Breast Milk Retinol Concentrations Research Articles

A Correlation Study of Plasma and Breast Milk Retinol Concentrations in Breastfeeding Women in China.

Retinol in breast milk is related to plasma concentration among breastfeeding women, but the linear or curvilinear relationships between the two remains unclear. We conducted a cross-sectional study in 403 Chinese breastfeeding women at 42 ± 7 days postpartum. Plasma and breast milk samples were assayed using high performance liquid chromatography to determine the concentration of retinol. Partial Spearman correlation and multivariable fractional polynomial regression were used to examine the relationships between the two retinol concentrations and between plasma retinol concentration and milk-to-plasma (M/P) retinol. The median (interquartile range, IQR) of the retinol concentration in the plasma was 1.39 (1.21, 1.63) μmol/L and 1.15 (0.83, 1.49) μmol/L in the breast milk, respectively. The partial correlation coefficient between them was 0.17 (p < 0.01). A linear relationship was observed with an adjusted regression coefficient of 0.34 (95% CI: 0.19, 0.49). The relationship between the plasma retinol and M/P ratio was nonlinear and segmented at 1.00 μmol/L of plasma retinol. The regression coefficients, below and above the segmented point, were -1.69 (95% CI: -2.75, -0.62) and -0.29 (95% CI: -0.42, -0.16), respectively. Plasma and breast milk retinol were positively correlated, whereas women with a low concentration of plasma retinol showed a stronger capacity of transferring retinol to breast milk.

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.

Breast Milk Retinol Concentrations Reflect Total Liver Vitamin A Reserves and Dietary Exposure in Thai Lactating Women from Urban and Rural Areas

Measuring vitamin A (VA) status during lactation is required to inform dietary recommendations. Limited data exist on VA stores in women. Our objective was to assess VA status in lactating Thai women by measuring total body VA stores (TBSs), serum and breast milk retinol concentrations, and dietary intake. Lactating women (n=94), 6-8 wk postpartum, were enrolled from rural (Ayutthaya) and urban (Bangkok) areas. TBSs were measured by the 13C-retinol isotope dilution (RID) technique using 2.0 μmol 13C-retinyl acetate and a single blood sample 14 d post-dose. Natural 13C-enrichment was determined in nonenrolled women (n=11). Estimated total liver VA reserves (TLRs) were determined using assumptions for lactation. Serum, foremilk, and hindmilk samples were analyzed for retinol by HPLC. Dietary VA intake was assessed by FFQ and 24-h dietary recalls for 3 d. Multiple regression and Pearson correlation were used to evaluate relations. Median VA intakes were 51.8% of 2003 Thai daily recommendations for lactating women, with the majority from animal-source foods. Many women in Ayutthaya consumed liver weekly. Considering TLRs as 50% TBS, 20% and 11% of mothers in Ayutthaya and Bangkok, respectively, showed deficient reserves (≤0.10μmol retinol/g). Median (quartile 1, quartile 3) serum [1.58 (1.34, 1.91) and 1.52 (1.30, 1.70) μmol/L] and milk [1.88 (1.29, 2.95) and 1.74 (0.96, 2.26) μmol/L] retinol in Ayutthaya and Bangkok, respectively, were normal. Women with deficient TLRs showed low milk retinol concentrations (≤1.0μmol/L) and consumed less dietary VA, especially from animal-source foods. Breast milk retinol concentrations, especially hindmilk, demonstrated strong correlation with TBSs and TLRs estimated from the RID test. Approximately 15% of Thai lactating women had deficient TLRs. Breast milk retinol concentrations in conjunction with dietary intake records show potential to screen mothers at risk of VA deficiency to guide interventions.The Thai Clinical Trials Registry number is TCTR20160824001 for the work in Thailand.

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother-Infant Pair: A Randomised Placebo-Controlled Trial in China.

Background: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. Results: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. Conclusions: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.

Simulated Impact of Vitamin A Fortified Sugar on Dietary Adequacy and Association of Usual Sugar Intake With Plasma and Breast Milk Retinol Among Lactating Women in Rural Zambia

ObjectivesZambia introduced mandatory sugar fortification with vitamin A (VA) in 1998; however, regulatory monitoring and evaluation have been limited. We studied the contribution of VA-fortified sugar intake to dietary adequacy, and examined associations between usual sugar and VA intakes with plasma and breast milk retinol concentrations in lactating women in rural Zambia. MethodsWe conducted three 24-h dietary recalls among each of 255 lactating women enrolled in a randomized trial, at the time of baseline venous blood and breast milk collection. We measured retinol in biospecimens using high-performance liquid chromatography. We simulated VA intake under various sugar fortification scenarios: 3.1 and 8.8 mg/kg (measured median fortification levels of VA in sugar from previous studies), 10 mg/kg (minimum legal requirement) and 15 mg/kg (minimum legal requirement at factory level). Usual intake distributions, prevalence of inadequate VA intake (< Estimated Average Requirement of 900 μg RAE/d) and prevalence of retinol intake above the tolerable upper intake level (UL, >3000 μg/d) for each scenario were estimated using the National Cancer Institute (NCI) method. We applied the NCI’s “bivariate model” as a regression calibration tool to examine associations of usual intake of sugar and dietary VA with plasma and breast milk retinol concentrations. ResultsIn the absence of sugar fortification, the prevalence of VA inadequacy was predicted to be 83% (SE: 6). Fortification of sugar with VA at 3.1 mg/kg, 8.8 mg/kg, 10 mg/kg and 15 mg/kg would reduce the prevalence of VA inadequacy by 7 (SE:6), 24 (SE:14), 30 (SE:15) and 47 (SE:18) percentage points, respectively, without increasing the risk of retinol intake above the UL. Usual sugar intake and usual VA intake were not associated with plasma retinol or breastmilk retinol concentrations. ConclusionsThe sugar fortification program has the potential to reduce dietary VA inadequacy, but the impact is likely to be limited if actual fortification levels are lower than mandated levels. Even if target fortification levels are achieved (10 mg/kg), sugar fortification alone is unlikely to eliminate dietary VA inadequacy among lactating women in rural Zambia. Funding SourcesHarvestPlus and the Sight and Life Global Nutrition Research Institute at Johns Hopkins University.

Breast Milk Retinol Is Negatively Associated With General Parameters of Obesity in Lactating Women

ObjectivesTo evaluate the correlation between breast milk retinol concentration and general parameters of obesity in lactating women. MethodsThis is a cross-sectional study design. Participants were 21 lactating women between 54.2 ± 2.35 d postpartum, and who declared exclusive or predominant breastfeeding practices. A casual sample of breast milk (∼3 mL) was collected and breast milk retinol was analyzed by HPLC. General anthropometric measurements (weight, height, waist and hip circumference) were performed. The Spearman test was used to assess the correlation between the variables. ResultsParticipating lactating women were 19–34 y of age. Breast milk retinol concentration was 1.84 ± 0.84 μmol/L; 38.1% (n = 8) of lactating women had low breast milk concentration of vitamin A (< 1.05 μmol/L). Body Mass Index (BMI) was 26.7 ± 4.32; 33.3% of the women had a normal BMI, 52.4% were overweight and 14.3% were obese. Waist (83.2 ± 8.81 cm) and hip circumference (104 ± 9.35 cm), were also recorded. BMI (r = –0.551, p = 0.010), waist (r = –0.480, p = 0.028) and hip circumference (r = –0.484, p = 0.030) negatively correlated with retinol concentrations in breast milk. ConclusionsIn this group of women, breast milk retinol concentration was lower in women with higher BMI, waist and hip circumference. Funding SourcesJA-P received a fellowship from the Mexican National Research and Technology Council.

Effect of vitamin A, calcium and vitamin D fortification and supplementation on nutritional status of women: an overview of systematic reviews

BackgroundMicronutrient deficiency affects the health and development of vulnerable population such as children and pregnant women. Measures such as fortification of food and supplementation have been implemented to prevent or control deficiencies related to micronutrients.ObjectiveTo assess the effect of vitamin A, vitamin D, and calcium fortification and supplementation on nutritional status of women in reproductive age group. To assess the toxicities and adverse events related to intervention.MethodologySystematic reviews including RCTs on women of reproductive age group provided with vitamin A, vitamin D, and calcium supplementation or fortified food were included, to report all malnutrition-related outcomes due to deficiency of the abovementioned micronutrients. The Cochrane Database of Systematic Reviews, EPPI Centre, Campbell Collaboration, PubMed, Web of Science, and Scopus were searched electronically for English language publications, until 31 March 2018. Hand searching of the articles was done from the Journal of Food Science and Technology. Two independent reviewers selected the systematic reviews, extracted data, and assessed for the quality.ResultsA total of 16 systematic reviews were included in narrative synthesis. Supplementation of vitamin A was reported to result in increased maternal serum retinol concentrations and increased breast milk retinol concentration. It reduced the risk of anemia (Hb < 11 g/dL) and reduced maternal clinical infection. Vitamin D supplementation increased 25-hydroxy vitamin D levels. There was insufficient evidence for the effect on bone mineral density and serum calcium levels. Calcium supplementation did not have any significant effect on body weight, weight gain, and body mass index of the participants.ConclusionThis overview of systematic reviews reiterates the nutritional importance of vitamin A, vitamin D, and calcium supplementation for the reproductive age women. However, there was no empirical evidence available for fortification of food with vitamin A, vitamin D, and calcium and nutritional benefits of the same for reproductive age women, therefore thrusting upon the need of conducting future quality research, i.e., clinical trials and systematic reviews for food fortification.Systematic review registrationA priori protocol for this overview of systematic reviews was registered in PROSPERO with registration number CRD42018089403.

Effectiveness of a Food-Based Intervention to Increase Breast Milk Vitamin A Content at One Month of Infancy

Abstract Objectives Vitamin A requirements in early infancy are met only by breast milk intake. It is critical to ensure adequate breast milk vitamin A levels which also helps develop liver stores. The objective of the study was to evaluate the effect of a maternal food-based intervention on breast milk vitamin A content Methods Pregnant women (n = 50; 24 ± 1 week of gestation) were recruited for the randomized study. A 10 g of a green leafy vegetable powder (mint/coriander/curry) providing about 3200 μg β-carotene/day, for a period of 4 months up to 1 month of lactation were provided for intervention arm. Breast milk (BM) retinol concentration and BM volume were assessed. BM retinol and beta-carotene were assayed by HPLC and BM fat by creamatocrit method. BM retinol: fat ratio was calculated. The dose-to-mother deuterium dilution technique was used to estimate BM volume through enrichment of saliva measured by Fourier Transform Infrared Spectroscopy. Total BM retinol content was calculated from BM volume and the BM retinol (including beta-carotene:1 vitamin A RAE = 12 μg β-carotene). Inadequacy of intake was defined as proportion of infants with intake below a requirement of 400 μg RAE/day. Analysis of co-variance was performed after adjusting for age of mother, change in maternal blood retinol from baseline and BM fat, to compare outcomes between intervention and control arm. Results Maternal age, gestational age, socio-demographic characteristics and baseline vitamin A intake were comparable in both arms. Mean BM volume was similar in the 2 arms (676 ± 102 in intervention vs 630 ± 100 ml/day in control). BM retinol content (0.72 ± 0.12 vs 0.64 ± 0.11 μg/mL; P = 0.029) and BM retinol: fat ratio [0.41 (0.31, 0.47) vs 0.29 (0.21, 0.41), P = 0.011] were significantly higher in the intervention arm. The mean total BM retinol content was significantly higher in the intervention (482.2 ± 100.7 vs 406.5 ± 89.2 μg/day; P = 0.015; Cohen's effect size 0.80). Inadequacy of infant vitamin A intake was 14.3% in the intervention arm as against 39.1% in the control arm (P = 0.065). Conclusions The food-based intervention was effective in increasing vitamin A content in breast milk and thereby vitamin A intake in infants. Funding Sources International Atomic Energy Agency.

Retinol-to-Fat Ratio and Retinol Concentration in Human Milk Show Similar Time Trends and Associations with Maternal Factors at the Population Level: A Systematic Review and Meta-Analysis.

Vitamin A in human milk is critical for meeting infant requirements and building liver stores needed after weaning. A number of studies have measured milk retinol, but only a subset have corrected for fat, which serves as the retinol carrier in breast milk. The purpose of the present work was to review and analyze studies in which human-milk retinol concentrations were reported in relation to milk fat and to compare these results with unadjusted breast-milk retinol concentrations in terms of time trends over the course of lactation, influences of maternal nutritional and constitutional factors, and effects of maternal vitamin A supplementation. A systematic approach was used to search the available literature by using the US National Library of Medicine's MEDLINE/PubMed bibliographic search engine. Observational and intervention studies were included if the research was original and the retinol-to-fat ratio (retinol:fat) in human milk was measured at ≥1 time point during the first 12 mo of lactation. Retinol:fat and retinol were highest in colostrum, declined rapidly in early lactation, and achieved statistical stability by 2 and 4 wk lactation, respectively. In mature milk, retinol concentration was positively correlated with milk fat (r=0.61, P=0.008). Breast-milk retinol:fat and retinol were positively associated with maternal vitamin A intake but were associated with plasma retinol only when dietary intake was inadequate. Postpartum supplementation with high-dose vitamin A (200,000-400,000 IU) resulted in significantly higher breast-milk retinol:fat for 3 mo and retinol for 6 mo (P<0.05). In populations, the 2 indexes show similar trends and associations with maternal factors. Future studies should monitor how the uptake of retinol into the mammary gland affects maternal vitamin reserves, particularly in women who are at risk of vitamin A deficiency.

Effect of regular consumption of provitamin A biofortified staple crops on Vitamin A status in populations in low-income countries

Biofortification of staple crops with provitamin A (PVA) carotenoids is an innovative strategy for controlling vitamin A (VA) deficiency in low-income countries (LIC). Plant breeding programs have been successful in developing biofortified varieties of cassava, maize, and orange-fleshed sweet potatoes that contain amounts of PVA-carotenoids that have the potential to impact VA status in human populations. Nutrition studies indicate that beta-carotene in biofortified staple crops is converted efficiently to VA in the body. Randomized, controlled, community-based efficacy and effectiveness trials have been conducted to assess the effect of regular consumption of PVA-carotenoid biofortified staple crops on VA status. Results indicate that regular consumption of biofortified staple crops increases plasma beta-carotene concentrations consistently, but has a moderate effect, or no effect, on VA status, when assessed by serum retinol concentration, breast milk retinol concentration, or total body VA stores. Studies are currently underway to further investigate whether consumption of biofortified staple crops improves VA status in population subgroups at risk of VA deficiency, and to better understand how to optimize the biological impact of these interventions in resource-poor settings. Keywords: Beta-carotene, Biofortification, Bioavailability, Cassava, Maize, Provitamin A, Sweet potatoes, Vitamin A

Breast milk retinol concentration in mothers of preterm newborns

BackgroundPreterm newborns have low vitamin A reserves at birth, which increases their risk of morbidity and mortality. In the absence of supplementation, breast milk is the only source of this nutrient for exclusively breastfed infants. AimsTo assess retinol concentration in preterm milk and the relationship between this retinol concentration and lactation phase, degree of prematurity, and maternal serum retinol level. Study designLongitudinal study. SubjectsFifty-eight preterm mothers. Outcome measuresColostrum (1–3d), transitional (7–15d), and mature human milk (30–55d) samples were collected. Maternal blood was collected once at postpartum. Retinol level was measured using high-performance liquid chromatography. ResultsMilk retinol concentration was statistically different between lactation phases (p<0.001): 2.84±1.05μmol/L in colostrum (58), 3.47±1.28μmol/L in transitional (58), and 2.03±0.61μmol/L in mature milk (30). No difference was found in milk retinol levels between groups with different degrees of prematurity (p>0.05). Maternal serum retinol (1.82±0.50μmol/L) did not correlate with milk levels (p>0.05). ConclusionsRetinol level in preterm milk seems to be independent of the degree of prematurity and maternal serum status. A significant increase in micronutrient levels in transitional milk was observed, which is likely to contribute to reserves in the premature liver.

Short-Term Daily Consumption of Provitamin A Carotenoid–Biofortified Maize Has Limited Impact on Breast Milk Retinol Concentrations in Zambian Women Enrolled in a Randomized Controlled Feeding Trial

Background: Provitamin A carotenoid–biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk—a critical source of vitamin A for breastfeeding infants.Objective: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.Methods: Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.Results: Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).Conclusions: Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.

Effect of Short‐Term Maternal Supplementation with Small Amounts of Vitamin A or Beta‐Carotene on Breast Milk Retinol Concentrations among Lactating Filipino Women

This study assessed the effect of daily supplementation with low doses of vitamin A (VA, as retinyl palmitate) or β‐carotene, in amounts that could be provided by fortified or biofortified foods, on breast milk and plasma retinol concentrations after 1 d or 3 wk of supplementation, and after 1 wk of discontinuing supplementation.Lactating women (18–45 y; n=85) were randomly assigned to receive capsules containing 600 μg RAE/d as either retinol (VA group) or β‐carotene (BC group) in corn oil, or 0 μg RAE/d (oil only; control). The daily dose was delivered as 2 capsules/d along with low‐VA meals, 6 d/week for 3 wk. Fasting blood samples were collected at baseline (d 0) and after 3‐wk of supplementation (d 22). Fasting breast milk samples were collected on days 0, 1, 2, 22 and 29, using both “full” and “casual” milk collection methods. Milk was also collected before and after a single meal (d1AM and d1PM) to assess the effect of one dose of VA or BC on milk VA. Plasma and milk retinol and BC concentrations were measured by HPLC, inflammatory markers by ELISA, milk fat by creamatocrit, and β‐carotene‐15,15″‐mono‐oxygenase (BCO1) polymorphisms by PCR.At baseline, the prevalence of low plasma retinol (22% &lt;1.05 μmol/L) and low milk retinol (64% (full) and 53% (casual) &lt;28 nmol/g fat) did not differ by group. After 3 wk of supplementation, controlling for baseline, mean plasma retinol concentration was greater in the VA group (inflammation‐adjusted mean±SE 1.56 ± 0.29 μmol/L) relative to the control group (1.31 ± 0.44 μmol/L; P&lt;0.01), whereas that of the BC group (1.48 ± 0.33 μmol/L) did not differ from either the VA or control groups (P&gt;0.1). Controlling for baseline, mean milk retinol concentration at d 22 was greater in the VA group relative to the control group (full: 33.8 ± 18.4 vs 24.0 ± 7.3 nmol/g fat; casual: 32.0 ± 13.4 vs 24.1 ± 9.4 nmol/g fat; P&lt;0.01); this difference persisted 1 wk after discontinuing supplementation (day 29; P&lt;0.05). In full milk samples, the mean milk retinol concentration in the BC group (d 22: 27.8 ± 10.1 nmol/g fat) did not differ from that of the control group at d 22 or d 29. In casual samples, the mean milk retinol concentration was greater in the BC group (d22: 29.2 ± 9.4 nmol/g fat) vs the control group on day 22 (P&lt;0.05) but not d 29, and did not differ from the VA group at either time. Mean milk retinol concentrations did not increase in response to a single VA or BC capsule (d1AM vs d1PM), or to a single day of VA or BC capsule receipt (d1AM vs d2AM) relative to the control group. BCO1 variants were prevalent but did not modify the effect of BC capsules on plasma or milk retinol (although power to detect interactions was limited).In summary, an effect of supplementation with small daily doses of retinol was detected in both plasma and breast milk after only 3 wk of supplementation, suggesting that breast milk is useful for evaluating food‐based interventions with retinol, such as fortification. The effect of BC was less consistent, so evaluation of the response to increased provitamin A intake may require a larger sample size or longer duration of supplementation.Support or Funding InformationThis study was supported by the Bill &amp; Melinda Gates Foundation.

Vitamin A supplementation for postpartum women.

In areas where vitamin A deficiency (VAD) is a public health concern, the maternal dietary intake of vitamin A may be not sufficient to meet either the maternal nutritional requirements, or those of the breastfed infant, due the low retinol concentrations in breast milk. To evaluate the effects of vitamin A supplementation for postpartum women on maternal and infant health. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (8 February 2016), LILACS (1982 to December 2015), Web of Science (1945 to December 2015), and the reference lists of retrieved studies. Randomised controlled trials (RCTs) or cluster-randomised trials that assessed the effects of vitamin A supplementation for postpartum women on maternal and infant health (morbidity, mortality and vitamin A nutritional status). Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. Fourteen trials of mainly low or unclear risk of bias, enrolling 25,758 women and infant pairs were included. The supplementation schemes included high, single or double doses of vitamin A (200,000 to 400,000 internation units (IU)), or 7.8 mg daily beta-carotene compared with placebo, no treatment, other (iron); or higher (400,000 IU) versus lower dose (200,000 IU). In all trials, a considerable proportion of infants were at least partially breastfed until six months. Supplement (vitamin A as retinyl, water-miscible or beta-carotene) 200,000 to 400,000 IU versus control (placebo or no treatment) Maternal: We did not find evidence that vitamin A supplementation reduced maternal mortality at 12 months (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.44 to 2.21; 8577 participants; 1 RCT, moderate-quality evidence). Effects were less certain at six months (risk ratio (RR) 0.50, 95% CI 0.09 to 2.71; 564 participants; 1 RCT; low-quality evidence). The effect on maternal morbidity (diarrhoea, respiratory infections, fever) was uncertain because the quality of evidence was very low (50 participants, 1 RCT). We found insufficient evidence that vitamin A increases abdominal pain (RR 1.28, 95% CI 0.95 to 1.73; 786 participants; 1 RCT; low-quality evidence). We found low-quality evidence that vitamin A supplementation increased breast milk retinol concentrations by 0.20 µmol/L at three to three and a half months (mean difference (MD) 0.20 µmol/L, 95% CI 0.08 to 0.31; 837 participants; 6 RCTs). Infant: We did not find evidence that vitamin A supplementation reduced infant mortality at two to 12 months (RR 1.08, 95% CI 0.77 to 1.52; 6090 participants; 5 RCTs; low-quality evidence). Effects on morbidity (gastroenteritis at three months) was uncertain (RR 6.03, 95% CI 0.30 to 121.82; 84 participants; 1 RCT; very low-quality evidence). There was low-quality evidence for the effect on infant adverse outcomes (bulging fontanelle at 24 to 48 hours) (RR 2.00, 95% CI 0.61 to 6.55; 444 participants; 1 RCT). Supplement (vitamin A as retinyl) 400,000 IU versus 200,000 IUThree studies (1312 participants) were included in this comparison. None of the studies assessed maternal mortality, maternal morbidity or infant mortality. Findings from one study showed that there may be little or no difference in infant morbidity between the doses (diarrhoea, respiratory illnesses, and febrile illnesses) (312 participants, data not pooled). No firm conclusion could be drawn on the impact on maternal and infant adverse outcomes (limited data available).The effect on breast milk retinol was also uncertain due to the small amount of information available. There was no evidence of benefit from different doses of vitamin A supplementation for postpartum women on maternal and infant mortality and morbidity, compared with other doses or placebo. Although maternal breast milk retinol concentrations improved with supplementation, this did not translate to health benefits for either women or infants. Few studies reported on maternal and infant mortality and morbidity. Future studies should include these important outcomes.

Lipid-Based Nutrient Supplements Providing Approximately the Recommended Daily Intake of Vitamin A Do Not Increase Breast Milk Retinol Concentrations among Ghanaian Women

Background: Vitamin A deficiency remains a global public health problem. Daily supplementation with a lipid-based nutrient supplement (LNS) has potential for increasing milk vitamin A concentrations.Objective: The objective of this study was to determine whether daily supplementation with approximately the recommended daily intake of vitamin A in an LNS or a multiple-micronutrient supplement (MMN) during pregnancy and the first 6 mo postpartum has an effect on breast milk retinol concentration at 6 mo postpartum.Methods: Women ≤20 wk pregnant (n = 1320) were randomly assigned to receive either the MMN providing 18 micronutrients, including 800 μg retinol equivalents of vitamin A, or the LNS with the same nutrients as the MMN group, plus 4 minerals and macronutrients, until 6 mo postpartum; a control group received iron and folic acid during pregnancy and a placebo (calcium tablet) during the first 6 mo postpartum. Breast milk samples collected at 6 mo postpartum were analyzed for retinol and fat concentrations by HPLC and creamatocrit, respectively, in a subsample of 756 women.Results: The breast milk retinol concentration was (mean ± SD) 56.3 ± 2.1 nmol/g fat, with no significant differences between groups [iron and folic acid (n = 243): 59.1 ± 2.8; MMN (n = 260): 55.4 ± 2.5; LNS (n = 253): 54.7 ± 2.5 nmol/g fat; P = 0.45], regardless of whether the woman had or had not received a high-dose vitamin A supplement (200,000 IU) soon after childbirth. Around 17% of participants had low milk retinol (≤28 nmol/g fat). We estimated that 41% of infants were potentially receiving vitamin A at amounts above the Tolerable Upper Intake Level (600 μg retinol activity equivalents/d), with no group differences in percentages with low or high milk retinol concentration.Conclusion: Daily consumption of approximately the recommended intake of vitamin A did not increase breast milk retinol concentrations in this sample of Ghanaian women. This trial was registered at clinicaltrials.gov as NCT00970866.

Influence of Inflammation on Breast Milk Retinol Concentrations of Apparently Healthy Women in Rural Zambia

Breast milk retinol concentration may be less influenced by inflammation than plasma retinol. However, evidence is available from only a single study which was conducted in early lactation. We investigated this question in a cross‐sectional sample of apparently healthy, lactating mothers (n=144) at 4‐12 months postpartum in rural Zambia. We measured milk and plasma retinol by HPLC and inflammatory proteins by ELISA. Inflammation (CRP &gt; 5 mg/L and/or AGP &gt; 1 g/L) was highly prevalent (69.2%), even though women with malaria parasitemia and/or fever or diarrhea in the past week were excluded from the study. Women with inflammation were older and had both higher parity and BMI. Unadjusted analyses suggested an elevated prevalence of low plasma retinol (7.4 vs. 2.3%; p=0.23), but reduced prevalence of low milk retinol (51.5 vs. 65.1%; p=0.14), with concurrent inflammation. In adjusted models; however, only plasma retinol was significantly associated with inflammatory proteins (p=0.04 for test of CRP and AGP parameters). Inflammatory proteins were not associated with milk retinol, expressed either as vitamin A per volume (μmol/L; p=0.63) or per gram milk fat (μg/g fat; p=0.37). Our findings are consistent with prior research, suggesting that breast milk retinol concentration may be useful for evaluating vitamin A interventions in populations with a high prevalence of infection and/or subclinical inflammation.

Dose to the Mother Method: Milk Intake and Vitamin A Transfer to the Lactating Infant of Mexican Mothers, Using Stable Isotopes

ObjectiveTo assess the breast milk intake and transfer of vitamin A (VA) from the mother to the breastfed child in lactating Mexican women from rural and urban areas.MethodsMilk intake was assessed with the dose to the mother method, briefly deuterated water is administered to the mother and the appearance of the isotope is measured in the breastfed child's and mother's saliva; deuterium enrichment (stable isotope) is analyzed by FTIR. Breast milk retinol (BMR) concentration was determined by HPLC and the cutoff to define VA deficiency was 1.05 µmol/L.ResultsSubjects were 27 and 32 women‐child pairs from urban and rural areas of northwest Mexico, respectively. Mean breast milk intake 727.35 ± 224 mL and it was significantly lower in children from the rural area (P=0.04). Mean BMR concentration was 1.11 μmol/L and 53% of women had VAD. BMR concentration was lower for the rural area (P=0.038). By combining both determinations (DTM and BMR), results showed that breastfed children from the rural and urban area reached only 47% and 64% of their VA recommended dietary intake (P=0.051), respectively.ConclusionVAD is still a public health problem in Mexico and requires new approaches to fight it effectively.Study supported by Universidad de Sonora.

PENILAIAN STATUS VITAMIN A SECARA BIOKIMIA

VITAMIN A ASSESSMENT BY BIOCHEMICAL METHODS Vitamin A has an important preventive effects on maternal and child mortality. Vitamin A deficiency (VAD) is one of the most devastating dietary deficiencies. Several methods are available to assess VAD. Tradisionally, clinical signs and symptoms of xerophthalmia were used to identify the severity of population with vitamin A deficiency. Biochemical assessment methods available which include serum retinol, serum retinol binding protein, serum retinyl ester, serum carotenoids, dose response test, the deuterated retinol isotope dilution test and breast milk retinol concentrations. The determination of of retinol in blood (serum retinol concentrations) is one of the most frequently used methods, have been used extensively to identify populations at risk of vitamin A deficiency. However, this method has several limitations. The major drawback of serum retinol is taking blood samples are required. Beside that, serum retinol is decreased only in sever VAD, when liver stores are nearly exhausted. Because the majority of vitamin A in the body is stored in the liver, then the tests to measure vitamin A stores should be developed in order to know the vitamin A status. Vitamin A concentration in breast milk is a prospective indicator of VAD. Breast milk collection is less invasive and usually easier than blood drawing, do not have to be further processed at the field station, thus shortening sample preparation. For the future indicator of vitamin A, methods that are in development include using isotope dilution. Keywords : breast milk retinol, serum retinol, vitamin A analysis

Breast Milk Retinol and Plasma Retinol-Binding Protein Concentrations Provide Similar Estimates of Vitamin A Deficiency Prevalence and Identify Similar Risk Groups among Women in Cameroon but Breast Milk Retinol Underestimates the Prevalence of Deficiency among Young Children1–3

Breast milk vitamin A (BMVA) has been proposed as an indicator of population vitamin A status but has rarely been applied in large-scale surveys or compared with conventional vitamin A biomarkers. We assessed the prevalence of, and risk factors for, low BMVA and its relation to vitamin A intake, plasma retinol-binding protein (pRBP), and markers of inflammation in a national survey in Cameroon. We randomly selected 30 clusters in each of 3 strata (South, North, and Cities). Casual milk samples were collected from approximately 5 women per cluster (n = 440). pRBP, plasma C-reactive protein (pCRP), plasma α1-acid glycoprotein (pAGP), and 24-h vitamin A intake were assessed in 10 women aged 15–49 y and 10 children aged 12–59 mo per cluster, including a subset of lactating women (n = 253). Low BMVA was infrequent: 7.2% (95% CI: 4.7, 9.8) of values were <1.05 μmol/L, and 9.3% (95% CI: 5.8, 12.7) were <8 μg/g fat, consistent with the low prevalence of pRBP <0.78 μmol/L among women (< 5%) but lower than the prevalence of pRBP <0.83 μmol/L among children (35%). Risk factors for both low BMVA and pRBP included living in the North and low maternal education. BMVA was positively associated with inflammation-adjusted pRBP among women in the lowest vitamin A intake tertile [<115 μg retinol activity equivalents (RAEs)/d, P < 0.01] but not in the highest tertile (>644 μg RAEs/d, P > 0.4). Controlling for milk fat, BMVA was negatively associated with pCRP (P < 0.02) but not pAGP (P > 0.5). BMVA and pRBP provide similar estimates of vitamin A deficiency prevalence and identify the same risk groups among women in Cameroon, but BMVA underestimates the prevalence of vitamin A deficiency among young children.

The effect of short‐term frozen storage of human milk on the validity of Vitamin A assays using the iCHECKTM rapid analyzer

BackgroundBreast milk retinol concentration is an indicator of both infant nutrient intake and population vitamin A status. Milk is easily and non‐invasively collected and rapid field methods for vitamin A analysis now exist.ObjectiveTo confirm or refute the assertion of restricting fluorescent assaying of milk vitamin A to “unfrozen” samples (Schweigert et al, Sight &amp; Life Magazine 2011 (2) 18–22).MethodsFull‐breast expression milk samples were collected in 21 women from Mam‐Mayan rural communities in the Western Highlands of Guatemala. A milk‐fat packing volume (creamatocrit), expressed in volume percent (vol%), was measured on a hematocrit microcentrifuge. Retinol concentration was assayed, both fresh and after 20–26 d at −20°C, on an iCHECKTM rapid field analyzer (Bioanalyt, Telbow, Germany).ResultsRespective retinol concentrations were 539±221 μg/L (fresh) and 528±205 μg/L (post‐freezing) (p=0.45), with a Pearson correlation coefficient (P) and Spearman coefficient (S) both of r=0.959 (p=0.001). The corresponding values for creamatocrit were 8.1±3.1 vol% vs 9.0±4.0 vol% (p=0.17), with r=0.774 (p=0.001)(P) and r=0.844 (p=0.001)(S).ConclusionsMilk samples can be stored for at least 3 wks without affecting the validity of iCHECKTMassays. Funded by Sight &amp; Life of Basel and Tufts University School of Medicine