Screening Tests to identify poor Outcomes in Pregnancy (STOP) Study

This is a prospective cohort study where women with a singleton pregnancy less than 12 weeks’ gestation attending the first antenatal clinic, their partners and babies will be recruited. The women will be monitored throughout pregnancy and pregnancy complications will be diagnosed using current international guidelines as follows. 1. Preeclampsia is defined as Systolic blood pressure greater than or equal to 140 mmHg and/or diastolic blood pressure greater than or equal to 90mmHg (Korotkoff V) on at least 2 occasions 4hours apart, after 20 weeks’ gestation, but before the onset of labour and Proteinuria greater than or equal to 300 mg/24h or spot urine protein:creatinine ratio greater than or equal to 30 mg/mmol creatinine or urine dipstick protein greater than or equal to plus 2 or any multi-system complication of preeclampsia including a. Haematological abnormalities consisting of thrombocytopenia (platelet count less than100 x 109/L), disseminated intravascular coagulation (DIC), haemolysis (diagnosed by features on blood film such as fragmented cells, helmet cells) and reduced haptoglobin b. Liver disease demonstrated by increased aspartate transaminase and/or alanine transaminase greater than 45 IU/L and/or severe right upper quadrant or epigastric pain, liver rupture, c. Neurological problems including eclampsia, imminent eclampsia (severe headache with hyperreflexia and persistent visual disturbance), cerebral haemorrhage d. Acute renal insufficiency demonstrated by new increase in serum creatinine to greater than 100 umol/L antepartum or greater than 130 umol/L postpartum e. Pulmonary oedema confirmed by chest x-ray 2. Small for gestational age birth defined as birthweight less than 10th percentile using customized centiles, adjusted for maternal weight, height, parity, ethnicity and infant sex 3. Spontaneous preterm birth defined as spontaneous preterm labour or preterm premature rupture of membranes resulting in preterm birth at less than 37 weeks 4. Gestational diabetes mellitus diagnosed by any of, Glucose tolerance test (GTT) fasting glucose greater than or equal to 5.5 mmol/L and/or 2 hour glucose greater than or equal to 7.8 mmol/L Polycose and no GTT available: 1h glucose greater than 11.0 mmol/l Fasting Glucose and no polycose or GTT available fasting glucose greater than or equal to 5.5 mmol/L Random Glucose and no polycose, GTT or fasting glucose, random glucose greater than 11.0 mmol/L Women with a singleton pregnancy less than 12 weeks’ gestation attending the first antenatal clinic will be invited to participate in the STOP study. At 12 weeks’, information will be obtained regarding baseline demographic characteristics including age, ethnicity, level of education, employment and income; medical/surgical and obstetric history, complications during the current pregnancy including hyperemesis and vaginal bleeding; family history of any medical or obstetric disorders; diet; exercise; intake of alcohol and recreational drugs and smoking. The height, weight and blood pressure will be measured and 20ml of peripheral blood and a sample of urine will be collected. Plasma will be used to assess selected biomarkers and micronutrients including folate, vitamin D, zinc and selenium. HbA1c will be measured in whole blood. A Doppler scan will be performed to assess the uterine artery blood flow. The women will also be given a lifestyle questionnaire to assess their level of anxiety and stress. At 18-20 weeks, at the time of the routine morphology ultrasound scan, a transvaginal ultrasound scan will be performed to measure the cervical length and a Doppler scan will be performed to assess the uterine and umbilical artery blood flow. At 28 weeks, an oral glucose tolerance test will be performed to screen for gestational diabetes mellitus. The women will be followed up throughout the pregnancy. If a pregnancy complication develops, a blood and a urine sample will be collected at the time of diagnosis of any complication for assessment of changes in the levels of the selected biomarkers. One in seven women who have uncomplicated pregnancies will be selected as late gestation controls and will be requested to give a blood and a urine sample for comparison. We will request the permission of the recruited women, to invite their partners to the STOP study. Consenting partners will be recruited at a time convenient to the participants. Information will be obtained regarding baseline demographic characteristics including age, ethnicity, level of education, employment and income; medical and surgical history, family history of any medical or obstetric disorders; diet; exercise; intake of alcohol and recreational drugs and smoking. The height, weight and blood pressure will be measured and 10ml of peripheral will be collected. Those who do not wish to provide a blood sample will be given the opportunity to provide a sample of saliva. We will request the permission of the women to obtain a sample of the placenta at delivery. 5ml of cord blood will also be collected at delivery. If a cord blood sample cannot be collected at delivery, a saliva sample or a buccal swab will be collected from the baby within 72 hours of delivery. We will obtain the baby’s length, weight, APGAR score and information on the presence/absence of any congenital malformations from clinical records. Babies that are admitted to a neonatal intensive care or special care unit will be followed up until discharge to identify the outcome. We will use the blood collected from women at the 12 weeks’ visit, the blood or saliva samples collected from the partners and the cord blood or buccal swabs collected from babies to extract DNA. Genotyping for selected polymorphisms will be performed using the Life Technologies Quant Studio Open Array system. We expect to validate our previous associations, as well as identify other candidate gene polymorphisms/haplotypes that are associated with pregnancy complications. We will identify clinical/lifestyle and environmental factors collected at 12 weeks’ gestation that interact with these polymorphisms to modify the risk of pregnancy complications.