Effect of fractional exhaled nitric oxide (FENO) based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs

• Whalen O.M.
• Campbell L.E.
• Lane A.E.
• Karayanidis F.
• Mallise C.A.
• Woolard A.J.
• Holliday E.G.
• Mattes J.
• Collison А.
• Gibson P.G.
• Murphy V.E.

Abstract

Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (F_ENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared F_ENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial – Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. 222 infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean=108.9 control, 108.5 intervention, p=0.93), language (mean=95.9 control, 95.6 intervention, p=0.87) and motor composite scores (mean=97.2 control, 97.9 intervention, p=0.25). Mean scores for secondary outcomes were also similar among infants born to control and F_ENO group mothers, with few results reaching p<0.05.

Conclusion. In this sample, F_ENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life.

Trial registration. ClinicalTrials. gov Identifier: ACTRN12613000202763.

Keywords: asthma; pregnancy; postpartum; FENO; child development; temperament; sensory processing; autism

References

1. Clark J.M., Hulme E., Devendrakumar V., Turner M.A., Baker P.N., Sibley C.P., et al. Effect of maternal asthma on birthweight and neonatal outcome in a British inner-city population. Paediatr Perinat Epidemiol. 2007; 21: 154–62.

2. Sawicki E., Stewart K., Wong S., Leung L., Paul E., George J. Medication use for chronic health conditions by pregnant women attending an Australian maternity hospital. Aust N Z J Obstet Gynaecol. 2011; 51: 333–8.

3. Clifton V.L., Engel P., Smith R., Gibson P., Brinsmead M., Giles W.B. Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population. Aust N Z J Obstet Gynaecol. 2009; 49: 619–26.

4. Perlow J.H., Montgomery D., Morgan M.A., Towers C.V., Pronto M. Severity of asthma and perinatal outcome. Am J Obstet Gynecol. 1992; 167: 963–7.

5. Wen S.W., Demissie K., Liu S. Adverse outcomes in pregnancies of asthmatic women: results from a Canadian population. Ann Epidemiol. 2001; 11: 7–12.

6. Dombrowski M.P., Schatz M., Wise R., Momirova V., Landon M., Mabie W., et al. Asthma during pregnancy. Obstet Gynecol. 2004; 103: 5–12.

7. Norjavaara E., de Verdier M.G. Normal pregnancy outcomes in a population-based study including 2968 pregnant women exposed to budesonide. J Allergy Clin Immunol. 2003; 111: 736–42.

8. Sobande A., Archibong E., Akinola S. Pregnancy outcome in asthmatic patients from high altitudes. Int J Gynecol Obstet. 2002; 77: 117–21.

9. Murphy V., Namazy J., Powell H., Schatz M., Chambers C., Attia J., et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG: Int J Obstet Gynaecol. 2011; 118: 1314–23.

10. Murphy V., Wang G., Namazy J., Powell H., Gibson P., Chambers C., et al. The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis. BJOG. 2013; 120: 812–22.

11. Lim R.H., Kobzik L., Dahl M. Risk for asthma in offspring of asthmatic mothers versus fathers: a meta-analysis. PLoS One. 2010; 5: e10134.

12. Namazy J.A., Murphy V.E., Powell H., Gibson P.G., Chambers C., Schatz M. Effects of asthma severity, eцxacerbations and oral corticosteroids on perinatal outcomes. Eur Respir J. 2013; 41: 1082–90.

13. Wang G., Murphy V.E., Namazy J., Powell H., Schatz M., Chambers C., et al. The risk of maternal and placental complications in pregnant women with asthma: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2014; 27: 934–42.

14. Croen L.A., Grether J.K., Yoshida C.K., Odouli R., Van de Water J. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case-control study. Arch Pediatr Adolesc Med. 2005; 159: 151–7.

15. Langridge A.T., Glasson E.J., Nassar N., Jacoby P., Pennell C., Hagan R., et al. Maternal conditions and perinatal characteristics associated with autism spectrum disorder and intellectual disability. PLoS One. 2013; 8: e50963.

16. Leonard H., De Klerk N., Bourke J., Bower C. Maternal health in pregnancy and intellectual disability in the offspring: a population-based study. Ann Epidemiol. 2006; 16: 448–54.

17. Patel S., Dale R.C., Rose D., Heath B., Nordahl C.W., et al. Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity. Transl Psychiatry. 2020; 10: 286.

18. Flannery K.A., Liederman J. A test of the immunoreactive theory for the origin of neurodevelopmental disorders in the offspring of women with immune disorder. Cortex. 1994; 30: 635–46.

19. Lyall K., Schmidt R.J., Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol. 2014; 43: 443–64.

20. Micali N., Chakrabarti S., Fombonne E. The broad autism phenotype: findings from an epidemiological survey. Autism. 2004; 8: 21–37.

21. Mouridsen S.E., Rich B., Isager T., Nedergaard N.J. Autoimmune diseases in parents of children with infantile autism: a case-control study. Dev Med Child Neurol. 2007; 49: 429–32.

22. Schatz M., Harden K., Kagnoff M., Zeiger R.S., Chilingar L. Developmental follow-up in 15-month-old infants of asthmatic vs control mothers. Pediatr Allergy Immunol. 2001; 12: 149–53.

23. Tamási L., Bohács A., Bikov A., Andorka C., Rigó J. Jr, Losonczy G., et al. Exhaled nitric oxide in pregnant healthy and asthmatic women. J Asthma. 2009; 46: 786–91.

24. Powell H., Murphy V.E., Taylor D.R., et al. Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial. Lancet. 2011; 378: 983–90.

25. Mattes J., Murphy V.E., Powell H., Gibson P.G. Prenatal origins of bronchiolitis: protective effect of optimised asthma management during pregnancy. Thorax. 2013; 69: 383–4.

26. Morten M., Collison A., Murphy V., Barker D., Meredith J., Powell H., et al. Asthma control during pregnancy, 17Q21 variants and childhood-onset asthma. Respirology. 2017; 22: 100.

27. Murphy V.E., Jensen M.E., Holliday E.G., Giles W.B., Barrett H.L., Callaway L.K., et al. Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes. Eur Respir J. 2022; 60: 2200298.

28. Murphy V.E., Jensen M.E., Mattes J., Hensley M.J., Giles W.B., Peek M.J., et al. The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (F_ENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health. BMC Pregnancy Childbirth. 2016; 16: 1–10.

29. NHMRC. National Statement on Ethical Conduct in Human Research. Canberra: NHMRC, 2007.

30. Dunn W. Sensory Profile 2. Bloomington, MN: Psych Corporation, 2014.

31. Medoff-Cooper B., Carey W.B., McDevitt S.C. The early infancy temperament questionnaire. J Dev Behav Pediatr. 1993; 14: 230–5.

32. Carey W.B., McDevitt S.C. Revision of the infant temperament questionnaire. Pediatrics. 1978; 61: 735–9.

33. Fullard W., McDevitt S.C., Carey W.B. Assessing temperament in one-to three-year-old children. J Pediatr Psychol. 1984; 9: 205–17.

34. Thomas A., Chess S., Birch H.G., Hertzig M.E., Korn S. Behavioral Individuality in Early Childhood. New York: University Press, 1963.

35. Reznick J.S., Baranek G.T., Reavis S., Watson L.R., Crais E.R. A parent-report instrument for identifying one-year-olds at risk for an eventual diagnosis of autism: the first year inventory. J Autism Dev Disord. 2007; 37: 1691–710.

36. Turner-Brown L.M., Baranek G.T., Reznick J.S., Watson L.R., Crais E.R. The First Year Inventory: a longitudinal follow-up of 12-month-old to 3-year-old children. Autism. 2013; 17: 527–40.

37. Bayley N. Bayley scales of infant and toddler development. San Antonio, TX: Harcourt Assessment, 2006.

38. Wagenmakers E.-J. A practical solution to the pervasive problems of p values. Psychon Bull Rev. 2007; 14: 779–804.

39. Nelson C.A. Neural development and lifelong plasticity. In: Keating DP (ed.). Nature and Nurture in Early Child Development. Cambridge University Press, 2011: 45–69.

40. Whalen O.M., Karayanidis F., Murphy V.E., Lane A.E., Mallise C.A., Campbell L.E. The effects of maternal asthma during pregnancy on child cognitive and behavioral development: a systematic review. J Asthma. 2019; 56: 130–41.

41. Mallise C.A., Murphy V.E., Campbell L.E., Woolard A.J., Whalen O.M., Milton G., et al. Early sensory and temperament features in infants born to mothers with asthma: a cross-sectional study. Front Psychol. 2021; 12: 713804.

42. Gordon M., Niswander K.R., Berendes H., Kantor A.G. Fetal morbidity following potentially anoxigenic obstetric conditions: VII. Bronchial asthma. Am J Obstet Gynecol. 1970; 106: 421–9.

43. Robijn A.L., Jensen M.E., Gibson P.G., Powell H., Giles W.B., Clifton V.L., et al. Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017. J Asthma. 2019; 56: 594–602.

44. Murphy V.E., Gibson P., Talbot P.I., Clifton V.L. Severe asthma exacerbations during pregnancy. Obstet Gynecol. 2005; 106: 1046–54.

45. Whalen O.M., Campbell L.E., Murphy V.E., Lane A.E., Gibson P.G., Mattes J., et al. Observational study of mental health in asthmatic women during the prenatal and postnatal periods. J Asthma. 2020; 57: 829–41.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)