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      Zone-specific reference ranges of fetal adrenal artery Doppler indices: a longitudinal study

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          Abstract

          Background

          The fetal adrenal gland is a highly vascularized organs and develops two recognizable distinct zones in uetro, inner fetal zone (FZ) and outer definitive zone (DZ). Based on the region supplied, middle adrenal artery (MAA) mainly contribute to FZ while inferior adrenal artery (IAA) mainly to the inferior part of DZ. The purpose of this study was to establish reference ranges of adrenal artery Doppler indices of IAA and MAA, and assess zonal difference of blood supply to fetal adrenal gland.

          Methods

          The pulsatility index (PI), resistance index (RI), and systolic:diastolic ratio (S/D) of the IAA and MAA were obtained serially at 4-week intervals in normal fetuses. The MAA and IAA were referred based on the course and location in the gland: IAA referring the artery that mainly branches from the renal artery and walks along the renal upper pole, distributing the inferoposterior part of DZ in the adrenal gland while MAA as arterial blood flowing along the single central adrenal vein in the medial part of the gland. Multilevel modeling was performed to establish the gestational age-associated reference ranges for IAA and MAA. Differences in Doppler indices between the IAA and MAA were assessed.

          Results

          One hundred sixty-eight fetuses with 843 observations were included. The IAA had a higher detection rate than the MAA (100% vs 89.2%, p < 0.05). The resistance of IAA had a reduction around 35 weeks of gestation and that of MAA remained unchanged throughout the second half of pregnancy. Lower PI, RI and S/D were observed in the MAA than in the IAA ( p < 0.05) from 752 paired measurements.

          Conclusion

          There is a zonal difference in blood supply in favor of the fetal zone, which may correspond to its unique function. Reference ranges of Doppler parameters in adrenal artery maybe beneficial for further evaluation of fetal hemodynamics.

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          Most cited references19

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          Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit.

          Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex.
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            Calculation of unconditional and conditional reference intervals for foetal size and growth from longitudinal measurements.

            P Royston (1995)
            Methods for estimating unconditional and conditional reference intervals for foetal size and growth based on longitudinal observations are presented. The methods are based on simple random-effects regression models and involve transforming both the response and the covariate (timepoint). A dataset from a designed longitudinal study of foetal size is analysed in detail as a motivating example.
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              In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development.

              In humans, sexual differentiation of the external genitalia is established at 7-12 weeks post conception (wpc). During this period, maintaining the appropriate intrauterine hormone environment is critical. In contrast to other species, this regulation extends to the human fetal adrenal cortex, as evidenced by the virilization that is associated with various forms of congenital adrenal hyperplasia. The mechanism underlying these clinical findings has remained elusive. Here we show that the human fetal adrenal cortex synthesized cortisol much earlier than previously documented, an effect associated with transient expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B) and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under the regulation of ACTH. Negative feedback was apparent at the anterior pituitary corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione and testosterone. In concert, these data promote a distinctive mechanism for normal human development whereby cortisol production, determined by transient NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to modulate androgen biosynthesis and safeguard normal female sexual differentiation.
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                Author and article information

                Contributors
                shizeng@csu.edu.cn
                Journal
                BMC Pregnancy Childbirth
                BMC Pregnancy Childbirth
                BMC Pregnancy and Childbirth
                BioMed Central (London )
                1471-2393
                11 December 2020
                11 December 2020
                2020
                : 20
                : 774
                Affiliations
                [1 ]GRID grid.452708.c, ISNI 0000 0004 1803 0208, Department of Urology, , The Second Xiangya Hospital, Central South University, ; Changsha, 410011 Hunan China
                [2 ]GRID grid.452708.c, ISNI 0000 0004 1803 0208, Department of Ultrasound Diagnosis, , The Second Xiangya Hospital, Central South University, ; 139 Renmin Road (M), Changsha, 410011 China
                Author information
                http://orcid.org/0000-0001-8325-3481
                Article
                3480
                10.1186/s12884-020-03480-z
                7733276
                33308174
                0a4eaf7d-312a-4bda-9381-38191fde5965
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 18 August 2020
                : 4 December 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81871372,81501497
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Obstetrics & Gynecology
                adrenal artery,fetal,pulsatility index,doppler
                Obstetrics & Gynecology
                adrenal artery, fetal, pulsatility index, doppler

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