Hypertensive Disorders of Pregnancy:A Systematic Review of International Clinical Practice Guidelines

Background Clinical practice guidelines (CPGs) are developed to assist health care providers in decision-making. We systematically reviewed existing CPGs on the HDPs (hypertensive disorders of pregnancy) to inform clinical practice. Methodology & Principal Findings MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessments, and Database of Abstracts of Reviews of Effects (Ovid interface), Grey Matters, Google Scholar, and personal records were searched for CPGs on the HDPs (Jan/03 to Nov/13) in English, French, Dutch, or German. Of 13 CPGs identified, three were multinational and three developed for community/midwifery use. Length varied from 3–1188 pages and three guidelines did not formulate recommendations. Eight different grading systems were identified for assessing evidence quality and recommendation strength. No guideline scored ≧80% on every domain of the AGREE II, a tool for assessing guideline methodological quality; two CPGs did so for 5/6 domains. Consistency was seen for (i) definitions of hypertension, proteinuria, chronic and gestational hypertension; (ii) pre-eclampsia prevention for women at increased risk: calcium when intake is low and low-dose aspirin, but not vitamins C and E or diuretics; (iii) antihypertensive treatment of severe hypertension; (iv) MgSO4 for eclampsia and severe pre-eclampsia; (v) antenatal corticosteroids a

Early-onset fetal growth restriction:A systematic review on mortality and morbidity

Introduction: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. Material and methods: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. Results: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. Conclusions: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction:post hoc reflections on the Dutch STRIDER study

The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02). Conclusion: Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a “rebound” vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00431-021-04355-x

Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth. Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis

Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

Objective: This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension (. http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext) to provide a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy. Evidence: Published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library in March 2012 using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, postpartum follow-up). Results were restricted to systematic reviews, randomized control trials, controlled clinical trials, and observational studies published in French or English between January 2006 and February 2012. Searches were updated on a regular basis and incorporated in the guideline to September 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence in the guideline summarized here was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (. Table 1)

Influence of gestational age at initiation of antihypertensive therapy: Secondary analysis of CHIPS trial data (control of hypertension in pregnancy study).

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight 48 hours (Pinteraction=0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks (Pinteraction=0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes

Safety and Efficacy of Ferric Carboxymaltose in Anemic Pregnant Women: A Retrospective Case Control Study

Background. Anemia during pregnancy is commonly caused by iron deficiency and can have severe consequences for both the mother and the developing fetus. The aim of this retrospective study was to assess the safety and efficacy of intravenous ferric carboxymaltose (FCM) in pregnant women. Methods. All women treated with FCM for anemia during pregnancy between 2010 and 2012 at our institution were included. A matched control group was selected, including women who either were nonanemic or had anemia but were not considered for intravenous iron. Main outcome measures were maternal safety and pregnancy outcomes. Results. The study included 128 patients (FCM: 64; control: 64). Median FCM dose was 1000 mg and median gestational age at the time of first treatment was 34 weeks and 6 days. Median Hb increased from 8.4 g/dL (interquartile range 7.7; 8.9 g/dL) at the first FCM administration to 10.7 g/dL (9.8; 11.5 g/dL; = 46 with available Hb at delivery) at the time of delivery, achieving levels similar to those in the control group (10.8 g/dL [9.8; 11.8 g/dL; = 48]). No treatment-related adverse events were reported and no statistically significant differences in pregnancy outcomes were observed between groups. Conclusions. Within the limitations of this case control study, FCM was a safe and efficient treatment of anemia during pregnancy

Safety and Efficacy of Ferric Carboxymaltose in Anemic Pregnant Women: A Retrospective Case Control Study

Background. Anemia during pregnancy is commonly caused by iron deficiency and can have severe consequences for both the mother and the developing fetus. The aim of this retrospective study was to assess the safety and efficacy of intravenous ferric carboxymaltose (FCM) in pregnant women. Methods. All women treated with FCM for anemia during pregnancy between 2010 and 2012 at our institution were included. A matched control group was selected, including women who either were nonanemic or had anemia but were not considered for intravenous iron. Main outcome measures were maternal safety and pregnancy outcomes. Results. The study included 128 patients (FCM: 64; control: 64). Median FCM dose was 1000 mg and median gestational age at the time of first treatment was 34 weeks and 6 days. Median Hb increased from 8.4 g/dL (interquartile range 7.7; 8.9 g/dL) at the first FCM administration to 10.7 g/dL (9.8; 11.5 g/dL; n = 46 with available Hb at delivery) at the time of delivery, achieving levels similar to those in the control group (10.8 g/dL [9.8; 11.8 g/dL; n = 48]). No treatment-related adverse events were reported and no statistically significant differences in pregnancy outcomes were observed between groups. Conclusions. Within the limitations of this case control study, FCM was a safe and efficient treatment of anemia during pregnanc