Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana.

BACKGROUND: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies. METHODS: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87). CONCLUSIONS: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).

Creating an anti-ableist learning environment: Development of a novel disability-related microaggressions session for medical and dental students and mixed methods analysis of impact on learning and empowerment.

BACKGROUND: Disability-related microaggressions are unique among microaggressions in the assumptions they reflect and the verbal and non-verbal forms they take. They impact patients and providers alike. Yet, medical and dental students are not routinely educated about disability-related microaggressions. A medical school student-faculty team harnessed Kern's six-step curriculum design process to co-produce a novel 90-min educational intervention centered on recognizing and responding to disability-related microaggressions. The session was piloted in February 2022 as a required element of the school's mandatory professional development training for first-year medical and dental students. OBJECTIVE: This mixed-methods study examined session impact on student-reported learning pertinent to addressing and mitigating disability-related microaggressions. METHODS: Voluntary surveys were distributed to all first-year students to capture pre-/post-session self-assessment of knowledge, skills, and comfort, as well as post-session reflection on lessons learned. Quantitative data was analyzed using summary statistics, unpaired t-tests, and Mann Whitney U tests; qualitative data was analyzed using a hybrid inductive-deductive approach. RESULTS: Survey response rate was 61 % (100/164) pre-session and 25 % (41/164) post-session. Post-session, there was significantly increased student agreement with statements addressing microaggressions knowledge, comfort teaching others, and strategies to support disability-sensitive workplaces. Post-session narrative reflections revealed learning within five themes: nature of microaggressions, identifying microaggressions, preventing microaggressions, responding to microaggressions, and medical student empowerment. Ninety-three percent of post-session respondents (38/41) agreed the session empowered them to actively contribute to anti-ableist learning environments. CONCLUSIONS: The pilot educational intervention provides a promising strategy to foster anti-ableism and advocacy among first-year medical/dental students. While limited by low response rate, small sample size, participant self-selection for survey participation, and unlinked individual pre- and post-session responses, mixed methods analysis suggests the session had a positive impact on student action-oriented knowledge and empowerment.

Prevalence and outcomes of twin pregnancies in Botswana: a national birth outcomes surveillance study.

OBJECTIVES: This study aims to evaluate the prevalence and outcome of twin pregnancies in Botswana. SETTING: The Tsepamo Study conducted birth outcomes surveillance at 8 government-run hospitals (~45% of all births in Botswana) from August 2014 to June 2018 and expanded to 18 hospitals (~70% of all births in Botswana) from July 2018 to March 2019. PARTICIPANTS: Data were collected for all live-born and stillborn in-hospital deliveries with a gestational age (GA) greater than 24 weeks. This analysis included 117 593 singleton and 3718 twin infants (1859 sets (1.6%)) born to 119 477 women between August 2014 and March 2019 and excluded 73 higher order multiples (23 sets of triplets and 1 set of quadruplets). OUTCOMES MEASURED: Our primary outcomes were preterm delivery (<37 weeks GA), very preterm delivery (<32 weeks GA) and stillbirth (APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of 0, 0, 0). RESULTS: Women with twin pregnancies had a similar median number of antenatal care visits (9 vs 10), but were more likely to deliver in a tertiary centre (54.8% vs 45.1%, p<0.001) and more likely to have a cesarean-section (54.6% vs 22.0%, p<0.001) than women with singletons. Compared with singletons, twin pregnancies had a higher risk of preterm delivery (<37 weeks GA) (47.6% vs 16.7%, adjusted risk ratio (aRR) 2.8, 95% CI 2.7 to 2.9) and very preterm delivery (<32 weeks) (11.8% vs 4.0%, aRR 3.0 95% CI 2.6 to 3.4). Among all twin pregnancies, 128 (6.9%) had at least one stillborn infant compared with 2845 (2.4%) stillbirths among singletons (aRR 2.8, 95% CI 2.3 to 3.3). CONCLUSION: Adverse birth outcomes are common among twins in Botswana, and are often severe. Interventions that allow for earlier identification of twin gestation and improved antenatal management of twin pregnancies may improve infant and child survival.

Weight gain during pregnancy among women initiating dolutegravir in Botswana.

BACKGROUND: Recent data suggests clinically significant weight gain among non-pregnant HIV-positive adults after starting dolutegravir-based ART (DTG). Excess or insufficient weight gain in pregnancy could adversely impact pregnancy outcomes, but data for pregnant women receiving DTG are limited. METHODS: The Tsepamo Study captured data at delivery sites in Botswana from 2014 to 2019. HIV testing, HIV treatment information, and weight measurements during antenatal care were abstracted from the maternity obstetric record at delivery. HIV-positive women initiating DTG or efavirenz-based ART (EFV) between conception and 17 weeks gestation and HIV-uninfected women first presenting for antenatal care before 17 weeks gestation were included. We evaluated weekly weight gain, total 18-week weight gain, excess weight gain (>0.59 kg/week), insufficient weight gain (<0.18 kg/week), and weight loss between 18±2 and 36±2 weeks gestation, adjusting for demographic and clinical variables. FINDINGS: Baseline characteristics were similar by exposure group, including pre-pregnancy and early pregnancy weight. Compared with EFV, mean weekly weight gain between 18 and 36 weeks gestation was 0.05 (95% CI 0.03, 0.07) kg/week higher for women initiating DTG and 0.12 (0.10, 0.14) kg/week higher for HIV-uninfected women. Mean 18-week weight gain was 1.05 (95% CI 0.61, 1.49) kg higher for women initiating DTG and 2.31 (1.85, 2.77) kg higher for HIV-uninfected women, compared with EFV. Women initiating DTG were more likely to gain excess weight but less likely to gain insufficient weight or lose weight than women initiating EFV. INTERPRETATION: Women initiating DTG compared with EFV during pregnancy gained more weight between 18 and 36 weeks gestation. Neither group gained as much weight as HIV-uninfected women. Initiating DTG compared with EFV during pregnancy could increase the risk of excess weight gain but decrease the risk of insufficient weight gain and weight loss, which could have positive and negative consequences in pregnancy. Our findings are consistent with prior studies in non-pregnant adults.

Mother-to-Child HIV Transmission With In Utero Dolutegravir vs. Efavirenz in Botswana.

BACKGROUND: A large-scale evaluation of mother-to-child transmission (MTCT) with dolutegravir (DTG)-based antiretroviral treatment (ART) has not been conducted previously. SETTING: Botswana was the first African country to change from efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC) to DTG/TDF/FTC first-line ART. METHODS: From April 2015 to July 2018, the Early Infant Treatment Study offered HIV DNA testing at <96 hours of life. Maternal ART regimen was available for screened infants who could be linked to the separate Tsepamo surveillance study database. We evaluated characteristics of HIV-positive infants, and compared MTCT rates by ART regimen for linked infants. RESULTS: Of 10,622 HIV-exposed infants screened, 42 (0.40%) were HIV-positive. In total, 5064 screened infants could be linked to the surveillance database, including 1235 (24.4%) exposed to DTG/TDF/FTC and 2411 (47.6%) exposed to EFV/TDF/FTC. MTCT was rare when either regimen was started before conception: 0/213 [0.00%, 95% confidence interval (CI): 0.00% to 1.72%] on DTG, 1/1497 (0.07%, 95% CI: 0.00% to 0.37%) on EFV. MTCT was similar for women starting each ART regimen in pregnancy: 8/999 (0.80%, 95% CI: 0.35% to 1.57%) for DTG and 8/883 (0.91%, 95% CI: 0.39% to 1.78%) for EFV (risk difference 0.11%, 95% CI: -0.79% to 1.06%). Most MTCT events (4/8 with DTG, 6/9 with EFV) occurred when ART was started <90 days before delivery. Infants exposed to DTG in utero had lower baseline HIV RNA compared with other HIV-infected infants. CONCLUSION: In utero MTCT in Botswana remains rare in the DTG era. No significant MTCT differences were observed between DTG/TDF/FTC and EFV/TDF/FTC. Risk was highest for both groups when ART was started in the third trimester.