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Aims

1		Control blood sugars.  Poorly controlled diabetes is associated with a higher rate of miscarriage, which can be reduced to that of the background population if good glycaemic control is established. The miscarriage rate relates to HbA1c levels and first trimester hyperglycaemia. Type 2 diabetics on oral hypoglycaemic agents should be changed to diet+/- insulin as oral hypoglycaemic agents may not allow optimal control and are not licensed in pregnancy. Congenital anomalies are now the leading cause of perinatal mortality and morbidity in diabetic pregnancies. The incidence is three to four times that of non diabetic pregnancies and is related to hyperglycaemia. However, this can be reduced with good glycaemic control, which needs to be pre conceptual as fetal malformations occur before the seventh gestational week (1,2). Thus at routine presentation to antenatal clinic any potential structural damage will have been done. In vitro studies have identified three main contributing factors:
		i   Hyperglycaemia causes a reduction in myo-inositol, which in turn reduces arachidonic acid and prostaglandins. This causes glucose-induced neural-tube closure defects in rodents but can be prevented by supplementation with myoinositol, arachidonic acid and prostaglandin E2 (3). ii   Evidence for the involvement of free oxygen radicals in diabetes related malformations has been provided by the ability of oxygen radical scavengers to reduce the frequency of congenital malformations in rats (4). iii   Maternal diabetes has been linked to disruptions of DNA synthesis and structure; for example, beta-hydroxybuterate has been shown in high concentration to inhibit the pentose phosphate pathway that usually provides ribose molecules for nucleic acid synthesis. This has resulted in neural tube defects (5).
2		Early morning hypoglycaemia is more common in early pregnancy (see Antenatal Care) as tighter control is established. Both the woman and her partner must be made aware of this and be able to deal with such events by administering glucagon if necessary. Pregnant women must also be made aware of the dangers of hyperglycaemia and ketoacidosis.
3		All pregnant women should receive folic acid for at least 3 months preconceptually and until 12 weeks gestation.
4		All pregnant women should be screened for retinopathy. The presence and severity of retinopathy is strongly predictive of fetal outcome (6). In addition the severity is related to the degree of progression during pregnancy. Those with minimal or no retinopathy at the beginning of pregnancy have a 10% chance of progression whilst those with proliferative retinopathy have a 50% chance of progression (7). The deterioration is worst for those whose control undergoes rapid improvement in early pregnancy. Laser photocoagulation is safe in pregnancy and should be used for those who develop proliferative retinopathy. Fortunately post partum regression is common.
5		Renal function as assessed by urea and electrolytes, creatinine clearance and proteinuria estimation should be checked pre pregnancy. Diabetic nephropathy is present in 5-10% of diabetic pregnancies (8). For those with pre existing nephropathy, pregnancy outcome is partly dependant on the degree of renal impairment. Those with a creatinine clearance<50ml or a serum creatinine >150μmol/l have a much higher chance of poor pregnancy outcome. Renal impairment is associated with prematurity, growth restriction and perinatal mortality. Those with severe renal insufficiency also risk permanent deterioration of renal function.
6		Those with hypertension pre pregnancy have a higher risk of preeclampsia in pregnancy. Preconceptual care should aim to optimise hypertension control. Angiotensin converting enzyme inhibitors may cause fetal renal impairment, growth restriction and incomplete skull ossification and should therefore be stopped and changed to safer alternatives such as methyldopa or labetalol.

Pre conceptual care does improve outcome (9) and is cost effective (10). However, attendance is usually 25-35% in this country and this was identified as one of the potential reasons for suboptimal outcome in this country.

References

1. Steel JM, Johnstone FD, Hepburn DA, Smith AF. Can pre pregnancy care of diabetic women reduce the risk of abnormal babies? BMJ 1990; 301:1070-1074, Abstract

2. Miller E, Hare JW, Cloherty JP, Dunn PJ, Gleason RE, Soeldner JS, Kitzmiller JL. Elevated maternal haemoglobin A1c in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 1981; 304: 1331-4, Abstract

3. Baker L, Piddington R, Goldman A, Egler J.Myoinositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos. Diabetologia 1990; 33:593-596, Abstract

4. Eriksson UJ, Borg LAH. Diabetes and embryonic malformations: role of substrate-induced free oxygen radical production for dysmorphogenesis in cultured rat embryos.Diabetes.1993; 42:411-419, Abstract

5. Hunter ES, Sadler TE, Wynn RE. A potential mechanism of DL-B-hydroxybuterate-induced malformations in mouse embryos. Am J. Physiol. 1987; 253:E72-E80, Abstract

6. Klein BE, Klein R, Meuer SM, Moss SE. Does the severity of diabetic retinopathy predict pregnancy outcome? J. Diabetes complications. 1988;2:179-184, Abstract

7.Chew E et al. Metabolic control and progression of retinopathy: the diabetes in early pregnancy study. Diabetes Care. 1995; 18:950-954, Abstract

8.Landon MB, Gabbe SG. Diabetes mellitus and pregnancy. Obstet Gyn Clin North Am 1992; 19:633-48, Abstract

9. Fuhrmann K, Reiher H, Semmler K, Fischer F, Fischer M, Glockner E. Prevention of congenital malformations in infants of insulin-dependent diabetic mothers. Diabetes care. 1993; 6:219-23, Abstract

10. Elixhauser A et al. Cost benefit analysis of preconceptual care for women with established diabetes mellitus. Diabetes care. 1993; 16(8): 1146-57