Plasma concentrations of leptin at mid-pregnancy are associated with gestational weight gain among pregnant women in Tanzania: a prospective cohort study.

BACKGROUND: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated. This study evaluated associations between a panel of inflammatory, angiogenic, and metabolic proteins measured in mid-pregnancy and gestational weight gain. METHODS: Pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. The participants were enrolled at mid-pregnancy (12 to 27 weeks of gestation) and followed up until delivery. This analysis focused on a cohort of 1002 women who were primigravid, had singleton live births, had longitudinal measures of gestational weight, and whose mid-pregnancy plasma samples underwent analysis for 18 proteins. RESULTS: Higher plasma concentrations of leptin (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 10.24; 95% CI 3.31, 17.16; p-trend = 0.003) and chitinase-3-like protein-1 (CH3L1) (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 7.02; 95% CI 0.31, 13.72; p-trend = 0.007) were associated with greater GWG in a dose-response pattern. Higher leptin concentrations were associated with a lower risk of inadequate GWG (risk ratio comparing highest with lowest quartiles: 0.77; 95% CI 0.65, 0.91; p-trend = 0.001) and a higher risk of excessive GWG (risk ratio comparing highest with lowest quartiles: 1.57; 95% CI 1.03, 2.39; p-trend = 0.03). Higher CH3L1 concentrations were associated with a higher risk of excessive GWG (p-trend = 0.007). The associations of leptin and CH3L1 with inadequate GWG were stronger during the second than the third trimester. The other 16 proteins examined were not significantly associated with GWG. CONCLUSIONS: Mid-pregnancy plasma leptin concentrations may be associated with GWG and have clinical predictive utility in identifying women at a higher risk of inadequate or excessive gestational weight gain.

Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania.

OBJECTIVE: We sought to investigate the relationship between a panel of angiogenic and inflammatory biomarkers measured in midpregnancy and small-for-gestational-age (SGA) outcomes in sub-Saharan Africa. STUDY DESIGN: Concentrations of 18 angiogenic and inflammatory biomarkers were determined in 432 pregnant women in Dar es Salaam, Tanzania, who participated in a trial examining the effect of multivitamins on pregnancy outcomes. Infants falling below the 10th percentile of birthweight for gestational age relative to the applied growth standards were considered SGA. Multivariate binomial regression models with the log link function were used to determine the relative risk of SGA associated with increasing quartiles of each biomarker. Restricted cubic splines were used to test for nonlinearity of these associations. RESULTS: A total of 60 participants (13.9%) gave birth to SGA infants. Compared to those in the first quartile, the risk of SGA was reduced among those in the fourth quartiles of vascular endothelial growth factor-A (adjusted risk ratio [RR], 0.38; 95% confidence interval [CI], 0.19-0.74), placental growth factor (adjusted RR, 0.28; 95% CI, 0.12-0.61), soluble fms-like tyrosine kinase-1 (adjusted RR, 0.48; 95% CI, 0.23-1.01), monocyte chemoattractant protein-1 (adjusted RR, 0.48; 95% CI, 0.25-0.92), and leptin (adjusted RR, 0.46; 95% CI, 0.22-0.96). CONCLUSION: Our findings provide evidence of altered angiogenic and inflammatory mediators, at midpregnancy, in women who went on to deliver SGA infants.

Measles vaccination coverage estimates from surveys, clinic records, and immune markers in oral fluid and blood: a population-based cross-sectional study.

BACKGROUND: Recent outbreaks of measles and polio in low-income countries illustrate that conventional methods for estimating vaccination coverage do not adequately identify susceptible children. Immune markers of protection against vaccine-preventable diseases in oral fluid (OF) or blood may generate more accurate measures of effective vaccination history, but questions remain about whether antibody surveys are feasible and informative tools for monitoring immunization program performance compared to conventional vaccination coverage indicators. This study compares six indicators of measles vaccination status, including immune markers in oral fluid and blood, from children in rural Bangladesh and evaluates the implications of using each indicator to estimate measles vaccination coverage. METHODS: A cross-sectional population-based study of children ages 12-16 months in Mirzapur, Bangladesh, ascertained measles vaccination (MCV1) history from conventional indicators: maternal report, vaccination card records, 'card+history' and EPI clinic records. Oral fluid from all participants (n=1226) and blood from a subset (n=342) were tested for measles IgG antibodies as indicators of MCV1 history and compared to conventional MCV1 coverage indicators. RESULTS: Maternal report yielded the highest MCV1 coverage estimates (90.8%), followed by EPI records (88.6%), and card+history (84.2%). Seroprotection against measles by OF (57.3%) was significantly lower than other indicators, even after adjusting for incomplete seroconversion and assay performance (71.5%). Among children with blood results, 88.6% were seroprotected, which was significantly higher than coverage by card+history and OF serostatus but consistent with coverage by maternal report and EPI records. Children with vaccination cards or EPI records were more likely to have a history of receiving MCV1 than those without cards or records. Despite similar MCV1 coverage estimates across most indicators, within-child agreement was poor for all indicators. CONCLUSIONS: Measles IgG antibodies in OF was not a suitable immune marker for monitoring measles vaccination coverage in this setting. Because agreement between conventional MCV1 indicators was mediocre, immune marker surveillance with blood samples could be used to validate conventional MCV1 indicators and generate adjusted results that can be compared across indicators.

Validation of an anti-measles virus-specific IgG assay with oral fluid samples for immunization surveillance in Bangladesh.

Immune marker surveys may be used as substitutes or in conjunction with traditional surveys to monitor immunization program performance. This study assessed the validity and reliability of the Microimmune anti-measles virus-specific IgG ELISA with oral fluid samples (OF-ELISA) among a random sample of children ages 12-16 months in Bangladesh. Up to two oral fluid samples and one serum sample were analyzed for the presence of protective levels of anti-measles IgG antibodies. Results from the OF-ELISA were compared to the Enzygnost anti-measles IgG ELISA with serum and multivariate logistic regression models were developed to identify risk factors for false negative oral fluid results. Anti-measles IgG antibodies were measured in 330 paired oral fluid and serum samples. Immune marker prevalence of measles IgG antibodies was significantly higher in serum (88.1%, 95% CI: [84.1, 91.5]) than oral fluid (56.1% [50.2, 61.5]). Sensitivity (60.2% [54.1, 66.0]) and specificity (75.7% [58.8, 88.2]) of the OF-ELISA were lower than expected, but sensitivity significantly improved for individuals with higher anti-measles IgG in serum. False negative oral fluid results were associated with month of sample collection and variability between data collectors and assay procedures. Due to poor performance, caution should be exercised when using oral fluid samples to assess population immunity to measles virus, especially in highly vaccinated populations.