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.
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.


METHODS
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 > 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 > or = 32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036).


CONCLUSIONS
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.
Sawady
Joram
J
Department of Pathology, Metro Health Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Mercer
Brian M
BM
Wapner
Ronald J
RJ
Zhao
Yuan
Y
Sorokin
Yoram
Y
Johnson
Francee
F
Dudley
Donald J
DJ
Spong
Catherine Y
CY
Peaceman
Alan M
AM
Leveno
Kenneth J
KJ
Harper
Margaret
M
Caritis
Steve N
SN
Miodovnik
Menachem
M
Thorp
John M
JM
Ramin
Susan
S
Carpenter
Marshall W
MW
Rouse
Dwight J
DJ
D000328:Adult; D001623:Betamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D010920:Placenta / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology*; D010929:Placentation; D011247:Pregnancy; D049188:Prenatal Injuries / Q000139:chemically induced*