Cheston M. Berlin

Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning.

Background Conventional wisdom regarding exposures to persistent organic chemicals via breast-feeding assumes that concentrations decline over the course of lactation and that the mother’s body burden reflects her cumulative lifetime exposure. Two important implications stemming from these lines of thought are, first, that assessments of early childhood exposures should incorporate decreasing breast milk concentrations over lactation; and, second, that there is little a breast-feeding mother can do to reduce her infant’s exposures via breast-feeding because of the cumulative nature of these chemicals. Objectives We examined rates of elimination and milk/serum partition coefficients for several groups of persistent organic chemicals. Methods We collected simultaneous milk and blood samples of 10 women at two times postpartum and additional milk samples without matching blood samples. Results Contrary to earlier research, we found that lipid-adjusted concentrations of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and furans, and organochlorine pesticides in serum and milk do not consistently decrease during lactation and can increase for some women. Published research has also suggested an approximate 1:1 milk/serum relationship (lipid adjusted) on a population basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin; however, our results suggest a more complex relationship for persistent, lipophilic chemicals with the milk/serum relationship dependent on chemical class. Conclusions Decreases in concentration of lipophilic chemicals on a lipid-adjusted basis during lactation should no longer be assumed. Thus, the concept of pumping and discarding early milk as means of reducing infant exposure is not supported. The hypothesis that persistent lipophilic chemicals, on a lipid-adjusted basis, have consistent concentrations across matrices is likely too simplistic.

METHODOLOGY FOR CHARACTERIZING DISTRIBUTIONS OF INCREMENTAL BODY BURDENS OF 2,3,7,8-TCDD AND DDE FROM BREAST MILK IN NORTH AMERICAN NURSING INFANTS

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to examine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

Criteria for chemical selection for programs on human milk surveillance and research for environmental chemicals

The people of the United States is exposed to a large number of chemicals in their daily lives. In order to prioritize chemicals that should be considered for surveillance of and/or research in human milk, criteria were developed at the Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States. The criteria include (1) lipid solubility and/or persistence in the environment; (2) extensive exposure (e.g., high-production-volume chemicals and chemicals in personal care products); (3) known or suspected toxicity in a biological system; (4) historical interest, trend information; (5) chemicals of emerging concern; and (6) chemicals for medicinal use and chemicals in occupational settings. A working list of chemicals was developed for each of the criteria. It should be noted that more than one criterion may be applicable to a selected chemical, but the selected chemical should possess at least one of these designated criteria. It is hoped that by following a cohort of nursing women through their lactational cycle for a group of these chemicals, data generated will indicate the extent of infant exposure and may suggest methods for risk management to decrease inadvertent exposure for breastfeeding mothers and infants. While not the focus of this article, certain endogenous chemicals in human milk beneficial to the health of the infant warrant study as well.

Quinine‐induced alterations in drug disposition

In normal volunteers, chronic quinine administration shortened plasma antipyrine half‐life and significantly increased the intra individual correlation between the disposition of quinine and antipyrine. Decreased plasma antipyrine half‐life appears to be due to a quinine‐induced enhancement of antipyrine metabolism. A dose‐dependent prolongation of plasma quinine half‐life was observed and attributed primarily to an increased apparent volume of distribution of quinine, although our data did not permit separation of an effect on quinine metabolism from an effect on quinine distribution between the peripheral and central compartments. Plasma protein binding of quinine was similar at both the low and high doses of quinine. Studies in dogs given quinine intravenously revealed a biphasic plasma decay curve compatible with a 2‐compartment open model for quinine disposition. Dose dependence of plasma quinine half‐life in the dog after intravenous quinine eliminated altered gastrointestinal absorption of quinine as a cause for the dose dependence of plasma quinine half‐life. These studies illustrate the importance of such conditions as dose and time of administration in determining the type and magnitude of interaction observed between drugs.

Safety Issues of Maternal Drug Therapy During Breastfeeding

Two goals when counseling breastfeeding mothers taking medication are protecting the infant from adverse events and permitting necessary maternal therapy. Madadi et al. report a case–control study of neonatal and maternal opioid toxicity after codeine administration. Therapeutic considerations in counseling breastfeeding mothers include susceptibility to drug toxicity of the very young and/or premature infant, significant interindividual variations in drug response, the dose–response relationship with respect to drug toxicity, and the role of pharmacogenetics in both the mother and the infant. These host factors may combine in a particular patient to act synergistically to produce an adverse reaction.

Alternative Modified Infant-Feeding Practices to Prevent Postnatal Transmission of Human Immunodeficiency Virus Type 1 Through Breast Milk: Past, Present, and Future

Preventing mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) through breastfeeding is important to reduce the number of infected children. Research on making breastfeeding safer is a high priority. The authors reviewed the attempts to develop alternative methods, other than antiretroviral (ARV) therapy of mothers and/or babies, to decontaminate breast milk of infectious HIV-1 (free and associated with lymphocytes). They also review how these methods affect milk constituents, as well as their current and prospective status. A PubMed search for English publications on methods to prevent MTCT through breast milk was completed. Methods that have been tested, other than systemicuse or ARV or immunoprophylaxis, to reduce or prevent MTCT of HIV-1 through breast milk were broadly classified into 5 groups: (1) modified feeding practices, (2) heat treatment of milk, (3) lipolysis, (4) antimicrobial treatment of the breastfeeding mother, and (5) microbicidal treatment of infected milk. Their advantages and disadvantages are discussed, as well as future directions in the prevention of MTCT through breastfeeding.

The Heart of the Matter on Breastmilk and Environmental Chemicals: Essential Points for Healthcare Providers and New Parents

Abstract The increasing number of environmental chemicals measured in breastmilk is a consequence of improved analytical capabilities and the increased interest in biomonitoring. It has been generally concluded that the benefits to the infant from breastfeeding outweigh potential risks associated with environmental chemical exposures associated with breastfeeding. However, there have been reports of subtle effects on infants associated with chemicals in breastmilk. Associations between concentrations of chemicals in breastmilk and a biochemical or other change in infants may signal the need for further study or regulatory action, whereas on an individual level, these changes may not be considered adverse. For healthcare providers, this distinction is critical, as many in the field are being asked for nuanced information on risks and benefits associated with breastfeeding, and this information is not readily available. Recognizing the challenge faced by healthcare providers, we have explored and developed a case study on dioxins in breastmilk. The essential conclusion for healthcare providers and new parents is that in studies of breastfed versus formula-fed infants across time, including times when levels of environmental chemicals such as dioxins were higher, beneficial effects associated with breastfeeding have been found. The current evidence does not support altering the World Health Organization recommendations promoting and supporting breastfeeding.

TECHNICAL WORKSHOP ON HUMAN MILK SURVEILLANCE AND RESEARCH ON ENVIRONMENTAL CHEMICALS IN THE UNITED STATES: AN OVERVIEW

Interest in human milk research and monitoring for environmental chemicals is growing, and as studies of chemicals in human milk are initiated, it is of the utmost importance that these studies be conducted using harmonized methods. Due to numerous limitations in previous studies and the fact that few studies on environmental chemicals in human milk have been conducted in the United States, there is a growing need for a human milk sampling and analysis protocol in this country. The Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States was organized to develop state-of-the-science protocols describing the various aspects of such a program. An expert panel, comprised of specialists in the fields of pediatrics, family medicine, nursing, lactation, human milk sampling, analytical chemistry, epidemiology, pharmacology, toxicology, nutrition, and risk evaluation and communication, was assembled to participate in a 2-day workshop at the Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine. The expert panel was tasked with carefully describing and defining the components of well-conducted human milk surveillance and research studies, including participant selection, sample collection and analysis techniques, questionnaire development, chemical selection, and data reporting and interpretation, especially for use in the United States. The articles that follow this overview describe the results of the expert panels deliberations on the components of human milk surveillance and research programs.

Biochemical Analysis of Human Milk Treated With Sodium Dodecyl Sulfate, an Alkyl Sulfate Microbicide That Inactivates Human Immunodeficiency Virus Type 1

Reduction of transmission of human immunodeficiency virus type 1 (HIV-1) through human milk is needed. Alkyl sulfates such as sodium dodecyl sulfate (SDS) are microbicidal against HIV-1 at low concentrations, have little to no toxicity, and are inexpensive. The authors have reported that treatment of HIV-1-infected human milk with ≤ 1% (10 mg/mL) SDS for 10 minutes inactivates cell-free and cell-associated virus. The SDS can be removed with a commercially available resin after treatment without recovery of viral infectivity. In this article, the authors report results of selective biochemical analyses (ie, protein, immunoglobulins, lipids, cells, and electrolytes) of human milk subjected to SDS treatment and removal. The SDS treatment or removal had no significant effects on the milk components studied. Therefore, the use of alkyl sulfate microbicides to treat milk from HIV-1-positive women may be a simple, practical, and nutritionally sound way to prevent or reduce transmission of HIV-1 while still feeding with mother’s own milk.

Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS)

BackgroundReducing transmission of HIV-1 through breast milk is needed to help decrease the burden of pediatric HIV/AIDS in society. We have previously reported that alkyl sulfates (i.e., sodium dodecyl sulfate, SDS) are microbicidal against HIV-1 at low concentrations, are biodegradable, have little/no toxicity and are inexpensive. Therefore, they may be used for treatment of HIV-1 infected breast milk. In this report, human milk was artificially infected by adding to it HIV-1 (cell-free or cell-associated) and treated with ≤1% SDS (≤10 mg/ml). Microbicidal treatment was at 37°C or room temperature for 10 min. SDS removal was performed with a commercially available resin. Infectivity of HIV-1 and HIV-1 load in breast milk were determined after treatment.ResultsSDS (≥0.1%) was virucidal against cell-free and cell-associated HIV-1 in breast milk. SDS could be substantially removed from breast milk, without recovery of viral infectivity. Viral load in artificially infected milk was reduced to undetectable levels after treatment with 0.1% SDS. SDS was virucidal against HIV-1 in human milk and could be removed from breast milk if necessary. Milk was not infectious after SDS removal.ConclusionThe proposed treatment concentrations are within reported safe limits for ingestion of SDS by children of 1 g/kg/day. Therefore, use of alkyl sulfate microbicides, such as SDS, to treat HIV1-infected breast milk may be a novel alternative to help prevent/reduce transmission of HIV-1 through breastfeeding.