HHS Public Access Author manuscript Author Manuscript
J Pediatr. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: J Pediatr. 2016 July ; 174: 132–138.e1. doi:10.1016/j.jpeds.2016.03.028.
A Comparison of Three Vitamin D Dosing Regimens in Extremely Preterm Infants: a randomized controlled trial Prem Fort, MD1, Ariel A. Salas, MD, MSPH1, Teodora Nicola, PhD1, Carolyne M. Craig, BS1, Waldemar A. Carlo, MD1, and Namasivayam Ambalavanan, MD1 1Department
of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
Author Manuscript
Abstract Objective—To determine the optimal dose of vitamin D supplementation to achieve biochemical vitamin D sufficiency in extremely low gestational age newborns in a masked randomized controlled trial. Study design—100 infants 23 0/7 to 27 6/7 weeks gestation were randomized to vitamin D intakes of placebo (n=36), 200 IU (n=34), and 800 IU/day (n=30) (approximating 200, 400, or 1000 IU/day, respectively, when vitamin D routinely included in parenteral or enteral nutrition is included). The primary outcomes were serum 25 (OH) vitamin D concentrations on postnatal day 28 and the number of days alive and off respiratory support in the first 28 days.
Author Manuscript
Results—At birth, 67% of infants had 25(OH) vitamin D < 20 ng/mL suggesting biochemical vitamin D deficiency. Vitamin D concentrations on day 28 were (Median [25th–75th centiles], ng/ mL): Placebo: 22 [13–47], 200 IU: 39 [26–57], 800 IU: 84.5 [52–99], p < 0.001. There were no differences in days alive and off respiratory support (Median (25th–75th centiles), days: Placebo: 1 (0–11), 200 IU: 0 (0–8), 800 IU: 0.5 (0–22), p=0.63), or other respiratory outcomes among groups. Conclusion—At birth, most extremely preterm infants have biochemical vitamin D deficiency. This biochemical deficiency is reduced on day 28 by supplementation with 200 IU/day and prevented by 800 IU/day. Larger trials are required to determine if resolution of biochemical vitamin D deficiency improves clinical outcomes. ClinicalTrials.gov: NCT01600430 Trial registration—ClinicalTrials.gov: NCT01600430
Author Manuscript
Vitamin D is a fat soluble vitamin involved in multiple physiological processes. Developmental processes regulated by vitamin D include lung development– and maturation of the immune system.– As vitamin D is mostly transferred to the fetus during the third trimester,, preterm infants are born with lower vitamin D stores. Extremely low gestational
Corresponding author: Namasivayam Ambalavanan MD, 176F Suite 9380, Women and Infants Center, 619 South 19th Street, University of Alabama at Birmingham, Birmingham, AL 35249, Tel (205) 934 4680, Fax (205) 934 3100, [email protected]. The author declares no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fort et al.
Page 2
Author Manuscript
age newborns (ELGAN) are at high risk of mortality and multiple morbidities. It is not known if vitamin D insufficiency contributes to mortality or morbidity in these infants. The American Academy of Pediatrics (AAP) has recommended a dose of 200–400 IU of vitamin D per day for preterm infants, and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) recommends 800–1000 IU. However, evidence is lacking for the magnitude of improvement in serum vitamin D concentrations or clinical outcomes in ELGAN with either target range of vitamin D supplementation. In addition, as vitamin D is critical for many essential physiological processes, it is possible that higher than normal (supra-physiological) but non-toxic concentrations of vitamin D may benefit this vulnerable population similar to vitamin A supplementation.
Author Manuscript
This was a pilot trial to identify the optimal dose of vitamin D before embarking on a large multicenter trial using the optimal dose for evaluating clinical outcomes. Our objective was to determine the optimal dose of vitamin D supplementation in ELGAN using a masked randomized controlled trial in which infants were randomized to vitamin D intakes of placebo, 200 IU, and 800 IU/day.
Methods
Author Manuscript
This multiple-dose, randomized, double-blinded, placebo-controlled trial was approved by the Institutional Review Board at the University of Alabama at Birmingham. Entry criteria were inborn infants with gestational age between 23–27 completed weeks admitted to the neonatal intensive care unit at the University of Alabama Hospital. Exclusion criteria included major congenital or chromosomal anomalies, moribund infant with low likelihood of survival as outborn infants.
Author Manuscript
Parents or guardians were approached by research staff soon after birth for informed consent. After consent, infants were randomly allocated by the research pharmacy staff using computer-generated stratified randomization codes to one of three groups: (1) placebo (intake of approximately 200 IU/day in parenteral nutrition or feeds), (2) 200 IU supplement (daily intake of approximately 400 IU due to 200 IU supplement + 200 IU in parenteral nutrition or feeds), or (3) 800 IU supplement (daily intake of approximately 1000 IU due to 800 IU supplement +200 IU in parenteral nutrition or feeds). The 200 IU in enteral or parenteral nutrition is an estimate, based on the daily intake of feeds and TPN by infants in our NICU over the first month. As fortified human milk has approximately the same amount of vitamin D as preterm formula, and fortification is started early in our unit, no adjustments were made for daily variations in intake or for unfortified human milk. Infants received 0.25 mL of study drug (either vitamin D (Enfamil D-Vi-Sol ™) or normal saline (placebo)) every 6 hours through the orogastric tube just before feeds. The medication was dispensed by a research pharmacist in an amber syringe to mask the caregivers. Infants in the placebo group received only saline, and infants in the 200 IU/day group received one dose of vitamin D and three doses of saline and infants in the 800 IU/day group received four doses of vitamin D and none of saline. Each infant was randomized during the first
J Pediatr. Author manuscript; available in PMC 2017 July 01.
Fort et al.
Page 3
Author Manuscript
seven days after birth and within 72 hours after initiating enteral feeds. Infants were monitored before every feed for feeding intolerance (abdominal distension or increased gastric residuals). Serum electrolytes, blood gases, and ionized calcium were measured every day while on parenteral nutrition and twice weekly while on enteral feeds during the first month. The intervention was continued until postnatal day 28. Infants were discontinued from study drug administration if they developed necrotizing enterocolitis Bell’s stage II or greater, spontaneous intestinal perforation, or if feeds were stopped for more than 24 hrs by the clinical team. Clinical data were collected by a trained research coordinator.
Author Manuscript
For the estimation of serum 25(OH) vitamin D concentration, whole blood (0.2 mL to 0.25 mL) was collected at birth (cord blood) and at the time of routine sampling on day 14 (± 2 days), and day 28 of life (± 3 days) and centrifuged to collect serum. The samples were stored in −80°C for later analysis. Analysis of the serum 25(OH) vitamin D concentrations was with an enzyme-linked immunosorbent assay (ELISA; Eagle Biosciences, Inc, Nashua, NH) with a dynamic range of 4–120 ng/mL, 100% cross-reactivity between 25(OH)-vitamin D3 and D2, 21% FiO2 at 28 days
Respiratory support, n (%)
Pulmonary hemorrhage
1 (3)
80 (80)
13 (36)
21 (58)
1 (3)
1 (3)
0 (0)
1 (3)
21 (21–38)
35 (21–50)
17 (47)
1 (0–11) 6.8 ± 9.5
13 (36)
12 (36)
21 (58)
15 (42)
25 (69)
11 (31)
26 (72)
90 (90)
Received Surfactant < 72 hrs
31 (86)
Placebo (N = 36)
Respiratory distress syndrome
Respiratory Disease, n (%)
All Infants (N = 100)
Author Manuscript
Clinical Outcomes
8 (24)
18 (53)
2 (6)
2 (6)
2 (6)
4 (12)
23 (21–35)
29 (22–39)
19 (56)
0 (0–8) 5.5± 9.1
8 (24)
10 (43)
12 (35)
12 (35)
21 (62)
5 (15)
1 (3)
4 (12)
30 (88)
32 (94)
200 IU/day (N = 34)
8 (27)
19 (63)
3 (10)
1 (3)
0 (0)
1 (3)
21 (21–30)
30 (21–50)
11 (37)
0.5 (0–22) 7.0 ± 10.3
6 (20)
8 (31)
12 (40)
9 (30)
17 (57)
2 (7)
0 (0)
4 (13)
24 (80)
27 (90)
800 IU/day (N = 30)
Author Manuscript
Clinical outcomes of enrolled infants
0.48
0.70
0.47
0.78
0.14
0.22
0.62
0.55
0.63
0.63 0.78
0.29
0.84
0.12
0.61
0.55
0.18
0.65
0.09
0.25
0.71
p
Author Manuscript
Table 2 Fort et al. Page 15
Author Manuscript 7 (7) 4 (4) 62 (62)
IVH Grade IV Seizures > 72 hrs Head imaging normal > 28 days
11 (11) 20 (20) 5 (5) 7 (7) 3 (3) 6 (6) 1 (1)
Immature vessels zone III ROP in zone I and II Stage I or II; zone III ROP stage III or higher Plus disease Treatment with Avastin Other treatments
Author Manuscript
J Pediatr. Author manuscript; available in PMC 2017 July 01. 4 (4) 10 (10) 62 (62) 7 (7)
Methicillin-resistant Staphylococcus aureus Other organisms Lumbar puncture Meningitis, culture positive
91 (91) 50 (50) 14 (14)
First feed with human milk, n (%) At day 14 on human milk, n (%) At day 14 on human milk or formula, n (%)
Nutrition
3 (3)
Escherichia coli
29 (29)
Late onset sepsis (> 72 hrs)
12 (12)
29 (29)
Antibiotics > 5 days starting < 72hrs
Coagulase negative staphylococci
6 (6)
Early onset sepsis (≤ 72 hrs)
Infection, n (%)
26 (26)
Immature vessels zone I and II
ROP diagnosed
43 (43)
12 (12)
IVH Grade IIII
Retinopathy of prematurity (L or R), n (%)
21 (21)
IVH Grade II
7 (19)
21 (58)
34 (94)
3 (8)
24 (67)
5 (14)
1 (3)
1 (3)
7 (19)
13 (36)
11 (31)
1 (3)
1 (3)
2 (6)
2 (6)
3 (8)
3 (8)
10 (28
4 (11)
9 (25)
18 (50)
24 (67)
0 (0)
1 (3)
3 (8)
7 (19)
Placebo (N = 36)
Author Manuscript All Infants (N = 100)
5 (15)
12 (35)
30 (88)
1 (3)
20 (59)
2 (6)
2 (6)
2 (6)
4 (12)
11 (32)
4 (12)
4 (12)
0 (0)
2 (6)
0 (0)
2 (6)
0 (0)
6 (18)
6 (18)
10 (29)
10 (29)
18 (53)
3 (9)
4 (12)
6 (18)
10 (29)
200 IU/day (N = 34)
2 (7)
17 (57)
27 (90)
3 (10)
18 (60)
3 (10)
1 (3)
0 (0)
1 (3)
5 (17)
7 (23)
1 (3)
0 (0)
2 (7)
1 (3)
2 (7)
2 (7)
4 (13)
1 (3)
7 (23)
15 (50)
20 (67)
1 (3)
2 (7)
3 (10)
4 (13)
800 IU/day (N = 30)
Author Manuscript
Clinical Outcomes
0.33
0.11
0.65
0.50
0.77
0.54
0.78
0.39
0.13
0.19
0.16
0.22
0.41
0.98
0.39
0.92
0.25
0.32
0.19
0.85
0.14
0.41
0.17
0.34
0.45
0.28
p
Fort et al. Page 16
Author Manuscript 1 (3)
9 (9)
Death ≤ 36 wks, n (%)
13 (36)
32 (32)
33 (92)
10 (5–13)
14 (11–18)
Still in hospital at 120 days
10 (6–14)
13 (10–18)
82 (82)
Centiles)
Centiles)
14 (11–18)
131 ± 34
113 ± 48
2 (6)
17 (47)
In hospital at 36 wks
Hospitalization, n (%)
Days on TPN, median
(25th–75th
Days to 120 ml/kg/day, median
(25th–75th
14 (10–19)
131 ± 35
At day 28, total feeding volumes, mean±SD Centiles)
113± 50
At day 14, total feeding volumes, mean±SD
Days until BW regained, median
7 (7)
At day 28 on human milk or formula, n (%)
(25th–75th
37 (37)
At day 28 on human milk, n (%)
Placebo (N = 36)
Author Manuscript All Infants (N = 100)
7 (21)
10 (29)
23 (68)
11 (7–17)
12 (11–20)
16 (12–19)
137± 30
102± 58
1 (3)
8 (24)
200 IU/day (N = 34)
1 (3)
9 (30)
26 (87)
9 (5–14)
12 (9–15)
11 (9–20)
124 ± 41
127± 39
4 (13)
12 (40)
800 IU/day (N = 30)
Author Manuscript
Clinical Outcomes
0.02
0.80
0.02
0.46
0.53
0.39
0.71
0.22
0.24
0.11
p
Fort et al. Page 17
Author Manuscript
J Pediatr. Author manuscript; available in PMC 2017 July 01.
J Pediatr. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: J Pediatr. 2016 July ; 174: 132–138.e1. doi:10.1016/j.jpeds.2016.03.028.
A Comparison of Three Vitamin D Dosing Regimens in Extremely Preterm Infants: a randomized controlled trial Prem Fort, MD1, Ariel A. Salas, MD, MSPH1, Teodora Nicola, PhD1, Carolyne M. Craig, BS1, Waldemar A. Carlo, MD1, and Namasivayam Ambalavanan, MD1 1Department
of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
Author Manuscript
Abstract Objective—To determine the optimal dose of vitamin D supplementation to achieve biochemical vitamin D sufficiency in extremely low gestational age newborns in a masked randomized controlled trial. Study design—100 infants 23 0/7 to 27 6/7 weeks gestation were randomized to vitamin D intakes of placebo (n=36), 200 IU (n=34), and 800 IU/day (n=30) (approximating 200, 400, or 1000 IU/day, respectively, when vitamin D routinely included in parenteral or enteral nutrition is included). The primary outcomes were serum 25 (OH) vitamin D concentrations on postnatal day 28 and the number of days alive and off respiratory support in the first 28 days.
Author Manuscript
Results—At birth, 67% of infants had 25(OH) vitamin D < 20 ng/mL suggesting biochemical vitamin D deficiency. Vitamin D concentrations on day 28 were (Median [25th–75th centiles], ng/ mL): Placebo: 22 [13–47], 200 IU: 39 [26–57], 800 IU: 84.5 [52–99], p < 0.001. There were no differences in days alive and off respiratory support (Median (25th–75th centiles), days: Placebo: 1 (0–11), 200 IU: 0 (0–8), 800 IU: 0.5 (0–22), p=0.63), or other respiratory outcomes among groups. Conclusion—At birth, most extremely preterm infants have biochemical vitamin D deficiency. This biochemical deficiency is reduced on day 28 by supplementation with 200 IU/day and prevented by 800 IU/day. Larger trials are required to determine if resolution of biochemical vitamin D deficiency improves clinical outcomes. ClinicalTrials.gov: NCT01600430 Trial registration—ClinicalTrials.gov: NCT01600430
Author Manuscript
Vitamin D is a fat soluble vitamin involved in multiple physiological processes. Developmental processes regulated by vitamin D include lung development– and maturation of the immune system.– As vitamin D is mostly transferred to the fetus during the third trimester,, preterm infants are born with lower vitamin D stores. Extremely low gestational
Corresponding author: Namasivayam Ambalavanan MD, 176F Suite 9380, Women and Infants Center, 619 South 19th Street, University of Alabama at Birmingham, Birmingham, AL 35249, Tel (205) 934 4680, Fax (205) 934 3100, [email protected]. The author declares no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fort et al.
Page 2
Author Manuscript
age newborns (ELGAN) are at high risk of mortality and multiple morbidities. It is not known if vitamin D insufficiency contributes to mortality or morbidity in these infants. The American Academy of Pediatrics (AAP) has recommended a dose of 200–400 IU of vitamin D per day for preterm infants, and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) recommends 800–1000 IU. However, evidence is lacking for the magnitude of improvement in serum vitamin D concentrations or clinical outcomes in ELGAN with either target range of vitamin D supplementation. In addition, as vitamin D is critical for many essential physiological processes, it is possible that higher than normal (supra-physiological) but non-toxic concentrations of vitamin D may benefit this vulnerable population similar to vitamin A supplementation.
Author Manuscript
This was a pilot trial to identify the optimal dose of vitamin D before embarking on a large multicenter trial using the optimal dose for evaluating clinical outcomes. Our objective was to determine the optimal dose of vitamin D supplementation in ELGAN using a masked randomized controlled trial in which infants were randomized to vitamin D intakes of placebo, 200 IU, and 800 IU/day.
Methods
Author Manuscript
This multiple-dose, randomized, double-blinded, placebo-controlled trial was approved by the Institutional Review Board at the University of Alabama at Birmingham. Entry criteria were inborn infants with gestational age between 23–27 completed weeks admitted to the neonatal intensive care unit at the University of Alabama Hospital. Exclusion criteria included major congenital or chromosomal anomalies, moribund infant with low likelihood of survival as outborn infants.
Author Manuscript
Parents or guardians were approached by research staff soon after birth for informed consent. After consent, infants were randomly allocated by the research pharmacy staff using computer-generated stratified randomization codes to one of three groups: (1) placebo (intake of approximately 200 IU/day in parenteral nutrition or feeds), (2) 200 IU supplement (daily intake of approximately 400 IU due to 200 IU supplement + 200 IU in parenteral nutrition or feeds), or (3) 800 IU supplement (daily intake of approximately 1000 IU due to 800 IU supplement +200 IU in parenteral nutrition or feeds). The 200 IU in enteral or parenteral nutrition is an estimate, based on the daily intake of feeds and TPN by infants in our NICU over the first month. As fortified human milk has approximately the same amount of vitamin D as preterm formula, and fortification is started early in our unit, no adjustments were made for daily variations in intake or for unfortified human milk. Infants received 0.25 mL of study drug (either vitamin D (Enfamil D-Vi-Sol ™) or normal saline (placebo)) every 6 hours through the orogastric tube just before feeds. The medication was dispensed by a research pharmacist in an amber syringe to mask the caregivers. Infants in the placebo group received only saline, and infants in the 200 IU/day group received one dose of vitamin D and three doses of saline and infants in the 800 IU/day group received four doses of vitamin D and none of saline. Each infant was randomized during the first
J Pediatr. Author manuscript; available in PMC 2017 July 01.
Fort et al.
Page 3
Author Manuscript
seven days after birth and within 72 hours after initiating enteral feeds. Infants were monitored before every feed for feeding intolerance (abdominal distension or increased gastric residuals). Serum electrolytes, blood gases, and ionized calcium were measured every day while on parenteral nutrition and twice weekly while on enteral feeds during the first month. The intervention was continued until postnatal day 28. Infants were discontinued from study drug administration if they developed necrotizing enterocolitis Bell’s stage II or greater, spontaneous intestinal perforation, or if feeds were stopped for more than 24 hrs by the clinical team. Clinical data were collected by a trained research coordinator.
Author Manuscript
For the estimation of serum 25(OH) vitamin D concentration, whole blood (0.2 mL to 0.25 mL) was collected at birth (cord blood) and at the time of routine sampling on day 14 (± 2 days), and day 28 of life (± 3 days) and centrifuged to collect serum. The samples were stored in −80°C for later analysis. Analysis of the serum 25(OH) vitamin D concentrations was with an enzyme-linked immunosorbent assay (ELISA; Eagle Biosciences, Inc, Nashua, NH) with a dynamic range of 4–120 ng/mL, 100% cross-reactivity between 25(OH)-vitamin D3 and D2, 21% FiO2 at 28 days
Respiratory support, n (%)
Pulmonary hemorrhage
1 (3)
80 (80)
13 (36)
21 (58)
1 (3)
1 (3)
0 (0)
1 (3)
21 (21–38)
35 (21–50)
17 (47)
1 (0–11) 6.8 ± 9.5
13 (36)
12 (36)
21 (58)
15 (42)
25 (69)
11 (31)
26 (72)
90 (90)
Received Surfactant < 72 hrs
31 (86)
Placebo (N = 36)
Respiratory distress syndrome
Respiratory Disease, n (%)
All Infants (N = 100)
Author Manuscript
Clinical Outcomes
8 (24)
18 (53)
2 (6)
2 (6)
2 (6)
4 (12)
23 (21–35)
29 (22–39)
19 (56)
0 (0–8) 5.5± 9.1
8 (24)
10 (43)
12 (35)
12 (35)
21 (62)
5 (15)
1 (3)
4 (12)
30 (88)
32 (94)
200 IU/day (N = 34)
8 (27)
19 (63)
3 (10)
1 (3)
0 (0)
1 (3)
21 (21–30)
30 (21–50)
11 (37)
0.5 (0–22) 7.0 ± 10.3
6 (20)
8 (31)
12 (40)
9 (30)
17 (57)
2 (7)
0 (0)
4 (13)
24 (80)
27 (90)
800 IU/day (N = 30)
Author Manuscript
Clinical outcomes of enrolled infants
0.48
0.70
0.47
0.78
0.14
0.22
0.62
0.55
0.63
0.63 0.78
0.29
0.84
0.12
0.61
0.55
0.18
0.65
0.09
0.25
0.71
p
Author Manuscript
Table 2 Fort et al. Page 15
Author Manuscript 7 (7) 4 (4) 62 (62)
IVH Grade IV Seizures > 72 hrs Head imaging normal > 28 days
11 (11) 20 (20) 5 (5) 7 (7) 3 (3) 6 (6) 1 (1)
Immature vessels zone III ROP in zone I and II Stage I or II; zone III ROP stage III or higher Plus disease Treatment with Avastin Other treatments
Author Manuscript
J Pediatr. Author manuscript; available in PMC 2017 July 01. 4 (4) 10 (10) 62 (62) 7 (7)
Methicillin-resistant Staphylococcus aureus Other organisms Lumbar puncture Meningitis, culture positive
91 (91) 50 (50) 14 (14)
First feed with human milk, n (%) At day 14 on human milk, n (%) At day 14 on human milk or formula, n (%)
Nutrition
3 (3)
Escherichia coli
29 (29)
Late onset sepsis (> 72 hrs)
12 (12)
29 (29)
Antibiotics > 5 days starting < 72hrs
Coagulase negative staphylococci
6 (6)
Early onset sepsis (≤ 72 hrs)
Infection, n (%)
26 (26)
Immature vessels zone I and II
ROP diagnosed
43 (43)
12 (12)
IVH Grade IIII
Retinopathy of prematurity (L or R), n (%)
21 (21)
IVH Grade II
7 (19)
21 (58)
34 (94)
3 (8)
24 (67)
5 (14)
1 (3)
1 (3)
7 (19)
13 (36)
11 (31)
1 (3)
1 (3)
2 (6)
2 (6)
3 (8)
3 (8)
10 (28
4 (11)
9 (25)
18 (50)
24 (67)
0 (0)
1 (3)
3 (8)
7 (19)
Placebo (N = 36)
Author Manuscript All Infants (N = 100)
5 (15)
12 (35)
30 (88)
1 (3)
20 (59)
2 (6)
2 (6)
2 (6)
4 (12)
11 (32)
4 (12)
4 (12)
0 (0)
2 (6)
0 (0)
2 (6)
0 (0)
6 (18)
6 (18)
10 (29)
10 (29)
18 (53)
3 (9)
4 (12)
6 (18)
10 (29)
200 IU/day (N = 34)
2 (7)
17 (57)
27 (90)
3 (10)
18 (60)
3 (10)
1 (3)
0 (0)
1 (3)
5 (17)
7 (23)
1 (3)
0 (0)
2 (7)
1 (3)
2 (7)
2 (7)
4 (13)
1 (3)
7 (23)
15 (50)
20 (67)
1 (3)
2 (7)
3 (10)
4 (13)
800 IU/day (N = 30)
Author Manuscript
Clinical Outcomes
0.33
0.11
0.65
0.50
0.77
0.54
0.78
0.39
0.13
0.19
0.16
0.22
0.41
0.98
0.39
0.92
0.25
0.32
0.19
0.85
0.14
0.41
0.17
0.34
0.45
0.28
p
Fort et al. Page 16
Author Manuscript 1 (3)
9 (9)
Death ≤ 36 wks, n (%)
13 (36)
32 (32)
33 (92)
10 (5–13)
14 (11–18)
Still in hospital at 120 days
10 (6–14)
13 (10–18)
82 (82)
Centiles)
Centiles)
14 (11–18)
131 ± 34
113 ± 48
2 (6)
17 (47)
In hospital at 36 wks
Hospitalization, n (%)
Days on TPN, median
(25th–75th
Days to 120 ml/kg/day, median
(25th–75th
14 (10–19)
131 ± 35
At day 28, total feeding volumes, mean±SD Centiles)
113± 50
At day 14, total feeding volumes, mean±SD
Days until BW regained, median
7 (7)
At day 28 on human milk or formula, n (%)
(25th–75th
37 (37)
At day 28 on human milk, n (%)
Placebo (N = 36)
Author Manuscript All Infants (N = 100)
7 (21)
10 (29)
23 (68)
11 (7–17)
12 (11–20)
16 (12–19)
137± 30
102± 58
1 (3)
8 (24)
200 IU/day (N = 34)
1 (3)
9 (30)
26 (87)
9 (5–14)
12 (9–15)
11 (9–20)
124 ± 41
127± 39
4 (13)
12 (40)
800 IU/day (N = 30)
Author Manuscript
Clinical Outcomes
0.02
0.80
0.02
0.46
0.53
0.39
0.71
0.22
0.24
0.11
p
Fort et al. Page 17
Author Manuscript
J Pediatr. Author manuscript; available in PMC 2017 July 01.
