Asthma and especially allergic asthma are encountered with an increasing frequency (1). While there are many etiological reasons for this disease, it is obvious that it is also affected by some special conditions. Physiological temporary changes such as pregnancy can also significantly affect the course of this disease. It is reported that this disease, which is still a common health problem in the world, occurs in 3.4-12.4% of pregnant women (2,3). Many consensus reports have also been published for the follow-up and treatment of this disease in pregnant women (4-8).
Does pregnancy affect asthma?
In many cohort and prospective studies published in the past, it was emphasized that asthma during pregnancy is subject to the 1/3 rule. In other words, it has been reported that asthma is not affected in 1/3 of pregnancies, worsens in 1/3, and improves in 1/3 of pregnancies (9,10). In addition, in two prospective studies, it was shown that the disease worsened in 52-65% of pregnant women with severe asthma, and worsened in only 8-13% of pregnant women with mild asthma (11,12). Asthma exacerbations are generally 24-36. It has been reported to occur between weeks (11,13). In the study of Murphy et al., it was shown that viral respiratory tract infections (34%) were the primary factor responsible for exacerbations in asthmatic patients, followed by non-compliance with inhaled steroid treatment (29%) (11). In another study, respiratory or urinary infections were found in 69% of pregnant women with severe asthma, 31% of pregnant women with mild asthma, and only 5% of pregnant women without asthma (14). Based on this information, it can be said that we should follow our pregnant asthma patients very well, regardless of the severity of asthma.
Physiological changes affecting asthma during pregnancy are shown in table.1.
Table.1: Physiological factors affecting asthma in pregnancy.
– Increase in free cortisol levels may have a protective effect against inflammatory triggers
– Increase in bronchodilator substances (such as progesterone) may cause improvement in airway responses
– Increase in bronchoconstrictor substances (such as prostaglandin F2-alpha may increase airway responsiveness) .
– Decreased activity of placental 11 beta hydroxysteroid dehydrogenase type 2 causes low birth weight by increasing placental cortisol concentration
– Placental gene expressions of inflammatory cytokines may increase the risk of low birth weight
– Modification of cell-mediated immune system to infection and inflammation may affect the maternal response.
Does asthma affect pregnancy?
We have very limited information on how pre-pregnancy asthma control will affect the course of pregnancy. In the study conducted by Martel et al., examining 1808 pregnant women with asthma, which can be considered the first study on this subject, an increased risk of hypertension was found in pregnant women who had the criteria for poorly controlled asthma before their pregnancy (15). Although some previous studies gave conflicting results, it was noted that some problems occurred in pregnant women with asthma who had asthma of varying severity and did not receive uncontrolled and appropriate treatment. Although there are studies showing that women with asthma have babies with low birth weight or intrauterine growth retardation (9,16), this has not been shown in large prospective studies (13,17,18). In a review that systematically reviewed 4 studies examining 1453 pregnant women with asthma, the relative risk of having a baby with a low birth weight was found to be 1.55 in pregnant women who did not use inhaled steroids (19). In another review that systematically evaluated another three studies that reviewed 934 patients, it was shown that the risk of having a low-birth-weight baby is increased in pregnant women with asthma exacerbation compared to pregnant women without asthma and pregnant women without asthma exacerbation (16). As a result of most studies, it has been determined that the use of inhaled steroids in pregnant women with asthma has positive effects on fetal development (20). On the other hand, significantly low birth weight babies were reported in pregnancies that were considered mild asthmatic and were not treated with steroids (20).
Apart from previous studies revealing the increased incidence of hypertension in pregnant women with asthma, two large, multicenter, prospective and well-designed studies have shown that gestational hypertension is more common in pregnant women with asthma symptoms or low airflow velocities (21,22). In addition, it has been reported that the requirement for cesarean section is increased in pregnant women with asthma compared to pregnant women without asthma in both previous and prospective studies (9,13,17).
Approach to asthma during pregnancy:
Approach and treatment principles for asthma during pregnancy generally do not show any difference compared to women and male patients outside of pregnancy (4-8). However, some precautions should be taken, especially during an asthma exacerbation, as shown in table-2. According to the results of a large prospective study examining pregnant women with asthma, an appropriate approach to asthma during pregnancy reduces both maternal and fetal problems (12,17). Frequency of antenatal fetal evaluation should be determined based on asthma severity, intrauterine growth retardation and pre-eclampsia risk (fetal ultrasonography, non-stress test).
Table.2: Approach in pregnant with acute asthma.
– Early intervention
– The well-being of mother and fetus should be followed closely
– Oxygen saturation should be kept above 95%
– PaCO2 should be kept below 40 mmHg
– The mother should be placed in the left side position
– If fluid intake is not possible, intensive IV fluid (125 ml/hour) should be given
– Hypotension should be avoided with appropriate position, hydration and treatments
– If there is only an anaphylactic condition, adrenaline should be used
– If necessary, early intubation should be performed, but a specialist may be required for this situation in pregnant women due to edema.
Education:
A pregnant woman with asthma should be well informed about the basic mechanisms of asthma; Information should be given about triggers, asthma control, tools to be used, medications, and personal behaviors. Both the physician and the patient should be alert, especially about environmental factors such as allergens.
Pharmacological treatment:
Some mothers and physicians are very concerned about the potential side effects of asthma medications on the mother and baby. According to a recent study, it was observed that 23% of women reduce their inhaled steroids, 13% reduce their short-acting ?2 agonists, and 54% reduce their oral steroids given for attacks when they become pregnant (23). In another study, pregnant women who applied to the emergency department started steroid treatment at a lower rate than non-pregnant women, and they also reduced the steroid doses used (24). Although such approaches seem safe, it has been shown that many perinatal problems are associated with low expiratory flow and uncontrolled asthma (21,22). In addition, prospective studies, case-control studies and systematic reviews have also shown that inhaled steroids, theophylline, and short-acting ?2 agonists do not increase the risk of fetal congenital malformation, preeclampsia, preterm birth or low birth weight (15,25-27). Therefore, good asthma control should be ensured during pregnancy, medications should be used regularly and patient compliance should be ensured.
Although the pharmacokinetics and absorption rates of many drugs change during pregnancy, there is no need for dose adjustment for drugs required for the treatment of asthma during pregnancy. It has been shown that systemic decongestants used in the first trimester cause a slight increase in the risk of fetal gastroschisis, intestinal atresia and hemifacial microsomia (28).
There are epidemiological studies showing that oral corticosteroids used in the first trimester cause fetal cleft lip-palate anomaly (29). However, such side effects can be ignored due to their life-saving effects, especially in severe asthmatic cases.
Large prospective case-controlled studies have shown that corticosteroids are associated with preterm labor and preeclampsia (15,30). Among these drugs, there is no fetal side effect since 90% of prednisone is inactivated in the placenta (31).
Inhaled steroids are the most important treatment tools in pregnant asthmatics and they do not cause any fetal marformation or perinatal mortality (15,19,25-27).
Cromolyn sodium and short-acting beta-2 agonists seem to be safe during pregnancy (21,25,30). There are few studies on long-acting beta-2 agonists. Although formeterol and salmeterol have been shown to cause fetal malformation in animal experiments, it did not cause fetal malformation, preterm birth or low birth weight in humans in prospective studies involving a small number of subjects (21,32,33). It has been shown that the best long-acting beta-2 agonists are used in combination with corticosteroids (34).
There are very few studies on the use of leukotriene antagonists in pregnant women. Fetal malformation was not observed in two studies evaluating a very limited number of patients (21,35).
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Wishing you healthy days…
Prof. Dr. Cengiz KIRMAZ
