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OBJECTIVE: To quantify maternal hypertensive disorder of pregnancy (HDP) prevalence in late preterm and term infants admitted to neonatal units (NNU) and assess opportunities to avoid admissions. DESIGN: A retrospective population-based study using the National Neonatal Research Database. SETTING: England and Wales. POPULATION: Infants born ≥34 weeks' gestation admitted to NNU between 2012 and 2020. METHODS: Outcomes in HDP infants are compared with non-HDP infants using regression models. MAIN OUTCOME MEASURES: Hypertensive disorder of pregnancy, primary reason for admission, clinical diagnoses and resource use. RESULTS: 16 059/136 220 (11.8%) of late preterm (34+0 to 36+6 weeks' gestation) and 14 885/284 646 (5.2%) of term (≥37 weeks' gestation) admitted infants were exposed to maternal HDP. The most common primary reasons for HDP infant admission were respiratory disease (28.3%), prematurity (22.7%) and hypoglycaemia (16.4%). HDP infants were more likely to be admitted with primary hypoglycaemia than were non-HDP infants (odds ratio [OR] 2.1, 95% confidence interval [CI] 2.0-2.2, P < 0.0001). 64.5% of HDP infants received i.v. dextrose. 35.7% received mechanical or non-invasive ventilation. 8260/30 944 (26.7%) of HDP infants received intervention for hypoglycaemia alone (i.v. dextrose) with no other major intervention (respiratory support, parenteral nutrition, central line, arterial line or blood transfusion). CONCLUSIONS: The burden of maternal HDP on late preterm and term admissions to NNU is high, with hypoglycaemia and respiratory disease being the main drivers for admission. Over one in four were admitted solely for management of hypoglycaemia. Further research should determine whether maternal antihypertensive agent choice or postnatal pathways may reduce NNU admission.
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Hipertensión Inducida en el Embarazo , Hipoglucemia , Preeclampsia , Recién Nacido , Lactante , Embarazo , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/terapia , Estudios Retrospectivos , Glucosa , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The fullPIERS risk prediction model was developed to identify which women admitted with confirmed diagnosis of preeclampsia are at highest risk of developing serious maternal complications. The model discriminates well between women who develop (vs. those who do not) adverse maternal outcomes. It has been externally validated in several populations. We assessed whether placental growth factor (PlGF), a biomarker associated with preeclampsia risk, adds incremental value to the fullPIERS model. METHODS: Using a cohort of women admitted into tertiary hospitals in well-resourced settings (the USA and Canada), between May 2010 to February 2012, we evaluated the incremental value of PlGF added to fullPIERS for prediction of adverse maternal outcomes within 48 h after admission with confirmed preeclampsia. The discriminatory performance of PlGF and the fullPIERS model were assessed in this cohort using the area under the receiver's operating characteristic curve (AUROC) while the extended model (fullPIERS +PlGF) was assessed based on net reclassification index (NRI) and integrated discrimination improvement (IDI) performances. RESULTS: In a cohort of 541 women delivered shortly (< 1 week) after presentation, 8.1% experienced an adverse maternal outcome within 48 h of admission. Prediction of adverse maternal outcomes was not improved by addition of PlGF to fullPIERS (NRI: -8.7, IDI - 0.06). Discriminatory performance (AUROC) was 0.67 [95%CI: 0.59-0.75] for fullPIERS only and 0.67 [95%CI: 0.58-0.76]) for fullPIERS extended with PlGF, a performance worse than previously documented in fullPIERS external validation studies (AUROC > 0.75). CONCLUSIONS: While fullPIERS model performance may have been affected by differences in healthcare context between this study cohort and the model development and validation cohorts, future studies are required to confirm whether PlGF adds incremental benefit to the fullPIERS model for prediction of adverse maternal outcomes in preeclampsia in settings where expectant management is practiced.
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Muerte Materna/estadística & datos numéricos , Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Trastornos Puerperales/epidemiología , Adulto , Biomarcadores/sangre , Femenino , Humanos , Modelos Estadísticos , Preeclampsia/mortalidad , Embarazo , Resultado del Embarazo , Pronóstico , Estudios Prospectivos , Curva ROC , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. STUDY DESIGN: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. MAIN OUTCOME MEASURES: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. RESULTS: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20-33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20-33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. CONCLUSIONS: DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.
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Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Preeclampsia/diagnóstico , Valor Predictivo de las Pruebas , Embarazo , Diagnóstico Prenatal/métodos , Estudios ProspectivosRESUMEN
BACKGROUND: Chronic kidney disease is estimated to affect up to 6% of women of reproductive age. Maternity care represents an opportunity for early diagnosis but there is limited understanding of chronic kidney disease aetiology occurring in or revealed by pregnancy. METHODS: A retrospective evaluation of renal biopsies during and after pregnancy between 2000 and 2015 was undertaken. A large academic health centre pathology database was searched for free text pregnancy-related terms, restricted to typology code 71000 (kidney). Indications and findings of postpartum renal biopsies were reviewed. RESULTS: Sixty-three renal biopsy reports were identified. Of 45 biopsies performed postpartum, 34 (75.6%) investigated persistent postpartum proteinuria. 20/34 (70.6%) of these biopsies yielded a primary renal disease, and 6/34 (17.6%) women had progressed to end stage renal disease at latest follow-up. CONCLUSION: Renal biopsy findings of women investigated for persistent postpartum proteinuria revealed a high incidence of histological diagnosis of de novo renal disease.
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BACKGROUND: Current guidelines recommend viral, autoimmune, coagulation and liver ultrasound testing in intrahepatic cholestasis of pregnancy to exclude alternative diagnoses. METHODS: Electronic health records were searched for investigations and diagnoses in women with raised bile acid concentrations (>10 µmol/L) between January 2016 and December 2017 at two UK maternity units. RESULTS: Five hundred and thirty-one women had a raised bile acid concentration (median (IQR): 18 (13-32 µmol/L)) at a median gestation of 35.1 (IQR 31.8-37.0) weeks. Out of 531 women, 250 (47.1%) had full virology, autoimmune and ultrasound tests, and 348 (65.5%) had coagulation performed. Positive hepatitis B and C results were previously known. No new Epstein-Barr virus, cytomegalovirus or hepatitis A diagnoses were made. There were 11 positive autoimmune results, but no new diagnoses. No woman had an unexplained prolonged prothrombin time. No ultrasound liver (n = 38) or gallbladder (n = 85) abnormalities were of acute clinical significance. CONCLUSION: Intrahepatic cholestasis of pregnancy investigations provided no new diagnoses that influenced clinical management during pregnancy.
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Pregnancy-related acute kidney injury (AKI) is a rare but serious complication in high-income settings and remains an important cause of maternal and foetal morbidity and mortality in low- and middle-income settings. Hypertensive disorders of pregnancy are the leading cause of pregnancy-related AKI worldwide. In this article, we outline the epidemiology, aetiology, recognition, investigation and management of pregnancy-related AKI. Difficulties in the definition of AKI, approaches to determine the cause of AKI in diagnostically challenging circumstances and diagnosis of new renal disease in pregnancy are discussed.
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Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/terapia , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Biopsia , Femenino , Fluidoterapia , Humanos , Riñón/patología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo , Diálisis RenalRESUMEN
AUTHORS: Frances Conti-Ramsden MBBS Academic Clinical Fellow1, Carolyn Gill PhD BRC Research Assistant1, Paul T Seed MSc CStat Senior Lecturer in Medical Statistics1, Kate Bramham PhD Clinical Senior Lecturer in Nephrology2, Lucy C Chappell PhD NIHR Research Professor in Obstetrics1, Fergus P McCarthy PhD Clinical Senior Lecturer in Obstetrics and Gynaecology1,3. OBJECTIVES: To determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-eclampsia and superimposed pre-eclampsia (SPE), demonstrating cardiac ischaemia and strain. STUDY DESIGN: A nested case-control study was performed using samples and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-eclampsia (SPE) (n = 19). Plasma samples were taken at time of disease or the third trimester in controls. MAIN OUTCOME MEASURES: Plasma concentrations of GPBB and BNP. RESULTS: There was no significant difference in GPBB plasma concentrations between controls and pre-eclampsia (geometric mean (GM) [95% CI]: 4.74 [2.54-8.84]ng/mL vs 5.01 [2.58-9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93-18.25]ng/mL vs 10.24 [5.27-19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-eclampsia compared to controls (GM [95% CI]: 31.83 [20.18-50.22]pg/mL vs 11.33 [7.34-17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls. CONCLUSIONS: GPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-eclampsia compared to controls. This suggests cardiac strain at the time of pre-eclampsia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease.
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Glucógeno Fosforilasa/sangre , Isquemia Miocárdica/diagnóstico , Péptido Natriurético Encefálico/sangre , Preeclampsia/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Isquemia Miocárdica/sangre , Embarazo , Tercer Trimestre del Embarazo/sangre , Estudios Prospectivos , Adulto JovenRESUMEN
Preeclampsia is a common cause of acute kidney injury (AKI) in low- and middle-income countries, but AKI incidence in preeclampsia, its risk factors, and renal outcomes are unknown. A prospective observational multicenter study of women admitted with preeclampsia in South Africa was conducted. Creatinine concentrations were extracted from national laboratory databases for women with maximum creatinine of ≥90 µmol/L (≥1.02 mg/dL). Renal injury and recovery were defined by Kidney Disease Improving Global Outcomes creatinine criteria. Predefined risk factors, maternal outcomes, and neonatal outcomes were compared between AKI stages. Of 1547 women admitted with preeclampsia 237 (15.3%) met AKI criteria: 6.9% (n=107) stage 1, 4.3% (n=67) stage 2, and 4.1% (n=63) stage 3. There was a higher risk of maternal death (n=7; relative risk, 4.3; 95% CI, 1.6-11.4) and stillbirth (n=80; relative risk, 2.2; 95% CI, 1.8-2.8) in women with AKI compared with those without. Perinatal mortality was also increased (89 of 240; 37.1%). Hypertension in a previous pregnancy was the strongest predictor of AKI stage 2 or 3 (odds ratio, 2.24; 95% CI, 1.21-4.17). Renal recovery rate reduced with increasing AKI stage. A third of surviving women (76 of 230 [33.0%]) had not recovered baseline renal function by discharge. Approximately half (39 of 76; 51.3%) of these women had no further creatinine testing post-discharge. In summary, AKI was common in women with preeclampsia and had high rates of associated maternal and perinatal mortality. Only two-thirds of women had confirmed renal recovery. History of a previous hypertensive pregnancy was an important risk factor.
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Lesión Renal Aguda/epidemiología , Muerte Materna/tendencias , Muerte Perinatal , Preeclampsia/epidemiología , Mortinato/epidemiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Adolescente , Adulto , Comorbilidad , Intervalos de Confianza , Creatinina/sangre , Países en Desarrollo , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Recién Nacido , Pruebas de Función Renal , Oportunidad Relativa , Pobreza , Preeclampsia/diagnóstico , Preeclampsia/terapia , Embarazo , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Sudáfrica , Análisis de SupervivenciaRESUMEN
The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48â¯h for women admitted with pre-eclampsia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset. The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of ≥30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-eclampsia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.
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Modelos Biológicos , Preeclampsia/diagnóstico , Resultado del Embarazo/epidemiología , Adulto , Femenino , Edad Gestacional , Humanos , Modelos Logísticos , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Hypertensive disorders of pregnancy contribute to 14% of all maternal deaths, the majority of which occur in low- and middle-income countries. The aim of the study was to describe the maternal and perinatal clinical outcomes of women with pre-eclampsia living in middle- and low-income countries. METHODS: The study was a prospective observational study of women with pre-eclampsia (n = 1547, 42 twin pregnancies) at three South African tertiary facilities. Using stepwise logistic regression model area under the receiver operating characteristic curve (AUROC) values, the association between maternal baseline and admission characteristics and risk of adverse outcomes was evaluated. Main outcome measures were eclampsia, kidney injury and perinatal death. RESULTS: In 1547 women with pre-eclampsia, 16 (1%) died, 147 (9.5%) had eclampsia, four (0.3%) had a stroke and 272 (17.6%) had kidney injury. Of the 1589 births, there were 332 (21.0%) perinatal deaths; of these, 281 (84.5%) were stillbirths. Of 1308 live births, 913 (70.0%) delivered <37 completed weeks and 544 (41.7%) delivered <34 weeks' gestation. Young maternal age (AUROC = 0.76, 95% confidence interval (CI) = 0.71-0.80) and low Body Mass Index BMI (AUROC 0.65, 95% CI = 0.59-0.69) were significant predictors of eclampsia. Highest systolic blood pressure had the strongest association with kidney injury, (AUROC = 0.64, 95% CI = 0.60-0.68). Early gestation at admission was most strongly associated with perinatal death (AUROC = 0.81, 95% CI = 0.77-0.84). CONCLUSIONS: The incidence of pre-eclampsia complications, perinatal death and preterm delivery in women referred to tertiary care in South Africa was much higher than reported in other low- and middle-income studies and despite access to tertiary care interventions. Teenage mothers and those with low BMI were at highest risk of eclampsia. This information could be used to inform guidelines, the research agenda and policy.
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Lesión Renal Aguda/epidemiología , Eclampsia/epidemiología , Muerte Perinatal , Preeclampsia/terapia , Adolescente , Adulto , Índice de Masa Corporal , Femenino , Humanos , Recién Nacido , Edad Materna , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Factores de Riesgo , Sudáfrica/epidemiología , Atención Terciaria de Salud , Adulto JovenRESUMEN
BACKGROUND: Chronic hypertension complicates around 3% of all pregnancies. There is evidence that treating severe hypertension reduces maternal morbidity. This study aimed to systematically review randomized controlled trials of antihypertensive agents treating chronic hypertension in pregnancy to determine the effect of this intervention. METHODS AND RESULTS: Medline (via OVID), Embase (via OVID) and the Cochrane Trials Register were searched from their earliest entries until November 30, 2016. All randomized controlled trials evaluating antihypertensive treatments for chronic hypertension in pregnancy were included. Data were extracted and analyzed in Stata (version 14.1). Fifteen randomized controlled trials (1166 women) were identified for meta-analysis. A clinically important reduction in the incidence of severe hypertension was seen with antihypertensive treatment versus no antihypertensive treatment/placebo (5 studies, 446 women; risk ratio 0.33, 95%CI 0.19-0.56; I2 0.0%). There was no difference in the incidence of superimposed pre-eclampsia (7 studies, 727 women; risk ratio 0.74, 95%CI 0.49-1.11; I2 28.1%), stillbirth/neonatal death (4 studies, 667 women; risk ratio 0.37, 95%CI 0.11-1.26; I2 0.0%), birth weight (7 studies, 802 women; weighted mean difference -60 g, 95%CI -200 to 80 g; I2 0.0%), or small for gestational age (4 studies, 369 women; risk ratio 1.01, 95%CI 0.53-1.94; I2 0.0%) with antihypertensive treatment versus no treatment/placebo. CONCLUSIONS: Antihypertensive treatment reduces the risk of severe hypertension in pregnant women with chronic hypertension. A considerable paucity of data exists to guide choice of antihypertensive agent. Adequately powered head-to-head randomized controlled trials of commonly used antihypertensive agents are required to inform prescribing.