Despite advancements in neonatal health care over the last 2 decades, children born extremely preterm or very preterm between 1990 and 2008 did not demonstrate improvements in cognitive outcomes and continued to show large deficits in intelligence, according to the results of a meta-analysis and meta-regression conducted in The Netherlands and published in JAMA Pediatrics.

The investigators sought to examine the cognitive abilities of children born extremely or very preterm, and the role played by perinatal and demographic risk factors in predicting outcomes. In their analysis, they selected peer-reviewed studies that reported intelligence scores of children born extremely or very preterm (ie, <32 weeks of gestation) and children born at full term (controls) at ≥5 years of age who were born during the time that antenatal corticosteroids and surfactants were used. Among a total of 268 studies that met selection criteria, 71 covered unique cohorts of patients.

The primary outcome was intelligence. Covariates in the study included gestational age, birth weight, birth year, age at assessment, race/ethnicity, gender, socioeconomic status, small for gestational age, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, periventricular leukomalacia, sepsis, necrotizing enterocolitis, and postnatal corticosteroid use.

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Among the 71 studies included in the analysis, there were 7752 children born extremely or very preterm and 5155 controls. The median gestational age of the participants was 28.5±2.4 weeks. Mean patient age at assessment ranged from 5.0 to 20.1 years.

A significant difference (0.86 standard deviation; 95% CI, –0.94 to –0.78; P <.001) in intelligence was reported between children born extremely or very preterm and their full-term peers, corresponding to approximately 13 points in intelligence quotient (IQ). This difference was stable over age (5-20 years) and birth year (1990-2008). Results were shown to be heterogeneous across the studies (P <.001), which could not be attributed to birth year of the cohort.

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Moreover, when a wide range of perinatal and demographic risk factors were considered, a strong association was demonstrated between BPD and long-term cognitive outcomes in children born extremely or very preterm. In fact, BPD explained 65% of the variance in intelligence across studies, with each percent increase in BPD rate across studies linked to a 0.01 standard deviation decrease in IQ (0.15 IQ points; P <.001).

The investigators concluded that the findings of this study highlight that improving outcomes following extremely and very preterm births remains a major challenge. With BPD shown to be a critical factor in cognitive development, preventive strategies for reducing the high incidence of the disorder among this population may be key to the improvement of long-term outcomes in children born extremely or very preterm.


Twilhaar ES, Wade RM, de Kieviet JF, van Goudoever JB, van Elburg RM, Oosterlaan J. Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: a meta-analysis and meta-regression [published online February 19, 2018]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.5323