Fetal heart rate responses in chronic hypoxaemia with superimposed repeated hypoxaemia consistent with early labour: a controlled study in fetal sheep.

OBJECTIVE: Deceleration area (DA) and capacity (DC) of the fetal heart rate can help predict risk of intrapartum fetal compromise. However, their predictive value in higher risk pregnancies is unclear. We investigated whether they can predict the onset of hypotension during brief hypoxaemia repeated at a rate consistent with early labour in fetal sheep with pre-existing hypoxaemia. DESIGN: Prospective, controlled study. SETTING: Laboratory. SAMPLE: Chronically instrumented, unanaesthetised near-term fetal sheep. METHODS: One-minute complete umbilical cord occlusions (UCOs) were performed every 5 minutes in fetal sheep with baseline pa O2 <17 mmHg (hypoxaemic, n = 8) and >17 mmHg (normoxic, n = 11) for 4 hours or until arterial pressure fell <20 mmHg. MAIN OUTCOME MEASURES: DA, DC and arterial pressure. RESULTS: Normoxic fetuses showed effective cardiovascular adaptation without hypotension and mild acidaemia (lowest arterial pressure 40.7 ± 2.8 mmHg, pH 7.35 ± 0.03). Hypoxaemic fetuses developed hypotension (lowest arterial pressure 20.8 ± 1.9 mmHg, P < 0.001) and acidaemia (final pH 7.07 ± 0.05). In hypoxaemic fetuses, decelerations showed faster falls in FHR over the first 40 seconds of UCOs but the final deceleration depth was not different to normoxic fetuses. DC was modestly higher in hypoxaemic fetuses during the penultimate (P = 0.04) and final (P = 0.012) 20 minutes of UCOs. DA was not different between groups. CONCLUSION: Chronically hypoxaemic fetuses had early onset of cardiovascular compromise during labour-like brief repeated UCOs. DA was unable to identify developing hypotension in this setting, while DC only showed modest differences between groups. These findings highlight that DA and DC thresholds need to be adjusted for antenatal risk factors, potentially limiting their clinical utility.

Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep.

OBJECTIVE: Cardiotocography is widely used to assess fetal well-being during labour. The positive predictive value of current clinical algorithms to identify hypoxia-ischaemia is poor. In experimental studies, fetal hypotension is the strongest predictor of hypoxic-ischaemic injury. Cohort studies suggest that deceleration area and deceleration capacity of the fetal heart rate trace correlate with fetal acidaemia, but it is not known whether they are indices of fetal arterial hypotension. DESIGN: Prospective, controlled study. SETTING: Laboratory. SAMPLE: Near-term fetal sheep. METHODS: One minute of complete umbilical cord occlusions (UCOs) every 5 minutes (1:5 min, n = 6) or every 2.5 minutes (1:2.5 min, n = 12) for 4 hours or until fetal mean arterial blood pressure fell <20 mmHg. MAIN OUTCOME MEASURES: Deceleration area and capacity during the UCO series were related to evolving hypotension. RESULTS: The 1:5 min group developed only mild metabolic acidaemia, without hypotension. By contrast, 10/12 fetuses in the 1:2.5-min group progressively developed severe metabolic acidaemia and hypotension, reaching 16.8 ± 0.9 mmHg after 71.2 ± 6.7 UCOs. Deceleration area and capacity remained unchanged throughout the UCO series in the 1:5-min group, but progressively increased in the 1:2.5-min group. The severity of hypotension was closely correlated with both deceleration area (P < 0.001, R2  = 0.66, n = 18) and capacity (P < 0.001, R2  = 0.67, n = 18). Deceleration area and capacity predicted development of hypotension at a median of 103 and 123 minutes before the final occlusion, respectively. CONCLUSIONS: Both deceleration area and capacity were strongly associated with developing fetal hypotension, supporting their potential to improve identification of fetuses at risk of hypotension leading to hypoxic-ischaemic injury during labour. TWEETABLE ABSTRACT: Deceleration area and capacity of fetal heart rate identify developing hypotension during labour-like hypoxia.

Inverse changes in fetal insulin-like growth factor (IGF)-1 and IGF binding protein-1 in association with higher birth weight in maternal diabetes.

OBJECTIVE: The insulin like growth factor (IGF) system plays a key role in regulating fetal growth, is metabolically regulated, and may influence development of increased birth weight in offspring of mothers with diabetes. We examined IGF-1 and IGF binding protein-1 (IGFBP-1) concentrations in cord blood samples from offspring of mothers with gestational and type 2 diabetes. DESIGN AND PATIENTS: Case-control study of Maori and Pacific Island mothers recruited prospectively at Middlemore Hospital, South Auckland, New Zealand. MEASUREMENTS: Cord blood (for insulin, IGF-1 and IGFBP-1) was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation from138 mothers with gestational diabetes (GDM), 39 mothers with type 2 diabetes (T2DM) and 95 control mothers. RESULTS: Babies born to mothers with both GDM and T2DM had significantly increased birth weight (Z-score birth weight mean +/- SD: GDM 0.94 +/- 1.31, T2DM 0.53 +/- 1.1) compared to controls (Z-score birth weight -0.08 +/- 1.10). IGFBP-1 was significantly reduced in both diabetic groups (median interquartile range: GDM 67(31-137) ng/ml, T2DM 59(29-105) ng/ml, control 114(56-249) ng/ml). Cord IGF-1 was significantly increased in cord blood of infants of mothers with GDM (42.2 +/- 16.3 ng/ml vs. control 34.7 +/- 18.5 ng/ml) but not T2DM (38.7 +/- 17.4 ng/ml). In all offspring, IGF-1 and IGFBP-1 were positively and negatively correlated with birth weight, respectively. CONCLUSIONS: Maternal diabetes results in inverse changes of circulating fetal IGF-1 and IGFBP-1 at birth. A decrease in circulating IGFBP-1 and to a lesser extent an increase in circulating IGF-1 may present an important mechanism that contributes to increased birth weight in diabetic pregnancies.

ST waveform changes during repeated umbilical cord occlusions in near-term fetal sheep.

OBJECTIVE: This study was undertaken to determine whether changes in the fetal ST waveform during repeated umbilical occlusion reflect the development of hypotension and acidosis. STUDY DESIGN: Chronically instrumented, near-term fetal sheep received 1-minute total umbilical cord occlusion either every 5 minutes for 4 hours (1:5 group, n = 8), or every 2.5 minutes until blood pressure fell <20 mm Hg on 2 successive occlusions (1:2.5 group, n = 8). RESULTS: Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH = 7.34 +/- 0.07 after 4 hours). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.1 after the final occlusion). There was a marked increase in ST waveform height during occlusions; this increase was greater in the 1:2.5 group (P <.001), but there was overlap between the groups. ST waveform height between occlusions was significantly higher in the 1:2.5 group (P <.001) until negative and biphasic ST waveforms developed in these fetuses between occlusions in the final 30 minutes. CONCLUSION: ST waveform elevation occurs during umbilical cord occlusions but only crudely reflects the severity of hypoxia. Interocclusion waveform height may be a better reflection of the severity of hypoxia. The appearance of biphasic and negative waveforms between occlusions may be a useful marker for severe decompensation.

Fetal heart rate overshoot during repeated umbilical cord occlusion in sheep.

OBJECTIVE: To assess the clinical utility of overshoot fetal heart rate (FHR) decelerations by examining their occurrence after umbilical cord occlusions of varying frequency and length in near-term fetal sheep. METHODS: Fetuses were allocated to the following three groups: 1-minute umbilical cord occlusion repeated every 5 minutes (1:5 group, n = 8) or every 2.5 minutes (1:2.5 group, n = 8) or 2-minute occlusions repeated every 5 minutes (2:5 group, n = 4). Occlusions were continued for 4 hours or until fetal mean arterial pressure decreased below 20 mmHg during two successive occlusions. RESULTS: In the 1:5 group, fetuses tolerated 4 hours of occlusion without hypotension or clinically significant acidosis and overshoot never occurred. In the 2:5 group, fetuses rapidly became hypotensive and acidotic, and occlusions were terminated at 116.3 +/- 22.9 min (mean +/- standard deviation). Overshoot was seen after every occlusion, starting with the first occlusion. In the 1:2.5 group, fetuses became progressively acidotic and hypotensive and occlusions were stopped at 183.1 +/- 42.8 min. Overshoot occurred after 91.6 +/- 42.5 minutes, at a pH of 7.17 +/- 0.06, base deficit 9.3 +/- 4.5 mmol/L. After the appearance of overshoot there was a more rapid decrease in fetal mean arterial pressure (0.25 [0.21, 0.35, 25-75th percentile] mmHg/minute versus 0.11 [0.03, 0.15] mmHg/minute before overshoot appeared, P <.01). CONCLUSION: These data suggest that overshoot is related to longer (2-minute) occlusions or to developing fetal acidosis and hypotension during 1-minute occlusions. This pattern could have clinical utility, as 1-minute contractions are typical of active labor.

The evaluation of an expert system for the analysis of umbilical cord blood.

An assessment of neonatal outcome may be obtained from analysis of blood in the umbilical cord of an infant immediately after delivery. This can provide information on the health of the new-born infant, guide requirements for neonatal care, but there are problems with the technique. Samples frequently contain errors in one or more of the important parameters, preventing accurate interpretation and many clinical staff lack the expert knowledge required to interpret error-free results. The development and implementation of an expert system to overcome these difficulties has previously been described. This expert system validates the raw data, provides an interpretation of the results for clinicians and archives all the results, including the quality control and calibration data, for permanent storage. Issues regarding the clinical evaluation of this system are now detailed further, along with some clinical results illustrating the potential of such a system.

Fetal seizures causing increased heart rate variability during terminal fetal hypoxia.

Fetal seizures together with both abnormal breathing movements and fluctuations in fetal blood pressure and heart rate resulting in increased fetal heart rate variability have been observed in brain-damaged fetal sheep shortly after an asphyxial insult. We report a clinical example of convulsions and increased heart rate variability during terminal fetal hypoxia.

Antecedents of neonatal encephalopathy with fetal acidaemia at term.

OBJECTIVE: To identify the relative contribution of antenatal hypoxia, obstetric catastrophe during labour and fetal monitoring practice to the occurrence of neonatal encephalopathy associated with acidaemia at term. DESIGN: Prospective study. SETTING: Tertiary referral hospital in Auckland, New Zealand. SAMPLE: Twenty-two term babies born between January 1996 and October 1997 with umbilical artery pH < or = 7.09 (median 6.88) or 5 minute Apgar score < 7 (median 5.0), and moderate to severe encephalopathy within five hours of birth. METHODS: Antenatal and intrapartum events and fetal heart rate monitoring practice were reviewed by an experienced obstetrician. RESULTS: More than half the cases were associated with events beyond the control of the clinician: 5 of 22 (23%) had evidence of antenatal hypoxia and 5 of 22 (23%) experienced an obstetric catastrophe during labour. Use of continuous fetal monitoring techniques or the interpretation of fetal heart rate changes was suboptimal in 8 of 12 cases. Continuous monitoring was not performed at all in three cases. All pregnancies were of either low or medium risk; none had proteinuric hypertension and no case was breech, small for gestational age or had a gestational age > or = 42 weeks. CONCLUSIONS: A significant proportion of babies with encephalopathy associated with acidaemia at term experienced either antenatal hypoxia or catastrophic events beyond the control of the clinician. Further improvements in obstetric care will require greater vigilance in low to medium risk pregnancies and improved fetal monitoring practice during both induction and labour.

Fetal heart rate variability changes during brief repeated umbilical cord occlusion in near term fetal sheep.

OBJECTIVE: To determine whether changes in fetal heart rate variation during repeated umbilical cord occlusions reflect evolving cardiovascular compromise in near term fetal sheep. DESIGN: Fetal heart rate variation, fetal mean arterial pressure, electroencephalogram (EEG) and acid-base status were measured during one minute umbilical cord occlusions, repeated either every five minutes (1:5 group) or every 2.5 minutes (1:2.5 group) for four hours or until mean arterial pressure fell below 20 mmHg for two successive occlusions. SAMPLE: Fourteen chronically instrumented fetal sheep, mean gestation 126.3 (2.6) days. RESULTS: Cord occlusion caused variable decelerations with initial sustained hypertension. In the 1:5 occlusion group mean arterial pressure remained elevated throughout, with little change in acid-base status (pH = 7.34 (0.07), base deficit = 1.3 (3.9) after 4 hours) and no significant change in fetal heart rate variation. In contrast, in the 1:2.5 group from the third occlusion there was progressive hypotension during occlusions, severe progressive metabolic acidaemia (pH 6.92 (0.1), base deficit 17.0 mmol/L (4.7) after the last occlusion) and marked EEG suppression (P < 0.01). Fetal heart rate variation increased with the onset of occlusions (P < 0.05) and then progressively fell with continued occlusions. During the last 30 minutes of occlusions, fetal heart rate variation was severely suppressed in four, but increased in two fetuses, while all six fetuses developed overshoot-instability of fetal heart rate and mean arterial pressure following each occlusion. CONCLUSIONS: Acute progressive asphyxia was typically associated with an immediate, transient increase in fetal heart rate variation. Subsequently variation became suppressed in only two-thirds of fetuses during terminal acidaemia and hypotension. Fetal heart rate overshoot-instability may be a useful marker of fetal decompensation following variable decelerations.

The incidence and management of failed Pipelle sampling in a general outpatient clinic.

A prospective audit was performed on 100 consecutive patients who underwent Pipelle endometrial sampling in a general outpatient clinic setting. The indications for sampling were abnormal menstrual bleeding (AMB, 65), intermenstrual or postcoital bleeding (IMB/PCB, 7), postmenopausal bleeding (PMB, 28). An insufficient sample was obtained in 33 women: (AMB 14, 21.5%); IMB/PCB, (0); PMB 19,68%). In 3 women the Pipelle was unable to be introduced through the cervix; in the remainder an insufficient sample for histological diagnosis was obtained. Registrars and resident doctors were more likely to sample insufficiently. In the AMB group all but 1 woman with an insufficient sample had further investigations or treatment but 7 of 19 (37%) of PMB patients had no further investigations. Where definitive histology was available, endometrial polyps or submucous fibroids were found in half of the cases with an inadequate Pipelle sample. Pipelle sampling detected only 1 of the 2 cases of endometrial cancer in this study.

Do fetal electrocardiogram PR-RR changes reflect progressive asphyxia after repeated umbilical cord occlusion in fetal sheep?

The aim of this study was to determine whether there is a relationship between changes in PR-RR correlation of the fetal ECG and progressive changes in fetal acid-base status and blood pressure (BP) during repeated umbilical occlusion. Chronically instrumented fetal sheep at 126.8+/-0.6 d (mean+/-SEM) were randomized to receive 1 min of total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n=8), or every 2.5 min until BP fell <2.7 kPa (20 mm Hg) on two successive occlusions (1:2.5 group; n=8). The PR-RR correlation was determined in 5- or 2.5-min intervals. Umbilical cord occlusion caused variable decelerations with initial sustained hypertension. In the 1:5 group BP remained elevated throughout, and there was little change in acid-base status (pH=7.34+/-0.07, base deficit=1.3+/-3.9 after 4 h). In contrast, after the third occlusion the 1:2.5 group showed progressive hypotension during occlusions, and severe progressive metabolic acidemia (pH 6.92+/-0.1, base deficit 17.0+/-4.7 mmol/L after the last occlusion). In both groups, the PR-RR relationship switched from positive to negative with the onset of occlusions, then reverted to positive after a variable interval. In the 1:2.5 group later reversion of the PR-RR to positive was associated with earlier and more prolonged hypotension during the middle and end of the occlusion series (p < 0.001). We conclude that the initial switch to a negative PR-RR relationship during repetitive umbilical occlusion was due to a reflex-mediated response unrelated to fetal acidosis or hypotension. Both stable well compensated fetuses and severely hypoxic, hypotensive fetuses subsequently showed a positive PR-RR correlation.

The development and implementation of an expert system for the analysis of umbilical cord blood.

An assessment of neonatal outcome may be obtained from analysis of blood in the umbilical cord of the infant immediately after delivery. This can provide information on the health of the newborn infant, guide requirements for neonatal care, and is recommended practice of the Royal College of Obstetricians and Gynaecologists. However, there are problems with the technique. Samples frequently contain errors in one or more of the important parameters, preventing accurate interpretation and many clinical staff lack the expert knowledge required to interpret error-free results. In this paper the development and implementation of an expert system to overcome these difficulties is described. The expert system validates results, provides a textual interpretation and archives all results to database for audit, research and medico-legal purposes. The system has now been in routine clinical use for over 3 years in Plymouth, and has also been installed in several other hospitals in the UK. Results are presented in which the types and frequency of errors are established and the user acceptance of the system is determined.

A multicentre comparative study of 17 experts and an intelligent computer system for managing labour using the cardiotocogram.

OBJECTIVES: To investigate 1. whether an intelligent computer system could obtain a performance in labour management comparable with experts when using cardiotocograms (CTGs), patient information, and fetal blood sampling and 2. whether experts could be consistent and agree in their management of labour. SUBJECTS: An intelligent computer system and 17 clinicians experienced in fetal monitoring from 16 centres in the UK. DESIGN: Fifty cases with complete intrapartum CTGs and clinical data were reviewed by each expert and the system independently on two occasions, at least one month apart. Each CTG was scored in 15 min segments according to a protocol and estimates of the cervical dilatation and fetal scalp blood pH were given when requested. MAIN OUTCOME MEASURES: Consistency and agreement in the recorded scores, agreement and timing of cases recommended for caesarean sections, fetal blood sampling rates, intervention in cases with poor outcome and intervention in cases with good clinical outcome. RESULTS: The system: 1. Agreed with experts well and significantly better than chance (67.33%, kappa = 0.31, P << 0.001). 2. Was highly consistent (99.16%, kappa = 0.98, P << 0.001) when used by two operators independently. 3. Recommended no unnecessary intervention in cases with normal delivery and good condition (cord artery pH > 7.15, vein pH > 7.20, 5 min Apgar > or = 9 and no resuscitation). This was better than all but two of the experts. 4. Recommended delivery by caesarean section in 11 cases; at least 15 of the 17 experts in each review also recommended caesarean section delivery in these cases. The majority did so within 15 min of the system and two-thirds did so within 30 min. 5. Identified as many of the birth asphyxiated cases (cord arterial pH < 7.05 and BDecf > or = 12, and Apgar score at 5 min < or = 7 with neonatal morbidity) as the majority of experts and one more than was acted upon clinically. The experts were found to be consistent and to agree. There was good agreement in the cases and the timing of caesarean section recommendations. The majority of experts did not recommend operative intervention in cases which had a normal delivery and good outcome, but did recommend operative interventions in 10 of 12 cases delivered with cord arterial pH < 7.05. However, in one of the cases delivered with birth asphyxia, 14 of the 17 experts and the system failed to recommend intervention. CONCLUSIONS: The system's performance was found to be indistinguishable from the experts' in the 50 cases examined, but it was more consistent. This demonstrates the potential for an intelligent computer system to improve the interpretation of the CTG and decrease intervention. Furthermore, the good performance of most experts in this study demonstrates the potential effectiveness of the CTG and raises important questions regarding why the CTG has fallen short of expectations in current practice.

Four channel foetal ECG data collection system.

Recently there has been an increased interest in the development of improved techniques for the diagnosis of foetal distress during labour. Many of the techniques have been based on extracting extra information from the foetal ECG obtained from a scalp electrode. To fully develop and test the prototypes of these systems requires recorded data from patients. However due to the poor level of prediction of these cases at present, it is very difficult to collect the data using simple single channel data collection systems. The system described here will automatically collect and document data from up to four deliveries at the same time and does not add to the work load of the clinical staff.