Can fetal abdominal visceral adipose tissue and subcutaneous fat thickness be used for correct estimation of fetal weight? A preliminary study.

The aim of this study was to assess the accuracy of a new formula for the calculation of an estimated fetal weight (EFW) and to evaluate value of fetal visceral adipose tissue (VAT) and abdominal subcutaneous fat (SF) thickness on the prediction of birth weight. In this prospective study, fetal biometry, EFW, fetal VAT and SF thickness were measured in low-risk 37-41 gestational weeks pregnant women by ultrasonography. The linear regression analysis was performed to investigate the relationship between birth weight and obstetric measurements. It was found that the most important factors in the prediction of a birth weight were the abdominal circumference (AC), SF and VAT. The new formula for EFW was EFW=-2748.622+13.811*AC+56.795*SF+17.913*VAT According to the Hadlock 3 and the new formula, 92% and 95% of all fetal weight estimations were within 10% of actual birth weight, respectively. Measurement of VAT and SF thickness in prediction of fetal weight could reduce a weight estimation error. Impact statement What is already known on this subject? An accurate prediction of fetal weight during gestation provides useful information for assessing the fetal and newborn health status. As the detection of growth abnormalities is vital, there is a need for a reliable method of assessing birth weight during labour. Unfortunately, although different methods are available, a simple, quick and reliable method of assessing birth weight is still in debate. Fetal visceral adipose (VAT) tissue measurement is a new method which could be used for the correct estimation of fetal weight. Like adults, the VAT and subcutaneous fat tissue (SF) thickness could be correlated with the weight and body-mass index. What do the results of this study add? It was found that SF and VAT are important factors in the prediction of birth weight, like the abdominal circumference (AC). What are the implications of these findings for clinical practice and/or further research? The measurement of VAT and SF thickness in prediction of fetal weight could reduce a weight estimation error.

Fetal development of subcutaneous white adipose tissue is dependent on Zfp423.

OBJECTIVE: Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of Zfp423 in the fetal stages of early adipose development in vivo have not been clarified. METHOD: Here, we utilize two models that confer adipose-specific Zfp423 inactivation during fetal adipose development (Adiponectin-Cre; Zfp423loxP/loxP and Adiponectin-rtTA; TRE-Cre; Zfp423loxP/loxP). We assess the impact of fetal adipose Zfp423 deletion on the initial formation of adipose tissue and evaluate the metabolic consequences of challenging these animals with high-fat diet feeding. RESULTS: Deletion of Zfp423 during fetal adipose development results in a different phenotype than is observed when deleting Zfp423 in adipocytes of adult mice. Inactivation of Zfp423 during fetal adipose development results in arrested differentiation, specifically of inguinal white adipocytes, rather than a white-to-beige phenotypic switch that occurs when Zfp423 is inactivated in adult mice. This is likely explained by the observation that adiponectin driven Cre expression is active at an earlier stage of the adipocyte life cycle during fetal subcutaneous adipose development than in adult mice. Upon high-fat diet feeding, obese adipose Zfp423-deficient animals undergo a pathological adipose tissue expansion, associated with ectopic lipid deposition and systemic insulin resistance. CONCLUSIONS: Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.

Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

Relationship between sonographically estimated fetal subcutaneous adipose tissue measurements and neonatal skinfold measurements.

OBJECTIVE: Increased subcutaneous adipose tissue is a well known characteristic of diabetic fetopathy. Prenatal estimation of adipose tissue can be performed by ultrasound, while postnatally skinfold measurements are performed using a Holtain caliper. The aim of this study was to compare these methods in the same patients. METHODS: This was a prospective study of 172 pregnant patients (142 controls and 30 with gestational diabetes) at ≥ 37 gestational weeks. In addition to fetal weight estimation, fetal subcutaneous tissue was measured at the anterior abdomen lateral to the umbilicus (SonoSfAbd) and at the middle of the femur (SonoSfFem). Within 72 h after delivery, a Holtain caliper was used to measure neonatal skinfold thickness at the left anterior iliac spine (SfAbd), at the lower angle of the left scapula (SfSca), at the middle of the femur, above the left quadriceps femoris (SfFem) and at the middle of the left triceps (SfHum). Ultrasound and mechanical measurements were correlated. RESULTS: The sonographic and mechanical methods showed good correlation with each other. Linear regression analysis gave the following equations: SfAbd (mm) = SonoSfAbd (mm) × 0.489 + 1.988 (r(2) = 0.34, P < 0.001); SfSca (mm) = SonoSfAbd (mm) 0.457 + 2.043 (r(2) = 0.40, P < 0.001); SfFem (mm) = SonoSfFem (mm) × 0.714 + 1.763 (r(2) = 0.41, P < 0.001); SfHum (mm) = SonoSfFem (mm) 0.564 + 2.09 (r(2) = 0.39, P < 0.001). CONCLUSIONS: Ultrasound examination is a reliable method for non-invasive intrauterine measurement of fetal subcutaneous tissue and can be used to predict mechanical neonatal skinfold thickness measurements.

Influence of maternal glycemia on intrauterine fetal adiposity distribution after a normal oral glucose tolerance test at 28 weeks gestation.

OBJECTIVE: To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation. STUDY DESIGN: We recruited 231 women with a singleton pregnancy. At 28 and 37 weeks gestation, sonographic measurements of fetal body composition were performed. Multiple regression analysis was used to study the influence of different maternal variables on fetal adiposity distribution. RESULTS: Maternal glucose levels correlated with the fetal abdominal subcutaneous tissue measurements (r = 0.2; P = 0.014) and with birth weight (r = 0.1; P = 0.04). Maternal glucose levels did not correlate with the fetal mid-thigh muscle thickness and mid-thigh subcutaneous tissue measurements. CONCLUSION: We found that in nondiabetic women maternal glucose levels not only influence fetal adiposity and birth weight, but also influence the distribution of fetal adiposity. This supports previous evidence that maternal glycemia is a key determinant of intrauterine fetal programming.

Quantification of the subcutaneous fat layer with MRI in fetuses of healthy mothers with no underlying metabolic disease vs. fetuses of diabetic and obese mothers.

OBJECTIVE: To assess the age-dependent fetal subcutaneous fat layer (SCFL) of non-diabetic, normal-weight mothers and fetuses of mothers with gestational diabetes (GDM) and normal body weight or obesity. METHODS: In a prospective study, we evaluated 115 MRI examinations of fetuses with no history of (maternal) metabolic disease [gestational week (GW) 29 to 39/40] and 50 examinations of mothers with GDM and normal body weight or obesity. The SCFL was measured at predetermined anatomical landmarks. Measurements were correlated with the maternal body mass index (BMI) and glycated hemoglobin A1c (HbA1c)-values in diabetic mothers. RESULTS: In fetuses of non-diabetic, normal-weight mothers, measurements showed high consistency within the respective GW and ranged from 2 mm at GW 29 at all measured points, up to 4.5 mm at the trunk and 6.0 mm at the extremities at GW 39/40. In 47/50 fetuses of mothers with GDM, the SCFL was within the range of fetuses of mothers with no metabolic disease. In three patients with GDM and BMI<30, the SCFL-thickness was decreased. No fetuses showed an increased SCFL-thickness. CONCLUSION: The SCFL of normally developed fetuses is easily detectable from GW 29 on T1-weighted images (T1-W), and increases with gestational age. The presented data provide physiological benchmarks to evaluate developmental status and may help in the prenatal diagnosis of abnormal growth and macrosomia. In pregnant women with well-controlled GDM, an increase of the SCFL is not expected.

Differential gene expressions in subcutaneous adipose tissue pointed to a delayed adipocytic differentiation in small pig fetuses compared to their heavier siblings.

Intra-uterine growth retardation in piglets is associated to neonatal losses and a greater susceptibility to fat deposition in the long term. Dietary l-arginine supplementation to gilts during early gestation has been proposed as a way to enhance fetal survival. This study aims to investigate the effects of variation in fetal growth within litters and dietary l-arginine treatment during early gestation in pregnant sows on expression levels of several genes involved in early adipose tissue development and lipid deposition in the fetuses. At day 75 of pregnancy, sows fed a standard gestation diet throughout pregnancy and sows fed 26g L-arginine daily from days 14 to 28 of gestation in supplement to the standard diet were sacrificed. Six pairs of littermates in each dietary group with the smallest or the heaviest fetal weights within each litter were collected (total: 24 fetuses). Expression levels of DLK1/PREF1 and FZD7 were significantly greater in subcutaneous backfat of the smallest fetuses. Conversely, transcriptional adipogenic regulators PPARG, SREBP1, and CEBPA, and genes involved in terminal adipocytic differentiation LPL, ME1, and FABP4 were less expressed in those piglets. Fetal weight has no effect on expression levels of genes involved in cell cycle progression and DNA content in subcutaneous adipose tissue. Maternal dietary L-arginine treatment did not affect subcutaneous adipose tissue features in 75-day old fetuses. The gene expression changes observed in the smallest fetuses are likely associated to a lower body fat content at birth, and could predispose to catch-up fat growth during the postnatal period.

Gelatinase B (MMP-9) deficiency does not affect murine adipose tissue development.

This study was performed to follow up on the observation that gelatinase A (MMP-2) deficiency impairs adipose tissue development in mice. The aim was to evaluate the role of its functional homologue gelatinase B (MMP-9) in adipose tissue growth. MMP-9 antigen levels were determined in lean and in obese women before and after weight loss. MMP-9-deficient mice and wild-type littermates (genetic background 50% 129sv : 50% CDI or 99.975% C57Bl/6, ten generations backcrossed into C57Bl/6 background) were kept on a high-fat diet (HFD) for 15 weeks. Subcutaneous and gonadal fat pads were analysed in terms of weight and size/density of adipocytes and blood vessels. Obese women had higher MMP-9 serum levels than lean controls (383 +/- 29 vs. 304 +/- 27 ng/ml, p = 0.02); after weight reduction MMP-9 levels dropped to 334 +/- 17 ng/ml (p = 0.1 vs. obese). However, MMP-9-deficient and littermate wild-type mice kept on HFD were indistinguishable in terms of body and fat weight. No effect of MMP-9 deficiency was observed on size or density of adipocytes or blood vessels in subcutaneous or gonadal fat depots. Similar observations were made when mice were kept on normal chow. In conclusion, in lean and obese women, body mass index correlates positively with MMP-9 serum levels (p < 0.0001). However, MMP-9 does not seem to play a major role in adipose tissue development in murine models of diet-induced obesity.

Could birthweight prediction models be improved by adding fetal subcutaneous tissue thickness?

AIM: The aims of the study were to: (i) compare the accuracy of standard ultrasonic algorithms in the estimation of fetal weight and; (ii) test two new algorithms in order to improve the global performance of birthweight prediction by adding fetal subcutaneous tissue thickness. METHODS: We enrolled 398 patients who were between 34 and 42 weeks' gestation. Routine ultrasonographic biometric parameters as well as subcutaneous tissue thickness ultrasound parameters were measured. Correlation matrices between ultrasound parameters, in order to evaluate the degree of multicollinearity between these parameters, were assessed to develop a stepwise multiple regression birthweight predictive model. RESULTS: Contributions of single ultrasound measurements in predicting birthweight were examined, by fitting Log-transformed birthweight versus single ultrasound measurements. We found that the mid-thigh tissue area was able to significantly improve the performance of the birthweight prediction process when added to the other standard ultrasound measurements. We derived two new algorithms which appeared to be better at predicting birthweight. Furthermore there was a lower minimum absolute estimation error noted when compared to other reported formulae. CONCLUSIONS: Our algorithms showed that the addition of the mid-thigh tissue evaluation in birthweight prediction was valuable in comparison to birthweight prediction models which are based on routine ultrasound parameters.