Interpretation (in light of other evidence)
Sub-Saharan Africa is undergoing a rapid demographic and nutritional
transition associated with rapid urbanisation. With an emerging epidemic
of type 2 diabetes across the continent, hyperglycaemia in pregnancy is
likely to pose a major health challenge in this region in the future.
Screening and management of HIP are resource intensive. To give some
context, the per capita health expenditure in Uganda is $37.6 per year,
compared to $3,958 per year in the UK (2016
figures).17 Although there are no cost-effectiveness
studies for GDM screening from Africa, a study from India estimated a
cost of $1626 per life year gained.18 Costs of
management, often requiring insulin therapy and ambulatory capillary
glucose monitoring, are absorbed by women and are currently
prohibitively expensive to most.5 In order to
prioritise resources efficiently, it is therefore imperative to generate
local evidence to ensure only women most at risk of clinically relevant
adverse pregnancy outcomes are identified and treated.
In our study, the milder form of hyperglycaemia, GDM, was not associated
with birthweight >90th centile. Whilst
having larger babies is not a disorder in itself, it may lead to
obstructed labour and operative delivery, and is therefore commonly used
as a marker of perinatal adversity. This may have particularly grave
consequences in the low-income setting where antenatal and perinatal
care is suboptimal.19,20 Additionally, women in
sub-Saharan Africa are already more prone to obstructed labour due to
cephalopelvic disproportion.21–24 While the HAPO
study described a clear association between glycaemia and LGA, our study
did no show this relationship. The reasons for this discrepancy are
unclear, but they may relate to sample size. Nonetheless, if there is
association within our population, this is unlikely to have significant
clinical relevance.25
However, in accord with HAPO (which revealed that BMI was a stronger
predictor than glycaemia26), our data show that
mid-gestational BMI was a strong predictor of LGA. In the HAPO study,
78% of LGA babies were born to mothers with normal glucose
tolerance,27 whilst in our study nearly 90% of LGA
infants were from normoglycaemic mothers. These data underscore the
contribution of other (non-glucose) physiological determinants of fetal
growth. While there are few studies that have explored associations
between HIP and birthweight in Africa,11 those that do
exist also point towards BMI as a more reliable predictor of LGA than
glycaemia.9,28,29
GDM was also not associated with an increased risk of perinatal
mortality. However, we observed few perinatal deaths, and the study may
not have been sufficiently powered for this outcome. The background rate
of perinatal mortality in Uganda 41 per 1,000 births (eight times
greater than the HAPO study13,30), but we observed a
lower than expected figure of 28 per 1,000 births – perhaps because our
study was biased towards the urban population.
Mean arterial pressure (MAP) >90 mmHg (equivalent to blood
pressure of >130/85 mmHg) was the strongest predictor of
perinatal mortality. High mid-trimester MAP may be indicative of
pre-existing hypertension, or evolving gestational hypertension or
preterm pre-eclampsia. The strong association between such hypertensive
disorders and perinatal mortality in this setting is well
recognised.31 High blood pressure is linked to other
determinants such as maternal age, BMI and hyperglycaemia. Indeed GDM is
associated with a higher risk of hypertensive disorders, and treating
GDM might have benefit of reducing the incidence.6However, in our study, the significant contribution of MAP to perinatal
mortality was independent of GDM diagnosis, maternal age, and
mid-trimester BMI. This supports identification of high blood pressure
as a key strategy to reduce stillbirth and neonatal death.
Of our secondary outcomes, there was a significant association between
GDM, glucose concentrations and Caesarean delivery. We did not have the
depth of data to conclude whether clinicians were more likely to
intervene with Caesarean delivery merely from the diagnosis of
GDM,27,32 or due to true clinical indication from
obstructed labour or neonatal issues. Three quarters of Caesarean
deliveries were coded as ‘emergency’ rather than ‘elective’ in our
study, which may suggest suboptimal delivery planning. This warrants
further study as any unindicated Caesarean section in the low-resource
setting carries undue risk, particularly when performed as
emergencies.19 There was a tendency for a positive
association between fasting glucose and c-peptide concentration in
umbilical cord blood. This is in accord with previous data, including
from the HAPO study, that have shown that maternal fasting glucose is a
strong predictor of umbilical cord c-peptide concentration and clinical
neonatal hypoglycaemia.3 The difference in reported
neonatal hypoglycaemia between the GDM and normoglycaemic groups in our
study is limited by the predilection to test babies born to mothers with
a label of GDM. The rarity of the outcome reflects the challenges faced
in this setting to detect neonatal hypoglycaemia which offers a
potential argument in favour of testing for and managing GDM if the
association with high cord c-peptide is true. However, no reduction in
neonatal hypoglycaemia was detected in either of the large trials
assessing treatment of GDM, even in the context of management strategies
that would nonetheless be unfeasible in our
setting.6,7
Conclusion (to include practical and research recommendations)
Our data from Uganda indicate that GDM, even when not optimally managed,
is not associated with significant short term adverse outcomes, notably
excessive birthweight or perinatal death. Instead, simple screening and
interventions to manage obesity and hypertension may be more important
in reducing adverse pregnancy outcomes. However, more studies will also
be required to examine the effect of GDM beyond immediate peripartum
complications, as HIP has been implicated in fetal programming – with
potential to increase lifetime cardiovascular risk for both mother and
baby.33,34