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In utero exposure to 17α-hydroxyprogesterone caproate and risk of cancer in offspring
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1 2022
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Source: Am J Obstet Gynecol. 226(1):132.e1-132.e14
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Alternative Title:Am J Obstet Gynecol
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Description:Background:
17α-hydroxyprogesterone caproate (17-OHPC) is a synthetic progestogen initially approved in the 1950s to treat gynecological and obstetrical conditions. Despite repeated concerns of safety and short-term efficacy regarding the use of 17-OHPC for the prevention of preterm birth in pregnant women, little is known about long-term effects of 17-OHPC on health of offspring.
Objective:
To examine the association between in utero exposure to 17-OHPC and risk of cancer in offspring.
Study Design:
The Child Health and Development Studies is a population-based cohort of more than 18,000 mother-child dyads receiving prenatal care in the Kaiser Foundation Health Plan (Oakland, California) between 1959 and 1966. Clinical information was abstracted from mothers’ medical records beginning six months prior to pregnancy through delivery. We identified the number and timing of 17-OHPC injections during pregnancy. Incident cancers diagnosed in offspring were ascertained through 2019 by linkage to the California Cancer Registry. We used Cox proportional hazards models to estimate adjusted hazard ratios (aHR) and their 95% confidence intervals, with follow-up time accrued from date of birth through date of cancer diagnosis, death, or last contact.
Results:
1,008 offspring were diagnosed with cancer over 730,817 person-years of follow-up. About 1.0% of offspring (n=234) were exposed in utero to 17-OHPC. Exposure in the first trimester was associated with increased risk of any cancer (aHR 2.57, 95% CI 1.59, 4.15), and risk increased with number of injections (1–2 injections: aHR 1.80, 95% CI 1.12,2.90; ≥3 injections: aHR 3.07, 95% CI 1.34, 7.05). Exposure in the second or third trimester conferred an additional risk for male (aHR 2.59, 95% CI 1.07, 6.28) but not female (aHR 0.30, 0.04, 1.11) offspring. Risk of colorectal (aHR 5.51, 95% CI 1.73, 17.59), prostate (aHR 5.10, 95% CI 1.24, 21.00), and pediatric brain (aHR 34.72, 95% CI 7.29, 164.33) cancer was higher in offspring first exposed to 17-OHPC in the first trimester compared to offspring not exposed.
Conclusions:
Caution using 17-OHPC in early pregnancy is warranted, given the possible link with cancer in offspring.
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Pubmed ID:34767803
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Pubmed Central ID:PMC8748293
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