HIV, Placental Lesions, and Adverse Perinatal Outcomes.

Africa has the highest number of pregnant women with human immunodeficiency virus (HIV). In some studies, HIV has been associated with adverse perinatal outcomes. However, the pathophysiological mechanism leading to adverse fetal outcomes is not known. Maternal vascular malformation, chorioamnionitis, and decreased placental weight have been described as placental features associated with HIV in some studies. The use of antiretroviral therapy has reduced perinatal transmission of HIV and adverse fetal outcomes. However, placental mechanisms associated with HIV and the fetal immune response to maternal HIV infection are poorly understood. Additional research is required to understand whether altered maternal immunity in women living with HIV can trigger fetal responses leading to stillbirth or preterm birth.

Clinical features and outcomes of pregnant women with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The recent COVID-19 outbreak in Wuhan, China, has quickly spread throughout the world. In this study, we systematically reviewed the clinical features and outcomes of pregnant women with COVID-19. METHODS: PubMed, Web of Science, EMBASE and MEDLINE were searched from January 1, 2020, to April 16, 2020. Case reports and case series of pregnant women infected with SARS-CoV-2 were included. Two reviewers screened 366 studies and 14 studies were included. Four reviewers independently extracted the features from the studies. We used a random-effects model to analyse the incidence (P) and 95% confidence interval (95% CI). Heterogeneity was assessed using the I2 statistic. RESULTS: The meta-analysis included 236 pregnant women with COVID-19. The results were as follows: positive CT findings (71%; 95% CI, 0.49-0.93), caesarean section (65%; 95% CI, 0.42-0.87), fever (51%; 95% CI, 0.35-0.67), lymphopenia (49%; 95% CI, 0.29-0.70), coexisting disorders (33%; 95% CI, 0.21-0.44), cough (31%; 95% CI, 0.23-0.39), fetal distress (29%; 95% CI, 0.08-0.49), preterm labor (23%; 95% CI, 0.14-0.32), and severe case or death (12%; 95% CI, 0.03-0.20). The subgroup analysis showed that compared with non-pregnant patients, pregnant women with COVID-19 had significantly lower incidences of fever (pregnant women, 51%; non-pregnant patients, 91%; P < 0.00001) and cough (pregnant women, 31%; non-pregnant patients, 67%; P < 0.0001). CONCLUSIONS: The incidences of fever, cough and positive CT findings in pregnant women with COVID-19 are less than those in the normal population with COVID-19, but the rate of preterm labor is higher among pregnant with COVID-19 than among normal pregnant women. There is currently no evidence that COVID-19 can spread through vertical transmission.

Hepatitis E virus infection during pregnancy.

BACKGROUND: Hepatitis E virus (HEV) generally causes self-limiting viral hepatitis. However, in pregnant women, HEV infection can be severe and has been associated with up to 30% mortality in the third trimester. Additionally, HEV infection in pregnancy is also associated with high rates of preterm labor and vertical transmission. MAIN BODY: HEV is now recognized as a global health problem in both developing and industrialized countries. HEV can be transmitted via the fecal-oral route, zoonotic route, and blood transfusion route. An altered immune status, hormonal levels, and viral factors may be related to the severity of the disease. Currently, no established treatment is available for HEV in pregnant women. A Chinese vaccine has been demonstrated to be protective against HEV in the general population and seems to be safe in pregnancy; however, its safety and efficacy in a large population of pregnant women remain to be determined. CONCLUSION: This review summarizes the current knowledge about HEV infection during pregnancy and focuses on the epidemiology, clinical manifestations, mechanisms underlying severe liver injury, and management and prevention of HEV infection during pregnancy. Considering that HEV infection during pregnancy may result in poor outcomes, screening for and monitoring HEV infection early in pregnancy should be taken into account. In addition, a better understanding of the pathogenesis will help to develop potential treatment strategies targeting HEV infection in pregnancy.

Chronic hepatitis B virus infection and preterm labor(birth) in pregnant women-an updated systematic review and meta-analysis.

We aimed to explore whether maternal chronic hepatitis B virus (HBV) infection certainly affects preterm labor (birth) in pregnant women. Four databases were systematically searched up to May 31, 2017, without language restriction. Any study was included if it clearly defined exposure to chronic HBV infection, reported risk of preterm labor or birth in pregnant women, and reported relative risks (RRs) or odds ratios (ORs) or provided data for estimation. RRs (or ORs) with 95% confidence intervals were pooled using random-effects models. Statistical heterogeneity was assessed with Cochran's Q statistic and I2 statistic. Twenty-two observational studies involving 6 141 146 pregnant women (three prospective cohort studies, n = 1 116 799; 15 retrospective cohort studies, n = 5 022 513 and four case-control studies, n = 1834) were included. The risk of preterm labor was significantly intensified with chronic HBV infection compared with uninfected women, with substantial heterogeneity. Chronic HBV infection was also significantly associated with a 16% increase in the risk of preterm birth, with substantial heterogeneity. The risk of preterm birth significantly increased by 21% in HBsAg+/HBeAg+ pregnant women compared with uninfected pregnant women. Chronic HBV infection intensifies the risk of preterm labor and birth in pregnant women, but this conclusion should be interpreted with caution given the possibility of residual confounding and be confirmed by well-designed studies in the future.

High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

INTRODUCTION: This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. MATERIAL AND METHODS: We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). RESULTS: The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. CONCLUSION: Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

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.

Retrospective observation of therapeutic effects of adult auxiliary partial living donor liver transplantation on postpartum acute liver failure: a case report.

We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage III and coma. After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation. Emergency liver transplantation was recommended after multidisciplinary panel consultations. The donor, her mother, consented to donate her right liver. Auxiliary partial orthotopic living donor liver transplantion (APOLDLT) was performed. After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression. The combination of anti-hepatitis B virus (HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy. Both the patient and the donor recovered well without any complications. The patient was followed up regularly. Her liver function, clinical signs and symptoms improved significantly. Until now, the recipient has been living for more than 78 mo free of any complications. The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.

Understanding the complexity of the immune system during pregnancy.

Progress in our understanding of the role of the maternal immune system during healthy pregnancy will help us better understand the role of the immune system in adverse pregnancy outcomes. In this review, we discuss our present understanding of the 'immunity of pregnancy' in the context of the response to cervical and placental infections and how these responses affect both the mother and the fetus. We discuss novel and challenging concepts that help explain the immunological aspects of pregnancy and how the mother and fetus respond to infection.

Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy complications.

Toll-like receptors (TLRs) form the major family of pattern recognition receptors (PRRs) that are involved in innate immunity. Innate immune responses against microorganisms at the maternal-fetal interface may have a significant impact on the success of pregnancy, as intrauterine infections have been shown to be strongly associated with certain complications of pregnancy. At the maternal-fetal interface, TLRs are expressed not only in the immune cells but also in non-immune cells such as trophoblasts and decidual cells; moreover, their expression patterns vary according to the stage of pregnancy. Here, we will update potential functions of TLRs in these cells, their recognition and response to microorganisms, and their involvement in the innate immunity. The impact of TLR-mediated innate immune response will be discussed via animal model studies, as well as clinical observations.

A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes.

PROBLEM: The diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses. METHOD OF STUDY: AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined. RESULTS: (i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4-22; (P < 0.001); 70% (7/10) versus 35% (39/112); (P = 0.04); 1 (IQR: <1-2) days versus 25 (IQR: 5-51) days; (P = 0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). CONCLUSION: (i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.

Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy.

A role for microbial invasion leading to inflammation in the amniotic cavity and subsequent pre-term delivery has been well established. For years, the role of viral infections in pregnancy has been minimized and thought of as harmless, with a few exceptions. Recent evidence now encourages us to expand our thinking and realize that viral infections during pregnancy may influence pregnancy more that we thought.

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.

Prevention of mother-to-child transmission of HIV in resource-rich and -poor settings.

Without prevention, a third of HIV-exposed infants acquire HIV in breastfeeding populations before, during, or after delivery through mother-to-child transmission (MTCT). Whereas MTCT is now a sentinel event in resource-rich countries with antiretroviral prophylaxis, caesarean section, and avoidance of breastfeeding, this is not yet the case in resource-poor settings because breastfeeding is crucial to infant survival. Recent advances in postpartum maternal and infant prophylaxis enables safer breastfeeding, and increasing numbers of women accessing treatment and prevention of MTCT services in sub-Saharan Africa is leading to optimism that MTCT could be eliminated here also, as reflected in the UNAIDS target of 2015.

Placental infection with human papillomavirus is associated with spontaneous preterm delivery.

BACKGROUND: We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction. METHODS: We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at <37 weeks and controls who delivered at term. RESULTS: Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls. CONCLUSIONS: HPV infection of extravillous trophoblast induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may cause placental dysfunction and is associated with adverse pregnancy outcomes, including spontaneous preterm delivery.

Pregnancy, delivery and perinatal outcome in female survivors of polio.

OBJECTIVE: To investigate possible effects on pregnancy, delivery and perinatal outcome in female survivors of polio. METHODS: In a cohort design, data from the national population based Medical Birth Registry of Norway (MBRN) were used to compare all 2495 births recorded 1967-1998 by female survivors of polio with all 1.9 mill non-polio deliveries. The results were adjusted for time period, maternal age, and birth order by unconditional logistic regression, with effects presented as adjusted Odds Ratios (OR) with a corresponding 95% Confidence Interval (CI) and p values. RESULTS: Female polio survivors had a higher occurrence of pre-eclampsia (3.4% vs. 2.8%, p=0.003, OR=1.4, CI=1.1-1.7), gestational proteinuria (1.3% vs. 0.5%, p<0.001, OR=2.0, CI=1.4-2.8), renal disease prior to pregnancy (1.4% vs. 0.9%, p=0.001, OR=1.8, CI=1.2-2.5), vaginal bleeding (3.8% vs. 2.0%, p<0.001, OR=1.7, CI=1.4-2.1), and urinary tract infection during pregnancy (3.5% vs. 2.4%, p<0.001, OR=1.7, CI=1.4-2.1). Deliveries complicated by obstruction of the birth process were more common in the polio group (6.1% vs. 2.0%, p<0.001, OR=4.8, CI=4.0-5.6), and cesarean section was performed at a higher rate throughout the time period (13.2% vs. 8.3%, p<0.001, OR=2.7, CI=2.4-3.1). Infants of polio mothers had a lower mean birth weight (3383 g vs. 3483 g, p<0.001), and more often had a birth weight below 2500 g (6.9% vs. 5.2%, p=0.001, OR=1.3, CI=1.1-1.5). There was no difference regarding pregnancy length. The risk of perinatal death was increased (2.1% vs. 1.1%, p=0.05, OR=1.3, CI=1.0-1.7). CONCLUSION: Pregnancy in female survivors of polio is associated with an increased risk for complications during pregnancy and delivery, as well as an adverse perinatal outcome. Awareness towards risk factors should improve pre-natal care and possibly prevent complications.

Neurotropic viruses and cerebral palsy: population based case-control study.

OBJECTIVE: To investigate the association between cerebral palsy and direct evidence for perinatal exposure to neurotropic viruses. DESIGN: Population based case-control study. SETTING: Adelaide Women's and Children's Hospital Research Laboratory. PARTICIPANTS AND MAIN OUTCOME MEASURES: Newborn screening cards of 443 white case patients with cerebral palsy and 883 white controls were tested for viral nucleic acids from enteroviruses and herpes viruses by using polymerase chain reaction. Herpes group A viruses included herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 8 (HHV-8), and herpes group B viruses included varicella zoster virus (VZV) and human herpes viruses 6 and 7 (HHV-6 and HHV-7). RESULTS: The prevalence of viral nucleic acids in the control population was high: 39.8% of controls tested positive, and the prevalence was highest in preterm babies. The detection of herpes group B viral nucleic acids increased the risk of developing cerebral palsy (odds ratio 1.68, 95% confidence interval 1.09 to 2.59). CONCLUSIONS: Perinatal exposure to neurotropic viruses is associated with preterm delivery and cerebral palsy.

Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in HIV-infected pregnant women.

A successful pregnancy is characterised by an increase in Th2 cytokines and suppression of Th1 cytokine production. A Th1 to Th2 cytokine shift is also observed in the disease progression of HIV infection. Highly active antiretroviral therapy (HAART) suppresses HIV viremia, increases CD4+ cell counts and counteracts the Th1 to Th2 shift. We hypothesised that the increased risk of premature delivery reported in HIV-infected, HAART-treated pregnant women is mediated through changes in the cytokine environment in pregnancy. Here, we present results relating to levels of interleukin (IL)-2 (Th1) and IL-10 (Th2) in peripheral blood mononuclear cells (PBMCs) measured three times during pregnancy in 49 HIV-infected women. Slope values representing the trend of repeated cytokine (IL-2-PHA, IL-2-Env, IL-10-PHA and IL-10-Env) measurements within women during pregnancy were estimated and median values compared by prematurity and HAART use. Multiple regression adjusted for HAART and cytokine slope clarified the additional and independent effect of HAART on prematurity risk. Results showed favourable immunomodulation induced by HAART with increased IL-2 and decreased IL-10. HAART use and IL-10-Env slopes were not significantly associated with prematurity risk, but each unit increase in IL-2-PHA slope was associated with an 8% increased risk of premature delivery (AOR, 1.08; 95% CI, 1.0-1.17; p=0.005). HAART use in pregnancy provides significant benefits in delaying HIV disease progression and reducing the risk of mother-to-child-transmission, but may be counterproductive in terms of successful pregnancy outcome.

The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study.

BACKGROUND/AIMS: To examine the impact of maternal HBsAg carrier status on pregnancy outcomes. METHODS: Two hundred and fifty-three carriers of hepatitis B surface antigen (HBsAg) with singleton pregnancy, were retrospectively compared with 253 controls matched for age and parity and year of delivery. RESULTS: On univariable analysis, HBsAg carriers had higher incidences of threatened preterm labour at <37 weeks (11.9% vs. 6.3%, P=0.030), preterm birth at <34 weeks (4.7% vs. 1.2%, P=0.033), gestational diabetes mellitus (19.0% vs. 11.1%, P=0.012) and antepartum haemorrhage (11.5% vs. 5.5%, P=0.026). Their infants had lower Apgar scores at the 1st (8.47+/-1.67 vs. 8.87+/-1.07, P=0.001) and 5th minute (9.56+/-1.29 vs. 9.80+/-0.54, P=0.007), and increased incidence of intraventricular haemorrhage (4.7% vs. 0.8%, P=0.007). On multivariable analysis, the association between HBsAg carrier state with antepartum haemorrhage, gestational diabetes mellitus and threatened preterm labour were confirmed. CONCLUSIONS: HBsAg carriers have increased risk of gestational diabetes mellitus, antepartum haemorrhage, and threatened preterm labour. This may be related to the chronic inflammatory state in these subjects. The role of chronic HBV infection in pregnancy complications has to be further elucidated.

Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome.

OBJECTIVE: This study was undertaken to evaluate the pregnancy and perinatal outcomes of pregnant women with severe acute respiratory syndrome (SARS). STUDY DESIGN: All pregnant women (12) who presented with SARS in Hong Kong between February 1 and July 31, 2003, were included. The pregnancy and perinatal outcomes were collected. Evidence of perinatal transmission of virus was assessed with the SARS-associated coronavirus reverse-transcriptase polymerase chain reaction on cord blood, placenta tissue, and subsequent follow-up of the neonate on serology. RESULTS: Three deaths occurred among the 12 patients, giving a case fatality rate of 25%. Four of the 7 patients (57%) who presented in the first trimester had spontaneous miscarriage. Four of the 5 patients who presented after 24 weeks were delivered preterm. Two mothers recovered without delivery, but their ongoing pregnancies were complicated by intrauterine growth restriction. No newborn infant had clinical SARS and all investigations were negative for SARS. CONCLUSION: SARS during pregnancy is associated with high incidences of spontaneous miscarriage, preterm delivery, and intrauterine growth restriction. There is no evidence of perinatal SARS infection among infants born to these mothers.