Perinatal Infections and Neurodevelopmental Outcome in Very Preterm and Very Low-Birth-Weight Infants A Meta-Analysis

JAMA pediatrics 05/2013; 167(7):1-7. DOI: 10.1001/jamapediatrics.2013.1199
Source: PubMed


IMPORTANCE Perinatal infections are commonly present in preterm and very low-birth-weight (VLWB) infants and might contribute to adverse neurodevelopmental outcome. OBJECTIVE To summarize studies evaluating the effect of perinatal infections on neurodevelopmental outcome in very preterm/VLBW infants. EVIDENCE REVIEW On December 12, 2011, we searched Medline, PsycINFO, Embase, and Web of Knowledge for studies on infections and neurodevelopmental outcome. All titles and abstracts were assessed for eligibility by 2 independent reviewers. We also screened the reference lists of identified articles to search for additional eligible studies. Preselected criteria justified inclusion in this meta-analysis: (1) the study included infants born very preterm (≤32 weeks) and/or with VLBW (≤1500 g); (2) the study compared infants with and without perinatal infection; (3) there was follow-up using the Bayley Scales of Infant Development 2nd edition; and (4) results were published in an English-language peer-reviewed journal. The quality of each included study was assessed using the Newcastle-Ottawa Scale. FINDINGS This meta-analysis includes 18 studies encompassing data on 13.755 very preterm/VLBW infants. Very preterm/VLBW infants with perinatal infections had poorer mental (d = -0.25; P < .001) and motor (d = -0.37; P < .001) development compared with very preterm/VLBW infants without infections. Mental development was most impaired by necrotizing enterocolitis (d = -0.40; P < .001) and meningitis (d = -0.37; P < .001). Motor development was most impaired by necrotizing enterocolitis (d = -0.66; P < .001). Chorioamnionitis did not affect mental (d = -0.05; P = .37) or motor (d = 0.19; P = .08) development. CONCLUSIONS AND RELEVANCE Postnatal infections have detrimental effects on mental and motor development in very preterm/VLBW infants.

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    • "Consequently, abnormal WM development in these regions may be useful for identifying infants with higher risk for adverse outcomes. Known risk factors for poor neurodevelopment following preterm birth include sepsis (Stoll et al., 2002; Schlapbach et al., 2011; Hentges et al., 2013; Mitha et al., 2013), bronchopulmonary dysplasia (Schmidt et al., 2003; Vohr et al., 2005; Karagianni et al., 2011; Schlapbach et al., 2012), necrotizing enterocolitis (NEC) (Hintz et al., 2005; van Vliet et al., 2013), and male sex (Wood et al., 2005; Vohr et al., 2005; Rose et al., 2009; Beaino et al., 2010; Morsing et al., 2011). The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain microstructure in VLBW preterm infants at near-term age, based on qualitative analysis of structural MRI and on semi-automated, atlas-based DTI analysis. "
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    ABSTRACT: Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 wks), who were admitted to the Lucile Packard Children’s Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010–2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p = .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p = .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r = .382, p = .002; right: r = .400, p = .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = –.322, p = .009; r = –.381, p = .002), lower mean albumin (r = –.276, p = .029; r = –.385, p = .002), and lower mean bilirubin (r = –.293, p = .020; r = –.337 p = .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.
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