Fetal Zone Research Articles

FETAL ADRENAL GLAND BIOMETRY: A POTENTIAL PREDICTOR OF PRETERM BIRTH

Background: Preterm birth is an important challenge in obstetrics and contemporary perinatology in India. Timely recognition, intervention and appropriate management is integral in curbing the upsurge in its incidence and consequent poor perinatal outcome. This study was conducted taking into account the potential mechanism of preterm labor: premature activation of the placental-adrenal endocrine axis wherein elevation of maternal cortisol leads to an increased production of placental corticotrophin releasing hormone which causes an increase in dehydroepiandrosterone produced by the fetal zone of the adrenal gland and its enlargement. This activates a cascade leading to early loss of uterine quiescence, consequently causing cervical modelling, ripening and preterm birth.
 Aim and Objectives: To assess fetal adrenal gland volume and fetal zone enlargement on ultrasound and evaluate its efficacy in the prediction of preterm birth. 
 Methods: This was a hospital based prospective study in which pregnant women with an uncomplicated live singleton pregnancy between 28 to 34 weeks of gestation were subjected to obstetric ultrasonography wherein fetal adrenal gland volume and fetal zone enlargement was measured. They were then followed up until their delivery, whether term or preterm and its correlation with fetal adrenal gland parameters was assessed. 
 Result: Corrected fetal adrenal gland volume showed the highest sensitivity of 90.0% and a specificity of 96.7% with a cut off value of 632.50 mm3/kg while fetal zone enlargement showed a sensitivity and specificity of 72.7% and 60.9% respectively. 
 Conclusion: This study concludes that fetal adrenal gland biometry can be used as a noninvasive, cost effective and potential new marker for the prediction of preterm birth.

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography.

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract‐based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super‐resolution algorithm and DTI images processed with a motion‐tracked slice‐to‐volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor‐to‐tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto‐occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within‐tract changes. We found tract‐specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within‐tract developmental trajectories for the CST, IFOF, and forceps major.

Ultrasound Assessment of Fetal Adrenal Gland in Term and Preterm Labor Cases

Background: Preterm birth (PTB) remains a major cause of perinatal morbidity and mortality worldwide. Compared with term deliveries, early PTB (< 34 weeks' gestation) carries a 7-fold increased risk of neonatal death. Objective: To compare the Fetal Zone Depth (FZD) of fetal adrenal gland in term and preterm labor cases Patients and Methods: Thirty-three preterm pregnant women at 29-36 weeks of gestation with single pregnancy and clinical diagnosis of preterm labor and control group of 33 pregnant women at 37-40 weeks with term pregnancy were included in this study. FZD and Total Gland Depth (TGD) of fetal adrenal gland were ultrasonographically measured and FZD/TGD ratios were calculated and compared between the two groups. Results: No difference was found between the two groups in respect of age and number of pregnancies (P > 0.05). Yet, preterm birth history rupture of membrane, cervical dilatation and mode of delivery were higher in preterm group (P <0.05). Fetal adrenal gland FZD/TGD ratio was statistically significantly higher in preterm group compared to the term group (52% ± 5% vs. 29% ±9%; P <0.001). Conclusion: The growth in FZ as a fetal adaptation mechanism in increased fetal stress in preterm labor cases was at a significant level. Once supported by more comprehensive studies, we think that this result would be beneficial in the prediction of preterm labor in clinical practice.

Fetal Zone Steroids and Estrogen Show Sex Specific Effects on Oligodendrocyte Precursor Cells in Response to Oxidative Damage

Oxygen causes white matter damage in preterm infants and male sex is a major risk factor for poor neurological outcome, which speculates the role of steroid hormones in sex-based differences. Preterm birth is accompanied by a drop in 17β-estradiol (E2) and progesterone along with increased levels of fetal zone steroids (FZS). We performed a sex-based analysis on the FZS concentration differences in urine samples collected from preterm and term infants. We show that, in preterm urine samples, the total concentration of FZS, and in particular the 16α-OH-DHEA concentration, is significantly higher in ill female infants as compared to males. Since we previously identified Nup133 as a novel target protein affected by hyperoxia, here we studied the effect of FZS, allopregnanolone (Allo) and E2 on differentiation and Nup133 signaling using mouse-derived primary oligodendrocyte progenitor cells (OPCs). We show that the steroids could reverse the effect of hyperoxia-mediated downregulation of Nup133 in cultured male OPCs. The addition of FZS and E2 protected cells from oxidative stress. However, E2, in presence of 16α-OH-DHEA, showed a negative effect on male cells. These results assert the importance of sex-based differences and their potential implications in preterm stress response.

Impact of Gestational and Postmenstrual Age on Excretion of Fetal Zone Steroids in Preterm Infants Determined by Gas Chromatography-Mass Spectrometry.

Fetal zone steroids (FZSs) are excreted in high concentrations in preterm infants. Experimental data suggest protective effects of FZSs in models of neonatal disease. We aimed to characterize the postnatal FZS metabolome of well preterm and term infants. Twenty-four-hour urinary FZS excretion rates were determined in early preterm (<30 weeks' gestation), preterm (30-36 weeks), and term (>37 weeks) infants. Pregnenolone and 17-OH-pregnenolone metabolites (n = 5), and dehydroepiandrosterone sulfate and metabolites (n = 12) were measured by gas chromatography mass spectrometry. Postnatal concentrations of FZSs were compared with already published prenatal concentrations in amniotic fluid. Excretion rates of total FZSs and most of the single metabolites were highest in early preterm infants. In this group, excretion rates approach those of term infants at term equivalent postmenstrual age. Preterm infants of 30-36 weeks had more than half lower median excretion rates of FZSs than early preterm infants at the same time of postmenstrual age. Postnatal concentrations of FZSs were partly more than 100-fold higher in all gestational age groups than prenatal concentrations in amniotic fluid at midgestation. The excretion rates of FZSs as a proxy of the involution of the fetal zone of the most immature preterm infants approached those of term infants at term equivalent. In contrast, the fetal zone in more mature preterm infants undergoes more rapid involution. These data in exclusively well neonates can serve as a basis to investigate the effects of illness on the FZS metabolome in future studies.

Adrenal cortex development and related disorders leading to adrenal insufficiency

The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation. It consists of three histologically distinct and functionally specialized zones. The fetal adrenal forms from mesodermal material and produces predominantly adrenal C19 steroids from its fetal zone, which involutes after birth. Transition to the adult cortex occurs immediately after birth for the formation of the zona glomerulosa and fasciculata for aldosterone and cortisol production and continues through infancy until the zona reticularis for adrenal androgen production is formed with adrenarche. The development of this indispensable organ is complex and not fully understood. This article gives an overview of recent knowledge gained of adrenal biology from two perspectives: one, from basic science studying adrenal development, zonation and homeostasis; and two, from adrenal disorders identified in persons manifesting with various isolated or syndromic forms of primary adrenal insufficiency.

The neuroendocrine effects of dehydroepiandrosterone and 17β-estradiol in the in vitro preterm hyperoxia infant model

Preterm birth causes neurological deficits. Previously, we demonstrated that fetal zone steroids reduce hyperoxia-mediated cell death in vitro. In immature oligodendrocytes (OLN-93 cells), dehydroepiandrosterone + 17β-estradiol co-treatment had synergistic beneficial effects while signals were transduced through different receptors. In immature astrocytes (C6 cells), both hormones compete for the same receptor and no synergistic effects were observed. 17β-estradiol and progesterone drastically decrease while fetal zone steroids, mainly dehydroepiandrosterone, remain persistently high within preterm infants until term. Substitution of 17β-estradiol and progesterone does not improve neurological outcomes. We investigated the influence of dehydroepiandrosterone, 17β-estradiol or dehydroepiandrosterone + 17β-estradiol treatment in C6 or OLN-93 cells on steroid receptor availability and activation of intracellular signaling molecules in hyperoxic cell culture. We sought explanations of the observed synergistic effect in preliminary study. In C6 cells, the generated signaling of dehydroepiandrosterone + 17β-estradiol treatment has no synergistic effects. The combined effect on this particular pathway does not potentiate cell survival. In OLN-93 cells, we observed significant differences in the early generated signaling of 17β-estradiol + dehydroepiandrosterone treatment to either 17β-estradiol dehydroepiandrosterone alone but never to both at the same time. The latter finding needs, therefore, further investigation to explain synergistic effects. Nevertheless, we add insight into the receptor and signaling cascade alterations induced by 17β-estradiol, dehydroepiandrosterone or 17β-estradiol + dehydroepiandrosterone treatment of C6 and OLN-93 cells in hyperoxia.

Simple ultrasound evaluation of fetal adrenal glands as a marker of imminent preterm birth: a preliminary report.

We present a simple 2D big ultrasound measurement of the fetal adrenal glands and their biometrical growth analysis highlighted as a potential preterm birth marker. This was a prospective observational case-control study. Sixty-four patients were included in the study (32 with the diagnosis of imminent preterm birth before 37 and 32 controls) from January 2018 to May 2020. Anteroposterior dimensions and circumferences of the whole adrenal glands and their central zones were measured by simple B-mode ultrasound imaging. For the statistical analysis, StatsDirect 3.0 and ROC curves were used. As a studied descriptor, routine standard ultrasound cervical measurements were added (cervical length, funneling, sludge, cervical dilatation, and cervical glandular area). In biometrics of gestational age-related changes, a significant analysis of the overall growth of the adrenal gland was observed (circumference p < 0.001, anteroposterior diameter p = 0.02). The growth of the central zone was observed independently of gestational age. The growth of the central zone of the fetal adrenal glands revealed significant changes between the group of patients who delivered prematurely and control groups (p < 0.01). The ideal cut-off value of the proportion of enlargement of the fetal zone as a predictor of preterm delivery before week 37 was 45.1 %, with the sensitivity of 87.5 % and specificity of 85.4 %. A simple 2D B-mode measurement of the fetal adrenal glands´ central zone growth can be applied as an additional marker in the prediction of true preterm delivery. The natural biometrical overall growth of the adrenal glands seems to be dependent on gestational age, whereas that of the central adrenal gland zone seems to be independent on gestational age (Tab. 3, Fig. 5, Ref. 26).

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

BackgroundThe 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.MethodsThe 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.ResultsOne 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.ConclusionThere 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.

Longitudinal adrenal gland measurements and growth trajectories as risk markers for late preterm delivery

BackgroundThe fetal adrenal gland receives rising awareness as a predictor of spontaneous preterm birth. We hereby provide longitudinal growth assessments of the fetal adrenal gland in a low risk population with an additional focus on trajectories in fetuses born preterm.MethodsFetal adrenal gland was assessed via transabdominal ultrasound at gestational weeks (gw) 24–26, 28–30, and 34–36 in a low-risk pregnancy cohort. Longitudinal trajectories of the total gland and the mark (so called fetal zone) as well as ratio of fetal zone width/ total widths (w/W) were analyzed using repeated ANOVA analyses. To compare trajectories of the ratio w/W for preterm and term fetuses respectively, as well as women with and without clinical signs of preterm labor, the propensity score method was applied.ResultsFetal zone width increased over the course of pregnancy (p < 0.0001), while the ratio w/W decreased (p < 0.0001) (n = 327). Comparing the trajectories of the ratio w/W in fetuses born preterm (n = 11) with propensity-score matched term born fetuses (n = 22), a decrease between gw 24–26 and 28–30 was observed in both groups, which continued to decrease for the term born fetuses. However, in preterm born fetuses, the ratio increased above the term born values at gw 34–36.ConclusionOur study provides for the first time longitudinal growth data on the fetal adrenal gland and supports the hypothesis that fetal zone enlargement is associated with preterm birth which could play an important role in risk-prediction.

Study on the gestational age-related histogenesis of human fetal suprarenal glands

Background: Fetal suprarenal gland consists of three zones. They are the outer definitive zone or neocortex (DZ) that forms adult Zona Glomerulosa (ZG), the centrally located fetal zone and a third transitional zone (TZ) the future adult Zona Fasciculata (ZF) which lies just between the neocortex and fetal zone (FZ). The inner ZF that consists of large eosinophilic cells, and the outer definitive zone (DZ) consists of small, densely packed basophilic cells. As early as in 6th week of gestational Age, pheochromoblasts derived from the neural crest migrate through the fetal cortex to form the medulla at a later stage of development. The medulla unrecognizable as a distinct structure in the suprarenal gland throughout most of the gestation, except for small clusters or nests of chromaffin cells scattered throughout the body of the cortex.&#x0D; Aims and Objective: The study was designed and aimed to understand the early developmental histology of suprarenal gland.&#x0D; Materials and Methods: Study conducted at the Department of Anatomy, SV Medical College, Tirupati, Andhra Pradesh, India. The study was carried out by processing representative samples of fetal suprarenal tissues of 13 weeks, 17 weeks, 24 weeks, 25 weeks and 38 weeks gestational age. While processing, we observed the standard dissection procedure and histopathological tissue processing for the human samples.&#x0D; Results: Peripheral narrower and darker definitive zone or true cortex and an inner wider and lighter fetal zone was observed at 13, 17, 24 weeks with 10x objective. The demarcation between cortex and medulla could be seen clearly at 24 weeks. At 25 weeks capsule is very thick and vascular. A well-differentiated gland tissue with clear demarcation of cortex and medulla and a large central vein was observed. At 38 weeks degeneration of fetal zone with a thick-walled central vein was observed at lower magnification (10x objective)&#x0D; Conclusion: Observations on prenatal microscopic structure and gestational age-related changes in suprarenal glands form the basis for understanding structural changes and a foetal database for the local population.

Foetal development of endocrine organs in dog.

The canine adenohypophysis starts to be identifiable from 25day of pregnancy. ACTH-immunoreactive cells migrate until day 38 after which the number of ACTH-producing cells increases but their distribution does not change. The STH- and LH-producing cells first appear on day 38 of pregnancy. The primordium of the adrenal glands appears as a slender structure on day 27 and forms the definitive cortical structure on day 35. The histological pattern of the foetal adrenal cortex differs from the post-natal structure in so far as the three cortical zones (definitive zone, transitional zone and foetal zone) extend from the outside towards the inside of gland. The mass of foetal and neonatal adrenals is more than 10 times larger than the adult adrenals relative to body weight. The cortisol concentration in the amnion is slightly lower than in the allantois but the foetal serum cortisol concentration is significantly higher than in the maternal and foetal fluid compartments. The thyroxine concentrations in the allantois and amnion fluids exceed the foetal serum concentrations except in the ninth week of pregnancy, but thyroxine levels in foetal fluids and serum are below the physiological levels of adult animals. The exocrine and endocrine functions of the pancreas develop and act in parallel. Pancreatic cells are first detected at 30days when the branched structure is clearly detectable immunohistochemically, and at that time, insulin-positive β-cells and α-cells are visible as well. The foetal serum glucose concentration exceeds the healthy adult range, but the glucose concentration in the allantois and amnion fluid remains below the physiological blood glucose concentration of mature dogs. The insulin concentration in the allantois fluid greatly exceeds the foetal serum and amnion insulin concentrations.

SUN-LB41 The Role of Androgen Receptors in Female Mouse X-Zone Loss During Aging and Pregnancy

Introduction: Sex differences are prevalent in the risk and manifestation of numerous human diseases as well as in the response to most therapeutic interventions. While marked sexual dimorphism is observed in the development, homeostasis and most diseases of the adrenal cortex, the impact of these differences on adrenal function remains poorly understood. Sex differences include the timing of adrenal fetal zone (X-zone) regression, which occurs during male mouse puberty but only after pregnancy or advanced age in females. The mechanisms driving regression, particularly in females, are unknown. A potential regulator of adrenal sexual dimorphism and X-zone regression is androgen exposure. Through adrenocortical-specific deletion of the androgen receptor (AR), we tested the hypothesis that androgen signaling is responsible for X-zone post-pubertal regression in male mice and post-pregnancy/aging related regression in female mice. Methods: Adrenocortical-targeted Ar deletion was accomplished by crossing heterozygous aldosterone synthase-Cre mice to mice with a floxed exon 2 of Ar (ARΔAdr). Mice were sacrificed at 25 or 50 weeks of age and compared to ARf/f littermates (controls). Adrenals were processed for histology (H&E), immunofluorescence (IF) and whole adrenal mRNA RT-PCR to detect AR and X-zone specific markers Akr1c18 (20αHSD) and Pik3c2g. Results: In all mice, Ar mRNA expression was significantly decreased in ARΔAdr mice compared to control littermates. As expected, 25 week control females had higher expression of Akr1c18 (6740-fold) and Pik3c2g (198-fold) compared to 25 week control males. 25 week ARΔAdr males retained expression of Akr1c18 (20864-fold) and Pik3c2g (2802-fold) compared to controls, and also exhibited positive 20αHSD staining, confirming X-zone retention. 50 week control females exhibited histologic loss of the X-zone with negligible expression of Akr1c18 and Pik3c2g compared with 25 week control females. However, 50 week female ARΔAdr mice exhibited a histologic X-zone retention and concomitant high expression of X-zone genes (Akr1c18 67-fold, Pik3c2g 75-fold) compared to female control littermates. Furthermore, 20αHSD IF demonstrated undetectable levels in controls and positive staining in ARΔAdr, indicating that age-associated X-zone loss may be AR-mediated. Post-pregnant 25 week control mice had ~99% lower expression of both X-zone markers compared to virgin female controls. Post-pregnant ARΔAdr mice displayed higher expression of Akr1c18 (19-fold) and Pik3c2g (5-fold) compared to post-pregnant controls, though neither group had detectable 20αHSD by IF. Conclusion: Our findings indicate that AR signaling not only causes post-pubertal X-zone loss in males, but also plays a major role in the loss of the X-zone observed in aged female mice. Conversely, AR signaling may only play a minor role in X-zone regression following pregnancy.

Fetal adrenal gland: Total gland volume and fetal zone to total gland ratio as markers of small for gestational age.

Fetal adrenal gland changes have previously been investigated as novel markers of preterm labor and small for gestational age (SGA) fetuses. We aimed to compare the fetal adrenal gland parameters in SGA and appropriate for gestational age (AGA) fetuses. A prospective cohort study was conducted on SGA fetuses with estimated fetal weight (EFW) ≤10th centile and AGA (EFW >10th centile) at 17 to 34 weeks gestation. Fetal adrenal total gland volume (TGV), TGV corrected for EFW (cTGV), fetal zone volume (FZV), FZV corrected for EFW (cFZV), and FZV:TGV ratio were compared and correlated with gestational age and EFW. Receiver operator curves assessed FZV:TGV ratio, cTGV, and cFZV in detecting SGA. Ultrasound examinations from 103 AGA and 50 SGA fetuses showed that (a) SGA fetuses had higher TGV (P = .002), FZV (P = .001), and FZV:TGV (P = .036) compared to AGA fetuses; (b) fetal adrenal TGV, FZV, cFZV, and FZV:TGV increase with advancing gestational age and EFW while cTGV does not; (c) Fetal adrenal changes in cTGV, cFZV, and FZV:TGV have ability to differentiate SGA; (d) FZV:TGV ratio 10 and 25 may be used to identify or exclude SGA in antenatally suspected SGA. We investigated the concept that SGA fetuses have measurable changes to the adrenal gland. We have shown that fetal TGV, TGV, and FZV:TGV ratio show differences between AGA and SGA with TGV remaining significant after accounting for GA at scan. These findings may be useful as potential biomarkers for diagnosing or excluding SGA.

Predictive Accuracy of Three Dimensional Ultrasound Measurement of Fetal Adrenal Gland Volume in Preterm Labor Cases

Abstract Background Preterm birth is one of the major clinical problems in obstetrics and neonatology as it is associated with perinatal mortality, serious neonatal morbidity and in some cases childhood disability. It is reported that more than 80% of all neonatal mortality and morbidity is due to preterm birth. Objective In this study fetal adrenal gland volume and fetal zone measurement were used as a predictors for occurrence of labor in singleton pregnancies complicated by threatened preterm labor in comparison to cervical length and cervicovaginal fetal fibronectin. Methodology The study was carried out at Ain Shams University Maternity Hospital. The current study include 88 pregnant women who presented with symptoms or signs of threatened preterm labor (PTL). All women were subjected to full history taking, full general, abdominal, pelvic examination, in addition to ultrasound fetal biometry, measurement of cervical length, measurement of fetal fibronectin, fetal adrenal gland volume AGV and fetal zone acquisitions. Results Our results showed high statistically significant difference between the two groups of women regarding CL measurement, FZE and cAGV with P values &amp;lt; 0.001 suggesting that ultrasound examination of fetal adrenal gland and assessment of FZE at time of evaluation for symptoms of PTL may be clinically beneficial in predicting the occurrence of labor in pregnant women at risk of preterm labor. Conclusion Our results demonstrate that in women presenting with threatened preterm labor, cAGV and FZE measured by 3-dimensional ultrasound seem to be significant predictors of delivery within 7 days, when compared to CL and cervicovaginal fetal fibronectin.

Antenatal Fetal Adrenal Measurements at 22 to 30 Weeks' Gestation, Fetal Growth Restriction, and Perinatal Morbidity.

Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. There were 1,709 eligible neonates. Seven percent (n = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38-0.67). In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR.

Fetal adrenal gland size and the ability to predict spontaneous term labor

ObjectiveThe objective of this study was to evaluate whether ultrasound measured fetal adrenal gland size can be a predictor of spontaneous term labor. Study designThis study was a diagnostic test accuracy study using a prospective cohort design evaluating the ability of 2-dimensional ultrasound measurement of fetal adrenal gland total length, total width, fetal zone length and fetal zone width in women in the third trimester to predict the primary outcome of spontaneous term labor. Secondary outcomes were vaginal delivery, length of labor, and maternal and neonatal morbidities. ResultsOf 43 patients recruited, 3 were excluded. 11 (25.6%) presented in spontaneous labor and 29 (67.4%) underwent induction of labor. Patient demographics were similar for all included except for admission cervical exam and oxytocin use. A receiver operative curve was created to assess test predictability. Weighted width of fetal adrenal gland was the best predictor of spontaneous labor amongst variables measured with an area under the curve of 0.674, p = 0.93. w/W ≥ 0.41 had a sensitivity of 91.0%, specificity of 44.8%, positive predictive value of 38.5% and a negative predictive value of 92.3%. Maternal and neonatal morbidities were not different between the spontaneous labor group and the induction of labor group. ConclusionUltrasound measured fetal w/W was moderately predictive of spontaneous labor.

Histogenesis of suprarenal glands at different gestational age groups

Background: The human foetal suprarenal gland is structurally variant from its adult counterpart. The most distinctive features of human foetal suprarenal gland and histologically unique foetal zone, was described first by Elliott and Armour in 1911. After the first trimester, the centrally located foetal zone accounts for most of the foetal adrenal mass. The outer zone of the foetal suprarenal gland is called the “definitive zone or neo cortex”; this zone likely gives rise to the adult adrenal glomerulosa. A third zone called “transitional zone”, lies just between the neocortex and foetal zone and is believed to develop into the zona fasciculata.&#x0D; Aims and Objectives: The current study was designed to study the histogenesis of suprarenal glands at different gestational age groups.&#x0D; Materials and Methods: Twenty-eight formalin preserved dead embryos and foetuses of both sexes, were obtained from the Govt. Maternity Hospital &amp; S.V.Medical College, Tirupati, Andhra Pradesh, India. Specimens were grouped according to their gestational age groups (A,B,C,D) A= 0-12 weeks, B= 13-24 weeks, C= 25-36 weeks and D= more than 36 weeks of gestation. Specimens from group A were subjected to serial section as this group consists of embryos, and other groups were sectioned coronal and subjected to routine histological processing for H&amp;E staining. Sections were observed for cellular details under light microscopy with 10X and 40X magnifications, and the same were photographed by microphotography.&#x0D; Results: Based upon the gestational age groups, histogenesis of the suprarenal gland was observed and correlated with the available literature, and the detailed results, discussion will be dealt at the time of discussion.&#x0D; Conclusions: Histological observation of the all the specimens observed in the present study are in agreement with those reported in the literature except that they appeared earlier in the present study than that reported in the literature. Capsule of suprarenal gland appeared at 12 weeks, sympatho-chromaffin bundles appeared before 6 weeks and zonation of cortex was observed at 8 weeks in the present study when compared to the time of appearance reported in the literature as 14 weeks, after 6 weeks and after 12 weeks respectively in the literature.

SUN-039 Characterization of Human Adrenal Steroidogenesis during Fetal Development

Context: The endocrine function of human fetal adrenals (HFA) is activated already during first trimester, but changes in adrenal steroidogenesis during fetal life are not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from 1st and 2nd trimester. Design and Setting: Male and female HFA samples from gestational week (GW) 8-19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2 and SULT2A1 was significantly higher in 2nd trimester compared with 1st trimester (P<0.05), while expression levels of 3β-HSD2 and ARK1C3 were unaltered between GW 8-19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout GW 8-19 with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2 which was mainly expressed in the definitive zone. The abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1,071-2,723 ng/g tissue, in average) and testosterone levels the lowest (2-14 ng/g tissue, in average). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from 1st to 2nd trimester, with no major differences between male and female samples. The intra-adrenal steroid hormone concentrations confirms that cortisol is produced throughout 1st and 2nd trimester, suggesting continued regulation of the HPA axis during this entire period.

Adrenal Steroids in Female Hypothyroid Neonates: Unraveling an Association Between Thyroid Hormones and Adrenal Remodeling.

The adrenal gland undergoes substantial remodeling during the neonatal period, an essential developmental process that remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (THs), no human studies have been published. The effects of both hypo- and hyperthyroidism have only been evaluated in adults, focusing on the mature adrenal. Recent studies have identified expression of the TH receptor β1 in the mouse adrenal X-zone and have demonstrated that TH administration could alter the postnatal adrenal remodeling process. To address whether THs influence adrenal steroid profiles and adrenal remodeling during the neonatal period. We compared the adrenal steroid profile of a naturally occurring prototype, female neonates with severe congenital hypothyroidism (CH) (n = 22, upon diagnosis of CH), with that of euthyroid neonates (n = 20). Significantly higher levels of adrenal steroids (17-OH-progesterone, dehydroepiandrosterone sulfate, Δ4-androstenedione, and testosterone) were measured in neonates with severe CH compared with euthyroid neonates and returned to within normal range after euthyroid state had been established on l-thyroxine replacement therapy, whereas cortisol levels did not differ. TSH values in the CH group were positively correlated with circulating adrenal steroids, whereas free T4 levels were negatively correlated with circulating adrenal steroids. The hormonal profile of female neonates with severe CH suggests a more active adrenal fetal zone compared with control subjects. These data indirectly associate THs with the adrenal remodeling and maturation process in humans. Based on our results, we suggest that severe hypothyroidism decelerates the involution of the adrenal fetal zone that normally occurs postnatally.