Table 1 Study characteristics of 21 randomized-controlled trials analyzing the effects of different doses of vitamin D supplementation for preterm infants.
Study (First author, year) | Country | Gestation (weeks) | Vitamin D dose (IU/day) | Starting point of supplementation | Duration or endpoint of supplementation | Timing of outcome assessment | Primary outcomes | Exclusion criteria | ||
|---|---|---|---|---|---|---|---|---|---|---|
High-dose (n) | Low-dose (n) | Short-term | Long-term | |||||||
Robinson [34] | United Kingdom | Preterm | 1000 (9) | 400 (9) | Postnatal 15 days | PMA 39 weeks | Postnatal 14 days, PMA 36 weeks, 39 weeks | 25(OH)D | - | Not described |
Evans [24] | Canada | Birth weight < 1500 g | 2000 (41) | 400 (40) | Postnatal 72 hours | 6 weeks | 2, 4, 6 weeks | Ca, P, ALP, uCa/Cr, 25(OH)D, radiologic score | - | Major congenital anomaly, congenital infection, or inherited metabolic disease. Infants who did not survive to 6 weeks of postnatal age or developed prolonged obstructive jaundice |
Pittard [33] | USA | Low birth weight preterm | 800 (9) | 400 (8) | Within postnatal 12 hours | 16 weeks | Biweekly, 16 weeks | 25(OH)D | 25(OH)D | Minima respiratory disease. Infants who did not reach solely enteral feeding-420J/kg per day or more by 2 weeks of age |
Koo [30] | USA | Birth weight ≤ 1500 g | 800 (21) | 400 (21), 200 (20) | Clinically stable, recovering from pre-existing respiratory illness, not receiving chronic diuretic therapy, tolerating enteral nutrition 75 kcal/kg/day, weight gain at full enteral nutrition | NICU discharge or 2-kg body weight | Termination of formula feeding | Vitamin D and biochemical metabolites | - | Major congenital malformation, necrotizing enterocolitis, major abdominal surgery, chronic diuretic therapy or failure to tolerate feeding for 7 consecutive days after commencement of the study. |
Backström, 1999a | Finland | <33 | 960 (18) | 200/kg~400 (21) | Full enteral nutrition | 3 months old | 6 and 12 weeks, Corrected age of 3 and 6 months | Vitamin D metabolites | Vitamin D metabolites, bone densitometry | Major congenital malformation, failure to supplement vitamin D according to protocol |
Backström, 1999b | Finland | <37 | 1000 (36) | 500 (34) | Full enteral nutrition | 3 months old | 3 months old, 9–11 years | - | Vitamin D metabolites, bone densitometry | Major congenital malformation, failure to supplement vitamin D according to protocol |
Alizade [17] | Iran | <38 | 1000 (36) | 400 (32) | Full enteral nutrition | body weight 3000–3500 g | Postnatal 9 weeks | Ca, P, ALP, wrist X-ray | - | Maternal specific medication (anticonvulsants, diuretics, corticosteroids), maternal diabetes mellitus, SGA baby, chronic use of furosemide, NPO for more than 2 weeks, failure of taking vitamin D supplements according to the protocol |
Kislal [29] | Turkey | <33 | 800/kg (11) | 400/kg (15), 200/kg (11) | Postnatal 15 days | Postnatal 30 days | 15 days after supplementation | Ca, P, ALP, osteocalcin and urinary deoxypyridinoline | - | Congenital malformation and failure to supplement vitamin D according to protocol. |
Natarajan [32] | India | 28–34 | 800 (42) | 400 (45) | Enteral nutrition ≥100 mL/kg/day by postnatal 2 weeks | Corrected age of 3 months | PMA 40 weeks, Corrected age of 3 months | VDD | VDD | Major malformations, those who received parenteral nutrition for ≥2weeks, or born to mothers receiving phenytoin therapy or with HIV infection |
Fort, 2016a | USA | 23–27 | 800 (30) | 200 (34) | During postnatal 7 days and within 72 hours after initiating enteral nutrition | Postnatal 28 days | Postnatal 28 days | 25(OH)D, total number of days alive and off respiratory support | - | Major congenital or chromosomal anomalies, moribund infant with low likelihood of survival as outborn infants, necrotizing enterocolitis Bell’s stage II or greater, spontaneous intestinal perforation, or if feeds were stopped for more than 24 h by the clinical team. |
Mathur [31] | India | <37 and Birth weight < 1500 g | 1000 (25) | 400 (25) | Enteral nutrition ≥100 mL/kg/day | . | 6 weeks after supplementation | Ca, P, ALP, 25(OH)D, PTH | - | Major congenital malformations or those not tolerating at least 100 ml/kg/day enteral feeds by day 10 of life. |
Hanson [27] | USA | <32 | 800 (16) | 400 (16) | As per unit protocol | As per unit protocol | 4 weeks, 8 weeks | Vitamin D metabolites | - | Congenital anomaly, gastrointestinal, liver, or kidney disease, inborn errors of metabolism, parathyroid disease, disorders of calcium metabolism, and infants receiving seizure medication or steroids |
Tergestina [36] | India | 27–34 | 1000 (60) | 400 (60) | Enteral nutrition ≥100 mL/kg | PMA 40 weeks | PMA 40 weeks | VDD | - | Major congenital anomaly, maternal condition or medications likely to influence vitamin D or calcium metabolism and neonates not attaining 100 ml/kg feeds by 14 days of life |
Anderson-Berry [19] | USA | 24–32 | 800 (16) | 400 (16) | Initiation of enteral nutrition | NICU discharge | 4 weeks and 8 weeks after supplementation | 25(OH)D, PTH, Ca, DEXA | - | Congenital anomaly, gastro-intestinal, liver, or kidney disease, inborn errors of metabolism, parathyroid disease, disorders of calcium metabolism, and infants receiving seizure medication or steroid |
Bozkurt [23] | Turkey | 24–32 | 1000 (40), 800 (41) | 400 (40) | 75% of total nutrition by enteral nutrition in potnatal 2 weeks | PMA 36 weeks | PMA 36 weeks | VDD, 25(OH)D | - | Perinatal asphyxia, major congenital or chromosomal anomalies, twin-twin transfusion syndrome, requirement of dopamine >15ug/kg/min or more than inotrope, those with no expectation of survival in first 2 weeks and those that total parenteral nutrition was not ceased by the first 2 weeks |
Salas, 2018a | USA | 23–27 | 800 (20) | 200 (22) | During postnatal 7 days and within 72 hours after initiating enteral nutrition | Postnatal 28 days | 22–26 months | - | BSID-III cognitive composite score | Major congenital or chromosomal anomalies, moribund infant with low likelihood of survival as outborn infants, necrotizing enterocolitis Bell’s stage II or greater, spontaneous intestinal perforation, or if feeds were stopped for more than 24 h by the clinical team |
Abdel-Hady [16] | Egypt | 28–36 | 800 (25) | 400 (25) | Postnatal >72 hours | NICU discharge | 1 week after supplementation, PMA 40 weeks | TNF-a, Interleukin-6 | - | Major congenital anomalies, chromosomal anomalies, known inborn errors of metabolism, and immunodeficiency disorders |
Aly [18] | Egypt | 28–33 | 800 (20) | 400 (20) | Enteral nutrition ≥100 mL/kg/day | 4 weeks | 1 week and 4 weeks after supplementation | T regulatory cells | - | Congenital and chromosomal anomalies, necrotizing enterocolitis, infants who were not fed for >24 hours |
Kishore, 2019b | India | 28–36 | 800 (46) | 400 (46) | Unknown | Unknown | PMA 40 weeks | VDD, vitamin D level | - | Not described |
Golan-Tripto [26] | Israel | 32–36 | 800 (25) | 400 (25) | Within postnatal 72 hours | 12 months | 6 months, 12 months | - | 25(OH)D, respiratory morbidity | Not described |
Aristizabal, 2023a | USA | ≤28 | 800 (23) | 200 (19) | During postnatal 7 days and within 72 hours after initiating enteral nutrition | Postnatal 28 days | Postnatal 28 days, PMA 36 wks | 25(OH)D, Ca, Predictive risk of BPD, postnatal growth faltering, stunting | - | Major congenital or chromosomal anomalies, moribund infant with low likelihood of survival as outborn infants, necrotizing enterocolitis Bell’s stage II or greater, spontaneous intestinal perforation, or if feeds were stopped for more than 24 h by the clinical team. |
