Development of a nonlinear hierarchical model to describe the disposition of deuterium in mother-infant pairs to assess exclusive breastfeeding practice

Abstract

The World Health Organization recommends exclusive breastfeeding (EBF) for the first 6 months after birth. The deuterium oxide dose-to-the-mother (DTM) technique is used to distinguish EBF based on a cut-off (< 25 g/day) of water intake from sources other than breastmilk. This value is based on a theoretical threshold and has not been verified in field studies. The aim of this study was to estimate the water intake cut-off value that can be used to define EBF practice. One hundred and twenty-one healthy infants, aged 2.5-5.5 months who were deemed to be EBF were recruited. After administration of deuterium to the mothers, saliva was sampled from mother and infant pairs over a 14-day period. Validation of infant feeding practices was conducted via home observation over six non-consecutive days with caregiver recall. A fully Bayesian framework using a gradient-based Markov chain Monte Carlo approach implemented in Stan was used to estimate the cut-off of non-milk water intake of EBF infants. From the original data set, 113 infants were determined to be EBF and provided 1500 paired mother-infant observations. The deuterium saliva concentrations were best described by two linked 1-compartment models (mother and infant), with body weight as a covariate on the mother's volume of distribution and infant's body weight on infant's water clearance rate. The cut-off value was based on the 90th percentile of the posterior distribution of non-milk water intake and was 86.6 g/day. This cut-off value can be used in future field studies in other geographic regions to determine exclusivity of breast feeding practices in order to determine their potential public health needs.

Keywords: Bayesian; Breastfeeding; Deuterium-oxide turnover method; Human milk; MCMC; Pharmacokinetics; Stan.

Figures

Fig. 1

D2O disposition model for mother and infant. The term V denotes the D2O volume of distribution with subscript m and b for mother and infant; CLmb is the water clearance from mother to infant; CLbo is the water clearance from infant to out; the term CLmo represents the water clearance from mother to out

Fig. 2

Individual Visual Predictive Checks for model evaluation. Open circles are the observations. The solid lines represent the median, 2.5% and 97.5% quantiles of the posterior distribution of the model predicted response. The upper curves represent the mother and lower curves the infant. ID = 25 and 39 are later classified as EBF. ID = 1 and 12 are later classified as non-EBF

Fig. 3

The individual posterior densities of Rs and the Rs cut-off value (at 86.6 g/day). Black dot is the mean of individual Rs posterior distribution. Thick red line is the 25 and 75% quantiles and thin black line is the 2.5 and 97.5% quantiles (Color figure online)

Fig. 4

The pooled probability density function of Rs and the identified cut-off value distinguishing EBF and non-EBF

Fig. 5

Mass balance model structure of water in infant’s compartment