Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study.

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years' active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.

Altered TLR7 Expression-Mediated Immune Modulation Is Supportive of Persistent Replication and Intrauterine Transmission of HBV.

Hepatitis B Virus (HBV) is posing as a serious public health threat mainly due to its asymptomatic nature of infection in pregnancy and vertical transmission. Viral sensing toll-like receptors (TLR) and Interleukins (IL) are important molecules in providing an antiviral state. The study aimed to assess the role of TLR7-mediated immune modulation, which might have an impact in the intrauterine transmission of HBV leading to mother to child transmission of the virus. We investigated the expression pattern of TLR7, IL-3, and IL-6 by RT-PCR in the placentas of HBV-infected pregnant women to see their role in the intrauterine transmission of HBV. We further validated the expression of TLR7 in placentas using Immunohistochemistry. Expression analysis by RT-PCR of TLR7 revealed significant downregulation among the Cord blood (CB) HBV DNA positive and negative cases with mean ± standard deviation (SD) of 0.43 ± 0.22 (28) and 1.14 ± 0.57 (44) with p = 0.001. IL-3 and IL-6 expression revealed significant upregulation in the CB HBV DNA-positive cases with p = 0.001. Multinomial logistic regression analysis revealed that TLR7 and IL-3 fold change and mother HBeAg status are important predictors for HBV mother to child transmission. Immunohistochemistry revealed the decreased expression of TLR7 in CB HBV DNA-positive cases. This study reveals that the downregulation of TLR7 in the placenta along with CB HBV DNA-positive status may lead to intrauterine transmission of HBV, which may lead to vertical transmission of HBV.

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

INTRODUCTION: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. METHODS: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. RESULTS: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A). CONCLUSIONS: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

Language outcomes of preschool children who are HIV-exposed uninfected: An analysis of a South African cohort.

INTRODUCTION: There are approximately 16 million children who are HIV-exposed and uninfected (CHEU) worldwide. Studies suggest that CHEU are at risk for developmental impairment in infancy, particularly in language domains. However, there is limited research examining neurocognitive function in CHEU older than 2 years, including important pre-school years. This study aimed to investigate associations between HIV exposure without infection and neurocognitive outcomes and to determine risk factors for neurodevelopment in CHEU at age 3-4 years. METHODS: The Drakenstein Child Health Study is a South African population-based birth cohort which enrolled women in pregnancy with ongoing follow up. Neurocognitive outcomes were assessed in children at 3.5 years by trained assessors blinded to HIV status including general cognitive function, language, and memory, measured using the Kaufmann Assessment Battery for Children, Second Edition (KABC-II). Data were compared between CHEU and children who were HIV-unexposed uninfected (CHUU) using multivariable logistic and linear regression, including testing for effect modification; sex-stratified risk factor analyses were performed. RESULTS: A total of 497 children were included (97 [20%] CHEU; 400 [80%] CHUU; 50% male), with a mean age of 3.5 years (range 3.4-3.6). Groups had similar birth and household characteristics, although mothers of CHEU were older, on average. Overall, CHEU had lower expressive language scores compared to CHUU on unadjusted and adjusted analyses (effect size: -0.23 [95% CI -0.45, -0.01]). There were no group differences in general cognitive or memory function (p>0.05). On sex-stratified analyses, male CHEU were found to have higher odds of suboptimal cognitive development compared to male CHUU (aOR 2.28 [95% CI 1.06, 4.87], p = 0.034). Several other factors including birthweight, maternal education, maternal ART duration and HIV viral load during pregnancy were associated with cognition, memory, or expressive language outcomes in CHEU, dependent on child sex. INTERPRETATION: The findings suggest that perinatal HIV exposure continues to be associated with impaired language development across the preschool years, highlighting the importance of targeting early interventions to optimise language outcomes. Further, the results suggest the importance of demographic, biological and HIV-related variables influencing developmental outcomes in CHEU. The greater risk of suboptimal cognitive development in male CHEU requires investigation around sex-specific mechanisms.

Development and validation of an individualised nomogram to predict mother-to-child transmission in pregnant women with syphilis in China: a retrospective cohort study.

OBJECTIVES: The elimination of mother-to-child transmission (MTCT) of syphilis has been set as a public health priority. However, an instrument to predict the MTCT of syphilis is not available. We aimed to develop and validate an intuitive nomogram to predict the individualised risk of MTCT in pregnant women with syphilis in China. DESIGN: Retrospective cohort study. SETTING: Data was acquired from the National Information System of Prevention of MTCT of Syphilis in Guangdong province between 2011 and 2020. PARTICIPANTS: A total of 13 860 pregnant women with syphilis and their infants were included and randomised 7:3 into the derivation cohort (n=9702) and validation cohort (n=4158). PRIMARY OUTCOME MEASURES: Congenital syphilis. RESULTS: Among 13 860 pregnant women with syphilis and their infants included, 1370 infants were diagnosed with congenital syphilis. Least absolute shrinkage and selection operator regression and multivariable logistic regression showed that age, ethnicity, registered residence, marital status, number of pregnancies, transmission route, the timing of syphilis diagnosis, stage of syphilis, time from first antenatal care to syphilis diagnosis and toluidine red unheated serum test titre were predictors of MTCT of syphilis. A nomogram was developed based on the predictors, which demonstrated good calibration and discrimination with an area under the curve of the receiver operating characteristic of 0.741 (95% CI: 0.728 to 0.755) and 0.731 (95% CI: 0.710 to 0.752) for the derivation and validation cohorts, respectively. The net benefit of the predictive models was positive, demonstrating a significant potential for clinical decision-making. We have also developed a web calculator based on this prediction model. CONCLUSIONS: Our nomogram exhibited good performance in predicting individualised risk for MTCT of syphilis, which may help guide early and personalised prevention for MTCT of syphilis.

Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants.

Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33-3.27), and increased 1.6-fold for each log10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11-2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940.

Enhanced peer-group strategies to support the prevention of mother-to-child HIV transmission leads to increased retention in care in Uganda: A randomized controlled trial.

INTRODUCTION: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. METHODS: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. RESULTS: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199-4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. CONCLUSIONS: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). TRIAL REGISTRATION: NCT02515370 (04/08/2015) on ClinicalTrials.gov.

Comparison of safety and effectiveness of antiretroviral therapy regimens among pregnant women living with HIV at preconception or during pregnancy: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. RESULTS: We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). CONCLUSIONS: Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Epidemiological and virological surveillance of the prevention of mother-to-child transmission of HIV among pregnant women in Togo.

BACKGROUND: In 2015, Togo introduced the "test-and-treat" strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Pediatric HIV infection remains a public health problem in Togo, with a mother-to-child transmission (MTCT) rate of 3.6% in 2020. This study aimed to estimate cases of HIV seroconversion during pregnancy and to identify pregnant women at high risk of transmitting HIV to their children in Lomé, Togo. METHODS: A descriptive cross-sectional study was carried out from 18 March to 22 May 2022 among women who had given birth in five maternity units providing PMTCT services in Lomé. Umbilical cord blood samples were taken from the maternal side by midwives after delivery. HIV serology was performed in the laboratory using the Alere™ HIV Combo SET and First Response HIV 1-2. Card Test version 2.0. A sample was considered positive if both tests were positive. The HIV-1 viral load in HIV-1-positive samples was measured using Cobas/Roche 4800 equipment. Information on the women was extracted from maternal antenatal records and antenatal consultation registers. RESULTS: A total of 3148 umbilical cord blood samples (median maternal age: 28 years (interquartile range [24-32]) were collected. Among them, 99.3% (3145/3148) had presented for at least one antenatal clinic visit before giving birth, and 78.7% (2456/3122) had presented for at least four visits. One hundred and twenty-one (121) cord samples were HIV-1 positive, representing a seroprevalence of 3.8% (95% CI = [3.2-4.6]). Among them, 67.8% (82/121) were known HIV-positive before the current pregnancy, 29.7 (36/121) were diagnosed as HIV-positive at the antenatal visits and 2.5% (3/121) were diagnosed as HIV-positive in the delivery room. Of the HIV-positive women, 85.9% (104/121) were on ARV treatment before delivery. The viral load was < 1000 copies/ml in 97.5% (118/121) cases. CONCLUSION: This study explored the virologic and epidemiological aspects of HIV among pregnant women in Togo. The results show significant viral suppression at delivery in women ART. Surveillance based on umbilical cord blood specimen screening is an interesting approach for monitoring the effectiveness of PMTCT programmes.

Unusual cerebral intraventricular hemorrhage and cardiomyopathy related to congenital cytomegalovirus from non-primary maternal infection: a case report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1). CASE PRESENTATION: An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months. CONCLUSION: Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.

The cost-effectiveness of syphilis screening in pregnant women: a systematic literature review.

Introduction: The cost-effectiveness study of syphilis screening in pregnant women has not been synthesized. This study aimed to synthesize the economic evidence on the cost-effectiveness of syphilis screening in pregnant women that might contribute to making recommendations on the future direction of syphilis screening approaches. Methods: We systematically searched MEDLINE, PubMed, and Web of Science databases for relevant studies published before 19 January 2023 and identified the cost-effectiveness analyses for syphilis screening in pregnant women. The methodological design quality was appraised by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist. Results: In total, 17 literature met the eligibility criteria for a full review. Of the 17 studies, four evaluated interventions using different screening methods, seven assessed a combination of syphilis testing and treatment interventions, three focused on repeat screening intervention, and four evaluated the interventions that integrated syphilis and HIV testing. The most cost-effective strategy appeared to be rapid syphilis testing with high treatment rates in pregnant women who were positive. Discussion: The cost-effectiveness of syphilis screening for pregnancy has been widely demonstrated. It is very essential to improve the compliance with maternal screening and the treatment rates for positive pregnant women while implementing screening.

Treponema pallidum PCR with blood and cerebrospinal fluid of newborns exposed and not exposed to syphilis during pregnancy.

INTRODUCTION: Congenital syphilis (CS) has severe adverse outcomes, including abortion and death. Diagnosis of CS in asymptomatic newborns remains difficult. This study aims to evaluate an in-house polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) and blood samples (BS) to identify T. pallidum DNA in newborns. METHODOLOGY: We performed an exploratory cross-sectional study that included newborns exposed to syphilis during pregnancy (SEG) and non-exposed (SNEG) newborns, between 2019 and 2020. In-house conventional PCR for T. pallidum targeting the tpp47 gene was used to analyze CSFS and dried blood spots. RESULTS: BS was obtained from 54 newborns (33 SEG/21 SNEG) and CSF from 55 newborns (33 SEG/22 SNEG). Twenty-five (71.4%) SEG newborns had reactive BS rapid plasmatic reagins (RPR), and all of them had RPR titers less than or equal to the corresponding maternal titers. All RPR CSF tests were negative. PCR for T. pallidum DNA was positive in 19/33 (57.6%) BS, and in 22/33 CSF. The only SEG newborn with clinical signs of early CS had a positive CSF PCR and a negative BS PCR. Conversely, among SNEG newborns, PCR was positive in 2/21 BS and 5/22 (22.7%) CSF. CONCLUSIONS: T. pallidum DNA was identified using our PCR tests. The exposed group did not present abnormalities that would indicate CS. This prevented conclusions regarding sensitivity and specificity. Dried spot permitted bedside collection, easy transportation, and storage. Further research is needed to evaluate and improve the accuracy of CS low-cost PCR tests, especially for limited resource settings.

Understanding the uptake and determinants of prevention of mother-to-child transmission of HIV services in East Africa: Mixed methods systematic review and meta-analysis.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) of HIV service is conceptualized as a series of cascades that begins with all pregnant women and ends with the detection of a final HIV status in HIV-exposed infants (HEIs). A low rate of cascade completion by mothers' results in an increased risk of HIV transmission to their infants. Therefore, this review aimed to understand the uptake and determinants of key PMTCT services cascades in East Africa. METHODS: We searched CINAHL, EMBASE, MEDLINE, Scopus, and AIM databases using a predetermined search strategy to identify studies published from January 2012 through to March 2022 on the uptake and determinants of PMTCT of HIV services. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool. A random-effects model was used to obtain pooled estimates of (i) maternal HIV testing (ii) maternal ART initiation, (iii) infant ARV prophylaxis and (iv) early infant diagnosis (EID). Factors from quantitative studies were reviewed using a coding template based on the domains of the Andersen model (i.e., environmental, predisposing, enabling and need factors) and qualitative studies were reviewed using a thematic synthesis approach. RESULTS: The searches yielded 2231 articles and we systematically reduced to 52 included studies. Forty quantitative, eight qualitative, and four mixed methods papers were located containing evidence on the uptake and determinants of PMTCT services. The pooled proportions of maternal HIV test and ART uptake in East Africa were 82.6% (95% CI: 75.6-88.0%) and 88.3% (95% CI: 78.5-93.9%). Similarly, the pooled estimates of infant ARV prophylaxis and EID uptake were 84.9% (95% CI: 80.7-88.3%) and 68.7% (95% CI: 57.6-78.0) respectively. Key factors identified were the place of residence, stigma, the age of women, the educational status of both parents, marital status, socioeconomic status, Knowledge about HIV/PMTCT, access to healthcare facilities, attitudes/perceived benefits towards PMTCT services, prior use of maternal and child health (MCH) services, and healthcare-related factors like resource scarcity and insufficient follow-up supervision. CONCLUSION: Most of the identified factors were modifiable and should be considered when formulating policies and planning interventions. Hence, promoting women's education and economic empowerment, strengthening staff supervision, improving access to and integration with MCH services, and actively involving the community to reduce stigma are suggested. Engaging community health workers and expert mothers can also help to share the workload of healthcare providers because of the human resource shortage.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

BACKGROUND: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women. METHODS: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates. RESULTS: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data. CONCLUSION: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study.

BACKGROUND: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. METHODOLOGY: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. RESULTS: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. CONCLUSION: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

BACKGROUND AND AIMS: To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. METHODS: We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. RESULTS: There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106 IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). CONCLUSION: HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

Has Zika been forgotten? A qualitative exploration of knowledge gaps, perceived risk and preventive practices in pregnant women in Malaysia.

BACKGROUND: Although Zika virus infection is rarely reported now, continuous prevention is needed to achieve sustained eradication. This study aimed to explore the knowledge gaps, risk perception and preventive measures against Zika virus infection (ZIKV) in pregnant women in Malaysia. METHODS: We conducted in-depth virtual interviews with pregnant women between February and April 2022. The interviews were recorded and transcribed, and data were analyzed by content analysis. RESULTS: The majority of the participants demonstrated a commendable level of awareness regarding the signs and symptoms associated with ZIKV infection. They also exhibited a clear understanding of preventive measures, particularly emphasizing the importance of avoiding mosquito bites to minimize the risk of ZIKV transmission. However, a noteworthy gap in knowledge surfaced as a subset of participants remained uninformed about the potential for sexual transmission of ZIKV, which could lead to congenital ZIKV in pregnant women. Even among women who were cognizant of ZIKV and its potential negative health outcomes, associated with the infection, many of them did not perceive themselves to be at risk, mainly because ZIKV infection is infrequently discussed or heard of, leading to a sense of infections' rarity. While the adoption of preventive measures such as mosquito bite prevention during pregnancy was a common practice, however, prevention of sexually transmitted infections (STIs) including mosquito-borne diseases such as Zika is low. A minority of women express concerns about the sensitivity surrounding discussions and prevention of STIs within the context of marriage. Most of the participants were supportive of the provision of awareness of ZIKV infection in women during pregnancy and the involvement of men, especially in initiatives aimed at preventing transmission through sexual contact. CONCLUSION: This study uncovered gaps in both knowledge and practices pertaining ZIKV infection among pregnant women in the aftermath of the ZIKV pandemic. The insights gleaned from our research are valuable for shaping future interventions geared towards preventing the resurgence or facilitating the sustainable eradication of ZIKV.