Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island.

BACKGROUND: Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. METHODS: The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ ≤ 85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. RESULTS: The mean DQ score was 86.3 (95%CI: 81.0-91.5) in infected children compared to 100.2 (95%CI: 98.0-102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45-5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <-2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children. CONCLUSIONS: The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.

Mother-to-child transmission of Chikungunya virus infection.

BACKGROUND: In 2005-2006 Reunion Island experienced a massive outbreak of chikungunya, a mosquito-borne alphavirus infection. During this epidemic, early neonatal cases were observed with a highly probable mother-to-child transmission. METHODS: A retrospective descriptive study was conducted in 5 neonatal medicine departments. Chikungunya virus infection was confirmed by reverse transcription-polymerase chain reaction or specific serology in mothers and their newborns. Mothers were screened if they presented signs at delivery or if their neonates became ill on the first days of life. RESULTS: Thirty-eight neonates were enrolled. All mothers, except 2 asymptomatic mothers, presented signs during the perinatal period (range, day(D) -4 to D+1). All neonates were symptomatic and presented symptoms on D3 to D7 (mean, D4). The mean interval between onset of maternal illness and onset of neonatal illness was 5 days (range, 3-9). The most frequent clinical signs in neonates were fever (79%), pain (100%), rash (82%), and peripheral edema (58%). Thrombocytopenia (76%), lymphopenia (47%), decreased prothrombin value (65%), and elevation of aspartate aminotransferase (77%) were detected. Complications included seizures (6), hemorrhagic syndrome (6), and hemodynamic disorders (10). Reverse transcription-polymerase chain reaction in cerebrospinal fluid was positive in 22 of 24 cases, and abnormal findings on brain magnetic resonance imaging (14 of 25) with white matter lesions or intraparenchymal hemorrhages or both were found. Echocardiography (16) showed myocardial hypertrophy (5), ventricular dysfunction (2), pericarditis (2), and coronary artery dilatation (6). One neonate died of necrotizing enterocolitis. CONCLUSIONS: The chikungunya epidemic that occurred on La Reunion Island revealed for the first time the possibility of mother-to-child transmission in the perinatal period with a high rate of morbidity.