The literature on gestational diabetes uses observational data to study risk factors and outcomes but it has not rigorously analysed the effects interventions such as life style advice or metformin/insulin. On the other hand, clinical trials have investigated the impact of such interventions but are undertaken with a limited time horizon, and only capture pre-specified outcomes. Furthermore, the sample size in clinical trials is often too small to perform adequate subgroup analyses and evaluate heterogeneous treatment effects.
In combination with a regression discontinuity (RD) design, CPRD data allows us to exploit multiple advantages. To establish causality, the RD design takes advantage of the glucose threshold rules set by UK clinical guidelines that recommend gestational diabetes interventions.
Due to the CPRD’s long time horizon and large sample size, we will not only analyse antenatal and perinatal outcomes but will also evaluate postnatal effects of gestational diabetes interventions in different subgroups of patients.
We will evaluate the robustness of results by gradually narrowing down the bandwidth around the treatment threshold and thus only including patients with glucose levels increasingly close to the treatment threshold level.
Since gestational diabetes intervention may not only affect mean outcomes but also other distributional features such as the variance, we combine the RD design with a distributional regression approach (GAMLSS, Generalized additive models for location, scale and shape) to evaluate the impact on the whole conditional distribution of the outcomes.
The findings of this study are expected to provide novel insights into the effectiveness of gestational diabetes therapy in a real-life setting and can directly inform clinical practice.
Child outcomes: birth weight, gestational age at birth, size for gestational age, macrosomia, mortality, Apgar score, need for respiratory support, still birth/neonatal death, birth trauma (e.g. shoulder dystocia, fracture of humerus or clavicle, brachial plexus injury), neonatal hypoglycaemia, neonatal hyperbilirubinaemia, admission to the neonatology department, childhood obesity, childhood diabetes; childhood asthma, poor mental health.
Maternal outcomes: caesarean delivery or other interventions during labour, preeclampsia, plasma glucose and HbA1c levels during pregnancy, post-natal depression, later life outcomes of overweight or obesity, poor mental health, type 2 diabetes and complications (retinopathy, etc.), hypertension, strokes and MIs, renal disease, peripheral vascular disease, all cause mortality, cardiovascular mortality.
Till Bärnighausen - Chief Investigator - University of Heidelberg
Maike Hohberg - Corresponding Applicant - University Hospital Heidelberg
Anant Jani - Collaborator - University of Oxford
Anuradhaa Subramanian - Collaborator - University of Birmingham
Christian Bommer - Collaborator - University of Heidelberg
Duy Do - Collaborator - University of Heidelberg
Justine Davies - Collaborator - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Pascal Geldsetzer - Collaborator - University of Heidelberg
Sebastian Vollmer - Collaborator - Georg-August-Universität Göttingen