The impact of diabetes mellitus in pregnancy on maternal health outcomes
Date
2021
Authors
Nicolaou, Veronique
Journal Title
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Abstract
Hyperglycaemia in pregnancy, encompassing all types of diabetes, is on the rise with an alarming
global prevalence of 17%, of which 84% of these being accounted for by hyperglycaemia first
detected in pregnancy (HFDP). Alongside the well-established adverse short-term outcomes of
poorly managed or untreated disease, HFDP has a significant impact on the future health of
both mother and offspring, playing a crucial role in the global diabetes epidemic. Until recently,
HFDP, for which the highest prevalence occurs in low to middle income countries (LMIC),
played a minor role in the shadow of more obvious determinants of maternal and fetal
morbidity in these low-resource settings. More recently it has been recognised as an important
public health issue given its immediate burden on maternal health services and the
transgenerational and population level impact of the far-reaching ramifications for mother and
child alike. Though our knowledge surrounding the burden, determinants, and immediate
consequences of HFDP in South Africa (SA) is growing, the appreciation of its long-term
consequences is poorly explored. Understanding and appreciating the adverse health
consequences of HFDP creates an informed platform for developing health interventions for a
condition which is aggressively fuelling the non-communicable diseases (NCD) burden.
Objective:
Our study seeks to investigate the cardiometabolic outcomes in an urban cohort of black SA
women with a history of HFDP, 3-6 years following their delivery, compared to a group of
women non-exposed to HFDP on the backdrop of a high human immunodeficiency virus (HIV)
burden. Additionally, we explore the safety and efficacy of exposure to oral hypoglycaemic
agents (OHAs) on maternal and neonatal outcomes.
Design and Methods:
An initial retrospective review of all women identified with diabetes in pregnancy, including
type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and HFDP at the
Gestational Endocrine Clinic at Chris Hani Baragwanath Academic Hospital (CHBAH) for the
period 2012 through to 2018 was performed in order to investigate the immediate maternal
and neonatal outcomes as well as to explore the impact of HIV infection and exposure to OHAs
on these outcomes. Twin pregnancies and more than one pregnancy for the same individual
during the time frame were excluded. Secondly, a prospective follow up study of women
identified with prior HFDP between 2014 and 2017 were recruited for a cross-sectional
analysis between March and November 2019 (3-6 years following their index pregnancy) and
compared with women time-matched post-partum, who tested negative for HFDP (non-HFDP
group) using the same diagnostic test and criteria. Two hundred and four participants were
enrolled of which 103 were exposed and 101 non-exposed to HFDP. All participants were
subject to a detailed questionnaire as well as various measurements including anthropometric
parameters, blood pressure, the performance of an oral glucose tolerance test (OGTT), fasting
serum creatinine, insulin, lipids, and glycated haemoglobin (HbA1C), urine analysis, body
composition analysis via dual-energy x-ray (DXA) and ultrasonography of the carotid arteries
to determine intima media thickness (cIMT) and the presence of plaque. For the retrospective
review, descriptive statistics were used for comparing various maternal and neonatal outcomes
by diabetes groups and for statistically significant outcomes, logistic regression analysis was
performed using backwards selection following univariate analysis. For the prospective
evaluation of HFDP exposed vs. non-exposed HFDP participants, unadjusted and multivariate
adjusted odds ratio were estimated for the outcomes T2DM, metabolic syndrome (MetS) and
10-year cardiovascular risk calculated using Framingham risk score (FRS) from logistic
regression models. Further multivariate models were designed to explore the potential
association of historical maternal factors with the outcomes including fat mass index (FMI),
T2DM, and cIMT using logistic or linear regressions.
Results:
Of the initial 1071 diabetic pregnancies retrospectively identified, majority of the women had
pregestational diabetes (57%), with the remainder having HFDP (43%). Within the HFDP
group, 51% had “overt” GDM (DIP) vs. 49% “true” gestational diabetes (GDM). Despite good
glycaemic control across all the groups (as measured by HbA1C at term), adverse maternal and
neonatal outcomes were higher than in the background population with initial maternal HbA1C
and body mass index (BMI) being predictors of poorer neonatal outcomes. Overall HIV
prevalence within the group was 24%, lowest in those with HFDP (17.4%) and accounted for
significantly higher perinatal mortality (PNM) in HIV-infected 9.4% than non-HIV-infected
pregnancies 1.8%, p<0.001. The exposure to either oral hypoglycaemic agents (metformin and
glibenclamide) versus insulin on immediate maternal and neonatal outcomes in two cohorts of
women diagnosed with HFDP, was found to be safe and effective and was only significant for
an association between glibenclamide and macrosomia. In the prospective, cross-sectional
analysis of 103 women exposed to HFDP (identified using 75g OGTT, adopting IADPSG
criteria) versus 101 women not exposed to HFDP, higher rates of progression to all three
outcomes were noted with 44.6% of those exposed progressing to T2DM (adjusted risk of
10.5(95%CI 3.7-29.5)), 40.8% having MetS (adjusted risk 6.3(2.2-18.1)) and higher
cardiovascular risk as identified by FRS (adjusted risk 4.3(1.6-11.5)), however cIMT did not
remain significant after adjusting for confounders. Though HFDP exposure was a significant
predictor for T2DM, MetS and cardiovascular risk, certain maternal factors present either prepregnancy,
during the index pregnancy and/or post-partum were significantly associated with
the outcomes. HIV, however, was not found to play a role in progression to any of these
outcomes. Body composition was significantly altered in women exposed to HFDP versus
those non-exposed with significantly higher FMI (13.9 vs. 12.3, p=0.008) and visceral fat
indices between the groups and this remained significant after adjusting for confounders.
Conclusion:
The growing epidemic of obesity, T2DM, and cardiovascular diseases (CVD), particularly
amongst LMIC, poses a significant public health burden in addition to the persistent infectious
disease scourge. Our study confirmed the significant immediate adverse maternal and neonatal
outcomes in women with diabetes in pregnancy and provided reassuring data on the safety and
efficacy of OHAs in pregnancy when compared with the gold standard of insulin. Additionally,
we identified a group of young black women at high risk of cardiometabolic diseases in the
short-term following HFDP exposure. Appreciating these risks on the background of the
growing prevalence of HFDP assists in providing evidence to incorporate universal screening
programmes for detecting HFDP, expansion of specialized antenatal services for these women
in addition to the post-partum interventions including targeted screening, counselling, and
lifestyle and/or therapeutic interventions in order to preserve future maternal health and
interrupt the intergenerational cycle of chronic diseases. Future prospective studies are needed
to explore the best timing and impact of these interventions in curtailing these adverse
outcomes and improving cardiometabolic health in this vulnerable group of women.
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2021