Standards for the quantification of serial changes in Doppler resistance indices from the umbilical arteries Philip Owen”‘*, Simon Ogston” “Department of Obstetrics and Gynaecology, Ninewells Hospital and Medical School. Dundee DDI TSY, Scotland hDepartment of Epidemiology and Public Health, Ninewells Hospital ami Medico/ School. Dundee DDl 9SY, Scotland Received 29 May 1996; revised 7 January 1997; accepted 7 January 1997 Abstract Two-hundred-and-seventy-four low-risk pregnancies underwent serial ultrasound examina- tions in order to determine the mean and standard deviation of the change in umbilical artery resistance indices with advancing gestation. There is an almost constant rate of reduction in the A/B ratio and the Pulsatility index over time from 28 weeks gestation until term. By calculating the standard deviation score of such changes, these reference ranges allow the change in the A/B ratio and Pulsatility index to be quantified. Such appropriately derived standards permits the further investigation of the evolution of abnormalities of feto-placental perfusion with regards to perinatal outcome. 0 1997 Elsevier Science Ireland Ltd. All rights reserved Kqvwords: Doppler; Resistance index; Longitudinal 1. Introduction The investigation of feto-placental perfusion with Doppler ultrasound has become an important component of the modem assessment of fetal well-being in the late second and third trimesters [l]. In order to calculate the amount of blood flowing in a *Corresponding author. Tel.: +44 1382 660111 ext. 2147; fax: +44 1382 633847. 037%3782/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reerved PII SO378-3782(97)01873-2
Transcript
Standards for the quantification of serial changes in Doppler resistance indices from the umbilical
arteries
Philip Owen”‘*, Simon Ogston”
“Department of Obstetrics and Gynaecology, Ninewells Hospital and Medical School. Dundee DDI TSY, Scotland
hDepartment of Epidemiology and Public Health, Ninewells Hospital ami Medico/ School. Dundee DDl 9SY, Scotland
Received 29 May 1996; revised 7 January 1997; accepted 7 January 1997
Abstract
Two-hundred-and-seventy-four low-risk pregnancies underwent serial ultrasound examina- tions in order to determine the mean and standard deviation of the change in umbilical artery resistance indices with advancing gestation. There is an almost constant rate of reduction in the A/B ratio and the Pulsatility index over time from 28 weeks gestation until term. By calculating the standard deviation score of such changes, these reference ranges allow the change in the A/B ratio and Pulsatility index to be quantified. Such appropriately derived standards permits the further investigation of the evolution of abnormalities of feto-placental perfusion with regards to perinatal outcome. 0 1997 Elsevier Science Ireland Ltd. All rights reserved
Kqvwords: Doppler; Resistance index; Longitudinal
1. Introduction
The investigation of feto-placental perfusion with Doppler ultrasound has become an important component of the modem assessment of fetal well-being in the late
second and third trimesters [l]. In order to calculate the amount of blood flowing in a
037%3782/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reerved PII SO378-3782(97)01873-2
40 P. Owen, S. Ogston I Early Human Development 49 (1997) 39-47
vessel, accurate estimation of the angle of insonation and the diameter of the vessel must be possible. Significant errors in estimating these parameters together with errors in estimating fetal weight means that the measurement of actual blood flow is not useful in clinical practice [2]. In contrast, the semi-quantitative assessment of the flow velocity waveform (FVW) has been widely adopted since the signals required are easily obtained and reproducible [3]. The fetal and umbilical circulations are typified by low resistance flow patterns demonstrating continuous forward flow where the velocity in diastole is inversely related to peripheral impedance [4].
In a manner similar to that where fetal size is described in relation to reference ranges derived from cross-sectional studies and fetal growth quantified with reference to longitudinally derived standards [5,6], single measures or serial changes in the Doppler resistance index should be expressed with reference to cross-sectional and longitudinally derived datasets respectively.
Currently available reference ranges for the umbilical artery resistance indices are variously based upon cross-sectional datasets [7-91 although some reference ranges include more than one measurement from each subject [lo]. Published longitudinal studies are often based on small numbers of pregnancies or with the data analysed and presented as if it were derived from a cross-sectional study [ 1 l-161. Other reference ranges are open to criticism on the basis of their post-recruitment exclusions such that the studied population no longer represents a low-risk population at initial presentation [ 16- 191.
This paper describes the construction of new reference ranges appropriate for the serial analysis of the A/B ratio and Pulsatility index of the umbilical artery derived from the longitudinal study of a large, well defined and accurately dated low-risk antenatal population.
2. Subjects and methods
Three-hundred-and-thirteen women attending the ante-natal clinic at our hospital were enrolled into a study of fetal growth which has been reported in detail elsewhere [20]. Entry criteria were gestational age of less than 85 days confirmed by crown- rump length measurement, singleton pregnancy and the absence of recognised risk factors for accelerated or retarded fetal growth including a history of a previous small for gestational age (SGA) infant, existing medical disorders such as hypertension, diabetes mellitus and auto-immune disease or heavy smoking ( > 20 cigarettes per day). Informed consent was obtained from all women prior to trial entry and local ethical committee approval was obtained for a study of serial ultrasound in low-risk pregnancy.
All the subjects were scanned for fetal anomaly at 18 weeks’ gestation which is routine practice in our department. Thereafter, they were sequentially entered into one of four pre-determined scanning schedules (n, number continuing in the study).
l A. 26, 30, 32, 34, 36, 38, 40 weeks. (FZ = 72) l B. 27, 31, 33, 35, 37, 39, 41 weeks. (n = 72)
P. Owen, S. Ogston I Early Human Development 49 (1997) 39-47 ‘11
l C. 28, 32, 34, 36, 38, 40 weeks. (n = 63) l D. 29, 33, 35, 31, 39, 41 weeks. (n = 67)
All umbilical artery resistance index measurements were made using an Aloka SSD650 real-time ultrasound scanner using a 3.5 MHz probe and duplex pulsed wave Doppler ultrasound by the first author. A free floating segment of cord was insonated during a period of fetal quiescence and in the absence of fetal breathing movements and if the fetal heart rate was between 110 and 150 beats per min. Efforts were made to obtain a signal from approximately mid-way along the length of the cord since the waveform obtained can be influenced by the site of insonation 1211. Three consecu- tive waveforms were analysed and the mean of the three measurements recorded. The A/B ratio and Pulsatility index are in common usage and these resistance indices were therefore recorded [22].
Neonatal data was collected from the infant’s discharge summary and scrutiny ot the mother’s case notes. Birthweight was adjusted to take account of the mothers height and mid-pregnancy weight then accorded a centile position according to gestational age, sex and birth-order according to standard nomograms 1231. Neonatal nutritional status was assessed from the Ponderal index which was available in 257 (94%) cases. Neonatal length was measured on a neonatal anthropometer on the third day of life by the first author and the mean of three measurements recorded. A centile position for the Ponderal index was accorded with reference to established standards
[241.
2.1. Statistical analysis
To analyse the rates of change of the A/B ratio and the PI we looked at pairs of observations made 28 days apart. From these we calculated the daily change in A/B and PI rates for each individual (Y, - Y,.,,)/28 and the average size at the mid time- point (mean; (Y, + Y,.Z,)/2). In subjects where the measurement was not made at exactly 28 days, but within 2 days either side, the daily change was the observed difference divided by the difference in days. Similar calculations were performed for differences based on 14 day separations. Daily change in the A/B and PI was plotted against maturity where maturity is taken as the value at the second measurement. The mid-point of the interval is the indicated value minus 14 days for the 28 day rates. For each week of gestation the mean and standard deviation (S.D.) of the observed rates were calculated.
3. Results
Two-hundred-and-seventy-four women continued in the study. A lower incidence of unemployment was the only significant demographic feature between those subjects continuing and those defaulting from the study. There was one stillbirth and one neonatal death amongst the 274 subjects continuing in the study. The stillbirth
42 P. Owen, S. Ogston I Early Human Development 49 (1997) 39-47
Table 1 Obstetric features of volunteers
No. %
Livebirth Stillbirth Neonatal death Induction of labour Mode of delivery
was at term and ‘unexplained’. The neonatal death followed intrapartum fetal hypoxia. No exclusions from the analysis were made since we were interested in the characteristics of a population considered low-risk at the initial ante-natal visit. The mean number of Doppler recordings for each subject was 6.5.
The obstetric outcome for the studied population is shown in Table 1. The incidence of induction of labour, instrumental vaginal and abdominal delivery is similar to that of the obstetric population in our hospital with rates of 10.3, 16.1 and 16% respectively (Ninewells Hospital Obstetric Report 1993). Neonatal data is shown in Table 2 and the distribution of Ponderal index in Table 3. The mean birthweight was 3450 g (S.D. 595) and mean gestational age 279 days (S.D. 13). Fourteen subjects (5%) were delivered preterm with a median gestational age of 36 weeks (range; 32-36). After adjusting birthweight for maternal and obstetric features (23) the mean birthweight standard deviation score was 0.036. Eight and four percent of pregnancies fell below the tenth and third birthweight for gestation percentiles respectively.
The mean daily change and standard deviation of the A/B ratio and PI at specific gestational ages is presented in Table 4 and Table 5 respectively. In general the mean
Table 2 Neonatal data of subjects
No. %
Gestational >37 age weeks Adjusted birthweight
< 10th percentile < 3rd percentile
Apgar score
<7 at 1 min <7 at 5 min Admission to SCBU
260 95
22 8 11 4
33 12 3 1
14 5
SCBU, special care baby unit.
P. Owen. S. Ogston I Early Human Development 49 (1997) 39-47 43
Table 3 Distribution of neonatal Ponderal index amongst low-risk volunteers (n = 257)
Percentile n %
Ponderal index <IO IO-25 25-50 50-7s 75-90 >90
6 2.3 34 13 88 34.4 88 34.4 36 14
5 1.9
and SD. varied little with gestation. These reference ranges are derived from measurements made at 28 day intervals (values obtained from 14 day measurement intervals are very similar and can be obtained from the authors).
The change in resistance index (CRI) over time in an individual pregnancy can easily be quantified and expressed with these reference ranges by calculating the standard deviation score (Z score) for the CR1 from the following equation;
CR1 - mean CR1 Z score = S.D. -
where the CR1 is the daily change in the A/B ratio or PI between the two measurements and mean and S.D. refer to the reference range mean and standard deviation appropriate for the gestational age at which the second measurement of the resistance index was made.
Table 4 Mean and standard deviation of daily change in the A/B ratio
Based on 28 day measurement intervals (n, number paired observations) Mean value for all observations is -0.0032. S.D. 0.007.
4. Discussion
The umbilical artery flow velocity waveform (FVW) is characterised by continuous forward flow typical of a low resistance circuit, with a gradual fall in the resistance indices as gestation increases due to enlargement of the placenta with corresponding expansion of its vascular tree [l 11. A reduction in end-diastolic velocity suggests increased resistance to blood flow originating in the placenta and this pattern is seen in pregnancies complicated by apparent growth retardation and fetal compromise [25,26].
Analysis of the umbilical FVW has been employed to screen for small for gestational age (SGA) pregnancies 127,281 although standard fetal biometry is more reliable [29-3 11. The umbilical FVW is more usefully and appropriately employed in the identification of the fetus at increased risk of adverse perinatal outcome due to hypoxia and acidosis [32-341 and to discriminate between the SGA fetus with impaired placental function and that which is constitutionally small [27,35]. Random- ised controlled trials of umbilical Doppler ultrasound have demonstrated significant improvements in the use of resources and a reduction in perinatal mortality rates [36,37].
A potential criticism of this study’s methodology is the fact that we made no correction for the possible influence of fetal heart rate (FHR) upon the Doppler resistance indices. Some observers have reported a negative correlation between FHR and resistance indices [38,39] whereas other reports, involving a larger number of observations have failed to demonstrate a significant relationship [9,40]. The difference between the findings of these reports may be a reflection of differing sample sizes or methodology [41]. With very few exceptions [17], published reference
P. Owen, S. Ogston I Early Human Development 49 (1997) 39-47 35
ranges for umbilical Doppler indices have not corrected for the possible influence of FHR [9,10,13,14,16,18,19].
Furthermore, the Doppler recordings made in this study were performed during episodes of fetal apnoea and quiescence, when the individual fetus’ FHR would be expected to be at its baseline rate.
The evaluation of serial Doppler measurements from various maternal and fetal vessels has been reported in a number of studies. The method of quantifying the change in the Doppler resistance indices with time has involved the calculation of the difference of the standard deviation scores between two gestational ages [42-441. In all such studies the reference ranges have been obtained from cross-sectional datasets which are not specifically designed or appropriate for the quantification of serial measurements.
The importance of employing appropriate reference ranges for the interpretation of antenatal investigations should not be underestimated, particularly since the categori- zation of an individual pregnancy according to those reference ranges may directly influence clinical management. The recommended criteria for establishing reference ranges of fetal measurements have been highlighted [S]. To date, none of the published reference ranges for umbilical Doppler resistance indices adequately fulfils the criteria necessary for serial analysis. This study fulfils these criteria for the serial analysis of the A/B ratio and Pulsatility index from the umbilical artery (but is not suitable for the evaluation of a single value).
The value of the serial assessment of resistance indices from the umbilical artery, quantified with reference to appropriately derived normal data remains to be proven by prospective evaluation. The reference ranges presented in this study permit the appropriate quantification of changes in those resistance indices and therefore the further study of the role of placental vascular resistance in the evolution of intrauterine growth retardation and perinatal hypoxia.
Acknowledgments
PO was supported by Birthright to whom he is grateful.
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