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Randomized Controlled Trial
. 2024 Nov 19;24(1):764.
doi: 10.1186/s12884-024-06958-2.

Human papillomavirus infections during pregnancy and adverse pregnancy outcomes: a Scandinavian prospective mother-child cohort study

Magdalena R Værnesbranden  1   2 , Anne Cathrine Staff  3   4 , Johanna Wiik  5   6 , Katrine Sjøborg  5 , Corina S Rueegg  7 , Meryam Sugulle  3   4 , Karin C Lødrup Carlsen  3   8 , Berit Granum  9 , Guttorm Haugen  3   4 , Gunilla Hedlin  10   11 , Katarina Hilde  3   4 , Björn Nordlund  10   11 , Eva M Rehbinder  3   12 , Knut Rudi  13 , Håvard O Skjerven  3   8 , Birgitte K Sundet  3   4 , Cilla Söderhäll  10   11 , Riyas Vettukattil  3   8 , Christine M Jonassen  14   15
Affiliations
Randomized Controlled Trial

Human papillomavirus infections during pregnancy and adverse pregnancy outcomes: a Scandinavian prospective mother-child cohort study

Magdalena R Værnesbranden et al. BMC Pregnancy Childbirth. .

Abstract

Background: Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age.

Materials and methods: Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation.

Results: At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections.

Conclusion: In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age.

Trial registration: Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015.

Keywords: Gestational diabetes mellitus; Human papillomavirus and pregnancy; Hypertensive disorders of pregnancy; Placental dysfunction syndromes; Small for gestational age.

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Conflict of interest statement

Declarations Ethical approval Statement and consent to participate The PreventADALL study with the current sub-study was approved by the Regional Ethical Committee for Medical and Health Research in South-Eastern Norway (REC 2014/518 and REC 2017/1053) and in Sweden (2014/2242-31/4). All women included in the current study signed an informed consent form, with the opportunity to withdraw from the study at any time and without the need to disclose reason for withdrawal. Consent for publication Not applicable. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of enrolled women in the current study
Fig. 2
Fig. 2
Directed acyclic graph of covariates of hypertensive disorders of pregnancy. Abbreviations HDP- hypertensive disorders of pregnancy, HPV-human papillomavirus, Mat.edu-maternal education, Mat.chornic dis.-maternal chronic disease, including chronic hypertension and pregestational diabetes mellitus, Mat.pre-preg.BMI- maternal pre-pregnancy Body Mass Index, Mat.age-maternal age, preg-pregnancy. Color explanation: green with arrow-exposure, blue with l- outcome of interest, green- ancestor (covariate) of exposure, blue- ancestor of outcome, pink-covariates needed for the adjustment analyses
Fig. 3
Fig. 3
Directed acyclic graph of covariates for gestational diabetes mellitus. Abbreviations GDM-gestational diabetes mellitus, HPV-human papillomavirus, Mat.pre-preg.BMI- maternal pre-pregnancy Body Mass Index, Mat.age-maternal age. Color explanation: green with arrow-exposure, blue with l- outcome of interest, pink-covariates needed for the adjustment analyses, grey- other variable
Fig. 4
Fig. 4
Directed acyclic graph of covariates of newborn small of gestational age. Abbreviations: SGA- newborn of small gestational age, HPV-human papillomavirus, Mat.edu-maternal education, Mat.chornic dis.-maternal chronic disease, including chronic hypertension and pregestational diabetes mellitus, Mat.age-maternal age, preg-pregnancy, HDP- hypertensive disorders of pregnancy. Color explanation: green with arrow-exposure, blue with l- outcome of interest, blue- ancestor (covariate) of outcome, pink-covariates needed for the adjustment analyses
See this image and copyright information in PMC

References

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