ASSESSMENT OF KNOWLEDGE AND PRACTICE OF PERICONCEPTIONAL FOLIC ACID SUPPLEMENTATION (PFAS) AMONG CHILDBEARING AGE WOMEN (18-45YEARS) ATTENDING ANTENATAL CLINICS IN ENUGU, NIGERIA.

1 CHAPTER ONE 1.0 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 Culled from Wardlaw (2003) 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 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 in 10 cases of NTDs provided the supplementation is started prior to conception (Wald, 2004) 1.1 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 2025% 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: i assess knowledge, and practice among the target population of the benefits of periconceptional folic acid supplementation; ii assess the level of knowledge amongst the target population about foods rich in folate; iii evaluate pattern of consumption of such foods using 24 hour dietary recall and food frequency questionnaire; and iv 1.3 correlate evidence between the variables, different antenatal clinics, private versus public 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 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 Folic acid structure (Taylor and May, 2008) 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 th or 10th positions or both positions Folate co-enzymes are polyglutamyl forms of THF including those with methyl (-CH 3-), 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 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 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 2.5 Biochemical functions of folates Folate requiring reactions collectively referred to as 1-C metabolism; include those involved in different phases of amino acid metabolism, purine and pyrimidine synthesis, and the formation of the primary methylating agent, S-adenosylmethionine (SAM) The production of 5-methyl tetrahydrofolicacid (5-methyl THF) by methylene tetrahydrofolate reductase (MTHFR) is necessary for the major reaction that forms methionine from homocysteine This remethylation pathway requires the enzyme methionine synthetase and cobalamin (vitamin B12) as well as 5-methyl THF Homocysteine remethylation to produce methionine is the only known reaction for this form of folate A methyl group is removed from 5-methyl THF and is sequentially transferred first to the cobalamin coenzyme then to homocysteine thus forming methionine and reconverting 5-methyl THF to THF The 10 dependence of methionine synthetase on both folate and cobalamin provides an explanation why a single deficiency of either vitamin leads to the same megaloblastic changes in the bone marrow and other tissues with rapidly dividing cells C O O I H - C - Nh3+ I C H2 I C H2 I SH - H N H o m o c y s te in e M e t h y ltra n s f e s e + M e t h y lc o b a la m in N C H3 C H2 N H C O O I H - C - NH3+ I C H2 I C H2 I S I C H3 H N + N H C H2 N H Another interesting function of folates is in the degradation of histidine Histidine is deaminated and hydrolyzed to form N-formiminoglutamate (FIGlu) which donates its formimino group to THF leaving glutamate Folate metabolism involves more than 30 genes, enzymes and transporters Future analysis of genes encoding the various enzymes involved in folate metabolism coupled with continued assessment of interaction of polymorphism, nutrition and disease prevalence will greatly enhance understanding of their metabolic effects 2.6 Folate deficiency Folate deficiency is a lack of folate in the diet and the signs are often subtle Clinically, chronic severe folate deficiency is associated with megaloblastic anemia Which is characterized by large abnormally nucleated erythrocytes that accumulate in the bone marrow (Lindenbaun and Allen, 1995).There are also decreased numbers of white blood cells and platelets as a result of general impairment of cell division Also the intestinal 57 in their homes Also about one third of them were going through their first pregnancies and therefore primigravidas Djientcheua et al., 2008 noted that 40.6% of the NTD cases he studied were among primi mothers, this was significant given the fact that ante natal ultrasound was able to diagnose less than one third of the cases This couldn’t help much as abortion is illegal in most sub-Saharan African countries though 56.4% ended up as still births Incidence of at least one episode of adverse pregnancy outcome was noted in about 16% of the population under study though a majority could not indicate the reason for their loss The use of oral contraceptives was found to be uncommon in the respondents and approximately half of those that had taken it at some point had done so without the benefit of prescription from qualified medical personnel This could be attributed to sociocultural factors which could also account for the high percentage of respondents who neither smoked nor consumed alcohol Smoking, increased alcohol intake, anti seizure medication, diabetes and oral contraceptive intake have all been previously identified as risk factors for neural tube defect occurrence In the population under study none was found epileptic while minorities indicated that they had used oral contraceptives at some point or were diabetic This aptly shows that the problem lies in areas other than these and the trend was similar in both institutional types 5.3 Knowledge of folate supplementation by the respondents Eighty-three percent of the respondents indicated that they had heard of folic acid, but an analysis of data shows that approximately 30% of them knew that folic acid is a vitamin In addition very few (16%) knew that folic acid could prevent neural tube defects Comparing these results to that of similar studies that have investigated knowledge and practice of periconceptional folic acid supplementation among the reproductive age group shows that, in Norway, Volset and Lande (2000) reported that 50.5% of their respondents had heard of folic acid Approximately one third of their study population could connect it to neural tube defect prevention In the present study, correct knowledge of food source of folate was present in 54% of the respondents with green leafy vegetables being the most commonly identified source Only 23% of the respondents could identify long term benefits of optimal 58 blood folate level as lowering cancer risk or homocysteine level in the blood thereby preventing oxidative damage to blood vessels The rest were largely ignorant Doctors (52%) were the most common source of information for the respondents which could account for the haphazard nature of such information This in turn could be attributed to the ratio of medical personnel to patients in Enugu (1:1,581) as reported by Okeibunor, Onyeneho and Okonofua, 2010 Knowledge of correct dosage for supplementation was practically absent at 0.8%, these had mostly gotten their information from the World Wide Web which shows that it can be a valuable tool Dietitians /Nutritionists had a better showing at 7.6% as a source of information compared to their 1.8% in the United Arab Emirates 2010 study 5.4 Practice of folate supplementation by the respondents The approximate 10% of respondents that knew the correct time for folate supplementation to protect against neural tube defect occurrence was much lower than the over 75% observed by Sen et al(2001) and 21% reported by Sayers and coworkers(1997) Approximately 62% of the respondents had started supplementation on booking and from analysis of data on the preferred/normal booking time of the respondents it shows that a high percentage of them book from the third month onwards This shows that a majority of the respondents start supplementation too late to proffer any meaningful protection against neural tube defect occurrence A small percentage (2.8%) of the respondents had supplemented periconceptionally About 88% reported that they took folic acid in the present pregnancy with their routine drug regimen but only 61% take it daily Those who reported that they not take folic acid largely gave their reasons as ignorance of both the benefits and importance of folate supplementation during the periconceptional period 5.5 Food consumption pattern of the respondents The results of the 24-hour dietary recall and food frequency data shows in summary that, only a minor percentage of the women had made adequate adjustments to their daily diets to include a larger percentage of folate dense foods like fruits and vegetables They generally stuck to the normal routine of tea/bread for breakfast, carbohydrate dense 59 formulation of some sort (fufu, semovita or garri) combined with a variety of soups for lunch Dinner was rice, yam or bean based food combinations 5.6 Biochemical investigation Low birth weight infants, fetal impairment and infant deaths have been shown to be linked to anemia during pregnancy (VanderJagt et al., 2007) A myriad of studies indicate that anemia in developing countries like sub-Saharan black Africa is mostly normocytic and normochromic or anemia of mixed origin Folate deficiency is common among women of reproductive age due to dietary inadequacy and increased demand in pregnancy Folate deficiency is a contributory factor to nutritional anemia in pregnancy (Karaoglu, 2010) Fifty percent of the respondents presented with borderline value of hemoglobin at < 11g/dl at booking which places both themselves and their off springs at increased risk of aforementioned morbidities 5.7 Conclusion As judged by the results, a large percentage of the women had limited information on the use and importance of folate in pregnancy Many missed supplementation at the critical periconceptional period and began from the third month onwards Maternal education was an important factor that influenced knowledge of folate use in pregnancy more than maternal age or parity Due to the great disparity between incidence and prevalence statistics of NTDs people tend to feel that it is uncommon in sub-Saharan black Africa but Djientcheua Vincent de PaulA et al., (2008) confirm that it is not a rare disease in sub-Saharan black Africa contrary to prior convictions Huge amounts of money is spent yearly by NGOs to fund reconstructive surgery for children with cleft lip and palate, some others yet help victims of hydrocephalus, conditions that are commonly associated with NTDs None as yet has undertaken sensitization of the effects of sub optimal folate level at the critical periconceptional period This anomaly should be addressed by appropriate authorities given the huge emotional and economic burden this largely preventable condition can cause 60 5.8 Recommendations Results of this study show that there are loopholes that need to be addressed in maternal and child healthcare to ensure compliance with MDG targets  The wide array of foods indicated in their dietary recall indicates that contrary to the recommendations of Idowu, Disu, Anga and Fabanwo, (2008) fortification might not have a significant impact on overall folate intake for the population under study Intensive public sensitization and enlightenment campaigns on importance of optimal blood folate concentration in both the periconceptional period and throughout the life span might be the solution  Correct information is imperative for mothers from healthcare personnel Patient’s active participation in their own health care is very essential Information as regards reason for certain procedures should be made known to them thereby empowering them to even educate others  Women should also be told the probable reason for their occasions of adverse pregnancy outcome so that they not make the same mistakes over and over again  Government should start birth anomaly registries and also morbidity and mortality reports as obtains in some more developed countries, these figures will help plan and execute projects aimed at reducing birth defects including NTDs to the barest minimum  Government should spearhead widespread enlightenment campaigns on folate importance in pregnancy, also legislation should be passed to encourage manufacturers of feminine hygiene products like sanitary pads to put reminders on the importance of increasing folate intake before conception This will go a long way in increasing awareness and compliance  Churches also should be targeted to reach couples preparing for marriage  Hospitals both private and public ones should ensure that a qualified Nutritionist/Dietitian is attached to their antenatal clinics to disseminate correct information to pregnant women 61  Part of the massive funds spent yearly by NGOs 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(i) 18- 24 (ii) 25- 31 (iii) 32-38 (iv) 39- 45 Marital Status? ……………………………………………………………………………………………… Parity (Number of ………………………………………………………………………… 3b Number of Pregnancies (Gravidium)? Educational Status? (i) FSLC (ii) SSCE/WASC (iii) (iv) Higher (MBA, MSc, PhD) Children)? B.Sc./HND (v)none Occupation?:……………………………………………… …………………………………………… Estimated monthly income in naira? (i) Less than 7,500 (ii) between 7,500 and 45,000 (iii) 45,000 to 60,000 (iv) More than 60,000 Have you ever had any adverse pregnancy outcome? (i) Yes (ii) No (b) Any idea of the cause/reason?………………………………………………………… Do you smoke? (i) Yes (ii) No 68 Do you consume alcohol regularly? (i) Yes (ii) No 10 Are you on any prescription medication? (i) Yes (ii) No (b) If yes, Name? KNOWLEDGE QUESTIONS Have you ever heard of folic acid? idea What is folic acid? (i) Vitamin (i) No (ii) Mineral supplement (ii) (iii) No Strong Baby (iii)Preventing Neural tube defects (iv) No idea Do you know the recommended dose? What is it? (i) Yes (ii) No How did you get the information about folic acid? (i) Doctor (iv) (ii) Nurse (iii) Nutritionist/Dietician Mass media (Television/magazine/newspapers) (v) Friends and relations (ii) What is the use of folic acid in pregnancy? Please tick (i)Healthy pregnancy Yes (vi) Other means ………………………… Do you know any locally available food sources of folic acid? Tick them (i) Green leafy vegetables (ugu) (iv) Oranges (ii) Yam (iii) Rice (v) no idea Do you know any long term benefits of optimal blood folate level? Tick two (i) Lowers cancer risk (iii) Cures HIV (ii) Lowers homocysteine level in blood (iv) cures tuberculosis (v) no idea PRACTICE QUESTIONS Do you take folic acid during pregnancy? (i) Yes (ii) No Do you take it religiously? (Daily) 69 (i) Yes (ii) No What is the ideal time to start taking folic acid tablets? (i)Before you miss a period are sick (ii) first month of pregnancy (iv)Whenever you start antenatal (iii) when you (v) no idea When you normally start taking it? (i) Before your last period (ii) once you miss a period (iii) When you start ante-natal (iv) Never If you ticked never, can you please give your reason? (i) Unplanned pregnancy (iii) Feeling sick (ii) Not prescribed by Doctor (iv) get enough folates from food (v) Didn’t know it was important Have you ever taken oral contraceptives? (i) Yes (ii) No b Was it prescribed by a doctor? Are you epileptic ? Are you diabetic ? When you normally start antenatal care…………………………………… Can you briefly recall all you ate from dawn to dusk yesterday? 24 HOURS DIET RECALL Breakfast Snack Lunch Snack Dinner 70 FOOD FREQUENCY QUESTIONNAIRE Daily Foods Black eyed peas (Beans) Cowpea (fiofio) Peanuts (groundnuts) Orange Green leafy vegetables Organ meats pawpaw Spinach Okro 2x weekly 3x 2x 3x and abov e Monthl y Never Occasionall y 71 ... assessing knowledge and practice among childbearing age women in Enugu metropolis about periconceptional folic acid supplementation and accruing health benefits 3.3 Study population All pregnant women, ... higher in rural areas She pinpointed independent predictors of folic acid deficiency as low income, including low folic acid and ascorbate intake Presently, no European Union country has imposed mandatory... 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