Investigating the Transfer of Lisinopril into Human Milk: A Quantitative Analysis.

Lisinopril is commonly prescribed to manage conditions such as hypertension and heart failure. While concerns about fetal toxicity have traditionally limited the use of lisinopril in women of reproductive age, recent ACOG guidelines promote aggressive treatment of hypertension, which may require the use of pharmacologic agents not previously considered in the postpartum period. We aimed to estimate infant exposure to maternal lisinopril via breastmilk and report the tolerance of the breastfed infant. Five volunteers taking lisinopril provided samples of their human milk and their associated health information for research through the InfantRisk Center Human Milk Biorepository. The milk pharmacokinetics of lisinopril were measured using liquid chromatography-mass spectrometry. The mean milk concentration of lisinopril was 0.49 ng/mL per 10 mg daily dose. The Relative Infant Dose (RID) was 0.06% for lisinopril, more than 100 times lower than the standard 10% safety threshold. The minimal transfer of lisinopril into human milk in this study suggests the drug is unlikely to pose a clinically significant risk to healthy breastfed infants.

Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk.

Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5-30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide's bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions.

Minimal Transfer of Atorvastatin and Its Metabolites in Human Milk: A Case Series.

Background: Statins are historically contraindicated during breastfeeding due to theoretical concerns of disruptions in infant development from drug exposure and nutritional changes in milk. Breastfeeding mothers requiring statins often discontinue statins or postpone treatment until breastfeeding cessation, contributing to delays in treatment up to 14 years. This study aims to determine the transfer of atorvastatin and its active metabolites into human milk and evaluate the infant's risk of drug exposure. Materials and Methods: Milk samples and health information were released from the InfantRisk Human Milk Biorepository for three women taking 20 mg, 40 mg, and 80 mg of atorvastatin daily at steady state conditions. The concentration of atorvastatin (AT) and its active metabolites, ortho-hydroxy AT (2OH AT) and para-hydroxy AT (4OH AT), was quantified in timed milk samples using liquid chromatography-mass spectrometry. Results: The highest absolute infant dose of AT was 0.00027 mg/kg/day, and the highest weight-adjusted relative infant dose of the combined analytes was 0.09%, far below established thresholds for infant safety. Milk cholesterol levels were within previously established norms in the range of 10 mg/dL. The mothers reported no adverse outcomes in the two exposed infants. Conclusions: The transfer of atorvastatin and its metabolites was exceedingly low. While the impact on milk composition in states of hyperlipidemia (whether treated or untreated) is not well understood, it is unlikely that the drug in the milk would be present in clinically significant levels to adversely affect a breastfed infant.

Low Nirmatrelvir and Ritonavir Exposure through Breastmilk: Analyzing Milk Concentrations and Infant Risk.

This research study investigates the intricate relationship among COVID-19, maternal and infant health, and breastfeeding practices, with a specific focus on assessing the transfer of nirmatrelvir and ritonavir into human milk. Our aim is to provide critical insights to those managing COVID-19 treatment in lactating individuals. The InfantRisk Center Human Milk Biorepository contained human milk and corresponding health information for eight mother-infant dyads exposed to standard doses of maternal nirmatrelvir with ritonavir (300 mg nirmatrelvir and 100 mg ritonavir taken orally twice daily for 5 days). The primary outcomes measured were drug levels in milk using liquid chromatography-mass spectrometry and reporting the tolerance of the breastfed infant. Nirmatrelvir with ritonavir was measurable in all participants at a mean concentration of 33.48 ng/mL (ritonavir) and 729 ng/mL (nirmatrelvir). The estimated infant dose via milk was 0.0024 mg/kg/12 h (ritonavir) and 0.054 mg/kg/12 h (nirmatrelvir). The estimated relative infant dose was 0.19% (ritonavir) and 1.43% (nirmatrelvir) well under the standard 10% safety threshold. Among the eight infants exposed in this study, there were no reported adverse events. Nirmatrelvir with ritonavir is the recommended treatment for ambulatory COVID-19 patients with mild-to-moderate COVID-19 infection at high risk for progression to severe disease. Although its use is recommended in lactating women, there are no previous studies on the transfer of nirmatrelvir into human milk. The study findings endorse the current approach of nirmatrelvir/ritonavir use in lactating women and encourage healthcare providers to consider prescribing this treatment irrespective of lactation status when indicated.

The concentration of maternal sacubitril/valsartan transferred into human milk is negligible.

Background: Peripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan (Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise. Objectives: This study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant's risk of drug exposure. Methods: The InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal-infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions. Results: Valsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants. Conclusion: The transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of <0.25%, which is far lower than the industry safety standards (RID <10%).

Alleviating anxiety while breastfeeding: evaluating buspirone transfer into human milk.

PURPOSE: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk. METHODS: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration-time profile of buspirone and 1-PP was determined using liquid chromatography-mass spectrometry. RESULTS: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants. CONCLUSION: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant.

Mixing Meds and Milk: Evaluation of a Performance Gap Intervention for Provider Education in Breastfeeding and Maternal Medication Use.

The need for maternal medications is a known barrier to breastfeeding. Though most medications are compatible with lactation, healthcare providers use abundant caution, often viewing medications and breastfeeding as mutually exclusive. A dual intervention of an educational webinar and access to a mobile app for lactation pharmacology was used to enhance provider familiarity, confidence, and access to knowledge in medication use during breastfeeding. Surveys were administered before, one week after, and three months after the webinar to evaluate performance gap improvement. Usage data of the mobile app was collected over twelve months to monitor topic engagement. Results suggested the interventions temporarily increased provider confidence in maternal medication use during lactation; however, the increase was not sustained at three months. Even with one-time training and lactation-specific mobile app access, simply providing an informational resource is insufficient to support evidence-informed care for lactating patients. Longitudinal training on evidence-based medication safety is critical to care for the lactating dyad.

Psychiatric medication use among pregnant and breastfeeding mothers who used cannabis for mental health concerns: A cross-sectional survey study.

BACKGROUND: Use of cannabis during pregnancy and breastfeeding is increasing. Mental health concerns are reported as common reasons for maternal cannabis use, but little is known about the use of psychiatric medications in this population. OBJECTIVES: This study aimed to describe psychiatric medication use among pregnant and breastfeeding mothers who used cannabis for mental health concerns. DESIGN: Anonymous, online cross-sectional survey. METHODS: Data were collected from May 2018 to August 2019 among pregnant and breastfeeding mothers who used cannabis. This study included mothers who reported cannabis use for mental health concerns (n = 1363). The survey assessed the timing of cannabis use (during pregnancy and/or lactation); use of cannabis to address depression, posttraumatic stress disorder, or anxiety; use of psychiatric medications; psychiatric distress (Patient Health Questionnaire-4); and demographic information. Differences between groups were examined using t-test and chi-square test in SPSS. RESULTS: The mean age was 29.7 years; most were married (62%); 74% were White non-Hispanic, 9% Hispanic, and 17% Black, Indigenous or other People of Color. Mental health symptoms prompting cannabis use included anxiety (96%), depression (75%), and posttraumatic stress disorder (36%). Only 24% of respondents (n = 322) reported concomitant use of psychiatric medications, primarily selective serotonin reuptake inhibitors (72%, n = 232) and benzodiazepines (21%, n = 68). The composite Patient Health Questionnaire-4 showed most respondents had no (61%) or mild (27%) psychological distress; 14% screened positive for depression; and 17% screened positive for anxiety. Respondents who used psychiatric medications more often screened positive mental health concerns. CONCLUSION: Most mothers who used cannabis for mental health concerns were not taking psychiatric medications. This may be due to a mismatch between perceived mental health and screening results, un- or under-treated mental illness, or preference for cannabis over psychiatric medications. Improved management of perinatal mental health and effective patient education about risks of cannabis versus medication use are needed.

Pharmacokinetics of Ketamine Transfer Into Human Milk.

PURPOSE/BACKGROUND: Ketamine is an N -methyl- d -aspartate-antagonistic dissociative anesthetic infused intermittently for off-label management of treatment-resistant depression, acute suicidality, and postpartum depression. Despite the prevalence of postpartum depression nearing upward of 15% of deliveries, almost no research has been done to evaluate its safety during lactation. METHODS: In this study, human milk samples were released from the InfantRisk Center's Human Milk Biorepository of 4 participants treated with intermittent ketamine infusions (49-378 mg) to determine the levels of the drug and its active norketamine metabolite using liquid chromatography-mass spectrometry. RESULTS: The absolute infant dose of ketamine from human milk was 0.003 to 0.017 mg/kg per day, and norketamine was 0.005 to 0.018 mg/kg per day. The relative infant dose (RID) for ketamine ranged from 0.34% to 0.57%. The RID for norketamine ranged from 0.29% to 0.95%. There were no reported infant adverse effects. CONCLUSION: The findings of this study suggest that the transfer of ketamine, as well as its active metabolite, norketamine, into human milk is minimal, as estimated by RIDs less than 1% in all participants. These relative doses are well below standardly accepted safety thresholds.

The Transfer of Domperidone into Human Milk Remains Low at High Doses.

Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation in prolactin-deficient women. The case of a 43-year-old woman taking a high daily dose of domperidone (160 mg) is described from the InfantRisk Center Human Milk Biorepository. Milk samples were analyzed using a high-performance liquid chromatography-mass spectrometry method, detecting an average domperidone concentration of 7.0 ng/mL (range 6.2 to 8.4 ng/mL). Even at high doses, the transfer of domperidone into breast milk was negligible with a relative infant dose (RID) of 0.05%. The RID estimates the infant's potential exposure to a drug via lactation as a percentage of the weight-adjusted maternal dose. The standard threshold for reasonable infant exposure is an RID of 10%.

Persistence of Oxaliplatin Transfer into Human Milk: A Case Report.

Background: Oxaliplatin is an alkylating chemotherapeutic agent commonly used for malignancies in women of reproductive age, including colorectal cancer. No research previously exists regarding the transfer of platinum into milk after administration of oxaliplatin. Methods: We present a case of a lactating patient with stage 3a colorectal cancer requiring chemotherapy including oxaliplatin (130 mg/m2) infused every 4 weeks. Milk levels of platinum were tested at Lactation Lab, Inc., using a previously published mass spectrometry method. Results: Milk platinum concentrations 34 and 65 days after treatment were 7.8 and 10.3 ng/mL, respectively. Conclusion: These levels are similar to cisplatin or carboplatin in the immediate weeks after their administration, suggesting that the equivalent platinum exposure risk persists for longer with oxaliplatin than with other platinum analogues. Findings from this report support current recommendations to cease breastfeeding after oxaliplatin administration.

Psychiatric Manifestations of Withdrawal Following Domperidone Used as a Galactagogue.

Background: Domperidone is a dopamine-2 antagonist used off-label to increase breast milk production. Dosages commonly promoted for lactation are often far above those of studied on-label indications and might pose additional risks, especially upon discontinuation of the drug. Patients: Three U.S. patients are presented who used domperidone for lactation and experienced varying degrees of psychiatric withdrawal symptoms lasting months during dosage tapering and after cessation. Conclusion: Domperidone as a galactagogue may pose a significant psychiatric risk upon discontinuation. This presentation is commonly confused with, but clinically distinct from, postpartum depression. Lactating mothers who present with psychiatric symptoms should be explicitly probed about domperidone use, even in areas where domperidone is not authorized for use. Maternal hesitancy to disclose domperidone use may lead to suboptimal outcomes for the patient and delay management of withdrawal manifestations. The best course of treatment remains unknown, but a slow hyperbolic taper to gently discontinue domperidone may minimize withdrawal symptoms in these patients. Individuals exploring domperidone use should be informed of potential risks upon withdrawal, including psychiatric manifestations, requisite taper, and potential impacts of using unstudied high doses.

Maternal and Child Symptoms Following COVID-19 Vaccination Among Breastfeeding Mothers.

Background: The impact of COVID-19 vaccination on breastfeeding is unknown. The primary aim of this study was to determine whether vaccine-related side effects following COVID-19 vaccination were associated with an adverse impact on breastfeeding. Secondarily, we sought to determine perceived symptoms in breastfed children and maternal opinion about COVID-19 vaccination. Materials and Methods: We conducted a cross-sectional survey of breastfeeding mothers who underwent COVID-19 vaccination >2 days before the survey. Subjects were recruited through social media and websites. Data included sociodemographic information, vaccine history, maternal and child symptoms, and impact on lactation/breastfeeding. Bivariate statistics (chi-square, Wilcoxon rank sum, and t tests) and multivariable logistic regression models examined the association of vaccine side effects with lactation, symptoms in breastfed children, and maternal opinion on vaccination. Results: Analysis included 4,455 breastfeeding mothers. Maternal postvaccination symptoms were more common after the second dose (p < 0.001). Overall, 77 (1.7%) respondents reported a negative impact on breastfeeding postvaccination, and these mothers were more likely to have experienced fatigue, headache, muscle pain, injection site pain, chills, fever, or allergic reactions. After adjusting for confounding variables, higher odds of an adverse impact on lactation were associated with lower breastfeeding intensity, dose of vaccine, and child symptoms. Even among mothers who reported an adverse impact on breastfeeding, maternal opinion about vaccination and confidence in their decision to receive the COVID-19 vaccine were high. Conclusions: COVID-19 vaccination among breastfeeding mothers resulted in minimal disruption of lactation or adverse impact on the breastfed child. These findings may be considered in vaccination decision-making.

Transfer of the Serotonin Modulator Vortioxetine into Human Milk: A Case Series.

Background: Vortioxetine (Trintellix) is a serotonin modulator used in the treatment of major depressive disorder in adults. There are no data presently published on the transfer of vortioxetine into human breast milk. Case Report: The present study determined the drug concentration-time profile of vortioxetine in milk samples collected from three lactating mothers, two consuming 10 mg once daily and one consuming 20 mg once daily. Milk levels were measured using liquid chromatography mass spectrometry. At a dose of 10 mg/day, the maximum concentration of vortioxetine in milk was 13.89 ng/mL. At a dose of 20 mg/day, the maximum concentration in milk was 52.32 ng/mL. The relative infant dose was calculated to be 1.1% for 10 mg dose and 1.7% for 20 mg dose. Conclusion: In these three cases, we found the levels of vortioxetine in breast milk to be low and dose proportional. However, both RID's for 10 and 20 mg doses (1.1% and 1.7%, respectively) fall below the 10% theoretical level of concern and no adverse effects were reported by the mothers. As this is a small patient sample, caution should be exercised until further studies report the safety profile of vortioxetine in breastfeeding infants.