The course of asthma during pregnancy is variable and may remain unchanged, worsen, or improve, returning to the pre-pregnancy state within three months after parturition.1 Some patients experience the same changes in each pregnancy, but nearly half do not, suggesting some intrinsic or extrinsic factor unique to each pregnancy such as the sex of the fetus.1 We observed that the condition of patients with moderate to severe asthma generally deteriorated when they were pregnant with girls but not boys, raising the intriguing possibility that the sex of the fetus might influence the course of asthma during pregnancy. We investigated this possibility in a blind prospective study.
Subjects, methods, and results
All women aged 25-34 who were receiving regular drug treatment for asthma and were in the second trimester of pregnancy (12-21 weeks’ gestation) were approached directly to participate in the study. Twenty eight women were recruited from three hospital and four general practice antenatal clinics and six from an asthma clinic. Twelve had not taken inhaled steroids (beclomethasone or budesonide) regularly before pregnancy, 16 took 200-500 μg daily, and six more than 500 μg daily. None was taking oral steroids. None knew the sex of their baby before delivery. The study took the form of a questionnaire on symptoms of asthma, cough, shortness of breath, nocturnal waking due to asthma, drug treatment (frequency and amount), and visits to a doctor for asthma before and since the beginning of pregnancy, a minimum period of 12 weeks. Subjects were also asked to keep daily diary cards and peak expiratory flow readings throughout pregnancy. All 34 subjects completed the questionnaire; only 15 agreed to keep daily records and only 6 successfully completed these. We have therefore based our analysis on the questionnaire alone. Subjects were contacted again after parturition to ascertain the sex of the baby.
Eighteen women had boys and 16 girls. There was no difference in age range of mothers, gestation at time of questionnaire, or severity of asthma before pregnancy between the two groups. Roughly equal numbers of mothers of boys and mothers of girls reported no change in asthmatic symptoms. However, 4 of the 18 mothers of boys reported an overall deterioration in symptoms and 8 an improvement, while 8 of the 16 mothers of girls reported an overall deterioration and none an improvement. The table shows responses to questions on individual symptoms with the results of analysis using a 2×2 χ2 test comparing proportions of subjects with deteriorating symptoms with proportions of those who improved or showed no change for mothers of boys and girls. For most questions there was a trend for greater proportions of mothers of girls to report increased symptoms and for greater proportions of mothers of boys to report an improvement in their asthma. Significant differences were found in shortness of breath, nocturnal waking, and general symptoms of asthma.
Comment
This study suggests that asthmatic women pregnant with girls are more likely than those pregnant with boys to have increased symptoms of asthma during pregnancy. Any psychological basis for this difference is unlikely as none knew the sex of her baby before delivery. All patients were questioned early in the second trimester, making it unlikely that the results were influenced by the tendency for asthma to improve late in pregnancy.2,3 Minute hormonal differences may be implicated. Acute exacerbations of asthma increased fourfold in women from day 26 to day 4 of the menstrual cycle,4 and injection of progesterone can reduce premenstrual asthma.5 Male fetuses produce a surge of androgens at weeks 12-16, when most of our patients completed the questionnaire.
Our limited study suggests a relation between fetal sex and the potential development of unstable asthma in pregnancy, a clinically important observation for all concerned with antenatal care. This intriguing finding should stimulate further investigation.
Table.
Results of questionnaire survey of 34 women during second trimester of pregnancy according to sex of baby delivered. Values are numbers of women in each group
| Worse
|
Same
|
Better
|
χ2 (95% CI)* | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Boys | Girls | Boys | Girls | Boys | Girls | ||||
| Cough | 5 | 7 | 7 | 8 | 6 | 1 | 3.87 (−48% to 16%)† | ||
| Shortness of breath | 5 | 13 | 7 | 3 | 6 | 0 | 9.72 (−83% to −23%)‡ | ||
| Nocturnal waking | 6 | 10 | 5 | 5 | 7 | 1 | 5.37 (−8% to 62%)¶ | ||
| General state of asthma | 5 | 9 | 5 | 6 | 8 | 1 | 6.3 (−4% to 60%)¶ | ||
| Amount of drug treatment | 8 | 7 | 4 | 5 | 6 | 4 | 0.28 (−33% to 34%) | ||
| Frequency of drug treatment | 6 | 7 | 7 | 8 | 5 | 1 | 2.7 (−22% to 44%) | ||
| Visits to doctor | 3 | 5 | 10 | 11 | 5 | 0 | 3.84 (−15% to 43%)† | ||
Comparison of proportion of women who were worse with proportion who were not worse for boys and girls; 95% confidence interval given for difference in proportions.
P=0.05.
P<0.01.
P<0.05.
Acknowledgments
We thank the general practitioners and obstetricians who gave us access to antenatal clinics.
Footnotes
Funding: Abbott Laboratories gave a grant of £250 towards travelling expenses to clinics and to meet patients.
Conflict of interest: None.
References
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