Metabolomics signatures associated with an oral glucose challenge in pregnant women.

AIM: The oral glucose tolerance test (OGTT), widely used as a gold standard for gestational diabetes mellitus (GDM) diagnosis, provides a broad view of glucose pathophysiology in response to a glucose challenge. We conducted the present study to evaluate metabolite changes before and after an oral glucose challenge in pregnancy; and to examine the extent to which metabolites may serve to predict GDM diagnosis in pregnant women. METHODS: Peruvian pregnant women (n=100) attending prenatal clinics (mean gestation 25 weeks) participated in the study with 23% of them having GDM diagnosis. Serum samples were collected immediately prior to and 2-hours after administration of a 75-g OGTT. Targeted metabolic profiling was performed using a LC-MS based metabolomics platform. Changes in metabolite levels were evaluated using paired Student's t-tests and the change patterns were examined at the level of pathways. Multivariate regression procedures were used to examine metabolite pairwise differences associated with subsequent GDM diagnosis. RESULTS: Of the 306 metabolites detected, the relative concentration of 127 metabolites were statistically significantly increased or decreased 2-hours after the oral glucose load (false discovery rate [FDR] corrected P-value<0.001). We identified relative decreases in metabolites in acylcarnitines, fatty acids, and diacylglycerols while relative increases were noted among bile acids. In addition, we found that C58:10 triacylglycerol (ß=-0.08, SE=0.04), C58:9 triacylglycerol (ß=-0.07, SE=0.03), adenosine (ß=0.70, SE=0.32), methionine sulfoxide (ß=0.36, SE=0.13) were significantly associated with GDM diagnosis even after adjusting for age and body mass index. CONCLUSIONS: We identified alterations in maternal serum metabolites, representing distinct cellular and metabolic pathways including fatty acid metabolism, in response to an oral glucose challenge. These findings offer novel perspectives on the pathophysiological mechanisms underlying GDM.

Plasma concentrations of carotenoids, retinol, and tocopherols in preeclamptic and normotensive pregnant women.

This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether plasma concentrations of carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) are decreased in women with preeclampsia. A total of 125 pregnant women with preeclampsia and 179 normotensive pregnant women were included. Plasma concentrations of antioxidants were determined using high performance liquid chromatography. After adjusting for maternal demographic, behavioral, and reproductive characteristics and total plasma lipid concentrations, the authors found a linear increase in risk of preeclampsia with increasing concentrations of alpha-tocopherol (odds ratio of the highest quartile = 3.13; 95% confidence interval: 1.06, 9.23, with the lowest quartile as the reference group; p value of the test of linear trend = 0.040). The risk of preeclampsia decreased across increasing quartiles of concentrations for retinol (odds ratio of the highest quartile = 0.32; 95% confidence interval: 0.15, 0.69, with the lowest quartile as the reference group; p value of the test of linear trend = 0.001). Some of these results are inconsistent with the prevailing hypothesis that preeclampsia is an antioxidant-deficient state. Preliminary findings confirm an earlier observation of increased plasma concentrations of alpha-tocopherol among women with preeclampsia as compared with normotensive pregnant women.

Plasma folate, vitamin B(12), and homocyst(e)ine concentrations in preeclamptic and normotensive Peruvian women.

The authors measured maternal third trimester plasma folate, vitamin B(12), and homocyst(e)ine concentrations among 125 women with preeclampsia and 179 normotensive women in Lima, Peru (1997-1998), to determine whether these analytes were associated with the occurrence of preeclampsia. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Relative to women in the upper quartile of the control distribution of maternal plasma folate concentrations, women with values in the lowest quartile experienced a 1.6-fold increased risk of preeclampsia (odds ratio = 1.6; 95% confidence interval: 0.8, 3.2). There was no evidence of an increased risk of preeclampsia associated with low plasma vitamin B(12) concentrations. The unadjusted relative risk of preeclampsia increased across successively higher quartiles of plasma homocyst(e)ine level (odds ratios were 1.0, 1.0, 1.5, and 2.9, respectively, with the lowest quartile used as the referent; p for linear trend = 0.0004). After adjustment for maternal age, parity, gestational age, use of prenatal vitamins, whether the pregnancy had been planned, and educational attainment, the relative risk between extreme quartiles was 4.0 (95% confidence interval: 1.8, 8.9). These findings are consistent with earlier reports suggesting that hyperhomocyst(e)inemia in pregnancy may be a risk factor for preeclampsia.

Tumor necrosis factor-alpha soluble receptor p55 (sTNFp55) and risk of preeclampsia in Peruvian women.

We conducted a large case-control study to assess the risk of preeclampsia with elevated sTNFp55 concentrations (markers of excessive TNF-alpha release) in Peruvian women. A total of 125 women with preeclampsia and 179 normotensive women were included in a study conducted during the period, June 1997 through January 1998. Antepartum (third-trimester) plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Mean plasma sTNFp55 concentrations were 32.4% higher among preeclampsia cases (920.1+/-30.4 pg/ml) as compared with controls (694.8+/-15.0 pg/ml, Student's t-test P<0.001). There was a strong linear increase in risk of preeclampsia with increasing concentrations of sTNFp55 (linear trend P-value <0. 001). After adjusting for confounding factors, women in the highest quartile experienced a 10-fold increased risk of preeclampsia as compared with women in the lowest quartile (adjusted odds ratio, 10.3; 95% confidence interval, 4.1-25.9). Compared with women in the highest quartile, women in the second and third quartiles experienced a 3-fold or greater increased risk of preeclampsia (adjusted odds ratios were 3.1 and 3.8, respectively). Excessive TNF-alpha release (as measured by the detection of the soluble receptor sTNFp55 in maternal plasma collected before delivery) is increased in pregnancies complicated by preeclampsia as compared with normotensive pregnancies. These findings are consistent with most previous studies.

[PREVALENCE OF HBsAg AND anti-HBs CARRIERS IN PREGNANT WOMEN WHO RESIDE IN DIFFERENT ENDEMIC AREAS LOCATED IN CENTRAL-SOUTHERN DEPARTAMENTS OF PERU] / Prevalencia de Portadoras de HBsAg y anti -HBs en Gestantes Residentes en Areas de Diferente Endemicidad de HVB en Departamentos del Centro - Sur del Perú

The present study was performed to estimate the prevalence of HBV in pregnant women (mean age among groups 25,0 6,9) who live in areas of different endemicity, and located in the Departments of Lima, Junin, Apurimac, and Ayacucho in Peru. All studies were carried out using radioimmunological techniques. In the Instituto Materno Perinatal in Lima, located in a low endemical area, 2086 pregnant women whose ages ranged between 14 and 44 years were evaluated (for laboratory tests) at their first prenatal examination. A prevalence of 9,38% (HbsAG+), 0,38% (Ratio), and 3,18% (HBsAg+, anti-HBsAg+) was found, corresponding to 107 HBsAg+ pregnant women whose treated newborn wouId prevent the HBV chronic infection of approximate 21 newborn each year. 63% HBsAg+ pregnant women were born in Departments other than Lima. In the Hospital de Apoyo La Merced, located in Chanchamayo, Junin, which is a medium endemic area, 217 pregnant women whose ages ranged between 14 and 48 years were evaluated. The prevalence found in this Hospital was of 1,38% (HBsAg+), 1,2% (Ratio), and 17,8% (HBsAg+, anti-HBs+). All positive HBsAg were negative for HBeAg. The projection of results corresponded to a total of 9 HbsAg+ pregnant women and 2 newborn preventive of chronic disease per year. In the Guillermo D az de la Vega Hospital in Abancay, Apurimac, located in a medium to high endemic area, 221 pregnant women whose ages ranged between 15 and 46 years were evaluated. A prevalence of 1,36% (HBsAg+), 1,0% (Ratio), and 36,16% (HBsAg+, anti-HBs+) was found. All positive HBsAg were negative for HBeAg. Projected results corresponded to a total of 37 HBsAg+ pregnant carriers and 7 newborn preventive of chronic disease per year. The Hospital General de Huanta, in Ayacucho, located in a high endemicity area, presented a prevalence of 3,2% (HBsAg+), 1,9% (Ratio), and 76,2% (HBsAg+, anti-HBs+) from 126 pregnant women evaluated with ages between 15 and 48 years old. These results gave a total projection per year of 39 HBsAg+ pregnant women and 8 newborn preventive of chronic hepatic disease. Among a total of 4 positive HBsAg cases, 3 positive pregnant women were studied for HBeAg. All 3 were negative. These results establish the prevalence of HbsAg and antiHBs in pregnant women from different endemical areas with significant prevalence in the Departments of Ayacucho (Huanta), and Apurimac (Abancay). They also contribute towards the costbenefit analysis for the prevention of HBV chronic infection.

Prevalencia de portadoras de HBsAG y anti-HBs en gestantes residentes en áreas de diferente endemicidad de HVB en departamentos del Centro - Sur del Perú / Prevalence of HBsAg and anti-HBs carriers in pregnant women who reside in different endemic areas located in central southern departaments of Peru

Desde febrero de 1996 a febrero de 1997 se evaluaron, mediante estudio prospectivo, diferentes grupos muestrales de gestantes aparentemente sanas (edad promedio entre grupo 25 ñ 6,9 años) atendidas en instituciones hospitalarias ubicadas en los Departamentos de Lima, Junín, Apurímac y Ayacucho en el Perú, con la finalidad de estimar la prevalencia de Hepatitis viral B en la población de gestantes residentes en dichas áreas. Todos los estudios fueron realizados mediante procedimientos radioinmunológicos en fase sólida. En el Instituto Materno Perinatal, ubicado en Lima en un área de baja endemicidad; fueron evaluadas 2086 gestantes, con edades mínimas y máxima entre 14 y 44 años, en su primera atención por consulta externa para las pruebas requeridas de laboratorio. Se encontró una prevalencia del 0.38 por ciento (HBsAG+) y 3.18 por ciento (HBsAg+, anti-HBs+), correspondiendo este hallazgo a un total anual proyectado de 107 gestantes HBsAg positivas cuyos recién nacidos tratados podrían prevenir la infección crónica de HVB de aproximadamente 21 casos cada año. De los casos HBsAg positivos encontrados, el 63 por ciento de gestantes no había nacido en Lima. En el Hospital de Apoyo La Merced en Chanchamayo, área de endemicidad intermedia; fueron evaluadas un total de 217 gestantes, con edades entre 14 y 48 años. La prevalencia encontrada en el Hospital fue de 1,38 por ciento (HBsAg+) y 17,8 por ciento (HBsAg+, anti-HBs+). Las gestantes positivas para HBsAg no fueron positivas para HBeAg. Con estos resultados se estimó un total anual de 9 gestantes HBsAg positivas y 2 RN prevenibles de enfermedad crónica. En el Hospital Guillermo Diaz de la Vega en Abancay, en área de endemicidad intermedia a alta; se evaluaron 221 gestantes, con edades entre 15 y 46 años, encontrándose una prevalencia de 1.36 por ciento (HBsAg+) y 36.16 por ciento (HBsAg+, anti-HBs+). Las gestantes positivas para HBsAg no fueron positivas para HBeAg. Se estimó como proyección un total anual de 37 gestantes HBsAg+ y 7 RN prevenibles de infección crónica. El Hospital General de Huanta, en área de alta endemicidad; presentó una prevalencia de 3.2 por ciento (HBsAg+) y 76.2 por ciento (HBsAg+, anti-HBs+), a partir de 126 gestantes evaluadas con edades entre 15 y 48 años. De las cuatro gestantes positivas para HBsAg, se evaluaron tres que resultaron negativas para HBeAg. Se proyectó un total de 39 gestantes HBsAg+ y 8 RN prevenibles de enfermedad hepática crónica...