Deviant intrauterine growth and risk of schizophrenia: A 34-year follow-up of the Northern Finland 1966 Birth Cohort

Abstract

Background

Low birth weight conveys a modest risk for schizophrenia. The effects of high birth weight and deviant birth length are less clear.

Methods

We linked perinatal data from 10,934 subjects from the Northern Finland 1966 Birth Cohort (n = 12 058) to the Finnish Hospital Discharge Register where we identified 111 cases of DSM-III-R schizophrenia up to age 35 years. Adjusted odds ratios between the risk of schizophrenia and birth weight, birth length and ponderal index and the risk of schizophrenia were analyzed.

Results

Both low (OR 2.5; 95% CI 1.2–5.1) and high birth weight (OR 2.4; 95% CI 1.1–4.9) increased the risk of later schizophrenia. In addition, short (OR 2.6; 95% CI 1.1–5.9) and long babies had an elevated risk of schizophrenia as adults (OR 1.8; 95% CI 1.0–3.5). A reverse J-shape curve described the associations between birth weight, length and schizophrenia.

Conclusions

Deviant intrauterine growth of the fetus in either direction was associated with increased risk of schizophrenia.

Introduction

Brain abnormalities in schizophrenia may begin during fetal development (Gilmore et al., 2001). As an index of intrauterine growth, birth weight may be considered an important indicator of fetal brain maturation. Several (Hultman et al., 1997, McNeil et al., 1993, Sacker et al., 1995) but not all studies (Jones et al., 1998, Kendell et al., 2000) have demonstrated that lower mean birth weight is associated with an increased risk of later schizophrenia. In their meta-analysis Kunugi et al. (2001) concluded that it is not clear-cut whether mean birth weight is lower in schizophrenia cases than in control population.

An excess of particularly low birth weight (< 2500 g) in individuals who will develop schizophrenia is well replicated (Dalman et al., 1999, Hultman et al., 1999, Ichiki et al., 2000, Jones et al., 1998, Kunugi et al., 2001, Rifkin et al., 1994, Sacker et al., 1995, Smith et al., 2001). Kunugi et al. (2001) concluded that low birth weight is a modest but definite risk factor for schizophrenia; odds ratios ranged between 1.7 and 3.9 with a pooled effect of 2.6. A meta-analysis of published prospective, population-based studies (Cannon et al., 2002) reported a similar result (OR 1.67; 95% CI 1.22–2.29), with a more stringent definition of low birth weight (< 2000 g) resulting in a higher risk (OR 3.9; 95% CI 1.4–10.8).

There are four reports concerning the association of high birth weight with schizophrenia, two from Sweden (Hultman et al., 1997, Hultman et al., 1999), one from Italy (Bersani et al., 2007) and our preliminary report from Finland (Moilanen et al., 2002). Hultman et al. (1997) showed that a disproportional birth weight for body length (1 SD heavy for length) was associated with an increased risk of schizophrenia (OR 4.42; 95% CI 1.97–9.91). In their later study, high birth weight for gestational age was related to elevated risk of reactive psychosis among females, but not among males, although detailed data were not presented (Hultman et al., 1999). In the case–control study of Bersani et al. (2007) high birth weight (> 4000 g) increased the risk of schizophrenia (OR 4.52; 95% CI 1.00–20.48).

Gunnell et al. (2003) noted a reverse J-shape association between gestation-adjusted birth weight and schizophrenia among Swedish male conscripts born in 1974–1980. In their later study with a further 5 years of follow-up of the cohort of Swedish men and women born in 1974–1980, they found little evidence of an association between deviant birth weight and schizophrenia. However, the authors concluded that the study did not rule out a small increased risk among babies > 4.0 kg (Gunnell et al., 2005).

Studies of deviant birth length and schizophrenia provide conflicting results. In the study by Wahlbeck et al. (2001) a unit (cm) decrease in birth length was associated with increased risk of schizophrenia (OR 1.12 95% CI 1.03–1.22). In addition, Gunnell et al. (2005) found an inverse association between birth lengths with schizophrenia. Short babies were at increased risk, the risk halving per 10 cm increase in birth length (hazard ratio 0.53; 95% CI 0.31–0.89). On the other hand, studies by Hultman et al., 1999, Dalman et al., 1999, Dalman et al., 2001 and meta-analysis based on these studies showed no evidence of shortness at birth and increased risk of schizophrenia; pooled odds ratio 1.06; 95% CI 0.86–1.31 (Cannon et al., 2002).

The current study addresses these issues by extending the earlier findings from the Northern Finland 1966 Birth Cohort that low birth weight (Jones et al., 1998) increases the risk of schizophrenia. Here, we report the risk of schizophrenia across the entire distribution of birth weight among both sexes, as well as the relation between birth length and schizophrenia.