Oral hormone pregnancy tests and the risks of congenital malformations

A systematic review and meta-analysis [version 1; referees: 3 approved]

Carl Heneghan, Jeffrey K. Aronson, Elizabeth Spencer, Bennett Holman, Kamal R. Mahtani, Rafael Perera, Igho Onakpoya

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I 2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I 2 =0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I 2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I 2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I 2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I 2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

Original languageEnglish
Article number1725
JournalF1000Research
Volume7
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Pregnancy Tests
Meta-Analysis
Hormones
Odds Ratio
Case-Control Studies
Cohort Studies
Imperforate Anus
Nervous System Malformations
Norethindrone
Maternal Exposure
Pregnancy
Defects
Ethinyl Estradiol
Congenital Heart Defects
Neurology
Pregnant Women
Extremities
Prospective Studies
Kidney
Control Groups

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Heneghan, Carl ; Aronson, Jeffrey K. ; Spencer, Elizabeth ; Holman, Bennett ; Mahtani, Kamal R. ; Perera, Rafael ; Onakpoya, Igho. / Oral hormone pregnancy tests and the risks of congenital malformations : A systematic review and meta-analysis [version 1; referees: 3 approved]. In: F1000Research. 2018 ; Vol. 7.
@article{cc0664a364f248d2b00a69e40276f027,
title = "Oral hormone pregnancy tests and the risks of congenital malformations: A systematic review and meta-analysis [version 1; referees: 3 approved]",
abstract = "Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40{\%} increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95{\%} CI 1.18 to 1.66; P<0.0001; I 2 = 0{\%}). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95{\%} CI 1.32 to 2.72; P = 0.0006; I 2 =0{\%}); nervous system malformations OR = 2.98 (95{\%} CI 1.32 to 6.76; P = 0.0109 I 2 = 78{\%}); gastrointestinal malformations, OR = 4.50 (95{\%} CI 0.63 to 32.20; P = 0.13; I 2 = 54{\%}); musculoskeletal malformations, OR = 2.24 (95{\%} CI 1.23 to 4.08; P= 0.009; I 2 = 0{\%}); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95{\%} CI 2.92 to 19.07; P < 0.0001; I 2 = 0{\%}). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.",
author = "Carl Heneghan and Aronson, {Jeffrey K.} and Elizabeth Spencer and Bennett Holman and Mahtani, {Kamal R.} and Rafael Perera and Igho Onakpoya",
year = "2018",
month = "1",
day = "1",
doi = "10.12688/f1000research.16758.1",
language = "English",
volume = "7",
journal = "F1000Research",
issn = "2046-1402",
publisher = "F1000 Research Ltd.",

}

Oral hormone pregnancy tests and the risks of congenital malformations : A systematic review and meta-analysis [version 1; referees: 3 approved]. / Heneghan, Carl; Aronson, Jeffrey K.; Spencer, Elizabeth; Holman, Bennett; Mahtani, Kamal R.; Perera, Rafael; Onakpoya, Igho.

In: F1000Research, Vol. 7, 1725, 01.01.2018.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Oral hormone pregnancy tests and the risks of congenital malformations

T2 - A systematic review and meta-analysis [version 1; referees: 3 approved]

AU - Heneghan, Carl

AU - Aronson, Jeffrey K.

AU - Spencer, Elizabeth

AU - Holman, Bennett

AU - Mahtani, Kamal R.

AU - Perera, Rafael

AU - Onakpoya, Igho

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I 2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I 2 =0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I 2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I 2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I 2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I 2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

AB - Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I 2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I 2 =0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I 2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I 2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I 2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I 2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

UR - http://www.scopus.com/inward/record.url?scp=85058224136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058224136&partnerID=8YFLogxK

U2 - 10.12688/f1000research.16758.1

DO - 10.12688/f1000research.16758.1

M3 - Review article

VL - 7

JO - F1000Research

JF - F1000Research

SN - 2046-1402

M1 - 1725

ER -