Is the fetus fit for labor? Introducing fast-and-frugal trees (FFTrees) to simplify triage of women for STAN monitoring: An interobserver agreement comparison with traditional classification.

INTRODUCTION: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable "yes" or "no" responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. MATERIAL AND METHODS: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss' kappa (κ). RESULTS: The proportions of agreement for "not suitable for STAN" were for FIGO 47% (95% confidence interval [CI] 42%-52%) and for FFTree 60% (95% CI 56-64), ie a significant difference; the corresponding figures for "yes, suitable" were 74% (95% CI 71-77) and 70% (95% CI 67-74). For "intervention needed" the figures were 52% (95% CI 47-56) vs 58% (95% CI 54-62) and for "expectant management" 74% (95% CI 71-77) vs 72% (95% CI 69-75). Fleiss' κ agreement on "suitability for STAN" was 0.50 (95% CI 0.44-0.56) for the FIGO classification and 0.57 (95% CI 0.51-0.63) for the FFTree classification; the corresponding figures for "intervention or expectancy" were 0.53 (95% CI 0.47-0.59) and 0.57 (95% CI 0.51-0.63). CONCLUSIONS: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.

Umbilical cord pH, blood gases, and lactate at birth: normal values, interpretation, and clinical utility.

Normal birth is a eustress reaction, a beneficial hedonic stress with extremely high catecholamines that protects us from intrauterine hypoxia and assists in the rapid shift to extrauterine life. Occasionally the cellular O2 requirement becomes critical and an O2 deficit in blood (hypoxemia) may evolve to a tissue deficit (hypoxia) and finally a risk of organ damage (asphyxia). An increase in H+ concentration is reflected in a decrease in pH, which together with increased base deficit is a proxy for the level of fetal O2 deficit. Base deficit (or its negative value, base excess) was introduced to reflect the metabolic component of a low pH and to distinguish from the respiratory cause of a low pH, which is a high CO2 concentration. Base deficit is a theoretical estimate and not a measured parameter, calculated by the blood gas analyzer from values of pH, the partial pressure of CO2, and hemoglobin. Different brands of analyzers use different calculation equations, and base deficit values can thus differ by multiples. This could influence the diagnosis of metabolic acidosis, which is commonly defined as a pH <7.00 combined with a base deficit ≥12.0 mmol/L in umbilical cord arterial blood. Base deficit can be calculated as base deficit in blood (or actual base deficit) or base deficit in extracellular fluid (or standard base deficit). The extracellular fluid compartment represents the blood volume diluted with the interstitial fluid. Base deficit in extracellular fluid is advocated for fetal blood because a high partial pressure of CO2 (hypercapnia) is common in newborns without concomitant hypoxia, and hypercapnia has a strong influence on the pH value, then termed respiratory acidosis. An increase in partial pressure of CO2 causes less increase in base deficit in extracellular fluid than in base deficit in blood, thus base deficit in extracellular fluid better represents the metabolic component of acidosis. The different types of base deficit for defining metabolic acidosis in cord blood have unfortunately not been noticed by many obstetrical experts and organizations. In addition to an increase in H+ concentration, the lactate production is accelerated during hypoxia and anaerobic metabolism. There is no global consensus on definitions of normal cord blood gases and lactate, and different cutoff values for abnormality are used. At a pH <7.20, 7% to 9% of newborns are deemed academic; at <7.10, 1% to 3%; and at <7.00, 0.26% to 1.3%. From numerous studies of different eras and sizes, it can firmly be concluded that in the cord artery, the statistically defined lower pH limit (mean -2 standard deviations) is 7.10. Given that the pH for optimal enzyme activity differs between different cell types and organs, it seems difficult to establish a general biologically critical pH limit. The blood gases and lactate in cord blood change with the progression of pregnancy toward a mixed metabolic and respiratory acidemia because of increased metabolism and CO2 production in the growing fetus. Gestational age-adjusted normal reference values have accordingly been published for pH and lactate, and they associate with Apgar score slightly better than stationary cutoffs, but they are not widely used in clinical practice. On the basis of good-quality data, it is reasonable to set a cord artery lactate cutoff (mean +2 standard deviations) at 10 mmol/L at 39 to 40 weeks' gestation. For base deficit, it is not possible to establish statistically defined reference values because base deficit is calculated with different equations, and there is no consensus on which to use. Arterial cord blood represents the fetus better than venous blood, and samples from both vessels are needed to validate the arterial origin. A venoarterial pH gradient of <0.02 is commonly used to differentiate arterial from venous samples. Reference values for pH in cord venous blood have been determined, but venous blood comes from the placenta after clearance of a surplus of arterial CO2, and base deficit in venous blood then overestimates the metabolic component of fetal acidosis. The ambition to increase neonatal hemoglobin and iron depots by delaying cord clamping after birth results in falsely acidic blood gas and lactate values if the blood sampling is also delayed. Within seconds after birth, sour metabolites accumulated in peripheral tissues and organs will flood into the central circulation and further to the cord arteries when the newborn starts to breathe, move, and cry. This influence of "hidden acidosis" can be avoided by needle puncture of unclamped cord vessels and blood collection immediately after birth. Because of a continuing anaerobic glycolysis in the collected blood, it should be analyzed within 5 minutes to not result in a falsely high lactate value. If the syringe is placed in ice slurry, the time limit is 20 minutes. For pH, it is reasonable to wait no longer than 15 minutes if not in ice. Routine analyses of cord blood gases enable perinatal audits to gain the wisdom of hindsight, to maintain quality assurance at a maternity unit over years by following the rate of neonatal acidosis, to compare results between hospitals on regional or national bases, and to obtain an objective outcome measure in clinical research. Given that the intrapartum cardiotocogram is an uncertain proxy for fetal hypoxia, and there is no strong correlation between pathologic cardiotocograms and fetal acidosis, a cord artery pH may help rather than hurt a staff person subjected to a malpractice suit based on undesirable cardiotocogram patterns. Contrary to common beliefs and assumptions, up to 90% of cases of cerebral palsy do not originate from intrapartum events. Future research will elucidate whether cell injury markers with point-of-care analysis will become valuable in improving the dating of perinatal injuries and differentiating hypoxic from nonhypoxic injuries.

Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis.

BACKGROUND: Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin. OBJECTIVE: To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment. METHODS: Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO2), and photoplethysmographic digital pulse wave analysis variables were recorded before and at 1, 5, 20, and 60 min after drug administration. Vasopressor use, uterine tonus, total bleeding, and need for additional uterotonics were also assessed. Repeated measurement ANOVA was used for statistical analyses. RESULTS: The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO2, or subjective cardiac symptoms. Uterine tonus, need for additional uterotonics, or total bleeding did not differ significantly between the groups. CONCLUSION: Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Time to reconsider: Have the 2015 FIGO and 2017 Swedish intrapartum cardiotocogram classifications led us from Charybdis to Scylla?

In 2015, FIGO revised the 1987 intrapartum cardiotocography (CTG) classification (FIGO1987). A less radical FIGO2015 version was introduced in Sweden 2017 (SWE2017). Now, post hoc simulation studies show that FIGO2015 and SWE2017 are less reliable than (a modified) FIGO1987. FIGO2015 shows significantly better interobserver agreement for normal CTG traces than FIGO1987, but significantly worse for pathological traces. Agreements between templates are moderate to good, but different classifications of mainly variable decelerations and tachycardia cause significant heterogeneities. FIGO2015 shows insufficient sensitivity to identify fetal acidemia compared with FIGO1987. In connection with fetal electrocardiogram ST analysis, one study showed no template was superior in identifying fetal acidemia, but in a series of only academia, FIGO1987 had significantly higher sensitivity than FIGO2015 (73% vs. 43%) and set of an alarm for fetal acidemia considerably earlier. With SWE2017, operative interventions declined significantly in Sweden but several adverse neonatal outcomes increased significantly. It remains to investigate the development with FIGO2015.

NK cells integrate signals over large areas when building immune synapses but require local stimuli for degranulation.

Immune synapses are large-scale, transient molecular assemblies that serve as platforms for antigen presentation to B and T cells and for target recognition by cytotoxic T cells and natural killer (NK) cells. The formation of an immune synapse is a tightly regulated, stepwise process in which the cytoskeleton, cell surface receptors, and intracellular signaling proteins rearrange into supramolecular activation clusters (SMACs). We generated artificial immune synapses (AIS) consisting of synthetic and natural ligands for the NK cell-activating receptors LFA-1 and CD16 by microcontact printing the ligands into circular-shaped SMAC structures. Live-cell imaging and analysis of fixed human NK cells in this reductionist system showed that the spatial distribution of activating ligands influenced the formation, stability, and outcome of NK cell synapses. Whereas engagement of LFA-1 alone promoted synapse initiation, combined engagement of LFA-1 and CD16 was required for the formation of mature synapses and degranulation. Organizing LFA-1 and CD16 ligands into donut-shaped AIS resulted in fewer long-lasting, symmetrical synapses compared to dot-shaped AIS. NK cells spreading evenly over either AIS shape exhibited similar arrangements of the lytic machinery. However, degranulation only occurred in regions containing ligands that therefore induced local signaling, suggesting the existence of a late checkpoint for degranulation. Our results demonstrate that the spatial organization of ligands in the synapse can affect its outcome, which could be exploited by target cells as an escape mechanism.

Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5 years.

AIM: It is not clear whether perinatal acidosis can predict poor outcomes in extremely preterm infants and we investigated associations between intrapartum hypoxia and mortality and neurodevelopmental outcomes. METHODS: We used nationwide data on 705 infants from the Extremely Preterm Infants in Sweden Study, delivered at 22-26 weeks of gestation during 2004-2007. Comprehensive neurodevelopmental assessments were performed on survivors at 2.5 (n = 456) and 6.5 (n = 441) years of corrected age. Gestational age-related changes in umbilical cord arterial pH were compared with reference values for term newborn infants, and base excess was also calculated. Associations between low blood gas values (<10th percentile) and mortality and neurodevelopmental outcome were estimated. RESULTS: Cord blood determination was more common in surviving infants (P < .001), with pH determined in 322/705 (46%) and base excess in 311/705 (44%). Extremely preterm infants had higher pH values than term infants (P < .0001), with no change from 22 to 26 weeks of gestation (P = .61, r2  = .001). Multiple logistic regression showed no association between low blood gas values and risk of death or neurodevelopmental impairment at 6.5 years (P ≥ .17). CONCLUSION: Hypoxia with acidosis at birth was not associated with an increased risk of death or impaired neurodevelopmental in extremely preterm born children at 6.5 years.

Identifying newborns with umbilical cord blood metabolic acidosis by intrapartum cardiotography combined with fetal ECG ST analysis (STAN): comparison of the new and old FIGO systems to classify cardiotocograms.

Introduction: The intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) was introduced to simplify CTG interpretation, but it is not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007), which is based on the FIGO CTG system from 1987. The study aimed to determine time courses and sensitivity between the systems in classifying CTG + ST events to indicate metabolic acidosis at birth.Material and methods: Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. CTG patterns and timing of the first occurring significant ST events were evaluated post hoc in consensus by an expert panel and sensitivity statistics were performed. Wilcoxon's matched-pairs signed-ranks test and McNemar's test were used with a two-tailed p < .05 regarded significant.Results: STAN2007 had a higher sensitivity (73 versus 43%, p = .0002) and alarmed for metabolic acidosis in mean 34 min earlier than the FIGO2015 system did (p = .002). In every fourth case, the time difference was ≥20 min.Conclusions: In this simulation study, surveillance with STAN2007 combined with fetal ECG ST analysis had a significantly higher sensitivity and would have alarmed for metabolic acidosis significantly earlier than the new FIGO system would have.

A collagen-based microwell migration assay to study NK-target cell interactions.

Natural killer (NK) cell cytotoxicity in tissue is dependent on the ability of NK cells to migrate through the extracellular matrix (ECM) microenvironment. Traditional imaging studies of NK cell migration and cytotoxicity have utilized 2D surfaces, which do not properly reproduce the structural and mechanical cues that shape the migratory response of NK cells in vivo. Here, we have combined a microwell assay that allows long-term imaging and tracking of small, well-defined populations of NK cells with an interstitial ECM-like matrix. The assay allows for long-term imaging of NK-target cell interactions within a confined 3D volume. We found marked differences in motility between individual cells with a small fraction of the cells moving slowly and being confined to a small volume within the matrix, while other cells moved more freely. A majority of NK cells also exhibited transient variation in their motility, alternating between periods of migration arrest and movement. The assay could be used as a complement to in vivo imaging to study human NK cell heterogeneity in migration and cytotoxicity.

Gestational age-related reference values for Apgar score and umbilical cord arterial and venous pH in preterm and term newborns.

INTRODUCTION: Despite much literature on reference values of acid-base status in umbilical cord blood at birth, there are as yet no studies performed to determine gestational age-dependent references in cord venous blood and no studies on preterm acid-base standards. Similarly, the normal reference range of Apgar scores for term and preterm infants has not yet been determined. MATERIAL AND METHODS: Data were obtained from the maternity units of Skåne University Hospital, Malmö and Lund, Sweden, from 2001 to 2010. Validated paired arterial and venous cord pH values were obtained from 27 175 newborns, of whom 18 584 had spontaneous, non-instrumental vaginal deliveries and a 5-minute Apgar score equal to or greater than the median value for the individual gestational week. Simple linear and polynomial regression analyses were performed. Values were reported as mean ± standard deviation and median with 2.5th and 97.5th percentiles. RESULTS: Median 5-minute Apgar score was 7 for gestations shorter than 28 weeks, 8 for 28 weeks, 9 for 29-30 weeks, and 10 from 31 weeks onwards. A linear decline in pH for both cord arterial and venous blood was seen with advancing gestational age (P < 0.001). CONCLUSIONS: Median 5-minute Apgar scores were <10 before 31 weeks of gestation. Both umbilical cord arterial and venous pH decreased linearly with increasing gestational age. Further studies are needed to show whether gestational age-related pH reference ranges might be preferred to fixed cut-offs in the estimation of umbilical cord acidemia at birth.

Arterial stiffness in normal pregnancy as assessed by digital pulse wave analysis by photoplethysmography - A longitudinal study.

INTRODUCTION: It might in the future be valuable to screen for increased maternal arterial stiffness, i.e. low compliance, since it is associated with development of hypertensive complications in pregnancy. Digital pulse wave analysis (DPA) is an easy and manageable method for arterial stiffness assessment. We aimed to investigate gestational influence on DPA variables longitudinally, and establish gestational age-adjusted reference values in normal pregnancy. METHODS: DPA measurements were performed longitudinally up to five times during pregnancy in 139 healthy women. Reference curves for DPA variables aging index (AI), b/a and d/a relative to gestational age were calculated with linear and polynomial mixed-effects models, and the influences of age and parity investigated with analysis of variance and analysis of covariance. A p < 0.05 was regarded significant. RESULTS: All DPA variables were significantly associated with GA with best fit for a quadratic model. Arterial compliance peaked in the late second trimester. Age and parity independently influenced DPA variables but did not change the associations with gestational age. CONCLUSIONS: DPA reflects longitudinal changes in arterial compliance in normal pregnancy but individual variance of DPA changes were greater than the influence of GA. Normal distributions of AI, b/a and d/a at 14-24 weeks are presented, but it remains to show whether these can be used to detect pathological hemodynamic alterations in pregnancy.

Arterio-venous blood gas Δvalues for validation of umbilical cord blood samples at birth are not only biased by sample mix ups but also affected by clinical factors.

INTRODUCTION: Traditional validation of umbilical cord blood samples with positive veno-arterial ΔpH and arterio-venous ΔpCO2 values confirms the source of samples, whereas negative Δvalues represent mix-up of samples. To investigate whether this is true, the distributions of V-A ΔpO2 and A-V Δlactate were also explored and related to clinical characteristics. In addition, different cord blood sampling techniques were evaluated. MATERIAL AND METHODS: Register study with cord blood acid-base and clinical data from 27 233 newborns. Clinical characteristics were related to positive, zero and negative Δvalues. Blood samplings from unclamped and double-clamped cords were compared. A two-sided P < 0.05 was considered significant. RESULTS: ΔpH and ΔpCO2 values distributed into positive, around zero, and negative sub-populations, with significant differences in pH and clinical characteristics between sub-populations. No such sub-populations were distinguished for ΔpO2 and Δlactate. The 2.5th and 5th ΔpH percentiles were 0.013 and 0.022, respectively, and for ΔpCO2 0.30 and 0.53 kPa. Applying 5th percentile criteria resulted in 3.5% of "approved" cases showing a ΔpO2  ≤ 0. Puncture and sampling of the unclamped cord resulted in significantly better sample quality. CONCLUSIONS: Unphysiological negative ΔpO2 values occurred despite correct validation with traditional criteria. Δlactate cannot be used for validation because both positive and negative values are physiological. Positive/around zero/negative ΔpH and ΔpCO2 sub-populations were associated with significant differences in pH and clinical characteristics, indicating that defective sampling and sample handling are not the sole explanations for negative Δvalues. Prompt puncture and sampling of the unclamped cord resulted in best sample quality.

Effects of oxytocin and anaesthesia on vascular tone in pregnant women: a randomised double-blind placebo-controlled study using non-invasive pulse wave analysis.

BACKGROUND: Oxytocin is an uterotonic drug with profound cardiovascular effects, which in compromised patients could lead to serious events. The objective was to investigate whether oxytocin affects cardiac function and vascular tone in large and small arteries. We hypothesized that oxytocin decreases arterial vascular tone and elevates cardiac output. METHODS: 51 pregnant women were randomised to treatment with 8.3 µg (5 U) oxytocin or placebo injection during first trimester surgical evacuation of the gravid uterus under general anaesthesia. Oxytocin or placebo was administered once either early or late in the procedure, in a double-blind fashion. Digital photoplethysmography pulse wave analysis variables, heart rate, mean arterial blood pressure and electrocardiographic ST index were recorded before and after anaesthesia and after each injection. Non-parametric statistics were used with a two-sided P value < 0.05 considered significant. RESULTS: Anaesthesia induced a significant fall in blood pressure, heart rate and vascular tone in small and peripheral arteries. Oxytocin had a vasodilatory effect on small and peripheral arteries and increased the left cardiac ventricular ejection time. The ST index decreased. CONCLUSIONS: Pulse wave analysis indicated peripheral vasodilation and increased cardiac output after oxytocin, implying increased myocardial oxygen demand. These effects might have been enhanced by the vasodilating effects of anaesthesia. Previous studies have demonstrated myocardial ischaemia after oxytocin, as reflected by a decrease in ST index in the present study. TRIAL REGISTRATION: Trial registration number ISRCTN17860978 , 2018/03/14, Retrospectively registered.

Arterial stiffness during controlled ovarian hyperstimulation and early pregnancy in women exposed to assisted reproduction.

INTRODUCTION: Female sex hormones have vasorelaxing effects in non-pregnant and pregnant women. We aimed to investigate the effect of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF), and early pregnancy, on arterial stiffness as assessed by digital pulse wave analysis (DPA), hypothesizing reduced arterial stiffness as an effect of increased estrogen levels. MATERIAL AND METHODS: A total of 68 women undergoing IVF were examined with DPA before conception and during IVF treatment with COH and embryo transfer (ET), and in gestational week seven in 19 women who became pregnant. Heart rate (HR), mean arterial pressure (MAP) and the DPA variables cardiac ejection elasticity index (EEI), b/a, dicrotic index (DI), d/a and aging index (AI) were measured. RESULTS: HR was significantly increased at all measuring points (p ≤ 0.003) but MAP only at ET (p 0.007). DPA variables representing large arteries (EEI, b/a) and peripheral arteries (DI, but not d/a), and the global variable AI, indicated increased arterial stiffness at ET compared with baseline (p ≤ 0.035). No DPA variable was significantly changed at pregnancy measurements compared to baseline. CONCLUSION: During COH for IVF treatment, DPA showed no changes in arterial stiffness during the follicular phase or in early pregnancy, but increased arterial stiffness in central and peripheral arteries in the early luteal phase. The result suggests a hormonal hemodynamic activation counteracting the effects of estrogen.

Assessment of lactate production as a response to sustained intrapartum hypoxia in large-for-gestational-age newborns.

INTRODUCTION: Lactate concentration in umbilical cord blood is an important measure of intrapartum anaerobic metabolism. The aim of the study was to compare lactate production of large-for-gestational-age (LGA) fetuses against appropriate-for-gestational-age (AGA) fetuses during hypoxia, in diabetic and non-diabetic mothers. MATERIAL AND METHODS: A total of 17 358 validated paired arterial and venous umbilical cord blood samples taken at birth with a full panel of pH, glucose, and lactate were analyzed relative to LGA (n = 2789) and AGA (n = 14 569). Umbilical cord blood acidemia (pH < mean minus 2 SD) was identified in 518 cases. RESULTS: Diabetes, but not acidemia, was more common among LGA (5.4%) than AGA cases (2.9%) (respectively P < .0001 and P < .69). At normal pH, glucose was lower in non-diabetes LGA cases, but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .067). Glucose levels were higher in all groups during acidemia (P ≤ .0005), with lower values in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P = .005 and P < .58). At normal pH, lactate was lower in non-diabetes LGA but not in diabetes LGA compared with corresponding AGA cases (respectively P < .0001 and P < .98); during acidemia, lactate levels were higher in all groups (P < .0001), resulting in no significant difference between LGA and AGA in diabetes as well as in non-diabetes cases (respectively P = .29 and P < .084). CONCLUSIONS: Considering cord acidemia a proxy for intrapartum hypoxia, LGA fetuses showed no impaired ability to produce lactate during hypoxia. Maternal diabetes did not hamper the ability of LGA fetuses to produce lactate during hypoxia.

The small-for-gestational-age fetus has an intact ability to develop lacticemia when exposed to hypoxia: a retrospective comparative register study.

OBJECTIVE: To investigate the ability of small-for-gestational-age (SGA) fetuses to develop lacticemia during hypoxia. METHODS: Umbilical cord arterial and venous pH, lactate and glucose concentrations were determined in 1777 SGA (<10th percentile) and 14,569 AGA newborns and related to acidemia (pH < mean -2SD). Non-parametric statistics with two-sided p < .05 were considered significant. RESULTS: Glucose and lactate were linearly related and both variables correlated negatively with pH. Glucose was equal in SGA and AGA at a normal pH, but at severe acidemia it was lower in SGA. Glucose was higher in both groups during acidemia. Lactate was higher in SGA at both a normal and a low pH, and in both groups lactate increased progressively with the severity of acidemia. CONCLUSIONS: In both SGA and AGA fetuses, glucose was mobilized during acidemia; lactate was higher in SGA at both a normal and low pH. Considering SGA being a proxy for fetal growth restriction, and acidemia a proxy for hypoxia, it is concluded that growth-restricted fetuses have an intact ability to develop lacticemia during hypoxia.

Fetal and maternal temperatures during labor and delivery: a prospective descriptive study.

OBJECTIVE: The objective of this study is to study the fetal scalp temperature (FST) and maternal axillary temperature (MAT) during vaginal delivery relative to progression of labor, uterine contractions (UC) and epidural analgesia (EDA), and to construct normal temperature reference ranges related to stage of labor. MATERIAL AND METHODS: Temperatures were recorded continuously in labor of 132 women with a bi-metal temperature sensor attached to the axilla (MAT) and a similar sensor mounted in a scalp electrode (FST). The temperature data were stored electronically and analyzed offline at cervical dilatations of 2-3, 5, 7-8, and 10 cm, and at full retraction. The FST was read before, at increasing, at peak, at decreasing, and after UC. The MAT and FST curves were compared with mixed-effect models statistics for repeated measurements. A two-tailed p <.05 was considered significant. RESULTS: The FST did not vary during UC (p = .24). Both FST and MAT increased linearly by progression of labor (both p < .001). The increases in temperatures were greater with EDA than without (p < .001). CONCLUSIONS: During UC, the FST showed no alteration. Both FST and MAT increased significantly by progression of labor, and significantly more in the presence of EDA. The presented normal temperature reference ranges can be used for future research.

New FIGO and Swedish intrapartum cardiotocography classification systems incorporated in the fetal ECG ST analysis (STAN) interpretation algorithm: agreements and discrepancies in cardiotocography classification and evaluation of significant ST events.

INTRODUCTION: The updated intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) and the FIGO2015-approached classification by the Swedish Society of Obstetricians and Gynecologist in 2017 (SSOG2017) are not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007). The study aimed to reveal homogeneity and agreement between the systems in classifying CTG and ST events, and relate them to maternal and perinatal outcomes. MATERIAL AND METHODS: Among CTG traces with ST events, 100 traces originally classified as normal, 100 as suspicious and 100 as pathological were randomly selected from a STAN database and classified by two experts in consensus. Homogeneity and agreement statistics between the CTG classifications were performed. Maternal and perinatal outcomes were evaluated in cases with clinically hidden ST data (n = 151). A two-tailed p < 0.05 was regarded as significant. RESULTS: For CTG classes, the heterogeneity was significant between the old and new systems, and agreements were moderate to strong (proportion of agreement, kappa index 0.70-0.86). Between the new classifications, heterogeneity was significant and agreements strong (0.90, 0.92). For significant ST events, heterogeneities were significant and agreements moderate to almost perfect (STAN2007 vs. FIGO2015 0.86, 0.72; STAN2007 vs. SSOG2017 0.92, 0.84; FIGO2015 vs. SSOG2017 0.94, 0.87). Significant ST events occurred more often combined with STAN2007 than with FIGO2015 classification, but not with SSOG2017; correct identification of adverse outcomes was not significantly different between the systems. CONCLUSION: There are discrepancies in the classification of CTG patterns and significant ST events between the old and new systems. The clinical relevance of the findings remains to be shown.

Can flavonoid-rich chocolate modulate arterial elasticity and pathological uterine artery Doppler blood flow in pregnant women? A pilot study.

INTRODUCTION: Dark chocolate has shown beneficial effects on cardiovascular health and might also modulate hypertensive complications in pregnancy and uteroplacental blood flow. Increased uteroplacental resistance is associated with systemic arterial stiffness. We aimed to investigate the short-term effect of flavonoid-rich chocolate on arterial stiffness and Doppler blood flow velocimetry indexes in pregnant women with compromised uteroplacental blood flow. METHODS: Doppler blood flow velocimetry and digital pulse wave analysis (DPA) were performed in 25 women pregnant in the second and third trimesters with uterine artery (UtA) score (UAS) 3-4, before and after 3 days of ingestion of chocolate with high flavonoid and antioxidant contents. UtA pulsatility index (PI), UtA diastolic notching, UAS (semiquantitative measure of PI and notching combined), and umbilical artery PI were calculated, and DPA variables representing central and peripheral maternal arteries were recorded. RESULTS: Mean UtA PI (p = .049) and UAS (p = .025) significantly decreased after chocolate consumption. There were no significant changes in UtA diastolic notching or any DPA indexes of arterial stiffness/vascular tone. CONCLUSION: Chocolate may have beneficial effects on the uteroplacental circulation, but in this pilot study, we could not demonstrate effects on arterial vascular tone as assessed by DPA.

Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns.

BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating condition resulting from a sustained lack of oxygen during birth. The interest in identifying a relevant biomarker of HIE has thrown into limelight the role of protein S100B as a clinical diagnostic marker of hypoxic brain damage in neonates. AIMS: To evaluate the diagnostic value of protein S100B, measured in umbilical cord blood immediately after birth, as a useful biomarker in the diagnosis of HIE Sarnat stages II-III as well as a marker for long-term mortality and morbidity. STUDY DESIGN: Protein S100B was analyzed in cord blood sampled at birth from 13 newborns later diagnosed with stage II-III HIE and compared with 21 healthy controls. S100B concentrations were related to cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death/sequelae up to an age of 6years. Both parametric and non-parametric statistics were used with a two-sided P<0.05 considered significant. RESULTS: The difference in S100B concentration was marginally statistically significant between HIE cases and controls (P=0.056). Cord blood acidosis (P=0.046), aEEG pattern severity (P=0.030), HIE severity (P=0.027), and condition at 6-year follow-up (healthy/permanent sequelae/death; P=0.027) were all related to an increase in S100B concentration. CONCLUSIONS: Protein S100B in neonates suffering from HIE stages II-III appeared elevated in umbilical cord blood at birth. The S100B concentrations were positively associated to the severity of disease and the risk of suffering from neurodevelopmental sequelae and even death.