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It appears from the HAPO study19 _{that screening}

could use FPG. However we need further analysis before we can adopt that policy.

Research need 1: analysis of HAPO data to

determine how many women in categories 1–4 by FPG are in categories 5 to 7 by post-load PG.

85 HAPO data could also be used to address the

question of selective or universal screening, by comparing risk factors, and different thresholds, with each category. The hypothesis might be that women with risk factors are more likely to be in the higher categories.

There is one issue which needs to be considered if we relied on FPG for screening, which is that of later maternal T2DM. Retnakaran et al. (2009)131

found that FPG was better for predicting LGA infants, but that the post-load PGs were better for predicting post-gestational T2DM. The risk of T2DM has been thoroughly reviewed by Bellamy et al. (2009),132 _{with a meta-analysis showing that}

women who had had GDM (defined in various ways) had a relative risk of 7.4 compared with those who were normoglycaemic during pregnancy. Research need 2: can risk factors identify a group of women whose risk of adverse outcomes is very low and who need not be screened?

The third research need concerns screening at booking clinic and how that should be done. At this stage we would be looking for pre-gestational diabetes or non-diabetic hyperglycaemia, so HbA_1c might be useful. It has been recommended by the National GDM Technical Working Party in New Zealand.133

Research need 3: is HbA_1c a useful test at booking clinic for detecting pre-gestational diabetes, and also pre-gestational insulin resistance likely to be followed by HGP?

The above needs concern how best to screen, but an unresolved issue is the level of glucose at which intervention is worthwhile, which requires a cost- effectiveness analysis. This has been addressed by Lee et al. (2008)37 _{(whose results are available only}

as an abstract). It needs to be repeated in a UK context, by re-running the National Collaborating Centre for Women’s and Children’s Health modelling with updated assumptions and for the seven HAPO categories.

Research need 4: at which HAPO category does treatment become cost-effective, taking into account infant and maternal outcomes, and treatment with the cheaper oral agents when lifestyle measures fail, with insulin being used only when the oral drugs fail?

As mentioned above, it would be better to reduce the problem at source, by persuading women to

achieve normal weight before conception. Trials of targeted health education are necessary.

Research need 5: could a health education campaign raise awareness of the problems of HGP amongst women of child-bearing age, and reduce the number becoming pregnant while overweight? Or at least reduce the BMI, and hence the risk? The time continuum: research need 6: given the increasing age and weight of mothers-to-be, should screening start earlier? Screening is usually done at 24–28 weeks. Agarwal et al. (2007)134 _described

GDM as a form of T2DM which comes on over months not years. Are there studies which report the prevalence of HGP by gestational age, perhaps at 2-week intervals? Could such studies identify optimum time to screen, perhaps depending on age and BMI? Several commentators have noted that there can be delays between screening, diagnostic testing and treatment, and that these can occur during the ‘therapeutic window’ and hence result in poorer outcomes.

Research need 7: the HAPO study19 _recorded

head circumference. Given that the reported macrosomic babies will consist of a mixture of large healthy babies and truly macrosomic ones, the HAPO investigators could isolate the abnormal macrosomic ones by comparing weight with head circumference. This might allow a more refined analysis of macrosomia by HAPO category.

Research need 8: Reece et al. (2009)135 _{report that in}

the USA, the prevalence of pre-gestational diabetes in pregnancy has increased, but that of GDM has not. Conversely, Massicotte et al. (2009)136 _reported

that the prevalence of GDM in Canada had tripled over the last 10 years. It would be of interest to monitor trends in the UK.

One issue, raised by one of the peer reviewers for this report, was whether GDM should be defined on the basis of glucose at all. It may seem odd to define any diabetic condition on the basis of anything other than glucose, but the referee’s point was presumably that we are looking at a metabolic condition with abnormalities in physiological variables other than glucose, and that some of these other variables, such as lipids, might have a stronger relationship with adverse outcomes than glucose. Hadden and McLaughlin in a 2009 review note that normal pregnancy is hyperlipidaemic, and that birthweight is positively correlated with both plasma triglycerides and free fatty acid concentrations.137 _{Is what we call GDM, part of a}

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set of ‘metabolic syndromes of pregnancy’, with some women displaying changes more in glucose homeostasis, but others more in lipids, and some in both?