INTRODUCTION:Breastfeeding women receiving anti-TNFs for chronic inflammatory disease face concerns surrounding their potential transfer into breast milk. CRADLE was the first sponsored study to ...evaluate certolizumab pegol (CZP) concentrations in breast milk and estimate CZP Average Daily Infant Dose.
METHODS:CRADLE (NCT02154425) studied lactating mothers (≥6 weeks postpartum) receiving CZP. After ≥3 CZP doses, breast milk samples were collected across 1 dosing period (14 days for 200 mg Q2W; 28 days for 400 mg Q4W). Optimal analytical methods were developed to determine CZP and total polyethylene glycol (PEG) levels in breast milk.
RESULTS:18 CZP-treated mothers were screened, and 17 entered the sampling period16 on 200 mg Q2W and 1 on 400 mg Q4W. 77/137 (56%) samples had no measurable CZP in breast milk. For 4/17 mothers, all samples were below LLQ. Estimated Average Daily Infant Dose was 0FIGURE DASH0.0104 mg/kg/day; median relative infant dose (RID)0.125%. PEG was undetectable in 134/137 samples (3 had indeterminate results upon retesting). Infants of CZP-exposed mothers had a safety profile consisting of events occurring in unexposed infants of similar age.
CONCLUSION:CZP was undetectable in 56% of breast milk samples. When detectable, CZP concentrations were < 3xLLQ (< 1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was below 0.5% of maternal dose < 10% is considered unlikely to be of clinical concern. No transfer of PEG was observed. CZP absorption by infants via breast milk is unlikely, due to its low oral bioavailability and Fc-free structure. These findings are reassuring and support continuation of CZP treatment during breastfeeding.
Morbidly placenta accreta as a cause of postpartum morbidity is increasing in incidence. One conservative option is use of methotrexate as an adjuvant therapy for the management of placenta accreta. ...There is concern that use of methotrexate in a lactating mother could potentially expose her neonate to harmful effects of this medication.
Here we report a 29-year-old woman subjected to methotrexate treatment for placenta accreta. Her child was delivered at 32 weeks weighing 3 lbs. On postpartum day 5, this patient was diagnosed with placenta accreta and treated with intramuscular methotrexate for 3 consecutive days. She received 92 mg methotrexate intramuscularly daily, and was advised not to breastfeed. She collected milk samples on day 2, the 0 hour before the second dose and at 1, 2, 4, 8, 12, and 24 hours after taking the dose. A high-performance liquid chromatography mass spectrometry method was developed to measure methotrexate and its metabolite 7-hydroxymethotrexate levels in milk samples.
Very low levels were found for both methotrexate and 7-hydroxymethotrexate in the milk samples obtained. The results indicate that methotrexate or its metabolite receded to minimum concentration over a period of 24 hours.
This case report found the relative infant dose of methotrexate to be 0.11%. Methotrexate does transfer into breast milk, although the levels detected were very low. However, caution should still be used in counseling mothers regarding breastfeeding with this toxic drug.
Oral mesalamine (5-amino salicylic acid 5-ASA) is an anti-inflammatory agent commonly used to treat inflammatory bowel disease such as ulcerative colitis and Crohn's disease. The transfer of ...mesalamine into human milk has to date been poorly described at the current dosages and newer formulations. This study was designed to determine transfer of mesalamine into human milk as a function of maternal dose and time, and dosage form.
Ten breastfeeding mothers (age 28-41 years) suffering from inflammatory bowel disease were recruited who provided milk samples at 0, 1, 2, 4, 8, 12, and 24 hours after a single daily dose of oral mesalamine in pH-dependent gastroresistant coated tablets (1.2, 2.4, 3.6, and 4.8 g). Milk samples were analyzed using liquid chromatography/tandem mass spectrometry.
A total of 10 women were enrolled for the study. The calibration curve for mesalamine was linear over a concentration range of 0.32-200 ng/mL. Irrespective of maternal dose, mesalamine levels in milk were exceedingly low. However, a wide range of mesalamine levels were observed among all the participants. The relative infant doses were all lower than 0.1% (range 0.003-0.085%).
Regardless of dose and high variability, mesalamine levels in human milk were present in exceedingly low levels. The mothers in this study reported no side effects with their infants. These results suggest that the transfer of mesalamine into milk is very low and poses minimal risks to the breastfed infant.
People aging with HIV are living with increased risk for functional decline compared with uninfected adults of the same age. Early preclinical changes in biomarkers in middle-aged individuals at risk ...for mobility and functional decline are needed.
This pilot study aims to compare measures of free-living activity with lab-based measures. In addition, we aim to examine differences in the activity level and patterns by HIV status.
Forty-six men (23 HIV+, 23 HIV-) currently in the MATCH (Muscle and Aging Treated Chronic HIV) cohort study wore a consumer-grade wristband accelerometer continuously for 3 weeks. We used free-living activity to calculate the gait speed and time spent at different activity intensities. Accelerometer data were compared with lab-based gait speed using the 6-minute walk test (6-MWT). Plasma biomarkers were measured and biobehavioral questionnaires were administered.
HIV+ men more often lived alone (P=.02), reported more pain (P=.02), and fatigue (P=.048). In addition, HIV+ men had lower blood CD4/CD8 ratios (P<.001) and higher Veterans Aging Cohort Study Index scores (P=.04) and T-cell activation (P<.001) but did not differ in levels of inflammation (P=.30) or testosterone (P=.83). For all participants, accelerometer-based gait speed was significantly lower than the lab-based 6-MWT gait speed (P<.001). Moreover, accelerometer-based gait speed was significantly lower in HIV+ participants (P=.04) despite the absence of differences in the lab-based 6-MWT (P=.39). HIV+ participants spent more time in the lowest quartile of activity compared with uninfected (P=.01), who spent more time in the middle quartiles of activity (P=.02).
Accelerometer-based assessment of gait speed and activity patterns are lower for asymptomatic men living with HIV compared with uninfected controls and may be useful as preclinical digital biomarkers that precede differences captured in lab-based measures.
Antidepressants are one of the most commonly prescribed medications for pregnant and lactating women. However, there have been some recent concerns about their safety. This article summarizes recent ...research on the impact of untreated depression on the baby, the effects of antidepressants on the baby when prescribed during pregnancy, the short- and longer-term effects of prenatal exposure on infants and children, and the passage of medications into breast milk. Recommendations are made on providing mothers and their health care providers with information so they can make accurate risk/benefit analyses about using these medications while pregnant or breastfeeding.
High-dose intravenous methylprednisolone, a glucocorticoid with powerful anti-inflammatory activities, has become increasingly important in treating acute relapses of multiple sclerosis (MS). This is ...a case report of a 36-year-old lactating female who was receiving a 3-day course of high-dose methylprednisolone (1000 mg IV) to treat MS. Breast milk samples were obtained at 1, 2, 4, 8, and 12 hours following a 2-hour intravenous infusion on days 1, 2, and 3. The relative infant dose was found to be 1.45%, 1.35%, and 1.15% for days 1, 2, and 3, respectively. Using the average measured concentrations (Cavg) for days 1, 2, and 3, the estimated infant exposure was 0.207, 0.194, and 0.164 mg/kg/day, respectively, which is below the recommended dose given to neonates requiring methylprednisolone drug therapy. Infant exposure is low and mothers could continue to breastfeed if treatment with IV methylprednisolone is very brief. However, if the mother wishes to limit infant exposure further, she could wait 2 to 4 hours after IV methylprednisolone administration, thus significantly limiting the amount of drug in the breast milk.
Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are ...increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes.
Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes.
The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse.
These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.
Investigate whether rimegepant-an oral small molecule calcitonin gene-related peptide receptor antagonist for the treatment of migraine-is excreted in human milk after a single 75 mg dose and ...characterize its concentration-time profile in the plasma and milk of healthy lactating women to determine the relative infant dose (RID).
This open-label, single-center study enrolled healthy lactating women aged 18-40 years with a gestation of 37-42 weeks and uncomplicated delivery of a single healthy child ≥2 weeks (14 days) and ≤6 months before study drug administration. Plasma samples were collected 0, 1, 2, 4, and 8 hours postdose; human milk samples were collected at 0, 1, 2, 4, 8, 12, 16, 24, 32, and 36 hours. The milk:plasma drug concentration ratio was estimated as the ratio of the human milk:plasma areas under the curve. The RID (%) was calculated as 100 times the quotient of the body weight-normalized infant and maternal doses.
Subjects (
= 12) were enrolled between 25 January and 15 September 2020. The mean (standard deviation SD) age was 29.8 (3.6) years; mean (SD) body mass index was 26.8 (4.9) kg/m
. The mean (SD) RID of rimegepant was 0.51% (0.14). The mean (SD) body-weight normalized infant dose was 0.005 (0.001) mg/kg/day, the mean (SD) body-weight normalized maternal dose was 1.04 (0.18) mg/kg/day, and mean (SD) maternal body weight was 74.0 (13.3) kg.
On a weight-adjusted basis, the mean RID of rimegepant was <1% of the maternal dose.
Women with a history of sexual assault are at increased risk for sleep difficulties and depression in their first year of motherhood. Breastfeeding improves sleep parameters and lowers risk of ...depression for women in general. However, it is unknown whether breastfeeding is related to maternal depression, sleep quality, and maternal well-being in sexual assault survivors. We examined the association between sexual assault and several indices of sleep, depression, and maternal well-being in a large sample of sexual assault survivors in the first year postpartum. We also explored whether feeding method was related to our outcome variables for both sexually assaulted and non-assaulted women.
A sample of 6,410 mothers of infants 0-12 months old participated in the online Survey of Mothers' Sleep and Fatigue; 994 women had a history of sexual assault.
As predicted, women with a history of sexual assault had a number of sleep difficulties, increased risk of depression, and overall poorer subjective well-being than their non-assaulted counterparts. However, sexual assault survivors who were breastfeeding were at lower risk on all of the sleep and depression parameters than sexual assault survivors who were mixed or formula feeding.
Sexual assault has a pervasive negative effect on new mothers' sleep quality and risk of depression. However, these negative effects were less severe for the breastfeeding mothers than they were for the mixed- or formula-feeding mothers.
PDF
