2 Clinical need and practice

Guidance

The problem addressed
The condition
The diagnostic and care pathways

2 Clinical need and practice

The problem addressed

2.1 Placental growth factor (PlGF)‑based tests are intended to be used with clinical judgement and other diagnostic tests, to help diagnose suspected pre‑eclampsia. This assessment focuses on diagnosing pre‑eclampsia in the second and third trimesters of pregnancy. Using PlGF‑based tests in addition to standard clinical assessment could result in a faster and more accurate diagnosis of pre‑eclampsia, and better risk assessment for adverse outcomes in women with suspected pre‑eclampsia. It could also allow women in whom pre‑eclampsia has been ruled out with a PlGF‑based test to return to community care instead of being admitted to hospital for observation.

2.2 PlGF‑based tests measure the amount of PlGF in blood plasma or serum. PlGF is a protein involved in placental angiogenesis (the development of new blood vessels). In pre‑eclampsia, levels of PlGF can be abnormally low. In normal pregnancy, PlGF levels rise and peak at 26–30 weeks, so when PlGF levels do not rise during pregnancy there may be placental dysfunction.

2.3 In addition, some PlGF‑based tests measure soluble FMS‑like tyrosine kinase‑1 (sFlt‑1), a protein that is thought to disable other proteins associated with blood vessel formation, such as PlGF. In women who develop pre‑eclampsia, the levels of sFlt‑1 are higher than those seen in normal pregnancy.

2.4 Four PlGF‑based tests were identified during scoping as relevant to this assessment: the Triage PlGF test (Alere International); the Elecsys immunoassay sFlt‑1/PlGF ratio (Roche Diagnostics); the DELFIA Xpress PlGF 1‑2‑3 test (Perkin Elmer); and the BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio (Thermo Fisher Scientific).

The condition

2.5 Pre‑eclampsia is a potentially serious complication of some pregnancies, which when identified, needs referral to a specialist and hospital admission for both maternal and fetal monitoring. It is thought to be related to problems with the development of the placenta. Pre‑eclampsia is characterised by high blood pressure (hypertension) and proteinuria, which occurs when the kidneys leak protein into the urine. The presence of either hypertension or proteinuria alone during pregnancy can also indicate a risk of developing pre‑eclampsia. Other symptoms include headache, visual disturbances, right upper quadrant abdominal (epigastric) pain, oedema (swelling of the hands, face or feet) and oliguria (low output of urine).

2.6 If pre‑eclampsia is not diagnosed and closely monitored, it can lead to potentially life-threatening complications including eclampsia, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, stroke, or organ dysfunction. Women who have hypertension or pre‑eclampsia during pregnancy may have a higher risk of placental abruption. Women who develop pre‑eclampsia during pregnancy may also be at greater risk of cardiovascular disease in later life.

2.7 Gestational hypertension and pre‑eclampsia may also affect the fetus, placing it at increased risk of intrauterine growth restriction, prematurity and intrauterine death.

The diagnostic and care pathways

2.8 The NICE guideline on antenatal care recommends measuring blood pressure and testing urine for proteinuria to screen for pre‑eclampsia at each routine antenatal visit.

2.9 The NICE pathway on pre-eclampsia describes the assessment and treatment of women at risk of pre‑eclampsia or with pre‑eclampsia. The NICE guideline on hypertension in pregnancy was used to create the pathway.

Identifying and managing the risk of developing pre‑eclampsia

2.10 The NICE guideline on hypertension in pregnancy states that women who are classified as being at high risk of pre‑eclampsia are those who have any of the following risk factors identified during the booking appointment:

hypertensive disease during a previous pregnancy
chronic kidney disease
autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome
type 1 or type 2 diabetes
chronic hypertension.

2.11 Women who are classified as being at moderate risk of pre‑eclampsia are those who have any of the following risk factors identified during the booking appointment:

first pregnancy
age 40 years or older
pregnancy interval of more than 10 years
BMI of 35 kg/m² or more at first visit
family history of pre‑eclampsia
multiple pregnancy.

2.12 Women with either 1 high risk factor, or more than 1 moderate risk factor for pre‑eclampsia, are advised to take 75 mg of aspirin daily from 12 weeks' gestation until the birth of the baby. They are also considered for more frequent blood pressure monitoring, and assessment for proteinuria. Women who have significant hypertension (diastolic pressure of 90–110 mmHg) or a proteinuria result of 1+ on urinalysis reagent strips need increased surveillance.

Management of pregnancy with gestational hypertension

2.13 The NICE guideline on hypertension in pregnancy defines gestational hypertension as new hypertension presenting after 20 weeks' gestation without significant proteinuria. Increased surveillance is needed to confirm a diagnosis of gestational hypertension, because some women may present with transient hypertension. Women with gestational hypertension are recommended to have assessment for proteinuria at each visit to detect the onset of suspected pre‑eclampsia (see table 1).

Table 1 Management of pregnancy with gestational hypertension

Degree of hypertension	Mild (140/90 mmHg to 149/99 mmHg)	Moderate (150/100 mmHg to 159/109 mmHg)	Severe (160/110 mmHg or higher)
Admit to hospital	No	No	Yes (until blood pressure is 159/109 mmHg or lower)
Treat	No	With oral labetalol as first-line treatment	With oral labetalol as first-line treatment
Measure blood pressure	Not more than once a week	At least twice a week	At least 4 times a day
Test for proteinuria	At each visit	At each visit	Daily
Blood tests	Only those for routine antenatal care	Test kidney function, electrolytes, full blood count, transaminases, bilirubin	Test at presentation and then monitor weekly: kidney function, electrolytes, full blood count, transaminases, bilirubin
Birth before 37 weeks should not be offered to women with gestational hypertension whose blood pressure is lower than 160/110 mmHg with or without antihypertensive treatment.

Management of pregnancy with pre‑eclampsia

2.14 The NICE guideline on hypertension in pregnancy defines pre‑eclampsia as new hypertension with significant proteinuria after 20 weeks' gestation. Women diagnosed with pre‑eclampsia should be assessed at each consultation by a healthcare professional trained in the management of hypertensive disorders of pregnancy and offered an integrated package of care that includes admission, testing and treatment that relates to the severity of hypertension (see table 2).

Table 2 Management of pregnancy with pre‑eclampsia

Degree of hypertension	Mild (140/90 mmHg to 149/99 mmHg)	Moderate (150/100 mmHg to 159/109 mmHg)	Severe (160/110 mmHg or higher)
Admit to hospital	Yes	Yes	Yes
Treat	No	With oral labetalol as first-line treatment	With oral labetalol as first-line treatment
Measure blood pressure	At least 4 times a day	At least 4 times a day	More than 4 times a day
Test for proteinuria	Do not repeat quantification of proteinuria	Do not repeat quantification of proteinuria	Do not repeat quantification of proteinuria
Blood tests	Monitor the following twice a week: kidney function, bilirubin, electrolytes, full blood count, transaminases	Monitor the following 3 times a week: kidney function, bilirubin, electrolytes, full blood count, transaminases	Monitor the following 3 times a week: kidney function, bilirubin, electrolytes, full blood count, transaminases