ASSESSMENT OF KNOWLEDGE AND PRACTICE OF PERICONCEPTIONAL FOLIC ACID SUPPLEMENTATION AMONG CHILDBEARING AGE WOMEN ATTENDING ANTENATAL CLINICS IN ENUGU NIGERIA

CHAPTER ONE

1.         INTRODUCTION

Folic acid (vitamin B₉₎ is important in a vast number of human metabolic pathways. Examples include; interconversion of amino acids serine to glycine, conversion of homocysteine to methionine, synthesis of purines and pyrimidines, growth and healthy development of a fetus. The nutritional benefits of folic acid were first discovered by Lucy Wills in 1931 but it was finally synthesized in pure form by Bob Stroksand in 1943. Unambiguous evidence has been available for more than two decades on the effectiveness of periconceptional folic acid supplementation (PFAS) in preventing neural tube defects (NTDs). However, though this information exists a large population of its target audience (the childbearing age women) remain blissfully unaware of this very important fact.

Birth defects are documented as the leading cause of infant mortality worldwide and neural tube defects are the third leading birth defects (United States Institute of Medicine [USIM], 1998). Periconceptional folic acid supplementation, the oral ingestion of folic acid supplements of not less than 0.4mg per day; from preconception period to 12 weeks post conception has been proven to reduce the risk of occurrence and 4mg per day the risk of reoccurrence of neural tube defects. Neural tube defects are series of congenital anomalies that result as a consequence of faulty or aberrant neural tube development, which has been shown to be linked to less than optimal maternal blood folate concentration. The most common NTDs are Spina bifida and anencephaly. Spina bifida is the embryologic failure of fusion of one or more vertebral arches, sub-types of Spina bifida are based on degree and pattern of deformity. Two broad types of Spina bifida are Spina bifida occulta and Spina bifida cystica. Basically, the neonate is born with an exposed spinal cord (Pitkin, 2007). Anencephaly on the other hand is a congenital defective development of the brain with absence of bones of the cranial vault and absent or rudimentary cerebral and cerebella hemispheres, brainstem and basal ganglia. This condition is almost invariably fatal.

The neural tube is the early spinal cord found in embryo’s which forms within 28 days after conception. Due to the fact that this is very early in pregnancy most NTDs develop before women realize that they are pregnant, therefore too late for them to do anything to avert it. In developed economies though, there are a number of prenatal tests that are carried out to test for NTDs especially in those perceived to be at risk. The most commonly employed test is alpha fetoprotein (AFP). This is because abnormally high levels are recorded in open NTD cases. Other tests include amniocentesis and ultrasonography, though no one testing procedure is infallible.

The link between folate deficiency and NTDs was first suggested by Hibbard (1964). Further research was reported by Smithels (1983).  Since then, many other trials using folic acid supplements in pregnant women have been done all over the world. The results demonstrated conclusively the link between folate deficiency and increased risk of NTDs (Hoffbrand, 2001). Due to the early development of NTDs in fetuses, it is important that women in childbearing age increase their folate intake prior to conception as well as during the first 12 weeks of pregnancy. Both the United States Public Health Service and the British National Health Service (1992) recommend that women intending to become pregnant should take folate supplements of 0.4mg per day until the 12^th week of pregnancy (Mesereau and Kilker, 2004). Research has shown that a daily folate supplement of 0.4mg reduces the chance of neural tube defects by an estimated 36%; also that 4mg per day has been estimated to prevent 8 in 10 cases of NTDs provided the supplementation is started prior to conception (Wald, 2004).

1. Statement of the Problem

During pregnancy there is a marked increase in folate utilization. This is primarily as a result of increase in reactions requiring single carbon transfers, rapid rate of cell division in maternal and fetal tissues also deposition of folate in the fetus. Even though the benefits of folate to general health of the population are well documented, the current daily intake of folates among women aged 19-65 years is only 0.292mg (Butriss, 2005) a value well below the recommended daily intake (RDI) for pregnant women .The recommended daily intake for pregnant women is 0.6mg this is based on the amount that maintained erythrocyte concentrations during clinical trials (Allen, 2004).

Randomized clinical trials have shown that folic acid supplements taken prior to conception and through approximately the first twelve weeks of pregnancy lowers the risk that a genetically predisposed woman will have a baby with a neural tube defect (Hoffbrand, 2004; Taylor and May, 2008). Neural tube defects occur in approximately 0.1% of births in the United States (King, 2004). It affects 4,500 pregnancies yearly in the European Union (Tita, 2005) and approximately 0.9% of births in other countries. Neural tube defects tend to reoccur in subsequent pregnancies if aggressive periconceptional supplementation is not undertaken. Higher intake of dietary folate, and not less than 4mg daily of folic acid supplements, including higher erythrocyte folate concentrations are inversely related to the risk of neural tube defects (Weller, 1993; Shaw, Schaffer, Verlie, Morland & Haris, 1995). Clinical trials have shown that women with neural tube affected pregnancies absorb 20-25% less folate from either supplements or foods than women in the control group. The mechanism by which folate lowers the risk of NTDs is not fully understood. Presumably, women at risk have a metabolic defect that hinders folate metabolism. This affects bioavailability and impedes transport of folate and critical metabolites to the rapidly growing embryo.

Periconceptional folic acid supplementation is both simple and cost effective. This is because not only does it prevent occurrence and reoccurrence of NTDs it also ensures optimal blood folate concentration. It prevents hyperhomocystenemia (elevated blood homocysteine level) which is associated with a myriad of other health conditions. Elevated blood homocysteine has been associated with greater risk of pre-eclampsia, preterm delivery and a greater risk of low birth weight infants (Volset, 2000). A rise in incidence of abrupt placentas, spontaneous abortions and club foot were also documented. Periconceptional folic acid supplementation is very important in the case of adolescent mothers. This is because they are still growing and have increased folate needs; they easily deplete their folate stores placing both themselves and their babies at risk. Another point on its scoreboard is the fact that dietary folate is not as easily assimilated as the supplement due to reduced bioavailability.

1.2       Objective of the study

The general objective of the study was to assess knowledge and practice among childbearing age women in Enugu metropolis of Enugu State, Nigeria about periconceptional folic acid supplementation (PFAS) and its health implications.

1.2.1    Specific objectives

The specific objectives of this study were to:

1. assess knowledge, and practice among the target population of the benefits of periconceptional folic acid supplementation;

1. assess the level of knowledge amongst the target population about foods rich in folate;

1.  evaluate pattern of consumption of such foods using  24 hour dietary recall and food frequency questionnaire; and

1. correlate evidence between the variables, different antenatal clinics, private versus public.

1.3       Significance of the study

The result of this study will serve as a guide to health care providers and Nutritionists/Dietitians, on the urgent need for concerted effort on educating the target audience on the importance of periconceptional folic acid supplementation and the health implications of poor supplementation practices. The results will also show the vitamin supplementation habits of the expectant mothers and the implication of their preferred antenatal booking times. It will also fill a knowledge gap because there is a dearth of good quality studies pertaining to knowledge and practice of folate usage in the Nigerian setting. This is compounded with the fact that there is widespread ignorance on the health implications of less than optimal blood folate concentration especially during the critical periconceptional period.

CHAPTER TWO

2.0     LITERATURE REVIEW

Folate is derived from the Latin word folium which means foliage (Wardlaw, 2003; Taylor and May, 2008). This is because it is found in abundance in many green leafy vegetables including spinach. Folate is a collective name for a group of substances with a chemical structure related to pteroylmonoglutamic acid (PGA) or folic acid. The term folic acid refers specifically to the fully oxidized monoglutamate form of the vitamin that is synthesized for commercial use in supplements and fortified foods; it rarely occurs in nature. Basically two forms exist; dietary folate –folate occurring in food and synthetic folate (folic acid) which is present in dietary supplements (Kromhout, 2008).

2.1       Chemistry

Folic acid is composed of 3 large subunits; a bicyclic nitrogenous compound called pteridine, a molecule of para-amino benzoic acid and glutamic acid (a non-essential amino acid). In the course of metabolism, folic acid is converted into dihydrofolic acid (DHFA) then tetrahydrofolic acid THFA (the absorptive form of folate) which polymerizes to form various polyglutamates found in living organisms.

The molecule can vary in structure by reduction of the pteridine moiety to dihydrofolic acid or tetrahydrofolic acid (THF); elongation of the glutamate chain to form polyglutamates and substitution of 1-C units at the 5^th or 10^th positions or both positions. Folate co-enzymes are polyglutamyl forms of THF including those with methyl (-CH₃-), methylene (-CH₂-), methenyl(-CH=), formyl(-CH=O), or formimino(-CH=NH-).

2.2      Folate content of foods

Green leafy vegetables, asparagus, spinach, cabbage, organ meats, okra, wheat germ, bean sprouts, peanuts, kidney beans, avocado, papaya and black eyed peas are all good folate sources. However the folate content of orange is notably the most bioavailable. This is largely due to the stability conferred on it by the ascorbic acid (vitamin C) which is abundantly present in the fruit. Food processing and preparation destroy 50-90% of the folate in foods. Folates are very heat labile, therefore to conserve folate in green leafy vegetables, processing methods such as steaming, stir frying and microwaving are advised (Wardlaw, 2003). These methods involve limited contact with water which can leach out water soluble vitamins.

Milk also is a well known folate source. It contains up to 7 milligrams per 100grams and fermented milk products are reported to contain even higher amounts (Forssen, Jagerstad, Wigertz & Wittloft, 2000).The high level of folate is the result of additional folate production by bacteria. Folate producing ability has been reported in some bacterial species used as yogurt starter cultures. This ability varies greatly even amongst strains of the same species. Some bacteria are able to synthesize this vitamin (co-factor) by themselves from simple precursors, but some autotrophic bacteria have a strict growth requirement for folic acid (Hugenholtz, Hunik, Santos & Smid, 2000).An interesting study by Holasova, FiedLerova, Roubal & Pechacova (2004) outlines Streptococcus thermophilus as a good folate producing agent. They postulate that by careful selection of microbial strains used as starter cultures the folate content of fermented milk products can be enhanced naturally. Studies are also ongoing on the ability of healthy adults to increase their vitamin notably folate status by consuming vegetables with prebiotic qualities like the commonly consumed Venonia amygdalina (bitter leaf).

2.3       Physiology and metabolism

When naturally occurring food folate is consumed it must first be converted to the monoglutamate form by the enzyme pteropolyglutamate hydrolase, also referred to as folate conjugase or glutamate carboxypeptidase II. This is located primarily in the jejunal brush-border membrane (Halsted, 1990). The optimum pH for brush border conjugase is 6.5-7.0. After deconjugation to the monoglutamyl form, folate is transported across the membrane by a pH dependent carrier mediated mechanism (Zimmerman and Gilula, 1989). Luminal pH changes with chronic drug use (as in oral contraceptives) or diseases that alter jejunal pH can impair folate absorption (Mason, 1990). Before entry into the portal blood, folic acid undergoes reduction to THF and either methylation or formylation in mucosal cells (Gregory, 1995). The predominant form of folate in plasma is 5-methyl THF, which is primarily bound loosely to albumin with a smaller percentage bound with high affinity to folate binding protein (Stokstad, 1990). Folate transport across membranes into cells in certain tissues including kidney, placenta and choroid plexus occurs via membrane associated folate binding proteins that act as folate receptors and thereby facilitate cellular uptake of folate. Once within the cells 5- methyl THF is demethylated and converted to a polyglutamyl form. Due to the fact that folate polyglutamates do not cross the cell membranes as a result of the charge on their side chain, polyglutamylation helps sequester folate inside the cell. Tissues are limited in their ability to store folate beyond their normal requirement.

Knowledge of in vivo kinetics of a nutrient aids in understanding the requirements of that nutrient and providing insight into experimental design involving interventions to alter nutritional status. Priorities in further studies include determining the effects of pregnancy and other conditions of altered physiology, also effects of various disease states and effects of genetic polymorphism of key enzymes of folate metabolism on whole body folate kinetics.

2.4      Bioavailability of folates

Folate occurs naturally in small amounts in foodstuff. It is usually bound to glutamic acid chains. In the context of folate, bioavailability is most appropriately used to describe the overall efficiency of utilization, including physiological and biochemical processes involved in intestinal absorption, transport, metabolism and excretion. Bioavailability of folates from naturally occurring sources is variable and frequently incomplete, many dietary variables, physiological conditions, and pharmaceuticals may affect the bioavailability of folate (Kromhout, 2008). Dietary authorities therefore conservatively estimate that the absorption of dietary folate is about 50% lower than that of folic acid. The foregoing supports the case for supplementation because to absorb the correct quantity to attain the Recommended Daily Allowance, a pregnant woman would have to eat approximately five servings of black eyed peas per day (Blade, 1998).

In broad terms, folate bioavailability is measured by intestinal absorption, tissue uptake, enterohepatic circulation and rate of urinary excretion. However, intestinal absorption plays the largest role in influencing folate bioavailability (Mckillop et al., 2006). Analysis of food folacin content is also complicated. This is because there is a variety of natural vitamin forms, variable gamma glut-amyl polymer lengths and inherent instability of folates (Eitenmiller and Landen, 2009). Mckillop et al. (2006) conducted a research to determine factors that affect the absorption of food folate with different levels of glutamylation. They used spinach, egg yolk and yeast as sources of folate. Their results proved conclusively that level of folate conjugation has absolutely no effect on bioavailability.