Outline of the new definition and classification of “Hypertensive Disorders of Pregnancy (HDP)”; a revised JSSHP statement of 2005

In this report, we present the terminology, definition and classification of Hypertensive Disorders of Pregnancy (HDP) by the Japan Society for the Study of Hypertension in Pregnancy (JSSHP).

Terminology

In 2017, “Pregnancy induced Hypertension was revised to “Hypertensive disorders of Pregnancy (HDP) in Japan.^1,2)

Definition

HDP is defined as hypertension (blood pressure ≥140/90 mmHg) in pregnancy.

Classification

Preeclampsia (PE)

PE is gestational hypertension accompanied by one or more of the following new-onset conditions at or after 20 weeks gestation, but all symptoms are normalized by 12 weeks postpartum.

1. Proteinuria

2. Other maternal organ dysfunctions, including:

 1) liver involvement without any underlying diseases (elevated transaminases, e.g. ALT or AST>40 IU/l with or without severe persistent right upper quadrant or epigastric abdominal pain which cannot be diagnosed as other diseases and is treatment-resistant)

 2) Progressive kidney injury (creatinine >1.0 mg/dl, other renal diseases are denied)

 3) Stroke, neurological complications (including clonus, eclampsia, visual field disturbance, severe headaches except for primary headache, etc.)

 4) Haematological complications (thrombocytopenia due to HDP – platelet count below 150,000/μL, DIC, hemolysis)

3. Uteroplacental dysfunction (^*1fetal growth restriction, ^*2abnormal umbilical artery Doppler wave form analysis, or ^*3stillbirth)

Gestational hypertension (GH)

GH is persistent de novo hypertension that develops at or after 20 weeks gestation in the absence of features of pre-eclampsia; and hypertension that normalizes by 12 weeks postpartum.

Superimposed preeclampsia (SPE)

SPE is diagnosed in the following cases.

1. Hypertension that is diagnosed pre-pregnancy or before 20 weeks of gestation is followed by newly onset proteinuria, liver or renal involvement without any underlying diseases, stroke, neurological complications, or hematological complications at or after 20 weeks of gestation same as written in the preeclampsia.

2. Hypertension and proteinuria are diagnosed pre-pregnancy or before 20 weeks gestation. One or both of the symptoms worsen after 20 weeks gestation.

3. Renal disease, which only involves proteinuria, is diagnosed pre-pregnancy or before 20 weeks gestation. Hypertension develops after 20 weeks gestation.

4. Hypertension is diagnosed pre-pregnancy or before 20 weeks gestation. Uteroplacental dysfunction develops after 20 weeks gestation.

Chronic hypertension (CH)

Hypertension is diagnosed pre-pregnancy or before 20 weeks gestation in the absence of features of superimposed preeclampsia.

Supplement

*1. FGR shall be defined as a case for which the estimated fetal body weight is less than −1.5SD according to the classification of the Japan Society of Ultrasonics in Medicine “Standardization of ultrasonic fetal measurement and Japanese reference values”³⁾ with neither chromosomal abnormalities nor malformation syndrome.

*2. Abnormal umbilical artery doppler wave form is assumed to be abnormally high umbilical arterial vascular resistance, end-diastolic blood flow disruption, or regurgitation.

*3. This stillbirth has neither chromosomal abnormality nor malformation syndrome.

Subclassification by symptoms

1. Severity

Those falling under either of the following categories are defined as severe. As the term “mild” can be misunderstood as riskless HDP, it is not used in principle.

1) Blood pressure exceeds 160/110 mmHg in GH, PE, SPE, or CH.

2) Maternal organ involvement or uteroplacental dysfunction is recognized in PE or SPE.

* Severe classification by the amount of proteinuria is excluded.

2. Classification by onset

HDP excluding CH that emerges earlier than 34 weeks gestation is defined as early onset (EO) type, and HDP excluding CH that emerges after 34 weeks gestation is defined as late onset (LO) type.

Criteria of hypertension and proteinuria

1. Defined as systolic BP≥140 mmHg and/or diastolic BP≥90 mmHg

Blood pressure measurement method:

 1) After resting for 5 minutes or more, check that the cuff wrapped around the upper arm is at the height of the heart, measure the blood pressure twice in a seated position at intervals of 1 to 2 minutes, and calculate the average value.

 2) Measure with the left and right upper arm at the time of the first measurement and adopt the higher one if different by 10 mmHg or more.

 3) Following device is recommended in measuring blood pressure at office, either mercury sphygmomanometer or properly calibrated automatic sphygmomanometer with the same accuracy as the mercury sphygmomanometer.

2. Diagnosis of proteinuria can be made by any of the following methods.

 1) 24 hour urinary protein ≥300 mg per day by the Esbach method

 2) a spot urine protein/creatinine ratio ≥0.3 mg/mg CRE

* Guidelines for obstetrics and gynecology clinical practices in Japan (Obstetrics 2017) is more strict than this, at >0.27 mg/mg CRE.

3. In the event that neither 24 hour urinary protein nor a spot urine P/C ratio measurement can be performed, if urine protein of 1+ or more positive is continuously detected twice or more by dipstick testing, diagnosis of significant/positive proteinuria can be made.

Appendix

1. Gestational proteinuria

Gestational proteinuria is persistent de novo proteinuria that develops at or after 20 weeks gestation and disappears by 12 weeks postpartum, but is excluded from HDP classification.

2. Diagnosis of hypertension

Blood pressure measurements in the physician office/clinic may not reflect the original blood pressure due to white-coat or masked hypertension. In particular, 24 h ambulatory BP monitoring (ABPM) or automated home blood pressure monitoring (HBPM) is needed for those with chronic hypertension for the differential diagnosis of white-coat or masked hypertension, as well as other adventitious hypertensive disorders.

3. HDP related disease

1) Eclampsia

Eclampsia is defined as the onset of convulsions in women with HDP that is not attributed to other diseases including epilepsy and secondary convulsion. Seizures are categorized as antepartum, intrapartum, and puerperal eclampsia, according to the onset time. Eclampsia is thought to be a convulsive seizure due to reversible angiogenic edema in the cerebral cortex; however, edema also occurs in the occipital lobe and brainstem, and may present as various central nervous system manifestations.

2) Central nervous system disorders associated with HDP

Cortical blindness, posterior reversible encephalopathy syndrome (PRES), cerebral hemorrhage associated with hypertension and cerebral vasospasm.

3) HELLP syndrome

It refers to one that is accompanied by haemolysis, elevated liver enzymes, and thrombocytopenia at the same time antepartum, intrapartum, or postpartum, not due to other adventitious complications. HELLP syndrome is not diagnosed by only one or two manifestation described above. The diagnosis of HELLP syndrome should be made in accordance with the diagnostic criteria of Sibai^4,5) (Table 1).

Table 1. The diagnostic criteria of Sibai^4,5)

Hemolysis: Serum indirect bilirubin>1.2 mg/dl, Serum LDH>600 IU/l, Abnormal peripheral blood smear Liver function: Serum AST (GOT)>70 IU/l, Serum LDH >600 IU/l Thrombocytopenia: Platelet count<100,000/mm3

4) Pulmonary edema

HDP enhances vascular permeability by vascular endothelial dysfunction and frequently causes edema. In severe cases, pulmonary edema also appears.

5) Perinatal cardiomyopathy

Sudden development of heart failure during pregnancy or postpartum in a woman without a past history of cardiac disease. Severe cases can result in maternal death. HDP patients are high risk.

Table 2. Diagnostic name and classification of HDP in Japan and other countries

JSSHP · HRP2013		ISSHP · A revised statement from the ISSHP2014	ACOG · Task Force on Hypertension in Pregnancy2013	SOGC · Working Group. 2014	SOMANZ · Guidline2014	NHBPEP · Working Group on High Blood Pressure in Pregnancy 2000
Pregnancy induced Hypertension (PIH)		Hypertensive disorders of pregnancy	Hypertensive disorders of pregnancy	Hypertensive disorders of pregnancy	Hypertensive disorders of pregnancy	Hypertensive disorders of pregnancy
Gestational hypertension (GH)		Gestational hypertension	Gestational hypertension	Gestational hypertension · With comorbid condition(s) · With evidence of preeclampsia	Gestational hypertension	Gestational hypertension
Preeclampsia (PE)		Pre-eclampsia–de novo or superimposed on chronic hypertension	Preeclampsia-eclampsia	Preeclampsia	Preeclampsia–eclampsia	Preeclampsia-eclampsia
Eclampsia (E)
Superimposed preeclampsia (S-PE)			Chronic hypertension with superimposed preeclampsia	Pre-existing (chronic) hypertension · With comorbid condition(s) · With evidence of preeclampsia =superimposed preeclampsia	Preeclampsia superimposed on chronic hypertension	Preeclampsia superimposed upon chronic hypertension
Appendix	Chronic hypertension	Chronic hypertension	Chronic hypertension		Chronic hypertension – essential – secondary – white coat	Chronic hypertension
		White coat hypertension		‘Other hypertensive effects’ · Transient hypertensive effect · White coat hypertensive effect · Masked hypertensive effect
			Postpartum hypertension

JSSHP: Japan Society for the Study of Hypertension in Pregnancy

ISSHP: International Society for the Study of Hypertension in Pregnancy

ACOG: American College of Obstetricians and Gynecologists

SOGC: Society of Obstetricians & Gynecologists of Canada

SOMANZ: Society of Obstetric Medicine of Australia and New Zealand

NHBPEP: National High Blood Pressure Education Program

Table 3. Definition of preeclampsia in Japan and other countries

JSSHP	ISSHP	ACOG	SOGC	SOMANZ	NHBPEP
Preeclampsia (PE)	Pre-eclampsia–de novo	Preeclampsia-eclampsia	Preeclampsia	Pre-eclampsia–eclampsia	Preeclampsia-eclampsia
BP≥140/90 mmHg+ Proteinuria≥300 mg/day	BP≥140/90 mmHg+ One or more of the following new-onset conditions 1. Proteinuria protein/creatinine ≥0.3 mg/dl Proteinuria≥300 mg/day 2+on dipstick 2. Other maternal organ dysfunctions · Renal insuficiency Cr>90 μmol/l; 1.02 mg/dl · Liver involvement elevated transaminases and/or severe right upper quadrant or epigastric pain · Neurological complications eclampsia, altered mental status, blindness, stroke, or more commonly hyperreflexia when accompanied by clonus, severe headaches when accompanied by hyperreflexia, persistent visual scotoma · Haematological complications thrombocytopenia, DIC, haemolysis 3. Uteroplacental dysfunction · FGR	BP≥140/90 mmHg+ Proteinuria Proteinuria≥300 mg/day protein/creatinine ≥0.3 mg/dl 1+on dipstick One or more of the following new-onset conditions without proteinuria · Thrombocytopenia <100,000/μl · Renal insufficiency Cr>1.1 mg/dl or a doubling of serum creatinine concentration in the absence of other renal disease · Liver involvement To twice normal concentration,severe persisitent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnose, or both · Pulmonary edema · New-onset cerebral or visual disturbances	BP≥140/90 mmHg+ · Proteinuria (The same standard as ACOG) One of the following new-onset conditions · Adverse condition · Severe complication Adverse conditions · CNS Headache/visual symptoms · Cardiorespiratory Chest pain Oxygen saturation <97% · Haematological Elevated WBC count Elevated INR or aPTT Low platelet · Renal Elevated serum creatinine Elevated serum uric acid · Hepatic Nausea or vomiting RUQ or epigastric pain Elevated serum AST, ALT, LDH, or bilirubin Low plasma albumin · Feto-placental Non-reassuring FHR FGR Oligohydramnions Absent or reversed end-diasolic flow by Doppler velocimetry	BP≥140/90 mmHg+ · Renal invlovement proteinuria · protein/creatinine≥0.3 mg/dl · Cr>90μmol/l · oligouria<80 ml/4 h · Haematological involuvement · Thrombocytopenia <100,000/dl · Haemolysis: schistocytes or red cell fragments on blood film, raised bilirubin, raised LDL>600 mIU/l, decreased haptoglobin, DIC · Liver involvement Raised serum transaminases, Severe epigastric and/or right upper quadrant pain · Neurological involvement Convulsion (eclampsia) Hyperefflexia with sustained clonus Persitent, new headache Persistent visual disturbances (photopsia, scotomata, cortical blindness, posterior reversible encephalopathy syndrome and retinal vasospasm) Stroke · Plumonary edema · FGR	BP≥140/90 mmHg+ Proteinuria · ≥300 mg/day · 1+on dipstick

Table 4. Definition of severe HDP in Japan and other countries

JSSHP	ISSHP	ACOG	SOGC	SOMANZ6)	NHBPEP7)
Severe PIH	Severe pre-eclampsia	Severe Features of Preeclampsia	Severe complications (that warrant delivery)	Severe pre-eclampsia	Severe preeclampsia
BP≥160/110 mmHg or proteinuria ≥2.0 g/day, 3+dipstick	The following criteria are stated to be consensus. · Severe hypertension · HELLP syndrome · Eclampsia · Progressive falling platelet count · failure of FGR	· BP ≥160/110 mmHg · Thombocytopenia <100,000/μl · Liver involvement To twice normal concentration, severe persisitent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnose, or both · Renal insufficiency Cr >1.1 mg/dl or a doubling of serum creatinine concentration in the absence of other renal disease · Pulmonary edema · New-onset cerebral or visual disturbances	CNS · Eclampsia · PRES · Cortical blindness or retinal detachment · GCS <13 · Stroke, TIA, RIND Cardiorespiratory · uncontrolled severe hypertension (over a period of 12 h despite use of three antihypertensive agents) · Oxygen saturation<90%, need for ≥50% oxygen for >1 h, intubation (other than for Casesarean section), pulmonary oedema · Positive inotropic support · Myocardial ischemia or infarction Haematological · Platelet<50x109/l · Transfusion of any blood product Renal · Acute kidney injury (creatinine>150 μM with no prior renal disease) · New indication for dialysis Hepatic · Hepatic dysfunction (INR>2 in absence of DIC or warfarin) · Hepatic haematoma or rupture Feto-placental · Abruption with evidence of maternal or fetal compromise · Reverse ductus venoosus A wave · Stillbirth	Although it is not clearly stated,it is cited the contens of the ISSHP definition.	Although it is not clearly stated,it is stated that strict management including termination of pregnancy is necessary in the following cases. · BP ≥160/110 mmHg · Proteinuria of ≥2.0 g/day or 2+, 3+ dipstick · Serum creatinine levels is increased (>1.2 mg/dl unless known to be previously elevated) · Platelet count is < 100,000/μl, there is evidence of micoangiopathic hemolytic anemia (with increased LDL concentration), or both 微小血管内溶血性 · Hepatic enzyme activities (either alanine aminotransferase, aspartate aminotransferase, or both) are elevated. · Patient reports persistent headache or other cerebral or visual disturbances. · Patient reports persistent epigastric pain.

References

• 1.   Watanabe  K,  Naruse  K,  Tanaka  K,  Metoki  H,  Suzuki  Y. Outline of Definition and Classification of “Pregnancy induced Hypertension (PIH)”. Hypertens Res Pregnancy. 2013; 1: 3–4.
• 2.   Watanabe  K,  Matsubara  K,  Nakamoto  O, et al. New definition and classification of “Hypertensive Disorders of Pregnancy (HDP)”. Hypertens Res Pregnancy. 2017; 5: 39–40.
• 3.  Japan Society of Ultrasonics in Medicine. On the advertisement of “Standardization of ultrasonic fetal measurement and Japanese reference values”. 2003; 30: J415–440 (In Japanese).
• 4.   Sibai  BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004; 103: 981–991.
• 5.   Sibai  BM,  Ramadan  MK,  Usta  I,  Salama  M,  Mercer  BM,  Friedman  SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol. 1993; 169: 1000–1006.