Browsing by Subject "preterm birth"
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Item Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV(Elsevier, 2017-12) Conroy, Andrea L.; McDonald, Chloe R.; Gamble, Joel L.; Olwoch, Peter; Natureeba, Paul; Cohan, Deborah; Kamya, Moses R.; Havlir, Diane V.; Dorsey, Grant; Kain, Kevin C.; Pediatrics, School of MedicineBackground Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings. Objective We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. Study Design This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda. Pregnant women living with HIV were enrolled between 12-28 weeks of gestation. Plasma samples were evaluated for angiogenic biomarkers (angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin) by enzyme-linked immunosorbent assay between: 16-<20, 20-<24, 24-<28, 28-<32, 32-<36, 36-<37 weeks of gestation. The primary outcome was preterm birth. Results In all, 1115 plasma samples from 326 pregnant women and adolescents were evaluated. There were no differences in angiogenic factors according to antiretroviral therapy group (P > .05 for all). The incidence of adverse birth outcomes was 16.9% for spontaneous preterm births, 25.6% for small-for-gestational-age births, and 2.8% for stillbirth. We used linear mixed effect modelling to evaluate longitudinal changes in angiogenic factor concentrations between birth outcome groups adjusting for gestational age at venipuncture, maternal age, body mass index, gravidity, and the interaction between treatment arm and gestational age. Two angiogenic factors–soluble endoglin and placental growth factor–were associated with adverse birth outcomes. Significantly higher concentrations of soluble endoglin throughout gestation were found in study participants destined to deliver preterm [likelihood ratio test, χ2(1) = 12.28, P < .0005] and in those destined to have stillbirths [χ2(1) = 5.67, P < .02]. By contrast, significantly lower concentrations of placental growth factor throughout gestation were found in those destined to have small-for-gestational-age births [χ2(1) = 7.89, P < .005] and in those destined to have stillbirths [χ2(1) = 21.59, P < .0001]. Conclusion An antiangiogenic state in the second or third trimester is associated with adverse birth outcomes, including stillbirth in women and adolescents living with HIV and receiving antiretroviral therapy.Item Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort(Taylor & Francis, 2022-12) Burchard, Julja; Markenson, Glenn R.; Saade, George R.; Laurent, Louise C.; Heyborne, Kent D.; Coonrod, Dean V.; Schoen, Corina N.; Baxter, Jason K.; Haas, David M.; Longo, Sherri A.; Sullivan, Scott A.; Wheeler, Sarahn M.; Pereira, Leonardo M.; Boggess, Kim A.; Hawk, Angela F.; Crockett, Amy H.; Treacy, Ryan; Fox, Angela C.; Polpitiya, Ashoka D.; Fleischer, Tracey C.; Garite, Thomas J.; Boniface, J. Jay; Zupancic, John A. F.; Critchfield, Gregory C.; Kearney, Paul E.; Obstetrics and Gynecology, School of MedicineObjectives Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. Methods The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects’ gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher’s exact test for neonatal morbidity/mortality (significance, p < .05). Results The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs’ point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. Conclusions Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.Item Ethanol for preventing preterm birth in threatened preterm labor(Wiley, 2015) Haas, David M.; Morgan, Amanda M.; Deans, Samantha J.; Schubert, Frank P.; Department of Obstetrics and Gynecology, IU School of MedicineBackground Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. Objectives To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. Selection criteria We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. Data collection and analysis At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. Main results Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review. Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas.Item Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia(Massachusetts Medical Society, 2022-03-24) Watterberg, Kristi L.; Walsh, Michele C.; Li, Lei; Chawla, Sanjay; D’Angio, Carl T.; Goldberg, Ronald N.; Hintz, Susan R.; Laughon, Matthew M.; Yoder, Bradley A.; Kennedy, Kathleen A.; McDavid, Georgia E.; Backstrom-Lacy, Conra; Das, Abhik; Crawford, Margaret M.; Keszler, Martin; Sokol, Gregory M.; Poindexter, Brenda B.; Ambalavanan, Namasivayam; Hibbs, Anna Maria; Truog, William E.; Schmidt, Barbara; Wyckoff, Myra H.; Khan, Amir M.; Garg, Meena; Chess, Patricia R.; Reynolds, Anne M.; Moallem, Mohannad; Bell, Edward F.; Meyer, Lauritz R.; Patel, Ravi M.; Van Meurs, Krisa P.; Cotten, C. Michael; McGowan, Elisabeth C.; Hines, Abbey C.; Merhar, Stephanie; Peralta-Carcelen, Myriam; Wilson-Costello, Deanne E.; Kilbride, Howard W.; DeMauro, Sara B.; Heyne, Roy J.; Mosquera, Ricardo A.; Natarajan, Girija; Purdy, Isabell B.; Lowe, Jean R.; Maitre, Nathalie L.; Harmon, Heidi M.; Hogden, Laurie A.; Adams-Chapman, Ira; Winter, Sarah; Malcolm, William F.; Higgins, Rosemary D.; Eunice Kennedy Shriver NICHD Neonatal Research Network; Pediatrics, School of MedicineBACKGROUND Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.)Item Nutrition and growth in infants with established bronchopulmonary dysplasia(Wiley, 2021-11) Bauer, Sarah E.; Vanderpool, Charles P. B.; Ren, Clement; Cristea, Aura Ioana; Pediatrics, School of MedicineBronchopulmonary dysplasia (BPD) remains the most common late morbidity of preterm birth. Ongoing clinical care and research have largely focused on the pathogenesis and prevention of BPD in preterm infants. However, preterm infants who develop BPD have significant medical needs that persist throughout their neonatal intensive care unit course and continue post-discharge, including those associated with growth and nutrition. The objective of this manuscript was to provide a review on nutrition and growth in infants with established BPD after discharge from the hospital and to identify the knowledge and research gaps to provide direction for future studies.Item Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries(Elsevier, 2021) Short, Vanessa L.; Hoffman, Matthew; Metgud, Mrityunjay; Kavi, Avinash; Goudar, Shivaprasad S.; Okitawutshu, Jean; Tshefu, Antoinette; Bose, Carl L.; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Garces, Ana; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Das, Prabir Kumar; Patel, Archana; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Bucher, Sherri; Nowak, Kayla J.; Goco, Norman; Nolen, Tracy L.; McClure, Elizabeth M.; Koso-Thomas, Marion; Miodovnik, Menachem; Derman, Richard J.; Medicine, School of MedicineBACKGROUND The daily use of low-dose aspirin may be a safe, widely available, and inexpensive intervention for reducing the risk of preterm birth. Data on the potential side effects of low-dose aspirin use during pregnancy in low- and middle-income countries are needed. OBJECTIVE This study aimed to assess differences in unexpected emergency medical visits and potential maternal side effects from a randomized, double-blind, multicountry, placebo-controlled trial of low-dose aspirin use (81 mg daily, from 6 to 36 weeks’ gestation). STUDY DESIGN This study was a secondary analysis of data from the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial, a trial of the Global Network for Women's and Children's Health conducted in India (2 sites), Pakistan, Guatemala, Democratic Republic of the Congo, Kenya, and Zambia. The outcomes for this analysis were unexpected emergency medical visits and the occurrence of the following potential side effects—overall and separately—nausea, vomiting, rash or hives, diarrhea, gastritis, vaginal bleeding, allergic reaction, and any other potential side effects. Analyses were performed overall and by geographic region. RESULTS Between the aspirin (n=5943) and placebo (n=5936) study groups, there was no statistically significant difference in the risk of unexpected emergency medical visits or the risk of any potential side effect (overall). Of the 8 potential side effects assessed, only 1 (rash or hives) presented a different risk by treatment group (4.2% in the aspirin group vs 3.5% in the placebo group; relative risk, 1.20; 95% confidence interval, 1.01–1.43; P=.042). CONCLUSION The daily use of low-dose aspirin seems to be a safe intervention for reducing the risk of preterm birth and well tolerated by nulliparous pregnant women between 6 and 36 weeks’ gestation in low- and middle-income countries.Item The Impact of Self-Reported Alcohol, Tobacco, and Recreational Drug Use during Pregnancy on Adverse Pregnancy Outcomes in First-Time Mothers(Thieme Medical Publishers, 2022-09-12) Daggy, Joanne K.; Silver, Robert M.; Guise, David; Haas, David M.; Biostatistics and Health Data Science, School of MedicineObjective: The objective of this study was to derive profiles of alcohol, tobacco, and recreational drug use during pregnancy for first-time mothers with latent class growth analysis (LCGA) and determine the association of these classes with the risk of adverse pregnancy outcomes (APO). Study Design: A secondary analysis of a prospective cohort of Nulliparous Outcomes in Pregnancy: Monitoring Mothers-to-Be was conducted in eight medical centers across the United States from September 30, 2010, to September 23, 2013. Self-reported use of any alcohol, tobacco, or recreational drugs in the 1 month prior to the visit was assessed at up to four visits throughout pregnancy, and APOs included a composite of preterm birth, hypertensive disorder of pregnancy (HDP), small for gestational age (SGA) infant, or stillbirth, and each adverse outcome separately. Results: Four latent classes were identified from the LCGA for 10,031 nulliparous pregnant women that were on average 26.9 years old (standard deviation [SD] = 5.7) and mostly non-Hispanic White (59.7%). Classes included consistent tobacco users (N = 517, 5.2%), nonusers (N = 8,945, 89.2%), alcohol users (N = 500, 5.0%), and a combination of alcohol/tobacco/drug users (N = 69, 0.7%). Logistic regression demonstrated that the class of tobacco users was more likely to have an APO (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.22–1.81), preterm birth (OR = 1.53, 95% CI = 1.15–2.02), and SGA (OR = 1.79, 95% CI = 1.36–2.35) relative to the class of nonusers. The class of alcohol users was more likely to have HDP (OR = 1.37, 95% CI = 1.11–1.70) and less likely to have preterm birth (OR = 0.59, 95% CI = 0.38–0.90) and SGA (OR = 0.61, 95% CI = 0.40–0.93) compared to nonusers. Conclusion: Trajectories of substance use are associated with APOs; thus, interventions to mitigate the use when encountered early in pregnancy are warranted. Key Points: - Four classes of substance use were identified. - Tobacco users were at a higher risk of APO and alcohol users were at higher risk of HDP. - Mitigation strategies are warranted to reduce APO.Item Uterocervical angle measurement improves prediction of preterm birth in twin gestation(Thieme, 2017-01) Knight, Jordan C.; Tenbrink, Emily; Onslow, Mitchell; Patil, Avinash S.; Obstetrics and Gynecology, School of MedicineObjective An obtuse uterocervical angle (UCA) has been associated with increased risk of preterm birth in singleton gestations. Our objective was to compare the performance of UCA to cervical length (CL) as sonographic predictors of spontaneous preterm birth (sPTB) in patients with twin gestation. Study Design We conducted a retrospective cohort study of twin gestations at a single academic center from May 2008-2016 who received a transvaginal ultrasound for the evaluation of the cervix between 16 0/7 - 22 6/7 weeks. An investigator blinded to clinical outcomes reviewed images of cervical morphology and measured UCA and CL parameters. Data on obstetrical outcomes was extracted from the medical record. The primary outcome was prediction of preterm birth <28 weeks and <32 weeks by UCA and CL. Receiver operator characteristic (ROC) curves and binary logistic regression were used for statistical analysis. Statistical significance was defined as p <0.05. Results Among 259 women with twin gestation, the mean gestational age at birth was 34.83 +/- 3.48 weeks, and 44.7% (n=116) delivered prior to 36 weeks. ROC curves demonstrated optimal prediction of sPTB prior to 32 weeks at a UCA > 110o (80% sensitivity, 82% specificity) vs. CL < 25mm (27% sensitivity, 93% specificity; p<0.001) and similarly, prior to 28 weeks at a UCA>114o (80% sensitivity, 84% specificity) vs. CL< 25mm (35% sensitivity, 90% specificity; p<0.001, Figure). Binary logistic regression revealed UCA > 110o conferred an OR 15.7 (95% CI 7.2-34.4) for delivery prior to 32 weeks, and UCA > 114o an OR 24.3 (95% CI 6.7-88.5) for delivery prior to 28 weeks. In comparison, CL<25mm had an OR 5.2 (95% CI 2.2-12.2) and OR 6.0 (95% CI 2.0-18.1) prior to 32 and 28 weeks respectively. Conclusion Uterocervical angles >110o performed better than the traditional cervical length threshold (25mm) for the prediction of sPTB in a cohort of twin gestations. Measurement of the UCA during the mid-trimester may improve identification of twin gestations at risk for sPTB.