Placental protein 13

Clinical investigations of PP13  

Continuous monitoring in pregnant women’s serum

As pregnancy progresses the level of PP13 in maternal serum slowly rises.

In a prospective study (Huppertz, personal communication, publication in preparation) samples were collected from Swiss women starting at 6-8 weeks gestation. The samples were continuously tested for PP13 serum levels throughout pregnancy and for some weeks after delivery.

For unaffected control patients, serum PP13 increased moderately from a basic level during the 2nd to 3rd trimesters. In contrast, the PP13 values in women who went on to develop late-onset PE were lower in the 1st trimester but continuously increased to exceed the level of unaffected women in the 3rd trimester.

Separating PE cases from false positives

PerkinElmer has assessed the changes in the level of PP13 in samples collected in the UK during the course of pregnancy. The study characterized three groups:

• 15 women who went on to develop PE (PE)
• 26 women who were considered high risk according to risk factors but were unaffected (HR)
• 31 women who by risk factors and by outcome were unaffected (SR).

The risk factors were as follows:

• Chronic hypertension
• Previous PE
• Diabetes
• Chronic renal disease
• Anti-phospholipid syndrome
• Body mass index >30
• Abnormal uterine artery Doppler at 18-22 weeks GA

Continuously monitoring the disease progression between 11-13 and 23-25 weeks showed that PE cases started with low PP13 in the 1st trimester and reached normal level later. Women with risk factors who did not develop PE started with low PP13 in the 1st trimester but remained low throughout. The women with no clinical risk factors and who did not develop PE remained at approximately the same level throughout the period of monitoring (figure 1).

Differentiating between PE and PIH pregnancy induced hypertension

In a prospective study in association with the Maccabi Healthcare System in Israel Meiri et al. (unpublished data) have compared levels of PP13 in pregnant women with PE and with pregnancy induced hypertension (PIH). The ELISA assay described by Burger et al. was used. From weeks 6-28 of pregnancy, PP13 levels in women with PIH was no different from controls, but during the fi rst trimester, PP13 in PE is signifi cantly lower compared to controls or PIH (figure 2).

A screening study involving Doppler ultrasound

Doppler ultrasound at 20-24 weeks can achieve an acceptable detection performance, but may provide results too late to allow much time for preparation. When Doppler ultrasound alone is used in the fi rst trimester, the false-positive rate is unacceptably high.

Gestational age group Nicolaides et al. have shown that fi rst trimester screening involving both Doppler ultrasound and maternal serum PP13 detection may provide the specifi city lacked by Doppler ultrasound alone. In their nested case-control prospective study, PP13 was measured in 10 samples from PE pregnancies that had required delivery before 34 weeks, and 423 unaffected controls. The ELISA assay described by Burger et al. was used.

Possible screening strategies

It is likely that future programs for PE screening will be established as extensions to existing successful programs for Down’s screening. In Down’s screening circles there is considerable interest in contingent screening strategies, in which markers are measured at two different time points, for example in the fi rst trimester and the second trimester. Because, in many cases it is possible to categorize the pregnancies into high and low risk already in early pregnancy, it is only necessary to perform the second stage tests if the fi rst stage tests indicate intermediate risk.

Such an approach may indicate the path forward for PE screening. PP13 could represent a marker that can be measured relatively cheaply at the same time as the Down’s early markers were measured. Nicolaides et al. estimate that a contingent screening strategy for PE could could achieve a detection rate of 90% with 100% of pregnancies tested for PP13 but on the basis of the PP13 results only the 6% less equivocal risks submitted for Doppler ultrasound. A big advantage of this approach is that PP13 can be determined relatively easily, whereas Doppler assessment of the uterine arteries is less easily accessible and currently confi ned to specialist centres.