Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Clinical and Translational Science

First Advisor

Alan S. Rubin

Second Advisor

Ira M. Bernstein


Worldwide, more than 1 million infants die as a result of premature birth. In the United States, where 1 in 10 births occurs preterm, premature birth is the leading cause of infant mortality. Premature infants have high rates of mortality and morbidity, with the highest rates seen in those infants born extremely preterm -- prior to 30 weeks gestation. Severe morbidity in these infants often contributes to life-long health problems. Maternal hypertension (HTN) is one contributor to preterm birth and also contributes to fetal growth restriction, resulting in birth weights which are small for gestational age (SGA, and generally within the lowest 10th percentile). Within this high risk population, SGA infants have increased risk of mortality compared to appropriate for gestational age infants. Therefore the impact of maternal HTN on neonatal outcome might be presumed to be negative. Previous studies however, have been contradictory, with both higher and lower rates of infant mortality reported in infants born to mothers with HTN, as well as differing reports analyzing the relationship between serious morbidity and maternal HTN.

Utilizing the Vermont Oxford Network Very Low Birth Weight database, a collaborative database of Level III Neonatal Intensive Care Units across the world, 88,275 North American infants born between 22+0 and 29+6 weeks gestational age between 2008 and 2011 were identified. This dissertation explores the relationship between maternal HTN and gestational age at time of birth within this population, and the reported rates of morbidity and mortality in infants born prior to 30 weeks gestation. The independent contributions of maternal HTN with neonatal morbidity and mortality in our population were estimated using logistic regression and adjusting for factors previously known to be associated with risk, including birth weight, antenatal steroid exposure, infant sex, maternal race/ethnicity, prenatal care, inborn/outborn status, and birth year. We hypothesized that mortality rates would be lower for infants born to mothers with HTN compared to those born due to other factors, when corrected for the noted confounding variables and surviving infants would have better prognoses, as evidenced by lower rates of severe morbidity, including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and infection. Within the higher-risk SGA population, we hypothesized that mortality rates would be higher than observed in appropriately grown infants, but decreased in those born to mothers with HTN, despite the association between maternal HTN and SGA.

This dissertation begins with an explanation of current knowledge about preterm birth, maternal HTN, and their associations. Chapter 2 focuses on the relationship between maternal HTN and infant mortality in extremely preterm infants. Chapter 3 examines the risk associated with severe morbidities in surviving infants. In addition, we also use a combined morbidity risk assessment score which has previously been used to determine future risk of long term disability. In Chapter 4, SGA infants are separately evaluated for their risk of mortality and the association with maternal HTN.

These analyses support the high mortality and morbidity rates seen in extremely preterm infants. Maternal HTN, after adjustment, results in reduced risk of both mortality and severe morbidities in infants compared to infants born to mothers with other underlying contributors to preterm birth. This suggests that clinical practices and parental counseling should reflect differing risk profiles in sub-populations of extremely preterm infants.



Number of Pages

122 p.

Available for download on Thursday, May 25, 2017