Impact of Vitamin D Status on Bones in Breastfed Infants

Vitamin D Deficiency Clinical Trial

Official title:

Vitamin D Status and Impact on Bone Mineralization in Human Milk Fed Hispanic and Caucasian Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00697294
• Other study ID #: H-22293
• Status: Completed
• Phase: N/A
• First received: June 3, 2008
• Last updated: December 2, 2011
• Start date: July 2008
• Est. completion date: November 2011

Study information

• Verified date: December 2011
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Vitamin D deficiency is widespread and linked to decreased bone mineral content. Little data exists regarding the vitamin D status and the relationship of 25-hydroxyvitamin D (25-OHD) status to functional bone health outcomes in Hispanic infants. To evaluate this, we plan an observational cohort of full term, healthy, exclusively breastfed Hispanic and Caucasian infants. We hypothesize serum 25-OHD measured in cord blood will be significantly lower in Hispanic than Caucasian infants, with 25-OHD less than 20 ng/mL found in at least 50% of Hispanic neonates. Secondary aims evaluate the relationship between 25-OHD levels and bone mineral status at baseline and after 3 months of 400 IU/day supplemental vitamin D3. Whole body bone density scan (DXA) and bone ultrasound (SOS U/S) will be measured shortly after birth, then again after supplementation. Data from this study will provide information needed to design further randomized trials and interventions.

Description:

In recent years, severe vitamin D deficiency has resurfaced as a major public health concern. Nutritional rickets is widespread, and a recent report on this disease in Texas showed Hispanic children are at increased risk. Long-term follow-up has demonstrated that vitamin D deficient infants are more likely to have decreased bone mineral status in late childhood. Additionally, vitamin D deficiency has been linked to changes in fetal "imprinting" and increased susceptibility to autoimmune diseases, immune deficiency, and malignancy. At birth, an infant's vitamin D status is entirely dependent on the vitamin D status of the mother. Many studies have shown vitamin D deficiency is very common in mother-child pairs, especially in dark-skinned individuals. However, few data exist regarding the vitamin D status in Hispanic infants. Low milk intakes and decreased sun exposure with urbanization makes this a very high-risk group among infants in Texas.

Potential subjects will be identified by study personnel in labor and delivery at St. Luke's and Ben Taub Hospitals and in the normal newborn nurseries. The parent/guardian will be approached and the study will be explained in full. A time for questions will be allowed. Once the parent/guardian agrees to his/her child's participation, an informed written consent form will be signed. Subject confidentiality will be maintained within limits of the law. All names and personal information will be accessed only by the investigators and authorized personnel. There will be no possibility of coercion as subjects will not have any relationship of dependency with the investigators.

A cohort of Hispanic and Caucasian infants will be recruited and followed. Other ethnic groups will not be excluded, but will not be analyzed in terms of the primary outcome. Race and ethnicity will be classified according to mother's self classification. The interventions will not differ between the groups.

This study includes 3 study visits:

1. Baseline inpatient visit at birth - while hospitalized to obtain consent, obtain cord blood sample, and mother to complete a questionnaire

2. 1 week after initial hospital discharge - first outpatient visit to obtain other baseline data (see below) and to start the vitamin D drops

3. At 3 mo of life - second outpatient visit to obtain final data (see below) and discontinue vitamin D drops

Visit 1 (Inpatient): After consent has been obtained and upon birth, cord blood will be obtained and analyzed using the Diasorin RIA for 25-OHD. In addition, serum ionized calcium and intact parathyroid hormone (PTH) concentration will be measured on cord blood. Mothers will be given a brief questionnaire to determine their risk of vitamin D deficiency (do they take vitamins, supplements, sun exposure). Follow-up outpatient appointments will be scheduled.

Visit 2 (First Outpatient Visit): Infants will have a speed of sound ultrasound (SOS U/S) and whole body dual-energy x-ray absorptiometry (DXA) performed at 1 week after hospital discharge. Supplements of 400 IU of vitamin D per day will be provided for all infants free of charge starting at the time of the body composition analysis (Vitamin D supplementation is recommended by the American Academy of Pediatrics for all infants who are exclusively breastfeeding).

Visit 3 (Second Outpatient Visit): Infants will return at three months of age and repeat measurements of serum 25-OHD, PTH, bone SOS U/S, and whole body DXA will be performed. At this time a second brief questionnaire will be given to the mother to assess the risks of vitamin D deficiency in the child. Vitamin D drops will be discontinued.

Between visits, investigators will call the family to check on breast feeding status.

At delivery, cord blood will be obtained and analyzed for 25-OHD, serum ionized calcium, and intact parathyroid hormone (PTH) concentration. At three months of age blood will be drawn for 25-OHD and PTH. The purpose of the blood draw is to assess the vitamin D status in the newborn infant. This is the primary aim of the study.

• 5 cc (one teaspoon) of cord blood will be obtained at visit 1, and 5 cc (one teaspoon) blood will be drawn from patient at the third visit (three months of age).

• Total = 2 teaspoons

There will be no study costs passed on the subject's family. Study investigations (laboratory, bone mineral assessment) will be paid for by the researchers. Costs for routine medical care, not associated with the study, but associated with delivery and hospitalization of the newly born child will be the responsibility of the family and their insurance company.

A total of 60 subjects will be enrolled in the protocol. Enrollment of 30 Hispanic infants and 30 Caucasian infants will provide a power > 80% to demonstrate a significantly lower cord 25-OHD concentration in Hispanic infants at p<0.05, the primary outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 2 Hours

Eligibility

Inclusion Criteria:

• Full term infants (37-42 weeks)

• Appropriate for gestational age

• Free of major congenital anomalies

• Born to mothers without a history of diabetes or chronic illness who intend to exclusively breastfeed

Exclusion Criteria:

• Any child who does not meet the above inclusion criteria

• Insufficient cord blood available to determine cord 25-hydroxyvitamin D status

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Tri-Vi-Sol
All subjects will begin vitamin D supplementation at the first outpatient visit (at 1 week of life) and will continue through the second outpatient visit (at 3 months of age). Dosage will be 400 IU/day of vitamin D in the form of Tri-Vi-Sol vitamin drops.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	St Lukes Episcopal Hospital	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (19)

Abrams SA, Copeland KC, Gunn SK, Stuff JE, Clarke LL, Ellis KJ. Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American and Caucasian girls despite hormonal differences. J Nutr. 1999 Mar;129(3):666-71. — View Citation

Alfaham M, Woodhead S, Pask G, Davies D. Vitamin D deficiency: a concern in pregnant Asian women. Br J Nutr. 1995 Jun;73(6):881-7. — View Citation

Ashraf A, Mick G, Atchison J, Petrey B, Abdullatif H, McCormick K. Prevalence of hypovitaminosis D in early infantile hypocalcemia. J Pediatr Endocrinol Metab. 2006 Aug;19(8):1025-31. — View Citation

Basile LA, Taylor SN, Wagner CL, Quinones L, Hollis BW. Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of deficiency. J Perinatol. 2007 Sep;27(9):568-71. Epub 2007 Jul 12. — View Citation

Brooke OG, Butters F, Wood C. Intrauterine vitamin D nutrition and postnatal growth in Asian infants. Br Med J (Clin Res Ed). 1981 Oct 17;283(6298):1024. — View Citation

Brunvand L, Hågå P, Tangsrud SE, Haug E. Congestive heart failure caused by vitamin D deficiency? Acta Paediatr. 1995 Jan;84(1):106-8. — View Citation

Cockburn F, Belton NR, Purvis RJ, Giles MM, Brown JK, Turner TL, Wilkinson EM, Forfar JO, Barrie WJ, McKay GS, Pocock SJ. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. Br Med J. 1980 Jul 5;281(6232):11-4. — View Citation

Datta S, Alfaham M, Davies DP, Dunstan F, Woodhead S, Evans J, Richards B. Vitamin D deficiency in pregnant women from a non-European ethnic minority population--an interventional study. BJOG. 2002 Aug;109(8):905-8. — View Citation

Dijkstra SH, van Beek A, Janssen JW, de Vleeschouwer LH, Huysman WA, van den Akker EL. High prevalence of vitamin D deficiency in newborn infants of high-risk mothers. Arch Dis Child. 2007 Sep;92(9):750-3. Erratum in: Arch Dis Child. 2007 Nov;92(11):1049. — View Citation

Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C; Princess Anne Hospital Study Group. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006 Jan 7;367(9504):36-43. Erratum in: Lancet. 2006 May 6;367(9521):1486. — View Citation

Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr (Phila). 2007 Jan;46(1):42-4. — View Citation

Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res. 1997 Nov;12(11):1761-8. — View Citation

McGrath J. Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders? Med Hypotheses. 2001 Mar;56(3):367-71. — View Citation

Molla AM, Al Badawi M, Hammoud MS, Molla AM, Shukkur M, Thalib L, Eliwa MS. Vitamin D status of mothers and their neonates in Kuwait. Pediatr Int. 2005 Dec;47(6):649-52. — View Citation

Nicolaidou P, Hatzistamatiou Z, Papadopoulou A, Kaleyias J, Floropoulou E, Lagona E, Tsagris V, Costalos C, Antsaklis A. Low vitamin D status in mother-newborn pairs in Greece. Calcif Tissue Int. 2006 Jun;78(6):337-42. Epub 2006 Jul 7. — View Citation

Reasner CA 2nd, Dunn JF, Fetchick DA, Liel Y, Hollis BW, Epstein S, Shary J, Mundy GR, Bell NH. Alteration of vitamin D metabolism in Mexican-Americans. J Bone Miner Res. 1990 Jan;5(1):13-7. — View Citation

Shah M, Salhab N, Patterson D, Seikaly MG. Nutritional rickets still afflict children in north Texas. Tex Med. 2000 Jun;96(6):64-8. — View Citation

Waiters B, Godel JC, Basu TK. Perinatal vitamin D and calcium status of northern Canadian mothers and their newborn infants. J Am Coll Nutr. 1999 Apr;18(2):122-6. — View Citation

Zadshir A, Tareen N, Pan D, Norris K, Martins D. The prevalence of hypovitaminosis D among US adults: data from the NHANES III. Ethn Dis. 2005 Autumn;15(4 Suppl 5):S5-97-101. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the relative frequency of vitamin D deficiency in human milk fed Hispanic compared to Caucasian newborn infants in Houston, Texas.		End of study	No
Secondary	To determine if infant vitamin D status is related to bone mineral status at birth		End of study	No
Secondary	To determine the effects of vitamin D supplementation on 25-hydroxyvitamin D (25-OHD) concentration and bone mineral status vitamin D deficient and vitamin D replete infants at 3 months of age.		End of study	No