Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence
Abstract
1. Introduction
2. The Role of Maternal Vitamin D in Neonatal and Infant Growth
3. Clinical Implications of Vitamin D Deficiency in Neonates and Infants
3.1. Respiratory Distress Syndrome (RDS)
3.2. Mini-Puberty
3.3. Atopic Dermatitis
3.4. Hypoxic–Ischemic Encephalopathy (HIE)
3.5. Early Onset Sepsis (EOS)
3.6. Retinopathy of Prematurity (RoP)
3.7. Osteopenia and Rickets
4. Optimizing Vitamin D Levels During Pregnancy and in Neonates and Infants
Institution/Scientific Society | Authors (Year) | Recommended Vitamin D Intake During Pregnancy |
---|---|---|
Recommended Nutrient Intake (RNI) by WHO/U.N. FAO | WHO (2004) [70] | 200 IU/day |
Expert Panel in Central Europe | Płudowski (2013) [75] | 1500 to 2000 IU/day |
The Royal College of Obstetricians and Gynaecologists | RCOG (2014) [76] | 400 IU/day to 1000 IU/day for high-risk women. In addition, for women with pre-eclampsia, min. 800 IU/day combined with calcium |
European Food Safety Authority (EFSA) and USA Institute of Medicine | EFSA (2016) [77] | 600 IU/day |
5. Management of Neonatal Hypovitaminosis D
6. Conclusions
Author Contributions
Funding
Informed Consent Statement
Conflicts of Interest
Abbreviations
1,25(OH)2D | 1,25-Dihydroxyvitamin D |
25(OH)D | 25-Hydroxyvitamin D |
APA | Acceleration Time-to-Ejection Time Ratio |
AT/ET | Alkaline Phosphatase Activity |
BMI | Body Mass Index |
CYP27B1 | Cytochrome P450 Family 27 Subfamily B Member |
DBS | Dried Blood Spot |
EOS | Early-Onset Sepsis |
HIE | Hypoxic–Ischemic Encephalopathy |
LGA | Large for Gestational Age |
LRTIs | Lower Respiratory Tract Infections |
PTH | Parathyroid Hormone |
PI | Pulsatility Index |
PMCA | Plasma Membrane Calcium-Dependent ATPase |
PSV | Peak Systolic Velocity |
RDS | Respiratory Distress Syndrome |
RoP | Retinopathy of Prematurity |
ROC | Receiver Operating Characteristic |
SGA | Small for Gestational Age |
TPN | Total Parenteral Nutrition |
TTN | Transient Tachypnea of the Newborn |
UVB | Ultraviolet B |
VEGF | Vascular Endothelial Growth Factor |
WB-BMC | Whole-Body Bone Mineral Content |
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Society | Authors (Year) | Severe Deficit | Deficit | Insufficiency | Sufficiency |
---|---|---|---|---|---|
Lawson Wilkins Pediatric Endocrine Society | Misra M (2008) [14] | <5 ng/mL | 5–14 ng/mL | 15–19 ng/mL | ≥20 ng/mL |
Endocrine Society | Holick MF (2011) [10] | - | <20 ng/mL | 20–29 ng/mL | ≥30 ng/mL |
ESPHGAN | Braegger C (2013) [15] | <10 ng/mL | <20 ng/mL | - | ≥20 ng/mL |
Australian and New Zealand Bone and Mineral Society | Paxton GA (2013) [16] | <5 ng/mL | 5–11 ng/mL | 12–19 ng/mL | ≥20 ng/mL |
American Academy of Pediatrics | Golden NH (2014) [3] | - | <20 ng/mL | - | ≥20 ng/mL |
Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics | Saggese G (2018) [17] | <10 ng/mL | 10–20 ng/mL | 20–29 ng/mL | ≥30 ng/mL |
System Involved | Type of Complication | Main Clinical Consequences |
---|---|---|
Respiratory system | Respiratory Distress Syndrome (RDS), Transient Tachypnea of the Newborn (TTN), Lower Respiratory Tract Infections (LRTIs) | Increased risk of RDS and TTN [33]; impaired fetal lung function (Doppler indices) [34]; higher incidence of bronchiolitis and pneumonia [35]. |
Reproductive system | Alterations During Mini-Puberty | Higher testosterone and reduced inhibin B in girls [39]; prolonged activation of reproductive axis in children of mothers with vitamin D deficiency during pregnancy [40]. |
Immune system | Atopic Dermatitis | Higher risk of atopic eczema in infants with low cord blood vitamin D levels [41,42]; vitamin D supplementation during pregnancy could reduce the risk [42,43]. |
Central nervous system | Hypoxic–Ischemic Encephalopathy (HIE) | Predictor of poorer neurological outcomes and higher neonatal mortality in newborns with HIE [46]; possible reduction in S100-B levels and improvement in blood parameters in case of vitamin D supplementation [44]; 25(OH)D supplementation during pregnancy could reduce risk of asphyxia [45]. |
Hematologic/immune system | Early-Onset Sepsis (EOS) | Increased risk of EOS [48]; improved sepsis scores and reduced CRP levels in case of vitamin D supplementation [49]. |
Visual system | Retinopathy of Prematurity (RoP) | Higher risk and severity of ROP [52]; potential influence of supplementation on disease progression [53]. |
Skeletal system | Osteopenia and Rickets | Higher prevalence of biochemical rickets in infants of mothers with vitamin D deficiency [7]; improved bone mineralization in case of supplementation during pregnancy and lactation [68]. |
Scientific Society/Nation | Authors (Year) | Recommendation |
---|---|---|
ESPGHAN | Agostoni (2010) [81] | 800–1000 IU/day (avoiding a per kg dosage) for the first months of life. |
Australian and New Zealand Bone and Mineral Society | Paxton GA (2013) [16] | 200 IU/kg/day, with a maximum of 400 IU/day. |
American Academy of Pediatrics | Abrams SA (2013) [92] | Newborns with birth weights more than 1500 g should take 400 IU/day. Newborns with birth weights less than 1500 g should take 200–400 IU/day, which should be increased to 400 IU/day when infants reach a weight of 1500 g and tolerate total enteral feeding. |
Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics | Saggese G (2018) [17] | 400–800 IU/day for preterm infants with a weight ≥ 1500 g. 200–400 IU/day by enteral feeding in preterm infants with a weight < 1500 g. |
Poland | Płudowski P (2023) [85] | Neonates born at <32 weeks of gestation: if enteral nutrition is possible, 800 IU/day of cholecalciferol from the first days of life, regardless of the feeding method, during the first month of life. The intake from a diet should be calculated from the second month of life. Neonates born at 33–36 weeks of gestation: 400 IU/day of cholecalciferol from the first days of life, regardless of the feeding method. |
Scientific Society/Nation | Authors (Year) | Recommendation |
---|---|---|
Endocrine Society | Holick MF (2011) [10] | 400–1000 IU/day. |
Australian and New Zealand Bone and Mineral Society | Paxton GA (2013) [16] | Children at risk of vitamin D deficiency should receive supplementation with 400 IU/day for at least the first year of life. Children at risk: children born to mothers with vitamin D deficiency and fed with exclusive breastfeeding and with at least one other risk factor among reduced sun exposure, dark skin (phototypes V and VI), and disease or medication that interferes with vitamin D metabolism. |
ESPGHAN | Braegger C (2013) [15] | 400 IU/day throughout the first year of life in all children. |
Canadian Paediatric Society | Critch JN (2014) [88] | 0–6 months: 400 IU/day of vitamin D in breastfed infants. Children who are not breastfed do not require vitamin D prophylaxis. Partially breastfed infants should receive 400 IU/day, regardless of the amount of formula milk taken. 6–12 months: Continued supplementation with 400 IU/day in children who are still exclusively breastfed or who are taking breast milk. |
American Academy of Pediatrics | Golden NH (2014) [3] | Breastfed or partially breastfed infants should be supplemented with 400 IU/day until at least the time of weaning. |
Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics | Saggese G (2018) [17] | 400 IU/day in all newborns independent of the type of feeding. |
Poland | Płudowski P (2023) [85] | 0–6 months: 400 IU/day (10 µg/day) of cholecalciferol from first days of life, regardless of the feeding method. 6–12 months: 400–600 IU/day (10–15 µg/day) of cholecalciferol, depending on the daily amount of vitamin D consumed with meals. |
Scientific Society/Nation | Authors (Year) | Recommendation |
---|---|---|
Endocrine Society | Holick MF (2011) [10] | 2000 IU/d of vitamin D2 or vitamin D3 or 50,000 IU of vitamin D2 or vitamin D3 once weekly for 6 weeks followed by maintenance therapy with 400–1000 IU/day. |
Australian and New Zealand Bone and Mineral Society | Paxton GA (2013) [16] | Between 0 and 3 months: if 25(OH)D levels are 12–20 ng/mL, 400 IU/day for 3 months; if 25(OH)D levels < 12 ng/mL, 1000 IU/day for 3 months. Between 3 and 12 months: if levels of 25(OH)D are 12–20 ng/mL, 400 IU/day for 3 months; if levels of 25(OH)D < 12 ng/mL, 1000 IU/day for 3 months or a bolus of 50,000 IU (consider repeating another dose after one month). Thereafter, maintenance with 400 IU/day. |
American Academy of Pediatrics | Golden NH (2014) [3] | 2000 IU/day for 6 weeks or 50,000 IU per week for 6 weeks; subsequent maintenance with 400–1000 IU/day. |
Canadian Paediatric Society | Critch JN (2014) [88] | 0–6 months: 400 IU/day of vitamin D in breastfed infants. Children who are not breastfed do not require vitamin D prophylaxis. Partially breastfed infants should receive 400 IU/day, regardless of the amount of formula milk taken. 6–12 months: Continued supplementation with 400 IU/day in children who are still exclusively breastfed or who are taking breast milk. |
Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics | Saggese G (2018) [17] | In the case of asymptomatic vitamin D deficiency [25(OH)D < 20 ng/mL]: 2000 IU/day or 50,000 IU/week of vitamin D2 or D3 for 6–8 weeks). After the completion of treatment, serum concentrations should be reevaluated. In the presence of an adequate vitamin D status [25(OH)D ≥ 30 ng/mL], continue vitamin D supplementation as recommended for the age. |
Poland | Płudowski P (2023) [85] | 0–12 months: 2000 IU/day. Calcifediol is not recommended. |
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Ferrari, V.; Biasucci, G.; Candela, E.; Ortolano, R.; Baronio, F.; Lanari, M. Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence. Endocrines 2025, 6, 21. https://doi.org/10.3390/endocrines6020021
Ferrari V, Biasucci G, Candela E, Ortolano R, Baronio F, Lanari M. Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence. Endocrines. 2025; 6(2):21. https://doi.org/10.3390/endocrines6020021
Chicago/Turabian StyleFerrari, Vittorio, Giacomo Biasucci, Egidio Candela, Rita Ortolano, Federico Baronio, and Marcello Lanari. 2025. "Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence" Endocrines 6, no. 2: 21. https://doi.org/10.3390/endocrines6020021
APA StyleFerrari, V., Biasucci, G., Candela, E., Ortolano, R., Baronio, F., & Lanari, M. (2025). Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence. Endocrines, 6(2), 21. https://doi.org/10.3390/endocrines6020021