Elsevier

The Lancet

Volume 358, Issue 9276, 14 July 2001, Pages 110-114
The Lancet

Articles
Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth

https://doi.org/10.1016/S0140-6736(01)05329-6Get rights and content

Summary

Background

DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) is highly effective against most malaria-transmitting mosquitoes and is being widely used in malaria-endemic areas. The metabolite, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene), has been linked to preterm birth in small studies, but these findings are inconclusive. Our aim was to investigate the association between DDE exposure and preterm birth.

Methods

Our study was based on the US Collaborative Perinatal Project (CPP). From this study we selected a subset of more than 44 000 eligible children born between 1959 and 1966 and measured the DDE concentration in their mothers' serum samples stored during pregnancy. Complete data were available for 2380 children, of whom 361 were born preterm and 221 were small-for-gestational age.

Findings

The median maternal DDE concentration was 25 μg/L (range 3–178)—several fold higher than current US concentrations. The adjusted odds ratios (OR) of preterm birth increased steadily with increasing concentrations of serum DDE (ORs=1, 1·5, 1·6, 2·5, 3·1; trend p<0·0001). Adjusted odds of small-for-gestational-age also increased, but less consistently (ORs=1, 1·9, 1·7, 1·6, 2·6; trend p=0·04). After excluding preterm births, the association of DDE with small-for-gestational-age remained.

Interpretation

The findings strongly suggest that DDT use increases preterm births, which is a major contributor to infant mortality. If this association is causal, it should be included in any assessment of the costs and benefits of vector control with DDT.

Introduction

DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) was banned or restricted in industrialised countries in the 1970s but it is still widely used against malaria-transmitting mosquitoes in many countries.1 DDT is fairly inexpensive, the concentrations to which human beings are exposed during mosquito control are thought to have no serious toxic effects,2 and the benefits of the decrease in malaria are substantial.3, 4 International debate continues about the urgency of eliminating its use.5

DDT is a well established reproductive toxin in certain bird species. Although mammals are less susceptible to its effects than are birds,6 large doses of DDT produce premature delivery in rabbits,7 and might have the same effect on Californian sea lions.8 In man, DDT exposure has been associated with preterm birth and spontaneous abortion.9, 10, 11, 12 However, studies are small and have not received much attention. Overall, the effects of DDT on reproduction in man are unclear and understudied.

We have measured concentrations of p, p≪-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), a persistent metabolite of DDT, in 2613 maternal serum samples from the US Collaborative Perinatal Project (CPP). Most mothers were enrolled in the early 1960s, when DDT use in the USA was at a peak.13 Thus, we were able to examine the association between DDE exposure and preterm birth with greater statistical power than previously, and with adjustment for potentially confounding factors.

Section snippets

Study participants

The CPP was a prospective study of the cause of neurological disorders and other conditions in US children.14 Pregnant women were enrolled between 1959 and 1966 when they presented for prenatal care at any of 11 university hospital clinics or at one group of private practices. Researchers selected these mothers on the basis of centre-specific methods, such as the last digit of the patient's hospital number. Mothers lived in urban areas, and had a median socioeconomic index 7% below the USA

Results

Of the mothers and infants included in the analysis (table 1), the excess of male babies compared with the CPP overall was due to our selection design, which included boys with cryptorchidism, hypospadias, and polythelia. Similarly, the slightly higher proportion of black mothers was due to the high frequency of polythelia in this ethnic group. The median age of the mothers was 23 years (IQR 20–28). Most mothers did not complete formal education and were non-smokers. The median concentration of

Discussion

Our finding of a high frequency of preterm births in male and black infants, in mothers who had a low socioeconomic index, and those who were smokers are in accordance with previous reports.19 The high frequency of preterm birth in mothers who were young, of short stature, had a low body-mass index before pregnancy, and had a low rate of weight gain during pregnancy has also been reported but less consistently.19 The greater proportion of small-for-gestational-age births in girls was expected

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