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

Louise Linsell, BSc, MSc1; Reem Malouf, MSc, MD1; Joan Morris, MA, MSc, PhD2; Jennifer J. Kurinczuk, BSc, MBChB, MSc, MD1; Neil Marlow, BA, MBBS, MRCP, MD3
[+] Author Affiliations
1National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England
2Centre for Environmental and Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, England
3Institute of Women’s Health, University College London, London, England
JAMA Pediatr. 2015;169(12):1162-1172. doi:10.1001/jamapediatrics.2015.2175.
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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.

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Figure 1.
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aReviewed in this article.

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Figure 2.
Risk-of-Bias Assessment

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

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

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.

aNonwhite (B and E), black (C), or Afro-Caribbean (G).

bIntraventricular 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).

cAny high-frequency (B), any mechanical ventilation (J), or mechanical ventilation days (C, F, I, Q, S, and T).

dPerforated 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).

eOxygen requirement at 36 weeks’ gestational age (B, D, F, G, J, L, M, N, O, and R) or not specified (H and P).

fMore than 24 hours before labor (G) or not specified (A and F).

gStage 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).

hIncrease 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).

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