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Medicines for oral treatment in pregnancy
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Table 22
Medicines for oral treatment in pregnancy
| Dose per tab | Elemental iron | |
| Ferrous fumarate | 200mg | 65mg |
| Ferrous gluconate | 300mg | 35mg |
| Ferrous sulphate | 200mg | 65mg |
| Ferrous feredetate (Sytron) | 190mg/5ml | 27. 5mg/5ml |
Parenteral iron therapyshould bereserved for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron. (Table 22)
Table 22
Parenteral iron therapy
| Cosmofer Iron hydroxide dextran complex | Venofer Ironhydroxide sucrose complex | Ferinject Iron carboxymaltose | Monofer Iron isomaltoside | |
| Dose of elemental iron | 50mg/ml | 20mg/ml | 50mg/ml | 100mg/m |
| Test dose required | Yes before every iv dose | First dose new patients only | No | No |
| Able to administer total dose | Yes up to 20mg/kg over 4 6 hours | No | Yes up to 20mg/kg maximum of 1000mg/week over 15 min | Yes 20mg. kg over 1 hour |
Pregnants with anemia should be hospitalized at the in-patient department 2 weeks before labor to plan an obstetric management and preparation to birth.
The most preferable type of delivery for patients with anemia is delivery through the natural maternal passages, with prophylaxis of weakness of labor pains, fetal hypoxia and asphyxia of neonate. The 3rd stage of labor should be conducted with a needle in the vein; 1 ml of methylergometrine should be injected during crawning of the head (in multiparae) or disengagement of the fetal head (in primiparae). The obstetrician should be ready for manual control of the uterine cavity during labor. After delivery the puerperal septic diseases are common for these patients, so their prophylaxis should be carried out. The treatment of iron deficiency should be continued in postpartum period.
For women, whose pregnancy was complicated with anemia, the next pregnancy may be recommended not earlier than in 2-3 years.
Pregnancy and Thrombocytopenias
Thrombocytopenias are a group of diseases, at which the number of thrombocytes is lower than the existing norm — 150х109/l — 400х109/l. The decrease of thrombocyte quantity can be caused by their increased destruction, elevated consumption and insufficient formation.
The hereditary and acquired forms of thrombocytopenias are distinguished. At hereditary forms the change of functional properties of thrombocytes takes place that gives grounds to refer them to the group of thrombocytopathies.
Acquired forms of thrombocytopenias are divided into:
· Immune forms;
· Forms caused by mechanical traumas of thrombocytes (at hemangiomas, splenomegaly);
· Suppression of cell proliferation of bone marrow (at aplastic anemia, chemical and radiation damage of bone marrow);
· Replacement of bone marrow by a tumor tissue (at Marchiafava-Micheli disease);
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· Increased consumption of thrombocytes (at thromboses, syndrome of disseminated intravascular coagulation);
· Vitamin B12 or folic acid deficiency.
The most common form encountered in obstetric practice is the idiopathic Werlhof's disease, which is in 90 % of cases is the acquired autoimmune form of thrombocytopenia. Werlhof's disease is the common name of thrompocytopenias, which are not connected with acute leucosis, Marchiafava-Micheli disease, vitamin B12 or folic acid deficiency. In case of Werlhof's disease the quantity of megakaryocytes is increased, while the size of spleen is normal.
Pathogenesis
The insufficient quantity of thrombocytes and related to it reduction of thrombocyte’s component in the system of blood coagulation is the basis of pathogenesis of the disease. The decrease of quantity of circulating thrombocytes is connected with duration of their life which shortens to several hours instead of 7-10 days. The reasons of destruction of thrombocytes on the periphery are antibodies to circulating thrombocytes.
It is known that thrombocytes participate in maintenance of a normal condition of endothelium of microvessels, form primary thrombocytic plaques at damage of vessels, participate in blood coagulation and are one of inhibitors of fibrinolysis. The thrombocytes take a leading role in bleeding arrest in a zone of microcirculation (primary hemostasis), whereas the formation of fibrinous clots occurs later (secondary coagulatory hemostasis).
At thrombocytopenia hemorrhagic diathesis has a microcirculatory character and occurs due to increased fragility of vessels, as well as due to escape of erythrocytes from bloodstream via capillaries (bleeding per diapedesin).
Clinical Picture
Acute, subacute and chronic forms of disease are distinguished.
Clinically the disease is manifested by hemorrhages from fine vessels of the skin and mucous membranes. Petechial hemorrhage occurs on the skin at slightest traumas: taking somebody's blood pressure, rubbing of skin in places of injections, at palpation. The patients can be disturbed by bleedings: nasal, gastrointestinal, metrorrhagia, etc., especially frequent at severe forms of disease.
On investigation of peripheric blood the decrease of thrombocyte quantity up to 50-40 х109/l, down to their complete disappearance is marked. There are gigantic forms of platelets in peripheric blood. The quantity of plasma elements of blood is normal; sometimes even increase of quantity of factors of blood coagulation is possible, apparently of a compensatory character. The level of haemoglobin and erythrocytes can be normal or, owing to bleedings, reduced. The duration of bleeding by Duke (Duke’s test) is lengthened, while coagulatory hemostasis (time of blood coagulation) can be not disturbed or even slightly accelerated (at compensated forms). The retraction of a bloody clot is impaired. Aggregative properties of thrombocytes and their adhesion can be reduced due to sharp decrease of quantity of circulating thrombocytes. Diagnostics of disease is possible at a sternal puncture to exclude hemoblastoses, Marchiafava-Micheli disease, cancer metastases, etc. The normal content of megacaryocytes in a punctate of the bone marrow is characteristic of idiopathic purpura.
Effect of Thrombocytopenia on Pregnancy
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The course of pregnancy and labor depends on form of disease and character of previous treatment (treatment before pregnancy).
At acute form of disease proceeding with appreciable bleedings from nose and gums, at hematencephalon, at chronic form with frequent relapses, pregnancy is contraindicated.
Pregnancy at idiopathic thrombocytopenia can be complicated by premature interruption of pregnancy at different terms (up to 30 %), bleedings at placental stage of labor and in early puerperal period (20 %); a characteristic and severe complication is premature separation of normally located placenta. The incidence of EPH-complex is also a little bit higher than in the other part of pregnant women. Besides labor is complicated by disturbance of uterine action (weakness of labor pains), asphyxia of intrauterine fetus, intracranial hemorrhages owing to disturbance of blood circulation in cerebrum.
In puerperal period the bleedings in places of slightest ruptures, cuts, and cracks are dangerous which assume a persistent character.
Approximately 2-8 % of maternal mortality at idiopathic thrombocytopenia are caused by bleedings during labor and in early puerperal period. The incidence of perinatal mortality makes up 50 %, the greater part of which is connected with intracranial hemorrhages.
Effect of Pregnancy on Thrombocytopenia
In 50-60 % of patients with Werlhof's disease exacerbations of the basic disease are observed at pregnancy. In some cases the signs of disease decrease.
Treatment
The modern therapy of disease is based on application of corticosteroids, immunosuppressive agents and performing splenectomy.
At presence of thrombocytopenia with a number of 40х109/l without hemorrhagic manifestations the treatment at pregnancy is not required. Two weeks before the expected term the pregnant woman should be hospitalized at the in-patient department for examination and preparation for labor. 10 days prior to term of labor prednisolone in a dose of 30-40 mg/day is usually administered. After labor the dose is gradually reduced within 5-6 days, and then the preparation is cancelled.
On occurrence of the first signs of hemorrhagic diathesis during pregnancy, prednisolone in a dose of 30-40 mg/day should be prescribed; the dose can be enlarged up to 60 mg/day. If it is ineffective and aggravation of hemorrhagic diathesis and anemia takes place, a dose of prednisolone is enlarged up to 80 mg/day, hemotransfusion of fresh blood in amount of 150-200 ml every 3-5 days is given. The prescription of prednisolone in doses of 80-100 mg/day during labor for such patients is obligatory, with a gradual decrease of dose in puerperal period. The question on necessity of splenectomy arises in case of inefficiency of all above-stated medical measures. Making such operation in late terms of pregnancy (and also in puerperal period) is connected with a high rate of maternal (up to 10 %) and perinatal (25-30 %) mortality. Therefore splenectomy for pregnant women with an idiopathic Werlhof's disease is considered to be a forced measure and is carried out by life-saving indication, when hormonal and substitutive therapy is ineffective. At increased hemorrhages, anemia, and worsening of fetal general condition, cesarean section is indicated. In some cases simultaneously with cesarean section splenectomy may be made.
Labor Management
At number of thrombocytes equal to 40х109/l without hemorrhagic manifestations the obstetric management remains expectant. Labor management, as a rule, is conservative with prevention of bleeding. At intensifying hemorrhagic diathesis in labor and ineffective medicamental therapy the extreme measures, i. e. cesarean section, are indicated.
In puerperal period antibacterial drugs for prophylaxis of puerperal septic diseases should be prescribed.
Diabetes Mellitus in Pregnancy
During each antenatal visit a routine examination of urine for sugar is practiced for each pregnant in many clinics of the world. This is due to the fact that asymptomatic forms of diabetes are responsible for significant fetus wastage.
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The incidence of diabetes in pregnancy is about 10%.
Diabetes in pregnant women is generally categorized as either gestational or pregestational diabetes. Gestational diabetes firstly appears after 28 weeks of pregnancy and means a transient glucose malabsorption during pregnancy.
Classification of Diabetes Mellitus
· Clinical forms of diabetes.
§ - Insulin-dependent diabetes (type I DM).
§ - Insulin-independent diabetes (type II DM).
§ - Other forms of diabetes (secondary diabetes associated with other endocrine diseases, etc. ).
§ - Gestational diabetes.
· Degrees of diabetes.
§ - Mild degree (1st degree).
§ - Moderate degree (2nd degree)
§ - Severe degree (3d degree).
· Dependence on compensation.
§ - Compensated diabetes.
§ - Subcompensated diabetes.
§ - Decompensated diabetes.
Types of Diabetes during Pregnancy
· Potential diabetes. Potential diabetes is probable in patients with normal glucose tolerance test but who have a positive family history of diabetes or previous birth of an overweight baby.
· Latent diabetes. The individual has normal glucose tolerance in non-pregnant condition. But in stress conditions, there is impairment of glucose tolerance which becomes normal when the stress is removed.
· Subclinical diabetes. There is a persistent abnormal glucose tolerance test irrespective of stress. Symptoms of diabetes have not appeared yet.
· Prediabetic condition. The features of the state are history of previous delivery of overweight baby (more than 4 kg), unexplained perinatal death with hypertrophy of the pancreas on autopsy and diabetes in the family.
· Overt or clinical diabetes. These are patients with abnormal glucose tolerance test, with or without symptoms and a raised fasting blood glucose level. The condition may be pre-existing or detected primarily during present pregnancy. The diagnosis can be presumptive if: 1) the fasting blood sugar exceeds 110 mg; 2) the peak level exceeds 180 mg%, and 3) a 2-hour value exceeds 140 mg% in glucose tolerance test.
Effect of Diabetes on Pregnancy
There are a lot of complications during pregnancy, delivery, and in postpartum period due to diabetes. Maternal complications are: abortions, prematurity, increased incidence of EPH-complex, more often in severe forms (severe preeclampsia, eclampsia). Hydramnios is one of the commonest complications, which is connected with fetal congenital abnormalities (incidence is 25-50%). Abruptio placentae, placental incompetence are not so rare.
During labor complications are: abnormalities of labor pains, obstructed delivering due to a big fetus, shoulder dystocia, perineal injuries, hemorrhages in the 3rd stage of labor and in early postpartum period. In the late postpartum period more often endometritis occurs.
Fetal complications are very serious too. These are: fetal macrosomia, diabetic fetopathy, congenital malformations, birth injuries. After birth secondary asphyxia, respiratory distress syndrome, perinatal infections may occur, so the level of perinatal death is very high.
Effect of Pregnancy on Diabetes
Pregnancy is a metabolic stress test for diabetes leading to aggravation of diabetes in pregnancy. In the first trimester, after the 10th week of gestation, the glucose tolerance increases due to action of HCG, so the insulin requirement decreases. The doses of insulin have to be diminished. In 24-28 wk of gestation the glucose tolerance decreases due to insulin antagonism, resulting in development of hyperglycemia, glucosuria, so the dose of insulin has to be increased. The insulin antagonism is probably due to the combined action of human placental lactogen, estrogen, progesterone, free cortisol and degradation of insulin by the placenta. During the 3rd trimester the insulin requirement decreases, probably, due to the action of fetal pancreas.
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Insulin requirement falls significantly in puerperium.
Vascular changes, specially retinitis aggravate during pregnancy.
Diabetes in pregnant is compensated when the level of glucose is 4. 4 mmol/l to 6. 6 mmol/l.
Because of these complications pregnancy and delivery may be contraindicated for the following groups of patients with diabetes:
· patients with progressive vascular changes;
· insulin-resistant forms of diabetes;
· diabetes in both partners;
· combination of diabetes with active pulmonary tuberculosis;
· ketoacidosis;
· antenatal and intranatal mortality in previous history;
· some other states.
Management of Pregnancy at Diabetes Mellitus
Each pregnant with diabetes should be hospitalized in term before 12 weeks of gestation to be sure that there is no contraindications for pregnancy and delivery. The aims of this hospitalization are: to determine the term of gestation, to correct the dose of insulin, to evaluate contraindications to prolongation of pregnancy.
The next prophylactic hospitalization should be in term of 20-24 weeks. Apart from those undertaken during the first hospitalization, the following should be done: examination of the condition of fetal-placental complex, diagnostics of congenital anomalies of the fetus, if any, revealing the onset of obstetric complications, such as EPH-complex, and their treatment.
The third prophylactic hospitalization should be undertaken in the term of 30-34 weeks of pregnancy to prepare the patient for delivery.
The optimal term of delivery for patient with diabetes is from 36-37 weeks, because after this term the placental incompetence is more progressive due to “growing old” and fetus may die. Prior to this term the delivery is dangerous due to dismaturity of the baby.
It is much better for these patients to have labor via natural generative passages of delivery. Cesarean section is indicated in the following cases: vascular changes during pregnancy, neuroretinopathy, ketoacidosis during pregnancy or labor, acute renal incompetence, a big fetus, a severe form of EPH-complex, hemorrhages due to abruptio placentae, placenta previa, etc.
Diabetic Fetopathy of Newborn
The body weight of baby of 36 weeks of gestation is the same as of full-term child. There is a disproportion in sizes of head and shoulders (the circumference of shoulders is bigger than that of the head) which can lead to mechanical injuries to infant. Due to chronic hypoxia intracranial hemorrhages may happen during labor. In spite of big mass these infants usually have significant signs of prematurity — soft bones, enlarged fontanelles, respiratory distress syndrome are typical of them. So the prognosis is unfavourable for them.
Pyelonephritis in Pregnancy
The incidence of pyelinephritis during pregnancy is 6-10%. It is an infectious disease; the most frequent causative agents are E. coli, enterococci, staphilococci, streptococci, and mixed infection. Pregnancy may contribute to the development of pyelonephritis because of dilatation of ureters and renal pelves and stasis of urine in the bladder and ureters, which are more expressed in term after 20 weeks of gestation due to increase of progesterone level in blood. Therefore the term of 20-24 weeks of pregnancy is of high risk of occurrence or aggravation of pyelonephritis.
Acute pyelonephritis usually occurs after 16 weeks of pregnancy.
Its symptoms are the following: acute aching pain in the area of loin, often radiating to the groin, fever with chill and rigor, anorexia, nausea and vomiting occurring due to general intoxication. Micturition or dysuria is a typical symptom. Pasternatsky’s symptom is positive. Blood analysis usually reveals bacteriuria, leukocyturia, proteinuria.
Chronic pyelonephritis may have a chronic course from the onset, or may develop as a result of ineffective treatment of acute or recurrent pyelonephritis. Asymptomatic bacteriuria may alternate with the periods of exacerbation at chronic pyelonephritis.
Diagnostics may be difficult due to long asymptomatic period when neither proteins nor pus cells are detected in the urine. Chronic pyelonephritis is frequently accompanied by chronic hypertension. Maternal and fetal prognosis depends on degree of renal damage.
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Effect of Pyelonephritis on Pregnancy
The most common complication of pregnancy at pyelonephritis is preeclampsia and eclampsia, prematurity, intrauterine damage of the fetus. The incidence of EPH-complex in pregnants with pyelonephritis is about 40%, thus severe forms develop more often. The incidence of premature labor is about 30%, perinatal mortality is about 25%. The occurrence of asphyxia of newborn, hypotrophy, dismaturity, infections may take place.
Effect of Pregnancy on Pyelonephritis
The course of pyelonephritis exacerbates during pregnancy. Chronic pyelonephritis becomes acute during pregnancy, and, if not treated, it may occur twice or thrice during gestation.
Management of Pregnancy at Pyelonephritis
High risk groups for pregnants with pyelonephritis include the following:
· Women with acute pyelonephritis occurred firstly during pregnancy are determined as patients of the first degree of risk.
· Pregnants with chronic pyelonephritis occurred prior to pregnancy are determined as patients of the second degree of risk.
· Women with pyelonephritis complicated with azotemia or hypertension, or women with pyelonephritis of the only kidney refer to the highest risk group in pregnancy, called the third degree of risk.
Pregnancy is contraindicated for patients with the third group of risk, because it may lead to maternal and perinatal death.
Treatment of pyelonephritis during pregnancy should be only at the in-patient department.
Patients with chronic pyelonephritis should be hospitalized thrice during pregnancy for prophylactic treatment.
The first hospitalization is in term before 10 weeks of pregnancy to examine the general condition of pregnant, the state of the renal system and find the opportunity to prolong pregnancy
The treatment includes: antibiotic therapy (penicillin 10, 000, 000 units daily intramuscularly, or ampicillin 500 mg four times a day, or pyopen 1g four times a day) during 7-8 days.
The second prophylactic hospitalization should be arranged in term of 20-22 weeks of gestation to treat a patient for prevention of pyelonephritis.
The following treatment is administered: antibiotic therapy (cephuroxim 500 mg 4 times a day; gentamicin, kanamycin, oleandomycin may also be used). Nevigramon, negram should be administered in doses of 2 capsules 4 times a day during 10 days. Furagin may be administered in a dose of 0. 1 g 4 times a day during 4 days, and then 0. 2 g 3 times a day during 10 days. Urosulfan is usually prescribed by 0. 5 g 3-4 times a day during 12-14 days. Diet limited in salt and water should be administered. Bed regimen in cases of elevated temperature is necessary. Antihistaminic drugs, spasmolytics, treatment to prevent fetal hypoxia and premature labor are of importance for these patients.
The third hospitalization is necessary in the third trimester of pregnancy, in term of 34-36 weeks of pregnancy, for general examination, choice of way of delivery and preparation for delivery. Antibiotics may be used by indication, the treatment for fetal hypoxia, for improvement of placental microcirculation is usually provided.
The natural maternal passages are the best way for patients with pyelonephritis. Cesarean section is contraindicated due to infectious process and may be done only by absolute indication; intraperitoneal operation is preferable.
During postpartum period there is a high risk of development of infections, so antibiotic therapy is administered with the prophylactic purpose.
Pregnancy and Glomerulonephritis
Glomerulonephritis is an infectious-allergic disease of kidneys with glomerular affection. Glomerulonephritis is encountered in 0. 1-0. 2 % of pregnants; it is the most dangerous kidney disease, because a complicated course of pregnancy accompanying it is more frequent than at other diseases. The nephrogenous culture of β -hemolitic streptococcus of A group, type 12 is a causative agent of this disease. Glomerulonephritis develops in 10-15 days after the suffered scarlatina, quinsy, streptococcic pyodermia. Noninfectious glomerulonphritis after vaccination, inoculations is encountered more rarely. The essence of pathological process at glomerulonephritis is determined by autoallergization. An infectious factor quickly loses its dominant value, and illness acquires the form of autoagressive process.
Acute and chronic forms of glomerulonephritis are distinguished. The clinical picture of acute glomerulonephritis at pregnancy is vague. During pregnancy acute glomerulonephritis usually proceeds as severe forms of gestoses. The clinical manifestations in such cases are elevation of arterial blood pressure, edema, proteinuria. In contrast to gestoses acute glomerulonephritis is marked by expressed hematuria, cylindruria. The titre of antistreptolysin and antihyaluronidase rises. The onset of the disease is acute, with occurrence of chill, headache, edema. All these symptoms appear in pregnant in 1-2 weeks after quinsy. Acute glomerulonephritis is contraindication to prolongation of pregnancy.
Chronic glomerulonephritis can proceed in a latent, nephrotic, hypertensive and mixed form.
A more frequent is a latent form (approximately in 65% of pregnant). It is characterized by inconstant microproteinuria, microhematuria; single cylinders can be determined (not constantly) in urinary sediment. The latent form of glomerulonephritis proceeds without a hydropic syndrome and hypertension.
A nephrotic form is encountered approximately in 5% of pregnant with glomerulonephritis. A complex of symptoms is characteristic of this form: proteinuria (up to 30-40 g/l), hypoproteinemia (blood protein decreases down to 40-50 g/l), the expressed edema and hypercholesterinemia. In urinary sediment red corpuscles and different cylinders are revealed — hyaline, granular, waxy. Permeability of endothelium of glomerular capillary net is sharply increased; canalicular reabsorption of albumen is disturbed.
A hypertensive form is characterized by expressed hypertensive syndrome, moderate hematuria, proteinuria and cylindruria. Edema is not characteristic of this form of glomerulonephritis. On a background of expressed hypertension, hypertrophy of the left heart ventricle, spasm of arterioles of eye grounds are revealed in patients. Arterial hypertension at chronic glomerulonephritis develops due to decrease of renal blood flow and increase of renin and angiotensin production, as well as the increased production of aldosterone. The incidence of this form makes up approximately 7% of the total number of pregnant with glomerulonephritis.
A mixed (edematous-nephrotic) form is characterized by the most expressed vascular changes and hypertension accompanied with hypertrophy of the left ventricle, vascular change of eye grounds, marked dystrophic processes in kidneys, severe proteinuria, cylindruria, hematuria, edema. The incidence of this form is approximately 25%. At this form of glomerulonephritis the attack of cramps, similar to eclampsia, can develop even in the absence of late gestosis.
Effect of Glomerulonephritis on Pregnancy
Pregnancy on a background of chronic glomerulonephritis proceeds with serious complications. Approximately in 40 % of women with this pathology the EPH-complex develops very early (before 28 weeks), it proceeds in a very serious form (preeclampsia of a serious degree, eclampsia, HELLP-syndrome). Acute respiratory infections, influenza, tonsillitis provoke the occurrence of gestosis. The most common complication of pregnancy at glomerulonephritis is disturbance of uteroplacental circulation. Vascular spasms, kidney ischemia, hypertension, increase of fibrinogen content lead to insufficiency of placenta blood supply. Besides, the immunological balance between a maternal organism and fetus is broken. Getting into mother’s blood flow, antigens of placental tissue cause sensibilization with development of antibodies not only to tissues of placenta, but also to vital organs of the pregnant woman, including kidneys, resulting in changes known as a vicious circle. The disturbances of uteroplacental circulation lead to pathology of fetus. In 12-15 % of cases the pregnancy is complicated by intrauterine death of fetus, congenital anomalies of fetus, intrauterine growth retardation, hypoxia of the fetus. The adverse conditions of fetation are aggravated by anemia accompanying glomerulonephritis. The rate of perinatal mortality is extremely high — from 140 up to 400‰ and over. Pregnancy at glomerulonephritis is frequently complicated by premature detachment of normally located placenta, which proceeds in a serious form, and is accompanied by a massive hemorrhage, fast addition of coagulopathic disturbances. In 15 % of patients with glomerulonephritis, fetus wastage occurs prematurely in various terms (early and late abortions, premature labor). The frequency of maternal mortality at glomerulonephritis makes up 27. 1 %.
Effect of Pregnancy on Glomerulonephritis
The course of glomerulonephritis at pregnancy is worsened. Decrease of tonus of ureters and renal pelves, retention of urine in the urinary bladder and ureters contribute to addition of a secondary infection, deterioration of kidney condition, thus causing the development of renal failure. These processes are more expressed after 20 weeks of pregnancy, in connection with increase of progesterone level in blood. Neuroendocrinal changes, characteristic of gestational process, the immune derangements at pregnancy produce an unfavourable effect on the course of glomerulonephritis, contribute to the development of functional decompensation, progressing of disease. Pregnancy represents a high degree of risk for transition of disease into a terminal stage of chronic uremia.
Management of Pregnancy at Glomerulonephritis
Management and treatment of pregnant with glomerulonephritis are carried out by obstetrician-gynecologist and therapeutist-nephrologist. In early terms of gestation (about 12 weeks) general examination of pregnant should be made to specify the form of disease, to study features of anamnesis and to decide the question of conducting pregnancy.
There are three degrees of risk for pregnant women at glomerulonephritis:
I degree of risk — a latent form of glomerulonephritis;
II degree of risk — a nephrotic form of glomerulonephritis;
III degree of risk — a hypertonic and mixed form of glomerulonephritis.
Pregnancy may be prolonged at chronic, latent form of glomerulonephritis.
The problem of prolongation of pregnancy at I and II degree of risk is solved individually: pregnancy can be prolonged in the absence of signs of exacerbation, expressed hypertension and azotemia, presence of opportunity of strict control of kidney function. Management and treatment of pregnant women are carried out on the basis of a large in-patient department.
Pregnancy is contraindicated in case of III degree of risk in view of high rate of maternal mortality at this pathology.
Pregnancy is absolutely contraindicated at any form of glomerulonephritis proceeding with renal failure.
Thus, the first hospitalization of pregnant with a chronic glomerulonephritis is arranged in term of 10-11 weeks of gestation at a nephrological department for examination and solving the problem of pregnancy prolongation.
The second planned hospitalization is carried out at 20-22 weeks of pregnancy for examination and preventive course of treatment (nonspecific desensitizing therapy, antibacterial therapy for prophylaxis of secondary infection, spasmolytic and metabolic therapy). The treatment aimed at improvement of uteroplacental circulation and prophylaxis of fetus should be administered.
Except for preventive hospitalization in the I and II trimester of pregnancy, the in-patient treatment at any term of gestation is indicated at worsening of general condition, occurrence of signs of threatened abortion, late gestosis, hypoxia of the fetus, etc.
The common therapy of glomerulonephritis with the use of corticosteroids, cytostatic agents and immunodepressants cannot be applied to pregnant women in view of teratogenic effect of these medicines. Therefore a symptomatic therapy is basically administered. A diet limited in salt up to 2 g/day, liquid up to 800 ml/day should be administered; saluretic diuretics (hydrochlorothiazide, ethacrynic acid, furosemide in a dose of 0. 04-0. 08 g, spironolactone — 0. 025 g 6-8 times a day, gradually reducing a dose up to 0. 025 g/day. ) should be applied. In combination with diuretic medicines potassium chloride, hypotensive therapy (raunatinum, dibazol, papaverine, clophelinum, atenolol, etc) should be applied. With the purpose of albumen replenishment, transfusion of protein and fresh frozen plasma are indicated. Nonspecific desensitizing therapy (dimedrol, pipolphen, suprastin, etc) is administered too. A sedative therapy, metabolic therapy for prophylaxis and treatment of intrauterine fetus are necessary.
The third planned hospitalization should be arranged in term of 36-37 wk of pregnancy. The pregnant is hospitalized at pathologic pregnancy department for examination, determining obstetric management and preparation for labor.
In some cases it is expedient to cause premature labor in woman to avoid fetus death.
Management of Labor
A preferable approach of delivery for pregnant women with glomerulonephritis is delivery through natural maternal passages with a wide application of spasmolytics and analgesics. Management of the 2 stage of labor depends on level of arterial blood pressure, condition of the fetus. Controlled hypotension, shortening of expulsive stage of labor by applying obstetrical forceps or perineotomy are indicated. Cesarean section of patients suffering from glomerulonephritis is operation of choice which is performed basically by urgent indication, for example, at a threatened asphyxia of the fetus.
In puerperal period the observation over a general condition of puerperant, function of kidneys should be continued; in case of aggravation of the disease course the patients should be removed to specialized hospitals or therapeutic departments.
Heart Diseases in Pregnansy
For the last years a clear tendency to increase of cardiac disease incidence in pregnant has been marked. It is explained by improvement of diagnostics, medical treatment of patients with heart diseases, progress of cardiosurgery, perfection of methods of pregnancy and delivery management at heart diseases. Cardiovascular diseases and pregnancy are not a simple combination of two states of woman’s organism.
Pregnancy and labor impose an additional load on the cardiovascular system of the woman. A healthy pregnant overcomes a new burden with ease but patients with cardiovascular diseases often develop circulatory disorders and other complications.
Incidence. The incidence of cardiac diseases is less than 1% among hospital deliveries. The commonest cardiac disease is of rheumatic origin followed by congenital defects.
Effect of Gestation on Cardiovascular Diseases
During pregnancy there is an increased blood vascularity of the enlarging uterus with the interposition of utero-placental circulation. The activities of all systems are increased. To fill up the additional intravascular spaces, the blood volume is markedly raised during pregnancy. The rise is progressive and inconsistent. All the constituents of blood increase in volume during pregnancy.
The increase of plasma volume starts from the 10th week, expands rapidly thereafter to maximum 35-40% above the non-pregnant level at 32-34 weeks. Total plasma volume increases to the extent of 1. 3 litres. Erythrocyte number is increased during pregnancy. The rate of increase almost parallels that of plasma but the maximum is reached to the extent of 20%. The total hemoglobin mass increases during pregnancy to the extent of 18-25%, thus the disproportionate increase in plasma and blood cell volume produces a state of hemodilution during pregnancy. The increased volume of circulatory blood, hemodilution mean extra load for cardiovascular system in pregnancy.
The volume of circulatory blood remains almost static till the term. During labor or shortly thereafter, there is a slight decrease due to dehydration and blood loss during delivery. Blood volume almost returns to normal non-pregnant level by the second week in puerperium.
A normal heart has sufficient reserve power so that the extra load can be well tackled. While a damaged heart with good reserve can even withstand strain but if the reserve is poor, the cardiac failure occurs sooner or later. The cardiac failure occurs during pregnancy between 30-32 weeks but mostly during labor or soon following delivery. Additional factors responsible for determination of cardiac function of the damaged heart are: advancing age, history of previous heart failure, cardiac arrhythmias or left ventricular hypertrophy, pregnancy complications such as anemia, EPH-complex, infection.
Effect of Cardiovascular Disease on Gestation
There is a 38% incidence of fetal death in pregnancies of women with severe heart diseases. Severe maternal hypoxia results in abortions, premature delivery, intrauterine hypoxia, intrauterine growth delay. Excessive anemia, EPH-complex, hemorrhages may occur during pregnancy in women with cardiac diseases. The risk of maternal mortality is considerable and depends on the specific cardiac lesion. Patients with pulmonary hypertension, Eisenmenger’s syndrome, coarctation of aorta with valvular involvement, or Marfan’s syndrome with aortic involvement have a mortality rate in pregnancy of 25-50%. Other conditions such as small septal defects, patent ductus arteriosus, and corrected tetralogy of Fallot have a maternal mortality rate of less than 1%.
Management of Pregnancy
Every patient with cardiovascular disease should be hospitalized thrice during pregnancy, even if she feels well.
The 1st hospitalization is at term prior to 12 weeks of gestation (thereafter the pregnancy was determined). Hospitalization should be in a hospital of cardiologic type.
The aim of this hospitalization is to examine woman’s condition and determine contraindications to pregnancy, if any.
The basic tasks of examination of pregnant during the first hospitalization are:
· establishment of obstetric diagnosis;
· determination of form and stage of development of heart disease;
· establishment of degree of cardiac insufficiency, state of myocardium, activity of rheumatic process;
· revealing the foci of chronic infection (pyelonephritis, tonsillitis, otitis, etc).
Because of high risk of maternal death rate, pregnancy and birth are contraindicated in case of the following heart diseases:
· Presence of cardiac insufficiency regardless of form of heart disease already at small terms of pregnancy.
· Active rheumatic carditis, recurrent rheumatic carditis, bacterial rheumatic carditis.
· Mitral stenosis of III-IV stages (according to A. Bakulev’s classification).
· Combination of mitral stenosis and aortic insufficiency.
· Tricuspid incompetence.
· All congenital defects with cyanotic syndrome (all Fallot’s defects, transposition of great vessels, common arterial trunk).
· Eisenmenger’s syndrome, Marfan’s syndrome.
· Combination of congenital and acquired defects.
· Restenosis after surgical treatment.
· Presence of mitral incompetence with disturbance of blood circulation, blood regurgitation.
· Some others.
In patients with recurrent myocarditis the conducting of pregnancy will depend on results of antirheumatic therapy. If the treatment is ineffective, the artificial termination of pregnancy is indicated. Aortic diseases during pregnancy remain compensated for a long time. In absence of cardiac insufficiency the pregnancy may be prolonged; at decompensated diseases the termination of pregnancy should be done in early terms of gestation.
In connection with growing number of women having the previous operations on the heart, it is necessary to decide the question of permissibility of pregnancy and labor for them. Thus, pregnancy after mitral commissurotomy may be allowed not earlier than 7 months and not later than 1. 5 years after the operation. Pregnancy is allowed at excellent and good results after the operation in case of absence of operated heart trouble. At second-rate results of commissurotomy the pregnancy and birth are contraindicated.
Pregnancy and labor are contraindicated for patients after the operation of aortic and mitral valve replacement.
If necessary, the artificial termination of pregnancy should be performed with a single-stage operation (curettage of the uterine cavity, vacuum aspiration).
The 2nd hospitalization should be at term of 26-32 weeks of gestation in the period of maximal hemodynamic loading on the heart.
Significant hemodynamic changes occur at this term, so the aim of hospitalization is to prevent decompensation of cardiovascular system. Observation of the patient, examination, prophylaxis and treatment of fetal and maternal complications, if any, should be provided.
Medical treatment at the in-patient department during the second hospitalization includes the following:
· Limitation of physical exertion (bed regimen) during 2-3 weeks.
· Sedative therapy (preparations of valerian, motherwort).
· Diet limited in salt up to 1-3 g/d and liquid up to 1, 000 ml/d. In pregnant with cardiovascular diseases the mucous membrane of gastrointestinal tract is edematous, the absorption is labored; therefore it is recommended to take meals rich in vitamins, potassium, in small portions, 5-6 times a day.
· The main drugs for treatment are cardiac glycosides, which increase cardiac output and diuresis, decrease congestion of blood in lungs and liver, diminish edema. Cardiac glycosides change potassium and sodium transport through the myofibril membrane, and promote muscular contractions. Cardiac glycosides improve blood supply of organs and tissues, restore metabolic processes. The index of efficiency of medical treatment with cardiac glycosides is decrease of pulse rate (if there was tachycardia), elimination of other symptoms of decompensation: breathlessness, edema. Cardiac glycosides for these patients should be administered by a cardiologist with an individual choice of preparation and dose. Strophanthine, then corglycon, digoxin, digitoxin produce the greatest effect. To achieve a good therapeutic effect 0. 5 mg of strophanthine or 1. 8 mg of corglycon a day should be introduced; or digitoxin in a dose of 2 tablets 4 times, or 2 tablets of digoxin (izolanid) 4 times a day orally should be administered. The overdose of cardiac glycosides is accompanied by intoxication (nausea, vomiting, diarrhea, visual impairment: painting of visual field in a green or yellow color). Intoxication is quickly controlled by introduction of unithiol: 5 mg intramuscularly 3-4 times a day. With the same purpose β -blockers, such as inderal, obzidan in small doses are recommended. In case of absence of these drugs 2 ml of a 2% solution of sodium citrate may be introduced.
· Diuretic therapy is also administered. At I stage of blood circulation insufficiency diuretics are not administered. In such cases it is possible to prescribe aminophylline, which improves renal blood flow and indirectly results in moderate increase of diuresis. It should be remembered about the features of individual tolerance of preparation during pregnancy; in addition, there is information that aminophylline somehow “robs” myocardium. At IIA stage of blood circulation insufficiency, thiazide diuretics and non-thiazide sulfanilamides (brinaldix) in combination with potassium-saving diuretics (verospiron) are effective.
· At IIB stage of blood circulation insufficiency more powerful diuretics are administered: furosemide, uregit in combination with potassium-saving diuretics. At III stage of insufficiency of blood circulation the medical treatment is similar to the above-stated. The courses of medical treatment with diuretics can last 3-5 days, in milder cases they are irregular. It is recommended to begin the treatment with small doses, gradually increasing them, achieving 2-3 litres of diurnal urine excretion.
· Along with diuretics and cardiac glycosides preparations of camphor and caffeine are applied.
· Metabolic therapy is administered for improvement of cardiac muscle function. Medical treatment is long, not less than a month: panangin 1-3 pills 3 times a day, potassium orotate (vitamin B13) by 0. 25 g 3-4 times a day, folic acid 0. 001g three times a day, inosine 0. 4 g 3 times a day.
· Oxygen therapy (oxygen froth, inhalation of moist oxygen, hyperbaric oxygenation).
· Antirheumatic medical treatment: a) antibiotics — etiotropic medical treatment (penicillin and his analogues depress vitality of hemolytic streptococcus), b) antiinflammatory therapy (glucocorticoids, salicylates, pyrazolone, indole derivative).
The 3rd hospitalization should be at term of 36-37 weeks of gestation for examining the patient before labor and choosing the obstetric management.
Management during Delivery
The choice of obstetric management for pregnant with heart diseases is determined not only by form of disease, but also by presence and degree of insufficiency of blood circulation, i. e. functional condition of the heart. The delivery through the maternal passages is the most preferable type of birth, of course in the absence of obstetric indications for cesarean section. The incidence of maternal morbidity and death at such patients is lower at vaginal birth than at cesarean section.
The patient should be placed in a lateral position. The maternal pulse and respiratory rate should be monitored. The increase of pulse over 100 beats per minute or respiratory rate over 24/min is a sign of possible cardiac decompensation. The obstetric management is directed at shortening of the second (expulsive) stage of labor: up to 2 hours in primiparae, and up to 1 hour in multiparae. For this purpose a dynamic evaluation of contractile activity of the uterus is made at birth, prophylaxis and medical treatment of anomalies of labor pains is performed.
An adequate analgesia, better a continuous epidural anesthesia, is appropriate for most patients to relieve pain. Avoidance of hypotension is of importance. A continuous hemodynamic monitoring is indicated for the patient and her fetus. The treatment before full opening of the cervix includes promedol, oxygen, digitalization. The basic danger in respect of developing decompensation of cardiac activity in birth is presented by expulsive (the second) stage of labor because of highest physical load which the woman’s organism undergoes in this period. Therefore the main question to decide for obstetrician-gynecologist and cardiologist at choice of obstetric approach is the question about the necessity of elimination of expulsive pains. The choice of obstetric approach in the second stage of labor should be oriented to degree of risk of unfavorable outcome of pregnancy in patients with cardiac diseases (according to Vanina L. V. ).
The I degree of risk: pregnancy at heart disease without expressed signs of insufficiency and without exacerbation of rheumatic process. Women of this risk group do not require elimination of expulsive pains.
During birth the following urgent indications for forceps delivery can occur:
· worsening of state in the second period of birth;
· hypoxia of the fetus;
· bleedings.
The II degree of risk is pregnancy at heart disease with the initial signs of cardiac insufficiency (breathlessness, tachycardia), presence of signs of active phase of rheumatism (AI stage by Nesterov). Delivery is conducted through maternal passages with maximum anaesthetizing, in the presence of cardiologist; elimination of expulsive pains is absolutely indicated in the second stage of labor.
The III degree of risk: pregnancy at a decompensated heart disease with signs of predominance of the right ventricular failure, at presence of active phase of rheumatism (AII), recently occurred fibrillation, pulmonary hypertension of II stage.
The IV degree of risk is pregnancy at a decompensated heart disease with signs of the
left ventricular failure, or total insufficiency, presence of active phase of rheumatism (AIII), long-existing fibrillation, pulmonary hypertension of III stage.
Pregnancy and birth for women of III and IV degree of risk are contraindicated.
Cesarean section in patients with decompensated heart diseases presents an increased risk for mother, so there are no generally accepted, expressly grounded indications for this operation. In patients with severe decompensation the cesarean section is the “operation of despair”, which is performed in the absence of requisite condition for delivery through maternal passages. Indications for cesarean section in pregnant women with heart diseases are the following:
· blood circulation insufficiency of IIB, III degree, maintained to the term of birth irrespective of disease causing decompensation;
· septic endocarditis;
· acute cardiac insufficiency, observed during pregnancy or developed in birth;
· severe pulmonary hypertension combined with IIB-III degree of insufficiency of blood circulation.
Management in Puerperium
The patient is to be closely observed for the first 24 hours. Autotransfusion that occurs after delivery of placenta can cause a marginally compensated woman to go into heart failure. Absolute bed rest, intramuscular injections of promedol just after delivery; oxygen continuously or intermittently should be administered. For prophylaxis of bleeding 0. 25 mg (1 ml) of methylergometrine is introduced intravenously in combination with 20 ml of a 40% glucose solution at the end of the second stage of labor. Methylergometrine is additionally introduced after delivery of afterbirth. Methylergometrine leads to effective contraction of uterus and decreases pressure in pulmonary circulation.
An early puerperal period (the first 2 hours after birth) is conducted depending on form of disease. To patients with mitral stenosis (pulmonary hypervolemia) it is not recommended to place weight on the abdomen in order to avoid repletion of lungs with blood from the abdominal cavity. To patients with aortic insufficiency, mitral incompetence (increased cardiac output), placing of weight on the abdomen is indicated, because it provides sufficient inflow of blood to the heart, helping to avoid hypervolemia.
In subsequent days patients with heart diseases need careful medical supervision. Regardless of type of delivery, there are 2 two critical periods in such patients after labor:
· from the first hours to 3-5 days;
· 7-8th day after labor (danger of exacerbation of rheumatic process).
In this connection patients with heart diseases are administered bed regimen from the 1st to 7-8th day after delivery; prophylaxis of exacerbation of rheumatic process should be carried out. Patients may be discharged from maternity hospital 2 weeks after birth.
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