Fatores associados ao crescimento extrauterino restrito na alta hospitalar em recém-nascidos de muito baixo peso: uma coorte multicêntrica brasileira

Abstract

Introduction: Extrauterine growth restriction (EUGR) is a common comorbidity in very low birth weight infants (VLBWIs), resulting from the challenges in achieving adequate nutrition during hospitalization in neonatal intensive care units. This condition is associated with poorer neurological and cardiovascular outcomes in VLBWIs. In low- and middle-income countries, studies on EUGR are scarce, yet highly relevant, as these settings present higher rates of maternal hypertensive disorders, fetal growth restriction (FGR), and small for gestational age (SGA) newborns compared to high-income countries. Objective: The aim of this study is to describe the prevalence and analyze factors associated with EUGR in VLBWIs in a cohort from the Brazilian Neonatal Research Network (BNRN)), and to assess the progression of weight and head circumference for age at birth and at hospital discharge. Methods: A prospective cohort study utilizing the BNRN database from 17 hospitals, covering the period from 2011 to 2020. EUGR was defined as weight for corrected gestational age below the 10th percentile at discharge, according to the INTERGROWTH-21st standard. The initial sample comprised 16,351 newborns, with exclusions applied to those with congenital anomalies, twins, large for gestational age, those who died, were transferred, remained hospitalized for over one year, or had missing data or unavailable nutritional status classification. Mean Z-scores for weight and head circumference at birth and at discharge were compared between SGA and appropriate for gestational age (AGA) VLBWIs. Associations were evaluated between maternal sociodemographic characteristics, prenatal, delivery, and postnatal variables with the outcome of EUGR. Univariate logistic regression was performed for each predictor variable, followed by hierarchical multivariate logistic regression for variables with p<0.20. Results: Among the 7,802 VLBWIs included, the prevalence of EUGR at hospital discharge was 62%, higher among SGA compared to AGA infants (92.5% vs. 43.6%, p<0.001, respectively). A decrease in Z-scores for both weight and head circumference was observed from birth to discharge, more pronounced among AGA compared to SGA infants. Factors positively associated with EUGR included SGA status at birth (Odds Ratio [OR]=15.8, 95% Confidence Interval [CI]=13.3–18.8), maternal self-reported skin color Black/Brown/Indigenous (OR=1.33, 95% CI=1.21–1.46), male sex (OR=0.59, 95% CI=0.53–0.66), maternal hypertension (OR=1.50, 95% CI=1.32–1.72), early-onset sepsis (OR=1.21, 95% CI=1.05–1.40), late-onset sepsis (OR=1.70, 95% CI=1.47–1.96), bronchopulmonary dysplasia (OR=1.65, 95% CI=1.35–2.01), and patent ductus arteriosus requiring surgical intervention (OR=1.96, 95% CI=1.32–2.93). Negative associations were observed for antenatal corticosteroid exposure (OR=0.72, 95% CI=0.62–0.84) and a 1-minute Apgar score ≥7 (OR=0.74, 95% CI=0.65–0.82). Conclusion: EUGR was identified in nearly two-thirds of VLBWIs, a rate higher than that observed in high-income countries. Ensuring equitable access and quality prenatal care, including prevention and management of maternal hypertension and FGR, as well as the treatment and prevention of neonatal comorbidities, are essential to reduce EUGR occurrence. This study also highlights the importance of antenatal corticosteroid administration in pregnancies at risk of preterm birth.