Comparison of diurnal variations, gestational age and gender related differences in fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) fetuses in the home environment

Objective To assess the influence of gender, time of the day and gestational age on fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) fetuses using a portable fetal ECG monitor employed in the home setting. Methods We analysed and compared the antenatal FHR data collected in the home setting on 61 healthy pregnant women with singleton pregnancies from 24 weeks gestation. Of the 61 women, 31 had SGA fetuses (estimated fetal weight below the tenth gestational centile) and 30 were pregnant with AGA fetuses. FHR recordings were collected for up to 20 h. Two 90 min intervals were deliberately chosen retrospectively with respect to signal recording quality, one during day-time and one at night-time for comparison. Results Overall, success rate of the fetal abdominal ECG in the AGA fetuses was 75.7% compared to 48.6% in the SGA group. Based on randomly selected episodes of heart rate traces where recording quality exceeded 80% we were able to show a marginal difference between day and night-time recordings in AGA vs. SGA fetuses beyond 32 weeks of gestation. A selection bias in terms of covering different representation periods of fetal behavioural states cannot be excluded. In contrast to previous studies, we neither controlled maternal diet and activity nor measured maternal blood hormone and heart rate as all mothers were monitored in the home environment. Conclusion Based on clinically unremarkable, but statistically significant differences in the FHR parameters between the AGA and SGA group we suggest that further studies with large sample size are required to assess the clinical value of antenatal fetal ECG monitoring

Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis.

OBJECTIVE: The cerebroplacental ratio (CPR) has been proposed for the routine surveillance of pregnancies with suspected fetal growth restriction (FGR), but the predictive performance of this test is unclear. The aim of this study was to determine the accuracy of CPR for predicting adverse perinatal and neurodevelopmental outcomes in suspected FGR. METHODS: PubMed, EMBASE, CINAHL and Lilacs were searched from inception to 31 July 2017 for cohort or cross-sectional studies reporting on the accuracy of CPR for predicting adverse perinatal and/or neurodevelopmental outcomes in singleton pregnancies with FGR suspected antenatally based on sonographic parameters. Summary receiver-operating characteristics (ROC) curves, pooled sensitivities and specificities, and summary likelihood ratios (LRs) were generated. RESULTS: Twenty-two studies (including 4301 women) met the inclusion criteria. Summary ROC curves showed that the best predictive accuracy of CPR was for perinatal death and the worst was for neonatal acidosis, with areas under the summary ROC curves of 0.83 and 0.57, respectively. The predictive accuracy of CPR was moderate to high for perinatal death (pooled sensitivity and specificity of 93% and 76%, respectively, and summary positive and negative LRs of 3.9 and 0.09, respectively) and low for composite of adverse perinatal outcomes, Cesarean section for non-reassuring fetal status, 5-min Apgar score < 7, admission to the neonatal intensive care unit, neonatal acidosis and neonatal morbidity, with summary positive and negative LRs ranging from 1.1 to 2.5 and 0.3 to 0.9, respectively. An abnormal CPR result had moderate accuracy for predicting small-for-gestational age at birth (summary positive LR of 7.4). CPR had a higher predictive accuracy in pregnancies with suspected early-onset FGR. No study provided data for assessing the predictive accuracy of CPR for adverse neurodevelopmental outcome. CONCLUSION: CPR appears to be useful in predicting perinatal death in pregnancies with suspected FGR. Nevertheless, before incorporating CPR into the routine clinical management of suspected FGR, randomized controlled trials should assess whether the use of CPR reduces perinatal death or other adverse perinatal outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

A novel contact interaction formulation for voxel-based micro-finite-element models of bone

Voxel-based micro-finite-element (μFE) models are used extensively in bone mechanics research. A major disadvantage of voxel-based μFE models is that voxel surface jaggedness causes distortion of contact-induced stresses. Past efforts in resolving this problem have only been partially successful, ie, mesh smoothing failed to preserve uniformity of the stiffness matrix, resulting in (excessively) larger solution times, whereas reducing contact to a bonded interface introduced spurious tensile stresses at the contact surface. This paper introduces a novel "smooth" contact formulation that defines gap distances based on an artificial smooth surface representation while using the conventional penalty contact framework. Detailed analyses of a sphere under compression demonstrated that the smooth formulation predicts contact-induced stresses more accurately than the bonded contact formulation. When applied to a realistic bone contact problem, errors in the smooth contact result were under 2%, whereas errors in the bonded contact result were up to 42.2%. We conclude that the novel smooth contact formulation presents a memory-efficient method for contact problems in voxel-based μFE models. It presents the first method that allows modeling finite slip in large-scale voxel meshes common to high-resolution image-based models of bone while keeping the benefits of a fast and efficient voxel-based solution scheme

Fetal epigenetic programming of the IGF axis in pregnancies affected by growth disorders, gestational diabetes and obesity

Gestational diabetes and maternal obesity are associated with impaired maternal glycaemic control and increased risk of delivering a macrosomic fetus. Macrosomic as well as growth restricted neonates have an increased risk of metabolic syndrome and cardiovascular disease in adult life which may be mediated through an altered intra-uterine environment. The placenta acts as a mediator between the mother and the fetus and handles placental nutrient exchange and transfer. Insulin-like growth factors 1 and 2 (IGF1 and IGF2) are hormones similar to insulin and are known for their growth promoting function in the body. They are also present in the placenta and play an important role in regulating placental and fetal growth. Animal and human studies have shown that IGF1 and IGF2 deletions are associated with growth restriction. The IGFs are bound to their binding proteins called insulin-like growth factor binding proteins (IGFBPs) which modulate their bioavailability and can therefore modulate fetal growth. The IGFs and IGFBPs are associated with glucose regulation but their role in gestational diabetes is unclear. We hypothesized that the placental gene expression of IGF system related genes is altered in pregnancies complicated by fetal growth disorders (pregnancies with small or large fetuses) and in those women who had gestational diabetes mellitus (GDM) or increased body mass index (BMI>30). Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence. DNA methylation is an epigenetic mechanism which involves addition of methyl group to a cytosine base in the DNA forming a methylated cytosine-phosphate-guanine (CpG) dinucleotide which is known to silence gene expression. This can potentially alter the expression of IGFs and their binding proteins. We have also hypothesized that a relationship existed between DNA methylation and gene expression of components of the IGF axis in the placenta. The placental IGF1 expression was found to be reduced in women with small for gestational age (SGA) neonates. The expression of IGFBPs was upregulated in SGA neonates and downregulated in large for gestational age (LGA) neonates. The placental IGF1 gene promoter was found to be hypermethylated while the promoters of the binding proteins were hypomethylated in the placentas of SGA neonates. The umbilical cord levels of IGF1 and the binding proteins in SGA and LGA neonates showed a similar trend to the placental gene expression changes. We have also analysed the placental gene expression and umbilical levels of imprinted gene GRB10 which has been investigated in mice studies and is known to cause growth restriction. We found increased placental expression of GRB10 and hypomethylation of its promoter in SGA neonates. The placental expression of IGF1, IGFBP1 and IGFBP2 was found to be decreased in women with GDM on diet and on metformin but not in those on insulin. The IGF1, IGFBP1 and IGFBP2 promoters were noted to be hypermethylated but only in women on diet treatment and not on metformin on insulin. The umbilical levels of IGF1 and IGFBP1 but not IGFBP2, were increased in GDM thus showing an inverse trend to the placental gene expression changes. In conclusion our results suggest that in SGA neonates, changes in CpG methylation contribute to the changes in gene expression of components of the IGF axis and GRB10 in fetal growth disorders. Differential methylation of the IGF1 gene, its binding proteins and GRB10 is likely to play a role in the pathogenesis of SGA neonates. Our results also suggest that GDM is associated with gene expression and epigenetic alterations in the IGF1, IGFBP1 and IGFBP2 genes, which could be part of the wider metabolic complexities associated with GDM.Open Acces