Folate and vitamin B12 deficiencies are detected in pregnant mothers in Tarragona province

The Unit of Preventive Medicine and Biostatistics of the URV and IISPV have carried out a study to investigate folic acid supplementation patterns in pregnant women in Tarragona province and their status in folate and vitamin B12. The study of 831 pregnant women has shown that only 36% of them adhere to folic acid supplementation recommendations and low status in folate and vitamin B12 was detected in almost half of the women at some point of pregnancy. Deficiencies in these vitamins, essential for foetal development, can cause miscarriage, malformations and other health problems in mothers and their children.

Folic acid and vitamin B12 are essential nutrients for a successful pregnancy and for optimal maternal and child Health. The former is the synthetic form of folate, vitamin B9, found in supplements. Folates are found in green leafy vegetables, legumes, nuts and some meats and is especially crucial for the nervous and cardiovascular systems and key cellular division processes during pregnancy. Vitamin B12, or cobalamin, also plays a key role in the nervous system and DNA synthesis, among others. Both vitamins are vital during the foetal developmental process, from conception until birth. Deficit in either of these vitamins is a risk factor for both maternal and child Health, and can cause miscarriage, grave foetal malformations, deficiency and anaemia in late pregnancy as well as adverse child health.

“Although pregnant women are recommended to take folic acid supplements, they often do not receive this advice until their first prenatal check-up”, Michelle Murphy, researcher from the Department of Basic Medical Sciences, URV and researcher on this project, points out. Prenatal care guidelines recommend daily supplementation with 400 µg of folic acid from 1 month before conception until the end of the first trimester of pregnancy. However, the first prenatal medical check-up usually occurs weeks or even months after conception. “For this reason, many women are unaware of the importance of folic acid supplementation before becoming pregnant”, Murphy says.

The Unit of Preventive Medicine and Biostatistics of the URV and IISPV have carried out a study to investigate folic acid supplementation patterns in pregnant women in Tarragona province and their status in folate and vitamin B12. The study of 831 pregnant women has shown that only 36% of them adhere to folic acid supplementation recommendations and low status in folate and vitamin B12 was detected in almost half of the women at some point of pregnancy. Deficiencies in these vitamins, essential for foetal development, can cause miscarriage, malformations and other health problems in mothers and their children.

Folic acid and vitamin B12 are essential nutrients for a successful pregnancy and for optimal maternal and child Health. The former is the synthetic form of folate, vitamin B9, found in supplements. Folates are found in green leafy vegetables, legumes, nuts and some meats and is especially crucial for the nervous and cardiovascular systems and key cellular division processes during pregnancy. Vitamin B12, or cobalamin, also plays a key role in the nervous system and DNA synthesis, among others. Both vitamins are vital during the foetal developmental process, from conception until birth. Deficit in either of these vitamins is a risk factor for both maternal and child Health, and can cause miscarriage, grave foetal malformations, deficiency and anaemia in late pregnancy as well as adverse child health.

“Although pregnant women are recommended to take folic acid supplements, they often do not receive this advice until their first prenatal check-up”, Michelle Murphy, researcher from the Department of Basic Medical Sciences, URV and researcher on this project, points out. Prenatal care guidelines recommend daily supplementation with 400 µg of folic acid from 1 month before conception until the end of the first trimester of pregnancy. However, the first prenatal medical check-up usually occurs weeks or even months after conception. “For this reason, many women are unaware of the importance of folic acid supplementation before becoming pregnant”, Murphy says.

The Reus-Tarragona Birth Cohort Study (RTBC) is the biggest study on folate and B12 status in pregnant women in high income countries to date. The research team monitored status in these vitamins in 831 women, receiving prenatal care in the University Hospitals Sant Joan de Reus and Hospital Joan XXIII de Tarragona, from very early pregnancy until birth. The study collected data on supplementation patterns of the women and measured their status in folate and cobalamin, at 5 different time points of pregnancy.

Folate status can be measured in 2 different ways: measuring plasma folate, that is, the level of B9 in blood; or measuring red blood folate concentration, indicative of the amount of the vitamin contained within the red blood cells. The former measurement, plasma folate, is susceptible to fluctuations due to recent changes in the diet, in a matter of hours. The latter measurement, red blood cell folate concentration, offers a more realistic idea of long term B9 status. The study has revealed that 47% of the pregnant women studied had red blood cell folate status below the level recommended by the WHO for the prevention of foetal developmental anomalies. Measuring plasma folate, the research team identified very low levels of this vitamin in 5% of the women during early pregnancy and in 25% by late pregnancy.

Furthermore, the researchers observed that more than 16% of the mothers in the study had the variant form of a genetic polymorphism associated with increased requirements of folic acid. This genotype, occurring frequently in Southern Europe, causes greater propensity in women – and in men – to low reserves in this vitamin that is so important during pregnancy. “There is no reason for alarm, but the message is that we need to adhere to recommendations to take folic acid supplements”, Murphy states. In parallel, the results of the study show that even though 80% of the women planned their pregnancy, only 36% took folic acid before becoming pregnant.

Regarding vitamin B12, low status was detected in 7% of the women at their first prenatal check-up. This proportion increased substantially in subsequent check-ups, with 44% of the women having low cobalamin status by the end of pregnancy. “Historically it has been considered that low B12 status in pregnant women is due to the higher demand for this vitamin for placental function and foetal development and growth”, Murphy explains. However, the URV researcher points out that this explanation is only true for 35% of the cases with low status in the vitamin in late pregnancy. The researcher alerts to the false belief that the diet covers everything in Mediterranean countries: “We have shown that deficiency in this vitamin occurs in sectors of the population, generally considered low risk”.

Folic acid supplementation during pregnancy is so important in the prevention of foetal developmental anomalies that more than eighty countries around the world have implemented the mandatory fortification of flour with folic acid, to guarantee its supply to all women. European countries have not implemented this policy, but they haven’t intensified their campaigns to raise awareness in women of reproductive age of the importance of folic acid supplementations. Michelle Murphy states that more research is required in this area and claims that media campaigns are necessary to raise awareness in the population of the importance of folic acid supplementation before and during pregnancy: “They are not perfect because they never reach everyone, but they have been shown to work in other countries”.

Reference: Santos-Calderón LA, Cavallé-Busquets P, Ramos-Rodríguez C, Grifoll C, Rojas-Gómez A, Ballesteros M, Ueland PM, Murphy MM. Folate and cobalamin status indicators, modulators, interactions and reference ranges from early pregnancy until birth. The Reus-Tarragona Birth Cohort. Am J Clin Nutr 2024; Sep 24: doi: 10.1016/j.ajcnut.2024.09.015.

The Reus-Tarragona Birth Cohort Study (RTBC) is the biggest study on folate and B12 status in pregnant women in high income countries to date. The research team monitored status in these vitamins in 831 women, receiving prenatal care in the University Hospitals Sant Joan de Reus and Hospital Joan XXIII de Tarragona, from very early pregnancy until birth. The study collected data on supplementation patterns of the women and measured their status in folate and cobalamin, at 5 different time points of pregnancy.

Folate status can be measured in 2 different ways: measuring plasma folate, that is, the level of B9 in blood; or measuring red blood folate concentration, indicative of the amount of the vitamin contained within the red blood cells. The former measurement, plasma folate, is susceptible to fluctuations due to recent changes in the diet, in a matter of hours. The latter measurement, red blood cell folate concentration, offers a more realistic idea of long term B9 status. The study has revealed that 47% of the pregnant women studied had red blood cell folate status below the level recommended by the WHO for the prevention of foetal developmental anomalies. Measuring plasma folate, the research team identified very low levels of this vitamin in 5% of the women during early pregnancy and in 25% by late pregnancy.

Furthermore, the researchers observed that more than 16% of the mothers in the study had the variant form of a genetic polymorphism associated with increased requirements of folic acid. This genotype, occurring frequently in Southern Europe, causes greater propensity in women – and in men – to low reserves in this vitamin that is so important during pregnancy. “There is no reason for alarm, but the message is that we need to adhere to recommendations to take folic acid supplements”, Murphy states. In parallel, the results of the study show that even though 80% of the women planned their pregnancy, only 36% took folic acid before becoming pregnant.

Regarding vitamin B12, low status was detected in 7% of the women at their first prenatal check-up. This proportion increased substantially in subsequent check-ups, with 44% of the women having low cobalamin status by the end of pregnancy. “Historically it has been considered that low B12 status in pregnant women is due to the higher demand for this vitamin for placental function and foetal development and growth”, Murphy explains. However, the URV researcher points out that this explanation is only true for 35% of the cases with low status in the vitamin in late pregnancy. The researcher alerts to the false belief that the diet covers everything in Mediterranean countries: “We have shown that deficiency in this vitamin occurs in sectors of the population, generally considered low risk”.

Folic acid supplementation during pregnancy is so important in the prevention of foetal developmental anomalies that more than eighty countries around the world have implemented the mandatory fortification of flour with folic acid, to guarantee its supply to all women. European countries have not implemented this policy, but they haven’t intensified their campaigns to raise awareness in women of reproductive age of the importance of folic acid supplementations. Michelle Murphy states that more research is required in this area and claims that media campaigns are necessary to raise awareness in the population of the importance of folic acid supplementation before and during pregnancy: “They are not perfect because they never reach everyone, but they have been shown to work in other countries”.

Reference: Santos-Calderón LA, Cavallé-Busquets P, Ramos-Rodríguez C, Grifoll C, Rojas-Gómez A, Ballesteros M, Ueland PM, Murphy MM. Folate and cobalamin status indicators, modulators, interactions and reference ranges from early pregnancy until birth. The Reus-Tarragona Birth Cohort. Am J Clin Nutr 2024; Sep 24: doi: 10.1016/j.ajcnut.2024.09.015.