Maternal HIV Infection Research Articles

Identifying Clinical Criteria for an Expanded Targeted Approach to Screening for Congenital Cytomegalovirus Infection-A Retrospective Study.

Targeted screening for congenital CMV infection (cCMV), which entails CMV testing of infants who fail newborn hearing screening (NBHS), has become common practice. However, this strategy misses nearly all infected infants with normal hearing at birth who are nonetheless at high risk of subsequent hearing loss and would benefit from timely cCMV diagnosis. The objective of this study was to identify expanded criteria predictive of cCMV to increase the scope and utility of targeted newborn CMV screening. In this retrospective study, 465 newborns were tested for cCMV at a single tertiary care center with a targeted screening program between 2014 and 2018. Twenty-two infants were diagnosed with cCMV, representing 0.2% of the 12,189 births over this period and 4.7% of the infants tested. The highest prevalence of cCMV infection was among infants tested because of primary maternal CMV infection (8/42, 19%), followed by failed initial NBHS (10/88, 11.4%), maternal HIV infection (3/137, 2.2%), and clinical suspicion alone (5/232, 2.2%). The symptoms with the highest prevalence of infection among all infants tested included an enlarged liver and/or spleen (33.3%) (3/9), followed by petechiae (33.3%), microcephaly (9.4%), direct hyperbilirubinemia (7.7%), thrombocytopenia (6%), and growth impairment (4.3%). In addition to CMV screening of newborns who fail the NBHS, these data suggest that certain clinical signs of cCMV-in particular: thrombocytopenia, growth impairment, and HIV exposure in pregnancy-should be additional criteria for expanded targeted newborn CMV screening, where universal screening is not yet the standard of care.

Maternal anemia is associated with adverse maternal and neonatal outcomes in Mbarara, Uganda

Purpose Maternal anemia is a significant risk factor for maternal morbidity and mortality, increasing risk of preterm birth, intrauterine growth restriction, stillbirth, and death. Moderate and severe anemia in pregnancy is defined as hemoglobin (Hb) <10 g/dl and Hb < 7 g/dl, respectively. We aimed to characterize the association of maternal anemia with maternal, neonatal, and placental outcomes in a resource-limited setting. Methods Data were collected from a prospective cohort of 352 pregnant women at a tertiary academic Ugandan hospital. One hundred and seventy-six (50%) of women were living with HIV. Hemoglobin was measured in labor, and placentas were collected postpartum. Maternal outcomes included mode of delivery, hemorrhage, blood transfusion, intensive care unit admission, and maternal mortality. Neonatal outcomes included gestational age at delivery, birthweight, stillbirth, and neonatal mortality. Placental descriptors included weight and thickness. Categorical variables were analyzed using Chi-squared and Fisher’s exact tests. Results Hemoglobin < 10 g/dl, was present in 17/352 (5%) of women. Significantly more women with moderate or severe anemia were HIV-infected: 14/17 (82%) versus 162/335 (48%) (p = .006). Blood transfusions (2/17, 12% versus 5/335, 2%, p = .04) and neonatal deaths (2/17, 12% versus 9/335, 3%, p = .01) were more common in the anemia group. Placental thickness was lower in the anemia group (1.4 cm versus 1.7 cm, p = .04). Conclusions Moderate and severe anemia was associated with maternal HIV infection, maternal blood transfusion, neonatal death, and decreased placental thickness. The overall rate of moderate and severe anemia among this cohort was lower than previously reported.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Syphilis screening coverage and positivity by HIV treatment status among South African pregnant women enrolled in the 2019 antenatal HIV sentinel survey

We describe coverage of maternal syphilis screening, syphilis positivity, coverage of treatment and their association with maternal HIV infection and antiretroviral treatment (ART) status among pregnant women attending South African antenatal clinics. The 2019 antenatal care sentinel survey was a cross-sectional survey conducted from 1 October to 15 November 2019 at 1589 sentinel sites in all nine provinces of the country and aimed to enrol 36,000 pregnant women ages 15–49 years regardless of HIV, ART or syphilis status. Data collection procedures included obtaining written informed consent, a brief interview, medical record review and blood specimen collection. Completed data collection forms and specimens were sent to designated regional laboratories for data capture and HIV serology testing. Data analysis determined four outcomes i) syphilis screening coverage ii) syphilis positivity iii) coverage of any treatment and iv) with Benzathine penicillin G (BPG). Multivariable logistic regression models with or without interaction between HIV infection and ART status with province were used to determine factors associated with syphilis positivity. Of the 41 598 women enrolled, 35 900 were included in the analysis for syphilis screening coverage. The weighted syphilis screening coverage was 96.4% [95% Confidence Interval (CI) 95.9–96.7%] nationally and was lowest among HIV positive women not on ART at 93.5% (95% CI 92.2–94.5%). Syphilis positivity was 2.6% (95% CI 2.4–2.9%) nationally. Among those who were syphilis positive, 91.9% (95% CI 89.8–93.7%) had documentation of syphilis treatment status, of whom 92.0% (95% CI 89.8–93.9%) were treated, with the majority treated with one or more doses of BPG [92.2% (95% CI 89.8–94.3%)]. HIV-positive women, not on ART [adjusted odd ratio (aOR) 2.24 (95% 1.71–2.93)] and those on ART [aOR 2.25 (95% CI 1.91–2.64)] were more likely to be syphilis positive compared to those who were HIV negative. The national syphilis screening coverage met the global screening target of 95%. Syphilis positivity was higher among HIV positive women compared to negative women. Introduction of rapid syphilis testing and ensuring a universal supply of appropriate treatment for syphilis will reduce the likelihood of mother-to-child transmission of syphilis.

Maternal biomarkers of endothelial dysfunction and pregnancy outcomes in women with and without HIV in Botswana.

Women living with HIV-1 (WLHIV) are at higher risk of having an adverse birth outcome, but the underlying mechanism(s) are unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth. We used stored samples from WLHIV and HIV-negative women who had enrolled during pregnancy in the observational Botswana Tshipidi cohort. Written informed consent was obtained from the participants. We measured plasma levels of markers of endothelial activation (soluble vascular adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1] and E-selectin) from samples taken during pregnancy. We compared log10 biomarker levels by maternal HIV status and by the timing of ART initiation (ART prior to conception vs. during pregnancy; ART prior to sample collection vs. no ART prior to sampling) using t-tests and the Kruskal-Wallis rank test. We evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or small for gestational age [SGA]) using univariate and multivariate log-binomial regression controlling for maternal age (continuous) and timing of ART start. We also used generalized linear models (GLM) to evaluate the association between continuous birthweight (in grams) and gestational age (in weeks) and markers of endothelial dysfunction, adjusting for maternal age (continuous) and timing of ART relative to sample collection. Specimens collected before delivery were available for 414 women (372 WLHIV and 42 HIV-negative women), with a median age of 28 years and median gestational age at sample collection of 30 weeks (range 26, 35 weeks). WLHIV had significantly higher median VCAM1 (p = 0.002) than HIV-negative women, but HIV-negative women had higher median ICAM1 (p = 0.01); e-Selectin levels did not differ by maternal HIV status. Women starting ART during pregnancy had higher log10 VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p = 0.02) or after (p = 0.03) ART initiation. However, ICAM1 and e-Selectin did not differ significantly by ART status or ART timing. Ninety-eight women (91 WLHIV and 7 HIV-negative), or 9 (2%) and 89 (22%) included in this study, had a stillborn or SGA baby respectively. Univariate and adjusted analyses did not show significant associations between levels of any of the biomarkers with these adverse birth outcomes. However, lower birthweight (p = 0.03) and lower gestational age at delivery were associated e-Selectin and ICAM (p = 0.008), respectively. Maternal HIV infection and lack of ART (or recent ART initiation) were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. e-Selectin was associated with lower birthweight and every unit increase in log ICAM-1 at delivery was associated with lower gestation age at delivery.

The gut microbiome and early-life growth in a population with high prevalence of stunting

Stunting affects one-in-five children globally and is associated with greater infectious morbidity, mortality and neurodevelopmental deficits. Recent evidence suggests that the early-life gut microbiome affects child growth through immune, metabolic and endocrine pathways. Using whole metagenomic sequencing, we map the assembly of the gut microbiome in 335 children from rural Zimbabwe from 1–18 months of age who were enrolled in the Sanitation, Hygiene, Infant Nutrition Efficacy Trial (SHINE; NCT01824940), a randomized trial of improved water, sanitation and hygiene (WASH) and infant and young child feeding (IYCF). Here, we show that the early-life gut microbiome undergoes programmed assembly that is unresponsive to the randomized interventions intended to improve linear growth. However, maternal HIV infection is associated with over-diversification and over-maturity of the early-life gut microbiome in their uninfected children, in addition to reduced abundance of Bifidobacterium species. Using machine learning models (XGBoost), we show that taxonomic microbiome features are poorly predictive of child growth, however functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predict both attained linear and ponderal growth and growth velocity. New approaches targeting the gut microbiome in early childhood may complement efforts to combat child undernutrition.

Leveraging External Validation Data: The Challenges of Transporting Measurement Error Parameters.

Approaches to address measurement error frequently rely on validation data to estimate measurement error parameters (e.g., sensitivity and specificity). Acquisition of validation data can be costly, thus secondary use of existing data for validation is attractive. To use these external validation data, however, we may need to address systematic differences between these data and the main study sample. Here, we derive estimators of the risk and the risk difference that leverage external validation data to account for outcome misclassification. If misclassification is differential with respect to covariates that themselves are differentially distributed in the validation and study samples, the misclassification parameters are not immediately transportable. We introduce two ways to account for such covariates: (1) standardize by these covariates or (2) iteratively model the outcome. If conditioning on a covariate for transporting the misclassification parameters induces bias of the causal effect (e.g., M-bias), the former but not the latter approach is biased. We provide proof of identification, describe estimation using parametric models, and assess performance in simulations. We also illustrate implementation to estimate the risk of preterm birth and the effect of maternal HIV infection on preterm birth. Measurement error should not be ignored and it can be addressed using external validation data via transportability methods.

Breastfeeding in the first hour of life in Brazilian private hospitals participating in a quality-of-care improvement project

BackgroundThe Baby-Friendly Hospital Initiative’s Step 4 recommends: “support mothers to start breastfeeding as soon as possible after birth”, thus contributing to the reduction of neonatal mortality. The objective of this study is to estimate the prevalence of breastfeeding in the first hour of life in private maternity hospitals participating in the “Adequate Childbirth Project”, a quality-of-care improvement project, and to analyze determinants of this outcome.MethodsSecondary analysis of data collected by the cross-sectional evaluative “Healthy Birth Study”, conducted in 2017 in 12 maternity hospitals participating in the Adequate Childbirth Project, where 4800 mothers were interviewed, and hospital records were observed. Conditions that prevented breastfeeding at birth, such as maternal HIV-infection and newborns’ severe malformations, were excluded. Multiple logistic regression was performed according to a hierarchical theoretical model.ResultsThe prevalence of breastfeeding in the first hour of life was 58% (CI 95% 56.6–59.5%). Lower maternal education (aOR 0.643; CI 95% 0.528–0.782), lower economic status (aOR 0.687; CI 95% 0.504–0.935), cesarean section delivery (ORa 0.649; CI 95% 0.529–0.797), preterm birth (aOR 0.660; CI 95% 0.460–0.948) and non-rooming-in at birth (aOR 0.669; CI 95% 0.559–0.800) were negatively associated with the outcome. Receiving information during prenatal care about the importance of breastfeeding at birth (aOR 2.585; CI 95% 2.102–3.179), being target of the quality-of-care improvement project (aOR 1.273; CI 95% 1.065–1.522), skin-to-skin contact at birth (aOR 2.127; CI 95% 1.791–2.525) and female newborn (aOR 1.194; CI 95% 1.008–1.415) were factors positively associated with the outcome.ConclusionsThe private maternities participating in the Healthy Birth Study showed a good prevalence of breastfeeding in the first hour of life, according to WHO parameters. Prenatal guidance on breastfeeding at birth, being target of the quality-of-care improvement project and skin-to-skin contact at birth contributed to breastfeeding in the first hour of life.

CLINICAL AND ANAMNESTIC FEATURES OF THE NEWBORNS WITH PERINATAL HIV EXPOSURE

Introduction. Maternal HIV infection has many adverse effects, including low birth weight, which is the primary cause of neonatal, infant, and under-five mortality. In the literature, the issue of intrauterine growth restriction (IUGR) in children who were born to HIV-positive mothers is being discussed, and the causes that may be the result of the direct effect of the virus, immunosuppression, or concomitant diseases are being studied. The association between maternal HIV infection and low birth weight (LBW) was not adequately explored and the available studies suggested inconsistent findings. Objective: to analyze the clinical and anamnestic data of the newborns with perinatal HIV exposure and to assess their physical development according to the gestational age and HIV stage of the mother. Material and methods. In order to achieve this goal, 34 medical histories of the patients who had been treated in the neonatal center of Vinnytsya Regional Children's Clinical Hospital from 2015 to 2022 with a diagnosis of perinatal HIV exposure were retrospectively analyzed. Results. According to the results of the study, a third of the children were born prematurely (12 (35 ± 8) %, 95%CI: 27–43 %). Сhildren born to mothers with stage IV of HIV infection had the lowest mean gestational age. When assessing the physical development of newborns according to gestational age, it was established that 9 children ((26 ± 8) %, 95%CI: 18–34 %) were small for gestational age, and 3 children ((9 ± 5) %, 95%CI: 4–14 %) were small-for-date. The lowest body weight values were observed in children born to mothers with stage IV of HIV infection – (1561.42 ± 0.21) g, which significantly differs from the weight of newborns whose mothers had HIV infection of stage I (2550.10 ± 1.51) g and stage II (2646.36 ± 1.69) g, p &lt; 0.05. Conclusions. Among children with perinatal HIV exposure, there is a risk of premature birth with IUGR. Children born to mothers with stage IV HIV infection had significantly lower gestational age and body weight values.

Early Childhood Growth Parameters in South African Children with Exposure to Maternal HIV Infection and Placental Insufficiency.

Maternal HIV exposure and intrauterine growth restriction (IUGR) due to placental insufficiency both carry major risks to early child growth. We compared the growth outcomes of children aged 18 months who had abnormal umbilical artery resistance indices (UmA-RI), as a marker of placental insufficiency, with a comparator group of children with normal UmA-RI during pregnancy, as mediated by maternal HIV infection. The cross-sectional study included 271 children, grouped into four subgroups based on HIV exposure and history of normal/abnormal UmA-RI, using available pregnancy and birth information. Standard procedures were followed to collect anthropometric data, and z-scores computed as per World Health Organization growth standards. Lower length-for-age z-scores (LAZ) were observed in children who were HIV-exposed-uninfected (CHEU) (-0.71 ± 1.23; p = 0.004) and who had abnormal UmA-RI findings (-0.68 ± 1.53; p < 0.001). CHEU with abnormal UmA-RI had lower LAZ (-1.3 ± 1.3; p < 0.001) and weight-for-age z-scores (WAZ) (-0.64 ± 0.92; p = 0.014) compared to the control group. The prevalence of stunting was 40.0% in CHEU with abnormal UmA-RI and 16.0% in CHEU with normal UmA-RI (p < 0.001; p = 0.016, respectively). In conclusion, maternal HIV exposure and placental insufficiency are independent risk factors for childhood stunting, with this risk potentiated when these two risk factors overlap.

Adolescent mothers and their children affected by HIV-An exploration of maternal mental health, and child cognitive development.

Some children born to adolescent mothers may have developmental challenges, while others do not. Research focusing on which children of adolescent mothers are at the highest risk for cognitive delay is still required. Both maternal HIV status and maternal mental health may affect child development. An examination of maternal mental health, especially in the presence of maternal HIV infection may be timely. This study explores the relationship between the mental health of adolescent mothers (comparing those living with and not living with HIV) and the cognitive development performance scores of their children. Additional possible risk and protective factors for poor child development are explored to identify those children born to adolescent mothers who may be at the greatest risk of poor cognitive development. Cross-sectional data utilised within the analyses was drawn from a large cohort of adolescent mothers and their children residing in South Africa. Detailed study questionnaires were completed by adolescent mothers relating to their self and their child and, standardised cognitive assessments were completed by trained researchers for all children using in the Mullen Scales of Early Learning. Chi-square, t-tests (Kruskal Wallis tests, where appropriate), and ANOVA were used to explore sample characteristics and child cognitive development scores by maternal mental health status (operationalised as likely common mental disorder) and combined maternal mental health and HIV status. Multivariable linear regression models were used to explore the relationship between possible risk factors (including poor maternal mental health and HIV) and, child cognitive development scores. The study included 954 adolescent mothers; 24.1% (230/954) were living with HIV, 12.6% (120/954) were classified as experiencing likely common mental disorder. After adjusting for covariates, maternal HIV was found to be associated with reduced child gross motor scores (B = -2.90 [95%CI: -5.35, -0.44], p = 0.02), however, no other associations were identified between maternal likely common mental disorder, or maternal HIV status (including interaction terms), and child cognitive development scores. Sensitivity analyses exploring individual maternal mental health scales identified higher posttraumatic stress symptomology scores as being associated with lower child cognitive development scores. Sensitivity analyses exploring potential risk and protective factors for child cognitive development also identified increased maternal educational attainment as being protective of child development scores, and increased child age as a risk factor for lower development scores. This study addresses a critical evidence gap relating to the understanding of possible risk factors for the cognitive development of children born to adolescent mothers affected by HIV. This group of mothers experience a complex combination of risk factors, including HIV, likely common mental disorder, and structural challenges such as educational interruption. Targeting interventions to support the cognitive development of children of adolescent mothers most at risk may be of benefit. Clearly a basket of interventions needs to be considered, such as the integration of mental health provision within existing services, identifying multiple syndemics of risk, and addressing educational and structural challenges, all of which may boost positive outcomes for both the mother and the child.

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

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. 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. 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. 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). 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.

Incidence and Risk Factors for Low Birthweight and Preterm Birth in Post-Conflict Northern Uganda: A Community-Based Cohort Study.

Background: Annually, an estimated 20 million (13%) low-birthweight (LBW) and 15 million (11.1%) preterm infants are born worldwide. A paucity of data and reliance on hospital-based studies from low-income countries make it difficult to quantify the true burden of LBW and PB, the leading cause of neonatal and under-five mortality. We aimed to determine the incidence and risk factors for LBW and preterm birth in Lira district of Northern Uganda. Methods: This was a community-based cohort study, nested within a cluster-randomized trial, designed to study the effect of a combined intervention on facility-based births. In total, 1877 pregnant women were recruited into the trial and followed from 28 weeks of gestation until birth. Infants of 1556 of these women had their birthweight recorded and 1279 infants were assessed for preterm birth using a maturity rating, the New Ballard Scoring system. Low birthweight was defined as birthweight <2.5kg and preterm birth was defined as birth before 37 completed weeks of gestation. The risk factors for low birthweight and preterm birth were analysed using a multivariable generalized estimation equation for the Poisson family. Results: The incidence of LBW was 121/1556 or 7.3% (95% Confidence interval (CI): 5.4–9.6%). The incidence of preterm births was 53/1279 or 5.0% (95% CI: 3.2–7.7%). Risk factors for LBW were maternal age ≥35 years (adjusted Risk Ratio or aRR: 1.9, 95% CI: 1.1–3.4), history of a small newborn (aRR: 2.1, 95% CI: 1.2–3.7), and maternal malaria in pregnancy (aRR: 1.7, 95% CI: 1.01–2.9). Intermittent preventive treatment (IPT) for malaria, on the other hand, was associated with a reduced risk of LBW (aRR: 0.6, 95% CI: 0.4–0.8). Risk factors for preterm birth were maternal HIV infection (aRR: 2.8, 95% CI: 1.1–7.3), while maternal education for ≥7 years was associated with a reduced risk of preterm birth (aRR: 0.2, 95% CI: 0.1–0.98) in post-conflict northern Uganda. Conclusions: About 7.3% LBW and 5.0% PB infants were born in the community of post-conflict northern Uganda. Maternal malaria in pregnancy, history of small newborn and age ≥35 years increased the likelihood of LBW while IPT reduced it. Maternal HIV infection was associated with an increased risk of PB compared to HIV negative status. Maternal formal education of ≥7 years was associated with a reduced risk of PB compared to those with 0–6 years. Interventions to prevent LBW and PBs should include girl child education, and promote antenatal screening, prevention and treatment of malaria and HIV infections.

Maternal-foetal transfer of severe acute respiratory syndrome coronavirus 2 antibodies among women with and those without HIV infection.

In pregnant women, antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We measured SARS-CoV-2 full-length antispike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and from paired cord-blood samples. Antispike IgG was measured in maternal blood at delivery on the Luminex platform. Cord-blood samples from newborns of women in with detectable antispike IgG were analysed. The IgG geometric mean concentrations (GMCs) and the percentage of cord-blood samples with detectable antispike IgG were compared between WLWHIV and without HIV. A total of 184 maternal and cord-blood pairs were analysed, including 47 WLWHIV and 137 without HIV. There was no difference in antispike GMCs between WLWHIV and without HIV [157 binding antibody units (BAU)/ml vs. 187 BAU/ml; P = 0.17)]. Cord-blood samples from newborns of WLWHIV had lower GMCs compared with those without HIV (143 vs. 205 BAU/ml; P = 0.033). Cord-to-maternal blood antibody ratio was 1.0 and similar between the two HIV groups. In WLWHIV, those who were 30 years old or less had lower cord-to-maternal blood antibody ratio (0.75 vs. 1.10; P = 0.037) and their newborns had lower cord-blood GMCs (94 vs. 194 BAU/ml; P = 0.04) compared with the older women. Independently of maternal HIV infection status, there was efficient transplacental transfer of antispike antibodies. The GMCs in cord-blood from newborns of WLWHIV were lower than those in HIV-unexposed newborns.

Determinants of small for gestational age among HIV exposed infants delivered at the Women and Newborn hospital, Lusaka, Zambia

Objectives: To explore the factors that influence small for gestational age outcome among HIV exposed infants delivered at the Women and Newborn Hospital, Lusaka, Zambia.&#x0D; Materials and Methods: This was a facility-based unmatched case control study nested in the Zambia Preterm Birth Prevention Study (ZAPPS) conducted at the Women and Newborn Hospital in Lusaka district between October 2017 and February 2021. Convenience sampling was used to select all the 53 HIV exposed small for gestational age infants (as cases) and 152 HIV unexposed small for gestational age infants (as controls). An excel data extraction tool was used to extract categorised variables from the ZAPPS data set into Stata version 19. Chi-square test was used to test for association, foetal and maternal variables with a p-value of 0.2 at univariate analyses were entered into a multiple logistic regression model.&#x0D; Results: The proportion of SGA, though not statistically significant, was found to be 19.9% among the HIV exposed infants compared to 17.3% in the unexposed group (p= 0.34). More than three quarters of participants in both the HIV positive arm (71.7%) and HIV negative arm (81.3%) were aged between 20-35 years. On multivariate analysis, Maternal chronic illness [AOR: 4.39, 95% CI: (1.66 - 11.6), p=0.003] and spontaneous preterm delivery [AOR: 1.58, 95% CI: (1.02 - 2.46), p=0.040] had a strong association with small for gestational age. Tertiary Level of education [AOR: 0.45, (0.24 - 0.85), p=0.014] was found to be significantly protective against small for gestational age. Maternal factors such as married status [AOR: 0.74, (0.48 - 1.13), p=0.164], secondary level of education [AOR: 0.82, (0.54 - 1.24), p=0.743], history of stillbirth [AOR: 1.31, (0.92-1.85), p=0.123] and the Mid-upper arm circumference [AOR: 0.96, (0.92-1.00), p=0.064] was not associated with small for gestational age. &#x0D; Conclusion: There was no association between maternal HIV infection and SGA. Maternal chronic illness and spontaneous preterm birth increase the odds of SGA outcome while tertiary level of education is protective. Further research is needed to broaden the evidence base for addressing small for gestational age as a gateway to improve perinatal mortality, and for policy implementers to devise cost-effective and sustainable ways of reaching the at-risk population.

Determinants of small for gestational age among HIV exposed infants delivered at the Women and Newborn hospital, Lusaka, Zambia

Objectives: To explore the factors that influence small for gestational age outcome among HIV exposed infants delivered at the Women and Newborn Hospital, Lusaka, Zambia.&#x0D; Materials and Methods: This was a facility-based unmatched case control study nested in the Zambia Preterm Birth Prevention Study (ZAPPS) conducted at the Women and Newborn Hospital in Lusaka district between October 2017 and February 2021. Convenience sampling was used to select all the 53 HIV exposed small for gestational age infants (as cases) and 152 HIV unexposed small for gestational age infants (as controls). An excel data extraction tool was used to extract categorised variables from the ZAPPS data set into Stata version 19. Chi-square test was used to test for association, foetal and maternal variables with a p-value of 0.2 at univariate analyses were entered into a multiple logistic regression model.&#x0D; Results: The proportion of SGA, though not statistically significant, was found to be 19.9% among the HIV exposed infants compared to 17.3% in the unexposed group (p= 0.34). More than three quarters of participants in both the HIV positive arm (71.7%) and HIV negative arm (81.3%) were aged between 20-35 years. On multivariate analysis, Maternal chronic illness [AOR: 4.39, 95% CI: (1.66 - 11.6), p=0.003] and spontaneous preterm delivery [AOR: 1.58, 95% CI: (1.02 - 2.46), p=0.040] had a strong association with small for gestational age. Tertiary Level of education [AOR: 0.45, (0.24 - 0.85), p=0.014] was found to be significantly protective against small for gestational age. Maternal factors such as married status [AOR: 0.74, (0.48 - 1.13), p=0.164], secondary level of education [AOR: 0.82, (0.54 - 1.24), p=0.743], history of stillbirth [AOR: 1.31, (0.92-1.85), p=0.123] and the Mid-upper arm circumference [AOR: 0.96, (0.92-1.00), p=0.064] was not associated with small for gestational age. &#x0D; Conclusion: There was no association between maternal HIV infection and SGA. Maternal chronic illness and spontaneous preterm birth increase the odds of SGA outcome while tertiary level of education is protective. Further research is needed to broaden the evidence base for addressing small for gestational age as a gateway to improve perinatal mortality, and for policy implementers to devise cost-effective and sustainable ways of reaching the at-risk population.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.

The Impact of Maternal Syphilis and Associated Factors on HIV Vertical Transmission.

Maternal syphilis may increase HIV vertical transmission or it may be a marker of other risk factors. In a Brazilian historical series, HIV vertical transmission risk was higher in newborns exposed to maternal syphilis-HIV co-infection than in newborns exposed to maternal HIV infection alone. Maternal syphilis was a risk factor for HIV vertical transmission independent of education and prenatal visits but not independent of maternal elevated HIV viral loads or inadequate maternal antiretroviral treatment.

Microbial antigen in human milk: a natural vaccine?

Microbial antigen in human milk: a natural vaccine?

Effect of Maternal HIV Infection on Infant Development and Outcomes

Early life represents a period of profound immunological development and heightened susceptibility to infectious disease. The developmental trajectory over this period is influenced by a number of factors, including gestational age, mode of delivery, mode of feeding, microbiome development, and environmental exposures. There are also several maternal factors that have been shown to have a negative effect on both immune development and clinical outcomes, including maternal infection and inflammation. Studies have associated maternal HIV infections with an increase in infectious morbidity and mortality and decreased growth measures among their HIV-exposed uninfected (HEU) offspring. Among HEU infants, socioeconomic factors, maternal nutrition, maternal viral load, and maternal inflammation have also all been associated with impaired infant immune status and clinical outcomes. However, the mechanisms underlying these observations have not been elucidated and, apart from measures of disease severity, few studies thus far have undertaken in-depth assessments of maternal health status or immune function during gestation and how these influence developmental outcomes in their infants. The lack of a mechanistic understanding of how these gestational influences affect infant outcomes inhibits the ability to design and implement effective interventions. This review describes the current state of research into these mechanisms and highlights areas for future study include; how HIV infection causes the inflammatory trajectory to deviate from normal gestation, the mechanism(s) by which in utero exposure to maternal inflammation influences infant immune development and clinical outcomes, the role of socioeconomic factors as an inducer of maternal stress and inflammation, and maternal nutrition during gestation.