Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: A meta-analysis and meta-regression

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Abstract

IMPORTANCE: Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth. OBJECTIVE: To examine the cognitive abilities of children of EP/VP birth (EP/VP children) and the role of perinatal and demographic risk factors. DATA SOURCES: PubMed, Web of Science, and PsycINFO were searched without language restriction (last search March 2, 2017). Key search terms included preterm, low birth weight, and intelligence. STUDY SELECTION: Peer-reviewed studies reporting intelligence scores of EP/VP children (<32 weeks of gestation) and full-term controls at age 5 years or older, born in the antenatal corticosteroids and surfactant era, were included. A total of 268 studies met selection criteria, of which 71 covered unique cohorts. DATA EXTRACTION AND SYNTHESIS MOOSE: guidelines were followed. Data were independently extracted by 2 researchers. Standardized mean differences in intelligence per study were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using multivariate, random-effects meta-regression analysis. MAIN OUTCOMES AND MEASURES: Primary outcome was intelligence. Covariates included gestational age, birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic status, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, sepsis, and postnatal corticosteroid use. RESULTS: The 71 included studies comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5 weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment ranged from 5.0 to 20.1 years. The median proportion of males was 50.0% (IQR, 8.7%). Preterm children had a 0.86-SD lower IQ compared with controls (95% CI, -0.94 to - 0.78, P <.001). Results were heterogeneous across studies (I2 = 74.13; P <.001). This heterogeneity could not be explained by birth year of the cohort. Multivariate meta-regression analysis with backward elimination revealed that BPD explained 65% of the variance in intelligence across studies, with each percent increase in BPD rate across studies associated with a 0.01-SD decrease in IQ (0.15 IQ points) (P <.001). CONCLUSIONS AND RELEVANCE: Extremely or very preterm children born in the antenatal corticosteroids and surfactant era show large deficits in intelligence. No improvement in cognitive outcome was observed between 1990 and 2008. These findings emphasize that improving outcomes after EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be key to improving long-term outcomes after EP/VP birth.
LanguageEnglish
Pages361-367
JournalJAMA Pediatrics
Volume172
Issue number4
DOIs
Publication statusPublished - 2018

Cite this

@article{1f7b8c05113242c691b2ea245a056def,
title = "Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: A meta-analysis and meta-regression",
abstract = "IMPORTANCE: Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth. OBJECTIVE: To examine the cognitive abilities of children of EP/VP birth (EP/VP children) and the role of perinatal and demographic risk factors. DATA SOURCES: PubMed, Web of Science, and PsycINFO were searched without language restriction (last search March 2, 2017). Key search terms included preterm, low birth weight, and intelligence. STUDY SELECTION: Peer-reviewed studies reporting intelligence scores of EP/VP children (<32 weeks of gestation) and full-term controls at age 5 years or older, born in the antenatal corticosteroids and surfactant era, were included. A total of 268 studies met selection criteria, of which 71 covered unique cohorts. DATA EXTRACTION AND SYNTHESIS MOOSE: guidelines were followed. Data were independently extracted by 2 researchers. Standardized mean differences in intelligence per study were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using multivariate, random-effects meta-regression analysis. MAIN OUTCOMES AND MEASURES: Primary outcome was intelligence. Covariates included gestational age, birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic status, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, sepsis, and postnatal corticosteroid use. RESULTS: The 71 included studies comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5 weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment ranged from 5.0 to 20.1 years. The median proportion of males was 50.0{\%} (IQR, 8.7{\%}). Preterm children had a 0.86-SD lower IQ compared with controls (95{\%} CI, -0.94 to - 0.78, P <.001). Results were heterogeneous across studies (I2 = 74.13; P <.001). This heterogeneity could not be explained by birth year of the cohort. Multivariate meta-regression analysis with backward elimination revealed that BPD explained 65{\%} of the variance in intelligence across studies, with each percent increase in BPD rate across studies associated with a 0.01-SD decrease in IQ (0.15 IQ points) (P <.001). CONCLUSIONS AND RELEVANCE: Extremely or very preterm children born in the antenatal corticosteroids and surfactant era show large deficits in intelligence. No improvement in cognitive outcome was observed between 1990 and 2008. These findings emphasize that improving outcomes after EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be key to improving long-term outcomes after EP/VP birth.",
author = "Twilhaar, {E. Sabrina} and Wade, {Rebecca M.} and {de Kieviet}, {Jorrit F.} and {van Goudoever}, {Johannes B.} and {van Elburg}, {Ruurd M.} and Jaap Oosterlaan",
year = "2018",
doi = "10.1001/jamapediatrics.2017.5323",
language = "English",
volume = "172",
pages = "361--367",
journal = "JAMA Pediatrics",
issn = "2168-6203",
publisher = "American Medical Association",
number = "4",

}

TY - JOUR

T1 - Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: A meta-analysis and meta-regression

AU - Twilhaar, E. Sabrina

AU - Wade, Rebecca M.

AU - de Kieviet, Jorrit F.

AU - van Goudoever, Johannes B.

AU - van Elburg, Ruurd M.

AU - Oosterlaan, Jaap

PY - 2018

Y1 - 2018

N2 - IMPORTANCE: Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth. OBJECTIVE: To examine the cognitive abilities of children of EP/VP birth (EP/VP children) and the role of perinatal and demographic risk factors. DATA SOURCES: PubMed, Web of Science, and PsycINFO were searched without language restriction (last search March 2, 2017). Key search terms included preterm, low birth weight, and intelligence. STUDY SELECTION: Peer-reviewed studies reporting intelligence scores of EP/VP children (<32 weeks of gestation) and full-term controls at age 5 years or older, born in the antenatal corticosteroids and surfactant era, were included. A total of 268 studies met selection criteria, of which 71 covered unique cohorts. DATA EXTRACTION AND SYNTHESIS MOOSE: guidelines were followed. Data were independently extracted by 2 researchers. Standardized mean differences in intelligence per study were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using multivariate, random-effects meta-regression analysis. MAIN OUTCOMES AND MEASURES: Primary outcome was intelligence. Covariates included gestational age, birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic status, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, sepsis, and postnatal corticosteroid use. RESULTS: The 71 included studies comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5 weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment ranged from 5.0 to 20.1 years. The median proportion of males was 50.0% (IQR, 8.7%). Preterm children had a 0.86-SD lower IQ compared with controls (95% CI, -0.94 to - 0.78, P <.001). Results were heterogeneous across studies (I2 = 74.13; P <.001). This heterogeneity could not be explained by birth year of the cohort. Multivariate meta-regression analysis with backward elimination revealed that BPD explained 65% of the variance in intelligence across studies, with each percent increase in BPD rate across studies associated with a 0.01-SD decrease in IQ (0.15 IQ points) (P <.001). CONCLUSIONS AND RELEVANCE: Extremely or very preterm children born in the antenatal corticosteroids and surfactant era show large deficits in intelligence. No improvement in cognitive outcome was observed between 1990 and 2008. These findings emphasize that improving outcomes after EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be key to improving long-term outcomes after EP/VP birth.

AB - IMPORTANCE: Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth. OBJECTIVE: To examine the cognitive abilities of children of EP/VP birth (EP/VP children) and the role of perinatal and demographic risk factors. DATA SOURCES: PubMed, Web of Science, and PsycINFO were searched without language restriction (last search March 2, 2017). Key search terms included preterm, low birth weight, and intelligence. STUDY SELECTION: Peer-reviewed studies reporting intelligence scores of EP/VP children (<32 weeks of gestation) and full-term controls at age 5 years or older, born in the antenatal corticosteroids and surfactant era, were included. A total of 268 studies met selection criteria, of which 71 covered unique cohorts. DATA EXTRACTION AND SYNTHESIS MOOSE: guidelines were followed. Data were independently extracted by 2 researchers. Standardized mean differences in intelligence per study were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using multivariate, random-effects meta-regression analysis. MAIN OUTCOMES AND MEASURES: Primary outcome was intelligence. Covariates included gestational age, birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic status, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, sepsis, and postnatal corticosteroid use. RESULTS: The 71 included studies comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5 weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment ranged from 5.0 to 20.1 years. The median proportion of males was 50.0% (IQR, 8.7%). Preterm children had a 0.86-SD lower IQ compared with controls (95% CI, -0.94 to - 0.78, P <.001). Results were heterogeneous across studies (I2 = 74.13; P <.001). This heterogeneity could not be explained by birth year of the cohort. Multivariate meta-regression analysis with backward elimination revealed that BPD explained 65% of the variance in intelligence across studies, with each percent increase in BPD rate across studies associated with a 0.01-SD decrease in IQ (0.15 IQ points) (P <.001). CONCLUSIONS AND RELEVANCE: Extremely or very preterm children born in the antenatal corticosteroids and surfactant era show large deficits in intelligence. No improvement in cognitive outcome was observed between 1990 and 2008. These findings emphasize that improving outcomes after EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be key to improving long-term outcomes after EP/VP birth.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044972867&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29459939

U2 - 10.1001/jamapediatrics.2017.5323

DO - 10.1001/jamapediatrics.2017.5323

M3 - Article

VL - 172

SP - 361

EP - 367

JO - JAMA Pediatrics

T2 - JAMA Pediatrics

JF - JAMA Pediatrics

SN - 2168-6203

IS - 4

ER -