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Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin
Published on: August 25, 2022
The interplay between birth weight and intraventricular hemorrhage in very preterm neonates-a retrospective cohort
Beth R Piscopo1, Atul Malhotra2, Rod W Hunt3
1The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia (Piscopo, Malhotra, Hunt, Davies-Tuck, Palmer, Sutherland, Polglase, Allison, and Miller); Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton VIC, Australia (Piscopo, Davies-Tuck, Palmer, Sutherland, Polglase, Allison, and Miller).
Insights
Infants born small for gestational age (SGA) or with suspected fetal growth restriction (FGR) have a lower incidence of intraventricular hemorrhage (IVH). This finding suggests placental insufficiency may offer protection against IVH in very preterm infants.
Area of Science:
- Neonatalogy
- Perinatal Medicine
- Pediatric Neurology
Background:
- Intraventricular hemorrhage (IVH) is a common complication in very preterm infants (<32 weeks' gestation).
- The association between small for gestational age (SGA) or fetal growth restriction (FGR) and IVH risk remains unclear.
- Clarifying this relationship is crucial for optimizing clinical management of high-risk neonates.
Purpose of the Study:
- To determine the incidence and severity of IVH in very preterm infants with SGA or suspected FGR.
- To identify risk factors associated with IVH in a large, contemporary cohort of preterm neonates.
- To stratify IVH rates based on the severity of FGR.
Main Methods:
- A population-based retrospective cohort study utilizing data from the Australian and New Zealand Neonatal Network (2014-2019).
- Inclusion criteria: infants born between 22 and 31 weeks' gestation.
- Classification of small infants: SGA (<10th percentile), suspected FGR (3rd-10th percentile with abnormal ultrasound), severe FGR (<3rd percentile). Multivariate regression analysis was performed.
Main Results:
- The study included 20,551 very preterm infants; overall IVH incidence was 20.02%, with severe IVH (Grade 3-4) at 3.23%.
- Infants with SGA (7.7%) or suspected FGR (6.23%) showed a significantly reduced incidence of IVH (aOR 0.82 for SGA, aOR 0.69 for suspected FGR).
- A negative association was observed between SGA and FGR and IVH severity; severe FGR was not associated with IVH presence or severity.
Conclusions:
- In very preterm infants, the presence of SGA or suspected FGR is associated with a lower rate of IVH.
- This suggests potential protective mechanisms related to placental insufficiency against IVH development.
- Further research is warranted to explore if placental insufficiency can be leveraged for novel neuroprotective strategies in preterm infants.
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. Participants were babies born before 32 weeks' gestation (22-31 weeks + 6 days gestation) between 2014 and 2019 inclusive. The primary outcomes were IVH and severity of IVH. Small babies were classified as being SGA (SGA; birth weight <10th percentile), suspected FGR (birth weight <10th and ≥3rd birth weight percentile and abnormal antenatal ultrasound), or severe FGR (birth weight <3rd 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 (25th, 75th) 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% vs 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% vs 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 (<3rd birth weight percentile) was not associated with either the presence (1.9% with IVH, vs 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.
