.1%) and the mean gestational age at delivery was term (38.2 ± 2.3 weeks). RESULTS: Doublings in the expressions of sFlt1 and sEng were associated with 39% (95% CI = 3%, 86%) and 74% (95% CI = 1%, 198%) increased risks of preeclampsia respectively. CONCLUSIONS: We conclude that second trimester high sFlt1 and sEng levels were possibly associated with an increased risk of preeclampsia after adjustment for maternal factors traditionally associated with the syndrome.

Low Apgar scores and risk of childhood attention deficit hyperactivity disorder.

OBJECTIVE: To examine whether low Apgar scores at 5 minutes are associated with increased risks of attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: We conducted a nationwide population-based cohort study of all 980 902 singletons born in Denmark from 1988 to 2001. All children were monitored from 3 years of age until a first International Classification of Diseases diagnosis of hyperkinetic disorder, a first medication for ADHD, migration, death, or the end of 2006, whichever came first. We used Cox regression models to examine the association between Apgar scores at 5 minutes and ADHD. RESULTS: Apgar scores were inversely associated with risk of ADHD (hazard ratio 0.92; 95% CI: 0.88-0.96, P trend < .001). Compared with children with Apgar scores of 9 or 10 at 5 minutes, the risk for ADHD was 75% higher in children with Apgar scores of 1 to 4 (hazard ratio 1.75; 95% CI: 1.15 to 2.11) and 63% higher for those with Apgar scores of 5 to 6 (95% CI: 1.25 to 2.11). CONCLUSIONS: A low Apgar score was associated with an increased risk of ADHD in childhood. Low Apgar scores and ADHD may share common causes or a low Apgar score reflects at least one causal pathway leading to ADHD.

Breastfeeding and risk of epilepsy in childhood: a birth cohort study.

OBJECTIVE: We asked whether breastfeeding reduces the risk of epilepsy in childhood. STUDY DESIGN: We included 69 750 singletons born between September 1997 and June 2003 in the Danish National Birth Cohort and observed them to August 2008. Information on breastfeeding was reported by mothers in two computer-assisted telephone interviews at 6 and 18 months after birth. Information on epilepsy (inpatients and outpatients) was retrieved from the Danish National Hospital Register. Cox proportional hazards regression models were used to estimate incidence rate ratios and 95% CIs. RESULTS: Breastfeeding was associated with a decreased risk of epilepsy, with a dose-response like pattern. For example, children breastfed for 3 to 5, 6 to 8, 9 to 12, and ≥ 13 months had a 26%, 39%, 50%, and 59% lower risk of epilepsy after the first year of life, respectively, compared with children who were breastfed for <1 month. The association remained when we excluded children who had adverse neonatal conditions or children who were exposed to adverse maternal conditions during pregnancy. CONCLUSIONS: The observed protective effect of breastfeeding may be causal. Breastfeeding may decrease epilepsy in childhood, thereby adding another reason for breastfeeding.