Umbilical Cord Abnormalities in the Prediction of Adverse Pregnancy Outcomes

The objective of our study is to investigate the association of umbilical cord abnormalities with adverse pregnancy outcomes. The umbilical cord parameters that will be investigated as part of this study include the umbilical cord coiling index (UCI), umbilical cord (UC) diameter, umbilical vein (UV) diameter, UV flow velocity and the presence of nuchal cord. The UCI, UC, UV diameter \& flow and presence of nuchal cord will be measured in routine unselected populations at 20-22 weeks and 35-37 weeks gestation during the study period. We will also measure the UC and UV diameter in a nested population of high-risk pregnancies attending our placental disorders clinic which have been deemed to be at risk of having adverse pregnancy outcomes.

Primary objective:

To investigate if prenatal assessment of UCI, UC, UV diameter \& flow and presence of nuchal cord measured routinely in unselected screened populations at 20-22 weeks and 35-37 weeks' can provide an independent prediction of pregnancies that develop adverse pregnancy outcomes.

Secondary objectives:

To assess the correlation of UC and UV diameter measured by ultrasound scan and fetal magnetic resonance imaging in prediction of pregnancy outcome. To examine the association of these umbilical cord measurements and observations in a nested cohort of pregnancies in the high-risk placental disorders clinic.

The umbilical diameter is less than 2 cm, grows to a length of 50-60 cm by 28 weeks gestation and contains around 40 helical turns, which are twisted to the left rather than right because of the arrangement of helical muscle fibers in the vessels of the umbilical cord. These twists in the umbilical cord add to the strength of the cord by providing protection and resistance against compression of umbilical vessels. The overall final length of the UC and the number of coils is thought to be determined by the tensile forces due to fetal movements, rate of growth of UA and UV, fetal hemodynamics, distribution of the muscle fibers in the UA and amniotic fluid volume.

One of the common causes of fetal and neonatal adverse outcomes such as stillbirths or hypoxic ischaemic encephalopathy (HIE) is fetal hypoxia. The optimally oxygenated blood is transferred from the maternal blood to the fetus, crossing the placenta and the UC to reach fetal circulation. There are several studies which demonstrate that fetal hypoxia due to placental causes, whether chronic or acute, can lead to reduced transfer of oxygen and nutrition to the fetus. There is evidence from clinical and histological studies that impaired trophoblastic proliferation causes impaired placentation and leads to reduced oxygen transfer to the fetus resulting in preeclampsia (PE), fetal growth restriction (FGR) or stillbirth. However, there is limited and uncertain evidence regarding the contribution of UC abnormalities in the prediction of pregnancies with fetal hypoxia that result in hypoxic adverse outcomes such as HIE and stillbirth. There is need for further research to investigate the causes related to UC as not all hypoxic adverse outcomes have a placental etiology and a significant proportion of pregnancies with FGR, stillbirth and HIE have no ultrasound or histological evidence of impaired placentation, suggesting that there may be other factors in addition to the placenta that lead to such hypoxic morbidity.

There are studies published in literature demonstrating an association between UC abnormalities and adverse pregnancy outcomes such as FGR, PE, stillbirth or adverse outcomes such as caesarean section (CS) for fetal distress; but many of these are postnatal studies based on morphological and histological examination rather than prospective cohort studies carried out in the antenatal period. The few studies that investigate UC abnormalities in prenatal period are retrospective case-control studies with a relatively small sample size. This makes the findings less generalizable and overall difficult to effectively assess the precise contribution of UC abnormalities detected on ultrasound in the prenatal period that can potentially improve management and prevent such adverse outcomes.

This is a prospective observational cohort study carried out at a single center. This study will be conducted in compliance with the study protocol, the Declaration of Helsinki (1996), the principles of Good Clinical Practice (GCP) and applicable regulatory requirements. The study will be reviewed and approved by the Research Ethics Committees (REC) and competent authorities.

At our centre, all women booked for their maternity care are offered 3 routine ultrasound scans in their pregnancy: 11-13 weeks', 20-22 weeks' and at 35-37 weeks' gestation. Pregnancies that are deemed to be at high risk for delivery of a small for gestational age neonate are referred to a specialist placental disorders clinic for closer antenatal monitoring and fetal surveillance. At these visits, we ensure that there is a complete record of their personal, medical and obstetric history and perform an ultrasound scan to assess fetal growth, amniotic fluid and Doppler studies. This prospective study has two parts: first, a prospective observational cohort study in an unselected population and a nested cohort study in a high-risk population. Those agreeing to take part will be offered a patient information sheet and requested to sign a consent form, confirming their willingness to participate.

Prospective cohort study: In the screening study of an unselected population at 20-22 weeks' and 35-37 weeks' gestation, women are offered an ultrasound scan as part of standard care and will be invited to take part in the study which will involve taking the following additional ultrasound measurements:

1. Umbilical cord coiling index (UCI)
2. Transverse diameter of umbilical cord (UC)
3. Transverse diameter of umbilical vein (UV) and artery (UA)
4. Umbilical vein (UV) Doppler flow characteristics
5. Presence of nuchal cord

Nested cohort study: In the nested cohort study of the high-risk pregnancies, women are offered measurement of fetal biometry and Doppler assessments including UA Doppler as part of the standard care. Women will be invited to take part in the study which will involve taking the following additional ultrasound measurements:

1. Umbilical cord coiling index (UCI)
2. Transverse diameter of umbilical cord (UC)
3. Transverse diameter of umbilical vein (UV) and artery (UA)
4. Umbilical vein (UV) Doppler flow characteristics

The additional measurements of UC, UV and nuchal cord will only add 2-3 minutes of examination time and will not affect the care of women attending for their routine assessments as well as in the high-risk placental disorders clinic. These measurements taken as part of the study will not be available for clinical management and will be analysed after the completion of the study period.

Eligibility Criteria:
Inclusion Criteria:

1. Singleton pregnancies.
2. Women booked at our unit prior to 20 weeks' gestation.

Exclusion Criteria:

1. Multiple pregnancies.
2. Age \< 16 years.
3. Those unable to provide consent.
4. Pregnancies with fetal abnormalities.