The Association of Pregnancy-induced Hypertension with Bronchopulmonary Dysplasia – A Retrospective Study Based on the Korean Neonatal Network database

Abstract

The prevalence of pregnancy-induced hypertension (PIH) and preeclampsia (PE) are 5-10% and 2-4%, respectively. PIH might affect angiogenesis in preterm neonates, but its association with bronchopulmonary dysplasia (BPD) remains controversial. This study evaluated the association between PIH and BPD in very low-birth weight infants. We retrospectively analysed the maternal, perinatal, and neonatal data of preterm infants born before 30 weeks of gestation, selected from the nationwide registry of very low-birth weight infants, between January 2013 and December 2014. As a result, 1,624 infants without maternal PIH (gestational age: 27.3 ± 1.8 weeks) and 203 infants with maternal PIH (28.0 ± 1.4 weeks, p < 0.001) were included. Birth weight was higher in the non-PIH group, compared with the PIH group (1027.4 ± 250.2 vs. 876.4 ± 261.5 g, p < 0.001). Multivariate logistic regression showed that PIH was associated with BPD (adjusted OR 1.474, 95% confidence interval 1.025-2.121), after adjusting for confounders, including small-for-gestation age (SGA). The result of present study is consistent with the current concept of BpD as an early form of pulmonary vascular disease, for both PIH and BPD are attributed by abnormal vascular formation. Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth among very low-birth weight (VLBW) infants. Although the progression of prematurity care, including the use of antenatal steroids and surfactant therapy, has improved neonatal outcomes, the incidence of BPD has not decreased with the increased survival of preterm infants 1-4. These extremely preterm infants present with arrest in the development of the alveolar-capillary unit, characterized by enlarged and simplified alveolar structure, prominent interstitial fibrosis, and abnormal pulmonary vasculature 5. For angiogenesis and alveolar development are interactive in the foetal lung, BPD has been recently recognized as a manifestation of vascular disease of the lungs in this population 6. The prevalence of pregnancy-induced hypertension (PIH) and preeclampsia (PE) are 5-10% and 2-4%, respectively 7-10. Although the pathophysiology of PIH and PE are not established, inadequate placental implantation and abnormal vascularization might play certain roles in the development of PIH 11. Several maternal angiogenic factors and anti-angiogenic factors regulate placental growth and vascular development in PE 12-14. Inappropriate vascular endothelial growth factor (VEGF) signalling could also alter vascular development and reactivity in foetus, leading to neonatal pulmonary vascular disease 15. In a clinical study, the pulmonary outcomes of preterm infants were predicted by measurements of the placental growth factor from the mother 16. Since both PIH and BPD are associated with abnormal angiogenesis, there has been efforts to evaluate the association between PIH and BPD in preterm infants. A small prospective study showed that moderate to severe BPD

Association of Maternal Hypertensive Disorders During Pregnancy With Severe Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

“…4 ), unlike previous studies. 8 9 Moreover, the incidence of BPD and duration of mechanical ventilation did not differ between the pre-eclampsia and non-pre-eclampsia groups in the study of Shin et al 65 It is possible that we found no association between HDP and BPD (other than severe BPD) because the clinical definitions of BPD were inconsistent. The risk of BPP in the HDP group without fetal growth restriction did not differ from that of the group without HDP, and maternal HDP was associated with BPD in cases exhibiting antenatal fetal growth restriction.…”

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis

“…Another retrospective study included 1,827 preterm infants with gestational age below 30 weeks in the Korean Neonatal Network, and the infants were divided into pregnancy-induced hypertension (PIH) groups and non-PIH groups. It showed that the incidence of BPD was not significantly different between the two groups; after adjusting for sex, gestational age, RDS, and treated PDA, there was no correlation between PIH and BPD in EP infants below 27 weeks of gestation ( 37 ). As the risk factors for BPD are multifactorial, in addition to abnormal vascular growth caused by maternal factors, there are many other risk factors that can contribute to the development of BPD ( 37 ), while gestational age and low birth weight are the two strongest risk factors ( 39 ).…”

“…It showed that the incidence of BPD was not significantly different between the two groups; after adjusting for sex, gestational age, RDS, and treated PDA, there was no correlation between PIH and BPD in EP infants below 27 weeks of gestation ( 37 ). As the risk factors for BPD are multifactorial, in addition to abnormal vascular growth caused by maternal factors, there are many other risk factors that can contribute to the development of BPD ( 37 ), while gestational age and low birth weight are the two strongest risk factors ( 39 ). Therefore, after matching gestational age, birth weight and sex, HDP had no significant effect on the incidence of BPD in EP/ELBW infants.…”

Lung recruitment improves the efficacy of intubation-surfactant-extubation treatment for respiratory distress syndrome in preterm neonates, a randomized controlled trial

“…In this study, neonates of hypertensive mothers had a higher risk of the need for MV within 72 h after extubation than those of normotensive mothers. It has been shown that gestational hypertension can promote maternal production of soluble fms-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor that can block vascular endothelial growth factor (VEGF) signaling [ 26 , 27 ]. Since VEGF signaling is essential for the growth of pulmonary blood vessels and the production of surfactants, sFlt-1 may lead to increased incidence and severity of RDS in preterm neonates with hypertensive mothers.…”