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Multicenter Study
. 2021 Sep 1;4(9):e2125308.
doi: 10.1001/jamanetworkopen.2021.25308.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth

Joseph Niyibizi  1   2 , Marie-Hélène Mayrand  1   3   4 , François Audibert  3   5 , Patricia Monnier  6   7 , Paul Brassard  7   8 , Louise Laporte  2 , Julie Lacaille  4 , Monica Zahreddine  2 , Marie-Josée Bédard  3 , Isabelle Girard  9 , Diane Francoeur  3   5 , Ana Maria Carceller  2   10 , Jacques Lacroix  10 , William Fraser  11 , François Coutlée  4   12   13   14 , Helen Trottier  1   2 ; HERITAGE Study Group
Collaborators, Affiliations
Multicenter Study

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth

Joseph Niyibizi et al. JAMA Netw Open. .

Abstract

Importance: Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated.

Objective: To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth.

Design, setting, and participants: The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021.

Exposures: Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection.

Main outcomes and measures: The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score.

Results: The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment.

Conclusions and relevance: The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mayrand reported receiving grants from the Canadian Institutes of Health Research (CIHR) during the conduct of the study. Dr Coutlée reported receiving grants through his institution from Becton-Dickson, Roche Diagnostics, and Merck Sharp Dohme outside the submitted work. Dr Trottier reported receiving grants from the CIHR during the conduct of the study and personal fees from Merck and unrestricted grants from ViiV Healthcare outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
HPV indicates human papillomavirus. aA total of 22 participants underwent first-trimester prophylactic cerclage because of a history of cervico-isthmic insufficiency in a previous pregnancy. bWithdrawn or deliveries at nonparticipating site.
Figure 2.
Figure 2.. Subgroup Analyses for Human Papillomavirus 16/18 (HPV-16/18) Persistent Infection vs No HPV-16/18 Persistent Infection
NE indicates nonestimable. aAdjusted odds ratios (aORs) by inverse propensity treatment weights of the propensity score of any HPV at the first trimester, excluding the variable for which we stratified. Persistent HPV-16/18 infection was defined as a positive test result for HPV-16 or HPV-18 at the first trimester and third trimester. No persistent HPV-16/18 infection was defined as a negative test result for any HPV at both trimesters, any HPV transient infection at the first and third trimesters, or any persistent HPV infection other than HPV-16/18.
See this image and copyright information in PMC

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