Maternal asthma is associated with reduced female fetal growth.

Asthma during pregnancy is associated with a low birth weight, although the mechanisms contributing to this outcome remain unknown. The relationship between maternal asthma and its treatment, placental function, fetal sex, and low birth weight was examined to establish the effect of asthma on fetal growth. Glucocorticoid intake by women with asthma was assessed throughout pregnancy. The placenta was collected after delivery, and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was measured. Fetal cortisol and estriol were measured in the umbilical vein plasma at delivery. Those with asthma were compared with a nonasthmatic control group. In women with asthma who did not use inhaled steroids and were pregnant with a female fetus, we observed significantly reduced birth weights, whereas male birth weights were unaffected. The presence of a female fetus was associated with significantly increased maternal circulating monocytes, significantly reduced placental 11beta-HSD2 activity and fetal estriol, and a trend toward elevated fetal plasma cortisol. This study provides evidence that in pregnancies complicated by asthma there is a fetal sex-specific effect on the maternal immune system with adverse effects on placental function and female fetal growth.

[1]  C. Osmond,et al.  Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth , 2004, Diabetologia.

[2]  L. Akinbami,et al.  Trends in childhood asthma: prevalence, health care utilization, and mortality. , 2002, Pediatrics.

[3]  M. Hayashi,et al.  Elevated levels of serum macrophage colony-stimulating factor in normotensive pregnancies complicated by intrauterine fetal growth restriction. , 2002, Experimental hematology.

[4]  A. Varner The increase in allergic respiratory diseases: survival of the fittest? , 2002, Chest.

[5]  P. Gibson,et al.  Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma. , 2002, The Journal of clinical endocrinology and metabolism.

[6]  H. Hagberg,et al.  Aberrations in Placental Cytokine mRNA Related to Intrauterine Growth Retardation , 2002, Pediatric Research.

[7]  John W. Wilson,et al.  Asthma Management Handbook , 2002 .

[8]  S. Rennard,et al.  Interactions between monocytes and smooth-muscle cells can lead to extracellular matrix degradation. , 2001, The Journal of allergy and clinical immunology.

[9]  R. Smith,et al.  Alterations of placental vascular function in asthmatic pregnancies. , 2001, American journal of respiratory and critical care medicine.

[10]  M. Hlastala,et al.  Perfluorocarbon enhanced gas exchange: the easy way. , 2001, American journal of respiratory and critical care medicine.

[11]  M. Kramer,et al.  Maternal asthma and pregnancy outcomes: a retrospective cohort study. , 2001, American journal of obstetrics and gynecology.

[12]  R L Andres,et al.  Perinatal complications associated with maternal tobacco use. , 2000, Seminars in neonatology : SN.

[13]  Increased fetal glucocorticoid exposure delays puberty onset in postnatal life. , 2000, Endocrinology.

[14]  H. Okamura,et al.  IL-18 in pregnancy; the elevation of IL-18 in maternal peripheral blood during labour and complicated pregnancies. , 2000, Journal of reproductive immunology.

[15]  R. Kurth,et al.  Interleukin‐16 stimulates the expression and production of pro‐inflammatory cytokines by human monocytes , 2000, Immunology.

[16]  G. Peluso,et al.  Phenotypic features of alveolar monocytes/macrophages and IL‐8 gene activation by IL‐1 and TNF‐α in asthmatic patients , 2000, Allergy.

[17]  P. Barnes,et al.  Increased interleukin‐10 and macrophage inflammatoryprotein‐1α release from blood monocytes ex vivo duringlate‐phase response to allergen in asthma , 2000, Allergy.

[18]  S Senn,et al.  Repeated measures in clinical trials: simple strategies for analysis using summary measures. , 2000, Statistics in medicine.

[19]  J. Seckl,et al.  Inhibition of 11β‐hydroxysteroid dehydrogenase, the foeto‐placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety‐like behaviour in the offspring , 2000, The European journal of neuroscience.

[20]  P. Barnes,et al.  Increased interleukin-10 and macrophage inflammatory protein-1 alpha release from blood monocytes ex vivo during late-phase response to allergen in asthma. , 2000, Allergy.

[21]  S. Meshnick,et al.  Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. , 1999, The Journal of infectious diseases.

[22]  S. Matthews,et al.  Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain , 1999, Brain Research.

[23]  L. Dodds,et al.  Use of asthma drugs is less among women pregnant with boys rather than girls , 1999, BMJ.

[24]  N. Aggarwal,et al.  Pregnancy in Patients With Systemic Lupus Erythematosus , 1999, The Australian & New Zealand journal of obstetrics & gynaecology.

[25]  J. Newnham,et al.  Repeated antenatal corticosteroids: size at birth and subsequent development. , 1999, American journal of obstetrics and gynecology.

[26]  H. Sørensen,et al.  Pregnancy outcome for women with Crohn's disease: a follow-up study based on linkage between national registries , 1998, American Journal of Gastroenterology.

[27]  K. Demissie,et al.  Infant and maternal outcomes in the pregnancies of asthmatic women. , 1998, American journal of respiratory and critical care medicine.

[28]  G. Cochrane,et al.  Effect of sex of fetus on asthma during pregnancy: blind prospective stud , 1998, BMJ.

[29]  F. Thien,et al.  Differential regulation of allergen-specific T(H2)- but not T(H1)-type responses by alveolar macrophages in atopic asthma. , 1998, The Journal of allergy and clinical immunology.

[30]  P. Burton,et al.  Extending the simple linear regression model to account for correlated responses: an introduction to generalized estimating equations and multi-level mixed modelling. , 1998, Statistics in medicine.

[31]  P. Sly,et al.  Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. , 1998, Journal of immunology.

[32]  M. Kilby,et al.  11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. , 1998, Human reproduction.

[33]  E. Walters,et al.  Alveolar macrophages from atopic asthmatics, but not atopic nonasthmatics, enhance interleukin-5 production by CD4+ T cells. , 1998, American journal of respiratory and critical care medicine.

[34]  M. Fried,et al.  Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. , 1998, Journal of immunology.

[35]  V. Baste,et al.  Obstetrical and neonatal outcome in pregnant patients with rheumatic disease. , 1998, Scandinavian journal of rheumatology. Supplement.

[36]  R. Gilmour,et al.  The effects of cortisol on the growth rate of the sheep fetus during late gestation. , 1996, The Journal of endocrinology.

[37]  R J Walter,et al.  Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. , 1995, Cellular immunology.

[38]  R. Louis,et al.  Acute bronchial and hematologic effects following inhalation of a single dose of PAF. Comparison between asthmatics and normal subjects. , 1994, Chest.

[39]  A. Bellini,et al.  Detection of cytokines and their cell sources in bronchial biopsy specimens from asthmatic patients. Relationship to atopic status, symptoms, and level of airway hyperresponsiveness. , 1994, Chest.

[40]  Clark Sl Asthma in pregnancy. National Asthma Education Program Working Group on Asthma and Pregnancy. National Institutes of Health, National Heart, Lung and Blood Institute. , 1993 .

[41]  W. Karmaus,et al.  Sensitization to four common inhalant allergens within 302 nuclear families , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[42]  G. Marone,et al.  A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group. , 1993, The European respiratory journal.

[43]  S. Clark Asthma in pregnancy. National Asthma Education Program Working Group on Asthma and Pregnancy. National Institutes of Health, National Heart, Lung and Blood Institute. , 1993, Obstetrics and gynecology.

[44]  Clive Osmond,et al.  Fetal and placental size and risk of hypertension in adult life. , 1990, BMJ.

[45]  M. Schatz,et al.  Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study Group. , 1990, Chest.

[46]  T. Lao,et al.  Labour and delivery in mothers with asthma. , 1990, European journal of obstetrics, gynecology, and reproductive biology.

[47]  D. Barker,et al.  WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE , 1989, The Lancet.

[48]  D. Persaud,et al.  Inflammatory bowel disease: a controlled study of late pregnancy outcome. , 1989, American journal of obstetrics and gynecology.

[49]  J Golding,et al.  Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. , 1989, BMJ.

[50]  R. Patterson,et al.  Outcome of pregnancy in women requiring corticosteroids for severe asthma. , 1986, The Journal of allergy and clinical immunology.

[51]  W. Kitchen,et al.  Revised intrauterine growth curves for an Australian hospital population , 1983, Australian paediatric journal.

[52]  B. Brabin An analysis of malaria in pregnancy in Africa. , 1983, Bulletin of the World Health Organization.

[53]  Joseph J. Smith Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. , 1981, American journal of obstetrics and gynecology.

[54]  M. Gelfand,et al.  Incidence of Respiratory Distress Syndrome following Antenatal Betamethasone: Role of Sex, Type of Delivery, and Prolonged Rupture of Membranes , 1981, Pediatrics.

[55]  M. Schatz,et al.  Corticosteroid therapy for the pregnant asthmatic patient. , 1976, JAMA.

[56]  T. Bjerkedal,et al.  THE COURSE AND OUTCOME OF PREGNANCY IN WOMEN WITH BRONCHIAL ASTHMA , 1972, Acta allergologica.

[57]  P. Siiteri,et al.  Placental Estrogen Biosynthesis During Human Pregnancy1 , 1966 .

[58]  P. Siiteri,et al.  Placental estrogen biosynthesis during human pregnancy. , 1966, The Journal of clinical endocrinology and metabolism.