On the Distribution of Summary Statistics for Missing Data.

Under an assumption that missing values occur randomly in a matrix, formulae are developed for the expected value and variance of six statistics that summarize the number and location of the missing values. For a seventh statistic, a regression model based on simulated data yields an estimate of the expected value. The results can be used in the development of methods to control the Type I error and approximate power and sample size for multilevel and longitudinal studies with missing data.

Calculating Power for the General Linear Multivariate Model With One or More Gaussian Covariates.

We describe a noncentral ℱ power approximation for hypotheses about fixed predictors in general linear multivariate models with one or more Gaussian covariates. The results apply to both single and multiple parameter hypotheses. The approach extends power approximations for models with only fixed predictors, and for models with a single Gaussian covariate. The new method approximates the noncentrality parameter under the alternative hypothesis using a Taylor series expansion for the matrix-variate beta distribution of type I. We used a Monte Carlo simulation to evaluate the accuracy of both the novel power approximation, and published power approximations. The simulation study accounted for randomness in both the predictors and the errors. We varied the number of outcomes, the number of parameters in the hypothesis, the per-treatment sample size, and the correlations between the random predictors and the outcomes. We demonstrate that our approximation is more accurate than published methods, both in small and large samples. We show that the run time for a single power calculation with the new method is on the order of milliseconds, compared to an average empirical simulation time of roughly three minutes. Approximate and simulated power can be calculated using the free, open-source rPowerlib package. (http://github.com/SampleSizeShop/rPowerlib).

Exposure to secondhand smoke, exclusive breastfeeding and infant adiposity at age 5 months in the Healthy Start study.

BACKGROUND: Infant adiposity may be influenced by several environmental risk factors, but few studies have explored these interactions. OBJECTIVE: To examine the interaction between exposure to secondhand smoke and breastfeeding exclusivity on adiposity at age 5 months. METHODS: We studied 813 mother-offspring pairs from the longitudinal Healthy Start study. Fat mass and fat-free mass were measured by air displacement plethysmography. Linear regression analyses were used to estimate the association between household smokers (none, any) with fat mass, fat-free mass, percent fat mass, weight-for-age z-score, weight-for-length z-score and BMI-for-age z-score as separate outcomes. Interaction terms between household smokers and breastfeeding exclusivity (<5 months, ≥5 months) were added to separate models. RESULTS: The combination of exposure to secondhand smoke and a lack of exclusive breastfeeding was associated with increased adiposity at age 5 months. For example, within the not exclusively breastfed strata, exposure to secondhand smoke was associated with increased fat mass (0.1 kg; 95% CI: 0.0-0.2; P = 0.05). Conversely, within the exclusively breastfed strata, there was virtually no difference in fat mass between exposed and non-exposed infants (coefficient: -0.1; 95% CI: -0.3-0.1; P = 0.25). CONCLUSIONS: Our findings may inform new public health strategies with potential relevance for both smoking cessation and obesity prevention.

Fetal overnutrition and offspring insulin resistance and ß-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study.

AIMS: To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, ß-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS: A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. RESULTS: Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of ß-cell function (HOMA2-ß), P=0.04]. Each 5-kg/m2 increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-ß, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (ß=1.12, P=0.03) and lower Matsuda index (ß=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. CONCLUSIONS: Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.

Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study.

OBJECTIVE: The objective of this study is to estimate associations between changes in maternal arterial pressure during normotensive pregnancies and offspring birth weight and body composition at birth. STUDY DESIGN: Prospective study of 762 pregnant normotensive Colorado women, recruited from outpatient obstetrics clinics. Repeated arterial pressure measurements during pregnancy were averaged within the second and third trimesters, respectively. Multivariable regression models estimated associations between second to third trimester changes in arterial pressure and small-for-gestational-age birth weight, fat mass, fat-free mass and percent body fat. RESULTS: A greater second to third trimester increase in maternal arterial pressure was associated with greater odds of small-for-gestational-age birth weight. Greater increases in maternal diastolic blood pressure were associated with reductions in offspring percent body fat (-1.1% in highest vs lowest quartile of increase, 95% confidence interval: -1.9%, -0.3%). CONCLUSION: Mid-to-late pregnancy increases in maternal arterial pressure, which do not meet clinical thresholds for hypertension are associated with neonatal body size and composition.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

BACKGROUND/OBJECTIVES: Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition. METHODS: Our analysis was conducted using a prebirth observational cohort of 1079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age. RESULTS: Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (ß=0.58, 95% confidence interval (CI) 0.07-1.1, P<0.05) and FM (ß=20.74; 95% CI 1.49-40.0; P<0.05) but no difference in FFM. CONCLUSIONS: Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study.

AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score ≥64), physical activity level (estimated energy expenditure ≥170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, ≥1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia.

Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study.

BACKGROUND: Prenatal multivitamin supplementation is recommended to improve offspring outcomes, but effects on early infant growth are unknown. OBJECTIVES: We examined whether multivitamin supplementation in the year before delivery predicts offspring mass, body composition and early infant growth. METHODS: Multivitamin use was assessed longitudinally in 626 women from the Healthy Start Study. Offspring body size and composition was measured with air displacement plethysmography at birth (<3 days) and postnatally (median 5.2 months). Separate multiple linear regressions assessed the relationship of weeks of daily multivitamin use with offspring mass, body composition and postnatal growth, after adjustment for potential confounders (maternal age, race, pre-pregnant body mass index; offspring gestational age at birth, sex; breastfeeding exclusivity). RESULTS: Maternal multivitamin use was not related to offspring mass or body composition at birth, or rate of change in total or fat-free mass in the first 5 months. Multivitamin use was inversely associated with average monthly growth in offspring percent fat mass (ß = -0.009, p = 0.049) between birth and postnatal exam. Offspring of non-users had a monthly increase in percent fat mass of 3.45%, while offspring at the top quartile of multivitamin users had a monthly increase in percent fat mass of 3.06%. This association was not modified by exclusive breastfeeding. CONCLUSIONS: Increased multivitamin use in the pre-conception and prenatal periods was associated with a slower rate of growth in offspring percent fat mass in the first 5 months of life. This study provides further evidence that in utero nutrient exposures may affect offspring adiposity beyond birth.