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This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities.
Study Eligibility Criteria
Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German.
Study Appraisal and Synthesis Methods
Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus.
Results
Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed “clinically useful” and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with “severe” preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of “severe” preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia.
Conclusion
Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.
Although some countries have recently achieved reductions in pregnancy hypertension–related maternal mortality, serious maternal and perinatal morbidity persists, maintaining pregnancy hypertension as a healthcare priority.
on behalf of MBRRACE-UK Saving lives, improving mothers’ care: surveillance of maternal deaths in the UK 2012-14 and lessons learned to inform maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-14.
National Perinatal Epidemiology Unit, University of Oxford,
Oxford, England2016
There are many national and international clinical practice guidelines (CPGs) covering pregnancy hypertension classification, diagnosis, and management, generally, and preeclampsia prediction and prevention, specifically. In our 2014 systematic review,
we found that there were areas of consistency appropriate for auditable standards and areas of inconsistency to be addressed by future research.
We sought to update our previous systematic review of CPGs to summarize current thinking about pregnancy hypertension designed to inform clinical practice and future research.
To review pregnancy hypertension clinical practice guidelines (CPGs) to inform international practice and research.
Key findings
Key consistencies between CPGs include: blood pressure measurement, dipstick proteinuria testing with confirmation by protein:creatinine ratio, a broad definition of preeclampsia, preeclampsia prevention with aspirin, treatment of severe hypertension, antihypertensive agents used for any severity of hypertension, magnesium sulphate for eclampsia prevention and treatment (for “severe” preeclampsia), delivery for term preeclampsia, and acknowledgement of the long-term health consequences of hypertensive pregnancy. Key differences between CPGs include: definitions of preeclampsia severity, biomarkers for prediction or time-of-disease assessment, and normalization of blood pressure when non-severely elevated.
What does this add to what is known?
CPGs are increasingly evidence-based and their recommendations aligned. Consistent recommendations should be implemented and audited. Inconsistencies should guide research priorities.
Materials and Methods
The review was registered with the international prospective register of systematic reviews (reference, CRD42019123787). As a systematic review of published material, research ethics board approval was not required.
Literature search
We replicated the comprehensive search strategy of bibliographic databases as in Gillon et al,
updating the search from January 2013 to October 2019. Key words and medical subject headings, relating to the themes of “pregnancy,” “hypertension,” “hypertensive disorders of pregnancy,” and “guidelines,” were combined to search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Health Technology Assessments, and the Database of Abstracts of Reviews of Effects. In addition, we searched “Guidelinecentral.com” and Google Scholar, applying the key words “hypertensive disorders of pregnancy,” “hypertension during pregnancy,” “hypertension in pregnancy,” “preeclampsia,” and “gestational hypertension,” combined with “guideline” or “clinical practice guideline.” For Google Scholar searches, the first 100 results were screened based on the assumption that the most relevant results would appear first. A manual search was conducted for the website of every society listed as a member of the International Federation of Gynecology and Obstetrics.
Finally, specific efforts were made to identify updates (be they comprehensive or only relating to certain aspects of the previous guideline) of CPGs included in Gillon et al,
by searching the websites of the relevant societies and utilizing personal contacts to ascertain if (and when) an update had occurred or was pending (Supplemental Table 1). Results were filtered according to our eligibility criteria.
Eligibility
We defined a CPG as an evidence-based document issued by a professional medical society, government body, or a similar organization that offered structured advice for healthcare professionals. As done previously,
we included multidisciplinary CPGs that were published within the last decade (2009–2019); covered diagnosis, assessment, and management of at least 1 hypertensive disorder of pregnancy (HDP); and were written in (or officially translated into) English, French, Dutch, or German (understood by the review authors). In addition, articles that were explicit updates to the CPGs in Gillon et al
we excluded publications that did not reference primary literature and so were not deemed to be evidence based, were adapted entirely from existing CPGs and so did not offer original information, or were local or regional in scope when there was a relevant national document.
Evaluation
CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool
that has the following 6 domains (number of items): scope and purpose (n=3), stakeholder involvement (n=3), rigor of development (n=8), clarity of presentation (n=3), applicability (n=4), and editorial independence (n=2). Each reviewer assessed whether the guideline could be recommended for use; if so, the recommendations were abstracted. Previous AGREE II assessments
were carried forward if only 1 aspect of the CPG was updated and similar methods were used. If CPGs were published by a single issuer as separate documents intended for concurrent use, they were assessed collectively using the AGREE II tool. In addition, 2 authors (G.S. and either T.E.G., A.P., P.v.D., or L.A.M.) rated each CPG independently for quality, methods to grade evidence quality, and recommendation strength and content. Disagreements were resolved through discussion.
to abstract CPG recommendations and related text from CPGs. Results are presented descriptively, for diagnosis, classification, prediction, prevention, and management. Expectant care was inferred when CPGs advised, “do not offer planned birth,” “aim to prolong pregnancy,” or “continue surveillance,” and not just when a CPG recommended delivery at a certain gestational age.
Results
Our search strategy yielded 252 articles—192 from bibliographic database searches and 60 from other sources (Figure). After the duplicates were removed and the titles screened, 62 full-text articles were retrieved for closer scrutiny; 36 were excluded because they did not reference HDP literature (n=2),
Société française d'anesthésie et de réanimation (Sfar); Collège national des gynécologues et obstétriciens français (CNGOF); Société française de médecine périnatale (SFMP); Société française de néonatalogie (SFNN) [Multidisciplinary management of severe pre-eclampsia (PE). Experts’ guidelines 2008. Société française d'anesthésie et de réanimation. Collège national des gynécologues et obstétriciens français. Société française de médecine périnatale. Société française de néonatalogie].
A best practice position statement on the role of the nephrologist in the prevention and follow-up of preeclampsia: the Italian study group on kidney and pregnancy.
SEC Working Group for the ESC 2018 guide on the treatment of cardiovascular diseases during pregnancy Comments on the 2018 ESC Guidelines for the Management of Cardiovascular Diseases During Pregnancy.
Expertos Intervinientes. Guias de la Sociedad Argentina de Hipertension para el diagnostico, estudio, tratamiento y seguimiento de la hipertension arterial. 2007.
Representantes del Grupo Desarrollador de la Guía - Universidad Nacional de Colombia - Alianza Cinets Clinical practice guidelines for approaching pregnancy-associated hypertensive complications [Article in Spanish].
Federation of Anaesthesiologists and Reanimatologists Emergency care for eclampsia and its complications. Eclampsia, HELLP-syndrome [Article in Russian].
METODIKA nėštumo sukelta hipertenzinė BŪKLĖ (nėščiųjų hipertenzija, preeklampsija, EKLAMPSIJA). Lietuvos akušerių-ginekologų draugija Lietuvos akušerių sąjunga.
Postępowanie w nadciśnieniu tętniczym u kobiet w ciąży. Zapobieganie, diagnostyka, leczenie i odległe rokowanie. Stanowisko Polskiego Towarzystwa Nadciśnienia Tętniczego, Polskiego Towarzystwa Kardiologicznego oraz Polskiego Towarzystwa Ginekologów i Położników.
European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC).
American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on hypertension in pregnancy.
Committee on Obstetric Practice Committee Opinion no. 692: emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period.
European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the management of cardiovascular diseases during pregnancy of the European Society of Cardiology (ESC).
American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on hypertension in pregnancy.
Year of publication refers to the date of the main document, even if there have been subsequent partial updates of information.
CPG full name and references
International
WHO
2011
World Health Organization 2011 with updates on calcium supplementation to prevent preeclampsia, management of severe hypertension, and timed delivery for severe preeclampsia
American College of Obstetricians and Gynecologists (ACOG) 2019 in three publications on gestational hypertension and preeclampsia, chronic hypertension, and the Committee Opinion on emergent therapy of severe hypertension
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics ACOG Practice Bulletin no. 203: chronic hypertension in pregnancy.
Institute of Obstetricians and Gynaecologists Royal College of Physicians of Ireland (RCPI) 2016 in two publications about hypertensive disorders and severe preeclampsia and eclampsia
Clinical practice guideline The diagnosis and management of severe pre-eclampsia and eclampsia. Institute of Obstetricians and Gynaecologists, Royal College of Physicians of Ireland and the Clinical Strategy and Programmes Division, Health Service Executive.
Clinical practice guideline The manangement of hypertension in pregnancy. Institute of Obstetricians and Gynaecologists, Royal College of Physicians of Ireland and the Clinical Strategy and Programmes Division, Health Service Executive.
Werkgroep NO. Addendum bij multidisciplinaire richtlijn Hypertensieve aandoeningen in de zwangerschap uit 2011. Nederlandse Vereniging voor Obstetrie en Gynaecologie,
Utrecht2014
NVOG-module ‘Wat is de rol van acetylsalicylzuur, gestart ≤16 weken amenorroeduur, ter preventie van pre-eclampsie bij zwangere vrouwen?’ (behorende bij de richtlijn Hypertensieve aandoeningen in de Zwangerschap). Ned Ver Obstet Gynecol (NVOG) 2019:1–32.
Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy in New Zealand: a clinical practice guideline. Ministry of Health, New Zealand Government,
2018
BRA, Brazil; CAN, Canada; CPG, clinical practice guideline; DEU, Germany; FRA, French Society of Hypertension; IRL, Ireland; ITA, Italy; NLD, Netherlands; NOR, Norway; NZL, New Zealand; POL, Poland; TUN, Tunisia; UK, United Kingdom; USA, United States of America.
Scott. Pregnancy hypertension guidelines—similarities and dissimilarities. Am J Obstet Gynecol 2022.
a Year of publication refers to the date of the main document, even if there have been subsequent partial updates of information.
Characteristics of included clinical practice guidelines
Notably, 4 CPGs were intended for a multinational audience (the World Health Organization [WHO], the Society of Obstetric Medicine of Australia and New Zealand [SOMANZ], the International Society for the Study of Hypertension in Pregnancy [ISSHP], and the European Society of Cardiology [ESC]), and 13 were for national use—11 from high-income and 2 from upper–middle-income countries—across 5 continents. For the 6 non-English publications, 3 were reviewed in their original languages (Netherlands [NLD], Germany [DEU], Tunisia [TUN]) and 3 as official English translations (France [FRA], Norway [NOR], and Poland [POL]). Most CPGs were produced by professional societies, but 2 were produced by government organizations (National Institute for Health and Care Excellence [NICE], Ministry of Health, New Zealand [NZL]) and 1 by the WHO.
Most CPGs were published as a single document, but the number varied (1–11), and the pages were from 5 (Italy [ITA]) to 1139 (NICE) (median, 55) (Supplemental Table 2).
Quality of clinical practice guidelines
No CPG had an AGREE II score of ≥80% in all domains (Supplemental Table 2), but this high score was seen in 5 of 6 domains for governmental CPGs (NICE and NZL) and 4 of 6 domains for WHO. CPGs scored best on “scope and purpose” and “clarity of presentation,” when 15 of 17 scored ≥50%; the lowest scores for presentation clarity resulted from not formulating key recommendations (ITA and SOMANZ). Poor scores were most commonly seen for applicability (14 CPGs scoring ≤50%), failure to report audit criteria (specified by the following 3 CPGs: WHO, SOMANZ, and NICE), and failure to report facilitators and barriers to recommendation implementation and proposed resource implications (10/17 and 11/17 CPGs scoring the minimum, respectively). Editorial independence from funders was poorly reported (11/17). Overall, all but ITA and NOR were deemed clinically useful (n=15) and their content was abstracted.
Quality of evidence and strength of recommendations
Using 9 different grading systems, 8 of 15 CPGs rated both the quality of evidence and strength of their recommendations (WHO, Canada [CAN], FRA, Brazil [BRA], NZL, ESC, POL, and TUN), 3 only the quality of evidence (NICE, NLD, United States [USA]), 1 just the strength of recommendations (DEU), and 3 neither (SOMANZ, Ireland [IRL], and ISSHP).
Practice recommendations
Hypertension and proteinuria: diagnosis and measurement
Hypertension and its severity were defined by all CPGs but the WHO (Table 2). Hypertension was defined as a systolic blood pressure (BP) of ≥140 mm Hg and a diastolic BP of ≥90 mm Hg (n=13/14). Most CPGs (n=10) recommended in-office repeat measurement for confirmation, and many acknowledged that out-of-office confirmation may be useful (n=8), although few (n=3) formally recommended this. Severe hypertension was defined as BP of ≥160/110 mm Hg (n=13/14) other than by SOMANZ that advocated ≥170/110 mm Hg.
Table 2Hypertension and proteinuria diagnosis and measurement recommendations
Number of CPGs
CPGs reporting
Hypertension and measurement of BP
Hypertension definition
14
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, DEU, UK, POL
sBP of ≥140 mm Hg or dBP of ≥90 mm Hg
13
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, UK, POL
Both sBP of ≥140 mm Hg and dBP of ≥90 mm Hg
1
DEU
In-office confirmation is recommended
10
WHO, CAN, SOMANZ, IRL, BRA, ISSHP, NZL, ESC, USA, POL
Out-of-office confirmation is recommended or acknowledged as being useful
3 (recommended)
FRA, ISSHP, POL
8 (potentially useful)
CAN, SOMANZ, IRL, BRA, TUN, ESC, USA, DEU
Severe hypertension
14
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, DEU, UK, POL
sBP of ≥160 mm Hg or dBP of ≥110 mm Hg
13
NLD, CAN, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, DEU, UK, POL
sBP of ≥170 mm Hg or dBP of ≥110 mm Hg
1
SOMANZ
Measurement of BP
Rest before measurement
9
NLD, IRL, BRA, FRA, TUN, NZL, USA, DEU, POL
Should be seated
11
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, NZL, USA, DEU, POL
Choose arm with higher values
6
NLD, CAN, BRA, TUN, UK, POL
Cuff appropriate size
13
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, DEU, POL
Cuff length 1.5 times arm circumference
4
NLD, CAN, TUN, USA
Korotkoff phase for dBP
Phase V
9
NLD, CAN, SOMANZ, IRL, BRA, TUN, ESC, NZL, DEU
Phase IV
5
SOMANZ, IRL, BRA, NZL, DEU
BP measurement device
12
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, POL
Mercury sphygmomanometer
9
NLD, CAN, SOMANZ, BRA, TUN, ESC, ISSHP, NZL, USA
Aneroid device
6
NLD, CAN, SOMANZ, IRL, BRA, TUN
Automated device validated in pregnancy and preeclampsia
12
NLD, CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, POL
If quantitative testing not available, dipstick proteinuria value considered diagnostic
8
SOMANZ, IRL, BRA, TUN, ISSHP, USA, UK, POL
Repeated ≥1+
1
SOMANZ
≥2+
6
IRL, TUN, ISSHP, USA, UK, POL
A positive result in ≥2 samples
1
BRA
Proteinuria quantification method specified
13
CAN, SOMANZ, IRL, BRA, FRA, TUN, ESC, ISSHP, NZL, USA, DEU, UK, POL
Urinary PrCr ≥30 mg/mmol
11
CAN, SOMANZ, IRL, FRA, TUN, ISSHP, NZL, USA, DEU, UK, POL
24-h urinary protein of ≥0.3 g/d
8
CAN, IRL, BRA, FRA, TUN, USA, DEU, POL
Urinary ACR
3
BRA, ESC, UK
ACR, albumin-to-creatinine ratio; BP, blood pressure; BRA, Brazil; CAN, Canada; CPG, clinical practice guideline; dBP, diastolic blood pressure; DEU, Germany; ESC, European Society of Cardiology; FRA, France; IRL, Ireland; ISSHP, International Society for the Study of Hypertension in Pregnancy; ITA, Italy; N/A, not applicable; NLD, Netherlands; NOR, Norway; NZL, New Zealand; UK, United Kingdom; POL, Poland; PrCr, protein-to-creatinine ratio; sBP, systolic blood pressure; SOMANZ, Society of Obstetric Medicine of Australia and New Zealand; TUN, Tunisia; USA, United States of America; WHO, World Health Organization.
Scott. Pregnancy hypertension guidelines—similarities and dissimilarities. Am J Obstet Gynecol 2022.
Most CPGs provided recommendations about BP measurement. Of note, 9 CPGs specified that the woman should be rested before BP measurement, but rest time varied from a few minutes (BRA and POL) to “preferably greater than 10 minutes” (USA) or was unspecified. Advice on positioning always had the woman seated (n=11). Few CPGs commented on the choice of arm when interarm BP readings differ (n=6); all recommended using the arm with the higher value or the right arm if the difference was <10 mm Hg (NLD). Advice about the appropriate cuff size was common (n=13), but few CPGs specified that the cuff length should be 1.5 times the circumference of the patient’s arm (n=4).
Most CPGs advised on BP devices that were acceptable (n=12), all recommending an automated device validated for use in pregnancy (n=12/12) with 5 recommending a reference website for specific devices as www.dableducational.org (CAN, FRA, ISSHP, and ESC) or http://bhsoc.org/bp-monitors/bp-monitors (POL) and 2 stating specifically that wrist devices are not appropriate for use (FRA and DEU). If the use of a validated device is not possible, 7 CPGs highlighted that BP device should regularly be compared with and calibrated against a reference device (NLD, CAN, SOMANZ, IRL, FRA, BRA, and ISSHP). Most CPGs mentioned an acceptable use of the mercury sphygmomanometer (n=9/12) and fewer aneroid devices (n=6/12). Of the 10 CPGs that recommended nonautomated devices, most (n=8/10) advised on Korotkoff phase V for diastolic BP (with DEU also noting this), but some said that phase IV would be acceptable (n=5/10).
Most CPGs recommended that dipstick testing be used for initial detection of proteinuria (n=12), with a “positive” result usually designated as ≥1+ (n=10/12) rather than ≥2+ (n=1/12) or not defined (n=1/12). All CPGs recommended that a positive dipstick result should be confirmed by quantitative testing (n=12/12). If quantitative testing was not available, dipstick proteinuria testing considered diagnostic was usually specified (n=8) as ≥2+ by all but BRA that recommended that “a positive result in ≥2 samples” be considered diagnostic or repeated results ≥1+ (SOMANZ).
Proteinuria quantification method was usually specified (n=13)—usually urinary protein-to-creatinine ratio (PrCr) of ≥30 mg/mmol (n=11/13), but also 24-hour urinary protein of ≥0.3 g/d (n=8/13). Urinary albumin-to-creatinine ratio (ACR) was not often recommended (n=3/13) and significant levels varied from ≥8 mg/mmol (NICE) to ≥30 mg/mmol (BRA and ESC).
Classification of the hypertensive disorders of pregnancy
All CPGs defined chronic or “preexisting” hypertension and gestational hypertension (GH), other than the WHO that focused only on preeclampsia. Chronic hypertension was defined as hypertension detected before pregnancy or during pregnancy before 20 weeks’ gestation by all relevant CPGs (n=14/14). Although 4 specified that hypertension must persist after delivery (ESC, USA, DEU, POL), 2 stipulated persistence beyond 6 weeks (ESC, POL), 1 for ≥12 weeks (DEU), and 1 for an unspecified time (USA). Few CPGs mentioned potential secondary causes of hypertension, however uncommon (CAN, SOMANZ, IRL, ISSHP, USA, NICE, and POL). (Superimposed preeclampsia is defined below.)
GH was defined as new-onset hypertension detected after 20 weeks’ gestation for all but DEU that did not specify the gestational age of onset. In addition, 6 CPGs specified that GH must resolve after delivery, within 6 weeks (ESC and POL) or 12 weeks (NLD, SOMANZ, IRL, and NZL). Only CAN mentioned the potential for a secondary cause of hypertension.
Preeclampsia was defined by all CPGs, as hypertension after 20 weeks’ gestation in association with at least 1 other target organ manifestation. A total of 3 CPGs defined preeclampsia traditionally and regarded proteinuria as mandatory (WHO, NLD, and FRA). Other CPGs defined preeclampsia “broadly,” without proteinuria as mandatory (n=12), but among the many potential target organ manifestations, there was a widespread agreement that target organ involvement was defined by maternal symptoms of headache or visual disturbances (n=12/12), proteinuria (n=12/12), abnormal routine laboratory testing of low platelet count (all but DEU; n=11/12), raised serum creatinine (all but ESC; n=11/12), or elevated liver enzymes (n=12/12). However, there was no agreement on definitions that were often unspecified. Fetal manifestations were not widely endorsed; the most common criterion was fetal growth restriction (n=9/12), followed by abnormal umbilical artery Doppler (n=3/12), stillbirth (n=4/12), or abruption (n=2/12). Only CAN mentioned oligohydramnios or abnormal fetal heart rate.
Eclampsia was defined as seizures during pregnancy, associated with preeclampsia or another HDP; 3 CPGs specified that seizures must have no other cause (WHO, DEU, and USA).
Only 3 CPGs recommended biomarkers for preeclampsia diagnosis, so-called “time-of-disease” assessment (ESC, NICE, and DEU), 2 as a “rule-out” test (ESC and NICE) and 1 as a “rule-in” test (DEU). ESC stated that a soluble fms-like tyrosine kinase-1-to-placental growth factor ratio of ≤38 could be used to exclude the onset of preeclampsia in the next week. NICE recommended the measurement of angiogenic markers on 1 occasion in women with GH
but formally adopted the ISSHP definition of preeclampsia that does not include angiogenic markers. DEU advised that preeclampsia can be diagnosed in the context of pregnancy hypertension if there are “abnormal findings of preeclampsia-specific markers, such as angiogenic factors,” even if other target organ manifestations are absent.
“Severe” preeclampsia was not defined by 4 CPGs (SOMANZ, ESC, ISSHP, and DEU); ISSHP and SOMANZ stated specifically they had not done so to encourage cautious management of all women with preeclampsia that can progress unpredictably. Among the 3 CPGs with a restrictive definition of preeclampsia, “severe” preeclampsia was defined as the development of severe hypertension, worsening proteinuria, or other target organ manifestations (that defined any preeclampsia for other CPGs) (WHO, NLD, and FRA). Of the remaining 8 CPGs, “severe” preeclampsia was defined by the presence or development of usually graver manifestations. Only CAN had mutually exclusive criteria for preeclampsia and “severe” preeclampsia, considered to be an indication for delivery. The only manifestation that was almost uniformly designated as “severe” preeclampsia was severe hypertension (n=7/11; CAN, IRL, BRA, TUN, NZL, NICE, and POL).
Superimposed preeclampsia was defined by 8 CPGs, always as the development of preeclampsia (n=8; NLD, CAN, SOMANZ, IRL, FRA, ISSHP, USA, and POL) in a woman with preexisting hypertension. Notably, 3 CPGs specifically excluded a deterioration in BP control from the definition (SOMANZ, IRL, and ISSHP).
White-coat hypertension was defined by most CPGs (n=10) as a BP elevated in the clinic but normal outside the clinic, defined as <135/85 mm Hg (CAN, FRA, TUN, and ISSHP), <20/10 mm Hg lower than in the clinic (BRA), or undefined (SOMANZ, IRL, NZL, USA, and POL). Masked hypertension was defined by few CPGs (n=5) as a normal BP in the clinic but an elevated reading outside the clinic (CAN, SOMANZ, BRA, ISSHP, and POL).
Prediction of preeclampsia
A total of 14 CPGs presented risk factors for preeclampsia, either as a list without specifying associated risk (WHO, SOMANZ, TUN, ISSHP, and DEU) or stratified as “major” or other (CAN and NZL) or “high” or “moderate” (IRL, NLD, ESC, USA, NICE, and POL). “High” or “major” risk factors were consistently chronic hypertension, pregestational diabetes, and antiphospholipid antibody syndrome (n=8/8 relevant CPGs); previous preeclampsia (n=4/8), chronic kidney disease (n=5/8), systemic lupus (n=7/8), autoimmune disease (n=5/8), multiple pregnancy (n=2/8), and family history of preeclampsia (mother or sister, n=1/8) were endorsed less frequently. “Moderate” risk factors were consistently advanced maternal age, obesity, family history of preeclampsia, nulliparity, and interpregnancy interval of ≥10 years; all but the USA endorsed multifetal pregnancy, and only the USA specified “previous adverse pregnancy outcome,” African American race, low socioeconomic status, and low maternal birthweight.
Most CPGs advocated using clinical factors to assess preeclampsia risk. However, 2 CPGs recommended a combination of clinical markers, biomarkers, and ultrasonography for early pregnancy screening (TUN and DEU). Although 3 CPGs recommended uterine artery Doppler velocimetry for risk assessment (ISSHP, ESC, and POL), 4 recommended against it (CAN, SOMANZ, NZL, and USA).
Prevention of preeclampsia
Aspirin
All CPGs recommended low-dose aspirin for preeclampsia prevention, although who should receive it, at what dose, and from and until which gestational age were inconsistent. Indications for aspirin varied: previous preeclampsia (TUN and FRA), a history of pregnancy hypertension or a preeclampsia risk of >1:150 (POL); 1 “high” or at least 2 “moderate” risk factors (NLD, IRL, ESC, USA, NICE, and POL), a list of “high” risk factors (ISSHP), or risk assessment left to the clinician’s discretion (WHO, CAN, SOMANZ, NZL, and DEU), even when no risk factors had been specified (BRA).
Aspirin dosage was specified (n=5) or a dose range suggested (n=9) by all but SOMANZ: 75 mg (WHO and IRL), 81 mg (USA), 100 mg (NZL), 150 mg (DEU), 80 to 150 mg (NLD), 75 to 162 mg (CAN and ISSHP), 75 to 160 mg (FRA), 100 to 150 mg (ESC, POL), or 75 to 150 mg (BRA, TUN, and NICE).
All CPGs advised early initiation of aspirin, optimally before 16 weeks (n=9; NLD, CAN, IRL, TUN, ISSHP, NZL, USA, DEU, and POL), but definitely from 12 weeks (NLD, IRL, BRA, ESC, and NICE), before 20 weeks (WHO, FRA, and ISSHP), or at 12 to 28 weeks (USA).
Recommendations about when to stop aspirin varied from not before 35 weeks (FRA and TUN), at 36 weeks (POL), at 36 to 37 weeks (ESC), 1 week before parturition (NLD), not before 37 weeks (SOMANZ), or continue until delivery (n=5; CAN, IRL, NZL, USA, and NICE).
Calcium
Recommendations to take calcium for preeclampsia prevention (n=9 CPGs, 1–2.5 g/d) varied according to the baseline intake and preeclampsia risk: low calcium intake regardless of preeclampsia risk (WHO, CAN, IRL, TUN, and ESC), moderate to high preeclampsia risk, regardless of calcium intake (SOMANZ), or low intake and an intermediate or high risk of preeclampsia (BRA, ISSHP, and NZL). Low calcium intake was defined by a minority of CPGs, as <600 mg/d (CAN, BRA, ISSHP, and ESC) or <1000 mg/d (IRL).
Treatment
Antihypertensive therapy
All CPGs recommended that severe hypertension be treated with antihypertensive agents, usually after referral to hospital (n=11), but few specified a BP target below the treatment threshold of 160/110 mm Hg (Table 3). First-line options were usually intravenous (IV) labetalol, oral nifedipine, or IV hydralazine, in line with medications studied most commonly in randomized trials
Situations where diuretics may be used were listed as: thiazides for chronic hypertension as they do not cause volume depletion (BRA), furosemide for oliguria (ESC), or pulmonary edema (SOMANZ)
6
WHO, SOMANZ, BRA, ESC, DEU, POL
Methyldopa postnatally
6
IRL, NZL, ESC, USA, UK, POL
Atenolol
5
CAN, FRA, BRA, ESC, USA
Magnesium sulfate as antihypertensive
3
CAN, SOMANZ, USA
Thiazide diuretics
3
WHO, FRA, UK
Spironolactone
2
USA, POL
Prazosin
2
CAN, BRA
Sublingual nifedipine
1
IRL
Diltiazem
1
POL
Sodium nitroprusside
1
WHO
Target BP on antihypertensive therapy
Severe hypertension
<160/110 mm Hg
2
CAN, POL
<160/105 mm Hg (MAP <125 mm Hg)
1
IRL
130–150 mm Hg/80–100 mm Hg
1
NZL
140–150/90–100 mm Hg
1
USA
Nonsevere hypertension (or unspecified)
<160/110 mm Hg
1
NLD
<160 mm Hg/85–100 mm Hg
2
FRA, TUN
150/80–99 mm Hg (without comorbidity)
1
IRL
130–150/80–100 mm Hg
2
BRA, DEU
<140/100 mm Hg
1
NZL
140/80–90 mm Hg (with comorbidity)
1
IRL
dBP of 85 mm Hg specifically
1
CAN
<135/85 mm Hg
1
UK
110–140/80–85 mm Hg
1
ISSHP
110–139 mm Hg/81–85 mm Hg
1
POL
Use of home BP assessment for ongoing of hypertension control
ISSHP recommends home BP monitoring for white-coat, transient, and masked hypertension, and acknowledges that such monitoring may be potentially useful in other hypertensive disorders of pregnancy.
ISSHP recommends home BP monitoring for white-coat, transient, and masked hypertension, and acknowledges that such monitoring may be potentially useful in other hypertensive disorders of pregnancy.
ACR, albumin-to-creatinine ratio; BP, blood pressure; BRA, Brazil; CAN, Canada; CPG, clinical practice guideline; CV, cardiovascular; dBP, diastolic blood pressure; DEU, Germany; ESC, European Society of Cardiology; FRA, France; ISSHP, International Society for the Study of Hypertension in Pregnancy; IV, intravenous; N/A, not applicable; NLD, Netherlands; NOR, Norway; NZL, New Zealand; POL, Poland; PrCr, protein-to-creatinine ratio; IRL, Ireland; sBP, systolic blood pressure; SOMANZ, Society of Obstetric Medicine of Australia and New Zealand; TUN, Tunisia; UK, United Kingdom; USA, United States of America; WHO, World Health Organization.
Scott. Pregnancy hypertension guidelines—similarities and dissimilarities. Am J Obstet Gynecol 2022.
a Situations where diuretics may be used were listed as: thiazides for chronic hypertension as they do not cause volume depletion (BRA), furosemide for oliguria (ESC), or pulmonary edema (SOMANZ)
b ISSHP recommends home BP monitoring for white-coat, transient, and masked hypertension, and acknowledges that such monitoring may be potentially useful in other hypertensive disorders of pregnancy.
Antihypertensive treatment thresholds for nonsevere hypertension were inconsistent and sometimes varied according to the comorbidity: BP of ≥140/90 mm Hg with (n=2) or without (n=7) comorbidities, BP of ≥150/100 mm Hg (n=4), BP of <160/110 mm Hg with comorbidities (n=1), or otherwise BP of ≥160/110 mm Hg (n=2; WHO and NLD). All but 3 CPGs (WHO, SOMANZ, and ESC) specified a BP target, but inconsistently, as between 140/90 and 160/110 mm Hg (n=7) or below 140/90 mm Hg (n=5). Many CPGs either recommended (n=3) or acknowledged as potentially useful (n=6) home BP monitoring for hypertension control. First-line antihypertensive agents were most commonly labetalol, methyldopa, and nifedipine, in line with those most commonly studied in randomized trials of antihypertensive vs placebo or no therapy or other antihypertensive therapy.
Other than ISSHP, all CPGs specified antihypertensive agents not to use in pregnancy, always recommending against renin-angiotensin system (RAS) blockers (n=14), and frequently against diuretics (n=6, other than for chronic hypertension or diuresis) and atenolol (n=5). Of note, 3 CPGs specifically recommended against and 1 recommended for thiazides.
Antenatal corticosteroids
Most CPGs (n=12) advised on the administration of antenatal corticosteroids (Supplemental Table 3). Most (n=9) made recommendations according to pregnancy hypertension type (usually preeclampsia) and gestational age. For women with chronic hypertension, antenatal corticosteroids were recommended by NICE 2019 for planned “early” birth. For women with GH, few CPGs recommended steroids (n=3) for delivery anticipated to be within the next 7 days, at <36 weeks, or “early” (n=1, each). For preeclampsia at <34 weeks (or <346 weeks for CAN), some CPGs (n=5) advised steroids for all women, whereas others made recommendations conditional on an indication for imminent delivery (n=2) and when there were associated complications that would make imminent delivery likely, such as “severe” preeclampsia (n=3); hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (n=2); eclampsia (n=1); or abnormal fetal growth or monitoring (n=1). Some CPGs offered recommendations according only to gestational age at presentation (n=3) or related to elective cesarean delivery at <39 weeks (n=1). A total of 6 CPGs specifically advised against steroids for HELLP, whereas FRA 2016 suggested that they could be used for severe thrombocytopenia.
Only 4 CPGs advised on repeated doses of steroids—ISSHP against and others for if the first course were ≥7 days before (n=1), within the final 2 weeks but the maternal or fetal condition had deteriorated (n=1), >14 days before, and before 30 weeks (n=1).
Timing of birth
For women with chronic hypertension, 5 CPGs confirmed that expectant care was appropriate before term (Supplemental Table 4). Half of CPGs (n=8) made recommendations at term as delivery by 37 weeks if on antihypertensive agents or by 38 weeks if untreated (n=1), at 39 weeks (n=1), at 37 to 39 weeks (n=1), at 38 to 39 weeks (n=3), according to expectant care with enhanced surveillance (n=1), or according to a plan agreed with the woman (n=1). For women with GH, few CPGs confirmed expectant care was appropriate until term (n=6). At term, most CPGs (n=12) made recommendations for delivery at 37 weeks (n=7), to be discussed from 37 weeks (n=4), or by 39 weeks (n=1).
Most CPGs focused on the timing of birth for women with preeclampsia. Three CPGs considered “severe” preeclampsia to be an indication for birth, regardless of gestational age (n=3). Before fetal viability, most CPGs recommended delivery for preeclampsia (n=4 of 5 that made recommendations, n=6 of 6 when “severe”). Expectant care was advised by many CPGs from fetal viability to 33 weeks (n=9/9, n=5/8 when “severe”) and 34 to 36 weeks (n=8/8, n=1/9 when “severe”). Delivery was advocated at term (n=12/12, n=9/9 when “severe”).
Other than IRL, all CPGs provided indications for delivery regardless of gestational age or pregnancy hypertension type. The most highly endorsed were uncontrollable or worsening hypertension (n=10/14) and eclampsia (n=7/14).
Labor and delivery
Mode of delivery was addressed by most (n=12) CPGs; none recommended a specific course of action but emphasized usual obstetrical indications (n=10/12) and joint decision making with women (n=3/12) (Supplemental Table 5). Many CPGs emphasized general obstetrical practice, related to the success of labor induction (n=7), cervical ripening (n=2), or active management of the third stage of labor (n=3) (Supplemental Table 5). Of note, 5 CPGs specifically advised against the use of ergometrine.
Magnesium sulfate
CPGs recommended magnesium sulfate for eclampsia treatment (n=15, 100%) and prevention (n=13) for women with “severe” preeclampsia (n=10/13) or with serious end-organ involvement with preeclampsia (n=2/13) or according to individual protocol (n=1/13) (Supplemental Table 6).
Magnesium sulfate was otherwise recommended for imminent preterm birth by a few CPGs (n=6), at ≤296 weeks (n=2/6), ≤316 weeks (n=3/6), or ≤326 weeks (n=1/6). The stated indication was fetal neuroprotection (n=5/6) or to improve fetal outcomes without specifying further (n=1/6).
After delivery
A total of 6 CPGs highlighted that hypertension may worsen after delivery, between days 3 and 6 (n=5), or the first 1 to 2 weeks (n=1); 6 CPGs acknowledged that preeclampsia may worsen or appear after delivery (Supplemental Table 7). Most (n=12) CPGs recommended for (and none against) continuing antihypertensive agents after delivery. However, a number of CPGs (n=6) recommended methyldopa be switched to an alternative.
Treatment of severe hypertension followed similar recommendations as antenatally (n=7), although 2 CPGs advised lower targets. Targets for nonsevere hypertension varied from as antenatally (n=4), lower (n=3), higher (n=1), or according to standard guidelines for women with comorbidities (n=1). CPGs commonly (n=11) acknowledged the association between pregnancy hypertension and future health, particularly cardiovascular. Lifestyle counseling and modification of risk factors were frequently suggested (n=11).
Other
Not discussed are the frequency of investigations and aspects of care discussed by few CPGs, such as anesthetic management (CAN, SOMANZ, IRL, and NZL), pediatric outcomes (CAN), application of recommendations to low-resource settings (ISSHP), women’s experience (NZL), management of secondary causes of hypertension (POL), or auditable standards (NICE and SOMANZ).
Discussion
Summary of findings
We identified 15 clinically useful pregnancy hypertension CPGs of variable quality.
Areas of consistency were diagnosis of hypertension, use of automated BP measurement devices, proteinuria screening using dipsticks with confirmatory testing by PrCr, and classification (ie, chronic or GH, white-coat hypertension, and a broad definition of preeclampsia that does not mandate proteinuria). Most guidelines listed risk factors for preeclampsia and recommended their use to identify women at increased risk, all of whom should receive low-dose aspirin. All guidelines recommended magnesium sulfate for eclampsia treatment and usually prevention, and most recommended antenatal corticosteroids for preeclampsia with birth likely before 34+0 weeks. Delivery at term was recommended for women with preeclampsia and from 34 weeks, for “severe” preeclampsia, with emphasis on usual obstetrical practices and avoidance of ergometrine. There is recognition that BP and preeclampsia may worsen after delivery and that women are at increased risk of future cardiovascular and other health problems.
However, a lack of uniformity remains with regard to components of a broad definition of preeclampsia, whether “severe” preeclampsia should be used and, if so, how it should be defined, which is important because most guidelines link magnesium sulfate and timing of birth to “severe” preeclampsia. The use of biomarkers for classification is emerging. Although most guidelines list preeclampsia risk factors, there is inconsistency in how they should be used to identify risk and eligibility for aspirin. Calcium for preeclampsia prevention is variably recommended based on the level of risk and/or baseline calcium intake. There is a movement toward normalization of BP in pregnancy, but this is recommended by fewer than half of CPGs. Many guidelines do not advise practitioners about the timing of birth for women with preterm preeclampsia.
Comparison with current literature
The current review included 70% more “clinically useful” CPGs than our 2014 review (n=15 vs 9)
The diagnostic criteria for hypertension and its severity were unchanged and consistent among the CPGs. Advice about self-monitoring devices reflects progressive interest in home BP monitoring
and the fact that most CPGs now define white-coat hypertension. Although most guidelines recommend that a normal self-monitored BP is ≤135/85 mm Hg, systematic review of relevant literature has not found that home measurements are consistently lower than clinic measurement, although there was a wide variability and home measurements may have been lower for hypertensive women specifically.
CPGs have deemphasized aneroid devices but, despite its withdrawal from the market, most guidelines continued to discuss mercury sphygmomanometry.
Current CPGs were clearer about proteinuria testing than previously. Dipstick proteinuria testing was widely endorsed as a screening test, followed by quantitative testing. There is a move toward the use of urinary PrCr and away from 24-hour urine collection, although both are still supported. There is little attention given to urinary ACR and no consensus on its cutoff for an abnormal result despite the publication of DAPPA in 2017.
Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based economic evaluation and acceptability analysis.
Diagnostic criteria for chronic and GH remain consistent and unchanged. However, there has been a move away from the traditional definition of preeclampsia that mandates proteinuria (55% previously) and toward a broad definition (now 80%), with most endorsing target organ manifestations of headache or visual symptoms and/or laboratory abnormalities of platelets, creatinine, or liver enzymes. This means that women may have GH by 1 CPG and preeclampsia by another when proteinuria is not a mandatory criterion. In addition, “severe” preeclampsia use and definition remain controversial; what constitutes “severe” preeclampsia by CPGs that mandate proteinuria now defines any preeclampsia for most CPGs.
There has been an emergence of recommendations to use multivariable models for preeclampsia risk prediction—models that add biomarkers and ultrasonography to clinical risk markers in early pregnancy. This is likely related to the Aspirin for Evidence-Based Preeclampsia Prevention trial that revealed that aspirin prescribed based on multivariable screening substantially reduced the incidence of preterm preeclampsia.
All CPGs now advise on aspirin use and recommend it for women at increased risk, but there remain inconsistencies about the dosing and gestational ages for starting and stopping. Calcium is more frequently recommended than aspirin in Gillon et al
(by 9/15 vs 3/9 CPGs, respectively), particularly when there is both low intake and increased risk of preeclampsia.
Antihypertensive therapy is now addressed by all CPGs rather than 6 of 9 in our previous review. All continue to agree that severe hypertension should be treated, most commonly with IV labetalol, oral nifedipine, or IV hydralazine. Although the target BP for nonsevere hypertension remains inconsistent, there is a movement toward normalization of BP even for women without comorbidities (4/12) compared with the previous one (0/4) when target BP was reported, citing the international Control of Hypertension In Pregnancy Study
First-line agents are the same, although oral labetalol is now more frequently endorsed than methyldopa or nifedipine, which were similarly recommended previously. There is no change in the recommendation not to use RAS blockers.
For women anticipated to deliver preterm, particularly women with preeclampsia, antenatal corticosteroid administration is now more clearly presented by the majority (as opposed to just under half previously) of CPGs, and when discussed, all recommend against its use for HELLP syndrome. Fetal indications have emerged as an indication for magnesium sulfate, but recommendations for eclampsia treatment and prevention have changed a little. Of note, however, indications for prevention were still tied to the definition of “severe” preeclampsia.
Recommendations have become consistent in recommending birth for women with preeclampsia at term, previously recommended by only half of CPGs, even with “severe” preeclampsia; about half of guidelines make similar recommendations for women with GH. Nevertheless, when women present preterm, about half of the guidelines for preeclampsia and most for GH give practitioners advice about the timing of birth. Evidence continues to emerge.
Management of labor and delivery remains as previously, with a focus on usual care but avoidance of ergometrine.
There remains an appreciation that BP and preeclampsia can worsen after delivery, antihypertensive therapy may still be required, and long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification.
Strengths and limitations
The strengths of this review include a comprehensive search strategy and rigorous methodology informed by the AGREE II, as followed for our 2014 review.
We included recommendations and information from tables and text to provide a comprehensive picture. Most CPGs were explicitly evidence based, according to the grading of the quality of evidence and/or strength of recommendations.
Limitations include potential selection bias because we only included CPGs published in English, French, German, or Dutch. We did not include a discussion of the strength of recommendations in our summary because 6 CPGs provided no such evaluation of recommendations and there were 9 different evidence-grading systems. Given the word count constraints, it is possible that some CPGs were downgraded in quality based on the failure to report an activity when it was actually undertaken.
Conclusion and future direction
Increasingly, there is consistency in CPG recommendations that are appropriate for implementation and as auditable standards. Key definitions and most aspects of classification are automated BP measurement, preeclampsia prediction and aspirin prophylaxis, magnesium sulfate for eclampsia prevention and treatment, antenatal corticosteroids for preterm birth, and delivery at term for preeclampsia. A lack of uniformity was seen for components of a broad definition of preeclampsia (with biomarkers emerging), the utility of “severe” preeclampsia as a term and how it should be defined to inform care pathways, how preeclampsia risk should be identified, aspirin dose, and calcium intake. There is a movement toward normalization of BP with antihypertensive agents. Consistent recommendations should be implemented and audited, and inconsistencies should inform future research.
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