RESUMO
During the treatment of neonatal apnea, formula-fed infants, compared to breastfed infants, show nearly three-fold increase in clearance of caffeine, a substrate of cytochrome P450 1A (CYP1A) and in part CYP3A4. However, human milk is known to contain higher concentrations of environmental pollutants than infant formula, which are potent CYP1A inducers. To gain insight into the mechanism underlying this apparent contradiction, we characterized CYP1A and CYP3A4 induction by human milk and cow milk-based infant formula. The mRNA and protein expression of CYP1A1/1A2 were significantly induced by cow milk-based formula, but not by human milk, in HepG2 cells. Luciferase reporter assay demonstrated that cow milk-based formula but not human milk activated aryl hydrocarbon receptor (AhR) significantly. The cotreatment of 3,4-dimethoxyflavone, an AhR antagonist, abolished the formula-induced CYP1A expression. In addition, AhR activation by dibenzo[a,h]anthracene, a potent AhR agonist, was significantly suppressed by infant formula and even more by human milk. In contrast, CYP3A4 mRNA expression was only mildly induced by formula and human milk. Consistently, neither formula nor human milk substantially activated pregnane X receptor (PXR). Effects of whey and soy protein-based formulas on the AhR-CYP1A and the PXR-CYP3A4 pathways were similar to those of cow milk-based formula. In conclusion, infant formula, but not human milk, enhances in vitro CYP1A expression via an AhR-mediated pathway, providing a potential mechanistic basis for the increased caffeine elimination in formula-fed infants.
Assuntos
Sistema Enzimático do Citocromo P-450/biossíntese , Alimentos Infantis/efeitos adversos , Leite Humano/química , Leite/química , Animais , Western Blotting , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Desvio de Mobilidade Eletroforética , Poluentes Ambientais/toxicidade , Indução Enzimática/efeitos dos fármacos , Genes Reporter/genética , Humanos , Lactente , Recém-Nascido , Isoenzimas/biossíntese , Luciferases/genética , Proteínas do Leite/farmacologia , Dibenzodioxinas Policloradas/toxicidade , Receptor de Pregnano X , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Esteroides/efeitos dos fármacos , Receptores de Esteroides/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas de Soja/farmacologia , Proteínas do Soro do LeiteRESUMO
AIM: This paper presents the findings of research comparing the incremental costs associated with the provision of home-based vs. hospital-based support for breastfeeding by nurse lactation consultants for term and near-term neonates during the first week of life. BACKGROUND: A consequence of both consumer demands and increasing health resource constraints is that alternative care delivery models for safe, efficacious and cost-effective breastfeeding programmes have steadily evolved. To date, the economic impact of the setting (home or hospital) where lactation support is delivered has received little research attention. METHODS: Mother-infant dyads were stratified by gestational age as term (>37 weeks gestational age; n = 101) or near term (35-37 weeks gestational age; n = 37) and randomized to standard hospital care and postpartum follow-up (standard care), or to standard hospital care plus home support from certified nurse lactation consultants (experimental). Data collection occurred at study entry, hospital discharge and at a seventh day postpartum follow-up session. Costs to the family (out-of-pocket and time costs) and to the healthcare system (during hospitalization and after hospital discharge) were measured. Total societal costs were defined as the sum of both family and healthcare system costs. RESULTS: Compared with standard hospital-based care, home support by nurse lactation consultants showed no statistically significant differences in either time costs to the family or total societal costs. Term infants who received home support had statistically significantly greater postdischarge system costs (P < 0.0001), with a trend towards lower out-of-pocket expenses to their families (P = 0.12). There were no statistically significant differences between the two groups in overall combined family and healthcare system costs. CONCLUSIONS: These results suggest that the cost of home lactation support programmes were comparable with the costs of hospital-based standard care. Breastfeeding support at home by lactation consultants should be considered as an option as it was no more costly than support from lactation consultants in the hospital setting. The findings for near-term infants need to be interpreted with caution, given the small sample size.