Karl G. Rosén

Developmental Outcome at 6.5 Years After Acidosis in Term Newborns: A Population-Based Study

OBJECTIVES: Infants who develop encephalopathy after perinatal asphyxia have an increased risk of death and adverse neurologic outcome. Conflicting results exist concerning outcome in healthy infants with metabolic acidosis at birth. The aim of the current study was to evaluate whether metabolic acidosis at birth in term infants who appear healthy is associated with long-term developmental abnormalities. METHODS: From a population-based cohort (14 687 deliveries), 78 infants were prospectively identified as having metabolic acidosis (umbilical artery pH < 7.05 and base deficit in the extracellular fluid >12.0 mmol/L). Two matched controls per case were selected. The child health and school health care records were scrutinized for developmental abnormalities. RESULTS: Outcome measures at 6.5 years of age for 227 of 234 children (97%) were obtained. No differences were found concerning neurologic or behavioral problems in need of referral action or neurodevelopmental diagnosis in comparison of control children with acidotic children who had appeared healthy at birth, ie, had not required special neonatal care or had no signs of encephalopathy. CONCLUSIONS: Infants born with cord metabolic acidosis and who appear well do not have an increased risk for neurologic or behavioral problems in need of referral actions or special teaching approaches at the age of 6.5 years.

Marked fetal acidosis and specific changes in power spectrum analysis of fetal heart rate variability recorded during the last hour of labour

Objective  To assess whether intrapartum acidosis affects specific components of fetal heart rate variability.

Postasphyxial Cerebral Survival in Newborn Sheep after Treatment with Oxygen Free Radical Scavengers and a Calcium Antagonist

ABSTRACT: Acute, severe intrapartum asphyxia was mimicked by tying the umbilical cord in the exteriorized fetal sheep. After a standard time period cardiopulmonary resuscitation was instituted. In the treatment group (n = 14) the lambs were given a composition of scavengers of oxygen-derived free radicals and a calcium channel blocker. The control group of lambs (n = 12) was given placebo. The trial was blind and randomized. Hemodynamic and neurophysiological variables were measured from 30 min before asphyxia to 2 h postresuscitation. Mean arterial blood pressure, sagittal sinus venous pressure, heart rate, and cardiac output did not differ between the two groups although dramatic changes took place during asphyxia and resuscitation. Cerebral blood flow measured by 133-Xe washout method increased in both groups immediately after resuscitation. The treated animals retained an augmented cerebral blood flow during the 2 h postresuscitation while the control animals lost the increase of cerebral blood flow. The treated lambs recovered their somatosensory evoked potentials partially or completely in eight of 14 cases while the same figures for the control lambs were one of 12 cases. Immediately after resuscitation the cerebral reactions recovered to some extent in both groups but during the following 2 h the cerebral cortical function deteriorated in the control group but improved in the treated lambs. It is concluded that part of the brain damage in connection with acute, severe asphyxia may be inflicted by oxygen-derived free radicals released during the reoxygenation phase after resuscitation and that oxygen-derived free radical scavengers and calcium channel blockers may find a place in cardiopulmonary resuscitation.

Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram revisited: analysis of data according to standard versus modified intention-to-treat principle

Objective. To undertake a renewed analysis of data from the previously published Swedish randomized controlled trial on intrapartum fetal monitoring with cardiotocography (CTG‐only) vs. CTG plus ST analysis of fetal electrocardiogram (CTG+ST), using current standards of intention‐to‐treat (ITT) analysis and to compare the results with those of the modified ITT (mITT) and per protocol analyses. Methods. Renewed extraction of data from the original database including all cases randomized according to primary case allocation (n=5 049). Main outcome measure. Metabolic acidosis in umbilical artery at birth (pH <7.05, base deficit in extracellular fluid >12.0mmol/l) including samples of umbilical vein blood or neonatal blood if umbilical artery blood was missing. Results. The metabolic acidosis rates were 0.66% (17 of 2 565) and 1.33% (33 of 2 484) in the CTG+ST and CTG‐only groups, respectively [relative risk (RR) 0.50; 95% confidence interval (CI) 0.28–0.88; p=0.019]. The original mITT gave RR 0.47, 95%CI 0.25–0.86 (p=0.015), mITT with correction for 10 previously misclassified cases RR 0.48, 95%CI 0.24–0.96 (p=0.038) and per protocol analysis RR 0.40, 95%CI 0.20–0.80 (p=0.009). The level of significance of the difference in metabolic acidosis rates between the two groups remained unchanged in all analyses. Conclusion. Re‐analysis of data according to the ITT principle showed that regardless of the method of analysis, the Swedish randomized controlled trial maintained its ability to demonstrate a significant reduction in metabolic acidosis rate when using CTG+ST analysis for fetal surveillance in labor.

A new tool for the validation of umbilical cord acid–base data

Please cite this paper as: Kro G, Yli B, Rasmussen S, Norèn H, Amer‐Wåhlin I, Didrik Saugstad O, Stray‐Pedersen B, Rosén K. A new tool for the validation of umbilical cord acid–base data. BJOG 2010;117:1544–1552.

A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring

BackgroundIntrapartum fetal hypoxia remains an important cause of death and permanent handicap and in a significant proportion of cases there is evidence of suboptimal care related to fetal surveillance. Cardiotocographic (CTG) monitoring remains the basis of intrapartum surveillance, but its interpretation by healthcare professionals lacks reproducibility and the technology has not been shown to improve clinically important outcomes. The addition of fetal electrocardiogram analysis has increased the potential to avoid adverse outcomes, but CTG interpretation remains its main weakness. A program for computerised analysis of intrapartum fetal signals, incorporating real-time alerts for healthcare professionals, has recently been developed. There is a need to determine whether this technology can result in better perinatal outcomes.Methods/designThis is a multicentre randomised clinical trial. Inclusion criteria are: women aged ≥ 16 years, able to provide written informed consent, singleton pregnancies ≥ 36 weeks, cephalic presentation, no known major fetal malformations, in labour but excluding active second stage, planned for continuous CTG monitoring, and no known contra-indication for vaginal delivery. Eligible women will be randomised using a computer-generated randomisation sequence to one of the two arms: continuous computer analysis of fetal monitoring signals with real-time alerts (intervention arm) or continuous CTG monitoring as previously performed (control arm). Electrocardiographic monitoring and fetal scalp blood sampling will be available in both arms. The primary outcome measure is the incidence of fetal metabolic acidosis (umbilical artery pH < 7.05, BDecf > 12 mmol/L). Secondary outcome measures are: caesarean section and instrumental vaginal delivery rates, use of fetal blood sampling, 5-minute Apgar score < 7, neonatal intensive care unit admission, moderate and severe neonatal encephalopathy with a marker of hypoxia, perinatal death, rate of internal monitoring, tracing quality, and signal loss. Analysis will follow an intention to treat principle. Incidences of primary and secondary outcomes will be compared between groups. Assuming a reduction in metabolic acidosis from 2.8% to 1.8%, using a two-sided test with alpha = 0.05, power = 0.80, and 10% loss to follow-up, 8133 women need to be randomised.DiscussionThis study will provide evidence of the impact of intrapartum monitoring with computer analysis and real-time alerts on the incidence of adverse perinatal outcomes, intrapartum interventions and signal quality. (Current controlled trials ISRCTN42314164)

Allopurinol Reduces Oxidative Stress in the Ovine Fetal Cardiovascular System After Repeated Episodes of Ischemia-Reperfusion

In complicated labor, neonatal outcome may depend not only on the extent of fetal asphyxia and acidosis but also on the effects on the fetal cardiovascular system of reactive oxygen species (ROS) generated during the ischemia-reperfusion (I/R) associated with repeated compressions of the umbilical cord. This study tested the hypothesis that maternal treatment with clinical doses of the antioxidant allopurinol in the setting of fetal asphyxia would reduce oxidative stress in the fetal cardiovascular system. The hypothesis was tested in chronically instrumented fetal sheep in late gestation by investigating the effects of maternal treatment with therapeutic doses of allopurinol or vehicle on the fetal cardiovascular system during and after episodes of I/R. The latter were produced by repeated, measured compressions of the umbilical cord. The data show that maternal treatment with allopurinol helped maintain umbilical blood flow and it reduced fetal cardiac oxidative stress after I/R of the type associated with clinically relevant acidemia and repetitive fetal heart rate decelerations. The data support the hypothesis tested and suggest that maternal treatment with allopurinol may offer plausible clinical intervention in the management of perinatal asphyxia in complicated labor.

STAN, a clinical audit: the outcome of 2 years of regular use in the city of Varberg, Sweden

Objective. To monitor and analyze (audit) the introduction of the STAN methodology in a district hospital. Design. Retrospective study covering the total population of deliveries at term during 2004 and 2005. Material and methods. 1,875 out of 3,193 term pregnancies (59%) were monitored using the STAN® fetal heart monitor (Neoventa Medical, Moelndal, Sweden) and the associated clinical guidelines. Cord metabolic acidosis, neonatal outcome, and rates of operative deliveries for fetal distress were recorded. Results. The overall cesarean section rate was significantly reduced in the STAN group. Emergency (crash) cesarean sections were significantly reduced from 1.51% to 0.27% in the cardiotocography‐ and STAN‐monitored groups, respectively (OR 0.18, 95% CI 0.07–0.49). When cesarean section was performed only because of non‐reassuring cardiotocography, cord acid base was significantly higher, 7.26 versus 7.19 (p<0.01), as compared to when STAN guidelines were followed. Total population rates for operative deliveries for fetal distress and cesarean section rates were 6.7% and 3.5% respectively. The corresponding metabolic acidosis rate was 0.5%. Conclusion. High STAN usage in a busy labor ward setting provided an outcome equaling that noted previously in a larger academic unit, demonstrating the safe implementation of the STAN methodology in a nonacademic unit.

A Comparative Study of Fetal Heart Rate Variability Analysis Techniques

This study examines a novel methodology for continuous fetal heart rate variability (FHRV) assessment in a non-stationary intrapartum fetal heart rate (FHR). The specific aim was to investigate simple statistics, dimension estimates and entropy estimates as methods to discriminate situations of low FHRV related to non-reassuring fetal status or as a consequence of sedatives given to the mother. Using a t-test it is found that the dimension of the zero set and sample entropy reveal a difference in mean distribution of significance >99%. Thus it may prove possible to build a discriminating system based on either one or a combination of these techniques

Change in heart rate variability in relation to a significant ST‐event associates with newborn metabolic acidosis

Objective  To find whether low‐to‐high frequency (LF/HF) ratio of fetal heart rate (FHR) variability changes in relation to a significant ST‐event during delivery, and if the change is predictive of metabolic acidosis of the newborn.