Parental childhood growth and offspring birthweight: pooled analyses from four birth cohorts in low and middle income countries.

OBJECTIVE: Associations between parental and offspring size at birth are well established, but the relative importance of parental growth at different ages as predictors of offspring birthweight is less certain. Here we model parental birthweight and postnatal conditional growth in specific age periods as predictors of offspring birthweight. METHODS: We analyzed data from 3,392 adults participating in four prospective birth cohorts and 5,506 of their offspring. RESULTS: There was no significant heterogeneity by study site or offspring sex. 1SD increase in maternal birthweight was associated with offspring birthweight increases of 102 g, 1SD in maternal length growth 0-2 year with 46 g, and 1SD in maternal height growth Mid-childhood (MC)-adulthood with 27 g. Maternal relative weight measures were associated with 24 g offspring birth weight increases (2 year- MC) and 49 g for MC-adulthood period but not with earlier relative weight 0-2 year. For fathers, birthweight, and linear/length growth from 0-2 year were associated with increases of 57 and 56 g in offspring birthweight, respectively but not thereafter. CONCLUSIONS: Maternal and paternal birthweight and growth from birth to 2 year each predict offspring birthweight. Maternal growth from MC-adulthood, relative weight from 2-MC and MC-adulthood also predict offspring birthweight. These findings suggest that shared genes and/or adequate nutrition during early life for both parents may confer benefits to the next generation, and highlight the importance of maternal height and weight prior to conception. The stronger matrilineal than patrilineal relationships with offspring birth weight are consistent with the hypothesis that improving the early growth conditions of young females can improve birth outcomes in the next generation.

Are field measures of adiposity sufficient to establish fatness-related linkages with metabolic outcomes in adolescents?

OBJECTIVE: To examine the associations between the adiposity-related information conveyed by field fatness measures: body mass index (BMI), waist circumference (WC) and sum of triceps and subscapular skinfolds (SUM SF) relative to dual-energy X-ray absorptiometry (DXA), beyond their common intercorrelations, with three important metabolic variables in US adolescents. METHODS: We analyzed data on adiposity and insulin resistance (HOMA-IR), serum triglycerides (TGs) and total cholesterol (TC) from three US national surveys. In two-stage least-square modeling, we first calculated the common adiposity variance, and then used multivariate linear and quantile regressions to access residual associations with each measure. RESULTS: Basic associations for each of the adiposity measures were similar but differences emerged in residual adiposity analyses scaled by s.d. units. While a 1 s.d. change in residual variance in DXA total fat beyond that accounted for by BMI (DXA|BMI) was strongly and significantly associated with all outcomes, associations with DXA accounting for SUM SF (DXA|SUM SF) and WC (DXA|WC) were weak or nonsignificant. Contrasted amongst themselves, the residual score association between BMI|SUM SF (ß=0.06, P<0.0001) and HOMA-IR was weaker, and half as strong as that for the converse, SUM SF|BMI (ß=0.13, P=0.020). SUM SF|WC was stronger than WC|SUM SF (ß=0.08, P<0.0001 vs SUM SF|WC ß=0.13, P<0.0001). Associations were similar for TGs and TC. CONCLUSIONS: Laboratory methods like DXA offer minimal explanatory advantage over field methods in assessing adiposity-related contributions to metabolic outcomes in adolescents. Among the simple fatness measures, skinfolds convey additional information beyond BMI and WC when estimating associations both at the population mean and at the upper extremes of metabolic factors.

Inhibin B and luteinizing hormone levels in girls aged 6-11 years from NHANES III, 1988-1994.

OBJECTIVE: To evaluate inhibin B and luteinizing hormone (LH) levels in a large, representative cross-sectional sample of US girls and characterize the relationships of these laboratory values with age, clinical signs of puberty and other correlates. DESIGN: Cross-sectional analysis of LH and inhibin B in banked serum from 720 girls aged 6-11 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III). MEASUREMENTS: Levels of inhibin B and LH, race, ethnicity and anthropometric measurements were compared for all girls. Visual assessment of pubertal stage was performed on girls aged 8 years and older. A two-part model was used to establish normative data and Tobit regression models were used to evaluate associations with participant characteristics. Receiver operating characteristic (ROC) analysis was performed to identify optimum cut points predictive of puberty onset. RESULTS: Mean hormone levels progressively increased with age. LH levels progressively increased with pubertal stage. Inhibin B levels increased gradually from breast stage I to II, then more sharply to peak at stage III, followed by a plateau at stages IV and V. ROC curves indicated that both hormones were consistent with pubertal onset as indicated by breast stage II. CONCLUSIONS: This study characterizes inhibin B and LH values in a large, representative cross-sectional sample of US girls. Inhibin B can be a useful tool in combination with other clinical and biochemical parameters to evaluate gonadal function as a reflection of pubertal progression in girls.

Comparability of skinfold thickness to DXA whole-body total fat in their associations with serum triglycerides in youths.

OBJECTIVE: To determine the comparability of triceps and subscapular skinfold thicknesses with dual X-ray absorptiometry (DXA) whole-body total fat (kg) in relation to serum triglyceride (TG) levels and increased risk of elevated TG levels, and identified optimum skinfold cutoffs for screening purposes in US adolescents. SUBJECTS/METHODS: Data from triceps and subscapular skinfold thickness, DXA whole-body total fat and serum TGs were obtained from 1505 US adolescents ages 12.00-17.99 years, who participated in two continuous National Health and Nutrition Examination Survey (NHANES) cycles 2001-2004. Study associations were examined with linear and logistic models, and ROC (receiver operating characteristic) analyses were used to derive skinfold cutoffs for identifying the risk of elevated TG levels. RESULTS: Using area under the curves (AUCs) as metrics of prediction accuracy (with bootstrapped 95% CIs), no significant differences were found between skinfolds and DXA logistic models for predicting elevated TG levels. Similarly, skinfold and DXA models had comparable precision in predicting continuous serum TG from bootstrapped root mean squared errors for both sexes. Population-adjusted marginal mean estimates indicated that youths whose skinfolds are in the top quartile had TG levels within 83-108 mg/dl. Skinfold cutoffs for predicting elevated estimated TG using ROC analyses showed that cutoffs decreased with age and ranged from 13 to 30 mm for ages 12-17, in yearly intervals. CONCLUSION: Skinfold thicknesses were comparable to DXA whole-body total fat in predicting serum TG levels. These skinfold cutoffs could be used in practical settings as a first pass screener for identifying US adolescents at risk of elevated serum TGs.

A two-part model for reference curve estimation subject to a limit of detection.

Reference curves are commonly used to identify individuals with extreme values of clinically relevant variables or stages of progression which depend naturally on age or maturation. Estimation of reference curves can be complicated by a technical limit of detection (LOD) that censors the measurement from the left, as is the case in our study of reproductive hormone levels in boys around the time of the onset of puberty. We discuss issues with common approaches to the LOD problem in the context of our pubertal hormone study, and propose a two-part model that addresses these issues. One part of the proposed model specifies the probability of a measurement exceeding the LOD as a function of age. The other part of the model specifies the conditional distribution of a measurement given that it exceeds the LOD, again as a function of age. Information from the two parts can be combined to estimate the identifiable portion (i.e. above the LOD) of a reference curve and to calculate the relative standing of a given measurement above the LOD. Unlike some common approaches to LOD problems, the two-part model is free of untestable assumptions involving unobservable quantities, flexible for modeling the observable data, and easy to implement with existing software. The method is illustrated with hormone data from the Third National Health and Nutrition Examination Survey.