The transversus abdominis plane block in conjunction with intrathecal morphine use after cesarean section in women with severe pre-eclampsia: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. METHODS: Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. RESULTS: 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P < 0.001; at 8 h:1(1,1) vs. 1(1.5,2),P < 0.001; at 12 h:1(1,2) vs. 2(1,2),P = 0.001] and higher satisfaction [53(89.9%) vs.45(75.0%), P < 0.05]. There were no differences between groups in VAS score at 24 h at rest and at all time points above with movement, times of use of PCA within 12 h after anesthesia, maternal side-effect, and Apgar score at 1 and 5 min of newborns. CONCLUSIONS: In conclusion, The TAP block performed in conjunction with intrathecal morphine may not reduce opioid consumption, but it could reduce VAS scores at rest in the first 12 h after cesarean section in women with severe pre-eclampsia, and improve maternal satisfaction, which is worthy of clinical promotion. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry( http://www.chictr.org.cn ) on 13/12/2021: ChiCTR2100054293.

Reduced left ventricular function and sustained hypertension in women seven years after severe preeclampsia.

Objective. To study left ventricular (LV) function and blood pressure (BP) at a long-term follow-up in women after severe pre-eclampsia. Design. In this single-centre, cross-sectional study, 96 patients were eligible for inclusion. LV function was examined by transthoracic echocardiography including tissue Doppler echocardiography and speckle tracking. BP was measured at rest using repeated non-invasive techniques. Results. We compared 36 patients with early-onset and 33 patients with late-onset pre-eclampsia with 28 healthy controls. Mean age (40 ± 3 years) and median time since delivery (7 ± 2 years) were similar across the study groups. The patients had 18% higher systolic BP (139 ± 15 mmHg) and 24% higher diastolic BP (87 ± 19 mmHg) than controls (p < .01). Hypertension was present in 23 patients (33%), where the estimated LV mass was 16% higher (p = .05) than in controls. The LV ejection fraction was 19% lower in the early-onset group (51 ± 4%; p = .01) and 14% lower in the late-onset group (54 ± 6; p = .04) compared with controls. LV global longitudinal strain was 18% lower in the patient group (-17.7 ± 2.1%) compared with controls (p = .01). Indicative of a more restrictive filling pattern, the diastolic indices showed a lower e' mean (p < .01) and subsequently higher E/e' ratio (p < .01). There were no significant differences in BP, systolic or diastolic function indices between the patient groups. Conclusion. We found sustained hypertension, higher LV mass and reduced LV systolic and diastolic function 7 y after severe pre-eclampsia. Our findings emphasize the importance of early risk stratification and clinical counselling, and follow-up for such cases.

Incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital.

BACKGROUND: The presence of acute kidney injury (AKI) in pre-eclampsia complicates treatment including; increasing length of hospital stay and a need to access services like dialysis which are largely expensive in resource-limited settings. We aimed to determine incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital in southwestern Uganda. METHODS: We carried out a hospital-based prospective cohort study from 16 November  2018 to 18 April 2019, among pregnant women with severe pre-eclampsia followed up in the hospital. We enrolled 70 mothers with severe pre-eclampsia and eclampsia; we excluded patients with a history of chronic kidney disease, chronic hypertension, and gestational hypertension. Data on socio-demographics, laboratory parameters, health system, obstetric and medical factors were collected. Baseline serum creatinine, complete blood count, and CD4 T-cell count were all done at admission (0-hour). A second serum creatinine was done at 48-hours to determine the presence of AKI and AKI was defined as a relative change of serum creatinine value at least 1.5 times the baseline (i.e., at admission) within 48 h. The proportion of women diagnosed with acute kidney injury among the total number of women with severe pre-eclampsia was reported as incidence proportion. Univariate and multivariate logistic regression was used to establish the association between acute kidney injury and severe pre-eclampsia. RESULTS: Incidence of acute kidney injury was high (42.86%) among women with severe pre-eclampsia. Antenatal care attendance was protective with an odds ratio of 0.14 (0.03, 0.73), p-value 0.020 at bivariate analysis but had no statistical significance at multivariate analysis. Eclampsia was an independent risk factor for acute kidney injury. (aOR 5.89 (1.51, 38.88), p-value 0.014. CONCLUSION: The incidence of acute kidney injury in patients with severe pre-eclampsia is high. Eclampsia is an independent risk factor of acute kidney injury. The findings of this study highlight the urgent need for more research and better perinatal care for these women.

A retrospective review of the risk factors affecting the therapeutic serum concentrations of magnesium sulfate in pre-eclamptic patients.

WHAT IS KNOWN AND OBJECTIVE: To identify factors that may affect the therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis in pre-eclamptic patients. METHODS: One hundred and two women with PE with severe features were identified categorized into two groups: subtherapeutic and therapeutic group. Multivariate logistic regression analysis and receiver operation characteristic curve analysis were conducted for the risk factors influencing the serum magnesium concentration. RESULTS: Among 102 eligible patients, 63 (62%) patients did not attain ideal therapeutic serum magnesium levels. Those patients had elevated albumin levels (p < 0.05), higher creatinine clearance (Ccr) (p < 0.001), and higher body mass index (BMI) (p < 0.001). Logistic regression analysis identified BMI and Ccr as independent risk factors for subtherapeutic serum magnesium concentration (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for BMI than for Ccr in predicting subtherapeutic serum magnesium levels (0.787 vs. 0.774). WHAT IS NEW AND CONCLUSION: Maternal body weight and renal function were independent risk factors for subtherapeutic serum magnesium concentration in the early stage after administration.

Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study.

OBJECTIVE: To assess in women with early-onset severe pre-eclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome. DESIGN: Prospective cohort study. SETTING: Maternity units in two Spanish hospitals. POPULATION: Women with diagnosis of early-onset severe pre-eclampsia. METHODS: Levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-) and sFlt-1/PlGF ratio were measured at admission and before delivery, and average daily change calculated. The association of longitudinal changes of angiogenic factors with the time interval to delivery and with complications was evaluated by logistic and Cox regression. MAIN OUTCOME MEASURES: Interval to delivery and composite of adverse outcomes. RESULTS: We included 63 women, of which 26 (41.3%) had a complication. Longitudinal changes of sFlt-1 were more pronounced in complicated pregnancies (median: 1047 versus 342 pg/ml/day; P = 0.04). On the multivariate analysis, the clinical risk score and sFlt-1 at admission explained 6.2% of the uncertainty for complication; the addition of sFlt-1 longitudinal changes improved this to 25.3% (P = 0.002). The median time from admission to delivery was 4 days (95% CI 1.6-6.04) in those in the highest quartile of sFlt-1 longitudinal changes versus 16 days (95% CI 12.4-19.6) in the remaining women (Log-rank test P < 0.001). CONCLUSIONS: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe pre-eclampsia add to baseline characteristics in the prediction of adverse outcome and interval to delivery. TWEETABLE ABSTRACT: In early-onset severe pre-eclampsia, longitudinal changes in sFlt-1 levels improve the prediction of complications and interval to delivery.

Association of Elevated Cord Blood Oxidative Stress Biomarkers with Neonatal Outcomes in Mothers with Pre-Eclampsia: A Case-Control Study.

OBJECTIVES: The objective of this study was to determine the relationship between the levels of stress biomarkers in cord blood and pre-eclampsia (PE) in a hospital-based population of pregnant patients and evaluate the effects on pregnancy outcomes. DESIGN: This was an observational, case-control study. Participants/Materials, Setting, Methods: This case-control study included 282 patients with severe PE and 534 women with normal pregnancy. The umbilical cord was collected at delivery and tested for malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, and homocysteine (Hcy) analysis. We performed a univariate general linear regression model analysis to control potential confounders and determined the underlying influencing factors for high MDA and ROS. A receiver operating characteristic curve analysis was conducted to determine the cutoff values for identifying severe PE. Further, the severe PE group was divided into the low- or high-MDA and low- or high-ROS subgroups according to the cutoff values. Finally, we created logistic regression models to estimate the adjusted odds ratio for each perinatal outcome in the high-MDA and high-ROS subgroup. RESULTS: The levels of MDA and ROS levels were higher in women with severe PE than in normotensive pregnant patients. However, when adjusted for cord blood Hcy levels, the difference was insignificant. Additionally, both MDA (r = 0.359, p < 0.001) and ROS (r = 0.473, p < 0.001) were positively correlated with the cord blood Hcy level. The areas under the curve of MDA and ROS levels were 0.65 (95% confidence interval [CI]: 0.60-0.69) and 0.88 (95% CI: 0.86-0.90), respectively. Higher MDA and ROS levels were associated with increased risks of a low Apgar score, admission to the NICU, and assisted ventilation for the newborn. LIMITATIONS: The study design led to the exclusion of several participants. CONCLUSIONS: Increased levels of oxidative stress markers in the cord blood might be significantly associated with negative effects on newborns. High levels of Hcy in the cord blood might be associated with elevated MDA and ROS concentrations in women with severe PE.

Maternal near miss and mortality attributable to hypertensive disorders in a tertiary hospital, Tanzania; a cross-sectional study.

BACKGROUND: Hypertensive disorders in pregnancy is the second most common direct cause of maternal deaths accounting for 14% of maternal deaths worldwide. Severe pre-eclampsia and eclampsia are among the hypertensive disorders in pregnancy causing significant morbidity and mortality, hence categorized as Maternal Near Miss. At Muhimbili National Hospital these are the leading causes of maternal deaths accounting for 19.9% of maternal death. This study aimed to determine the proportion of severe maternal outcomes and maternal near-miss indices among patients with severe pre-eclampsia and eclampsia at Muhimbili National Hospital in Tanzania. METHODS: A descriptive cross-sectional study was conducted between September 2017 to January 2018 at Muhimbili National Hospital. Women with severe pre-eclampsia and eclampsia were recruited. Data were extracted from patient files after admission, and followed up until discharge or death; after discharge was categorized as maternal near miss or death as maternal death. The outcome indicators were calculated using the total number of live births during the study period, the number of maternal deaths and maternal near-miss due to severe pre-eclampsia/ eclampsia in the same period. RESULTS: Nearly two-thirds of women recruited, 199 (62.2%) had severe preeclampsia while 121 (37.8%) had eclampsia, 71 (22.1%) had severe maternal outcome whereby 63 had maternal near-miss with organ dysfunction and 8 maternal deaths. The overall maternal near-miss ratio was 87.4 while that for severe pre-eclampsia was 54, and 33 per 1000 live births for eclampsia. Overall severe maternal outcome ratio was 19.4 while that for severe pre-eclampsia was 12 and that for eclampsia was 9.5 per 1000 live births. Mortality index was 11% and the Case fatality rate was 2.5%. CONCLUSION: There is a high proportion of women with severe maternal outcome attributable to severe pre-eclampsia and eclampsia, with a reduced proportion of maternal deaths. This signifies improvement of performance in our facility in dealing with patients with severe morbidities due to severe pre-eclampsia and eclampsia, however, more effort should be put to further reduce maternal mortality.

Severe pre-eclamptic women with headache: is posterior reversible encephalopathy syndrome an associated concurrent finding?

BACKGROUND: A high incidence of posterior reversible encephalopathy syndrome (PRES) has been observed in women with eclampsia on imaging. However this association was documented mostly after convulsions occurred. This study aimed to detect the development of PRES using magnetic resonance imaging (MRI) in women with severe preeclampsia and headache, and evaluate the clinical and radiological findings in obstetric outcomes. METHODS: A prospective single-center cohort study comprising 20 pregnant women with severe pre-eclampsia related headache was conducted using Numeric Rating Scale (NRS) score of ≧4. Additionally, non-contrast brain MRI was used to detect PRES and related radiological central nervous system (CNS) abnormalities. RESULTS: Patients were enrolled at a mean gestational age of 32 weeks (range 29-38 weeks). Two women were unable to complete the scanning. Of the 18 MRI scans, 15 (83%) revealed abnormal findings. One patient developed an altered mental state and diffuse PRES, with the occipital, temporal, thalamus, and basal ganglia, the brain stem, and the cerebellum being affected. Two patients had abnormal susceptibility-weighted imaging (SWI) findings, indicating micro-hemorrhages. The majority (12 cases, 66%) of the patients had abnormal cortical hyperintensities in the occipital and temporal lobes. Only three patients had normal MRI pictures. None of the women had eclampsia occurred during the peripartum period, and only one unrelated neonatal death due to congenital anomalies. CONCLUSION: A high incidence of abnormal cortical hyperintensity changes at locations typical for PRES on MRI was noted in women with severe pre-eclampsia and headache. These early hypertensive neurological signs allowed prompt and efficient obstetrical management, to prevent the development of eclampsia and PRES.

Prevalence and risk factors associated with severe pre-eclampsia among postpartum women in Zanzibar: a cross-sectional study.

BACKGROUND: Severe pre-eclampsia is more dominant in low and middle-income countries. In Sub-Saharan Africa, severe pre-eclampsia remains a major public health problem contributing to high rates of maternal mortality. Few studies have investigated the relationship between severe pre-eclampsia and associated factors in East Africa. The aim of this study was to determine the prevalence and risk factors associated with severe pre-eclampsia among postpartum women in Zanzibar. METHODS: A hospital based analytical cross-sectional study design was used. Purposive sampling was utilized for the selection of hospitals. Proportionate sampling was used for selection of representatives from each hospital and participants were selected using systematic random sampling. Postpartum mothers were included in the study. The study was conducted by an interviewer who administered a questionnaire with close ended questions and chart review for data gathering. SPSS version 23 was used for data analysis and descriptive and multiple logistic regression was performed for control of confounders. RESULTS: This study included a total of 400 participants with a 100% response rate. Participants ranged from 17 to 45 years of age with mean age (SD) of 28.78 (±6.296). The prevalence of severe pre-eclampsia among postpartum women was 26.3% (n = 105). After adjusting for the possible confounders, factors associated with severe pre-eclampsia were; maternal age group of 15-20 years (AOR 3.839; 95% C. I 1.037-14.210), pregnancy from new partner/husband (AOR 7.561; 95% C. I 3.883-14.724), family history of high blood pressure (AOR 6.446; C. I 3.217-12.917), diabetes prior to conception (AOR 55.827; 95% C. I 5.061-615.868), having high blood pressure in a previous pregnancy (AOR 19.382; 95% C. I 4.617-81.364), paternal age above 45 (AOR 2.401; 95% C. I 1.044-5.519) and multifetal gestation (AOR 7.62; 95% CI 2.01-28.84). CONCLUSION: The prevalence of severe pre-eclampsia among postpartum women in Zanzibar is high. Common risk factors in this setting include maternal age of 15-20 years, pregnancy with a new partner, family history of high blood pressure, pre-existing diabetes prior to conception, a history of high blood pressure in previous pregnancy paternal age greater than 45 and multifetal gestation.

Renalase rs10887800 polymorphism is associated with severe pre-eclampsia in southeast Iranian women.

Evidence has shown that pre-eclampsia (PE) is associated with an increased level of catecholamines. Renalase is a catecholamine-metabolizing enzyme, which contributes to the occurrence of hypertension. In the current study, we aimed to assess the relation between two renalase gene ( RNLS) polymorphisms, including rs2576178 at the 5'-flanking region and rs10887800 at intron 6, near the exon/intron border and PE susceptibility. In this case-control study, 179 women with PE and 202 normotensive pregnant women were genotyped for RNLS rs2576178 and rs10887800 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. There was no association between RNLS rs10887800 and rs2576178 polymorphisms and PE, neither in the dominant nor in the recessive model. Although there was no association between RNLS rs10887800 polymorphism and mild PE, this polymorphism was associated with 2.2-fold higher risk of severe PE in the recessive model (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.4; P = 0.01) but not in the dominant model. The RNLS rs2576178 and rs10887800 polymorphisms were not associated with PE severity. The RNLS rs10887800 and rs2576178 GG/GG combined genotypes were associated with 8.4- and 16.7-fold higher risk of PE and severe PE, respectively (OR, 8.4; 95% CI, 1-71.1; P = 0.048 and OR, 16.7; 95% CI, 1.6-167; P = 0.018). Also, the G-G haplotype was associated with 1.7-fold risk of PE and mild PE (OR, 1.7; 95% CI, 1.1-2.4; P = 0.009 and OR, 1.7; 95% CI, 1.1-2.5; P = 0.02). The RNLS rs10887800 polymorphism was associated with severe PE. The RNLS rs10887800 and rs2576178 GG/GG combined genotypes and G-G haplotype were associated with higher risk of PE.

Expression profile of Let-7s in peripheral blood mononuclear cells of normal and severe preeclampsia pregnant women.

HEADINGS AIM: We aimed to investigate if the let-7 s expression level in the serum of peripheral blood from pregnant women with severe pre-eclampsia and normal pregnant women is related to the incidence of severe pre-eclampsia. METHODS: Total RNA was extracted from collected peripheral blood mononuclear cells from 20 or over weeks pregnant women diagnosed with severe pre-eclampsia (age: 31.57 ±â€¯4.94) and normal pregnant women (age: 29.75 ±â€¯4.6) respectively, followed by real-time PCR to examine the expression of let-7 s. Correlation between let-7 s expression level and maternal age or body mass index of the normal pregnant women were also analyzed using SPSS21.0 software. RESULTS: Let-7a and let-7 g were significantly increased in pregnant women with severe pre-eclampsia by 4.67 fold and 2.37 fold respectively compared to the normal pregnant women, whereas there was no significant difference in let-7b and let-7i. Moreover, there was no correlation between maternal age or body mass index and the expression level of let-7a, let-7b, let-7 g, and let-7i. CONCLUSIONS: In conclusion, let-7a and let-7 g were significantly increased in the PBMCs of severe pre-eclampsia women compared to normal controls. Moreover, their expression level was not correlated to the maternal age or body mass of patients. Our data indicated that let-7a and let-7 g may be considered as predictive markers for SPE.

Evaluation of elabela, apelin and nitric oxide findings in maternal blood of normal pregnant women, pregnant women with pre-eclampsia, severe pre-eclampsia and umbilical arteries and venules of newborns.

Pre-eclampsia is multisystem metabolic diseases, commonly accompanied by hypertension and proteinuria, which are among the important causes of maternal and perinatal mortality and morbidity worldwide. In a pre-eclampsia animal model study in the last year, Elabela (ELA) infusion was reported to correct hypertension and proteinuria and to normalise the birth weights of the offspring. Therefore, our main goal in this human study is to compare ELA, apelin (APLN) and nitric oxide (NO) levels in the maternal blood of pregnant women with pre-eclampsia and severe pre-eclampsia and in their newborns' venous-arterial cord blood with maternal blood of healthy pregnant women and their newborns' venous-arterial cord blood. Thirty controls, 28 pre-eclampsia and 24 severe pre-eclampsia cases and their newborns participated in this study. Maternal blood and newborn venous-arterial cord blood samples were collected from these patients. ELA, APLN and NO levels in these samples were measured by ELISA method. When the maternal blood ELA, APLN and NO amounts were compared with control groups, there was a significant decrease in both pre-eclamptic and severe pre-eclamptic women and this was more prominent in the women with severe pre-eclampsia. When ELA, APLN and NO levels in the newborn venous-arterial cord blood of control group was compared with that of severe pre-eclamptic and pre-eclamptic women; it was parallel with maternal findings. ELA, APLN and NO levels appear to play a role in the pathophysiology of pre-eclampsia. It is predicted that if these molecules, which are reduced due to pre-eclampsia and severe pre-eclampsia, are brought to physiological limits in the future; pre-eclampsia related maternal and perinatal mortality and morbidity can be reduced. Impact Statement What is already known on this subject? There are two studies (one human and one animal) in the literature evaluating only maternal elabela (ELA) levels in pre-eclamptic pregnancies. The animal study demonstrated decreased blood ELA levels in pre-eclamptic animals and the human study found increased blood ELA levels in pre-eclamptic patients. There are no studies evaluating maternal ELA levels in severe pre-eclampsia patients and also there are no studies evaluating maternal ELA levels in pre-eclampsia and severe pre-eclampsia patients. There are no studies evaluating newborns' venous-arterial blood APLN and NO levels. Apelin (APLN) and nitric oxide (NO) results were controversial in pre-eclampsia and severe pre-eclampsia patients. What the results of this study add? The present study, for the first time, demonstrates that decreased blood ELA, APLN and NO levels in maternal blood of pregnant women with pre-eclampsia and severe pre-eclampsia and in their newborns' venous-arterial blood. Furthermore, we have also demonstrated for the first time that decreased ELA, APLN and NO are also related with low birth weights. What the implications are of these findings for clinical practice and/or further research? The low levels of ELA, APLN and NO in maternal blood and newborns' venous-arterial blood may be the result or the cause of pathologic changes in pre-eclampsia and severe pre-eclampsia. Also, ELA, APLN and NO may be new indicator parameters of systemic endothelial dysfunction together. More studies are needed to evaluate the relationship between of ELA, APLN and NO and pre-eclampsia and severe pre-eclampsia and in newborns' venous-arterial blood.

[Analysis of clinical early warning informations of severe preeclampsia before onset].

Objective: To explore the early warning informations of severepre-eclampsia before onset. Methods: The study was an observational case-control study. The study group consisted of 77 single-pregnancy preeclampsia pregnant women and the control group took 154 normal cases who were delivered to Tianjin Fifth Central Hospital (Peking University binhai Hospital) from January 2014 to December 2017 in the perinatal care referral system in Tianjin. To analyze changes in clinical indicators before the onset of severe pre-eclampsia with statistical methods. Results: Prehypertension, weight gain>0.85 kg/week, fetal growth restriction, edema and decline of plasma albumin, thrombocytopenia, poor compliance, perinatal examinations and examinations in tertiary hospitals were associated with severe pre-eclampsia (P<0.001). Multivariate regression analysis showed that the risk factors of severe preeclampsia were pre-hypertension, weight gain>0.85 kg/week, edema, thrombocytopeniaand poor compliance. The increase in the number of prenatal examinations in tertiary hospitals was a protective factor for severe preeclampsia. Conclusion: Prehypertension, weight gain during pregnancy (>0.85 kg/week), edema, thrombocytopenia, and poor compliance were warning informations of severe pre-eclampsia, and the increased number of prenatal examinations in tertiary hospitals was a protective factor for severe pre-eclampsia.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models.

BACKGROUND: The proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGß, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort. METHODS: We studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models. RESULTS: We found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGß higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity. CONCLUSIONS: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number ISRCTN14030412 , Date of registration 6/09/2007, retrospectively registered.

Pregnancy and Kidney Outcomes in Patients With IgA Nephropathy: A Cohort Study.

BACKGROUND: The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are controversial. This cohort study assessed the effects of pregnancy on kidney disease progression and risk factors for adverse pregnancy outcomes in patients with IgAN. STUDY DESIGN: A cohort study. SETTING & PARTICIPANTS: Women of child-bearing age with IgAN and minimum follow-up of 1 year after biopsy from December 2003 to September 2014. PREDICTORS: Pregnancy, treated as a time-dependent variable; baseline (at time of biopsy) estimated glomerular filtration rate (eGFR), proteinuria, blood pressure, and kidney pathology (Oxford MEST classification). OUTCOMES: Kidney disease progression event, defined as 30% decline in eGFR or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe preeclampsia and fetal loss. RESULTS: Of 413 patients enrolled, 266 (64.4%), 101 (24.5%), 40 (9.6%), and 6 (1.5%) had chronic kidney disease (CKD) stages 1, 2, 3, and 4, respectively. During follow-up, 104 had 116 pregnancies, of which 110 continued beyond week 20; 309 patients did not become pregnant. After adjustment for age, eGFR, mean arterial pressure, proteinuria, and pathology class at the time of biopsy, subsequent pregnancy among patients with CKD stages 3 to 4, but not CKD stages 1 to 2, was associated with faster eGFR decline (-7.44 vs -3.90mL/min/1.73m2 per year; P=0.007) and increased incidence of kidney progression events (HR, 5.14; 95% CI, 1.16-22.74) compared with patients who did not become pregnant. LIMITATIONS: Relatively small sample size and single-center experience. CONCLUSIONS: Pregnancy accelerated kidney disease progression in women with IgAN and CKD stage 3, but not in those at stage 1 or 2.

Maternal and neonatal outcomes in women with severe early onset pre-eclampsia before 26 weeks of gestation, a case series.

OBJECTIVE: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation. DESIGN: Nationwide case series. SETTING: All Dutch tertiary perinatal care centres. POPULATION: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014. METHODS: Women were identified through computerised hospital databases. Data were collected from medical records. MAIN OUTCOME MEASURES: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival). RESULTS: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days. CONCLUSIONS: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling. TWEETABLE ABSTRACT: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival.

Serious maternal complications in relation to severe pre-eclampsia: a retrospective cohort study of the impact of hospital volume.

OBJECTIVE: We examined rates of serious maternal complications in relation to severe pre-eclampsia based on the delivering hospital's annualised volume. DESIGN: Retrospective cohort study. POPULATION AND SETTING: Singleton deliveries (n = 25 782 235) in 439 hospitals in the USA. METHODS: Annualised hospital volume was categorised as 25-500, 501-1000, 1001-2000 and >2000. MAIN OUTCOME MEASURES: Rates of in-hospital maternal death and serious maternal complications, including puerperal cerebrovascular disorders, pulmonary oedema, disseminated intravascular coagulation, acute renal, heart and liver failure, sepsis, haemorrhage and intubation in relation to severe pre-eclampsia. We derived adjusted risk ratio (RR) and 95% confidence interval (CI), from hierarchical Poisson regression models. RESULTS: Severe pre-eclampsia was associated with an 8.7-fold (95% CI 7.6, 10.1) risk of composite maternal complications, with similar RRs across levels of hospital volumes. However, compared with hospitals with low annual volume (<2000), maternal mortality rates in relation to severe pre-eclampsia were lower in high volume hospitals. The rates of serious maternal complications were 410.7 per 10 000 to women who delivered in hospitals with a high rate of severe pre-eclampsia (≥2.12%) and 584.8 per 10 000 to women who delivered in hospitals with low severe pre-eclampsia rates (≤0.41; RR 1.75, 95% CI 1.24, 2.45). CONCLUSIONS: While the risks of serious maternal complications in relation to severe pre-eclampsia was similar across hospital delivery volume categories, deaths showed lower rates in large delivery volume hospitals than in smaller volume hospitals. The risk of complications was increased in hospitals with low compared with high severe pre-eclampsia rates. TWEETABLE ABSTRACT: Hospital volume had little impact on the association between severe pre-eclampsia and maternal complications.

Ovarian reserve in women with a previous history of severe pre-eclampsia.

PURPOSE: Severe pre-eclampsia affects maternal health with long-term consequences. It is postulated that during the process of implantation and cell differentiation, embryos resulting from the fertilization of ageing oocytes produce malfunctioning trophoectoderm leading to placental dysfunction. Therefore, severe pre-eclampsia may be associated with a decreased ovarian reserve. The objective of this study was to compare serum markers of ovarian reserve and function between women who had severe pre-eclampsia and those who had normal pregnancies. METHODS: Twenty women who had severe pre-eclampsia (PE) and 20 who had uncomplicated pregnancies (controls) matched for age and body mass index were included in the study. Fasting blood samples were taken during the follicular phase (day 5) of the menstrual cycle 6 months to 5 years after the delivery. Serum was separated and frozen at -70 °C until analyzed for anti-Mϋllerian hormone (AMH), total and free testosterone (TT), free-androgen index (FAI), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) hormone to evaluate ovarian reserve and function, and the results were compared between two groups. RESULTS: The median AMH was 0.91 ng/mL in PE group compared to 0.72 ng/mL in controls (p = 0.995). No significant differences were found between the two groups in the levels of LH (5.65 vs. 5.4 IU/L, respectively, p = 0.897) and FSH (4.95 vs. 5.1 IU/L, respectively, p = 0.523). However, total and free-TT levels as well as FAI were significantly lower in the PE group compared to controls (p = 0.017, p = 0.006, and p = 0.011, respectively). CONCLUSIONS: Ovarian reserve and function are not altered significantly in women with a previous history of pre-eclampsia compared with women who had an uncomplicated pregnancy.

Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes.

AIMS/HYPOTHESIS: Women with type 1 or type 2 diabetes are at increased risk of pre-eclampsia. Overweight and obesity are associated with an increased risk of pre-eclampsia in women without diabetes. The aim of the study was to investigate the impact of maternal overweight and obesity on the risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. METHODS: In a population-based cohort study including singleton births in Sweden, we estimated the risk of pre-eclampsia among women with type 1 diabetes (n = 7062) and type 2 diabetes (n = 886), and investigated whether maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)) modified the risk. Logistic regression analyses were used to estimate crude and adjusted ORs with 95% CIs, using women without diabetes as the reference group (n = 1,509,525). RESULTS: Compared with women without diabetes, the adjusted ORs for pre-eclampsia in women with type 1 and type 2 diabetes were 5.74 (95% CI 5.31, 6.20) and 2.11 (95% CI 1.65, 2.70), respectively. The corresponding risks of pre-eclampsia combined with preterm birth were even higher. Risks of pre-eclampsia increased with maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)), foremost in women without diabetes, to a lesser extent in women with type 1 diabetes but not in women with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Maternal overweight and obesity increased risks of pre-eclampsia in women with type 1 diabetes but not in women with type 2 diabetes. Even so, considering associations between maternal BMI and overall maternal and offspring risk, all women (with and without diabetes) should aim for a normal weight before pregnancy.

Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Oral nifedipine is recommended along with labetalol and hydralazine for treatment of severe hypertension during pregnancy by most authorities. Although nifedipine is cheap and easily administered, the usage pattern among health care providers suggests a strong preference for labetalol despite lack of evidence for the same. OBJECTIVES: To determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. SEARCH STRATEGY: We systematically searched for articles comparing oral nifedipine with intravenous labetalol for the treatment of severe hypertension during pregnancy in any language, over Medline, Cochrane Central Register of Clinical Trials and Google Scholar from inception till February 2014. SELECTION CRITERIA: We included all RCTs that compared intravenous labetalol with oral nifedipine for treatment of severe hypertension during pregnancy, addressing relevant efficacy and safety outcomes. DATA COLLECTION AND ANALYSIS: Eligible studies were reviewed, and data were extracted onto a standard form. We used Cochrane review manager software for quantitative analysis. Data were analysed using a fixed effect model. MAIN RESULTS: The pooled analysis of seven trials (four from developing countries) consisting of 363 woman-infant pairs showed that oral nifedipine was associated with less risk of persistent hypertension (RR 0.42, 95% CI 0.18-0.96) and reported maternal side effects (RR 0.57, 95% CI 0.35-0.94). However, on sensitivity analysis the outcome 'persistent hypertension' was no longer significant. Other outcomes did not reach statistical significance. CONCLUSION: Oral nifedipine is as efficacious and safe as intravenous labetalol and may have an edge in low resource settings. TWEETABLE ABSTRACT: Although studies to date are few in number and small, nifedipine shows promise for severe hypertension in pregnancy.