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Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

Abstract

OBJECTIVE

Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring.

METHOD

Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy.

RESULTS

In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk.

CONCLUSIONS

Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.

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  • Authors+Show Affiliations

    ,

    Danish Epidemiology Science Center, Institute of Preventive Medicine, Copenhagen University Hospital, Denmark. holgerjs@dadlnet.dk

    , ,

    Source

    The American journal of psychiatry 160:3 2003 Mar pg 464-8

    MeSH

    Child of Impaired Parents
    Cohort Studies
    Denmark
    Diuretics
    Embryonic and Fetal Development
    Female
    Humans
    Hypertension
    Infant, Newborn
    Logistic Models
    Maternal Exposure
    Pregnancy
    Pregnancy Complications, Cardiovascular
    Pregnancy Trimester, Third
    Prenatal Exposure Delayed Effects
    Prevalence
    Registries
    Risk Factors
    Schizophrenia

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12611826

    Citation

    Sørensen, Holger J., et al. "Do Hypertension and Diuretic Treatment in Pregnancy Increase the Risk of Schizophrenia in Offspring?" The American Journal of Psychiatry, vol. 160, no. 3, 2003, pp. 464-8.
    Sørensen HJ, Mortensen EL, Reinisch JM, et al. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? Am J Psychiatry. 2003;160(3):464-8.
    Sørensen, H. J., Mortensen, E. L., Reinisch, J. M., & Mednick, S. A. (2003). Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? The American Journal of Psychiatry, 160(3), pp. 464-8.
    Sørensen HJ, et al. Do Hypertension and Diuretic Treatment in Pregnancy Increase the Risk of Schizophrenia in Offspring. Am J Psychiatry. 2003;160(3):464-8. PubMed PMID: 12611826.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? AU - Sørensen,Holger J, AU - Mortensen,Erik L, AU - Reinisch,June M, AU - Mednick,Sarnoff A, PY - 2003/3/4/pubmed PY - 2003/4/26/medline PY - 2003/3/4/entrez SP - 464 EP - 8 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 160 IS - 3 N2 - OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk. CONCLUSIONS: Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life. SN - 0002-953X UR - https://www.unboundmedicine.com/medline/citation/12611826/full_citation L2 - https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.160.3.464?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -