Sheldon Zablow, MD

Author of
Your Vitamins Are Obsolete

B-Vitamin Deficiency Based Maternal Mortality —A Public Health Challenge

Mar 09, 2022 by Dr. Sheldon Zablow

The foundation of the health of the public and of public health programs is optimal nutrition. The foundation of nutrition is the ample intake of the essential vitamins, the most essential of which are B12 and folate. Interventions implemented to improve health across the lifecycle are based on getting the necessary nutrients to those populations at risk. Any factor—dietary, monetary, genetic, environmental, supplemental, iatrogenic—that contributes to a deficiency of either of these two vitamins will reduce the response to any public health or medical intervention. A few examples follow.

It is recommended that all individuals over 65 years receive a pneumococcal vaccine to reduce pneumonia mortality. When people have a B12 and/or folate deficiency, the protective antibody response to the vaccine can be reduced by 50% leaving millions at risk for disability and early death. If someone is at risk for osteoporosis and is instructed to take plenty of vitamin D, C and calcium, they will still develop brittle bones if they have a B12 or folate deficiency. When a woman is pregnant, she is at the highest requirement for B12 and folate in the human lifecycle. A deficiency of these vitamins increases the risk of maternal disability and death due to pre-eclampsia, abruptio placenta, gestational diabetes, heart attacks, strokes, thromboemboli, and post-partum depression.

Understanding the connection between B vitamin deficiencies and maternal illness requires some understanding of basic cell chemistry. The bioactive (natural) forms of B12 and folate are partner vitamins because both are required in optimal amounts for each to work helping human cells function at peak performance. When there is a B vitamin deficiency, the first symptom patients complain of is fatigue because all cells are functioning in a suboptimal way—they are fatigued.

Normal cells produce a toxic waste called homocysteine which, at elevated levels, becomes harmful. This by-product is usually converted by B12 and folate into non-toxic molecules used to make DNA, proteins, energy molecules, nerve cells, and natural antidepressants(neurotransmitters). When B vitamins are lacking, homocysteine increases causing inflammation of the cells lining all blood vessels. Excess homocysteine also leads to thicker more viscous blood, heightening the risk of blood clots and the resultant maternal morbidity and mortality due to the illnesses mentioned above.

A major public health intervention in 1998 was the required fortification of grains with folic acid—the artificial form of folate (B9). This requirement reduced the occurrence of spinal birth defects by a significant percentage. Some women, however, are genetically unable to convert the artificial vitamins in prenatal supplements into the natural forms found in food, e.g., they lack the MTHFR enzyme that converts synthetic folic acid into natural L-methylfolate. This leaves them at greater risk of fatal maternal complications and their children at risk of birth defects or the less obvious developmental and academic delays. In these genetically impaired women, fortification by the artificial B9 is of no use. Most physicians incorrectly assume prenatal vitamins are reducing risks in all pregnancies when they are not.

Most physicians also assume incorrectly that the body stores three years’ worth of B12 and that prenatal supplements prescribed allow enough B vitamins to be absorbed as needed. These are significant and at times fatal miscalculations. The body cannot store the water soluble B12 and many multivitamin supplements are poorly made, poorly absorbed, poorly dosed and poorly metabolized leaving women and their newborns in unnecessary peril.

Anything that decreases B12 or folate is a significant public health risk for pregnant women and their newborns. Some women have a dietary deficiency of B vitamins because they are voluntary or involuntary vegans with limited B12 intake. An involuntary vegan has food insecurity with a reduction in access to sources high in B12 and folate. If a woman has obesity as a health challenge, excess adipose tissue uses up and lowers folate. This is why women with increased BMI have greater maternal mortality.

Air and ground pollution as well as exposure to secondhand cigarette smoke increases maternal mortality by lowering B12 and folate because these vitamins are consumed detoxifying chemical exposures. Studies have shown that B12 and folate can provide protective benefits against toxins such as BPA and mercury.

Many physicians are unaware that women are being prescribed medications that make a B vitamin deficiency even unhealthier. Metformin prescribed to reduce the risk of gestational diabetes lowers B12 and folate as does the GERD medications prescribed for acid reflux. NSAIDs reduce B12 and/or folate as well as the use of nitrous oxide anesthesia.

Any hormones prescribed before pregnancy such as birth control pills (BCP) will deplete the body of folate which is why BCP or hormone replacement therapy increase the risk of blood clots in the brain (strokes), in the coronary arteries (heart attacks), or the lungs (pulmonary emboli).

Imagine a not infrequent scenario of a pregnant woman who is vegan with slight obesity, is exposed to secondhand smoke, has a MTHFR deficiency, is prescribed metformin, NSAIDs, and GERD medications. She will start her delivery at a disadvantage with eight factors contributing to B12 and folate deficiency resulting in an increase in the prospect of maternal morbidity and mortality.

Women at risk for maternal disability and death due to B12 and folate deficiencies are an increasing public health challenge. MTHFR deficiencies are hiding folate deficiencies putting new mothers and newborns at risk. All perspective mothers and their physicians should know their MTHFR status just as they do their blood type. The inexpensive solution for reducing these threats is to make sure the bioactive forms of B12 and folate are taken in the most optimal way.

I have included references below:

Thelma E. Patrick, et al., Homocysteine and Folic Acid Are Inversely Related in Black Women With Preeclampsia 19 Apr 2004 Hypertension. 2004;43:1279–1282

“Black women have an increased risk of preeclampsia compared with white women. Plasma homocysteine is increased in preeclampsia. Homocysteine concentrations are affected by nutritional deficiencies, particularly decreased folic acid and B12, leading to increased homocysteine.”

Tate J, Bushnell C. Pregnancy and stroke risk in women. Womens Health (Lond). 2011 May;7(3):363-74.

“The women who are at the highest risk for pregnancy-related stroke are those who are over the age of 35 years; those who are of African–American race-ethnicity; and those with preeclampsia/eclampsia/gestational hypertension, thrombophilias, migraine headaches, diabetes, prepregnancy hypertension, hyperemesis gravidarum, anemia, thrombocytopenia, postpartum hemorrhage, transfusion, fluid, electrolyte and acid-base disorders and infection.”

Ghafoor S, Ali N, Salah F, Hussain SF, Zareen S. Assessment of association of Folate and Homocysteine levels with development of Preeclampsia among pregnant women. Isra Med J. 2021; 13(2): 92-95.

“The study's findings indicated homocysteine is significantly associated with the development of pre-eclampsia and could act as a potential biomarker in its detection.”

Stanger O, et al., “Clinical Use and Rational Management of Homocysteine, Folic Acid, and B Vitamins in Cardiovascular and Thrombotic Diseases,” Z Kardiol, June 2004; 93(6):439–53.

“Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25 percent of cardiovascular events.” 

Wilcken B, et al., Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003 Aug;40(8):619-25.

“We documented distinctive geographical and racial/ethnic variation in the prevalence of the 677C>T allele of the MTHFR gene among a large international sample of newborns.” “Ethnic variation was apparent among and within geographical areas. In metropolitan Atlanta, for example, TT homozygosity was common among newborns of Hispanic origin (15%)…”

Shravya Govindappagari , et al. Severe Vitamin B12 Deficiency in Pregnancy Mimicking HELLP Syndrome Case Rep Obstet Gynecol   2019 Mar 25;2019:4325647.

“Severe vitamin B12 deficiency may present with hematologic abnormalities that mimic thrombotic microangiopathy disorders such as hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.”  “Moreover, providers should consider B12 deficiency and pernicious anemia in the differential diagnosis of pregnancy-associated thrombotic microangiopathy.”

Krishnaveni, G.V., et al. Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes. Diabetologia 52, 2350–2358 (2009).

“Maternal vitamin B12 deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM.”

Kouroglou E, et al., Vitamin B12 insufficiency is associated with increased risk of gestational diabetes mellitus: a systematic review and meta-analysis. Endocrine. 2019 Nov;66(2):149-156.

“Vitamin B12 deficiency has been associated with a plethora of metabolic abnormalities, such as hyperhomocysteinaemia, insulin resistance and defective synthesis of neurotransmitters and fatty acids.” “Vitamin B12 deficiency seems to be associated with increased risk of GDM.”

Sukumar N, et al., Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes. Nutrients. 2016 Dec 1;8(12):768.

“This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia.”

Mujawar SA, et al., Study of serum homocysteine, folic Acid and vitamin b(12) in patients with preeclampsia. Indian J Clin Biochem. 2011;26(3):257-260.

“The present study found hyperhomocysteinemia and deficiency of folic acid and vitamin B12 along with increased blood pressure as a risk factor for cardiovascular disease (CVD) in preeclampsia.”

Maher A, Sobczyńska-Malefora A. The Relationship Between Folate, Vitamin B12 and Gestational Diabetes Mellitus With Proposed Mechanisms and Foetal Implications. J Family Reprod Health. 2021 Sep;15(3):141-149.

“Studies have suggested a relationship between maternal folate (vitamin B9) and vitamin B12 status and GDM risk.”

Arendas K, et al., Obesity in pregnancy: pre-conceptional to postpartum consequences. J Obstet Gynaecol Can. 2008 Jun;30(6):477-488.

“Obesity causes significant complications for the mother and fetus. Interventions directed towards weight loss and prevention of excessive weight gain must begin in the pre-conception period.” 

Singh N, Acharya N, Acharya S. Homocysteinemia: A Rare Cause of Recurrent Pregnancy Loss Coexisting with Deep Vein Thrombosis. J South Asian Feder Obst Gynae 2020;12(5):328–330

“Homocysteinemia should be considered as a possible diagnosis in a pregnant woman presenting with recurrent pregnancy loss and DVT. Early diagnosis and a simple regimen of vitamin supplementation can prevent pregnancy loss especially recurrent pregnancy loss which is physically and emotionally taxing for a couple.”

Liu C, Wang Q, Zhang Z. Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis. Arch Gynecol Obstet. 2018 Oct;298(4):697-704.

Our findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk.”

Liu F, et al., MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous Thromboembolism: A Retrospective Chart Review Study. Acta Haematol 2017;138:208-215.

“Heterozygous or homozygous MTHFR variants, especially a compound mutation, are associated with increased risk of VTE.”

Shahbazian N, et al., The evaluation of serum homocysteine, folic acid, and vitamin B12 in patients complicated with preeclampsia. Electron Physician. 2016;8(10):3057-3061. Published 2016 Oct 25.

“Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12.”

Chaudhry, S.H., et al. The role of maternal homocysteine concentration in placenta-mediated complications: findings from the Ottawa and Kingston birth cohort. BMC Pregnancy Childbirth 19, 75 (2019).

“In the high-risk subgroup homocysteine was associated with increased odds of preeclampsia.”

Li, M, et al. Prepregnancy habitual intakes of total, supplemental, and food folate risk of gestational diabetes mellitus: a prospective cohort study. Diabetes Care. 2019; 

“Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk.”

Maru L, et al., Homocysteine as Predictive Marker for Pregnancy-Induced Hypertension-A Comparative Study of Homocysteine Levels in Normal Versus Patients of PIH and Its Complications. J Obstet Gynaecol India. 2016;66(Suppl 1):167-171.

“Homocysteine levels are directly correlated with hypertension in pregnancy. The levels also correlate with the severity of hypertension and complication with preeclampsia and eclampsia. It is an easy and less time-consuming test that can be reliably be considered as the predictive marker for pregnancy-induced hypertension.”

Chen, Sha, et al.,  Homocysteine during the third trimester is a risk factor for preeclampsia: A prospective study ResearchGate  May 2020

“The variation in homocysteine level in the third trimester might be associated with preeclampsia, especially early-onset preeclampsia and severe preeclampsia, and MTHFR, folic acid and vitamin B12 might be the three critical factors responsible for the changing homocysteine levels during pregnancy.”

Kim, B., et al.,(2020). Adverse effects of prenatal mercury exposure on neurodevelopment during the first 3 years of life modified by early growth velocity and prenatal maternal folate level. Environmental Research, 191, 109909.

“Prenatal mercury exposure adversely affects infant neurodevelopment and is associated with rapid growth during the first 3 years of life. This effect was limited to children whose mothers had low prenatal folate levels, suggesting a protective effect of folate against developmental neurotoxicity due to mercury exposure and rapid catch-up growth.”

Dolinoy D.C., Huang D., Jirtle R.L., Maternal Nutrient Supplementation Counteracts Bisphenol A-Induced DNA Hypomethylation in Early Development, Proc Natl Acad Sci U.S.A. 2007; 104(32):13056–61.    “Thus, we present compelling evidence that early developmental exposure to BPA can change offspring phenotype by stably altering the epigenome, an effect that can be counteracted by maternal dietary supplements.”

Pregnancy Hypertension  Vol. 13, Supplement 1, October 2018, Pages S136-S137

361. Folate deficiency in pregnancy presenting with severe anaemia and thrombocytopenia: A case series

Folate requirement increases in pregnancy and deficiency is easily and rapidly treated, and does not necessarily require the administration of blood products. Adequate antenatal correction of vitamin deficiency like this avoids bone marrow suppression and helps minimize poor obstetric outcomes associated with pre-existing anaemia should haemorrhage ensue.”