- Extreme preterm infants need a total of 1,000 IU of vitamin D daily – RCT April 2016
- Preemies have increased need for vitamin D and Calcium (Rickets)– May 2013
- Stunting OR “low birth weight” OR LBW OR preemie OR preemies OR preterm
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- Preterm babies have low vitamin D, but recover with 800 IU
- 400 or 800 IU - Letter to Editor March 2015
- 800 IU better than 400 IU for preemies – Sept 2015
- 800 IU for premature – RCT Aug 2015
- 99% of preterm infants have insufficient vitamin D – Nov 2015
- Preterm: 500 to 1000 IU daily - July 2015
- Premature infants getting 800-1000 IU of vitamin D were much healthier – March 2017
- (Preterm babies have low vitamin D, but recover in 6 weeks with 800 IU supplementation – Jan 2019))
Vitamin D Supplementation in Premature Infants
Am Fam Physician. 2015 Mar 15;91(6):352-353. Letters to the Editor
Original article: Common Questions About Outpatient Care of Premature Infants
Issue date: August 15, 2014
Available at: http://www.aafp.org/afp/2014/0815/p244.html
to the editor: Thank you for this very informative article. It did not specifically discuss the importance of vitamin D supplementation. The American Academy of Pediatrics (AAP) recommends that all infants consume a minimum of 400 IU per day of vitamin D beginning shortly after birth, particularly breastfed or partially breastfed infants.1 Human breast milk is low in vitamin D, containing less than 25 IU per L.2 Even with adequate oral intake, a premature infant would still receive far less than the recommended daily amount of vitamin D.
The article does mention that breast milk can be supplemented with a multinutrient fortifier, but that benefit postdischarge is not clear. Although common commercial preparations, (e.g., Similac Human Milk Fortifier, Enfamil Human Milk Fortifier) contain vitamin D, breastfed infants discharged without fortified milk will not benefit from this type of vitamin D supplementation. Sequelae of vitamin D deficiency among breastfed infants, such as rickets and hypocalcemia, are not common; however, supplementation is essential to prevent potential illness in this already vulnerable patient population.
SONYA SHIPLEY, MD, Flowood, Miss., sshipley at umc.edu, Author disclosure: No relevant financial affiliations.
1. Wagner CL, et al. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents [published correction appears in Pediatrics. 2009;123(1):197]. Pediatrics. 2008;122(5):1142–1152.
2. Centers for Disease Control and Prevention. Breastfeeding. Vitamin D supplementation. http://www.cdc.gov/breastfeeding/recommendations/vitamin_D.htm Accessed by VitaminDWiki March 2016
in reply: We thank Dr. Shipley for the astute observation regarding vitamin D deficiency, osteopenia, and metabolic bone disease in graduates of neonatal intensive care units. Prematurity and the metabolic demands of sick newborns can put them at high risk of poor bone growth and health.1
Our article focused on guidelines for the outpatient follow-up of newborns discharged from neonatal intensive care units that deviate from routine newborn care and guidelines. As Dr. Shipley stated, the AAP recommends that all infants, shortly after birth, begin receiving 400 IU per day of vitamin D.2,3 This can be achieved with consumption of greater than 1 L per day of formula (which usually occurs by approximately one month of age) or vitamin D supplementation for those infants consuming breast milk or less than 1 L per day of formula (i.e., mixed feeding). This recommendation does not differ for graduates of neonatal intensive care units.
Regarding fortification of human breast milk, our discussion was to address concerns of extrauterine growth failure, not vitamin deficiencies. If breast milk is to be fortified as an outpatient, it is typically done with formula, as human milk fortifiers are not readily available other than for inpatient use. Because the amount of vitamin D provided would likely be less than 400 IU per day, supplementation is recommended. 2–4
Recently published studies suggest increasing the recommended vitamin D dosage to 800 IU per day. In a randomized double-blind trial (n = 96), the prevalence of vitamin D deficiency was significantly lower in preterm infants receiving 800 IU per day than in those receiving 400 IU per day at 40 weeks (38% vs. 67%) and at three months corrected age (12% vs. 35%). However, there was no improvement in bone mineralization between the two groups. One infant receiving 800 IU per day had vitamin D excess.5 In 2008, the AAP released new recommendations increasing the dosage of vitamin D from 200 to 400 IU per day based on growing evidence of vitamin D deficiencies in infants receiving lower dosages. Until larger trials are completed, 400 IU per day of vitamin D supplementation is the best evidence-based recommendation.
Interestingly, a longitudinal survey from 2010 revealed that very few infants were receiving adequate vitamin D supplementation. Only 5% to 13% of breastfed infants, 9% to 14% of mixed-fed infants, and 20% to 37% of formula-fed infants met the AAP recommendation. 6 This evidence underscores the importance of vitamin D supplementation. Clinicians are encouraged to inquire about ingestion of vitamin D in this at-risk population.
ROBERT L. GAUER, MD, Fort Bragg, N.C., robert.l.gauer2.civ at mail.mil
1. Vachharajani AJ, et al. Metabolic bone disease of prematurity. Neoreviews. 2009;10(8):e402–e411....
Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants.
J Pediatr Endocrinol Metab. 2015 Sep;28(9-10):1107-14. doi: 10.1515/jpem-2015-0089.
Hanson C, Lyden E, Nelson A, Thoene M, Wagner J, Wu A, Rennard S, Anderson-Berry A.
The objective of this study was to evaluate the relationship between 25(OH)D, Vitamin D Binding Protein (DBP), and free vitamin D in premature infants.
Thirty-two infants <32 weeks' gestation were randomized to two different levels of vitamin D3 supplementation (400 vs. 800 IU/day). 25(OH)D levels were measured by LC-MS/MS; DBP was measured by validated ELISA. Free vitamin D was calculated using molar ratios of 25(OH)D and DBP. The Wilcoxon signed rank test was used to compare DBP, free D and 25(OH)D levels; Spearman's correlation coefficients were used to assess correlations.
The mean gestational age at birth was 30.5 weeks; mean birth weight was 1405 g. Mean 25(OH)D levels at birth were 17.3 ng/mL; DBP levels were 297 mg/L, and estimated free vitamin D levels were 18.9. There was a statistically significant change in 25(OH)D levels after 8 weeks (24.6 vs. 39.1 ng/mL in the 400 vs. 800 group, respectively, p=0.02). DBP levels from birth to 8 weeks showed a statistically significant decrease (267 vs. 208, p=0.04). Estimated free 25(OH)D concentrations increased over the study period, from 18.9 at birth to 64.7 at 8 weeks of age (p=0.0001). Free vitamin D levels at birth were associated with global DEXA bone mineral content at discharge from the NICU (r=0.58, p=0.05).
Supplementation with vitamin D3 increased the free portion of the vitamin D metabolite, providing increased bioavailable substrate. Improved free vitamin D levels may improve measurable outcomes such as bone mineral content and deserve further evaluation.
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Vitamin D metabolism in the premature newborn: A randomized trial.
Clin Nutr. 2015 Aug 13. pii: S0261-5614(15)00219-8. doi: 10.1016/j.clnu.2015.07.023. [Epub ahead of print]
Hanson C1, Jones G2, Lyden E3, Kaufmann M4, Armas L5, Anderson-Berry A6.
1University of Nebraska Medical Center, School of Allied Health Professionals, Medical Nutrition Education, 984045 Nebraska Medical Center, Omaha, NE 68198-4045, USA. ckhanson at unmc.edu.
2Queen's University, Department of Biomedical and Molecular Sciences Kingston, Ontario K7L 3N6, Canada. gj1 at queensu.ca.
3University of Nebraska Medical Center, College of Public Health, 984375 Nebraska Medical Center, Omaha, NE 68198-4375, USA. elyden at unmc.edu.
4Queen's University, Department of Biomedical and Molecular Sciences Kingston, Ontario K7L 3N6, Canada. Martin.kaufmann at queensu.ca.
5Creighton Osteoporosis Research Center, Creighton University 601 N 30th Street, Omaha, NE 68131, USA. larmas at creighton.edu.
6University of Nebraska Medical Center, Pediatrics, 981205 Nebraska Medical Center, Omaha, NE 68198-1205, USA. alanders at unmc.edu.
BACKGROUND & AIMS:
Vitamin D status during infancy has been associated with important pediatric health outcomes; however concentrations of many vitamin D metabolites in premature infants are not yet described. The objective of this study was to evaluate concentrations of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 in premature infants.
32 infants <32 weeks gestation were randomized to receive 400 or 800IU/day of vitamin D3 orally. Vitamin D metabolites from serum obtained monthly were analyzed in triplicate using a novel, very sensitive Liquid Chromatography-Tandem Mass Spectrometry-based method. Statistical analysis was conducted using the Fisher's exact test, Wilcoxon Rank Sum test, and Spearman correlation coefficients. Measurements over time were fit with linear mixed effect models. A p-value of <0.05 was considered statistically significant.
Mean serum 25(OH)D3 concentrations in cord blood were 17.3 ng/mL; mean 3-epi-25(OH)D3 were 1.3 ng/mL, mean 24,25(OH)2D3 were 1.4 ng/mL. Both 25(OH)D3 and 3-epi-25(OH)D3 increased significantly over time, and the percent of total 25(OH)D3 concentration that was 3-epi-25(OH)D3 also increased significantly (7.2% vs. 29.7%, p < 0.0001 for cord blood vs. 8 weeks). Serum 25(OH)D3:24,25(OH)2D3 ratios at weeks 4 and 8 were higher than ratios reported in older children and adults.
Vitamin D metabolism in infants appears to have distinct differences from adults. Vitamin D supplementation was effective in raising 25(OH)D3 concentrations; however significant increases in 3-epi-25(OH)D3 also occurred. Increased 25(OH)D3: 24,25(OH)2D3 ratios in premature infants may be due to immature expression of CYP24A1. Further work is necessary to determine if there are developmental advantages to this unique vitamin D metabolism.
Severe vitamin D deficiency in preterm infants: maternal and neonatal clinical features.
Korean J Pediatr. 2015 Nov;58(11):427-33. doi: 10.3345/kjp.2015.58.11.427. Epub 2015 Nov 22.
Park SH1, Lee GM1, Moon JE1, Kim HM1.
1Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea.
We investigated the vitamin D status of preterm infants to determine the incidence of vitamin D deficiency.
A total of 278 preterm infants delivered at Kyungpook National University Hospital between January 2013 and May 2015 were enrolled. The serum concentrations of calcium, phosphorous, alkaline phosphatase, and 25-hydroxyvitamin D (25-OHD) were measured at birth. We collected maternal and neonatal data such as maternal gestational diabetes, premature rupture of membranes, maternal preeclampsia, birth date, gestational age, and birth weight.
Mean gestational age was 33(+5)±2(+2) weeks of gestation and mean 25-OHD concentrations were 10.7±6.4 ng/mL. The incidence of vitamin D deficiency was 91.7%, and 51.1% of preterm infants were classified as having severe vitamin D deficiency (25-OHD<10 ng/mL). The serum 25-OHD concentrations did not correlate with gestational age. There were no significant differences in serum 25-OHD concentrations or incidence of severe vitamin D deficiency among early, moderate, and late preterm infants.
The risk of severe vitamin D deficiency in twin preterm infants was significantly higher than that in singletons (odds ratio, 1.993; 95% confidence interval [CI], 1.137-3.494, P=0.016). In the fall, the incidence of severe vitamin D deficiency decreased 0.46 times compared to that in winter (95% CI, 0.227-0.901; P=0.024).
Most of preterm infants (98.9%) had vitamin D insufficiency and half of them were severely vitamin D deficient.
Younger gestational age did not increase the risk of vitamin D deficiency, but gestational number was associated with severe vitamin D deficiency.
MONITORED SUPPLEMENTATION OF VITAMIN D IN PRETERM NEONATES- -A PRIMARY REPORT
Dev Period Med. 2015 Jul-Sep;19(3 Pt 1):313-8.
Kołodziejczyk A, Borszewska-Kornacka MK.
To evaluate vitamin D (vitD) monitored therapy effectiveness and safety in preterm neonates.
PATIENTS AND METHODS:
Our observational study was carried out in 80 neonates born before 33 weeks' gestational age (GA) hospitalized in the Clinical Department of Neonatology and Neonatal and Intensive Care Department Medical University of Warsaw from July 2013 to July 2014. Daily vitamin D oral supplementation was provided from 1 to 3 weeks of age at the dose of 500-1000 IU/24 h. The dosage was modified according of 25-hydroxyvitamin-D blood serum concentration. Both blood serum 25(OH) D concentration and calcium-phosphate metabolism were assessed at 4 weeks of age, at 34-37 weeks' post-conceptual age (on discharge) and at 39-41 weeks PCA.
Mean serum 25(OH)D level was 40 ng/ml at 4 weeks of age, 61 ng/ml at 34-37 weeks PCA, and 53 ng/ml at 39-41 weeks PCA. Higher concentrations were observed in ELBW neonates. Deficiency was noted most often at the first measurement. 52.5% of neonates received 500IU vitD before discharge, 19% had stopped supplementation due to overdosing. High dose vitD supplementation was provided in 34% cases. Disturbance of calcium-phosphate metabolism due to vitD deficiency was observed in one patient. Hypervitaminosis was associated with higher calcium-creatinine ratio. Very high individual heterogeneity of 25(OH)D concentration changes were observed (from 70 ng/ml/4 weeks decrease to 92 ng/ml/4 weeks increase).
Supplementation of vitamin D in preterm neonates needs monitoring.
A safe time interval to monitor vitamin D supplementation seems to be 1 month.
The schedule of the therapy requires further studies.