毒理性
哺乳期间的使用总结：维生素D是人类乳汁的正常成分。每日母亲维生素D补充量在400至2,000 IU（10至50 mcg）范围内产生的乳汁浓度不足以满足仅通过母乳喂养的婴儿的每日需求，也不足以仅通过母乳喂养纠正婴儿预先存在的维生素D缺乏。在此剂量范围内服用维生素D补充剂的哺乳母亲应给予其婴儿每日至少400 IU（10 mcg）的维生素D补充剂，以满足儿科营养指南。每日母亲维生素D剂量在4,000 IU（100 mcg）或以上时，可以达到的乳汁水平可能满足婴儿每日至少400 IU（10 mcg）的目标摄入量，这取决于母亲的基础维生素D状况和婴儿每日的乳汁摄入量。肥胖的母亲可能需要更高的剂量。
巴氏杀菌在一个研究中将乳汁中主要形式维生素D的中位数水平降低了20%。
对哺乳婴儿的影响：每日400至6,400 IU的母亲剂量与哺乳婴儿的任何短期生化异常无关。
一名11天大的、仅通过母乳喂养的足月女婴出现了无症状的轻度高钙血症（总血清钙为11.4 mg/dL）。母亲在怀孕和哺乳期间每天服用维持剂量的维生素D2 100,000 IU以维持正常的钙和磷状态，此前因甲状腺-甲状旁腺切除手术，同时服用含有400 IU每日维生素D的孕妇维生素（未指明形式）。维生素D2和25-OH-维生素D2在脐带血和14天大时的乳汁中均显著升高。未测量婴儿的血清维生素D水平。高每日乳汁维生素D2摄入量加上出生时婴儿高血清水平可能是异常钙值的贡献因素。
在印度北部的一项研究中，母亲在出生后短期内每天一次服用60,000 IU维生素D3，持续10天，与安慰剂组相比，其仅通过母乳喂养的婴儿在14周和6个月大时血清钙、磷水平或尿钙/肌酐比率没有差异。与安慰剂组相比（17%），服用维生素D的母亲的婴儿生化性佝偻病的发生率较低（0%），但放射性佝偻病的发生率没有差异（3.6% vs 3.4%）。
在一项关于母体维生素D补充对母亲和婴儿表观遗传影响的初步研究中，10名女性在孕24至28周开始并持续到产后4至6周，每天一次服用3,800 IU或400 IU的口服维生素D3。出生时的孕周数未报告，但假定是足月。所有婴儿都是完全或部分通过母乳喂养。那些部分通过母乳喂养的婴儿在研究期间平均每天只接受了大约10 mL的配方奶。婴儿白细胞基因组DNA中胞嘧啶-鸟嘌呤二核苷酸的甲基化在两组之间显著不同。由于低剂量组中有2/3的婴儿在产后接受了维生素D补充，而高剂量组中有5/7的婴儿没有，因此需要更大规模的对照研究来确定通过母乳喂养的维生素D暴露对婴儿表观遗传的影响。
在印度北部的152名母亲中，其中大多数维生素D缺乏，被随机分配在产后7天内一次性接受120,000 IU（3000 mcg）的维生素D，然后在6、10和14周后重复同样的剂量，以配合婴儿的预定免疫接种，或接受安慰剂。安慰剂组中母亲的婴儿每天接受400 IU（10 mcg）的维生素D，而治疗组中的婴儿接受安慰剂。在14周时，两组婴儿的生长参数和血清骨矿物质及肝稳态的生化指标相似。在9个月时，牙齿生长和腹泻或呼吸道疾病的频率也没有差异。
在印度拉贾斯坦邦的114名维生素D缺乏的母亲中被随机分配接受60,000 IU（1,500 mcg）的维生素D3或安慰剂作为单次剂量，在分娩后24至48小时内开始，然后在6、10和14周后重复。超过90%的参与者是仅通过母乳喂养。在6个月大时，对照组有6名婴儿和治疗组的0名婴儿发生了生化性佝偻病，分别有2名和1名婴儿发生了放射性佝偻病。据报道，治疗组中母亲的婴儿在6个月大时血清钙和磷浓度正常，尽管没有给出具体结果，而且这一结果对照组没有报告。
在卡塔尔的190名母亲中被随机分配在产后4周内开始接受600 IU或6000 IU的维生素D。低剂量组中母亲的婴儿每天接受400 IU，而高剂量组的婴儿接受每日安慰剂。在预定的产后4个月和7个月的研究访问中，两组婴儿的生长参数、血清钙和甲状旁腺激素水平以及父母报告的婴儿健康状况没有差异。
在印度拉贾斯坦邦的220名健康、非肥胖的哺乳母亲中被随机分配在第一个月后开始每月一次接受120,000 IU或12,000
◉ Summary of Use during Lactation:Vitamin D is a normal component of human milk. Daily maternal vitamin D supplementation in the 400 to 2,000 IU (10 to 50 mcg) range produces milk concentrations that are inadequate to deliver the daily requirement to an exclusively breastfed infant, and inadequate to correct pre-existing infant vitamin D deficiency through breastfeeding alone. Breastfeeding mothers who take vitamin D supplements in this range should give their infants a daily vitamin D supplement of at least 400 IU (10 mcg) to meet pediatric nutritional guidelines. Daily maternal vitamin D dosages at or above 4,000 IU (100 mcg) achieve milk levels can potentially meet the daily infant goal intake of at least 400 IU (10 mcg), depending on the mother's underlying vitamin D status and daily infant milk intake. Obese mothers may have higher requirements.
Holder pasteurization decreased median levels of the major forms of vitamin D in breastmilk by 20% in one study.
◉ Effects in Breastfed Infants:Maternal daily doses of 400 to 6,400 IU have not been associated with any short-term biochemical abnormalities in breastfed infants.
An 11-day-old, exclusively breastfed, term, female neonate experienced asymptomatic, mild hypercalcemia (total serum calcium 11.4 mg/dL). The mother was taking maintenance vitamin D2 100,000 IU daily to maintain normal calcium and phosphorus status after a pre-pregnancy thyroid-parathyroidectomy, plus a prenatal vitamin containing 400 IU daily vitamin D (form not specified) during pregnancy and lactation. Vitamin D2 and 25-OH-vitamin D2 levels in cord blood and in milk at 14 days of age were both markedly elevated. Serum vitamin D levels were not measured in the infant. The combination of high daily breastmilk vitamin D2 intake plus a high infant serum level present at birth likely contributed to the abnormal calcium value.
In a study in northern India, short-term maternal use of oral 60,000 IU vitamin D3 once daily for 10 days beginning after birth was not associated with any differences in serum calcium or phosphorus levels, or of urinary calcium/creatinine ratios, in their exclusively breastfed infants at 14 weeks and 6 months of age compared to infants of mothers given placebo. Infants of mothers given vitamin D had a lower frequency of biochemical rickets compared to placebo (0 vs 17%), but no difference in the frequency of radiological rickets (3.6% vs 3.4%).
In a pilot study measuring the epigenomic effects of maternal vitamin D supplementation on the mother and infant, 10 women were given 3,800 IU or 400 IU of oral vitamin D3 once daily beginning at 24 to 28 weeks gestation and continuing through 4 to 6 weeks postpartum. Gestational age at birth was not reported, but presumed to be term. All infants were fully or partially breastfed. Those partially breastfed only received an average of about 10 mL formula daily during the study period. Methylation of cytosine-guanine dinucleotides in infant leukocyte genomic DNA were significantly different between the two groups. Since 2 out of 3 infants in the low-dose group received postpartum vitamin D supplementation and 5 out of 7 in the high-dose group did not, larger controlled studies are needed to determine the effects of vitamin D exposure through breastmilk on the infant epigenome.
One hundred fifty-two mothers in northern India, most of whom were vitamin D deficient, were randomized to receive 120,000 IU (3000 mcg) of vitamin D one time within 7 days postpartum followed by the same dose at 6, 10, and 14 weeks postpartum to coincide with scheduled infant immunization, or placebo. Infants of mothers in the placebo group received 400 IU (10 mcg) of daily vitamin D while those in the treatment group received placebo. At 14 weeks, infant growth parameters and serum biochemical indicators of bone mineral and liver homeostasis were similar between the two groups. At 9 months, dental growth and diarrheal or respiratory illness frequency were also not different.
One hundred fourteen vitamin D deficient mothers in northern India were randomized to receive vitamin D3 60,000 IU (1,500 mcg) or placebo as a single dose starting between 24 and 48 hours after delivery, and then repeated at 6, 10, and 14 weeks postpartum. Over 90% of participants were exclusively breastfeeding. At 6 months of age, 6 infants in the control group and no infants in the treatment group developed biochemical rickets, while 2 infants and 1 infant, respectively, developed radiological rickets. Infants of mothers in the treatment group reportedly had normal serum calcium and phosphorus concentrations at 6 months of age, although specific results were not given, and this outcome was not reported for the control group.
One hundred ninety mothers in Qatar were randomized to receive either 600 IU or 6000 IU vitamin D beginning within 4 weeks postpartum. Infants of the mothers in the low-dose group were given 400 IU daily while those in the high-dose group received daily placebo. At the scheduled 4- and 7-month postpartum study visits, infant growth parameters, serum calcium and parathyroid hormone levels, and parent reported infant health status, were not different between the two groups.
Two hundred twenty healthy, non-obese, breastfeeding mothers in Rajasthan, India were randomized to receive 120,000 IU or 12,000 IU of vitamin D3 once a month for 12 months beginning in the first postpartum month. Infants in both groups had normal serum calcium, phosphate, and alkaline phosphate levels at baseline and at 12 months. There was no significant differences in growth parameters, bone mineral content or density between the two groups at 12 months.
One thousand three hundred pregnant women in Dhaka, Bangladesh were randomized to receive an oral tablet of 4,200 IU, 16,800 IU, 28,000 IU of vitamin D3, or placebo once weekly beginning prenatally between 17- and 24-weeks gestational age. The placebo group and some in the 28,000 IU group continued to receive their assigned treatment for 26 weeks postpartum while the others stopped treatment after delivery. Baseline maternal vitamin D status was similar across all participants with 65% biochemically vitamin D deficient. Breastfeeding duration was similar between each of the groups. The median duration of exclusive breastfeeding was 12 to 14 weeks. Infant vitamin D supplementation was uncommon (<10%). One thousand one hundred sixty-four infants were available for analysis. There were no differences between the groups in infant growth at 1 year postpartum. There were also no differences in infant mortality, hospitalizations, respiratory tract infections, rickets, serum calcium status, or early childhood bone mineral density and grip strength. Infant hypercalcemia and hypercalciuria occurred rarely (0-1%) and did not differ between groups.
One hundred forty-eight exclusively breastfeeding postpartum patients were given either 400 or 6,400 IU daily of vitamin D3 beginning within 4 to 6 weeks of delivery. Average baseline infant serum 25-OH-vitamin D was <50 nmol/L (range undetectable to 113.8 nmol/L). Infants of mothers in the 400 IU daily group were given a 400 IU daily vitamin D supplement, while those in the 6,400 IU daily group were given placebo. There were no differences between the two groups in biochemical markers of calcium status, bone mineral content or density at 1, 4, or 7 months of age.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
