Chapter 5 Vitamin B12 in pregnancy – preparing for a healthy child To shame what is strong, God has chosen what the world counts as weakness. He has chosen things low and contemptible, near nothings, to overthrow the existing order. 1 Corinthians 1:27b to 30 Chapter 5 Vitamin B12 in pregnancy – preparing for a healthy child page 103 Figure 5-1 Preventive programme summary 4 to 6 months before pregnancy: Routine blood test for: FBC + B12 + folic acid, serum ferritin, fasting blood sugar, TSH - T3 - Mother and Father should: T4, LFT + U+E, Lipid/Vitamin D/AM Cortisol Stop smoking (CO + CN poisoning). (if indicated). Reduce alcohol consumption. Follow up one- to three-monthly as required. Follow a healthy balanced diet. Newborn: Withdraw and stop any harmful or unneeded prescription medication. Routine B12 and folic acid screening test in thee newborn, along with current practice of Guthrierie Avoid stress and have adequate rest and leisure and phenylketonuria. activities. Commence without delay optimum replacementent therapytherapy Identify vegetarian and vegan would-be mothers, for any of the above deficiencies diagnosed. advise appropriately and follow them up monthly. Achieve these beneficial results: Avoid these potential problems: Baby advanced neurologically and physically Hypotonia (floppy baby syndrome); (milestones); cleft lip; cleft palate; Down Syndrome; Avoids many neurological and psychiatric diseases in Neural tube defects (NTDs); Spina Bifida; later life: impact on dementia and cancer; Attention Deficit Hyperactivity Disorder (ADHD); foetal Mother enjoys pregnancy and breast-feeding without alcohol spectrum disorder (FASD); Meningocele. fatigue or depression; Mother avoids miscarriages, haemorrhage, postnatal Baby continues to receive B12 and folic acid via breast depression, hair loss, fainting, eclampsia and morning milk – and maternal bonding achieved. sickness during pregnancy. Chapter 5 Vitamin B12 in pregnancy – preparing for a healthy child page 104 Advance preparation for a healthy pregnancy In this chapter we explain that women contemplating pregnancy should be tested for vitamin B12 deficiency and supplemented if necessary just as they are currently for folate (folic acid). Vitamin B12 is completely safe for adults, for pregnant women, for foetuses and babies, for small children, for any age in fact. Lack of vitamin B12 presents a serious risk for the health of both mother and child. It is vital to provide an optimum vitamin and nutritional status in the mother to achieve gene expression correctly in the neonate. Couples preparing to conceive should consider all factors illustrated in the Preventive Programme Summary (Figure 5-1). Vitamin B12 is needed for folate metabolism in the body which leads in various steps to compounds necessary for the synthesis of DNA (which contains the instructions for all life processes) and the correct functioning of every cell in the human body (see Figure 9-1). It is also needed to convert homocysteine to methionine, which in turn leads to production of S-adenosyl methionine (SAMe) used in building thousands of compounds and proteins needed for healthy cells, tissues and organs. Vitamin B12 has wide-ranging effects on fertility, the health of the mother during pregnancy, the health of the child as embryo, neonate, infant and into later life. Low vitamin B12 levels in pregnant women have been linked to increased risk of early and recurrent miscarriage, premature births and low birth weight (Obeid et al., 2017). They have also been linked to increased risk of having a child with congenital heart defects and hyperhomocysteinaemia in the mother, leading to risk of cardiovascular problems in both mother and child in later life (Verkleij-Hagoort et al., 2006). Most importantly, vitamin B12 deficiency can lead to functional folic acid deficiency (because of the interaction between the two vitamins) which is well known to cause neural tube defects (NTDs). The following summarises some key points regarding vitamin B12 in pregnancy: 1. “Both folate and cobalamin [B12] deficiency have been implicated in recurrent fetal loss and fetal neural tube defects” at birth (Hoffbrand, 2018, pp. 701-702). Folate deficiency is now rare due to dietary supplementation, but B12 deficiency is largely ignored. 2. Vitamin B12 and folic acid (together) lower homocysteine in both mother and baby, and prevent future cardiovascular disease risk. 3. “Long-term nutritional cobalamin deficiency in infancy leads to poor brain development and impaired intellectual development. In infancy there may be feeding difficulties, lethargy, and coma” (Hoffbrand, 2018, p. 701). Continued vitamin B12 deficiency, if left untreated, may predispose a person to dementia in later life. 4. The nutritional status in mother, foetus and neonate has a substantial impact on all aspects of development at this critical time. Vitamin B12 is a methyl donor for DNA and gene expression. Providing a methyl donor in the diet, before and during pregnancy, alters the state of methylation of the offspring's DNA. This means that genes either express correctly or incorrectly. 5. Mononuclear DNA damage is increased in children and their mothers as a result of vitamin B12 deficiency (Minnet et al., 2011). As well as the importance of vitamin B12 in enabling genes to turn on and off (vital for correct development of the child), the donated methyl groups appear to be important in preventing damage to DNA. (The importance of nutrition in epigenetic alterations in the embryo is discussed in Wu et al. (2004)). Chapter 5 Vitamin B12 in pregnancy – preparing for a healthy child page 105 6. Vitamin B12 is needed for folate metabolism, and interaction of the two vitamins is essential for the conversion of homocysteine to methionine, for the synthesis of purines and pyrimidine, for methylation reactions, and for the maintenance of cellular levels of folate. One consequence of vitamin B12 deficiency is raised homocysteine which may lead to pregnancy complications. Research has suggested that maintaining optimal vitamin B12 status may be crucial to lowering homocysteine levels in the mother (Molloy et al., 2002). Birth defect preventive programme: vitamin B12 supplementation A couple planning to conceive should consider healthy lifestyle choices and have blood test checks for deficiencies and then appropriate supplementation. It is well understood that pregnant mothers usually need nutritional supplements, because of the high nutritional demands of pregnancy. We recommend that mothers-to-be should have vitamin B12 supplementation to ensure optimal health of the foetus and baby. There are many different causes of B12 deficiency (see Chapter 2) but the most common are limited dietary intake and problems with absorption (Hoffbrand, 2012). If the mother is not getting enough vitamin B12, then the foetus will not get enough vitamin B12 through the placenta and umbilical cord. Case 5-1 Teenage female: delayed periods In an unusual case, the mother of a fifteen-year-old girl requested a home visit. Her concern was that although her daughter had the normal breast development of a teenager, so far there had been no sign of her starting a monthly period. The hospital performed a vaginal examination and identified that she had only a rudimentary vagina. There was no visible or palpable cervix or uterus. An ultrasound scan confirmed the above abnormality. This mother and several members of her family had been diagnosed with vitamin B12 deficiency in previous years. Sadly, compliance to regular B12-replacement therapy had been very poor. We suggest that non-compliance with both folic acid oral supplements and B12 injections by the mother during pregnancy resulted in this birth defect (mononuclear DNA damage) which would have been totally preventable, since the treatment was preventive rather than reactive medicine. Vitamin B12 and fertility It is well known that severe vitamin B12 deficiency (as in pernicious anaemia, for example) leads to temporary infertility (NHS, 2016a). Research has shown that prolonged B12 deficiency results in infertility by causing changes in ovulation or development of the ovum or changes leading to defective implantation (Bennett, 2001). Vitamin B12 is necessary for the proper functioning of the endocrine system, which is necessary both for preparing a woman’s body for pregnancy, and for maintaining the pregnancy. A significant number of women diagnosed with vitamin B12 deficiency in our Practice also suffered from hormonal disturbances (see, for example, Cases 7-5 and 7-6 in Chapter 7). Chapter 5 Vitamin B12 in pregnancy – preparing for a healthy child page 106 Case 5-2 Cardiomyopathy and mitral-aortic defect in pregnant mother Hayley Matthews (born 1979) presented in February 2011 with cardiomyopathy/mitral-aortic regurgitation and closure of the ventricular tunnel. She was concerned about getting pregnant because of her own frailty and likely heart defects in the baby. Her blood serum level was found to be 283 ng/L (normal range 350-900 ng/L) and replacement therapy commenced. She rapidly gained strength, and when she wanted a baby folic acid supplements were added. Hospital cardiology clinics were surprised that she had a healthy pregnancy and no post-natal problems. Her baby was born in July 2013 healthy and with no heart defect. Case 5-3 Vital role of vitamin B12 and folic acid in fertility Donna Dyson already had an 11-year-old daughter. For the previous three years or so she had been trying for a baby but unfortunately had been having irregular periods, or no periods for months. She suspected some early miscarriages, and experienced extreme fatigue, headaches, mood swings and depression, and fainting attacks. She was losing hope of becoming pregnant again. A routine blood test confirmed vitamin B12 deficiency, and we commenced her on B12-replacement therapy. Following the initial loading doses, she was given weekly (and subsequently monthly) injections as part of ongoing treatment programmes. Her regular periods returned; her fatigue symptoms diminished, and she became energetic. Folic acid was commenced and given alongside vitamin B12 as she was very keen to have another child.