DISEASE IN PREGNANCY
Educational Objectives
| The goal of this program is to improve the care of pregnant patients with asthma and improve the detection and
management of thyroid disease in pregnancy. After hearing and assimilating this program, the clinician will be
better able to:
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 | 1. Identify the objective measures of pulmonary function.
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| 2. Classify the severity of asthma based on symptoms.
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| 3. Implement the step-care approach to asthma management.
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| 4. Discuss the impact of pregnancy on thyroid function.
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| 5. Discuss issues in the diagnosis and management of thyroid disease in pregnancy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning
committee reported nothing to disclose.
Acknowledgments
Dr. Field was recorded at Antepartum and Intrapartum Management, sponsored by the University of California, San
Francisco, School of Medicine, and held June 7-9, 2007, in San Francisco. Dr. McIver was recorded at OB/GYN Clinical
Reviews, sponsored by Mayo School of Continuing Medical Education, and held November 8-9, 2007, in Rochester,
MN. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of
this program.
| ASTHMA IN PREGNANCY —Robin Field, MD, Clinical Professor of Obstetrics, University of California, San
Francisco, School of Medicine, and Director of Perinatal Services, Kaiser Permanente Medical Center, San Francisco
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| General considerations: asthma characterized by chronic airway inflammation; increased airway responsiveness to
variety of stimuli causes constriction of smooth muscle and airway obstruction; obstruction reversible; prevalence—
increasing, especially among pediatric population; currently >20 million Americans with asthma; 2 million hospitalizations;
11 asthma-related deaths each day; affects 4% to 8% of pregnancies; excellent perinatal outcome if controlled;
poorly controlled asthma associated with intrauterine growth retardation, prematurity, cesarean delivery, and
preeclampsia
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| Diagnosis: episodic symptoms of airflow obstruction (eg, wheezing, cough, shortness of breath [(SOB)]; objective
measures of reversible airway obstruction—forced expiratory volume in 1 second (FEV1) best measurement of airflow;
requires spirometry; peak expiratory flow rate (PEFR) can be measured in office and by patient; measures
large airway function; correlates well with FEV1 ; measured with inexpensive and easy-to-use peak flow meters;
380 to 550 L/min typical PEFR in pregnancy (PEFR does not change in pregnancy)
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| Principles of management: objective monitoring of lung function; avoidance or control of asthma triggers; patient
education; individualized pharmacologic treatment; inhaled corticosteroids preferred baseline daily medication;
step-care therapeutic approach used for fluctuating symptoms; prevention of hypoxic episodes and delivery of
healthy baby ultimate goals; important to classify asthma severity; studies show peak in asthma exacerbation between
17 and 24 wk gestation (hypothesis that due to patient discontinuing medications early in pregnancy); fewer
asthma exacerbations later in pregnancy; study showed 12% exacerbation rate and 2% hospitalization rate among
patients with mild persistent asthma; patient with severe asthma had exacerbations >50% of time and required hospitalization
25% of time; mild asthma in conjunction with upper respiratory infection can become fatal
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| Classification of asthma severity: mild intermittent—2 symptoms per week; <2 nocturnal symptoms per month;
PEFR or FEV1 >80%; little day-to-day variability in PEFR; mild persistent—>2 symptoms per week, but not daily;
exacerbations may affect activity; nocturnal symptoms >2 times per month; more PEFR variability; moderate
persistent—daily symptoms; regular medications necessary to control symptoms; >1 nocturnal symptom per week;
PEFR or FEV1 >60% to <80% predicted value; more day-to-day variability; severe persistent—continuous symptoms
and frequent exacerbations; multiple courses of oral corticosteroids may be necessary; frequent nocturnal
symptoms; lung function significantly affected; increased variability; important to address symptoms; untreated
chronic inflammation causes remodeling of bronchioles and degrading of pulmonary function
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| Pharmacologic therapy and patient education: medications for long-term control—anti-inflammatory agents
and inhaled corticosteroids; quick-relief medications—short-acting; inhaled β2 -agonists; patient education—chronic
inflammatory process; roles of medication; importance of self-monitoring of PEFRs and correct use of inhalers; environmental
control measures; when and how to take rescue measures; asthma triggers—diary useful if patient unsure;
dust mites, pet dander, irritants (eg, tobacco smoke); nonsteroidal anti-inflammatory drugs (NSAIDs)
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| Treatment: individualize therapy; assess asthma status and integrate care during prenatal visit (peak flow meters in examination
room recommended); use step-care approach to therapy; inhalation medications and medications with long
history of use in pregnancy preferred; inhaled corticosteroids—budesonide preferred during pregnancy; only inhaled
corticosteroid that is pregnancy class B (others pregnancy class C); appropriate to continue medication that enables
patient to be well controlled; most effective for long-term control of persistent asthma; no significant risk for systemic
effects in low- to medium-dose range; at high doses, adverse effects minimized by using holding chamber or spacer
and rinsing mouth afterwards; rapid-acting bronchodilators—albuterol preferred during pregnancy; instructions on using
metered dose inhalers—shake canister for 5 min; exhale; place mouth tightly around mouth piece; inhale slowly for
4 to 6 sec; while inhaling, push down canister to administer medication; hold breath 6 sec (allows medication to go
down to lungs); studies show 75% of patients do not use inhalers correctly; inhaling too quicky, breathing in through
nose, and not breathing after activation all interfere with drug delivery; spacer tube or holding chamber can improve
medication delivery; more on rapid-acting bronchodilators—salmeterol long-acting inhaler; leukotriene moderators
oral medications (pregnancy class B)
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| Step-care therapeutic approach: general principles—medications titrated to minimum doses required for control;
step up if control not maintained; doses may differ from that shown on package label; rescue course of systemic
steroids may be needed at any step; mild intermittent asthma—no daily medication needed; quick-relief
bronchodilator as needed for symptoms; if bronchodilator used >2 times/wk, low-dose inhaled corticosteroids
needed; mild persistent asthma—low-dose inhaled corticosteroid and short-acting β2 -agonist for quick relief; moderate
persistent asthma—2 options; 1) low-dose inhaled corticosteroid in combination with long-acting β2 -agonist
(eg, salmeterol) or 2) medium-dose inhaled corticosteroid; short-acting inhaled β2 -agonist also needed; increasing
or daily use indicates need for step-up in long-term control therapy; severe persistent asthma—consultation with
asthma specialist recommended; daily medications for long-term control; high-dose inhaled corticosteroids and
long-acting bronchodilator; short-acting inhaled β2 -agonist for quick relief; repetitive doses of oral corticosteroids
often needed
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| Written action plan: Cochrane Review showed patients with written action plan had better success in controlling
asthma; categories based on “personal best” PEFR (different from predicted value); green zone for patient with moderate
to severe asthma—80% to 100% of PEFR; asthma well controlled; high yellow zone—65% to 80% of personal
best PEFR; increase inhaled corticosteroid to medium dose range and increase bronchodilator until back in green
zone; call provider if dropping into high yellow zone frequently; low yellow zone—50% to 65% of personal best
PEFR; increase inhaled corticosteroids to high dose level; initiate aggressive bronchodilator therapy (2-6 puffs every
20 min for 1 hr), continuing for several hours until symptoms controlled; call provider if not improved; red
zone—emergency; personal best PEFR <50%; aggressive course of albuterol or rapid-action betamimetics every
10 to 20 min for 3 doses; prednisone; if not significantly improved, seek medical attention
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| Risk factors for fatal asthma: previous intubation; acute exacerbation despite oral corticosteroids; serious psychiatric
or psychosocial problems; emergency treatment—supplemental oxygen (keep O2 saturations >95% and
PO2 ≈70%); oral or inhaled medications; 24-hr observation after medication adjusted shows no deterioration; hospitalization
indicated for patient with poor response (FEV1 or PEFR 40%-70%), history of severe asthma or evidence
of nonreassuring fetal heart rate tracing; discharge regimen—minimal or no wheezing; FEV1 remains 60% to
70% of predicted value; oral or inhaled medication; 24-hr observation after medication adjusted shows no deterioration;
provide asthma education; follow-up appointment within 1 wk
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| Summary of management: mild intermittent asthma—quick-relief medication as needed; mild persistent—low-
dose inhaled corticosteroid daily; moderate persistent—medium-dose inhaled corticosteroid or low-dose with long-
acting bronchodilator (eg, salmeterol); severe persistent—high-dose inhaled corticosteroid plus long-acting bronchodilator;
prednisone for emergency care at home
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| THYROID DISEASE IN PREGNANCY —Bryan McIver, MBChB, PhD, Consultant, Mayo Clinic and Foundation,
Rochester, MN
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| Impact of thyroid disease in pregnancy: can affect fetal/maternal bonding, breast-feeding, and family relationship;
can cause postnatal thyrotoxicosis in baby and impact postpartum development, maturation and growth of
baby
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| Physiologic changes in thyroid function during pregnancy: total thyroxine measurement— majority of circulating
thyroid hormone bound to thyroid-binding proteins, which make it inactive; only free thyroid hormone active;
anything interfering with thyroid-binding proteins compromises total thyroxine measurement; high thyroid hormone
level or increased level of binding proteins may elevate total thyroxine; thyroid-binding globulin (TBG)—increases because
of estrogenic stimulation; rises through first trimester and remains high throughout pregnancy into postpartum
period; total thyroid hormone levels increase as TBG binds more thyroid hormone; human chorionic gonadotropin
(hCG)—concentrations increase; cross-reacts with thyrotropin (TSH) receptor; drives production of thyroid hormone;
TSH decreases in first trimester; total and free thyroxine rise; TBG rises significantly; dramatic turnover of
thyroid hormone; woman utilizes 1.5 to 2 times more thyroid hormone per day during pregnancy than when nonpregnant;
increased thyroid turnover—caused by increased renal clearance of iodine and increased TBG; maternal
plasma volume increases; fetal uptake of iodine and thyroid hormone through placenta drains thyroxine from maternal
circulation; placental deiodination of thyroid hormone; increased demand for thyroid hormone; thyroid increases
in volume and size (30% in normal pregnancy); thyroid antibodies (eg, thyroid peroxidase and thyroglobulin)—seen in
≈15% of women of childbearing age; presence does not confirm diagnosis of disease, but indicates predisposition to
development of thyroid disease; hypothyroidism more common than hyperthyroidism; ≈0.5% of women per year
through lifetime develop hypothyroidism
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| Hyperthyroidism: symptoms—heat intolerance, excessive sweating, anxiety, palpitations, weight loss, and hyperdefecation;
thyroid disease commonly missed; thyrotoxicosis and hyperthyroidism interchangeable terms; affects
≈2 in 1000 pregnancies; causes—Graves’ disease (preexisting or newly diagnosed), hyperemesis gravidarum, nodular
goiter, silent thyroiditis (believed caused by trigger to immune system), and exogenous thyrotoxicosis; hyperdynamic
circulation in pregnancy often masks signs (eg, vasodilation, warmth [peripherally], palmar erythema,
rapid or bounding pulse) and symptoms; look for eye and skin changes and evidence of goiter; hyperemesis
gravidarum—measuring TSH receptor antibodies can distinguish whether cause is Graves’ disease or hyperemesis;
characterized by prolonged severe nausea with intractable vomiting, failure to gain weight (important sign), and severe
dehydration leading to electrolyte imbalances; abnormal liver function can result; hyperthyroidism common in
women having hyperemesis; challenge is determining whether symptoms result of thyrotoxic state or thyroid
changes incidental to hyperemesis; ≈60% of women with hyperemesis gravidarum have suppressed TSH; results
from high hCG and nonthyroid illness (euthyroid sick syndrome); severe hyperemesis and dysfunction of thyroid
gland more likely with multiple gestations; acidic isoforms of hCG and high concentrations of hCG shown to trigger
nausea; hCG cross-reacts with thyroid TSH receptor and drives thyroid to become overactive; thyrotoxicosis
significant cause of nausea
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| Treatment: supportive (eg, fluid, bedrest, antiemetics); β-blockers useful for controlling tachycardia; use of antithyroid
medications may improve nausea by lowering thyroid hormone level; antithyroid medications associated with fetal
cutis aplasia (congenital skin defect of scalp [rare])
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| Consequences of Graves’ disease: low birth weight, premature labor, preeclampsia, and pregnancy-associated hypertension;
neonatal hyperthyroidism—transplacental transfer of immunoglobulin that binds to TSH receptor of neonate,
driving thyrotoxicosis; uncertain whether increased risk for congenital malformations related to Graves’
disease in first trimester
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| More on treatment: radioactive iodine or other isotopes contraindicated in pregnancy; thyroid surgery shown safe in
second trimester; antithyroid medications most common treatment of thyrotoxicosis caused by Graves’ disease;
thioamides—propylthiouracil (PTU) preferred; does not cross placenta as efficiently as methimazole; few case reports
of fetal cutis aplasia; use lowest possible dose of PTU to maintain maternal TSH at or below lower limit of
normal range; fetal heart rate monitoring warranted (indicator of fetal thyroid function); ultrasonography for assessment
of fetal goiter; high levels of maternal circulating TSH predictive of fetal thyrotoxicosis; combination of PTU
and methimazole associated with concern about fetal thyrotoxicosis; Graves’ disease and other autoimmune conditions
may go into remission; monitor thyroid function every 1 mo to 6 wk throughout pregnancy (medication may
need to be tapered or discontinued); consider discontinuing PTU ≥1 mo before delivery to avoid neonatal hypothyroidism
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| Postpartum: exacerbation of Graves’ disease common (autoimmune processes tend to lessen during second and
third trimesters and flare postpartum); postpartum thyroiditis—thyroid uptake of iodine shut down; occurs in first
2 or 3 mo after delivery; 6- to 12-mo supply of thyroid hormone in thyroid gland; 100-fold increased likelihood
in women with positive thyroid peroxidase antibodies; underrecognized and underdiagnosed; thyroid uptake of
iodine low; radioactive isotope uptake testing best way to distinguish between Graves’ disease and postpartum
thyroiditis
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| Hypothyroidism: likely to develop during pregnancy if patient’s thyroid function borderline before pregnancy; previously
treated women with hypothyroidism may require significant increase in dosage of thyroid hormone during
pregnancy in order to sustain normal circulating thyroid hormone levels; mimic normal function by giving extra
thyroid hormone and lowering TSH level; women with positive thyroid antibodies more likely to develop hypothyroidism
and other thyroid dysfunctions during pregnancy; untreated or undertreated hypothyroidism may significantly
affect child (as fetus and infant); thyroid hormone requirements increase by 30% to 50% during pregnancy
(normal increase in dose of thyroid hormone ≈30%); TSH often slightly higher in women with positive antibodies
during first and second trimesters; significant impact if untreated (eg, reduction in fertility, pregnancy-induced hypertension,
altered or delayed brain development in offspring); fetal brain development thyroid hormone-dependent
(mother must provide for thyroid requirements of fetus); severe morbidity associated with combination of hypothyroidism
and iodine deficiency (cretinism remains problem worldwide); data show significant intellectual sequelae
(loss of 7 IQ points, compared to controls) in women untreated for hypothyroidism; treatment—varying strengths
of thyroid hormone; no association with risks or complications; normal range controversial; normal range of TSH
should be narrower than that considered customary
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Suggested Reading
Bracken MB et al: Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2005 pregnancies.
Obstet Gynecol 102:739, 2003; Casey BM, Leveno KJ: Thyroid disease in pregnancy. Obstet Gynecol
108:1283, 2006; Committee on Patient Safety and Quality Improvement; Committee on Professional
Liability: ACOG Committee Opinion No. 381: Subclinical hypothyroidism in pregnancy. Obstet Gynecol 110:959,
2007; Dombrowski MP: Asthma and pregnancy. Obstet Gynecol 108:667, 2006; Neale DM et al: Thyroid disease
in pregnancy. Clin Perinatol 34:543, 2007; Surks MI et al: Subclinical thyroid disease: scientific review and
guidelines for diagnosis and management. JAMA 291:228, 2004.
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