Do WHO criteria for gestational diabetes fit a rural population in Tanzania? - A follow-up study assessing mother and child health six years after a pregnancy diagnosed with gestational diabetes.

AIMS AND METHODS: In low- and middle- income countries (LMICs) consequences of gestational diabetes (GDM) is understudied. Using a prospective cohort of mothers (n = 197)and children (n = 251), from rural north-eastern Tanzania, we assessed prediabetes and type 2 diabetes (T2D) prevalence six years after a pregnancy with/without GDM. RESULTS: The prevalence of prediabetes (49.4 % vs. 46.4 %) orT2D (20.0 % vs. 16.1 %), p ≥ 0.36, based on fasting plasma glucose (FPG) or HbA1clevels (prediabetes: 16.9 % vs. 13.8 % and T2D 1.2 % vs. 0 %, p = 0.47), andcardio-metabolic health parameters,weresimilar between women with/without previous GDM. These results were supported by similar perinatal outcomes and child health at follow-up.The overall prevalence ofprediabetes/T2D was high, but no differences in other cardio-metabolic risk markers were observed in women with prediabetes/T2D compared to women with normal glucose tolerance. CONCLUSIONS: Despite high prevalence of GDM amongTanzanian women, the diagnosis was not associated with adverse pregnancy outcomes, nor with increased risk of prediabetes or T2D at follow-up. FPG and HbA1c may be poor markers for diabetes in this population, and further follow-up studies with longer time intervals are warranted to evaluate which GDM diagnostic criteria are most optimal for women in rural Tanzania and similar LMIC settings.

Anaemia in the first trimester and poor physiological plasma expansion during pregnancy negatively impact foetal weight and newborn anthropometrics: An observational cohort study in Tanzania.

OBJECTIVES: Anaemia during pregnancy is a major health challenge affecting pregnancy outcome worldwide. The objectives of this study were to investigate the impact of severe-moderate anaemia in the first trimester, as well as changes in haemoglobin during pregnancy among non-anaemic women, on foetal weight, placental blood flow and newborn anthropometrics. METHODS: In a prospective cohort study, 346 women residing in rural Tanzania were followed throughout pregnancy with serial ultrasound and newborn anthropometrics assessed within 24 h of delivery. Associations between placental blood flow, foetal weight and newborn anthropometrics with either first trimester severe-moderate anaemia (haemoglobin≤9.5 g/dL) or changes in haemoglobin from the first to the third trimester among non-anaemic women, were assessed by mixed model regression and multiple linear regression, adjusting for maternal and foetal co-variables. Foetal weights and birthweight were converted to z-scores using a population based sex-specific weight reference. RESULTS: Severe-moderate anaemia in the first trimester was associated with significantly reduced foetal weight z-scores (adjusted mean difference (aMD) -0.44 (95% CI -0.81, -0.07)) and newborn anthropometric indices (birth weight z-score aMD -0.55 (-0.9, -0.13), abdominal circumference aMD -11 mm (95% CI -20, -3)). There were no association between first trimester severe-moderate anaemia and placental blood flow. Among women who were non-anaemic in the first trimester, women with the least reduction in haemoglobin (Δ ≥ -0.3 g/dL) delivered significantly smaller newborns (birthweight z-score aMD -0.55 (-0.91, -0.20), abdominal circumference aMD -10 mm (95% CI -17, -3), compared to women with the greatest reduction (Δ haemoglobin ≤ -1.4 g/dL)). CONCLUSIONS: Severe-moderate anaemia in early pregnancy was associated with smaller newborn anthropometrics which was reflected in smaller mean foetal weights in the second and third trimester. Furthermore, among women who were non-anaemic in the first trimester, there was an association between smaller newborn anthropometrics and limited haemoglobin decrease during pregnancy, possibly reflecting insufficient plasma expansion.

Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA.

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria.

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.

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.