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


METHODS
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.
Sørensen
Holger J
HJ
Danish Epidemiology Science Center, Institute of Preventive Medicine, Copenhagen University Hospital, Denmark. holgerjs@dadlnet.dk
Mortensen
Erik L
EL
Reinisch
June M
JM
Mednick
Sarnoff A
SA
D016241:Child of Impaired Parents; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007231:Infant, Newborn; D016015:Logistic Models; D018811:Maternal Exposure; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000209:etiology*
D004232:Diuretics