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Review |

Neurodevelopmental Outcomes at 4 to 8 Years of Children Born at 22 to 25 Weeks’ Gestational Age:  A Meta-analysis

Gregory P. Moore, MD, FRCPC1,2,3; Brigitte Lemyre, MD, FRCPC1,2,3; Nick Barrowman, PhD4; Thierry Daboval, MD, FRCPC1,2,3
[+] Author Affiliations
1Department of Pediatrics, Division of Neonatology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
2Department of Obstetrics and Gynecology, Division of Newborn Care, The Ottawa Hospital, General Campus, Ottawa, Ontario, Canada
3Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
4Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
JAMA Pediatr. 2013;167(10):967-974. doi:10.1001/jamapediatrics.2013.2395.
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Importance  Many centers delivering infants at 22 to 25 weeks’ gestation have limited data regarding their outcomes. A meta-analysis of the 4- to 8-year neurodevelopmental outcomes and exploration of the limitations of meta-analysis would aid physicians and parents to plan care for these infants.

Objectives  To determine the rate of moderate to severe and severe neurodevelopmental impairment by gestational age in extremely preterm survivors followed up between ages 4 and 8 years, as well as to determine whether there is a significant difference in impairment rates between the successive weeks of gestation of survivors.

Evidence Review  A peer-reviewed search strategy obtained English-language publications from MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, and EMBASE. Personal files and reference lists from identified articles were searched. Contemporary cohorts were obtained by restriction to those published after 2004. Inclusion criteria were prospective cohort studies, follow-up rate of 65% or more, use of standardized testing or classification for impairment, reporting by gestation, and meeting prespecified definitions of impairment. We excluded randomized clinical trials, highly selective cohorts, consensus statements, and reviews. Of 1771 identified records, 89 full-text publications were assessed for eligibility. Using the full text of each publication, 2 authors independently followed a 2-step procedure. First, they determined that 9 studies met inclusion criteria. Next, they extracted data using a structured data collection form. Investigators were contacted for data clarification.

Results  All extremely preterm infant survivors have a substantial likelihood of developing moderate to severe impairment. Wide confidence intervals at the lower gestations (eg, at 22 weeks, 43% [95% CI, 21%-69%]; heterogeneity I2, 0%) and high heterogeneity at the higher gestations (eg, at 25 weeks, 24% [95% CI, 17%-32%]; I2, 66%) limit the results. There was a statistically significant absolute decrease in moderate to severe impairment between each week of gestation (6.5% [95% CI, 2%-11%]).

Conclusions and Relevance  Knowledge of these data, including the limitations, should facilitate discussion during the shared decision-making process about care plans for these infants, particularly in centers without their own data. More prospective, high-quality, complete cohorts are needed.

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Figure 1.
Flow of Information Through Systematic Review

The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for selection and screening of data.49

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Figure 2.
Random-Effects Meta-analysis of Moderate to Severe and Severe Neurodevelopmental Impairment Rates

Data markers indicate mean value; whiskers, 95% CI; and diamonds, pooled estimate (width of the diamond represents the 95% CI).

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Figure 3.
Random-Effects Meta-analysis of the Risk Difference of Neurodevelopmental Impairment for Each Additional Week of Gestational Age (GA)

Data markers indicate mean value; whiskers, 95% CI; and diamonds, pooled estimate (width of the diamond represents the 95% CI).

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