Preeclampsia Screening at 12 Weeks and Preterm Birth Risk

Preeclampsia screening at 12 weeks combines the mother's history, her mean arterial pressure, uterine artery Doppler and a blood test for placental growth factor (PlGF) to estimate her risk of developing preeclampsia, a pregnancy disorder of raised blood pressure, later in pregnancy. Women at high risk are started on aspirin. The same 11 to 13 week scan can measure the cervix to predict preterm labour.

A chromosomally normal baby can still be lost to a pregnancy complication. Dr. Aanchal Sablok, Senior Consultant - Fetal Medicine, Artemis Hospitals, Gurugram, India, makes the point directly: if the mother develops hypertension or has a fit, the whole pregnancy is "taken for a toss", and a baby born too soon can face a long neonatal intensive care stay, severe morbidity or death. Two of the most consequential of these complications, preeclampsia and preterm birth, can be predicted at the 11 to 13 week scan, early enough to act. Her practice at Artemis Hospitals screens every pregnant woman for both.

Why screen for preeclampsia in the first trimester

The biological case for early screening rests on timing. During the first trimester, placental implantation is still under way and the maternal spiral arteries, the small arteries of the uterine lining, are still being remodelled to carry more blood to the developing pregnancy. That is why Dr. Sablok screens at this stage: it gives a window to estimate a woman's risk of developing preeclampsia later in pregnancy, while there is still time to act.

The same assessment also screens for small-for-gestational-age babies and fetal growth restriction (FGR).

The four components of the first-trimester preeclampsia risk model

The protocol Dr. Sablok follows, set out by the Fetal Medicine Foundation (FMF), combines maternal history with biophysical and biochemical measurements taken at 11 to 13 weeks. It has four components: maternal history, mean arterial pressure, uterine artery Doppler and placental biochemistry.

1. Maternal history and risk factors

A detailed history is taken from every woman. Several professional bodies list maternal risk factors for preeclampsia, and Dr. Sablok referred to the ACOG guidance of 2018, the NICE guidance of 2019 and more recent guidance from 2021. The factors she asks about include:

• which pregnancy this is
• hypertensive disease in a previous pregnancy
• chronic renal disease
• diabetes
• chronic hypertension
• maternal age
• body mass index
• a family history of preeclampsia, specifically whether the woman's own mother had preeclampsia in pregnancy
• multiple pregnancy

Pre-existing kidney disease deserves particular attention. As Dr. Sablok explained in the masterclass live discussion, a woman with chronic kidney disease is already at risk of chronic hypertension. When placental implantation takes place on top of that, the result is preeclampsia superimposed on chronic hypertension. A background of chronic renal disease, chronic hypertension or an autoimmune condition raises the risk of preeclampsia further, and may also raise the risk of a small-for-gestational-age baby.

2. Mean arterial pressure

Maternal blood pressure is measured in both arms, and Dr. Sablok stresses that it must be measured carefully. The figure used in the model is the mean arterial pressure (MAP), the average pressure in the arteries across one heartbeat.

3. Uterine artery Doppler

The uterine arteries carry maternal blood towards the pregnancy. Their pulsatility index (PI), a Doppler measure of resistance to blood flow, is measured at the first-trimester scan.

4. Placental biochemistry: from PAPP-A to PlGF

The double marker test drawn for aneuploidy screening measures pregnancy-associated plasma protein A (PAPP-A) and beta-hCG. PAPP-A carries information beyond aneuploidy: it also reflects placentation. A low PAPP-A is associated with impaired placental implantation. More recent work has shown that placental growth factor (PlGF) is a better biochemical marker than PAPP-A.

Preeclampsia screening detection rates

In the data Dr. Sablok presented, combining maternal history, uterine artery PI and PAPP-A detected about 62% of early preeclampsia, and detection rises further if a higher false-positive rate is accepted. Dr. Sablok put the detection rate for preeclampsia before 34 weeks at as high as 90% when PlGF is combined with mean arterial pressure and uterine artery PI.

In the Fetal Medicine Foundation's large screening studies, this combination detected about 90% of preeclampsia requiring delivery before 32 weeks and about 75% before 37 weeks, at a 10% false-positive rate.

For that reason, Dr. Sablok's current practice is to offer women the choice of a double marker test or NIPT for aneuploidy screening, and to ask every woman to have a PlGF test as well.

Ophthalmic artery Doppler: a newer preeclampsia marker

Maternal ophthalmic artery Doppler is the most recent addition to the model. The Fetal Medicine Foundation has studied it at the 11 to 13 week scan as an additional marker for preeclampsia, and it is measured in the mother at the same first-trimester visit.

The rationale is that preeclampsia affects not only the uterine arteries close to the placenta but also distant maternal vessels, notably the ophthalmic artery. As Dr. Sablok explained, in a woman at high risk of preeclampsia the resistance of the ophthalmic artery falls, its PI decreases and its velocity increases, allowing more blood to flow into the central nervous system.

The ophthalmic artery Doppler waveform shows a first peak systolic velocity (PSV1), a second peak systolic velocity (PSV2) and end-diastolic flow. In women at high risk of preeclampsia, PSV2 increases. Studies have examined the ophthalmic artery at several points in pregnancy, including 12 to 18 weeks, 19 to 23 weeks and 35 to 37 weeks. In the study Dr. Sablok singled out as most important, with velocities measured at 35 to 37 weeks, the ratio of the second to the first peak systolic velocity was higher in women who went on to develop preeclampsia than in the normal population.

Her unit at Artemis Hospitals performs ophthalmic artery Doppler routinely and is conducting research on its role in preeclampsia risk assessment. With maternal mean arterial pressure, uterine artery PI, PlGF and the ophthalmic artery combined, she put the detection rate for preeclampsia before 34 weeks at up to 90%.

Aspirin 150 mg for women at high risk

Women screened as high risk are started on aspirin, and those at low risk are not. Once the components are entered into the preeclampsia risk calculator, Dr. Sablok's unit sorts the result against a cut-off of 1 in 200:

• High risk. Aspirin is started at 150 milligrams per day, taken at bedtime, and the pregnancy is followed accordingly.
• Low risk. No aspirin is given.

Cut-offs vary between services. In the ASPRE trial, which established 150 milligrams of aspirin at night for women screened as high risk, high risk was defined as a risk of preterm preeclampsia above 1 in 100.

Her unit's calculators also look at early and late preeclampsia and at gestational hypertension.

Cervical length at 12 weeks to predict preterm labour

Cervical length can and should be measured at the first-trimester scan, between 11 and 14 weeks, in Dr. Sablok's view, rather than left until the 20-week anomaly scan where it often sits.

Her argument comes from what happens when it is not. She has recently seen women who came to her for the anomaly scan with cervical lengths of 16 and 18 millimetres, placing them at very high risk of preterm labour. Those findings would have been far more useful weeks earlier.

The principle is simple: the earlier a short cervix is detected, the earlier treatment can begin. Her management follows two tracks:

• Vaginal progesterone for a short cervix.
• A cervical stitch (cerclage) when the cervix is very short, or when there is a history of recurrent miscarriage or recurrent preterm labour.

Started early, these measures reduce the risk of the woman going into preterm labour and delivering preterm. In current RCOG and ACOG guidance, vaginal progesterone is the standard treatment for a short cervix found on its own, while cerclage is reserved mainly for women with a history of mid-trimester loss or spontaneous preterm birth, including those with such a history whose cervix is found to be short. As with preeclampsia, the findings are entered into software that calculates the risk of spontaneous delivery before 34 weeks of gestation.

Twin pregnancy: chorionicity at 12 weeks

The same first-trimester visit establishes chorionicity in twin pregnancies, that is, whether the twins share a placenta, and is used to predict twin complications. Dr. Sablok lists this as one of the core functions of the 12-week scan; it is also the visit at which conditions such as a cystic hygroma in one twin, or conjoined twins, can be diagnosed.

What this means for referring clinicians

Dr. Sablok's message to clinicians is that preeclampsia and preterm birth screening belong at the same visit as aneuploidy screening, not as later add-ons. The 12-week scan gives a window in which placentation can still be assessed, aspirin can still be started, and a short cervix can still be treated early. Early prediction enables risk stratification, timely referral to a specialist clinic and time for intervention.

The aneuploidy component of the same visit is covered in Down syndrome screening detection rates, and the full scope of the scan, including the structural abnormalities it can detect, is set out in the complete guide to the first trimester ultrasound.