Impact of Surfactant Protein-A on Immunomodulatory Properties of Murine and Human Breast Milk.

OBJECTIVES: Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk's immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice. METHODS: Human milk was collected at postpartum days 1-3 and 28. Mouse milk was collected at postpartum days 1-10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR. RESULTS: SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1ß, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams. CONCLUSIONS: SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.

Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P < 0.0001), n-6 docosapentaenoic acid (DPA) (0.275 ± 0.14% vs 0.04 ± 0.04%; P < 0.0001) and eicosapentaenoic acid (0.08 ± 0.08% vs 0.07 ± 0.07%; P < 0.0001) while decreasing n-3 DPA (0.16 ± 0.05% vs 0.17 ± 0.06%; P < 0.05). Supplementation changed the ratio of DHA to arachidonic acid (1.76 ± 1.55% vs 0.60 ± 0.31%; P < 0.0001) and n-6 to n-3 FA (0.21 ± 0.06% vs 0.17 ± 0.04%; P < 0.0001). DHA-rich algae supplementation successfully increased the DHA content of breast milk but also included secondary changes that are closely involved with inflammation and may contribute to changing clinical outcomes.

Use and experiences of galactagogues while breastfeeding among Australian women.

BACKGROUND: Galactagogues are substances thought to increase breast milk production, however evidence to support their efficacy and safety remain limited. We undertook a survey among Australian women to examine patterns of use of galactagogues and perceptions regarding their safety and effectiveness. METHODS: An online, cross-sectional survey was distributed between September and December 2019 via national breastfeeding and preterm birth support organisations, and networks of several research institutions in Australia. Women were eligible to participate if they lived in Australia and were currently/previously breastfeeding. The survey included questions about galactagogue use (including duration and timing), side effects and perceived effectiveness (on a scale of 1 [Not at all effective] to 5 [Extremely effective]). RESULTS: Among 1876 respondents, 1120 (60%) reported using one or more galactagogues. Women were 31.5 ± 4.8 years (mean ± standard deviation) at their most recent birth. Sixty-five percent of women were currently breastfeeding at the time of the survey. The most commonly reported galactagogues included lactation cookies (47%), brewer's yeast (32%), fenugreek (22%) and domperidone (19%). The mean duration of use for each galactagogue ranged from 2 to 20 weeks. Approximately 1 in 6 women reported commencing galactagogues within the first week postpartum. Most women reported receiving recommendations to use herbal/dietary galactagogues from the internet (38%) or friends (25%), whereas pharmaceutical galactagogues were most commonly prescribed by General Practitioners (72%). The perceived effectiveness varied greatly across galactagogues. Perceived effectiveness was highest for domperidone (mean rating of 3.3 compared with 2.0 to 3.0 among other galactagogues). Over 23% of domperidone users reported experiencing multiple side effects, compared to an average of 3% of women taking herbal galactagogues. CONCLUSIONS: This survey demonstrates that galactagogues use is common in Australia. Further research is needed to generate robust evidence about galactagogues' efficacy and safety to support evidence-based strategies and improve breastfeeding outcomes.

Monitoring topiramate concentrations at delivery and during lactation.

OBJECTIVE: To determine transplacental passage of topiramate and its transport to colostrum, mature maternal milk and breastfed infants, we examined data from 27 women treated with topiramate from 2004 to 2020. METHODS: In this cohort study, maternal serum, umbilical cord serum, milk and infant serum levels were measured by gas chromatography in the delivery subgroup, the colostrum subgroup (3-4 days postpartum) and the mature milk subgroup (7-30 days postpartum). Paired umbilical cord serum, maternal serum, breastfed infant serum, and milk levels were used to assess the ratios of umbilical cord/maternal serum, milk/maternal serum and infant/maternal serum levels. RESULTS: Topiramate levels varied from 1.0 to 7.1 mg/L in maternal serum and from 0.8 to 6.2 mg/L in umbilical cord serum, and the mean umbilical cord/maternal serum ratio was 0.93 ± 0.11. At 3-4 days after delivery, topiramate concentrations were 1.4-8.4 mg/L in maternal serum, 1.5-8.6 mg/L in milk and 0.3-4.4 mg/L in infant serum. The mean milk/maternal serum ratio was 0.99 ± 0.45, and the mean infant/maternal serum ratio was 0.25 ± 0.15. At 7-30 days after delivery, maternal serum levels varied from 1.9 to 9.7 mg/L, milk levels ranged from 2.3 to 10.6 mg/L and infant serum levels ranged from 0.3 to 6.5 mg/L. The mean milk/maternal serum ratio was 1.07 ± 0.31, and the mean infant/maternal serum ratio was 0.51 ± 0.27. CONCLUSIONS: We extended information about free transplacental passage of topiramate and its extensive transport to maternal milk with lower serum concentrations in breastfed infants in the largest group of patients ever reported to our knowledge. DATA AVAILABILITY STATEMENT: Authors declare that take full responsibility for the data, the analyses and interpretation, and the conduct of the research; that they have full access to all of the data; and that they have the right to publish all data. Authors were not participations in industry-sponsored research and corporate activities for evaluation of a manuscript.

Antidepressant transfer into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis.

OBJECTIVE: Data regarding the ability of antidepressants to enter fetal, newborn and infant fluids have become gradually available, but mechanisms of antidepressant transfer remain poorly understood. Here we calculated penetration ratios in an array of matrices from combined samples of pregnant/breastfeeding women taking antidepressants. METHOD: We performed a systematic literature search of PubMed and EMBASE to identify studies with concentrations of antidepressants from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal plasma concentration. When data from multiple studies were available, we calculated combined penetration ratios, weighting the study mean by study size. RESULTS: Eighty-five eligible studies were identified. For amniotic fluid, the highest penetration ratios were estimated for venlafaxine (mean 2.77, range 0.43-4.70 for the active moiety) and citalopram (mean 2.03, range 0.35-6.97), while the lowest ratios were for fluvoxamine (mean 0.10) and fluoxetine (mean 0.11, range 0.02-0.20 for the active moiety). For umbilical cord plasma, nortriptyline had the highest ratio (mean 2.97, range 0.25-26.43) followed by bupropion (mean 1.14, range 0.3-5.08). For breast milk, the highest ratios were observed for venlafaxine (mean 2.59, range 0.85-4.85), mianserin (mean 2.22, range 0.80-3.64) and escitalopram (mean 2.19, range 1.68-3.00). CONCLUSION: We observed considerable variability across antidepressants regarding their ability to enter fetal, newborn and infant fluids. Measuring antidepressant concentrations in a maternal blood sample can provide a reliable estimate of fetal/infant exposure, although further evidence for concentration-dependent effects is required.

A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers.

OBJECTIVE: The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess safety based on clinical and laboratory measurements and reporting of adverse events and/or adverse drug reactions. PATIENTS AND METHODS: This was an open label, non-comparative single-center study. Drospirenone 4 mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. RESULTS: Twelve volunteers completed the trial according to the protocol, and the samples of all 12 study completers were analyzed. The average concentration-time curve of drospirenone in plasma 24 h after the administration of the last dose (area under the curve (0-24 h)) was 635.33 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 1180.57 ng h/mL, respectively. The average Cmax was 48.64 ng/mL.The average concentration-time curve of drospirenone in milk 24 h after the administration of the last dose (area under the curve (0-24 h)) was 134.35 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 227.17 ng h/mL, respectively. The average Cmax was 10.34 ng/mL. CONCLUSION: On average, 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24-h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.

Breastfeeding and risk classification of medications used during hospitalization for delivery: 2015 Pelotas Birth Cohort. / Classificação de risco dos medicamentos usados na internação para o parto na amamentação: coorte de nascimentos de Pelotas/2015.

OBJECTIVE: To classify the drugs used during childbirth in relation to risks in breastfeeding, by using different sources of information and determining their disagreements. METHODS: Cross-sectional study, within the 2015 Pelotas Birth Cohort. Information about the use of drugs was collected, classified and compared regarding risk according to: 1) Brazil Ministry of Health Manual (MS), 2) World Organization (WHO), 3) Newton and Hale's classification and 4) American Academy of Pediatrics (AAP). RESULTS: A total of 1,409 mothers participated, and they had used 14,673 medicines, with 143 different drugs, of which 28 showed discordant classification with regard to breastfeeding risk. These 28 drugs included the following: morphine (64%), classified by AAP and WHO as compatible and as judicious use use by MS and Newton and Hale; hyoscine (23%), classified as judicious use by MS and compatible (A) by AAP; and metoclopramide (18%), classified as compatible by MS, of effects unknown (D) by AAP, and should be avoided according to WHO. Of the total drugs, 49.7% were classified as compatible during breastfeeding. Almost all women used oxytocin (97.4%), followed by lidocaine (75%), ketoprofen (69%), cephalothin (66%) and diclofenac (65%), which were classified as compatible. CONCLUSION: There was extensive use of drugs by mothers in labor during admission, most of the drugs being classified at the same risk and almost half classified as compatible with breastfeeding. However, there was disagreement between the sources for 19.6% of the drugs analyzed, which could endanger the infant's health or leave doubts about the use of the drug or breastfeeding.

Human Milk Oligosaccharide Supplementation Affects Intestinal Barrier Function and Microbial Composition in the Gastrointestinal Tract of Young Sprague Dawley Rats.

Human milk oligosaccharides (HMOs) are chief maternal milk constituents that feed the intestinal microbiota and drive maturation of the infant gut. Our objective was to determine whether supplementing individual HMOs to a weanling diet alters growth and gut health in rats. Healthy three-week-old Sprague Dawley rat pups were randomized to control, 2'-O-fucosyllactose (2'FL)- and 3'sialyllactose (3'SL)-fortified diets alone or in combination at physiological doses for eight weeks. Body composition, intestinal permeability, serum cytokines, fecal microbiota composition, and messenger RNA (mRNA) expression in the gastrointestinal tract were assessed. Males fed a control diet were 10% heavier and displayed elevated interleukin (IL-18) (p = 0.01) in serum compared to all HMO-fortified groups at week 11. No differences in body composition were detected between groups. In females, HMOs did not affect body weight but 2'FL + 3'SL significantly increased cecum weight. All female HMO-fortified groups displayed significant reductions in intestinal permeability compared to controls (p = 0.02). All HMO-fortified diets altered gut microbiota composition and mRNA expression in the gastrointestinal tract, albeit differently according to sex. Supplementation with a fraction of the HMOs found in breast milk has a complex sex-dependent risk/benefit profile. Further long-term investigation of gut microbial profiles and supplementation with other HMOs during early development is warranted.

Vancomycin and nisin A are effective against biofilms of multi-drug resistant Staphylococcus aureus isolates from human milk.

Human milk provides complete nutrition for infants and at the same time promotes the growth of specific bacteria in the infant gastrointestinal tract. Breastfeeding can often be discontinued due to mastitis which is an inflammation of the breast tissue. We isolated 18 Staphylococcus aureus strains from milk donated by healthy (n = 6), subclinical (n = 6), and mastitic (n = 6) mothers, two strains of which were VISA (Vancomycin Intermediate S. aureus). All tested strains (n = 12) were able to form biofilms. We then examined the impact of nisin A and vancomycin alone and in combination on biofilm formation and eradication of selected strains (n = 8). We observed strain-specific responses, with the combinatorial treatment at 1/4X MIC (for both singularly) significantly inhibiting biofilm formation for seven out of eight strains when compared with nisin A or vancomycin alone. None of the selected treatments were able to eradicate pre-formed biofilms. Finally, we selected two strains, namely a VISA (APC3814H) and a strong biofilm former (APC3912CM) and used confocal microscopy to evaluate the effects of the antimicrobial agents at 1X MIC on biofilm inhibition and eradication. All treatments inhibited biofilm formation of APC3814H but were ineffective in eradicating a pre-formed biofilm. Single treatments at 1X MIC against APC3912CM cells did not prevent biofilm formation whereas combination treatment caused increased death of APC3912CM cells. Finally, the combination treatment reduced the thickness of the pre-formed APC3912CM biofilm as compared with the single treatments.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use. OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification. MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome. AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

Hydroxyurea Exposure in Lactation: a Pharmacokinetics Study (HELPS).

Lactation is contraindicated for women with sickle cell anemia receiving hydroxyurea therapy, despite sparse pharmacokinetics data. In 16 women who were lactating volunteers, we documented hydroxyurea transferred into breastmilk with a relative infant dosage of 3.4%, which is below the recommended 5%-10% safety threshold. Breastfeeding should be permitted for women taking daily oral hydroxyurea.

Cannabis Use During Lactation: Literature Review and Clinical Recommendations.

Cannabis is the most commonly used psychoactive substance in Canada. The prevalence of cannabis use both during pregnancy and in the postpartum period has been estimated at 5% of the population. Women who use the drug during lactation place their infants at risk of exposure to cannabis and its metabolites in breast milk. This article provides a systematic review of infant outcomes associated with cannabis use by women during lactation followed by clinical recommendations. A review of the literature was conducted using Medline, Embase, and PsychInfo from their start to July 2018. Inclusion criteria consisted of articles addressing the impact of postpartum cannabis use by lactating women and providing developmental outcomes for infants. Two articles met these criteria and were included in our systematic review. Results indicate conflicting outcomes regarding the risk of exposure to cannabis in breast milk. Women should be advised to abstain from cannabis use during lactation or reduce consumption if abstinence is not possible. Furthermore, women should be advised to avoid breastfeeding within 1 hour of inhaled use to reduce exposure to highest concentration of cannabis in breast milk. Despite some evidence regarding health risks of post-natal exposure to cannabis, further research is needed to determine its impact on infant neurodevelopmental outcomes beyond the first year of life.

Mammary Dysbiosis and Nipple Blebs Treated With Intravenous Daptomycin and Dalbavancin.

INTRODUCTION: Mammary dysbiosis, also known as subacute mastitis, may be associated with nipple blebs. These overlapping diagnoses represent a challenging clinical scenario during lactation. Little research has been published on etiology, management strategies, and outcomes of these concurrent diagnoses. MAIN ISSUE: We document the treatment and outcome of a patient who presented with left-breast dysbiosis and nipple blebs and whose milk culture grew multi-drug-resistant, methicillin-resistant Staphylococcus aureus. She was treated safely and effectively with intravenous daptomycin and dalbavancin. This has not been described previously in the lactation literature. MANAGEMENT: The 35-year-old lactating gravida 3, para 3 patient presented at 6 months postpartum to a breast surgery clinic with a 1-week history of worsening deep left-breast pain, blebs, and recurrent plugging. She was afebrile and she had no erythema or induration on her breast exam. A culture of her milk grew multi-drug-resistant, methicillin-resistant Staphylococcus aureus, and she was referred to infectious disease for assistance with intravenous antibiotic therapy. She continued to feed expressed milk throughout treatment and demonstrated complete resolution of symptoms 8 weeks later. CONCLUSIONS: We report that in patients with a multi-drug-resistant, methicillin-resistant Staphylococcus aureus-positive human milk culture and a clinical presentation of mammary dysbiosis and nipple blebs, intravenous daptomycin and dalbavancin may be an effective treatment.

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

OBJECTIVE: To determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk. METHODS: Breast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion. RESULTS: The median average rituximab concentration in mature breast milk was low at 0.063 µg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 µg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion. CONCLUSIONS: We determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding.

Ivermectin concentration in breastmilk of a woman with Strongyloides stercoralis and human T-lymphotropic virus-I co-infection.

Ivermectin is a widely used drug for the treatment of various neglected tropical diseases, such as lymphatic filariasis, onchocerciasis, and strongyloidiasis among others. Despite its excellent safety profile, there are few published studies of the use of ivermectin in children, pregnant and nursing women. In the present study, we report clinical data on ivermectin concentrations in breastmilk of a woman with Strongyloides stercoralis and HTLV-I coinfection. Ivermectin levels in breastmilk ranged from 1.4 to 20.8 ng/ml, with a mean of 9.26 ng/ml after a single dose of 200 µg/kg. We estimated the possible ivermectin exposure of the infant to be 1.1 µg/kg, 0.55% of the weight-adjusted percentage of the maternal dose. This value is largely under the threshold established by the World Health Organization for safe breastfeeding. Our results bolster previous findings on the secretion of ivermectin into breastmilk in healthy volunteers. The findings from this case study do not support exclusion of lactating women or interrupting lactation to accommodate it.

Classificação de risco dos medicamentos usados na internação para o parto na amamentação: coorte de nascimentos de Pelotas/2015 / Breastfeeding and risk classification of medications used during hospitalization for delivery: 2015 Pelotas Birth Cohort

RESUMO: Objetivo: Classificar os medicamentos usados durante o parto quanto aos riscos na amamentação, utilizando diferentes fontes e verificando suas discordâncias. Métodos: Estudo transversal inserido na coorte de nascimentos de Pelotas de 2015. Coletaram-se informações sobre o uso de medicamentos, classificando-os quanto ao risco de acordo com: manual do Ministério da Saúde (MS), Organização Mundial da Saúde (OMS), classificação de Newton e Hale e Academia Americana de Pediatria (AAP). Resultados: Participaram 1.409 mães, utilizando 14.673 medicamentos, sendo 143 fármacos diferentes, dos quais 28 tiveram classificação de risco na amamentação discordante. Entre aqueles com classificação discordante estão morfina (64%), classificada pela AAP e OMS como compatível e pelo MS e por Newton e Hale como criterioso; hioscina (23%), criterioso pelo MS e compatível (A) pela AAP; e metoclopramida (18%), compatível pelo MS, de efeitos desconhecidos (D) pela AAP e evitado de acordo com a OMS. Do total de medicamentos, 49,7% foi classificado como compatível com a amamentação. Quase a totalidade das mulheres utilizou ocitocina (97,4%), seguida de lidocaína (75%), cetoprofeno (69%), cefalotina (66%) e diclofenaco (65%), classificados como compatíveis. Conclusão: Houve amplo uso de medicamentos pelas mães durante a internação para o parto, a maioria deles classificada no mesmo grau de risco, e quase a metade classificada como compatível com a amamentação, porém houve discordância entre as fontes para 19,6% dos medicamentos analisados, o que pode colocar em risco a saúde do lactente ou deixar dúvida quanto ao uso do medicamento ou à prática da amamentação.

ABSTRACT: Objective: To classify the drugs used during childbirth in relation to risks in breastfeeding, by using different sources of information and determining their disagreements. Methods: Cross-sectional study, within the 2015 Pelotas Birth Cohort. Information about the use of drugs was collected, classified and compared regarding risk according to: 1) Brazil Ministry of Health Manual (MS), 2) World Organization (WHO), 3) Newton and Hale's classification and 4) American Academy of Pediatrics (AAP). Results: A total of 1,409 mothers participated, and they had used 14,673 medicines, with 143 different drugs, of which 28 showed discordant classification with regard to breastfeeding risk. These 28 drugs included the following: morphine (64%), classified by AAP and WHO as compatible and as judicious use use by MS and Newton and Hale; hyoscine (23%), classified as judicious use by MS and compatible (A) by AAP; and metoclopramide (18%), classified as compatible by MS, of effects unknown (D) by AAP, and should be avoided according to WHO. Of the total drugs, 49.7% were classified as compatible during breastfeeding. Almost all women used oxytocin (97.4%), followed by lidocaine (75%), ketoprofen (69%), cephalothin (66%) and diclofenac (65%), which were classified as compatible. Conclusion: There was extensive use of drugs by mothers in labor during admission, most of the drugs being classified at the same risk and almost half classified as compatible with breastfeeding. However, there was disagreement between the sources for 19.6% of the drugs analyzed, which could endanger the infant's health or leave doubts about the use of the drug or breastfeeding.

Rivaroxaban Concentration in Breast Milk During Breastfeeding: A Case Study.

Background: Oral direct factor Xa inhibitors, collectively referred to as direct oral anticoagulants, are not recommended for breastfeeding women due to insufficient data about the transfer of these drugs into breast milk. In this study, we serially measured rivaroxaban concentrations in the breast milk of one nursing mother who was at high risk of deep vein thrombosis and evaluated the health of her breastfed infant. Materials and Methods: Breast milk rivaroxaban concentrations were measured 3 months after delivery by a validated liquid chromatography-tandem mass spectrometry method. Breast milk samples were collected sequentially after 15 mg of oral rivaroxaban administration after ethical approval and informed consent. Case report: A 38-year-old female diagnosed with the antiphospholipid syndrome had received rivaroxaban after delivery. The infant was partially breastfed until the age of 18 months. The mean minimum and maximum rivaroxaban concentrations in breast milk were 9.73 ng/mL before each dose and 53.9 ng/mL at 6 hours after each dose, respectively. The mean daily infant dose was 0.0034 mg/kg and the mean relative infant dose (RID) via breast milk was 1.79%. Discussion and Conclusion: The RIDs of rivaroxaban did not exceed 10% of the maternal dose, suggesting that exposure of rivaroxaban via breastfed is seldom clinically relevant for the infant. A pediatric assessment of the infant found no detectable drug-related adverse effects. Further studies are needed to elucidate how breastfeeding infants are impacted by exposure to rivaroxaban.

Postpartum hormonal contraception in breastfeeding women.

PURPOSE OF REVIEW: To provide an overview of recent research and guidelines regarding contraception and breastfeeding. RECENT FINDINGS: Recent studies assessed lactogenesis, breastfeeding rates, and milk supply concerns in patients starting postpartum hormonal contraception. One study showed a small but statistically significant increase in milk supply concerns between users and nonusers of postpartum hormonal contraception. Mean time to lactogenesis and breastfeeding rates were similar between patients with immediate and delayed insertion of the levonorgestrel (LNG) implant in one study and the LNG intrauterine device (IUD) in another study. Two studies assessed nursing knowledge and attitudes toward postpartum contraception in breastfeeding women, showing that postpartum nurses had incorrect knowledge of contraceptive safety in this patient population. Both studies demonstrated persistent erroneous beliefs that depot medroxyprogesterone acetate (DMPA) adversely affects breastfeeding. In postpartum patients intending to breastfeed, more than half intended to initiate contraception within 6 weeks postpartum and few indicated effect on breastfeeding as a factor in their decision. SUMMARY: There are no significant differences in lactogenesis, breastfeeding, and infant growth parameters between immediate postpartum (IPP) and delayed insertion of LNG implants and IUDs. Labor and delivery and postpartum nurses have persistent erroneous beliefs that DMPA negatively affects breastfeeding. Patients desire to use contraception postpartum but prenatal counseling rates and practices are of variable content and quality.