Vitamin D Deficiency, Prevalence and Treatment in Neonatal Period.

OBJECTIVE: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey. METHODS: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses. RESULTS: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05). CONCLUSION: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy.

Fetal and Maternal Genetic Variants Influencing Neonatal Vitamin D Status.

Objective: Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. Methods: We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Results: Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. Conclusions: We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.

Maternal vitamin D3 supplementation at 50 µg/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation.

BACKGROUND: Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown. OBJECTIVES: We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age. DESIGN: Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 µg vitamin D3/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum. RESULTS: At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-µg/d [75 (67, 83)] than in the 25-µg/d [52 (45, 58)] or 10-µg/d [45 (38, 52)] vitamin D groups (P < 0.05). Fewer infants born to mothers in the 50-µg/d group had a 25(OH)D concentration <30 nmol/L (indicative of deficiency) than infants in the 25- and 10-µg/d groups, respectively (2% compared with 16% and 43%; P < 0.05). Fewer than 15% of infants in the 10- or 25-µg/d groups achieved a 25(OH)D concentration >75 nmol/L compared with 44% in the 50-µg/d group (P < 0.05). Almost all infants (∼98%, n = 44) born to mothers in the 50-µg/d group achieved a 25(OH)D concentration >30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-µg/d [88 (84, 91)] than in the 25-µg/d [78 (74, 81)] or 10-µg/d [69 (66, 73)] groups (P < 0.05). CONCLUSIONS: Maternal supplementation beginning in gestation with 50 µg vitamin D3/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (<30 nmol/L) to at least 8 wk, whereas 10 or 25 µg vitamin D/d protects only 57% and 84% of infants, respectively.

Season of birth, neonatal vitamin D status, and cardiovascular disease risk at 35 y of age: a cohort study from Sweden.

BACKGROUND: Lower vitamin D status during gestation may be associated with cardiovascular disease risk later in life. No studies have assessed this hypothesis with a follow-up time reaching beyond childhood. OBJECTIVE: The objective was to assess the link between season of birth, neonatal 25-hydroxyvitamin D3 [25(OH)D3] status, and adult cardiovascular disease risk. DESIGN: Markers of cardiovascular and metabolic disease risk were measured in 284 subjects aged 35 y, born either at the end of the winter or at the end of the summer of 1975. In 275 of these 284 subjects, concentrations of neonatal 25(OH)D3 were measured in dried blood samples by using a highly sensitive liquid chromatography-tandem mass spectroscopy method. RESULTS: Subjects born after the winter had lower neonatal 25(OH)D3 concentrations than did those born after the summer (31.5 compared with 48.5 nmol/L; P < 0.001). In regression analyses adjusted for sex, season of birth, postnatal age at neonatal sample collection, preterm birth, maternal age, education, smoking, fish consumption per week, exercise per week, and current 25-hydroxyvitamin D, higher neonatal 25(OH)D3 (per 50 nmol/L) was associated with 25.8% (95% CI: 1.0%, 58.4%) higher fasting insulin in adult life, 29.6% (5.1%, 58.4%) higher triglycerides, and 4.64 (95% CI: 1.93, 7.36) mmol/L higher serum cholesterol in women. Neonatal 25(OH)D3 (per 1 nmol/L) was directly associated with risk of adult overweight (OR: 1.03; 95% CI: 1.01, 1.05) and with adult obesity in women (OR: 1.09; 95% CI: 1.02, 1.17). Neonatal 25(OH)D3 was not associated with adult aortic pulse wave velocity, blood pressure, fasting glucose, HDL, LDL, or C-reactive protein. Season of birth was not associated with any of the adult outcomes. CONCLUSIONS: Higher neonatal 25(OH)D3 was associated with higher fasting insulin, triglyceride, and cholesterol (in women) concentrations and with a higher risk of overweight at 35 y of age but not with other adult cardiovascular disease risk factors.

The role of vitamin D in pregnancy and lactation: insights from animal models and clinical studies.

Maternal adaptations during pregnancy and lactation appear to provide calcium to fetus and neonate without relying on vitamin D or calcitriol. Consequently, the blood calcium, calciotropic hormones, and skeleton appear normal at birth in the offspring of mothers who are severely vitamin D deficient or who lack calcitriol or its receptor. It remains unclear whether skeletal or extraskeletal problems will develop postnatally from exposure to vitamin D deficiency in utero. During the neonatal period, calcitriol-stimulated intestinal calcium absorption becomes the dominant mechanism of calcium delivery. The vitamin D-deficient neonate is at risk to develop hypocalcemia, rickets, and possibly extraskeletal disorders (e.g., type 1 diabetes). Breastfed babies are at higher risk of vitamin D deficiency because normally little vitamin D or 25-hydroxyvitamin D passes into breast milk. Dosing recommendations during pregnancy and lactation should ensure that the baby is born vitamin D sufficient and maintained that way during infancy and beyond.

Congenital vitamin D deficiency: a rare etiology of an acute life threatening event in early infancy.

Infants born to mothers with deficiency of vitamin D and/or calcium due to cultural modifications in their diets, life style and clothing habits, are at risk of developing early and fatal sequelae of hypocalcemic vitamin D deficiency. We present a 44-day-old infant with hypocalcemia secondary to congenital vitamin D deficiency, who presented as a recurrent Acute Life Threatening Event (ALTE) resulting in an unexpectedly prolonged intensive care course. This report suggests that evaluation of vitamin D status should be included as part of the workup of ALTE and we describe evidence-based preventive measures for both mothers and infants who are at risk for vitamin D deficiency.

Vitamin D and the adaptive immune system with special emphasis to allergic reactions and allograft rejection.

Tolerance induction is a fascinating option to prevent allergic diseases or allograft rejection. Calcitriol is the hormonal form of vitamin D and is produced by two hydroxylation steps: a hepatic 25-hydroxylation of vitamin D and a subsequent renal 1alpha-hydroxylation. Calcitriol has important immunomodulatory properties. Calcitriol can prevent those inflammatory processes which are responsible for allograft rejection, whereas its effects on immunological responses related to allergic reactions are more complex and not fully elucidated. This article summarizes present knowledge on vitamin D and the adaptive immune system. Experimental and clinical studies support the assumption that calcitriol can decrease the risk of allograft rejection. Prospective randomized clinical trials are however needed to clarify whether administration of calcitriol, some of its analogues, or simple vitamin D supplementation is able to prevent rejection in solid organ transplanted patients. With respect to allergic reactions, human data are inconsistent at present. Some argue that vitamin D deficiency may cause allergic reactions whereas others argue that vitamin D excess leads to an increased allergy risk. In this context, current strategy of vitamin D supplementation in infants and the possibility of a bimodal effect on allergic reactions of both, vitamin D deficiency and excess are discussed.

Incidental finding of vitamin-D deficient rickets in an otherwise healthy infant--a reappraisal of current vitamin-D supplementation guidelines.

In an effort to prevent rickets and vitamin-D deficiency in healthy infants, the American Academy of Pediatrics recommends a supplement of 200 IU per day of vitamin D to all breastfed and nonbreastfed infants unless they consume at least 500 ml per day of vitamin-D-fortified formula or milk. Case reports of infantile vitamin-D-deficient rickets secondary to maternal vitamin-D deficiency have been reported but focused on mothers who had predictable risk factors for such a deficiency. We report on an infant with vitamin-D-deficient rickets who did not have nutritional risk factors and whose mother did not have nutritional or medical risk factors for such a deficiency. We conclude that the current vitamin-D supplementation guidelines be extended to all infants, regardless of feeding volume or source, or at least to all infants born to dark-skinned mothers.

[Neonatal cardiac failure secondary to hypocalcemia caused by maternal vitamin D deficiency]. / Insuffisance cardiaque néonatale secondaire à une hypocalcémie par carence maternelle en vitamine D.

BACKGROUND: Heart failure is a rare manifestation of neonatal hypocalcemia. This paper describes such a case resulting from maternal vitamin D deficiency. CASE REPORT: A full-term boy, born in December after a normal pregnancy, was admitted at the age of 6 weeks because of dyspnea that appeared during suckling. Examination showed heart failure. Electrocardiogram showed that the corrected QT-interval was lengthened (0.54 s, normal < 0.45 s). Echocardiogram showed dilated, hypokinetic myocardiopathy. His serum calcium concentration was low (1.40 mmol/l) and phosphate was high (2.8 mmol/l); his alkaline phosphatase was 513 Ul/l. His blood PTH concentration was high (120 pg/ml) and his 25 (OH) D was low (5 ng/ml). The patient was given calcium (1 g/m2/day) and 1.25 (OH)2 D (2 micrograms/day orally). His serum calcium returned to normal within 4 days, and his cardiac abnormality was resolved within 3 months. His mother's blood 25 (OH) D concentration was very low (3 ng/ml), 6 weeks after birth. CONCLUSION: Neonatal hypocalcemia appears to have been compounded in this case by a maternal vitamin D deficiency. Hence, all pregnant women at risk of deficiency should be given vitamin D.

Congenital hyperparathyroidism and vitamin D deficiency secondary to maternal hypoparathyroidism.

A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 mulEq/ml (Normal: less than 50 mulEq/ml). A very low plasma 25-OH-D concentration (less than 4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remained high 3 weeks before (210 mulEq/ml) were found to be normal one week after this vitamin D load (37 mulEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.