Fetal echocardiographic evaluation before and after nifedipine treatment in preterm labor.

OBJECTIVE: To assess the effect of nifedipine used for tocolysis on cardiac morphology and functions. METHODS: The study included 47 pregnant women diagnosed with preterm labor at 32-33 weeks. Fetal echocardiographic evaluation was performed with two-dimensional (2D) imaging, M-mode, pulsed wave (PW) Doppler, and tissue Doppler imaging (TDI) before and after the 48th hour of nifedipine treatment. RESULTS: No significant change was observed in Doppler parameters (pulsatility indices of the umbilical artery, middle cerebral artery, ductus venosus) and cardiac morphology (cardiothoracic ratio, end-diastolic longitudinal diameters, sphericity indices, wall thickness) after nifedipine treatment. The parameters obtained with TDI (e', a', s', e'/a', E/e' of mitral and tricuspid valves), M- mode (TAPSE, MAPSE), pulsed Doppler (myocardial performance index, left cardiac output, right cardiac output, tricuspid E, A waves, tricuspid E/A ratio, mitral E, A waves, mitral E/A ratio) did not change after nifedipine treatment. CONCLUSION: To date, this is the first study to examine the effects of nifedipine on the fetal heart using the TDI. Since nifedipine is a drug that is frequently used and well-tolerated in the prevention of preterm labor, it is crucial that it does not cause changes in fetal cardiac parameters during tocolysis. Therefore, we used TDI in addition to conventional methods to evaluate the effect of nifedipine, which is frequently used in obstetrics, on cardiac functions in the early period. Nifedipine treatment seems not to affect systolic or diastolic functions. This indicates that nifedipine is reliable on cardiac functions and morphology in pregnancies treated for preterm labor.

Experiences and outcomes on the use of telemetry to monitor the fetal heart during labour: findings from a mixed methods study.

BACKGROUND: Wireless continuous electronic fetal monitoring (CEFM) using telemetry offers potential for increased mobility during labour. United Kingdom national recommendations are that telemetry should be offered to all women having CEFM during labour. There is limited contemporary evidence on experiences of telemetry use or impacts it may have. AIM: To gather in-depth knowledge about the experiences of women and midwives using telemetry, and to assess any impact that its use may have on clinical outcomes, mobility in labour, control or satisfaction. METHODS: A convergent parallel mixed-methods study was employed. Grounded theory was adopted for interviews and analysis of 13 midwives, 10 women and 2 partners. Satisfaction, positions during labour and clinical outcome data was analysed from a cohort comparing telemetry (n = 64) with wired CEFM (n = 64). Qualitative and quantitative data were synthesised to give deeper understanding. FINDINGS: Women using telemetry were more mobile and adopted more upright positions during labour. The core category A Sense of Normality encompassed themes of 'Being Free, Being in Control', 'Enabling and Facilitating' and 'Maternity Unit Culture'. Greater mobility resulted in increased feelings of internal and external control and increased perceptions of autonomy, normality and dignity. There was no difference in control or satisfaction between cohort groups. CONCLUSIONS: When CEFM is used during labour, telemetry provides an opportunity to improve experience and support physiological capability. The use of telemetry during labour contributes to humanising birth for women who have CEFM and its use places them at the centre and in control of their birth experience.

A 'holistic' sonographic view on congenital heart disease - How automatic reconstruction using fetal intelligent navigation echocardiography (FINE) eases the unveiling of abnormal cardiac anatomy part I: Right heart anomalies.

Attempting a comprehensive examination of the fetal heart remains challenging for unexperienced operators as it emphasizes the acquisition and documentation of sequential cross-sectional and sagittal views and inevitably results in diminished detection rates of fetuses affected by congenital heart disease. The introduction of four-dimensional spatio-temporal image correlation (4D STIC) technology facilitated a volumetric approach for thorough cardiac anatomic evaluation by the acquisition of cardiac 4D datasets. By analyzing and re-arranging of numerous frames according to their temporal event within the heart cycle, STIC allows visualization of cardiac structures as an endless cine loop sequence of a complete single cardiac cycle in motion. However, post-analysis with manipulation and repeated slicing of the volume usually requires experience and in-depth anatomic knowledge, which limits the widespread application of this advanced technique in clinical care and unfortunately leads to the underestimation of its diagnostic value to date. Fetal intelligent navigation echocardiography (FINE), a novel method that automatically generates and displays nine standard fetal echocardiographic views in normal hearts, has shown to be able to overcome these limitations. Very recent data on the detection of congenital heart defects (CHDs) using the FINE method revealed a high sensitivity and specificity of 98% and 93%, respectively. In this two-part manuscript, we focused on the performance of FINE in delineating abnormal anatomy of typical right and left heart lesions and thereby emphasized the educational potential of this technology for more than just teaching purposes. We further discussed recent findings in a pathophysiological and/or functional context.

A "holistic" sonographic view on congenital heart disease: How automatic reconstruction using fetal intelligent navigation echocardiography eases unveiling of abnormal cardiac anatomy part II-Left heart anomalies.

Volume ultrasound has been shown to provide valid complementary information on fetal anatomy. Four-dimensional assessment (4D) of the fetal cardiovascular system using spatial-temporal image correlation (STIC) allows for detailed examination of a highly complex organ from the early second trimester onward. There is compelling evidence that this technique harbors quite a number of diagnostic opportunities, but manual navigation through STIC volume datasets is highly operator dependent. In fact, STIC is not incorporated yet into daily practice. Application of the novel fetal intelligent navigation echocardiography (FINE) considerably simplifies fetal cardiac volumetric examinations. This automatic technique applied on cardiac volume datasets reportedly has both high sensitivity and specificity for the detection of congenital heart defects (CHDs). Part I reviewed current data regarding detection rates of CHDs and illustrated the additional value of an automatic approach in delineating cardiac anatomy exemplified by congenital lesions of the right heart. In part II of this pictorial essay, we focused on left heart anomalies and aimed to tabulate recent findings on the quantification of normal and abnormal cardiac anatomy.

Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.

Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

Providing mothers with fetal heart monitors.

Enabling mothers in labour to monitor their baby's heart is improving maternal and neonatal outcomes in Liberia. Tatum Anderson reports.

Research into the intervention effect of folic acid on arsenic-induced heart abnormalities in fetal rats during the periconception period.

BACKGROUND: The incidence of CHD is the highest among birth defects and is increasing year to year. CHD seriously harms the health of infants and young children and presents a large economic burden to families and society. The pathogenesis of CHD and preventive measures are the focus of current research. Our research aimed to explore the intervention effect of folic acid on heart abnormalities resulting from sodium arsenic (NaAsO2) exposure during the periconception period. METHODS: Sixty 35-day-old female SD rats were randomly divided into 5 groups with 12 rats in each group. Group A was the control group. The rats were given distilled water and ordinary chow. The rats in group B were given distilled water containing 75 mg/L NaAsO2 and ordinary chow. The rats in groups C, D, and E were given distilled water containing 75 mg/L NaAsO2 and chow containing 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg folic acid, respectively. The general condition of the embryos and the histopathology of the embryonic hearts were examined. The acetylation levels of histone H3K9 in heart tissues and the expression levels of Mef2C (which is related to heart development) were observed. RESULTS: The embryo weight and placental weight of groups B-E were significantly lower than those of group A (P < 0.05). The heart malformation rate of the fetal rats in groups B-E was significantly higher than that of the fetal rats in group A (P < 0.05). We found that the level of H3K9 acetylation in fetal rat cardiomyocytes in groups B-E was significantly higher than that in group A (P < 0.05) and that the level of H3K9 acetylation in groups C-E was lower than that in group B (P < 0.05). The mRNA level of Mef2C in fetal rat cardiomyocytes in group B-E was significantly higher than that in group A (P < 0.05), and the mRNA level of Mef2C in groups C-E was significantly lower than that in group B (P < 0.05). CONCLUSION: Supplementation with folic acid during the periconception period can interfere with the toxic effects of arsenic on the heart. The mechanism may be that lowering the acetylation levels of histone H3K9 in heart tissues leads to decreased expression levels of Mef2C, which may play a protective role in heart development in fetal rats.

Sustained Chronic Maternal Hyperoxygenation Increases Myocardial Deformation in Fetuses with a Small Aortic Isthmus at Risk for Coarctation.

BACKGROUND: We aimed to assess differences in myocardial deformation in fetuses at risk for coarctation (CoA) and the effects of maternal hyperoxygenation on deformation. METHODS: Fetal echocardiography and velocity vector imaging were performed prospectively and serially in 48 fetuses with a small aortic isthmus and 48 gestation age-matched normal fetuses. Fetuses with a small aortic isthmus were randomly divided into two groups: one group with and the other group without maternal supplemental oxygen administration. The strain (S) and strain rate (SR) in the left ventricle (LV) and right ventricle (RV) were measured and compared between the groups. Regression analyses were performed to identify potential factors associated with myocardial deformation. RESULTS: Compared with normal fetuses, fetuses with a small aortic isthmus exhibited a lower S and SR at baseline. A negative correlation was found between aortic isthmus velocity-time integrals and S and SR at baseline (P < .05). In the group that received supplemental oxygen therapy, the S and SR in both the LV and RV increased as a function of time, especially 4 weeks after the initiation of oxygen therapy (P < .05). The duration of oxygen therapy and increased combined cardiac index were associated with increased myocardial deformation (P < .05). CONCLUSIONS: Myocardial deformation appears abnormal in those at risk for CoA beginning in utero, and chronic oxygen therapy appears to increase deformation measures. These findings may improve patient counseling and perinatal management.

The effect of music therapy on the cardiac activity parameters of a fetus in a cardiotocographic examination.

OBJECTIVE: The assessment of cardiac parameters of the fetus in cardiotocographic record of pregnant women listening to classical music. STUDY DESIGN: Sixty NST records with no musical stimulation and 30 NST records during a 15-min auditive stimulation with Wolfgang Amadeus Mozart's "Turkish March" as well as 30 NST records during Johann Strauss's "Tritsch-Tratsch Polka" were performed for the study. The average stage of the responders' pregnancy was the 36rd week, the lowest - the 27th week, the highest - 41st. RESULTS: Following the listening to W.A. Mozart's composition, a significant increase was observed in values concerning: the number of fetal movements (p < 0.0001), accelerations >10 (p = 0.0063), accelerations >15 (p = 0.0011), high variability (p = 0.0019) and short-term variability (p < 0.0001). Meanwhile, parameters concerning baseline cardiac activity (p = 0.0003) and low variability (p = 0.0021) significantly decreased. The number of uterine contractions decreased insignificantly (p = 0.3718). Following listening to J. Strauss's composition, the following parameters underwent increase: fetal movements (p = 0.0021) and short-term variability (p = 0.0025). The remaining parameters of the cardiotocographic record: accelerations, uterine contractions - underwent an improvement, but the changes were not significant. CONCLUSION: Music therapy is a noninvasive and uncostly method, significantly improving wellbeing-indicative fetal parameters.

Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes.

Disease models are essential for understanding cardiovascular disease pathogenesis and developing new therapeutics. The human induced pluripotent stem cell (iPSC) technology has generated significant enthusiasm for its potential application in basic and translational cardiac research. Patient-specific iPSC-derived cardiomyocytes offer an attractive experimental platform to model cardiovascular diseases, study the earliest stages of human development, accelerate predictive drug toxicology tests, and advance potential regenerative therapies. Harnessing the power of iPSC-derived cardiomyocytes could eliminate confounding species-specific and interpersonal variations and ultimately pave the way for the development of personalized medicine for cardiovascular diseases. However, the predictive power of iPSC-derived cardiomyocytes as a valuable model is contingent on comprehensive and rigorous molecular and functional characterization.

Deficient maternal zinc intake-but not folate-is associated with lower fetal heart rate variability.

OBJECTIVE: Few studies of maternal prenatal diet and child development examine micronutrient status in relation to fetal assessment. METHODS: Twenty-four-hour dietary recall of zinc and folate and 20min of fetal heart rate were collected from 3rd trimester pregnant adolescents. RESULTS: Deficient zinc was associated with less fetal heart rate variability. Deficient folate had no associations with HRV. Neither deficient zinc nor deficient folate was related to fetal heart rate. CONCLUSIONS: These findings, from naturalistic observation, are consistent with emerging data on prenatal zinc supplementation using a randomized control design. PRACTICAL IMPLICATION: Taken together, the findings suggest that maternal prenatal zinc intake is an important and novel factor for understanding child ANS development.

Antithetical regulation of α-myosin heavy chain between fetal and adult heart failure though shuttling of HDAC5 regulating YY-1 function.

Molecular switches of myosin isoforms are known to occur in various conditions. Here, we demonstrated the result from fetal heart failure and its potential mechanisms. Fetal and adult heart failure rat models were induced by injections of isoproterenol as previously described, and Go6976 was given to heart failing fetuses. Real-time PCR and Western blot were adopted to measure the expressions of α-MHC, ß-MHC and YY-1. Co-immunoprecipitation was performed to analysis whether YY-1 interacts with HDAC5. Besides, histological immunofluorescence assessment was carried out to identify the location of HDAC5. α-MHC was recorded elevated in fetal heart failure which was decreased in adult heart failure. Besides, YY-1 was observed elevated both in fetal and adult failing hearts, but YY-1 could co-immunoprecipitation with HDAC5 only in adult hearts. Nuclear localization of HDAC5 was identified in adult cardiomyocytes, while cytoplasmic localization was identified in fetuses. After Go6976 supplied, HDAC5 shuttled into nucleuses interacted with YY-1. The myosin molecular switches were reversed with worsening cardiac functions and higher mortalities. Regulation of MHC in fetal heart failure was different from adult which provided a better compensation with increased α-MHC. This kind of transition was involved with shuttling of HDAC5 regulating YY-1 function.

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands.

Impact of a standardized training program on midwives' ability to assess fetal heart anatomy by ultrasound.

BACKGROUND: Studies of prenatal detection of congenital heart disease (CHD) in the UK, Italy, and Norway indicate that it should be possible to improve the prenatal detection rate of CHD in Sweden. These studies have shown that training programs, visualization of the outflow tracts and color-Doppler all can help to speed up and improve the detection rate and accuracy. We aimed to introduce a more accurate standardized fetal cardiac ultrasound screening protocol in Sweden. METHODS: A novel pedagogical model for training midwives in standardized cardiac imaging was developed, a model using a think-aloud analysis during a pre- and post-course test and a subsequent group reflection. The self-estimated difficulties and knowledge gaps of two experienced and two beginner midwives were identified. A two-day course with mixed lectures, demonstrations and hands-on sessions was followed by a feedback session three months later consisting of an interview and check-up. The long-term effects were tested two years later. RESULTS: At the post-course test the self-assessed uncertainty was lower than at the pre-course test. The qualitative evaluation showed that the color Doppler images were difficult to interpret, but the training seems to have improved their ability to use the new technique. The ability to perform the method remained at the new level at follow-up both three months and two years later. CONCLUSIONS: Our results indicate that by implementing new imaging modalities and providing hands-on training, uncertainty can be reduced and examination time decreased, but they also show that continuous on-site training with clinical and technical back-up is important.

Factors that increase reactivity during fetal nonstress testing.

PURPOSE OF REVIEW: The most common method of antepartum fetal surveillance is the nonstress test (NST). Although it has satisfactory false-negative rates, dubious nonreactive results may challenge the physician. Any method or factor increasing the reactive NST results or shortening the time to attain a reactive test may be considerably useful. RECENT FINDINGS: Most of the studies have found no effect of maternal glucose administration on fetal heart rate and fetal activity, specificity of NST, time to reactivity and percentage of reactive NST results when compared with the control group. Maternal intake of 70% cocoa or caffeine had stimulating action on the fetal reactivity, and this effect on the fetal heart rate was more marked with high concentrations of cocoa (80%). Studies on maternal positioning during NST had equivocal results. Fetal manipulation has no impact on the NST reactivity. Vibroacoustic and halogen light stimulation may be associated with a reduction in time to reactivity. SUMMARY: These methods may increase the reactivity during a NST and may facilitate the antenatal fetal surveillance.

Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart.

Barker's concept of 'foetal programming' proposes that intrauterine growth restriction (IUGR) predicts complex metabolic diseases through relationships that may be further modified by the postnatal environment. Dietary restriction and deficit in methyl donors, folate, vitamin B12, and choline are used as experimental conditions of foetal programming as they lead to IUGR and decreased birth weight. Overfeeding and deficit in methyl donors increase central fat mass and lead to a dramatic increase of plasma free fatty acids (FFA) in offspring. Conversely, supplementing the mothers under protein restriction with folic acid reverses metabolic and epigenomic phenotypes of offspring. High-fat diet or methyl donor deficiency (MDD) during pregnancy and lactation produce liver steatosis and myocardium hypertrophy that result from increased import of FFA and impaired fatty acid ß-oxidation, respectively. The underlying molecular mechanisms show dysregulations related with similar decreased expression and activity of sirtuin 1 (SIRT1) and hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). High-fat diet and overfeeding impair AMPK-dependent phosphorylation of PGC-1α, while MDD decreases PGC-1α methylation through decreased expression of PRMT1 and cellular level of S-adenosyl methionine. The visceral manifestations of metabolic syndrome are under the influence of endoplasmic reticulum (ER) stress in overnourished animal models. These mechanisms should also deserve attention in the foetal programming effects of MDD since vitamin B12 influences ER stress through impaired SIRT1 deacetylation of HSF1. Taken together, similarities and synergies of high-fat diet and MDD suggest, therefore, considering their consecutive or contemporary influence in the mechanisms of complex metabolic diseases.

Xanthine oxidase and the fetal cardiovascular defence to hypoxia in late gestation ovine pregnancy.

Hypoxia is a common challenge to the fetus, promoting a physiological defence to redistribute blood flow towards the brain and away from peripheral circulations. During acute hypoxia, reactive oxygen species (ROS) interact with nitric oxide (NO) to provide an oxidant tone. This contributes to the mechanisms redistributing the fetal cardiac output, although the source of ROS is unknown. Here, we investigated whether ROS derived from xanthine oxidase (XO) contribute to the fetal peripheral vasoconstrictor response to hypoxia via interaction with NO-dependent mechanisms. Pregnant ewes and their fetuses were surgically prepared for long-term recording at 118 days of gestation (term approximately 145 days). After 5 days of recovery, mothers were infused i.v. for 30 min with either vehicle (n = 11), low dose (30 mg kg(-1), n = 5) or high dose (150 mg kg(-1), n = 9) allopurinol, or high dose allopurinol with fetal NO blockade (n = 6). Following allopurinol treatment, fetal hypoxia was induced by reducing maternal inspired O2 such that fetal basal P aO 2 decreased approximately by 50% for 30 min. Allopurinol inhibited the increase in fetal plasma uric acid and suppressed the fetal femoral vasoconstrictor, glycaemic and lactate acidaemic responses during hypoxia (all P < 0.05), effects that were restored to control levels with fetal NO blockade. The data provide evidence for the activation of fetal XO in vivo during hypoxia and for XO-derived ROS in contributing to the fetal peripheral vasoconstriction, part of the fetal defence to hypoxia. The data are of significance to the understanding of the physiological control of the fetal cardiovascular system during hypoxic stress. The findings are also of clinical relevance in the context of obstetric trials in which allopurinol is being administered to pregnant women when the fetus shows signs of hypoxic distress.

Insulin receptor substrate signaling suppresses neonatal autophagy in the heart.

The induction of autophagy in the mammalian heart during the perinatal period is an essential adaptation required to survive early neonatal starvation; however, the mechanisms that mediate autophagy suppression once feeding is established are not known. Insulin signaling in the heart is transduced via insulin and IGF-1 receptors (IGF-1Rs). We disrupted insulin and IGF-1R signaling by generating mice with combined cardiomyocyte-specific deletion of Irs1 and Irs2. Here we show that loss of IRS signaling prevented the physiological suppression of autophagy that normally parallels the postnatal increase in circulating insulin. This resulted in unrestrained autophagy in cardiomyocytes, which contributed to myocyte loss, heart failure, and premature death. This process was ameliorated either by activation of mTOR with aa supplementation or by genetic suppression of autophagic activation. Loss of IRS1 and IRS2 signaling also increased apoptosis and precipitated mitochondrial dysfunction, which were not reduced when autophagic flux was normalized. Together, these data indicate that in addition to prosurvival signaling, insulin action in early life mediates the physiological postnatal suppression of autophagy, thereby linking nutrient sensing to postnatal cardiac development.

Environmental origins of congenital heart disease: the heart-placenta connection.

Although the mammalian embryo is well protected in the uterus, environmental chemicals, drugs, and maternal nutritional imbalances can interfere with regulatory pathways directing placental and embryonic development early in gestation. Embryonic cells are most susceptible to environmental influences during cellular specification and differentiation stages. Because biochemical differentiation precedes morphological outcome often by days, the period of susceptibility to environmental chemicals expectedly precedes visible morphogenic effects. The cellular mechanisms by which drugs and other environmental factors disrupt embryonic development and induce cardiac abnormalities have remained undefined.