The Effect of High-Dose Postpartum Maternal Vitamin D Supplementation Alone Compared with Maternal Plus Infant Vitamin D Supplementation in Breastfeeding Infants in a High-Risk Population. A Randomized Controlled Trial.

In view of continuing reports of high prevalence of severe vitamin D deficiency and low rate of infant vitamin D supplementation, an alternative strategy for prevention of vitamin D deficiency in infants warrants further study. The aim of this randomized controlled trial among 95 exclusively breastfeeding mother-infant pairs with high prevalence of vitamin D deficiency was to compare the effect of six-month post-partum vitamin D3 maternal supplementation of 6000 IU/day alone with maternal supplementation of 600 IU/day plus infant supplementation of 400 IU/day on the vitamin D status of breastfeeding infants in Doha, Qatar. Serum calcium, parathyroid hormone, maternal urine calcium/creatinine ratio and breast milk vitamin D content were measured. At baseline, the mean serum 25-hydroxyvitamin D (25(OH)D) of mothers on 6000 IU and 600 IU (35.1 vs. 35.7 nmol/L) and in their infants (31.9 vs. 29.6) respectively were low but similar. At the end of the six month supplementation, mothers on 6000 IU achieved higher serum 25(OH)D mean ± SD of 98 ± 35 nmol/L than 52 ± 20 nmol/L in mothers on 600 IU (p < 0.0001). Of mothers on 6000 IU, 96% achieved adequate serum 25(OH)D (≥50 nmol/L) compared with 52%in mothers on 600 IU (p < 0.0001). Infants of mothers on 600 IU and also supplemented with 400 IU vitamin D3 had slightly higher serum 25(OH)D than infants of mothers on 6000 IU alone (109 vs. 92 nmol/L, p = 0.03); however, similar percentage of infants in both groups achieved adequate serum 25(OH)D ≥50 nmol/L (91% vs. 89%, p = 0.75). Mothers on 6000 IU vitamin D3/day also had higher human milk vitamin D content. Safety measurements, including serum calcium and urine calcium/creatinine ratios in the mother and serum calcium levels in the infants were similar in both groups. Maternal 6000 IU/day vitamin D3 supplementation alone safely optimizes maternal vitamin D status, improves milk vitamin D to maintain adequate infant serum 25(OH)D. It thus provides an alternative option to prevent the burden of vitamin D deficiency in exclusively breastfeeding infants in high-risk populations and warrants further study of the effective dose.

Fatty Acids and Fat-Soluble Vitamins in Breast Milk: Physiological Significance and Factors Affecting Their Concentrations.

Fatty acids (FAs) and fat-soluble vitamins are vital components of the human milk lipid fraction. About two-thirds of the human milk FA fraction consist of oleic, linoleic, and palmitic FAs, but the precise composition depends on maternal geography, diet, and genetics. Mothers with high fish consumption have more docosahexaenoic acid (DHA) and other ω-3 FAs in their milk, while mothers with high dairy consumption have more branched-chain FAs in their milk. Vitamins A and E are the most common fat-soluble vitamins, but milk concentrations vary, depending on maternal diet and body stores. Vitamin D is typically low or undetectable in mother's milk and typically fails to meet the infant needs. However, trial data indicate that high maternal supplementation (6,400 IU/day) safely provides nutritionally adequate amounts of vitamin D in her milk. FA and fat-soluble vitamin levels in mother's milk can significantly influence infant health; for example, in preterm infants, low endogenous stores of DHA paired with low levels in maternal milk may influence the risk of chronic lung disease and other inflammatory conditions. Greater attention is warranted to the variation in FA and fat-soluble vitamin content of human milk in relation to infant health.

Decreasing birth asphyxia: utility of statistical process control in a low-resource setting.

The neonatal period is a critical time for survival of the child. A disproportionate amount of neonatal deaths occur in low-resource countries and are attributable to perinatal events, especially birth asphyxia. This project aimed to reduce the incidence of birth asphyxia by 20% by June 2014 through training in neonatal resuscitation and improving the availability of resuscitation equipment in the delivery room in the National Hospital Abuja, Nigeria. A prospective, longitudinal study using statistical process control analytical methods was done enrolling babies delivered at the National Hospital Abuja. Low Apgar scores or birth asphyxia (defined a priori as any score <7 at 1, 5 and/or at 10 min) was assessed. To ensure reliability and validity of Apgar scoring, trainings on scoring were held for labour and delivery staff. Interventions included provision of additional equipment and trainings on neonatal resuscitation. Apgar scores were aggregated weekly over 25 months. Control charts with three SE confidence limits were used to monitor the proportion of scores ≤7. The baseline incidence of low Apgar scores, as defined a priori, was 33%, 17% and 10% while postintervention the incidence was 18%, 17% and 6% at 1, 5 and 10 min, respectively-a reduction of 45% and 40% in the 1-min and 10-min low Apgar scores. Increased communication, additional resuscitation equipment and training of delivery personnel on neonatal resuscitation are associated with reductions in measures of birth asphyxia. These improvements have been sustained and efforts are ongoing to spread our interventions to other special care delivery units/nursery in adjoining states. Our study demonstrates the feasibility and utility of using improvement science methods to assess and improve perinatal outcome in low-resource settings.

Prevalence and risk factors for low vitamin D status among breastfeeding mother-infant dyads in an environment with abundant sunshine.

PURPOSE: Evaluation of vitamin D (vD) status and risk factors for low vD among breastfeeding mother-infant dyads in a population at high risk for vD deficiency. SUBJECTS AND METHODS: We measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone at 1 month postpartum in 60 consecutive exclusively breastfeeding Arab mother-infant dyads enrolled in a high dose vD supplementation study to prevent vD deficiency in Doha, Qatar, (latitude 25°N) during summer months. Data were collected on demography, sun exposure, and vD supplementation. Comparison with a US cohort was evaluated. vD deficiency was defined as serum 25(OH)D <50 nmol/L and severe deficiency categorized as 25(OH)D <25 nmol/L in mothers and infants. RESULTS: Mean maternal age was 29 years and 77% had college or university education. Maternal median 25(OH)D was 32.5 nmol/L and 78% were vD-deficient and 20% had 25(OH)D <25 nmol/L. Only 42% of mothers had reportedly taken vD supplements postpartum and median dietary vD intake (119 IU/day) and calcium (490 mg/day) were low. Maternal median sun index score (sun exposure [hours/week] × body surface area exposed while outdoors) was 0. Maternal 25(OH)D correlated with percent body surface area exposure while outdoors (rs=0.37, P=0.004). Infant median 25(OH)D was 20 nmol/L and 83% were deficient, while 58% had 25(OH)D <25 nmol/L. Infant 25(OH)D correlated with maternal levels (rs=0.41, P=0.001). None of the infants received vD supplement at 1 month of age and median sun index score was 0. Infant's parathyroid hormone showed negative correlations with 25(OH)D (rs=-0.28, P=0.03). Sun exposure, vD supplementation rate, and vD status were lower in Doha than Cincinnati, US cohort. CONCLUSION: vD deficiency is common in breastfeeding mother-infant dyads in this sunny environment and is associated with sun avoidance and low vD intake. We suggest corrective vD supplement of breastfeeding mothers and their infants, which should preferably start during pregnancy.

Serum Vitamin D Status and Outcome among Critically Ill Children Admitted to the Pediatric Intensive Care Unit in South India.

OBJECTIVES: To determine the vitamin D status and the association between vitamin D status and the clinical outcome of critically ill children admitted to pediatric intensive care unit (PICU) in South India. METHODS: Fifty-four consecutive children with medical and surgical diagnoses were included with parental consent. Severity of illness was assessed using PIM-2 score; Sequential Organ Failure Assessment Cardiovascular Score (CV-SOFA) was used to describe vasopressor use. Serum for 25(OH) D levels was obtained as close as possible to the ICU admission. Vitamin D deficiency was defined as serum 25(OH) D level < 20 ng/ml (50 nmol/L). Primary outcome measures were serum 25(OH) D level and in-hospital all cause mortality. Secondary outcomes were illness severity, vasopressor requirement, use of mechanical ventilation and duration of ICU stay. RESULTS: Of the 54 children, two were excluded due to insufficient serum for vitamin D analysis. Median age was 17.5 mo (IQR = 4.5-78); 38.5 % were infants. Higher age was associated with low vitamin D levels (r s = -0.34; p 0.01). Median serum 25(OH) D level was 25.1 ng/ml (IQR = 16.2-34.2). Shock (30.8 %), CNS conditions (23.1 %) and respiratory illnesses (21.2 %) were the three most common reasons for admission to the PICU. Vitamin D deficiency was seen in 40.3 % of the critically ill children. Higher PIM score or SOFA score were associated with low vitamin levels (r s = -0.29, p 0.04 and r s = -0.29, p 0.05 respectively). Children who were mechanically ventilated had a significantly lower median serum 25(OH) D level than those who were not on ventilation [19.5 ng/ml (IQR = 14.6-27.7)] vs. 32.1 ng/ml[(IQR = 16.5-50.9), p 0.01]. Serum 25(OH) D level was also positively associated with serum calcium levels (r s = 0.32, p 0.03). The proportion of children who died or were discharged terminally at parental request was 23.8 % among those with serum 25(OH) D level < 20 ng/ml as compared to 16.1 % among those with serum 25(OH) D level > 20 ng/ml (p 0.49). CONCLUSIONS: Vitamin D deficiency is common among pediatric patients admitted to PICU in South India. Low serum 25(OH) D level was associated with higher severity of illness, need for mechanical ventilation, more vasopressor use and lower serum calcium levels. No association between vitamin D status and mortality was demonstrated.

Sun exposure and vitamin D supplementation in relation to vitamin D status of breastfeeding mothers and infants in the global exploration of human milk study.

Although vitamin D (vD) deficiency is common in breastfed infants and their mothers during pregnancy and lactation, a standardized global comparison is lacking. We studied the prevalence and risk factors for vD deficiency using a standardized protocol in a cohort of breastfeeding mother-infant pairs, enrolled in the Global Exploration of Human Milk Study, designed to examine longitudinally the effect of environment, diet and culture. Mothers planned to provide breast milk for at least three months post-partum and were enrolled at four weeks postpartum in Shanghai, China (n=112), Cincinnati, Ohio (n=119), and Mexico City, Mexico (n=113). Maternal serum 25(OH)D was measured by radioimmunoassay (<50 nmol/L was categorized as deficient). Serum 25(OH)D was measured in a subset of infants (35 Shanghai, 47 Cincinnati and 45 Mexico City) seen at 26 weeks of age during fall and winter seasons. Data collected prospectively included vD supplementation, season and sun index (sun exposure×body surface area exposed while outdoors). Differences and factors associated with vD deficiency were evaluated using appropriate statistical analysis. vD deficiency in order of magnitude was identified in 62%, 52% and 17% of Mexican, Shanghai and Cincinnati mothers, respectively (p<0.001). In regression analysis, vD supplementation (p<0.01), obesity (p=0.03), season (p=0.001) and sites (p<0.001) predicted maternal vD status. vD deficiency in order of magnitude was found in 62%, 28%, and 6% of Mexican, Cincinnati and Shanghai infants, respectively (p<0.001). Season (p=0.022), adding formula feeding (p<0.001) and a higher sun index (p=0.085) predicted higher infant vD status. vD deficiency appears to be a global problem in mothers and infants, though the prevalence in diverse populations may depend upon sun exposure behaviors and vD supplementation. Greater attention to maternal and infant vD status starting during pregnancy is warranted worldwide.

Vitamin D status and hospitalisation for childhood acute lower respiratory tract infections in Nigeria.

BACKGROUND: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood deaths in most developing countries, including Nigeria. Vitamin D is associated with innate immunity and may play a role in the control of infections. Case-control studies, including a small study from Nigeria, show inconsistent results for the association between vitamin D status and risk of ALRTI. AIMS: To examine the relationship between vitamin D status and hospitalization for ALRTI in Nigerian children. METHODS: Fifty children aged 2-60 months hospitalised with ALRTI were studied prospectively. ALRTI was diagnosed on the basis of modified WHO criteria. Each patient was matched with controls for age and gender. The controls were enrolled either from children attending well-child clinics or general clinics without evidence of respiratory infection or admitted to the hospital for elective surgery. A structured questionnaire collected data on demography, health, diet, duration of exposure to sunlight and percentage of body surface exposed to sunlight (according to type of clothing) while outdoors, and potential risk factors for ALRTI. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured using a chemiluminescenceimmuno-assay. The differences between cases and controls in serum 25(OH)D concentrations, association between vitamin D status and ALRTI and risk factors for vitamin D deficiency were assessed. RESULTS: Mean (SD) 25(OH)D concentrations in patients and controls were similar [61·5 (25·8) vs 63·1 (22·9) nmol/L,P = 0·95].25% of all 100 subjects studied had serum 25(OH)D<50 nmol/L. In a multiple conditional logistic regression model, only lower percentage of body surface area exposed to sunlight was associated with increased risk of ALRTI. The percentage of body surface area exposed to sunlight while outdoors (P = 0·028) and vitamin D supplement use (P = 0·009) were independent determinants of vitamin D deficiency in the overall study population. CONCLUSIONS: ALRTI was not associated with vitamin D status, but was associated with less exposure to sunlight. Exposure to sunlight and vitamin D supplementation contributed to vitamin D status in this population.

Heightened attention to supplementation is needed to improve the vitamin D status of breastfeeding mothers and infants when sunshine exposure is restricted.

Although exclusively breastfed infants are at increased risk of vitamin D (vit D) deficiency if vit D supplementation is lacking and sun exposure is limited, assessment of both risk factors in the first year of life is lacking. We evaluated the contribution of vit D intake and sunlight exposure to vit D status in 120 healthy, breastfeeding mother-infant dyads, who were followed up for 1 year. Vitamin D intake and skin sunlight exposure were evaluated using questionnaires. Serum 25-hydroxyvitamin D, parathyroid hormone (PTH) and alkaline phosphatase levels were determined post-natally in mothers at 4 weeks and in infants at 4, 26 and 52 weeks. Vitamin D supplementation was low (<20%) and sunlight exposure was common (93%) in study infants. At 4 weeks, 17% of mothers were vit D deficient (<50 nmol L(-1)) and 49% were insufficient (50-<75 nmol L(-1)), while 18% of infants were severely vit D deficient (<25 nmol L(-1)) and 77% were deficient (<50 nmol L(-1)). At 26 weeks, winter/spring birth season and shorter duration of months of exclusive breastfeeding were protective of vit D deficiency in infants. Vitamin D deficiency in infants decreased to 12% at 52 weeks with sunlight exposure. Serum PTH levels were significantly higher in severely vit D deficient than sufficient infants. Vitamin D deficiency was widespread in early post-partum breastfeeding mothers and infants, and declined to one in eight infants at 52 weeks due mostly to sunshine exposure. When sunlight exposure is limited or restricted, intensified vit D supplementation of breastfeeding mothers and infants is needed to improve vit D status.

Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay.

OBJECTIVES: To evaluate vitamin D (vitD) status in early preterm infants (EPTIs) at birth and during birth hospitalisation on current vitD intake. DESIGN/METHODS: Serum 25-hydroxyvitamin-D [25(OH)D] concentrations, vitD intake and risk factors for low vitD status were assessed in 120 infants born at ≤32 weeks gestation. RESULTS: Mean (SD) serum 25(OH)D at birth was 46.2 (14.0) nmol/L with lower concentrations in infants born <28 weeks than at 28-32 weeks gestation, p=0.02. Serum 25(OH)D was <50 nmol/L in 63% of mothers, 64% of infants at birth and 35% of infants at discharge. Mean daily vitD intake was 289±96 IU at 4 weeks of age and 60% achieved 400 IU/day intake at discharge. CONCLUSIONS: Serum 25(OH)D <50 nmol/L was widespread in parturient women and in EPTIs at birth and at discharge. Optimising maternal vitD status during pregnancy and improving postnatal vitD intake may enhance infant vitD status during hospitalisation.

Vitamin D nutrition in pregnancy: current opinion.

There is increasing interest in vitamin D nutrition during pregnancy because of widespread reports of a high prevalence of low vitamin D status in pregnant women. While vitamin D is important for calcium and phosphorus homeostasis and for bone health, it also plays important roles in many other physiologic functions in the body. Consistent with the expanded role of vitamin D, recent observational studies have demonstrated that low vitamin D status in pregnancy is associated with multiple potential adverse maternal, fetal, and infant outcomes and contributes to low vitamin D status in infants at birth. Therefore, an overview of the current understanding of vitamin D nutrition in pregnancy and a review of the results of studies to optimize vitamin D status during pregnancy and in the offspring is of public health importance and timely.

Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency.

BACKGROUND: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial. OBJECTIVE: The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a randomized controlled trial in population in which vD deficiency is endemic. DESIGN/METHODS: Arab women were randomized at 12-16 weeks of gestation to 400, 2000, and 4000 IU/d vD3, which were continued to delivery. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during pregnancy and at delivery. The primary outcome was the maternal and cord blood 25(OH)D, and the secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL or greater (≥80 nmol/L) at delivery. SETTING: The locations were primary care and tertiary perinatal care centers. RESULTS: Of 192 enrolled, 162 (84%) continued to delivery. Mean serum 25(OH)D of 8.2 ng/mL (20.5 nmol/L) at enrollment was low. Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group (P < .001) and was highest in the 4000 IU/d group. The percent who achieved 25(OH)D greater than 32 ng/mL and greater than 20 ng/mL concentrations in mothers and infants was highest in 4000 IU/d group. Safety measurements were similar by group and no adverse event related to vD supplementation. CONCLUSIONS: Vitamin D supplementation of 2000 and 4000 IU/d appeared safe in pregnancy, and 4000 IU/d was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants. These findings could apply to other populations in which vD deficiency is endemic.

Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus.

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D's indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Maternal vitamin D status: effect on milk vitamin D content and vitamin D status of breastfeeding infants.

There are increasing reports of rickets and vitamin D deficiency worldwide. Breastfeeding without adequate sunlight exposure and vitamin D supplementation are the major risk factors. In view of the drive to promote and increase the rate of exclusive breastfeeding, the relationship among maternal vitamin D status, vitamin D concentration of human milk, and hence vitamin D status of breastfeeding infants deserves reassessment. This review provides current information on the interrelationship between maternal vitamin D status and the vitamin D status of the breastfeeding infant. It also reviews the results of ongoing research on the effect of high-dose maternal vitamin D supplementation alone as a possible option to prevent vitamin D deficiency in the breastfeeding mother-infant dyad.

High prevalence of moderately severe vitamin D deficiency in preterm infants.

BACKGROUND: The recommended dose of vitamin D supplementation of preterm infants is based on data from populations in which severe vitamin D deficiency is uncommon and may be inadequate for infants in high risk population. However, data on vitamin D status of preterm infants in high-risk populations, such as Middle Eastern countries is scarce. METHODS: This study investigates the vitamin D status of Arab mothers and their preterm infants. Maternal serum and cord blood 25(OH)D, calcium (Ca), phosphorus (P) and alkaline phosphate (ALP) were measured at delivery. Serum 25(OH)D was measured by HPLC while the other biochemical parameters were measured by standard autoanalyzer. RESULTS: Thirty-four preterm infants were studied. The mean gestational age was 31.4 weeks and birth weight was 1667g. The median serum 25(OH)D of 17.0nmol/L in 28 mothers and 14.5nmol/L in 34 cord blood samples were low. The median maternal and cord blood Ca, P and ALP levels were within normal range. Fifteen (44%) of the infants had moderately severe vitamin D deficiency (serum 25 (OH)D levels <12.5nmol/L). The median serum 25(OH)D levels of mothers who had reportedly taken prenatal vitamin D supplementation and those who had not were similar (17.3 vs 16.3) nmol/L. The mean serum 25(OH)D levels among preterm infants in this study were low when compared to levels in Caucasians preterm infants on which the current vitamin D recommendations are based. CONCLUSION: The high prevalence of moderately severe vitamin D deficiency in Arab preterm infants provides a justification to investigate vitamin D requirement of preterm infants in this and other high-risk populations.

Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants.

Severe vitamin D deficiency in mothers and their breastfed infants is a significant health problem in the Middle East. Supplementation of the breastfed infant alone with the recommended dose of vitamin D may be insufficient in high-risk population. We investigated the effect of combined maternal and infant vitamin D supplementation on vitamin D status of the breastfed infant. We examined also the effect of supplementation on vitamin D antirachitic activity of breast milk in a subset of mothers. Healthy breastfeeding mothers (n = 90) were randomly assigned to 2000 IU daily (group 1) or 60,000 IU monthly (group 2) of vitamin D(2), and all their infants (n = 92) received 400 IU daily of vitamin D(2) for 3 months. Most infants had vitamin D deficiency - 25-hydroxyvitamin D [25(OH)D]

Efficacy of daily and monthly high-dose calciferol in vitamin D-deficient nulliparous and lactating women.

BACKGROUND: We previously found a high prevalence of vitamin D deficiency and low medication regimen compliance in Arab and East Indian women residing in the United Arab Emirates (UAE). The appropriate dosing regimen for improving vitamin D status in this population is not known. OBJECTIVE: We aimed to determine the efficacy of daily and monthly supplementation with vitamin D2, the only high-dose calciferol available in the UAE, in lactating and nulliparous women. DESIGN: Healthy lactating (n = 90) and nulliparous (n = 88) women were randomly assigned to consume 2000 IU vitamin D2/d or 60,000 IU vitamin D2/mo for 3 mo. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured by radioimmunoassay at baseline and every month. RESULTS: Most women had vitamin D deficiency [ie, 25(OH)D < 50 nmol/L] at study entry. Mean +/- SD 25(OH)D concentrations at 3 mo were significantly higher than baseline in both lactating (39.8 +/- 12.4 and 25.2 +/- 10.7 nmol/L, respectively) and nulliparous (40.4 +/- 23.4 and 19.3 +/- 12.2 nmol/L, respectively) women (P < 0.001 for both). In total, vitamin D supplementation was effective in achieving serum 25(OH)D concentrations of >or=50 nmol/L in 21 (30%) of 71 women at endpoint. CONCLUSIONS: Oral vitamin D2 supplementation with 2000 IU/d or 60,000 IU/mo for 3 mo was safe, and it increased serum 25(OH)D concentrations significantly; however, only a small proportion of the women studied achieved concentrations of >or=50 nmol/L. This suggests that, when sunlight exposure is limited, doses of vitamin D2 higher than those currently studied may be needed. Monthly dosing appears to be a safe and effective alternative to daily dosing.