Association of Preeclampsia and Perinatal Complications With Offspring Neurodevelopmental and Psychiatric Disorders

Key Points Question Is maternal preeclampsia, alone or together with perinatal complications (preterm birth and/or small birth size) associated with an increased risk of neurodevelopmental and psychiatric disorders in offspring? Findings In this cohort study of 1 012 723 singleton live births in Finland, exposure to both maternal preeclampsia and perinatal complications was associated with higher risks of specific neurodevelopmental disorders as well as attention-deficit/hyperactivity disorder and conduct disorders in offspring compared with exposure to either preeclampsia or perinatal complications alone. Meaning These results suggest that children exposed to both preeclampsia in utero and perinatal complications have modestly increased risks of developing specific neurodevelopmental disorders as well as attention-deficit/hyperactivity disorder and conduct disorders.


ICD-10 codes
1.81 (1.71-1.90) a Exclusion: Births with maternal in-hospital psychiatric disorder and those with maternal pre-gestational diabetes. Preeclampsia was ICD-10 codes O11 or O14. Perinatal complications referred to SGA or delivery before 34 gestational weeks. The no preeclampsia, no perinatal complications group excluded maternal chronic hypertension and gestational hypertension. b The analyses were adjusted for offspring birth year, sex, maternal age at delivery, mother's country of birth (Finland or not), mother married at birth (yes/no), maternal occupation (SES, upper white collar worker, lower white collar worker, blue collar worker, and other status), maternal smoking (yes/no), parity (0 or ≥1), maternal obesity (ICD-10: E65-E66, yes/no), maternal gestational diabetes (yes/no), maternal outpatient psychiatric disorders (yes/no), maternal N05/N06 purchase during pregnancy, and maternal systemic inflammatory disease (yes/no).

No. (%) Exposures a
Any medication ( Both of the siblings in the pair were exposed (n=142) NA 0.51 (0.07-3.61) NA

Model 2 d
None of the siblings in the pair was exposed (n=435 997) Both of the siblings in the pair were exposed (n=120) NA 0.55 (0.08-3.89) NA

Model 2 d
None of the siblings in the pair was exposed (n=298 066) Both of the siblings in the pair were exposed (n=120) NA 0.54 (0.08-3.81) NA NA, not applicable. a First sibling pairs were included, i.e. sibling 1&2. b Exclusion: Maternal in-hospital psychiatric disorder and maternal pre-gestational diabetes. Reference group was no preeclampsia (no ICD-10 O11 or O14) and no perinatal complications after excluding maternal chronic hypertension and gestational hypertension. c Model 1: The analyses were adjusted for offspring birth year, sex, maternal age at delivery, mother's country of birth (Finland or not), mother married at birth (yes/no), maternal occupation (SES, upper white collar worker, lower white collar worker, blue collar worker, and other status), maternal smoking (yes/no), parity (0 or ≥1), maternal obesity (ICD-10: E65-E66, yes/no), maternal gestational diabetes (yes/no), maternal outpatient psychiatric disorders (yes/no), maternal N05/N06 purchase during pregnancy (yes/no), maternal systemic inflammatory disease (yes/no), and intra-pregnancy interval. d Model 2: Adjusted for the variables in Model 1 and presence of the studied F diagnosis in the first child.

eTable 9. Sibling Pair Analysis in All Mothers With a Singleton Sibling Pair (n = 427 591) Among the 1 012 723 Births (Born 1996-2014) for Any Psychiatric Disorder and Specific Neurodevelopmental Disorders in the Second Child
Adjusted Cox hazard ratios (HRs) and 95% CIs for the outcomes (columns) in the second child being (i) any psychiatric disorder (ICD-10 F diagnoses), and (ii) specific developmental disorders (F80-83) from birth until 2018, in relation to exposure for the sibling pair to preeclampsia.

Adjusted HR (95% CI)
Any F-diagnosis Specific developmental disorders (F80-83) Model 1 b None of the siblings in the pair was exposed (n=415 393)

Model 2 c
None of the siblings in the pair was exposed (n=415 393) The analyses were adjusted for offspring birth year, sex, maternal age at delivery, mother's country of birth (Finland or not), mother married at birth (yes/no), maternal occupation (SES, upper white collar worker, lower white collar worker, blue collar worker, and other status), maternal smoking (yes/no), parity (0 or ≥1), maternal obesity (ICD-10: E65-E66, yes/no), maternal gestational diabetes (yes/no), maternal outpatient psychiatric disorders (yes/no), maternal N05/N06 purchase during pregnancy, and maternal systemic inflammatory disease (yes/no).