Fetal Adrenal Gland Volume and Cortisol/Dehydroepiandrosterone Sulfate Ratio in Inflammation-Associated Preterm Birth
ABSTRACT Fetal adaptation to stress is regulated in part by the pituitary-adrenocortical system. The stress hormones dehydroepiandrosterone sulfate (DHEAS) and cortisol have opposing effects: cortisol suppresses while DHEAS enhances immune functions. We sought to estimate the impact of intraamniotic inflammation on fetal adrenal gland volume and cortisol-to-dehydroepiandrosterone sulfate ratio (fetal stress ratio) in pregnancies complicated by preterm birth.
Fifty-one consecutive singleton fetuses of mothers who had an indicated amniocentesis to rule out infection were analyzed. Intraamniotic inflammation was assessed by proteomic profiling of amniotic fluid for the biomarkers of the Mass Restricted score. The Mass Restricted score ranges from 0 (biomarkers absent) to 4 (all biomarkers present), with Mass Restricted scores of 3 or 4 indicating severe intraamniotic inflammation. Fetal adrenal gland volume was assessed by three-dimensional ultrasonography and corrected for estimated fetal weight. Interleukin-6 (IL-6), cortisol, and DHEAS were measured by immunoassay.
Women with intraamniotic inflammation delivered earlier (27.8+/-3.4 weeks, n=16, compared with 32.3+/-3.0 weeks, n=35, P<.001), and their fetuses had higher cord blood IL-6 (P=.011) and higher corrected adrenal gland volumes (P=.027). Cord blood IL-6 levels were in direct relationship with corrected adrenal volume (r=0.372, P=.019), fetal cortisol (r=0.428, P=.010), and DHEAS (r=0.521, P<.001). However, fetuses exposed to intraamniotic inflammation had an overall lower fetal stress ratio (P=.034). These results maintained after adjusting for gestational age, uterine contractions, and steroid exposure.
Fetuses exposed to intraamniotic inflammation have higher adrenal gland volumes and lower cortisol-to-DHEAS ratios, suggesting that the fetal adrenocortical axis plays a role in the intrauterine adaptation to inflammation.
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ABSTRACT: PURPOSE.: To determine whether the measurement of the transverse diameter of the fetal thymus is of value in the identification of either histologic chorioamnionitis or funisitis in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). METHODS.: The transverse diameter of the fetal thymus was measured in 216 fetuses from PPROM pregnancies. A small thymus was defined as a transverse thymic diameter below the fifth percentile according to a previously published nomogram. The placenta, the fetal membranes, and the umbilical cord were assessed for the presence of inflammation. RESULTS.: A small thymus was identified in 69% (150/216) of fetuses. A small thymus was present in 80% (106/133) and 88% (36/41) of women with histologic chorioamnionitis or funisitis, respectively. The presence of a small thymus had a sensitivity of 79%, specificity of 47%, positive predictive value of 71%, negative predictive value of 59% for the identification of chorioamnionitis (p < 0.0001; odds ratio 3.5) and a sensitivity of 88%, specificity of 35%, positive predictive value of 24%, and negative predictive value of 92% in the identification of funisitis (p = 0.004; odds ratio 4.4). CONCLUSIONS.: The sonographic finding of a small thymus is a sensitive indicator of histologic chorioamnionitis or funisitis; low specificity excludes it as a possible clinical implication in the management of PPROM pregnancies. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 2013;Journal of Clinical Ultrasound 06/2013; 41(5). DOI:10.1002/jcu.22027 · 0.80 Impact Factor
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ABSTRACT: The vast majority of the current knowledge on immune development in the fetal period has been gained from animal studies, particularly from mouse models. This has led to a great improvement in our current understanding of immune ontogeny. However, it has also become clear that in many ways the mouse model of pregnancy differs from the situation in human pregnancy, such as the degree and importance of trophoblast invasion, the kind of MHC class repertoire of the extravillous trophoblast cells, and differences concerning the development and regulation of T-cells. It will be of paramount importance to develop non-invasive screening methods to assess fetal immune development in humans. The focus of this mini-review is to discuss how prenatal ultrasound evaluation can be used as a tool to monitor fetal immune development in human pregnancies. To identify the fetuses at risk of immune disorders could be the first step to developing prevention strategies in the future.Journal of Reproductive Immunology 10/2014; DOI:10.1016/j.jri.2014.06.001 · 2.37 Impact Factor
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ABSTRACT: Steroid hormones are critical regulators of reproductive life history, and the steroid sensitive traits (morphology, behavior, physiology) associated with particular life history stages can have substantial fitness consequences for an organism. Hormones, behavior and fitness are reciprocally associated and can be used in an integrative fashion to understand how the environment impacts organismal function. To address the fitness component, we highlight the importance of using reliable proxies of reproductive success when studying proximate regulation of reproductive phenotypes. To understand the mechanisms by which the endocrine system regulates phenotype, we discuss the use of particular endocrine proxies and the need for appropriate functional interpretation of each. Lastly, in any experimental paradigm, the responses of animals vary based on the subtle differences in environmental and social context and this must also be considered. We explore these different levels of analyses by focusing on the fascinating life history transitions exhibited by the bi-directionally hermaphroditic fish, Lythrypnus dalli. Sex changing fish are excellent models for providing a deeper understanding of the fitness consequences associated with behavioral and endocrine variation. We close by proposing that local regulation of steroids is one potential mechanism that allows for the expression of novel phenotypes that can be characteristic of specific life history stages. A comparative species approach will facilitate progress in understanding the diversity of mechanisms underlying the contextual regulation of phenotypes and their associated fitness correlates.Frontiers in Neuroscience 02/2015; 9. DOI:10.3389/fnins.2015.00008