Eduardo Villamor1, Kristina Tedroff2, Mark Peterson3, Stefan Johansson4, Martin Neovius5, Gunnar Petersson5, Sven Cnattingius5. 1. Department of Epidemiology, School of Public Health, Center for Human Growth and Development, University of Michigan, Ann Arbor2Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 2. Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 3. Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor. 4. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden5Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. 5. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract
Importance: Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms. Objective: To study the associations between early pregnancy body mass index (BMI) and rates of cerebral palsy by gestational age and to identify potential mediators of these associations. Design, Setting, and Participants: Population-based retrospective cohort study of women with singleton children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012. Exposures: Early pregnancy BMI. Main Outcomes and Measures: Incidence rates of cerebral palsy and hazard ratios (HRs) with 95% CIs, adjusted for maternal age, country of origin, education level, cohabitation with a partner, height, smoking during pregnancy, and year of delivery. Results: Of 1 423 929 children included (mean gestational age, 39.8 weeks [SD, 1.8]; 51.4% male), 3029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up (risk, 2.13 per 1000 live births; rate, 2.63/10 000 child-years). The percentages of mothers in BMI categories were 2.4% at BMI less than 18.5 (underweight), 61.8% at BMI of 18.5 to 24.9 (normal weight), 24.8% at BMI of 25 to 29.9 (overweight), 7.8% at BMI of 30 to 34.9 (obesity grade 1), 2.4% at BMI of 35 to 39.9 (obesity grade 2), and 0.8% at BMI 40 or greater (obesity grade 3). The number of cerebral palsy cases in each BMI category was 64, 1487, 728, 239, 88, and 38; and the rates per 10 000 child-years were 2.58, 2.35, 2.92, 3.15, 4.00, and 5.19, respectively. Compared with children of normal-weight mothers, adjusted HR of cerebral palsy were 1.22 (95% CI, 1.11-1.33) for overweight, 1.28 (95% CI, 1.11-1.47) for obesity grade 1, 1.54 (95% CI, 1.24, 1.93) for obesity grade 2, and 2.02 (95% CI, 1.46-2.79) for obesity grade 3. Results were statistically significant for children born at full term, who comprised 71% of all children with cerebral palsy, but not for preterm infants. An estimated 45% of the association between maternal BMI and rates of cerebral palsy in full-term children was mediated through asphyxia-related neonatal morbidity. Conclusions and Relevance: Among Swedish women with singleton children, maternal overweight and obesity were significantly associated with the rate of cerebral palsy. The association was limited to children born at full term and was partly mediated through asphyxia-related neonatal complications.
Importance: Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms. Objective: To study the associations between early pregnancy body mass index (BMI) and rates of cerebral palsy by gestational age and to identify potential mediators of these associations. Design, Setting, and Participants: Population-based retrospective cohort study of women with singleton children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012. Exposures: Early pregnancy BMI. Main Outcomes and Measures: Incidence rates of cerebral palsy and hazard ratios (HRs) with 95% CIs, adjusted for maternal age, country of origin, education level, cohabitation with a partner, height, smoking during pregnancy, and year of delivery. Results: Of 1 423 929 children included (mean gestational age, 39.8 weeks [SD, 1.8]; 51.4% male), 3029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up (risk, 2.13 per 1000 live births; rate, 2.63/10 000 child-years). The percentages of mothers in BMI categories were 2.4% at BMI less than 18.5 (underweight), 61.8% at BMI of 18.5 to 24.9 (normal weight), 24.8% at BMI of 25 to 29.9 (overweight), 7.8% at BMI of 30 to 34.9 (obesity grade 1), 2.4% at BMI of 35 to 39.9 (obesity grade 2), and 0.8% at BMI 40 or greater (obesity grade 3). The number of cerebral palsy cases in each BMI category was 64, 1487, 728, 239, 88, and 38; and the rates per 10 000 child-years were 2.58, 2.35, 2.92, 3.15, 4.00, and 5.19, respectively. Compared with children of normal-weight mothers, adjusted HR of cerebral palsy were 1.22 (95% CI, 1.11-1.33) for overweight, 1.28 (95% CI, 1.11-1.47) for obesity grade 1, 1.54 (95% CI, 1.24, 1.93) for obesity grade 2, and 2.02 (95% CI, 1.46-2.79) for obesity grade 3. Results were statistically significant for children born at full term, who comprised 71% of all children with cerebral palsy, but not for preterm infants. An estimated 45% of the association between maternal BMI and rates of cerebral palsy in full-term children was mediated through asphyxia-related neonatal morbidity. Conclusions and Relevance: Among Swedish women with singleton children, maternal overweight and obesity were significantly associated with the rate of cerebral palsy. The association was limited to children born at full term and was partly mediated through asphyxia-related neonatal complications.
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