Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study.

OBJECTIVES: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. METHODS: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. RESULTS: In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% confidence interval]: malaria = -0.18 [-0.31,-0.04], P = 0.01; STIs/RTIs = -0.14 [-0.26,-0.03], P = 0.01; both = -0.20 [-0.33,-0.07], P = 0.003). Paucigravidae experienced the greatest impact. CONCLUSION: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

High anti-SARS-CoV-2 seroprevalence among unvaccinated mother-child pairs from a rural setting in north-eastern Tanzania during the second wave of COVID-19.

Background: The reported infection rates and burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in low- and middle-income countries, including those in sub-Saharan Africa, are relatively low compared to the rates and burden in Europe and America, partly due to limited testing capability. Unlike many countries, Tanzania has implemented neither mass screening nor restrictive measures such as lockdowns to date. The prevalence of SARS-CoV-2 infection in rural mainland Tanzania is largely unknown. Methods: A cross-sectional study was conducted between April and October 2021 to assess the anti-SARS-CoV-2 seroprevalence among mother-child pairs (n = 634 children, n = 518 mothers) in a rural setting in north-eastern Tanzania. Results: A very high prevalence of anti-SARS-CoV-2 antibody titres was found, with seroprevalence rates ranging from 29% among mothers and 40% among children, with a dynamic peak in seropositivity incidence at the end of July/early August being revealed. Significant differences in age, socioeconomic status, and body composition were associated with seropositivity in mothers and children. No significant associations were observed between seropositivity and comorbidities, including anaemia, diabetes, malaria, and HIV. Conclusions: The transmission of SARS-CoV-2 in a rural region of Tanzania during 2021 was high, indicating a much higher infection rate in rural Tanzania compared to that reported in the UK and USA during the same period. Ongoing immune surveillance may be vital to monitoring the burden of viral infection in rural settings without access to molecular genotyping, where the load of communicable diseases may mask COVID-19. Surveillance could be implemented in tandem with the intensification of vaccination strategies.

Mapping the Cord Blood Transcriptome of Pregnancies Affected by Early Maternal Anemia to Identify Signatures of Fetal Programming.

CONTEXT: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mothers and children. Offspring of women with EP anemia often have low birth weight, which increases risk for cardiometabolic diseases, including type 2 diabetes (T2D), later in life. OBJECTIVE: We aimed to elucidate mechanisms underlying developmental programming of adult cardiometabolic disease, including epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth. METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEGs) in UCB exposed to maternal EP anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function. RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming, which included the birth weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL, which potentially influence beta-cell development. Insulin levels were lower in EP anemia-exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of mothers with EP anemia. CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.

High Prevalence of Gestational Diabetes Mellitus in Rural Tanzania-Diagnosis Mainly Based on Fasting Blood Glucose from Oral Glucose Tolerance Test.

Gestational diabetes mellitus (GDM) is associated with poor pregnancy outcomes and increased long-term risk of metabolic diseases for both mother and child. In Tanzania, GDM prevalence increased from 0% in 1991 to 19.5% in 2016. Anaemia has been proposed to precipitate the pathogenesis of GDM. We aimed to examine the prevalence of GDM in a rural area of Tanzania with a high prevalence of anaemia and to examine a potential association between haemoglobin concentration and blood glucose during pregnancy. The participants were included in a population-based preconception, pregnancy and birth cohort study. In total, 538 women were followed during pregnancy and scheduled for an oral glucose tolerance test (OGTT) at week 32-34 of gestation. Gestational diabetes mellitus was diagnosed according to the WHO 2013 guidelines. Out of 392 women screened, 39% (95% CI: 34.2-44.1) had GDM, the majority of whom (94.1%) were diagnosed based solely on the fasting blood sample from the OGTT. No associations were observed between haemoglobin or ferritin and glucose measurements during pregnancy. A very high prevalence of GDM was found in rural Tanzania. In view of the laborious, costly and inconvenient OGTT, alternative methods such as fasting blood glucose should be considered when screening for GDM in low- and middle-income countries.

Anemia in late pregnancy induces an adaptive response in fetoplacental vascularization.

INTRODUCTION: Anemia during pregnancy may compromise fetal and newborn's health, however, little is known about how and when the fetoplacental vascularization is most vulnerable to anemia. METHODS: Using systematic and isotropic uniform random sampling, placental samples were collected from 189 placentas in a cohort study of Tanzanian women whose hemoglobin concentration was measured throughout pregnancy. Fetoplacental vessels and villi were defined as exerting either a transport or diffusion function. The vascularization patterns for transport and diffusion vessels and villi were assessed by stereology. Blood vessel length, surface area and diffusion distance as well as placental villi volume were calculated. RESULTS: Anemia from a gestational age of 23 weeks was significantly associated with increased fetoplacental vascularization in vessels and villi compared to women who were non-anemic throughout pregnancy. Transport surface vessel area: 0.31 m2 [95% CI: 0.18-0.55], P = 0.01; Transport villi volume 19.8 cm3 [95% CI: 6.37-33.2], P = 0.004, Transport vessel diameter 7.23 µm [95% CI: 1.23-13.3], P = 0.02. Diffusion vessel surface: 3.23 m2 [95% CI: 1.55-4.91], P < 0.001 and diffusion villi volume: 29.8 cm3 [95% CI: 10.0-49.5], P = 0.003). Finally, all the measured transport vessel and villi significantly parameters and diffusion vessel surface, vessel diameter and diffusion distance were associated with birth weight. DISCUSSION: Increased fetoplacental vascularization related to anemia from a gestational age of 23 weeks in pregnancy together with the association between fetoplacental vascularity and birth weight suggest that the timing of anemia determines the effect on fetoplacental vascularization and underlines the clinical relevance for proper development of fetoplacental vasculature.

Anthropometric measurements can identify small for gestational age newborns: a cohort study in rural Tanzania.

BACKGROUND: Small-for-gestational-age (SGA) is associated with increased neonatal mortality and morbidity. In low and middle income countries an accurate gestational age is often not known, making the identification of SGA newborns difficult. Measuring foot length, chest circumference and mid upper arm circumference (MUAC) of the newborn have previously been shown to be reasonable methods for detecting low birth weight (< 2500 g) and prematurity (gestational age <  37 weeks). The aim of this study was to investigate if the three anthropometric measurements could also correctly identify SGA newborns. METHODS: In the current study from a rural area of northeastern Tanzania, 376 live newborns had foot length, chest circumference, and MUAC measured within 24 h of birth. Gestational age was estimated by transabdominal ultrasound in early pregnancy and SGA was diagnosed using a sex-specific weight reference chart previously developed in the study area. Receiver operating characteristic curves were generated for each of the anthropometric measurements and the area under the curve (AUC) compared. Operational cutoffs for foot length, chest circumference, and MUAC were defined while balancing as high as possible sensitivity and specificity for identifying SGA. Positive and negative predictive values (PPV and NPV) were then calculated. RESULTS: Of the 376 newborns, 68 (18.4%) were SGA. The AUC for detecting SGA was 0.78 for foot length, 0.88 for chest circumference, and 0.85 for MUAC. Operational cut-offs to detect SGA newborns were defined as ≤7.7 cm for foot length, ≤31.6 cm for chest circumference and ≤ 10.1 cm for MUAC. Foot length had 74% sensitivity, 69% specificity, PPV of 0.35 and NPV of 0.92 for identifying SGA. Chest circumference had 79% sensitivity, 81% specificity, PPV of 0.49 and NPV of 0.95 for identifying SGA. Finally, MUAC had 76% sensitivity, 77% specificity, PPV of 0.43 and NPV of 0.94 for identifying SGA. CONCLUSION: In a setting with limited availability of an accurate gestational age, all three methods had a high NPV and could be used to rule out the newborn as being SGA. Overall, chest circumference was the best method to identify SGA newborns, whereas foot length and MUAC had lower detection ability. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02191683 ). Registered 2 July 2014.

Preconceptional factors associated with haemoglobin concentration in early pregnancy: a community-based cohort study in rural northeastern Tanzania.

OBJECTIVE: Maternal anaemia in early pregnancy is associated with poor pregnancy outcomes. Furthermore, preconceptional health can influence the health during pregnancy. The aim of this study was to investigate which preconceptional factors were associated with haemoglobin (Hb) concentration in early pregnancy. METHODS: In Tanzania, 226 women were followed at preconception and during early pregnancy. Red blood cell (RBC) morphology, serum micronutrient concentration, demographic characteristics and health status were assessed in preconception and in early pregnancy. The association between preconceptional factors and Hb concentration in early pregnancy was investigated using simple and multiple linear regression analyses stratified by preconceptional anaemia status. RESULTS: Mean Hb was 123 and 119 g/l before conception and during early pregnancy (median gestational age 53 days) respectively. Preconceptional mid-upper arm circumference (MUAC) (adjusted coefficient (AC) 0.35 95% CI 0.9-0.61) and preconceptional Hb concentration (AC 0.45 95% CI 0.36-0.54) were positively associated with early pregnancy Hb concentration, whereas preconceptional microcytic hypochromic RBC morphology (AC -6.00 95% CI -9.56 to -2.44) was negatively associated with early pregnancy Hb concentration. In addition, treatment of preconceptional malaria was positively associated with early pregnancy Hb concentration (AC 6.45 95% CI 0.74-12.2) among women with preconceptional anaemia. In contrast, among preconceptional non-anaemic women, only preconceptional Hb concentration and medium socio-economic status was positively associated with early pregnancy Hb concentration. CONCLUSIONS: Mid-upper arm circumference (MUAC) and Hb measurements in preconception can help to detect women at increased risk of low Hb concentration in early pregnancy.

OBJECTIF: L'anémie maternelle en début de grossesse est associée à de mauvais résultats de grossesse. En outre, la santé préconceptionnelle peut influer sur la santé pendant la grossesse. Le but de cette étude était d'investiguer les facteurs préconceptionnels associés à la concentration d'hémoglobine (Hb) en début de grossesse. MÉTHODES: En Tanzanie, 226 femmes ont été suivies avant la conception et durant le début de la grossesse. La morphologie des globules rouges (GR), la concentration sérique en micronutriments, les caractéristiques démographiques et l'état de santé ont été évalués avant la conception et durant le début de la grossesse. L'association entre les facteurs préconceptionnels et la concentration d'Hb au début de la grossesse a été investiguée en utilisant des analyses de régression linéaire simples et multiples stratifiées selon le statut d'anémie préconceptionnelle. RÉSULTATS: Les concentrations moyennes d'Hb étaient respectivement de 123 g/L et de 119 g/L avant la conception et en début de grossesse (âge gestationnel médian: 53 jours). Le périmètre brachial (PB) préconceptionnel (coefficient ajusté (AC): 0.35; IC 95%: 0.9 à 0.61) et la concentration préconceptionnelle d'Hb (AC: 0.45; IC 95%: 0.36 à 0.54) étaient positivement associés à la concentration d'Hb au début de la grossesse, alors que la morphologie hypochrome microcytaire des GR préconceptionnelle (AC: −6.00; IC 95%: −9.56 à −2.44) était négativement associée à la concentration d'Hb en début de grossesse. De plus, le traitement du paludisme préconceptionnel était positivement associé à la concentration d'Hb au début de la grossesse (AC: 6.45; IC 95%: 0.74 à 12.2) chez les femmes souffrant d'anémie préconceptionnelle. En revanche, chez les femmes non anémiques en préconception, seule la concentration d'Hb préconceptionnelle et le statut socioéconomique moyen présentaient une association positive avec la concentration d'Hb en début de grossesse. CONCLUSIONS: Les mesures du PB et de la concentration d'Hb avant la conception peuvent aider à détecter les femmes à risque accru de faible concentration d'HB en début de grossesse.