Our goal in asthma treatment is 'asthma control'. What is meant by this, is to both control asthma symptoms and also prevent possible future risks (1).
We frequently encounter in clinical practice that expectant mothers tend to discontinue their routine asthma medications during pregnancy (29). It is understandable that pregnant women may have a bias that anti-asthmatic drugs may harm their baby. However, sometimes obstetricians may react in an oversensitive manner and reduce or stop anti-asthmatic drugs without consulting a pneumologist first.
In our discussion, we will sometimes refer to pregnancy categories suggested previously by the US Food and Drug Administration (FDA) as the literature we have used mention them. However, FDA removed pregnancy categories A, B, C, D and X by “Pregnancy and Lactation Labeling Rule (PLLR or final rule)”, stating that this type of labeling caused misinterpretation and misuse among clinicians (30).
Thirty-three (78,6%) of the obstetricians participating in our survey think that inhaled beta2-mimetics are safe in pregnancy. Terbutaline should be the first choice among short-acting beta2-agonists in pregnancy (28). Long-acting beta2-agonist drugs, salmeterol and formoterol, should not be preferred in the first trimester (23, 28). Moreover, long-acting beta2-agonists should not be used alone, but should be given in combination with inhaled corticosteroids. It is known that low-dose inhaled corticosteroid and long-acting beta2-agonist combination used in the treatment of pregnant women with asthma does not pose a different risk in terms of major congenital malformations when compared to high-dose inhaled corticosteroids used alone (31). Budesonide is a category B inhaled steroid that can be safely used in patients with asthma (32). Although systemic corticosteroids are generally thought to be non-teratogenic, dexamethasone and betamethasone cross the placenta more than prednisone, prednisolone and methylprednisolone (23, 33).
Twenty-six (61,9%) of the physicians that completed our questionnaire, believe that oral and 21 (50%) physicians believe intranasal antihistamine drugs are safe in pregnancy. However, one should keep in mind that intranasal antihistamines such as azelastine and first generation oral antihistamines like brompheniramine and hydroxyzine should be avoided during pregnancy. Desloratidine, fexofenadine and azelastine are among category C antihistamines. Cetirizine, levocetirizine and loratidine, aka 'second generation' antihistamines (caution: not all of them), do not pose any problems during pregnancy and they are thought to be safe (23, 32, 34). Cetirizine, a a carboxylic acid metabolite of hydroxyzine (35), has been shown to have no adverse adverse outcomes even in the first trimester of pregnancy (36).
Some leukotriene receptor antagonists namely, montelukast and zafirlukast are considered among category B drugs in pregnancy (23), whereas zileuton is contraindicated (32). A cross-sectional epidemiological study conducted in Denmark showed no increase in major congenital anomalies risk fort the babies of asthmatic pregnant women on montelukast therapy (37). Similarly, a Japanese group of researchers detected no increase in major congenital anolaies due to montelukast use, even in the first trimester (38). However, only 13 (31%) of the obstetricians participating in the study believe they are safe during pregnancy.
There is little data on the safety of biologic agents such as omalizumab in pregnant women with asthma (39). Although it has been reported that Omalizumab, as a category B drug during pregnancy, do not increase the risk of major congenital anomalies in infants of pregnant women with asthma, it would be appropriate to evaluate on patient basis regarding the initiation or continuation of biological treatments during pregnancy (23, 40, 41, 42). The patient should be informed about the possible benefits and side effects of the treatment, and the patient should be made aware of the harm that severe and uncontrolled asthma can cause to the baby. The obstetricians participating in the present study seem to be rather abstaining, only 4 (9,5%) of all the doctors think that this treatment is suitable for the pregnant.
As to allergen specific immunotherapy during pregnancy: although no fetal complications due to immunotherapy have been reported till now, as present data on the effect of immunotherapy mainly focuses on therapy initiated prior to pregnancy, it is not recommended to start or increase the dose of immunotherapy during pregnancy, but previously started immunotherapy can be continued (23, 43). The obstetricians participating in the study were even more reluctant about immunotherapy: all but 2 (4,8%) think it is best to avoid allergen specific immunotherapy during pregnancy.
When asthma is accompanied by allergic rhinitis, intranasal budesonide should be the drug of choice. All intranasal steroids except budesonide are considered category C (23). Although, no increased risk of major congenital malformations or spontaneous abortion was detected with intranasal triamcinolone, respiratory system malformations (for example, choanal atresia) were higher in the children of mothers using this nasal steroid (44).
Although they should be avoided in the first trimester, oral corticosteroids are considered safe to be used in pregnancy if the benefit outweighs the potential harmful outcomes (34).
Twelve (28,6%) of the obstetricians believe that herbal cough syrup is safe during pregnancy. One of the most common used herbal cough syrups contains Hedera helix (English ivy) leaf extract and, alhough there is only one review suggesting that it is safe for short-term use during pregnancy (45), European Union herbal monograph on it does not recommend it use through pregnancy due to lack of data (46). Some herbal cough syrups contain Thymus serpyllum (wild thyme), on which there is no data available on its effect in pregnancy (47). Similarly, these cough syrups may also contain Althea officinalis (marshmallow), also having not enough safety data in pregnancy (48). One of the other ingredients often used in herbal cough syrups is Glycyrrhiza glabra (licorice), which is known to cause hypokalmia and hypertension, even with excess use, preterm birth might be expected (49). A study by Räikkönen et al., showed that children of pregnant women who used 500 mg or more glycyrrhiza extract per week had cognitive or psychiatric problems at the age of 8,1 years, compared to none or small dose of glycyrrhiza extract (50). Besides a handful of other herbal ingredients, an over-the-counter herbal cough syrup used in our country contains 825 mg of licorice extract in 30 mL, and it is recommended to be used 10 mL thrice a day. Even this daily dose in the syrup is well above the dose causing cognitive/psychiatric outcomes mentioned by Räikkönen et al.
Twenty eight (66,7%) of the doctors in our study believe that asthma treatment differs in pregnant women compared to non-pregnant individuals. However, the same asthma management principles should be applied in pregnant women as compared to non-pregnant asthmatics (26, 27, 51).
Thirty two (76,2%) of the obstetricians in our study state that they prefer vaginal delivery to cesarean section. According to the Asthma Diagnosis and Treatment Guide 2020 Update of Turkish Thoracic Society and Turkish National Allergy and Clinical Immunology Association, in mild and moderate asthmatics whose asthma is under control, a different approach is not followed from normal pregnant women and cesarean section should not be preferred. Epidural or spinal anesthesia can be used (23).
Twenty two (52,4%) of the obstetricians participating in our study think that asthmatic pregnant patients should visit their pulmonologist once a month, 14 (33,3%) think once in three months visit is enough, and 6 (14,3%) of the obstetricians believe the asthmatic patient does not need to see the pulmonologist until she has an exacerbation. We recommend an asthmatic patient to be called for pulmonary evaluation once a month throughout pregnancy, rather than as routinely followed, as proposed in GINA report (1).
In fact, well-controlled asthma is not expected to cause serious problems for both the mother and the baby (1). Supporting this statement, all of the obstetricians included in the study, agreed with this.
Expectant mothers have been vaccinated for tetanus for years, and most of the pregnant women do not state concern for this vaccine. In fact, all vaccines apart from live vaccines are considered safe in pregnancy (52). Live vaccines in pregnancy should only be administered if there is a major risk of morbidity and mortality for the mother or fetus.
When a pregnant woman is vaccinated during pregnancy, the antibodies formed pass through the placenta to protect the newborn baby.
Influenza complications tend to be worse in pregnant women than non-pregnant females (53). Inactivated influenza vaccine is accepted to be safe during pregnancy (52). Thirty-eight (90,5%) of the obstetricians in our study agree with this statment. Similarly, both the polysaccharide and conjugate pneumococcal vaccines are safe in pregnancy (52, 53, 54).
Streptococcus pneumoniae (also called Pneumococcus), a gram-positive encapsulated bacterium, was discovered by Pasteur and Sternberg in 1881 and caused many fatal pneumonia infections during the 1918 influenza pandemic (55, 56). When the expectant mother has a severe medical condition requiring pneumococcal vaccination, and both of the pneumococcal vaccines have to be administered, 13-valent conjugal vaccine should be administered before the polysaccharide vaccine. Interestingly only 23 (54,8%) of the obstetricians in our study think that pneumococcal vaccine is safe during pregnancy. However, it should be kept in mind that Pneumococcus is one of the most common airway pahtogens, sometimes causing serious outcomes, especially in patients with underlying pulmonary disesase. It can cause not only upper and lower respiratory tract infections (it is responsible for 20–50% of the pneumonias) (57) but also infections such as otitis media, sinusitis, meningitis and sepsis (58, 59).
A systematic review by Fu et al. suggests that vaccination against COVID does not promote any significant adverse reactions either on the pregnant or the fetus (60). Another review by Badell et al. confirms these results (61).