The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study

impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings

Joram Sawady, Brian M. Mercer, Ronald J. Wapner, Yuan Zhao, Yoram Sorokin, Francee Johnson, Donald J. Dudley, Catherine Y. Spong, Alan M. Peaceman, Kenneth J. Leveno, Margaret Harper, Steve N. Caritis, Menachem Miodovnik, John M. Thorp, Susan Ramin, Marshall W. Carpenter, Dwight J. Rouse

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. Study Design: In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. Results: One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at <32 or ≥32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at ≥32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). Conclusion: Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume197
Issue number3
DOIs
StatePublished - Sep 2007

Fingerprint

National Institute of Child Health and Human Development (U.S.)
Adrenal Cortex Hormones
Steroids
Mothers
Medicine
Growth
Placenta
Pregnancy
Fibrin
Infarction
Edema
Fibrosis
Inflammation
Chorioamnionitis
Betamethasone

Keywords

  • antenatal corticosteroid
  • histopathologic finding
  • placenta
  • preterm birth

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study : impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings. / Sawady, Joram; Mercer, Brian M.; Wapner, Ronald J.; Zhao, Yuan; Sorokin, Yoram; Johnson, Francee; Dudley, Donald J.; Spong, Catherine Y.; Peaceman, Alan M.; Leveno, Kenneth J.; Harper, Margaret; Caritis, Steve N.; Miodovnik, Menachem; Thorp, John M.; Ramin, Susan; Carpenter, Marshall W.; Rouse, Dwight J.

In: American Journal of Obstetrics and Gynecology, Vol. 197, No. 3, 09.2007.

Research output: Contribution to journalArticle

Sawady, Joram ; Mercer, Brian M. ; Wapner, Ronald J. ; Zhao, Yuan ; Sorokin, Yoram ; Johnson, Francee ; Dudley, Donald J. ; Spong, Catherine Y. ; Peaceman, Alan M. ; Leveno, Kenneth J. ; Harper, Margaret ; Caritis, Steve N. ; Miodovnik, Menachem ; Thorp, John M. ; Ramin, Susan ; Carpenter, Marshall W. ; Rouse, Dwight J. / The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study : impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings. In: American Journal of Obstetrics and Gynecology. 2007 ; Vol. 197, No. 3.
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abstract = "Objective: In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. Study Design: In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. Results: One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at <32 or ≥32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at ≥32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). Conclusion: Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.",
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T2 - impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings

AU - Sawady, Joram

AU - Mercer, Brian M.

AU - Wapner, Ronald J.

AU - Zhao, Yuan

AU - Sorokin, Yoram

AU - Johnson, Francee

AU - Dudley, Donald J.

AU - Spong, Catherine Y.

AU - Peaceman, Alan M.

AU - Leveno, Kenneth J.

AU - Harper, Margaret

AU - Caritis, Steve N.

AU - Miodovnik, Menachem

AU - Thorp, John M.

AU - Ramin, Susan

AU - Carpenter, Marshall W.

AU - Rouse, Dwight J.

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N2 - Objective: In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. Study Design: In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. Results: One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at <32 or ≥32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at ≥32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). Conclusion: Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.

AB - Objective: In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. Study Design: In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. Results: One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at <32 or ≥32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at ≥32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). Conclusion: Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.

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