The infant of the diabetic mother: The critical developmental windows

The 1989 St Vincents Declaration stated, as a 5-year goal, ".that the outcome of the diabetic pregnancy should approach that of non-diabetic pregnancies" and indeed, over the last 20 years, significant reductions in spontaneous abortions, stillbirths, congenital malformations and perinatal mortality have been achieved. However, recent reports have shown that even in western countries, spontaneous abortions may be as high as 17%, stillbirths rate to be 5-times greater, congenital malformations to range from 4 to l0 times the usual rate, perinatal mortality to be 5-fold, neonatal mortality 15 times greater and that infant mortality might be trebled as the result of diabetic pregnancies. It can be argued that these bad results are the consequences of poor medical and social care, from prior to conception to perineonatal services and they most probably are. Nevertheless, even in the best series, corrected rates for diabetes-related malformations are considerably higher than the rest of the population and macrosomia poses a major problem, ranging from 20% in gestational diabetes to 35% or more in pre-existing diabetes. Again, it can be argued that good metabolic control has not been achieved or that good is not necessarily optimal. Alternatively, it can be put forward that there might be an abnormal genetic background contribution (and the evidence is pretty scanty) or that there might be other metabolic fuels besides glucose operating at different developmental stages of pregnancy and accounting for the aetiopathogenesis of the whole syndrome of the infant of the diabetic mother from congenital malformations to macrosomia, hypoglycaemia, RDS, polycythaemia, hyperbilirrubinaemia and so forth. Over the last 10 years there has been increasing evidence from animal and human studies to support the theory that in addition to sugars, other metabolic fuels, from ketones to deranged lipid peroxidation, may be responsible for the pathomechanisms of congenital malformations providing that they are present at certain (high) levels for a reasonable amount of time and especially at crucial developmental windows. Similarly, the same general principles of multifactorial influences at critical gestational ages have been postulated to explain the macrosomia, respiratory complications, the hypoglycaemia and the whole metabolic disturbances of the infant of the diabetic mother. It is quite possible that some, or all of these metabolic fuels may per se or in synergy, play a significant role and it is quite conceivable that besides the classical approach to strict glucose control, other dietary manipulations with supplementation or replacement of deficient substracts, free oxygen radical scavengers and antioxidants, might hold a promise for the near future. Whether the unfavourable intra-uterine diabetic millieu will also condition the later appearance of adult diseases from cardiovascular disorders to insulin resistant syndromes, remains to be confirmed, or conversely, disproved. For the moment, although priority should focus on pre-conceptional planning and strict metabolic control throughout pregnancy, special attention should nevertheless be paid to the various, but critical, developmental stages of the diabetic pregnancy.