Pre eclampsia & eclampsia

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PRE-ECLAMPSIA & ECLAMPSIA BY Dr SHANZA AUROOJ

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Pre eclampsia & eclampsia

  1. 1. By Dr Shanza aurooj Post Graduate Trainee Gynea unit III SPH Quetta
  2. 2.  Gestational Hypertension  Pre-eclampsia  Chronic hypertesion essential secondary  Pre-eclampsia superimposed on chronic hypertension  Eclampsia
  3. 3.  Gestational hypertension new hypertension presenting after 20 weeks without significant proteinuria and features of preeclampsia,BP levels return to normal within 3 months postpartum  Pre-eclampsia is new hypertension presenting after 20 weeks with significant proteinuria.  Severe pre-eclampsia is pre-eclampsia with severe hypertension and/or with symptoms,and/or biochemical and/or haematological impairment. after 20 weeks
  4. 4.  Eclampsia is a convulsive condition associated with pre-eclampsia  Chronic hypertension is hypertension that is present before 20 weeks characterized by a BP of 140/90 mmHg or greater . It can be primary or secondary in aetiology  Pre-eclampsia superimposed on chronic hypertension is hypertension present before 20 weeks with development of symptoms of pre- eclampsia after 20 weeks
  5. 5.  Significat proteinuria excretion of 300mg/24hr of urinary proteins in 24hr urine collection or a concentration of 30mg/dl >1+ on dipstick in atleast two random urine samples collected 4 to 6 hrs apart  Grades of hypertension Mild hypertension diastolic blood pressure 90–99 mmHg, systolic blood pressure140–149 mmHg. Moderate hypertension diastolic blood pressure 100–109 mmHg, systolic blood pressure 150–159 mmHg. Severe hypertension diastolic blood pressure 110 mmHg or greater, systolic bloodpressure 160 mmHg or greater
  6. 6. A pregnancy specific syndrome characterized by variable degrees of placental dysfunction and a maternal response featuring systemic infammation
  7. 7.  The etiology of preeclampsia is unknown. However, placental delivery reverses the symptoms of preeclampsia, suggesting that the placenta has a controlling role in the condition. Additionally, women with increased placental tissue for gestational age, such as hydatiform moles and twin pregnancies, have an increased incidence of preeclampsia.  Several theories attempt to explain the pathophysiology of preeclampsia  Most popular theory holds that improper placental development results in placental vascular endothelial dysfunction and a relative uteroplacental insufficiency. The vascular endothelial dysfunction results in increased permeability, hypercoagulability, and diffuse vasospasm
  8. 8. Changes in normal pregnancy  In normal pregnancy spiral arteries of the placental bed undergoes a series of physiological changes  cytotrophoblasts replace the endothelial cells in the spiarl arteries resulting in destruction of medial elastic and muscular tissue,these physiological changes reach the inner third of myometrium and create a low vascular arterioler system that allows a dramatic increase in blood supply necessary to serve the growing fetus.The end result is that 100 to 120 spiral arteries are converted into dilated inelastic tubes without maternal vasomotor control Changes in preeclampsia  In pre-eclampsia about half to 2/3rd of spiral arteries escape this transformation ,in these arteries the myometrial segment remain anatomically intact,do not dilate,many vessels are occluded by fibrinoid material and exhibit adjacent foam cell invasion (atherosis).Atherosis and thrombosis leads to microinfarcts in placenta and are responsible for abruption due to decidual necrosis,separation and hemmorhage.
  9. 9. Cardiovuscular system Severe pre-eclampsia is characterized by vasoconstriction and a leaky microcirculation,with extravasation of fluid in E.C.S and relative hypovolemia leading to hemoconcentration,edema and swelling often facial particularly peroorbital edema in contrast to physiological pedal edema Renal system Primary renal manifestation of endothelial cell activation is inflammatory swelling of glomeruler endothelial capillaries causing an increase in the renal vascular resistance with a decrease in the renal blood flow resulting in decreased GFR and EFRP complicating to ANURIA or OLIGURIA leading to ARF. The first change in the renal system involvement is tubular dysfunction resulting in decreased uric acid clearance from the body and hyperuicemia,the next event is proteinuria due to loss of negative charge from the GBM ,finally there is rise in levels of urea and creatinine . Proteinuria further leads to hypoalbunemia with extravasation of fluid in ECS resulting in genearilzed edema and,ascites,pleural effusion,pulmonary,cerebral and laryngeal edema.
  10. 10. Abnormal hemostasis Platelet activation a feature of normal pregnancy is exaggerated in pre-eclampsia as sysytemic endothelial cell activation cause platelet adherence to site of endothelial damage.Platelets consumption result in thrombocytopenia while platelet adherence leads to formation of microthrombi effecting microcirculation leading to increased intravuscuar coagulation with a rise in fibrin degradation products and hemolysis of RBC’s in microvessels leading to HELLP syndrome. HELLP syndrome It is Hemolysis,elevated liver enzymes and low platelets caused by abnormal hemostasis and liver involvement due to excessive fibrinogen deposition in hepatic sinusoids also obstructing blood flow leading to hepatic capsular distension and epigastric pain,nausea,vomiting. It may complicate to subcapsular hematoma and liver rupture presenting with severe epigastric pain,shoulder pain,shock, hemoperitoneum,respiratory difficulties or pleural effusion.
  11. 11.  Nulliparity  extremes of maternal age  multifetal gestation  pre-eclampsia in a previous pregnancy  family history  chronic hypertension or renal disease  chronic infections  maternal low birth weight  obesity and insulin resistance  Pre-gestational DM  smoking  maternal genes  chronic inflammatory conditions like (SLE & RA)  Anti-phospholipid antibody syndrome  molar pregnancy
  12. 12. Symptoms of pre-eclampsia  severe headache  problems with vision, such as blurring or flashing before the eyes  severe pain just below the ribs  vomiting  sudden swelling of the face, hands or feet.  Seizures (eclampsia) grand mal in character with tonic clonic phases Physical signs:  Asymptomatic hypertension is discovered on routine prenatal examination.  Diffuse edema has a high specificity for preeclampsia.  Neurologic findings such as papilledema and hyperreflexia must be addressed quickly, as they can herald the onset of eclampsia.  Petechiae and bruising could suggest coagulopathy.  Right upper quadrant or mid epigastric tenderness develops as a result of hepatocellular necrosis.
  13. 13. Complications Maternal complications  Abruption placenta  DIC/HELLP syndrome  Acute Renal Failure  Eclampsia  Liver failure & Hemmorhage  Stroke  Death  Long term cardiovascular morbidity Neonatal complications  Preterm delivery  IUGR  Hypoxic neurological injury  Perinatal death  Low birth weight with long term morbidity
  14. 14. DIFFERENTIALS  Disseminated Intravascular Coagulation  Fatty Liver  Cholecystitis  Perforated peptic ulcer  Systemic Lupus Erythematosus  Thrombotic Thrombocytopenic Purpura
  15. 15. BASELINE •CBC •BLOOD GROUP •HEPATITUS B & C Urine analysis of a clean catch specimen Proteinuria 2+ or higher is significant and warrants further evaluation to rule out preeclampsia. A 24-hour urine collection with more than 300 mg of protein RFT’s • UREA > 40 mmol/l or >11 mg/dl • Creatinine>1 mg/dl • Serum uric acid levels >6.3 mg/dl LFT’s • AST or ALT >50 IU/L • Biluribin >25 IU/L Clotting profile • PT/APTT • Fibrin degradation products
  16. 16. Ultrasound  Confirmation of normal fetal development is important and standard prenatal care in all pregnancies.Points to study in US are  Fetal biometry(AC,HC,BPD,FL)  AOL & estimated fetal weight  Placental localization Doppler velocimetry  Screening test in first trimester to detect changes in spiral arteries and is considered abnormal if there is an early diastolic notch or high RI
  17. 17. Management can be discussed under following headings  Prevention  Antihypertensive treatment  Anticonvulsant treatment  Steroids for lung maturation  Fluid balance  Mode and timing of birth  Fetal monitoring in high risk patient  Intrapartum care  Postnatal monitoring,treatment and investigations  Breast feeding  Advice and follow up care
  18. 18. Primary prevention  Pre pregnancy weight control in high risk patients  Vitamin B and folate supplementations  Cessation of smoking  Control of Hypertension in women having chronic hypertension  Control of sugar levels in women having Diabetes pre-pregnancy Secondary prevention  Calcium supplementations:it reduces parathyroid and renin release thereby reducing intracellular calcium and smooth muscle contractility,the ideal patient is the one who is obese with raised BP at booking visit  Antiplatelet agents:low dose aspirin is recommended in high risk patients as it inhibits thromboaxane synthesis thus altering the balance in favor of PGI usually before 23 weeks and therefore helps in proper placentation in a dose of 75mg OD starting from 12 weeks until birth  For other agents like Mg and Zinc supplements,fish oil,salt restriction, antioxidants like vitamin C,E there is insufficient data to recommend their use in primary prevention
  19. 19. Degree of hypertension Mild hypertension (140/90 to 149/ 99 mmHg) Moderate hypertension (150/100 to 159/ 109 mmHg Severe hypertension (160/110 mmHg or higher) Admit to hospital NO YES YES Treat NO With oral labetalol† as first-line treatment to keep: diastolic blood pressure between 80–100 mmHg systolic blood pressure less than 150 mmHg With oral labetalol† as first-line treatment to keep: diastolic blood pressure between 80–100 mmHg systolic blood pressure less than 150 mmHg Measure blood pressure At least four times a day At least four times a day More than four times a day, depending on clinical circumstances Test for proteinuria Do not repeat quantification of proteinuria Do not repeat quantification of proteinuria Do not repeat quantification of proteinuria Blood tests Monitor using the following tests twice a week: kidney function, electrolytes, full blood count, transaminases, bilirubin Monitor using the following tests three times a week: kidney function, electrolytes, full blood count, transaminases, bilirubin Monitor using the following tests three times a week: kidney function, electrolytes, full blood count, transaminases, bilirubin
  20. 20.  Only offer women with pre-eclampsia antihypertensive treatment other than labetalol after considering side-effect profiles for the woman, fetus and newborn baby.  Alternatives include methyldopa† and nifedipine†
  21. 21. Adult Dose 5-10 mg IV; repeat 20min to maximum of 60 mg Contraindications Documented hypersensitivity, dissecting aortic aneurysm, mitral valve rheumatic heart disease Interactions:MAO inhibitors and beta-blockers may increase hydralazine toxicity; pharmacological effects of hydralazine may be decreased by indomethacin Adverse effects headache, flushing, overshoot hypotension, peripheral edema, implicated in myocardial infarction; Pregnancy C (safety not established) Hydralazine (Apresoline) -- First-line therapy against preeclamptic hypertension in past decades. Decreases systemic resistance through direct vasodilation of arterioles resulting in reflex tachycardia..
  22. 22. Labetalol (Normodyne) -- Second-line therapy that produces vasodilatation and decrease in systemic vascular resistance. Has alpha-1 and beta antagonist effects and beta-2 agonist effects. Has more rapid onset than hydralazine and less overshoot hypotension. Adult Dose 50-100 mg IV; repeat 30min to a maximum of 300 mg Preganacy C (safety not established) Contraindications Documented hypersensitivity, cardiogenic shock, pulmonary edema, bradycardia, heart block, uncompensated CHF, reactive airway disease Precautions Caution in impaired hepatic function; discontinue therapy if there are signs of liver dysfunction; in elderly patients, a lower response rate and higher incident of toxicity may be observed; intensified bronchospasms, heart block, CHF
  23. 23. Nifedipine  Potent direct vasodilators,rapid onset of action,safe and effective  Adverse effects severe headache,hypotension and flushing Nitroprusside (Nitropress) -- Used when hydralazine and labetalol are ineffective. Reduces peripheral resistance by acting directly on arteriolar and venous smooth muscle.  Pregnancy C - Safety for use during pregnancy has not been established.  adverse effects of nitroprusside include tinnitus, blurred vision, altered mental status, hypotension, and methemoglobinemia Diazoxide powerful direct vasodilator  mini-bolus dose of 15mg of diazoxide is as effective as hydralazine with less side effects
  24. 24. When to use?  If a woman in a critical care setting who has severe hypertension or severe pre-eclampsia has or previously had an eclamptic fit, give intravenous magnesium sulphate*.  Consider giving intravenous magnesium sulphate* to women with severe preeclampsia who are in a critical care setting if birth is planned within 24 hours
  25. 25.  If considering magnesium sulphate* treatment, use the following as features of severe pre-eclampsia:  severe hypertension and proteinuria or  mild or moderate hypertension and proteinuria with one or more of the following: 1. symptoms of severe headache 2. problems with vision, such as blurring or flashing before the eyes 3. severe pain just below the ribs or vomiting 4. papilloedema 5. signs of clonus (≥3 beats) 6. liver tenderness 7. HELLP syndrome 8. platelet count falling to below 100 x 109 per litre 9. abnormal liver enzymes (ALT or AST rising to above 70 iu/litre).
  26. 26.  Use the Collaborative Eclampsia Trial[2] regimen for administration of magnesium sulphate*:  loading dose of 4 g should be given intravenously over 5 minutes, followed by an infusion of 1 g/hour maintained for 24 hours  recurrent seizures should be treated with a further dose of 2–4 g given over 5 minutes.  Do not use diazepam, phenytoin as an alternative to magnesium sulphate* in women with eclampsia. (NICE GUIDELINE)
  27. 27. Continous intravenous infusion  Give 4-6 gm of loading dose in 100 ml of IV fluid administered over 15-20 min  Begin 2 gm/h in 50 ml of IV maintainance infusion  Measure serum magnesium level at 4-6 hrs and adjust between 4-7 meq/l  Magnesium sulfate is discontinued 24 hrs after delivery
  28. 28.  Give loading dose of 4 g of magnesium sulfate as a 20% solution intravenously at a rate of 1g/min  Follow with 10g of magnesium sulfate ,one half(5 g) injected deeply in the upper outer quadrant of both buttocks using a 3-inch long 20 guage needle  If convulsions persist after 15 minutes give 2 gm more IV as a 20%solution as 1g/min.,for a large women 4 gm can be given slowly and safely  Every 4 hrs thereafter give 5 gm of Mg sulphate in alternate buttocks after assuring 1. the patellar reflex is present 2. Respirations are not depressed 3. Urine output during the previous 4 hrs exceed 400ml Discontinue 24 hrs after delivery (William obstetrics)
  29. 29. Magnesium Sulfate – First-line therapy for seizure prophylaxis. Antagonizes calcium channels of smooth muscle. Adult Dose 4-6 g IV over 20 min, with maintenance of 1-2 g/h Contraindications Hypermagnesemia, heart block, severe hepatitis renal disease, Addison disease, myocardial damage Overdose calcium gluconate, 10-20 mL IV of 10%; serum magnesium level should be checked one hour after initiation of therapy with goal of therapeutic level of 4-7 mEq/L
  30. 30. Phenytoin (Dilantin) -- The major site of action is the motor cortex where it acts by preventing the spread of seizure activity. Indicated for eclampsia. Adult Dose 20 mg/kg IV infused at a rate of 12.5 mg/min, not to exceed 1500 mg/24h Contraindications Documented hypersensitivity, sinoatrial block, sinus bradycardia, Adam-Stokes syndrome Pregnancy D - Unsafe in pregnancy Diazepam (Valium) -- For treatment of seizures resistant to magnesium sulfate. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Indicated for status epilepticus in eclamptic patients. Adult Dose 5-10 mg IV, repeat to total of 30 mg Contraindications Documented hypersensitivity; narrow angle glaucoma Fetal respiratory depression, fetal heart beat variability, maternal respiratory depression, delivery of fetus imminent Pregnancy D - Unsafe in pregnancy Precautions Monitor respiratory status during administrati on
  31. 31. Corticosteroids for fetal lung maturation • If birth is considered likely within 7 days in women with pre- eclampsia: give two doses of betamethasone* 12 mg intramuscularly 12 hours apart in women between 24 and 34 weeks  consider giving two doses of betamethasone* 12 mg intramuscularly12 hours apart in women between 35 and 36 weeks. Corticosteroids to manage HELLP syndrome Do not use dexamethasone or betamethasone for the treatment of HELLP syndrome.
  32. 32.  Do not use volume expansion in women with severe pre-eclampsia unless hydralazine is the antenatal antihypertensive.  In women with severe pre-eclampsia, limit maintenance fluids to 80 ml/hour unless there are other ongoing fluid losses (for example, haemorrhage).
  33. 33.  Manage pregnancy in women with pre-eclampsia conservatively (that is, do not plan same-day delivery of the baby) until 34 weeks.  Consultant obstetrician should document in the woman's notes the maternal (biochemical, haematological and clinical) and fetal thresholds for elective birth before 34 weeks in women with pre- eclampsia.  Consultant obstetrician should write a plan for antenatal fetal monitoring during birth. Before 34 weeks  Offer birth to women with pre-eclampsia before 34 weeks, after discussion with neonatal and anaesthetic teams and a course of corticosteroids has been given if:  severe hypertension develops refractory to treatment  maternal or fetal indications develop as specified in the consultant plan
  34. 34. After 34 weeks  Recommend birth for women who have pre-eclampsia with severe hypertension after 34 weeks when their blood pressure has been controlled and a course of corticosteroids has been completed (if appropriate). Between 34+0 to 36+6 weeks  Offer birth to women who have pre-eclampsia with mild or moderate hypertension at 34+0 to 36+6 weeks depending on maternal and fetal condition,risk factors and availability of neonatal intensive care. At 37+0 weeks  Recommend birth within 24–48 hours for women who have pre-eclampsia with mild or moderate hypertension after 37+0 weeks (nice guideline)
  35. 35.  Carry out cardiotocography at diagnosis of severe gestational hypertension or pre-eclampsia.  If conservative management of severe gestational hypertension or pre-eclampsiais planned, carry out all the following tests at diagnosis: • ultrasound for fetal growth and amniotic fluid volume assessment • umbilical artery doppler velocimetry.  If the results of all fetal monitoring are normal in women with severe gestational hypertension or pre- eclampsia, do not routinely repeat cardiotocography more than weekly.  In women with severe gestational hypertension or pre-eclampsia, repeat cardiotocography if if any of the following occur:  the woman reports a change in fetal movement  vaginal bleeding  abdominal pain  deterioration in maternal condition.
  36. 36.  In women with severe gestational hypertension or pre-eclampsia, do not routinely repeat ultrasound for fetal growth and amniotic fluid volume assessment or umbilical artery doppler velocimetry more than every 2 weeks.  If the results of any fetal monitoring in women with severe gestational hypertension or pre-eclampsia are abnormal, tell a consultant obstetrician  For women with severe gestational hypertension or pre-eclampsia, write a careplan that includes all of the following: o the timing and nature of future fetal monitoring o fetal indications for birth and if and when corticosteroids should be given o when discussion with neonatal paediatricians and obstetric anaesthetists should take place and what decisions should be made
  37. 37.  Blood pressure During labour, measure blood pressure: • hourly in women with mild or moderate hypertension • continually in women with severe hypertension. • Continue use of antenatal antihypertensive treatment during labour.  Haematological and biochemical monitoring Determine the need for haematological and biochemical tests during labour in women with mild or moderate hypertension using the same criteria as in the antenatal period even if regional analgesia is being considered.  Care during epidural analgesia Do not preload women who have severe pre-eclampsia with intravenous fluids before establishing low-dose epidural analgesia and combined spinal epidural analgesia.
  38. 38.  Do not routinely limit the duration of the second stage of labour: in women with stable mild or moderate hypertension or if blood pressure is controlled within target ranges in women with severe hypertension.  Recommend operative birth in the second stage of labour for women with severe hypertension whose hypertension has not responded to initial treatment.
  39. 39. Blood pressure In women with pre-eclampsia who did not take antihypertensive treatment and have given birth, measure blood pressure:  at least four times a day while the woman is an inpatient  at least once between day 3 and day 5 after birth  on alternate days until normal if blood pressure was abnormal on days 3–5. In women with pre-eclampsia who did not take antihypertensive treatment and have given birth, start antihypertensive treatment if blood pressure is 150/100 mmHg or higher. Ask women with pre-eclampsia who have given birth about severe headache and epigastric pain each time blood pressure is measured.
  40. 40. In women with pre-eclampsia who took antihypertensive treatment and have given birth, measure blood pressure: o at least four times a day while the woman is an inpatient o every 1–2 days for up to 2 weeks after transfer to community care until the woman is off treatment and has no hypertension. For women with pre-eclampsia who have taken antihypertensive treatment and have given birth:  continue antenatal antihypertensive treatment  consider reducing antihypertensive treatment if their blood pressure falls below 140/90 mmHg
  41. 41.  reduce antihypertensive treatment if their blood pressure falls below 130/80 mmHg.  If a woman has taken methyldopa† to treat pre-eclampsia, stop within 2 days of birth.  Offer women with pre-eclampsia who have given birth transfer to community care if all of the following criteria have been met: 1. there are no symptoms of pre-eclampsia 2. blood pressure, with or without treatment, is 149/99 mmHg or lower 3. blood test results are stable or improving.  Write a care plan for women with pre-eclampsia who have given birth and are being transferred to community care that includes all of the following: • who will provide follow-up care, including medical review if needed • frequency of blood pressure monitoring • thresholds for reducing or stopping treatment • indications for referral to primary care for blood pressure review • self-monitoring for symptoms.
  42. 42.  Offer women who have pre-eclampsia and are still on antihypertensive treatment 2 weeks after transfer to community care a medical review.  Offer all women who have had pre-eclampsia a medical review at the postnatal review (6–8 weeks after the birth).  Offer women who have had pre-eclampsia and who still need antihypertensive treatment at the postnatal review (6–8 weeks after the birth) a specialist assessment of their hypertension.
  43. 43. Haematological and biochemical monitoring  In women who have pre-eclampsia with mild or moderate hypertension, measure platelet count, transaminases and serum creatinine 48– 72 hours after birth  do not repeat platelet count, transaminases or serum creatinine measurements if results are normal at 48–72 hours.  If biochemical and haematological indices are improving but stay within the abnormal range repeat measurements as clinically indicated and at the postnatal review (6–8 weeks after the birth).
  44. 44.  If biochemical and haematological indices are not improving , repeat platelet count, transaminases and serum creatinine measurements as clinically indicated.  carry out a urinary reagent-strip test at the postnatal review (6–8 weeks after the birth).  Offer women who had pre-eclampsia and still have proteinuria (1+ or more) at the postnatal review (6–8 weeks after the birth) a further review at 3 months after the birth to assess kidney function and consider offering them a referral specialist kidney assessment.
  45. 45.  In women who still need antihypertensive treatment in the postnatal period,avoid diuretic treatment for hypertension if the woman is breastfeeding or expressing milk.  Tell women who still need antihypertensive treatment in the postnatal period that the following antihypertensive drugs have no known adverse effects on babies receiving breast milk:  labetalol  nifedipine  enalapril  captopril  atenolol  metoprolol  Tell women who still need antihypertensive treatment in the postnatal period that there is insufficient evidence on the safety in babies receiving breast milk of the following antihypertensive drugs: • ARBs • amlodipine • ACE inhibitors other than enalapril† and captopril†.  Assess the clinical wellbeing of the baby, especially adequacy of feeding, at least daily for the first 2 days after the birth.
  46. 46. Long-term risk of cardiovascular disease increased later in life Long-term risk of end-stage kidney disease Tell women with a history of pre-eclampsia who have no proteinuria and no hypertension at the postnatal review (6–8 weeks after the birth) that although the relative risk of end-stage kidney disease is increased the absolute risk is low and no further follow-up is necessary Thrombophilia and the risk of pre-eclampsia Do not routinely perform screening for thrombophilia in women who have had pre-eclampsia.
  47. 47. Risk of recurrence of hypertensive disorders of pregnancy  Tell women who had gestational hypertension that their risk of developing: • gestational hypertension in a future pregnancy ranges from about 16 to 47% • pre-eclampsia in a future pregnancy ranges from 2 to 14%  Tell women who had pre-eclampsia that their • risk of gestational hypertension in a future pregnancy ranges from about 13 to 53% • pre-eclampsia in a future pregnancy is up to about (16%) • pre-eclampsia in a future pregnancy is about (25%) pregnancies if their preeclampsia was complicated by severe pre-eclampsia, HELLP syndrome or eclampsia and led to birth before 34 weeks, and about (55%) pregnancies if it led to birth before 28 weeks.
  48. 48.  Inter-pregnancy interval and recurrence of hypertensive disorders of pregnancy Tell women who have had pre-eclampsia that there is no additional risk of recurrence with inter-pregnancy interval up to 10 years  Body mass index and recurrence of hypertensive disorders of pregnancy Advise women who have had pre-eclampsia to achieve and keep a BMI within the healthy range before their next pregnancy (18.5–24.9 kg/m2)

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