Time series analysis of comprehensive maternal deaths in Brazil during the COVID-19 pandemic.

The effects of the COVID-19 pandemic on comprehensive maternal deaths in Brazil have not been fully explored. Using publicly available data from the Brazilian Mortality Information (SIM) and Information System on Live Births (SINASC) databases, we used two complementary forecasting models to predict estimates of maternal mortality ratios using maternal deaths (MMR) and comprehensive maternal deaths (MMRc) in the years 2020 and 2021 based on data from 2008 to 2019. We calculated national and regional standardized mortality ratio estimates for maternal deaths (SMR) and comprehensive maternal deaths (SMRc) for 2020 and 2021. The observed MMRc in 2021 was more than double the predicted MMRc based on the Holt-Winters and autoregressive integrated moving average models (127.12 versus 60.89 and 59.12 per 100,000 live births, respectively). We found persisting sub-national variation in comprehensive maternal mortality: SMRc ranged from 1.74 (95% confidence interval [CI] 1.64, 1.86) in the Northeast to 2.70 (95% CI 2.45, 2.96) in the South in 2021. The observed national estimates for comprehensive maternal deaths in 2021 were the highest in Brazil in the past three decades. Increased resources for prenatal care, maternal health, and postpartum care may be needed to reverse the national trend in comprehensive maternal deaths.

Contribution of Syphilis to Adverse Pregnancy Outcomes in People Living With and Without HIV in South Brazil: 2008 to 2018.

BACKGROUND: Syphilis coinfection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis coinfection on pregnancies in south Brazil. METHODS: Data were extracted from hospital records between January 1, 2008, and December 31, 2018. Preterm birth (PTB), low birth weight (LBW <2500 g), and a composite adverse infant outcome (AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis, stillbirth, congenital syphilis) were evaluated among pregnancies without HIV and syphilis (PWOH + S), PLH monoinfection, syphilis monoinfection (PLS), and PLH with syphilis (PLH + S). RESULTS: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis coinfected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were lost to follow-up before HIV diagnosis. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. Thirty-seven percent of PLH + S did not initiate antiretroviral therapy versus 15.4% of PLH monoinfection ( P < 0.001). Less than half (37.6%) of PLH + S had VDRL titers ≥1:16 compared with 21.7% of PLS only ( P < 0.001). Among PLH, syphilis coinfection and unknown/high VDRL titers (≥1:16) increased AIO risk more (adjusted relative risk [aRR], 3.96; 95% confidence interval [CI], 3.33-4.70) compared with low VDRL titers (≤1:8; aRR, 3.51; 95% CI, 2.90-4.25). Unsuppressed viremia (≥50 copies/mL) was associated with risk of PTB (aRR, 1.43; 95% CI, 1.07-1.92) and AIO (aRR, 1.38; 95% CI, 1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS monoinfection. CONCLUSIONS: Syphilis coinfection worsens AIOs in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV viral load suppression are paramount for optimal obstetric care.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018.

BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008-2018.

BACKGROUND: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. STUDY DESIGN: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. RESULTS: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). CONCLUSION: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Ineffective penicillin treatment and absence of partner treatment may drive the congenital syphilis epidemic in Brazil.

BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35-8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77-23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07-4.58), and maternal nontreponemal titers ≥1:64 (1.09-1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59-1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02-1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17-1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.

Repercussions of the COVID-19 pandemic on preventive health services in Brazil.

INTRODUCTION: The increasing burden of non-communicable diseases and limited public financing are major challenges facing health care systems in Latin America. Although COVID-19 severely impacted the Brazilian health care system, it is crucial to further characterize the degree of disruption caused to public health efforts, in order to address and manage long term effects of this pandemic. We therefore quantified the demand for preventive and treatment services from the Brazilian Unified Health System (Sistema Único de Saúde/SUS) in 2020 to evaluate potential repercussions of COVID-19 in this setting. METHODS: Using the SUS database, we compared preventative and treatment services rendered in 2020 to the same services rendered from 2017 to 19. We also evaluated the frequency of respiratory infection (RI) diagnoses during the pandemic, relative to the preceding years. RESULTS: Compared to 2017-19, in 2020 non-urgent medical appointments decreased 1.4-fold (p = 0.0017), dental consultations 2.8-fold (p = 0.05), and immunization coverage 1.5 fold (p = 0.0005). The number of RI visits to SUS ambulatory care units in 2020 was 4.2 times higher than in preceding years (p = 0.0014), with a peak of 280,898 diagnoses in July 2020. CONCLUSION: The COVID-19 pandemic appears to have led to a dramatic decline in preventative and treatment services provided by SUS to the Brazilian population. Our findings may aid decision-makers in formulating policies to increase the availability of outpatient services in the aftermath of the pandemic. Counter measures will be critical to avoid a resurgence in vaccine-preventable diseases and complications stemming from non-communicable, chronic health conditions.

Maternal HIV and syphilis are not syndemic in Brazil: Hot spot analysis of the two epidemics.

While the annual incidence of HIV diagnosis in pregnancy in Brazil remains relatively stable, rates of maternal syphilis increased over six-fold in the past decade. We hypothesized that maternal HIV and syphilis are two distinct epidemics. Data on all cases of maternal HIV or syphilis detected in pregnancy between January 1, 2010 to December 31, 2018 were requested from the Brazilian Ministry of Health. In order to evaluate how the epidemics evolved over the time period, ArcGIS software was used to generate spatiotemporal maps of annual rates of detection of maternal HIV and syphilis in 2010 and 2018. We utilized Euclidean-distance hot spot analysis to identify state-specific clusters in 2010 and 2018. From 2010 to 2018, there were 66,631 cases of maternal HIV, 225,451 cases of maternal syphilis, and 150,414 cases of congenital syphilis in Brazil. The state of Rio Grande do Sul had the highest rate of maternal HIV detection in both 2010 and 2018. Hot spots of maternal HIV were identified in the three most Southern states in both 2010 and 2018 (99% confidence, z-score >2.58, p <0.01). While syphilis incidence >30 per 1,000 live births in 2018 in four states, only the two coastal states of Rio de Janeiro and Espirito Santo in Southeastern Brazil were significant hot spots (90% confidence, z-score 1.65-1.95, p <0.10). Contrary to the general assumption, HIV and syphilis epidemics in Brazil are not syndemic in pregnant women. There is a spatial cluster of maternal HIV in the South, while syphilis is increasing throughout the country, more recently on the coast. Focusing on maternal HIV hot spots in the Southern states is insufficient to curtail the maternal and congenital syphilis epidemics throughout the country. New strategies, including ongoing hot spot analysis, are urgently needed to monitor, identify and treat maternal syphilis.

Prospective cohort study of children exposed to hepatitis C virus through a pregnancy screening program.

OBJECTIVES: Porto Alegre, in south Brazil, has one of the highest hepatitis C virus (HCV) infection rates in the country (84.4 cases/100 000 in 2018). Prenatal screening of HCV, however, has not been routinely offered. METHODS: A longitudinal study of pregnant women with HCV and their infants was conducted between January 2014 and December 2018. Screening for HCV antibodies was offered to all women delivering at the study tertiary institution. HCV RT-PCR was performed if the woman was seropositive. Infants were followed prospectively. RESULTS: Among 18 953 pregnant women delivering infants during the study period, 17 810 were screened for HCV antibodies (93.9%) with 130 positive results (HCV seroprevalence 0.7%). HCV-RNA was detectable in 57/117 cases (48.7%). HCV viremia was associated with the use of injectable drugs (P = 0.03), inhaled/crack drug use (P = 0.02), having an HCV-seropositive partner, and ≥3 lifetime sexual partners (P < 0.01). Genotype 1 was most prevalent (68%) during pregnancy. Among 43 children with follow-up, six (13%) were HCV-infected (transmission rate 13.9%); 50% were infected with genotype 3. Two infants (33%) cleared their infection; the mothers had genetic polymorphisms associated with clearance. CONCLUSION: HCV vertical transmission was high in the study population, with HCV infection during pregnancy being vastly underdiagnosed. Public health efforts must focus on this vulnerable population for disease prevention and early treatment.

Failure to recognize Low non-treponemal titer syphilis infections in pregnancy May lead to widespread under-treatment.

OBJECTIVES: Rates of maternal syphilis have increased five-fold in Brazil in the past decade. While penicillin remains the only appropriate treatment for maternal syphilis, we hypothesized that low non-treponemal titers (<1:16) may lead to reduced penicillin treatment in Brazil. METHODS: Using Brazilian Ministry of Health data on women diagnosed with maternal syphilis between January 1, 2010, and December 31, 2018, we conducted a random-effects logistic regression model with a cluster correction at the state level to evaluate predictive factors of penicillin treatment. RESULTS: We observed yearly increases in cases of pregnant women with syphilis from 2010 to 2018. There was significant variation by state: 52,451 cases were reported in São Paulo, followed by 26,838 in Rio de Janeiro. Among 215,937 cases of maternal syphilis, 91·3% received penicillin. In the random-effects model, a non-treponemal titer ≥1:16 was associated with 1·44 higher odds of receiving penicillin (95% confidence interval [CI]: 1·391·48), and prenatal care was associated with a 2·12 increased odds of receiving penicillin (95% CI: 2·022·21). Although there is an association between the absence of prenatal care and inadequate treatment for syphilis, 83·2% of women in this cohort who did not receive penicillin were engaged in prenatal care. CONCLUSIONS: Providers may inappropriately exclude low non-treponemal titers and thereby fail to use penicillin treatment in maternal syphilis. While the cause of the maternal syphilis epidemic in Brazil is multifactorial, we believe our findings can be used to develop targeted interventions throughout Brazil as well as shape public health initiatives globally.

A cross-sectional study of high-risk human papillomavirus clustering and cervical outcomes in HIV-infected women in Rio de Janeiro, Brazil.

BACKGROUND: In Brazil, the rate of cervical cancer remains high despite the availability of screening programs. With ongoing vaccine development and implementation, information on the prevalence of specific HPV types is needed, particularly among high-risk populations, such as HIV-infected women. METHODS: We performed a study of HIV-infected women in Rio de Janeiro, Brazil, who underwent cervical HPV genotype testing between 2005-2013. We examined the prevalence of high-risk HPV types and the patterns of high-risk HPV type clustering. Using logarithmic binomial regression, we estimated the risk of abnormal cytology by HPV genotype result. RESULTS: Of the 562 women included, 498 (89 %) had at least one HPV type detected. 364 women (65 %) had at least one high-risk HPV type detected and 181 (32 %) had more than one high-risk type detected. HPV 58 was the most frequent HPV type detected overall (prevalence 19.8 % [95 % confidence interval 16.4-23.1]), followed by HPV 53 (prevalence 15.5 % [12.5-18.5]) and HPV 16 (prevalence 13 % [10.2-15.8]). Women infected with more than one high-risk HPV type were younger, had lower CD4+ lymphocyte counts, and were more likely to be infected with HPV 16 or 18. In adjusted analyses, presence of more than one high-risk HPV type was associated with a two-fold increased risk of abnormal cytology after adjusting for presence of individual high-risk type, age, and CD4+ lymphocyte count (adjusted prevalence ratios 1.88-2.07, all p <0.001). No single high-risk HPV type was statistically associated with abnormal cytology after adjusting for the presence of more than one high-risk HPV type. CONCLUSIONS: In the largest study of cervical HPV genotypes among HIV-infected women in Latin America, infection by high-risk HPV types other than 16 or 18 and infection by more than one high-risk HPV types were common. Infection by more than one high-risk type was more strongly associated with abnormal cervical cytology than any individual high-risk HPV type, highlighting the need for multi-valent HPV vaccines.