Maternal Asthma Is Associated with Reduced Female Fetal Growth

Abstract

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.

Review: Placental adaptations to the presence of maternal asthma during pregnancy

“…There are known sex specific differences in fetal growth and survival in 34 pregnancies complicated by asthma which include females being more 35 susceptible to low birthweight (LBW, <2500g) and small for gestational age 36 (SGA, <10 th birthweight centile), and males more likely to deliver preterm (<37 37 weeks gestation) and at higher risk of stillbirth especially as asthma worsens 38 with increasing gestation [1][2][3]. These sex specific differences may be conferred 39 by the placenta which adapts to reduce female growth but as a result increases survival and considers the consequences of that adaptation for life long health.…”

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

“…Moreover, maternal asthma during pregnancy has been shown to result in dysfunction of bronchial relaxation in offspring rats via inhibition of epinephrine synthesis. 47 Furthermore, maternal hypoxia has been shown to affect fetal growth, placental function, and length of gestation, [48][49][50] and these birth outcomes have been linked with adverse health outcomes in numerous studies. 51,52 Therefore, maternal hypoxia may, via restricted fetal oxygenation, result in multiple organ pathology that manifests in a wide range of offspring diseases.…”

Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

“…Normal physiological glucocorticoid levels: During pregnancy, the term female placenta has significantly higher expression of the GR [31] and 11 HSD2 activity [76] than placentas of male fetuses. Glucocorticoids are known to negatively regulate GR expression [66,77], therefore the higher GR expression within placentas of female fetuses may be physiological evidence that the female fetal-placental unit is exposed to less bioactive cortisol at term than the male.…”

“…Female babies born to asthmatic mothers, who utilised inhaled glucocorticoid treatments to manage their symptoms, were found to be growth-reduced unlike male babies born to asthmatic mothers, who were normally grown, despite similar cord blood cortisol levels [76]. Placentas of male and female babies born to these mothers, had reduced vascularisation within the placental villi, resulting in reduced absolute fetal capillary volume [94], although this was most striking in placentas of male fetuses.…”

“…This reduction in 11 HSD2 activity would be expected to compound the already increased exposure of the male fetus to cortisol brought about by the decreased term 11 HSD2 activity within male placentas during a normal pregnancy [76]. This may further compound the reduced immune function in male fetuses, thus increasing their susceptibility to disease.…”