Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

Background

Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Methods

From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.

Results

166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).

Conclusions

Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup.     

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1

BackgroundPatients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients.MethodsConcentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia).ResultsCRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients.ConclusionsPredomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.     

Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants

Objective

Anemia in infancy is a global public health problem. We evaluated the relative contributions of iron deficiency and inflammation to infant anemia.

Methods

We measured plasma hepcidin, ferritin, soluble transferrin receptor (sTfR), alpha-1-acid glycoprotein and C-reactive protein (CRP) by ELISA on archived plasma from 289 HIV-unexposed anemic or non-anemic Zimbabwean infants at ages 3mo, 6mo and 12mo. Among anemic infants, we determined the proportion with iron-deficiency anemia (IDA) and anemia of inflammation (AI). We undertook regression analyses of plasma hepcidin and anemia status, adjusting for sex, age and birthweight.

Results

Anemic infants at 3mo were more stunted and had higher CRP (median 0.45 vs 0.21mg/L; P = 0.037) and hepcidin (median 14.7 vs 9.7ng/mL; P = 0.022) than non-anemic infants, but similar levels of ferritin and sTfR; 11% infants had IDA and 15% had AI. Anemic infants at 6mo had higher hepcidin (median 7.9 vs 4.5ng/mL; P = 0.016) and CRP (median 2.33 vs 0.32mg/L; P<0.001), but lower ferritin (median 13.2 vs 25.1μg/L; P<0.001) than non-anemic infants; 56% infants had IDA and 12% had AI. Anemic infants at 12mo had lower ferritin (median 3.2 vs 22.2μg/L; P<0.001) and hepcidin (median 0.9 vs 1.9ng/mL; P = 0.019), but similar CRP levels; 48% infants had IDA and 8% had AI. Comparing anemic with non-anemic infants, plasma hepcidin was 568% higher, 405% higher and 64% lower at 3mo, 6mo and 12mo, respectively, after adjusting for sex and birthweight (all p<0.01). Plasma hepcidin declined significantly with age among anemic but not non-anemic infants. Girls had 61% higher hepcidin than boys, after adjusting for age, anemia and birthweight (p<0.001).

Conclusion

Anemia is driven partly by inflammation early in infancy, and by iron deficiency later in infancy, with plasma hepcidin concentrations reflecting the relative contribution of each. However, there is need to better characterize the drivers of hepcidin during infancy in developing countries.     

Plasma Levels of Apoliporptoein A1 in Malaria-Exposed Primigravidae Are Associated with Severe Anemia

Background

Plasmodium falciparum placental malaria (PM) contributes to 10,000 maternal deaths due to severe anemia (SA) each year in Africa, primarily among primigravid women who are most susceptible. Increased levels of proinflammatory cytokines like TNF-α are associated with maternal anemia in first time mothers but not in other women. Here we aimed to identify additional changes in the plasma proteome associated with pregnancy malaria that may contribute to the development of malaria-related maternal anemia.

Principal Findings

A semi-quantitative mass spectrometry approach was used to compare the relative abundance of plasma proteins in anemic versus non-anemic women with PM. Levels of 24 proteins differed significantly between anemic and non-anemic primigravidae, including several lipid metabolism proteins and molecular transport proteins involved in the acute phase response signaling network. These differences were not observed in multigravid women who enjoy specific immunity that protect them from PM. In a confirmatory study of a larger cohort of primigravid women, levels of the lipid metabolism protein Apolipoprotein (Apo)-AI were significantly lower in PM+ women with SA.

Conclusions

Apo-AI levels are significantly lower in severely anemic primigravidae with PM, and ApoA1 levels positively correlate with hemoglobin levels in primigravid but not multigravid women. Apo-AI is known to have anti-inflammatory effects, and thus Apo-AI reductions may contribute to the inflammatory processes that result in SA.     

Evaluation of Status of Trace and Toxic Metals in Biological Samples (Scalp Hair, Blood, and Urine) of Normal and Anemic Children of Two Age Groups

Anemia affects a substantial portion of the world’s population, provoking severe health problems as well as important economic losses to the region in which this condition is found. This study was designed to compare the levels of essential trace and toxic elements in scalp hair, blood, and urine samples of anemic children (n = 132) with age range 1–5 and 6–10 years of both genders. For a comparative study, 134 non-anemic age- and sex-matched children as control subjects, residing in the same city, were selected. The metals in the biological samples were measured by flame atomic absorption spectrophotometry/electrothermal atomic absorption spectrometry prior to microwave-assisted acid digestion. The proposed method was validated using certified reference samples of hair, blood, and urine. The results indicated significantly lower levels of iron, copper, and zinc in the biological samples as compared to the control children of both genders (p = 0.01–0.008). The mean values of lead and cadmium were significantly high in all three biological samples of anemic children as compared to non-anemic children of both age groups (p = 0.005–0.001). The ratios of essential metal to toxic metals in the biological samples of anemic children of both age groups were significantly lower than that of controls. Deficiency of essential trace metals and high level of toxic metals may play a role in the development of anemia in the subjects under study.     

Incidence of low birth weight infants born to mothers with multiple risk factors

Low birth weight (LBW) is associated with a large number and variety of risk conditions during pregnancy. The number and types of risk conditions per pregnancy were determined in 1,864 white and 872 black mothers delivered at the University of Kansas Medical Center between 1975 and 1978. The incidence of LBW infants increased steadily among white and black mothers as the number of risk factors increased from none to three or four per pregnancy. Among pregnancies without spontaneous premature rupture of membranes (PROM), 51 percent of the LBW infants were born to mothers who had multiple risk factors associated with their pregnancies, even though only 18 percent of these pregnancies were associated with multiple risk factors. Among pregnancies with PROM, 72 percent were associated with multiple risk conditions, and 31 percent resulted in LBW infants. About 90 percent of LBW infants from PROM pregnancies had mothers with multiple risk factors. For all numbers of risk conditions, black mothers had a higher incidence of LBW infants than white mothers. Among black mothers without spontaneous premature rupture of membranes (PROM), the incidence of LBW infants increased from 3.2 percent (10/308) in low (zero)-risk condition pregnancies to 33 percent (16/49) among mothers with three or four risk conditions during the pregnancy. Among white mothers without PROM, the incidence of LBW infants increased from 1.7 percent (12/708) in low (zero)-risk condition pregnancies to 30 percent (19/64) in pregnancies with three or four risk conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between anemia and cholesterol metabolism in 'sex-linked anemic' (gene symbol, sla) mouse

The relationship between hypocholesterolemia and anemia has been recognized in humans. However, no metabolic studies in humans have been reported, nor has an animal model been developed to investigate the effects of anemia on cholesterol metabolism. We have identified an animal model, the 'sex-linked anemic' (gene symbol, sla) mouse, characterized by iron deficiency anemia, to study the relationship between anemia and cholesterol metabolism. Results from our studies showed that the serum cholesterol was significantly lower in anemic male SLA mice compared to non-anemic littermates. The lower serum cholesterol observed in anemic SLA mice was related to a decreased in vivo hepatic cholesterol synthesis. However, the decreased hepatic cholesterol synthesis in anemic SLA mice was not due to a block at the primary regulatory site, the hydroxymethylglutaryl-CoA reductase, nor at one of the secondary regulatory sites: the acetoacetyl-CoA thiolase and hydroxymethylglutaryl-CoA synthase.     

Association of mild anemia with cognitive, functional, mood and quality of life outcomes in the elderly: the "Health and Anemia" study

Background

In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons.

Methods

Among the 4,068 eligible individuals aged 65–84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia.

Results

In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable.

Conclusions

Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings.     

Relationship between anemia and cholesterol metabolism in ‘sex-linked anemic’ (gene symbol,sla) mouse

The relationship between hypocholesterolemia and anemia has been recognized in humans. However, no metabolic studies in humans have been reported, nor has an animal model been developed to investigate the effects of anemia on cholesterol metabolism. We have identified an animal model, the ‘sex-linked anemic’ (gene symbol, sla) mouse, characterized by iron deficiency anemia, to study the relationship between anemia and cholesterol metabolism. Results from our studies showed that the serum cholesterol was significantly lower in anemic male SLA mice compared to non-anemic littermates. The lower serum cholesterol observed in anemic SLA mice was related to a decreased in vivo hepatic cholesterol synthesis. However, the decreased hepatic cholesterol synthesis in anemic SLA mice was not due to a block at the primary regulatory site, the hydroxymethylglutaryl-CoA reductase, nor at one of the secondary regulatory sites: the acetoacetyl-CoA thiolase and hydroxymethylglutaryl-CoA synthase.     

Interactive effects of anemia and muscle oxidative capacity on exercise endurance

We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls.     

High iron level in early pregnancy increased glucose intolerance

High iron stores in pregnancy are essential in preventing negative outcomes for both infants and mothers; however the risk of gestational diabetes mellitus (GDM) might also be increased. We intend to study the relationship between increased iron stores in early pregnancy and the risk of glucose intolerance and GDM. This prospective, observational, single-hospital study involved 104 non-anemic pregnant women, divided into 4 groups based on the quartile values for ferritin at the first trimester of pregnancy. All participants were screened for GDM with 75-g oral glucose tolerance test (OGTT) at 24–28 weeks’ gestation. We observed that ferritin levels at early pregnancy were significantly correlated to glucose level after OGTT at 1-h and 2-h (rho = 0.21, p < 0.05; rho = 0.43, p < 0.001 respectively). Furthermore, in the higher quartile for ferritin (>38.8 μg/L) glycemia at 2-h OGTT was significantly higher than in the others quartiles (p = 0.002). In multivariate regression analysis, serum ferritin was a significant determinant of glycemia at 2-h OGTT. Although we did not find a significant association in the incidence of GDM in women with higher serum ferritin levels, probably in reason to the limit power of our study, our data demonstrated that the role of iron excess is tightly involved in the pathogenesis of glucose intolerance. We report for the first time that high ferritin values in early pregnancy are predictors of impaired glucose tolerance in non-anemic women. Individual iron supplementation should be evaluated in order to minimize glucose impairment risk in women with high risk of diabetes.     

Low Birth Weight,Small for Gestational Age and Preterm Births before and after the Economic Collapse in Iceland: A Population Based Cohort Study

Objective

Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes.

Study design

The study population constituted all Icelandic women giving birth to live-born singletons from January 1^st 2006 to December 31^st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD''s) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6^th 2008.

Results

Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse.

Conclusion

The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation.     

新生儿坏死性小肠结肠炎病原菌分布、耐药性及发病的影响因素分析

摘要 目的：观察新生儿坏死性小肠结肠炎（NEC）病原菌分布、耐药性,并分析NEC患儿发病的影响因素。方法：选取2016年8月~2020年9月期间在我院接受治疗的NEC患儿50例（NEC组）,另选取同期于我院出生的100例健康新生儿作为对照组。观察NEC患儿病原菌分布、耐药性,并分析NEC发病的影响因素。结果：50例NEC患儿共培养出病原菌63株。病原菌中革兰阴性菌38株,占比60.32%;革兰阳性菌23株,占比36.51%;真菌2株,占比3.17%。大肠埃希菌、肺炎克雷伯菌均对氧氟沙星、头孢哌酮、头孢他啶、头孢唑林、阿莫西林、氨苄青霉素、环丙沙星、头孢曲松的敏感性较低,对亚胺培南/西司他丁、哌拉西林/他唑巴坦、美罗培南、多粘菌素高度敏感。单因素分析结果显示,NEC发病与新生儿体重、母乳喂养、产前使用糖皮质激素、妊娠期糖尿病、妊娠期高血压、新生儿Apgar评分、是否合并肺部感染、合并败血症有关（P<0.05）。多因素Logistic回归分析发现：母乳喂养是NEC发病的保护因素,合并败血症、妊娠期糖尿病、新生儿体重、合并肺部感染、新生儿Apgar评分均是NEC发病的危险因素（P＜0.05）。结论：NEC患儿的病原菌以革兰阴性菌为主,同时影响NEC发病的因素较多,应结合相关的影响因素制定针对性干预或治疗措施,以减少NEC的发病风险。     

Maternal nativity status and pregnancy outcome among U.S.‐born Filipinos

Abstract

Using 1979–87 Hawaii vital record data on single live births, this study compares by nativity status of the mother the maternal characteristics and pregnancy outcomes of resident Filipino women. Among ethnic minorities in the United States, the pregnancy outcomes of U.S.‐born mothers have been reported to compare unfavorably to their foreign‐born counterparts. In this study, unequivocally preferential pregnancy outcome indicators were not observed for foreign‐born women. Contrary to expectations, a significant, but modest, increase in the risk of preterm delivery was found for infants of Philippines‐born mothers, along with a less favorable mean birth weight and gestational age. As a growing minority population in the United States, the atypical determinants and patterns of pregnancy outcome in this population warrants further investigation.     

Khat Chewing and Restrictive Dietary Behaviors Are Associated with Anemia among Pregnant Women in High Prevalence Rural Communities in Eastern Ethiopia

Background

Anemia affects a high proportion of pregnant women in the developing countries. Factors associated with it vary in context. This study aimed to determine the prevalence and predictors of anemia among pregnant women in the rural eastern Ethiopia.

Methods

A community-based cross-sectional study was done on 1678 pregnant women who were selected by a cluster random sampling technique. A pregnant woman was identified as anemic if her hemoglobin concentration was <11 g/dl. Data were collected in a community-based setting. Multilevel mixed effect logistic regression was used to determine the adjusted odds ratios (AOR) with 95% confidence intervals (CI) for the predictors of anemia.

Results

Anemia was observed among 737(43.9%) of the 1678 pregnant women studied (95% CI 41.5%–46.3%). After controlling for the confounders, the risk of anemia was 29% higher in the women who chewed khat daily than those who sometimes or never did so (AOR, 1.29; 95% CI, 1.02–1.62). The study subjects with restrictive dietary behavior (reduced either meal size or frequency) had a 39% higher risk of anemia compared to those without restrictive dietary behavior (AOR, 1.39; 95% CI, 1.02–1.88). The risk of anemia was increased by 68% (AOR, 1.68; 95% CI, 1.15–2.47), and 60% (AOR, 1.60; 95% CI, 1.08–2.37) in parity levels of 2 births and 3 births, respectively. Compared to the first trimester, the risk of anemia was higher by two-fold (AOR, 2.09; 95% CI, 1.46–3.00) in the second trimester and by four-fold (AOR, 4.23; 95% CI, 2.97–6.02) in the third trimester.

Conclusion

In this study, two out of five women were anemic. Chewing khat and restrictive dietary habits that are associated with anemia in the setting should be addressed through public education programs. Interventions should also focus on the women at higher parity levels and those who are in advanced stages of pregnancy.     

Malaria Infection,Poor Nutrition and Indoor Air Pollution Mediate Socioeconomic Differences in Adverse Pregnancy Outcomes in Cape Coast,Ghana

Background

The epidemiological evidence linking socioeconomic deprivation with adverse pregnancy outcomes has been conflicting mainly due to poor measurement of socioeconomic status (SES). Studies have also failed to evaluate the plausible pathways through which socioeconomic disadvantage impacts on pregnancy outcomes. We investigated the importance of maternal SES as determinant of birth weight and gestational duration in an urban area and evaluated main causal pathways for the influence of SES.

Methods

A population-based cross-sectional study was conducted among 559 mothers accessing postnatal services at the four main health facilities in Cape Coast, Ghana in 2011. Information on socioeconomic characteristics of the mothers was collected in a structured questionnaire.

Results

In multivariate linear regression adjusting for maternal age, parity and gender of newborn, low SES resulted in 292 g (95% CI: 440–145) reduction in birth weight. Important SES-related determinants were neighborhood poverty (221 g; 95% CI: 355–87), low education (187 g; 95% CI: 355–20), studentship during pregnancy (291 g; 95% CI: 506–76) and low income (147 g; 95% CI: 277–17). In causal pathway analysis, malaria infection (6–20%), poor nutrition (2–51%) and indoor air pollution (10–62%) mediated substantial proportions of the observed effects of socioeconomic deprivation on birth weight. Generalized linear models adjusting for confounders indicated a 218% (RR: 3.18; 95% CI: 1.41–7.21) risk increase of LBW and 83% (RR: 1.83; 95% CI: 1.31–2.56) of PTB among low income mothers. Low and middle SES was associated with 357% (RR: 4.57; 95% CI: 1.67–12.49) and 278% (RR: 3.78; 95% CI: 1.39–10.27) increased risk of LBW respectively. Malaria infection, poor nutrition and indoor air pollution respectively mediated 10–21%, 16–44% and 31–52% of the observed effects of socioeconomic disadvantage on LBW risk.

Conclusion

We provide evidence of the effects of socioeconomic deprivation, substantially mediated by malaria infection, poor nutrition and indoor air pollution, on pregnancy outcomes in a developing country setting.     

Thyroid hormone dysregulation in intrauterine growth retardation associated with maternal malnutrition and/or anemia.

Data on the effect of maternal malnutrition and/or anemia on thyroid hormone regulation in human fetuses are scarce, and would be of great importance in examining the relevance of Barker's hypothesis, which proposes adaptation of fetuses to undernutrition leading to permanent metabolic and endocrine changes that form the basis of adult diseases. To examine the quantitative variations in thyroid hormone profile of neonates born to malnourished and/or anemic mothers, we quantitated the T3, T4, rT3 and TSH levels in cord blood of neonates and maternal blood of their corresponding mothers that are malnourished and/or anemic. Further, we classified neonates born to each of these groups of mothers into Small for Gestational Age (SGA) or Appropriate for Gestational Age (AGA) based on the intrauterine growth curve for our population, and examined the thyroid hormone profile in these neonates. Our results show that firstly, the effects of malnutrition or anemia on thyroid hormone profile are distinct, secondly, significantly higher levels of cord blood T4 and correspondingly lower levels of T3 and rT3 are observed in the neonates born to anemic and malnourished mothers and thirdly, decreases in cord blood T3 levels were observed in Small for Gestational Age neonates born to anemic mothers. These observations lead us to speculate that alterations in the pituitary-thyroid function result in beneficial adaptations to the hostile intrauterine environment in malnutrition related growth retardation and anemia.     

Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.