Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-22T20:20:29.708Z Has data issue: false hasContentIssue false

Degree of fetal growth restriction associated with schizophrenia risk in a national cohort

Published online by Cambridge University Press:  09 January 2013

M. G. Eide*
Affiliation:
Norwegian Institute of Public Health, Bergen, Norway Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway
D. Moster
Affiliation:
Locus of Registry-Based Epidemiology, Department of Public Health and Primary Health Care, University of Bergen, Norway Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
L. M. Irgens
Affiliation:
Locus of Registry-Based Epidemiology, Department of Public Health and Primary Health Care, University of Bergen, Norway The Medical Birth Registry of Norway, Norwegian Institute of Public Health, Norway
T. Reichborn-Kjennerud
Affiliation:
Division of Mental Health, Norwegian Institute of Public Health, Norway Institute of Psychiatry, University of Oslo, Norway
C. Stoltenberg
Affiliation:
Norwegian Institute of Public Health, Bergen, Norway
R. Skjærven
Affiliation:
Locus of Registry-Based Epidemiology, Department of Public Health and Primary Health Care, University of Bergen, Norway The Medical Birth Registry of Norway, Norwegian Institute of Public Health, Norway
E. Susser
Affiliation:
Mailman School of Public Health and New York State Psychiatric Institute, Columbia University, New York, NY, USA
K. Abel
Affiliation:
Centre for Women's Mental Health, Community-Based Medicine, University of Manchester, UK
*
*Address for correspondence: Dr M. G. Eide, Department of Obstetrics and Gynecology, Haukeland University Hospital, N-5021 Bergen, Norway. (Email: [email protected])

Abstract

Background

Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia.

Method

A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n = 873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ‘birth weight for gestational age’ and ‘birth length for gestational age’. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria.

Results

The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend = 0.005). Compared with the reference group (z scores 0.01–1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (< − 3.00) was 2.0 (95% CI 1.2–3.5). A similar pattern was observed for birth length for gestational age z scores. Forty-nine individuals with schizophrenia were identified among 15 622 births with pre-eclampsia. The adjusted OR for schizophrenia following maternal pre-eclampsia was 1.3 (95% CI 1.0–1.8).

Conclusions

Associations of schizophrenia risk with degree of fetal growth restriction and pre-eclampsia suggest future research into schizophrenia etiology focusing on mechanisms that influence fetal growth, including placental function.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abel, KM (2004). Foetal origins of schizophrenia: testable hypotheses of genetic and environmental influences. British Journal of Psychiatry 184, 383385.CrossRefGoogle ScholarPubMed
Abel, KM, Allin, M (2006). Placental programming leading to mental ill health: fetal growth and schizophrenia. Clinics in Developmental Medicine 169, 118136.Google Scholar
Abel, KM, Wicks, S, Susser, E, Dalman, C, Pedersen, MG, Mortensen, PB, Webb, RT (2010). Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? Archives of General Psychiatry 67, 923930.CrossRefGoogle Scholar
Boden, R, Lundgren, M, Brandt, L, Reutfors, J, Kieler, H (2012). Antipsychotics during pregnancy: relation to fetal and maternal metabolic effects. Archives of General Psychiatry 69, 715721.CrossRefGoogle ScholarPubMed
Byrne, M, Agerbo, E, Bennedsen, B, Eaton, WW, Mortensen, PB (2007). Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. Schizophrenia Research 97, 5159.CrossRefGoogle ScholarPubMed
Dalman, C, Allebeck, P, Cullberg, J, Grunewald, C, Koster, M (1999). Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort. Archives of General Psychiatry 56, 234240.CrossRefGoogle ScholarPubMed
Donovan, SJ, Susser, E (2011). Commentary: Advent of sibling designs. International Journal of Epidemiology 40, 345349.CrossRefGoogle ScholarPubMed
Dunger, DB, Ong, KK (2005). Endocrine and metabolic consequences of intrauterine growth retardation. Endocrinology and Metabolism Clinics of North America 34, 597615, ix.CrossRefGoogle ScholarPubMed
Ellison, PT (2010). Fetal programming and fetal psychology. Infant and Child Development 19, 620.CrossRefGoogle Scholar
Eriksen, W, Sundet, JM, Tambs, K (2010). Birth weight standardized to gestational age and intelligence in young adulthood: a register-based birth cohort study of male siblings. American Journal of Epidemiology 172, 530536.CrossRefGoogle ScholarPubMed
Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL (2008) Effect of in utero and early-life conditions on adult health and disease. New England Journal of Medicine 359, 6173.CrossRefGoogle ScholarPubMed
Gunnell, D, Harrison, G, Whitley, E, Lewis, G, Tynelius, P, Rasmussen, F (2005). The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women. Schizophrenia Research 79, 315322.CrossRefGoogle Scholar
Hultman, CM, Sparen, P, Takei, N, Murray, RM, Cnattingius, S (1999). Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. British Medical Journal 318, 421426.CrossRefGoogle ScholarPubMed
Irgens, LM (2000). The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years. Acta Obstetricia et Gynecologica Scandinavica 79, 435439.CrossRefGoogle Scholar
Jacobsson, B, Ahlin, K, Francis, A, Hagberg, G, Hagberg, H, Gardosi, J (2008). Cerebral palsy and restricted growth status at birth: population-based case-control study. British Journal of Obstetrics and Gynecology 115, 12501255.CrossRefGoogle ScholarPubMed
Jansson, T, Powell, TL (2007). Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clinical Science 113, 113.CrossRefGoogle ScholarPubMed
Jarvis, S, Glinianaia, SV, Torrioli, MG, Platt, MJ, Miceli, M, Jouk, PS, Johnson, A, Hutton, J, Hemming, K, Hagberg, G, Dolk, H, Chalmers, J; Surveillance of Cerebral Palsy in Europe (SCPE) collaboration of European Cerebral Palsy Registers (2003). Cerebral palsy and intrauterine growth in single births: European collaborative study. Lancet 362, 11061111.CrossRefGoogle ScholarPubMed
Jones, P (1999). Longitudinal approaches to the search for the causes of schizophrenia: past, present and future. In Searches for the Causes of Schizophrenia. Vol. IV. Balance of the Century (ed. Gattaz, W. F. and Hafner, H.), pp. 91119. Steinkopf: Darmstadt Berlin.CrossRefGoogle Scholar
Jones, PB, Rantakallio, P, Hartikainen, AL, Isohanni, M, Sipila, P (1998). Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 North Finland general population birth cohort. American Journal of Psychiatry 155, 355364.CrossRefGoogle ScholarPubMed
Khashan, AS, Abel, KM, McNamee, R, Pedersen, MG, Webb, RT, Baker, PN, Kenny, LC, Mortensen, PB (2008). Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Archives of General Psychiatry 65, 146152.CrossRefGoogle ScholarPubMed
Kuh, D, Ben-Shlomo, Y (2004). A Life Course Approach to Chronic Disease Epidemiology. Oxford University Press: Oxford.CrossRefGoogle Scholar
Lucas, A (1991). Programming by early nutrition in man. Ciba Foundation Symposium 156, 3850.Google ScholarPubMed
Ludwig, DS, Currie, J (2010). The association between pregnancy weight gain and birthweight: a within-family comparison. Lancet 376, 984990.CrossRefGoogle ScholarPubMed
McClellan, JM, Susser, E, King, MC (2006). Maternal famine, de novo mutations, and schizophrenia. Journal of the American Medical Association 296, 582584.CrossRefGoogle ScholarPubMed
McNeil, TF, Cantor-Graae, E, Ismail, B (2000). Obstetric complications and congenital malformation in schizophrenia. Brain Research. Brain Reearch Reviews 31, 166178.CrossRefGoogle ScholarPubMed
Moster, D, Lie, RT, Irgens, LM, Bjerkedal, T, Markestad, T (2001). The association of Apgar score with subsequent death and cerebral palsy: a population-based study in term infants. Journal of Pediatrics 138, 798803.CrossRefGoogle ScholarPubMed
Moster, D, Lie, RT, Markestad, T (2008). Long-term medical and social consequences of preterm birth. New England Journal of Medicine 359, 262273.CrossRefGoogle ScholarPubMed
Murray, RM, Lewis, SW (1987). Is schizophrenia a neurodevelopmental disorder? British Medical Journal (Clinical Research Edition) 295, 681682.CrossRefGoogle ScholarPubMed
Nilsson, E, Stalberg, G, Lichtenstein, P, Cnattingius, S, Olausson, PO, Hultman, CM (2005). Fetal growth restriction and schizophrenia: a Swedish twin study. Twin Research and Human Genetics 8, 402408.CrossRefGoogle ScholarPubMed
Rifkin, L, Lewis, S, Jones, P, Toone, B, Murray, R (1994). Low birth weight and schizophrenia. British Journal of Psychiatry 165, 357362.CrossRefGoogle ScholarPubMed
Roberts, JM, Cooper, DW (2001). Pathogenesis and genetics of pre-eclampsia. Lancet 357, 5356.CrossRefGoogle ScholarPubMed
Roberts, JM, Lain, KY (2002). Recent insights into the pathogenesis of pre-eclampsia. Placenta 23, 359372.CrossRefGoogle ScholarPubMed
Sacker, A, Done, DJ, Crow, TJ, Golding, J (1995). Antecedents of schizophrenia and affective illness. Obstetric complications. British Journal of Psychiatry 166, 734741.CrossRefGoogle ScholarPubMed
Schaefer, CA, Brown, AS, Wyatt, RJ, Kline, J, Begg, MD, Bresnahan, A, Susser, E (2000). Maternal prepregnant body mass and risk of schizophrenia in adult offspring. Schizophrenia Bulletin 26, 275286.CrossRefGoogle ScholarPubMed
Skjaerven, R, Gjessing, HK, Bakketeig, LS (2000). Birthweight by gestational age in Norway. Acta Obstetricia et Gynecologica Scandinavica 79, 440449.CrossRefGoogle ScholarPubMed
Skjaerven, R, Wilcox, AJ, Lie, RT (2002). The interval between pregnancies and the risk of preeclampsia. New England Journal of Medicine 346, 3338.CrossRefGoogle ScholarPubMed
Smith, GN, Flynn, SW, McCarthy, N, Meistrich, B, Ehmann, TS, MacEwan, GW, Altman, S, Kopala, LC, Honer, WG (2001). Low birthweight in schizophrenia: prematurity or poor fetal growth? Schizophrenia Research 47, 177184.CrossRefGoogle ScholarPubMed
Susser, E, Hoek, HW, Brown, A (1998). Neurodevelopmental disorders after prenatal famine: the story of the Dutch Famine Study. American Journal of Epidemiology 147, 213216.CrossRefGoogle ScholarPubMed
Tsuang, MT, Stone, WS, Faraone, SV (2001). Genes, environment and schizophrenia. British Journal of Psychiatry (Suppl.) 40, s18s24.CrossRefGoogle ScholarPubMed
Vestrheim, LC, Austgulen, R, Melve, KK, Roten, LT, Tappert, C, Araya, E (2010). Classification of pre-eclamptic pregnancies in health registries. Pregnancy Hypertension 1, 54.CrossRefGoogle Scholar
Wahlbeck, K, Forsen, T, Osmond, C, Barker, DJ, Eriksson, JG (2001). Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood. Archives of General Psychiatry 58, 4852.CrossRefGoogle ScholarPubMed
Zondervan, KT, Cardon, LR (2007). Designing candidate gene and genome-wide case-control association studies. Nature Protocols 2, 24922501.CrossRefGoogle ScholarPubMed