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Item Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants(American Thoracic Society, 2017-08-01) Morrow, Lindsey A.; Wagner, Brandie D.; Ingram, David A.; Poindexter, Brenda B.; Schibler, Kurt; Cotten, C. Michael; Dagle, John; Sontag, Marci K.; Mourani, Peter M.; Abman, Steven H.; Pediatrics, School of MedicineRATIONALE: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. OBJECTIVES: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. METHODS: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. MEASUREMENTS AND MAIN RESULTS: After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. CONCLUSIONS: We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth.Item Association of Adverse Pregnancy Outcomes With Hypertension 2 to 7 Years Postpartum(Wiley Open Access, 2019-10-01) Haas, David M.; Parker, Corette B.; Marsh, Derek J.; Grobman, William A.; Ehrenthal, Deborah B.; Greenland, Philip; Merz, C. Noel Bairey; Pemberton, Victoria L.; Silver, Robert M.; Barnes, Shannon; McNeil, Rebecca B.; Cleary, Kirsten; Reddy, Uma M.; Chung, Judith H.; Parry, Samuel; Theilen, Lauren H.; Blumenthal, Elizabeth A.; Levine, Lisa D.; Mercer, Brian M.; Simhan, Hyagriv; Polito, LuAnn; Wapner, Ronald J.; Catov, Janet; Chen, Ida; Saade, George R. Saade; NHLBI nuMoM2b Heart Health Study; Medicine, School of MedicineBackground Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk.Item Functional Differences Between Placental Micro- and Macrovascular Endothelial Colony-Forming Cells(Wiley, 2016-03) Solomon, Ioana; O’Reilly, Megan; Ionescu, Lavinia; Alphonse, Rajesh S.; Rajabali, Saima; Zhong, Shumei; Vadivel, Arul; Shelley, W. Chris; Yoder, Mervin C.; Thébaud, Bernard; Department of Pediatrics, IU School of MedicineAlterations in the development of the placental vasculature can lead to pregnancy complications, such as preeclampsia. Currently, the cause of preeclampsia is unknown, and there are no specific prevention or treatment strategies. Further insight into the placental vasculature may aid in identifying causal factors. Endothelial colony-forming cells (ECFCs) are a subset of endothelial progenitor cells capable of self-renewal and de novo vessel formation in vitro. We hypothesized that ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Human placentas were collected from term pregnancies delivered by cesarean section (n = 16). Placental micro- and macrovasculature was collected from the maternal and fetal side of the placenta, respectively, and ECFCs were isolated and characterized. ECFCs were CD31(+), CD105(+), CD144(+), CD146(+), CD14(-), and CD45(-), took up 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein, and bound Ulex europaeus agglutinin 1. In vitro, macrovascular ECFCs had a greater potential to generate high-proliferative colonies and formed more complex capillary-like networks on Matrigel compared with microvascular ECFCs. In contrast, in vivo assessment demonstrated that microvascular ECFCs had a greater potential to form vessels. Macrovascular ECFCs were of fetal origin, whereas microvascular ECFCs were of maternal origin. ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Although macrovascular ECFCs demonstrated greater vessel and colony-forming potency in vitro, this did not translate in vivo, where microvascular ECFCs exhibited a greater vessel-forming ability. These important findings contribute to the current understanding of normal placental vascular development and may aid in identifying factors involved in preeclampsia and other pregnancy complications.Item Toward Automation of the Supine Pressor Test for Preeclampsia(American Society of Mechanical Enginners, 2019-11) Qureshi, Hamna J.; Ma, Jessica L.; Anderson, Jennifer L.; Bosinski, Brett M.; Acharya, Aditi; Bennett, Rachel D.; Haas, David M.; Cox, Abigail D.; Wodicka, George R.; Reuter, David G.; Goergen, Craig J.; Medicine, School of MedicinePreeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.Item Weight gain in early, mid, and late pregnancy and hypertensive disorders of pregnancy(Elsevier, 2020-04) Dude, Annie M.; Kominiarek, Michelle A.; Haas, David M.; Iams, Jay; Mercer, Brian M.; Parry, Samuel; Reddy, Uma M.; Saade, George; Silver, Robert M.; Simhan, Hyagriv; Wapner, Ronald; Wing, Deborah; Grobman, William; Obstetrics and Gynecology, School of MedicineObjective: To examine the relationship of weight change during early, mid, and late pregnancy with the development of a hypertensive disorder of pregnancy (HDP). Study design: These data are from a prospective cohort study of nulliparous women with live singleton pregnancies. "Early" weight change was defined as the difference between self-reported pre-pregnancy weight and weight at the first visit (between 6 and 13 weeks' gestation); "mid" weight change was defined as the weight change between the first and second visits (between 16 and 21 weeks' gestation); "late" weight change was defined as the weight change between the second and third visits (between 22 and 29 weeks' gestation). Weight change in each time period was further characterized as inadequate, adequate, or excessive based on the Institute of Medicine's (IOM's) trimester-specific weekly weight gain goals based on pre-pregnancy body mass index. Multivariable Poisson regression was performed to adjust for potential confounders. Main outcome measure: Development of any hypertensive disorder of pregnancy. Results: Of 8296 women, 1564 (18.9%) developed a HDP. Weight gain in excess of the IOM recommendations during the latter two time periods was significantly associated with HDP. Specifically, trimester-specific excessive weight gain in the mid period (aIRR 1.16, 95% CI 1.01-1.35) as well as in the late period (aIRR = 1.19, 95% CI = 1.02-1.40) was associated with increased risk of developing HDP. The weight gain preceded the onset of clinically apparent disease. Conclusions: Excessive weight gain as early as the early second trimester was associated with increased risks of development of HDP.