Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow-up study.

INTRODUCTION: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long-lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8-9 years. This follow-up study aimed to examine whether these findings persisted into adolescence. MATERIAL AND METHODS: Prospective observational follow-up study involving twenty-one 14- to 15-year-old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty-five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention-deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus-pituitary-adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. RESULTS: No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference -2.0, 95% confidence interval [CI]: -7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress-induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency-adjusted means: 16.0 Hz vs 17.8 Hz, mean difference -1.83 Hz, 95% CI: -3.21 to -0.45, p = 0.01). CONCLUSIONS: In 14- to 15-year-old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow-up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.

Cerebroplacental hemodynamics in fetuses with transposition of the great arteries and usefulness in predicting neonatal condition.

OBJECTIVES: Literature on cerebroplacental hemodynamics in fetuses with transposition of the great arteries (TGA) is scarce and provides conflicting results regarding the presence of a brain-sparing effect. The aims of this study were to examine Doppler parameters in the middle cerebral artery (MCA) and umbilical artery (UA) in a large cohort of fetuses with TGA, and to assess their possible utility in predicting the need for urgent balloon atrial septostomy (BAS) in the neonate. METHODS: This was a retrospective observational study of fetuses diagnosed with TGA between 2008 and 2022 and an age-matched cohort of normal fetuses, conducted in a single tertiary fetal cardiology center. Medical records and echocardiographic examinations were reviewed to collect demographic, sonographic and follow-up data. Selected Doppler parameters were compared between fetuses with TGA and normal fetuses, as well as between TGA fetuses with and those without an associated ventricular septal defect (VSD), to assess the impact of this congenital heart defect on cerebroplacental circulation. Additionally, Doppler indices in patients with a restrictive foramen ovale (FO) were analyzed to identify potential predictors of the need for urgent BAS. RESULTS: A total of 541 examinations of 159 fetuses with TGA performed between 19 and 40 weeks' gestation and 1300 examinations of 1215 age-matched normal fetuses were included in the study. MCA pulsatility index (PI) and UA-PI followed expected trends throughout pregnancy, with slightly higher values observed in TGA fetuses, albeit within the limits for the normal population. Cerebroplacental ratio (CPR) values were similar in normal and TGA fetuses. The presence of a small VSD did not have a clinically significant impact on Doppler parameters. Peak systolic velocity (PSV) in the MCA increased gradually after 35 weeks' gestation, especially in fetuses that did not develop restriction of the FO after birth. MCA-PSV values below 1.16 multiples of the median measured at 38 weeks or later predicted the need for urgent BAS with 81.4% sensitivity and 52.4% specificity. CONCLUSIONS: MCA-PI, UA-PI and CPR values in fetuses with TGA usually fall within normal limits throughout pregnancy. The presence of a small VSD does not affect the Doppler parameters significantly. MCA-PSV increases in TGA fetuses after 35 weeks, and its value measured at the last prenatal examination (ideally after 37 weeks) may serve as an additional predictive factor for the need for urgent BAS. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A second look at intrapartum fetal surveillance and future directions.

Intrapartum fetal surveillance aims to predict significant fetal hypoxia and institute timely intervention to avoid fetal injury, and do so without unnecessary operative delivery of fetuses at no risk of intrapartum hypoxia. However, the configuration and application of current clinical guidelines inadvertently undermine these aims because of persistent failure to incorporate increased understanding of fetal cardiovascular physiology and adaptations to oxygen deprivation, advances in signal acquisition/processing, and related technologies. Consequently, the field on intrapartum fetal surveillance is stuck in rudimentary counts of the fetal R-R intervals and visual assessment of very common, but nonspecific fetal heart decelerations and fetal heart rate variability. The present authors argue that the time has come to move away from classifications of static morphological appearances of FHR decelerations, which do not assist the thinking clinician in understanding how the fetus defends itself and compensates for intrapartum hypoxic ischaemic insults or the patterns that suggest progressive loss of compensation. We also reappraise some of the controversial aspects of intrapartum fetal surveillance in modern obstetric practice, the current state of flux in training and certification, and contemplate the future of the field particularly in the context of the emerging role of artificial intelligence.

Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8- to 9-year-old children: A prospective observational study.

INTRODUCTION: Glucocorticoid (GC) -induced fetal programming of the activity of the hypothalamus-pituitary-adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood. MATERIAL AND METHODS: Prospective observational study in 31 children whose mothers received single (n = 19) or multiple (n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+6  weeks of gestation) compared with 38 non-exposed, age-matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention-deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG). RESULTS: There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM-exposed children had lower IQ scores than the unexposed group. BM-exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose-response relation between BM exposure and activity of the ANS and IQ was estimated in post-hoc analyses. CONCLUSIONS: Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life-saving therapy, but its prescription may warrant a well-balanced risk-benefit assessment.

Cardiac hemodynamics in fetuses with transposition of the great arteries and intact ventricular septum from diagnosis to end of pregnancy: longitudinal follow-up.

OBJECTIVES: Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS: This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 ) < 65% or ≥ 65%, as a neonatal outcome, in fetuses with TGA-IVS. RESULTS: In total, 59 fetuses with TGA-IVS and 160 normal fetuses were included. Global cardiac output was significantly higher in fetuses with TGA-IVS than in controls, mainly owing to higher global pulmonary output, while global systemic cardiac output did not differ between TGA-IVS fetuses and controls throughout pregnancy. Aortic flow (right ventricular output in fetuses with TGA-IVS, left ventricular output in controls) was significantly higher in fetuses with TGA-IVS than in normal fetuses. Ductal flow was significantly lower in fetuses with TGA-IVS at every timepoint, and this difference increased considerably after 28-32 weeks. In parallel, the diameter of the foramen ovale was significantly smaller in fetuses with TGA-IVS at 28-32 and 35-38 weeks, with a stagnation in growth after 28 weeks, compared with continuous growth in normal fetuses. Most of these cardiac hemodynamic anomalies in fetuses with TGA-IVS were already present at 18-22 weeks, and the differences became greater at 28-32 weeks' gestation. TGA-IVS neonates with TcSO2 < 65% had lower fetal left ventricular output, higher diastolic ductal retrograde flow and smaller foramen ovale at 28-32 weeks, compared with fetal values in those with postnatal TcSO2 ≥ 65%. CONCLUSIONS: Compared with normal fetuses, those with TGA-IVS undergo a complex redistribution of blood flow during the second half of pregnancy, with higher global pulmonary flow, lower ductal flow (with negative diastolic flow at the end of pregnancy) and a smaller foramen ovale. In addition, fetal cardiac hemodynamic anomalies observed at 28-32 weeks' gestation were associated with lower postnatal TcSO2 . These observations may provide a better understanding of premature closure of the foramen ovale and postnatal hypoxia that are specific to TGA-IVS physiology. © 2019 International Society of Ultrasound in Obstetrics and Gynecology.

Selective perfusion of coronary vasculature in preterm sheep: a methodological innovation undermined by unfavourable operation of the foramen ovale.

Antenatal cardiac intervention affords new prospects for hypoplastic left heart syndrome. Its success, however, may come not only from absence of impediments to blood flow but also from a sufficiently developed cardiac wall. Here, we examined the feasibility to perfuse selectively the fetal coronary circulation for treatment with growth promoting agents. Pregnant sheep (94-114 days gestation, term 145 days) were used. An aortic stop-flow procedure was developed for intracoronary access in the nonexposed fetus and human mesenchymal stem cells and their exosomes served as test agents. We found that aortic stop-flow ensures preferential distribution of fluorescent microspheres to the heart. However, intracoronary administration of stem cells or exosomes was detrimental, with fetal demise occurring around surgery or at variable intervals afterwards. Coincidentally, stop-flow caused by itself a marked rise of intraluminal pressure within the occluded aorta along with histological signs of coronary obstruction. We conclude that it is feasible to perfuse selectively the coronary circulation of the preterm fetus, but treatments are not compatible with survival of the animals. The cause for failure is found in the absence of hemodynamic compensation to stop-flow via a left-to-right shunt. This unexpected event is attributed to a largely membranous foramen ovale, characteristic of sheep, that collapses under pressure.

Prediction of the Secretome and the Surfaceome: A Strategy to Decipher the Crosstalk between Adipose Tissue and Muscle during Fetal Growth.

Crosstalk between adipose and muscular tissues is hypothesized to regulate the number of muscular and adipose cells during fetal growth, with post-natal consequences on lean and fat masses. Such crosstalk largely remains, however, to be described. We hypothesized that a characterization of the proteomes of adipose and muscular tissues from bovine fetuses may enhance the understanding of the crosstalk between these tissues through the prediction of their secretomes and surfaceomes. Proteomic experiments have identified 751 and 514 proteins in fetal adipose tissue and muscle. These are mainly involved in the regulation of cell proliferation or differentiation, but also in pathways such as apoptosis, Wnt signalling, or cytokine-mediated signalling. Of the identified proteins, 51 adipokines, 11 myokines, and 37 adipomyokines were predicted, together with 26 adipose and 13 muscular cell surface proteins. Analysis of protein-protein interactions suggested 13 links between secreted and cell surface proteins that may contribute to the adipose-muscular crosstalk. Of these, an interaction between the adipokine plasminogen and the muscular cell surface alpha-enolase may regulate the fetal myogenesis. The in silico secretome and surfaceome analyzed herein exemplify a powerful strategy to enhance the elucidation of the crosstalk between cell types or tissues.

Effects of ketamine on the fetal transcriptomic response to umbilical cord occlusion: comparison with hypoxic hypoxia in the cerebral cortex.

KEY POINTS: The cerebral response to fetal asphyxia is characterized by an upregulation of nucleic acid and chromatin modification processes, as well as a downregulation of metabolic processes at 1 h post-umbilical cord occlusion (UCO). Twenty-four hours post UCO, there was an upregulation of metabolic processes and protein modifications. UCO did not alter bacterial gene expression levels, nor did it produce a robust inflammatory response compared to maternal hypoxia. The administration of ketamine produced minimal effects on the fetal response to UCO in the cerebral cortex. ABSTRACT: Umbilical cord occlusion (UCO) is known to cause neurological disorders in the neonate. Previously, we have reported that hypoxic hypoxia (HH) stimulates the appearance of bacteria in the fetal brain and upregulates the expression of inflammatory markers in fetal cerebral cortex (CTX) and also that ketamine attenuates these responses. In the present study, we aimed to test the hypothesis that UCO, similar to HH, produces an inflammatory response in the fetal CTX and also that treatment with ketamine reduces these effects. In chronically instrumented fetal sheep (∼125 days), 30 min of partial UCO decreased fetal PaO2 levels by ∼50%. Half of the fetuses received ketamine (3 mg kg-1 ) 10 min prior to UCO (n = 4 per group). Fetal brains were collected 1 and 24 h after the experiment and mRNA was extracted and hybridized for microarray analyses. Differentially-expressed genes were analysed for significant association with gene ontologies and pathways. After 1 h, UCO upregulated nucleic acid processing and chromatin modification and downregulated metabolic processes compared to control. After 24 h, UCO upregulated metabolic and protein modification processes. Ketamine produced minimal effects. UCO did not alter the abundance of bacterial DNA in fetal brain, nor did it upregulate inflammation pathways compared to HH. We conclude that UCO produced time-dependent responses that did not include bacterial invasion or upregulation of inflammation pathways in fetal CTX. This contrasts with the response to HH, which resulted in the appearance of bacteria in the CTX and upregulated inflammation pathways. These responses in fetal CTX to oxygen deprivation are therefore modified by the maternal or placental response to the stimulus.

Recipient Twin Circular Shunt Physiology Before Fetal Laser Surgery: Survival and Risks for Postnatal Right Ventricular Outflow Tract Obstruction.

OBJECTIVES: To evaluate risk for congenital heart disease (CHD) in recipient twins with circular shunt physiology (CSP). METHODS: This prospective study enrolled twin-twin transfusion syndrome (TTTS) cases from 2006 to 2015. Fetal echocardiography (FE) was performed before laser surgery when cardiac involvement was suspected. Diagnosis of recipient twin CSP required tricuspid and pulmonary regurgitation, right ventricular dysfunction, and flow reversal in the ductus arteriosus. Outcomes were assessed at 30 days after birth. RESULTS: Of the 496 TTTS pregnancies, 20 (4%) met the criteria for CSP. Among those born alive, who had documented cardiac outcomes (n = 457), patients with CSP were more likely to have CHD, specifically right ventricular outflow tract obstruction (5 of 18 [27.8%] versus 22 of 439 [5.0%], odd ratio [OR] 7.29, 95% confidence interval [CI] 2.05-24.72, P = .0025). Of the recipient twins with preoperative FE (n = 259, 52%) who were born alive and had documented cardiac outcomes (n = 242), those with CSP were still more likely to have right ventricular outflow tract obstruction (5 of 18 [27.8%] versus 14 of 224 [6.3%], OR 5.77, CI 1.54-20.92, P = .0077). With both analyses, twins with CSP had higher Quintero stage, but similar patient characteristics and 30-day mortality compared with those without CSP. Subgroup analyses of the CSP cohort identified no differences in preoperative characteristics or FE findings predictive of CHD. CONCLUSIONS: Recipient twins with preoperative CSP were at increased risk for postnatal right ventricular outflow tract obstruction, but appeared to have comparable survival after fetal laser surgery despite these dramatic pathophysiological prenatal findings. Preoperative FE in TTTS remains important for prediction of postnatal CHD.

Ductus venosus Doppler in the assessment of fetal cardiovascular health: an updated practical approach.

The ductus venosus has a central role in the distribution of highly oxygenated umbilical venous blood to the heart. Its waveform is related to the pressure-volume changes in the cardiac atria and it is therefore important in the monitoring of any fetal condition that may affect forward cardiac function. The cardiovascular parameters that can influence forward cardiac function include afterload, myocardial performance and preload. Decreased forward flow during atrial systole (a-wave) is the most sensitive and ubiquitous finding when any of these parameters is affected. In contrast, decreased forward velocities during end-systolic relaxation (v-wave) are more specifically related to myocardial performance. The ductus venosus pulsatility index alone does not accurately reflect cardiac function, and in cases of suspected fetal cardiac dysfunction, echocardiography is required to identify the underlying mechanism. The role of ductus venosus Doppler in the assessment of fetal growth restriction, supraventricular tachycardia, fetal hydrops, complicated monochorionic twins and congenital heart disease is discussed with these considerations in mind.

Blood pressure evaluation in children treated with laser surgery for twin-twin transfusion syndrome at 2-year follow-up.

OBJECTIVE: Twin survivors of twin-twin transfusion syndrome (TTTS) may be at risk for early onset of cardiovascular disease. The aim of this study was to determine prevalence and risk factors for elevated blood pressure (BP) among children treated with selective laser photocoagulation of communicating vessels. STUDY DESIGN: Data were prospectively collected from surviving children treated for TTTS with laser surgery from 2008 through 2010. Systolic BP (SBP) and diastolic BP (DBP) were obtained from 91 child survivors at age 24 months (±6 weeks) and evaluated based on age, sex, and height percentile. BP percentiles were calculated for each patient and categorized as normal (<95%) or abnormal (>95%). Clinical variables were evaluated using multilevel regression models to evaluate risk factors for elevated BP. RESULTS: BP was categorized as normal in 38% and abnormal in 62% of twin survivors based on percentile for sex, age, and height; a comparable distribution was found for DBP elevation. There were no differences between donor and recipient twins for absolute SBP and DBP or BP classification. In a multivariate analysis, significant risk factors for higher SBP included prematurity (ß -0.54; 95% confidence interval [CI], -0.99 to -0.09; P = .02), higher weight percentile (ß 0.24; 95% CI, 0.05-0.42; P = .01), and presence of cardiac disease (ß 0.50; 95% CI, 0.10-0.89; P = .01). Prematurity was also a significant risk for abnormal DBP (odds ratio, 0.89; 95% CI, 0.80-1.00; P = .05). CONCLUSION: Child survivors of TTTS had elevated SBP and DBP measurements at 2 years of age, with no differences seen between former donor and recipient twins. Prematurity may be a risk factor for elevated BP measurements in this population. Future studies are warranted to ascertain whether these cardiovascular findings persist over time.

The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound.

BACKGROUND: There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. METHODS: Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20. RESULTS: HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼ 60% reduction) 2 hours after dosing with recovery after 24 h of >60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while >90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with >85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects. CONCLUSIONS: Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human.

Ketamine affects the neurogenesis of rat fetal neural stem progenitor cells via the PI3K/Akt-p27 signaling pathway.

Ketamine is widely used as an anesthetic, analgesic, or sedative in pediatric patients. We reported that ketamine alters the normal neurogenesis of rat fetal neural stem progenitor cells (NSPCs) in the developing brain, but the underlying mechanisms remain unknown. The PI3K-PKB/Akt (phosphatidylinositide 3-kinase/protein kinase B) signaling pathway plays many important roles in cell survival, apoptosis, and proliferation. We hypothesized that PI3K-PKB/Akt signaling may be involved in ketamine-altered neurogenesis of cultured NSPCs in vitro. NSPCs were isolated from Sprague-Dawley rat fetuses on gestational day 17. 5-bromo-2'-deoxyuridine (BrdU) incorporation, Ki67 staining, and differentiation tests were utilized to identify primary cultured NSPCs. Immunofluorescent staining was used to detect Akt expression, whereas Western blots measured phosphorylated Akt and p27 expression in NSPCs exposed to different treatments. We report that cultured NSPCs had properties of neurogenesis: proliferation and neural differentiation. PKB/Akt was expressed in cultured rat fetal cortical NSPCs. Ketamine inhibited the phosphorylation of Akt and further enhanced p27 expression in cultured NSPCs. All ketamine-induced PI3K/Akt signaling changes could be recovered by N-methyl-d-aspartate (NMDA) receptor agonist, NMDA. These data suggest that the inhibition of PI3K/Akt-p27 signaling may be involved in ketamine-induced neurotoxicity in the developing brain, whereas excitatory NMDA receptor activation may reverse these effects.

Transferring an extremely premature infant to an extra-uterine life support system: a prospective view on the obstetric procedure.

To improve care for extremely premature infants, the development of an extrauterine environment for newborn development is being researched, known as Artificial Placenta and Artificial Womb (APAW) technology. APAW facilitates extended development in a liquid-filled incubator with oxygen and nutrient supply through an oxygenator connected to the umbilical vessels. This setup is intended to provide the optimal environment for further development, allowing further lung maturation by delaying gas exposure to oxygen. This innovative treatment necessitates interventions in obstetric procedures to transfer an infant from the native to an artificial womb, while preventing fetal-to-neonatal transition. In this narrative review we analyze relevant fetal physiology literature, provide an overview of insights from APAW studies, and identify considerations for the obstetric procedure from the native uterus to an APAW system. Lastly, this review provides suggestions to improve sterility, fetal and maternal well-being, and the prevention of neonatal transition.

The effect on rat embryonic heart rate of Na+, K+, and Ca2+ channel blockers, and the human teratogen phenytoin, changes with gestational age.

In this study, we compared the effects of four ion channel blockers on rat embryonic heart function during the organogenic period from gestational day (GD) 10 to 15, to determine the changes in dependence on ion channels during rat cardiac development. Rat embryos in culture were exposed to either the human ether-á-go-go-related gene potassium channel blocker, dofetilide (400 nM); the sodium channel blocker, lidocaine (250 µM); the L-type calcium channel blocker, nifedipine (1.8 µM); or the multichannel blocker, phenytoin (200 µM). Lidocaine slowed the heart rate (HR) with the effect becoming more severe with increasing GD. Dofetilide slowed the embryonic HR and caused arrhythmias with the most severe effect on GD 11 to 13. Nifedipine primarily caused a negative inotropic effect except on GD 10 when it stopped the heart in most embryos. Phenytoin stopped the heart of most GD 10 to 12 embryos while on GD 13 to 15 phenytoin slowed the heart. The results demonstrate that as the rat heart develops during the organogenic period its functional dependence on ion channels changes markedly. These changes are important for understanding drug effects on the embryo during pregnancy and the methodology used provides a simple procedure for assessing drug effects on the developing heart.

Continuous monitoring of fetal gross movement and maternal glucose level using newly developed methods.

BACKGROUND: There is no consensus on the relationship between maternal glucose levels and fetal movements. OBJECTIVE: This study aimed to investigate the correlation between gross fetal movements and maternal glucose levels in the hours around food intake. STUDY DESIGN: This was an observational study with 2 newly developed technologies, which were a glucose monitoring system and a fetal movement acceleration measurement recorder. A total of 15 women with singleton pregnancies were provided with the glucose monitoring system that automatically recorded their glucose levels every 15 minutes. In addition, fetal movements were recorded using the fetal movement acceleration measurement recorder, for 4 hours starting from 1 hour before lunch, once a week beginning at 28 weeks of gestation. For the four 1-hour periods, the ratios of the number of 10-second epochs with fetal movement divided by the total number of epochs (defined as the fetal movement parameter) were compared at the earlier (28-33 weeks of gestation), later (34-39 weeks of gestation), and overall (28-39 weeks of gestation) gestational weeks using analysis of variance analyses. A linear regression analysis was developed between the glucose level and the movement parameter for the earlier, later, and overall gestational weeks. All data were divided into 4 categories: (1) both the glucose level and the fetal movement parameter increased from the previous 15 minutes; (2) the glucose level increased, but the fetal movement parameter did not increase; (3) the glucose level did not increase, but the fetal movement parameter increased; and (4) both glucose level and fetal movement parameter did not increase. The numbers for each category were compared for the earlier, later, and overall gestational weeks using χ2 analyses. RESULTS: There was no significant change in the fetal movement parameter among the four 1-hour periods at the earlier (P=.509), later (P=.884), and overall (P=.816) gestational weeks. There was a positive correlation between the glucose level and the movement parameter at 28 to 33 weeks of gestation (P=.001), but not at 33 to 39 (P=.129) and 28 to 39 (P=.115) weeks of gestation. Compared with fetuses whose mothers did not have increased glucose levels, fetuses whose mothers had increased glucose levels moved more at 28 to 33 weeks of gestation (P=.031), but not at 34 to 39 (P=.398) and 28 to 39 (P=.238) weeks of gestation. CONCLUSION: Having a meal did not change gross fetal movement counting; however, there are positive correlations between maternal glucose level and gross fetal movement at 28 to 33 weeks of gestation, but not at 34 to 39 weeks of gestation, for both glucose values and value changes under natural conditions of the mother and fetus.

Noninvasive imaging of ethanol-induced developmental defects in zebrafish embryos using optical coherence tomography.

In this article, we report the use of optical coherence tomography for noninvasive cross-sectional real-time imaging of ethanol-induced developmental defects in zebrafish embryos larvae. For ethanol concentration of over 300 mM, developmental defects of eye (shrinkage and retinal abnormalities), malformation of the notochord and ataxia arising due to the toxic effects of ethanol were observed in OCT images from 3 days post fertilization onwards. The results suggest that OCT could be a valuable tool for noninvasive assessment of birth defects in small animal systems.

Is It Time to Redefine Fetal Decelerations in Cardiotocography?

Historically, fetal heart rate (FHR) decelerations were classified into "early", "late", and "variable" based on their relationship with uterine contractions. So far, three different putative etiologies were taken for granted. Recently, this belief, passed down through generations of birth attendants, has been questioned by physiologists. This narrative review aimed to assess the evidence on pathophysiology behind intrapartum FHR decelerations. This narrative review is based on information sourced from online peer-reviewed articles databases and recommendations from the major scientific societies in the field of obstetrics. Searches were performed in MEDLINE/PubMed, EMBASE, and Scopus and selection criteria included studies in animals and humans, where the physiology behind FHR decelerations was explored. The greater affinity for oxygen of fetal hemoglobin than the maternal, the unicity of fetal circulation, and the high anaerobic reserve of the myocardium, ensure adequate oxygenation to the fetus, under basal conditions. During acute hypoxic stress the efficiency of these mechanisms are increased because of the peripheral chemoreflex. This reflex, activated at each uterine contraction, is characterized by the simultaneous activation of two neural arms: the parasympathetic arm, which reduces the myocardial consumption of oxygen by decreasing the FHR and the sympathetic component, which promotes an intense peripheric vasoconstriction, thus centralizing the fetal blood volume. This review summarizes the evidence supporting the hypoxic origin of FHR decelerations, therefore archiving the historical belief that FHR decelerations have different etiologies, according to their shape and relationship with uterine contractions. The present review suggests that it is time to welcome the new scientific evidence and to update the CTG classification systems.