First trimester preeclampsia screening (FTS) has the potential to radically change the delivery of obstetric care and the experience of pregnancy. At the same time, it will require changes from healthcare providers to shift the focus of care from the diagnosis and management of preeclampsia (PE) to screening and prevention.
The last century has seen this paradigm shift build alongside increases in obstetric knowledge and research — in large part due to a deeper understanding of biomarkers for the disease process of preeclampsia. Yet as PE is decoded and conquered, this achievement is only feasible with universal FTS access.
Tracing Preeclampsia's History
Globally, 76,000 pregnant parents and 500,000 babies die each year as a result of PE, according to the International Federation of Obstetrics and Gynecology (FIGO). When the disease strikes earlier in a pregnancy, the increased morbidity and mortality of preterm delivery can add tremendous burdens to families and the medical system.
The first victory against PE came in 1979 when a study published in The Lancet showed a significant reduction in the incidence of PE when taking low-dose aspirin throughout pregnancy. Since then, more than 30 studies have explored the dose and duration of aspirin use in pregnancy for the prevention of PE.
A 2017 study published in the New England Journal of Medicine confirmed that preterm PE was reduced by 60 percent for singleton high-risk pregnancies when first-trimester screening was combined with daily low-dose aspirin (150 mg/day) taken from 12 weeks through 36 weeks gestational age.
Although the beneficial effects of a simple aspirin have been repeatedly demonstrated, using maternal risk factors alone to identify candidates for this therapy only detected 40 percent of cases of preterm PE and 33 percent of term PE. Indiscriminate treatment of all pregnancies would risk potential adverse events related to aspirin use. This raises the need for a more exacting low false-negative screening tool that can be adapted and leveraged even in underserved regions — and that is where combined first trimester screening finds its use.
Understanding Combined First Trimester Screening
Preeclampsia is a complex syndrome with the potential to impact many organ systems. Early PE has been linked in part to the aberrant re-modelling of the maternal spiral arteries in pregnancy. These end branches of the uterine artery supply the intervillous spaces of the placenta and in a normal pregnancy undergo enormous change, or re-modelling, as blood flow increases. Other factors linked to PE include fetal growth restriction, placental infarct and immunological and chronic inflammatory states that impact placental function.
A lack of a common clinical language has historically impeded the diagnosis and management of PE. In 2019, FIGO published a comprehensive guide on screening for and preventing preeclampsia in the first trimester. The guide uses diagnostic criteria for PE proposed by the International Society for the Study of Hypertension in Pregnancy, which include blood pressure measurements, proteinuria and other possible indications. FIGO recommends universal FTS for all pregnant patients using the combined testing format.
The combined first trimester preeclampsia screening approach includes a standardized assessment of risk using four key factors:
- Maternal risk factors such as smoking, diabetes or lupus
- Measurement of mean arterial pressure (MAP)
- Serum placental growth factor (PLGF)
- Uterine artery pulsatility index (UtPI)
Finding an elevated UtPI augments a clinician's ability to predict PE. This noninvasive Doppler method for measuring vascular resistance is performed bilaterally on the uterine arteries at the level of the internal cervical os. It can be performed transabdominally or transvaginally in the first trimester.
If resources to measure PLGF and UtPI are not available, the combined screening undergoes modifications to include a combination of maternal risk factor screening and MAP. If there is a lack of sophisticated equipment to calculate MAP, all clinicians need is the ability to measure accurate blood pressure; from there, they can obtain the MAP through a simple formula or online calculator.
Other permissible modifications include substituting pregnancy-associated plasma protein when PLGF is not available, especially when used for screening for aneuploidy. The Fetal Medicine Foundation provides a free preeclampsia risk calculator that considers some of these factors.
How Can Providers Start Offering FTS?
The complete four-component method is ideal — however, any individual clinician can provide FTS within their constraints.
For clinicians looking to expand their preeclampsia prevention work, some options include:
- Reviewing patient and family medical history related to PE and identifying high-risk maternal characteristics during a preconception or first-trimester visit.
- Educating patients on the importance of knowing their blood pressure numbers.
- Training staff in the performance of blood pressure measurement and risk assessment for pregnant patients.
- Participating in continuing medical education about prevention, diagnosis and management of PE.
- Exploring locally available resources for lab work.
- Updating sonographers' first-trimester ultrasound skills to include UTPI.
- Perform UTPI in all first-trimester ultrasounds.
- Completing the Fetal Medicine Foundation free training on FTS.
- Educating at-risk patients on the importance of adherence to low-dose aspirin therapy.
Coupling FTS screening with the initiation of low-dose aspirin therapy enables clinicians to take part in reducing the incidence of preterm delivery due to preeclampsia and have a hand in promoting a better future for both patient and fetal health.
