Obstetrical & Neonatal Respiratory Issues

1. Obstetrical & Neonatal Respiratory Issues MikeClark, M.D., M.B.A., M.S. Obstetrics & Gynecology Visit me at Williammclarkmd.com

2. Maternal Topics I. Normal Anatomical and Physiologic Respiratory Changes in Pregnancy II. Maternal Respiratory Disorders in Pregnancy A. Pulmonary Edema associated with Preeclampsia B. Pulmonary Embolism in Pregnancy C. Amniotic Fluid Embolism D. Asthma in Pregnancy E. Pneumonia in Pregnancy F. Tuberculosis in Pregnancy G. Idiopathic Pulmonary Fibrosis H. Kyphoscoliosis I. Sarcoidosis J. Lung Cancer

3. Fetal and Neonatal Topics III. Fetal and Neonatal Respiratory Problems A. Fetal Distress diagnosed by Fetal Monitoring B. Viability C. Amniotic Fluid Testing for Lung Maturation D. Respiratory Distress Syndrome of the Newborn E. Meconium Aspiration F. Hypoplastic Lungs G. Asphyxiating Thoracic Dystrophy H. Patent Ductus Arteriosus I. Patent Foramen Ovale (Atrial Septal Defect) J. Tetralogy of Fallot K. Anomalous Venous Return L. Transposition of the Great Vessels

4. MATERNAL ISSUES

5. Normal physiologic changes during pregnancy Major hemodynamic alterations occur during pregnancy, labor, delivery and the postpartum period. These changes begin to take place during the first 5 to 8 weeks of pregnancy and reach their peak late in the second trimester. In patients with preexisting cardiac disease, cardiac decompensation often coincides with this peak.

6. Uterine Changes in Pregnancy Enlarging uterus decreases chest wall compliance Figure 28.15

7. 36 week fetus Ribs and sternum pushed out. Subcostal angle widened. Diaphragm pushed up

8. Anatomical Respiratory Changes in Pregnancy (1) • Capillary engorgement of the nasal and oropharyngeal mucosae and larynx begins early in the first trimester and increase progressively throughout pregnancy. • Nasal breathing commonly becomes difficult, and epistaxis may occur because of nasal mucosal engorgement.

9. Anatomical Respiratory Changes in Pregnancy (2) • Airway conductance increases, indicating dilation of the large airways below the larynx, mainly due to direct effects of progesterone, cortisone, and relaxin and possibly enhanced beta-adrenergic activity induced by progesterone. However, FEV1 and FEV1/FVC does not change. Flow = ΔP/R R (Resistance) = 8ηL/πr4 r is the radius raised to the fourth power– thus dilation increases flow

10. Anatomical Respiratory Changes in Pregnancy (3) • The thoracic cage increases in circumference by 5 to 7 cm during pregnancy because of increases in both the anteroposterior and transverse diameters. • Flaring of the ribs, which begins at the end of the first trimester, results in an increase in the subcostal angle from 68.5 degree to 103.5 degree at term. • The pregnant female becomes more barrel chested • Lung compliance is decreased as the uterus pushes up on the diaphragm

11. Jugular notch Clavicular notch Manubrium Sternal angle Body Sternum True ribs (1–7) Xiphisternal joint Xiphoid process False ribs (8–12) Intercostal spaces Costal cartilage Costal margin L1 Vertebra Floating ribs (11, 12)

12. Pregnancy places a great demand on the physiology of the maternal body – many organ-systems are changed and stressed. • Many preexisting medical conditions in the female are exacerbated during pregnancy.

13. Physiological Changes • Major hemodynamic alterations occur during pregnancy, labor, and delivery and the postpartum period. These changes begin to take place during the first 5 to 8 weeks of pregnancy and reach their peak late in the second trimester. In patients with preexisting respiratory disease, cardiac disease, decompensation often coincides with this peak.

14. Note that blood pressure generally goes down in pregnancy due to decreased vascular Resistance.

15. Physiological Respiratory Changes in Pregnancy Oxygen consumption: • Several authors have reported that oxygen consumption increases by 30% to 40% during pregnancy, the progressive rise is due primary to the metabolic needs of the fetus, uterus, and placenta and secondarily to increased cardiac and respiratory work. Carbon dioxide production shows changes similar to those of oxygen consumption

16. Ventilation • Minute ventilation increases by 45% during pregnancy, with increase evident early in the first trimester, as a *result of increase in tidal volume. Although respiratory rate declines slightly during mid gestation, it is essentially unaltered during pregnancy. Some females complain of *dyspnea as a result of no change in the respiratory rate. • The increased ventilation during pregnancy results from hormonal changes (particularly progesterone elevation) and increased carbon dioxide production. Though there is increased CO2 production – the increased minute ventilation actually drops the PaCO2 from 40 Hg in the non-pregnant state to 32 – 34 Hg in the pregnant state. • The central chemoreceptors become more sensitive to carbon dioxide levels due to progesterone level increases. • * Discussed on next slide

17. Physiologic Dyspnea • The increased minute ventilation in pregnancy is often perceived as a shortness in breath. • Shortness of breath at rest or with mild exertion is so common that it is often referred to a “physiologic dyspnea.” • About 75% of pregnant women have exertional dyspnea by 30 weeks of gestation • The proposed causes of dyspnea are increased drive to breath and the load imposed by the enlarging uterus • Other factors are increased pulmonary blood volume, anemia, and nasal congestion

18. The tidal volume expansion is a result of a decrease in Expiratory Reserve Volume

19. Progesterone and Breathing • Progesterone is a smooth muscle relaxant – thus it can dilate the tracheal-bronchial tree – providing increased airway conductance. • Progesterone is a known stimulant of respiration and respiratory drive, and its levels rise gradually rise from approximately 25 ng/mL at six weeks to 150 ng/mL at term • The respiratory centers in the brain appear to change their homeostatic set points during pregnancy; this is probably a function of the increasing levels of progesterone . • The mechanism is thought to involve an increasing sensitivity of the medulla (central chemoreceptor) to carbon dioxide such that increases in PaCO2 elicit an exaggerated respiratory effort , although a direct effect of progesterone on the respiratory center (DRG) cannot be excluded.

21. Maternal Respiratory Complications of Pregnancy A. Pulmonary Edema associated with Preeclampsia B. Pulmonary Embolism in Pregnancy C. Amniotic Fluid Embolism D. Asthma in Pregnancy E. Pneumonia in Pregnancy F. Tuberculosis in Pregnancy G. Idiopathic Pulmonary Fibrosis H. Kyphoscoliosis I. Sarcoidosis J. Lung Cancer

22. Preeclampsia • A pregnancy-specific syndrome characterized by new-onset hypertension and proteinuria, occurring usually after 20 weeks' gestation – most commonly after 34 weeks • Diagnosis - • BP of 140/90 mm Hg or greater after 20 weeks' gestation in a women with previously normal blood pressure and with proteinuria (>0.3 g protein in 24-h urine specimen).  • Eclampsia is defined as seizures that cannot be attributable to other causes in a woman with preeclampsia

23. Preeclampsia Preeclampsia can be mild, moderate or severe Severe preeclampsia is defined as the presence of one of the following symptoms or signs in the presence of preeclampsia: • Systolic BP of 160 mm Hg or higher or diastolic BP of 110 mm Hg or higher on 2 occasions at least 6 hours apart • Proteinuria of more than 5 g in 24-hour period • Pulmonary edema • Oliguria (<400 mL in 24 h) • Persistent headaches • Epigastric pain and/or impaired liver function • Thrombocytopenia • Intrauterine growth restriction

24. Pulmonary Embolism in Pregnancy • Pregnancy 5X increases the risk for Deep Venous Thrombosis (DVT) and a subsequent PE • Occurs in 1-5/1,000 deliveries • Leading cause of maternal death • DVT most common in left leg • Clotting factor V seems to be most involved • Difficult to diagnose since many pregnant patients have lower extremity edema and dyspnea • Perfusion scans generally used for diagnosis • Primary Treatment is Heparin (Coumadin cannot be used in pregnancy) Coumadin can cross the placenta • Thrombolytic agents can be used but cautiously due to increased bleeding

25. The Food and Drug Administration (FDA) created the following rating system in 1979 to categorize the potential risk to the fetus for a given drug.  Category A:    Controlled human studies have demonstrated no fetal risk Category B:    Animal studies indicate no fetal risk, but no human studies OR adverse effects in animals , but not in well- controlled human studies Category C:    No adequate human or animal studies, OR adverse fetal effects in animal studies, but no available human data. Category D:    Evidence of fetal risk, but benefits outweigh risks. Category X:    Evidence of fetal risk. Risks outweigh any benefits. 

26. Amniotic Fluid Embolus (1) • Occurs in 1/ 8,000 – 1/ 80,000 Pregnancies • Accounts for 10% of maternal deaths • Major risk factors are maternal age and multiparity • Lesser risk factors are amniotomy, cesarean section, intrauterine fetal monitoring, induction of labor, term pregnancy with an IUD in place • Most occur during labor – but can happen during any trimester, usually in the setting of uterine manipulation or trauma

28. Amniotic Fluid Embolus (2) Classic presenting signs and symptoms are; • Severe dyspnea and tachypnea • Pulmonary Edema • Tachycardia with cardiovascular collapse • Cyanosis • Disseminated Intravascular Coagulation (DIC) The diagnosis is made clinically- may aspirate from right atrium • Respiratory treatment is supportive – maximize oxygenation through mechanical ventilation with high oxygen concentrations using low tidal volumes • Cardiovascular treatment is to stabilize circulation using inotropic agents and vasoactive agents. The goal is to maximize cardiac output with the lowest possible left ventricular end diastolic pressures

29. Asthma in Pregnancy (1) • The prevalence of asthma in pregnancy is on the rise • In the world the asthma incidence in pregnancy ranges from 3.7 % - 13% (lower rate in U.S. and higher rate in the UK) • It is well known and widely reported that one third of women experience worsening of asthma during pregnancy, one third improve, and one third remain the same. • Between 25 and 32 weeks gestation, there was a significant increase in asthma symptoms for women that reported asthma worsening – whereas those reporting asthma improving – there was a decrease in wheezing • In all women there was a significant improvement in symptoms between 37 and 40 weeks

30. Asthma in Pregnancy (2) • The improvement of some pregnant patients with asthma is most likely due to increased levels of cortisol and progesterone during pregnancy • An interesting finding is that pregnant females carrying boys have less asthma symptoms than those with girls • Another interesting finding is smoking is more common among pregnant females with asthma those without the condition • Women having an exacerbation of their asthma during pregnancy had a higher incidence of Low Birth Weight babies– but not of premature babies • Inhaled corticosteroids have proven to be the most effective management of asthma in pregnancy

31. Sarcoidosis in Pregnancy Sarcoidosis is a systemic granulomatous inflammatory disease characterized by caseating granulomas (small inflammatory nodules). Its cause is unknown. Granulomas most often appear in the lungs or the lymph nodes, but virtually any organ can be affected. Normally the onset is gradual. Sarcoidosis may be asymptomatic or chronic and may cause death.

32. Pneumonia in Pregnancy • The most common cause of fatal non-obstetric infection • Can have adverse consequences for both the mother and her fetus, with certain infections (particularly viral and fungal) assuming greater virulence and mortality than in non-pregnant women of similar age • The pathogens for Community-Acquired Pneumonia are similar in pregnant and non-pregnant patients, with Streptococcus pneumoniae, Haemophilus influenza, Mycoplasma pneumoniae, Legionella spp., Chlamydophila pneumoniae, and influenza A accounting for the majority of cases • However, reduction in cell mediated immunity particularly in the third trimester increases the risk for more severe pneumonia infections with organisms such as herpes, varicella and coccidiomycosis

33. Pneumonia in Pregnancy • The incidence of pneumonia in pregnancy is widely varied among studies in different regions of the world – Finland has one of the higher rates and the U.S. one of the lower rates • The incidence of pneumonia in the U. S. has declined with the highest rate being found in the large urban hospitals • The onset of pneumonia can be at any time during gestation – with the mean gestational age being 24 – 31 weeks. • Major risk factors for pneumonia in pregnancy are anemia and history of asthma, use of tocolytic (labor stopping) agents, cigarette smoking and drug abuse • Viral and fungal pneumonia bear more significance in pregnancy than the bacterial pneumonias • Pregnancies having a pneumonia complication have an increased chance of preterm delivery and small for gestational age babies

34. Pregnancy changes predisposing to an increased incidence and Mortality from Pneumonia Immunologic changes • Reduced lymphocyte proliferative response • Delayed cell-mediated cytotoxicity • Reduced number of T-helper cells • Reduced lymphokine response to alloantigens Physiologic changes • Increase in Oxygen Consumption • Increase in lung water • Elevation of the diaphragm • Aspiration more likely in labor and delivery Coexisting illnesses • Smoking • Anemia • Asthma • Cystic Fibrosis • Illicit Drug Use • Immunosuppressive illness and therapy • Placental Abruption

35. Pneumonia in Pregnancy • The clinical presentation in pregnancy is not substantially different from the non-pregnant presentation – fever, cough, pleuritic chest pain, rigors, chills, and dyspnea • Most women with pneumonia do not have multilobar involvement – but when present does complicate the course of illness • The Pneumonia Severity Index (PSI) is the most widely used tool in the U.S. to determine if the patient needs inpatient care and the need for the ICU. • The PSI uses demographics (whether someone is older, and is male or female), the coexistence of co-morbid illnesses, findings on physical examination and vital signs, and essential laboratory findings. This study demonstrated that patients could be stratified into five risk categories, Risk Classes I-V, and that these classes could be used to predict 30-day survival.

36. Pneumonia in Pregnancy • Initial treatment is towards Streptococcus pneumoniae, Haemophilus influenza, Mycoplasma pneumoniae, Legionella spp., Chlamydophila pneumoniae – in that these are the most common organisms • Antibiotics that are safe in pregnancy against Community-Acquired Pneumonia are the penicillins, cephalosporins and erythromycin. Clindamycin may also be safe – but not adequately tested. • The fluoroquinolones should not be used in pregnancy

37. Antibiotics not to use in Pregnancy“unless absolutely necessary‘’ • Fluoroquinolones – due to risk of arthropathy, malformations, and carcinogenic (Baloxin, Raxar) • Chloramphenicol – can cause bone marrow suppression in fetus and if given near term can cause “gray baby syndrome” with gray facies, flaccidity and cardiovascular collapse • Tetracyclines – mother at risk for fulminant hepatitis and staining of teeth in newborn along with other dental abnormalities • Sulfa drugs can cause fetal kernicterus • Aminoglycosides – can cause fetal ototoxicity • Vancomycin poses a risk to the fetus in terms of nephrotoxicity and ototoxicity

38. The Food and Drug Administration (FDA) created the following rating system in 1979 to categorize the potential risk to the fetus for a given drug.  Category A:    Controlled human studies have demonstrated no fetal risk Category B:    Animal studies indicate no fetal risk, but no human studies OR adverse effects in animals , but not in well- controlled human studies Category C:    No adequate human or animal studies, OR adverse fetal effects in animal studies, but no available human data. Category D:    Evidence of fetal risk, but benefits outweigh risks. Category X:    Evidence of fetal risk. Risks outweigh any benefits. 

39. Viral Pneumonia in Pregnancy • The most common viral organism causing pneumonia is influenza A although other viral infections can also occur • Pregnant women are at increased risk for both acquiring influenza, and developing complications of the infection • Historically, influenza in pregnancy has been associated with a higher rate of morbidity and mortality (with the mortality highest in the last 3 months of pregnancy) • The clinical presentation is not altered by pregnancy • Antibiotics should be given to prevent secondary bacterial infections • Some antiviral medications can be given in pregnancy – such as Amantadine

40. Fungal Pneumonia in Pregnancy • Fungal pneumonia in pregnancy is rare – and if the women is healthy normally resolves without treatment. • If the fungal infection becomes widely disseminated – it carries a more serious prognosis • Cryptococcus neoformans, Histoplasma capsulatum, Sporothrix Schenckii, Blastomyces dermatitis, and Coccidioides immitis are the most common fungal organisms • For disseminated disease or severe pneumonia treatment with intravenous amphotericin B (pregnancy category B) is recommended followed by oral fluconazole post-partum.

41. Tuberculosis in Pregnancy Caused by infection with Mycobacterium tuberculosis • Attacks mostly the lungs – but can attack other organs • 1/3 of the world’s population now carries the TB bacterium • Not all that are infected with TB show signs (active TB) -many have a latent infection (asymptomatic)

42. Tuberculosis in Pregnancy • Two millennia ago – the Greeks believed that pregnancy made TB get better – thus women with TB were encouraged to get pregnant • This idea persisted until the 19th and 20th centuries when the concept completely changed – pregnancy is bad for TB • Currently – the concept is pregnancy does not alter the course of TB • Testing for TB in pregnancy is the same as in the non-pregnant patient – PPD, Chest X-ray and sputum cultures • Treatment for TB is virtually the same as in the non-pregnant state – Isoniazid (INH) and Rifampin

43. Tuberculosis in Pregnancy • INH does cross the placenta – but causes no problems in the fetus – however it does have some degree of hepatoxicity in the mother during pregnancy – thus if therapy can be delayed till after pregnancy – that it preferable • Treatment can generally be delayed if the patient has latent TB • Breast feeding while taking TB medication is OK if the mother does not have active TB – if the mother has active TB – it could be transferred to the newborn in cough droplets while breast feeding • Congenital transplacental transmission of TB is rare and occurs most commonly through hematogenous infection via the umbilical vein in mothers who have active TB of the placenta or genital tract

44. C= ∆V ⁄∆P Idiopathic Pulmonary Fibrosis in Pregnancy • Not common in pregnancy due to a higher incidence in males and usually occurs in women past childbearing age • The pregnancy outcome depends on the severity of the disease at the time of conception • In all restrictive lung diseases in pregnancy – patients experience breathing difficulties as pregnancy progresses since the expected increase in tidal volume is limited by the restrictive physiology and the much needed increase in minute ventilation is then achieved by an increase in respiratory rate. • Patients with severe IPF should avoid pregnancy • Epidural anesthesia is advised to minimize the stress of labor

45. Kyphoscoliosis in Pregnancy The severity of spinal curvature is measured by the Cobb angle, which is the angle formed by the intersection of perpendicular lines drawn superior to the highest vertebrae and the inferior angle to The lower vertebrae involved in the curvature. When the angle is greater than 100°, the vital capacity is reduced by 50%. Historically, patients with this condition were cautioned against pregnancy. However, studies of patients with a Cobb angle greater than 60° - show successful vaginal deliveries in most cases. Anesthetic considerations in pregnant patients during labor and delivery follow the same principles as other patients with restrictive lung disease.

46. Sarcoidosis in Pregnancy • Account for approximately 0.02 – 0.06% of normal deliveries • Has not been associated with an increased risk of fetal or maternal complications • The effect of pregnancy on the course of the disease is variable • Treatment during pregnancy is the same as in the non-pregnant state

47. Lung Cancer in Pregnancy (1) • Lung cancer has surpassed colon cancer as the leading cause of death in women • There is an increased incidence of smoking among adolescent girls • Evaluation for lung malignancy is generally delayed in pregnancy due to signs and symptoms being misinterpreted as respiratory changes of pregnancy and apprehension by doctors to do radiographic studies during pregnancy • Unfortunately many cases of lung cancer in pregnancy are diagnosed once the disease is locally advanced or metastatic. • Of 19 reported cases of lung cancer in pregnancy, placental metastasis were found in 8. • While the infant outcome is usually healthy – two reports describe metastasis to the infant- found months after delivery

48. Lung Cancer in Pregnancy (2) • Treatment depends on histologic cell type, gestational age at the time of diagnosis, clinical stage, possibility of surgery, and desires of the patient. • Generally surgery is delayed till the second trimester after organogenesis has been completed unless the patient opts for a therapeutic abortion • Low dose radiation with the abdomen shielded has not produced deleterious outcomes for the fetus • Overall chemotherapy is best reserved for the second or third trimester ,if necessary • If amniocentesis shows fetal lung maturity, early delivery may be an option – particularly for women that do not want to risk fetal exposure to radiation and/or chemotherapy

49. FETAL ISSUES LMP Date of Delivery ? ORGANOGENESIS ORGAN GROWTH AND INITIAL FUNCTIONING ORGAN MATURATION Trimester One Trimester Two Trimester Three LMP till end of 12th week Start of 13th week till 28th week 28th week till delivery

50. Fetal CardiorespiratoryDevelopment and Anatomy