Hostname: page-component-7c8c6479df-27gpq Total loading time: 0 Render date: 2024-03-29T07:08:16.132Z Has data issue: false hasContentIssue false

Parental mental illness and fatal birth defects in a national birth cohort

Published online by Cambridge University Press:  13 December 2007

R. T. Webb*
Affiliation:
Centre for Women's Mental Health Research, The University of Manchester, Manchester, UK Biostatistics/Health Methodology Research Group, The University of Manchester, Manchester, UK
A. R. Pickles
Affiliation:
Biostatistics/Health Methodology Research Group, The University of Manchester, Manchester, UK
S. A. King-Hele
Affiliation:
Centre for Women's Mental Health Research, The University of Manchester, Manchester, UK
L. Appleby
Affiliation:
Centre for Women's Mental Health Research, The University of Manchester, Manchester, UK
P. B. Mortensen
Affiliation:
National Centre for Register-based Research, University of Aarhus, Denmark
K. M. Abel
Affiliation:
Centre for Women's Mental Health Research, The University of Manchester, Manchester, UK
*
*Address for correspondence: Dr R. T. Webb, Centre for Women's Mental Health Research/Health Methodology Research Group, Williamson Building, The University of Manchester, Oxford Road, Manchester M13 9PL, UK. (Email: roger.webb@manchester.ac.uk)

Abstract

Background

Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.

Method

A population-based birth cohort was created by linking Danish national registers. We identified all singleton live births during 1973–1998 (n=1.45 m), all parental psychiatric admissions from 1969 onwards, and all fatal birth defects until 1 January 1999. Linkage and case ascertainment were almost complete. Relative risks were estimated using Poisson regression.

Results

Risk of fatal birth defect was elevated in relation to history of any maternal admission and also with affective disorders specifically, although the strongest effect found was with maternal schizophrenia. The rate was more than doubled in this group compared to the general population [relative risk (RR) 2.34, 95% confidence interval (CI) 1.45–3.77], which also represented a significant excess risk compared with all other admitted maternal disorders (p=0.018). Risk of death from causes other than birth defect was no higher with schizophrenia than with other maternal conditions. There was no elevation in risk of fatal birth defect if the father was admitted with schizophrenia or any other psychiatric diagnosis.

Conclusions

There are many possible explanations for a higher risk of fatal birth defect with maternal schizophrenia and affective disorder. These include genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication toxicity, and gene–environment interactions. Further research is needed to elucidate the causal mechanisms.

Type
Original Articles
Copyright
Copyright © 2007 Cambridge University Press

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

Bar-Oz, B, Einarson, T, Einarson, A, Boskovic, R, O'Brien, L, Malm, H, Bérard, A, Gideon, K (2007). Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors. Clinical Therapeutics 29, 918926.CrossRefGoogle ScholarPubMed
Bennedsen, BE, Mortensen, PB, Olesen, AV, Henriksen, TB (2001). Congenital malformations, stillbirths, and infant deaths among children of women with schizophrenia. Archives of General Psychiatry 58, 674679.CrossRefGoogle ScholarPubMed
Chambers, CD, Hernandez-Diaz, S, Van Marter, LJ, Werler, MM, Louik, C, Jones, KL, Mitchell, AA (2006). Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New England Journal of Medicine 354, 579587.Google Scholar
Gardner, W, Mulvey, EP, Shaw, EC (1995). Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models. Psychological Bulletin 118, 392404.Google Scholar
Habbick, BF, Nanson, JL, Snyder, RE, Casey, RE (1997). Mortality in foetal alcohol syndrome. Canadian Journal of Public Health 88, 181183.CrossRefGoogle ScholarPubMed
Hallmayer, J (2000). The epidemiology of the genetic liability for schizophrenia. Australian and New Zealand Journal of Psychiatry 34 (Suppl.), S47S55.Google Scholar
Hansen, SS, Munk-Jørgensen, P, Gulbæk, B, Solgård, T, Lauszus, KS, Albrechtsen, N, Borg, L, Egander, A, Faurholdt, K, Gilberg, A, Godsen, NP, Lorenzen, J, Richelsen, B, Weischer, K, Bertelsen, A (2000). Psychoactive substance use among psychiatric in-patients. Acta Psychiatrica Scandinavica 102, 432438.Google Scholar
Honein, MA, Paulozzi, LJ, Watkins, ML (2001). Maternal smoking and birth defects: validity of birth certificate data for effect estimation. Public Health Reports 116, 327335.Google Scholar
Howard, L, Webb, R, Abel, K (2004). Safety of antipsychotic drugs for pregnant and breastfeeding women with non-affective psychosis. British Medical Journal 329, 933934.Google Scholar
Ismail, B, Cantor-Graae, E, McNeil, TF (1998). Minor physical anomalies in schizophrenic patients and their siblings. American Journal of Psychiatry 155, 16951702.Google Scholar
Juel, K, Helweg-Larsen, K (1999). The Danish registers of causes of death. Danish Medical Bulletin 46, 354357.Google ScholarPubMed
Kallen, B, Tanberg, A (1983). Lithium and pregnancy. A cohort study on manic-depressive women. Acta Psychiatrica Scandinavica 68, 134139.Google Scholar
Kelly, RH, Danielson, BH, Golding, JM, Anders, TF, Gilbert, WM, Zatzick, DF (1999). Adequacy of prenatal care among women with psychiatric diagnoses giving birth in California in 1994 and 1995. Psychiatric Services 50, 15841590.Google Scholar
Kessing, LV (1998). A comparison of ICD-8 and ICD-10 diagnoses of affective disorder – a case register study from Denmark. European Psychiatry 13, 342345.CrossRefGoogle Scholar
King-Hele, SA, Abel, KM, Webb, RT, Mortensen, PB, Appleby, L, Pickles, AR (2007). Risk of sudden infant death syndrome with parental mental illness. Archives of General Psychiatry 64, 13231330.Google Scholar
Lam, PK, Torfs, CP (2006). Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Research 76, 182186.CrossRefGoogle ScholarPubMed
Lloyd, T, Doody, G, Brewin, J, Park, B, Jones, P (2003). Minor physical anomalies in schizophrenia: is age a confounding factor? Schizophrenia Research 61, 6773.CrossRefGoogle ScholarPubMed
McKenna, K, Einarson, A, Levinson, A, Koren, G (2004). Significant changes in antipsychotic drug use during pregnancy. Veterinary and Human Toxicology 46, 4446.Google Scholar
McKenna, K, Koren, G, Tetelbaum, M, Wilton, L, Shakir, S, Diav-Citrin, O, Levinson, A, Zipursky, RB, Einarson, A (2005). Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. Journal of Clinical Psychiatry 66, 444449.CrossRefGoogle ScholarPubMed
McNeil, TF, Cantor-Graae, E, Ismail, B (2000). Obstetric complications and congenital malformation in schizophrenia. Brain Research Reviews 31, 166178.Google Scholar
Moldin, SO (1994). Indicators of liability to schizophrenia: perspectives from genetic epidemiology. Schizophrenia Bulletin 20, 169184.CrossRefGoogle ScholarPubMed
Munk, EM, Norgaard, B, Gislum, M, Mortensen, PB, Sorensen, HT (2005). Use of antipsychotic drugs during pregnancy and the risk of adverse birth outcomes: a population-based cohort study. Schizophrenia Bulletin 31, 233.Google Scholar
Munk-Jørgensen, P (1995). Decreasing first admission rates for schizophrenia in Denmark 1970–1991 [in Danish]. Thesis, Department of Psychiatric Demography, University of Copenhagen.Google Scholar
Munk-Jørgensen, P, Mortensen, PB (1997). The Danish Psychiatric Central Register. Danish Medical Bulletin 44, 8284.Google ScholarPubMed
Pedersen, CB, Gøtzsche, H, Moller, JO, Mortensen, PB (2006). The Danish Civil Registration System. A cohort of eight million persons. Danish Medical Bulletin 53, 441449.Google ScholarPubMed
Pierce, DA, Preston, DL (1993). Joint analysis of site-specific cancer risks for the atomic bomb survivors. Radiation Research 134, 134142.CrossRefGoogle ScholarPubMed
Scialli, AR (2006). Teratology public affairs committee position paper: maternal obesity and pregnancy. Birth Defects Research 76, 7377.Google Scholar
Shaw, GM, Velie, EM, Morland, KB (1996). Parental recreational drug use and risk for neural tube defects. American Journal of Epidemiology 144, 11551160.CrossRefGoogle ScholarPubMed
Strudsholm, U, Johannessen, L, Foldager, L, Munk-Jørgensen, P (2005). Increased risk for pulmonary embolism in patients with bipolar disorder. Bipolar Disorders 7, 7781.CrossRefGoogle ScholarPubMed
Tuthill, DP, Stewart, JH, Coles, EC, Andrews, J, Cartlidge, PH (1999). Maternal cigarette smoking and pregnancy outcome. Paediatric and Perinatal Epidemiology 13, 245253.Google Scholar
Webb, R, Abel, K, Pickles, A, Appleby, L (2005). Mortality in offspring of parents with psychotic disorders: a critical review and meta-analysis. American Journal of Psychiatry 162, 10451056.Google Scholar
Webb, RT, Abel, KM, Pickles, AR, Appleby, L, King-Hele, SA, Mortensen, PB (2006). Mortality risk among offspring of psychiatric inpatients: a population-based follow-up to early adulthood. American Journal of Psychiatry 163, 21702177.Google Scholar
Webb, RT, Pickles, AR, Appleby, L, Mortensen, PB, Abel, KM (2007). Death by unnatural causes during childhood and early adulthood in offspring of psychiatric inpatients. Archives of General Psychiatry 64, 345352.Google Scholar
Weinberg, SM, Jenkins, EA, Marazita, ML, Maher, BS (2007). Minor physical anomalies in schizophrenia: a meta-analysis. Schizophrenia Research 89, 7285.Google Scholar
WHO (1967). Manual of the International Classification of Diseases (ICD-8). World Health Organization: Geneva.Google Scholar
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders. World Health Organization: Geneva.Google Scholar