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Background: Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens.Methods: We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy.Results: Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03-1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55-.93).Conclusions: With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes. [ABSTRACT FROM AUTHOR]

Background: Two billion people in low- and middle-income countries (LMICs) are deficient in key nutrients. Nutritional deficiencies worsen during pregnancy, causing adverse outcomes for the mother and the fetus, with consequences after pregnancy. These effects may be mitigated by providing micronutrient supplementation to women during pregnancy and lactation. However, the effects of micronutrient supplementation on the nutritional status of pregnant and lactating women and that of their infants remain largely unclear in LMICs. Objective: The purpose of this systematic review and meta-analysis is to determine the effects of single, double, or multiple micronutrient supplements during pregnancy or lactation on maternal and infant nutritional status in LMICs. Methods: Randomized controlled trials of single, double, or combinations of micronutrients assessing effects on the maternal (serum, plasma, and breastmilk) and infant (serum and plasma) nutritional status will be included. MEDLINE (through PubMed), EMBASE, CENTRAL (through Cochrane Library), and the World Health Organization (WHO) library database will be used to identify relevant published studies, starting from the inception of each database until February 28, 2022. The Cochrane Risk of Bias Tool will be used to assess the risk of bias in the included studies. The selection of studies, data extraction, and risk of bias assessment will be carried out independently by 2 reviewers. A narrative summary will be provided of all the included studies. Meta-analyses will be performed whenever possible, and the heterogeneity of effects will be evaluated using I², subgroup analyses, and metaregression. The certainty of the evidence for each outcome will be assessed using the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. Results: We will conduct meta-analyses using Stata software (version 16, StataCorp) and present both a narrative and systematic summary of all studies included in this review in text and table form. For continuous outcomes, effect estimates will be expressed as mean differences and standardized mean differences, while for binary outcomes, they will be expressed as risk ratios, rate ratios, hazards ratios, or odds ratios, all with 95% CIs and comparing the intervention group with the control group. When studies for an outcome are adequately consistent with respect to intervention, comparator, and definition of the outcome, a random-effects, inverse variance-weighted meta-analysis will be conducted. We will provide a narrative synthesis for outcomes with insufficient data or extreme heterogeneity. Conclusions: This review will provide evidence upon which to base policy and programming for women in LMICs to supplement micronutrients in pregnancy and lactation. Detailed results disaggregated by variables such as maternal age, sex of infant, duration, and dose of intervention may also help policy makers, researchers, practitioners, and government agencies to adopt more effective maternal and child health policies and programs in LMICs. The review will also identify any gaps in the existing evidence. Trial Registration: PROSPERO CRD42022308715; https://tinyurl.com/y33cxekr. International Registered Report Identifier (IRRID): PRR1-10.2196/40134 [ABSTRACT FROM AUTHOR]

Some evidence suggests that aflatoxin may contribute to the high prevalence of stunting observed in low‐income countries. Whereas several studies have been conducted in West Africa, fewer exist in East Africa and even fewer in nonagricultural contexts. We analyzed serum samples from 400 iron‐replete, nonanemic pregnant women from a cohort in Dar es Salaam, Tanzania to determine the extent and magnitude of exposure to aflatoxin and to study the relationship between levels of aflatoxin exposure in utero and infant birth and growth outcomes. Ninety‐nine percent of women had detectable concentrations of aflatoxin B1‐lysine (AFB1‐lysine), with a median level of 1.4‐pg/mg albumin, indicating a much lower level compared to studies of rural populations in sub‐Saharan Africa. Our results do not show a statistically significant relationship between AFB1‐lysine levels and birth weight, small for gestational age, or prematurity. We observe a small statistically significant reduction in gestational age at delivery (0.47 weeks; 95% CI: −0.86, −0.07) as the natural log of AFB1‐lysine levels increases by 1 unit of pg/mg of albumin, after controlling for potential confounders. Among a nonrandom set of infants who had measurements for placental weight, haemoglobin at delivery, and follow‐up z‐score measurements, we find no association between aflatoxin plasma concentrations and these variables. These findings suggest a high prevalence of chronic low‐level exposure to aflatoxin, though its effect on birth outcomes in this population remains unclear. Our research adds to a growing body of literature finding mixed associations between aflatoxins on pregnancy outcomes and child growth. [ABSTRACT FROM AUTHOR]

Background: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited.Objective: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania.Methods: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin.Results: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 μg/L, 95% CI: 1.84, 29.11 μg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations.Conclusions: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation. [ABSTRACT FROM AUTHOR]

Highlights • About one tenth of pregnant women had acute rubella infections. • IgM seropositivity decreased significantly with gestation age. • More than ¾ of IgM seropositive women had adverse pregnancy outcomes. • One tenth of IgM positive women delivered neonates with CRS. Abstract Objective This study investigated the adverse pregnancy outcomes among pregnant women with acute Rubella infections in the city of Mwanza, Tanzania. Methods A longitudinal study was conducted between 2014 and 2016 among pregnant women attending antenatal clinics. Women were screened for Rubella IgG and IgM antibodies using enzyme immunoassay (EIA). IgM seropositive pregnant women were followed up until the end of the pregnancy to determine Congenital Rubella Syndrome, congenital infections and other pregnancy outcomes. Results The median age of 685 enrolled pregnant women was 23 (IQR: 19–27) years. A total of 629(91.8%) were Rubella IgG seropositive while 61 (8.9%) were IgM seropositive. The IgM seropositivity was found to decrease significantly from first trimester to third trimester, p < 0.001. Forty six (83.6%) of 55 Rubella IgM seropositive women had adverse pregnancy outcomes and 6 (10.9%) delivered neonates with CRS, making the overall incidence of CRS to be 6/685 (0.87%). First trimester IgM seropositive women had significantly higher adverse pregnancy outcomes than those in second/third trimesters (70.4% vs. 35.7, p = 0.01). Conclusion There is one case of CRS in every 100 pregnancies necessitating additional strategies to reach a goal of elimination of CRS in developing countries. [ABSTRACT FROM AUTHOR]

Introduction: Placental vascular development, and ultimately placental weight, is essential to healthy fetal development. Here, we examined placental weight in a cohort of Tanzanian women in association with angiogenic proteins known to regulate placental vascular development and perinatal outcomes. Methods: A total of n = 6579 women with recorded placental weight were included in this study. The relative risk of adverse perinatal outcomes (Apgar score, death, asphyxia, respiratory distress, seizures, pneumonia and sepsis) was compared between placental weight in the bottom and top 10th percentiles. We quantified angiogenic mediators (Ang-1, Ang-2, VEGF, PGF and sFlt-1) in plasma samples (n = 901) collected between 12 to 27 weeks of pregnancy using ELISA and assessed the relative risk of placental weight in the bottom and top 10th percentiles by protein levels in quartiles. Results: Women with Ang-2 levels in the highest quartile had an increased relative risk of placental weight in the bottom 10th percentile (RR = 1.45 (1.10, 1.91), p = 0.01). Women with VEGF-A (RR = 0.73 (0.56, 0.96), p = 0.05) and PGF (RR = 0.58 (0.44, 0.72), p = 0.002) in the highest quartile had a reduced relative risk of placental weight in the bottom 10th percentile. Low placental weight (in bottom 10th percentile) was associated with an increased relative risk of Apgar score of <7 at 1 minute (RR = 2.31 (1.70, 3.13), p = 0.001), at 5 minutes (RR = 3.53 (2.34, 5.33), p = 0.001), neonatal death (RR = 5.02 (3.61, 7.00), p = 0.001), respiratory distress (RR = 4.80(1.71, 13.45), p = 0.001), and seizures (RR = 4.18 (1.16, 15.02), p = 0.03). Discussion: The association between low placental weight and risk of adverse perinatal outcomes in this cohort suggests that placental weight could serve as a useful indicator, providing additional insight into high-risk pregnancies and identifying neonates that may require additional monitoring and follow-up. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes.Objective: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women.Methods: We identified 600 iron-deficient (serum ferritin ≤12 μg/L) pregnant women, aged 18-45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 μg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 μg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes.Results: There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 μg/L; 95% CI: 49.5, 58.8 μg/L), and serum hepcidin (14.0 μg/L; 95% CI: 12.4, 15.6 μg/L) and decreases in sTfR (-1.7 mg/L; 95% CI: -2.0, -1.3 mg/L) and ZPP (-17.8 mmol/L; 95% CI: -32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline - up to 12.1 g/L and 14.5 μg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76).Conclusion: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits. [ABSTRACT FROM AUTHOR]

ObjectiveAnaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania.DesignProspective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period.SettingAntenatal clinics in Dar es Salaam, Tanzania.SubjectsParticipants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995–1997).ResultsMalaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1·4 and 2·3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period.ConclusionsParasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings – particularly during the pre- and postpartum periods. [ABSTRACT FROM PUBLISHER]

Objective: We assessed the effect of prenatal and peripartum antibiotics on maternal morbidity and mortality among HIV-infected and uninfected women.Methods: A multicenter trial was conducted at clinical sites in 4 Sub-Saharan African cities: Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. A total of 1558 HIV-infected and 271 uninfected pregnant women who were eligible to receive both the prenatal and peripartum antibiotic/placebo regimens were enrolled. Pregnant women were interviewed at 20-24 weeks of gestation and a physical examination was performed. Women were randomized to receive either antibiotics or placebo. At the 26-30 week visit, participants were given antibiotics or placebo to be taken every 4 hours beginning at the onset of labor and continuing after delivery 3 times a day until a 1-week course was completed. Logistic regression and Cox proportional hazards models were used.Results: There were no significant differences between the antibiotic and placebo groups for medical conditions, obstetric complications, physical examination findings, puerperal sepsis, and death in either the HIV-infected or the uninfected cohort.Conclusion: Administration of study antibiotics during pregnancy had no effect on maternal morbidity and mortality among HIV-infected and uninfected pregnant women. [ABSTRACT FROM AUTHOR]

Background: In observational studies, the zinc status of HIV infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women. Objective: We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women. Design: Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment. Results: We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality betweenwomen in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x × SD: 11.5 × 17.9 g/L) than in the placebo group (15.2×18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4+, CD8+, or CD3+ cell counts during the follow-up period. Conclusion: Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women. [ABSTRACT FROM AUTHOR]

Objective Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania. Design Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period. Setting Antenatal clinics in Dar es Salaam, Tanzania. Subjects Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995–1997). Results Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1·4 and 2·3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period. Conclusions Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings – particularly during the pre- and postpartum periods.

Women who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). We conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D 3 supplementation. Depressive symptoms were assessed at 12–27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. Approximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. Depression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. Our findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy. • Two out of three women had symptoms consistent with major depressive disorder. • More recent initiation of ART associated with greater risk of antenatal depression • No association of antenatal depression with adverse birth outcomes • Magnitude of the association not modified by the timing of ART initiation [ABSTRACT FROM AUTHOR]

We examined the effect of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, á- and â-carotene (AC and BC), and á-, ä-, and ã-tocopherols (AT, DT, and GT) among 643 HIV-infected Tanzanian women. Women were randomly assigned to one of four daily oral supplements: vitamin A + BC (VA+BC); vitamins B, C, E (MV); MV + VA+BC; or placebo. Concentrations of breast milk nutrients were determined by HPLC at birth and every 3 mo thereafter. At birth, supplementation with VA+BC significantly increased the concentrations of retinol, AC, and BC by 4799, 84, and 1791 nmol/L, respectively, compared to no VA+BC (all p<0.0001). MV supplementation had no effect on AT or DT but significantly decreased GT by an average of 522 nmol/L (p=0.003). The concentrations of all nutrients decreased significantly after birth irrespective of supplementation. Retinol, AC, and BC remained significantly higher among those receiving VA+BC at 3, 6, and 12 mo compared to no VA+BC. AT was significantly higher and GT lower among women receiving MV compared to no MV at 3, 6, and 12 mo. There were no significant interactions between treatment arms. Daily supplementation with VA+BC increases retinol and carotenoid concentrations in breast milk of HIV-infected women. MV supplementation increases AT but decreases GT concentrations in breast milk. [ABSTRACT FROM AUTHOR]