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Objective: Echocardiographic studies have reported that fetuses with low birth weight, compared to those with normal birth weight, have globular hearts and reduced cardiac function. Dichotomizing continuous variables, such as birth weight, may be helpful in describing pathology in small studies but can prevent us from identifying physiological responses in relation to change in size. The aim of this study was to explore associations between fetal cardiac morphology and function and birth weight, as a continuous variable, as well as uterine artery (UtA) pulsatility index (PI), as an indirect measure of placental perfusion, and the cerebroplacental ratio (CPR), as an indirect measure of fetal oxygenation. Methods: This was a prospective study of 1498 women with singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Pregnancies complicated by pregestational or gestational diabetes mellitus, chronic hypertension, pregnancy‐induced hypertension or pre‐eclampsia were excluded from the analysis. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricles. The morphology of the fetal heart was assessed by calculating the right and left sphericity indices. In addition, the PI of the UtA, umbilical artery (UA) and fetal middle cerebral artery (MCA) was determined and the CPR was calculated by dividing MCA‐PI by UA‐PI. Multiple linear regression models were used to assess determinants of fetal echocardiographic parameters. Results: The study population included 146 (9.7%) small‐for‐gestational‐age (SGA) fetuses with birth weight < 10th percentile and 68 (4.5%) with fetal growth restriction (FGR). In the SGA and FGR groups, compared to the non‐SGA and non‐FGR fetuses, respectively, there was a more globular right ventricle and reduced left and right ventricular systolic function, and, from the left ventricular diastolic functional indices, the E/A ratio was increased. There was a linear association of right ventricular sphericity index, indices of left and right ventricular systolic function and E/A ratio with birth‐weight Z‐score. There were no significant associations between cardiac morphological and functional indices and UtA‐PI Z‐score or CPR Z‐score. Conclusions: This screening study at 35–37 weeks' gestation has demonstrated that birth weight is a determinant of fetal cardiac morphology and function but UtA‐PI and CPR, as indirect measures of placental perfusion and fetal oxygenation, are not. This suggests that the differences in fetal cardiac indices between small and appropriately grown fetuses may be part of a normal physiological response to change in fetal size rather than part of a pathological adaptation to abnormal placental perfusion and fetal oxygenation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology [ABSTRACT FROM AUTHOR]

Objective: To determine whether cardiac functional and structural changes in fetuses of mothers with gestational diabetes mellitus (GDM) persist in the offspring beyond the neonatal period. Design: Longitudinal study. Setting: Fetal Medicine Unit in a UK teaching hospital. Methods: 73 women with GDM and 73 women with uncomplicated pregnancy were recruited and fetal cardiac scans were performed at 35–36 weeks' gestation. Repeat echocardiogram was performed in their offspring during infancy. Main outcome measures: Fetal and infant cardiac functional and structural changes. Results: Fetuses of mothers with GDM, compared with controls, had more globular right ventricles (sphericity index 0.7, interquartile range [IQR] 0.6/0.7 versus 0.6, IQR 0.5/0.6, P < 0.001) and reduced right global longitudinal systolic strain (−16.4, IQR −18.9/−15.3 versus −18.5, IQR −20.6/−16.8, P = 0.001) and left global longitudinal systolic strain (−20.1, IQR −22.5/−16.9 versus −21.3, IQR −23.5/−19.5), P = 0.021). In the GDM group, compared with controls, in infancy there was higher left ventricular E/e' (8.7, IQR 7.3/9.7 versus 7.9 IQR, 6.8/8.9 P = 0.011) and lower left ventricular global longitudinal systolic strain (−21.0, IQR −22.5/−19.4 versus −22.3, IQR −23.5/−20.7, P = 0.001) and tricuspid annular plane systolic excursion (13.8, IQR 12.7/16.1 versus 15.2, IQR 13.8/16.8, P = 0.003). These differences remained following multivariable analysis. Conclusion: Gestational diabetes mellitus is associated with alterations in fetal cardiac function and structure compared with controls and persistent cardiac changes in infancy. Gestational diabetes mellitus, even when well controlled, is associated with fetal cardiac changes and these persist in infancy. Gestational diabetes mellitus, even when well controlled, is associated with fetal cardiac changes and these persist in infancy. [ABSTRACT FROM AUTHOR]

Several in vitro and in vivo studies have demonstrated suppression of tumour necrosis factor-α (TNF-α) synthesis by pentoxifylline. In the present study we compared the effect of pentoxifylline with that of five other xanthine derivatives. We addressed two questions. First, what is the relative potency of those chemically related compounds in suppressing the lipopolysaccharide (LPS)-induced production of TNF-α in human mononuclear cells? Second, does suppression of TNF-α production by these xanthine derivatives correlate with their capacity to inhibit 3',5'-cAMP phosphodiesterase (PDE) activity? The experimental drug A 80 2715 [1-(5-hydroxy-5-methylhexyl)-3-methyl-7-propylxanthine] was identified as the most potent agent with an IC50 (concentration exerting 50% suppression of LPS-induced TNF-α production) of 41 μM (mean of 13 individuals). The IC50 values of the other substances ranged between 106 μM for HWA 138 and 419 μM for theophylline. The LPS-induced interleukin-1β (IL-1β) production was not influenced by all substances tested at comparable concentrations. inhibition of PDE activity was determined in a cell-free system using PDE isolated from bovine heart. All xanthine derivatives dose-dependently inhibited PDE activity. Furthermore, with the exception of theophylline, there was a high degree of correlation between the potency to suppress TNF-α production in the cell culture system and the potency to inhibit PDE activity in the cell-free enzymatic assay. This argues for a crucial role of PDE inhibition in the suppression of TNF-α synthesis by xanthine derivatives. [ABSTRACT FROM AUTHOR]