Relationship Between Vitamin D During Perinatal Development and Health

Abstract and Introduction

Abstract

Vitamin D deficiency is a highly prevalent condition that is present in 40% to 80% of pregnant women. There is emerging evidence that vitamin D deficiency may be a risk modifying factor for many chronic diseases, including osteomalacia, rickets, multiple sclerosis, schizophrenia, heart disease, type 1 diabetes, and cancer. Heightened susceptibility to these diseases may originate in early life during the development of tissue structure and function. It is suspected that biologic mechanisms can "memorize" the metabolic effects of early nutritional environment through fetal and neonatal imprinting. Inadequate vitamin D nutrition during perinatal life may establish a poor foundation that may produce long-term threats to human health. This review summarizes the risks of vitamin D deficiency for human health and provides the current vitamin D recommendations for mothers and their newborns.

Introduction

The United Nations Standing Committee on Nutrition has proposed that a window of opportunity exists from prepregnancy to 24 months of a child's life during which nutrition can affect the structural and functional development of an organism.^[1] Such changes in structural or functional development can result in long-term consequences on human health.^[2] Vitamin D, a fat-soluble molecule acquired through exposure to sunlight or diet, has been identified as a steroid hormone precursor that modulates long-term programming of human health. Low vitamin D intakes during perinatal development have traditionally been linked to poor bone health. However, scientists are beginning to realize that vitamin D deficiency during perinatal development is a risk modifying factor for a range of diseases, including multiple sclerosis, schizophrenia, heart disease, type 1 diabetes, and cancer.

Historically, humans obtained most of their vitamin D through sun exposure. However, in contemporary society, sun avoidance and the use of topical sunscreen are strongly encouraged because of the association of sun exposure with skin cancer. To sustain adequate vitamin D levels in such an environment, oral consumption of vitamin D is required. However, very few foods in nature contain vitamin D. Fish (e.g., salmon, tuna, and mackerel) and fish liver oils are among the best sources.^[3] Small amounts of vitamin D are found in beef liver, cheese, egg yolk, and some forms of mushrooms.^[3] Given the importance of vitamin D and its lack of availability from the sun and diet, vitamin D supplementation is required. This need is even more significant during sensitive stages of development, such as the prenatal and neonatal stages of life.

The purpose of this review is to illustrate that inadequate vitamin D nutrition during perinatal development is a threat to human health and to provide health care professionals with current recommendations for vitamin D supplementation.

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

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