Relationship Between Vitamin D During Perinatal Development and Health

Vitamin D Effects on Heart Disease

Findings from the National Health and Nutrition Examination Survey (1988–1994) revealed that serum 25(OH)D concentrations are inversely associated with cardiovascular disease, hypertension, myocardial infarction, congestive heart failure, and stroke in a large sample representative of the US adult population.^[47] Exposure to low concentrations of 25(OH)D during early development may alter function in later life because during perinatal life, the mammalian heart undergoes tremendous growth and development. Emerging epidemiologic evidence (Table 1) suggests that both maternal and neonatal vitamin D deficiency may be associated with heart disease later in life, but the mechanism remains unknown. One hypothesis is that vitamin D deficiency substantially lowers intestinal calcium absorption (50–60%), which triggers parathyroid hormone release.^[48] Parathyroid hormone, in addition to its actions on calcium reabsorption and vitamin D production, stimulates insulin resistance, inflammation, and the renin–angiotensin aldosterone system. Over time, these three metabolic modifications upregulate the atherosclerotic process, which can lead to heart disease (Figure 2).^[48]

A study conducted in rodents examined how maternal vitamin D deprivation affected metabolic and contractile development of the neonatal heart.^[49] Pups exposed to low levels of vitamin D (<200 IU/day) during perinatal life exhibited a reduction in protein (myofibrillar) accumulation and cardiac growth, which may seriously compromise cardiac functional capacity. In humans, there was no association between maternal 25(OH)D levels and cardiac measures in offspring at 9 years of age.^[29] However, changes in cardiac measures typically manifest in later life, suggesting that human studies need to be followed more long-term to determine the true association between vitamin D and heart disease.

During pregnancy, vitamin D may also affect heart development by modulating kidney function. In humans, nephron synthesis is complete at 36 weeks of gestation. Perturbations in nephrogenesis during the early stages of development may have long-term implications for renal health and hypertension. A study by Maka et al.^[50] revealed that rat pups born to vitamin D–deficient mothers had a 20% increase in nephron endowment and a reduction in renal corpuscle size. These changes suggest that vitamin D does modulate nephrogenesis. However, without examining tubule resorption or kidney perfusion, the long-term implications of these changes for hypertension or heart health are unknown.

Table 1. Epidemiologic Evidence Linking Vitamin D and Disease
Disease Relationship	Variables Used in Epidemiology to Infer a Relationship to Vitamin D
Sun Exposure	Migration Away From High Sun Exposure	Season of Birth	Skin Pigmentation	Dietary Vitamin D
Osteomalacia and rickets	Decreased sun exposure in third trimester is associated with decreased bone mass²⁹	Afro-Caribbean immigrants in the UK are associated with an increased incidence of rickets⁶⁸	To our knowledge, no epidemiologic studies have shown this relationship	Children with darker skin have a higher prevalence of having poor bone health and rickets^17,69,70	Low maternal 25(OH)D concentrations during pregnancy are associated with decreased bone mineral content in children at 9 years of age²⁹ Vitamin D deficiency in early life is associated with rickets, mild respiratory distress, weak muscle tone, decreased calcium and increased parathyroid hormone levels⁷¹
Multiple sclerosis (MS)	Increased sun exposure during early life is associated with a decreased risk of MS⁷² MS relapse is inversely associated with UV exposure and 25(OH)D levels⁷³	Indian and Pakistani immigrants who enter the UK between 0–4 years of age are at increased risk of having MS⁷⁴ Second-generation Afro-Caribbean immigrants in the UK are associated with an increased MS risk⁷⁵	Data pooled from 4 countries shows that spring births are associated with an increased MS risk and fall births are associated with a decreased MS risk⁷⁶	Having white skin lowers the prevalence of MS disability⁷⁷	Consumption of fish 3–4 times a week is associated with a decreased MS risk⁷² Diets low in fish but high in meat and dairy products are associated with an increased prevalence of MS⁷⁸ Intake of vitamin D from supplements is inversely associated with MS risk⁷⁹
Schizophrenia	Increased sun exposure is associated with decreased risks of having schizophrenia, and schizophrenia-induced symptoms are weaker and less regular⁸⁰	Second-generation immigrants from Morocco and Surinam to the Netherlands are associated with an increased risk of schizophrenia⁸¹ Afro-Caribbean immigrants to the UK are associated with an increased risk of schizophrenia⁸²	Data pooled from 6 countries shows that winter births are associated with an increased incidence of schizophrenia^{83, 84}	Having black skin may be associated with an increased incidence of schizophrenia⁸⁵	Vitamin D supplementation during the first year of life lowered the risk of developing schizophrenia in males, but not females⁸⁶ Maternal 25(OH)D was not a risk factor for schizophrenia. But the results in the black subgroup raise the possibility that below a certain threshold low levels of 25(OH)D may be associated with an increased risk of schizophrenia⁸⁵
Type 1 diabetes	Monthly sunshine availability is inversely associated with having type 1 diabetes⁸⁷	Children who migrated to an area prevalent in diabetes (northern region) had a greater risk of developing type 1 diabetes⁸⁸	Winter and spring births are associated with higher frequency of type 1 diabetes^89–91 than summer births⁹¹	Children with black skin are at a higher risk of having type 1 diabetes than children with white skin⁹²	In a meta-analysis, vitamin D supplementation was associated with a decreased risk of type 1 diabetes⁹³ Children who consumed vitamin D supplements had an 80% lower risk of having type 1 diabetes⁵⁵ Use of cod liver oil by mothers during pregnancy and infants in the first year of life lowered the infants' risk of developing type 1 diabetes⁵⁶

Table 1. Epidemiologic Evidence Linking Vitamin D and Disease

Disease Relationship

Variables Used in Epidemiology to Infer a Relationship to Vitamin D

Sun Exposure

Migration Away From High Sun Exposure

Season of Birth

Skin Pigmentation

Dietary Vitamin D

Osteomalacia and rickets

Decreased sun exposure in third trimester is associated with decreased bone mass²⁹

Afro-Caribbean immigrants in the UK are associated with an increased incidence of rickets⁶⁸

To our knowledge, no epidemiologic studies have shown this relationship

Children with darker skin have a higher prevalence of having poor bone health and rickets^17,69,70

Low maternal 25(OH)D concentrations during pregnancy are associated with decreased bone mineral content in children at 9 years of age²⁹
Vitamin D deficiency in early life is associated with rickets, mild respiratory distress, weak muscle tone, decreased calcium and increased parathyroid hormone levels⁷¹

Multiple sclerosis (MS)

Increased sun exposure during early life is associated with a decreased risk of MS⁷²
MS relapse is inversely associated with UV exposure and 25(OH)D levels⁷³

Indian and Pakistani immigrants who enter the UK between 0–4 years of age are at increased risk of having MS⁷⁴
Second-generation Afro-Caribbean immigrants in the UK are associated with an increased MS risk⁷⁵

Data pooled from 4 countries shows that spring births are associated with an increased MS risk and fall births are associated with a decreased MS risk⁷⁶

Having white skin lowers the prevalence of MS disability⁷⁷

Consumption of fish 3–4 times a week is associated with a decreased MS risk⁷²
Diets low in fish but high in meat and dairy products are associated with an increased prevalence of MS⁷⁸
Intake of vitamin D from supplements is inversely associated with MS risk⁷⁹

Schizophrenia

Increased sun exposure is associated with decreased risks of having schizophrenia, and schizophrenia-induced symptoms are weaker and less regular⁸⁰

Second-generation immigrants from Morocco and Surinam to the Netherlands are associated with an increased risk of schizophrenia⁸¹
Afro-Caribbean immigrants to the UK are associated with an increased risk of schizophrenia⁸²

Data pooled from 6 countries shows that winter births are associated with an increased incidence of schizophrenia^{83, 84}

Having black skin may be associated with an increased incidence of schizophrenia⁸⁵

Vitamin D supplementation during the first year of life lowered the risk of developing schizophrenia in males, but not females⁸⁶
Maternal 25(OH)D was not a risk factor for schizophrenia. But the results in the black subgroup raise the possibility that below a certain threshold low levels of 25(OH)D may be associated with an increased risk of schizophrenia⁸⁵

Type 1 diabetes

Monthly sunshine availability is inversely associated with having type 1 diabetes⁸⁷

Children who migrated to an area prevalent in diabetes (northern region) had a greater risk of developing type 1 diabetes⁸⁸

Winter and spring births are associated with higher frequency of type 1 diabetes^89–91 than summer births⁹¹

Children with black skin are at a higher risk of having type 1 diabetes than children with white skin⁹²

In a meta-analysis, vitamin D supplementation was associated with a decreased risk of type 1 diabetes⁹³
Children who consumed vitamin D supplements had an 80% lower risk of having type 1 diabetes⁵⁵
Use of cod liver oil by mothers during pregnancy and infants in the first year of life lowered the infants' risk of developing type 1 diabetes⁵⁶

Relationship Between Vitamin D During Perinatal Development and Health

Vitamin D Effects on Heart Disease

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References

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