The interplay between birth weight and intraventricular hemorrhage in very preterm neonates - a retrospective cohort study.

Abstract

Background: Intraventricular hemorrhage (IVH) most commonly occurs in infants born very preterm (<32 weeks' gestation). There are mixed findings on whether infants small for gestational age (SGA) or with suspected fetal growth restriction (FGR) are at higher risk for IVH. Understanding the relationship between SGA or FGR and IVH is critical to inform clinical care.

Objective: The primary aim was to determine the rates of IVH in very preterm newborns, with SGA or suspected FGR, and to stratify for severity of both FGR and IVH. The secondary aim was to identify risk factors for IVH in a large contemporary cohort.

Study design: A population-based retrospective cohort study using data from the Australian and New Zealand Neonatal Network (ANZNN). Participants were babies born before 32 weeks' gestation (22 to 31 weeks + 6 days gestation) between 2014-2019 inclusive. The primary outcomes were IVH and severity of IVH. Small babies were classified as being SGA (SGA; birth weight <10^th percentile), suspected FGR (birth weight <10^th and ≥3^rd birth weight percentile and abnormal antenatal ultrasound), or severe FGR (birth weight <3^rd percentile). Multivariate regression was then performed, adjusting for potential maternal and fetal confounders to determine the association between FGR and IVH.

Results: 20,551 very preterm newborns were included in the study with a median gestational age (25^th, 75^th) of 29 (27,30) weeks gestation and birth weight of 1201(383.9) grams. The incidence of any IVH was 20.02% (n=4115) and increased with decreasing gestation at birth (10% of infants born at 31 weeks had IVH compared with 70% of infants born at 22 weeks). The rate of severe IVH (Grade 3 or 4) was 3.23%. In this cohort, 7.7% were SGA (n=1583) and 6.23% (n=1281) of babies had suspected early-onset FGR. The incidence of SGA was reduced in babies with IVH (6.0% versus 8.1%, respectively, aOR, 0.82; 95% CI 0.68-0.97). Similarly, suspected FGR was significantly lower in infants with IVH (any grade) compared to those without (2.5% versus 4.6%, respectively, adjusted odds ratio (aOR), 0.69; 95% CI 0.54-0.89). Further, there was a negative association between SGA (aOR, 0.80; 95% CI 0.67-0.95) and FGR (aOR 0.69; 95% CI 0.54-0.88) and the severity of IVH. Severe FGR (<3^rd birth weight percentile) was not associated with either the presence (1.9% with IVH, versus 2.1% without IVH, aOR, 0.86; 95% CI 0.64-1.16) or severity of IVH (aOR, 0.85; 95% CI 0.63-1.14).

Conclusion: This large retrospective cohort study identified that in very preterm infants born with a median gestational age at birth of 29 weeks and who survive to the neonatal unit, the presence of SGA or suspected FGR is associated with a reduced rate of IVH, compared to infants without SGA/FGR. Future studies should directly assess whether placental insufficiency prevents the development of IVH, so that novel neuroprotective strategies for the very preterm infant can be implemented.