Association of Gestational Weight Gain and Maternal Body Mass Index in Early Pregnancy With Risk for Nonaffective Psychosis in Offspring

IMPORTANCE Prenatal exposure to famine is associated with a 2-fold risk for nonaffective psychoses. Less is known about whether maternal nutrition states during pregnancy modify offspring risk for nonaffective psychoses in offspring in well-fed populations. OBJECTIVE To determine whether gestational weight gain (GWG) during pregnancy and maternal body mass index (BMI) in early pregnancy are associated with risk for nonaffective psychoses in offspring. DESIGN, SETTING AND PARTICIPANTS This population-based cohort study used data from Swedish health and population registers to follow up 526 042 individuals born from January 1, 1982, through December 31, 1989, from 13 years of age until December 31, 2011. Cox proportional hazards regression models adjusted for socioeconomic status and potential risk factors were used to examine the risk for developing nonaffective psychoses. Family-based study designs were used to further test causality. Data were analyzed from February 1 to May 14, 2016. EXPOSURES Gestational weight gain during pregnancy, maternal body mass index at the first antenatal visit, and paternal body mass index at the time of conscription into the Swedish military (at 18 years of age). MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for the diagnosis of nonaffective psychoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20 to F29 and International Classification of Diseases, Ninth Revision [ICD-9] codes 295, 297 and 298, except 298A and 298B) and narrowly defined schizophrenia (ICD-9 code 295 and ICD-10 code F20). RESULTS The 526 042 individuals in the cohort (48.52% female and 51.47% male; mean [SD] age, 26 [2.3] years) included 2910 persons with nonaffective psychoses at the end of follow-up, of whom 704 had narrowly defined schizophrenia. Among the persons with nonaffective psychosis, 184 (6.32%) had mothers with extremely inadequate GWG (<8 kg for mothers with normal baseline BMI), compared with 23 627 (4.52%) of unaffected individuals. Extremely inadequate GWG was associated with an increased risk for nonaffective psychoses among offspring in adjusted models (HR, 1.32; 95% CI, 1.13-1.54) and in matched-sibling analysis (HR, 1.61; 95% CI, 1.02-2.56). Similar patterns were observed when considering narrowly defined schizophrenia as the outcome. Maternal mild thinness in early pregnancy was weakly associated with an increased risk for nonaffective psychosis in offspring (HR for BMI >= 17.0 and <18.5, 1.21; 95% CI, 1.01-1.45), as was paternal severe thinness (HR for BMI<16.0, 2.53; 95% CI, 1.26-5.07) in mutually adjusted models. In matched-sibling analysis, no association was observed between maternal underweight (HR, 1.46; 95% CI, 0.90-2.35), overweight (HR, 1.11; 95% CI, 0.73-1.68), or obesity (HR, 0.56; 95% CI, 0.23-1.38) and risk for nonaffective psychosis in offspring. CONCLUSIONS AND RELEVANCE Inadequate GWG was associated with an increased risk for nonaffective psychosis in offspring, consistent with historical studies on maternal starvation. These findings support the role of maternal undernutrition in nonaffective psychosis pathogenesis.