Complications

Complication
Timeframe
Likelihood
long term
high

Inadequately treated or untreated patients will have megaloblastic anaemia, leukopenia, and thrombocytopenia.

long term
high

Insufficient folate in pregnant women increases the incidence of fetal NTDs.[20][60][61]​​​

There is conclusive evidence that folic acid supplementation pre-conceptually and during pregnancy reduces the incidence of fetal NTDs.[19][20][21]

Guidelines recommend pre-conception folic acid supplementation at a dose of 400-800 micrograms/day for the prevention of NTDs in women who are planning to conceive or who are capable of becoming pregnant.[34][35][36]

US recommendations vary from 400 to 800 micrograms/day depending upon factors such as diet, inclusion of food fortified with folic acid, socio-economic status, and individual medical history.​ NIH: dietary supplement fact sheet - folate Opens in new window

Higher folic acid doses (up to 5 mg/day) may be recommended for certain at-risk groups pre-conceptually and during the first 12 weeks of pregnancy.[34][39]

Spina bifida and neural tube defects

long term
high

Initiation of folic acid therapy may mask neuropathy and cognitive impairment in underlying vitamin B12 deficiency.[66][67][68] This can be prevented by prompt diagnosis and treatment of vitamin B12 deficiency before instituting folic acid therapy.

Vitamin B12 deficiency

long term
low

Moderate elevation of plasma homocysteine is associated with cardiovascular disease, stroke, and venous thrombosis.[62][63]

Although folic acid supplementation may reduce plasma homocysteine levels, there is insufficient evidence to show that homocysteine-lowering interventions can reduce the risk of cardiovascular and cerebrovascular diseases.[64][65]

variable
low

Low serum folate level is associated with a higher risk of developing schizophrenia spectrum disorders.[69]

One meta-analysis identified significantly lower serum folate levels in patients with a first episode of psychosis compared with healthy controls.[70]

One randomised placebo-controlled trial found that vitamin B12 and folic acid supplements reduced the negative symptoms of schizophrenia in patients with low-functioning folate hydrolase 1 polymorphisms.[71]

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