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.

ECG and heart rate variability changes in preterm and near-term fetal lamb following LPS exposure.

The aim of this study is to evaluate the myocardial response in the preterm and near-term fetal lamb with infection. Chronically instrumented fetal lambs were exposed to lipopolysaccharide (LPS), and the fetal electrocardiogram (FECG) ST waveform was examined using STAN. Fetal heart rate variability (FHRV) was automatically analyzed by adapting a polynomial function to the RR sequence in the FECG. Preterm fetuses exposed to >90 ng/kg LPS died within 8 hours of LPS administration, a response not seen in near-term fetuses. In both surviving and nonsurviving preterm fetuses, cardiovascular responses were characterized by decreased arterial pressure, negative T waves, and tachycardia accompanied by an increase in FHRV. Similar changes were not observed in the near-term fetuses after LPS. The study shows that preterm lambs are more sensitive to LPS in terms of myocardial/cardiovascular response than the more mature fetuses are. High FHRV and negative ST waveform seem to characterize the LPS-induced stress response in preterm fetuses.

Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to cardiotocography to predict fetal acidosis in labor--a multi-center, case controlled study.

OBJECTIVE: To assess the relationship between scalp pH (FBS) and ST analysis in situations of acidosis with special emphasis on the timing of cardiotocography (CTG), FBS and ST changes during labor. STUDY DESIGN: From a European Union multicenter study on clinical implementation of the STAN methodology, 911 cases were identified where a scalp-pH had been obtained. In 53 cases, marked cord artery acidosis was found (cord artery pH<7.06) and 44 cases showed moderate acidemia at birth (pH 7.06-7.09). Comparisons were made with 97 control cases (pH>or=7.20). RESULTS: Of those cases with FHR+ST events recorded within 16 min of delivery, 61% (17/28) had a cord artery pH>or=7.20. The corresponding figure for cases where STAN indications occurred for more than 16 min was 19% (13/69) (OR 6.66, 2.53-17.55, P<0.001). Out of the 121 cases with an abnormal CTG, 84 (69%) showed a cord artery pH of <7.10. STAN indicated abnormality in 83% (70 out of 84). The corresponding figure for scalp pH<7.20 was 43% (36/84). In the case of CTG changes at the start of an adequate recording STAN guidelines provided information on developing acidosis in all cases but one (16 out of 17) in the marked acidosis group. STAN guidelines indicated abnormality prior to an abnormal FBS in 14 out of 17 cases. The median duration between STAN indications to intervention and an abnormal FBS was 29 (95% CI 11-74) min. CONCLUSIONS: ST analysis, as an adjunct to CTG, identifies adverse fetal conditions during labor similar to that of FBS but on a more consistent basis. The timing of CTG+ST changes relates to the level of acidosis at birth.

STAN in clinical practice--the outcome of 2 years of regular use in the city of Gothenburg.

OBJECTIVE: The purpose of this study was to monitor the introduction of the STAN-methodology (Noventa Medical, Moelndal, Sweden). STUDY DESIGN: This was a prospective observational study covering the total population of deliveries at term during 2 years. Four thousand eight hundred and thirty out of 14,687 term pregnancies were monitored using the STAN S 21 fetal heart monitor and the associated clinical guidelines. Cord artery metabolic acidosis, neonatal outcome, and rates of operative deliveries for fetal distress were assessed. RESULTS: The annual rate of STAN usage increased from 28.1% to 37.7% and was associated with a significant reduction in metabolic acidosis rate in the total population from 0.76% to 0.44% (P < .05). The compliance with the clinical guidelines increased in cases requiring intervention. The rates for moderate/severe hypoxic neonatal encephalopathy were consistently low, 0.55 and 0.68 per 1000 deliveries, respectively, and corresponding to previous findings. The rate of operative delivery did not change during the 2 years in the total population. CONCLUSION: Increasing STAN usage provided consistent improvements in fetal outcome equalling those noted in the Swedish randomized controlled trial (RCT) without increasing operative interventions for fetal distress.

Electrocardiographic changes following umbilical cord occlusion in the midgestation fetal sheep.

BACKGROUND: Clinical studies show that analysis of the fetal electrocardiographic (FECG) ST waveform at term gives important information on the myocardial response to intrapartum asphyxia. However, it is not known whether the preterm fetus responds in a similar fashion. The objective of the present study was to evaluate the FECGST response to umbilical cord occlusion in the preterm fetal sheep. METHODS: Fetal sheep at midgestation were subjected to 25 min umbilical cord occlusion (n = 7) and compared to controls (n = 5). Changes in the FECGST waveform were recorded together with arterial blood pressure, heart rate, and acid base status during the occlusion and for 3 days afterward. RESULTS: Umbilical cord occlusion resulted in immediate bradycardia (control: 187 +/- 7 bpm versus occlusion: 102 +/- 7 bpm), hypertension (control: 43.2 +/- 1.1 mmHg versus occlusion: 59.8 +/- 2.2 mmHg), and an initial increase in the T/QRS ratio (control: 0.10 +/- 0.02 versus occlusion: 0.60 +/- 0.10, P < 0.001), followed by hypotension (21.7 +/- 1.2 mmHg), normalization of the T/QRS ratio, and in some cases the development of negative T waves toward the end of the occlusion. CONCLUSIONS: These studies show that the midgestation fetal sheep has the capacity to react to umbilical cord occlusion with a significant increase in the amplitude of the ST waveform together with an augmentation of blood pressure, which then subsides as the occlusion continues. The appearance of negative ST segment appears to signify significant cardiac dysfunction. The characteristic progression of ST-waveform changes in response to umbilical cord occlusion in midgestation fetal sheep, suggests that monitoring the ST waveform may contribute clinically important information also in the preterm individual.

Maturational effects of lipopolysaccharide on white-matter injury in fetal sheep.

White-matter damage has been associated with the development of cerebral palsy in children born both prematurely and at term, and it has been suggested that intrauterine infection can contribute to the brain injury. However, the relative importance of age on white-matter injury following infectious exposure in utero remains unclear. In this study, fetal sheep were exposed to systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (88.7 +/- 7.7 ng/kg) at 65% or 85% of gestation. These gestational ages approximately correspond to human brain development in preterm and near-term infants respectively. White-matter injury was evaluated 3 days after lipopolysaccharide exposure with regard to microglia activation and loss of neurofilament and myelin basic protein. The expression of oligodendrocytes at different maturational stages was demonstrated in preterm and near-term fetuses with the oligodendroglial markers O4 and 2 ,3 -cyclic nucleotide 3 -phospodiesterase. Forty percent of the fetuses in the preterm group and 22% in the near-term group died within 8 hours of the endotoxin exposure. Three of six preterm and two of seven near-term surviving fetuses demonstrated pathologic changes in the brain with regard to increased microglia activation and loss of neurofilament staining. The number of activated microglia was enhanced in the subcortical white matter in both the preterm lipopolysaccharide-exposed fetuses (lipopolysaccharide: 235 +/- 64 cells/mm2; control: 72 +/- 28 cells/mm2; P = .0374) and the near-term fetuses (lipopolysaccharide: 180 +/- 40 cells/mm2; control 23 +/- 16 cells/mm2; P = .0152). There was a loss of neurofilament staining in both preterm fetuses (lipopolysaccharide: 2.20 +/- 0.77 pixel units; control: 0.20 +/- 0.10 pixel units; P = .0306) and near-term fetuses (lipopolysaccharide: 1.15 +/- 0.48 pixel units; control: 0.06 +/- 0.06 pixel units; P = .0285). O4-positive cells were detected at both gestational ages, whereas 2,3-cyclic nucleotide 3-phospodiesterase-positive cells and myelin basic protein staining were mainly detected in the near-term fetuses. In summary, we found white-matter injury in a proportion of both preterm and near-term fetuses after administration of lipopolysaccharide. These results are in agreement with clinical evidence suggesting that both preterm and term infants are at risk of periventricular leukomalacia in association with intrauterine infection.

Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to CTG. A multi-center, observational study.

OBJECTIVE: To evaluate the relationships between scalp-pH and CTG plus ST waveform analysis of the fetal ECG (STAN) clinical guidelines as indicators of intrapartum hypoxia in term fetuses born with cord artery acidemia. STUDY DESIGN: Data from 6999 term deliveries monitored by the STAN (R) S 21 as part of an EU multi-center study on clinical implementation of the STAN methodology for intrapartum fetal surveillance were analyzed. We identified 911 cases where a scalp-pH was obtained, including 53 cases with cord artery acidemia (pH < 7.06). Lag times between ST events and scalp-pH and time to delivery were related to cord artery metabolic and respiratory acidosis and neonatal outcome. RESULTS: 43 fetuses were identified by CTG plus ST as being in need of intervention 31 (25-46) minutes before delivery (median, 95% Cl). In five, no indications were given and in another five there were inadequate data. Fifteen cases with metabolic acidosis required special neonatal care, all 14 cases adequately monitored on STAN had indications to intervene for 19 minutes or more. In 30 adequately recorded cases, fetal blood sampling (FBS) was obtained within the last hour of labor. In 22 cases, FBS was obtained 13 (7-24) minutes after STAN guidelines had indicated abnormality and in eight no ST changes had occurred at time of FBS. The corresponding FBS data were pH 7.10 (7.01-7.15) and pH 7.21 (7.08-7.31), respectively, P = 0.01. In cases of metabolic acidosis, scalp-pH fell 0.01 units per minute after a baseline T/QRS rise was recorded during the second stage of labor. Apart from one newborn that died at 2 h from E. Coli septicemia, none of the neonates were affected neurologically. CONCLUSION: Cardiotocography plus ST analysis provides accurate information about intrapartum hypoxia similar to that obtained by scalp-pH.

The effects of intrapartum hypoxia on the fetal QT interval.

BACKGROUND: The morphology of the fetal ECG complex provides information on the fetal condition during labour, such as the ST segment and T-wave configuration. We hypothesised that the intrapartum fetal QT interval may provide additional information on the condition of the fetus, as it is known that the QT interval reacts to situations of stress and exercise. DESIGN: Retrospective study. SETTING: Data were substracted from a European community multicentre trial. METHODS: The intrapartum QT interval was measured in 68 fetuses who were acidemic at birth (pH <7.05 and BD (ecf) >12 mmol/L) and in a control group of similar size. All of these cases were monitored by STAN S21. Measurements were performed at the start of the recording at baseline heart rate, during variable decelerations and at the end of the recording. The QTc was calculated using Bazett's formula: QT/ radical RR. The intervals were compared using the Wilcoxon signed ranks test. MAIN OUTCOME MEASURES: Fetal QT interval, and the corrected QT interval: QTc. RESULTS: In the acidemic fetuses, there was a significant shortening of the QTc interval at the end of the recording compared with the start of the recording (397 ms at the end vs 359.3 ms at start; P < 0.001), in association with a significantly lowered heart rate (136.3 vs 110.9 bpm, P < 0.001). Measurements of QT and QTc during variable decelerations at the start and end of the recording also showed a shortening of the QT interval (301.9 vs 273.3 ms, P< or = 0.001) and QTc interval (381.6 vs 340.3, P < 0.001), and this was not dependent on heart rate. In the control cases, no differences in FHR, QT and QTc intervals were present. CONCLUSIONS: In intrapartum hypoxia, resulting in metabolic acidosis, a significant shortening of the fetal QT and QTc is present, irrespective of changes in heart rate. In control cases, this shortening does not occur. The intrapartum fetal QT interval may therefore provide additional information on the condition of the fetus.