Browsing by Subject "Hypertensive disorders of pregnancy"

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    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 Medicine
    RATIONALE: 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.
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    Genetic Risk and First-Trimester Cardiovascular Health Predict Hypertensive Disorders of Pregnancy in Nulliparous Women
    (Elsevier, 2025) Mathew, Vineetha; Khan, Raiyan R.; Jowell, Amanda R.; Yan, Qi; Pe'er, Itsik; Truong, Buu; Natarajan, Pradeep; Yee, Lynn M.; Khan, Sadiya S.; Sharma, Garima; Patel, Aniruddh P.; Cho, So Mi Jemma; Pabon, Maria A.; McNeil, Rebecca B.; Spencer, Jillyn; Silver, Robert M.; Levine, Lisa D.; Grobman, William A.; Catov, Janet M.; Haas, David M.; Honigberg, Michael C.; Obstetrics and Gynecology, School of Medicine
    Background: Hypertensive disorders of pregnancy (HDPs) (preeclampsia/eclampsia and gestational hypertension) are a leading cause of maternal and perinatal morbidity and mortality and are associated with long-term maternal cardiovascular disease. High genetic risk and poor cardiovascular health (CVH) are each associated with HDPs, but whether genetic risk for HDP is modified by CVH status in early pregnancy is unknown. Objectives: In this study, the authors sought to test the independent and joint associations of genetic risk and first-trimester CVH with development of HDP. Methods: We examined genotyped participants from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort that enrolled nulliparous individuals with singleton pregnancies from 2010 to 2013 at 8 U.S. clinical sites. Genetic risk was calculated according to a validated genetic risk score for HDP. A first-trimester CVH score was closely adapted from the American Heart Association Life's Essential 8 model. Genetic risk and CVH were each categorized as low (bottom quintile), intermediate (quintile 2-4), or high (top quintile). The primary outcome was development of HDP. Multivariable-adjusted logistic regression was used to test the independent and joint associations of genetic risk and CVH with development of HDPs. Results: Among 7,499 participants (mean age 27.0 years), the median first-trimester CVH score was 77.1 (Q1-Q3: 67.1-85.7). Overall, 1,032 participants (13.8%) developed an HDP (487 [6.5%] preeclampsia, 545 [7.3%] gestational hypertension). Genetic risk and CVH were each independently and additively associated with HDP (high vs low genetic risk: adjusted OR [aOR]: 2.21 [95% CI: 1.78-2.77; P < 0.001]; low vs high CVH: aOR: 2.92 [95% CI: 2.28-3.74; P < 0.001]). There was no significant interaction between genetic risk and CVH regarding risk of HDPs (Pinteraction > 0.05). HDP incidence ranged from 4.5% (low genetic risk, high CVH) to 25.7% (high genetic risk, low CVH). Compared with low CVH, high CVH was associated with 53%-74% lower risk of HDP across genetic risk strata. Findings were consistent when examining preeclampsia/eclampsia and gestational hypertension separately. Conclusions: Lower genetic risk and higher first-trimester CVH were independently and additively associated with lower risk of developing HDPs in nulliparous individuals. Favorable CVH in early pregnancy may mitigate high genetic risk for HDP.
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    Pharmacokinetic Characterization of Labetalol in Pregnancy (The CLIP Study): A Prospective Observational Longitudinal Pharmacokinetic/Pharmacodynamic Cohort Study During Pregnancy and Postpartum
    (MDPI, 2025-04-18) Bhamidipaty-Pelosi, Surya; Muralidharan, Suhaas; Yeley, Brittany C.; Haas, David M.; Quinney, Sara K.; Medicine, School of Medicine
    Background/Objectives: Hypertensive disorders of pregnancy are a leading cause of pregnancy-related deaths in the United States, accounting for 7% of maternal mortality. Labetalol and nifedipine are the first-line drugs for the management of hypertension in pregnancy, but there are little data guiding the choice of one drug over the other. The current pilot longitudinal study aims to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of labetalol stereoisomers throughout pregnancy and postpartum. Methods: This is a single-center clinical study recruiting up to 40 pregnant individuals ≥ 18 years of age at the time of enrollment, taking labetalol as per the standard of care. The exclusion criteria include any pathophysiology impacting the PK of labetalol, e.g., liver failure. Maternal plasma, urine, amniotic fluid, cord blood, and breast milk will be collected, and labetalol stereoisomers will be measured using a validated LC-MS/MS assay. Heart rate and blood pressure will be measured as the PD endpoints. These may be assessed throughout a participant's dosing interval at scheduled PK study visits, which will occur every 6-10 weeks during pregnancy, at delivery, during the 1st week postpartum, and up to 20 weeks postpartum. The primary aim is to characterize the PK and PD of labetalol during pregnancy and in the postpartum period. The secondary aim is to determine the extent of breast milk excretion of and infant exposure to labetalol from breast milk. The data will be analyzed using population PK modeling to evaluate the PK/PD relationship and ultimately develop trimester-specific dosing recommendations. Results/Conclusions: To our knowledge, this is the first study aiming to characterize the PK of labetalol stereoisomers across pregnancy and postpartum, utilizing individual stereoisomer data to evaluate the PK/PD relationship, and collecting postpartum samples, including breast milk, to model infant exposure to labetalol through breast milk. This study will provide important PK/PD data and knowledge which will be combined with large multi-center clinical trial data to develop trimester-specific dosing regimens for anti-hypertensive agents.