Peripartum events associated with severe neurologic morbidity and mortality among acidemic neonates.

PURPOSE: To identify peripartum events that may predict the development of short-term neurologic morbidity and mortality among acidemic neonates. METHODS: Retrospective case-control study conducted at a single-teaching hospital on data from January 2010 to December 2015. The study cohort group included all acidemic neonates (cord artery pH ≤ 7.1) born at ≥ 34 weeks. Primary outcome was a composite including any of the following: neonatal encephalopathy, convulsions, intra-ventricular hemorrhage, or neonatal death. The study cohort was divided to the cases group, i.e., acidemic neonates who had any component of the primary outcome, and a control group, i.e., acidemic neonates who did not experience any component of the primary outcome. RESULTS: Of all 24,311 neonates born ≥ 34 weeks during the study period, 568 (2.3%) had a cord artery pH ≤ 7.1 and composed the cohort study group. Twenty-one (3.7%) neonates composed the cases group. Multivariate logistic regression analysis revealed that cases were significantly more likely to have experienced placental abruption (OR 18.78; 95% CI 5.57-63.26), born ≤ 2500 g (OR 13.58; 95% CI 3.70-49.90), have meconium (OR 3.80; 95% CI 1.20-11.98) and cord entanglement (OR 5.99; 95% CI 1.79-20.06). The probability for developing the composite outcome rose from 3.7% with isolated acidemia to 97% among neonates who had all these peripartum events combined with intrapartum fetal heart rate tracing category 2 or 3. CONCLUSION: Neonatal acidemia carries a favorable outcome in the vast majority of cases. In association with particular antenatal and intrapartum events, the short-term outcome may be unfavorable.

Inborn errors of ketone body utilization.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency and mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase or T2) deficiency are classified as autosomal recessive disorders of ketone body utilization characterized by intermittent ketoacidosis. Patients with mutations retaining no residual activity on analysis of expression of mutant cDNA are designated as severe genotype, and patients with at least one mutation retaining significant residual activity, as mild genotype. Permanent ketosis is a pathognomonic characteristic of SCOT-deficient patients with severe genotype. Patients with mild genotype, however, may not have permanent ketosis, although they may develop severe ketoacidotic episodes similar to patients with severe genotype. Permanent ketosis has not been reported in T2 deficiency. In T2-deficient patients with severe genotype, biochemical diagnosis is done on urinary organic acid analysis and blood acylcarnitine analysis to observe characteristic findings during both ketoacidosis and non-episodic conditions. In Japan, however, it was found that T2-deficient patients with mild genotype are common, and typical profiles were not identified on these analyses. Based on a clinical study of ketone body utilization disorders both in Japan and worldwide, we have developed guidelines for disease diagnosis and treatment. These diseases are treatable by avoiding fasting and by providing early infusion of glucose, which enable the patients to grow without sequelae.

Suboptimal care and metabolic acidemia is associated with neonatal encephalopathy but not with neonatal seizures alone: a population-based clinical audit.

OBJECTIVE: To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome. DESIGN: Clinical audit. SETTING: Two university hospitals in Sweden. POPULATION: Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed. METHODS: Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome. MAIN OUTCOME MEASURES: Encephalopathy and seizures alone. RESULTS: We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone. CONCLUSION: Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Added value of umbilical vein flow as a predictor of perinatal outcome in term small-for-gestational-age fetuses.

OBJECTIVE: To compare umbilical vein (UV) flow with standard Doppler parameters in prediction of adverse perinatal outcome in late-onset small-for-gestational age (SGA) fetuses. METHODS: Umbilical, uterine and middle cerebral arteries, and UV blood flow were evaluated by Doppler before delivery in a cohort of 193 term SGA fetuses. The value of the Doppler parameters to predict risk of emergency delivery for non-reassuring fetal status and neonatal metabolic acidosis was analyzed. RESULTS: Fifty-three (27%) fetuses had non-reassuring fetal status requiring emergency delivery, whereas 21 (11%) newborns developed neonatal metabolic acidosis. Multivariable analysis showed that significant contributions to prediction of emergency delivery for non-reassuring fetal status and neonatal metabolic acidosis were provided by middle cerebral artery (MCA) pulsatility index (PI) and UV blood flow normalized by fetal weight. Decision tree analysis defined three groups with increasing risk of need for emergency delivery for non-reassuring fetal status: MCA-PI > 1.46 (risk 15.6%); MCA-PI ≤ 1.46 and UV blood flow > 68 mL/min/kg (risk 25%); and MCA-PI ≤ 1.46 and UV flow ≤ 68 mL/min/kg (risk 53.1%); and two groups with different risks of neonatal metabolic acidosis: UV flow > 68 mL/min/kg or UV flow ≤ 68 mL/min/kg and MCA-PI > 1.23 (risk ≤ 10%); and UV flow ≤ 68 mL/min/kg and MCA-PI ≤ 1.23 (risk 39.1%). CONCLUSION: The evaluation of UV blood flow with spectral brain Doppler allows better identification of SGA fetuses with late-onset intrauterine growth restriction at risk of adverse perinatal outcome.

[Prospective study of the relationship between heart rate fetal anomalies, pH umbilical cord at birth and Apgar]. / Etude prospective de la relation entre anomalie du rythme cardiaque fœtale, pH ombilical et Apgar à la naissance

BACKGROUND: The search for an acute fetal distress during labor remains one of the objectives of obstetrical surveillance. AIM: To find a relationship between different aspects of fetal heart rate (FHR) occurring during labor, Apgar score at first minute and the pH blood at birth. METHODS: A prospective study which involved 170 single-fetal pregnancies to term. RESULTS: In our population, by comparing the APGAR score in the first minute and umbilical pH, it was found that only 25.7% of newborns with Apgar at 1st minute less than 7 had an umbilical arterial pH <7.15. Thus in our study, the Apgar score did not predict umbilical acidosis and the difference was significant (p = 0.02). In the same population, by comparing the analysis of FCR and umbilical PH, we found that fetal bradycardia was associated with pH umbilical lowest with an average of 7008 and the difference was significant (p = 0.008). Other types of ERCF were also significantly associated with neonatal acidosis. CONCLUSION: Recording fetal heart rate is a limited review to assess the exact condition of the fetus. It has a good negative predictive value but there is little specific consideration. Combination with other techniques to better assess the fetal state.

The clinical interpretation and significance of electronic fetal heart rate patterns 2 h before delivery: an institutional observational study.

PURPOSE: To evaluate the clinical significance of intrapartum fetal heart rate (FHR) monitoring in low-risk pregnancies according to guidelines and specific patterns. METHODS: An obstetrician, blinded to neonatal outcome, retrospectively reviewed 198 low-risk cases that underwent continuous electronic fetal monitoring (EFM) during the last 2 h before delivery. The tracings were interpreted as normal, suspicious or pathological, according to specific guidelines of EFM and by grouping the different FHR patterns considering baseline, variability, presence of decelerations and bradycardia. The EFM groups and the different FHR-subgroups were associated with neonatal acid base status at birth, as well as the short-term neonatal composite outcome. Comparisons between groups were performed with Kruskal-Wallis test. Differences among categorical variables were evaluated using Fisher's exact test. Significance was set at p < 0.05 level. RESULTS: Significant differences were found for mean pH values in the three EFM groups, with a significant trend from "normal" [pH 7.25, 95 % confidence interval (CI) 7.28-7.32] to "pathological" tracings (pH 7.20, 95 % CI 7.17-7.13). Also the rates of adverse composite neonatal outcome were statistically different between the two groups (p < 0.005). Among the different FHR patterns, tracings with atypical variable decelerations and severe bradycardia were more frequently associated with adverse neonatal composite outcome (11.1 and 26.7 %, respectively). However, statistically significant differences were only observed between the subgroups with normal tracings and bradycardia. CONCLUSIONS: In low-risk pregnancies, there is a significant association between neonatal outcome and EFM classification. However, within abnormal tracings, neonatal outcome might differ according to specific FHR pattern.

[Targeted temperature management in critical care : current 2011 recommendations]. / Gezieltes Temperaturmanagement auf der Intensivstation : Aktuelle Empfehlungen 2011.

Since October 2011 new guidelines exist for temperature management in critical care. According to the guidelines the term targeted temperature management (TTM) should replace the term therapeutic hypothermia. There is now a strong recommendation for TTM using 32-34°C as the preferred treatment for out-of-hospital adult cardiac arrest with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation. A TTM of 32.5-35.5°C is also recommended for the treatment of term newborns who sustain asphyxia and exhibit acidosis and/or encephalopathy.

Outcome of severe intrapartum acidemia diagnosed with fetal scalp blood sampling.

AIM: To analyze short-term neonatal outcome and the sampling to delivery interval in cases with severe intrapartum acidemia diagnosed with fetal scalp blood sampling (FBS). METHODS: This is a secondary analysis of data from a trial of 2992 women, who were, when indicated, randomized to either lactate or pH analyses by FBS. Median and 95(th) centile values for lactate analyses were 2.9 mmol/L and 6.6 mmol/L, respectively. Corresponding pH values were 7.30 and 7.17. We defined severe intrapartum acidemia as lactate >6.6 mmol/L or pH <7.17. Outcome measures were cord artery pH <7.00, Apgar <7 at 5 min, hypoxic ischemic encephalopathy and time interval from FBS to delivery. RESULTS: Severe intrapartum acidemia was present in 85/1355 (6.3%) cases with lactate analyses and in 69/1008 (6.8%) cases with pH analyses. Cord artery pH <7.00 occurred in 12/154 (7.8%), Apgar <7 at 5 min in 16/154 (10.4%) and hypoxic ischemic encephalopathy in 4/154 (2.6%) of the cases. There were no differences in outcomes between the two groups. However, delivery was expedited more rapidly in the pH management group (median 16 vs. 21 min; P=0.01). CONCLUSION: Severe neonatal morbidity occurred in 10% or less in this high-risk group. FBS is an early marker of intrapartum hypoxia and can be used to prevent severe birth acidemia. Lactate might be an earlier marker than pH in the hypoxic process.

Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis.

A complete deficiency in the pyruvate dehydrogenase system activity contributed to the death of a 6-month-old infant with congenital lactic acidosis. The enzymatic block could be isolated to the first component, pyruvate decarboxylase (E1) of the pyruvate dehydrogenase complex. This enzymatic deficiency allowed a demonstration of an "intercomplex" exchange of the components of the mammalian pyruvate dehydrogenase system and indicated that the first component is normally present in an apparent excess.

Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain.

An inherited defect affecting the tricarboxylic acid cycle in a patient with congenital lactic acidosis.

Cultured skin fibroblasts from a 3 yr old girl with severe, diffuse neurologic disease and persistant lactic acidosis, oxidized radioactive citrate, palmitate, and pyruvate at less than one-third the rate of control cells. Her fibroblasts oxidized isocitrate and glutamate at rates comparable with controls. In disrupted cells from this patient, the activity of aconitate hydratase appeared normal. The binding of citrate to aconitate hydratase and the activities of the NAD- and NADP-linked isocitrate dehydrogenases were also normal, while the activity of citrate synthase was slightly below control values. A significant defect was, however, apparent in the activity of the pyruvate dehydrogenase complex although not in the thiamine-dependent first enzyme of that complex. This patient appears to have a partial genetic defect affecting the tricarboxylic acid cycle.

[Fetal scalp pH during labor: Which threshold for intervention?] / pH au scalp pendant le travail : quel seuil décisionnel pour intervenir ?

OBJECTIVE: In case of abnormal fetal heart rate, there is no consensus on the decision threshold pH scalp leading to a rapid birth. The objective of this study was to compare neonatal issues and cesarean rate in two maternity using different decision thresholds of scalp pH. MATERIAL AND METHODS: A comparative retrospective study conducted in two level III maternity units between January 2013 and May 2014, one maternity unit used a decision threshold of 7.20 (maternity unit 7,20), and the other one a threshold of 7.25 (maternity unit 7,25). An adverse neonatal outcome was defined by a composite endpoint of neonatal morbidity. The risk of cesarean was assessed using a multivariate analysis. RESULTS: One hundred and four patients were included in the maternity unit 7,20 and 163 patients in the maternity 7,25. Adverse neonatal outcome was similar in both maternities (25% vs. 30,1%; P=0.4). The average pH at birth was similar in both maternities, as well as the Apgar score at 5minutes and neonatal transfer rates. However, BE<-12 was more frequent in maternity using 7,20 scalp pH threshold (7% vs. 0%; P<0.01). The cesarean rate was higher in maternity 7,25 (adjusted OR=2.23 95% CI [1.17-4.25]). CONCLUSION: It seems that a decisional threshold fixed to 7,20 could be used reasonably. It could allow to reduce cesarean rate. Other studies are, however, needed to confirm that such threshold of 7,20 does not increase the risk of severe acidosis.

Is trial of labor harmful in breech delivery? A cohort comparison for breech and vertex presentations.

INTRODUCTION: Planned vaginal delivery in breech presentation is accompanied by an excess neonatal risk that has, however, rarely been compared to that of delivery in vertex presentation. Because of the severity of complications that can occur in long-term follow-up, the risk of asphyxia is of particular concern. MATERIAL AND METHODS: To assess immediate neonatal status after a planned vaginal delivery of fetuses in breech compared with vertex presentation, we planned a retrospective hospital cohort study of singleton term deliveries from 2000 to 2011. The indicators used to assess neonatal status were: 5-min Apgar score<7, acidosis, both moderate (pH<7.15) and severe (pH<7.0), asphyxia (pH<7.0 and base deficit≥12.0mmol/L), transfer to the neonatal intensive care unit (NICU), and in-hospital neonatal death. RESULTS: Compared with 43,595 trials of vaginal delivery in vertex presentation at term during the 12-year study period (93.8% of all vertex presentations), the 665 breech deliveries for which planned vaginal delivery was planned (43.2% of all breech presentations) had a quadrupled risk of severe acidosis (ORa 4.3 [2.2-7.5]), but no increase in the risk of asphyxia (ORa 0.7 [0.1-3.0]), NICU transfer (ORa 0.8 [0.4-1.3]) or in-hospital death (ORa 1.3 [0.1-6.0]). Moreover, compared with the 876 planned cesareans, the risk of severe acidosis in the 665 trials of vaginal delivery in breech presentation was four times higher (OR 4.3 [2.3-4.7]), but we observed no increase in neither asphyxia nor other risks studied. CONCLUSION: In our hospital, planned vaginal delivery is safe for breech presentations because it is associated with an increase of severe acidosis but not asphyxia.

Asphyxia in the Newborn: Evaluating the Accuracy of ICD Coding, Clinical Diagnosis and Reimbursement: Observational Study at a Swiss Tertiary Care Center on Routinely Collected Health Data from 2012-2015.

BACKGROUND: The ICD-10 categories of the diagnosis "perinatal asphyxia" are defined by clinical signs and a 1-minute Apgar score value. However, the modern conception is more complex and considers metabolic values related to the clinical state. A lack of consistency between the former clinical and the latter encoded diagnosis poses questions over the validity of the data. Our aim was to establish a refined classification which is able to distinctly separate cases according to clinical criteria and financial resource consumption. The hypothesis of the study is that outdated ICD-10 definitions result in differences between the encoded diagnosis asphyxia and the medical diagnosis referring to the clinical context. METHODS: Routinely collected health data (encoding and financial data) of the University Hospital of Bern were used. The study population was chosen by selected ICD codes, the encoded and the clinical diagnosis were analyzed and each case was reevaluated. The new method categorizes the diagnoses of perinatal asphyxia into the following groups: mild, moderate and severe asphyxia, metabolic acidosis and normal clinical findings. The differences of total costs per case were determined by using one-way analysis of variance. RESULTS: The study population included 622 cases (P20 "intrauterine hypoxia" 399, P21 "birth asphyxia" 233). By applying the new method, the diagnosis asphyxia could be ruled out with a high probability in 47% of cases and the variance of case related costs (one-way ANOVA: F (5, 616) = 55.84, p < 0.001, multiple R-squared = 0.312, p < 0.001) could be best explained. The classification of the severity of asphyxia could clearly be linked to the complexity of cases. CONCLUSION: The refined coding method provides clearly defined diagnoses groups and has the strongest effect on the distribution of costs. It improves the diagnosis accuracy of perinatal asphyxia concerning clinical practice, research and reimbursement.

Chorioamnionitis and neonatal encephalopathy in term infants with fetal acidemia: histopathologic correlations.

The aim of this study was to determine whether the presence or severity of histologic abnormalities of infection/inflammation such as chorioamnionitis, vasculitis, or funisitis confers an additional risk for neonatal encephalopathy in term infants delivered in the presence of severe fetal acidosis. The medical records as well as placental pathology of term infants (n = 51) born with a cord umbilical arterial pH <7.00 were reviewed. Abnormal outcome was predefined as Sarnat stage 2 or 3 neonatal encephalopathy in the first week of life or neonatal death as a consequence of severe brain injury. Consistent with prior data, the presence of severe fetal acidemia, a low 5-minute Apgar score, and need for cardiopulmonary resuscitation were significantly associated with neonatal encephalopathy. However, the presence of histologic chorioamnionitis had a poor predictive value and did not confer additional risk for the subsequent development of neonatal encephalopathy.

Mechanism of reduction of newborn metabolic acidemia following application of a rule-based 5-category color-coded fetal heart rate management framework.

UNLABELLED: Abstracts Objective: We have reported a 7-fold reduction in newborn umbilical arterial (UA) metabolic acidemia after adoption of a rule-based 5-category color-coded fetal heart rate (FHR) management framework. We sought evidence for the relationship being causal by detailed analysis of FHR characteristics and acid-base status before and after training. METHODS: Rates of UA pH and base excess (BE) were determined over a 5-year period in a single Japanese hospital, serving mainly low-risk patients, with 3907 deliveries. We compared results in the 2 years before and after a 6-month training period in the FHR management system. We used a previously published classification schema, which was linked to management guidelines. RESULTS: After the training period, there was an increase in the percentage of normal patterns (23%), and a decrease in variable decelerations (14%), late decelerations (8%) and prolonged decelerations (12%) in the last 60 min of labor compared to the pre-training period. There was also a significant reduction in mean UA pH and BE in the groups with decelerations after introduction of the FHR management framework. CONCLUSIONS: The adoption of this FHR management system was associated with a reduction of decelerations and metabolic acidemia, without a change in cesarean or vacuum delivery rates. These results suggest that the obstetrical providers were able to better select for intervention those patients destined to develop more severe acidemia, demonstrating a possible causal relationship between the management system and reduced decelerations and metabolic acidemia.

Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: responses to dichloroacetate and benzoate.

We describe the successful use of sodium benzoate in a neonate with hyperammonemia associated with congenital lactic acidosis caused by a partial deficiency of the E1 component of pyruvate dehydrogenase (PDH); of note, this biochemical disturbance has not been previously described in PDH deficiency. The pyruvate dehydrogenase complex in skin fibroblasts had 48% of normal activity with a deficiency of the E1 component. The infant presented with rapid onset of a severe metabolic lactic acidosis, hyperventilation, hyperammonemia, and coma. At 30 hours of age continuous peritoneal dialysis was started; however, plasma NH3 concentrations remained in the 300-400 micrograms/dl range over the next 12 hours. Sodium benzoate, 250 mg/kg, was infused intravenously with a decrease in plasma ammonia of 25 micrograms/dl/hr. Hippurate was documented in the urine and peritoneal fluid after benzoate therapy. At 10.5 months of age, 50 mg/kg dichloroacetate was administered orally under fasting conditions, which resulted in a 56 and 62% reduction in the serum lactate and pyruvate levels, respectively; after 2 weeks on dichloroacetate his fasting levels were significantly decreased. Fibroblast PDH activity responded similarly to this drug. In our patient sodium benzoate was rapidly effective in producing a decline in plasma ammonia that was associated with clinical improvement. We feel that its use in organic acidemias deserves further evaluation and, furthermore, that any child with suspected PDH deficiency requires a clinical trial of dichloroacetate.

The efficacy of individual computer heart rate indices in detecting acidemia at birth in growth-restricted fetuses.

OBJECTIVE: To determine the efficacy of individual fetal heart rate (FHR) indices, as determined by computer analysis of the FHR tracing, in detecting fetal acidemia at birth in growth-restricted fetuses. METHODS: The study population consisted of 38 growth-restricted fetuses at 26-37 weeks' gestation from pregnancies with abnormal uterine and/or umbilical artery Doppler velocimetry. The 1-hour FHR tracing was analyzed by computer within 4 hours of cesarean birth before the onset of labor. Umbilical artery cord blood was collected at birth, and pH was determined within 5 minutes of collection. RESULTS: On linear regression, the duration of episodes of low variation in minutes (r = -0.77, r2 = 0.59) and short-term (r = 0.72, r2 = 0.52) and long-term (r = 0.69, r2 = 0.47) variation in milliseconds were significantly related to umbilical artery pH at birth, and more so than the number of accelerations of ten (r = 0.57, r2 = 0.32) and 15 (r = 0.38, r2 = 0.14) beats per minute. There were significant differences in computer measurements of FHR accelerations and variation between the umbilical artery pH categories of acidemia (pH less than 7.20), preacidemia (7.20-7.25), and nonacidemia (greater than 7.25). Stepwise regression revealed that episodes of low variation best described the model for predicting umbilical artery pH at birth (P < .001), with no improvement provided by the addition of other computer-analyzed FHR characteristics. CONCLUSION: In this population of growth-restricted fetuses delivered by elective cesarean, the computer indices of duration of episodes of low variation and short-term and long-term variation were significantly associated with umbilical artery pH and predicted umbilical artery acidemia at birth.

Intrapartum fetal acidosis in preterm infants: fetal monitoring and long-term morbidity.

Fetal heart rate (FHR) and fetal acid-base status were studied prospectively in 61 patients in preterm labor of unknown etiology. Neonatal data were analyzed, and all surviving infants participated in a follow-up study for at least two years. Ominous FHR patterns correlated well with fetal acidosis. Infants with fetal acidosis (pH less than 7.25 in scalp blood) had more neurologic abnormalities in the neonatal period and a higher rate of neurodevelopmental disabilities at the follow-up than nonacidotic infants of the same gestational weeks. In the surveillance of patients in preterm labor electronic fetal monitoring is mandatory. At late or pronounced variable decelerations, pH analysis of fetal scalp blood should be performed immediately. If not available, prompt abdominal delivery is recommended.

Revised assays for the investigation of congenital lactic acidosis using 14C keto acids, eliminating problems associated with spontaneous decarboxylation.

Improved methods using 14C keto acids for the investigation of patients with congenital lactic acidoses are described. The addition of rat serum to assay media reduces the spontaneous decarboxylation of [1-14C] and [2-14C] pyruvate and alpha-[1-14C]ketoglutarate to low levels. A study of the stability of pyruvate dehydrogenase in fibroblasts has shown that the activity is rapidly lost when cell membranes are broken unless homogenisation is done gently at -15 degrees C. Under these conditions broken cell preparations may be stored for up to 3 hours without loss of activity. Freezing and thawing results in unpredictable changes in pyruvate dehydrogenase activity. A quality control solution containing pyruvate dehydrogenase activity has been prepared which is stable for at least 6 months (coefficient of variation = 7.7%). Normal values for pyruvate dehydrogenase in fibroblasts range from 0.59 to 1.26 nmol . min-1 . mg-1 protein (mean = 0.98, n = 8) and pyruvate dehydrogenase deficient fibroblasts can be detected with confidence.