Placental Health Study

As described in the previous section, women embarking on their first pregnancy are at an intermediate risk of developing placentally-mediated pregnancy complications. Therefore, in order to decrease their risk and help monitor their pregnancy progression, we suggest introducing a “placental health ultrasound” scan into their antenatal care, with the aim of catching complications as early as possible and customizing their health care plans to ensure a healthy pregnancy and a successful delivery of the baby.

The Placenta Health Study aims to determine if the “placental health ultrasound” performed at 20+0-22+6 weeks of pregnancy, in combination with other easily-available information (ex. first trimester blood results, maternal medical history, and pregnancy outcomes), can reliably identify the small subset of women in their first ongoing pregnancy that are at risk of significant placental complications.

Women who fit the following criteria are welcome to participate:

Inclusion Criteria:

• Nulliparous women (no previous pregnancy > 20 weeks)
• Singleton pregnancy (one fetus)
• With blood work done (IPS or FTS plus MSS testing)
• Antenatal care and anticipated delivery at Mount Sinai Hospital

Exclusion Criteria:

• Multiple pregnancy (e.g. twins or triplets)
• Recurrent vaginal bleeding during pregnancy
• Major fetal abnormality detected at the 19 week ultrasound scan
• Short cervix (<2.0cm) detected at 19 week ultrasound scan
• Ruptured membranes

The placental health ultrasound exam is performed between 20+0 and 22+6 weeks of gestation. This scan comprises of two parts: (1) assessment of placental shape and size which looks at placental length, thickness and insertion into the uterine wall; and (2) real-time Doppler ultrasound assessment of blood flow through maternal uterine arteries which looks at pulsatility of these blood vessels.

Before the placental health ultrasound exam:

You are required to obtain a photocopy of your antenatal 1 record (AN1) from your obstetrician, family physician or midwife affiliated with Mount Sinai Hospital and bring it to the Placental Health Study office (Room 3-904 in the Ontario Power Generation building) where you will meet Dr. Kingdom’s administrative secretary, Ms. Millie Xue. She will ask you to complete a brief 5-minute questionnaire (click here to view this form if you prefer to complete it at home). Assuming that you meet the eligibility criteria, she will book your appointment for the placental health ultrasound examination. Please note: you must have already had your detailed 19 week fetal anatomy “level 2” ultrasound examination the results of which were normal.

Placental health ultrasound examination:

The examination will be done by our RDMS-certified senior research sonographer Viji Ayyathurai at the same location (3rd floor of the Ontario Power Generation building). The ultrasound examination will take approximately 20 minutes and usually there is no wait-time for this appointment. Images of your placenta during the real-time 2D ultrasound will be obtained, after which a 3D sweep of the placenta will be done. These are part of the placental shape/size assessment. Next, maternal blood flow to the placenta will be examined using the Doppler ultrasound for both right and left uterine arteries. The panel of images below shows images from a placental health examination in normal (A and B) and abnormal (C and D) scans. If you bring a USB key or blank CD to your exam, we will provide you with a digital 3D image of your baby similar to the one seen on the left! (assuming the baby is in a good position to obtain a picture)

You will be told about the results of your exam immediately. The Placenta Clinic uses electronic records to keep track of your ultrasound results, and a copy of the scan will be faxed to your health care provider. Additionally, a copy can be provided to you upon your request.

Normal ultrasound results:

It is anticipated that 49 out of 50 women will have a “normal” result during this placental health ultrasound exam. A normal result predicts a low risk of a placental problem, equivalent to the level of a healthy “low risk” multiparous woman; this means that your risk of developing hypertension, impaired fetal growth and/or premature birth is very low.

Abnormal ultrasound results:

On the contrary, it is anticipated that 1 out of 50 women will be given an “abnormal” or “screen-positive” result. An abnormal result constitutes abnormalities in both placental morphology AND uterine artery Doppler reports. Abnormal placental pathology will be defined as a small (maximum length 95th percentile for gestational age.

What does an abnormal result mean?

Women with an abnormal result are at higher-than-average risk of a placental problem. We predict that their risk of preterm delivery

What happens once I am told I have an abnormal placental ultrasound exam?

If your ultrasound examination is abnormal, the following scenario will occur:

1. The ultrasound images will be reviewed in 24-48 hours by placental specialists Dr. Kingdom or Dr. Windrim.
2. A verified report will be faxed to your care provider and he or she will be contacted by Dr. Kingdom or Dr. Windrim.
3. You will be given a consultation appointment at the Placenta Clinic at Mount Sinai Hospital within 2 weeks to meet Dr. Kingdom or Dr. Windrim and for a repeat ultrasound examination.
4. At this time, you will have a chance to discuss with the doctors the subsequent course of your neonatal care, including the introduction of frequent ultrasounds to monitor your baby’s growth at the Placenta Clinic. All records obtained during ultrasound examinations at Mount Sinai Hospital will be shared with your care provider.

The following interventions will be available to women who have abnormal results during the placental health ultrasound exam:

1. Targeted education about the symptoms and signs of pre-eclampsia as well as more frequent antenatal clinic visits to detect the early signs of this disease and the option of home blood pressure monitoring;
2. Use of anti-hypertensive pills or “blood pressure lowering drugs” to control elevated blood pressure and thereby prevent unsafe elevations in blood pressure;
3. Ultrasound assessment of fetal growth and well-being by measuring blood flow to the baby’s brain and other parameters. These ultrasound examinations can be incorporated into a program of antenatal visits which would initially take place every 2 weeks, increasing to weekly if any evidence of growth restriction is found;
4. Admission to our hospital for more intensive monitoring of blood pressure of the mother, and for more frequent ultrasound or heart-beat tests (the non-stress test, NST) of fetal well-being. Our Hospital is a perinatal centre, designed to provide excellent care to babies that may need to be born prematurely as a result of placental or other complications;
5. Administration of 4 intra-muscular injections (into the thigh) of steroids (dexamethasone, 6mg) every 12 hours, to make the baby’s internal organs, especially the lungs, stronger in preparation for the need to deliver prematurely (before 34 weeks);
6. If delivery is required before 32 weeks, we may additionally give the mother an intravenous infusion of magnesium sulphate (MgSO4) to elevate baby’s magnesium levels at birth to protect the developing brain;
7. For pregnancies that continue successfully towards term, a pro-active plan to deliver (for example by induction of labour) at 37-40 weeks will avoid the risk of stillbirth due to placental insufficiency. Click here for the current level of evidence to support this intervention;
8. By taking a pro-active approach to assessing the mother and baby, we expect to avoid the potential complications that could arise from failure to make the correct diagnosis;
9. If the mother was not aware of her risk of pre-eclampsia, she may underestimate the severity of a medical emergency that headaches, vomiting and abdominal pain could indicate
10. If the health care provider was not aware of her risk of poor baby growth (IUGR), the developing baby is at risk of stillbirth

After you deliver your baby, we would like to send your placenta for a pathology exam. We believe this step is critical to test the accuracy of the concept of “placental health” assessment. Many studies have assessed these tests to predict pregnancy outcomes, though they have never included examination of the placenta, for two reasons. First, many hospitals do not have a major commitment to placental pathology. We know from our research that placental pathology is a highly-valuable guide to future pregnancy decisions, typically surpassing the value of blood tests. Our hospital has the focus and commitment to provide high-quality placental pathology services. The second factor is cost. Our current grant does not cover the placental pathology costs, but we are hoping to secure the necessary costs (at least $100/case) from future grants and grateful donations.

Capturing the placenta for pathology assessment in every woman screened in the Study is important for the several reasons:

1. Some women develop pre-eclampsia due to maternal clinical risk factors, ie, not due to placental dysfunction. These factors were identified by the SCOPE study (click here for more information).
2. Not all cases of pre-eclampsia/IUGR are associated with findings of a pathology characterized by small and infarcted placentas. We predict, however, that this common underlying pathology will be effectively detected by the placental health ultrasound (giving a “true positive” result).
3. By performing placental pathology in the entire screened cohort, we can evaluate the contributions from other types of serious placental pathology that in theory develop after the 20+0-22+6 week ultrasound examination and may be very difficult to detect, as they are essentially only visible under the microscope. These are fortunately rare and include:
   • Maternal immune cell invasion (inter-villositis, villitis of unknown etiology, histiocytosis)
   • Massive peri-villous fibrin deposition (maternal floor infarction)
   • Fetal thrombotic vasculopathy (including cord accidents)
4. Finally, it is possible that a certain level of “placental damage” is tolerated successfully by the mother and her developing baby. If this is true, we may be able to adjust the cut-off values for our screening ultrasound, so as to limit the proportion of “false-positive” women who are potentially harmed (anxiety, increased visits, interventions such as earlier induction of labour).

There are no direct risks to participating in the study, as the only addition to standard health care protocol is the placental ultrasound, which is a non-invasive technique, no different from the standard of care for high-risk pregnant women in the Special Pregnancy Program. The benefits of this study are most pronounced for women identified at-risk of placentally-mediated complications. With early detection, these women will be offered better antenatal care plans to carefully monitor baby’s growth and plan a timely delivery. This has the potential to prevent stillbirth and/or intrauterine fetal demise, as well as ensure the mother’s wellbeing by routinely measuring (and managing) her blood pressure and other vital functions. Furthermore, information obtained throughout the course of this study will benefit pregnant women in the future, in the event that the proposed placental health ultrasound scan is sufficiently accurate to identify a small subset of women at risk of developing placentally-driven pregnancy complications.

The results of this study will help determine what screening methods, or what combination of screening methods, are best at detecting placental dysfunction. These results could influence current Ontario Prenatal Screening program and the Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical practice guidelines of growth restricted infants, and may improve screening, diagnosis, and management of women at high risk of severe placental dysfunction and placentally-mediated complications of pregnancy.

We began the pilot phase of this program in February of 2012. To date, we have been very successful. We are currently following more than 1,000 women who have already delivered or are planning to give birth at Mount Sinai Hospital. We aim to recruit 5,000 women over the next 5 years. As shown below, we currently recruit 60-80 participants per month. This research has been very well received by our patient population, with approximately 80% of eligible women agreeing to participate.

The pilot phase of our study is complete, and we are in the process of analyzing the results. Updates on what these results show are coming soon!

Yes. We will collect the cord blood for stem cells immediately after delivery of the baby, while the placenta is still attached to the inside of your body. After this, we can send the placenta to pathology.

Yes. We strive to be inclusive of all cultures. We will simply record the clinical outcomes at delivery, weigh and describe your placenta. It will not go through a detailed pathology exam.

All abnormal pathology is reported to Dr. Kingdom. He will contact your care provider if he feels that the findings merit a discussion prior to your next pregnancy. A mutually-convenient time will be arranged for a meeting.

Yes. The energy output is low and the duration of exposure to obtain the image is quite short. We, therefore, believe that 3D ultrasound is as safe as normal 2D ultrasound, which is a standard part of prenatal care.