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.

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.

Racial and ethnic disparities in the association of maternal infection during pregnancy and risk of cyanotic congenital heart defects in the United States, 2011-2020.

PURPOSE: The etiology of cyanotic congenital heart defects (CCHD) is not well understood. There are scarce data on racial/ethnic disparities in maternal infection and CCHD. We evaluated the relation of maternal infections during pregnancy and risk of CCHD in the United States, and to assess if this association varies by race/ethnicity. METHODS: Data were from the National Vital Statistics System comprising 35.3 million singleton livebirths among mothers aged 15-49 years from 2011 to 2020. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjustment for sociodemographic and maternal health factors, including prepregnancy body mass index, diabetes, hypertension, and smoking during pregnancy, time to prenatal care was initiated and pregnancy complications, any maternal infection, was associated with elevated odds of CCHD (OR: 1.25, 95% CI: 1.15-1.37). The odds of CCHD were mainly evident for sexually transmitted infections, namely chlamydia and hepatitis-C viral infection. The association was limited to non-Hispanic Black (OR: 1.22, 95% CI: 1.03-1.45), Hispanic (OR: 1.61, 95% CI: 1.33-1.95), and Asian (OR: 2.03, 95% CI: 1.42-2.91) mothers. CONCLUSIONS: In this population-based study, maternal infection during pregnancy was associated with a modest risk of CCHD in offspring, which was the highest in racial/ethnic minority mothers.

Maternal age at birth of last child and cardiovascular disease mortality later in life among a national cohort of postmenopausal women from the United States.

Maternal age at last birth (ALB) of child is increasing in the United States, and it has been reported to influence future chronic diseases. However, the relationship of ALB and cardiovascular disease (CVD) events later in life has not been widely studied. We evaluated the association of ALB with CVD mortality. Data were from 7,971 parous postmenopausal women older than 45 years who participated in the US National Health and Nutritional Examination Survey from 1999 to 2018 and had mortality follow-up data through to December 31, 2019. ALB was self-reported, whereas CVD mortality was assessed using International Classification of Diseases codes. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). The mean age of participants was 63 ± 9.8 years, with 9.5% being non-Hispanic Black, 9.7% being Hispanic women, and 21% reporting ALB ≥35 years. During a median follow-up of 8.1 years, 443 participants died from CVD. In age-adjusted models, CVD mortality was elevated for women with ALB of <25 years (HR, 1.68; 95% CI, 1.23-2.29) and ALB of ≥35 years (HR, 1.37; 95% CI, 1.00-1.88). However, after additional adjustment for race and ethnicity, foreign born, education, marital status, poverty income ratio, parity, smoking status, age at menarche, oral contraceptive pills use and family history of myocardial infarction, these estimates were attenuated resulting in no association between ALB and CVD mortality. In this study of nationally representative sample of postmenopausal women, there was no conclusive association between maternal ALB and CVD mortality later in life.