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Item Do maternal demographics and prenatal history impact the efficacy of betamethasone therapy for threatened preterm labor?(BMC, 2021-06-24) Kinney, Mary T.; Quinney, Sara K.; Trussell, Hayley K.; Silva, Larissa L.; Ibrahim, Sherrine A.; Haas, David M.; Obstetrics and Gynecology, School of MedicineBackground: Betamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone. Methods: This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing. Results: Of 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06-1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67-0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models. Conclusions: Of maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use.Item The impact of glucocorticoid polymorphisms on markers of neonatal respiratory disease after antenatal betamethasone administration.(Elsevier, 2013-03) Haas, David M.; Dantzer, Jessica; Lehmann, Amalia S.; Philips, Santosh; Skaar, Todd C.; McCormick, Catherine L.; Hebbring, Scott J.; Jung, Jeesun; Li, LangOBJECTIVE: We previously demonstrated that maternal and fetal genotypes are associated independently with neonatal respiratory distress syndrome. The objective of the current study was to determine the impact of maternal and fetal single-nucleotide polymorphisms (SNPs) in key betamethasone pathways on respiratory outcomes that serve as markers for severity of disease. STUDY DESIGN: DNA was obtained from women who were given betamethasone and from their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis that controlled for relevant clinical variables to determine SNP impact on bronchopulmonary dysplasia (BPD), the need for respiratory support, and surfactant therapy use was performed. RESULTS: Data from 109 women who delivered 117 infants were analyzed: 14.5% of the infants experienced BPD; 70.8% of the infants needed some respiratory support after birth, and 27.5% of the infants needed surfactant therapy. In a multivariable regression analysis, gestational age at delivery was associated with most neonatal respiratory outcomes (P ≤ .01), and chorioamnionitis was associated with BPD (P < .03). The following genotypes were associated with respiratory severity outcomes: BPD-fetal Importin 13 gene (IPO13; rs4448553; odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00-0.92); surfactant use-maternal IPO13 (rs2428953 and 2486014; OR, 13.8; 95% CI, 1.80-105.5; and OR, 35.5; 95% CI, 1.71-736.6, respectively). CONCLUSION: Several discrete maternal and fetal SNPs in the IPO13 family may be associated with neonatal respiratory outcomes after maternal antenatal corticosteroid treatment for anticipated preterm birth.