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Prenatal Risk Factors for Cerebral Palsy in Very Preterm Singletons and Twins

Florence Livinec, MD^*, Pierre-Yves Ancel, MD, PhD^*, Stéphane Marret, MD, PhD, Catherine Arnaud, MD, PhD, Jeanne Fresson, MD, Véronique Pierrat, MD, PhD^¶, Jean-Christophe Rozé, MD, PhD^||, Benoít Escande, MD^**, Gérard Thiriez, MD^**, Béatrice Larroque, MD, PhD^*, Monique Kaminski, MSc^* for the Epipage Group^*

From the *Research Unit on Perinatal Health and Women's Health, INSERM U149, Villejuif, France; Charles Nicolle Hospital, Rouen, France; Research Unit on Epidemiology and Public Health, INSERM U558, Toulouse, France; Department of Neonatology, University Hospital, Nancy, France; ¶Jeanne de Flandre Hospital, Lille, France; ||Mère-Enfant Hospital, Nantes, France; **Hautepierre Hospital, Strasbourg, France; and Saint-Jacques Hospital, Besançon, France.

OBJECTIVE: To identify the main prenatal risk factors for cerebral palsy in very preterm singletons and twins.

METHODS: The data were from the Epipage study, which included all very preterm children (< 33 weeks) born in 1997 in 9 regions of France. The analysis included 1,954 children for whom a medical questionnaire was completed at the age of 2 years (83% of the surviving children). The risk factors studied were pregnancy complications and specific factors in twins (type of placenta and death of cotwin). Logistic regression analysis was carried out for singletons and generalized estimating equation models used for twins.

RESULTS: The proportion of cerebral palsy was 8% in singletons and 9% in twins. For singletons, spontaneous preterm labor (adjusted odds ratio [OR] 3.4, 95% confidence interval [CI] 1.7–6.7), preterm premature rupture of membranes (PPROM) with short latency (adjusted OR 4.9, 95% CI 2.0–11.8), and prolonged PPROM (adjusted OR 2.7, 95% CI 1.4–5.3) were associated with a higher risk of cerebral palsy than was hypertension. No such link was found between these pregnancy complications and cerebral palsy in twins. For twins, a monochorionic placenta (OR 1.9, 95% CI 1.0–3.6) increased the risk of cerebral palsy, but the OR became nonsignificant after adjustment (OR 1.7, 95% CI 0.8–3.4).

CONCLUSION: In very preterm singletons, spontaneous preterm labor and PPROM increased the risk of cerebral palsy compared with hypertension.

LEVEL OF EVIDENCE: II-2

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