BACKGROUND: Early infant diagnosis (EID) facilitates early initiation into HIV care for identified HIV-positive infants. According to the Uganda Ministry of Health, EID testing algorithm, testing for infants exposed to HIV (IEH) should occur at <6 weeks, 9 and 18 months of age, and 6 weeks after stopping breastfeeding. Uganda has faced challenges with loss to follow-up (LTFU) of IEH for EID. We assessed complete testing coverage (CTC) to the EID algorithm for IEH and associated factors. METHODS: We analyzed data from the 'Impact of the National Program for the Prevention of Vertical Transmission (PVT) of HIV in Uganda (2017-2019)' study. Mothers living with HIV whose infants tested HIV-negative at 4-12 weeks were enrolled in a prospective cohort (2017 - 2018) and followed until the IEH tested positive, died, was LTFU, or reached 18 months of age. We computed the proportion of IEH tested according to the EID algorithm among surviving infants. CTC was defined as undergoing HIV tests at three designated time points (excluding the 6 weeks after breastfeeding cessation) if HIV negative. IEH who were diagnosed with HIV but were tested at all recommended tests until that point were also considered to have CTC. We evaluated factors associated with CTC using modified Poisson regression. RESULTS: Among 1,804 IEH, 912 (51%) were male. Of the 1,804 IEH at baseline, 27 (1%) died. Among the 1,777 IEH included in the primary outcome analysis, 1,282 (72%) completed the study and 941 (53%) infants had CTC according to the EID testing algorithm including 40 (2%) who tested HIV-positive. Perceived discrimination due to HIV status [RR = 0.77, 95%CI (0.65-0.92)], having fewer pregnancies [RR = 0.97, 95%CI (0.68-0.99)], and reporting sexual violence [RR = 0.82, 95%CI (0.73-0.93)] by the mother of IEH were associated with non-CTC. CONCLUSION: About half of IEH were tested at the recommended time points. Interventions to address stigma and sexual violence for mothers may improve CTC for the EID algorithm. Investigations are needed to explore associations between sexual violence, parity, and CTC for the EID algorithm.

BACKGROUND: Uganda reported a significant reduction in the mortality rate of children under 5 years of age, from 146/1,000 live births in 2000-42/1,000 live births in 2021. With the rollout of Option B+, the vertical transmission rate of HIV decreased from 13.0% (2012) to 6.0% (2019). However, its impact on the mortality rate among children is not well documented. We determined the mortality rate and associated risk factors among infants exposed and not exposed to HIV attending immunization clinics in Uganda. METHODS: We conducted an observational prospective cohort study of mother-infant pairs (MIPs) with infants exposed or unexposed to HIV. We enrolled infants aged 4-12 weeks. The inclusion criteria were biological mothers attending health facilities that provide routine immunization for children and/or postnatal care visits who were able to provide signed written informed consent; mothers or infants who were not severely ill; and those who consented to have their infants tested for HIV antibodies at baseline and follow-up visits every 3 months until the children were aged 18 months. Child-HIV infection and death were censored events. Children lost to follow-up or withdrawn from the study were censored from analyses at the last documented study visit. The outcome of interest was child mortality, and the independent variables were mother's age; infant HIV exposure status; infant sex; family socioeconomic status; marital status; education level; malaria during pregnancy; birth attendee; mother's ART initiation; mode of transport to health facilities; breastfeeding pattern; 4 or more ANC visits; and mother's baseline viral load nonsuppression and place of delivery. We used Kaplan-Meier survival curves to estimate cumulative mortality probability and the Wilcoxon log-rank test to compare differences in cumulative survival functions. We used multivariate Weibull proportional hazards and Weibull accelerated failure time (AFT) regression models with 95% confidence intervals (CIs) to identify factors associated with child death. RESULTS: Among the 16,718 MIPs identified, 11,519 (68.9%) mothers consented to study follow-up. At the 18-month follow-up, 0.7% (79/11,519) of the infants had died, 40.5% (32/79) of whom were exposed to HIV. The overall child mortality rate per 1,000 person-years was 5.0 (95% CI: 4.0--6.2) and was significantly greater among the infants exposed to HIV (14.2; 95% CI: 10.0--20.0) than among the infants not exposed to HIV (3.5; 95% CI: 2.6--4.6). In the adjusted model, the mortality risk factors were HIV exposure status (aHR5.6 95% CI: 3.5--9.4), maternal age < 25 years (aHR1.8; 95% CI: 1.1--2.9), living without a partner (aHR1.8; 95% CI: 1.1--2.9), and delivery at home (aHR2.2; 95% CI: 1.3--4.0). CONCLUSION: Single young mothers living with HIV delivering at home increased the risk of child mortality. Identifying mothers with risk factors early for support could reduce the risk of child mortality.

BACKGROUND: Adverse birth outcomes (ABOs) cause significant infant morbidity and mortality in resource-limited settings. Many of the maternal risk factors associated with ABOs can be prevented. We present the prevalence, trends, and risk factors of selected ABOs from a hospital-based birth defects surveillance program in Kampala, Uganda. METHODS: We analyzed data for all mothers with singleton deliveries collected from four urban hospitals between 2015 and 2022. Prevalence of preterm birth [PTB], low birth weight [LBW], small for gestational age [SGA], and stillbirth [SB] and maternal HIV seroprevalence were calculated among 222,427 births. SB was defined as infant born without life ≥ 28 weeks of gestation, LBW as term live birth weighing < 2500 g and PTB as live birth born < 37 weeks of gestation. Time trends of ABOs by maternal HIV status and age were computed using quasi-Poisson regression model and presented graphically. Risk factor associations were estimated using robust Poisson models adjusting for infant sex, hospital of delivery, and birth year. RESULTS: Prevalence of PTB, LBW, SGA, and SB were 14.8%, 4.3%, 17.8%, and 3.1%, respectively. Maternal HIV seroprevalence was 7.7%. Compared to mothers aged 25-34 years, young adolescents 10-18 years was associated with PTB (adjusted risk ratio [aRR]: 1.44, 95% confidence interval (CI): 1.38-1.50); LBW (1.65,1.51-1.81); and SGA (1.18; 1.12-1.24). HIV seropositivity was associated with PTB (1.18; 1.14-1.22), LBW (1.54; 1.43-1.65), and SGA (1.28; 1.23-1.33). Compared to starting ANC in the first trimester, no antenatal care (ANC) was associated with PTB (2.44; 2.33-2.56), LBW (1.80; 1.55-2.09), SGA (1.37; 1.27-1.49), and SB (3.73; 3.32-4.15) and late attendance with LBW (1.09; 1.02-1.16), SGA (1.26; 1.22-1.30), and SB (1.09; 1.02-1.17). Our findings also indicate a rising trend in PTB among adolescent and young women aged 10-24 years, and a declining trend in LBW and SGA over time (ptrend < 0.05 for all). CONCLUSIONS: Young maternal age, maternal HIV, and late or no ANC attendance were associated with ABO. Childbearing in the ages 25-34, preventing HIV in women, and supporting early and frequent ANC attendance are important in improving birth outcomes.

INTRODUCTION: We assessed the risk of adverse pregnancy and birth outcomes and birth defects among women living with HIV (WLHIV) on antiretroviral therapy (ART) and HIV-negative women. METHODS: We analyzed data on live births, stillbirths, and spontaneous abortions during 2015-2021 from a hospital-based birth defects surveillance system in Kampala, Uganda. ART regimens were recorded from hospital records and maternal self-reports. Using a log-binomial regression model, we compared the prevalence of 16 major external birth defects and other adverse birth outcomes among WLHIV on ART and HIV-negative women. RESULTS: A total of 203,092 births were included from 196,373 women of which 15,020 (7.6%) were WLHIV on ART. During pregnancy, 15,566 infants were primarily exposed to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART (n=13,614; 87.5%). After adjusting for maternal age, parity, and number of antenatal care (ANC) visits, WLHIV on NNRTI were more likely than HIV-negative women to deliver preterm (adjusted prevalence ratio [aPR]=1.27, 95% confidence interval [CI]: 1.21,1.32), post-term (aPR=1.23, 95% CI: 1.16,1.32), or small for gestational age infants (aPR=1.35, 95% CI: 1.30,1.40). Spina bifida was more prevalent among infants born to WLHIV on ART periconceptionally compared to HIV-negative women (aPR=2.45, 95% CI 1.27,4.33). The prevalence of the other selected birth defects were similar between infants from WLHIV on ART and HIV-negative women. CONCLUSION: In Uganda, WLHIV on ART were more likely than HIV-negative women to experience selected adverse birth outcomes. Further surveillance of maternal ART exposure, including by drug class and ART regimen, is needed to monitor and prevent adverse birth outcomes in WLHIV.

BACKGROUND: Coronavirus disease 2019 (COVID-19) control measures presented impediments for prevention of mother-to-child transmission of HIV (PMTCT) programming in Uganda. Nationwide control measures implemented April-June 2020 included a public transport ban and mandatory travel permits for pregnant women to access clinics. Program adaptations instituted for continuity of services included community drug delivery and home-based DNA-PCR testing for HIV-exposed infants (HEI). We examined the effect of COVID-19 control measures and program adaptations on PMTCT service uptake in central Uganda. METHODS: We analysed data for pregnant women living with HIV (WLHIV) and HEI receiving PMTCT services in eight districts in central Uganda. We abstracted data from medical records at 96 public clinics for six months pre-lockdown (October 2019-March 2020), three months of lockdown (April-June 2020), and six months post-lockdown (July-December 2020). We measured monthly antiretroviral therapy (ART) refill attendance, health facility deliveries, and timely DNA-PCR testing of HEI for HIV (within two months of birth). We conducted segmented ordinary least squares regression of interrupted time series and adjusted for month-to-month changes using Cumby-Huizinga test. We reported results using coefficients and 95% confidence intervals (CIs). RESULTS: At the start of pre-lockdown (October 2019), there were 448 deliveries, 2,676 ART refills and 556 timely HEI tests. The pre-lockdown trend for ART refills increased while deliveries and HEI tests declined. At the start of lockdown (April 2020), all indicators declined, although significantly for facility deliveries (-60; 95% CI: -102, -18). Lockdown monthly trends were positive with 68 more HEI tested per month (95% CI:42, 93) and 51 more deliveries (95% CI: 9, 94) but insignificantly negative for ART refills. At start of post-lockdown (July 2020), HEI testing declined (-28; 95%CI: -48, -8). Post-lockdown HEI testing trend was negative with 70 fewer HEI tested per month (95%CI: -79, -62) while no difference in trend for deliveries and ART refills. CONCLUSION: COVID-19 control measures had a significant immediate negative impact on pregnancy deliveries at health facilities. During lockdown, all service rates rapidly recovered through program adaptations, significantly for HEI testing and deliveries. Maintaining these adaptations might help restore the positive trend in timely HIV testing for HEI.

OBJECTIVE: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. METHODS: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. FINDINGS: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. CONCLUSION: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

HIV infection is associated with poor maternal health outcomes. In 2016, the maternal mortality ratio (MMR) in Uganda was 336/100,000, and the neonatal mortality rate (NMR) was 19/1,000. Saving Mothers, Giving Life (SMGL) was a five-year maternal and neonatal health strengthening initiative launched in 2012 in Uganda. We extracted maternal and neonatal data for 2015-2016 from the initiative's population-based mortality surveillance system in 123 health facilities in Western Uganda. We collected data on the facilities, HIV status, antiretroviral drug (ARV) use, death, birth weight, delivery type, parity, Apgar scores, and complications. We compared mother and baby outcomes between HIV-positive or HIV-negative, computed risk ratios (RR) for adverse outcomes, and used the chi-square to test for significance in differences observed. Among 116,066 pregnant women who attended and gave birth at SMGL-implementing facilities during 2015-2016, 8,307 (7.7%) were HIV-positive, of whom 7,809 (94%) used antiretroviral drugs (ARVs) at the time of delivery. During birth, 23,993 (21%) women experienced ≥1 complications. Neonate Apgar scores <7 (8.8%) and maternal haemorrhage during birth (1.6%) were the most common outcomes. Overall facility MMR was 258/100,000 and NMR was 7.6/1,000. HIV infection increased risk of maternal death (RR = 3.6, 95% Confidence Interval (CI) = 2.4-5.5), maternal sepsis (RR = 2.1, 95% CI = 1.3-3.3), and infant birth weight <2,500g (RR = 1.2, 95% CI = 1.1-1.3), but was protective against maternal complications (RR = 0.92, 95% CI = 0.87-0.97) and perinatal death (RR = 0.78, 95% CI = 0.68-0.89). Among the HIV-positive, ARV non-use increased risk of maternal death (RR = 15, 95% CI = 7.1-31) and perinatal death (RR = 2.3, 95% CI = 1.6-3.4). SMGL reduced facility MMR and NMR below national rates. HIV-infection was associated with maternal sepsis and death. Failure to use ARVs among women living with HIV increased the risk of maternal and perinatal death. Use of the SMGL approach and complementary interventions that further strengthen HIV care, may continue to reduce MMR and NMR.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

OBJECTIVE: The United Nations' Sustainable Development Goal 3.7.1 addresses the importance of family planning. The objective of this paper is to provide information on family planning to policymakers to help increase access to contraceptive methods to women in sub-Saharan Africa. METHODS: We analyzed data from the Population-based HIV Impact Assessment studies conducted in 11 sub-Saharan African countries from 2015 to 2018 to assess the relationship between HIV services and family planning. Analyses were restricted to women aged 15-49 years who reported being sexually active within the past 12 months and had data on contraceptive use. RESULTS: Approximately 46.4% of participants reported using any form of contraception; 93.6% of whom used modern contraceptives. Women with a positive HIV status were more likely to use contraceptives (P < 0.0001) than HIV-negative women. Unmet need was higher among women who were confirmed to be HIV-negative in Namibia, Uganda, and Zambia than confirmed to be positive. Women aged 15-19 years used contraception less than 40% of the time. CONCLUSION: This analysis highlights crucial gaps in progress among HIV-negative and young women (aged 15-19 years). To provide access to modern contraception for all women, programs and governments need to focus on women who desire but do not have access to these family planning resources.

BACKGROUND: Saving Mothers, Giving Life (SMGL) is a 5-year initiative implemented in participating districts in Uganda and Zambia that aimed to reduce deaths related to pregnancy and childbirth by targeting the 3 delays to receiving appropriate care: seeking, reaching, and receiving. Approaches to addressing the third delay included adequate health facility infrastructure, specifically sufficient equipment and medications; trained providers to provide quality evidence-based care; support for referrals to higher-level care; and effective maternal and perinatal death surveillance and response. METHODS: SMGL used a mixed-methods approach to describe intervention strategies, outcomes, and health impacts. Programmatic and monitoring and evaluation data-health facility assessments, facility and community surveillance, and population-based mortality studies-were used to document the effectiveness of intervention components. RESULTS: During the SMGL initiative, the proportion of facilities providing emergency obstetric and newborn care (EmONC) increased from 10% to 25% in Uganda and from 6% to 12% in Zambia. Correspondingly, the delivery rate occurring in EmONC facilities increased from 28.2% to 41.0% in Uganda and from 26.0% to 29.1% in Zambia. Nearly all facilities had at least one trained provider on staff by the endline evaluation. Staffing increases allowed a higher proportion of health centers to provide care 24 hours a day/7 days a week by endline-from 74.6% to 82.9% in Uganda and from 64.8% to 95.5% in Zambia. During this period, referral communication improved from 93.3% to 99.0% in Uganda and from 44.6% to 100% in Zambia, and data systems to identify and analyze causes of maternal and perinatal deaths were established and strengthened. CONCLUSION: SMGL's approach was associated with improvements in facility infrastructure, equipment, medication, access to skilled staff, and referral mechanisms and led to declines in facility maternal and perinatal mortality rates. Further work is needed to sustain these gains and to eliminate preventable maternal and perinatal deaths.