Pregnancy Outcome Prediction StudyUniversity Department of Obstetrics and Gynaecology; PI – Professor Gordon CS Smith

BACKGROUNDThe current pattern of provision of antenatal care for low risk women in the UK was established in 1929. The primary purpose of ante-natal care is to monitor fetal wellbeing and to screen for maternal complications of pregnancy. The approach to screening for complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth has remained largely unchanged for many years and includes measurement of blood pressure and symphysis fundal height, plus urinalysis. Randomised controlled trials of more high tech screening methods, such as utero-placental Doppler flow velocimetry and ultrasonic fetal biometry in the general population have generally failed to show improvements in outcome. A range of ultrasonic and biochemical markers of abnormal placentation have been described, but their utility in planning clinical care remains uncertain. In a previous review of literature on stillbirth we concluded that “future work on population-based screening for stillbirth should be preceded by high-quality, non-interventional prospective cohort studies, characterising the screening properties of new methods of risk assessment in an unselected population” (Smith & Fretts, Lancet 2007;370:1715-25).

AIMS

1. To identify novel genetic and molecular markers for adverse perinatal outcome

2. To develop an integrated method of screening pregnant women to determine their risk of adverse perinatal outcomes.

STUDY DESIGN

• This is a 5-year prospective cohort study of women attending for antenatal care at the Rosie Hospital.

• The study aims to recruit approximately 4,000 women in their first pregnancy. • Participation will involve (1) obtaining clinical and socio-demographic

information, (2) additional ultrasound scans and (3) collection of biological samples from participant, partner and placenta.

PROGRESS

• Recruitment commenced on 14thJanuary 2008. In the first 18 months of the study a total of 2096 eligible women were approached and 1211 (57.8%) agreed to participate in the study.

• In this period, a total of 2520 research scans have been performed in Addenbrooke’s Clinical Investigation Ward.

• 692 women have completed the ante-natal component of the study. Only 3.3% (n=40) have not completed the study. Most of these women have transferred their care to another hospital.

• Serum and plasma samples are collected at the 12,20,28 and 36-week visits.• A total of 3668 serum and plasma samples have been collected.• Maternal and paternal DNA samples are collected at the 20-week visit and a

total of 972 samples have been collected. • The projected collection in the bio-bank are on Figure 1.

The Study Pathway

Booking visit (~12 weeks)

• Medical and socio-demographic factors

• Ultrasonic measurements

• Maternal serum and plasma samples

Scans at 20, 28 & 36 weeks

• Ultrasonic measurements for fetal growth and placental function

• Maternal serum and plasma samples

• Maternal & paternal samples for DNA

At delivery

• Pregnancy and labour outcome

• Fetal cord blood

• Placental samples for RNA, DNA, gene expression and

histology

The POPS Biobank

PATIENT

ANTENATAL BIRTH

UMBILICAL CORDPlasma & serum samples at 12, 20, 28 & 36 weeks

Maternal whole blood for DNA at 20 weeks

Paternal saliva for DNA

MEMBRANE Fixed in Formalin

PLACENTA

For fetal DNA Fixed in FormalinCord blood plasma

and serum

For RNA For DNA/Protein Fixed in Formalin

Samples collected & projected size of biobank

Figure 1

0 10 20 30 40 50 600

1000

2000

3000

4000Number recruited

Number of placentalcollection

Number completedantenatal scans andsampling

Dotted lines - projectednumbers for the periodof study

Months

No

(cu

mu

lati

ve)