Association between the Mode of Delivery and Vertical Transmission of Human Papillomavirus.

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36-48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03-12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10-17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.

Human Papillomavirus Transmission and Persistence in Pregnant Women and Neonates.

Importance: The prevalence of human papillomavirus (HPV) infection during pregnancy and its risk of transmission to newborns are not well documented. Objective: To ascertain the prevalence of HPV in pregnant women, the risk of HPV detection in the placenta and in children at birth, and the probability that HPV detected at birth may persist in newborns. Design, Setting, and Participants: The Human Papillomavirus Perinatal Transmission and Risk of HPV Persistence Among Children (HERITAGE) study was a prospective cohort study that recruited participants between November 8, 2010, and October 16, 2016. Participant follow-up visits were completed on June 15, 2017. Participants, which included pregnant women of at least 18 years of age and at 14 weeks or earlier of gestation, were recruited from 3 academic hospitals in Montreal, Québec, Canada. Laboratory and statistical analysis were completed on November 15, 2022. Exposures: HPV DNA testing on self-collected vaginal and placental samples. Among children of mothers positive for HPV, conjunctival, oral, pharyngeal, and genital samples were collected for HPV DNA testing. Main Outcomes and Measures: Vaginal HPV DNA testing was done on self-collected vaginal samples obtained among pregnant women recruited during their first trimester of pregnancy and in the third trimester for those who had HPV-positive samples in the first trimester. HPV DNA testing was also done on placental samples (swabs and biopsies) collected after birth in all participants. HPV DNA testing among children included conjunctival, oral, pharyngeal, and genital samples collected in children of HPV-positive mothers at birth, 3 months, and 6 months of age. Results: A total of 1050 pregnant women (mean [SD] age, 31.3 [4.7] years) were included in this study. Prevalence of HPV in pregnant women at recruitment was 40.3% (95% CI, 37.3%-43.3%). Among the 422 HPV-positive women, 280 (66.4%) harbored at least 1 high-risk genotype, and 190 (45.0%) were coinfected with multiple genotypes. HPV was detected in 10.7% of placentas (92 of 860; 95% CI, 8.8%-12.9%) overall, but only 3.9% of biopsies (14 of 361) on the fetal side under the amniotic membrane were positive. Neonatal HPV detection (at birth and/or at 3 months) was 7.2% (95% CI, 5.0%-10.3%) overall, with the most frequent site of infection being the conjunctiva (3.2%; 95% CI, 1.8%-5.6%), followed by the mouth (2.9%; 95% CI, 1.6%-5.2%), the genital area (2.7%; 95% CI, 1.4%-4.9%), and the pharynx (0.8%; 95% CI, 0.2%-2.5%). Importantly, all HPV detected in children at birth cleared before the age of 6 months. Conclusions and relevance: In this cohort study, vaginal HPV was frequently detected in pregnant women. Perinatal transmission was infrequent, and in this cohort, no infection detected at birth persisted at 6 months. Although HPV was detected in placentas, it remains difficult to differentiate contamination vs true infection.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth.

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.

Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: Design, methods and preliminary results of the HERITAGE study.

Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3-6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37-53%]) and in placentas (14%[8-21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10-14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV.

Leydig cell tumors in children: contrasting clinical, hormonal, anatomical, and molecular characteristics in boys and girls.

OBJECTIVE: To analyze the clinical, hormonal, anatomical, and molecular characteristics of Leydig cell tumors, a very rare cause of progressive hyperandrogenism in children. STUDY DESIGN: Description of a 9-year-old boy with isosexual precocious pseudopuberty, and of a 12-year-old girl with rapidly progressive virilization, both due to a pure Leydig cell tumor. Review of all cases of pediatric Leydig cell tumors published since 1999 (when the first somatic mutations of the luteinizing hormone receptor were described) and reporting hormonal and/or molecular data. RESULTS: Boys (n = 24) are younger than girls (n = 12) at diagnosis (median 6.5 vs 13.0 years, P = .04). Plasma gonadotrophins are more often completely suppressed in boys (6 cases) than in girls (2 cases). Pure Leydig cell tumors are exceedingly rare in girls (2 cases), who most often have Sertoli-Leydig tumors. These tumors affect either testis equally (11 left, 13 right) but occur more often in the left ovary (8 left, 3 right). Activating mutations of the alpha-subunit of the G(s) stimulatory protein have not been found in either boys or girls and activating mutations of the luteinizing hormone receptor have only been found in boys. CONCLUSIONS: Leydig cell tumors in children display clinical, hormonal, anatomical, and molecular sexual dimorphism.

Hypoplastic uterus and clitoris enlargement in Swyer syndrome.

BACKGROUND: Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. CASE: A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. SUMMARY AND CONCLUSION: The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads.

The use of depot-medroxyprogesterone acetate in contraception and its potential impact on skeletal health.

BACKGROUND: In the fall of 2007, the controversy about the contraceptive use of depot-medroxyprogesterone acetate (DMPA) and its potential impact on skeletal health reached the media in the province of Quebec, Canada, thereby becoming a matter of concern for the lay public and physicians. In order to discuss this subject openly, the National Institute of Public Health of Quebec (INSPQ) organized a scientific meeting on February 15, 2008, with targeted physicians delegated by their medical associations in the fields of general practice, obstetrics and gynaecology, rheumatology, orthopaedic surgery, physiatry and endocrinology. STUDY DESIGN: Participants reviewed the scientific literature using the study classification method according to the level of evidence, reviewed published guidelines of medical societies and organizations on the subject and reached a consensus position. This manuscript presents a review of the literature and describes the consensus position of the targeted medical associations. RESULTS: The consensus position adopted by all the targeted medical associations determined that DMPA was a cost-effective contraceptive option that must be considered in the light of the clinical situation and preference of each woman. Candidates for injectable contraception should be informed that the use of DMPA is associated with a slight decrease in bone mineral density (BMD), which is largely, if not completely, reversible. There should not be an absolute limit to the length of time that the DMPA contraceptive is used, regardless of the woman's age. Monitoring BMD is not recommended among users of DMPA for contraceptive purposes. Finally, the consensus statement declared that, although supplements of calcium and vitamin D are beneficial for skeletal health for women in general, such supplementation should not be recommended solely based on a woman's use of DMPA. CONCLUSION: Given the scientific evidences, DMPA use remains a valid contraceptive option for women. Its potential impact on BMD must be balanced against the significant individual, familial and social consequences of unintended pregnancy.

Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates.

OBJECTIVES: Our goals were to (a) describe neonatal behavioral signs in a group of newborns exposed in utero to selective serotonin reuptake inhibitors or venlafaxine at the time of delivery, (b) compare the rate of neonatal behavioral signs, prematurity, and admission to specialized neonatal care between a group of exposed and unexposed newborns, and (c) compare the effects in exposed preterm and term newborns. PATIENTS AND METHODS: This was a retrospective cohort study including mothers taking selective serotonin reuptake inhibitors or venlafaxine during the third trimester and mothers who were not taking any antidepressants, psychotropic agents, or benzodiazepines at the time of delivery of their newborns. Neonatal behavioral signs included central nervous, respiratory, and digestive systems, as well as hypoglycemia and the need for phototherapy. RESULTS: Seventy-six mothers taking antidepressants and 90 untreated mothers and their newborns were analyzed. Smoking, alcohol intake, and substance abuse were more frequent among treated mothers. In infants in the exposed group, signs involving the central nervous and the respiratory systems were often observed (63.2% and 40.8%, respectively). These signs appeared during the first day of life, with a median duration of 3 days for exposed newborns. The signs resolved in 75% of cases within 3 to 5 days for term and premature newborns, respectively. All exposed premature newborns presented behavioral manifestations compared with 69.1% of term exposed newborns. Median length of stay was almost 4 times longer for exposed premature newborns than for those who were unexposed (14.5 vs 3.7 days). CONCLUSIONS: Neonatal behavioral signs were frequently found in exposed newborns, but symptoms were transient and self-limited. Premature infants could be more susceptible to the effects of selective serotonin reuptake inhibitors and venlafaxine.