2000 American Academy of Pediatrics Annual Meeting



Vitamin D-Deficiency Rickets in Breast-Fed Infants
José F. Cara, MD 


The series of accomplishments leading to the discovery of vitamin D and 
culminating in its routine supplementation in formulas derived from cow's 
milk are largely responsible for the successful prevention and treatment of 
vitamin. D-deficiency rickets in infants and children.[1] In fact, by the 
1930s, vitamin D-deficiency rickets, once considered a "scourge of children," 
was considered to have vanished from the pediatric population. By the 1960s, 
it was considered a medical oddity.[2] In the 1970s, reports of vitamin-D 
deficiency began reappearing in the literature.[3-7] Since then, there has 
been growing concern about the apparent resurgence of the condition in 
breast-fed infants.
From a public health perspective, there is considerable controversy as to how 
to best deal with the problem of vitamin D-deficiency rickets.[1] At the 
heart of the argument is the lack of consensus regarding the need for routine 
vitamin-D supplementation in infants who are exclusively breast-fed. Whereas 
some have recommended routine vitamin-D supplementation of all breast-fed 
infants, others have suggested that the need for supplementation with vitamin 
D is not advisable or necessary. As a result, no formal policy has been 
adopted concerning vitamin D in this population of high-risk infants.


Physiology of Calcium Balance
Vitamin D is necessary for adequate maintenance of bone architecture and 
normal calcium homeostasis.[8] It plays an important role in the 
gastrointestinal absorption of calcium and phosphate and in bone dissolution 
and mineralization. An important source of vitamin D is the skin, where 
exposure to ultraviolet irradiation converts 7-dehydrocholesterol to 
cholecalciferol (vitamin D3). Vitamin D may also be absorbed through the 
gastrointestinal tract, where cholecalciferol and ergocalciferol (vitamin D2) 
obtained from animal and vegetable food sources, respectively, are absorbed 
into the circulation. Cholecalciferol and ergocalciferol (henceforth 
collectively referred to as vitamin D) undergo 25-hydroxylation in the liver 
and 1alpha-hydroxylation in the kidney to form 1,25-dihydroxyvitamin D, the 
most active form of the hormone. Vitamin D and its metabolites are 
transported to target tissues by vitamin D-binding protein (DBP), which also 
functions as a "reservoir" of vitamin D in the circulation.
Parathyroid hormone (PTH) is the most important hormonal regulator of serum 
calcium concentrations.[8] The hormone stimulates osteolysis, with release of 
calcium and phosphate from bone, and promotes renal phosphate excretion. The 
net result is an increase in the serum concentration of calcium. PTH also 
regulates vitamin-D homeostasis through its effects on renal 
1alpha-hydroxylase activity. In the presence of low calcium levels, the 
activity of the enzyme is increased, whereas high calcium levels lead to 
production of inactive metabolites.


Pathophysiology of Vitamin D-Deficiency Rickets in Breast-Fed Infants
Breast milk is deficient in vitamin K, vitamin D, and iron. According to Dr. 
Reginald Tsang,[9] Director of the Children's Center for Bone Research and 
Health in Cincinnati, Ohio, concentrations of vitamin D average only 35 IU/L 
in African American women and 68 IU/L in white women, far below the daily 
amount of 200 IU/day recommended for infants by the Food and Nutrition Board 
of the National Academy of Sciences[10] and 400 IU/day recommended for 
infants by the American Academy of Pediatrics Committee on 
Nutrition.[11]Whereas sun exposure and an appropriate diet may increase 
vitamin D levels in breast milk, studies have shown that significant 
increases in maternal ultraviolet light exposure and in vitamin D intake of 
up to 3000 IU/day fail to increase vitamin D levels to more than 100 IU/L, 
still short of the daily requirements of the vitamin.[1]
Most infants obtain their vitamin D from maternal breast milk, sun exposure, 
and other nutritional sources, including vitamin D-supplemented cereals, baby 
foods, milk, and vitamins. An infant who is exclusively breast-fed and who 
gets minimal sunlight exposure, or an infant who is on a nonfortified milk 
substitute, runs the risk of developing vitamin D-deficiency rickets by 4-6 
months of age. African American babies are particularly at risk because dark 
skin pigmentation interferes with the penetration of ultraviolet light in the 
skin and with vitamin D production. Also at risk are infants with minimal 
sunlight exposure because of climate or religious preferences and premature 
infants with diminished vitamin D reserves at birth. Sunscreens reduce 
vitamin D production because of impaired ultraviolet light penetration into 
the skin, according to Dr. Tsang[9] and a report by Marks.[10] 

The apparent increase in the incidence of vitamin-D deficiency in infants who 
are exclusively breast-fed may have several causes.[1] Air pollution, 
including the pollution caused by the explosion of Mount Pinatubo in the 
Philippines several years ago, may decrease ultraviolet light exposure and 
vitamin D production by the skin. The increase in the practice of 
breast-feeding, associated with the beliefs that "breast is best" and that 
breast milk does not require supplementation because it is a baby's "perfect 
food," may lead to decreased vitamin D intake from other sources and rickets. 
The lack of adequate training of physicians in a rickets-free era coupled 
with the lack of adequate recommendations for vitamin D supplementation by 
professional organizations may have also contributed to the development of 
rickets in exclusively breast-fed babies.


Clinical Presentation and Diagnosis
The clinical presentation of vitamin-D deficiency may be silent or dramatic, 
with hypocalcemic seizures and cardiorespiratory arrest. Dr. Susan Baker,[11] 
Codirector of Pediatric GI/Nutrition at Medical University of South Carolina, 
addressing members attending this year's American Academy of Pediatrics 
annual meeting, reported that rickets can be arbitrarily considered as mild, 
moderate, or severe based on the pathophysiology of the condition. In mild 
rickets (also referred to as phase 1 rickets), there is a slight decrease in 
serum calcium levels because of poor calcium absorption from the gut. Most 
infants are asymptomatic at this stage. In moderate (phase 2) rickets, 
hypocalcemia leads to secondary hyperparathyroidism, with calcium and 
phosphate release from bone, phosphate excretion by the kidney, and 
normalization of calcium levels in blood. At this stage, infants present with 
evidence of bone mineral loss and typical stigmata of rickets on physical 
examination and on x-ray. Serum calcium levels are typically normal but 
phosphate levels are depressed, 25-hydroxyvitamin D levels are low, and 
alkaline phosphatase and 1,25-dihydroxyvitamin D levels are elevated because 
of secondary hyperparathyroidism. In severe, or phase 3, rickets, severe 
depletion of calcium stores from bone ultimately result in hypocalcemia. When 
severe, hypocalcemia may cause tetany and seizures and, if persistent, 
hypocalcemia may lead to cardiorespiratory arrest and death.
The diagnosis of vitamin D-deficiency rickets in infants is made by a history 
of poor vitamin D intake and the clinical and biochemical characteristics 
described above. The biochemical abnormalities characteristic of the 
different stages of the disease help to confirm the diagnosis. According to 
Dr. Tsang, a low phosphate level combined with a low 25-hydroxyvitamin D 
concentration and radiologic evidence of rickets confirms the diagnosis.[9]


Treatment
Treatment of vitamin D-deficiency rickets involves the provision of vitamin D 
to correct the underlying deficit and correction of hypocalcemia, if present. 
In the child with mild or moderate rickets, vitamin D is recommended because 
of its low cost and enhanced efficacy. If compliance is a concern, the 
medication may be given as a single intramuscular injection of 300,000 to 
600,000 IU (10,000-15,000 mcg). Whereas Dr. Tsang reported that oral doses of 
only 400 IU/day may be sufficient to treat rickets, the generally recommended 
dose is 2000-6000 IU/day (50-150 mcg /day) for a total of 30 days. Healing 
can be documented by 2-4 weeks and is typically complete by 45-60 days. 
In cases of severe rickets with hypocalcemia, treatment should be directed at 
raising calcium levels to avoid further neuromuscular manifestations. 
Intravenous administration of 10 mL of 10% calcium gluconate (100 mg/mL) 
given slowly and with electrocardiographic monitoring is effective in most 
cases. Treatment can be continued with intravenous calcium gluconate 50-125 
mg/kg/dose every 6 hours (200-500 mg/kg/day) in order to raise the serum 
calcium to a level of 6.5-7.0 mg/dL. Vitamin D therapy must also be provided, 
at the doses described above. Low magnesium levels also need to be corrected 
before calcium levels will normalize. 

Infants found to have vitamin D-deficiency rickets and treated successfully 
with vitamin D and/or calcium therapy should be monitored for recurrence of 
the condition at intervals of 6 months to 1 year. Recurrence of rickets 
and/or hypocalcemia may suggest an underlying defect in the vitamin D system, 
including vitamin D-resistant rickets and vitamin D-dependent rickets due to 
abnormalities of the 1alpha-hydroxylase enzyme..[12,13]


Prevention 
According to Dr. Baker and others,[1,6,11] vitamin D-deficiency rickets may 
result in significant infant morbidity and mortality. Whereas most infants 
with rickets are easily recognized and treated, some may have lasting bone 
deformities or mild to severe neurologic sequelae when the case is severe. 
Dr. Baker reported that between 1900 and 1961, nearly 13,800 infant deaths 
were directly attributed to rickets. She added that these data were very 
disturbing given the ease with which vitamin D deficiency can be prevented.
The prevention of vitamin D-deficiency rickets in breast-fed infants can be 
easily achieved through routine supplementation with vitamin D. Sources 
differ as to time frame to begin supplementation, beginning as early as birth 
to 2 months of age and also with dose.[3,6,10,11] A daily dose ranging from 
200-400 IU is safe and effective and can be provided as simple vitamin D or 
in the form of a daily liquid multivitamin. Dr. Baker mentioned that the AAP 
is expected to put forth guidelines for vitamin D supplementation for 
breastfeeding infants by early next year. In addition, primary care providers 
need to provide ongoing patient and public education regarding the need for 
supplementation, stressing that the concept of "breast is best" should not 
override routine supplementation with vitamin D. 


References
Welch TR, Bergstrom WH, Tsang RC. Vitamin D-deficient rickets: the emergence 
of a once-conquered disease. J Pediatr. 2000;137:143-145. 
Harrison HE. The disappearance of rickets. Am J Public Health. 
1966;56:734-737. 
Eugster EA, Sane KS, Brown DM. Minnesota rickets. Need for a policy change to 
support vitamin D supplementation. Minn Med. 1996;79:29-32. 
Pugliese MT, Blumberg DL, Hludzinski J, Kay S. Nutritional rickets in 
suburbia. J Am Coll Nutr. 1998;17:637-641. 
Kaper BP, Romness MJ, Urbanek PJ. Nutritional rickets: report of four cases 
diagnosed at orthopaedic evaluation. Am J Orthop. 2000;29:214-218. 
Kreiter SR, Schwartz RP, Kirkman HN Jr, Charlton PA, Colikoglu AS, Davenport 
ML. Nutritional rickets in African-American breast-fed infants. J Pediatr. 
2000;137:153-157. 
Shah M, Salhab N, Patterson D, Seikaly MG. Nutritional rickets still afflict 
children in North Texas. Tex Med. 2000;96:64-68. 
Koo WW, Tsang R. Bone mineralization in infants. Prog Food Nutr Sci. 
1984;8:229-302. 
Tsang R. Endocrinology update for pediatricians. Vitamin D-deficiency 
rickets. Presented at the Annual Meeting of the American Academy of 
Pediatrics; October 29, 2000; Chicago, Illinois. 
The Food and Nutrition Board of the National Academy of Sciences. Available 
at http://books.nap.edu/books/0309071836/html/198.html#pagetop 
Committee on Nutrition. Pediatric nutrition handbook. 4th ed. Elk Grove 
Village (IL): American Academy of Pediatrics; 1998. p. 275-6. 
Marks R. Sunscreens and vitamin D. J Am Acad Dermatol. 1997;37:942-947. 
Baker S. Nutritional rickets in breastfeeding infants. Presented at the 
Annual Meeting of the American Academy of Pediatrics; October 29, 2000; 
Chicago, Illinois. 
Smith SJ, Rucka AK, Berry JL, et al. Novel mutations in the 
1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin 
D-deficient rickets resulting in loss of functional enzyme activity in 
blood-derived macrophages. J Bone Miner Res. 1999;14:730-739. 
Malloy PJ, Pike JW, Feldman D. The vitamin D receptor and the syndrome of 
hereditary 1,25-dihydroxyvitamin D-resistant rickets. Endocr Rev. 
1999;20:156-188. 



Nikki Lee RN, MSN, Mother of 2, IBCLC, CIMI
craniosacral therapy practitioner; childbirth educator
Elkins Park (a suburb of Philadelphia, Pennsylvania; northeastern USA)
supporting the WHO Code and the Mother Friendly Childbirth Initiative

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