Cerebral Palsy in Very Preterm Infants: A Nine-Year Prospective Study in a French Population-Based Tertiary Center.

OBJECTIVES: To describe the prevalence of cerebral palsy (CP) at age 2 years in infants born before 33 weeks of gestation and to analyze the fetal neuroprotective effect of the antenatal administration of magnesium sulfate (MgSO4) treatment on CP. STUDY DESIGN: Preterm infants born before 33 weeks of gestation and discharged from the Rouen University Hospital's Neonatal Intensive Care Unit between 2007 and 2015 were included. At age 2 years, pediatricians of the perinatal network of Eure and Seine-Maritime counties administered standardized questionnaires analyzing motor, cognitive, and behavioral items, derived from the Denver and Amiel-Tison scales. A routine protocol based on MgSO4 infusion was introduced in 2010. The primary outcome measure was the occurrence of CP according to the Surveillance of Cerebral Palsy in Europe network definition. RESULTS: A total of 1759 very preterm infants were included, among whom 138 (7.8%) died and 148 (9.1%) were lost to follow-up. Assuming that those lost to follow-up had no CP, at 2 years, 55 of 1621 infants (3.4%; 95% CI, 2.6%-4.4%) had CP. After statistical adjustment for birth term and antenatal corticosteroid use, a significant decrease in CP was observed after implementation of a protocol of MgSO4 administration in mothers before imminent preterm birth at <33 weeks of gestation (aOR, 0.53; 95% CI, 0.29-0.98; P = .04). CONCLUSIONS: The prevalence of CP at 2 years after very preterm birth was low. The implementation of a neuroprotective protocol with MgSO4 was associated with reduced CP occurrence; however, several relevant limitations must be considered for interpretation.

Time- and sex-dependent efficacy of magnesium sulfate to prevent behavioral impairments and cerebral damage in a mouse model of cerebral palsy.

Cerebral lesions acquired in the perinatal period can induce cerebral palsy (CP), a multifactorial pathology leading to lifelong motor and cognitive deficits. Several risk factors, including perinatal hypoxia-ischemia (HI), can contribute to the emergence of CP in preterm infants. Currently, there is no international consensus on treatment strategies to reduce the risk of developing CP. A meta-analysis showed that magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery reduces the risk of developing CP (Crowther et al., 2017). However, only a few studies have investigated the long-term effects of MgSO4 and it is not known whether sex would influence MgSO4 efficacy. In addition, the search for potential deleterious effects is essential to enable broad use of MgSO4 in maternity wards. We used a mouse model of perinatal HI to study MgSO4 effects until adolescence, focusing on cognitive and motor functions, and on some apoptosis and inflammation markers. Perinatal HI at postnatal day 5 (P(5)) induced (1) sensorimotor deficits in pups; (2) increase in caspase-3 activity 24 h after injury; (3) production of proinflammatory cytokines from 6 h to 5 days after injury; (4) behavioral and histological alterations in adolescent mice with considerable interindividual variability. MgSO4 prevented sensorimotor alterations in pups, with the same efficacy in males and females. MgSO4 displayed anti-apoptotic and anti-inflammatory effects without deleterious side effects. Perinatal HI led to motor coordination impairments in female adolescent mice and cognitive deficits in both sexes. MgSO4 tended to prevent these motor and cognitive deficits only in females, while it prevented global brain tissue damage in both sexes. Moreover, interindividual and intersexual differences appeared regarding the lesion size and neuroprotection by MgSO4 in a region-specific manner. These differences, the partial prevention of disorders, as well as the mismatch between histological and behavioral observations mimic clinical observations. This underlines that this perinatal HI model is suitable to further analyze the mechanisms of sex-dependent perinatal lesion susceptibility and MgSO4 efficacy.