PREDICTORS FOR ADVERSE MATERNAL AND FETAL OUTCOMES IN HIGH RISK PREGNANCY

Abstract

This thesis aims to undertake health technology assessments in high risk pregnancies through the following objectives:

1. In women with pre-eclampsia,

a) To evaluate the association of maternal genotype and severe pre-eclampsia

b) To assess the accuracy of tests in predicting adverse pregnancy outcomes

c) To develop composite outcomes for reporting in trials on late onset pre-eclampsia

2. In women with multiple pregnancy,

a) To study the association between chorionicity and stillbirth

b) To identify the optimal timing of delivery in monochorionic and dichorionic twin pregnancies 3. In the field of prediction research in obstetrics

a) To provide an overview of the existing prognostic models and their qualities

b) To evaluate the methodological challenges and potential solutions in developing a prognostic model for complications in pre-eclampsia

Methods

The following research methodologies were used: Delphi survey, systematic reviews and meta-analyses.

Results

1. a) Maternal genotype and severe pre-eclampsia:

57 studies evaluated 50 genotypes; increased risk of severe pre-eclampsia with thromobophilic genes.

b) Accuracy of tests in predicting pre-eclampsia complications: 37 studies evaluated 13 tests. No single test showed high sensitivity and specificity.

c) Delphi survey of 18/20 obstetricians and 18/24 neonatologists identified clinically important maternal and neonatal outcomes and maternal and neonatal composite outcomes were developed.

2. Prospective risk of stillbirth and neonatal deaths in uncomplicated monochorionic and dichorionic twin pregnancies: 32 studies were included. In dichorionic twin pregnancies, the risk of stillbirths was balanced against neonatal death at 37 weeks’ gestation. In monochorionic pregnancies, there was a trend towards increase in stillbirths after 36 weeks but this was not significant.

3. a) From 177 studies included, 263 obstetric prediction models were developed for 40 different outcomes, most commonly pre-eclampsia, preterm delivery, mode of delivery and small for gestational age neonates. b) The obstetric prognostic model challenge of dealing with treatment paradox was explored and seven potential solutions proposed by expert consensus.

Conclusion

I have identified the strength of association for genes associated with complications in pre-eclampsia, components for composite outcomes for reporting in studies on pre-eclampsia, and the optimal timing of delivery for twin pregnancies. My work has highlighted the gaps in prediction research in obstetrics and the limitations of individual tests in pre-eclampsia.