Prognostic Factors for Poor Cognitive Development in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review

Abstract

Importance: Cognitive delay is the most common form of impairment among children born very preterm (VPT) at 32 weeks or less or with very low birth weight (VLBW) of 1250 g or less. It is important to identify factors that are robust predictors of long-term outcome because the ability to predict future prognosis will assist in health care and educational service planning and provision.

Objective: To identify prognostic factors for poor cognitive development in children born VPT or with VLBW.

Evidence review: A systematic review was conducted using MEDLINE, EMBASE, and PyscINFO databases to identify studies published between January 1, 1990, and June 1, 2014, reporting multivariable prediction models for neurodevelopment in VPT or VLBW children. Thirty-one studies comprising 98 risk factor models for cognitive outcome were identified. Two independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, and reporting and conducted a risk-of-bias assessment.

Findings: There was evidence that male sex, nonwhite race/ethnicity, lower level of parental education, and lower birth weight were predictive of global cognitive impairment in children younger than 5 years. In older children, only the influence of parental education was sustained. Male sex was also predictive of language impairment in early infancy, but not in middle childhood. Gestational age was a poor predictor of cognitive outcome, probably because of a reduced discriminatory power in cohorts restricted to a narrow gestational age range. The prognostic value of neonatal brain injury was unclear; however, studies adopted mixed strategies for managing children with physical or neurosensory disability.

Conclusions and relevance: The influence of perinatal risk factors on cognitive development of VPT or VLBW children appears to diminish over time as environmental factors become more important. It is difficult to isolate cognitive outcomes from motor and neurosensory impairment, and the strategy for dealing with untestable children has implications for risk prediction.

Figure 1. Flow Diagram

^a Reviewed in this article.

Figure 2. Risk-of-Bias Assessment

Shown are 31 studies comprising 98 risk factor models for cognitive outcome.

Figure 3. Evidence Synthesis of Risk Factors for Global Cognitive Impairment in Children Born Very Preterm or With Very LowBirthWeight

Prognostic factors are presented if significant (P < .05) in the final model of at least 1 study with low-to-moderate risk of bias and entered into the final model of at least 3 studies (across all ages). A through T indicate study identifiers listed in Table 1 and Table 2 (* denotes an extremely preterm cohort); SES, socioeconomic status. ^a Nonwhite (B and E), black (C), or Afro-Caribbean (G). ^b Intraventricular hemorrhage or periventricular leukomalacia (B, C, D, F, H, I, L, M, O, S, and T), periventricular leukomalacia or ventricular dilatation (R), intraventricular hemorrhage grades 2 to 4 (A), parenchymal lesion (Q), intraventricular hemorrhage grades 1 to 3, echodensities, ventricular dilatation, cystic periventricular leukomalacia, or intraparenchymal hemorrhage (N). ^c Any high-frequency (B), any mechanical ventilation (J), or mechanical ventilation days (C, F, I, Q, S, and T). ^d Perforated necrotizing enterocolitis (A), necrotizing enterocolitis stages 2 to 3 (C and F), surgical or radiograph diagnosed (J), bowel perforation or necrotizing enterocolitis (T), or not specified (H, L, and N). ^e Oxygen requirement at 36 weeks’ gestational age (B, D, F, G, J, L, M, N, O, and R) or not specified (H and P). ^f More than 24 hours before labor (G) or not specified (A and F). ^g Stage 3 to 4 (I, K, and L), at least stage 3 with laser therapy (F), or stage 4 to 5 or treatment with cryotherapy or laser therapy (O). ^h Increase in head circumference from discharge to 5 years (I), occipitofrontal circumference 7-year centile (Q), or increase in head circumference less than 6 mm per week (T).