Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia.

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.

Anthropometric and ultrasound measures of maternal adiposity in the first trimester of pregnancy.

AIM: Estimations of central adiposity in pregnancy is a difficult undertaking due to physiological changes that occur in the body. Therefore, the value of some anthropometric measures particularly in pregnancy, such as body mass index (BMI), waist and hip measures are in doubt. The aim was to compare ultrasound (US) measured abdominal subcutaneous fat (USSFT) with other simple anthropometric methods for obesity assessment, evaluating these measures in pregnancy. METHOD: Recruited from a larger study, anthropometric measurements were performed between 11-14 weeks' gestation on 575 women. Measuring height, weight, hip, waist circumference, skin-folds of the triceps, thigh and supra-iliac and USSFT. Percentage maternal fat mass was calculated using skin-fold measures. Correlations of these measures were performed to gauge relationships. RESULTS: The anthropometric measures demonstrated good correlation (0.54-0.93) between individual adipose measures skin-folds, waist, hip, waist to height ratio (WSR) and USSFT with BMI, percentage fat mass and weight. USSFT correlated well with all anthropometric measures (0.54-0.73) correlating best with waist, WSR, BMI and weight. Waist/hip ratio demonstrated a poor correlation with USSFT, BMI, percentage fat mass and weight (0.3-0.41). Mean anthropometric measures were stratified across BMI categories describing adiposity distribution. CONCLUSION: USSFT correlates well with most anthropometric measures in early pregnancy. Limitations of the gravid uterus on waist measurements, hydration and compressibility of skin-fold measures and pregnancy influences on weight and BMI assessments could be overcome using US measures. There is a potential for post hoc evaluation using US for pregnancy complications. Maternal research could benefit from a more accurate measure of adiposity.

A novel evaluation of density differences in subcutaneous abdominal adipose tissue layers in pregnancy using elastography.

INTRODUCTION: Chronic inflammation leads to adipose tissue (AT) fibrosis through excessive accumulation of extracellular matrix proteins. An increasing degree of fibrosis in AT is associated with increasing body mass index (BMI) and insulin resistance. Anecdotally AT has been observed to vary with ease of ultrasound penetration on medical examinations. Ultrasound strain elastography (SE) is a useful tool in assessing fibrosis in liver disease but has not previously been used to assess AT fibrosis. This study assesses the variance in density of the two anatomical layers of subcutaneous AT, superficial subcutaneous adipose tissue (SSAT) and deep subcutaneous adipose tissue (DSAT) in pregnancy using SE. METHOD: Women (n = 210) recruited in early pregnancy. Density of SSAT and DSAT were assessed using SE at five-time points throughout pregnancy and post-partum. Semi-quantitative density measures were achieved using two methods, strain values (SV) of the two layers and ImageJ software to calculate the percentage colour pixels in the elastography image and correlated with the SSAT/DSAT thickness and BMI. RESULTS: Adipose tissue demonstrated a difference in density with the SSAT layer being denser than DSAT. Correlation of tissue density measures with BMI was poor. There was slight change of AT density during pregnancy with a tendency towards harder SSAT and softer DSAT in the third trimester. Post-partum SSAT became softer associated with an increase in SSAT thickness. CONCLUSION: Elastography demonstrated density differences in adipose tissue. SE is a new method of assessing the AT demonstrating density differences in adipose tissue. Information on AT density may determine AT fibrosis and be valuable for metabolic disease risk.

Changes in maternal abdominal subcutaneous fat layers using ultrasound: A longitudinal study.

BACKGROUND: Abdominal adiposity and subcutaneous fat (SF), an important endocrine organ for health outcomes, can be divided into two layers, superficial (SSAT) and deep subcutaneous adipose tissue (DSAT) each with a different histological and metabolic function. The aim was to investigate longitudinal changes in maternal abdominal SF thickness and its layers throughout pregnancy and post-partum within body mass index (BMI) categories. METHODS: A prospective longitudinal study of 214 women was performed measuring abdominal SF using ultrasound at 12-14(M1), 18-20(M2), 26-29(M3) and 33-36 weeks' gestation (M4) and 6-8 weeks post-partum. SF thickness (SFT), SSAT and DSAT were measured. A ratio of DSAT/SSAT (D/S) was calculated. Measurements were compared to baseline and BMI evaluating for interaction with changes over time. RESULTS: Of the 214 women, 43.5%(93) were normal weight, 25.7%(55) overweight and 30.8%(66) obese. SFT and SSAT decreased from M1 to M4 for the overweight and obese whilst remaining stable for normal weight women. For all BMI categories SFT and SSAT increased post-partum. DSAT decreased significantly in the obese and overweight and increased significantly in the normal weight. Obese women had a higher D/S at M1 that decreased at M2 and remained constant to post-partum. D/S increased at M2 then decreased in the overweight. Normal weight women increased D/S at M2-M4. CONCLUSION: The results indicate a difference in distribution and mobilisation of fat in SSAT, and DSAT abdominal subcutaneous compartments within the different BMI categories in pregnancy. Understanding how fat mobilises during pregnancy may be fundamental to understanding obesity related complications.

Automatic Measurement of Thalamic Diameter in 2-D Fetal Ultrasound Brain Images Using Shape Prior Constrained Regularized Level Sets.

We derived an automated algorithm for accurately measuring the thalamic diameter from 2-D fetal ultrasound (US) brain images. The algorithm overcomes the inherent limitations of the US image modality: nonuniform density; missing boundaries; and strong speckle noise. We introduced a "guitar" structure that represents the negative space surrounding the thalamic regions. The guitar acts as a landmark for deriving the widest points of the thalamus even when its boundaries are not identifiable. We augmented a generalized level-set framework with a shape prior and constraints derived from statistical shape models of the guitars; this framework was used to segment US images and measure the thalamic diameter. Our segmentation method achieved a higher mean Dice similarity coefficient, Hausdorff distance, specificity, and reduced contour leakage when compared to other well-established methods. The automatic thalamic diameter measurement had an interobserver variability of -0.56 ± 2.29 mm compared to manual measurement by an expert sonographer. Our method was capable of automatically estimating the thalamic diameter, with the measurement accuracy on par with clinical assessment. Our method can be used as part of computer-assisted screening tools that automatically measure the biometrics of the fetal thalamus; these biometrics are linked to neurodevelopmental outcomes.

Average fetal weekly weight gain: a novel measure of fetal growth velocity.

OBJECTIVE: To develop a simplified measure of intrauterine fetal growth velocity from birth weight and gestational age at term. METHODS: This concept is based on the observation that intrauterine fetal growth in the third trimester is quasi-linear. The average fetal weekly weight gain (AWG) was calculated by dividing the difference between birth weight (in g) and the 24-week median weight by the difference between gestational age at birth and 24 weeks, as follows: [Formula: see text] An obstetric database of 12,425 term live singleton pregnancies was studied to validate this measure. RESULTS: The mean AWG was 176.5 g/week, SD 29.1. There was a close correlation between birth weight z-scores and the AWG (R = 0.993). Pregnancy characteristics correlated with the AWG, the strongest being fetal gender and cigarette smoking (p < 0.0001). Females had an AWG 9 g lower than males; multiparae had an AWG 7 g higher. Other significant correlates include maternal weight, height and body mass index. CONCLUSIONS: The AWG is a novel estimate of intrauterine fetal growth velocity that is computationally simple, and could be used as an alternative to the birth weight z-score.

Congenital Epulis: a clinical case presentation.

Congenital Epulis (CE) is a rare, benign tumour of the mucosa of the mouth in a neonate. It presents as an intraoral tumour and is rarely diagnosed prenatally. Complications include neonatal airway compromise, difficulty feeding and aesthetic considerations. Ultrasound is useful in aiding decisions regarding site, age, method of delivery and preparing parents and staff for the appearances of the tumour at birth. We present a case where CE was identified at 35 weeks gestational age during a routine third trimester prenatal ultrasound. The patient was scanned at a rural centre, referred to a tertiary institution for follow up and delivered at a specialist perinatal surgical centre, in preparation for neonatal surgery. The outcome was excellent and this case is a good example of multi-centre cooperation.

Mid-Gestational Enlargement of Fetal Thalami in Women Exposed to Methadone during Pregnancy.

Methadone maintenance therapy is the standard of care in many countries for opioid-dependent women who become pregnant. Despite recent evidence showing significant neurodevelopmental changes in children and adults exposed to both licit and illicit substances in utero, data on the effects of opioids in particular remains scarce. The purpose of this study was to examine the effects of opiate use, in particular methadone, on various fetal cortical and biometric growth parameters in utero using ultrasound measurements done at 18-22 weeks gestation. Head circumference (HC), bi-parietal diameter, lateral ventricle diameter, transcerebellar diameter, thalamic diameter, cisterna magna diameter, and femur length were compared between fetuses born to methadone-maintained mothers and non-substance using controls. A significantly larger thalamic diameter (0.05 cm, p = 0.01) was observed in the opiate-exposed group. Thalamic diameter/HC ratio was also significantly raised (0.03 mm, p = 0.01). We hypothesize here that the increase in thalamic diameter in opiate-exposed fetuses could potentially be explained by regional differences in opioid and serotonin receptor densities, an alteration in monoamine neurotransmitter systems, and an enhancement of the normal growth increase that occurs in the thalamus during mid-gestation.

Impaired fetal thymic growth precedes clinical preeclampsia: a case-control study.

In preeclampsia the maternal adaptive immune system undergoes specific changes, which are different from the physiological processes associated with healthy pregnancy. Whether preeclampsia also affects the fetal immune system is difficult to investigate, due to limited access to the fetus. We hypothesized that if preeclampsia affects the fetal adaptive immune system this might be associated with early changes in thymic growth. In this case-control study, 53 preeclamptic and 120 healthy control pregnancies were matched for maternal age, gestational age and smoking. Fetal thymus diameter was measured as the greatest width perpendicular to a line connecting sternum and spine based on ultrasound images taken at 17-21 weeks gestation. Independent of fetal and maternal anthropometric measures, thymuses were found to be smaller in preeclamptic pregnancies than healthy controls (16.2 mm versus 18.3 mm, respectively, mean difference=2.1 mm, 95% CI: 0.8-3.3, p<0.001), and the odds of developing preeclampsia was estimated to be 0.72 (95% CI: 0.60-0.86, p<0.001) lower for each 1 mm increase in thymus diameter. There was no correlation between the onset of preeclampsia and fetal thymus size. This is the first study to suggest that fetal thymus growth is reduced before the clinical onset of preeclampsia and precedes any described fetal anomalies or maternal immunological changes associated with preeclampsia. We propose that the fetal adaptive immune system is either passively affected by maternal processes preceding clinical preeclampsia or is actively involved in initiating preeclampsia in later pregnancy.

The value of screening for major fetal abnormalities during the nuchal translucency examination.

The nuchal translucency (NT) scan provides an opportunity to examine fetal anatomy. Current opinion on the advantages and limitations of assessing fetal anatomy at this early gestation is divided. Two case studies from our centre will be presented where assessing fetal anatomy was of great benefit - one in finding abnormalities, the other in excluding them. These cases along with review of the literature support the view that a limited fetal anatomy scan should be performed as part of the NT examination.