Summary Background Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the ...fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. Methods We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. Findings 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 5% within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84–0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. Interpretation The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. Funding Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.
Objectives: To investigate effects of maternal smoking on the fetal heart rate (FHR) in ambulatory patients using a portable fetal electrocardiogram recording device.
Methods: A prospective cohort ...study of 43 pregnant smokers and 43 non-smoking gestation-matched controls with uncomplicated singleton pregnancies. Smokers were divided into light (1-10) and moderate (11-20 cigarettes/d). The FHR was recorded for 16 h with smokers smoking at will, using an event button to record when they lit a cigarette. Fifty recordings were made in the patients' homes with 36 in ambulatory inpatients. Three consecutive 30-min epochs (before, during and after smoking) were compared with the controls.
Results: Basal FHR was significantly lower before smoking in the foetuses of smokers compared with non-smokers (p = 0.048). During smoking, there was a significant dose-dependent fall in short-, long-term and true beat-to-beat variabilities (p = 0.004, p < 0.0001 and p = 0.024, respectively).
Conclusion: Maternal smoking leads to reversible changes in FHR variability that mimic those associated with an increased incidence of adverse cardiovascular events in adults. As heart rate and variability reflect the autonomic control of the heart, our findings suggest that maternal smoking interferes with the autonomic control of the FHR.
Progressive stenosis of the semilunar valves in utero can be life threatening. We treated two fetuses with complete or almost complete pulmonary atresia and imminent hydrops (increased cardiothoracic ...ratio, pericardial effusion, holosystolic tricuspid regurgitation extending into diastole, and abnormal venous Dopplers). We dilated the pulmonary valve of two fetuses in utero at 28 and 30 weeks' gestation, through the mothers' abdomens. After the procedure, the fetuses had decreased signs of circulatory failure and gestation continued until near term. In the neonatal period, we did a repeat valvuloplasty with systemic-to-pulmonary arterial shunt. Both children (now aged 18 months and 12 months) now have biventricular circulation. Surgery on selected fetuses with semilunar valve stenosis or atresia, or both, can extend pregnancy and favourably change the postnatal surgical options.
Previous researchers have studied circadian changes in the fetal heart rate (FHR) on small sample sizes and in a strictly controlled environment. This study was undertaken to investigate these ...changes during the late second and third trimesters, using a portable fetal electrocardiogram recording device (Monica AN24) in pregnant women in home and hospital environments with unrestricted mobility.
This was a prospective cohort study of 54 pregnant women with uncomplicated singleton pregnancies between 25 and 40 weeks gestation. FHR recordings were made up to 16 h at home or in the hospital setting in the United Kingdom. FHR data over 90 min periods were averaged and the day (7:00 am-11:00 pm) and night (11:00 pm-7:00 am) data from the same individual were compared. Data were examined for evidence of sex-related differences.
During the night, there was a significant reduction in basal heart rate (bFHR) and a significant increase in short term variation (STV) and long term variation (LTV) (P < 0.05). Basal FHR decreased (P < 0.002), whereas LTV increased (P = 0.014) with advancing gestation. Male fetuses showed greater day: night variation than females regardless of gestation (P = 0.014). There was a higher bFHR in fetuses monitored during the day in hospital (P = 0.04).
This study demonstrates that there are sex-, environment and time-related differences in the FHR parameters measured. These differences may need to be considered taken when interpreting FHR data.
Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of ...the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.
•Postpartum cardiovascular risk scores are not high in women with pre-eclampsia.•Women with gestational hypertension have higher postpartum cardiovascular risk scores.•Postpartum BNP, NGAL and PlGF ...are not associated with cardiovascular risk scores.
Postpartum stratification of cardiovascular risk for women with pregnancies complicated by pre-eclampsia is challenging. Our aim was to identify potential clinical and biomarker predictors of future cardiovascular risk at six weeks postpartum in women with hypertensive pregnancies.
Prospective longitudinal cohort.
Ten year-Framingham cardiovascular risk scores were calculated for 477 women (94 with gestational hypertension, 288 with pre-eclampsia, 30 with superimposed pre-eclampsia, 51 with chronic hypertension, 14 women with uncomplicated pregnancies). B-type natriuretic peptide (BNP), neutrophil gelatinase–associated lipocalin (NGAL) and placental growth factor (PlGF) were quantified at six weeks postpartum.
Framingham cardiovascular risk scores were not higher in women with pregnancies complicated by pre-eclampsia than healthy controls, nor were scores higher in women with pre-existing chronic hypertension complicated with superimposed pre-eclampsia compared with those without superimposed pre-eclampsia. Women with gestational hypertension had higher risk scores than women with pre-eclampsia and healthy controls. Established risk factors of cardiovascular disease including diastolic blood pressure and previously diagnosed chronic hypertension were associated with higher scores, and African ethnicity, parity and estimated glomerular filtration rate also were independently associated with higher Framingham risk scores at six weeks postpartum. PlGF, BNP and NGAL concentrations were not associated with Framingham cardiovascular risk scores after adjustment for independent variables.
A history of pre-eclampsia or superimposed pre-eclampsia in most recent pregnancy was not associated with elevated Framingham risk score at six weeks postpartum. Established clinical predictors may enable risk stratification at six weeks postpartum, which are not enhanced by the biomarkers included in this study.
This study investigates the contractile response to 5 hydroxytryptamine (5HT) of chorionic artery and vein segments from normotensive (NT) and pre-eclamptic (PE) placentae. It also looked at the ...effectiveness of ketanserin (KET), a 5HT(2A) receptor antagonist, in reducing 5HT-mediated vasoconstriction. 5HT induced vasoconstriction in all of the vessels was studied. Compared to NT vessels, Emax (%KCl) was significantly reduced in PE arteries (p<0.05) and veins (p<0.0005). The mean Emax for NT arteries was 104.1 (±10.71) whilst PE arteries showed a mean Emax of 57.02 (±12.13). KET produced a statistically significant reduction of Emax in both vessels in NT and the arteries in PE. However the antagonistic effect of KET was not pronounced in PE veins. The EC50 values for NT and PE arteries and veins did not change significantly. There were no noticeable changes in the expression profiles of 5HT(2A) receptor mRNA and protein expressions. The data from this study suggest that in PE, the vascular reactivity of chorionic vessels to 5HT is reduced and it was not due to the altered expression of 5HT(2A) receptors.
Affecting 2–4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine ...learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia.
We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (–LR) and positive (+LR) likelihood ratios.
Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 95% CI 0·76–0·84 vs the currently used logistic regression model, fullPIERS: AUROC 0·68 0·63–0·74) and categorised women into very low risk (–LR <0·1; eight 0·7% of 1103 women), low risk (–LR 0·1 to 0·2; 321 29·1% women), moderate risk (–LR >0·2 and +LR <5·0; 676 61·3% women), high risk (+LR 5·0 to 10·0, 87 7·9% women), and very high risk (+LR >10·0; 11 1·0% women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%).
The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers.
University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.
Abstract This study investigates the contractile response to 5 hydroxytryptamine (5HT) of chorionic artery and vein segments from normotensive (NT) and pre-eclamptic (PE) placentae. It also looked at ...the effectiveness of ketanserin (KET), a 5HT2A receptor antagonist, in reducing 5HT-mediated vasoconstriction. 5HT induced vasoconstriction in all of the vessels was studied. Compared to NT vessels, Emax (%KCl) was significantly reduced in PE arteries (p < 0.05) and veins (p < 0.0005). The mean Emax for NT arteries was 104.1 (± 10.71) whilst PE arteries showed a mean Emax of 57.02 (± 12.13). KET produced a statistically significant reduction of Emax in both vessels in NT and the arteries in PE. However the antagonistic effect of KET was not pronounced in PE veins. The EC50 values for NT and PE arteries and veins did not change significantly. There were no noticeable changes in the expression profiles of 5HT2A receptor mRNA and protein expressions. The data from this study suggest that in PE, the vascular reactivity of chorionic vessels to 5HT is reduced and it was not due to the altered expression of 5HT2A receptors.
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