C.W.G. Redman

Numerical analysis of the human fetal heart rate: The quality of ultrasound records

A method is described for the computerized numerical analysis of fetal heart periods (pulse intervals). It uses a digital filter to separate the record into its high- and low-frequency components and, after removal of baseline variation, identifies accelerations and decelerations of all sizes. It provides an objective method for separating episodes of high heart period variation, normally associated with fetal movements, from episodes of low variation. When Doppler ultrasound is used in the last 10 weeks of gestation, failure time averages 40%. Signal loss is not randomly distributed; it is on average 75% greater during episodes of high heart period variation, although it is not particularly associated with fetal movements as identified by nurse or patient. Nevertheless a comparison of simultaneous direct ECG and ultrasound records shows that the latter provide reasonable statistical measures of heart period variation, and also of accelerations and decelerations provided that signal loss is taken into account. The system thus provides a particularly useful adjunct to the analysis of antenatal human fetal heart rate records.

System 8000: computerized antenatal FHR analysis.

SYSTEM 8000 is a computerized system for antenatal fetal heart rate (FHR) analysis, with interaction online to ensure good quality recording and to minimize the time required to obtain the necessary information (based on fetal movements and tocodynamometer readings as well as FHR). The equipment consists of a Personal Computer with hard disk, interfaced to a fetal monitor. Software is written in C. An extensive definition is given on most of the functions and parameters as calculated by the system, e.g. record quality, uterine contraction peaks, basal heart rate, variation, decelerations and accelerations. System 8000 is designed to take account of the episodic changes in FHR and fetal movements characteristic of sleep states. Their presence naturally affects the mean FHR variation calculated over, say 20-30 mins. But, as the amplitude of these episodes is attenuated in association with growth retardation and hypoxaemia, the measurements of variation decline. In practice inter- and intra-observer variation is greatest in assessing FHR variation. Yet a decrease in variation is the most reliable index of fetal deterioration. The system measures FHR variation accurately and reproducibly, as well as fetal movements. In the synoptic display these two equally important fetal variables are given their rightful prominence. It has been interesting to observe how rarely the basal FHR changes in fetuses suffering progressive respiratory insufficiency, and how extreme tachycardia (a basal rate greater than 170/min) tends to reflect other fetal problems such as infection or maternal pyrexia.

Pattern of the normal human fetal heart rate

Summary. With an improved method for fitting baselines to human fetal heart‐rate traces, the patterns of episodic variations, accelerations and decelerations were similar in 215 64‐min records from normal pregnancies and in 95 with mild hypertension and normal outcome. The change in signal loss with gestational age, by Doppler ultrasound for recording heart rate, was entirely due to the greater loss in episodes of high heart‐rate variation. The changes in the numbers and sizes of accelerations and decelerations with gestational age were described. There were many records which had only one or no acceleration at 28–33 weeks gestation (16.2%) or 34–41 weeks (7.3%). However, only two (0.7%) had episodes of high heart‐rate variation lasting <10 min from 28 weeks onwards. The presence of these episodes, with clusters of fetal movements, is therefore likely to be a better numerical index of normality.

Short-term variation In abnormal antenatal fetal heart rate records

In a retrospective study the relation of reduced fetal heart rate variation to fetal acidemia was analyzed with a computerized system for numeric analysis. Between 1983 and 1987, 78 pregnancies were identified in which at least one record of the fetal heart rate had very low long-term variation. The outcome was analyzed to determine the numeric criteria of fetal heart rate variation that most efficiently detect a fetus that will die (preterminal) or is dying (terminal). Because fetal compromise was found on occasion to be associated with a slow sinusoidal fetal heart rate rhythm that increased measures of long-term variation. It was necessary to define a new index of short-term fetal heart rate variation (the 1/16 minute epoch-epoch variation). This was closely related to long-term variation (r = 0.9) but provided better detection of preterminal records as judged by metabolic acidemia at delivery or intrauterine death.

Improvements in the registration and analysis of fetal heart rate records at the bedside

Summary. A microprocessor system is described for on‐line analysis of the fetal heart rate detected by conventional Doppler systems. A brief account is given of the instrumentation and program structure. The system has been tested by analysing normal and abnormal antenatal fetal heart rate records. Pulse Doppler with autocorrelation measurement of the fetal pulse interval reduced the signal loss in clinical practice by a factor of 10, to an average of 2.1% in 629 records from uncomplicated pregnancies. Yet it is still necessary to identify signal loss, because it occasionally rises t o unacceptable levels in association with fetal movements or hiccups. Medium‐term measures of fetal heart rate variation (within 16–0.1 cycles/min) varied with gestational age, but were a better index of fetal well‐being than longer‐term measures. The application of the system t o fetal monitoring is illustrated.

NUMERICAL ANALYSIS OF THE NORMAL HUMAN ANTENATAL FETAL HEART RATE

A numerical method for separation of the frequency components of the fetal heart rate, and for identifying episodes of high or low variation, was applied to 196 64‐minute ultrasound records in normal pregnancies during the last half of gestation. Most variables of heart period variation increased with gestation, as did the incidence of accelerations. Before 35 weeks, accelerations of ≥14 beats/minute did not occur in all records. Cyclic episodes of low and high variation (‘unreactive’ and‘reactive’ episodes), associated with rest‐activity cycles, could be identified from 27 weeks onwards. After 36 weeks gestation the length of low variation episodes increased and the variation during these episodes fell. Near term, low variation episodes lasted up to 40 minutes. It is concluded that on scrutiny of fetal heart rate records for evidence of normality, or otherwise, due account should be taken of gestational age.

Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom

OBJECTIVE Because the trace element selenium behaves as an antioxidant and peroxynitrite scavenger when incorporated into selenoproteins, our objective was to determine whether low selenium status was associated with a greater risk of occurrence of preeclampsia. STUDY DESIGN Fifty-three preeclamptic patients and 53 matched pregnant controls at the John Radcliffe Hospital, Oxford, gave clippings of their toenails (laid down from 3-12 months previously) for selenium determination by neutron activation analysis. Clinical characteristics of the women and their infants were recorded. Statistical analysis was by Wilcoxon signed rank test and odds ratios were calculated by the ratio of discordant pairs. RESULTS Median toenail selenium concentrations in the preeclamptic subjects were significantly lower than in their matched controls (P=.001). Being in the bottom tertile of toenail selenium was associated with a 4.4-fold (95% CI 1.6-14.9) greater incidence of the condition. Within the preeclamptic group, lower selenium status was significantly associated (P=.029) with more severe expression of disease, as measured by delivery before 32 weeks. CONCLUSION In the light of the reduction in selenium status in a number of European countries in recent years, this study raises the question of whether a small increase in selenium intake might help prevent preeclampsia in susceptible women.

Women with Preeclampsia Have Increased Serum Levels of Pregnancy‐Associated Plasma Protein A (PAPP‐A), Inhibin A, Activin A and Soluble E‐selectin

Objective. Poor placentation in early pregnancy is thought to lead to an excessive maternal systemic inflammatory response, which causes the maternal syndrome of preeclampsia. The aims of this retrospective study were to confirm old reports of increased blood levels of pregnancy‐associated plasma protein A (PAPP‐A) in preeclampsia and how its levels correlate with the levels of other placental and endothelial proteins that are reported to be elevated in preeclampsia. Methods. Nineteen women with preeclampsia symptoms were matched with 19 normal pregnant controls for gestational age, maternal age, and parity. PAPP‐A, placental pregnancy‐specific β1‐glycoprotein (SP1), inhibin A, activin A, and sE‐selectin were measured in serum using specific ELISAs. Results. Maternal serum levels of PAPP‐A, inhibin A, activin A and sE‐selectin were increased in women with preeclampsia (mean 157.7 vs. 76.85 mIU/mL, p=0.005; 3.08 vs. 1.51 ng/mL, p=0.002, 32.36 vs. 3.77 ng/mL, p<0.001 and 62.15 vs. 46.37 ng/mL, p=0.02 respectively), compared to controls. Serum levels of SP1 were not altered in preeclampsia. PAPP‐A (r=0.636, p<0.01) had a positive correlation with sE‐selectin in patients with preeclampsia. Serum inhibin A and activin A had a significant positive correlation with each other in preeclampsia. Conclusions. Raised levels of PAPP‐A in preeclampsia confirm earlier reports. Activin A showed the highest increase over the controls and is thus likely to be a better serum marker for this pathology than the other markers that were tested.

Antenatal fetal heart rate variation in relation to the respiratory and metabolic status of the compromised human fetus

Summary. Three groups of women were delivered by caesarean section before labour: for an abnormal fetal heart rate (FHR) trace (21 cases, group 1), or for maternal deterioration in severe pre‐eclampsia without gross fetal heart rate abnormalities (20 cases, group 2), or to avoid mechanical difficulties in labour at term (30 cases, group 3). The mean gestational ages of the first two groups were 32 weeks with a high proportion of infants small‐for‐gestational‐age. In group 1, FHR variation (mean range of pulse intervals) was less than half (20·6 SE 1·2 ms) of the normal value at the same age (44·4 SE 1·5 ms). This was associated with hypoxaemia (mean umbilical artery Po2 of 6 mmHg at delivery), with evidence of compensation shown by an elevated amniotic fluid erythropoietin. The fetuses were hypoglycaemic and had greater umbilical artery blood alanine concentrations, but no large changes in adenine nucleotide or endorphin plasma concentrations. Although there was a minor degree of respiratory acidaemia at birth, there was not significant metabolic acidaemia. The results demonstrate that the reduced variation of ‘suboptimal’ and ‘decelerative’ fetal heart rate records is associated with fetal hypoxaemia and evidence of nutritional deprivation, but not with asphyxia.

Strategy for Standardization of Preeclampsia Research Study Design

Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies