Early onset preeclampsia and cerebral palsy: a double hit model?
BACKGROUND
Cerebral palsy (CP) is a late sequel of pregnancy, and the role of preeclampsia is debatable.


OBJECTIVE
The aims of this study were to determine the association between preeclampsia and cerebral palsy and to determine the risk factors for the development of cerebral palsy in these patients.


METHODS
A retrospective population-based cohort study was designed that included 229,192 singleton pregnancies. The study population was divided into 2 groups: (1) patients with preeclampsia (n = 9749) and (2) normotensive gestations (n = 219,443). Generalized Estimating Equation multiple logistic regression models were performed to study the associations among preeclampsia, small for gestational age, gestational age at delivery, and the risk factors for the development of cerebral palsy in neonates of women with preeclampsia.


RESULTS
The rate of cerebral palsy was double in patients with preeclampsia than in the normotensive group (0.2% vs 0.1%; P = .015); early onset preeclampsia and small for gestational age were independent risk factors for the subsequent development of cerebral palsy (odds ratio, 8.639 [95% confidence interval, 4.269-17.480]; odds ratio, 2.737 [95% confidence interval, 1.937-3.868], respectively). A second model was conducted to determine the risk factors for the development of cerebral palsy in women with preeclampsia. Birth asphyxia, complications of prematurity, and neonatal infectious morbidity, but not small for gestational age or gestational age at delivery, were independent risk factors for the development of cerebral palsy.


CONCLUSIONS
In a comparison with normal pregnant women, the rate of cerebral palsy is double among patients with preeclampsia, especially those with early-onset disease. Early-onset preeclampsia is an independent risk factor for cerebral palsy. Among women with preeclampsia, the presence of neonatal infectious morbidity, birth asphyxia, and complications of prematurity are independent risk factors for the development of cerebral palsy, which further supports the role of a multi-hit model in the pathogenesis of this syndrome.
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Omer
O
Mor
Center of Clinical Research, Ben Gurion University of the Negev, Faculty of Health Sciences, Beer Sheva, Israel.
Moshe
M
Stavsky
Center of Clinical Research, Ben Gurion University of the Negev, Faculty of Health Sciences, Beer Sheva, Israel.
Maayan
M
Yitshak-Sade
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel; Department of Obstetrics and Gynecology, Azienda Ospedaliera Universitaria Policlinico di Bari, Universita' degli Studi di Bari "Aldo Moro", School of Medicine, Bari, Italy.
Salvatore Andrea
SA
Mastrolia
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Ruthy
R
Beer-Weisel
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Tal
T
Rafaeli-Yehudai
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Limor
L
Besser
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Batel
B
Hamou
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel.
Moshe
M
Mazor
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben Gurion University of the Negev, School of Medicine, Beer Sheva, Israel. Electronic address: erezof@bgu.ac.il.
Offer
O
Erez
D000328:Adult; D001238:Asphyxia Neonatorum / Q000453:epidemiology; D002547:Cerebral Palsy / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000453:epidemiology*; D007236:Infant, Small for Gestational Age; D007239:Infections / Q000453:epidemiology; D008297:Male; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
SGA; asphyxia; gestational age; infection; inflammation; multi-hit model; prematurity