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OBJECTIVE: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS: We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.
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AIMS: Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability. METHODS: Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted. RESULTS: Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 µg kg-1 after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL-1 after maternal daily doses between 25 and 150 mg. CONCLUSIONS: Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding.
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AIMS: In breastfeeding women, anti-epileptic therapy can lead to infant toxicities, even with newer anti-epileptic drugs such as levetiracetam. This study assessed levetiracetam breastmilk excretion and its correlation with the maternal oral dose and serum concentrations. METHODS: Women with epilepsy treated with levetiracetam were recruited to this study and completed a questionnaire. Levetiracetam concentrations were determined in serial breastmilk samples (pre-dose to 12 h post-dose period) and in a single pre-dose maternal serum sample. RESULTS: Twenty breastfeeding women and 21 infants (one woman with twins; 16 fully and five partially breastfed infants) participated in this study. The trough breastmilk/serum ratio of levetiracetam was 0.98 ± 0.20. The infant levetiracetam daily dose was 5.39 ± 1.96 and 2.70 ± 0.98 mg. kg-1. d-1 , and the relative infant dose (RID) was 13.8 ± 3.1% and 6.9 ± 1.6% in the fully and partially breastfed infants, respectively. Substantial correlations between the levetiracetam dose, maternal serum and breastmilk trough concentrations, and breastmilk AUC values were found. Three women reported somnolence in their fully breastfed infants, which resolved shortly after switching to partial breastfeeding. All the infants gained weight according to their age. CONCLUSIONS: Infant levetiracetam exposure via the breastmilk was close to the safety thresholds (trough breastmilk/serum ratio slightly below 1, RID > 10% in fully breastfed infants), and infant somnolescence reports could be related to exposure of the infants to levetiracetam via breastmilk. Further studies are warranted to reveal the short- and long-term safety of levetiracetam in breastfeeding.
Assuntos
Aleitamento Materno , Leite Humano , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Lactente , Lactação , Levetiracetam/efeitos adversosRESUMO
BACKGROUND: The antiretroviral drug efavirenz is widely used during breastfeeding. Evaluating its safety requires an understanding of its breast milk pharmacokinetics, level of breastfed infants' exposure, and potential influence of polymorphisms in drug disposition genes. METHODS: For this observational study, we investigated plasma and breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in human immunodeficiency virus positive nursing mothers and their breastfed infants. We also evaluated potential variability due to genetic polymorphisms in CYP2B6, NR1I3, CYP2A6, ABCB1, ABCB5, and ABCG2. RESULTS: CYP2B6 516G>T was independently associated with efavirenz concentrations in maternal plasma, breast milk, and infant plasma (n = 134). When stratified based on CYP2B6 516G>T (n = 29 ; 11 GG, 10 GT and 8 TT), efavirenz pharmacokinetic parameters in plasma and breast milk differed significantly between patient groups. The median time-averaged milk-to-plasma concentration ratio was 1.10 (range: 0.57-1.71). The estimated maximum infant efavirenz dose from breast milk was 809 µg/kg/day (215-2760) and pediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). Infant plasma concentrations did not change significantly during the dosing interval, 157 ng/mL (28.6-1360) in pooled analysis and 315 ng/mL (108-1360) in CYP2B6 516TT group. Infant plasma concentrations were highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum day 9 to 3 months. No efavirenz related toxicity was reported. CONCLUSIONS: Most breastfed infants are exposed to <10% of the weight-adjusted therapeutic pediatric dose, the safety threshold for exposure to maternal drugs from breast milk.
Assuntos
Fármacos Anti-HIV/análise , Fármacos Anti-HIV/farmacocinética , Benzoxazinas/análise , Benzoxazinas/farmacocinética , Infecções por HIV/genética , Leite Humano/química , Adolescente , Adulto , Alcinos , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/sangue , Benzoxazinas/uso terapêutico , Aleitamento Materno , Receptor Constitutivo de Androstano , Ciclopropanos , Citocromo P-450 CYP2B6/genética , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Leite Humano/metabolismo , Farmacogenética , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
Children are especially sensitive to ionizing radiation and chemical carcinogens, and limiting their cancer risk is of great public concern. Calorie restriction (CR) is a potent intervention for suppressing cancer. However, CR is generally not appropriate for children. This study, therefore, examined to see if adult-onset CR influences the lifetime cancer risk in mice after early-life exposure to ionizing radiation. Infant male mice (1-week-old) were exposed to 3.8 Gy X-rays, fed a control 95 kcal/week or CR 65 kcal/week diet from 7 weeks of age (adult stage), and their lifespan and tumor development were assessed. Irrespective of CR, X-rays shortened lifespan by 38%, and irrespective of irradiation CR extended lifespan by 20%. Thymic lymphoma (TL) and early-occurring non-TL were induced by radiation. The liver and Harderian gland were more susceptible to radiation-induced tumors than the lungs and non-thymic lymphoid tissues (late occurring). CR reduced the risk of hepatocellular carcinoma, late-occurring non-TL, lung tumor, Harderian tumor, and hemangioma but had less impact on TL and early-occurring non-TL. Most notably, the effects of X-rays on induction of lung tumors, late-occurring non-TL and hemangioma were essentially canceled by CR. The ability of CR to prevent late-occurring tumors was the same for non-irradiated and irradiated mice, indicating that the mechanism by which CR influences cancer is independent of irradiation. Our results indicate that adult-onset CR significantly inhibits late-occurring tumors in a tissue-dependent manner regardless of infant radiation exposure.
Assuntos
Restrição Calórica , Longevidade/efeitos da radiação , Neoplasias Induzidas por Radiação/prevenção & controle , Raios X/efeitos adversos , Animais , Longevidade/fisiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Neoplasias Induzidas por Radiação/dietoterapia , Neoplasias Induzidas por Radiação/patologiaRESUMO
Per- and polyfluoroalkyl substances (PFAS) are persistent contaminants with documented harmful health effects. Despite increasing research, little attention has been given to studying PFAS contamination in low- and middle-income countries, including Samoa. Using data and biosamples collected through the Foafoaga o le Ola ("Beginning of Life") Study, which recruited a sample of mothers and infants from Samoa, we conducted an exploratory study to describe concentrations of 40 PFAS analytes in infant cord blood collected at birth (n = 66) and infant dried blood spots (DBS) collected at 4 months post-birth (n = 50). Of the 40 PFAS analytes tested, 19 were detected in cord blood, with 10 detected in >50% of samples (PFBA, PFPeA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFHxS, PFOS, and 9Cl-PF3ONS); and 12 analytes were detected in DBS, with 3 detected in >50% of samples (PFBA, PFHxS, and PFOS). PFAS concentrations were generally lower than those reported in existing literature, with the exception of PFHxS, which was detected at higher concentrations. In cord blood, we noted suggestive (p < 0.05) or significant (p < 0.006) associations between higher PFHxS and male sex; higher PFPeA and residence in Northwest 'Upolu (NWU) compared to the Apia Urban Area (AUA); lower PFUnA and 9Cl-PF3ONS and greater socioeconomic resources; lower PFOA and higher parity; higher PFDA and higher maternal age; and lower PFUnA, PFTrDA, and 9Cl-PF3ONS and higher maternal BMI. In DBS, we found suggestive (p < 0.05) or significant (p < 0.025) associations between lower PFBA and residence in NWU versus AUA; lower PFBA and PFHxS and higher maternal age; and higher PFBA and higher maternal BMI. Finally, we observed associations between nutrition source at 4 months and DBS PFBA and PFHxS, with formula- or mixed-fed infants having higher concentrations compared to exclusively breastfed infants. This study represents the first characterization of PFAS contamination in Samoa. Additional work in larger samples is needed to identify potentially modifiable determinants of PFAS concentrations, information that is critical for informing environmental and health policy measures.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Lactente , Feminino , Recém-Nascido , Humanos , Masculino , Fluorocarbonos/análise , SamoaRESUMO
The purposes of this study are to explore the contamination levels of perfluorinated and polyfluoroalkyl substances (PFASs) in breast milk and assess their exposure risk to infants. Based on data from a birth cohort study conducted in Yingcheng, Hubei Province, from 2018 to 2021, the contents of 23 types of PFASs in the breast milk of 324 pregnant women were determined using isotope dilution-high performance liquid chromatography-tandem mass spectrometry. Multiple linear regression was then performed to analyze the effects of various demographic characteristics and eating habits on the concentration of PFASs in breast milk. The daily PFASs intake of infants through breast milk was estimated, and the exposure risk of infants was also assessed. The results revealed that 23 types of PFASs in breast milk had good linear relationships in the range of 0.2-100 ng/mL, with correlation coefficients greater than 0.992. The limits of detection were 5-42 pg/mL, the limits of quantification were 15-126 pg/mL, the recoveries were 65.6%-108.1%, and the relative standard deviations were 1.6%-12.8%. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoate acid (PFOA), and perfluorohexanesulfonic acid (PFHxS), with median concentrations of 200.7, 63.5, and 25.2 pg/mL, respectively, were the main PFASs found in breast milk. The detection rates of these three contaminants were higher than 80%, whereas the detection rates of other compounds were lower than 45%. The results of multiple linear regression showed that older pregnant women and a higher frequency of pickled food intake may be related to increased PFAS levels in breast milk whereas a higher frequency of legume intake may be related to decreased PFAS levels in breast milk. The median estimated daily intakes (EDIs) of PFOS, PFOA, and PFHxS for infants were 25.1, 7.9, and 3.2 ng/(kg·d), respectively. In summary, this study found notable PFAS levels in breast milk in Yingcheng, Hubei Province. Among these PFASs, PFOS, PFOA, and PFHxS were the main contaminants. Maternal age as well as pickled food and legume intake may affect the PFAS level in breast milk. The health risk of PFAS intake through breast milk to some infants is worthy of attention and further study.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Ácidos Sulfônicos , Lactente , Humanos , Feminino , Gravidez , Leite Humano/química , Estudos de Coortes , Caprilatos/análise , Fluorocarbonos/análise , Verduras , Poluentes Ambientais/análiseRESUMO
Parabens, triclosan (TCS), and triclocarban (TCC) are antimicrobial additives that are widely used in personal care products (PCPs) and may dysregulate infant gut microbiota and induce a series of chronic diseases. Dietary intake may be an underestimated exposure route of such antimicrobial additives in infants, but relevant data remain scarce. Therefore, this study determined five common preservatives, including methyl- (MeP), ethyl- (EtP), propyl- (PrP), butyl- (BuP), and benzyl-paraben (BeP), and two antimicrobials TCS and TCC, in major infant food sources (breastmilk, milk-based infant formula [MIF], and cereal-based complementary food [CCF]) in southern China. The health risks associated with dietary exposure among infants across different months of age were also evaluated. The results demonstrated a high incidence of MeP, EtP, PrP, and BeP in processed infant food products, while TCS and TCC were mainly detected in maternal breastmilk. Notably, MeP and EtP were found in all of the MIFs tested, while MeP, EtP, and BeP were detected in 85.6 %-100 % of the CCFs. By incorporating the human equivalent dose and an additional 10-fold margin of safety for infants into the health risk assessment, the 95th percentile hazard quotient of PrP via the ingestion of breastmilk among neonates exceeded 1. For the first time, the results showed that exposure to PrP via breastmilk intake may pose a considerable health risk to urban neonates in southern China. The health risks caused by antimicrobial exposure via ingesting MIF and CCF among infants were negligible. Thus, we recommend breastfeeding women reduce their consumption of PCPs and processed food, especially during the first month after delivery.
Assuntos
Anti-Infecciosos , Triclosan , Lactente , Recém-Nascido , Humanos , Feminino , Parabenos/análise , Triclosan/análise , Aleitamento Materno , Anti-Infecciosos/efeitos adversos , Antibacterianos , China , Exposição Ambiental/análiseRESUMO
Introduction: Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. Case presentation: Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. Results: The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. Conclusion: These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.
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Importance: Lamotrigine use during breastfeeding has significantly increased in the recent years, whereas breast milk lamotrigine pharmacokinetics data are still sparse. Objectives: To assess lamotrigine exposure in breastfed infants by monitoring maternal serum and breast milk concentrations. Methods: Breastfeeding women treated with lamotrigine were recruited to this study. Maternal trough breast milk and serum samples were collected, and additional breast milk samples were collected 1, 3, 6, 9, 12 hours after lamotrigine consumption. Trough breast milk/serum ratios (M/S ratio) and breast milk area under the curve (AUC) values were calculated. Results: Twenty-one breastfeeding women were recruited to this study, and the final dataset was based on the samples collected from 17 women. Lamotrigine trough serum and mother's milk concentrations were 5.1 ± 3.3 mg/L and 3.1 ± 1.9 mg/L, respectively (mean ± standard deviation). The trough M/S ratio of lamotrigine was 0.66 ± 0.22. The lamotrigine breast milk average AUC was 41.7 ± 24.6 mg·h/L. The estimated infant dose of lamotrigine was 0.52 ± 0.31 mg/kg/day and 0.26 ± 0.15 mg/kg/day for fully and partially breastfed infants, respectively. Significant correlation was found between the maternal lamotrigine serum trough concentrations and the breast milk parameters: trough breast milk concentrations (Spearman's rho = 0.986, p < 0.0001) and breast milk AUC values (Spearman's rho = 0.941, p < 0.0001). No significant correlation was found between the maternal lamotrigine daily dose and serum trough concentrations, breast milk trough concentrations, and breast milk AUC values (Spearman's rho = 0.294, 0.285, and 0.438, p = 0.252, 0.396, and 0.078, respectively). Conclusion and Relevance: High correlation between the maternal lamotrigine trough serum concentrations and the breast milk AUC values was found, implying that monitoring the maternal lamotrigine serum concentrations can be useful for prediction of exposure of infants to lamotrigine through the breast milk. The trial was registered in the Israeli trials registry MOH_2021-09-05_010243 at September 5, 2021 Retrospectively registered https://my.health.gov.il/CliniTrials.
Assuntos
Aleitamento Materno , Leite Humano , Anticonvulsivantes/farmacocinética , Feminino , Humanos , Lactente , Lamotrigina/farmacocinéticaRESUMO
The risk of infant exposure to dextromethorphan (DM) and its active metabolite, dextrorphan (DX), through breast milk has not been evaluated. In this study, bound and unbound DM and DX concentrations in breast milk and plasma at 2 hours post-dose were measured in 20 lactating women (n = 20) following a single 30 mg oral dose of DM. The DM and DX concentrations in breast milk were positively correlated with their respective plasma concentrations. The breast milk-to-plasma (M/P) ratios of 1.0 and 1.6 and the unbound M/P ratios of 1.1 and 2.0 for DM and DX, respectively, suggested that DM and DX are extensively distributed into breast milk. The infant exposure following a single dose of 30 mg DM was estimated using breast milk concentrations of 0.33 ± 0.32 and 1.8 ± 1.0 µg/kg/day for DM and DX, respectively. The steady-state infant exposure was estimated using the M/P ratios and previously reported area under the concentration-time curve (AUC) of DM and DX following repeated dosing of DM 60 mg orally, twice daily, to be 0.64 ± 0.22 and 1.23 ± 0.38 µg/kg/day, respectively. Based on these estimated infant doses, the relative infant doses (RIDs) were estimated to be <1%, suggesting the infant is only exposed to a minor fraction of adult dose through breast milk; however, one nursing infant developed an erythematous rash during this study, which warrants additional research to fully elucidate the risks of infant exposure to DM and DX through breast milk.
Assuntos
Citocromo P-450 CYP2D6 , Dextrorfano , Adulto , Citocromo P-450 CYP2D6/metabolismo , Dextrometorfano , Dextrorfano/metabolismo , Feminino , Humanos , Lactação , Leite Humano/metabolismo , MãesRESUMO
Excessive intake of essential trace elements or exposure to potentially toxic elements above certain thresholds may cause adverse health effects in humans. To date, there is scarce evidence concerning Chinese infant exposure to trace elements and the associated risks. In this study, we collected 61 breast milk, 54 infant formula and 90 complementary food samples from southern China to investigate the levels of cobalt (Co), chromium (Cr), copper (Cu), selenium (Se), zinc (Zn), arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb). The concentrations of these elements in the breast milk samples ranged from under the limit of detection (Assuntos
Selênio
, Oligoelementos
, Cromo
, Feminino
, Humanos
, Lactente
, Fórmulas Infantis
, Leite Humano/química
, Selênio/análise
, Oligoelementos/análise
, Zinco/análise
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Breast milk is the preferred method of infant nutrition. Breastfeeding infants born to mothers treated for TB may be at risk of drug toxicity through breast milk exposure, or potentially be vulnerable to select for drug resistance with low level drug exposure. Except for isoniazid, the quantification of first-line TB drugs including rifabutin in breast milk has not been previously described and will provide much-needed insight to TB drug exposure in breastfeeding infants. We developed and validated a novel method to quantify several first-line TB drugs and their major metabolites in breast milk. Accuracy and precision were assessed during three consecutive, independent validation batches over a calibration range of 0.300-30.0 µg/mL for isoniazid and ethambutol, 0.150-15.0 µg/mL for acetyl isoniazid, desacetyl rifampicin, rifampicin, and pyrazinamide, 0.0150-1.50 µg/mL for rifabutin, and 0.00751-0.751 µg/mL for deacetyl rifabutin in breast milk. The method was reproducible for all analytes when using breast milk from six different sources and was not influenced by matrix effects with a mean regression precision (CV(%)) ranging between 1.0 and 2.8. The average recovery of analytes from the matrix was 76.7-99.1%, with a CV(%) between 0.4 and 4.4, while the average process efficiency was between 74.4 and 93.1% with a CV(%) between 1.9 and 8.3. Although only acetyl isoniazid, isoniazid, ethambutol, and pyrazinamide were successfully assayed in breast milk, samples taken from mothers treated for rifampicin-resistant TB and the inclusion of all first-line TB drugs, including rifabutin in the assay development and validation process will allow future quantification of these analytes in breast milk.
Assuntos
Antituberculosos , Isoniazida , Feminino , Humanos , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Etambutol , Pirazinamida , Rifabutina , Rifampina , Cromatografia Líquida , Leite Humano , Espectrometria de Massas em Tandem/métodosRESUMO
Polybrominated diphenyl ethers (PBDEs) are ubiquitous flame retardants and are environmentally persistent. PBDEs show endocrine disruption, neurotoxicity, and lower birth weight in infants, and their human body burden has become a public health concern. The infants' exposure begins in the prenatal period and continues via breast milk ingestion, although, little is known about the factors that may influence this exposure. In this study, PBDE levels in Brazilian breast milk were assessed in 200 lactating women. The risk assessment of infants' exposure to PBDE was performed through the estimated daily intake (EDI) calculation. The geometric mean (GM) of ∑PBDEs levels was 2.33 (0.14-6.05) ng/g wet weight. At least one PBDE congener was detected in the samples, and the 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) showed a 100% of detection rate (GM of 1.05 ng/g). Location of residence, maternal level education, monthly salary, and race were positively associated with PBDE levels (p < 0.05). The EDI of BDE-47 was higher in Belo Horizonte (8.29 ng/kg/day) than in Viçosa (6.36 ng/kg/day), as well as for the ∑PBDEs (19.77 versus 12.78 ng/kg/day) (p < 0.05). Taking the high detection rate of PBDEs in breast milk and their toxicity, continuous studies on infant exposure, fetal growth, and child neurodevelopment are requested.
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Poluentes Ambientais , Retardadores de Chama , Brasil , Criança , Poluentes Ambientais/análise , Feminino , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Humanos , Lactente , Lactação , Exposição Materna , Leite Humano/química , GravidezRESUMO
Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·glipid-1 in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·glipid-1 in blood. Mean TEDIs leading to values of 500 ng·glipid-1 in blood for children up to two years ranged between 110 and 220 ng·kg-1·bw·day-1, varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Poluentes Ambientais , Bifenilos Policlorados , Aleitamento Materno , Pré-Escolar , Poeira , Poluentes Ambientais/análise , Feminino , Humanos , Lactente , Lipídeos , Leite Humano/química , Bifenilos Policlorados/análise , GravidezRESUMO
For infants in the first months of life, breast milk is a complete source of nutrition; however, it can also contain elements that are harmful to the infant. It is therefore critical for infant health to characterize breast milk. The aim of this study was to determine the intra- and inter-day variation of elements in breast milk, for which there is currently limited information, as a pilot study for a larger study. Firstly, we developed a simple and robust analytical method for the determination of multiple elements in breast milk. It was accurate (accuracy ranged from 98% to 107%) for measurement of 26 elements in breast milk by quadrupole inductively coupled plasma-mass spectrometry. Intra- and inter-day variation of elements, protein, and fat in breast milk was determined by analyzing breast milk collected from 11 women at 12 sampling points over three days and calculating intraclass correlation coefficients. Intraclass correlation coefficients showed that while some elements were consistent across time points (e.g., Sr, Ca, and Cu), others showed very high variability (e.g., As, Cd, and Ni). Correlation analyses between elements in breast milk showed strong relationships between those including Fe and Mo, Ca and Sr, and Cd and Fe.
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The aim of this study was to estimate radionuclide levels in breast milk and the transferred dose to their infants in Sendai (100 km from Fukushima), Japan after the 2011 Fukushima nuclear disaster. Radionuclide concentrations were analyzed in 101 specimens of breast milk collected in 2012. Median values for minimum detectable activities were 0.39, 0.34, 1.1, 1.89, and 17.1 Bq/kg for 137Cs, 134Cs, 131I, 110mAg, and 40K, respectively. Only radionuclides from 40K were detected. To estimate potential exposure and radiocesium dose, we assumed that the samples contained each minimum detectable activity level. The mean minimum detectable activity concentrations (standard deviation) of 137Cs and 134Cs were 0.42 (0.15) and 0.37 (0.14) Bq/kg, respectively. Means of estimated dietary intakes of 137Cs and 134Cs among infants were 0.35 (0.12) and 0.31 (0.11) Bq/day, respectively. The committed effective doses of radiocesium in infants aged 3 and 12 months via breastmilk were estimated at 5.6 (2.1) and 3.3 (1.2) µSv/year, respectively. Dietary intakes of 137Cs and 134Cs in breastfeeding mothers were back-calculated at 1.9 (0.71) and 1.7 (0.65) Bq/day, respectively. The study verified no discernible exposure to radionuclides among infants. The most conservative estimates were below the Japanese internal exposure limit of 1 mSv/year.
Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação , Poluentes Radioativos da Água , Feminino , Humanos , Lactente , Japão , Leite Humano/química , Centrais Nucleares , Poluentes Radioativos da Água/análiseRESUMO
Persistent organic pollutants (POPs) are organic compounds that resist biochemical degradation, moving long distances across the atmosphere before deposition occurs. Our goal was to provide up-to-date data on the levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in breast milk from Chilean women and to estimate the exposure of infants due to breast milk consumption. In Chile, we conducted a cross-sectional study based on methodologies proposed by the WHO, with a sample of 30 women recruited from three defined areas: 10 from the Arica Region (urban; Arica and Parinacota Region), 10 from Coltauco (rural; O'Higgins Region), and 10 from Molina (40% rural; Maule Region). High-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS) was performed on pooled samples from each area. We calculated equivalent toxic concentrations (WHO-TEQ) based on the current WHO Toxic Equivalency Factors (TEF). The minimum and maximum values of ∑ PCDDs/Fs + DL-PCBs-TEQ were 4.317 pg TEQ/g fat in Coltauco and 6.31 pg TEQ/g fat in Arica. Molina had a total TEQ of 5.50 pg TEQ/g fat. The contribution of PCDD/Fs was approximately five-fold higher than that of DL-PCBs. The Estimated Daily Intake (EDI) of ∑ PCDDs/Fs + DL-PCBs based on the three pooled samples ranged between 6.71 and 26.28 pg TEQ/kg body weight (bw)/day, with a mean intake of 16.11 (±6.71) pg TEQ/kg bw/day in breastfed children from 0 to 24 months old. These levels were lower than those reported in international studies. Despite the fact that the observed levels were low compared to those in most industrialized countries, the detection of a variety of POPs in breast milk from Chilean women indicates the need for follow-up studies to determine whether such exposures during childhood could represent a health risk in adulthood.
Assuntos
Benzofuranos , Dioxinas , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Adulto , Animais , Benzofuranos/análise , Criança , Pré-Escolar , Chile , Estudos Transversais , Dibenzofuranos , Dioxinas/análise , Feminino , Furanos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactente , Recém-Nascido , Leite Humano/química , Projetos Piloto , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análiseRESUMO
A bioanalytical method by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS) for the simultaneous quantification of 17 drugs and 2 major active metabolites in breast milk was developed and validated. Breast milk samples (100 µL) were submitted to a simple protein precipitation for the extraction of the analytes after the addition of deuterated internal standards (10 µL). A Kinetex C8 column was used for the separation of analytes with mobile phases composed of acetonitrile with 0.1 % formic acid and water with 0.1 % formic acid in gradient elution mode. Analytes were detected using an AB/SCIEX 4000 QTRAP instrument with positive electrospray ionization and operating in scheduled multiple reaction monitoring mode. Validation covered a large range of concentrations (0.5-500 ng/mL) for most of the analytes except bisoprolol, lacosamide, vilazodone (1-500 ng/mL), acid mycophenolic, letrozole, clomiphene (2-500 ng/mL) and hydroxy-melatonin (10-500 ng/mL). Within-run and between-run accuracy and precision for 4 levels of quality controls (QC) spiked at the lower limit of quantification (LLOQ), at 3 times the LLOQ, 50 % of the upper limit of quantification (ULOQ) and 80 % of the ULOQ were in agreement with the criteria from international guidelines. Matrix effect and extraction recovery ranged from 40.7 to 106.5 % and 87.3 to 110.8 %, respectively with relative standard deviations less than 15 %. Furthermore, all analytes were stable in breast milk at room temperature for 24 h, at -20 °C for two weeks, at -80 °C for 1 month, and after 3 freeze-thaw cycles. Finally, the method was successfully applied to nursing women samples collected from an ongoing feasibility study on drug quantification in breast milk.
Assuntos
Leite Humano , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Feminino , Humanos , Reprodutibilidade dos TestesRESUMO
It is well established that breastfeeding improves the health of women, children, and populations. According to the 2018 Centers for Disease Control and Prevention Report Card, 83% of women initiated breastfeeding, but only 58% maintained breastfeeding at the 6-month mark, and 36% continued to 12 months. Reasons for cessation of breastfeeding are multifactorial and include issues surrounding safe use of medications while breastfeeding for acute or chronic conditions. There are a wide variety of resources that clinicians may consult to help decide if medications are compatible with breastfeeding. The resources have varying data and recommendations, which can make counseling challenging for the clinician. There are some resources that are updated regularly with the most current information about drug safety in lactation, as well as call centers that can answer questions from clinicians and patients. A case scenario is presented to help illustrate the many facets of how medication use can affect breastfeeding. Very few medications are absolutely contraindicated during lactation. Involving the woman and her family in a shared decision-making approach regarding medication use may help women feel more confident in the medication recommendations given and ultimately help women achieve their breastfeeding goals. (Clin Ther. 2020; 42:XXX-XXX)© 2020 Elsevier HS Journals, Inc.