A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction.

OBJECTIVE: To evaluate the use of plasma Placental Growth Factor (PlGF), recommended by the recent NICE guidance, in women with suspected pre-eclampsia (PE) and/or fetal growth restriction (FGR). STUDY DESIGN: Non-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit. METHODS: PlGF testing was performed in addition to routine clinical assessment in 260 women >20 weeks' gestation with chronic disease (hypertension, renal disease ±â€¯diabetes) with a change in maternal condition or in women with suspected FGR to determine the impact on clinical management. Results were revealed and standardised care pathways followed. MAIN OUTCOME MEASURES: Outcome of pregnancies with a low PlGF (<12 pg/ml and 13-100 pg/ml), impact on clinical service and the diagnostic accuracy of alternative PlGF cut-offs. RESULTS: 206/260 (79.2%) women had an adverse outcome (PE/birthweight < 10th centile/preterm birth). In our cohort, a low PlGF (<12 pg/ml) was associated with a shorter test-birth interval and universally (100% PPV) with an adverse pregnancy outcome, although 29/61 (47.5%) of women with PlGF < 12 pg/ml continued their pregnancy >14 days. The PlGF result altered clinical management (surveillance or timing of birth) in 196/260 (75.4%) cases. Alternative PlGF thresholds did not significantly improve diagnostic performance. CONCLUSIONS: Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice.

Third trimester placental volume and biometry measurement: A method-development study.

OBJECTIVES: To test the hypothesis that third trimester placental biometry and volume can be measured by two-dimensional (2D) and three-dimensional (3D) ultrasound in utero, determining which method of measurement was most strongly correlated with true placental size ex vivo. METHODS: Singleton pregnancies underwent placental ultrasound within seven days of delivery (n = 87, 29(+3)-41(+5) weeks). Length and width (linear and curvilinear) and depth were estimated. Placental volume (PV) was estimated using 2D ellipse and shell techniques and 3D rotational (15° and 30° rotation angles) and multiplanar (5 and 10 mm slicing intervals) techniques. Measurements were compared to their true correlates following delivery. Intra- and inter-observer reliabilities of candidate placental size estimates were assessed by intraclass correlation coefficient (ICC). RESULTS: Curvilinear placental length (Rs = 0.24, p = 0.031), width (Rs = 0.27, p = 0.013) and depth (Rs = 0.31, p = 0.0056) correlated well with ex vivo measurements. All methods of PV estimation were related to ex vivo volume (Rs ≥ 0.32, p < 0.01) but not placental weight (p > 0.05); 30° rotational estimation demonstrated the strongest biological correlation (Rs = 0.40, p = 0.0004). Intra- and inter-observer placental size measurements intraclass correlation coefficients were suboptimal (0.59-0.70 and 0.10-0.58 respectively). DISCUSSION: We have demonstrated that it is possible to obtain information about the size of the third trimester placenta in utero using 2D and 3D ultrasound. However it is essential that the reliability (particularly interobserver reliability) of these estimates is improved prior to prospective studies to determine their predictive value.

IFPA Gábor Than Award Lecture: Recognition of placental failure is key to saving babies' lives.

In high-income countries, placental failure is implicated in up to 65% of cases of stillbirth. Placental failure describes the situation where the placenta cannot meet the fetus' needs and may be the end-result of a variety of underlying pathological processes evident in the placental disc, membranes and umbilical cord. These include lesions with genetic, environmental, infectious, inflammatory, mechanical, metabolic, traumatic or vascular origin. Investigation of placental tissue from stillbirths and from pregnancies at an increased risk of stillbirth has demonstrated changes in macroscopic and microscopic structure which are themselves related to abnormal placental function. A better understanding and identification of placental failure may improve the management of pregnancy complications and of pregnancies after stillbirth (which have a 5-fold increased risk of stillbirth). The majority of current antenatal tests focus on the fetus and its response to the intrauterine environment; few of these investigations reduce stillbirths in low-risk pregnancies. However, some currently used investigations reflect placental development, structure and vascular function, while other investigations employed in clinical research settings such as the evaluation of placental structure and shape have a good predictive value for adverse fetal outcome. In addition, recent studies suggest that biomarkers of placental inflammation and deteriorating placental function can be detected in maternal blood suggesting that holistic evaluation of placental structure and function is possible. We anticipate that development of reliable tests of placental structure and function, coupled to assessment of fetal wellbeing offer a new opportunity to identify pregnancies at risk of stillbirth and to direct novel therapeutic strategies to prevent it.