Breast Milk Concentrations Research Articles

Development of a method for determination of 1,5-Anhydro-d-glucitol in milk and its content of human breast milk

Development of a method for determination of 1,5-Anhydro-d-glucitol in milk and its content of human breast milk

Effect of Nicotinamide Mononucleotide Concentration in Human Milk on Neurodevelopmental Outcome: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 μM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.

Determination of Persistent Organic Pollutants in Human Breast Milk and Their Health Effects

Breast milk, the primary source of nutrition for infants, contains the ideal combination of carbohydrates, lipids, and proteins, and provides immunological and other health benefits that protect against infections. Persistent Organic Pollutants (POPs) are lipophilic organic compounds that accumulate in adipose tissue after being assimilated by the mother from the environment. Infants can be exposed to POP through breast milk, making breastfeeding a significant source of exposure. This review aims to provide a comprehensive overview of the numerous POPs that are contaminated in breast milk, the analytical techniques used to detect them in breast milk, and the potential health impacts of these pollutants on mothers through bioaccumulation and on infants through breastfeeding. Peer-reviewed articles published between 1989 and 2023 that covered several key features, including methodologies, health consequences, and other significant factors, were abstracted to assess the major results and research gaps. The majority of research investigated the relationship between POP concentrations in breast milk and socio-demographic variables. The studies revealed that several Organochlorine Pesticides (OCPs), Polychlorinated Biphenyls (PCBs), and their derivatives and industrial by-products such as polyaromatic hydrocarbons (PAHs) can contaminate breast milk, posing potential health risks to infants exposed to POPs through breast milk in many regions of the world.

USE OF GALACTOGOG TO INCREASE BREAST MILK VOLUME AS THE MAIN GOAL OF SDGS IN REDUCING STUNTING

The first 1000 days of life are the most important and unique at the beginning of human life, from conception to two years after giving birth which have an impact on growth and development. This research aimed to determine the differences in breast milk production between the control group, the group given Torbangun leaves, and the group given fenugreek and to carry out an analysis of the zinc content of breast milk for each group. This research design uses a quasi-experiment with a control and intervention group. Purposive sampling technique. Sample Size 49 Responden The number of respondents in this study was 30 respondents, 10 in the control group, 10 respondents in the tobangun intervention group, and 10 respondents in the fenugreek capsule intervention. The analysis test used is the one-way ANOVA analysis test which is used to see the differences between each group. The research results showed a significant difference between the control group and the treatment group with a significance value in the laboratory test for zinc levels, namely 0.000, namely <0.05. Conclusion: Galactogues can be useful for breastfeeding mothers to increase breast milk volume. The suggestion is to use Galagtogog and Fenugreek for postpartum mothers to increase zinc levels and volume in the breast milk of nursing mothers. Keywords: Breast milk tablets; Galaktogogue; Torbangun leaves

Maternal Circadian Disruption from Shift Work and the Impact on the Concentration of Melatonin in Breast Milk.

Background and Objective: Melatonin in breast milk exhibits a 24-hour circadian rhythm, present in nighttime breast milk but nearly undetectable in daytime breast milk. Shift work can disrupt the circadian timing of individuals, evident in changes in melatonin in saliva and urine samples. However, it is unknown whether these changes are also reflected in breast milk from a shift working mother. The aim of this study was to investigate whether maternal circadian rhythm disturbance from shift work impacts the melatonin concentration in breast milk. Materials and Methods: Breast milk and saliva samples were collected from 11 shift working mothers at four timepoints across five consecutive days. This included during their day shift or nonworkdays to act as a control, night shift, subsequent night shifts and postnight shift. Where possible, pre- and postfeed collections were also undertaken. Samples were grouped into four-time intervals: 12-6:30 am, 7-11:30 am, 12-6:30 pm, 7-11:30 pm, and melatonin levels (picogram per milliliter) in the breast milk and saliva samples were analyzed. Results: There was a significant decrease in breast milk melatonin (p = 0.026) at the 12-6:30 am time interval on subsequent night shifts, compared with control days. However, there was no overall time and shift type interaction effect (p = 0.70). In addition, no observed difference in melatonin levels was found in saliva samples, or when comparing pre- and postfeed breast milk. Breast milk melatonin however was found to be significantly higher compared with saliva (p > 0.001), at all but one time interval. Conclusion: The findings suggest that there is a potential effect of maternal circadian rhythm disruption from shift work on breast milk melatonin levels. This is an important step in exploring the role of maternal circadian timing and the effect on breast milk composition. Expansion of this research and exploration of other circadian rhythm misalignment sleep disorders on breast milk is highly recommended.

High-intensity exercise increases breast milk adiponectin concentrations: a randomised cross-over study.

Adiponectin plays a role in glucose and fat metabolism and is present in human breast milk. It has been postulated that higher breast milk adiponectin concentrations may prevent rapid weight gain in infancy. Prior research indicates that circulating adiponectin increases acutely after endurance exercise, but no prior research has investigated the effect of exercise on breast milk adiponectin concentrations. The purpose of this randomised, cross-over study was to determine the acute effects of endurance exercise on adiponectin concentrations in human breast milk. Participants who were exclusively breastfeeding a 6-12 week-old term infant (N = 20) completed three conditions in the laboratory: (1) Moderate-intensity continuous training (MICT), (2) High-intensity interval training (HIIT), and (3) No activity (REST). At each condition, we collected breast milk at 07:00 h (before exercise/rest), 11:00 h (immediately after exercise/rest), 12:00 h (1 h after exercise/rest), and 15:00 h (4 h after exercise/rest) and determined adiponectin concentrations using enzyme-linked immunosorbent assay. We compared changes in adiponectin concentrations after MICT and HIIT, adjusted for the morning concentration on each test day, with those after REST, using paired t-tests. Adiponectin concentrations increased 1 h after HIIT, from 4.6 (± 2.2) μg/L in the 07:00 h sample to 5.6 (± 2.6) μg/L. This change was 0.9 μg/L (95% confidence interval 0.3 to 1.5) greater than the change between these two timepoints in the REST condition (p = 0.025). There were no other statistically significant changes in adiponectin concentrations. HIIT may increase adiponectin concentrations in breast milk acutely after exercise. Further studies should determine the impact of exercise-induced elevations in breast milk adiponectin concentrations on growth and metabolism in infancy.

Relationship between Eating Habits and 4-Nonylphenol Concentration in Breast Milk of Women in Slovakia.

4-Nonylphenol belongs to the alkylphenol group of chemicals, and its high occurrence in the environment can cause an adverse effect on human health. Breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this work, the influence of selected factors (the kind of water drank by the mothers; the consumption of fish, pork, and beef; wearing gloves; using nail polish, gel nails, vitamins, and medication) on the concentration on 4-nonylphenol in 89 breast milk samples was studied. The concentrations of nonylphenol in breast milk were determined by HPLC with fluorescence detection. The lowest and highest concentrations of 4-nonylphenol in breast milk were 0.97 ng/mL and 4.37 ng/mL, respectively. Statistical significance was observed for the consumption of pork (p = 0.048) and fish (0.041) in relation to the 4-nonylphenol concentration. Certain parameters (use of gel nails, beef consumption, and vitamin supplementation) were at the border of statistical significance (p = 0.06). Other parameters did not show any statistical significance. The results showed that breast milk in Slovakia does not contain a harmful dose of 4-nonylphenol and does not cause health problems. But it is necessary to continue this research and perform extended screening on a larger number of samples.

Novel fluorescence approach for trace quantification of levonorgestrel in breast milk based on click reaction with benzonitrofurazan azide (NBD-AZ)

Although the great importance of oral contraceptive agents in birth control, their existence in breast milk became a cause for concern, since infant exposure to these hormones is associated with many health problems. Consequentially, developing a sensitive bioanalytical method for monitoring their concentrations in breast milk is an urgent demand to examine the safety or the risk of these compounds on infants. Levonorgestrel is one of the most common contraceptive hormones under concern. Despite the high sensitivity of the fluorometric methods, detection of Levonorgestrel by them is confined because its structure does not exhibit any fluorescence. For the first time, we proposed a promising click fluorescent probe, 4-azido-7-nitrobenzoxadiazole to react with the alkyne group of Levonorgestrel, to give a highly fluorescent triazole derivative that exhibited strong signal at wavelength of 544 nm after excitation at 470 nm. Reaction parameters impacting the fluorescence were cautiously studied and optimized. The suggested approach has been successfully applied in Levonorgestrel estimation in breast milk samples with linearity of (0.4–80 ng.ml−1) and low detection limit of 0.12 ng.ml−1 without interferences from any biological components and with mean % recovery of 97.84 ± 2.73. Accuracy, sensitivity, selectivity, simplicity, and low-cost makes this approach a convincing, promising, and appealing alternative over reported analytical methods for Levonorgestrel bioanalysis in different matrices.

The relationship between creamatocrit and cumulative percentage of total milk volume: a cross-sectional study in mothers of very preterm infants in Bangkok, Thailand

BackgroundHuman hindmilk contains higher concentrations of fat than foremilk and is more desirable for growth in preterm infants who can tolerate limited volumes of breastmilk. There is currently no clear demarcation between foremilk and hindmilk. This study characterized the change in breastmilk’s fat content from the start to end of milk flow and defined this demarcation.MethodsMothers of infants born at ≤ 32 weeks gestational age and ≥ 14 days after childbirth in a University hospital in Bangkok, Thailand between July, 2011, and April, 2012 were included in this cross-sectional study. Breastmilk samples were sequentially collected from the start to end of milk flow in 5-mL aliquots using breast pumps. The fat content of each aliquot from each breast was determined through creamatocrit. The average creamatocrit of foremilk and hindmilk were compared in predefined foremilk to hindmilk ratios of 20:80, 25:75, 33:67, and 50:50. Creamatocrit of the first and last aliquots were compared for mothers who expressed low- (≤ 25-mL per breast) and high-volumes (> 25-mL per breast) of breastmilk.ResultsOf the 25 mothers enrolled, one was excluded due to unsuccessful creamatocrit measurement. The last aliquot of breastmilk had a significantly higher creamatocrit than the first from the same breast (median [interquartile range] of 12.7% [8.9%, 15.3%] vs. 5.6% [4.3%, 7.7%]; test statistic 1128, p < 0.001). Mean creamatocrit in hindmilk portions (9.23%, 9.35%, 9.81%, and 10.62%, respectively) was significantly higher than foremilk portions (6.28%, 6.33%, 6.72%, and 7.17%, respectively) at all predefined ratios. Creamatocrit increased by 1% for every 10% incremental increase in expressed breastmilk volume until the breast was emptied. Low-volume mothers had a significantly higher creamatocrit in the first aliquot compared with high-volume mothers (U = 437, p = 0.002). No significant difference in breastmilk volume was observed between mothers with and without breastfeeding experience.ConclusionsFat content in breastmilk increased on an incremental basis. More fluid definitions of foremilk and hindmilk should be adopted. Mothers should prepare their breastmilk into aliquots based on the required feeding volume of their infant. Hindmilk aliquots can be prioritized over foremilk aliquots to ensure infants obtain optimal caloric intake.

Assessment of vitamin A levels in breast milk and serum of lactating mothers in Southeast Nigeria

Background: Vitamin A (VA) is an essential micronutrient critical to human health, infants rely on their mother’s breast milk for sufficient supply. This makes the maternal diet a crucial source of VA for infant growth and development. Aims: This study aimed to assess maternal VA status by assessing serum and breast milk retinol concentrations as well as dietary intake in nursing mothers. Subjects and Methods: A clinic-based cross-sectional study, conducted in Awka, south-east Nigeria, was used to assess 127 lactating women at one to 24 months post-partum. Blood and breast milk samples were obtained from each participant in a fasted state while dietary intake was assessed via an interviewer-administered semi-structured food frequency questionnaire. Retinol concentration was analyzed by spectrophotometry. Descriptive statistics were used to summarize the data while Spearman rank correlation analysis was used to determine associations between breast milk and serum retinol concentrations and study variables. Results: The mean retinol concentration in the serum of the women was a borderline value of 0.75 ± 0.64 µmol/L while the mean retinol concentration in breast milk was 0.99 ± 0.71 µmol/L. Further, the mean milk fat content was 56.18 ± 32.32 g/L while the mean milk retinol to fat ratio was 0.027 ± 0.044 µmol/g. Maternal diet consisted of a preference for provitamin A foods with low bioavailability. The mean retinol concentration in breast milk increased with time post-partum. There was no statistically significant relationship found between the frequency of consumption of most foods and the concentration of retinol in breast milk. Conclusion: The evidence of VA deficiency highlights the need for screening and nutrition education of breastfeeding mothers during ante- and post-natal visits. Keywords: Human milk, serum, vitamin A, maternal diet.

Hubungan Pengetahuan Ibu Dengan Pemberian Air Susu Ibu (ASI) Eksklusif di Wilayah Kerja Praktek Mandiri Bidan (PMB) Siti Saleha S.Tr. Keb Desa Bantaianriau Tahun 2023

One of the efforts made to reduce MMR is the Antenatal Care (ANC) examination program which is mandatory for pregnant women. The Indonesian Ministry of Health stipulates that examinations for pregnant women or antenatal care be carried out at least 6 times over 9 months. The aim of this research was to determine the relationship between maternal knowledge and breastfeeding in the Independent Practice work area of ​​Midwife Siti Saleha, Bantaian Village, Riau. This research uses an analytical observational design using quantitative methods with a cross-sectional research design approach. The number of samples in this study was 28 respondents. The conclusion of this research is that there is a relationship between maternal knowledge and breastfeeding. It is recommended that mothers do not blindly accept advertisements about formula milk in electronic media and the internet, mothers should ask health workers to find out more about the benefits and contents of breast milk which are no less than those contained in formula milk.

A regression approach for assessing large molecular drug concentration in breast milk

The development of an effective method for predicting the transfer of biologics from plasma into breast milk is important to ensure the safe use of medications during lactation. The aim of this study was to develop a regression model that could predict the transfer of monoclonal antibodies (mAbs) and Fc-fusion proteins from plasma into breast milk. By searching various databases, a list of eleven mAbs and Fc-fusion proteins with available information of presence in the breast milk was generated. Physicochemical properties such as the isoelectric point (pI), molecular weight (MW), dissociation constant (Kd), and pharmacokinetic (PK) parameters such as clearance (CL), volume of distribution (Vd), and half-life (T1/2) were collected or calculated. A two-variable non-linear regression analysis and a multivariate regression analysis were employed to establish correlation of milk-to-plasma (M/P) ratios with different combinations of two physicochemical properties. The 3D isoelectric point (pI) of the Fv region and the buried surface area (BSA) between the light and heavy chains (LC_HC) were two factors that emerged as a promising predictor of the milk-to-plasma concentration ratio (M/P). The correlation between M/P ratio, 3D pI of Fv region, and BSA_LC_HC was found to be good with R2 of 0.9058. Other combinations of the physicochemical properties did not show a statistically significant correlation. The multivariate regression model was used to predict the MP ratios for 79 different mAbs. We believe that this regression model could serve as a valuable tool to estimate the M/P ratios of mAbs and Fc-fusion proteins. Further model validation is necessary when the M/P ratios of additional biologics are available. This could inform clinical decision-making and improve the safety of large molecule drug use during lactation.

Carotenoids in maternal and cord blood, breast milk and their association with maternal dietary intake: a longitudinal study in Shanghai, China.

Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). β-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). β-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.

Association between Exposure to Endocrine Disrupting Chemicals in Breast Milk and Maternal Lifestyle Factor

This study aimed to investigate the concentrations of nonpersistent endocrine-disrupting chemicals (EDCs) and per- and polyfluoroalkyl substances (PFAS) in human milk through a literature review and to affirm the association between EDCs and lifestyle factors based on the reviewed literature. We analyzed studies reporting EDC concentrations in breast milk from literature published on Google Scholar and PubMed between 2000 and 2022. In Korea, most EDC concentrations in breast milk were comparable to or lower than those in other countries. However, the concentrations of PFAS in breast milk, especially perfluorooctanoic acid, have shown an increasing trend compared to the past in Korea. Considering the potential risks of EDCs, breastfeeding mothers should take measures to minimize their exposure to these chemicals.

Effects of dietary PUFA patterns and FADS genotype on breast milk PUFAs in Chinese lactating mothers

BackgroundBreastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes.MethodsThree hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant.ResultsUnder the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother’s intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary.ConclusionsOur study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs.

Ornidazole Transfer into Colostrum and Assessment of Exposure Risk for Breastfeeding Infant: A Population Pharmacokinetic Analysis.

Ornidazole is frequently used for the prevention and treatment of anaerobic infections after caesarean section. There is still a lack of data on the excretion of ornidazole in breast milk. Therefore, the aim of this study was to investigate the transfer of ornidazole into colostrum and to assess the risk of infant exposure to the drug via breast milk. Population pharmacokinetic analysis was conducted using datasets of plasma and milk concentrations obtained from 77 breastfeeding women to examine the excretion kinetics of ornidazole. Various factors that may affect the excretion of ornidazole were investigated. The final model was then used to simulate ornidazole concentration-time profiles in both plasma and milk. The drug exposure in body fluids and the potential risk for breastfeeding were assessed based on the safety threshold. Plasma ornidazole concentration data could be described well by a one-compartment model, and concentrations in breast milk were linked to this model using an estimated milk-to-plasma concentration ratio (MPRcon). Significant variables that influenced drug exposure and MPRcon were identified as total bilirubin levels (TBIL) and postnatal sampling time, respectively. Simulations showed that women with abnormal liver function (TBIL > 17 μmol/L) had higher ornidazole levels in plasma and milk than those with normal liver function (TBIL < 17 μmol/L), but the exposures through colostrum of lactating women from both groups were below the safety threshold. This work provides a simple and feasible strategy for the prediction of drug exposure in breast milk and the assessment of breastfeeding safety.

Comparative analysis of the use of selective serotonin reuptake inhibitors during pregnancy and the postpartum period. Safety of sertraline

Depressive disorders and anxiety are the most common mental disorders in the perinatal period, occurring in 14–23% of women. Antidepressants from the selective serotonin reuptake inhibitor (SSRI) group are considered the drugs of choice for the treatment of these disorders. Although SSRIs are the best-studied antidepressants used in pregnant women, there are still conflicting opinions about their effect on pregnancy course and outcomes of pregnancy. At the same time, the risks associated with their use in pregnant women are often exaggerated, while the risks of untreated mental disorders are underestimated. SSRI use during pregnancy has been associated with a modestly increased risk of adverse events, including postpartum haemorrhage, miscarriage, preterm birth, cesarean delivery, fetuses small for their gestational age and low birth weight, low Apgar scores, and increased rates of neonatal hospitalization to intensive care units. However, depressive and anxiety disorders in the mothers themselves also contribute to similar outcomes, so it is not always possible to distinguish the contribution of medication and illness. Comparative data on the effects of different SSRI medications on outcome for the mother and fetus during pregnancy are limited, but paroxetine and fluoxetine are reported to pose the greatest risk to the fetus/neonate. Information on the safety of citalopram and escitalopram during pregnancy and lactation is limited. Citalopram has the highest concentrations in amniotic fluid of all SSRIs. According to current data, sertraline has the most favourable safety profile during pregnancy and lactation, which is explained by its low penetration through the placenta. Sertraline concentrations in the fetus are approximately 1/3 of those in maternal plasma. Sertraline has the lowest concentrations in breast milk of all SSRIs and is associated with a low risk of adverse effects in a baby, making it the drug of choice for nursing mothers. In conclusion, sertraline is one of the best studied SSRIs and has a favourable safety profile for both the mother and the fetus/neonate.

Trace elements status in human breast milk of mothers from Île-de-France region

Breastfeeding is the main source of nutrition during first months of life. Its composition varies according to parameters like mother’s diet and health, living area, number of pregnancies and lactation duration… Trace-elements concentration in breastmilk is then an important parameter that can affect infant’s health, growth or immune system and organ functions. Few data are available on this topic, and results are often very variable. The aim of this work is to determine reference values of Copper (Cu), Zinc (Zn), Selenium (Se), Cobalt (Co), Iron (Fe) and Iodine (I) in human breastmilk according to lactation duration and to study influencing parameters on its elementary composition. Regional Human Milk Bank of Necker Enfants Malades Hospital provided samples that came from breastfeeding woman involved in voluntary milk donation and epidemiologic data. Two hundred thirty-two breastmilk were analysed. After nitric acid mineralization of milk samples, Cu, Zn, Se, Co and I were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in a standard mode. Fe was measured by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Both assays were validated in terms of sensitivity, repeatability and accuracy.Studied breast milks came from mothers with an average age of 32 years and donation time ranged from one day after childbirth to 974 days (> 2.5 years); mean lactation duration is 59 days (> 8 weeks) while median duration is 29 days (around 4 weeks). In all studied samples, mean results and reference values are for Cu: 6.02 (1.71–13.23), Zn: 43.86 (7.3–107.0), Se: 0.12 (0.07–0.24), I: 0.29 (0.07–1.01) and Fe: 4.72 (1.25–11.49) µmol/L and for Co: 12.28 (5.27–25.82) nmol/L. Important number of studied milks allowed their distribution into seven classes of lactation durations. Samples were divided into four successive classes of fifteen days after childbirth, two other classes corresponding to the 3rd and 4th months and a last class for milks sampled after 4 months of lactation. Results were analysed in each class allowing study of evolution during lactation. That was particularly interesting for Zn, that presented an important variability in the total population (4–132 µmol/L) explained by variation along lactation evolution decreasing from 48 to 17 µmol/L in first and last duration classes respectively. In addition, Cu and Fe concentrations were also significantly correlated with lactation duration while Se and I were in a lesser extent (p = 0.002). In this study, we present reference values for studied trace elements at different lactation stages, allowing a fine interpretation of future breast milk samples results according to their sampling time. By continuing this study, we plan to increase number of samples in some of the classes and to study the influence of premature birth or twin pregnancy on breast milk elementary composition.

Characterization of the US Food and Drug Administration Post-Marketing Commitments and Requirements for Pregnancy and Lactation.

Enactment of the US Food and Drug Administration Amendments Act (FDAAA) in 2007 and the Pregnancy and Lactation Labeling Rule (PLLR) in 2015 are important milestones giving the FDA the authority to request studies in pregnant and lactating women. Our objective was to characterize trends of pregnancy and lactation-related postmarketing commitments (PMCs) and postmarketing requirements (PMRs) for new molecular entities approved by the FDA between 2000 and 2022. Approval letters of original New Drug Applications (NDAs, N = 488) for new molecular entities were obtained from the FDA website. NDAs with pregnancy and lactation-based PMCs/PMRs were identified, and data extracted. Data included: PMC/PMR timelines and attributes of requested study(ies) (type, design elements, and outcomes) when available. Fifty-nine NDAs included 92 PMCs/PMRs related to pregnancy and lactation. Forty-one NDAs had pregnancy-related PMRs/PMCs, 4 had lactation-related PMRs, and 14 had both. Most PMRs/PMCs were for nervous system medications (N = 33). Forty-seven NDAs specified safety data collection in infants in at least the first year of life. All pregnancy-related PMRs were issued after 2008, most PMCs (N = 8) were issued before 2008. Only one PMC requested a pharmacokinetic study in pregnant women. All lactation-related PMRs (N = 18) requested measurement of drug concentrations in breast milk with one also requiring measurement of maternal blood concentrations. Eighty-nine percent of lactation-related PMRs were requested after 2015. There was a steady increase in pregnancy and lactation-related PMRs following enactment of FDAAA and PLLR. Additions involved information collection pertaining to safety of the medication in pregnant and lactating women and children exposed to medications during pregnancy and breastfeeding.

Effects of pasteurization on osteopontin concentrations in human breastmilk.

Osteopontin (OPN) is an important breastmilk protein involved in infant intestinal, immunological, and brain development. However, little is known about how common milk pasteurization and storage techniques affect this important bioactive protein. Human milk osteopontin concentration was measured in single-donor fresh (n = 1) or frozen (n = 20) breastmilk, pooled Holder-pasteurized donor breastmilk (n = 11), and a shelf-stable (retort pasteurized) breastmilk product (n = 2) by ELISA. Single-donor breastmilk samples were subjected to pasteurization and/or freezing before measuring osteopontin concentrations. Holder pasteurization of breastmilk resulted in an ∼50% decrease in osteopontin concentration within single-donor samples. Breastmilk from mothers of preterm infants trended toward higher osteopontin concentration than mothers of term infants; however, samples from preterm mothers experienced greater osteopontin degradation upon pasteurization. A commercial breastmilk product that underwent retort pasteurization had lower osteopontin concentration than a Holder-pasteurized pooled breastmilk product. Finally, freezing breastmilk prior to Holder pasteurization resulted in less osteopontin degradation than Holder pasteurization prior to freezing. Commonly used breastmilk pasteurization and storage techniques, including freezing and Holder pasteurization, decrease the concentration of the bioactive protein osteopontin in human breastmilk. Holder pasteurization reduced osteopontin concentration by an average of 63%, while freezing resulted in an 8-12% decrease. Pasteurization of human breastmilk significantly decreases the concentration of the bioactive protein osteopontin. Use of both pasteurization and freezing techniques for breastmilk preservation results in greater loss of osteopontin. This study presents for the first time an analysis of osteopontin concentrations in single-donor pasteurized milk samples.