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Maternal nutrition during pregnancy and offspring cognitive development
Nutrition may be the most important environmental factor affecting fetal development. Sufficient intake of essential nutrients is critical for the normal development of every physiological function including growth, cell differentiation, and maintenance, such as the ability for each cell to exist in a steady-state. Malnutrition in utero impairs the development and later functioning of the brain. Although restoration of nutrition can sometimes ameliorate these impairments, should malnourishment occur during critical central nervous system development periods, permanent changes to cognition can occure due to physiological, morphological, and neurochemical alterations.

Omega 3 fatty-acids
All cell membranes require long-chain polyunsaturated fatty acids (LCPUFAs) which are related to many aspects of brain functioning including neurotransmission, brain blood flow and neuronal membrane fluidity. Of the LCPUFAs, Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) are of particular importance to the brain and are critical for the prenatal development of cortical structure and functioning. Since production of DHA in the fetus and placenta is inadequate for the rapidly developing brain, maternal DHA must be supplied through dietary intake. Increased maternal consumption of fish, which is a source of EPA and DHA, during pregnancy is associated with positive cognitive outcomes in the fetus. Pregnant mothers who ate fish 1-3 times per week had infants who scored higher on developmental indices of language comprehension, social activity, and visual motor skills. Another study of more than 11,000 participants observed an increased risk of poor development amongst mothers who ate less seafood when pregnant. Whereas, the offspring of mothers with higher seafood consumption were more pro-social and had higher verbal intelligence, fine motor, and social development scores at age 8 years. Randomized clinical-controlled trials of maternal DHA supplementation have also found positive fetal cognitive outcomes. Prenatal DHA has been shown to improve reading and spelling at age 7, as well as attention and executive function of the child at preschool age. One study found no improvement in offspring cognition in response to DHA supplementation at 18 months of age, although there was a reduced risk of delayed cognitive development. However, evidence is mixed on the benefits of prenatal fish consumption or EPA and DHA supplementation with some research showing no differences or negative associations with arithmetic at age 7. It should also be noted that fish may contain mercury and when consumed in excess is neurotoxic to the fetus, however, evidence is also mixed as to what level of prenatal mercury exposure from fish impairs later cognition.

Iodine
Iodine deficiency during pregnancy has direct, negative and irreversible effects on the cognition of the child. Thyroid hormones, which require iodine, are essential for neurological development, therefore, prenatal iodine deficiencies lead to fetal hypothyroidism and permanent cognitive deficits, such as intellectual disability and primitive reflexes. One study showed children of mothers who had mild to moderate iodine deficiency during pregnancy were more likely to have a lower IQ at age 8, and impaired reading comprehension and accuracy at age 9. Prenatal iodine deficiency is also associated with a lower mental development and psychomotor index at 18 and 24 months, poorer working memory up to the age of 4, and impaired spelling up to age 9.

Folate
Low folate levels in pregnant mothers is related to neural tube defects, where the neural tube fails to close during embryonic development, which can cause significant cognitive disability.

Low folate intake during pregnancy (defined as less than 400μg per day) appears to be connected with a lower mental, but not psychomotor, development index of the offspring at age 1-12 months. However, this was only observed in carrier mothers of the Methylenetetrahydrofolate reductase 677 TT genotype. Another study found that offspring’s receptive language scores increased by 1.6 points per 600μg a day increase in folate. Nonetheless, research is mixed with some finding no association between maternal folate intake and future cognition of the child.

Supplementing with folic acid during pregnancy yields more consistent positive associations with offspring cognition. Greater gross motor development and less risk of impaired psychomotor development has been observed in children at age 3, but only if they were African-American. Similarly, children at age 3 had a reduced probability of moderate and severe language delays. Mothers who supplemented with folic acid also had offspring who scored higher in verbal ability, verbal-executive function, and motor skills at 4 years of age, and better attention at 11 years of age.

Iron
The most common nutrient deficiency is iron deficiency, which affects 30-50% of pregnant women. Iron is important for fetal neurodevelopment with deficiencies potentially altering brain architecture, myelination, and neurotransmitter systems which causes permanent abnormalities despite reintroducing iron. Gene structure and transcription may also be altered by iron deficiency causing long-term neurological problems.

Increases in maternal hemoglobin concentration during the ninth month of pregnancy has been associated with better school performance of the offspring at age 14 and 16. Research has also observed that non-anaemic mothers, compared with anaemic mothers, have children who perform better at school, whereas the offspring of anaemic mothers have lower Bayley Scale of Infant Development scores at 6 months of age.

Vitamin D
Vitamin D is critical to fetal neurodevelopment. Animals studies show low prenatal vitamin D levels affects neurotrophin signaling, expression of neurotrophin receptor p75, neurotrophic factor, and nerve growth factor. Impaired nerve growth factor synthesis and cell proliferation, larger ventricles, and decreased expression of genes related to neuronal architecture have also been observed in prenatal vitamin D deficiency.

Human research has found that higher vitamin D status during pregnancy is related to higher offspring mental and psychomotor scores during early childhood, as assessed by the Bayley Scale of Infant Development. Low prenatal vitamin D status at 18 and 32 weeks of pregnancy has also been associated with a higher incidence of language impairment. However, the available evidence is undecided.

Vitamin B12
Vitamin B12 is fundamental for the developing human brain. Developing chick embryos deficient in B12 have central nervous system abnormalities. In humans, mothers highly deficient in B12 have offspring which may develop involuntary movements, possibly due to basal ganglia abnormalities. Further, methionine synthase is an enzyme dependent on B12 intake and deficiencies are linked with disrupted myelination in newborns.

In observational research, pregnant mothers with the lowest B12 concentrations had children with poorer sustained attention and short term memory at age 9 compared to mothers with the highest intake. However, no correlation with intelligence and visual recognition were observed. Another study conducted in Mexico found low maternal B12 consumption was linked with offspring that scored lower on Bayley’s Mental Development Index but not Psychomotor Development Index at age 1-12 months. Offspring receptive language, but not visuo-motor abilities, has also been found to be inversely related to maternal B12 intake, at 3 years of age. The same study also found no association between B12 intake and receptive language, verbal and non-verbal intelligence at age 7 years, although there was a ~50% attrition. A UK study of adequately nourished mothers found a significant correlation between certain maternal genetic variants connected with plasma B12 concentrations and the IQ of offspring.