Ashley N Battarbee1, Stephanie T Ros2,3,4, M Sean Esplin2,3, Joseph Biggio5, Radek Bukowski6, Samuel Parry7, Heping Zhang8, Hao Huang8, William Andrews5, George Saade6, Yoel Sadovsky9, Uma M Reddy10, Michael W Varner2,3, Tracy A Manuck1,2. 1. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC. 2. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Utah School of Medicine, Salt Lake City, UT. 3. Intermountain Healthcare Department of Maternal Fetal Medicine, Salt Lake City, Utah. 4. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of South Florida, Tampa, FL. 5. Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, AL. 6. Department of Women's Health, Dell Medical School, University of Texas at Austin, Austin, TX. 7. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA. 8. Collaborative Center for Statistics in Science, Yale University School of Public Health, New Haven, CT. 9. Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA. 10. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Yale University, New Haven, CT.
Abstract
Background: Antenatal corticosteroids reduce morbidity and mortality among preterm neonates. However, the optimal timing of steroid administration with regards to severe neonatal and early childhood morbidity is uncertain. Objective: To evaluate the association between the timing of antenatal corticosteroid adminstration and preterm outcomes. We hypothesized that neonates exposed to antenatal corticosteroids 2 to <7 days before delivery would have the lowest risks of neonatal and childhood morbidity. Study Design: Secondary analysis of two prospective multicenter studies enriched for spontaneous preterm birth, Genomics and Proteomics Network for Preterm Birth Research (11/2007-1/2011) and Beneficial Effect of Antenatal Magnesium (12/1997-5/2004). We included women with singleton gestations who received antenatal corticosteroids and delivered at 23 0/7-33 6/7 weeks' gestation. Women who received ≥1 course of corticosteroids were excluded. Neonatal outcomes were compared by the timing of the first dose of antenatal corticosteroids in relation to delivery: <2 days, 2 to <7 days, 7 to <14 days, and ≥14 days. The primary outcome was respiratory distress syndrome. Secondary outcomes included composite neonatal morbidity (death, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, bronchopulmonary dysplasia, or necrotizing enterocolitis), and early childhood morbidity (death or moderate to severe cerebral palsy at age 2). Multivariable logistic regression estimated the association between timing of antenatal corticosteroid administration and study outcomes. Results: A total of 2,259 subjects met inclusion criteria: 622 (27.5%) received antenatal corticosteroids <2 days before delivery, 821 (36.3%) 2 to <7 days, 401 (17.8%) 7 to <14 days, and 415 (18.4%) ≥14 days. The majority (78.1%) delivered following idiopathic spontaneous preterm labor or preterm premature rupture of membranes at a mean gestational age of 29.5 +/-2.8 weeks. Neonates exposed to antenatal corticosteroids 2 to <7 days before delivery were the least likely to develop respiratory distress syndrome (51.3%), compared to those receiving antenatal corticosteroids <2 days, 7 to <14 days, and ≥14 days before delivery (62.7%, 55.9%, and 57.6%, respectively, p<0.001). Compared to receipt 2 to <7 days before delivery, there was an increased odds of respiratory distress syndrome with receipt of antenatal corticosteroids <2 days (aOR 2.07, 95%CI 1.61-2.66), 7 to <14 days (aOR 1.40, 95% CI 1.07-1.83), and ≥14 days (aOR 2.34, 95%CI 1.78-3.07). Neonates exposed to antenatal corticosteroids ≥14 days before delivery were at increased odds for severe neonatal morbidity (aOR 1.57, 95%CI 1.12-2.19) and early childhood morbidity (aOR 1.74, 95%CI 1.02-2.95), compared to those exposed 2 to <7 days before delivery. There was no significant association between antenatal corticosteroid receipt <2 days or 7 to <14 days and severe neonatal morbidity or severe childhood morbidity. Conclusions: Preterm neonates exposed to antenatal corticosteroids 2 to <7 days before delivery had the lowest odds of respiratory distress syndrome, compared to shorter and longer time intervals between steroid administration and delivery. Antenatal corticosteroid administration ≥14 days before delivery is associated with an increased odds of severe neonatal and childhood morbidity, compared to 2 to <7 days before delivery. These results emphasize the importance of optimally timed antenatal corticosteroids to improve both short- and long-term outcomes.
Background: Antenatal corticosteroids reduce morbidity and mortality among preterm neonates. However, the optimal timing of steroid administration with regards to severe neonatal and early childhood morbidity is uncertain. Objective: To evaluate the association between the timing of antenatal corticosteroid adminstration and preterm outcomes. We hypothesized that neonates exposed to antenatal corticosteroids 2 to <7 days before delivery would have the lowest risks of neonatal and childhood morbidity. Study Design: Secondary analysis of two prospective multicenter studies enriched for spontaneous preterm birth, Genomics and Proteomics Network for Preterm Birth Research (11/2007-1/2011) and Beneficial Effect of Antenatal Magnesium (12/1997-5/2004). We included women with singleton gestations who received antenatal corticosteroids and delivered at 23 0/7-33 6/7 weeks' gestation. Women who received ≥1 course of corticosteroids were excluded. Neonatal outcomes were compared by the timing of the first dose of antenatal corticosteroids in relation to delivery: <2 days, 2 to <7 days, 7 to <14 days, and ≥14 days. The primary outcome was respiratory distress syndrome. Secondary outcomes included composite neonatal morbidity (death, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, bronchopulmonary dysplasia, or necrotizing enterocolitis), and early childhood morbidity (death or moderate to severe cerebral palsy at age 2). Multivariable logistic regression estimated the association between timing of antenatal corticosteroid administration and study outcomes. Results: A total of 2,259 subjects met inclusion criteria: 622 (27.5%) received antenatal corticosteroids <2 days before delivery, 821 (36.3%) 2 to <7 days, 401 (17.8%) 7 to <14 days, and 415 (18.4%) ≥14 days. The majority (78.1%) delivered following idiopathic spontaneous preterm labor or preterm premature rupture of membranes at a mean gestational age of 29.5 +/-2.8 weeks. Neonates exposed to antenatal corticosteroids 2 to <7 days before delivery were the least likely to develop respiratory distress syndrome (51.3%), compared to those receiving antenatal corticosteroids <2 days, 7 to <14 days, and ≥14 days before delivery (62.7%, 55.9%, and 57.6%, respectively, p<0.001). Compared to receipt 2 to <7 days before delivery, there was an increased odds of respiratory distress syndrome with receipt of antenatal corticosteroids <2 days (aOR 2.07, 95%CI 1.61-2.66), 7 to <14 days (aOR 1.40, 95% CI 1.07-1.83), and ≥14 days (aOR 2.34, 95%CI 1.78-3.07). Neonates exposed to antenatal corticosteroids ≥14 days before delivery were at increased odds for severe neonatal morbidity (aOR 1.57, 95%CI 1.12-2.19) and early childhood morbidity (aOR 1.74, 95%CI 1.02-2.95), compared to those exposed 2 to <7 days before delivery. There was no significant association between antenatal corticosteroid receipt <2 days or 7 to <14 days and severe neonatal morbidity or severe childhood morbidity. Conclusions: Preterm neonates exposed to antenatal corticosteroids 2 to <7 days before delivery had the lowest odds of respiratory distress syndrome, compared to shorter and longer time intervals between steroid administration and delivery. Antenatal corticosteroid administration ≥14 days before delivery is associated with an increased odds of severe neonatal and childhood morbidity, compared to 2 to <7 days before delivery. These results emphasize the importance of optimally timed antenatal corticosteroids to improve both short- and long-term outcomes.
Authors: M Sean Esplin; Karen Merrell; Robert Goldenberg; Yinglei Lai; Jay D Iams; Brian Mercer; Catherine Y Spong; Menachem Miodovnik; Hygriv N Simhan; Peter van Dorsten; Mitchell Dombrowski Journal: Am J Obstet Gynecol Date: 2010-11-11 Impact factor: 8.661
Authors: Femke F Wilms; Jolande Y Vis; Desiree A P M Pattinaja; Rosanna A Kuin; Monique C Stam; Janine M Reuvers; Ben Willem J Mol Journal: Am J Obstet Gynecol Date: 2011-03-26 Impact factor: 8.661
Authors: Allison M Ring; Jeffery S Garland; Brian R Stafeil; Margaret H Carr; Gail S Peckman; Richard A Pircon Journal: Am J Obstet Gynecol Date: 2007-05 Impact factor: 8.661
Authors: Jessica Smith; Kellie E Murphy; Sarah D McDonald; Elizabeth Asztalos; Amir Aviram; Stefania Ronzoni; Elad Mei-Dan; Arthur Zaltz; Jon Barrett; Nir Melamed Journal: Arch Gynecol Obstet Date: 2022-01-18 Impact factor: 2.493
Authors: Marian Kacerovsky; Rudolf Kukla; Radka Bolehovska; Pavel Bostik; Jana Matulova; Jan Mls; Jaroslav Stranik; Bo Jacobsson; Ivana Musilova Journal: Front Pharmacol Date: 2022-03-31 Impact factor: 5.810