Asthma in pregnancy

Table 1 Pregnancy associated asthma morbidity by severity classification

	Mild asthma n (%)		Moderate asthma n (%)		Severe asthma n (%)
	Schatz et al[51]	Murphy et al[55]	Schatz et al[51]	Murphy et al[55]	Schatz et al[51]	Murphy et al[55]
	(n = 873)	(n = 63)	(n = 814)	(n = 34)	(n = 52)	(n = 49)
Asthma Exacerbation	110 (12.6)	5 (8)	209 (25.7)b	16 (47)	27 (51.9)d	32 (65)
Unscheduled physician or ED presentation	99 (11.3)	4 (6.3)	157 (19.3)b	14 (41)	19 (36.5)b	20 (41)
Oral corticosteroid use	19 (2.2)	0 (0)	71 (8.7)b	4 (11.8)	20 (38.5)b	19 (38.8)
Hospitalization	20 (2.3)	2 (3.2)	55 (6.8)b	1 (2.9)	14 (26.9)b	9 (18.4)

^bP < 0.0001,

^dP < 0.001 vs preceding severity group (moderate to mild; severe to moderate). ED: Emergency Department.

Table 2 Stepwise approach to asthma therapy in pregnant and nonpregnant patients[49,60,62]

	Step	Preferred therapy in nonpregnant patients	Preferred therapy in pregnant patients	Alternative therapy in pregnant patients
Intermittent asthma	1	SABA, as needed1	SABA, as needed1	N/A
Persistent asthma	2	Low-dose ICS	Low-dose ICS	LTRA
	3	Low-dose ICS + LABA, or medium-dose ICS	Medium-dose ICS	LTRA
	4	Medium-dose ICS +LABA	Low-dose ICS + LABA	Medium-dose ICS, or
				high-dose ICS, or
				low-dose ICS + LABA + LTRA
	5	High-dose ICS + LABA	Medium-dose ICS +LABA, or high-dose ICS + LABA	LTRA + theophylline
	6	High-dose ICS + LABA + oral corticosteroid	High-dose ICS + LABA + oral corticosteroids	Omalizumab

¹SABA should be included as quick-acting rescue medication to be used as needed in all patients. SABA: Short-acting beta-agonist; LABA: Long-acting beta-agonist; ICS: Inhaled corticosteroid.

Table 3 Asthma medications in pregnancy and lactation

Medication	United States FDA pregnancy category1	Australian Drug Evaluation Committee pregnancy category2	German pregnancy risk category3	Lactation[85]
Inhaled corticosteroids
Beclomethasone	C	B3	Group 3	Unknown
Budesonide	B	A	Group 3	Unknown
Ciclesonide	C	B3	--	Unknown
Fluticasone	C	B3	Group 5	Unknown
Mometasone	C	B3	Group 5	Unknown
Short-acting β-agonists
Albuterol	C	A	--	Likely safe
Levalbuterol	C	A	--	Unknown
Terbutaline	C	A	--	Likely safe
Long-acting β-agonists
Formoterol	C	B3	Group 4	Unknown
Salmeterol	C	B3	Group 5	Unknown
Leukotriene inhibitors
Montelukast	B	B1	Group 5	Likely safe
Zafirlukast	B	B1	--	Possibly unsafe
Zileuton	C	--	--	Likely safe
Mast-cell stabilizers
Nedocromil	B	B1	Group 4	Unknown
Cromolyn	B	A	Group 1	Unknown
Systemic corticosteroids
Dexamethasone	C	A	--	Likely safe
Methylprednisolone	C	A	Group 3	Likely safe
Prednisone	C	A	Group 3	Likely safe
Theophylline	C	A	--	Likely safe
Omalizumab	B	B1	Group 4	Unknown

¹United States Federal Drug Association pregnancy categories[111]: Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters); Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women; Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks; Category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks; Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits;

²Australian Drug Evaluation Committee pregnancy categories[111]: Category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed; Category B1: Drugs that have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage; Category B2: Drugs that have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage; Category B3: Drugs that have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans; Category C: Drugs that, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible; Category D: Drugs that have caused are suspected to have caused or may be expected to cause an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects; Category X: Drugs that have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy;

³German pregnancy risk categories[113]: Group 1: Extensive human tests and animal studies have not shown the drug to be embryotoxic/teratogenic; Group 2: Extensive human tests of the drug have not shown the drug to be embryotoxic/teratogenic; Group 3: Extensive human tests of the drug have not shown the drug to be embryotoxic/teratogenic. However, the drug appears to be embryotoxic/teratogenic in animals; Group 4: No adequate and well-controlled studies of the drug’s effects on humans are available. Animal studies have shown no embryotoxic/teratogenic effects; Group 5: No adequate and well-controlled studies of the drug’s effects on humans are available; Group 6: No adequate and well-controlled studies of the drug’s effects on humans are available. Animal studies have shown embryotoxic/teratogenic effects”; Group 7: There is a risk that the drug is embryotoxic/teratogenic in humans, at least in the first trimester; Group 8: There is a risk that the drug is toxic to fetuses throughout the second and third trimesters; Group 9: There is a risk that the drug causes prenatal complications or abnormalities; Group 10: There is a risk that the drug causes hormone specific action on the human fetus; Group 11: There is a known risk that the drug is a mutagen/carcinogen.