Preventing symptomatic vitamin D deficiency and rickets among Indigenous infants and children in Canada

---

The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.

Background

Severe vitamin D deficiency (VitDD) presenting as rickets and other serious manifestations, including cardiomyopathy, hypocalcemic seizures, and fractures, persists among infants and children in Canada ^[1]. Breastfed Indigenous infants, particularly those living in northern communities, are disproportionately impacted ^[2], although formula-fed infants are not exempt ^[1][3]. The risk factors for infant symptomatic VitDD are both biophysical and social, and include maternal VitDD, darker skin, winter season, lower socio-economic status (SES), reduced sun exposure, northern latitude, and food insecurity ^[2][4]-[7]. There is evidence of increasing maternal VitDD in Indigenous women as the consumption of country foods (including fish and sea mammals) has decreased over time ^[8]-[10] as a consequence of forced displacement, residential schools, environmental concerns, poverty, and other factors ^[11][12]. Adherence to health professional recommendations for prenatal and infant supplementation also influences VitD status. Finally, genetic variability may play a role in individual risk for VitDD ^[13].

Population-based strategies such as formula fortification, dietary advice, and oral supplementation are generally effective in preventing symptomatic VitDD for most Canadians. Whether current guidelines intended for Canada’s general population of healthy term infants ^[14][15] are adequate for infants born to mothers with severe VitDD is much less certain ^[2]. The lack of adherence to current guidelines poses the greatest threat of symptomatic VitDD in vulnerable groups. Given the persistence of rickets despite well-publicized guidelines, present strategies seem insufficient ^[1][16].  

This revised statement and its recommendations focus more on preventing rickets and symptomatic VitDD than on optimizing VitD levels. It does not address other adverse outcomes with potential links to VitDD ^[17]. The statement revises the Canadian Paediatric Society’s 2007 position statement entitled “Vitamin D supplementation: Recommendations for Canadian mothers and infants” ^[18]. An extensive review of the English medical literature on VitDD was conducted using PubMed and the Cochrane database for articles published between 2007 and 2020. Emphasis was placed on randomized controlled trials (RCTs) and systematic reviews, Canadian studies, and reports involving Indigenous peoples.

Rickets and symptomatic VitDD

In infants and young children, severe VitDD can lead to impaired mineralization of bone tissue (osteomalacia) and growth plates (rickets), seizures, cardiomyopathy, and more subtle manifestations (Table 1) ^[1][19]-[21].

Table 1. Manifestations of severe vitamin D deficiency (VitDD) and rickets
Conditions	Manifestations
Skeletal deformities	Lower limb deformities (e.g., bowed femurs or tibias) Spinal deformities Enlargement of growth plates wrist ankles costochondral junctions (rachitic rosary) Craniotabes
Hypocalcemic seizures	Can sometimes be the first manifestations
Cardiomyopathy
Other	Dental abnormalities, including caries Leg pain Fractures Delayed motor milestones (delayed standing or walking, frequent falling) Delayed growth Failure to thrive
Based on references 1,19-21

As clinical features of VitDD can be subtle, true prevalence rates are likely under-estimated ^[20]. Post-mortem data suggest that histologic changes in growth plates can occur without radiographic or physical changes such that early signs of rickets may go undetected ^[22]. Maternal VitDD can lead to congenital rickets, defined as rickets presenting in the first 30 days of post-natal life ^[23].

Indigenous and northern children have been affected disproportionately with VitDD rickets ^[2][24][25]. All infants with VitDD rickets occurring at and before birth (i.e., congenital rickets) reported in the Canadian literature have been physician-reported as Indigenous ^[26][27]. The Canadian Paediatric Surveillance Program (CPSP) confirmed 104 cases of VitDD rickets across Canada in a 2-year period (2002 to 2004), excluding those with underlying disease ^[2]. The highest rates were in northern Canada, with the greatest number in Ontario. Based on physician reporting, 94% of these children were breastfed, 89% were intermediate- or darker-skinned, and 25% were First Nation (FN) or Inuit, altogether comprising 3% of the Canadian population ^[28]. None of the children with rickets had received the recommended amount of VitD supplementation of 400 IU/day. However, the few FN infants whose mother’s VitD levels were <27.5 nmol/L were receiving sufficient VitD-fortified formula to support normal growth. Another report confirmed that formula-fed infants were not exempt from rickets or symptomatic VitDD: six young Indigenous infants presented with hypocalcemic seizures between 5 days and 7 weeks of age while consuming formula containing 400 IU/L VitD and gaining weight appropriately ^[3]. Significant maternal VitDD was likely because none of these mothers were taking prenatal vitamins.

A CPSP survey in 2015 identified 48 cases of nutritional rickets and 101 cases of severe, symptomatic VitDD without rickets, including in two children who died from causes unrelated ^[29]. Although Indigenous identity was not reported, the vast majority of these children had darker skin.

A regional review in Manitoba, northern Ontario, and western Nunavut identified 46 cases of rickets in children younger than 7 years of age from 2003 to 2015 ^[16]. Their median age was 9.1 months, 50% of these infants or children were Indigenous (physician-reported), one-third were from Winnipeg, and >75% were living in low socio-economic census areas.

Guidelines for infants and children

Canadian recommendations include VitD supplementation of 400 IU/day for infants and children under 2 years of age who are partially or fully breastfed ^[14][15]. The ‘tolerable upper intake level’ (UL for short) is the highest level of continuing daily nutrient intake that is likely to pose no risk for adverse health effects in almost all individuals ^[30]. The VitD UL is 1000 IU/day for infants <6 months of age, 1500 IU/day for those 6 to 12 months, and 2500 and 3000 IU/day for children aged 1 to 3 and 4 to 8 years of age ^[31].

While evidence is inconsistent for levels of serum 25-hydroxyvitamin D (25(OH)D) above which rickets does not occur, the data suggest that values <30 nmol/L indicate increased risk for rickets. However, values as high as 50 nmol/L may not eliminate the risk for developing rickets ^[31]. There are limited studies assessing serum VitD status in Indigenous infants. The Nunavut Inuit Child Health Survey identified 13.6% and 36.5% of preschool children with 25(OH)D levels <25 nmol/L and <37.5 nmol/L ^[32]. 

Since 1988 the CPS has recommended a VitD supplementation of 800 IU/day for breastfed northern Indigenous infants in the winter, and 400 IU/day for those being formula fed, due to their higher risk ^[18][33]. One international consensus guideline recommended that a 400 IU/day supplement for infants was adequate to prevent rickets, though it also recommended special rickets prevention programs targeting groups of at-risk infants and children, and 25(OH)D monitoring for those with identified risk factors ^[34]. Serum testing in infants may be impractical in remote northern settings, and routine serum 25(OH)D testing is generally believed to be unnecessary because of VitD supplementation requirements ^[35].

Studies have shown increasing mean levels of serum 25(OH)D with daily 400 IU supplementation. However, significant percentages of infants remained VitD insufficient despite receiving a daily supplement of 400 IU, with levels ranging from 11% <27.5 nmol/L ^[36] to 30% <37.7 nmol/L ^[37]. This persistent insufficiency was confirmed by a southern Canada study of predominately Caucasian infants in higher socio-economic circumstances, which found 32% with a baseline of <50 nmol/L continuing below that level despite receiving 400 IU/day over a 3-month period ^[38].

Studies assessing the effectiveness of various doses of VitD supplements have been reassuring regarding the safety of higher doses. An RCT in Montreal of largely Caucasian, breastfed infants who were predominately VitD sufficient at birth (25(OH)D >50 nmol/L) found that 97% of infants reached >50 nmol/L by 3 months with supplements in amounts of 400, 800, 1200, or 1600 IU/day ^[38]. Only supplements of 1600 IU/day resulted in 25(OH)D levels that were unnecessarily high (>250 nmol/L). Other RCTs ^[39]-[41] have shown the effectiveness of supplementing 400 IU/day in reaching 25(OH)D >50 nmol/L. A study in Alberta found that 10% of exclusively breastfed infants on VitD supplements had 25(OH)D levels <50 nmol/L despite the fact that 90% of their predominately Caucasian mothers (87%) were taking prenatal VitD supplements ^[42]. Many of these studies are not generalizable to populations most at risk for VitDD because they were conducted in predominately Caucasian, higher SES populations. These studies do support the safety of doses ≤1200 IU/day, however, with one study ^[43] including pregnant women who received 2000 IU daily while their infants received 800 IU daily. Nor do these studies provide evidence for adequacy of a 400 IU daily supplement for infants of mothers with VitDD.  

The Canadian Academy of Health Sciences has supported varying VitD supplementation doses based on risk, especially for preterm and term infants with darker skin colour or those at risk for VitDD at birth because of maternal VitDD ^[44].

Since 2018, the Alaskan Division for Public Health recommends 800 IU/day of VitD for all infants in the state who are exclusively or partially breastfed, and 400 IU/day of VitD for those who are formula-fed ^[45]. These recommendations were based on the fact that a supplement of 400 IU/day may not eliminate rickets in infants born to severely VitDD mothers. Supplements of 800 IU/day of VitD appear to be more effective for safely achieving sufficient VitD levels (i.e., >50 nmol/L).

Maternal guidelines

Preventing maternal VitDD is an important strategy to reduce symptomatic VitDD, including congenital rickets in infants, because of the link between maternal and infant VitD levels ^[46]. Although studies of southern Canadian pregnant women of predominately European descent and living in higher socio-economic circumstances suggest that serum 25(OH)D levels are sufficient ^[47][48] to prevent this condition, high rates of VitDD are being found in Canadian Indigenous women ^[9][49]. In Saskatchewan FN pregnant women, 24% had 25(OH)D levels <37.5 nmol/L compared with <8.3% in non-FN pregnant women (^[50], Personal communication with Dr. Denis Lehotay, January 2015).

Maternal 25(OH)D levels are limited by use of certain medications, including some antiepileptic and antiretroviral drugs ^[51], skin pigmentation, decreased sun exposure, seasonal variation, living in higher latitudes (i.e., over 55° ^[52][53]), smoking, obesity, and lack of supplementation or decreased consumption of VitD-rich foods, such as fish and milk ^[7][53]. Dietary intake is influenced by access, availability, and cost of healthy and/or fortified foods, the harvesting of local country foods, cultural and traditional experience, peer use of VitD-rich foods, and SES ^[6][54].

The use of milk products may be limited because of lactose intolerance in Indigenous populations ^[55][56], which has been documented in various regional FN Food Nutrition and Environment Surveys (FNFNES) ^[57], the fact that milk and milk products are not part of the traditional diet, as well as cost. Food insecurity is significant in northern Canada, with 63% of Inuit households experiencing moderate or severe food insecurity compared with 8.4% of other Canadian households ^[58][59].

FNFNES evidence clearly shows that the VitD intake of Canadian Indigenous populations is higher when traditional foods are consumed. This finding has been confirmed by other Canadian studies ^{[9][49][60]-[62]}. There is also evidence that VitD intake ^[8], serum 25(OH)D levels ^[63], and the consumption of traditional foods ^[9][10] are decreasing in Indigenous populations.

For pregnant women, the recommended dietary allowance (RDA) of vitamin D is 600 IU/day ^[31]. The RDA was based on the amount meeting or exceeding requirements for 97.5% of the population, assuming minimal sun exposure. Health Canada recommends a daily multivitamin with folic acid and iron for pregnant women with no specific mention of VitD, although many multivitamins including prenatal vitamins contain VitD ^[64][65]. Vitamin D can be obtained from foods recommended by Canada’s Food Guide, notably fish, lower fat milk, and fortified soy beverages. Also, Canada’s Food Guide promotes the intake of traditional foods as a way to improve diet quality ^[66].

Some studies suggest that supplementation with 400 IU VitD daily may not ensure sufficient 25(OH)D levels in all pregnant women ^[67]-[69]. Other Canadian studies of pregnant women have shown that non-European ethnicity is associated with lower 25(OH)D levels ^[70], or with greater proportions <50 nmol/L ^[47][71][72]. One Canadian RCT has suggested that maternal supplementation of 2000 IU/day maintains infant 25(OH)D levels >30 nmol/L to 8 weeks of age without infant supplementation, while supplements of 400 to 1000 IU/day may still leave infants at risk (98% compared with 57% and 84%) ^[73].

The Canadian Consensus on Female Nutrition stressed the importance of balanced dietary intake for all women, but indicated that FN pregnant women are at particularly high risk for VitDD. They recommended a VitD supplement for all women who consume insufficient dietary VitD ^[74].  Multiple clinical trials have not shown adverse effects with supplements of 1000 to 2000 IU/day equivalent dosing, or of 60,000 IU monthly ^{[43][73][75][76]}, or even of up to 4000 IU/day ^[69]. Some systematic reviews of trials looking at pregnancy outcomes have shown weak or mixed results. However, there is some evidence regarding the safety of various doses of VitD. One study associated supplementation in pregnancy using doses ≤2000/day with lower risk for small for gestational age (SGA) infants and no evidence of adverse effects ^[75]. Another review of RCTs supplementing pregnant women with >600 IU/day (compared with receiving <600 IU/day) found no difference in adverse events and lower risk for gestational diabetes ^[77].

Recommendations for all pregnant women living in Alaska are for 1000 IU/day plus a daily prenatal vitamin containing 400 IU of VitD. These recommendations were made because a 400 IU supplement does not appear to be sufficient for all pregnant women. Higher doses appear to be safe while still being substantially below the UL for pregnant women of 4000 IU/day.

Observed, intermittent higher-dose supplementation

A limited number of RCTs have assessed the effectiveness and longer-term safety (beyond a couple of years) of intermittent higher-dose supplementation in high-risk infants or pregnant women. By contrast, however, multiple studies of intermittent therapy have revealed which doses show short-term safety and benefit when adherence is a challenge. 

Various professional organizations in Australia, France, New Zealand, and the United Kingdom, currently recommend higher doses for at-risk pregnant women, while some recommend intermittent therapy ^[78]-[81]. The use of cholecalciferol (D3), with its longer half-life, has benefits over ergocalciferol (D2) for intermittent dosing, while either is appropriate for daily dosage ^[34].

One international consensus guideline included this comment: “Among infants and toddlers with 25(OH)D levels <50 nmol/L for whom daily vitamin D supplements may not be ideal, intermittent bolus doses of 50,000–100,000 IU every 3 months hold promise, although a comprehensive understanding of the safety and efficacy of this approach remains to be studied” ^[34]. In infants of VitDD mothers, a single bolus of 30,000 IU of D3, followed by daily supplements of 400 IU, has shown a more rapid reduction of VitDD compared with 400 IU daily supplements alone ^[82]. One systematic review of alternatives to routine daily supplements suggested that intermittent VitD supplementation holds promise, but more research is required to verify the efficacy and safety of this approach before widespread routine use can be recommended ^[83].

Adherence to supplementing with vitamin D

Adherence to supplementation is the most significant barrier to effective VitDD prevention in Canada. Barriers to supplement use for socially disadvantaged pregnant women and infants must be removed. The strategies found to most improve adherence are habit-based and focus on behaviour, such as linking medication-taking with existing routines. Some evidence has suggested that knowledge by itself is inadequate to change adherence ^[84]. Providing supplements all year round may improve adherence ^[44]. Providing VitD supplements along with education is more successful than free coverage with a voucher or prescription alone ^[85]-[88]. Health care professional (HCP, including pharmacist) awareness and promotion of VitD at each health visit improve adherence rates. Having information with clear, easy-to-follow guidelines may also help. More critical to improving adherence, however, is having a positive relationship with an HCP that is based on trust and communication ^[89]. Intermittent, higher-dose oral supplementation can be considered in certain high-risk situations, in consultation with a vitamin D therapy expert, to assist with adherence.

Recommendations for vitamin D supplementation in high-risk Indigenous pregnant women, infants, and children

During routine prenatal, infant, and child care visits, health care providers (HCPs) should take three steps:

1. Assess mother and child for VitDD risk,
2.  Determine appropriate dosage for VitD supplements, and
3.  Support and monitor adherence to dietary and supplementation recommendations.

Step 1. Assess each pregnant woman, infant, and child for nutritional risks for VitDD at every health visit. Ask about dietary and supplemental intake of VitD to assess risk, but also consider the impacts of socio-economic and other social determinants of health.

Figure 1. Risk Factors for vitamin d (VitD) deficiency in Indigenous prenatal women, infants, and children*
Maternal Factors Low intake of VitD-rich foods (consuming <2 cups/day of milk or fortified soy beverage, low consumption of fish and sea mammals) Lack of VitD supplementation during pregnancy Use of certain medications (e.g., some antiretrovirals and antiepileptics) Multiple pregnancies Smoking	General Factors Darker skin pigmentation Food insecurity Obesity Living in communities north of 55° latitude† Living in an area where VitDD is prevalent Extensive use of sunblock or skin coverage by clothing, or lack of exposure to the outdoors Low socio-economic conditions
Infant Factors Mother not ingesting sufficient VitD supplements or otherwise at risk for VitDD, regardless of infant feeding mode
Child Factors Low intake of VitD-rich foods Mother has risk factors for VitDD Lack of VitD supplementation during infancy
* Even a single risk factor may put a patient in the “high risk” category. In uncertain cases, consider the individual at high risk. † Edmonton is at 53° VitD Vitamin D; VitDD Vitamin D deficiency

Step 2. Determine Vitamin D supplements based on risk.

Table 2. Daily, year-round* vitamin D (VitD) supplementation, based on risk
Prenatal and lactating women	Prenatal women in general, including Indigenous women	High-risk§ prenatal women
	Dietary advice‡ plus a daily prenatal vitamin containing 400 IU VitD, folic acid, and iron.	Dietary advice‡ plus daily prenatal vitamin containing 400 IU VitD, folic acid, and iron. Plus an additional 1000 IU/day VitD.
Infants: Birth to 12 months of age	Mode of feeding	Low-risk infants: Daily VitD supplement	High-risk§ infants: Daily VitD supplement
	Breast milk† (exclusively or partially)	400 IU/day in the first year of life	800 IU/day in the first year of life. If the high-risk infant transitions to cow’s milk, supplement with 400 IU/day.
	Formula	Supplement not required if infant is drinking more than 800 to 1000 mL/day. The same applies following transition to fortified cow’s milk.	400 IU/day in the first year of life. Continue supplementation beyond 12 months with 400 IU/day if the infant remains at high risk.
Children: 1 to 5 years of age	Low-risk children		High-risk† children
	Dietary advice†,‡		Dietary advice†,‡ and 400 IU/day
*Daily, year-round = starting at the first pre-natal visit (mothers) or within 72 hours of birth (infants) †Breastfeeding is recommended, exclusively for the first 6 months, and continued along with appropriate complementary feeding for up to 2 years or more. For infants younger than 2 years old who are no longer breastfed and cannot consume cow’s milk, soy-based commercial infant formula is recommended. ‡ For pregnant women and children over 2 years old, encourage consumption of quality, nutritious foods including VitD-fortified milk or fortified soya beverage (2 cups/day or more), and at least 2 servings of fish or sea mammals/week (unless local health advisories indicate otherwise). § High risk may be present if the infant, child, or mother has a single risk factor from Figure 1.

Step 3. Support and monitor adherence to supplementation at each visit.

• Assess barriers to supplement recommendations, such as cost and behaviour (e.g., forgetting  to take the medication). Provide electronic or other reminders when possible, and counsel each mother you see about how maternal and infant VitD is important for overall infant development and bone health. Consider using this Caring for Kids parent note as a handout: Vitamin D  
• For infants, start supplementing with VitD within the first few days post-birth. Show parents and other family caregivers how to administer supplements.
• When costs are covered by programs or insurance, provide VitD supplements directly for high-risk infants and prenatal women.

Paediatricans and HCPs should consider two additional steps:

Step 4. Determine an alternative course of action for particularly high-risk situations, especially when adherence is a problem. 

• Consult a clinician with vitamin D therapy expertise about administrating observed, intermittent, higher-dose, oral vitamin D supplementation in the following situations:
  • Mothers and infants who are assessed with multiple risk factors or living in specific communities where the diagnosis of rickets or symptomatic VitDD occurs frequently; and
  • Where there are ongoing concerns about the adequacy of maternal-infant adherence to guidelines for uninterrupted daily VitD supplementation.

• When feasible, consider measuring 25(OH)D to confirm VitDD, then monitor response to intermittent, higher-dose oral vitamin D therapy.

Step 5. Advocate.

• VitDD is only one consequence of food insecurity. Addressing VitDD in isolation cannot solve the many nutritional health issues affecting Indigenous populations. HCPs should also advocate for and support programs which:

  • Work with local Indigenous communities on food security and income support; and

  • Encourage and support the harvesting and consumption of country foods, such as game meat, birds, fish, and foraged foods.

• Paediatricians and other HCPs should advocate for free access to VitD supplements for Métis prenatal women and their infants on a par with the Non-Insured Health Benefits Program for First Nations women and children.  

Acknowledgements

This position statement has been reviewed by the Community Paediatrics, Drug Therapy and Hazardous Substances, and Nutrition and Gastroenterology Committees of the Canadian Paediatric Society. It was also reviewed by members of the Family Physician Advisory, Clinical Practice Obstetrics, and Indigenous Women’s Health Committees of the Society of Obstetricians and Gynaecologists of Canada.

---

CANADIAN PAEDIATRIC SOCIETY FIRST NATIONS, INUIT AND MÉTIS HEALTH COMMITTEE (2019-2020)

Members: Margaret Berry MD; Leigh Fraser-Roberts MD; Ryan Giroux MD (Resident member); James Irvine MD (past member); Radha Jetty MD (Chair); Véronique Anne Pelletier MD; Brett Schrewe MD; Raphael Sharon MD (Board Representative)

Liaisons: Karen Beddard, Inuit Tapiriit Kanatami; Shaquita Bell MD, American Academy of Pediatrics; Laura Mitchell BA, MA and Patricia Wiebe MD, MPH, Indigenous Services Canada, First Nations and Inuit Health Branch; Melanie Morningstar, Assembly of First Nations; Marilee Nowgesic RN, Canadian Indigenous Nurses Association; Eduardo Vides MD, Métis National Council.

Principal authors: James Irvine MD, Leanne M Ward MD

The views expressed in this document do not necessarily represent the positions, decisions or policies of the First Nations and Inuit Health Branch liaisons or their organization.

---

References

---

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.