An approach to hypertensive disorders in pregnancy for the primary care...

[Full title: An approach to hypertensive disorders in pregnancy for the primary care physician]

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Open Access South African Family Practice ISSN: (Online) 2078-6204, (Print) 2078-6190 Page 1 of 6 CPD Article Read online: Scan this QR code with your smart phone or mobile device to read online Authors: Mergan Naidoo 1 Robert C. Pattinson 2 Affiliations: 1 Department of Family Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 2 Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa Corresponding author: Mergan Naidoo, naidoom@ukzn.ac.za Dates: Received: 30 Jan. 2020 Accepted: 31 Jan. 2020 Published: 17 Feb. 2020 How to cite this article: Naidoo M, Pattinson RC. An approach to hypertensive disorders in pregnancy for the primary care physician. S Afr Fam Pract. 2020;62(1), a 5095. Copyright: © 2020. The Authors. Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License Introduction The recently published guidelines on the management of hypertensive disorders in pregnancy (HDP) highlighted the concerning trends in maternal deaths in South Africa. Although 78 % of deaths occurred at higher levels of care, many of the emergencies are thought to have originated at the primary healthcare (PHC) or the district hospital (DH) level. 1 The guidelines further highlight the large percentage (75 % ) of potentially preventable deaths because of HDP at all levels of care, which has been increasing over the last decade 1 Avoidable factors for HDP deaths were identified in 48 % and 60 % of the cases at the Community Health Centre (CHC) and DH level, respectively 1 The factors identified at a PHC and DH included inadequate assessment, errors in diagnosis, delayed or no referrals to higher levels of care, non-adherence to management protocols, poor monitoring and poor response to abnormal monitoring 1 These guidelines provide an approach to diagnosing, assessing and managing HDP at PHC and DH levels and are based on the national guidelines published in 2019 Diagnosis of hypertensive disorders in pregnancy Diagnosis of HDP is based on the classification of the International Society for the Study of Hypertension in Pregnancy (ISSHP) 2 : 1. Chronic hypertension (HT) may predate the pregnancy or is diagnosed before 20 weeks’ gestation 2. White-coat HT refers to elevated clinical ( ≥ 140/90 mmHg) blood pressure (BP), but normal BP measured at home may convey increased risk for pre-eclampsia (PE) 3. Masked HT is characterised by BP that is normal at the clinical level but elevated at other times, and it is diagnosed by 24-h ambulatory BP monitoring or automated home BP monitoring 4. Gestational HT arises after 20 weeks’ gestation in the absence of proteinuria and is not usually associated with foetal growth restriction or poor pregnancy outcomes 5. Pre-eclampsia is diagnosed by the presence of HT after 20 weeks’ gestation accompanied by proteinuria or evidence of maternal acute kidney injury, liver dysfunction, neurological features, haemolysis or thrombocytopenia, or foetal growth restriction. Pre-eclampsia may develop or can be recognised for the first time intrapartum or early postpartum. The haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a (serious) manifestation of PE and is not a separate disorder Measurement of blood pressure Blood pressure should be measured with the woman in a relaxed sitting position keeping the arm at the level of the heart with an appropriately sized cuff (1.5 times the circumference of the arm). Hypertensive disorders in pregnancy (HDP) are a leading obstetric cause for maternal morbidity and mortality nationally as well as globally. The Saving Mothers is a report published every three years by the National Committee for Confidential Enquiry, which reports the trends in maternal deaths in South Africa. The last three Saving Mothers reports identified many gaps in the management of HDP and interventions to address these gaps were recommended. The recently published national guidelines on the management of HDP have highlighted approaches for the diagnosis, assessment and management of HDP. This article synthesises the national guidelines and provides approaches for the primary care physician working at the primary healthcare or the district hospital level. The algorithms provide easy clinical pathways once the correct assessment has been made Keywords: hypertensive disorders in pregnancy; primary care; management An approach to hypertensive disorders in pregnancy for the primary care physician Read online: Scan this QR code with your smart phone or mobile device to read online.

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Page 2 of 6 CPD Article Open Access Korotkoff Phase 5 (K-5) should be used to designate diastolic BP. If the BP is consistently higher in one arm, then the arm with higher values should be used for all BP measurements. Blood pressure should be measured using a validated device. Hypertension in pregnancy is defined as a clinical systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, based on the average of at least two measurements taken at least 15 minute apart, using the same arm. 1,2,3 Patients presenting with pre-HT ( BP = 135/85–139/89) should have their BP repeated within 2 h and if BP is still at borderline, they should be asked to return within 3–7 days 1 Assessment of patients with hypertensive disorders in pregnancy A detailed history and examination of the patient is warranted at first presentation. This would include a history of prior PE, chronic HT, diabetes mellitus, antiphospholipid syndrome, systemic lupus erythematous, previous pregnancy outcomes and the use of assisted reproduction therapies. Examination may reveal multiple gestation and a high maternal body mass index (BMI > 35). Patients with any of these findings during history and examination should be started on prophylactic aspirin (75 mg - 162 mg) in early pregnancy with maximum benefits in preventing PE realised when initiated < 16 weeks of gestation. 1,2,4,5 All pregnant women should also be started on elemental calcium, minimum 500 mg daily, as prophylaxis for PE 1,2,5,6,7,8 Table 1 provides investigations that are to be carried out at various antenatal visits. 1,2,3 Defining the next level of expertise and referral patterns It is important for primary care providers to define the next level of expertise and the referral patterns. Primary healthcare clinics, CHCs and staff in some DHs need to identify the next level of expertise, which may include facilities that have an advanced midwife with special training or a doctor with expertise in managing pregnant women, and this facility should be able to perform basic laboratory investigations (defined in Table 1) and offer a basic obstetric sonar examination. The blood investigations must be processed rapidly so that management could be planned and an efficient communication network with obstetricians must be in place. These high-risk clinics may be present at CHCs and DHs. The referral routes for an identified catchment area should be defined by specialists based at the regional or tertiary hospitals in consultation with the district clinical specialist team (DCST). The main referral hospital should develop and circulate guidelines and protocols to all facilities in the catchment area. This helps to speed up referral through pathways and allows for the management of patient according to defined protocols. Discussions between staff at the PHC clinic, DH, DCST and the regional hospital (RH) help to define the level of expertise required at each level of care and the type of patient that could be managed at these levels. The emergency medical response service must be involved in these discussions as they are key in facilitating transfer across facilities Management of patients with hypertensive disorders in pregnancy Figures 1–3 have been extrapolated from the South African guidelines on managing HDP and have been included as easy reference aids. 1 Patients with PE and 1+ proteinuria with no severe features and BP that is controlled with one oral agent may be managed at a DH with caesarean section facilities, but these patients require inpatient management . It is important to inform the obstetrician at the RH that such a patient is being managed at the DH 1 Management of pre-eclampsia with severe features These patients may present to any facility and require emergency management. Such patients may present with headache, chest or epigastric pain or discomfort, visual disturbances, proteinuria 2+ or more and BP more than TABLE 1: Recommended investigations during antenatal care Investigation When Why Urine dipsticks At every visit To confirm the presence of proteinuria and make a diagnosis of PE Serum creatinine When a diagnosis of essential or gestational HT or PE with no severe features is made To establish renal damage Serum haemoglobin and platelets When a diagnosis of essential or gestational HT or PE with no severe features is made To confirm intravascular depletion Ultrasound examination When a diagnosis of essential or gestational HT or PE with no severe features is made To establish foetal well-being PCR or 24-hour urinary protein excretion When PE with no severe features is diagnosed To estimate the amount of protein excreted in urine Urine microscopy, culture and sensitivity When PE with no severe features is diagnosed To exclude an alternative cause of proteinuria ALT When PE with no severe features is diagnosed To confirm liver involvement Urea and electrolytes, liver function tests, INR, serum uric acid levels, full blood count, crude clotting time When PE with severe features is diagnosed To evaluate organ system involvement. Do not delay transfer waiting for investigations Arterial blood gas When pulmonary oedema is suspected To ascertain need for assisted ventilation Uterine artery Doppler velocimetry When placental insufficiency is suspected in a patient with HDP To exclude foetal compromise Source : Please see the full reference list of the article, Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy: 2019 National guideline. S Afr Med J. 2019;109(9):12723, for more information ALT, alanine aminotransferase; HDP, hypertensive disorders in pregnancy; HT, hypertension; INR, international normalised ratio; PE, pre-eclampsia; PCR, protein-creatinine ratio.

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Page 3 of 6 CPD Article Open Access Primary Healthcare Level Inial Assessment and Management Women with pre-hypertension (BP 135–139/85–89 mmHg) Repeat blood pressure aer rest (30 min – 2 h) Pre-HT / Borderline Review in 3–7 days at PHC #Risk factors? #Risk factors: No Refer to a district hospital for inves ga on for pre-eclampsia Pre-eclampsia, no severe features. HDP with risk factors but no proteinuria • Prior pre-eclampsia • Chronic hypertension • Mul ple gesta on • Pre-gesta onal diabetes • Maturnal BMI > 35 • An -Phospholipid syndrome/ • Start Aspirin • Start Methyldopa • Start Alpha Methyldopa (500 mg 8 hourly) and send to next level of exper se within 3 days 16 • Bloods • Sonar for fetal evalua on MCS P/Cr ratio or 24 h urine Screening Urine Tests: Screening Blood Tests: Haemoglobin Platelets Creatinine Liver enzymes (ALT) Sonar for Fetal Evaluation: Only monitor the foetus once the mother is stable and the decision has been taken that delivery is safe in DH • Inform receiving hospital • Give Magnesium sulphate if receiving doctor suggests it • GA ≥ 20 weeks. (if GA < 20 weeks: case to be discussed with receiving hospital re same day or next day referral) Same day referral to nearest hospital accredited for Caesarean Delivery Refer to Next Level of Expertise within 3 days Same day referral to DH * Stabilise woman HT with no risk factors, no proteinuria and no symptoms • Headache • Chest pain / epigastric pain / discomfort • Visual disturbances Severe Features HT with proteinuria one plus or more, no severe features Pre-eclampsia with severe features* OR BP > 160/110 mmHg 17 • Start Methyldopa. • Inves gate for Pre-eclampsia: Blood and Fetal sonar Yes No Yes No Yes Proteinuria? Proteinuria? Women with hypertension < 32 weeks Women with hypertension (BP 140/90 + mmHg) Source : Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy: 2019 National guideline. S Afr Med J. 2019;109(9):12723 HT, hypertension; PHC, primary healthcare, HDP, hypertensive disorders in pregnancy; ALT, alanine aminotransferase; DH, district hospital; MCS, microscopy, culture and sensitivity; P/Cr, protein to creatinine ratio of the urine; min, minute; h, hour FIGURE 1: Management of a patient with hypertensive disorders in pregnancy at a primary healthcare clinic.

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Page 4 of 6 CPD Article Open Access District Hospital (DH) with Caesarean Secon Capability Inial Assessment and Management Women with pre-hypertension (BP 135–139/85–89 mmHg) HT but no proteinuria Start 500 mg Alpha methyldopa 8 hourly, and follow-up in 3–7 days to see if BP controlled Follow-up weekly Consider delivery or transfer to higher level of cars depending diagnosis and context *Stabilise woman as described below : • Start magnesium sulphate: 4 g M in 200 ml N saline or ringers lactate over 20 min, 10 g IMI (5 g in each bu’ock) route (2, 18) • Give 1 g Alpha Methyldopa orally • Insert a urinary catheter and monitor the urine output every hour un”l the woman is transferred • Determine if the foetus is alive. Do not monitor the foetus Only monitor the foetus once the woman is stable and the decision has been taken that delivery is safe in DH • Monitor the woman’s BP, pulse, respiratory rate, every 15 min un”l the woman is transferred • Emergency transfer ideally accompanied by an experienced nurse if available Use SBAR from • Woman must be monitored and transferred in the lateral posi”on • Start one IV line with 200 ml ringers lactate or normal saline (whichever is available), run IV line slowly • Lower High blood pressure with 10 mg quick ac”ng nifedipine orally. This can be repeated every 30 min if the blood pressure does not drop below 160/110 mmHg. if the woman is unable to swallow put the 10 mg nifedipine under the woman’s tongue Confirm diagnosis establish gesta”onal age (e.g. HT < 32 weeks, foetal growth restricon, isolated proteinuria, hypentension and proteinuria) Features suggesve of pre-eclampsia Pre-eclampsia with severe features (referred or discovered) *Stabllise woman Labour? Stabilise and delivery at DH Transfer to higher level of care Transfer to higher level of care Yes No Steriods if ges”onal age < 34 weeks to s”mulate foetal lung maturity Pre-HT Review in 3-7 at PHC or DH which ever most convenient Repeat blood pressure a§er rest (30 min - 2 h) Women with hypertension (BP 140/90+ mmHg) Bloods Urine MCS, P/Cr ra”o 24 h urine Bloods Inves”gate for pre-eclampsia: Senar for fotal evaluva”on Sonar for foetal evaluva”on Inves”gate for pre-eclampsia: Source : Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy: 2019 National guideline. S Afr Med J. 2019;109(9):12723 SBAR, situation, background, assessment and referral; BP, blood pressure; HT, hypertension; MCS, microscopy, culture and sensitivity; IMI, intramuscular injection; IVI, intravenous infusion; DH, district hospital; PHC, primary healthcare; P/Cr, protein to creatinine ratio of the urine; IV, intravenous; min, minute; h, hour FIGURE 2: Management of a patient with hypertensive disorders in pregnancy at a district hospital. Standardised referral form used by public healthcare facilities in the Republic of South Africa.

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Page 5 of 6 CPD Article Open Access 160/110 mmHg. If the patient is at a PHC clinic or a CHC, one member of the team should inform the regional or tertiary referral hospital whilst other members should stabilise the patient according to the principles of resuscitation based on the Essential Steps in Managing Obstetric Emergencies (ESMOE), which follows a structured approach. 9 An intravenous line of ringer’s lactate running in at 80 mL/h should be started, and the patient should be loaded with magnesium sulphate 14 g (4 g intravenous infusion [IVI] in 200 mL of normal saline over 20 min and 10 g given as intramuscular injection [IMI] – 5 g in each buttock) 1 The BP could be brought down with 10 mg of oral nifedipine and a start dose of 1000 mg of oral alpha methyldopa. Emergency transfer to RH with monitoring by an experienced nurse during transit should take place with the patient continuously nursed in the lateral position Patients presenting with PE with severe features at a DH with caesarean delivery (CD) facilities are managed in a similar manner, but some DHs have access to intravenous labetalol and this could be used according to the standard protocol. 10 Many women die because of injudicious use of excessive fluids, so careful monitoring of fluid intake is important, with the recommended rate of administration of IVI fluids not exceeding 80 mL/h. Women with a gestational age of 28–34 weeks should be given steroids to improve the lung maturity of the foetus, especially if delivery is planned within 48 h. The first dose of steroids should be given at the DH, and the patient should be urgently transferred to a RH Management of pre-eclampsia with severe maternal complications Severe maternal complications in PE refer to a patient who presents with eclampsia, pulmonary oedema, cerebrovascular accident, HELLP syndrome, renal dysfunction (serum creatinine > 120 mmol/L), severe uncontrolled HT and coagulopathy. Such patient needs urgent delivery after stabilisation. There are still significant shortcomings in the management of these life-threatening emergencies because of lack of skills and knowledge as evidenced in two local studies 11,12 The management of eclampsia should be based on the National Maternity Care Guidelines, a summary of which is presented below 13 Call for help and turn the patient on her side, extend her neck, suction the airway and insert an oral airway if possible. Administer oxygen through facemask and initiate Source : Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy: 2019 National guideline. S Afr Med J. 2019;109(9):12723 BP, blood pressure; DH, district hospital; GA, general anaesthetic; MCS, microscopy, culture and sensitivity; P/Cr, protein to creatinine ratio of the urine FIGURE 3: Management of patients with hypertensive disorders in pregnancy according to gestational age Invesgate for pre-eclampsia: Bloods Urine MCS, P/Cr rao or 24 h urine Sonar for fetal evaluaon GA < 28 weeks pre-eclampsia with no severe features and GA 28–33 weeks, pre-eclampsia with no severe features GA 34 weeks or more, pre-eclampsia with no severe features Gestaonal hypertension (may be chronic, can only make disgnosis of chronic hypertension 6 weeks following delivery) Delivery at 38–40 weeks at DH 19 The woman must NOT be treated as outpaent In special circumstance the women can be managaed by the DH if sufficient experse is available. (Determined by the main referal hosptal) Ideally transfer to regional or terary hospital where specialist care is available See weekly at the antenatal clinic Transfer to higher level of care Consult with referral hospital about steriods and magnesium sulphate Stabilise woman Stabilise woman Women with hypertension (BP 140/90 + mmHg)

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Page 6 of 6 CPD Article Open Access magnesium sulphate according to the regimen listed above to arrest and prevent seizures. Start maintenance dose of magnesium sulphate, 4.5 g given by deep IMI every 4 h in alternative buttocks. If systolic or diastolic BP is > 160/110 mmHg, then use nifedipine orally, or labetalol intravenously. Nifedipine can be repeated after 30 min if BP remains > 160/110 mmHg. All patients should also be given 1000 mg methyldopa, with a repeated dose of 500 mg every 8 h orally. This is to ensure smoother control of BP at a later stage. Methyldopa is not a rapidly acting antihypertensive; hence, nifedipine or labetalol must be used in acute phase to control BP. If the patient is restless, administer 1 mg clonazepam as slow IVI After stabilisation, obtain full history and follow the ESMOE steps of evaluating the Big 5 (central nervous, respiratory, cardiovascular, liver and gastrointestinal and renal systems), Forgotten 4 (haematological, endocrine, immunological and musculo-skeletal systems) and Core 1 (female genital system). 9 Monitor BP every 15 min. Assess the uterus for tenderness, irritability, foetal size and liquor volume. Moreover, assess the cervix to check whether induction of labour is needed. Draw blood for haemoglobin, platelet count, creatinine, alanine aminotransferase and lactate dehydrogenase (LDH). Assess the foetal condition if the patient is completely stable and the platelet count is known. Ensure that abruptio placenta is ruled out. Confirm whether the patient is in labour, as eclamptic patients often go into spontaneous labour. If vaginal delivery is not contraindicated, go for spontaneous vaginal delivery before transfer, but ensure that there is no excessive bearing down. Only use oxytocin, 10 units IMI, for active delivery of the placenta and for prevention of postpartum haemorrhage. Advice must be obtained from an experienced obstetrician and ensure that detailed notes are kept. If the patient is not in labour and is stable, transfer her to a specialist level of care. Continue monitoring the patient whilst awaiting transfer, preferably every 15 min. Anaesthesia for patients who need urgent CD is complex and should preferably be given by an experienced anaesthetist. 13 Conclusion Managing HDP requires knowledge and skill, and the best way to obtain such competencies is through educational initiatives such as ESMOE. Participating in regular emergency obstetric simulations (fire drills) at the workplace allows primary care providers the opportunity to identify gaps in their knowledge and skills, and recognise and address shortcomings in equipment and drug stocks. The South African Academy of Family Physicians conducts interactive web-based educational programmes, and healthcare providers are strongly encouraged to participate in these activities Acknowledgements The authors would like to thank the various individuals who contributed to the 2019 national guidelines on hypertensive disorders in pregnancy Competing interests The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article Authors’ contributions All authors contributed equally to this work Ethical considerations This article followed all ethical standards for a research without direct contact with human or animal subjects Funding information This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors Data availability statement Data sharing is not applicable to this article as no new data were created or analysed in this study Disclaimer The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors References 1. Moodley J, Soma-Pillay P, Buchmann E, Pattinson R. Hypertensive disorders in pregnancy: 2019 National guideline. S Afr Med J. 2019;109(9):12723 2. Brown MA, Magee LA, Kenny LC, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;723. Magee LA, Pels A, Helewa M, et al. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: Executive summary. Journal of Obstetrics and Gynaecology Canada. 2014;36(5):416–438. 4. Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: Systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(2):110–120 e 6. 5. Firoz T, Sanghvi H, Merialdi M, Von Dadelszen P. Pre-eclampsia in low and middle income countries. Best Pract Res Clin Obstet Gynaecol. 2011;25(4):537–548. 6. Salam RA, Das JK, Ali A, Bhaumik S, Lassi ZS. Diagnosis and management of preeclampsia in community settings in low and middle-income countries. J Family Med Prim Care. 2015;4(4):501–506. 7. Hofmeyr GJ, Duley L, Atallah A. Dietary calcium supplementation for prevention of pre-eclampsia and related problems: A systematic review and commentary. BJOG. 8. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 9. Naidoo M. Maternal collapse: Training in resuscitation. Best Pract Res Clin Obstet Gynaecol. 10. South African Department of Health. Hospital level standard treatment guidelines and essential medicines list. Pretoria: National Department of Health; 2015 11. Makhanya V, Moodley J, Govender L. Eclampsia: Still a major problem in rural KwaZulu-Natal Province, South Africa. S Afr J Obstet Gynaecol. 2016;22(1):13–17. 12. Ramavhoya IT, Maputle MS, Lebese RT, Ramathuba DU, Netshikweta LM. Managing hypertensive disorders during pregnancy in low resource settings. Hypertens Pregnancy. 2019;38(4):230–236. 13. South African National Department of Health. Guidelines for maternity care in South Africa: A manual for clinics, community health centres and district hospitals. Pretoria: South African National Department of Health; 2015.

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