Pregnancy complications such as preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and gestational diabetes mellitus (GDM) occur in 25% of first pregnancies and can threaten the health of mother and/or baby. Currently, no reliable biomarkers exist in clinical practice that can predict which women are likely to have a complicated pregnancy. This is particularly important in first pregnancies where there is no prior pregnancy history to inform the clinician. The SCOPE (SCreening fOr Pregnancy Endpoints) international consortium has a biobank and detailed clinical and lifestyle database for nearly 6,000 women pregnant for the first time. In Adelaide, 1169 women were recruited prospectively with detailed clinical and lifestyle information, biological samples from mother, baby and father, as well as the known outcome of the pregnancy. Of the 1169 Adelaide SCOPE women 861 had uncomplicated pregnancies, 93 developed PE, 95 delivered SGA babies, 69 delivered preterm and 51 had GDM. Since the mechanisms by which environmental factors alter gene expression are thought to be epigenetic, and the most characterised epigenetic mechanism is DNA methylation, we investigated whether differential DNA methylation identifies biomarkers that predict pregnancy complications, either alone or in combination with clinical characteristics and genetic information. To identify biomarkers for predicting pregnancy complications, DNA was extracted from the buffy coat from maternal blood samples collected at 15 weeks gestation. Our preliminary data from 8 PE, 8 PTB and 8 uncomplicated term pregnancies suggests that analysis of DNA methylation could generate reliable diagnostic markers to predict pregnancy outcome, using a methodology known as methylation-sensitive genotyping-by-sequencing (MS-GBS) or methylation restriction enzyme sequencing (MRE-Seq). Currently we are analysing more than 400 samples from women with the 4 common pregnancy complications and uncomplicated pregnancies to validate DNA methylation changes that can be used for screening maternal blood samples for pregnancy complication prediction.