Breast Milk Transfer Research Articles

A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance

Minnesota has been grappling with extensive per- and polyfluoroalkyl substances (PFASs) groundwater contamination since 2002, in a major metropolitan setting. As toxicological information has accumulated for these substances, the public health community has become increasingly aware of critically sensitive populations. The accumulation of some PFAS in women of childbearing age, and the placental and breastmilk transfer to their offspring, require new risk assessment methods to protect public health. The traditional water guidance paradigm is inadequate to address maternal-to-infant transfer of accumulated levels of perfluorooctanoate (PFOA), in particular. Even short exposures during infancy have dramatic impacts on serum levels for many years. In addition, developmental effects are the critical effects anchoring recent risk assessments. In response, the Minnesota Department of Health created an Excel-based model that incorporates chemical-specific properties and exposure parameters for early life stages. Serum levels were assessed in both formula-fed and breastfed infants, with placental transfer in both scenarios. Peak breastfed infant serum levels were 4.4-fold higher than in formula-fed infants, with both of these scenarios producing serum levels in excess of the adult steady-state level. The development and application of this model to PFOA are described.

Simple physicochemical properties related with lipophilicity, polarity, molecular size and ionization status exert significant impact on the transfer of drugs and chemicals into human breast milk

ABSTRACTObjectives: The transfer of xenobiotic compounds into human breast milk has raised serious concerns in the last few years. The present study is aimed to assess whether simple physicochemical properties exert significant impact on human breast milk transfer of drugs and chemicals.Methods: A large data set of 375 xenobiotic compounds with available experimental milk to plasma (M/P) ratios was systematically compiled from the literature and explored with their physicochemical properties being further analyzed with respect to their extent to transfer into breast milk.Results: Xenobiotic compounds with increased breast milk transfer (M/P ≥ 1) were characterized by enhanced lipophilicity and decreased molecular size (p < 0.05). Enhanced polarity and hydrogen bonding capacity were more frequently observed in xenobiotic compounds with reduced breast milk transfer (p < 0.0001). Xenobiotic compounds presenting increased positive charge at pH 7.4 were characterized by enhanced breast milk transfer (p < 0.001). Xenobiotic compounds presenting increased negative charge at pH 7.4 were characterized by decreased breast milk transfer (p < 0.001).Conclusions: The present study supports evidence that simple physicochemical properties related with lipophilicity, polarity, molecular size and ionization status exert significant impact on drugs and chemicals transport into human breast milk.

A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate.

Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother-baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 μL of plasma, and with application to human breast milk. Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water-methanol-acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection. Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration-time curve for the interval 0-12 hours was 10,726 mcg·h·L, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration. An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.

Clinically significant anti-KEL RBC alloantibodies are transferred by breast milk in a murine model.

Fetuses affected by maternal RBC alloantibodies may have prolonged anaemia after birth, leading one to question whether maternal alloantibody transfer may occur outside the placenta. In response to a recent publication describing breast milk transfer of clinically significant amounts of maternal antiplatelet IgA antibodies from mother to nursing infant, we hypothesized that maternal RBC alloantibodies may also be capable of being transferred in breast milk. The presence and clinical significance of breast milk alloantibody transfer were tested through a series of pregnancy, fostering and transfusion experiments, using a murine model in which transgenic RBCs express the human KEL glycoprotein. Maternal anti-KEL immunoglobulins, induced through transfusion or pregnancy, were detected in the aqueous phase of breast milk. Further, efficient transfer of maternal anti-KEL IgG and IgA to nursing pups was observed in fostering experiments. The breast milk-acquired alloantibodies were clinically significant in wild-type pups in a transfusion setting, binding to 'incompatible' KEL RBCs and leading to premature clearance from the circulation. Although breast milk-acquired alloantibodies also bound to the RBCs of transgenic KEL-positive fostered pups, no anaemia resulted. Taking these murine data in combination with recently published human data of maternal antiplatelet IgA antibodies in breast milk leading to sequelae in some infants, it is theoretically possible that maternal anti-RBC IgA alloantibodies may also be transferred in human breast milk and may lead to sequelae in some infants under some circumstances.

The Use of Nipple Shields: A Review.

A nipple shield is a breastfeeding aid with a nipple-shaped shield that is positioned over the nipple and areola prior to nursing. Nipple shields are usually recommended to mothers with flat nipples or in cases in which there is a failure of the baby to effectively latch onto the breast within the first 2 days postpartum. The use of nipple shields is a controversial topic in the field of lactation. Its use has been an issue in the clinical literature since some older studies discovered reduced breast milk transfer when using nipple shields, while more recent studies reported successful breastfeeding outcomes. The purpose of this review was to examine the evidence and outcomes associated with nipple shield use. A literature search was conducted in Ovid MEDLINE, OLDMEDLINE, EMBASE Classic, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL. The primary endpoint was any breastfeeding outcome following nipple shield use. Secondary endpoints included the reasons for nipple shield use and the average/median length of use. For the analysis, we examined the effect of nipple shield use on physiological responses, premature infants, mothers' experiences, and health professionals' experiences. The literature search yielded 261 articles, 14 of which were included in this review. Of these 14 articles, three reported on physiological responses, two reported on premature infants, eight reported on mothers' experiences, and one reported on health professionals' experiences. Through examining the use of nipple shields, further insight is provided on the advantages and disadvantages of this practice, thus allowing clinicians and researchers to address improvements on areas that will benefit mothers and infants the most.

Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers.

Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range, 6 to 145 days). A blood sample was taken at delivery, and additional serial samples were available from 9 women who delivered within 42 days of dosing. Milk and plasma PQ were assayed by high-performance liquid chromatography. A population-based approach was used to model the loge(plasma) and milk concentration-time data. A sigmoid Emax model best described PQ breast milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body weight/day) was similar to the accepted value of 150 ml/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 μg and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 μg/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week postdelivery, and 6 weeks postdelivery showed that the highest median estimated relative total infant dose (0.36%; median absolute total dose of 101 μg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily doses from any scenario were 4.3% and 2.5%, respectively, which were lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses, but PQ exposure for suckling infants appears safe.

Dose to the Mother Method: Milk Intake and Vitamin A Transfer to the Lactating Infant of Mexican Mothers, Using Stable Isotopes

ObjectiveTo assess the breast milk intake and transfer of vitamin A (VA) from the mother to the breastfed child in lactating Mexican women from rural and urban areas.MethodsMilk intake was assessed with the dose to the mother method, briefly deuterated water is administered to the mother and the appearance of the isotope is measured in the breastfed child's and mother's saliva; deuterium enrichment (stable isotope) is analyzed by FTIR. Breast milk retinol (BMR) concentration was determined by HPLC and the cutoff to define VA deficiency was 1.05 µmol/L.ResultsSubjects were 27 and 32 women‐child pairs from urban and rural areas of northwest Mexico, respectively. Mean breast milk intake 727.35 ± 224 mL and it was significantly lower in children from the rural area (P=0.04). Mean BMR concentration was 1.11 μmol/L and 53% of women had VAD. BMR concentration was lower for the rural area (P=0.038). By combining both determinations (DTM and BMR), results showed that breastfed children from the rural and urban area reached only 47% and 64% of their VA recommended dietary intake (P=0.051), respectively.ConclusionVAD is still a public health problem in Mexico and requires new approaches to fight it effectively.Study supported by Universidad de Sonora.

A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection

Pregnant women and neonates represent high-risk groups for influenza infection, and in general have suppressed responses to standard influenza vaccines due to pregnancy-associated immune suppression and immune system immaturity, respectively. We therefore wished to test whether addition of Advax™, a polysaccharide adjuvant based on delta inulin, to an inactivated influenza vaccine (A/H1N1/PR8) administered during pregnancy would safely enhance vaccine immunogenicity and thereby provide improved protection of pregnant mothers and their newborns. Pregnant mice received a single intramuscular injection of β-propiolactone-inactivated H1N1 antigen alone or with Advax adjuvant. Pregnant dams receiving Advax-adjuvanted vaccine exhibited significantly increased serum and breast milk anti-influenza IgG titers. This translated into higher serum anti-influenza IgG titers in the pups of these dams. Complete protection was seen in pups of dams that received Advax-adjuvanted vaccine whereas no survival was seen in pups of control mothers or mothers immunized with unadjuvanted influenza vaccine. Cross-fostering studies confirmed that enhanced protection of pups of dams that received Advax-adjuvanted vaccine was mediated by enhanced transfer of maternal IgG to the pups via breast-feeding. The delta inulin adjuvant was not associated with any reproductive or developmental adverse effects. This study shows that Advax adjuvant was safe when administered with influenza vaccine during pregnancy and provided protection of pups via enhanced breast milk transfer of anti-influenza antibodies, not seen with administration of unadjuvanted vaccine.

Zinc Transferred through Breast Milk Does Not Differ between Appropriate- and Small-for-Gestational-Age, Predominantly Breast-Fed Bangladeshi Infants1–3

Information is needed on breast milk zinc concentration and amount of zinc transferred to the infant in relation to the time since birth for both appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) infants. Breast milk zinc concentration and total milk volume were measured among mothers of AGA and SGA infants, using deuterium oxide “dose-to-mother” tracer technique and plasma zinc concentrations of mothers and infants. Forty-six mother–infant pairs (20 AGA and 26 SGA infants) were recruited from a low-income community in Bangladesh. Each mother–infant pair was studied 3 times: at 4, 12, and 24 wk postpartum. During each round, 2-wk studies of breast milk transfer were performed, using deuterium oxide dose-to-mother tracer technique. Breast milk samples were collected on days 1 and 5 of each round to determine milk zinc concentration. Mean ± SD birth weight and length were 3.02 ± 0.2 kg and 0.482 ± 0.012 m, respectively, for AGA and 2.34 ± 0.20 kg and 0.462 ± 0.011 m, respectively, for SGA infants, and both variables were different between groups (birth weight, P < 0.001; length, P < 0.001). Breast milk intake increased gradually with time postpartum in both groups. Breast milk zinc concentration decreased with increasing infant age (P < 0.001) but did not differ for mothers of AGA and SGA infants. Breast milk zinc transfer decreased significantly with age in both groups (P < 0.001) but did not differ by birth-weight category. Breast milk zinc concentration among Bangladeshi mothers and patterns of change at 24 wk were similar to those of wealthier countries, and there was no relation between infant birth-weight category and milk zinc concentration or transfer. This trial was registered at www.clinicaltrials.gov> as NCT01728766.

1045 Longitudinal Studies of Breast Milk Zinc Transfer to Appropriate- and Small-For-Gestational-Age, Predominantly Breast Fed, Bangladeshi Infants

BackgroundIn developing countries, information is limited on concentration of breastmilk zinc, total amount of zinc transferred to infants through breast milk and whether zinc transfer through breastmilk differs among appropriate-for-gestational-age...

Weighing worth against uncertain work: the interplay of exhaustion, ambiguity, hope and disappointment in mothers breastfeeding late preterm infants.

Poor breastfeeding outcomes among late preterm infants (LPIs) have been attributed to inadequate breast milk transfer stemming from physiological immaturities. However, breastfeeding is more than a biological phenomenon, and it is unclear how mothers of LPIs manage other factors that may also impact the breastfeeding course. Using grounded theory methods and incorporating serial post-partum interviews with several novel data collection techniques, we examined breastfeeding establishment over a 6-8-week-period among 10 late preterm mother-infant dyads recruited from a maternity hospital in Pittsburgh, Pennsylvania, USA. We found that breastfeeding in the LPI population was a fluctuating, cascade-like progression of trial and error, influenced by a host of contextual factors and events and culminating with breastfeeding continuation (with or without future caveats for duration or exclusivity of breastfeeding) or cessation. The trajectory was explained by the basic psychosocial process Weighing Worth against Uncertain Work, which encompassed the tension among breastfeeding motivation, the intensity of breastfeeding work and the ambiguity surrounding infant behaviour and feeding cues. Several sub-processes were also identified: Playing the Game, Letting Him Be the Judge vs. Accommodating Both of Us and Questioning Worth vs. Holding out Hope. If valid, our theoretical model indicates a need for earlier, more extensive and more qualified breastfeeding support for mothers of LPIs that emphasizes the connection between prematurity and observed feeding behaviours.

Organochlorine pesticide residues in biological compartments of healthy mothers

The present study was conducted to detect placental and breast milk (BM) transfer of organochlorine pesticides (OCPs) between biological compartments in healthy lactating mothers. The study explores the effect of parity, breast-feeding and urban/rural residence on body burden of OCP residues. The study included 38 healthy participants submitted to cesarean delivery. Sociodemographic data and specimens of maternal and umbilical sera, adipose tissue (Adp T) and BM were collected. Specimens were analyzed to detect OCP residues. The lindane in BM, o,p'-dichlorodiphenyldichloroethane (DDD) in maternal serum (MS) and total dichlorodiphenyltrichloroethane (DDT) and o,p'-dichlorodiphenyldichloroethylene in umbilical serum were the only detected residues in significantly higher frequencies and/or means in the primigravidae than multigravidae. There was a high risk of detecting o,p'-DDD (odds ratio = 8.3) in umbilical serum of the mothers with o,p'-DDD detected in the MS. Total DDT was detected in about 65% of specimens of BM, MS and Adp T and in about 40% of the umbilical serum specimens. There was only a significant positive correlation between total DDT residues in the BM and Adp T. Total DDT residues in umbilical serum and Adp T were significantly higher in the urban than in the rural mothers. The detection of some OCPs in maternal biological compartments suggests their potential placental and BM transfer to her child during pregnancy and lactation, respectively. Furthermore, it might reflect the persistence or recent use of these pesticides in the environment.

Hypernatremia in Breastfed Newborns: a Review of 149 Cases

Inadequate transfer of breast milk may cause hypernatremic dehydration in neonates and is a potentially devastating condition. This study aimed to assess the frequency risk factors complaints and complications of hypernatremia among hospitalized breastfed neonates at a neonatal tertiary care center in the Northeast of Turkey. Neonatal hypernatremia is a frequent reason for hospitalization in the newborn unit at the Turkish hospital. However as birth rates are excessive in this region it is compulsory to discharge babies without 24 hours of hospital care after birth. For this reason the pressing issue is the education of mothers on signs of successful breastfeeding.

Nutritionally mediated programming of the developing immune system.

A growing body of evidence highlights the importance of a mother's nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a "layered" expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease.

The epidemic of HIV/AIDS in developing countries; the current scenario in Pakistan.

HIV (Human Immunodeficiency virus) causes (acquired immunodeficiency syndrome) AIDS, in which the immune system of body totally fails to develop any defense against the foreign invaders. Infection with HIV occurs by transfer of blood, semen, and breast milk. HIV/AIDS is a global problem and it results nearly 25 million deaths worldwide. Developing countries like Pakistan have issues regarding Public Health. Currently, epidemic of HIV/AIDS is established in Pakistan and there is a threat of an expanded HIV/AIDS outbreak in the country. The major reason is that population is engaging in high-risk practices, low awareness about HIV/AIDS, and treacherous blood transfusion practices. A supplementary threat to Pakistan is India because both sharing a border and India is facing a rapidly growing HIV/AIDS epidemic. Local NGOs, National and International organizations are warning that in near future Pakistan may experiences bad situation regarding HIV/AIDS.In the present article we focused current situation of surveillance of HIV/AIDS, its virology, genotype, diagnostics, high-risk groups, reasons of vulnerability in Pakistani population, and the role of different national and international organizations in this situation.

Breast Milk Zinc Transfer to Appropriate‐ for‐Gestational‐Age (AGA) and Small‐for‐Gestational‐Age (SGA) Bangladeshi Infants: Studies of Milk Volume, Using Deuterium‐To‐Mother, and Milk Zinc Concentrations

ObjectiveTo measure breast milk zinc transfer by mothers of AGA and SGA infants.MethodsWe studied breast milk transfer (using the deuterium “dose‐to‐the‐mother” technique) and milk zinc concentration of 73 mother‐infant pairs (33 AGA, 40 SGA) at 4, 12 and 24 wks post‐partum. In each round, 30 g deuterium was given orally to the mother following baseline blood and saliva collection from mothers and infants. Saliva samples were then obtained for deuterium analysis on days 1, 2, 3, 4, 13, and 14 from infants and days 1, 2, 13 and 14 from mothers. Breast milk zinc concentration was measured in milk collected at baseline and day 4 each round.ResultsBreast milk intake increased significantly with infant age (643 ± 190; 756 ± 150; 804 ± 150 g/d at 4, 12 and 24 weeks, respectively; p=0.000), and differed by birth weight (BW) groups only at 4 weeks post‐partum (AGA = 714 ± 193 vs SGA = 579 ± 164 g/d; p=0.005). Milk zinc concentration decreased significantly from 2.46 mg/L at 4 weeks to 1.02 mg/L at 24 weeks (p=0.000), but did not differ by BW group at any time point. Zinc transfer through breast milk declined significantly with infant age (1.60 ± 0.62; 1.08 ± 0.41; 0.81 ± 0.32 mg/d at 4, 12 and 24 weeks respectively; p=0.000), but did not differ by BW group.ConclusionsMilk zinc concentrations and total milk zinc transfer of Bangladeshi mothers are consistent with published data, and do not differ for mothers of AGA and SGA infants.

English

English

Management issues for women with epilepsy—Focus on pregnancy (an evidence‐based review): III. Vitamin K, folic acid, blood levels, and breast‐feeding

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.

To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Transfer of Buprenorphine Into Breast Milk and Calculation of Infant Drug Dose

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.