Results

Table 1 shows the positively skewed distribution of the lead concentrations of the water samples. When the pregnancy prevalence of neural tube defects for each 1000 live births from 1983 to 1995 and the proportions of lead values > 10 μg/litre for each postcode district are combined to produce a scatter graph, the points are widely spread (fig 1). There is no association between the two variables and this is confirmed by a Pearson correlation coefficient ofr = −0.33. For the reasons discussed previously, it was more appropriate to perform a scatter graph of pregnancy prevalence figures of neural tube defects for the period 1990–5 against the proportions of lead values > 10 μg/litre for each postcode district. This gave a similar result with a Pearson correlation coefficient ofr = −0.16.

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Figure 1

Scatter plot comparing the prevalence of neural tube defects (NTD) with the proportion of lead measurements > 10 μg/litre for each postcode district for the period 1983–95.

Four areas (Pollokshields, Cardonald, Hillhead, and Newlands) were thought to have had high domestic water lead concentrations in the past. Table 2 shows the pregnancy prevalence of neural tube defects for each 1000 live births in these areas compared with the pregnancy prevalence in the other areas combined. Over the 1983–95 and 1990–5 periods, the pregnancy prevalence of neural tube defects was relatively lower in these four areas compared with that in the combined other areas. The pregnancy prevalence of neural tube defects dropped further in the “high” domestic water lead areas than the other areas in 1990–5. There was no difference in the mean Carstairs deprivation category for the high areas (5.9) compared with the other areas (5.8).

The pregnancy prevalence of neural tube defects (1983–95) for each Carstairs deprivation category shows a clear trend (table 3). The highest pregnancy prevalence of neural tube defects is found in the highest deprivation category, with a risk almost double that of the lowest deprivation category. Table 3 also shows that the lowest proportion of samples containing water lead values > 10 μg/litre were in Carstairs deprivation categories 1, 6, and 7.

Discussion

The Glasgow Register of Congenital Anomalies participates in the multinational EUROCAT (European Registration of Congenital Anomalies and Twins) network funded by the EC. From 1980 to 1988 Glasgow reported the highest rate of neural tube defects of all contributing centres (3.4/1000 births), as a result of a combination of high ascertainment and high risk,11 and thus is an important area within which to study the epidemiology of this congenital anomaly. The register has been in existence long enough to enable secular trends to be identified. Stone et al showed that in Glasgow over the period 1974–85, the pregnancy prevalence of anencephaly fell by 50% (from 2.2 to 1.1/1000), whereas the birth prevalence fell by 89% (from 1.9 to 0.2/1000); the pregnancy prevalence of spina bifida fell by 38% (from 3.4 to 2.1/1000), whereas the birth prevalence fell by 76% (from 3.4 to 0.8/1000).12 The pregnancy prevalence rate produces a number equivalent to the number of affected births that would have occurred had there been no antenatal screening. The declining trend in pregnancy prevalence of neural tube defects is not confined to Glasgow but is recognised throughout the UK.13 It had occurred before the introduction of periconceptional folic acid supplementation for primary prevention of neural tube defects.

Risk factors for prenatal exposure to lead involve maternal exposure and body burden of lead. Drinking water is a major source of lead exposure in the general population.14 Studies have shown that there is no impairment to lead crossing the placenta and that maternal and fetal blood lead values are similar.15 16

During the 1960s, extensive water sampling in the Strathclyde region brought an increasing awareness of plumbosolvency.17 The Strathclyde water supply has an acidic character because of its weak buffering capacity and low pH, which makes it aggressive to a variety of metals including lead. Exposure to soft, highly plumbosolvent domestic water supplies in Scotland was postulated as the reason for Scotland having the highest mean blood lead concentrations found in the EC screening programme for blood lead.18 By 1968, the former water boards had banned the use of lead in household plumbing, and from 1970 Glasgow District Council removed all lead piping leading to the householders' tap, including the supply pipe, during modernisation of council owned houses.17 It was known that the plumbosolvency of water could be considerably decreased by increasing the pH of the water. The initial measure taken to alter the unsatisfactory pH of the water was that of the addition of lime to water supplies from Loch Katrine in 1978. Studies performed before and after lime dosing treatment showed that blood lead concentrations fell. In 1977, 6% of mothers tested had blood lead concentrations > 35 μg/litre, but in 1980 none fell into this category.19 A second programme involving the addition of orthophosphate to provide a further reduction in plumbosolvency was carried out in 1989.

In 1980, the European Union drinking water directive reduced the maximum admissible concentration for lead in water from 100 to 50 μg/litre. The EC has proposed that the legal limit be dropped from 50 to 25 μg/litre within the next five years and to 10 μg/litre within the next 15 years (S Robertson, personal communication, 1998). The WHO in 1993 suggested a guideline of 10 μg/litre for the concentration of lead in water.14

The Glasgow 93 lead study, although the largest random sample of domestic water lead values to be performed in Glasgow, was carried out after measures had been taken to reduce plumbosolvency and after many properties had disposed of lead piping. The results showed that most water lead values were < 10 μg/litre (well below the current UK legal limit of 50 μg/litre). We acknowledge that there was a response rate bias, in that only 56% of houses from the high lead areas responded and only 40% from the low lead areas.

Our study failed to confirm the findings of Boundet al,7 which suggested a higher risk of a neural tube defect pregnancy in houses with water lead concentrations > 10 μg/litre. In their study, the areas with high water lead concentrations tended to be the areas of highest deprivation, so it is possible that the observed association was confounded by some unknown factor related to deprivation.

We used the Carstairs index as an area based measure of deprivation. It is postcode sector linked and is derived from four census variables judged to represent material disadvantage in the population: overcrowding, male unemployment, social class, and car ownership. These variables are combined to create a composite score.20 The deprivation score is divided into seven separate categories designed so as to retain the discriminatory features of the distribution of the deprivation score, rather than to ensure equality of numbers between each deprivation category. We found that water lead values were lower in Carstairs deprivation categories 1 (least deprived), 6, and 7 (most deprived), thus not showing a clear association with deprivation. Those in category 1 might have lower amounts of lead because they are better informed about the dangers of lead pipes and/or they are better financially resourced to have lead piping removed from the domestic supply pipe. The lower amounts of lead in domestic water supplies in categories 6 and 7 can be explained by the fact that the housing is either post-1960s (without lead pipes) or the council has removed the lead pipes from council owned property.

There are some possible problems in the use of the Carstairs index. First, it is based on assumptions about the variables that best represent material deprivation. Second, areas are not homogenous: populations containing a mixture of deprived and less deprived households are likely to have middle ranking scores.21However, such mixed populations would be more likely to occur in rural areas. Third, the scores from postcode sectors with small populations (< 2000) are based on census counts, which are particularly susceptible to random variation.21 Lastly, the ecological fallacy is an important potential limitation of area based measures.22

We acknowledge that the population of Glasgow has not remained stable over the past 20 years. It has been declining steadily, with a disproportionate decline in children and young adults, as a result of the reducing birth rate and emigration.23 There has also been substantial internal migration, much of it of the “moonlighting” variety and therefore difficult to quantify.

The question of confounding factors is complex. Neural tube defects are positively correlated with deprivation (which was taken account of in the study design). There is a strong negative correlation between maternal age and deprivation.24 There is also a weak positive correlation between maternal age and the risk of neural tube defect.25 Therefore, any confounding as a result of maternal age differences across postcodes would tend to be more than counteracted by deprivation differences occurring in the opposite direction. In other words, the deprivation adjustment is the important one and should be sufficient.

We found that mothers from the most deprived areas had almost twice the risk of a neural tube defect pregnancy than mothers from the least deprived areas. The higher pregnancy prevalence of neural tube defects in the most deprived categories suggests possible exposure to an unspecified teratogen associated with some component of social deprivation. Recent evidence has shown that primary prevention of neural tube defects is possible through the use of periconceptional folic acid supplementation. It might be that the higher pregnancy prevalence can be explained, at least partly, by poorer, folic deficient diets in deprived mothers. However, there is no evidence that there had been any significant rise in dietary folic acid intake in Scotland over the 1980s and early 1990s to explain the decline seen in the prevalence of neural tube defects in Glasgow.26 This decline started in the 1970s and antedates the publication of the major folic acid trials and promotion of folic acid supplementation.

Our ecological study was carried out in an area known to have had high rates of neural tube defects and high domestic water lead concentrations. If even a weak association had been found it might then have been appropriate to proceed to a more expensive and time consuming case control study. In our opinion this is not now justifiable. The reasons behind the fall in pregnancy prevalence of neural tube defects in Glasgow (and other areas) since the 1970s remain unclear. The decline is partly but not wholly secondary to antenatal screening. There is no substantive evidence to suggest that the dietary folic status of women in Scotland has changed over this period. Our study has not provided any evidence that supports a hypothesis that there is an association between neural tube defects and domestic water lead concentrations. The causes of the decline in neural tube defects over this period remain largely unexplained.