Periventricular/Intraventricular Hemorrhage and Neurodevelopmental Outcomes: A Meta-analysis

CONTEXT: Periventricular/intraventricular hemorrhage (PIVH) is a common short-term morbidity in preterm infants, but its long-term neurodevelopmental impact, particularly with mild PIVH, remains unclear. OBJECTIVE: To systematically review and meta-analyze the neurodevelopmental outcomes of preterm infants <= 34 weeks' gestation with mild and severe PIVH, compared with no PIVH. DATA SOURCES: Medline, Embase, CINAHL, and PsychINFO databases from January 2000 through June 2014. STUDY SELECTION: Studies reporting long-term neurodevelopmental outcomes based on severity of PIVH were included. DATA EXTRACTION: Study characteristics, inclusion/exclusion criteria, exposures, and outcome assessment data extracted independently by 2 coauthors. RESULTS: The pooled unadjusted odds ratios of the primary outcome of death or moderate-severe neurodevelopmental impairment (NDI) were higher with both mild (1.48, 95% CI 1.26-1.73; 2 studies) and severe PIVH (4.72, 4.21-5.31; 3 studies); no studies reported adjusted odds ratios. Among survivors, odds of moderate-severe NDI were higher with mild and severe PIVH in both unadjusted (1.75, 1.40-2.20; 3 studies; 3.36, 3.06-3.68; 5 studies) and adjusted (1.39, 1.09-1.77; 3 studies; 2.44, 1.73-3.42; 2 studies) pooled analyses. Adjusted odds of cerebral palsy and cognitive delay were higher with severe but not mild PIVH. LIMITATIONS: Only observational studies were included. Fifteen of 21 included studies had a moderate-high risk of bias. CONCLUSIONS: Mild and severe PIVH are associated with progressively higher odds of death or moderatesevere NDI compared with no PIVH, but no studies adjusted for confounders. Among survivors, mild PIVH was associated with higher odds of moderate-severe NDI compared with no PIVH.