controlled for in the multivariate analvsis. Furthermore, the suggested risk factors occurring later in life, such as psychological mechanisms and drug availability and exposition, cannot explain the demonstrated associations between administration of drugs during the perinatal period and subsequent addiction in offspring. Also, genetic and socioeconomic factors were largely controlled for by matching addicts with their own siblings.In conclusion, effective pain relief is sometimes an important factor for a successful outcome of delivery, as well as for the ability of the mother to accept and care for the child in the future. At present, when considering the choice of analgesic method immediate risks and benefits are mainly taken into account. When depressant or sedative drugs are used their possible long term effects due to imprinting also seem to be important. From this point of view, analgesic methods not associated with passage of substantial amounts of drugs across the placenta are preferable. Our Abstract Objective-To see whether a prepregnancy clinic for diabetic women can achieve tight glycaemic control in early pregnancy and so reduce the high incidence of major congenital malformation that occurs in the infants of these women. Design-An analysis of diabetic control in early pregnancy including a record of severe hypoglycaemic episodes in relation to the occurrence of major congenital malformation among the infants.Setting-A diabetic clinic and a combined diabetic and antenatal clinic of a teaching hospital.Patients -143 Insulin dependent women attending a prepregnancy clinic and 96 insulin dependent women managed over the same period who had not received specific prepregnancy care.Main outcome measure-The incidence of major congenital malformation.Results-Compared with the women who were not given specific prepregnancy care the group who attended the prepregnancy clinic had a lower haemoglobin Al concentration in the first trimester (8.4% v 10-5%), a higher incidence of hypoglycaemia in early pregnancy (38/143 women v 8/96), and fewer infants with congenital abnormalities (2/143 v 10/96; relative risk among women not given specific prepregnancy care 7-4 (95% confidence interval 1-7 to 33.2)).Conclusion-Tight control of the maternal blood glucose concentration in the early weeks of pregnancy can be achieved by the prepregnancy clinic approach and is associated with a highly significant reduction in the risk of serious congenital abnormalities in the offspring. Hypoglycaemic episodes do not seem to lead to fetal malformation even when they occur during the period of organogenesis.

Human neutrophil elastase may be a major mediator of vascular damage and could contrihutc to the vascular damage seen in women with pregnancy-induced hypertension (PTH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal nonpregnant women, 32 women with normal pregnancies, 19 with mild/ moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimniunoassay. 'There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in iiormotensive pregnancies and this may contribute to thc vascular lesion associated with DIH. Concentrations were also significantly higher in normal pregnancy than in non-pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.Pregnancy-induced hypertension (PUT) remains a leading cause of maternal inortality in the UK (DHSS 1986) and is a major source of perinatal mortality and morbidity. Its precise aetiology remains obscure, but it is charactcrizcd by increased vascular reactivity (Gant r / al. 1973), platelet activation, coagulation changes (Howie 1977) and vascular damage (Robertson & Khong 1986). This last fcature has been termed

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Summary. Human neutrophil elastase may be a major mediator of vascular damage and could contribute to the vascular damage seen in women with pregnancy‐induced hypertension (PTH). Elevated plasma levels of this substance will reflect neutrophil activation in vivo. To determine neutrophil activation in PIH, we studied 30 normal nonpregnant women, 32 women with normal pregnancies, 19 with mild/moderate PIH and 16 with severe PIH between 28 and 39 weeks gestation. Plasma neutrophil elastase was measured by radioimmuno‐assay. There was a significantly higher concentration of plasma neutrophil elastase in both mild/moderate and severe PIH than in normotensive pregnancies and this may contribute to the vascular lesion associated with PIH. Concentrations were also significantly higher in normal pregnancy than in non‐pregnant women which suggests that neutrophil activation and degranulation are increased in normal pregnancy.