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.

Evidence for HPV DNA in the placenta of women who resorted to elective abortion.

BACKGROUND: It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. METHODS: We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA. RESULTS: HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90. CONCLUSION: The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.

Association between maternal human immunodeficiency virus infection and preterm birth: A matched case-control study from a pregnancy outcome registry.

ABSTRACT: This study aimed to evaluate the relationships between different types of antiretroviral therapy (ART) and preterm birth.Preterm birth was studied among all singleton pregnancies and compared between human immunodeficiency virus (HIV)-infected and uninfected women.We performed a matched case-control study from the pregnancy outcome registry of Cayenne Hospital. HIV-infected and uninfected women who delivered in the maternity ward of Cayenne Hospital from January 1, 2013 to December 31, 2015 were studied. We conducted an initial analysis to determine the risk factors for preterm birth among HIV-infected pregnant women. We also evaluated associations between exposure to antiretroviral therapy (ART) and preterm birth.There were 8682 deliveries; of these, 117 involved HIV-infected women, representing a prevalence of 1.34%. There were 470 controls. The sociodemographic characteristics were comparable. HIV-infected women were more likely to experience preterm birth (adjusted odds ratio [AOR] = 3.9, 95% confidence interval [CI] 1.5-9.9). Overall, 95.73% of the women received antiretroviral therapy before becoming pregnant, and they were in good clinical condition. The median CD4 count at the beginning of pregnancy was 500 cells/mm3 (357-722). Additionally, 53% of HIV-infected women had an undetectable viral load count (<20 copies/mL). Their median haemoglobin level was 120 g/L (100-120). There were 2 human immunodeficiency virus-infected babies. A higher rate of preterm birth was associated with protease inhibitor-based ART than a reverse transcriptase inhibitor-based ART regimen. The sample size being small this result would be considered with caution.The preterm birth rate among HIV-infected pregnant women was twice that of the general population; this trend was not explained by sociodemographic characteristics. Preterm birth was independently associated with combination ART, especially with ritonavir-boosted protease inhibitor therapy during pregnancy.

Maternal anemia and preterm birth among women living with HIV in the United States.

BACKGROUND: Women living with HIV (WLHIV) have a higher prevalence of anemia than women without HIV, possibly related to the effects of HIV and antiretroviral medications. OBJECTIVES: To estimate the prevalence of anemia in the third trimester of pregnancy and the effect of anemia on preterm births in WLHIV in the longitudinal, US-based Pediatric HIV/AIDS Cohort Study (PHACS). METHODS: During the third trimester, we obtained up to three 24-hour dietary recalls to estimate daily intakes of nutrients and measured serum concentrations of iron, vitamin B6, vitamin B12, zinc, folate, ferritin, total iron-binding capacity (TIBC), and high sensitivity C-reactive protein. Third trimester anemia was defined as hemoglobin < 11 g/d and iron-deficiency anemia (IDA) was defined as low ferritin, high TIBC, and low transferrin saturation. A preterm birth was defined as birth at < 37 completed weeks of gestation, regardless of etiology. We fit separate modified Poisson regression models for each outcome (anemia, preterm birth) and each main exposure, adjusted for confounders, and report adjusted prevalence ratios (aPR) and 95% CIs. RESULTS: Of the 267 WLHIV, 50% were anemic in the third trimester, of whom 43.5% (n = 57/131) had IDA. On average, women with anemia were younger, were more likely to be black, started antiretroviral medications in the second trimester, had a low CD4 count (<200 cells/mm3) early in pregnancy, and were less likely to meet recommended intakes for iron, B6, and folate. The prevalence of anemia was greater in WLHIV with a low CD4 count (aPR = 1.65; 95% CI: 1.20-2.27) and high HIV viral load (>10,000 copies/mL; aPR = 1.38; 95% CI: 1.02-1.87). In total, 16% of women delivered preterm. Anemia was associated with a 2-fold (aPR = 2.04; 95% CI: 1.12-3.71) higher prevalence of preterm births. CONCLUSIONS: Anemia is common in pregnant WLHIV, highlighting the need to address the underlying factors and clinical outcomes of anemia in this population.

Acceptability of a trial of vaginal progesterone for the prevention of preterm birth among HIV-infected women in Lusaka, Zambia: A mixed methods study.

Antenatal progesterone prevents preterm birth (PTB) in women with a short cervix or prior PTB in daily vaginal or weekly injectable formulations, respectively. Neither has been tested for the indication of maternal HIV, which is associated with an elevated risk of PTB. The Vaginal Progesterone (VP) Trial was a pilot feasibility study of VP to prevent HIV-related PTB in Lusaka, Zambia. Using mixed methods, we concurrently evaluated the acceptability of the trial and the study product among participants. Over a 1-year period, we enrolled 140 pregnant women living with HIV into a double-masked, placebo-controlled, randomized trial of daily self-administered VP or placebo. We administered an endline questionnaire to all participants and conducted in-depth interviews with 30 participants to assess barriers and facilitators to uptake and retention in the trial and to study product adherence. All interviews were audiotaped, transcribed, translated into English as needed, and independently coded by two analysts to capture emerging themes. Of 131 participants who completed the questionnaire, 128 (98%) reported that nothing was difficult when asked the hardest part about using the study product. When given a hypothetical choice between vaginal and injectable progesterone, 97 (74%) chose vaginal, 31 (24%) injectable, and 3 (2%) stated no preference. Most interviewees reported no difficulties with using the study product; others cited minor side effects and surmountable challenges. Strategies that supported adherence included setting alarms, aligning dosing with antiretrovirals, receiving encouragement from friends and family, sensing a benefit to their unborn baby, and positive feedback from study staff. Participants who reported preference of a vaginal medication over injectable described familiarity with the vaginal product, a fear of needles and resulting pain, and inconvenience of a weekly clinic visit. Those who would prefer weekly injections cited fewer doses to remember. Perceived barriers to study participation included mistrust about the motivations behind research, suspicion of Satanism, and futility or possible harm from a placebo. We report key influences on acceptability of a randomized trial of VP to prevent PTB among HIV-infected women in Zambia, which should inform methods to promote uptake, adherence, and retention in a full-scale trial.

SARS-CoV-2 and pregnancy: A review of the facts / SARS-CoV-2 e gestação: uma revisão dos fatos

Abstract Objective The present comprehensive review aims to show the full extent of what is known to date and provide a more thorough view on the effects of SARS-CoV2 in pregnancy. Methods Between March 29 and May, 2020, the words COVID-19, SARS-CoV2, COVID- 19 and pregnancy, SARS-CoV2 and pregnancy, and SARS and pregnancy were searched in the PubMed and Google Scholar databases; the guidelines from well-known societies and institutions (Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG], International Society of Ultrasound in Obstetrics & Gynecology [ISUOG], Centers for Disease Control and Prevention [CDC], International Federation of Gynecology and Obstetrics [FIGO]) were also included. Conclusion The COVID-19 outbreak resulted in a pandemic with > 3.3 million cases and 230 thousand deaths until May 2nd. It is caused by the SARS-CoV2 virus and may lead to severe pulmonary infection and multi-organ failure. Past experiences show that unique characteristics in pregnancy make pregnant women more susceptible to complications from viral infections. Yet, this has not been reported with this new virus. There are risk factors that seem to increase morbidity in pregnancy, such as obesity (body mass index [BMI] > 35), asthma and cardiovascular disease. Current reports describe an increased rate of pretermbirth and C-section. Vertical transmission

Resumo Objetivo A presente revisão detalhada busca fornecer dados objetivos para avaliar o que se sabe até o momento e possibilitar uma visãomais ampla dos efeitos do SARSCoV2 na gravidez. Métodos Entre 29 demarço e 2 de maio de 2020, foi realizada uma busca nos bancos de dados PubMed e Google Scholar com as palavras COVID-19, SARS-CoV2, COVID-19 e gravidez, SARS-CoV2 e gravidez, e SARS e gravidez. As recomendações dos principais órgãos sobre o tema também foram acessadas. Conclusão O surto de COVID-19 resultou em uma pandemia com> 3.3 milhões de casos e 230 mil mortes até 2 de maio. É uma condição causada pelo vírus SARS-CoV2 e pode levar ao acometimento pulmonar difuso e à falência de múltiplos órgãos. Características únicas da gestante tornam essa população mais propensas a complicações de infecções virais. Até o momento, essa tendência não foi observada para esse novo vírus. Os fatores que parecem estar associados à maior morbidade materno-fetal são obesidade (índice demassa corporal [IMC] > 35), asma e doença cardiovascular. Há descrição de aumento de parto prematuro e parto cesáreo. Não se pode descartar a possibilidade de transmissão vertical da doença, devido a relatos de positividade de reação em cadeia de polimerase (RT-PCR) de swab nasal, RT-PCR de líquido amniótico e imunoglobulina M (IgM) de recém-nascidos. Tratamentos devem ser analisados caso a caso, dada a falta de qualidade de estudos que comprovem a sua eficácia e segurança na gravidez. O corpo clínico deve utilizar equipamentos de proteção individual (EPI) ao manusear pacientes suspeitos ou confirmados e ficar atento aos sinais de descompensação respiratória.

The optimal time to test for sero-reversion in HIV-exposed uninfected infants: the later the better?

OBJECTIVES: HIV-exposed uninfected (HEU) infants are tested for loss of maternal antibody (sero-reversion) at 18 months of age. Highly sensitive fourth-generation antigen/antibody assays can detect very low levels of antibody, leading to retesting. We audited serological screening outcomes in HEU infants at two National Health Service (NHS) Trusts. METHODS: HEU infants born between January 2013 and August 2016 were identified via case records. Data collected included gestation; age at testing; test results and assay type. RESULTS: One hundred and forty-two infants were identified, of whom 21 were excluded from analysis. One hundred and one (83%) were born at term and 20 (17%) preterm (< 37/40 weeks of gestation), and the median age at first serology was 19.1 [interquartile range (IQR) 18.1; 21.4] months. Initial serology was positive in 10 of 121 infants (8.3%), and the median age of these 10 infants was 18.3 (IQR 18.1; 18.8) months, whereas those with negative serology (n = 111) had a median age of 19.2 (IQR 18.1; 21.5) months (P = 0.12). All infants with positive HIV serology were born at term. Seven of 10 infants had reactive serology on two fourth-generation assays. Subsequent serology was available for eight of 10 infants, with a median age of 21.3 months. Five of the eight (63%) were negative. One was reactive but HIV RNA polymerase chain reaction (PCR) was negative, and one was reactive on screening but negative on confirmatory testing. The remaining child was still seropositive at 24.7 months but had a non-reactive result at 29.4 months. CONCLUSIONS: Overall, 8.3% of HEU infants required repeat testing to confirm loss of antibody. Delaying testing until 22 months of age reduces retesting to < 2%, with associated resource and emotional implications. Positive serology at 22 months should prompt an HIV RNA PCR to exclude infection.

Association Between Maternal Human Papillomavirus Infection and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis.

BACKGROUND: Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes. METHODS: We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies. RESULTS: From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19-1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11-3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08-1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01-1.37), low birth weight (aOR, 1.91; 95% CI, 1.33-2.76), and fetal death (aOR, 2.23; 95% CI, 1.14-4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40-3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80-1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained. CONCLUSIONS: We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases.

Effect of maternal HIV infection, BMI and NOx air pollution exposure on birth outcomes in South African pregnant women genotyped for the p53 Pro72Arg (rs1042522).

Tumour suppressor protein, p53, plays a role in modulating innate immune responses, DNA repair, cell cycle arrest, senescence and apoptosis. Maternal nitrogen oxide (NOx) air pollution exposure, body mass index (BMI), human immunodeficiency virus (HIV) infection and p53 Pro72Arg (rs1042522) affect foetal growth. We investigated whether the aforementioned factors influence birth outcomes in a South African population. Pregnant women (n = 300; HIV -ve = 194 and HIV +ve = 106) were genotyped for the p53 rs1042522 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and further stratified based on HIV status, infants' birthweight (BW; NBW: normal BW [>2,500 g] and LBW: low BW [<2,500 g]) and gestational age (GA; NGA: normal GA [>37 weeks] and PTB: preterm birth [≤37 weeks]). A land use regression model was developed to characterize maternal NOx exposure. Pearson's correlation and multivariate regression analysis statistical tests were used to determine the effect of rs1042522 genotyped pregnant women's BMI and NOx exposure on maternal blood pressure and haemoglobin and iron levels, and infants' anthropometric measurements and Appearance Pulse Grimace Activity and Respiration (APGAR) scores. The prevalence of LBW and PTB was 14.7% and 18.7%, respectively. The LBW group had a higher frequency of the variant Arg-allele versus NBW group (47.7% vs. 31.4%, p = .0046, OR = 2.0, 95% CI = 1.26-3.17). No association was observed between NGA and PTB groups. A significant association between BMI and systolic blood pressure (r = .50, p = .00; B = 0.76, p = .002) and birth length (r = -.28, p = .01; B = -0.107, p = .011), and NOx and birth length (r = -.26, p = .08; B = -0.191, p = .046) and birthweight (B = -8.87, p = .048) was observed in HIV-infected mothers with the variant Pro/Arg + Arg/Arg genotypes. Mothers from the LBW group with the variant genotypes displayed an association between NOx and diastolic blood pressure (r = .58, p = .04), blood iron levels (r = -.60, p = .04; B = -0.204, p = .004), APGAR scores at 1 min (r = -.86, p = .00; B = -0.101, p = .003) and 5 min (r = -.75, p = .01) and birth length (r = -.61, p = .04), and BMI and diastolic blood pressure (r = .72, p = .01). In the PTB group, maternal variant genotypes and NOx were associated with blood haemoglobin levels (B = -0.132, p = .045) and APGAR scores at 1 min (B = -0.161, p = .045) and 5 min (B = -0.147, p = .043). Maternal rs1042522 Arg-allele, HIV infection, BMI and NOx exposure collectively play a role in lowering blood iron levels, gestational hypertension and LBW outcomes.

Human bocavirus infection in Belgian children with respiratory tract disease.

Human bocavirus (HBoV) has been detected primarily in children with acute lower respiratory tract disease (LRTD), but its occurrence, clinical profile, and role as a causative agent of RTD are not clear. The aim of this study was to investigate the prevalence and the potential clinical relevance of HBoV. Using molecular tests, we tested 1352 nasopharyngeal samples obtained between October 1, 2017 and April 30, 2018 from children up to the age of 16 with RTD for the presence of HBoV DNA and 20 other respiratory pathogens at three different hospitals in Belgium. HBoV was detected in 77 children with a median age of 10.6 months. Consecutive samples were available for 15 HBoV-positive children and showed persistent HBoV positivity in four of them. Monoinfection was observed in six infants. Four of them were born prematurely and were infected during hospitalization at the neonatal intensive care unit (NICU). Only one of these six monoinfected children was diagnosed with recurrent wheezing due to HBoV. This child was carried to term and had a high viral load. Coinfections, most frequently with rhinovirus (52.1%) and adenovirus (49.3%), were observed in 72 patients. In seventeen of them in which HBoV was present at high viral load or higher viral load than its copathogens, bronchi(oli)tis (n = 8), recurrent wheezing (n = 8) or episodic wheezing (n = 1) were diagnosed. Our results suggest that HBoV infection at high viral load in infants is associated with wheezing (P = 0.013, Cramer's V = 0.613).

Systemic inflammation is associated with malaria and preterm birth in women living with HIV on antiretrovirals and co-trimoxazole.

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes. Concentrations of CHI3L1, CRP, IL-18BP, IL-6, sICAM-1, and sTNFR2 were quantified by ELISA in 1115 plasma samples collected over pregnancy from 326 women. MiP was associated with increased sTNFR2, sICAM-1 and IL-18BP concentrations across pregnancy. Women who delivered preterm had elevated concentrations of sTNFR2 and altered levels of IL-6 during pregnancy. Women with sTNFR2 concentrations in the highest quartile within 6 weeks of delivery had an increased relative risk of preterm birth. Our results indicate that despite daily TMP/SXT, MiP in WLHIV induced a systemic inflammatory response that was associated with an increased risk of preterm birth. These findings highlight the need for additional strategies to protect WLHIV from malaria infection in pregnancy to promote healthy outcomes for mother and child.

The vaginal eukaryotic DNA virome and preterm birth.

BACKGROUND: Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Culture-independent sequencing of vaginal bacterial communities demonstrates community characteristics are associated with preterm birth, although none are specific enough to apply clinically. Viruses are important components of the vaginal microbiome and have dynamic relationships with vaginal bacterial communities. We hypothesized that vaginal eukaryotic DNA viral communities (the "vaginal virome") either alone or in the context of bacterial communities are associated with preterm birth. OBJECTIVE: The objective of this study was to use high-throughput sequencing to examine the vaginal eukaryotic DNA virome in a cohort of pregnant women and examine associations between vaginal community characteristics and preterm birth. STUDY DESIGN: This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial midvaginal swabs were obtained at routine prenatal visits. DNA was extracted, bacterial communities were characterized by 16S ribosomal RNA gene sequencing, and eukaryotic viral communities were characterized by enrichment of viral nucleic acid with the ViroCap targeted sequence capture panel followed by nucleic acid sequencing. Viral communities were analyzed according to presence/absence of viruses, diversity, dynamics over time, and association with bacterial community data obtained from the same specimens. RESULTS: Sixty subjects contributed 128 vaginal swabs longitudinally across pregnancy. In all, 24 patients delivered preterm. Participants were predominantly African American (65%). Six families of eukaryotic DNA viruses were detected in the vaginal samples. At least 1 virus was detected in 80% of women. No specific virus or group of viruses was associated with preterm delivery. Higher viral richness was significantly associated with preterm delivery in the full group and in the African American subgroup (P = .0005 and P = .0003, respectively). Having both high bacterial diversity and high viral diversity in the first trimester was associated with the highest risk for preterm birth. CONCLUSION: Higher vaginal viral diversity is associated with preterm birth. Changes in vaginal virome diversity appear similar to changes in the vaginal bacterial microbiome over pregnancy, suggesting that underlying physiology of pregnancy may regulate both bacterial and viral communities.

Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

INTRODUCTION: Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. MATERIAL AND METHODS: In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. RESULTS: Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. CONCLUSION: Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded.

Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery.

Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3-17.7) for cervix, 8.3% (95% CI; 7.6-9.1) for placental tissue, 5.7% (95% CI; 5.1-6.3) for amniotic fluid, and 10.9% (95% CI; 10.1-11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding.

Reduced glutathione in hepatitis E infection and pregnancy outcome.

AIM: To study reduced glutathione (GSH) as a marker of oxidative stress in hepatitis E virus (HEV) infection during pregnancy, and to clarify its association with pregnancy outcome. METHODS: A total of 30 pregnant and 30 non-pregnant women with HEV infection were enrolled in the present study, along with 30 age- and gestation-matched healthy pregnant controls. Serum GSH was measured using commercially available enzyme-linked immunoassay kit. RESULTS: Significantly lower GSH was observed in HEV-infected pregnant women than in healthy pregnant controls (10.44 ng/mL vs 19.77 ng/mL; P < 0.01). No significant association was observed between GSH and pregnant women and non-pregnant women with HEV infection (P = 0.54). Serum GSH ≤10.88 ng/mL was more likely to be associated with HEV infection during pregnancy, with sensitivity and specificity of 73.3%. Lower GSH was observed in pregnant women with HEV infection having preterm delivery and low birthweight newborns compared with healthy pregnant women (P < 0.01 and P < 0.05, respectively). Serum GSH was lower in pregnant women with HEV infection who had stillbirth compared with those having live births (7.21 ng/mL vs 6.12 ng/mL, P = 0.60). CONCLUSION: Oxidative stress is present in HEV infection during pregnancy, as shown by low GSH, and is associated with adverse pregnancy outcomes. Serum GSH ≤10.88 ng/mL during pregnancy can be used for risk stratification for HEV infection.

Evaluation of Human Papillomavirus as a Risk Factor for Preterm Birth or Pregnancy-Related Hypertension.

OBJECTIVE: To compare rates of preterm birth and pregnancy-related hypertension in women with and without human papillomavirus (HPV) infection. METHODS: We performed a retrospective cohort study of all women delivered at our institution in 2013 who had cervical cancer screening test results within 3 years before delivery. Patients were excluded if they had prior procedure(s) for cervical dysplasia other than biopsy. There were two primary outcomes: preterm birth (less than 37 weeks of gestation) and pregnancy-related hypertension (gestational hypertension, preeclampsia, or eclampsia). Multivariable logistic regression was performed to adjust for confounders including demographic variables, diabetes, prior preterm birth, chronic hypertension, and other genital infections. Assuming a 10% prevalence of HPV, a rate of 12% in the HPV-negative group for both preterm birth and pregnancy-related hypertension, α of 0.05, and ß of 0.2, we needed 2,207 patients to detect a 60% increase in the rate of either outcome in the HPV-positive group. RESULTS: A total of 3,958 patients delivered in 2013, of whom 2,321 met eligibility criteria, 242 (10.4%) of whom were HPV-positive and 2,079 (89.2%) of whom were HPV-negative. In multivariate analyses, the rate of preterm birth was not significantly different between HPV-positive and HPV-negative women (16.5% compared with 12.2%, adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 0.9-1.9); rates of pregnancy-related hypertension also were not significantly different between HPV-positive and HPV-negative women (17.0% compared with 16.4%, adjusted OR 1.0, 95% CI 0.7-1.5). CONCLUSION: Maternal HPV infection is not an independent risk factor for preterm birth or pregnancy-related hypertension.

Chronic hepatitis C virus infection is associated with increased risk of preterm birth: a meta-analysis of observational studies.

Although several epidemiological studies reported that maternal chronic hepatitis C virus (HCV) infection had significantly increased risk of undergoing adverse obstetrical and perinatal outcomes, studies on the relationship between HCV infection and risk of preterm birth (PTB) have yielded inconclusive and inconsistent results. Therefore, we conducted a meta-analysis to investigate the association between HCV infection and PTB. The electronic database was searched until 1 September 2014. Relevant studies reporting the association between HCV infection and the risk of PTB were included for further evaluation. Statistical analysis was performed using revmen 5.3 and stata 10.0. Nine studies involving 4186698 participants and 5218 HCV infection cases were included. A significant association between HCV infection and PTB was observed (odds ratio = 1.62, 95% CI 1.48-1.76, P < 0.001, fixed-effects model). Stratification according to maternal smoking/alcohol abuse, maternal drug abuse or coinfected with HBV and/or HIV matched groups still demonstrated that women with HCV infection had a high risk for PTB. Findings from our meta-analysis suggested that maternal HCV infection was significantly associated with an increased risk of PTB. In the future, pathophysiological studies are warranted to ascertain the causality and explore the possible biological mechanisms involved.

Association of HIV infection with spontaneous and iatrogenic preterm delivery: effect of HAART.

OBJECTIVES: To assess the association between HIV infection and both spontaneous and iatrogenic preterm delivery (PTD), and to explore the impact of HAART on both entities. METHODS: A matched retrospective cohort study was carried out on 517 HIV-infected pregnant women who consecutively attended a university referral hospital between 1986 and 2010. Two controls were assigned for each case. They were matched by ethnicity, smoking, maternal age and educational level. Exclusion criteria were multiple pregnancy and active injection drug use (IDU). PTD was defined as delivery less than 37.0 weeks. Spontaneous PTD included preterm premature rupture of membranes. Iatrogenic delivery was considered if medically indicated. Factors associated with PTD among HIV-infected women were analyzed by logistic regression. RESULTS: A total of 1557 pregnant women were analyzed (519 HIV-infected and 1038 noninfected). The incidence of PTD was 19.7% in HIV-infected women and 8.5% in controls [odds ratio (OR) 2.6; 95% CI 1.9-3.6]. There was a significantly higher incidence of both spontaneous [adjusted OR (AOR) 2.1; 95% confidence interval (CI) 1.5-3.0] and iatrogenic prematurity (AOR 3.2; 95% CI 1.8-5.7). Iatrogenic PTD was significantly associated with the use of HAART during the second half of pregnancy, whereas spontaneous PTD was not related to HAART. CONCLUSION: There is a significant association of HIV infection with PTD, both spontaneous and iatrogenic PTD. HAART use was predominantly associated with iatrogenic PTD.

Influenza A/H1N1v in pregnancy: an investigation of the characteristics and management of affected women and the relationship to pregnancy outcomes for mother and infant.

BACKGROUND: In April 2009 a novel influenza A virus (AH1N1v) of swine origin (swine flu) emerged, spreading rapidly and achieving pandemic status in June 2009. Pregnant women were identified as being at high risk of severe influenza-related complications and as a priority group for vaccination against AH1N1v. Limited information was available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy. OBJECTIVES: To assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management. METHODS: Prospective national cohort studies were conducted to identify pregnant women who were (1) suspected to be infected with AH1N1v or being treated with antiviral medication in primary care; (2) vaccinated against AH1N1v; and (3) admitted to hospital with confirmed AH1N1v. Characteristics of women with influenza-like illness (ILI) in primary care were compared with those of women without symptoms accepting or declining immunisation. Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK who were uninfected with AH1N1v. Outcomes examined in hospitalised women included maternal death, admission to an intensive care unit, perinatal mortality and preterm birth. Risk factors for hospital and intensive care unit admission were examined in a full regression model. RESULTS: The weekly incidence of ILI among pregnant women averaged 51/100,000 over the study period. Antiviral drugs were offered to 4.8% [95% confidence interval (CI) 4.0% to 5.9%] and vaccination to 64.8% (95% CI 64.7% to 68.9%) of registered pregnant women. Ninety pregnant women with ILI presenting in primary care were reported to the research team, 55 of whom were prescribed antiviral drugs and in 42 (76%) cases this was within 2 days of symptom onset. After comparison with 1329 uninfected pregnant women offered vaccination, pre-existing asthma was the only maternal factor identified as increasing risk of ILI presentation [adjusted odds ratio (OR) 2.0, 95% CI 1.0 to 3.9]. Maternal obesity and smoking during pregnancy were also associated with hospital admission with AH1N1v infection. Overall, 241 pregnant women were admitted to hospital with laboratory-confirmed AH1N1v infection. Eighty-three per cent of these women were treated with antiviral agents, but only 6% received antiviral treatment before hospital admission. Treatment within 2 days of symptom onset was associated with an 84% reduction in the odds of admission to an intensive therapy unit (OR 0.16, 95% CI 0.08 to 0.34). Women admitted to hospital with AH1N1v infection were more likely to deliver preterm; a three times increased risk was suggested compared with an uninfected population cohort (OR 3.1, 95% CI 2.1 to 4.5). CONCLUSIONS: Earlier treatment with antiviral agents is associated with improved outcomes for pregnant women and further actions are needed in future pandemics to ensure that antiviral agents and vaccines are provided promptly to pregnant women, particularly in the primary care setting. Further research is needed on longer-term outcomes for infants exposed to AH1N1v influenza, antiviral drugs or vaccines during pregnancy.