Emma Ingram

R1 changes in the human placenta at 3 T in response to a maternal oxygen challenge protocol

Oxygen-enhanced MRI non-invasively monitors placental oxygenation in-vivo. This technique has been demonstrated at 1.5 Tesla (T) in healthy pregnancies. The aim of this study was to investigate whether findings are comparable at 3T. Nine pregnant volunteers underwent MRI at 3T. Scans obtained R1 (1/T1) measures from T1 maps under air, followed by a dynamic series breathing 100% oxygen. A statistically significant negative correlation was found between dR1 and gestation (P = 0.0008, r = -0.90, Pearson correlation test). The effect of the field strength was not significant within regression analysis. Placental Oxygen-Enhanced MRI at 3T gives comparable results to those previously obtained at 1.5T.

MR Imaging Measurements of Altered Placental Oxygenation in Pregnancies Complicated by Fetal Growth Restriction

Purpose To evaluate oxygen-enhanced and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging parameters in normal pregnancies and those complicated by fetal growth restriction (FGR). Materials and Methods This case-control study was approved by the local research ethics committee. Informed consent was obtained from all subjects. From October 2010 to October 2015, 28 women with uncomplicated pregnancies (individualized birthweight ratio [IBR] >20th percentile and delivery >37 weeks) and 23 with pregnancies complicated by FGR (IBR <5th percentile and abnormal Doppler ultrasonography [US] studies) underwent MR imaging. Differences in placental longitudinal R1 (1/T1) and transverse R2* (1/T2*) were quantified, with subjects breathing either air or oxygen. The difference in R1 (ΔR1) after hyperoxia was converted to change in partial pressure of oxygen (ΔPo2). Data were acquired prospectively, with retrospective interpretation of group differences (unpaired t tests). Diagnostic models were developed by using logistic regression analysis with gestational age as a covariate. Results The mean baseline R1 and R2* for normal pregnancies (R1: 0.59 sec-1, 95% confidence interval [CI]: 0.58 sec-1, 0.60 sec-1; R2*: 17 sec-1, 95% CI: 14 sec-1, 20 sec-1) were significantly different from those of pregnancies complicated by FGR (R1: 0.63 sec-1, 95% CI: 0.62 sec-1, 0.65 sec-1; R2*: 26 sec-1, 95% CI: 22 sec-1, 32 sec-1) (P < .0001). The ΔR1 showed a significant negative association with gestational age (P < .0001) in the combined cohort, with the FGR group having a ΔR1 that was generally 61.5% lower than that in the normal pregnancy group (P = .003). The area under the receiver operating characteristic curve for the differentiation between pregnancy complicated by FGR and normal pregnancy by using ΔPo2, baseline R1, and baseline R2* was 0.91 (95% CI: 0.82, 0.99). Conclusion R1, R2*, and ΔPo2 were significantly different between normal pregnancies and those complicated by severe FGR. MR imaging parameters have the potential to help identify placental dysfunction associated with FGR and may have clinical utility in correctly identifying FGR among fetuses that are small for gestational age. A larger prospective study is needed to assess the incremental benefit beyond that offered by US.

Human placental oxygenation in late gestation: experimental and theoretical approaches

The placenta is crucial for life. It is an ephemeral but complex organ acting as the barrier interface between maternal and fetal circulations, providing exchange of gases, nutrients, hormones, waste products and immunoglobulins. Many gaps exist in our understanding of the detailed placental structure and function, particularly in relation to oxygen handling and transfer in healthy and pathological states in utero. Measurements to understand oxygen transfer in vivo in the human are limited, with no general agreement on the most appropriate methods. An invasive method for measuring partial pressure of oxygen in the intervillous space through needle electrode insertion at the time of Caesarean sections has been reported. This allows for direct measurements in vivo whilst maintaining near normal placental conditions; however, there are practical and ethical implications in using this method for determination of placental oxygenation. Furthermore, oxygen levels are likely to be highly heterogeneous within the placenta. Emerging non‐invasive techniques, such as MRI, and ex vivo research are capable of enhancing and improving current imaging methodology for placental villous structure and increase the precision of oxygen measurement within placental compartments. These techniques, in combination with mathematical modelling, have stimulated novel cross‐disciplinary approaches that could advance our understanding of placental oxygenation and its metabolism in normal and pathological pregnancies, improving clinical treatment options and ultimately outcomes for the patient.

75 How useful is placental growth factor in routine practice? A clinical evaluation in women presenting with suspected placental disease

Introduction Placental growth factor (PlGF) is increasingly recognised as a marker of placental dysfunction. PlGF for the diagnosis of pre-eclampsia (PE) has recently been recommended by the NICE diagnostic assessment panel to rule out PE within one week but the significance of a positive test remains uncertain. Objectives The aim of this study was to evaluate the use of PlGF in routine practice in women with suspected placental disease with and without features of maternal disease. Methods Women with chronic disease (hypertension, renal disease±diabetes, n =114) with a change in maternal condition or women with suspected fetal growth restriction (FGR) ( n = 146) had a PlGF performed >20weeks. Results were revealed and standardised care pathways followed. Outcomes were checked by two independent reviewers. Results In line with previous reports, we observed a much shorter median test-delivery interval in women with a low PlGF n =61) and those with an intermediate PlGF 12–100pg/ml (19 [1–104]days; n =76), compared to those with a normal PlGF (40 [2–111]days; n =123). Despite a strong association between low PlGF and poor outcome (62% delivered 14days. 62% ( n =18) of these women had PE and 28% ( n =8) had FGR without maternal disease. There was no significant difference in the test-delivery interval between these groups (13 [0–37] compared with 11 [1–35]days, p >0.05). There were 2 false positive cases of low PlGF without a diagnosis of PE, however these women had confounding medical comorbidities which made the diagnosis ambiguous. Similarly, 2/77 women had a false positive intermediate PlGFs associated with concurrent maternal disease. There were no normal pregnancy outcomes associated with low PlGF. Evaluation of the 7 false negative cases (a diagnosis of PE with a normal PlGF) demonstrated that none were obtained within a week of delivery (27 [7–63]days). Three of these cases had long test-delivery intervals and 3 cases were complicated by complex maternal disease. Of the women with a normal PlGF and small for gestational age (SGA) ( n =51), the median test-delivery interval was 48 [4–90]days. However, 48/51 (94%) were >7days before delivery.9/51 of these normotensive SGA pregnancies with normal PlGF were delivered for suspected FGR (abnormal growth velocity, oligohydramnios and/or abnormal Dopplers) and had a median birthweight (BW) centile of 2.8 (0–8–8.3), 17 for suspected SGA (median BW centile 3.6 [0.1–9.6]) and 25 delivered for other reasons (median BW centile 5.25 [1–9.3]). There were 3 cases of stillbirth, one of which had a normal PlGF (23days before delivery; BW centile 1.4). Conclusion In our cohort, a low PlGF was universally associated with a poor outcome and short test-delivery interval which was not affected by the indication (maternal or fetal) for the PlGF. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction, however it has highlighted that several evidence gaps remain before this test can be implemented in routine clinical practice and confirms that abnormal PlGF levels in isolation are not an indication for delivery. Further research linking placental pathology and maternal PlGF levels is urgently needed.

75 How useful is placental growth factor in routine practice? A clinical evaluation in women presenting with suspected placental disease: Angiogenic factors

Introduction Placental growth factor (PlGF) is increasingly recognised as a marker of placental dysfunction. PlGF for the diagnosis of pre-eclampsia (PE) has recently been recommended by the NICE diagnostic assessment panel to rule out PE within one week but the significance of a positive test remains uncertain. Objectives The aim of this study was to evaluate the use of PlGF in routine practice in women with suspected placental disease with and without features of maternal disease. Methods Women with chronic disease (hypertension, renal disease±diabetes, n =114) with a change in maternal condition or women with suspected fetal growth restriction (FGR) ( n = 146) had a PlGF performed >20weeks. Results were revealed and standardised care pathways followed. Outcomes were checked by two independent reviewers. Results In line with previous reports, we observed a much shorter median test-delivery interval in women with a low PlGF n =61) and those with an intermediate PlGF 12–100pg/ml (19 [1–104]days; n =76), compared to those with a normal PlGF (40 [2–111]days; n =123). Despite a strong association between low PlGF and poor outcome (62% delivered 14days. 62% ( n =18) of these women had PE and 28% ( n =8) had FGR without maternal disease. There was no significant difference in the test-delivery interval between these groups (13 [0–37] compared with 11 [1–35]days, p >0.05). There were 2 false positive cases of low PlGF without a diagnosis of PE, however these women had confounding medical comorbidities which made the diagnosis ambiguous. Similarly, 2/77 women had a false positive intermediate PlGFs associated with concurrent maternal disease. There were no normal pregnancy outcomes associated with low PlGF. Evaluation of the 7 false negative cases (a diagnosis of PE with a normal PlGF) demonstrated that none were obtained within a week of delivery (27 [7–63]days). Three of these cases had long test-delivery intervals and 3 cases were complicated by complex maternal disease. Of the women with a normal PlGF and small for gestational age (SGA) ( n =51), the median test-delivery interval was 48 [4–90]days. However, 48/51 (94%) were >7days before delivery.9/51 of these normotensive SGA pregnancies with normal PlGF were delivered for suspected FGR (abnormal growth velocity, oligohydramnios and/or abnormal Dopplers) and had a median birthweight (BW) centile of 2.8 (0–8–8.3), 17 for suspected SGA (median BW centile 3.6 [0.1–9.6]) and 25 delivered for other reasons (median BW centile 5.25 [1–9.3]). There were 3 cases of stillbirth, one of which had a normal PlGF (23days before delivery; BW centile 1.4). Conclusion In our cohort, a low PlGF was universally associated with a poor outcome and short test-delivery interval which was not affected by the indication (maternal or fetal) for the PlGF. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction, however it has highlighted that several evidence gaps remain before this test can be implemented in routine clinical practice and confirms that abnormal PlGF levels in isolation are not an indication for delivery. Further research linking placental pathology and maternal PlGF levels is urgently needed.

Clinical science75 How useful is placental growth factor in routine practice? A clinical evaluation in women presenting with suspected placental disease: Angiogenic factors

Introduction Placental growth factor (PlGF) is increasingly recognised as a marker of placental dysfunction. PlGF for the diagnosis of pre-eclampsia (PE) has recently been recommended by the NICE diagnostic assessment panel to rule out PE within one week but the significance of a positive test remains uncertain. Objectives The aim of this study was to evaluate the use of PlGF in routine practice in women with suspected placental disease with and without features of maternal disease. Methods Women with chronic disease (hypertension, renal disease±diabetes, n =114) with a change in maternal condition or women with suspected fetal growth restriction (FGR) ( n = 146) had a PlGF performed >20weeks. Results were revealed and standardised care pathways followed. Outcomes were checked by two independent reviewers. Results In line with previous reports, we observed a much shorter median test-delivery interval in women with a low PlGF n =61) and those with an intermediate PlGF 12–100pg/ml (19 [1–104]days; n =76), compared to those with a normal PlGF (40 [2–111]days; n =123). Despite a strong association between low PlGF and poor outcome (62% delivered 14days. 62% ( n =18) of these women had PE and 28% ( n =8) had FGR without maternal disease. There was no significant difference in the test-delivery interval between these groups (13 [0–37] compared with 11 [1–35]days, p >0.05). There were 2 false positive cases of low PlGF without a diagnosis of PE, however these women had confounding medical comorbidities which made the diagnosis ambiguous. Similarly, 2/77 women had a false positive intermediate PlGFs associated with concurrent maternal disease. There were no normal pregnancy outcomes associated with low PlGF. Evaluation of the 7 false negative cases (a diagnosis of PE with a normal PlGF) demonstrated that none were obtained within a week of delivery (27 [7–63]days). Three of these cases had long test-delivery intervals and 3 cases were complicated by complex maternal disease. Of the women with a normal PlGF and small for gestational age (SGA) ( n =51), the median test-delivery interval was 48 [4–90]days. However, 48/51 (94%) were >7days before delivery.9/51 of these normotensive SGA pregnancies with normal PlGF were delivered for suspected FGR (abnormal growth velocity, oligohydramnios and/or abnormal Dopplers) and had a median birthweight (BW) centile of 2.8 (0–8–8.3), 17 for suspected SGA (median BW centile 3.6 [0.1–9.6]) and 25 delivered for other reasons (median BW centile 5.25 [1–9.3]). There were 3 cases of stillbirth, one of which had a normal PlGF (23days before delivery; BW centile 1.4). Conclusion In our cohort, a low PlGF was universally associated with a poor outcome and short test-delivery interval which was not affected by the indication (maternal or fetal) for the PlGF. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction, however it has highlighted that several evidence gaps remain before this test can be implemented in routine clinical practice and confirms that abnormal PlGF levels in isolation are not an indication for delivery. Further research linking placental pathology and maternal PlGF levels is urgently needed.