A case-control study of maternal nutrition and neural tube defects in Northern Ireland

A case-control study of maternal nutrition and neural tube defects in

Northern Ireland Marion E. Wright Objective: to compare dietary intake and biochemical indices of nutritional status in women following birth of a baby/ termination of a pregnancy affected by neural tube defect ( N T D ) and women with a normal baby. Design: quantitative, using case control methods. Setting: dietary records were completed by women in their own home, blood samples were taken in the local health centres. Participants: 15 women referred to the study following an affected pregnancy (subjects), matched with 15 women whose pregnancy outcome was normal (controls). Measurements and findings: 7-day weighed dietary records indicated no statistically significant differences in nutrient intake but a tendency for lower fruit and vegetable consumption in subjects than in controls. Biochemical analysis of nutritional status showed that levels of serum vitamin B, 2 were significantly lower in subjects, and activities of two of the nucleotide salvage pathway enzymes were significantly higher. Key conclusions:the findings are consistent with the findings of other research on N T D and the metabolism of folate and vitamin Harion E Wright RGN, RM, BSc, D Phil, Lecturer, School of Health Sciences, Nursing, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 iSA, UK (Requests for offprints to

HEW) Manuscript accepted 6 April 1995

El2.

Implications for practice: this study, and other research in this area, has implications for health professionals, including midwives with their particular involvement in prenatal care, and also highlights the need for a clearer focus on nutrition in nursing and midwifery education.

Midwifery(1995) I I, 146-152 © 1995PearsonProfessionalktd

INTRODUCTION Although there has been a highly significant downward trend in the total prevalence of neural tube defects in Northern Ireland, the rate remains high at 33.1 per 10000 for 1980-1988 ( E U R O C A T Working Group 1991). Prevalence rates are high also in mid-western Scotland, south Wales and Dublin compared with south east England and continental Europe. Geographic and secular trends, as well as social class variation in prevalence, suggest that N T D aetiology includes an important environmental component, possibly nutritional. The term neural tube defect (NTD) is used to describe a group of abnormalities arising from failure o f fusion of the central nervous system in the first few weeks of embryonic life. Normally, the neural groove folds laterally and fuses to form the neural tube as early as the 22nd to the 30th day of gestation. Arrest in this process leads to defective closure of the neural tube and o f the vertebral column. N T D s comprise one of the most c o m m o n groups of congenital malformations and can have serious consequences for affected individuals and their families, whether the defect is anencephaly, encephalocele, or one of the forms o f spina bifida cystica - meningocele or the much more serious, but also commoner, myelomeningocele. Despite much research and encouraging results in prevention trials using folic acid with or without other vitamins, the exact aetiology of N T D is not clear. Apart from a minority of N T D s which are associated with specific genetic disorders, the vast majority (90%) are thought to be multifactorial. Since the defect itself occurs at such an early stage of pregnancy the mother may not have suspected that she is pregnant, and approximately 95% of NTDs are first occurrences of the defect. That there is a genetic component to N T D is suggested by ethnic variation, with N T D s being more common in races o f Celtic origin. Higher rates have also been found in Sikhs in British Columbia (Hall et al 1988). W o m e n who have already experienced an N T D pregnancy are at increased risk of having a second affected baby and there is also increased risk if either parent has spina bifida or if there is a history of N T D in the woman's immediate family. It has been shown that there are sex differences with prevalence higher in females particularly in areas with higher prevalence and when the defect is anencephaly (Seller 1987). An environmental component has been suggested by epidemiological studies showing, for example, geographic variations and also

A study of maternal nutrition and neural tube defects in Northern Ireland

variations with social class. Rates have been shown to be two to four times higher in social classes IV and V than in I and II (Elwood & Elwood 1980). Reductions in prevalence are not entirely due to early identification and pregnancy termination, having been noted in Dublin by Coffey in 1984 and in a study in Scotland which took into account figures for pregnancy termination (Carstairs & Cole 1984). Seasonal variations have also been noted but appear to become less obvious as prevalence decreases. It would therefore appear that both genetic and environmental factors play a part and the imposition ofunfavourable environmental factors on a genetic susceptibility, held in abeyance in more favourable conditions, comes into play and the neural tube fails to fuse. A m o n g the environmental factors suggested, most attention has been focused on nutritional status. In Liverpool in 1965 Hibbard and Smithells's findings suggested defective folate metabolism in w o m e n whose babies had severe malformations, mainly of the central nervous system. In Leeds, Smithells et al (1976) noted significantly, lower levels of vitamin C and red cell folate in w o m e n who had an N T D baby, while lower intakes of all nutrients, including folate, were found in w o m e n o f social classes III, IV and V (Smithells et al 1977). l=olate was also low in women under 20 years of age (Rogozinski et al 1983). Thus, w o m e n in the groups at highest risk for an N T D pregnancy, that is young women in social classes III, IV and V, were also at highest risk of nutritional deficiencies. Laurence et al (1980) showed that a group of women in Wales who received dietary counselling and improved their dietary patterns (mainly increasing folate rich foods) had a reduced recurrence risk. In Glasgow, Yates et al (1987) found no statistically significant dietary differences but lower red cell folate levels in women who had an N T D pregnancy compared with controls with a normal baby, while in Western Australia Bower and Stanley (1989) found a protective effect associated with increased dietary folate intakes in early pregnancy. In the UK, reduced recurrence rates followed periconceptional supplementation using either multivitamins (Smithells et al 1981, Smithells et al 1983, Smithells et al 1989) or folic acid 4 mg (Laurence et al 1981). In several studies in the USA multivitamins have also been shown to have a protective effect (Mulinare et al 1988, Milunsky et al 1989). The study ofMitls et al (1989) failed to show a protective effect for multivitamins, but it was noted that the work was carried out in California and Illinois, the former being a low prevalence area. Reduction in prevalence with

147

supplementation may not be as marked in areas which already have a low N T D prevalence. The Medical Research Council Vitamin Study was a large randomised controlled multi-centre supplementation trial with over 1000 pregnancies for which outcomes were known and showing a 72% reduction in N T D recurrence with periconceptional supplementation using folic acid 4 mg/day ( M R C Vitamin Study Research Group 199l). Subsequently, in Hungary, Czeizal and Dudas (1992) demonstrated a highly significant protective effect for 0.8 mg of folic acid/day with other vitamins in prevention of first occurrences of N T D . Some time after the publication of the MtKC report, the Department o f Health issued its recommendations on folate supplementation advising folic acid 5 mg/day for the prevention of N T D recurrences and 0.4 mg/day + increased dietary folate for the prevention o f first occurrences (Department of Health 1992). Although the exact mechanism by which this protective effect occurs is as yet unclear there is increasing evidence that a defect in folate metabolism may be an important factor in N T D aetiology rather than a dietary deficiency per se.

METHODS

The present case control study was carried out within the Human Nutrition Research Group o f the University of Ulster and in collaboration with the Department o f Medical Genetics, Queen's University of Belfast. Ethical approval was granted by the Research Ethics Committee, Faculty of Medicine, Queen's University of Belfast. Access to subjects was obtained from the Department of Medical Genetics and, on notification of her inclusion in the study to each subject's general practitioner, access to a suitable control was obtained. The overall aim was to identify possible dietary or physiological characteristics peculiar to women who had recently had a pregnancy affected by N T D . Subjects were matched with controls who had recently been delivered of a normal baby. The main objectives were to compare: 1. intakes of energy, macronutrients, dietary fibre and vitamins, minerals and trace elements; 2. the contribution of food groups to the intakes of energy and folate; 3. biochemical indices of nutritional status; and 4. aspects of lifestyle, including food preferences and frequency of consumption of certain foods. The sample comprised women who attended

148

Midwifery

the Department of Medical Genetics, within 3-12 months of the birth of a baby with an N T D or termination of an affected pregnancy and who were invited to participate in the study (n=15). A control woman was selected by each subject's general practitioner, matching for age + 5 years, parity, social class based on occupation of head of household (Office of Population Censuses and Surveys 1980) and length of time since delivery. The weighed inventory method was used to obtain a record of all food and drink consumed by subjects and controls for a period of seven days, using digital scales (Miniscale, graduation 1 g, capacity 2000 g). Nutrient intakes and their food group sources were calculated using a computerised version of the Food C o m position Tables of McCance and Widdowson (Paul & Southgate 1978) and supplementary food tables (Wiles et al 1980). On completion of the seven-day dietary recording period, 20 ml of blood was obtained from each subject/control. Haemoglobin (Hb), and other haematological indices were determined and enzyme activation assays were used to estimate riboflavin (Tillotson & Baker 1972) and pyridoxine (Bayoumi & lLosalki 1976). Minerals and trace elements including zinc and copper were measured in red cells. Serum ferritin and serum vitamin 812 were measured by radioassay, and serum folate by microbiological assay (O'Broin et al 1980). ILadioassays were also used to measure serum activity of several enzymes which play a key role in D N A synthesis, namely thymidine kinase (TK), adenine phosphoribosyl transferase (AP1LT) and hypoxanthine guanine phosphoribosyl transferase (HGP1KT) in serum (Amara 1990). At the final visit to each participant an interview schedule was completed, giving information about food habits and preference, lifestyle factors such as smoking and alcohol intake, medical and obstetric history and experience of nutrition education. Measurements of height and weight were taken, used later in validity checks of the dietary data using the equations of Schofield (1985). Statistical analysis was carried out using SPSS/PC+, employing non-parametric statistics. Results are presented as median values and interquartile ranges with differences between groups calculated by Wilcoxon matched-pairs signed-ranks test.

FINDINGS Subjects and controls were similar with regard to matching criteria. The numbers in each grouping of age, parity and social class are

shown in Table 1. There were no significant differences between subjects and controls in length of time since delivery, nor in height, weight or body mass index (Table 2). Average daily intakes of energy, macronutrients and dietary fibre were similar in both groups (Table 3) and were also similar to those of a subgroup of women aged 20-45 years from the Northern Ireland Diet, Health and Lifestyle Study (Barker et al 1989). The median intakes of most of the micronutrients in subjects tended to be slightly lower than in controls, except in the case of vitamins A and B12; however, none of the differences reached statistical significance although thiamin and vitamin C just failed to do so (Tables 4 & 5). Daily intakes of total folate in both groups were similar, 115 and 116 ug/day, and were also similar to the sub-group from the Northern Ireland Diet, Health and Lifestyle Study (115 ug/day) (Barker et al 1989). These folate intakes are considerably lower than the 200 ug/day reference nutrient intake (R.NI) recommended by the Department of Health (1991), although the possible underestimation of folate values by the food tables available at the time of these studies is discussed by Wright (1992). Analysis of food group sources of energy and total folate showed that the highest sources of energy for both subjects and controls were cereal products and cakes. Although the overall intake of the food group, including fruit and vegetables, was low it was higher for controls than subjects. When sources of folate were compared, once again there was a marked dig ference between groups in fruit and vegetable consumption, significantly higher in controls (P
i!iiii:iii:i:i:i

iii i: i i: iii i;ii:i:iiiiTi:iiiiiiiii Subjects (n = 15)

Controls (n = 15)

Age group 20--29 years 30-39 years 40-49 years

8 6 I

7 6 2

Parity I-3 4-6 7-9

9 5 I

6 7 2

Social class* I II III Non-manual III Manual IV V

0 5 I 7 2 0

0 5 0 5 3 2

* OPCS Classification of Occupations (1980).

A study of maternal nutrition and neural tube defects in N o r t h e r n Ireland

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Length of time since delivery (weeks) Height (cm) Weight (kg) Body Mass Index (Wt/Ht 2)

Subjects

Controls

Wilcoxon Z*

P value

29.0 (25.0)

30.0 (30.0)

43.1569

0.8753

163.0 (10.0) 64.0 (I 3.0) 24.4 (6.3)

158.0 (9.0) 58.0 (I 6.0) 23.4 (5.2)

43.5964 43.4260 43.1704

0.5509 0.670 I 0.8647

Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. * number of paired observations = 15. [iiii!ii i}iiiii i ~iiiiii!iiiiiiii i i ~iiiiiiil i iiliiii i l!iiiiiiliiiiiiiiiiiiii ~ i iiiiiiiiiiiiiiiiii!iiiiiii ! ~ i ii!i~iiilil!iiiiiii!i ~ i!iii!iii!i l !iii!iiiiiliiilliiiii!iiiiiliiiiiiiiiiiiiiiiiiiiiiiiii i ~iii}iiiiiiiiii ~ii!}iiiiiiiiiiiii!ii!iiiii!iii!!!iii!i i iiiiiiii!iiiiiii~iiiiiiiiiiiiiiiiiiiiii ~ {iiiii~iiiiiiiiii i iiiiiiiiiiiiiili~iii ~ii ~ili~~i!~!i i iilil lil}fill !!~i i!i!ili{~iii{i i i!iii!i }!iili!liiiiiiiiil i!li~iiiili ~ii i~l~ii~iliii{iii~i!iiiili ili~ilili{ii

Energy (MJ) (kcal) Protein (g) Fat (g) Carbohydrate (g) Fibre (g)

Subjects

Controls

7.6(I .3) 1824.0 (317.0) 52.0 (I 1.0) 80.0 (I 6.0) 212.0 (75.0) 14.0 (5.0)

8.1(3.7) 1936.0 (880.0) 61.0 (23.0) 82.0 (39.0) 218.0 (104.0) 15.0 (6.0)

Wilcoxon Z*

P value

-0.251 I 43.1704 -I.2495 -0.0568 -0.4828 - I . 1767

0.8017 0.8647 0.2115 0.9457 0.6293 0.2393

Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. * number of paired observations = 15.

149

There were no differences between subjects and controls in the biochemical indices of nutritional status measured, except for serum vitamin B12 , which was significantly higher in controls as reported previously (Wright et al 1993). There were no significant differences in Hb, serum ferritin, zinc, copper, nor in riboflavin or pyridoxine status, nor in serum folate (Table 6). Findings for nucleotide salvage pathway enzymes are shown in Table 7. These are enzymes which have been shown to be important in D N A synthesis, particularly in rapidly growing tissue. Folate is also important in D N A synthesis and when tissues are deficient in folate, or, when there is a block in the de n o v o synthesis ofnucleotides, these enzymes are raised. In this study no differences were found in A P R T , but H G P R T was significantly higher in subjects than in controls. The percentage of thymidine kinase made up of the TK 2 isozyme is lower in subjects. This means, therefore, that the percentage of TK 1 is higher and it is this portion that has been shown to play a more significant role in D N A synthesis (O'Neill et al 1990). Other researchers have reported elevated levels in patients with vitamin B12 deficiency (Hagberg et al 1984).

iiii! i {ii!ii{iNi{iNi}iN{iiiii{ i !!i{iii i i}iiiiiiiiii{i{i!ii{iiiii{i{i{iiiiiiiiii{i!iii{{iiii{i iiii !{{iiiiiiiiiiii!iiiiiiiiii!iiiiiii!iiiiiiii!iiiii!i!iiii!iiiii}ii{iiiiiiiiiii!iiii{i Retinol equivalent (ug) Vitamin D (ug) Vitamin E (mg) Thiamin (mg) Riboflavin (mg) Pyridoxine (mg) Nicotinic acid (mg) Vitamin C (mg) Total folate (ug) Vitamin B~ (ug)

Subjects

Controls

642.2 (408,20) 1.5 (2. I0) 3.2 (2.60) 0.8 (0.30) I.I (0.40) 0.9 (0.30) 23.0(4.10) 31.0 (14.00) 115.0(43.00) 2.5 (I.60)

518.2 (321.63) 1.6 (1.50) 3.6 (2.60) 1,0 (0.70) 1.3 (1.20) I. I (0.30) 28.0(13.10) 42.0 (30.00) 116.0(46.00) 1.8 (1.90)

Wilcoxon Z*

P value

43.5112 -0,2825 43.0568 - I .8743 -1,3183 -0.5883 -1.4199 -1.9027 -I.1927 43.2272

0.6092 0.7776 0.9547 0.0609 0.1874 0.5563 0.1556 0.0571 0.2330 0.8203

Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. * number of paired observations = 15.

iii

i i! ii i ii ii ii

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iiiiiiiiiiiiiiiii

Controls

Wilcoxon Z*

P value

2407.0(1038.0) 2566.0 (626.0) 820.0 (358.0) 8.4 (2.90) 1.2 (0.30) 8.1 (2.30)

-I.3063 43.1704 -1.0223 -0.2825 0.000 -I.4199

0.1914 0.8647 0.3066 0.7776 1.0000 0.1556

L i~::!i~ili~::~ ~ ~ ~i~:~~:i~:~i~:z~i~: ~i~:~: z~i~::ii: ~ ~:::~::::~i~i:~~: ~~:: ~:~i~~::~:#::::::i~:: i~: ~::~i~:::::~~::~:~::::::::::::::::::::::::::::::::::::::: ~i~i i:::#:~i~:::::::::::::::::::::::::: : ~::~:~:~~::~:~:#::::)::i:~~i:~:i~::~~i~:~:~:~i~~i~i~i:::. !~i~i¢ii::i :.~i:::.i !i:::: ::::ii::i:::.i::{ii:i:i::ii:;iiii:::;:::;i}::ii:;}::::; ::ii i:::::;:::: ::i{:;::i::i:::;:::;:::::::: :::::::;iif:::::;:::;i::::i::::::: : : : : :::i:::;::::ii:: ::::: Subjects Sodium (mg) Potassium (mg) Calcium (rag) Iron (rag) Copper (mg) Zinc (rag)

2113.0(558.0) 2375.0 (498.0) 620.0 (280.0) 8.2 (I .50) 1.2 (0.20) 6.6(I.40)

Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. number of paired observations = I 5.

DISCUSSION Because this was a small non-randomised study, findings cannot be generalised to the total population of w o m e n who have had an N T D affected pregnancy but are merely indicative. They should, however, be considered in the light of other recent research on nutritional aspects of N T D . The problems associated with obtaining accurate dietary intake data from flee-living subjects are recognised (Livingstone et al 1990), but such problems apply equally to subject and control groups in case-control studies. Therefore, while the absence of significant differences in nutrient intakes between subjects and controls is not surprising (Tables 3-5) it was interesting to note that the trend for intakes to be slightly higher in the control group, except for vitamins A and B12, was similar to that found in other studies, for example Yates et al (1987). There was also evidence of lower fruit and vegetable consumption in subjects. W h e n findings from the present study were compared with a corresponding age group of female subjects in a large dietary study carried out in Northern Ireland (Barker et al 1989) similar nutrient intakes and food group sources were found. Biochemical analyses indicated that the only statistically significant differences were for

150

Midwifery ~]~i~]~i~i~i~i~i~i~i~i~i~i~i~]ii~i~iiiiiiiiiiiii~ii~iii~ii]]ii~i~i~i~i~i~]~i~i~i~i~i~i~i]~i~iiiiiiiii~iii~iiiiii~i]iiiiiiiiiiii~]]iiiiiii~iiii!iiiiiiii]iiiiiiiii~i~iiii~i~iii]iii~iii~ii]iiiiiiiiiiiiiiiiiii!i~i!!i!i!iiii ¸

Haemoglobin (g/dl) Serum ferritin (ng/ml) Zinc (ug/ml) Copper (ug/ml) Riboflavin (glutathione reductase activity coefficient) Pyridoxine (aspartate aminotransferase % activation) Serum folate (ug/I) ** Serum vitamin B~ (ng/I) ~

Subjects

Controls

Wilcoxon Z *

P value

12.30 (2.30) 22.40 (43.60) 5.57 (I.68) 0.99 (0.24) 1.28 (0.12)

12.60 (2.20) 14. I 0 (20.30) 5.68 (I.25) 0.87 (0.39) 1.36 (0.18)

-0.1704 - 1.7891 -0.2840 ~0.8519 -1.4767

0.8647 0.0736 0.7764 0.3942 0.1398

52.50(19.90)

65.20(23.10)

-I.3915

0.1641

5.00 (7.60)

4.30 (2.40)

-0.6276

0.5303

200.00 (82.00)

295.00 (165.00)

-2.9003

0.0037

Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. number of paired observations = 15, except where noted ** number of paired obaservations = 13.

H G P R T , T K and serum vitamin B12 (Tables 6 & 7). The higher H G P R T and %TK i activity in subjects may suggest a block in folate metabolism and this is supported by the finding o f significantly lower levels o f vitamin B~2 in subjects. Schorah et a] (1980) found very low serum vitamin B~2 levels in mothers o f three anencephalic fetuses, and suggested an underlying defect o f vitamin B12 metabolism resulting in depletion o f tissue folate. In a recent study carried out in Dublin, Kirke et al (1993) found significantly lower serum vitamin B12 as well as serum and red cell folate in blood taken at antenatal booking in w o m e n w h o went on to have an N T D baby compared with controls. Vitamin B~2 is important in folate metabolism as a co-enzyme in the metabolism o f h o m o c y s teine to methionine. There is considerable interest at present in this aspect o f folate/vitarain B12 metabolism and N T D , and it is the focus o f groups in the Netherlands (Steegers-Theunissen et al 1991) and in Dublin

and Bethesda, Maryland (Kirke et al 1993, Mills et al 1995). Both nutritional and genetic factors may alter folate/vitamin B12 metabolism resulting in depleted levels o f the circulating form offolate, methyl-tetrahydrofolate. As folate has a key role in D N A synthesis, any resulting decrease in the rate o f cell division could be an important factor in the development o f N T D were it to occur at the critical stage o f neural tube formation. The report o f a possible inborn error in homocysteine metabolism in w o m e n with a history o f an N T D pregnancy (SteegersTheunissen et al 1991) supports this hypothesis. Since the precise cause o f N T D or the exact mechanism by which folic acid protects against recurrence are not yet known, these are important areas for further nutrition research. Issues such as nutrition education and food fortification are also important. Dietary recommendations to prevent N T D are similar to some o f those for the prevention o f coronary

:::ii~i~iii~iii~i~i~iiiiiiiiiii~i~i~iiiiiii~i~i~i~iii~i~iii~iii~iii~i!!~ii~i~i!ii~!ii~iiiii~ii~i~i~i~iiiiiiiiiiii~i~iiiiiiiii~i~iiiiiiiiii~i~i~i~iii~i~i~i~i!~!~iii!~ii~i~i!i~!i~iii~ii~i~i~i~i~iiiiiiiiiii~ii~i~iiiii~i~ii Subjects phosphoribosyl 596i .0 (I 238.0) transferase-APRT (cpm/ml/h) Hypoxanthine guanine 20096.0 (5910.0) phosphoribosyl transferase HGPRT (cpm/ml/h) Thymidine kinase-TK (cpm/ml/h) TK-ATP (TKI +TK2) 3162.0(1056.0) TK-CTP 1338.0 (602.0) TK (%CTP/ATP) (%TK2) 43. I (22.2)

Adenine

Controls

Wilcoxon Z *

P value

5306.0 (1697.0)

-1.5335

0.1252

10486.0 (4048.0)

-3.4078

0.0007

4756.0(2217.0) 3165.0 (I 820.0) 64.6 (I 6.0)

-3.1806 -3.1238 -2.6126

0.0015 0.0018 0.0090

Activity levels measured in counts per minute/ml/hour. Medians (interquartile ranges in parentheses). Differences calculated using Wilcoxon's matched-pairs signed-ranks test. * number of paired observations = 15.

A study of maternal nutrition and neural tube defects in Northern Ireland

h e a r t disease a n d certain cancers. H o w e v e r , increasing fruit a n d v e g e t a b l e intake can b e difficult, particularly for those m o s t at risk, y o u n g , l o w i n c o m e w o m e n w h o m a y n e e d particular advice a n d help. Breakfast cereals a n d s o m e breads are already fortified w i t h folate in this c o u n t r y , b u t t h e r e is c o n c e r n that a h i g h e r folate intake in t h e total p o p u l a t i o n resulting f r o m m o r e w i d e s p r e a d fortification c o u l d mask n e u r o l o g i c a l d a m a g e in individuals w i t h p e r n i cious a n a e m i a ( C h a n a r i n 1994). P e r i c o n c e p t i o n a l s u p p l e m e n t a t i o n needs to c o m m e n c e a p p r o x i m a t e l y 28 days before c o n c e p t i o n a n d c o n t i n u e to 12 w e e k s gestation. Several studies carried o u t since the p u b l i c a t i o n o f the D e p a r t m e n t o f H e a l t h r e c o m m e n d a t i o n s o n folic acid s u p p l e m e n t a t i o n ( D e p a r t m e n t o f H e a l t h 1992) h a v e s h o w n that m a n y w o m e n a t t e n d i n g antenatal clinics h a v e n o t b e e n u s i n g supplementation and have been either unaware o f t h e r e c o m m e n d a t i o n s or u n s u r e o f t h e i r p u r pose (Sutcliffe et al 1993, C l a r k & Fisk 1994, S m i t h et al 1994). R e s e a r c h a n n o u n c e d at the l a u n c h o f a Folic A c i d H e l p l i n e set u p b y the charity, M e d i c a l A d v i s o r y Service, i n d i c a t e d that nearly h a l f o f 150 m i d w i v e s s u r v e y e d felt that f e w e r t h a n 5% o f w o m e n h a d t a k e n folic acid p r i o r to c o n c e p t i o n (Association for Spina Bifida a n d H y d r O c e p h a l u s 1995). It is i m p o r t a n t to find ways o f raising p o t e n tial m o t h e r s ' awareness o f t h e c u r r e n t r e c o m m e n d a t i o n s a n d o f e n a b l i n g t h e m to take positive h e a l t h action. Since as m a n y as 50% o f pregnancies may be unplanned (Chanarin i 9 9 4 ) , t a r g e t i n g p r e p r e g n a n c y advice to those m o s t at risk is difficult. W h e t h e r in hospital or in the c o m m u n i t y , m i d w i v e s h a v e o p p o r t u n i ties to w o r k w i t h w o m e n at different stages as t h e y b e c o m e m o t h e r s a n d to b u i l d u p r e l a t i o n ships o f trust a n d c o n f i d e n c e w h i c h will e n c o u r a g e t h e m to seek a n d receive advice. In such an a t m o s p h e r e , particularly in the p o s t natal period, t h e r e m a y b e o p p o r t u n i t i e s to advise for s u b s e q u e n t pregnancies. A n issue w h i c h is f u n d a m e n t a l to t h e m i d wife's w o r k in this area o f p r i m a r y p r e v e n t i o n is a s o u n d u n d e r s t a n d i n g o f the principles u n d e r lying m a t e r n a l n u t r i t i o n . This can only b e a c h i e v e d w h e n n u t r i t i o n has its p r o p e r place in t h e curricula o f all p r o g r a m m e s o f n u r s i n g a n d midwifery education. The Core Curriculum for N u t r i t i o n in the E d u c a t i o n o f H e a l t h Professionals ( N u t r i t i o n Task Force P r o j e c t T e a m , 1994) l a u n c h e d in N o v e m b e r 1994 p r e sents an o p p o r t u n i t y for m i d w i f e r y a n d n u r s i n g educators to evaluate a n d d e v e l o p the n u t r i t i o n content of their programmes. ACKNOWLEDGEMENTS The assistance of the subjects and controls who participated in the study and of their general practitioners is gratefully

151

acknowledged, as is the support of the Nestld Nutrition Research Grant Programme and the Department of Healtli and Social Services for Northern Ireland. REFERENCES

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