C Vedel1,2, H Larsen3, A Holmskov4, K R Andreasen5, N Uldbjerg6, J Ramb7, B Bødker8, L Skibsted2,9, L Sperling2,10, L Krebs11, H Zingenberg12, L Laursen13, J T Christensen14, A Tabor1,2, L Rode1,15. 1. Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 2. University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark. 3. Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, Denmark. 4. Department of Obstetrics and Gynecology, Viborg Hospital, Viborg, Denmark. 5. Department of Obstetrics and Gynecology, Hvidovre Hospital, Hvidovre, Denmark. 6. Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby, Denmark. 7. Department of Obstetrics and Gynecology, Sønderborg Hospital, Sønderborg, Denmark. 8. Department of Obstetrics and Gynecology, Nordsjaellands Hospital, Hillerød, Denmark. 9. Department of Obstetrics and Gynecology, University Hospital Roskilde, Roskilde, Denmark. 10. Department of Obstetrics and Gynecology, Herlev Hospital, Herlev, Denmark. 11. Department of Obstetrics and Gynecology, Holbaek Hospital, Holbaek, Denmark. 12. Department of Obstetrics and Gynecology, Glostrup Hospital, Glostrup, Denmark. 13. Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark. 14. Department of Obstetrics and Gynecology, Gentofte Hospital, Hellerup, Denmark. 15. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, Denmark.
Abstract
OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months of age in children exposed prenatally to progesterone compared with a placebo and evaluate their medical histories up to 8 years of age. METHODS: In this study, Danish participants of the PREDICT study, including 989 surviving children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development was evaluated by the parent-completed Ages and Stages Questionnaire (ASQ) at either 48 or 60 months after the estimated date of delivery. We used the method of generalized estimating equation to account for the correlation within twins. RESULTS: A total of 492 children had been exposed prenatally to progesterone and 497 toplacebo. There was no difference in the number of admissions to or length of stay in hospital between the treatment groups, and we found no overall difference in the rates of diagnoses made. However, the odds ratios (ORs) for a diagnosis concerning the heart was 1.66 (95% CI, 0.81-3.37), favoring placebo, among all children, 2.38 (95% CI, 1.07-5.30) in dichorionic twins and 8.19 (95% CI, 1.02-65.6) in all children when excluding diagnoses made at outpatient clinic visits. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared with the placebo group (P = 0.03). In dichorionic twins, the risk of having a low ASQ score (< 10(th) centile) was decreased in the progesterone group (OR, 0.34 (95% CI, 0.14-0.86)). CONCLUSION: Second- and third-trimester exposure of the fetus to progesterone does not seem to have long-term harmful effects during childhood, but future studies should focus on cardiac disease in the child.
RCT Entities:
OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months of age in children exposed prenatally to progesterone compared with a placebo and evaluate their medical histories up to 8 years of age. METHODS: In this study, Danish participants of the PREDICT study, including 989 surviving children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development was evaluated by the parent-completed Ages and Stages Questionnaire (ASQ) at either 48 or 60 months after the estimated date of delivery. We used the method of generalized estimating equation to account for the correlation within twins. RESULTS: A total of 492 children had been exposed prenatally to progesterone and 497 to placebo. There was no difference in the number of admissions to or length of stay in hospital between the treatment groups, and we found no overall difference in the rates of diagnoses made. However, the odds ratios (ORs) for a diagnosis concerning the heart was 1.66 (95% CI, 0.81-3.37), favoring placebo, among all children, 2.38 (95% CI, 1.07-5.30) in dichorionic twins and 8.19 (95% CI, 1.02-65.6) in all children when excluding diagnoses made at outpatient clinic visits. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared with the placebo group (P = 0.03). In dichorionic twins, the risk of having a low ASQ score (< 10(th) centile) was decreased in the progesterone group (OR, 0.34 (95% CI, 0.14-0.86)). CONCLUSION: Second- and third-trimester exposure of the fetus to progesterone does not seem to have long-term harmful effects during childhood, but future studies should focus on cardiac disease in the child.
Authors: Agustin Conde-Agudelo; Roberto Romero; Eduardo Da Fonseca; John M O'Brien; Elcin Cetingoz; George W Creasy; Sonia S Hassan; Offer Erez; Percy Pacora; Kypros H Nicolaides Journal: Am J Obstet Gynecol Date: 2018-04-07 Impact factor: 8.661
Authors: R Romero; A Conde-Agudelo; W El-Refaie; L Rode; M L Brizot; E Cetingoz; V Serra; E Da Fonseca; M S Abdelhafez; A Tabor; A Perales; S S Hassan; K H Nicolaides Journal: Ultrasound Obstet Gynecol Date: 2017-03 Impact factor: 7.299
Authors: C J J Cuijpers; J Van't Hooft; C Schneeberger; J H Van Der Lee; N E Simons; M A Van Os; J Van Der Ven; C J M De Groot; B W J Mol; A G Van Wassenaer-Leemhuis Journal: Ultrasound Obstet Gynecol Date: 2021-02-12 Impact factor: 7.299
Authors: Roberto Romero; Agustin Conde-Agudelo; Eduardo Da Fonseca; John M O'Brien; Elcin Cetingoz; George W Creasy; Sonia S Hassan; Kypros H Nicolaides Journal: Am J Obstet Gynecol Date: 2017-11-17 Impact factor: 8.661