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Richard Neugebauer, PhD, MPH; Hans Wijbrand Hoek, MD, PhD; Ezra Susser, MD, DrPH

JAMA. 1999;282:455-462.

Context  Several observational epidemiological studies report an association of pregnancy and obstetric complications with development of antisocial personality disorder (ASPD) in offspring. However, the precise nature and timing of the hypothesized biological insults are not known.

Objective  To test whether severe maternal nutritional deficiency early in gestation is associated with risk for ASPD in offspring.

Design and Setting  Retrospective cohort study. From October 1944 to May 1945, the German army blockaded food supplies to the Netherlands, subjecting the western Netherlands first to moderate (official food rations, 4200-6300 kJ/d) then to severe (<4200 kJ/d) nutritional deficiency. The north and south were subjected to moderate nutritional deficiency only.

Participants  Dutch men born in large urban areas in 1944-1946 who were given psychiatric examinations for military induction at age 18 years (N=100,543) were classified by the degree and timing of their prenatal exposure to nutritional deficiency based on their birthdate and birthplace.

Main Outcome Measure  Diagnosis of ASPD by psychiatric interview at time of medical examination for military induction, using the International Classification of Diseases, Sixth Revision (ICD-6).

Results  Men exposed prenatally to severe maternal nutritional deficiency during the first and/or second trimesters of pregnancy exhibited increased risk for ASPD (adjusted odds ratio [OR], 2.5; 95% confidence interval [CI], 1.5-4.2). Third-trimester exposure to severe nutritional deficiency and prenatal exposure to moderate nutritional deficiency were not associated with risk for ASPD.

Conclusions  Our data suggest that severe nutritional insults to the developing brain in utero may be capable of increasing the risk for antisocial behaviors in offspring. The possible implications of these findings for both developed countries and developing countries, where severe nutritional deficiency is widespread and often exacerbated by war, natural disaster, and forced migration, warrant study.

Author Affiliations: Epidemiology of Developmental Brain Disorders Department, New York State Psychiatric Institute (Drs Neugebauer and Susser), G. H. Sergievsky Center, Faculty of Medicine (Dr Neugebauer), and Division of Epidemiology, Joseph L. Mailman School of Public Health (Dr Susser), Columbia University, New York, NY; and Parnassia the Hague Psychiatric Institute/Leiden University, the Hague, the Netherlands (Dr Hoek).

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