Emma Shawkat

A clinical evaluation of Placental Growth Factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction

OBJECTIVEnTo 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).nnnSTUDY DESIGNnNon-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit.nnnMETHODSnPlGF testing was performed in addition to routine clinical assessment in 260 women >20u202fweeks gestation with chronic disease (hypertension, renal diseaseu202f±u202fdiabetes) 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.nnnMAIN OUTCOME MEASURESnOutcome of pregnancies with a low PlGF (<12u202fpg/ml and 13-100u202fpg/ml), impact on clinical service and the diagnostic accuracy of alternative PlGF cut-offs.nnnRESULTSn206/260 (79.2%) women had an adverse outcome (PE/birthweightu202f<u202f10th centile/preterm birth). In our cohort, a low PlGF (<12u202fpg/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 PlGFu202f<u202f12u202fpg/ml continued their pregnancy >14u202fdays. 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.nnnCONCLUSIONSnOur 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.

The Effect Of Labetalol And Nifedipine MR On Blood Pressure In Women With Chronic Hypertension In Pregnancy

AIMnTo compare the blood pressure (BP) lowering effects of labetalol and nifedipine modified release (MR) in hypertensive pregnant women. We also investigated the effect on the heart rate (HR) and determined the proportion of time spent in target.nnnMETHODSnThis was an exploratory study. Women with chronic hypertension taking either labetalol or nifedipine were offered 24-h ambulatory blood pressure monitoring (ABPM). Sleep, wake and drug ingestion times were self-reported. An indirect response model was used to analyse the systolic BP (SBP), diastolic BP (DBP) and HR time-series; the effect of gestation and type of drug was evaluated.nnnRESULTSnForty-eight women were recruited: 24 in each group. There was no difference in clinical characteristics. In women taking nifedipine there was a positive association between the dose of nifedipine and pre-dose BP pu202f=u202f.002, this was not present in the labetalol group. There was a difference between the drug effects on both the SBP and DBP time-series (pu202f=u202f.014). In comparison to labetalol, there was less variation in day time BP in those women prescribed nifedipine. Women on labetalol spent a larger proportion of time with their DBP below target (<80u202fmmHg). The HR dynamics were qualitatively different, a stimulatory effect was found with nifedipine compared to an inhibitory effect with labetalol.nnnCONCLUSIONnThere are significant and important differences between the BP lowering effects of nifedipine and labetalol. A large randomised control trial is required to investigate the relationship between BP variability and time in target on pregnancy outcomes.

Breast milk: friend or foe?

Anaphylaxis can occur secondary to breastfeeding. The authors present a case of a 30-year-old woman who complained of chest tightness, shortness of breath and a rash on the third day postpartum. She was treated for anaphylaxis and her symptoms resolved. Because she had taken tramadol prior to this event, a drug reaction was initially suspected. However, she experienced further episodes related to breastfeeding, despite stopping tramadol. Effective control of her symptoms was achieved with regular antihistamines, enabling her to continue breastfeeding. Antihistamines were interrupted after 8 weeks at which point lactation (in hospital) was once again associated with anaphylaxis. The diagnosis of breastfeeding induced anaphylaxis was made. There are six previously reported cases of breastfeeding induced anaphylaxis. The authors describe the second case of breastfeeding anaphylaxis extending beyond the neonatal period, controlled with antihistamines.

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.

Breast milk: friend or FOE?

Background Anaphylaxis is potentially fatal and can occur secondary to breast-feeding. Case On day 3 postpartum, a 30-year-old patient complained of chest tightness, shortness of breath and a rash. She was treated for anaphylaxis and her symptoms resolved. Preceding this event, she had taken tramadol, which raised the suspicion of a drug reaction and the medication was stopped. Despite this action, she experienced further episodes related to breast-feeding and the possibility of breast-feeding induced anaphylaxis was considered. This was confirmed with a lactation challenge. The patient was able to continue breast-feeding with regular feeds and antihistamine with effective control of her symptoms. Conclusion There are four previously reported cases of breast-feeding induced anaphylaxis. Two case reports describe breast-feeding induced anaphylaxis on day 3 postpartum associated with ibuprofen. The ibuprofen was stopped and on day 4 postpartum both women were able to breastfeed without further reactions. In the other two cases, the women required suppression of breast-feeding. The pathophysiology is unknown but it may be due to an immune response to a component of the breast milk. There are reports of Jersey cattle developing an allergy to the α-casein in their own milk. If milking is delayed, the high intra-mammary pressure forces this protein into the bloodstream where it is recognised as a foreign antigen, stimulating an antibody response. Further leakage precipitates an immediate hypersensitivity reaction. We describe the first case of persistent anaphylaxis to be controlled, enabling the mother to continue breast-feeding.