Evidence map›Paper›PMID 34767803›Full record

ArticleAmerican journal of obstetrics and gynecology2022

In utero exposure to 17α-hydroxyprogesterone caproate and risk of cancer in offspring.

Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Open access · greenAbstract read
In one paragraph

Article in American journal of obstetrics and gynecology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023
    Guideline
  2. Review
  3. Progestogen supplementation to prevent miscarriage: Evidence and controversies.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
    Review
  4. Immunomodulatory Role of Natural Progesterone in Pregnancy: A Review.The journal of obstetrics and gynaecology research · 2026
    Review
  5. Father's occupation and colorectal cancer in his adult offspring.Journal of the National Cancer Institute · 2025
    Article
  6. Article
  7. Article
  8. Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
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  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Caitlin C MurphySchool of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX. Electronic address: caitlin.c.murphy@uth.tmc.edu.
Piera M CirilloChild Health and Development Studies, Public Health Institute, Berkeley, CA.
Nickilou Y KrigbaumChild Health and Development Studies, Public Health Institute, Berkeley, CA.
Barbara A CohnChild Health and Development Studies, Public Health Institute, Berkeley, CA.
Public Health Institute · USThe University of Texas Health Science Center · US

Funding

CALIFORNIA COORDINATED CANCER PREVENTION & CONTROL PROGRAMU58DP003862 · DP · CALIFORNIA STATE DEPT OF PUBLIC HEALTH · PI SNIPES, KURT P · 2012 to 2014
$31.5M
Early life exposures and risk of young-onset colorectal cancerR01CA242558 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MURPHY, CAITLIN C · 2019 to 2023
$1.5M
NCCDPHP CDC HHS U58 DP003862NCI NIH HHS HHSN261201000034CNCI NIH HHS HHSN261201000035CNCI NIH HHS HHSN261201000035INCI NIH HHS HHSN261201000140CNCI NIH HHS R01 CA242558NICHD NIH HHS HHSN275201100020C
6 · The paper itself

Abstract

background17α-hydroxyprogesterone caproate is a synthetic progestogen initially approved in the 1950s to treat gynecologic and obstetrical conditions. Despite continued concerns about safety and short-term efficacy regarding the use of 17α-hydroxyprogesterone caproate for the prevention of preterm birth in pregnant women, little is known about the long-term effects of 17α-hydroxyprogesterone caproate on the health of the offsprings.

objectiveTo examine the association between in utero exposure to 17α-hydroxyprogesterone caproate and the risk of cancer in the offspring. STUDY

designThe Child Health and Development Studies was a population-based cohort of >18,000 mother-child dyads receiving prenatal care in the Kaiser Foundation Health Plan (Oakland, CA) between 1959 and 1966. Clinical information was abstracted from the mothers' medical records beginning 6 months before pregnancy through delivery. We identified the number and timing of 17α-hydroxyprogesterone caproate injections during pregnancy. Incident cancers diagnosed in the offspring were ascertained through 2019 by linkage to the California Cancer Registry. We used the Cox proportional hazard models to estimate the adjusted hazard ratios and their 95% confidence intervals, with the follow-up time accrued from the date of birth through the date of cancer diagnosis, death, or last contact.

resultsA total of 1008 offspring were diagnosed with cancer over 730,817 person-years of follow-up. Approximately 1.0% of the offspring (n=234) were exposed in utero to 17α-hydroxyprogesterone caproate. Exposure in the first trimester was associated with an increased risk of any cancer (adjusted hazard ratio, 2.57; 95% confidence interval, 1.59-4.15), and the risk increased with the number of injections (1-2 injections: adjusted hazard ratio, 1.80; 95% confidence interval, 1.12-2.90; ≥3 injections: adjusted hazard ratio, 3.07; 95% confidence interval, 1.34-7.05). Exposure in the second or third trimester conferred an additional risk for the male (adjusted hazard ratio, 2.59; 95% confidence interval, 1.07-6.28) but not for the female (adjusted hazard ratio, 0.30; 95% confidence interval, 0.04-1.11) offspring. The risk of colorectal (adjusted hazard ratio, 5.51; 95% confidence interval, 1.73-17.59), prostate (adjusted hazard ratio, 5.10; 95% confidence interval, 1.24-21.00), and pediatric brain (adjusted hazard ratio, 34.72; 95% confidence interval, 7.29-164.33) cancer was higher in the offspring first exposed to 17α-hydroxyprogesterone caproate in the first trimester than the offspring not exposed.

conclusionCaution using 17α-hydroxyprogesterone caproate in early pregnancy is warranted, given the possible link with cancer in the offspring.

Indexed as

NeoplasmsPrenatal Exposure Delayed Effects17 alpha-Hydroxyprogesterone CaproateAdultCaliforniaFemaleHumansIncidenceMaleMiddle AgedPregnancyPregnancy TrimestersRegistries17 alpha-Hydroxyprogesterone Caproatecancerendocrine disruptionprogestogenrisk factor

Identifiers

PMID34767803
PMCPMC8748293
OpenAlexW3213980463

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.