Preemies have low vitamin D levels yet only get 400 IU – July 2013

Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay

Arch Dis Child Fetal Neonatal Online First, published on July 13, 2013 as 10.1136/archdischild-2013-303999
Nagendra Monangi,1 Jonathan L Slaughter,2,3 Adekunle Dawodu,4 Carrie Smith,5 Henry T Akinbi1 henry.akinbi at cchmc.org
1Neonatal Perinatal Medicine, Perinatal Institute, Cincinnati Children's Hospital Medical Center/University of Cincinnati, Cincinnati, Ohio, USA
2Center for Perinatal Research and Ohio Perinatal Research Network, Nationwide Children's Hospital, Columbus, Ohio, USA
3Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA
4Global Health Center,Cincinnati Children's Hospital Medical Center/University of Cincinnati, Cincinnati, Ohio, USA
University of Cincinnati Medical Center, Cincinnati, Ohio, USA

Objectives To evaluate vitamin D (vitD) status in early preterm infants (EPTIs) at birth and during birth hospitalisation on current vitD intake.
Design/methods Serum 25-hydroxyvitamin-D [25(OH)D] concentrations, vitD intake and risk factors for low vitD status were assessed in 120 infants born at <32 weeks gestation.
Results Mean (SD) serum 25(OH)D at birth was 46.2 (14.0) nmol/L with lower concentrations in infants born <28 weeks than at 28-32 weeks gestation, p=0.02. Serum 25(OH)D was <50 nmol/L in 63% of mothers, 64% of infants at birth and 35% of infants at discharge. Mean daily vitD intake was 289±96 IU at 4 weeks of age and 60% achieved 400 IU/day intake at discharge.
Conclusions Serum 25(OH)D <50 nmol/L was widespread in parturient women and in EPTIs at birth and at discharge. Optimising maternal vitD status during pregnancy and improving postnatal vitD intake may enhance infant vitD status during hospitalisation.

INTRODUCTION

Low vitamin D (vitD) status is a risk factor for rickets and has been associated with increased prevalence of respiratory infections and other adverse health outcomes in infants and children.12 In response to the concern about widespread childhood vitD deficiency, professional bodies have recommended vitD intake of 400 IU/ day for all infants.13 The European Society for Paediatrics Gastroenterology, Hepatology and Nutrition recommends 800-1000 IU/day for preterm infants.4 Based on biomarkers of vitD status mostly in adults, serum 25-hydroxyvitamin-D [25(OH)D] concentration >50 nmol/L was also recom-mended.13 However, the functional benefit of this level is controversial. Early preterm infants (EPTIs) are likely at risk of low vitD status because of high prevalence of vitD deficiency in pregnancy,5 lack of sunlight exposure during hospitalisation and difficulty in ensuring adequate enteral nutrition. We hypothesised that serum 25(OH)D concentrations would be low at birth in EPTIs (<32 weeks post-menstrual age (PMA)) and that current vitD intake during hospitalisation would be insufficient to achieve a serum 25(OH)D>50 nmol/L at discharge. We assessed the serum 25(OH)D concentrations at birth in EPTIs and the effect of current vitD intake during hospitalisation on vitD status.

MATERIALS AND METHODS

Infants born at <32 weeks PMA admitted to the newborn intensive care units (NICUs) at the University of Cincinnati Medical Center,

What is already known on this topic

• Vitamin D deficiency is common in infants that do not receive vitD supplements.
• Vitamin D intake of 400 IU/day is recommended for infants to achieve a target serum 25 (OH)D concentrations >50 nmol/L.

What this study adds

• Low serum concentrations (<50 nmol/L) are common in preterm infants during birth hospitalisation and at discharge from the neonatal intensive care unit.
• Current neonatal nutritional strategies for early preterm infants may be insufficient to achieve recommended vitD intake and target serum 25 (OH)D concentrations.
• Improving maternal vitD status during pregnancy and neonatal vitD supplementation is warranted to optimise vitD status of preterm infants in early infancy.

Table 1 Demographic characteristics and serum 25-hydroxyvitamin-D concentrations

RESULTS

A total of 120 mother/infant pairs were enrolled. Table 1 shows the demographic characteristics and serum 25 (OH)D concentrations. Mean serum 25(OH)D concentration at birth for the EPTI cohort was 46.3 nmol/L (SD 14.0) with lower concentrations in infants born <28 weeks PMA (42.0±9.8 nmol/L) than at 28-32 weeks (51.8±19.5 nmol/L), p=0.02.
Overall, 64% of infants had serum 25(OH)D concentrations <50 nmol/L at birth. Approximately 70% of infants born <28 weeks and 55% of infants born between 28 and 32 weeks had serum 25(OH)D concentrations <50 nmol/L, p=0.02. Maternal serum 25(OH)D concentration was 49.0±21.3 nmol/L. Sixty-three per cent of mothers had 25(OH)D concentrations <50 nmol/L. Infant serum 25(OH)D at birth correlated with maternal 25(OH)D (r=0.77, p=0.001) and with infant serum 25(OH)D at discharge (r=0.65, p=0.04).
Following multivariable logistic regression, the factors that were significantly associated with serum 25(OH)D <50 nmol/L were low maternal vitD status (adjusted OR (aOR), 5.2 (95% CI 2.9 to 9.6)), African-American ethnicity (3.2 (1.3 to 7.9)), PMA <28 weeks (2.6(1.1 to 6.2)), lack of maternal prenatal vitD use (4.2 (2.1 to 8.5)) and winter birth (4.3 (2.3 to 9.3)), (table 2).
Mean vitD intake at 4 weeks postnatal age was 289±96IU/ day and was not significantly different in infants born at <28 weeks PMA (232±106 IU) than at 28-32 weeks PMA (316 ±94 IU), p = 0.08. At discharge or 36 weeks PMA, 60% of the entire cohort of preterm infants attained 400 IU per day.
With the current vitD intake during hospitalisation in the NICUs, 40% of infants born <28 weeks PMA and 30% of infants born between 28 and 32 weeks had serum 25 (OH)D concentrations <50 nmol/L at 36 weeks PMA or at discharge.

DISCUSSION

In this multicentre study, two-thirds of preterm infants and their mothers had serum 25(OH)D concentrations <50 nmol/L, a value considered deficient by some professional bodies.1 Interestingly, the odds of a serum 25(OH)D level <50 nmol/L was increased 2.6-fold in infants born <28 weeks PMA than at 28 -32 weeks. Presumably, the high prevalence of serum 25 (OH)D concentrations <50 nmol/L at birth in our cohort of EPTIs and the higher prevalence in infants born <28 weeks than in infants born between 28 and 32 weeks are reflective of maternal vitD status.
Table 2 Factors associated with infant serum 25(OH)D <50 nmol/L at birth in multivariable analysis

Maternal vitD deficiency predisposes to low vitD status in term infants at birth.78Similarly, we found that maternal vitD deficiency predicted low vitD status in EPTIs in agreement with our hypothesis. Our data also suggest that vitD status of EPTIs at birth correlated with the vitD status at discharge, underscoring the importance of optimising the vitD status of infants at birth. As reported in studies in term infants,78African-American ethnicity, lack of maternal prenatal vitD intake and winter birth were predictive of low vitD status at birth in EPTIs. Since EPTIs are usually hospitalised after birth, vitD synthesis from sunlight exposure is lacking. Thus, repletion of vitD status during hospitalisation depends entirely on exogenous sources. There are limited recent reports on vitD intake in preterm infants during birth hospitalisation.910 Our study demonstrated that although total daily vitD intake from all sources increased progressively with age (data not shown), only 60% of this cohort of infants achieved an intake of 400 IU/day of vitD by 36 weeks PMA or at discharge. During hospitalisation, low vitD status at birth and suboptimal vitD intake appear to militate against the achievement of serum 25(OH)D concentrations >50 nmol/L in many preterm infants. Although professional bodies134recommend 25(OH)D concentrations >50 nmol/L to promote bone health, the effect of target serum 25(OH)D concentration on clinical outcomes in infants is lacking and merits evaluation.
Our study had several strengths. To our knowledge, it is the first reported multicentre investigation of vitD status in infants born <32 weeks gestation and monitored longitudinally from birth until hospital discharge. It provides data on the vitD status achieved by EPTIs born <32 weeks PMA based on conventional nutritional practices in the NICU settings. Thus, our results are likely generalisable to infants in NICUs and will inform future intervention trials to assess the effect of optimising vitD status in preterm infants on short- and long-term clinical outcomes.

CONCLUSIONS

In this study, neither the vitD intake, nor the recommended serum 25(OH)D concentrations of >50 nmol/L were attained in many EPTIs. The serum 25(OH)D concentrations of infants were directly correlated with maternal vitD status at birth. Therefore, vitD status should be optimised in pregnant women as part of strategy to replete the offspring. In addition, EPTIs require heightened attention to vitD supplementation in the NICU to improve vitD intake and vitD status. In view of potential putative roles for vitD in several biologic functions, studies are needed to test the effect of targeting serum 25(OH)D concentrations of >50 nmol/L on clinically relevant health outcomes.

REFERENCES

1 Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008;122:1 142-52.
2 Camargo CA Jr, Ingham T, Wickens K, et al. Cord-Blood 25-Hydroxyvitamin D Levels and Risk of Respiratory Infection, Wheezing, and Asthma. Pediatrics 2011;127:e180-7.
3 Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press, 2011.
4 Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010;50:85-91.
5 Dawodu A, Nath R. High prevalence of moderately severe vitamin D deficiency in preterm infants. Pediatr Int 2011;53:207-10.
6 Hollis BW, Roos BA, Draper HH, et al. Vitamin D and its metabolites in human and bovine milk. J Nutr 1981;111:1240-8.
7 Bodnar LM, Simhan HN, Powers RW, et al. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr 2007;137:447-52.
8 Hollis BW, Wagner CL. Assessment of dietary vitamin D requirements during pregnancy and lactation. Am J Clin Nutr 2004;79:717-26.
9 McCarthy RA, McKenna MJ, Oyefeso O, et al. Vitamin D nutritional status in preterm infants and response to supplementation. Br J Nutr 2012:1-8.
10 Taylor SN, Wagner CL, Fanning D, et al. Vitamin D status as related to race and feeding type in preterm infants. Breastfeed Med 2006;1:156-63.

See also VitaminDWiki

• No preemie had even 30 ng of vitamin D, lower D associated with more Respiratory Distress – Aug 2013
• Many preemies need at least 800 IU of vitamin D – RCT May 2013
• Preemies have increased need for vitamin D and Calcium (Rickets)– May 2013
• Recurrent pre term birth and low vitamin D – Dec 2012
• Low birth weight associated with vitamin D levels less than 11 ng – Nov 2012
• Infants born early had low vitamin D levels – Oct 2012
• Reminder – 400 IU is enough only when infant already had a good level of vitamin D – Nov 2012
• Infants born early had low vitamin D levels – Oct 2012
• Osteopenia in preterm infants – May 2012
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