Society for Maternal-Fetal Medicine Consult Series #69: Hepatitis B in pregnancy: updated guidelines.

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C).

Maternal neighbourhood-level social determinants of health and their association with paediatric hepatitis C screening among children exposed to hepatitis C in pregnancy.

BACKGROUND: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. OBJECTIVES: To evaluate the association between maternal neighbourhood-level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. METHODS: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. RESULTS: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1-year increase, 95% CI 0.97, 0.99), HIV co-infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. CONCLUSIONS: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening.

HPV infection and its correlation with p53 and Bcl-2 among pregnant mothers and their infants.

The investigation of perinatal transmission of HPV is vital for early screening of cervical/oral cancers. Here, transmission of HPV from the pregnant women to their infants was studied. p53 and Bcl-2 expressions and their correlations with HPV infection were examined. HPV infection was detected in the cervical and oral swabs of 135 mother-baby pairs employing both PCR and HC-II methods. 1 year follow-up with an interim visit at 3 months for mothers and 6 months for babies was performed. Immunocytochemistry of p53 and Bcl-2 using the streptavidin-biotin peroxidase method was performed. Prevalence of HPV infection in the mothers was 28.14%, (38/135) and 30.37% (41/135) determined by the PCR and HC-II methods respectively. HPV 16 and/or 18 was identified in 81.57% (31/38) and 82.92% (34/41) of the HPV + women estimated by PCR and HC-II methods respectively. Prevalence rate of HPV 16 among the HPV + pregnant women was 63.15% (24/38) and 65.85% (27/41) determined by PCR and HC-II methods respectively. The frequency of perinatal transmission was 21.05% (8/38) and 21.95% (9/41) determined by PCR and HC-II methods respectively at birth. The HPV + infants in the follow up study cleared the infection within 6 weeks. An abnormal nuclear expression of p53 and cytoplasmic expression of Bcl-2 were observed in the HPV + mother-baby pairs. Cesarean section did not protect the infants against perinatal HPV transmission. The detection of p53 and Bcl-2 proteins in the HPV + mother-baby pairs suggests that these biomarkers may be important in the early screening of oral/cervix cancers in positive cases.

Severely Restricting Abortion Threatens Equitable Health Outcomes for People With Human Immunodeficiency Virus.

Equitable access to abortion is a critical component of reproductive care. Women with human immunodeficiency virus (HIV) in the United States are disproportionately Black and will be disproportionately affected by abortion bans following the Supreme Court's decision to overturn Roe v Wade. We argue that this decision is directly in conflict with the National HIV/AIDS Strategies and Centers for Disease Control and Prevention's goals to eliminate perinatal HIV transmission.

Update of Perinatal Human Immunodeficiency Virus Type 1 Transmission in France: Zero Transmission for 5482 Mothers on Continuous Antiretroviral Therapy From Conception and With Undetectable Viral Load at Delivery.

BACKGROUND: Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception. METHODS: The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis. RESULTS: PT decreased between 3 periods, from 1.1% in 2000-2005 (58/5123) to 0.7% in 2006-2010 (30/4600) and to 0.2% in 2011-2017 (10/4907; P < .001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000-2005 to 0.03% (1/3117) in 2011-2017 (P = .007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011-2017 period. CONCLUSIONS: In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero.

Geographic variation in missed opportunities for the prevention of mother-to-child transmission of HIV among women receiving antenatal care in Nigeria.

There are missed opportunities for the prevention of mother-to-child transmission of HIV (PMTCT) in Nigeria. However, little is known about the geographic variation. We examined the geographic pattern in the missed opportunities for HIV testing among antenatal care (ANC) attendees and initiation t on antiretroviral therapy (ART) in Nigeria. This study was an analysis of aggregated state-level data on 2,875,370 ANC attendees from the 2019 national HIV/AIDS health sector data. We performed descriptive statistics and explanatory spatial data analysis. Overall, the missed opportunity for HIV testing was 9.3%, ranging from 1.8% in the South South to 14.5% in the North West. The missed opportunity for HIV testing ranged from 0.2% in Imo State to 25.2% in Kaduna State. The local indicator of spatial association cluster map showed a concentration of cold spots in the South and hot spots in the North. The overall missed opportunity for ART was 9.5%, ranging from 7.4% in the South West to 11.1% in the NorthCentral. It was lowest in Adamawa State (0%), while Enugu State had the highest (32.2%). Missed opportunities for PMTCT among women attending ANC in Nigeria occur at varying degrees across the states, with higher levels in the northern region.

Influence of hepatitis C viral parameters on pregnancy complications and risk of mother-to-child transmission.

BACKGROUND & AIMS: With the World Health Organization plan for hepatitis C elimination by the year 2030, and recent guideline recommendations to screen all women during pregnancy for HCV, data on HCV in pregnancy are needed to determine the association of HCV viremia with adverse pregnancy outcomes and mother-to-child transmission (MTCT). METHODS: This retrospective cohort study was performed in Ontario, Canada, using population-based administrative healthcare data. Individuals were stratified based on whether they had active HCV viremia during pregnancy or resolved viremia at time of pregnancy. Peak HCV viral load was determined. Logistic regression was used to determine the association of viremia with adverse pregnancy outcomes; maternal HCV RNA levels were evaluated as a predictor of MTCT. RESULTS: We identified a total of 2,170 pregnancies in 1,636 women who were HCV RNA positive prior to pregnancy; 1,780 (82%) pregnancies occurred in women who were HCV RNA positive during pregnancy. Patients who were HCV RNA positive during pregnancy were more likely to have preterm delivery (18% vs. 12%, p = 0.002), intrahepatic cholestasis of pregnancy (4% vs. <2%, p = 0.003), and post-partum hemorrhage (9% vs. 5%, p = 0.013), and less likely to have gestational diabetes (6% vs. 10%, p = 0.008) than those with resolved infection. Only 511 (29%) infants had screening consistent with guidelines after birth; there was an estimated 3.5% risk of MTCT. HCV RNA ≥6.0 log10 IU/ml was significantly associated with MTCT (exact odds ratio 3.4, p = 0.04). CONCLUSION: Active HCV viremia among individuals with a history of HCV infection significantly increases adverse pregnancy outcomes. Few infants are screened for MTCT. Higher HCV RNA is associated with increased risk of MTCT. LAY SUMMARY: The prevalence of hepatitis C has increased in women of child-bearing age and has important implications for women who become pregnant and their infants. We evaluated the effect that hepatitis C has on pregnancy outcomes as well as the rate of hepatitis C transmission to infants in a large database with linked mother-infant records. We found that active hepatitis C during pregnancy increased the risk of pregnancy complications. We also identified very low rates of testing of infants born to mothers with hepatitis C, but found higher rates of hepatitis C transmission to infants in mothers with higher virus levels.

Absence of chronicity in infants born to immunized mothers with occult HBV infection in Taiwan.

BACKGROUND & AIMS: In the Taiwanese population born in the universal vaccination era, HBsAg carrier rates have fallen below 2%, while approximately 5% develop occult hepatitis B infection (OBI). However, the potential for transmission from mothers with OBI to their infants has not been well studied. We aimed to investigate whether mothers with OBI could transmit HBV to their babies. METHODS: A total of 253 pregnant women who were born after July 1986 and had been fully vaccinated against HBV during infancy were recruited from a tertiary hospital in Northern Taiwan. HBV serology and DNA levels were determined. Babies born to mothers with OBI were followed-up until 1 year of age. The surface genes were sequenced. RESULTS: HBV infection was documented in 18 vaccinated mothers, 2 of whom were HBsAg-reactive (0.79 %). Seventeen were positive for HBV DNA, among whom 16 (6.32%) presented with OBI with a median DNA level of 145 IU/ml (interquartile range: 37.8-657.3 IU/ml). Eleven babies born to 10 mothers with OBI were recruited. Three babies were HBsAg-reactive, and 2 were positive for HBV DNA (17.0 and 212.0 IU/ml). Seven mothers with OBI carried multiple surface gene variants. Two transiently infected babies harbored variants originating from their mother's HBV quasi-species. All infants received complete hepatitis B vaccines. At 12 months of age, none of the babies were positive for HBsAg or HBV DNA. CONCLUSIONS: It was possible for mothers with OBI to transmit HBV to their babies, who consequently harbored surface gene variants originating from their mothers' minor variants. Viremia was cleared 1 year after completing the hepatitis B vaccination series. LAY SUMMARY: Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.

Tenofovir disoproxil fumarate therapy to prevent hepatitis B virus vertical transmission-A review of maternal and infant outcomes.

Hepatitis B virus (HBV) is a global health problem. Vertical transmission of HBV from HBV surface antigen (HBsAg)-positive mothers to their infants is the most common cause of HBV infection worldwide. The use of passive-active immunoprophylaxis is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to mothers with high viraemia. Thus, it is recommended that pregnant women with HBV-DNA level >200 000 IU/ml receive nucleos(t)ide analogue (NA) treatment [i.e. tenofovir disoproxil fumarate (TDF), lamivudine or telbivudine] during third trimester to prevent infant immunoprophylaxis failure. TDF is recommended as the first-line therapy based on available data on efficacy, safety and resistance profile. However, maternal immunological reconstitution following parturition can increase immune-mediated flares to viral antigens that is potentially exacerbated following TDF withdrawal. In this article, we review available data on the efficacy and safety of TDF administration to prevent HBV mother-to-child transmission. We also discuss changes in maternal viral markers [i.e. HBV-DNA, HBV e antigen and HBsAg] and alanine aminotransferase during follow-up post-partum in mothers received NA to prevent HBV vertical transmission.

Perinatal transmission of SARS-CoV-2 and transfer of maternal IgG/neutralizing anti-SARS-CoV-2 antibodies from mothers with asymptomatic infection during pregnancy.

PURPOSE: COVID-19 pandemic remains a serious public health threat worldwide. In view of the limited data on the risk of perinatal transmission of SARS-CoV-2 and transfer of maternal anti-SARS-CoV-2 antibodies, the present study was undertaken. METHODS: A prospective study including 57 pregnant women with a positive SARS-CoV-2 RNA test (SARS-CoV-2-RNA+) and 59 neonates born to them was conducted at Pune, India. 39 viral RNA negative (SARS-CoV-2-RNA-negative) pregnant women and their 39 neonates were included as controls. Neonatal nasal swab/cord blood samples were subjected to SARS-CoV-2 RNA detection by RT-PCR for investigation of perinatal transmission. Transfer of maternal antibodies was studied using ELISA and PRNT. RESULTS: 10/57 SARS-CoV-2-RNA+ mothers were symptomatic. The duration between COVID-19 diagnosis and delivery was ≤ 7 days for 82.4%. Perinatal transmission as evidenced by viral RNA in the neonatal nasal swab/cord blood (CB) was 3.6%. IgG-anti-SARS-CoV-2 positivity was 21.6%. Of the 39 neonates born to SARS-CoV-2-RNA-negative mothers, 20 (51%) and none, respectively, were positive for IgG-anti-SARS-CoV-2 and viral RNA. Preterm deliveries were higher in SARS-CoV-2-RNA+ (18.6%) than SARS-CoV-2 RNA-negative (0/39) mothers (p < 0.005). Respiratory distress at birth (< 4 h) was higher among neonates of SARS-CoV-2-RNA+ (20/59, 33.9%) than SARS-CoV-2-RNA-negative mothers (3/39, 7.7%; p < 0.001). ~ 75% IgG-positives exhibited neutralization potential with mean PRNT titers of 42.4 ± 24 (SARS-CoV-2-RNA+) and 72.3 ± 46.7 (SARS-CoV-2 RNA-negative); higher in the latter (p < 0.05). CONCLUSION: The rate of perinatal transmission was low. Transfer of maternal antibodies was lower among SARS-CoV-2-RNA+ mothers than SARS-CoV-2-RNA-negative mothers with subclinical infection during pregnancy. Presence of neutralizing antibodies in majority of IgG-positives suggests protection from SARS-CoV-2 in early life.

Neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections during pregnancy: a national prospective study in Kuwait.

BACKGROUND: An increasing proportion of women are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study was to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy. METHODS: In this prospective cohort study, the neurodevelopmental status of infants (N = 298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff scores ≤ 2 standard deviations (SDs) below the population mean) and no delays (scores > 2 SDs above the population mean). RESULTS: The majority (90%) of the infants born to mothers with SARS-CoV-2 infections during pregnancy had favorable outcomes and only 10% showed developmental delays. Two of the 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infections during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P = 0.039) and second trimesters (P = 0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. CONCLUSION: The neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections seem favorable. However, more studies with larger sample sizes and longer follow-up periods are required.

Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study.

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.

Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria.

BACKGROUND: The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis. While there have been major advances in the characterization of colibactin-positive E. coli and the toxin it produces, the infection route of the clb + strain remains poorly characterized. RESULTS: We examined infants and their treatments during and post-birth periods to examine potential transmission of colibactin-positive E. coli to infants. Here, analysis of fecal samples of infants over the first month of birth for the presence of a colibactin biosynthetic gene revealed that the bacterium may be transmitted from mother to infant through intimate contacts, such as natural childbirth and breastfeeding, but not through food intake. CONCLUSIONS: Our finding suggests that transmission of colibactin-positive E. coli appears to be occurring at the very early stage of life of the newborn and hints at the possibility of developing early preventive measures against colorectal cancer.

Lopinavir and tenofovir interaction observed in non-pregnant adults altered during pregnancy.

WHAT IS KNOWN AND OBJECTIVE: Tenofovir exposure is increased in non-pregnant adults when tenofovir disoproxil fumarate is coadministered with lopinavir/ritonavir. In pregnant women, tenofovir exposure is decreased. Our objective is to describe the effect of lopinavir/ritonavir on tenofovir pharmacokinetics during pregnancy. METHODS: Data were collected through the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network P1026s protocol. This was a nonrandomized, open-label, parallel-group and multicentre phase-IV prospective study in pregnant women with HIV. Intensive steady-state 24-h pharmacokinetic profiles were collected during the third trimester of pregnancy and postpartum. Tenofovir was measured in plasma using validated liquid chromatography-mass spectrometry method (quantification limit: 10 ng/ml). Statistical tests compared paired and between group pharmacokinetic data. RESULTS AND DISCUSSION: In women not receiving lopinavir/ritonavir (n = 28), tenofovir AUC0-24 was 27% lower (2.2 mcg·h/ml vs 2.8 mcg·h/ml, p = 0.002) and oral clearance was 27% higher (61 L/h vs 48 L/h, p = 0.001) during the third trimester compared to paired postpartum data. In women receiving lopinavir/ritonavir (n = 10), tenofovir AUC0-24 and oral clearance were not different antepartum compared to postpartum. Women with and women without concomitant lopinavir/ritonavir displayed no significant differences in postpartum tenofovir pharmacokinetics. WHAT IS NEW AND CONCLUSION: Tenofovir exposure during the third trimester was reduced compared to postpartum in pregnant women not receiving lopinavir/ritonavir, but not in pregnant women also receiving lopinavir/ritonavir. Our findings suggest that pregnancy confounds the expected decrease in tenofovir exposure with concomitant lopinavir/ritonavir in non-pregnant adults. These findings illustrate the need for drug-drug interaction studies in pregnant women as drug disposition differs significantly in pregnant women compared to non-pregnant adults.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

Efficacy of Three Antiretroviral Regimens Initiated during Pregnancy: Clinical Experience in Rio de Janeiro.

Few studies have compared the clinical efficacy and adverse events of combined antiretroviral therapy (cART) regimens in pregnant women seeking obstetrical care. The objective of this study was to compare the efficacy (virus load response), adverse events, and obstetrical and neonatal outcomes of three different regimens of cART in HIV-infected pregnant women initiating treatment in Rio de Janeiro, Brazil. This was a retrospective cohort study of cART-naive pregnant women who initiated either ritonavir-boosted protease inhibitors (atazanavir or lopinavir), efavirenz, or raltegravir plus a backbone regimen. From 2014 to 2018, 390 pregnant women were followed over time. At baseline, the median viral load (VL) for HIV was 4.1 log copies/ml. Among participants who received cART for 2 to 7 weeks, the VL decline was greater for raltegravir (2.24 log copies/ml) than for efavirenz or protease inhibitors (P < 0.001). Virologic suppression was achieved in 87% of women on raltegravir near delivery versus 73% on efavirenz and 70% on protease inhibitors (P = 0.011). Patients on raltegravir achieved virologic suppression faster than those on other regimens (P = 0.019). Overall, the HIV perinatal infection rate was 1.5%. This clinical study compared three potent and well-tolerated cART regimens and demonstrated that a higher proportion of participants on raltegravir achieved an undetectable HIV VL near delivery (P = 0.011) compared to the other arms. These findings suggest that raltegravir-containing regimens are optimal regimens for women with HIV initiating treatment late in pregnancy.

Enrollment and transition challenges in the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) network's PROMISE trial for resource-limited regions.

BACKGROUND: We describe enrollment and accrual challenges in the "Promoting Maternal and Infant Survival Everywhere" (PROMISE) trial conducted in resource-limited countries, as well as the challenges in transitioning participants from the antepartum to the postpartum components of the study. METHODS: PROMISE was a large multi-national randomized controlled trial of the safety and efficacy of interventions to reduce perinatal transmission of HIV-1 (HIV) during pregnancy and breastfeeding and of interventions to preserve maternal health after cessation of perinatal transmission risk. The PROMISE study included two protocols for HIV-infected pregnant women in resource-limited countries who intended to either breastfeed or formula-feed their infants and did not meet country criteria for antiretroviral treatment. The PROMISE breastfeeding protocol (1077BF) used a sequential randomization design with up to three randomizations (Antepartum, Postpartum, and Maternal Health). The PROMISE formula-feeding protocol (1077FF) had two randomizations (Antepartum and Maternal Health). Women presenting to the clinic during early or active labor or in the immediate postpartum period were registered as Late Presenters and screened to determine whether eligible to participate in the Postpartum randomization. RESULTS: The study was conducted at 14 sites in seven countries and opened to enrollment in April 2011. A total of 3259 pregnant women intending to breastfeed and an additional 284 pregnant women intending to formula feed were randomized in the Antepartum component. A total of 204 Late Presenters were registered during labor or after delivery. Enrollment was high among breastfeeding women (representing 96% of the target of 3400 women) but was lower than expected among women intending to formula feed (28% of 1000 expected) and late-presenting women (8% of 2500 expected). The successful overall enrollment and final primary study analyses results were attributed to substantial preparation before the study opened, collaboration among all stakeholders, close study monitoring during implementation and the flexibility to change and streamline the protocol. CONCLUSIONS: Experiences from the PROMISE study illustrate the challenges of enrolling in longer term studies in the setting of rapidly evolving prevention and treatment standards priorities. The lessons learned will help the community, site investigators, and study coordinators in the design and implementation of future clinical trials.

Maternal knowledge of the risk of vertical transmission and offspring acquisition of hepatitis B.

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B. MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed. RESULTS: A total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p=0.02) or diagnosis of HBV (p=0.02). CONCLUSIONS: While high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5-15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.

Risk factors for perinatal transmission of HIV among women attending prevention of mother-to-child transmission clinics in Northwest Nigeria.

Despite the effectiveness of antiretroviral therapy (ART) in the prevention of mother-to-child transmission of HIV (PMTCT), some HIV-infected women in PMTCT care are at risk of transmitting HIV to their babies. Using a 1:1 unmatched case-control study design, we assessed the risk factors for perinatal transmission among women who received ART for PMTCT in Sokoto State, Nigeria. Data were abstracted from medical records of cases (94 HIV-infected babies) and controls (94 HIV-uninfected babies) and their mothers who accessed PMTCT services in three purposefully selected secondary health facilities. We conducted univariate and multivariate logistic regressions to determine if sociodemographic characteristics, time of enrolment, type of maternal ART, receipt of infant antiretroviral (ARV) prophylaxis, place of delivery, or feeding practice were associated with HIV infection among HIV-exposed babies. Sixteen percent of the mothers of babies in the case group had early enrolment while 90% of those in the control group enrolled early. Infant prophylaxis was received in 54% of cases and 95% of controls. In both groups, 99% of the mothers practiced mixed feeding. In the univariate analysis, factors that were significantly associated with HIV infection were religion (islam), rural residence, late⁠ enrolment, and non-receipt of infant ARV prophylaxis. In the multivariate analysis, rural residence (Adjusted odds ratio (aOR) = 8.01, 95% CI = 1.79-35.78), late enrolment (aOR = 41.72, 95% CI = 15.16-114.79), and non-receipt of infant ARV prophylaxis (aOR = 4.1, 95% CI = 1.18-14.33) remained statistically significant. Findings from this study indicate that eliminating MTCT in Nigeria requires interventions that will enhance timely access of ART by mother-baby dyads.

Reproductive health, social life and plans for the future of adolescents growing-up with HIV: a case-control study in Thailand.

Most perinatally HIV-infected children receiving antiretroviral treatment now survive into adolescence. This is a period when young people experience puberty, shape their sexual identity and initiate their own social life. The aim of our analysis was to compare aspects of the sexual and reproductive health, social life and plans for the future of perinatally HIV-infected adolescents (PHIVAs) with a control group from the general population. We used data from the Teens Living with Antiretrovirals (TEEWA) survey carried out from 2010 to 2012 in Thailand among PHIVAs aged 12-19 years. Adolescents completed a self-administered questionnaire focusing on their daily life. Each PHIVA (case) was matched on sex, age and place of residence with a randomly selected adolescent from the general population (control). Analysis was stratified by gender and age; McNemar's test was used to compare cases and controls. A total of 1142 adolescents (571 cases and 571 controls) were included in the analysis, 42% boys and 58% girls. Cases experienced puberty delay compared to controls (p < 0.01). Cases and controls did not differ in terms of sex education, sexual initiation, romantic relationships or friendships, and risky behaviours. However, PHIVAs were less likely to attend the education system (p < 0.01), to plan for marriage (p < 0.01) or parenthood (p < 0.01). PHIVAs do not differ substantially from controls in terms of sexual and social life. Yet, affirmative action policies could help counterbalance their educational handicap. Provision of psychosocial support could enhance their ability to make informed decisions with regards to family formation.