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RISKY PREGNANCIES MANAGEMENT GUIDELINE RISKY PREGNANCIES MANAGEMENT GUIDELINE High-Risk Pregnancies Management Guideline Republic of Turkey Ministry of Health Public Health Agency of Turkey Department of Women’s Health and Reproductive Health Ankara, 2014 Ministry of Health Publication No: 926 This work was prepared and published by the Republic of Turkey, Ministry of Health, Public Health Agency of Turkey, Department of Women’s Health and Reproductive Health. All rights of publication of this work belong to the Public Health Agency of Turkey. No quotations can be made without citing the source. This work cannot be reproduced or published, even if partially. When quoting from this work, the source should be cited as follows: “Risky Pregnancies Management Guideline”, The Republic of Turkey, Ministry of Health, Public Health Agency of Turkey, Publication No, Place of Publication and Date of Publication. Free of charge. Not for commercial use. Cover Design: Graphic Designer Umman SEZGİN FOREWORD As a multidimensional development indicator, maternal and infant mortality rates are closely linked to the quality of reproductive health services delivery. Complications during pregnancy, labour and puerperium are leading causes of death and disability among women of reproductive age in developing countries. According to the estimations of World Health Organisation, each year about 287,000 maternal mortality cases occur. Millennium Development Goal 5 aims at improving maternal health. It has been determined that countries can attain this goal by reducing maternal mortality and by ensuring universal access to reproductive health. While in 2002 maternal mortality rate was 64 in one hundred thousand live births, according to National Maternal Mortality Survey conducted in 2005 it decreased to 28.5, and it was reduced to 15.4 in 2012 thanks to various programmes conducted. Turkey’s success in reducing maternal mortality is highly appreciated by WHO, and it has set an example for other countries. In achieving all these, besides overall development in Turkey, strengthening prenatal, delivery and postnatal care and emergency obstetric care and ensuring that delivery takes place at hospital have made a significant contribution. Maternal mortality due to any preventable reason cannot be accepted. Our efforts to prevent maternal mortality will continue increasingly. As is known, it becomes more challenging to go beyond what has already been achieved in the field of maternal and infant mortality. We have to do more than what has been done to date and we have to do it with higher quality. To do so, we have to keep the knowledge and skills of the health personnel at the highest level possible as well as making up the deficiencies of medical equipment and infrastructure in health institutions. Under the scope of “High-Risk Pregnancies Prevention Programme”, High-Risk Pregnancies Management Guideline has been prepared in order to deliver high-quality, standard and safe services to manage highly risky conditions leading to maternal mortality, and to achieve uniformity in practice. The Guideline is composed of Management Guideline for Venous Thromboembolism in Pregnancy, Pregnancy and Cardiovascular Diseases Management Guideline, Management Guideline for Pregnants with Epilepsy, Management Guideline for Pregnants with Diabetes and Management Guideline for Pregnants with Asthma. The Guideline encompasses actions and operations to be performed during prenatal period, delivery and postnatal period, and it requires coordination between primary care and other health institutions and a multidisciplinary approach through relevant specialities. High-Risk Pregnancies Management Guideline has been developed by the Scientific Commission of the Ministry presented below, and it has been finalized through the comments of relevant associations. In the process of the development of the Guideline, evidence-based medical practices have been taken into account, and it has been developed by taking into consideration country-specific features. It has been agreed that the guidelines will be updated minimum every two years, and new management guidelines will be developed on the basis of risks to be identified. We would like to render our thanks to members of the Scientific Commission who have contributed to the preparation of the guideline, institutional staff working for the programme, associations and staff working with devotion in the field in order to prevent maternal mortality and healthcare staff who will be implementing these guidelines. These guidelines are not a set of fixed rules and do not form legal standards of the services delivered to patient. In accordance with the main principle of the law “there are no diseases but patients”, it is recognized that the specific condition of each patient should be considered within his/her specific circumstances. Presidency of Public Health Agency of Turkey Members of the Scientific Commission and the Agency staff involved in the programmes are presented below in alphabetical order by their surname. Scientific Commission for High-Risk Pregnancies Management Guideline Prof. Dr. Nazlı ATAK Prof. Dr. Sinan AYDOĞDU Prof. Dr. Cengiz BEYAN Prof. Dr. Yahya BÜYÜKAŞIK Assoc. Prof. Dr. Zeki ÇATAV Prof. Dr. Selçuk DAĞDELEN Assoc. Prof. Dr. Nuri DANIŞMAN Prof. Dr. Özgür DEREN Specialist Deniz ERDEM Dietician Şeniz ILGAZ Assoc. Prof. Dr. Ömer KANDEMİR Prof. Dr. Gül KARAKAYA Prof. Dr. Faik Acar KOÇ Assoc. Prof. Dr. Gülnihal KUTLU Prof. Dr. Tamer MUNGAN Prof. Dr. Dilşat MUNGAN Specialist Veli Dündar ONGUN Prof. Dr. Necla ÖZER Assoc. Prof. Dr. Ferit SARAÇOĞLU Prof. Dr. Serap SAYGI Prof. Dr. Mehmet Zeki TANER Prof. Dr. Ahmet TEMİZHAN Prof. Dr. Yusuf ÜSTÜN Prof. Dr. Filiz Bilgin YANIK Prof. Dr. İlhan YETKİN Programme Officers of PHAT Department of Women’s Health and Reproductive Health Nurse Hacer BOZTOK Nurse Meltem KARAMAN Dr. Zübeyde ÖZKAN ALTUNAY Specialist Sema SANİSOĞLU Department Head Specialist Bekir KESKİNKILIÇ Deputy President of PHAT Prof. Dr. Seçil ÖZKAN President of PHAT Relevant Associations Sharing Their Comments Turkish Society of Obstetrics and Gynaecology Turkish Perinatal Society Turkish Chapter of International League Against Epilepsy Turkish Neonatology Society Turkish Thoracic Society Turkish Society of Cardiology Turkish Society of Hematology Turkish Society of Maternal Fetal Medicine and Perinatology The Turkish Diabetes Foundation The Society of Endocrinology and Metabolism of Turkey Turkish National Society of Allergy and Clinical Immunology Turkish Respiratory Society Publication Commission Assistant Prof. Dr. Hasan IRMAK Deputy President of PHAT Assoc. Prof. Dr. Nazan YARDIM PHAT, Department Head, Department of Obesity, Diabetes and Metabolic Diseases, Dr. Kanuni KEKLİK PHAT, Department Head, Department of Community Care Services, Specialist M. Bahadır SUCAKLI PHAT, Department Head, Department of Early WarningResponse and Field Epidemiology, Publication Coordinators Specialist Bekir KESKİNKILIÇ Deputy President of PHAT Specialist Sema SANİSOĞLU PHAT, Department Head, Department of Community Care Services, Dr. Zübeyde ÖZKAN ALTUNAY PHAT, Department of Community Care Services, Nurse Hacer BOZTOK (Editing) PHAT, Department of Women’s Health and Reproductive Health i TABLE OF CONTENTS MANAGEMENT GUIDELINE FOR VENOUS THROMBOEMBOLISM IN PREGNANCY………………………………………………...1 MANAGEMENT GUIDELINE FOR PREGNANCY AND CARDIOVASCULAR DISEASES …………………………………………………………………..23 DIABETIC PREGNANCY MANAGEMENT GUIDELINE ………………………………46 EPILEPTIC PREGNANCY MANAGEMENT GUIDELINE……………………………….…59 MANAGEMENT GUIDELINE FOR PREGNANTS WITH ASTHMA……………………………………..65 ii iii MANAGEMENT GUIDELINE FOR VENOUS THROMBOEMBOLISM IN PREGNANCY iv A-PRECONCEPTION THROMBOPROPHYLAXIS Pregnancy is an independent risk factor for deep vein thrombosis and pulmonary embolism. Pregnant women carry 5-6 times more risk of venous thromboembolism (VTE) compared to nonpregnant women in the same age group. About 1 out of every 1000 births is complicated by venous thrombosis, and 1 out of every 1000 women suffers from thrombosis in the postpartum period. Thus venous thromboembolic diseases are among the leading causes of maternal mortality and morbidity. Furthermore, venous thromboemlism incidence is 2-4 times higher in caesarean section delivery compared to vaginal delivery. Risk factors assessments concerning thromboembolism should begin with the monitoring of women in age group 15-49. Women with thromboembolism should receive counselling from healthcare staff before conception. Importance of regular follow-up and counselling should be underlined. If there is no intention of conception, patient should be referred to Family Planning Clinic. During counselling, information should be provided about the following: effect of thromboembolism on pregnancy, effect of pregnancy on thromboembolism and effects of medications used to treat thromboembolism on pregnancy, whether there is a need to change medicines, potion, and drug interactions. Follow-up in prenatal period, during pregnancy and in postpartum period should be conducted by specialists experienced in haemostasis and gestation (in line with principles specified in Table 2). Pregnancy should be planned. Change of medication change should be made minimum 6 weeks prior to the planned pregnancy. Individuals with high risk of thrombosis should be 2 monitored through pregnancy test every month, and medication should be changed when the test result is positive. In order to minimize malformations likely to occur in baby, folic acid supplement should be initiated 3 months prior to conception, and should continue until the end of 10th week of pregnancy. All pregnants should be subject to risk factors assessment in line with Table 1 against VTE in pregnancy period or in early pregnancy period. This assessment should be repeated when the pregnant is hospitalized for any reason or when accompanying problems develop. While assessing risk factors, routine hereditary thrombophilia screening should not be conducted in asymptomatic cases. 3 Table-1: Risk Factors Timing Preexisting Factors A- Previous venous thromboembolism B- Thrombophilia 1- Hereditary Antithrombin deficiency Protein C deficiency Protein S deficiency Factor V Leiden Protrombin gene G20210A 2- Acquired Antiphospholipid syndrome Persistent recurrent abortus Persistent medium/high titre anticardiolipin antibodies or β2 glikoprotein1 antibodies Medical disorders (for instance; heart or lung disorders, SLE, cancer, inflammatory diseases such as inflammatory bowel disease or inflammatory polartropathy, nephritic syndrome-proteinuira >3gr/day, sickle cell anaemia, diseases requiring intravenous medicine Above the age of 35 Obesity prior to pregnancy or during early pregnancy (BMI>30kg/m2) 4 Obstetric New on-set /temporary Reversible Parity ≥3 Smoking Apparent varicose veins (symptomatic and/or on knee or phlebitis, with oedema and/or skin changes) Paraplegia Multiple pregnancy, assisted reproductive techniques Preeclampsia Caesarean section Postpartum bleeding requiring transfusion (>1lt) Prolonged labour, labour through intervention Surgical intervention during pregnancy or p puerperality (appendectomy, postnatal sterilisation Hyperemesis, dehydration Ovarian hyperstimulation syndrome (OHSS) Hospitalisation or immobilisation (3-day and/or longer bed rest) Systemic infection (requiring hospitalization or use of antibiotics) (for instance; pneumonia, pyelonephritis, postnatal wound infection) Long-distance travel (> 4 hours) B- PRENATAL CARE AND THROMBOPROPHYLAXIS All pregnants should be subject to risk factors assessment against VTE during early pregnancy. Pregnant woman should be informed that thrombophilia risk normally increasing with pregnancy will increase further due to the risks she carries, and possible developments should be explained to the pregnant. 5 o As long as treatment is not contraindicated, every pregnant whose symptoms and findings support VTE should be treated with low molecular weight heparin or classic heparin (LMWH/AFH) until the diagnosis has been discarded through objective tests. Consider administering DMAH/AFH ON pregnants with 3 or more of risk factors demonstrated in Table 1 (except for previous VTE or thrombophilia) or with continuing risk factor. Consider continuing with prophylactic LMWH/AFH minimum for 7 days following delivery in pregnants with 2 or more of risk factors demonstrated in Table 1 (except for previous VTE or thrombophilia) or with continuing risk factor. It should be explained to the pregnant woman taking LMWH/AFH during prenatal period that when they have vaginal bleeding or when labour starts, they should not take LMWH /AFH doses until the causes of bleeding are understood. If there are clinical suspicions about deep vein thrombosis (DVT), compression duplex ultrasound scan should be carried out. 1. If ultrasound scan is negative and clinical suspicion is weak, stop anticoagulant therapy. 2. If ultrasound scan is negative but there are strong suspicions, continue with anticoagulant, and ultrasound scan should be repeated within one week. If D-dimer level is negative it can be considered sufficient to stop anticoagulant. Thromborophylaxis in Pregnants with Previous VTE and/or 6 Thrombophilia: Action is taken in line with Table 2. Counselling about the impacts of warfarin on baby should be provided to pregnant receiving warfarin therapy. If pregnancy is not planned, stop warfarin right after pregnancy is confirmed and begin LMWH /AFH. Begin LMWH /AFH immediately for pregnants not receiving warfarin. In pregnants with thrombosis accompanied by antiphospholipid syndrome LMWH and antenatal thromproplaxis should be administered. It was shown that aspirin at low doses improved the course of pregnancy in pregnants with antiphospholipid syndrome and thus should be recommended for all pregnant with antiphospholipid syndrome. In patients with no previous miscarriage or thrombosis which cannot be attributed to antiphospholipid syndrome, in the presence of antiphospholipid antibodies, LMWH or low-dose aspirin is not needed. D-dimer test should not be used for acute VTE diagnosis during pregnancy. Begin thromboprophylaxis in prenatal period upon seeing intrauterine gestational sac in early pregnancy period. When a Woman with Mechanic Cardiac Valve and Thus Using Warfarin Gets Pregnant: It is recommended that in the first 12 weeks, the adjusted dose of LMWH /AFH (twice a day subcutaneous) be administered with anti Xa control; as of week 13, begin warfarin and when labour gets closer, again LMWH /AFH and prophylaxis are administered. 7 It can be used during the length of pregnancy including the first 12 weeks in pregnants with old-type valve and that underwent thromboembolism previously. 75-100 mg/day aspirin therapy can be added to anticoagulant therapy in pregnants with prosthetic valve and in those found to be highly risky in terms of thromboembolism. Table-2: Tromboprophylaxis in pregnants with previous VTE and/or thrombophilia Risk Groups Previous VTE and/or trombophilia Very high VTE occurred while taking warfarin for a long time Antithrombin deficiency Previous VTE and antiphospholipid syndrome 8 Prophylaxis Specialities to plan pregnancy management Antenatal high prophylactic dose LMWH and postnatal LMWH /warfarin for minimum 6 weeks Perinatologist High Moderate Previous recurrent or idiopathic VTE, Previous oestrogen associated (medicine or pregnancy) VTE, Previous VTE together with thrombophilia, Previous VTE together with VTE history in family Asymptomatic thrombophilia (combined defects, homozygous Factor V Leiden, homozygous protrombin gene G20210A) Pregnants meeting antiphospholipid syndrome criteria Previous single case of VTE accompanying temporary risk factors without thrombophilia, family history or other risk factors Asymptomatic thrombophilia (except for antithrombin deficiency, combined defects, homozygous Factor V Leiden, homozygous protrombin gene G20210A) 9 Recommend antenatal prophylactic LMWH and postnatal prophylactic LMWH for six weeks Perinatologist Consider antenatal LMWH (not recommended routinely), Recommend postnatal prophylactic LMWH for six weeks Recommend postnatal prophylactic LMWH for seven days (or 6 weeks if there is family history or other risk factors) Obstetrician and Gynaecologist C- THROMBOPROHYLAXIS DURING LABOUR PAIN AND LABOUR Risk factors should be assessed at the admission of pregnant who has not been followed up previously and for whom there is no management plan; medications required and their doses should be organized by specialists experienced in haemostasis and gestation (in line with principles set in Table 2). Pregnancy related prothombotic changes in coagulation system are at their maximum right after delivery. Thus in pregnants taking LMWH/AFH at therapeutic or high prophylactic dose, one day before induction, heparin dose should be reduced to thromprohylaxis dose and if appropriate should be continued during labour and delivery. If labour is planned, before labour, and if regional anaesthesia is going to be used, then at the beginning of labour pain, use of LMWH/AFH should stop minimum 12-24 hours in advance in line with the features of anticoagulation that is preferred. If regional anaesthesia techniques are going to be used in order to reduce the risk of hematom; regional anaesthesia techniques should not be used before at least 12 hours have passed from last LMWH /AFH prophylactic dose and before at least 24 hours have passed from last therapeutic dose. LMWH/AFH should not be used for 4 hours following the application of spinal anaesthesia or epidural catheter. After last injection, cannula should not be removed for 10-12 hours. Pregnants taking LMWH/AFH during prenatal period and with possibility of caesarean section should take 10 LMWH/AFH thromprophilactic dose one day before labour; however, operation should be performed before the pregnant takes the morning dose. D-POSTPARTUM CARE AND THROMBOPROPHYLAXIS First thromboprophilactic LMWH/AFH dose should be administered as soon as possible after making sure that there is no postpartum haemorrhage and no regional analgesia has been used. In the case of regional analgesia, thromboprophilactic DMAH/AFH dose should be administered 4 hours after postoperative/epidural catheter. If epidural catheter is kept after labour for postpartum analgesia, the catheter should be removed 10-12 hours after the administration of LMWH/AFH dose, and once it has been removed no LMWH/AFH dose should be administered at least for 4 hours. In the case of puerperants taking LMWH/AFH in prenatal period and having caesarean section, thromboprophilactic LMWH/AFH dose should be administered 4 hours after postoperative/epidural catheter. Even if risk factors against VTE have been assessed during pregnancy, risk factors should be reassessed in postpartum period. While assessing the risk factors, routine hereditary thrombophilia screening should not be conducted in asymptomatic cases. In the case of pregnant women with 3 or more of the risk factors (except for previous VTE or thrombophilia) indicated in Table 1 or with continuing risk factor, thromboprophilactic 11 LMWH/AFH therapy should continue for 6 weeks in the postpartum period. In the case of pregnant women with 2 or more of the risk factors (except for previous VTE or thrombophilia) indicated in Table 1 or with continuing risk factor, consider thromboprophilactic DMAH/AFH therapy for at least 7 days in the postpartum period. In the case of puerperants with additional extended risk factors (lasting longer than 7 days after delivery) (for instance, in the case of long hospitalization or wound infections) thrombophilia should be extended for up to 6 weeks or until additional risk factors disappear. In the case of pregnant women with thrombosis accompanied by antiphospholipid syndrome, LMWH and postnatal thromboprophylaxis should be administered. Especially in the case of pregnant women with other risk factors, suffering from antiphopholipid syndrome with repeated miscarriages, there is no need for 6-week LMWH therapy in the postpartum period, and it is appropriate to apply a therapy of minimum 3-5 days. Regardless of the mode of delivery, LMWH/AFH or warfarin and thromboprophylaxis and haematology consultation should be recommended for minimum 6 weeks in the postpartum period for all puerperants with previous VTE history. All puerperants with known hereditary or acquired thrombophilia should be recommended to take LMWH/AFH for minimum 7 days in the postpartum period even if they have not taken thromboprophylaxis during prenatal period. If there is family history or any other risk factor, thromboprophylaxis should be extended for up to 6 weeks. 12 LMWH and thromboprophylaxis should be administered to all women undergoing emergency caesarean section for 7 days in the post-operative period. If there exists one or more risk factors following elective caesarean section (such as above the age of 35, BMI >30) LMWH and thromboprophylaxis should be administered for 7 days. All peurperants with morbid obesity (BMI > 40 kg/m2) should be considered for prophylactic LMWH/AFH administration for 7 days in postpartum period. E- MEDICATIONS USED FOR THROMBOPROPHYLAXIS MEDICATIONS USED IN PRENATAL AND POSTNATAL PERIOD LMWH: It is the first option for postpartum thromboprophylaxis. LMWH is as effective as unfractionated heparin and more reliable than it. It is safe to use in breastfeeding women. Recommended doses per kilogram for low molecule weight heparin are administered in line with Table 3. Table 3: Recommended doses for low molecule weight heparin Weight (kg) < 50 Enoxaparin Dalteparin Tinzaparin 20 mg/day 2500 u/ day 3500 u/ day 50–90 40 mg/ day 5000 u/ day 4500 u/ day 91–130 60 mg/ day * 7500 u/ day * 7000 u/ day * 131–170 80 mg/ day * 10 000 u/ day * 9000 u/ day * > 170 0.6 mg/kg/ day * 75 u/kg/ day * 13 75 u/kg/ day * High prophilactic dose 50-90 kg 40 mg for 12 hours5000 u for 12 hours 4500 u for 12 hours Therapeutic dose Antenatal 1 mg/kg/12 hours 100 u/kg/12 hours 175 u/kg/day Postnatal 175 u/kg/day 1.5 mg/kg/day 200 u/kg/day * Can be prescribed by dividing into two doses. Unfractionated heparin: It has shorter half-life compared to LMWH, and its effect can be completely neutralised with protamine sulphate. In pregnants with high risk of thrombosis or under the risk of bleeding, unfractional heparin can be used, if needed, during labour, labour process. Unfractionated heparin increases the risk of heparin associated thrombocytopenia. It is safe to use in breastfeeding women. Heparin related thrombocytopenia: Even if risk changes according to the form used, all heparin preparations have the risk of heparin related thrombocytopenia. Thus regardless of its type, thrombocyte counts should be monitored closely on the 5th-14th days following the start of the use of medication in all patients taking heparin. Warfarin: Its use during pregnancy is limited to situations where use of heparin is not appropriate. As it penetrates placenta, risk of congenital anomaly is high. Thus, a characteristic warfarin embryopathy of 5% is observed in exposure in the period between the 6th and 12th weeks of pregnancy. It depends on the dose, and it is more likely to be seen among pregnants taking more than 5 gr of warfarin per day. Other complications associated with warfarin therapy during pregnancy: Spontaneous abortion, stillbirth, neurological problems in baby, fetal and maternal bleeding. 14 Warfarin can be used safely in postpartum and breastfeeding periods through close monitoring of coagulation. If antithrombotic therapy with warfarin is to continue in postpartum period, it is appropriate to conduct LMWH thromboprophylaxis for 5-7 days additionally after delivery until the blood level adequate for warfarin is reached. Other anticoagulants: In the presence of heparin associated reactions, fondaparinux and parenteral thrombin inhibitors can be used in a limited manner. Use of oral direct thrombin inhibitors and oral factor Xa inhibitors should be avoided. Fondaparinux, oral direct thrombin inhibitors and oral factor Xa inhibitors should not be used in breastfeeding women. Patients using LMWH during pregnancy or postpartum period for acute VTE therapy: If the weight of the patient is not extraordinary (such as below 50 kg or above 90 kg) and if there exist no other accompying factors (such as renal failure, recurrent VTE) routine measurement of anti-factor Xa activity is not recommended. As long as unfractionated heparin (AFH) is not administered, it is not required to count have routine thrombocyte count. Thrombocyte count should be monitored closely in pregnants taking AFH at therapeutic dose. F-LMWH/AFH CONTRAINDICATIONS Once bleeding and clotting risk assessment has been conducted carefully, LMWH/AFT use should be avoided in patients under the risk of bleeding, or therapy should stop or be postponed. Risk factors for bleeding: 15 1. Women with active bleeding in prenatal and postpartum periods 2. Women with risk of severe bleeding (such as placenta previa) 3. Women with bleeding diathesis (such as Von Willebrand, haemophilia or acquired caogulopathy) 4. Women with thrombocytopenia (thrombocyte count less than 75,000) 5. Women who have undergone acute stroke in the last 4 weeks 6. Women with severe kidney dysfunction (GFR<30 2 ml/minute/1.73 m ) 7. Women with severe liver dysfunction (those with prothrombin time above normal limits) 8. Women with uncontrolled hypertension (systolic blood pressure ≥200mmHg and diastolic blood pressure ≥120mmHg) G-ELASTIC COMPRESSION STOCKINGS Studies supporting the use of elastic compression stocking is limited. If swelling continues, use of graduated elastic compression stockings for two years following acute event should be recommended in order to reduce the risk of post-thrombotic syndrome risk. Furthermore, it is believed that its proper use during pregnancy and postpartum period will be useful in the presence of the following conditions: Pregnants/puerperants who are hospitalised for whom anticoagulan therapy is contraindicated, 16 Pregnants/puerperants hospitalised following caesarean section (in addition to LMWH/AFH therapy) and considered to be in high risk group for VTE (with previous VET history or with more than 3 risk factors) Outpatients with previous VTE history (in addition to LMWH/AFH therapy) Pregnants/puerperants that are to travel for more than 4 hours REFERENCES 1. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO; American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e691S-736S. 2. Royal College of Obstetricians and Gynaecologists (RCOG). Thromboprophylaxis during pregnancy, labour and after vaginal delivery. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2004 Jan. 13 p. (Guideline; no. 37). 3. Royal College of Obstetricians and Gynaecologists (RCOG). Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2009 Nov. 35 p. (Green-top guideline; no. 37a). 4. Royal College of Obstetricians and Gynaecologists (RCOG). Thromboembolic disease in pregnancy and the puerperium: acute management. London (UK): Royal College of 17 Obstetricians and Gynaecologists (RCOG); 2007 Feb. 17 p. (Green-top guideline; no. 28). 18 FLOWCHART-1: PLANNING OF TREATMENT IN THE PREGNANT WITH VENOUS THROMBOSIS 19 FLOWCHART-2: ANTENATAL ASSESSMENT FOR THROMBOPROPHYLAXIS IN PREGNANCY GEBELİKTE VENÖZ TROMBOPROFİLAKSİ İÇİN ANTENATALDEĞERLENDİRME 20 FLOWCHART-3: POSTNATAL ASSESSMENT FOR VENOUS THROMBOPROPHYLAXIS TROMBOPROFİLAKSİ İÇİN POSTNATAL 21 PREGNANCY AND CARDIOVASCULAR DISEASES MANAGEMENT GUIDELINE 22 A- GENERAL INFORMATION In the follow-up of 15-49 ages, the treatment and counseling service should start long before the conception for the women with suspicion of cardiac disease. Counseling services should be provided to the women with congenital heart defect, long QT syndrome, cardiomyopathy, aortic disease or genetic formation disorders. If there is no intention to get pregnant, the woman should be referred to a family planning clinic. Barrier (condom) methods and levonorgestrel releasing intrauterine devices are the safest and most effective birth control methods for the women with cyanotic congenital heart disease and pulmonary vascular disease. Each woman with the known or suspected congenital or acquired cardiovascular diseases should be subjected to risk assessment and should receive counseling service before the conception. Women with critical congenital heart disease should be monitored jointly by a perinatologist and cardiologist. Functional capacity, findings of examination, resting electrocardiogram, echocardiography should be checked in patients planning to get pregnant. For the women using medicine due to a known cardiac disease, which medicines are inconvenient, and which of them should be discontinued and/or changed during the pregnancy should be determined in advance. If necessary, the woman should be subjected to a risk assessment before getting pregnant in order to utilize the other treatment options, and the treatment should be reviewed. Hemodynamic problems can be observed in future phases of pregnancy. This information should be shared and a follow-up plan should be discussed with the patient (and her husband if possible). 23 In the presence of followings, it should be stated that pregnancy poses risk for the mother and the unborn baby, and therefore termination of the pregnancy should be discussed. The safest period for elective pregnancy termination is the first three months. o Severe left ventricular dysfunction (ejection fraction <30%, NYHA class III-IV ) o History of peripartum cardiomyopathy leaving residue dysfunction in the left ventricle o Cyanotic congenital heart disease o Pulmonary hypertension o Severe mitral stenosis o Severe aortic stenosis o Marfan syndrome with aortic root dilatation (>45 mm) o Bicuspid aortic valve where aorta diameter enlarges (>50 mm) o Severe coarctation of aorta It should be ensured that women with cardiac diseases should deliver at hospital. An experienced team should decide the method and place of delivery. It should be planned that delivery takes place at a centre where multidisciplinary approach can be followed. Vaginal delivery is preferred with individual delivery plan. Vaginal delivery by using epidural anesthesia, and selectively, instrumental delivery should be considered for the patients with severe hypertension. Caesarean section should be considered for the aortic disease where the aorta diameter enlarges more than 45 mm or which occur due to the obstetric requirements, in case of the severe aortic stenosis; in case of women who will deliver early while receiving the treatment of oral 24 anticoagulant treatment, and in case of the pregnants with Eisenmenger syndrome or severe heart failure. BIN WHICH SUSPECTED? CASES CARDIAC DISEASE IS Cardiovascular Risk Criteria for the Pregnants History: Dyspnoea Chest pain Tachycardia Cough Haemoptysis Syncope Background: Hypertension Taking antihypertensive medicine before conception History of Acute Rheumatic Fever History of congenital heart disease History of acquired heart disease Family History: History of sudden death in the family History of congenital heart disease in the family Coronary artery disease at early age in the family Blood Pressure: Systolic > 140 mmHg Diastolic > 90 mmHg Physical Examination: Cyanosis Nail clubbing Fine crackles in the lung Pathological heart sound 25 (additional sound/murmur) CCARDIOVASCULAR DIAGNOSIS TREATMENT METHODS DURING PREGNANCY AND Cardiovascular diagnosis during pregnancy: It is based on patient history, clinical research, electrocardiography, echocardiography (including transesophageal echocardiography) and exercise test (until reaching 80% of foreseen heart rate). Echocardiography: Each female patient having unexplained and recent cardiovascular symptoms and findings should have echocardiography scan. Radiation: Exposure to radiation should be avoided. Survivals without any abnormality or death are the most likely results for those who take doses of more than 50 m Gray within the first 14 days after the impregnation. Fetal risk increases for those who continue taking 50 mGray even after the first two weeks. MRI: Although magnetic resonance imaging without gadolinium is safe, there are limited numbers of data. CT: Computerized tomography is not recommended due to high dose of radiation. Checking the Fetus: Fetal ultrasound scan is carried out in order to check fetus in the families with cardiac diseases. We can make the diagnosis of congenital formation disorders in heart as early as the 13th week. Interventions: Unless it is an absolute necessity, interventions for the mother should be avoided during the pregnancy. It is preferable to postpone the percutaneous coronary intervention for a date after the fourth month of pregnancy. Heart surgery having the purpose of rescuing mother’s life is performed between 13th and 28th weeks in the best possible way. 26 However, delivery rather than surgery should be taken into consideration after the 28th week. 1- MONITORING OF HEART FAILURE AND CARDIOMYOPATHY (CMP) DURING PREGNANCY 1.1 PREPREGNANCY The women with congenital or acquired CMP should be subjected to risk assessment before the conception, and should be provided with individual counseling by the experts. If there is no intention to get pregnant, the woman should be referred to a family planning clinic. The women with congenital CMP should be provided with counseling about genetics. 1.2 PREGNANCY It should be monitored by a multidisciplinary team at the specialized centers. In addition to routine pregnant follow-ups and tests for the pregnants with heart failure, the cardiological follow-up should be carried out: Once a month until 28th week for the patients with mild heart failure, Biweekly for the patients with moderate-severe heart failure Once a week starting from the 28th week until the labour. Checking the pregnant woman suspected of heart failure: Shortness of breath is a common problem during pregnancy. Heart failure can be encountered, too. Severe dyspnoea, orthopnea, paroxysmal nocturnal dyspnoea, severe or 27 incremental peripheral oedema are signs of heart failure. In the event of heart failure findings (crepitant rale in the lungs, S3/S4 gallop, severity >3/6 murmur), she is referred to a cardiologist for diagnosis and for checking in terms of the continuity of pregnancy. Peripartum CMP occurs suddenly in the last month of pregnancy or within the first five months postpartum. As there is an inclination towards thrombophilia and an increase in the thromboembolic events during pregnancy, anticoagulant treatment should begin especially for the peripartum CMP patients. First 48 hours postpartum are of the highest-risk in severe valve diseases in terms of hemodynamic changes. Heart Failure Treatment during Pregnancy: Treatment of the pregnants with heart failure should be carried out by cardiologists. Physical treatment and salt intake of the patient should be limited. ACE inhibitors and angiotensin II receptor blockers should be discontinued. Special attention should be paid to the occurrence of heart failure, sudden death and arrhythmia during the pregnancy in the patients with hypertrophic CMP. The patients with mildsevere left ventricular outflow tract obstruction should be monitored by cardiologists, and beta blockers should be considered for treatment. When beta blockers are not tolerated, verapamil can be used alternatively. Emergency Management In pregnants with heart failure, the risk of acute decompensation increases in the second trimester of pregnancy. 28 The pregnants with acute decompensated heart failure should be referred to tertiary care services immediately. The patient is placed in a half sitting position, vascular access is established, and a catheter is inserted for urine tracking. If hypoxemia is detected, oxygen should be administered. If ıntravenous dıuretıc (20-40 mg of (20-40 mg bolus furosemide), systolic blood pressure >110 mmHg; İ.V. nitrat (i.e nitroglycerin may be started as 10–20 mg/mn and be increased to 200 mg/mn), if inotropic drugs are needed in the case of hypoperfusion or resistant heart failure; dopamine, dobutamin and levosimendan can be used 1.3 DELIVERY Delivery should take place at the hospital as monitorization is required during pregnancy and early postnatal period. Labour induction, management and postpartum observation require that experienced cardiologists, perinatologists, anesthesiologist and neonatologists supervise collectively in centers with intensive care units. 1.4 POSTPARTUM PERIOD The pregnant should be encouraged to continue breastfeeding despite taking medicine. However, breastfeeding is not recommended for the patients with peripartum CMP. Some ACE inhibitors (benazepril, captopril, enalapril) are tested in detail, and using them in mothers is safe for infants. As an indicator of kidney dysfunction, body weight of the infant should be monitored during the first 4 weeks. 2- FOLLOW-UP OF VALVE DISEASES IN PREGNANCY 29 2.1 PREPREGNANCY Patients with valvular heart disease background should be certainly examined by a cardiologist before conception and checked for the severity of valve disease. The women with critical heart disease should be monitored jointly by an experienced perinatologist and cardiologist. It should be kept in mind that there could be deteriorations in hemodynamic status of those pregnants with valve stenosis (mitral stenosis, aortic stenosis) especially depending on the increase in the volume of intravascular area in future gestational weeks. The severity of valve failure should be certainly determined before conception. It should be taken into consideration that the course of valve failure is better than valve stenosis. 2.2 PREGNANCY It should be kept in mind that a decrease in the effort capacity and an increase in the symptoms can be observed in the pregnants with valve diseases as of the second trimester especially, depending on the increase of intravascular volume. Effort capacity and symptoms of shortness of breath should be checked especially in the examinations of the pregnants with mitral and aortic stenosis. The patients with an increase in their complaints should be referred to the division of cardiology. The patients who are not checked for valve disease before conception but have the symptoms of shortness of breath, tachycardia, chest pain, syncope and decrease in effort capacity should be definitely examined in detail. The patients with suspicion of valve disease should be referred to the division of cardiology. 30 It should be known that mild systolic murmur can be heard especially in the apical area of the patients whose examination revealed that she does not have severe valve disease or who is considered to be normal in preconception assessment. As long as there is no increase in their complaints, the follow-ups of those patients should continue. As it is necessary to administer anticoagulants to the pregnants with mechanical prosthetic valve diseases, cardiologist, perinatologist and the patient jointly decide which medicine should be chosen. INR follow-ups of the patients using warfarin oral should be carried out under the control of a cardiologist. The pregnants using low molecular weight heparin should be monitored at better equipped centers where anti actor Xa levels are measured. The patients whose symptoms and findings have progressed significantly during pregnancy should be referred to a better equipped centre by taking valve disease complications into consideration. When a Women with Mechanical Cardiac Valve and Consequently Using Warfarin Gets Pregnant: It is recommended that she is administered the adjusted dose LMWH/AFH (twice a day, subcutaneous) for the first 12 weeks with the control of anti Xa; proceeds with warfarin, and administered prophylaxis with LMWH/AFH again towards the end of pregnancy. It can be administered to the pregnants with old type of valve, who had thromboembolism previously, during the entire course of pregnancy including the first 12 weeks. 31 75-100 mg/day aspirin treatment can be added to the anticoagulant treatment of the pregnants with prosthetic valve having high risk of thromboembolism. 2.3 DELIVERY Patients diagnosed with critical valve disease during pregnancy should deliver in the centers having cardiology department, perinatalogy and intensive care units. Caesarean section should be considered for the aortic disease where the aorta diameter enlarges more than 45 mm or which occur due to the obstetric requirements, in case of the severe aortic stenosis; in case of women who will deliver early while receiving the treatment of oral anticoagulant treatment, and in case of the pregnants with Eisenmenger syndrome or severe heart failure. For the pregnants with mild-severe valve disease, the method of delivery is determined in line with the recommendations of cardiology and perinatalogy departments. As symptoms can appear in these patients during the labour depending on the hypervolemia, it should be kept in mind that it is harmful to load intravascular area more than necessary. 2.4 POSTPARTUM PERIOD Medicines of the patients with a known valve disease or who need to use anticoagulants should be adjusted under the control of a cardiologist. It is recommended that penicillin prophylaxy should continue during and after pregnancy in the pregnants with rheumatic heart disease. 32 The first 48 hours following delivery are the most risky period for the critical valve patients in terms of hemodynamic changes. 3- OTHER CARDIOVASCULAR DISEASES 3.1 CONGENITAL HEART DISEASE (CHD) AND PULMONARY HYPERTENSION 3.1.1. HIGH RISK CONDITIONS: The pregnants with CHD who have the functional capacity of class III-IV or the functional capacity of whom has declined according to the functional classification of “New York Heart Association” (NYHA) are considered to be high risk patients in following conditions: a. Pulmonary Hypertension: In order to prevent hypoxia and acidosis, and the development of heart failure and hypotension, the pregnant should be monitored in the centers having experienced cardiology teams. b. Patients with Eisenmenger's Syndrome: The pregnancy of the patients with Eisenmenger’s Syndrome, peripartum mortality rate of which is high, must be terminated. This procedure is highly risky. If the patient insists on continuing the pregnancy, she should be referred to a more experienced and equipped centre. c. Cyanotic Heart Disease without Pulmonary Hypertension: In the event of hypoxemia (oxygen saturation is 80%) in mother, conception of the mother is contraindicated. If the pregnancy continues, the pregnant should be closely monitored at the experienced centers during pregnancy. 33 d. Severe Left Ventricular Outflow Tract Obstruction: The pregnancy is contraindicated for the patients with severe left ventricular outflow tract obstruction. 3.1.2. SPECIFIC CONGENITAL HEART DEFECTS: a. Atrial septal defect (ASD): Pregnancy is tolerated well by most of the patients with ASD. Contraindications of pregnancy in these patients are eisenmenger and pulmonary hypertension. The follow-up should be carried out by relevant centers. b. Ventricular Septal Defect (VSD): Developing with PH, VSD is a high risk condition for pregnancy. However, small perimembranous VSD can be tolerated in pregnancy. c. Atrioventricular (AV) septal defect: Cases of ventricular dysfunction and PH are considered to be of high risk for the pregnancy. These pregnants should be closely monitored at the experienced centers. d. Coarctation of aorta: In case of non-operated coarctation of aorta and residual hypertension following the repair, the risk of miscarriage and aorta and cerebral artery aneurysm rupture has increased. These pregnants should be closely monitored at the experienced centers. e. Pulmonary Stenosis (PS) and pulmonic regurgitation (PR): All of the pregnants with PS and PR should be referred to experienced centers where they are subjected to the required test for right ventricular functions. f. Tetralogy of Fallot: Surgical repair is necessary for the women with unrepaired tetralogy of fallot. They should be referred to experienced centers where thromboembolism, 34 endocarditis, heart failure and obstetrical complications, which can develop during pregnancy, can be diagnosed and treated. g. Epstein Anomaly: The pregnancy is well-tolerated for the patients with Epstein anomaly who do not have cyanosis and heart failure. However, the risk of premature birth and fetal mortality has dramatically increased in the patients with tricuspid insufficiency and right heart failure. The pregnant follow-ups should be carried out at experienced centers. h. Large artery transposition and corrected transposition: The follow-ups of the pregnancies with these diseases, especially the right ventricle functions, should be carried out at experienced centers. i. Fontan Circulation: If the fontan circulation cycle is not at optimum level, the pregnants should be referred to experienced centers in order to monitor the heart failure and arrhythmia. 3.2 CORONARY ARTERY DISEASE The pregnant previously diagnosed with coroner artery disease: The pregnants without clinical heart failure and residual ischemia can plan a pregnancy. The pregnants with coronary artery disease should be monitored at experienced centers. Actions to be taken before conception: Detailed Anamnesis: Chest pain, shortness of breath, functional capacity, previous myocardial infarction and revascularization history should be checked. Physical Examination: Blood pressure, heart rate, additional sound, murmur, heart failure findings should be checked. 35 It should be asked which medicines are used (Acetylsalicylic acid B-Blocker can be used safely. ACE inhibitors, angiotensin receptor blockers, rennin inhibitors should be discontinued.) ECG scan should be carried out. The pregnant should be referred for the expert review (Evaluation of LV functions, effort test or residual ischemia analysis through exercise echocardiography). EMERGENCY MANAGEMENT Actions to be taken for the pregnant presenting with Acute Coronary Syndrome Clinic: ECK and vital signs (pulse, blood pressure) should be checked immediately. In case of hemodynamic disturbance: The pregnant should be immediately referred to a better equipped centre (preferably, to a centre with fullfledged Percutaneous Coronary Intervention (PCI)). In case of ST Elevation/Left Bundle Branch Block: Nonenteric coated acetylsalicylic acid should be administered. The pregnant should be immediately referred to a centre with fullfledged percutaneous coronary intervention. ST depression in ECG: The pregnant should be immediately referred to a better equipped centre (preferably, to a centre with PCI). There is no change in ECG: If rapid troponin test can be carried out, then troponin should be checked. o If positive, the pregnant should be immediately referred to a better equipped centre (preferably, to a centre with PCI). o If negative, the pregnant should be referred for the expert review. o If rapid troponin test is not available, the pregnant should be immediately referred for the expert review. 36 3.3ARYTHMIA The pregnant and women in reproductive age group are at higher risk of arrhythmia. Arrhythmia frequently reappears during the gestation period of women having chronic supraventricular and ventricular tachycardia. Deterioration of hemodynamics poses a risk for the health of infant and baby. Approach to the pregnant diagnosed with tachyarrhythmia: During pregnancy, sinus tachycardia or arterial or ventricular ectopic pulses are frequently observed. These conditions are generally associated with benign prognosis. In case of supraventricular and ventricular tachycardia: 1. When tachycardia is detected, vital signs of the pregnant should be checked, and her hemodynamic condition should be evaluated. 2. Treatment of the tachycardia causing hemodynamic disturbance is emergency cardioversion during pregnancy. 3. If the vagal manoeuvres fail, paroxysmal supraventricular tachycardia (SVT), which does not cause hemodynamic disturbance, adenosine and IV metoprolol can be used. 4. For the long-term treatment of SVT, oral digoxin or metoprolol/ propranolol are recommended. 5. Atenolol should not be used for any kind of cardiac arrhythmia. Approach to the pregnant diagnosed with bradyarrytmia: The pregnants can have sinus bradyarrytmia arising from lying on their backs. In this case, the mother should lie on her left side. In case of severe bradyarrytmia causing symptoms, the pregnant should be immediately referred to a better equipped centre. 3.4 INFECTIVE ENDOCARDITIS PROPHYLAXIS 37 With the current changes in the guidelines, same measures taken for the non-pregnant patients are applied. Endocarditis prophylaxis is recommended for patients whose risk of developing only endocarditis is still at maximum level (e.g. dental surgery). Antibiotic prophylaxis is recommended during vaginal delivery or caesarean section. D- FREQUENTLY USED MEDICINES DURING PREGNANCY Use of cardiovascular (CV) drug becomes obligatory in some cases. Physicians should make prudent choices by taking typical characteristics and potential adverse effects of the drug into consideration. Most frequently used CV drugs and their effects during pregnancy are summarized in the table below. When administering drug to the pregnant, its FDA category should be known. Classification ranges from A (the safest) to X (the unknown). Following categories are used for gestational and breastfeeding periods: Category B: Although studies on reproductive system in animals do not show any fetal risks controlled studies on the pregnant women have not been conducted. Furthermore, the adverse effect which was determined in the studies on the reproductive system of animals was not confirmed by controlled studies on women. Category C: Although animal studies have revealed that they had negative effects on fetus, controlled studies on women or any study on women and animals have not been conducted. The medicines which have more potential benefits than potential risks should be used. Category D: Although there is evidence of fetal risk the benefits of using it in the pregnant women are accepted despite this risk (e.g. treatment of life-threatening disorders). 38 Category X: Based on the experiences on animals or human, it has been demonstrated that there are abnormalities in fetus. There are evidences of risk both in human and animal studies. The risk of using it in pregnant women exceeds any potential benefits. It is not recommended that pregnant or fertile women take it. Group of medicine Medicines FDA category Possible adverse effects Getting into placenta Getting into breast milk (fetal doses) ACE-inhibitors Captopril Benazepril Enalapril Lisinopril Perindopril Ramipril Silazopril Teratogenicity (renal or tubular dysplasia, fetal hypocalvaria, etc.) Fetotoxicity (anuria-related oligohydramnios and induced pulmonary hypoplasia, extremity contractures, D persistent PDA, defects of skull ossification, intrauterine growth retardation, anemia, intrauterine fetal death, premature and severe neonatal hypotension) Angiotensin II Receptor Blockers 39 Yes It gets into (maximum 1.6%) Losartan Valsartan Olmesartan Irbesartan Candesartan D Teratogenicity (renal or tubular dysplasia, fetal hypocalvaria, etc.) Fetotoxicity (anuria-related oligohydramnios and induced pulmonary hypoplasia, extremity contractures, persistent PDA, defects of skull ossification, intrauterine growth retardation, anemia, intrauterine fetal death, premature and severe neonatal hypotension) Unknown C (D for Atenolol) Bradycardia and hypoglycaemia in fetus. [hypospadias with Atenolol (in the first three months); in fetus: birth defects, low birth weight (in the second and third months), intrauterine growth retardation and decrease in placenta weight for those with ISA negative] Yes Beta-Blockers Propranolol Bisoprolol Nebivolol Carvedilol Atenolol* Calcium Channel Blockers Amlodipin Even though the Isradipine experience is limited, C Nifedipine they are wellDiltiazem tolerated. Isradipine 40 Yes Unknown It gets into It gets into Verapamil may induce potential synergism hypotension with magnesium sulphate. It may be related to a more severe hypotension risk and fetal hypoperfusion in intravenous use. Diuretics (As they are characterized by gestational hypertension hypovolemia, it is not convenient to use them.) It is wellFurosemid C tolerated, Hidroklorotia B milk zid B production Oligohydramnios Yes Indapamid may decrease. Aldosterone Antagonists Spiranolacto n Statines Atorvastatin Fluvastatin Pravastatin Rosuvastatin Simvastatin D X Teratogenicity (cleft palate, first 3 months), Fetotoxicity (antiandrogen effects) Yes It gets into (maximum 1.2 %) milk production may decrease. Unknown, using them during pregnancy is considered as contraindication. There is risk of congenital anomaly. Yes Unknown Fibrates 41 Fenofibrates Gemfibrozil Bile Resins Colestipol, Cholestyrami ne C Unknown C They can disturb the absorption of fat soluble vitamins (e.g. Vitamin K), cerebral haemorrhage (in newborn). Yes Unknown Yes It gets into – it lowers the level of fat soluble vitamins. Antiaritmics There is no notified teratogenicity; the level of serum should not be trusted Hypothyroidism (9%), hyperthyroidism, goitre, bradycardia, growth retardation, premature delivery. C Amiodarone D Lidocaine C Meksiletin C Fetal bradycardia, acidosis, central system toxicity. Fetal bradycardia Propafenone C Unknown Yes Sotalol B Bradycardia and hypoglycaemia in fetus (limited experience). Yes It gets into Quinidine C Thrombopenia, premature delivery, VIII. nerve toxicity Yes It gets into They do not have any known teratogenic Yes It gets into (without Anticoagulative agents Aspirin B (Low dose) 42 Yes It gets into Digoxin Yes Yes Yes It gets into It gets into It gets into It is transferred Heparin B Lowmolecularweight heparin (Enoxaparin, etc.) B Clopidogrel C Ticlopidine C Warfarin X (Accordin g to ESC, D) Vasodilator agents Isosorbit dinitrat B Nitroglycerin e Hydralazine C Methyldopa B effects (broad data series) Long-term administration, continuous administration, osteoporosis and thrombocytopenia. Long-term administration, rarely osteoporosis, less thrombocytopenia when compared to UF heparin. There is no information on using it during pregnancy. There is no information on using it during pregnancy. Embryopathy in the first 3 months, bleeding if used late. No adverse effect has been observed in animals. The effects in human are unknown. Adverse effect in mother: symptoms similar to those of the lupus, fetal tachyarrhythmia. Mild neonatal 43 any problem) No It does not get into. No It does not get into. Unknown Unknown Unknown Unknown Yes It gets into (maximum 10%); Metabolite is well tolerated. Unknown Unknown Yes It gets into (maximum 1%) Yes It gets into. hypotension. Pulmonary Hypertension Medicines Teratogenic effects in animals are Bosentan X demonstrated. There is no data on human. It is reported that there is no problem in using Iloprost C it during pregnancy. There is not sufficient data. It is reported that there is no problem in using Sildenafil B it during pregnancy. There is not sufficient data. Yes Unknown Unknown Unknown Unknown Unknown REFERENCES: 1- 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). Eur Heart J. 2011 Dec;32(24):314797. 2- Gebelik ve Kalp Hastalıkları Video Konferans; http://www.tkd.tv.tr/FormVideo.aspx?category=3 44 45 MANAGEMENT GUIDELINE for PREGNANT WOMEN with DIABETES 46 PREPREGNANCY For 15-49 age follow-up, the importance of monitoring diabetic pregnant women before conception and providing them with counseling services should be emphasized, and cases should be assessed in accordance with risk groups. If there is no intention to get pregnant, the woman should be referred to a family planning clinic. 1) In case of women with body-mass index ≥ 25 kg/m2, if they belong to any of the below-mentioned risk groups, their Fasting Plasma Glucose (FPG) should be checked once a year (They should not be diagnosed through glucometer) Diabetes in immediate family Those who have delivered a big baby or previously diagnosed with Gestational Diabetes Mellitus (GDM), Hypertensive (Blood Pressure ≥140/90 mmHg), Dyslipidemics (HDLcholesterol ≤35mg/dl or triglyceride≥250 mg/dl), Previous Impaired Fasting Glucose (IGT) or Impaired Glucose Tolerance (IGT), Polycystic Ovarian Syndrome (PCOS), Bad obstetric history, Intrauterine death history, Clinic disease or findings on insulin resistance (acanthosis nigricans), Coronary, peripheric or cerebral vascular disease, Born with low birth weight, Sedentary lifestyle or little physical activity, Dietary habits with high-saturated fat and low-fiber foods, Schizophrenic patients and those who use atypical antipsychotics and other diabetogenic medicine (steroid, etc.). 47 2) If there is history of diabetes in the family of the women with body-mass index ≥ 25 kg/m2 or they are diagnosed with diabetes mellitus, they should be checked biennially. 3) Fasting Plasma Glucose level <100 mg/dl should be considered “normal”. If this figure is between 100 and 200, it should be considered “impaired”. If it is ≥126 mg/dl, it should be considered “diabetic”. The required interventions should be made according to general medical rules. 4) Counseling services should be provided for those whose Fasting Plasma Glucose is determined as impaired fasting glucose between 100-125 mg/dl. It should be ensured that obese people lose weight. 5) The people with Fasting Plasma Glucose≥126 mg/dl should be referred to an endocrinologist (if not available, they should be referred to an internist). If they intend to get pregnant, they should be referred to a perinatologist (if not available, they should be referred to an obstetrician and gynaecologist). THE PREGNANT WITH PREGESTATIONAL DIABETES Prepregnancy Follow-up; All pregnant women with diabetes should be informed about possible metabolic problems. The pregnant women should be recommended to receive help from medical personnel before conception. If not available, they should be referred to endocrinologist (if not, to an internist) and perinatologist (if not, obstetrician and gynecologist). Counseling should be provided about the requirements of planned pregnancy, the importance of 48 glycemic control and cessation of medicines which might have embryotoxic and teratogenetic effects. In such conditions as bad blood glucose regulation; patients with HbA1C ≥ 7%, patients with unstable fasting and postprandial blood glucose, patients using oral antidiabetic, patients suffering from diabetes for more than five years should see an endocrinologist. Subsequent follow-ups should be conducted in accordance with the recommendation of a specialist. The pregnancy should be certainly planned and glycemic control should be carried out (A1C≤ 6.5% (preferably %6.0≤) APG ≤95 mg/dl, postprandial 1st and 2nd hours, ≤120 mg/dl, it can be tolerated up to 140 mg/dl). 0.4 mg/day of folic acid should be administered three months before the conception, and it should be used throughout the first trimester of pregnancy. Embryopathy medicines should be ceased before conception or replaced with nonteratogenic medicines (ACE inhibitors, thiazide-type diuretics, angiotensin II receptor blockers (ARB) and statines). The patients using oral antidiabetic medicine should proceed with prepregnancy insulin. Diabetic women who want to get pregnant should be examined by ophthalmologist before conception. Diabetic women who want to get pregnant should be scanned for nephropathia. If microalbuminuria or apparent nephropathia is determined, optimal glycemic control and blood pressure control should be carried out in order to prevent complications in mother and fetus and to delay the progression of nephropathia. Maternal diabetes is not a risk factor for aneuploidy. Down syndrome diagnosis and scan should be carried out in the same way as with general population. However, it should be kept in 49 mind that the tests carried out in the second trimester should be adjusted as the serum α-fetoprotein (AFP) and unconjugated estriol (uE3) levels are low. Type 1 and Type 2 diabetes should also be diagnosed Pregnancy follow-up: The pregnants in the high-risk group (*brittle diabetes, those who suffer from diabetes for more than five years, those with 7% and above HbA1C level, those who have bad obstetric history) should be examined by an endocrinologist and perinatologist if possible. ---------------------------* Diabetic pregnants for whom unexpected hypoglycaemia is observed when insulin dose is increased by two units and unexpected hyperglycaemia is observed when insulin dose is decreased by two units. In addition to the routine follow-up and tests of diabetic pregnant: First follow-up: Perform it within the first 6-8 weeks. Carry out the following procedures and tests, or ensure that they are carried out. o Carry out an ultrasound scan to check whether the fetus is alive and to determine the gestational age. Analyze it in terms of genital pathologies. o Measure the level of HbA1C1. o Check the thyroid functions. o Retinal evaluation should be conducted by an ophthalmologist. 1 HbA1c≤ %6.5 (preferably %6.0) 50 o Ensure that the renal evaluation2 is conducted. o Have ECG scan. o Have urine culture test and inform patient about the complications of diabetes and diet, exercise, medication, and train the patient on self-glucose monitoring. Ensure that patients with poor feeding, HbA1C3 level ≥ %7, TSH ≥2.5 mU/l, retinopathy, kidney dysfunction and proteinuira, coronary artery disease are examined by an endocrinologist and perinatologist if possible. Second follow-up: Perform it within the 11-14th gestational week. Conduct the glycemic check 3,4. If cannot be checked, ensure that it is evaluated by an endocrinologist. Refer them to a perinatologist in order to carry out the ultrasonographic evaluation and the first trimester screen test of fetus. Third follow-up: Perform it within the 16-18th gestational week. Carry out fetal anomaly screening, or ensure that it is carried out. Carry out the following test, or ensure that they are carried. 2 RENAL EVALUATION Microalbumin/creatinin levels in spot urine are checked. This figure ‹30 µg/mg normal 30-300 µg/mg microalbuminuria >300 µg/mg macroalbuminuria 3 HbA1C≤ 6.5% (preferably 6.0%) 4 GLYCEMIC CONTROL Premeal blood glucose 60-100 mg/dl 1st and 2nd hour, preferably ≤120 mg/dl (It can be tolarable up to 140 mg/dl)(It should be counted as of the first bite) 51 o Carry out the glycemic check. o Carry out HbA1C measurement. o Carry out triple test. Carry out the retina control check those with retinopathy, or ensure that it is carried out. Carry out renal evaluation for those with nephropathy, or ensure that it is carried out. Fourth follow-up: Perform it within the 22-24th gestational week. Ensure that perinatologist carries out an expanded cardiac screening in addition to fetal anomaly screening. Carry out glycemic control, or ensure that it is carried out. Fifth follow-up: Perform it within the 28th week. Evaluate pregnancy through USG. Carry out glycemic check, or ensure that it is carried out. Measure HbA1C. Carry out the retina check for those with retinopathy, or ensure that it is carried out. Carry out renal evaluation for those with nephropathy, or ensure that it is carried out. Sixth follow-up: Perform it within the 32nd gestational week. Carry out the following procedures and tests, or ensure that they are carried out. o Carry out glycemic check, or ensure that it is carried out. o Check the fetal growth and amniotic fluid volume through USG. Carry out fetal doppler if available 52 o Carry out fetal monitorization5 Seventh follow-up: Conduct it within the 34th gestational week. Carry out glycemic check. Carry out fetal monitorization. Eight follow-up: Perform it within the 36th gestational week. Carry out the following procedures and tests, or ensure that they are carried out. o Carry out glycemic check. o Carry out fetal monitorization. o Measure HbA1C. o Carry out the retina check for those with retinopathy, or ensure that it is carried out. o Carry out renal evaluation for those with nephropathy, or ensure that it is carried out. Ninth follow-up: Perform it within the 37th gestational week. Carry out glycemic check. Carry out fetal monitorization. Tenth follow-up: Perform it within the 38th gestational week. Carry out glycemic check. Carry out fetal monitorization 5 Fetal Monitorization Fetal movement counting NST Biophysical profile 53 Carry out USG for fetal weight estimation. Ensure that patients with suboptimal glycemic check and/or the pregnants with additional disease (hypertension, nephropathy, retinopathy, preeclampsia, Intrauterine Growth Retardation) should be evaluated by a perinatologist in order to determine delivery method and time. Eleventh follow-up: Perform it within the 39th gestational week. Recommend labour induction for the pregnant women whose estimated fetal weight is below 4000 grams. Inform the pregnant women whose estimated fetal growth is above 4000 grams and fetal abdominal circumference is above 360 mm about delivery risks. Determine the delivery method after evaluation. Take into consideration not only USG but also clinical findings and pelvic examination finding when evaluating fetal weight through USG in these weeks as it can cause mistakes. GESTATIONAL DIABETES MELLITUS (GDM) All pregnants should undergo “Glucose Screening Test” between the 24 - 28th weeks. OGTT should be applied to the pregnant women having Fasting Plasma Glucose levels between 100-126 in the first application week of gestation. Available Screening Tests: 1- 50 grams glucose screening test o Fasting and postprandial states do not make any difference for the test. It can be applied when the pregnant presents herself to hospital. 54 o 50 grams of glucose is melted in 100-200 cc of water. After squeezing half lemon, it is drunk in one sip. 60 minutes later, plasma glucose is measured. o The pregnants, whose 50 grams glucose screening test results are above APG ≥140 mg/dl, should take Oral Glucose Tolerance Test (OGTT) with 100 grams of glucose into an empty stomach in another day. o The pregnants, whose 50 grams glucose screening test results are APG ≥180 mg/dl, are considered diabetic. It is not necessary for those patients to take OGTT. o If the results reveal that standard limits are exceeded in at least two of the below-stated hours in 100 grams of OGTT, they are diagnosed with GDM: APG ≥95 mg/dl, 1st hour ≥180 mg/dl, 2nd hour ≥155 mg/dl, 3rd hour ≥140 mg/dl o In the event that only one of the levels is high in 100 grams of OGTT, it is considered as impaired glucose tolerance (IGT) and the patient is referred to an endocrinologist (if not available, the patient should be referred to an internist.) 2- 75 grams Oral Glucose Tolerance Test o Following at least 8 hours (ideally 10 hours) of night fasting, preprandial blood glucose of the pregnant is checked before drinking 75 grams of oral glucose. o 75 grams of glucose is melted in 100-200 cc of water. After squeezing half lemon, it is drunk in one sip. 60 minutes and 120 minutes later, plasma glucose is measured. o If the results reveal that standard limits are exceeded in at least one of the below-stated hours in 75 grams of OGTT, they are diagnosed with GDM: 55 APG≥92 1st hour ≥180 mg/dl, 2nd hour ≥153 mg/dl, During the loading tests, the patient should be in sitting position, should not perform any activities, should not eat and smoke. The patients, who cannot tolerate glucose and vomit, should be tested again. There is no need for additional follow-ups apart from routine pregnancy follow-up for the patients with GDM, whose glucose level runs its course only with diet therapy and who do not have any complications (macrosomia, preeclampsia, growth retardation, poly/oligohydramnios, etc.). The patients with GDM, who use insulin, should be considered high-risk patients, and the protocols used for gestational diabetic patients should be followed. LABOUR PAIN AND LABOUR IN PREGNANTS WITH DIABETES The moment when labour is induced, insulin resistance disappears in the patients with pregestational diabetes and gestational diabetes. When the labour is induced, administer infusion equivalent to 5-7.5 grams of glucose per hour and administer 1-1.5 units of insulin infusion per hour to the patients (GDM and pregestational diabetes) who have used insulin during pregnancy. Put 5 units of regular insulin into 500 cc 5% dextrose, and administer at least 100 cc per hour. Rate of infusion and the amount of insulin to be added into liquid should be adjusted according to blood glucose. Continue using insulin liquid until oral intake begins. During labour pain, avoid maternal hyperglycemia and keep the intrapartum glucose at the level of 70-110 mg/dl. During labour pain, measure capillary glucose per hour. 56 POSTNATAL FOLLOW-UP OF THE PREGNANTS WITH DIABETES Monitor in accordance with the Postnatal Care Management Guideline. Encourage the mother to breastfeed early and frequently. Gestational Diabetes Mellitus; Keep the patients with GDM at hospital at least for 24 hours even though there is no complication. Measure fasting and postprandial blood glucose for 24 hours and 48 hours following vaginal delivery and caesarean section respectively. The required treatment should be applied to the patients with high levels of course. The patients whose results are normal should take two-hourOGTT with 75 grams of glucose between 6th and 8th weeks following delivery The patients having high levels in 75 grams of OGTT should be referred to an endocrinologist (if not available, the patient should be referred to an internist.) APG<100 mg/dL and OGTT 2.st PG<140 mg/dL APG<100 mg/dL and OGTT 2.st PG 140-199 mg/dL APG 100-125 mg/dL and OGTT 2.st PG<140 mg/dL APG 100-125 mg/dL and OGTT 2.st 140-199 mg/dL APG≥126 mg/dL and OGTT 2.st PG≥200 mg/dL 57 Normal Isolated IGT Isolated IFG IGT+IFG Apparent Diabetes Inform the individuals about the risk of developing type 2 diabetes in the subsequent pregnancies and in the upcoming years. Underline the importance of exercise, weight control and long-term follow-up. Lay emphasis on complying with the recommendations of type 2 diabetes screening and diabetes prevention. It is also important to note that they should be monitored again when they plan to get pregnant. Pregestational Diabetes; Readjust the treatment by taking preconceptional insulin dosages into consideration. At the end of postpartum period (in the 6th week), they should consult to an internist. 58 EPILEPTIC PREGNANT MANAGEMENT GUIDELINE 59 Preconception 1) In the follow up of women of 15–49 years of age, epileptic women should absolutely get counselling from the health personnel before becoming pregnant. Within the scope of counselling, information should be provided about the effect of pregnancy on epilepsy, how the drugs used for epilepsy affect pregnancy, whether it is necessary to change medications and the dose and interference of medications. The importance of regular follow-up and counselling should be emphasized. If there is no demand for pregnancy, the woman should be referred to a Family Planning Clinic. 2) In the preconception period, the opinions of a neurologist and a gynecologist should be received and the follow-ups in the preconception period, during pregnancy and postconception period should be conducted by these branches. 3) Pregnancy should absolutely be planned. Programs of medication change should be completed at least 6 months before the patient becomes pregnant. Monotherapy should be preferred and antiepileptic drugs should be recommended at the lowest dose possible. 4) 3 months before the patient becomes pregnant, a daily supplement of folic acid of 400 mcg should be initiated to minimize the malformations that may befall the infant and this supplement should be continued till the end of the tenth gestational week. 5) Antiepileptic drug should definitely be managed by a neurologist. The dose and active ingredient of the drug should not be changed without consulting the neurologist. The drugs 60 used in epilepsy treatment and their side effects are indicated in the table below. 6) Carbamazepine and Lamotrigine which pose lower risks are preferably used according to the type of seizure. Phenytoin and Valproate can only be used when their use is absolutely necessary at the appropriate dosage and by receiving the consent of the patient. Drug Potential side effects Valproate Spina bifida aperta, Cardiovascular complications, urogenital malformations, skeletal disorders, mental retardation Phenytoin Congenital heart disease, urogenital defect, face fissures, dysmorphic face, distal phalangeal hypoplasia Carbamazepine Neural tube defect, heart defect, hypospadias, knee dislocation, Inguinal hernia Lamotrigine Cleft palate Levetiracetam Limited study Zonisamide Limited study FDA category D D D C C C PRENATAL CARE 1) First follow-up: Do the first follow-up in 6th-8th gestational weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. 61 If preconception counselling has not been received, provide the patient with counselling. Right after the determination of the pregnancy, make sure that a neurologist controls the patient. 2) Second follow-up: Do the second follow-up in 11th–13+6 day gestational weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. In addition to the medical examination and other examinations that are in line with the guideline, the patient should be assessed by a perinatologist if possible. (measurement of NT (nucal translucency) through ultrasound and early anomaly screening) 3) Third follow-up: Do the third follow-up in the 16th gestational week. Monitor the pregnant in line with Prenatal Care Management Guideline. In addition to the medical examination and other examinations that are in line with the guideline; the level of α-fetoprotein is measured by looking at the MoM value. Triple-quadruple screen tests can also be used to that end. Refer the pregnants with a high level of αfetoprotein to the perinatologists. 4) Fourth follow-up: Do the fourth follow-up in 18-22nd weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. In addition to the medical examination and other examinations that are in line with the guideline; a general anomaly screening should be conducted and especially the development of heart should be well assessed and if possible recommend an echocardiography for the patient. Make sure that a perinatologist controls the patient. 62 Hold a consultation with a neurologist about the drug, blood level and the overall situation. 5) Fifth follow-up: Do the fifth follow-up in 24-28th weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. 6) Sixth follow-up: Do the sixth follow-up in 32-34th weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. 7) Seventh follow-up: Do the seventh follow-up in 36-38th weeks. Monitor the pregnant in line with Prenatal Care Management Guideline. Hold a consultation with a neurologist about the drug, blood level and the overall situation. Make sure that the delivery is conducted at hospital. The gynecologist determines the mode of delivery according to obstetric indications. EMERGENCY MANAGEMENT No matter in what week of pregnancy the pregnant is, if she has seizures, she should be assessed by a neurologist. If you see a status table that includes generalized tonic clonic seizures (Having 2 seizures within 5 minutes with ongoing loss of consciousness), the patient should be referred immediately after having performed the following interventions: Airway of the patient is opened. Respiration is ensured. The patient is administered oxygen. 63 The circulatory system is stabilized. Vascular access is established, fluid is administered and blood glucose level of the baby is measured and if there is hypoglycemia, this problem is addressed. Diazepam or midazolam should be the first choice. Diazem of 10 mg IV should be administered in such a way as to finish within 5-10 minutes. Midazolam of 0.05- 0.1 mg/kg IV should be injected slowly. If the seizure is continuing, 10 minutes after the first injection same dose of diazepam or midazolam IV should be injected slowly (If it is injected fast, there is the possibility of exitus due to respiratory depression.) Although the seizure stops as soon as diazepam/Midazolam IV is injected, you should proceed with the phenytoin step. Pehnytoin is added into normal saline of 100-150 cc at a dose of 18-20 mg/kg (4-6 ampoules on average) within 3-45 minutes (level of 50 mg per minute should not be exceeded). The pregnant is monitored during infusion for arrhythmia. If arrhythmia develops, the medication is discontinued immediately. If necessary, antiaritmic medication is administered and consultation is demanded of a cardiologist. While all of these procedures are being conducted, consultation is demanded of the neurologist. In this case, contact is made with 112 and the pregnant is referred by being accompanied by a doctor. POSTNATAL CARE 64 The puerperant should be monitored in line with Postnatal Care Management Guideline. The mother should proceed with breastfeeding despite using medication. The puerperant should be seen by a neurologist in the postpartum 1-3rd weeks for a change of dose and medication. 65 MANAGEMENT GUIDELINE FOR PREGNANTS WITH ASTHMA 66 GENERAL INFORMATION Asthma is a common and chronic inflammatory disease. The cause of the disease is unclear and it is characterized by airway inflammation, bronchial hyperactivity and diffuse reversible airway obstruction. The said inflammation causes stertorous respiration, shortness of breath, feeling of pain in the chest and cough in the form of repetitive attacks especially at night and/or in the morning. The symptoms are accompanied by airway obstruction that gets better by itself or through treatment. Due to the existing inflammation, hypersensitivity occurs in airways against certain stimuli. Asthma prevalence is between 2-17% in different countries of the world. This rate is 8-11 % in women of fertility age. In adults in our country the rate is 2-6%. Although the number of asthmarelated deaths decreases gradually, there is an increase in its prevalence and morbidity. Asthma is seen in around 4-8% of all pregnancies. These two conditions affect the course of each other. The effect of pregnancy on asthma is changeable, in one third of the phenomena asthma deteriorates, in another one third it gets better and in the last one third there is no change in the course of asthma. Taking asthma under control through an appropriate treatment is very important in terms of pregnancy complications and fetal risks. In pregnants with asthma who also have allergic rhinitis, the symptoms of rhinitis may increase especially in the third trimestre. In this case nasal steroid can be included in the treatment. Mild and moderate asthma under control does not pose an important risk against maternal and infant health. However, asthma that is not under control and severe asthma may cause increased prematurity, preeclampsia, low birth weight, fetal growth restriction, the obligation to have caesarean section and other perinatal complications. The main purpose of 67 asthma treatment during pregnancy is to make sure that the fetus gets enough oxygen by preventing asthma attacks. The principles of asthma treatment to be administered during pregnancy are no different from those that are valid in the normal period. This process is composed of training the patient, avoiding triggers and pharmacological treatment. Preconception 1) In the follow up of women of 15–49 years of age, women with asthma should absolutely get counselling from the health personnel before becoming pregnant. Within the scope of counselling; information should be provided about the effect of asthma on pregnancy, the effect of pregnancy on asthma, how the drugs used for asthma affect pregnancy, whether it is necessary to change medications and the dose and interference of medications. The importance of regular follow-up and counselling should be emphasized. If there is no demand for pregnancy, the woman should be referred to a Family Planning Clinic. 2) In the preconception period, the opinions of a pulmonologist and a gynecologist should be received and the follow-ups in the preconception period, during pregnancy and postconception period should be conducted by these branches. 3) The pregnancy should be planned when the asthma is under control. 4) The medication should not be discontinued. The medications should definitely be managed by a pulmonologist. The dose and active ingredient of the medications should not be changed without consulting the pulmonologist. 68 PREGNANCY It is safer for a pregnant with asthma to use asthma medications during pregnancy when compared to risks that may be caused by uncontrolled asthma and attacks that may develop when the patient is not treated. Pregnants with asthma should be monitored in line with the prenatal care management guideline. And in addition to these follow-ups regarding asthma; The pregnant with asthma should be informed of the fact that asthma medications are safe and that if she uses her medications regularly, she will have a healthy pregnancy and that otherwise, uncontrolled asthma may do more damage to the fetus. The main purpose of asthma treatment during pregnancy is to prevent hypoxic attacks in the mother to make sure that the fetus is oxygenated to a sufficient extent. Asthma is assessed through symptoms and respiratory function tests. The follow-up of the pregnant whose asthma is under control should be assessed by a pulmonologist every trimestre including once before the delivery. Then, a decision is made on whether the disease is under control and the medication is adjusted accordingly. Patients whose asthma is not under control or patients with severe asthma should be followed up more frequently as they carry an increased risk in terms of pregnancy complications. Pharmacological treatment is administered in the form of step treatment. The control level is determined in line with the frequency of symptoms and SFT finding and the doses of medications can be increased or decreased. 69 The principles of maintenance treatment and attack treatment in pregnants with asthma are no different than non-pregnant patients. Asthma medications are divided into two groups as control drugs (inhale steroids, long-acting agonists, LTRA, teophylline) and those used to eliminate symptoms (salbutamol, terbutalin). For a pregnant with asthma the first choice is inhale corticosteroids from the group of control drugs and among them preferably budesonides (pregnancy category B). If asthma is not under control or if the pregnant has severe asthma, other control drugs can be included in the treatment as in the case of non pregnant asthma patients. The recommended saving treatment for pregnants with asthma is inhale salbutomol or terbutalin. (Pregnancy categories C). In order to take asthma under control in pregnants with asthma, triggers like cigarette smoke, allergens and irritants should be avoided as well as administering pharmacological treatment as in the case of all asthma patients. Initiating immunotherapy during pregnancy is not recommended. Immunotherapy initiated before pregnancy can be sustained. The main purpose of asthma treatment during pregnancy should be taking asthma under control. Patient whose asthma has been taken under control through treatment should make sure that the treatment is sustained during pregnancy. Patients who are not under control (Table 1) should be referred to a pulmonologist. 70 ASSESSMENT OF ASTHMA CONTROL Features Controlled Partially Controlled Uncontrolled (All of the following) Symptoms seen during None (Two or More than two Partially day less / a week /a week controlled asthma with three or more Limitation of activity None Any of them features Symptoms seen at night None Any of them /waking up Need of immediate treatment None (Two or less/ a week More than two /a week Lung Functions (PEF or FEV1) Normal < %80 The best function value that is estimated or known (if it is known) 71 ATTACK TREAMENT The initial treatment for attack in pregnants with asthma is not different from the treatment of non-pregnant patients. TREATMENT DOSE EXPLANATION Nasal O2 5-6 Lt/min In such a way as to retain O2 saturation above 95%. Salbutamol dose inhaler or nebula 4-8 puff It can be administered every 20 minutes within the first 1 hour. 1-2 nebula Prednisolone 4060mg/day IV or oral If there is no improvement after the first dose of 40 mg, additional dose can be administered two hours later. (20-40mg) 72 Constant external fetal monitorization ( >24th week of pregnancy) DELIVERY MANAGEMENT Asthma medications should not be discontinued during delivery. Before delivery and for the ensuing 24 hours, steroid should be administered on the pregnant that has been using systemic steroid for the past 4 weeks. In vaginal delivery for a pregnant with asthma; pain control, control of breathing and stress reduction become more important. Especially in pregnants describing asthma attacks that are triggered by exercise, cold air, hyperventilation and stress; pain and tachypnea may trigger bronchoconstriction. Analgesia methods that could be used include: Systemic opioids: It prevents the formation of mucosal inflammation as well as having analgesic effect. However, it should be kept in mind that it could cause maternal and fetal respiratory depression if administered in high doses. Paracervical block: Effective in the 1st and 2nd phase of delivery. Pudental nerve block: Effective in the 1st and 2nd phase of delivery. Lumbar sympathetic block: Effective only in the 1st phase. Epidural and spinal anaesthesia: Ensures analgesia without sedation and fetal depression. Constant pain control is possible. It reduces hyperventilation stimuli. Unlike other analgesia methods, in continuous epidural analgesia, sensorial block can be ensured for caesarean section if necessary. General or 73 regional anaesthesia is conducted according to obstetric and respiratory situation of the patient in caesarean section. In the perioperative period, the most common cause of bronchospas is endotracheal intubation. In asthma patients, regional anaesthesia should be the first choice. The most important disadvantage of regional anaesthesia is the risk of high thoracic motor block and respiratory distress. In the block that may go up to T-8 maximum, the risk is minimal. POSTNATAL Asthma treatment should be continued in the puerperium. In general, small amounts of asthma medication are transferred to the breast milk. However, during breastfeeding asthma medications (prednisone, teophylline, antihistamines, inhale corticosteroids and beta2agonists) are not contraindicated. Oral contraceptives used for contraception does not interact with medications used for asthma maintenance treatment. REFERENCES: 1- Türk Toraks Derneği, Astım Tanı ve Tedavi Rehberi 2010 2- McCallister JW. Asthma in pregnancy: management strategies. Curr Opin Pulm Med. 2013 Jan;19(1):13-7 3- Rocklin RE. Asthma, asthma medications and their effects on maternal/fetal outcomes during pregnancy. Reprod Toxicol. 2011 Sep;32(2):189-97. 4- Mendola P, Laughon SK, Männistö TI, Leishear K, Reddy UM, Chen Z, Zhang J. Obstetric complications among US women with asthma. Am J Obstet Gynecol. 2013 Feb;208(2):127.e1-8 5- Virchow JC.Semin Respir Crit Care Med 2012;33:630-644 74 6- Kurt E, et al. Prevalence and risk factors of allergies in Turkey (PARFAIT): results of a multicentre cross-sectional study in adults. Eur Respr J 2009;33:724-33). 75 76 77 78 79