Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age

C. Vedel; H. Larsen; Anni Holmskov; Kirsten Riis Andreasen; Niels Uldbjerg; Jan Ramb; Birgit Bødker; Lillian Skibsted; Lene Søndergaard Sperling; L Krebs; H Zingenberg; Lone Laursen; J. T.  Christensen; Ann Tabor; Line Rode

doi:10.1002/uog.15948

Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age

C. Vedel, H. Larsen, Anni Holmskov, Kirsten Riis Andreasen, Niels Uldbjerg, Jan Ramb, Birgit Bødker, Lillian Skibsted, Lene Søndergaard Sperling, L Krebs, H Zingenberg, Lone Laursen, J. T. Christensen, Ann Tabor, Line Rode

21 Citations (Scopus)

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 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.

Original language	English
Journal	Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
Volume	48
Issue number	3
Pages (from-to)	382-389
Number of pages	8
ISSN	0960-7692
DOIs	https://doi.org/10.1002/uog.15948
Publication status	Published - 1 Sept 2016

Keywords

Journal Article

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Vedel, C., Larsen, H., Holmskov, A., Andreasen, K. R., Uldbjerg, N., Ramb, J., Bødker, B., Skibsted, L., Sperling, L. S., Krebs, L., Zingenberg, H., Laursen, L., Christensen, J. T., Tabor, A., & Rode, L. (2016). Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 48(3), 382-389. https://doi.org/10.1002/uog.15948

Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age. / Vedel, C.; Larsen, H.; Holmskov, Anni et al.
In: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Vol. 48, No. 3, 01.09.2016, p. 382-389.

Research output: Contribution to journal › Journal article › Research › peer-review

Vedel, C, Larsen, H, Holmskov, A, Andreasen, KR, Uldbjerg, N, Ramb, J, Bødker, B, Skibsted, L, Sperling, LS, Krebs, L , Zingenberg, H, Laursen, L, Christensen, JT, Tabor, A & Rode, L 2016, 'Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age', Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, vol. 48, no. 3, pp. 382-389. https://doi.org/10.1002/uog.15948

Vedel C, Larsen H, Holmskov A, Andreasen KR, Uldbjerg N, Ramb J et al. Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2016 Sept 1;48(3):382-389. doi: 10.1002/uog.15948

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doi = "10.1002/uog.15948",

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T1 - Long-term effects of prenatal progesterone exposure

T2 - neurophysiological development and hospital admissions in twins up to 8 years of age

AU - Vedel, C.

AU - Larsen, H.

AU - Holmskov, Anni

AU - Andreasen, Kirsten Riis

AU - Uldbjerg, Niels

AU - Ramb, Jan

AU - Bødker, Birgit

AU - Skibsted, Lillian

AU - Sperling, Lene Søndergaard

AU - Krebs, L

AU - Zingenberg, H

AU - Laursen, Lone

AU - Christensen, J. T.

AU - Tabor, Ann

AU - Rode, Line

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

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DO - 10.1002/uog.15948

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JO - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

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Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age

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