Low levels of tenofovir in breast milk support breastfeeding in HBV-infected mothers treated with tenofovir disoproxil fumarate

This study investigated the concentration of total mercury (THg) in maternal blood, cord blood, and breast milk, and its association with dietary factors. A total of 127 pregnant women in Busan, Korea were recruited. Maternal blood, cord blood, and breast milk were collected at 36 weeks of gestation, at delivery, and at one week after birth, respectively. Information about dietary habits and other factors were obtained from each subject. The mean THg concentrations in maternal blood, cord blood, and breast milk were 3.12±1.36 μg/L, 5.46±2.41 μg/L, and 0.91±2.08 μg/L, respectively. Positive correlations were found between log-transformed THg concentrations in maternal blood and cord blood (r=0.829, p<0.001), and between maternal blood and breast milk (r=0.296, p=0.001). Multiple linear regression analysis showed that the log-transformed concentration of THg in maternal blood was positively correlated with fish consumption (β=0.345, p<0.0001) and negatively correlated with bean consumption (β=-0.055, p=0.048). Fish consumption (β=0.482, p<0.0001) and maternal age (β=0.025, p=0.033) were positively associated with the concentration of THg in cord blood, while negative correlations were found for bean consumption (β=-0.134, p=0.027) and parity (β=-0.172, p=0.015). Beef consumption (β=0.031, p=0.007) was positively associated with log-transformed THg concentrations in breast milk, while negative correlations were found for bean consumption (β=-0.019, p=0.003) and maternal age (β=-0.083, p=0.004). Our study found that both the dietary and demographic factors differently affected to THg concentrations among samples of maternal blood, cord blood, and breast milk.

The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug. Concentrations of lamotrigine were measured in 19 mother–infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. A no-intercept model was applied for associations between maternal serum concentrations, amniotic fluid, umbilical cord blood, and breast milk concentrations. The mean daily dosage of lamotrigine was 351.32 mg (range 50–650 mg). We detected associations between maternal serum and amniotic fluid (β = 0.088, p < 0.001), as well as umbilical cord (β = 0.939, p < 0.001) and breast milk (β = 0.964, p < 0.001). The median penetration ratio into amniotic fluid, cord blood, and breast milk was 0.68, 0.92, and 0.77, respectively. Lamotrigine concentrations in amniotic fluid, cord blood, and breast milk give evidence that the fetus/newborn is constantly exposed to lamotrigine. Maternal serum concentrations predicted exposure via amniotic fluid, umbilical cord, and breast milk. Data suggest that therapeutic drug monitoring can be recommended as part of the clinical routine in psychopharmacotherapy for pregnant or breastfeeding women.

The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug. Concentrations of lamotrigine were measured in 19 mother-infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. A no-intercept model was applied for associations between maternal serum concentrations, amniotic fluid, umbilical cord blood, and breast milk concentrations. The mean daily dosage of lamotrigine was 351.32mg (range 50-650mg). We detected associations between maternal serum and amniotic fluid (β=0.088, p<0.001), as well as umbilical cord (β=0.939, p<0.001) and breast milk (β=0.964, p<0.001). The median penetration ratio into amniotic fluid, cord blood, and breast milk was 0.68, 0.92, and 0.77, respectively. Lamotrigine concentrations in amniotic fluid, cord blood, and breast milk give evidence that the fetus/newborn is constantly exposed to lamotrigine. Maternal serum concentrations predicted exposure via amniotic fluid, umbilical cord, and breast milk. Data suggest that therapeutic drug monitoring can be recommended as part of the clinical routine in psychopharmacotherapy for pregnant or breastfeeding women.

ABSTRACTBackgroundDHA (22:6n–3) is essential for neurodevelopment in children, and its concentration in human breast milk is historically high in Japan. Dietary patterns in Japan might affect the fatty acid (FA) composition among lactating mothers.ObjectivesThis study aimed to characterize the composition of milk FAs and to identify any dietary and sociodemographic factors associated with the variability of DHA concentration in breast milk in the Japanese population.MethodsThis cross-sectional study was performed as part of the Japanese Human Milk Study. Milk FAs were analyzed by GC at 1–6 mo postpartum, and maternal diet was estimated using an FFQ, including 11 types and cooking methods of seafoods, and the use of DHA supplements. The association of milk DHA with maternal diet and sociodemographic factors was investigated.ResultsMilk FA concentrations were measured in 78 mothers, including 24 who routinely used DHA supplements. The DHA concentration in milk (overall median: 0.62%; IQR: 0.47%–0.78%) was higher in women who took DHA supplements than in women who had never used DHA supplements (0.74%compared with 0.55%; P = 0.011). A linear regression model showed the association of milk DHA concentration with maternal dietary intake of grilled fish (β ± SE: 0.006 ± 0.003; standardized β: 0.234; r2 = 0.232, P = 0.036) after adjustment for DHA supplementation status, maternal and infant age, maternal BMI, and infant birth weight. Other FA concentrations were consistent, whereas caproic acid (6:0), undecylic acid (11:0), pentadecylic acid (15:0), palmitoleic acid (16:1n–7), and vaccenic acid (18:1n–7) varied by DHA supplementation status.ConclusionsThe DHA concentration in human milk may be influenced by maternal grilled fish consumption and frequent DHA supplementation in lactating Japanese women. Milk DHA concentrations may reflect a dietary habit in Japanese mothers.This trial was registered at www.umin.ac.jp/ctr as UMIN000015494.

Determinants of persistent organic pollutant (POP) concentrations in human breast milk of a cross-sectional sample of primiparous mothers in Belgium

Background: Hypnotics are frequently used for insomnia in pregnant and lactating women. This case study assessed zolpidem concentrations in the cord blood and breast milk and ramelteon concentrations in the breast milk of a woman who was treated with zolpidem and ramelteon for insomnia. Materials and Methods: Zolpidem concentrations were measured in maternal serum, breast milk, and cord blood. Concentrations of ramelteon and M-II, an active ramelteon metabolite, were measured in maternal serum and breast milk. Case Report: A 46-year-old female patient diagnosed with insomnia received 5-10 mg/day zolpidem during pregnancy and lactation and 8 mg/day ramelteon during lactation. A male infant weighing 3,329 g was born at 38 weeks' gestation, with no congenital abnormalities found during pregnancy or at birth. The infant was normal at the 1-month postpartum checkup. The maternal/placental ratio of zolpidem concentrations was 0.1 at 7.4 hours after maternal dosing, similar to that reported in previous studies. The calculated relative infant dose through breast milk based on the maximum drug concentration in breast milk at 2.2 hours after maternal dosing was 2.7% for zolpidem and 0.2% for ramelteon. Ramelteon and its metabolite (M-II) concentrations in the breast milk were equivalent to those in the maternal serum, although the infant exposure of these drugs was low for an oral dose. Conclusions: In the current case, zolpidem transferred into the placenta and breast milk, and ramelteon transferred into the breast milk. Further studies should assess the safety of zolpidem and ramelteon in fetus and breastfed infants.

Monitoring of PBDEs concentration in umbilical cord blood and breast milk from Korean population and estimating the effects of various parameters on accumulation in humans

Background: Zinc is an indispensable element, being involved in many biological processes. Correspondingly, insufficient zinc intake in early youth can detrimentally affect the function of a growing body. The aim of this study was to determine zinc content in breast milk among lactating women in Latvia and factors (maternal diet; mother’s and baby’s characteristics; breastfeeding pattern) affecting it. Methods: In total, 62 mature milk (at least one month postpartum) samples were collected and pooled within 24 h. Zinc content (mg 100 mL−1) was determined using inductively coupled plasma mass spectrometry (ICP-MS; Agilent 7700×, Agilent Technologies, Tokyo, Japan). Results: Zinc content in mature breast milk ranged from 0.01 to 0.34 mg 100 mL−1 with a median (interquartile range) content of 0.10 (0.05–0.15) mg 100 mL−1. Time postpartum was a significant negative predictor for zinc content in breast milk (r = −0.500; p = 0.000). Median maternal zinc intake was 10.70 (7.24–15.27) mg. Yet, zinc content in breast milk was unaffected by maternal dietary zinc intake (r = 0.155; p = 0.221). Conclusions: Maternal dietary zinc intake was nearly the recommended intake for lactating women (11 mg), but due to low zinc content in breast milk, babies in Latvia might not receive sufficient zinc intake. Future research should aim for the assessment of zinc status by evaluating plasma or serum levels of both mothers and babies.

Background: Breast milk is considered the optimal source of nutrition during infancy. Although the vitamin D concentration in human breast milk is generally considered poor for infants, vitamin D in breast milk is an important source for exclusively breastfed infants. Increases in vitamin D insufficiency and deficiency in lactating mothers may reduce vitamin D concentrations in breast milk. This study aimed to compare vitamin D and 25-hydroxyvitamin D (25OHD) concentrations in breast milk collected in 1989 and 2016–2017 and simultaneously analyze them with liquid chromatography-tandem mass spectrometry (LC-MS/MS); the association between the lifestyle of recent lactating mothers (2016–2017) and vitamin D status in human breast milk was also evaluated. Method: Lactating mothers were recruited from three regions of Japan in 1989 (n = 72) and 2016–2017 (n = 90), and milk from 3–4 months was collected in summer and winter. The samples were strictly sealed and stored at −80℃ until measurement. Breast milk vitamin D and 25OHD concentrations were analyzed by LC-MS/MS. Vitamin D intake, sun exposure, and sunscreen use of the lactating mothers in 2016–2017 were assessed. Results: Both vitamin D and 25OHD concentrations in breast milk were higher in the summer regardless of the survey year. Significantly lower vitamin D and 25OHD concentrations were observed in 2016–2017 compared with 1989 in summer, but no survey year difference was observed in winter. The stepwise multiple regression analyses identified season, daily outdoor activity, and suntan in the last 12 months as independent factors associated with vitamin D3 concentrations. Conclusion: The results suggest that low vitamin D status in recent lactating mothers may have decreased vitamin D and 25OHD concentrations in breast milk compared with the 1980s. These results are helpful for developing public health strategies to improve vitamin D status in lactating mothers and infants.

Breast milk (BM) is the only source of iodine and bioactive compounds that influence growth and development in infants. The content of BM may be influenced by maternal body mass index (BMI). The aim of this study was to investigate the effect of maternal weight on BM and cord blood iodine concentrations, growth-related hormones, infant anthropometric measurements. A total of 84 mother-infant pairs participated. Levels of leptin, adiponectin and insulin-like growth factor-I (IGF-I) in postnatal BM and cord blood were analysed by enzyme-linked immunosorbent assay (ELISA), iodine by Sandell-Kolthoff reaction. Dietary iodine intake of women was determined by food frequency questionnaire, and anthropometric measurements of infants at birth and 3 months were evaluated. Dietary iodine intake was found to be similar in normal weight (NW) and overweight/obese (OW/OB) women (p > 0.05). Breast milk iodine concentration (BMIC) was 17.4 μg in NW, 18.2 μg in OB/OW women. Adiponectin in cord blood and IGF-I in BM were higher OB/OW than NW women (p < 0.05). Positive correlations were found between the infant birth weight and adiponectin in BM, between the infant body weight at 3 months and leptin and adiponectin in BM, between the infant birth head circumference and IGF-I in BM (p < 0.05). In multiple linear regression model, leptin and adiponectin in BM had a positive effect on infant body weight (p < 0.05). Maternal BMI may influence infant body weight via leptin and adiponectin in BM and infant head circumference via IGF-I. No relationship was found between maternal BMI and iodine levels and anthropometric measurements of the infant. Longitudinal studies are recommended to understand the effect of BMIC on growth.

Vitamin D deficiency rickets occurs in sunny countries, mainly due to man-made environmental factors associated with avoidance of sunshine. This situation can be prevented by more health e...

Background: Belimumab is a recombinant human immunoglobulin G1 lambda monoclonal antibody that binds soluble B lymphocyte stimulator protein with high affinity and inhibits its biological activity. Belimumab is not recommended for breastfeeding women due to insufficient data about its excretion into breast milk. In this study, we measured belimumab concentrations in the breast milk of one nursing mother diagnosed with mixed connective tissue disease (MCTD) and evaluated the health of her breastfed infant. Materials and Methods: Maternal serum and breast milk belimumab concentrations were collected three times (2 weeks after the first dose, the day after the second dose, and 7 weeks after the second dose) after ethical approval and informed consent. An enzyme-linked immunosorbent assay was used to detect belimumab in serum and breast milk samples. Case Report: A 39-year-old para 4 female was diagnosed with MCTD. The serum concentrations at three times were 29.45, 76.82, and 33.95 mcg/mL. The concentrations in breast milk were 0.12, 0.17, and 0.12 mcg/mL. The milk-to-serum concentration ratios at each sampling point were 0.0041, 0.0022, and 0.0035, respectively. Her infant experienced no health problems. Routine vaccinations were administered without any adverse effects such as infection or immunoreaction. Discussion and Conclusions: Breast milk levels of belimumab ranged from 1/200 to 1/500 of those in serum, and no harmful effect occurred in her infant. This is the first study reporting belimumab concentrations in human breast milk. Further studies are needed to elucidate the impact of exposure on breastfeeding infants.

The aim of this research was to investigate the effect of fish oil supplementation, in the third trimester of pregnancy and early lactation period of healthy pregnant Danish women. Forty-four pregnant women were randomly allocated to fish oil supplementation (1.3 g EPA and 0.9 g DHA per day) from week 30 of gestation (FO-group) or to a control regimen (olive oil or no oil; controls). The FO-group was randomly subdivided into women stopping fish oil supplementation at delivery IFO(pregn)], and women continuing supplementation for an additional 30 d [FO(pregn/lact)]. Thirty-six women agreed to collect milk samples at days 4, 16, and 30 postpartum. The FA composition of the milk samples was determined by GLC. At days 4, 16, and 30 in lactation, FO(pregn/lact) women (n = 12) had, respectively 2.3 (P = 0.001), 4.1 (P = 0.001), and 3.3 (P = 0.001) times higher mean contents of LCPUFA(n-3) in their breast milk compared with controls (n = 13), and 1.7 (P = 0.005), 2.8 (P = 0.001), and 2.8 (P = 0.001) times higher LCPUFA(n-3) contents, respectively, at these days compared with FO(pregn) women (n = 11). The latter group did not differ significantly from controls with regard to LCPUFA(n-3) content in the breast milk. Similar results were obtained when analyzing separately for effects on the milk content of DHA. Dietary supplementation with 2.7 g LCPUFA(n-3) per day from week 30 of gestation and onward more than tripled the LCPUFA(n-3) content in early breast milk; supplementation limited to pregnancy only was much less effective.

Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk.

Limited information is available on breast milk transfer and subsequent infant systemic exposure to dolutegravir (DTG), tenofovir alafenamide (TAF), and tenofovir (TFV). We evaluated concentrations of DTG, TAF, and TFV in maternal and infant plasma and breast milk from participants of International Maternal Pediatric Adolescent AIDS Clinical Trials 2010, a clinical trial that enrolled women initiating either a DTG-containing or an efavirenz-containing antiretroviral treatment regimen during pregnancy. Time-matched postpartum maternal and infant samples were collected at 6 weeks postpartum. Validated assays quantitated concentrations of DTG, TAF, and TFV. Relative infant dose was estimated using an average milk intake of 150 mL/kg/d and observed breast milk concentrations. Data were available from 192 postpartum lactating women and their breastfed infants. Median maternal plasma concentrations of DTG, TAF, and TFV were 2810, 0.0, and 96 ng/mL, respectively. For DTG, median [interquartile range (IQR)] concentrations in breast milk and infant plasma were 91 ng/mL (67-123) and 69 ng/mL (41-95), respectively. TAF was below the quantitative limit (BQL) in nearly all breast milk and infant plasma samples. For TFV, median (IQR) concentrations in breast milk were 8 ng/mL (6-12), and nearly all infant plasma samples were BQL. The median RIDs of DTG, TAF, and TFV from breastfeeding were 1.9%, 0.00%, and 0.03%, respectively. Breast milk transfer of DTG, TAF, and TFV is low and results in minimal systemic exposure in breastfed infants. The clinical relevance of infant exposure to low concentrations of these antiretrovirals-particularly DTG-is unknown but should be considered in the context of the risk of drug resistance in infants who acquire HIV.