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

Cathrine Vedel; Helle Larsen; Anni Holmskov; Kirsten Riis Andreasen; Niels Uldbjerg; Jan Ramb; Birgit Bødker; Lillian Skibsted; Lene Sperling; Lone Krebs; Helle Zingenberg; Lone Laursen; Jeanette Tranberg 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

Cathrine Vedel, Helle Larsen, Anni Holmskov, Kirsten Riis Andreasen, Niels Uldbjerg, Jan Ramb, Birgit Bødker, Lillian Skibsted, Lene Sperling, Lone Krebs, Helle Zingenberg, Lone Laursen, Jeanette Tranberg Christensen, Ann Tabor, Line Rode

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

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Abstract

OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months in children exposed prenatally to progesterone compared to placebo and evaluate their medical histories up to 8 years of age.

METHODS: This follow-up of the Danish participants in the PREDICT study included 989 surviving children from 498 pregnancies. PREDICT is a placebo-controlled randomized trial examining 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 to progesterone prenatally and 497 to placebo. There were no differences between the groups in number or length of admissions, and we found no overall differences in rates of diagnoses. However, the odds ratio for a diagnosis related to the heart was 1.66 (95%CI 0.80;3.37) in favor of placebo among all children, 2.29 (1.02;5.12) in dichorionic twins, and 8.19 (1.02;65.6) in all children when outpatient diagnoses were excluded. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared to placebo (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 (0.14;0.86)).

CONCLUSIONS: Second and third trimester exposure to progesterone does not seem to have long-term harmful effects on children, but future studies should focus on cardiac disease in the offspring.

CLINICAL TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials. gov, www.clinicaltrials.gov, NCT00329914.

Original language	English
Journal	Ultrasound in Obstetrics & 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 - 2016

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Vedel, C., Larsen, H., Holmskov, A., Andreasen, K. R., Uldbjerg, N., Ramb, J., Bødker, B., Skibsted, L., Sperling, L., 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, 48(3), 382-389. https://doi.org/10.1002/uog.15948

@article{17b37d3176eb495ab102332bf5280519,

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

abstract = "OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months in children exposed prenatally to progesterone compared to placebo and evaluate their medical histories up to 8 years of age.METHODS: This follow-up of the Danish participants in the PREDICT study included 989 surviving children from 498 pregnancies. PREDICT is a placebo-controlled randomized trial examining 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 to progesterone prenatally and 497 to placebo. There were no differences between the groups in number or length of admissions, and we found no overall differences in rates of diagnoses. However, the odds ratio for a diagnosis related to the heart was 1.66 (95%CI 0.80;3.37) in favor of placebo among all children, 2.29 (1.02;5.12) in dichorionic twins, and 8.19 (1.02;65.6) in all children when outpatient diagnoses were excluded. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared to placebo (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 (0.14;0.86)).CONCLUSIONS: Second and third trimester exposure to progesterone does not seem to have long-term harmful effects on children, but future studies should focus on cardiac disease in the offspring.CLINICAL TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials. gov, www.clinicaltrials.gov, NCT00329914.",

author = "Cathrine Vedel and Helle Larsen and Anni Holmskov and Andreasen, {Kirsten Riis} and Niels Uldbjerg and Jan Ramb and Birgit B{\o}dker and Lillian Skibsted and Lene Sperling and Lone Krebs and Helle Zingenberg and Lone Laursen and Christensen, {Jeanette Tranberg} and Ann Tabor and Line Rode",

year = "2016",

doi = "10.1002/uog.15948",

language = "English",

volume = "48",

pages = "382--389",

journal = "Ultrasound in Obstetrics & Gynecology",

issn = "0960-7692",

publisher = "Wiley",

number = "3",

}

Vedel, C, Larsen, H, Holmskov, A, Andreasen, KR, Uldbjerg, N, Ramb, J, Bødker, B, Skibsted, L, Sperling, L, 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, vol. 48, no. 3, pp. 382-389. https://doi.org/10.1002/uog.15948

TY - JOUR

T1 - Long-term effects of prenatal progesterone exposure

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

AU - Vedel, Cathrine

AU - Larsen, Helle

AU - Holmskov, Anni

AU - Andreasen, Kirsten Riis

AU - Uldbjerg, Niels

AU - Ramb, Jan

AU - Bødker, Birgit

AU - Skibsted, Lillian

AU - Sperling, Lene

AU - Krebs, Lone

AU - Zingenberg, Helle

AU - Laursen, Lone

AU - Christensen, Jeanette Tranberg

AU - Tabor, Ann

AU - Rode, Line

PY - 2016

Y1 - 2016

N2 - OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months in children exposed prenatally to progesterone compared to placebo and evaluate their medical histories up to 8 years of age.METHODS: This follow-up of the Danish participants in the PREDICT study included 989 surviving children from 498 pregnancies. PREDICT is a placebo-controlled randomized trial examining 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 to progesterone prenatally and 497 to placebo. There were no differences between the groups in number or length of admissions, and we found no overall differences in rates of diagnoses. However, the odds ratio for a diagnosis related to the heart was 1.66 (95%CI 0.80;3.37) in favor of placebo among all children, 2.29 (1.02;5.12) in dichorionic twins, and 8.19 (1.02;65.6) in all children when outpatient diagnoses were excluded. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared to placebo (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 (0.14;0.86)).CONCLUSIONS: Second and third trimester exposure to progesterone does not seem to have long-term harmful effects on children, but future studies should focus on cardiac disease in the offspring.CLINICAL TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials. gov, www.clinicaltrials.gov, NCT00329914.

AB - OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months in children exposed prenatally to progesterone compared to placebo and evaluate their medical histories up to 8 years of age.METHODS: This follow-up of the Danish participants in the PREDICT study included 989 surviving children from 498 pregnancies. PREDICT is a placebo-controlled randomized trial examining 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 to progesterone prenatally and 497 to placebo. There were no differences between the groups in number or length of admissions, and we found no overall differences in rates of diagnoses. However, the odds ratio for a diagnosis related to the heart was 1.66 (95%CI 0.80;3.37) in favor of placebo among all children, 2.29 (1.02;5.12) in dichorionic twins, and 8.19 (1.02;65.6) in all children when outpatient diagnoses were excluded. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared to placebo (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 (0.14;0.86)).CONCLUSIONS: Second and third trimester exposure to progesterone does not seem to have long-term harmful effects on children, but future studies should focus on cardiac disease in the offspring.CLINICAL TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2006-000503-41, and ClinicalTrials. gov, www.clinicaltrials.gov, NCT00329914.

U2 - 10.1002/uog.15948

DO - 10.1002/uog.15948

M3 - Journal article

C2 - 27106105

SN - 0960-7692

VL - 48

SP - 382

EP - 389

JO - Ultrasound in Obstetrics & Gynecology

JF - Ultrasound in Obstetrics & Gynecology

IS - 3

ER -

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

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