Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI.

OBJECTIVE: To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth. METHODS: Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates. RESULTS: HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P < 0.03). Any amount of formula supplementation was associated with faster fat gain (P = 0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P = 0.056). CONCLUSIONS: Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI.

BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry. RESULTS: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

Thyroid-function tests in diphenylhydantoin-treated patients.

We compared the free-thyroxine index in normal adults and in euthyroid patients taking diphenylhydantoin. All subjects had normal serum thyrotropin concentrations. Serum thyroxine concentrations were determined by two commonly used competitive protein-binding assays, which yielded slightly different values, but which consistently showed the same degree of decrease in mean serum thyoxine concentration in drug-treated patients as compared to the normal subjects. When 14C-labeled diphenylhydantoin was added to serum before the assay, it was separated from thyroxine in the Ames method, whereas by the Murphy-Pattee method both drug and thyroxine were extracted together. Thus, the decrease in serum thyroxine concentrations during diphenylhydantoin therapy cannot be the result of drug interference with the binding of thyroxine to binding proteins in the assays. Triiodothyronine uptake, evaluated by two methods, was identical in the two groups. The free-thyroxine indexes for all normal persons were within the manufacturer's normal range, but 21% of the drug-treated patients had subnormal indexes by the Ames method; the indexes as measured by the Murphy Pattee method were in the lower half of the normal range. Because the triiodothyronine uptake was unaffected by the drug treatment, the decreases in the indexes must have resulted from the lower serum thyroxine concentrations. We conclude that the free-thyroxine index may not provide a valid estimate of either the clinical status or the free-thyroxine concentration in patients taking diphenylhydantoin.