Human milk research for answering questions about human health

Concerns regarding human milk in our society are diverse, ranging from the presence of environmental chemicals to the health of breastfed infants and the economic value of breastfeeding to society. The panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on 24--26 September 2004, considered how human milk research may contribute to environmental health initiatives to benefit society. The panel concluded that infant, maternal, and community health can benefit from studies using human milk biomonitoring. Unlike other biological specimens, human milk provides information regarding exposure of the mother and breastfed infant to environmental chemicals. Some of the health topics relevant to this field of research include disorders of growth and development in infants, cancer origins in women, and characterization of the trend of exposure to environmental chemicals in the community. The research focus will determine the design of the study and the need for the collection of alternative biological specimens and the long-term storage of these specimens. In order to strengthen the ability to interpret study results, it is important to identify reference ranges for the chemicals measured and to control for populations with high environmental chemical exposure, because the amount of data on environmental chemical levels in human milk that is available for comparison is extremely limited. In addition, it will be necessary to validate models used to assess infant exposure from breastfeeding because of the variable nature of current models. Information on differences between individual and population risk estimates for toxicity needs to be effectively communicated to the participant. Human milk research designed to answer questions regarding health will require additional resources to meet these objectives.     

Antibiotics and lactation: An overview of relative infant doses and a systematic assessment of clinical studies

Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling. The infant exposure has been calculated and expressed as a percentage of a normal infant therapeutic dose. Sixty‐six studies were included in five antibiotic groups (broad‐spectrum penicillin, cephalosporins, macrolides and lincosamides, quinolones and sulphonamides). Cephalosporins were the most studied group of antibiotics (n = 21). Fifteen studies met all the criteria of “mother exposure to antibiotic”. Six studies met every criterion related to “plasma sampling”. Only one case report met all listed criteria for lactation studies. The correct calculation of infant exposure to antibiotics via the milk:plasma ratio (AUC) varies between 13% for macrolides and 38% for broad‐spectrum penicillin. The highest assessed exposure as a percentage of infant therapeutic dose was for metronidazole (11%). The studies meet to a limited extent with the quality standards for lactation research. The breastfed infants are exposed to a subtherapeutic concentration of antibiotics.     

Collection and use of exposure data from human milk biomonitoring in the United States

Human milk is a unique biological matrix that can be used to estimate exposures in both the mother and the breastfed infant. In addition, the presence of environmental chemicals in human milk may act as a sentinel for exposures to a broader population. Several factors play a role in determining the quantity of chemicals transferred to milk and, subsequently, to the breastfeeding infant, including maternal, infant, and chemical characteristics. Exposure to certain environmental chemicals during critical periods can disrupt normal infant development, yet few data exist to quantify the hazards posed by environmental chemicals in human milk. Chemicals measured in human milk may also provide insights to agents suspect in altering breast development and breast-related disease risk. Carefully designed exposure assessment and toxicokinetic studies are needed to elucidate mechanisms and establish relationships between human milk and other biologic matrices. Data from human milk biomonitoring studies can be used to inform and validate models that integrate information about chemical properties, human metabolism, and biomarker concentrations. Additional research is needed to determine the degree to which environmental chemicals enter, are present in, and are excreted from human milk, their impact on the host (mother), and the extent of their bioavailability to breastfeeding infants. This article describes how the collection and use of exposure data from human milk biomonitoring in the United States can be designed to inform future research and policy.     

Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants

AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS: Six women (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high-performance liquid chromatography over a 12 h dose interval at steady-state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362, 1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 microg l(-1)), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day. CONCLUSIONS: The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5-7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.     

Anticonvulsant use during lactation.

The issue of prescribing anticonvulsant drugs during lactation is clinically important, but also complex. Data for some drugs are completely lacking and for other drugs information is only available from single dose or short term studies or case reports. Moreover, limited knowledge exists about the practical impact of the drug concentrations found in breast milk and there are great methodological problems in the assessment of possible adverse drug reactions in infants. Nevertheless, based on current knowledge, some recommendations can be suggested. Treatment with carbamazepine, valproic acid (sodium valproate) and phenytoin is considered compatible with breastfeeding. Treatment with ethosuximide or phenobarbital (phenobarbitone)/primidone should most probably be regarded as potentially unsafe and close clinical monitoring of the infant is recommended if it is decided to continue breastfeeding. Occasional or short term treatment with benzodiazepines could be considered as compatible with breastfeeding, although maternal diazepam treatment has caused sedation in suckling infants after short term use. During long term use of benzodiazepines, infants should be observed for signs of sedation and poor suckling. Only very limited clinical data are available for the new generation anticonvulsant drugs and no clearcut recommendations can be made until further data are present. If it is decided to continue breast feeding during treatment with these drugs, the infant should be monitored for possible adverse effects. In general, the drug should be given in the lowest effective dose, guided by maternal serum or plasma drug concentration monitoring. If breast feeding is avoided at times of peak drug levels in milk, the exposure of the infant can be reduced to some extent. As breast milk has considerable advantages over formula milk, the benefits of continuing breast feeding should always be taken into consideration in the risk-benefit analysis.     

Transfer of escitalopram and its metabolite demethylescitalopram into breastmilk

AIMS: To investigate the transfer of escitalopram and its demethyl metabolite into milk, the absolute and relative infant doses via milk and to assess any unwanted effects in the breastfed infant. METHODS: Multiple samples of blood and milk were obtained over a dose interval at steady state from eight women who were taking escitalopram for postnatal depression. Drug concentrations in plasma and milk were measured by high-performance liquid chromatography and milk/plasma ratio (M/P(AUC)), absolute infant dose and relative infant dose were estimated by standard methods. Their breastfed infants were also examined clinically and in five infants a blood sample was taken for drug analysis. RESULTS: The median dose taken by the women was 10 mg day(-1). The mean (95% confidence interval) M/P(AUC) was 2.2 (2.0, 2.4) for escitalopram and 2.2 (1.9, 2.5) for demethylescitalopram. Absolute infant doses were 7.6 microg kg(-1) day(-1) (5.2, 10.0) for escitalopram and 3.0 microg kg(-1) day(-1) (2.4, 3.6) for demethylescitalopram. The total relative infant dose for escitalopram plus its demethyl metabolite was 5.3% (4.2, 6.4) as escitalopram equivalents. All of the infants had met normal developmental milestones and no adverse effects were seen. Compared with average maternal plasma concentrations (24 microg l(-1)), the concentrations of the parent drug and its metabolite in plasma from five infants were most commonly below the limit of detection (相似文献   

Celecoxib in human milk: a case report

Many women of reproductive age take the nonsteroidal antiinflammatory drug celecoxib. No data exist, however, regarding its transfer into human breast milk and safety for breastfed infants. We had the opportunity to obtain such data when a woman who was breastfeeding her infant daughter underwent emergency surgery to remove a gangrenous appendix. She received four doses of oral celecoxib 100 mg and did not breastfeed her daughter for 48 hours after taking the last dose. We analyzed samples of her breast milk and found a concentration of 133 ng/ml at approximately 5 hours after a 100-mg dose and an elimination half-life of 4.0-6.5 hours. This initial report, which should be substantiated and expanded, provides information that can help counsel parents about breastfeeding and celecoxib.     

Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database

Purpose

Most drugs are excreted in maternal milk and may therefore be ingested by children during breastfeeding. Data concerning the safety of the use of drugs by breastfeeding women are patchy, and almost nothing is known about this issue for many drugs.

Methods

The aim of this study was to describe the adverse drug reactions of drugs transmitted in breast milk on the basis of the data collected in the French Pharmacovigilance Database. All spontaneous reports of adverse drug reactions (ADRs) in breastfed infants recorded in the National Pharmacovigilance Database by the 31 French regional pharmacovigilance centres between 1984 and June 2011 were investigated.

Results

Between January 1985 and June 2011, 276 adverse drug reactions in 174 breastfed children were notified to the French Pharmacovigilance Network. The most frequently reported adverse drug reactions were neurological (28.6 %) and gastrointestinal (20.3 %). Sixty-five of the adverse drug reactions recorded were considered to be serious (37.4 %). The results of our study confirm that certain drugs were frequently implicated in serious adverse drug reactions. Two cases of ADRs (1.1 %) had a ‘certain’ causality score (I4) and 13 (7.5 %) a ‘likely’ score (I3). The suspected drugs include antiepileptic drugs, opiate analgesics and benzodiazepines. These results also demonstrate that some drugs that were thought to be anodyne or for which no data were available, such as ketoprofen and hydroxyzine, may be implicated in adverse effects. Finally, these data show that certain drugs, like pseudoephedrine, which should not be used during breastfeeding, were nevertheless implicated in several of the adverse drug reactions recorded.

Conclusion

This study shows that ADR via breastfeeding are rarely reported due to low awareness or low occurrence of ADR via breast milk. These results highlight the need for additional pharmacokinetic, clinical and epidemiological studies, given the paucity of published data. They also demonstrate the need to improve information for the general public about drugs and self-medication during breastfeeding.     

Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk

AIMS

To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant.

METHODS

Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2–4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied.

RESULTS

At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) μg kg⁻¹ day⁻¹ and 30 (28, 32) μg kg⁻¹ day⁻¹, and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores.

CONCLUSIONS

The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant.

WHAT THIS STUDY ADDS

• We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant.
• We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk.

     

Metformin before and during pregnancy and lactation in polycystic ovary syndrome

Metformin improves the endocrinopathy of polycystic ovary syndrome (PCOS), facilitates conception, appears to reduce first trimester miscarriage and gestational diabetes and does not appear to be teratogenic. The concentrations of metformin in breast milk are generally low and the mean infant exposure to metformin has been reported in the range 0.28-1.08% of the weight-normalized maternal dose, well below the level of concern for breastfeeding. No adverse effects on blood glucose of nursing infants have been reported. Metformin during lactation versus formula feeding appears to have no adverse effects on infants' growth, motor-social development and intercurrent illness during the first 6 months of life. Systematic studies have not yet been done assessing how hyperinsulinemia, polycystic ovary syndrome and metformin may affect lactation.     

Changes in children hair-Hg concentrations during the first 5 years: maternal, environmental and iatrogenic modifying factors

Children are exposed to Hg from mothers (via placenta and lactation), environment (food), and in many parts of the world by thimerosal-containing vaccines (TCV) during immunization. Neurodevelopment studies based on infant hair-Hg (HHg) have been designed without explicit attention to the factors associated with changes in infant physiology and Hg sources of exposure. A longitudinal study of changes in HHg concentrations from birth to 5 years was done in a sample of children from Porto Velho (Rondonia), Brazilian Amazonia. The study extracted information from the asymmetry associated with maternal and infant HHg changes at specified sampling: birth (fetal exposure), 6 months of exclusive breastfeeding, 36 months (weaning) and 60 months (pre-school). The distribution of HHg in breastfed infants followed a pattern different from their mothers. While mothers had the highest HHg concentrations at childbirth, infants showed the highest HHg values at 6 months after the recommended full schedule (six shots) of immunization with TCV; after that, the downward trend in HHg shown by children coincided with both weaning and less frequent vaccination period (5 years). Extended lactation (up to 36 months) was not significantly associated with HHg of infants or mothers; however, significant association (Spearman's r) between maternal and infant HHg concentration was seen at birth (r=0.3534; P=0.001), 6 months (r=0.4793; P<0.0001), 3 years (r=0.0122; P=0.012) and 5 years (r=0.0357; P=0.005). Maternal postpartum metabolic changes, infant development and transitional diets and possibly Hg from TCV contribute to the asymmetry of HHg changes between mothers and children.     

Factors influencing the recruitment of lactating women in a clinical trial involving direct oral anticoagulants: a qualitative study

Background Robust human data on medication use during lactation is scarce. With increasing medication use in postpartum women, it is important to conduct clinical lactation studies measuring the excretion of drugs in human milk and generate evidence. We plan to conduct a clinical lactation study, involving the direct oral anticoagulants (DOACs). Objective This study aimed to identify factors influencing lactating women’s clinical trial participation and to improve the design of a proposed DOACs clinical lactation study. Setting Lactating women in London, UK. Methods Three focus groups were conducted in lactating women with differing experiences of being prescribed anticoagulants during puerperium. Main outcome measures Thematic framework approach was used to analyse and identify key themes, using NVivo version 11. Results Eight breastfeeding mothers participated. Women’s decision-making on clinical trial participation was largely influenced by the lactation stage and previous breastfeeding experience. The concern of harm to their infant caused by the test medication or interruption of lactation were the predominant barriers to potential participation. Around 6 months following the birth of their infant and second-time mothers appeared to be more amenable to clinical trial participation. The provision of home visits for the execution of the study was highly recommended. Conclusion Our findings suggest that lactating women would participate in a clinical trial during the breastfeeding period, if the timing is right and if the woman is an experienced mother. Home visits will be provided in our proposed DOACs clinical lactation study.     

Assessment of ethanol exposure from hand sanitizer use and potential for developmental toxicity in nursing infants

Ingestion of ethanol during pregnancy is known to have detrimental effects on the fetus. Although the potential developmental effects of maternal ethanol intake during lactation are less well characterized, public health guidelines recommend avoidance of alcohol or, if alcohol is consumed, to allow for 1–2 h to pass before nursing. A proposal to classify ethanol as potentially harmful to breast-fed children warrants an investigation of the potential adverse neurodevelopmental effects of low-dose ethanol exposure during lactation. There currently are no studies that have examined neurodevelopmental outcomes from lactational exposure to ethanol from the use of topical products that contain ethanol, such as alcohol-based hand sanitizers (ABHS). Furthermore, the epidemiological literature of lactational ethanol exposures from maternal alcohol consumption is limited in design, provides equivocal evidence of neurological effects in infants, and is insufficient to characterize a dose–response relationship for developmental effects. Toxicological studies that observed neurodevelopmental effects in pups from ethanol via lactation did so at exceedingly high doses that also caused maternal toxicity. In this investigation, blood ethanol concentrations (BECs) of breastfeeding women following typical-to-intense ABHS use were computationally predicted and compared to health benchmarks to quantify the risk for developmental outcomes. Margins of 2.2 to 1000 exist between BECs associated with ABHS use compared to BECs associated with neurotoxicity adverse effect levels in the toxicology literature or oral ethanol intake per public health guidelines. Neurodevelopmental effects are not likely to occur in infants due to ABHS use by breastfeeding women, even when ABHSs are used at intense frequencies.     

Transfer of reboxetine into breastmilk, its plasma concentrations and lack of adverse effects in the breastfed infant

Objective To investigate the transfer of reboxetine into milk, the absolute and relative infant doses via milk and to assess plasma concentrations and adverse unwanted effects in the breastfed infant.Methods Multiple samples of blood and milk were obtained over a dose interval at steady-state from four women who were taking reboxetine for postnatal depression. Drug concentrations in plasma and milk were measured by high performance liquid chromatography and milk/plasma ratio (M/P), absolute infant dose and relative infant dose were estimated by standard methods. Their four, breastfed, infants were also examined clinically, and a blood sample was taken for drug analysis.Results The median (range) dose taken by the women was 6 (4-10) mg/day. There was no significant difference in reboxetine concentration between paired fore-and hind-milk samples. The mean (95% CI) M/P was 0.06 (0.03, 0.09). Absolute infant dose was 1.7 (0.7, 2.4) μg/kg/day for reboxetine while the relative infant dose was 2.0% (1.3, 2.7%). Three of the infants met normal developmental milestones and no adverse effects were seen in any infant. The fourth infant had developmental problems that were not associated with the maternal reboxetine therapy. The concentrations of reboxetine in plasma from the four infants were <4 μg/l, 2.6 μg/l, 2.3 μg/l and 5 μg/l, respectively.Conclusion The study suggests that reboxetine use by lactating women is safe for the breastfed infant. Nevertheless, our study had only four mother/baby pairs, and each decision to breastfeed should always be made on the basis of an individual risk/benefit analysis.     

Human milk biomonitoring data: interpretation and risk assessment issues

Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person's body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant's exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a "dose" from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of "risk assessment" as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on several issues related to risk assessment and human milk biomonitoring. Discussion of these topics and the thoughts and conclusions of the panel are described in this article.     

乳汁中药物浓度测定的研究进展

母乳喂养对婴儿来说是一种非常健康及有营养的获取能量的方式，对母亲和婴儿都有益处。患有某些疾病的哺乳母亲在进行药物治疗时，需要考虑药物是否会进入乳汁而对婴儿产生一些不良反应或对母亲产生影响。由于许多药物的哺乳期用药安全性并不十分明确，因此在临床治疗中不推荐哺乳期妇女使用。测定乳汁中的药物浓度可以明确合理的给药时间和给药剂量，提高用药安全性，对临床用药具有非常重要的意义。但乳汁成分复杂，含有大量脂质和蛋白质等干扰物质，使乳药浓度测定有一定困难。本文综述了国内外乳药浓度测定方法，以期为哺乳期合理用药提供参考。     

Assessment of infant dose through milk in a lactating woman taking amisulpride and desvenlafaxine for treatment-resistant depression

This study presents the case of a 35-year-old breastfeeding mother who delivered her fourth child 5 months previously and was prescribed 100 mg amisulpride twice daily and 250 mg desvenlafaxine in the morning for treatment-resistant depression. Arriving at this regimen took approximately 2 months postbirth. Because she was keen to continue breastfeeding her infant, and published data on the use of amisulpride and desvenlafaxine were very limited, the clinical team sought assistance from the therapeutic drug monitoring laboratory to quantify infant dose-exposure to guide consideration of continuing breastfeeding. A sampling schedule for milk and plasma from mother and plasma from her infant was agreed and drug concentrations were measured by high-performance liquid chromatography. Absolute (theoretic) infant dose (μg/kg/d) was calculated as the product of the average concentration in milk and an assumed milk intake of 0.15 L/kg/day (294 mg/kg/day for desvenlafaxine and 183 mg/kg/day for amisulpride), and relative infant dose was estimated as absolute infant dose expressed as a percentage of the maternal dose in μg/kg/day (7.8% for desvenlafaxine and 6.1% for amisulpride). Consistent with the infant being partially breastfed, the ratio of drug in the infant's plasma to that in mother's plasma was lower at 1.7% for desvenlafaxine and 3.9% for amisulpride. A pediatric assessment of the infant found achievement of expected developmental progress for age and no detectable drug-related adverse effects. Assessing the safety of breastfeeding was difficult because it involved simultaneous use of two drugs for which there was limited previous experience. However, after discussion of the infant dose-exposure data and lack of adverse effects, the mother elected to continue partial breastfeeding for the next few months. The clinical team plans a reassessment of the infant's progress in 3 months.     

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 exam ine 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.     

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.