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.

Contact allergens in African countries: A review of published patch test studies.

Only few studies on contact allergy in African countries have been published. The aim of the present study was to provide an overview of the most common contact allergens identified by the use of patch tests in African countries based on a review of the existing literature. A total of twenty-four publications from eight African countries were initially identified by search in PubMed. The abstracts and method sections were screened, and 15 studies in which patch tests were actually used to identify the allergen causing the allergic contact dermatitis (ACD) were finally selected. Nickel, cobalt, chromium, fragrance mix and p-tert-butylphenol-formaldehyde resin were the dominating contact allergens responsible for 40%-90% of the positive patch test reactions. This study indicates that a targeted effort directed towards prevention, avoidance and regulation of reliably identified contact allergens could reduce the disease burden of ACD considerable in some African countries.

Endothelial protein C receptor binding induces conformational changes to severe malaria-associated group A PfEMP1.

Severe Plasmodium falciparum malaria infections are caused by microvascular sequestration of parasites binding to the human endothelial protein C receptor (EPCR) via the multi-domain P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands. Using cryogenic electron microscopy (Cryo-EM) and PfEMP1 sequence diversity analysis, we found that group A PfEMP1 CIDRα1 domains interact with the adjacent DBLα1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLα1 domain is displaced, and the EPCR-binding helix of CIDRα1 is turned, kinked, and twisted to reach a rearranged, stable EPCR-bound conformation. The unbound conformation and the required transition to the EPCR-bound conformation may represent a conformational masking mechanism of immune evasion for the PfEMP1 family.

In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria.

Severe malaria is mostly caused by Plasmodium falciparum, resulting in considerable, systemic inflammation and pronounced endothelial activation. The endothelium forms an interface between blood and tissue, and vasculopathy has previously been linked with malaria severity. We studied the extent to which the endothelial glycocalyx that normally maintains endothelial function is involved in falciparum malaria pathogenesis by using incident dark-field imaging in the buccal mucosa. This enabled calculation of the perfused boundary region, which indicates to what extent erythrocytes can permeate the endothelial glycocalyx. The perfused boundary region was significantly increased in severe malaria patients and mirrored by an increase of soluble glycocalyx components in plasma. This is suggestive of a substantial endothelial glycocalyx loss. Patients with severe malaria had significantly higher plasma levels of sulfated glycosaminoglycans than patients with uncomplicated malaria, whereas other measured glycocalyx markers were raised to a comparable extent in both groups. In severe malaria, the plasma level of the glycosaminoglycan hyaluronic acid was positively correlated with the perfused boundary region in the buccal cavity. Plasma hyaluronic acid and heparan sulfate were particularly high in severe malaria patients with a low Blantyre coma score, suggesting involvement in its pathogenesis. In vivo imaging also detected perivascular hemorrhages and sequestering late-stage parasites. In line with this, plasma angiopoietin-1 was decreased while angiopoietin-2 was increased, suggesting vascular instability. The density of hemorrhages correlated negatively with plasma levels of angiopoietin-1. Our findings indicate that as with experimental malaria, the loss of endothelial glycocalyx is associated with vascular dysfunction in human malaria and is related to severity.

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.