ClinicalPractice

Antepartum Identification
of the Fetus at Risk
SUMMARY.A simple scoring technique for the antepartum identi fication of the fetus at risk has been devised and applied to 936 preg nancies managed at the Women's College Hospital, Toronto. This tech nique takes into account accepted adverse conditions and makes use of a concept of cumulative fetal risk. The score itself consists of three categories: pre-pregnancy data, con ditions developing during the present pregnancy before the onset of labour, and the gestational age attained at the time of scoring. The lowest potential for risk to the fetus is indicated by a score of 0 and the highest potential by a score of 10. None of the 144 perinatal deaths scored 0 and none of the 792 survivors scored higher than 6. The technique would appear to be valid when compared to a more complex risk-scoring technique and to measured estriol excretion in 85 cases. This technique may provide a basis for a rapid mental tally of fetalrisk factors in the identification and selection of the potential high-risk pregnancy for intensive management before, during and after labour.
It is an embarrassing fact that perinatal mortality on the North American continent has not been reduced materially below approxi mately 25 to 30 deaths per 1000

TABLE L.Profiles of Hypothetical Low- and High-risk Pregnancies Low-risk Pregnancy

Para 2 Age 23 5' 6" tall Weight 120 lbs. Lives near a hospital No complications in previous pregnancy More than two years since last pregnancy Has paid several antenatal visits Hemoglobin 12 g. No bleeding during this pregnancy No renal disease, bacteriuria or hypertension No abnormality of glucose tolerance

live births over the past 15 years. In this respect Canada ranks twelfth among a group of countries in the Western World.1 One of the reasons for this dismal performance has been our failure to recognize the fetus at risk. In current jargon a high-risk preg nancy is taken to mean a pregnancy in which some feature of the ma ternal environment or reproductive performance in the past represents a substantial risk to fetal well-being. In recent years much emphasis has been placed on the management of so-called high-risk pregnancies by sophisticated electronic and bio chemical monitoring techniques in the expectation that this approach would effect a significant improve ment in perinatal salvage. Whether this in fact proves to be true awaits the intensive study and long-term follow-up of a large num ber of these pregnancies. In preg nancies of diabetics and in those in

By using data from perinatal mortality surveys2' 3 and by draw ing on one's own obstetrical experi ence, it is possible to create hypo thetical patients who would repre sent the extremes of what one might call a fetal-risk spectrum. Our imaginary low-risk patient is pre sented in Table I. This woman represents the optimal situation: low parity, good spacing of preg nancies, proved reproductive per formance, diligent attendance to antenatal care, absence of bleeding complications, no coincidental medical disorders and, in particular, no diminution of renal function and no abnormality of carbohydrate metabolism. On the other hand, our hypo thetical high-risk case is a horror with excessive parity, poor per formance with perinatal losses, ante partum bleeding, diminution of renal function, obesity, hypertension and abnormal glucose tolerance. Clearly, all pregnant women fall ex
somewhere between these two
tremes.

High-risk Pregnancy
Para 8 5' 0" tall Blood pressure 160/110 Weight 170 lbs. Hemoglobin 9 g. Lives in isolated community History of two premature infants and one stillbirth Last baby 11 months ago Bleeding earlier in this pregnancy One antenatal visit this pregnancy Chronic pyelonephritis with decreased renal function Has an abnormal glucose-tolerance curve

Age 39

which there is Rh iso-immunization, the fetal risk is readily recognized and prediction can virtually be quantitated. In other clinical situa tions identification is extremely dif ficult and has on occasion seemed impossible. It is obvious that if we are to select high-risk pregnancies for intensive management before, during and after labour, we require some practical method of identify ing the fetus at risk.

THE SYNERGISM OF FETAL RISK Perinatal mortality surveys tend to consider various clinical condi tions or associations as isolated entities affecting the welfare of the fetus or newborn infant. Almost invariably this treatment in "pure cul ture" is undertaken without any statistical adjustment. The fact that the fetal risk is compounded when

(Continued on page 59)

JAMES W.

GOODWIN,

M.D., F.R.C.S.[C], JAMES T. DUNNE, M.D.,

F.R.C.S.[C],
Toronto

From the Department of Obstetrics and Gynecology, University of Toronto and The Women's College Hospital, Toronto, Ontario. Reprint requests to: Dr. James W. Goodwin, Women's College Hospital, 76 Grenville Street, Toronto 5, Ontario.

BRUCE W. THOMAS, M.D.,

57

Canad. Med. Ass. J., Oct. 18. 1969, vol. 101.458

toxemia combines with diabetes or essential hypertension in pregnancy has been recognized for some time. Browne4 referred to this situation as the "double hazard". In a study of 549 prolonged labours at the Boston Lying-In Hospital,5 it was found that the basic perinatal risk caused by long labour itself was increased in a curriulative fashion by the coexistence of various maternal, fetal and operative complications such as toxemia, postmaturity and pro longed rupture of membranes which are themselves associated with an increased fetal risk. The perinatal mortality and morbidity depended upon the number of superimposed conditions (Table II).
TABLE IL.Perinatal Mortality and Neonatal Morbidity for an Increasing Number of Adverse Obstetric Factors

We decided to use this concept of the synergism of fetal-risk factors to devise a simple scoring technique for the identification of the fetus at risk. Our main premise was that seemingly unrelated events (prior obstetrical complications, parity, age, certain medical conditions, antepartum bleeding, ete.) may pro duce a cumulative effect on the ulti mate fetal risk. We considered that such a scoring technique might as sist the physician managing obstet rical patients to identify high-risk pregnancies in a simple and prac tical way so that they migjit be given the special attention which they deserve.

development of this scoring technique we decided that certain prerequisites should be met:
would only Any excessively complex system serve to discourage those who might other wise have come to use it, particularly resi dents in training. Accordingly, we decided on a score of 0 to 10, similar to the now
1. The
score

METHODS Early in the

should be

uncomplicated.

Superimposed on the Basic Event of Prolonged Labour (20 hours +): from Goodwin, J. W. and Reid, D. E.5 (by permission).

familiar Apgar score.6 2. The score might be applied any num ber of times during pregnancy but always before the onset of labour. We insisted upon this for two reasons. Since we have gone to the trouble of identifying a highrisk pregnancy, presumably we would wish to have some time to attempt to correct any antepartum condition before the fetus encounters the added risks of labour and the initiation of extra-uterine life. Secondly, the admixture of risks stemming from both antepartum and intrapartum sources would only prove to be confusing. We wanted to know to what extent an antepartum (prenatal analysis of strictly factors would enable us and pre-pregnancy) to predict the risk to the fetus. Furthermore, the insistence upon a purely antepartum score allows us the possibility of re-scoring at different times during the pregnancy, whereas assessment during labour would obviously give us but one opportunity. 3. We used only those fetal-risk factors upon which there is general agreement and which unequivocally give rise to a significant increase in fetal risk. Contentious factors, such as bacteriuria, and parameters which are difficult to measure, such as the socio economic and emotional status, were omitted. 4. We wished to make use of the syner gism of various factors which affect the fetal risk. 5. We excluded sophisticated antenatal assessment methods, such as the estimation of estrogen excreted in 24-hour collections of urine, because we assume that physicians who have made use of these methods have already decided that they are dealing with at least a potential high-risk pregnancy.

TABLE
Baseline data
Age 35+. Age 40+. ParaO., Para 6+. Interval<2 years. Obesity (200 lbs.+: 90 kg.+). Diabetes B, C, D.

III..Antepartum Fetal Risk Score Obstetrical history Abortion

F. Chronic renal disease. with diminished renal function. with increased BUN.

Hypertension (pre-existing) 1 140+. 90+

SCORE (circle one)

160+. 110+

Stillbirth Neonatal death Surviving premature infant Antepartum hemorrhage Toxemia Difficult mid-forceps delivery Cesarean section Major congenital anomaly Baby 10 lbs.+ (or 4.5 kg.+) One instance of above. Two or more instances in different pregnancies Rh iso-immunized mother + Homozygous father. + History of erythroblastosis.

Bleeding, early (<20 wks.) alone. with pain. Bleeding, late (>20 wks.)

Present pregnancy

ceased. continues. with pain. with hypotension. Spontaneous premature rupture of membranes. Latent period 24 hrs.+. Anemia < 10 g.
<

Eclampsia. Hydramnios (single fetus). Multiple pregnancy. Abnormal glucose tolerance. Decreasing insulin requirement.
3 Maternal acidosis. 1 Maternal pyrexia. Pyrexia+ FHR> 160. 2 Rh negative: With rising titre. 2 With amniotic fluid Liley zone III. 3

Toxemia I. Toxemia II.

8g.

No prenatal care. < 3 prenatal visits.

Canad. Med. Ass. J., Oct. 18, 1969, vol. 101.459

59

The format of the score itself is presented in Table Ill.

It seemed logical to divide our assessment of the antepartum fetal risk into three categories:
1. The status of the woman as the pregnancy began. These factors we have referred to as baseline data and they include age, parity, prior reproductive performance and pre-existent medical complications. 2. The complications which have developed during the present pregnancy. 3. The gestational age reached at the time of scoring. Each category has a maximum score: the first two are limited arbitrarily to a maximum score of three and the last is given a limit of four. We have weighted the score in favour of the effect of gestational age because of the undoubted pennatal risk of immaturity and early prematurity. In other words, we believe that, taken alone, gestational age has a greater effect on perinatal mortality and morbidity than almost any other single factor.

AU 144 perinatal deaths (in excess of 20 weeks gestational age) from 1965 through 1968. There were 77 stillbirths and 67 neonatal deaths. All 395 public ward deliveries with surviving infants for the year 1968. Eighty-five pregnancies in which at least three antepartum determinations of 24-hour urinary estriol excretion were made. Twenty-one private cases in which the initial Apgar score of the infant was less than 4. Two hundred and ninety-one randomly selected private cases in which the initial Apgar score of the infant was 4 or more.

For each clinical condition or gestational age range, we have assigned a score from 1 to 4 based approximately on the appropriate perinatal mortality data supplied by two large surveys. We believe the weighting given is as proportional as possible considering the fact that this is a simple numerical score. Obviously a score of 0 would then be taken to mean the least potential for risk to the fetus and 10 the largest potential. As increasing gestational age and thus fetal maturity is achieved, the score drops appropriately until from 38 to 41 weeks no score is given in the gestational age category. If the pregnancy exceeds 42 weeks, the score mounts again in proportion to the extent that the pregnancy is prolonged. In order to determine the validity of this scoring technique, we applied it retrospectively to various groups of patients admitted to the obstetrical service of the Women's College Hospital. These were as follows:

We therefore considered a total of 936 cases. These pregnancies were studied in several ways. They were scored by the simple technique proposed and the resulting scores were related to the fetal outcome. They were scored by an alternate method which makes use of a technique based on perinatal mortality rates per 1000 live births for each adverse condition taken individually. Each major category of the simple score proposed (baseline data, present pregnancy, gestational age attained) was compared with the fetal outcome in order to validate the weighting given by the score for each of these categories. The one biochemical method we have been using consistently for the assessment of fetal well-being (the measurement of 24-hour urinary estriol excretion) was related to the simple score given to each of these cases.

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RESULTS Table IV presents the distribution of survivors and perinatal deaths for each score from 0 to 10. It will be noted that no pregnancy with a surviving infant scored higher than 6. It will also be noted that no pregnancy resulting in perinatal death obtained a score of zero.

TABLE IV.-Tabulation of Scores for Perinatal Deaths and Surviving Infants

Score 0 1 2 3 4 5 6 7 8 9 10 Survivors Apgar 4+ 222 258 159 78 38 12 4 0 0 0 0 Survivors Apgar <4 2 4 2 1 5 4 3 0 0 0 0 Fetal 0 1 3 6 8 9 17 11 9 9 4 Deaths Neonatal 0 3 4 2 5 12 7 7 10 11 6

TABLE V.-Mean Scores for Perinatal Deaths and Surviving Infants (Figures in parentheses indicate number of pregnancies studied.)
All perinatal deaths (144).6.2 Neonatal deaths (67).6.5 Fetal deaths (77). Perinatal deaths, major congenital anomalies (18).3.6 Perinatal deaths <2500 g. (55).7.2 Surviving infants <2500 g. (26).3.9 Surviving infants, >4000 g. (24).1.9 Surviving infants, Apgar score>4 (771).1.2 Surviving infants, Apgar scorc<4 (21).3.0

(Continued on page 63)

Canad. Med. Ass. J., Oct. 18, 1969, vol. 101-460

Geigy Pharmaceuticals Geigy (Canada) Limited Montreal 308, P.Q.

'2' I',
o

60

(Continued from

page

60)
SCORE ASSIGNED FOR GESTATIONAL AGE

SCORE

<29WK.

29-32 WK.

33-35 WK.

36-37 WK.

GESTATIONAL AGE FIG. 1..Histogram relating mean scores of 144 perinatal deaths to various gestational age ranges. Open plus cross-hatched histogram columns indicate mean score. Cross-hatched columns indicate arbitrarily assigned score for individual gestational age category. In each instance, mean score significantly exceeds the score which can be assigned for gestational age alone.

last estriol value is related to the score assigned to the pregnancy. Linear regression analysis was carried out and the appropriate equation is y = 24.8 2.5x. The correlation coefficient (0.39) is highly significant (P < 0.01) for the population studied. Even when one takes the expected variability of measured urinary estriols into account, it is noteworthy that a value of less than 10 mg. was ob tained in only one case scoring less than 3. The average gestational age of the cases in which these final urinary estriol determinations were done was 38 weeks.

A score was assigned to the 85 pregnancies in which three or more 24-hour urinary estriol determina tions were performed. In Fig. 2 the

SCORE

10 ESTRIOL m*/24 hrs.

30

40 60

FIG. 2..Relationship between final 24-hour estriol excretion value and antepartum fetal-risk score in 85 oases. Linear regression equation is y = 24.8 2.5x (r = 0.39, P <0.01).

Table V gives the mean scores for perinatal deaths and surviving infants. It is interesting that peri natal death due to major congenital anomalies obtained as low a mean score as 3.6. Of the 19 deaths scoring 1, 2 or 3, 10 were due to major congenital anomalies. Of the four perinatal deaths scoring 1, three were due to congenital anomalies. Prematurity and therefore deaths due to prematurity are frequently stated to be unpredictable. By this is implied an absence of any premonitory conditions or factors which lead one to suspect impending pre

maturity. Accordingly, we con sidered that it was important to de

quite simply (Fig. 1) by averaging the scores obtained for perinatal

Canad. Med. Ass. J., Oct. 18, 1969, vol. 101.461

termine if any such additional factors could be detected at various gestational ages. This was done

deaths in the various gestational age used in this scoring sys tem. In each gestational age cate gory, the mean score obtained noticeably exceeds the score given for the appropriate gestational age. Thus, a gestational age of 33 to 35 weeks would be assigned a score of 2, but the average score attained by the cases of perinatal death in this category was 6.1. Clearly, adverse factors other than gestational age alone were operative in these pregnancies which terminated in prematurity and death. There were 26 surviving in fants who weigjhed less than 2500 g. regardless of gestational age, and the mean score assigned to these pregnancies was 3.9. The average gestational age of these infants was 36 weeks, giving the total group an average score for gestational age of 1.

categories

VALIDATION OF THE METHOD Validation will come only with the prospective scoring of a large number of cases. However, in an attempt to justify the rating that we have arbitrarily assigned to each of the adverse factors in this simple scoring technique, we have com pared the simple scores obtained with a more detailed scoring tech nique suggested to us by Effer.7 This method is based on the addition of a score for each adverse factor which is equivalent to the perinatal mortality rate per 1000 live births for that particular condition given in either the Ontario or the British perinatal mortality surveys. In practice, each perinatal mor tality score was rounded off to the nearest 5 to avoid giving the im pression of undue precision in these data. Now in a sample case of a 35-year-old primigravida who had one episode of bleeding without pain before 20 weeks of gestation and a diagnosis of grade I preeclampsia, and who had reached but not exceeded 36 weeks of gestation, the scoring would be as follows (our simple score follows in paren

theses) :

.Primigravida 25 (1)
.35 years of age+ 30 (1) .One episode of bleeding without pain before 20 weeks 45 (1) .Has reached 36 weeks of gestation 60 (1) .rTotal perinatal mortality score 210 .Proposed simple score 4

63

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With the addition of new 642 Tablets, the physician now has the choice of a plain or compound propoxy

earlier, the total for each category (baseline data, complications of the present pregnancy and the gesta tional age attained at the time of scoring) was limited quite arbi trarily. It would seem important to validate the weighting given each category in some simple way. The mean score for all 144 perinatal deaths was 6.2. The mean score for each of the categories was al most exactly one-third of this figure (baseline data 2.08; present pregnancy 2.04; gestational age 2.08). Thus no undue weighting is given to any of the categories, particularly not to that for gesta tional age.
As indicated
score

0.001).

When we apply these techniques entire group of cases, the re lationship between the two scoring systems can be expressed as a linear regression which has a very higjh coefficient of correlation (0.982) with an equally high sta tistical significance level (P <
to the

possible

DISCUSSION
It is important to point out that this scoring technique is not in tended to be predictive of perinatal death or morbidity. It is intended to be a rough practical assessment of the potential in any given pregnancy for increased risk to the unborn fetus. Accordingly, it is possible to state the following conclusions about this series of cases, scored using the technique described: 1. If a woman manifests none of the adverse conditions or risk fac tors embodied in the score (i.e. if she scores 0), the probability of perinatal death is very remote. 2. Perinatal deaths are usually associated with a number of adverse conditions which combine to pro duce an unfavourable environment. It seems a not unreasonable con clusion that the concept of cumulative fetal risk is valid. 3. Congenital anomalies do seem to account for a considerable hum ber of deaths with low scores (1-3). 4. One must remember that this scoring was done in retrospect and that the score assigned for gesta tional age was that appropriate for the furthest point that these preg nancies attained in fact. Prospective
Canad. Med. Ass. J., Oct. 18, 1969, vol. 101.462

phene analgesic made by Frosst. 642 Tablets are f ilm-coated and small in size, ensuring tastelessness and ease in swallowing. They provide a useful alternative to established analgesics when there is a need to prescribe for the relief of mild to moderate pain or where a single-drug analgesic is desirable. 692 Tablets, combining the analgesic effects of pro poxyphene with the well-known combination of acetyl salicylic acid, phenacetin and caffeine, provide greater analgesia plus antipyretic/anti-inflammatory benefits.
occasionally been noted, as well as dizziness in ambulant patients. Skin rashes, itching and gastrointestinal disturbances, including constipation, have been observed. Propoxyphene has little addicting liability, although a few cases of addiction have been reported. CONTRAINDICATIONS: Drug sensitivity can occur in rare in stances, in which case, medication should be discontinued. Con comitant use with orphenadrine compounds is not recommended. Excessive doses of any preparation containing acetylsalicylic acid or phenacetin taken for a prolonged period of time may produce nephrotoxicity. Particular caution should be observed when treating patients with chronic renal disease. The acetylsalicylic acid ingredient may cause gastric intolerance and, occasionally, occult bleeding.

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64

glucose-tolerance testing, screening of mid-stream urines significant bacteriuria and the measurement of serum folate levels.10 The application of these screening tests and the use of serial 24-hour urinary estriol excretion levels enable us to arrive at a more precise impression of risk to the fetus, but these methods are expen sive and some form of preliminary identification of high-risk preg nancies must be employed. So-called epidemiological profiles have been developed by workers in the public health field to relate peri natal mortality, prematurity, neuro logical sequelae and socioeconomic
meters as

cations. It is instructive to examine the methods by which the high-risk pregnancy has been recognized in the past. For the most part this sort of identification has been accomplished by luck or by the applica tion of considerable experience as an educated guess. Because of care ful study and excellent management, White8 has been able to grade dia betic pregnancies with respect to fetal risk in a semi-quantitative fashion. She has also been able to demonstrate convincingly the synergism of fetal risk when, for ex ample, toxemia is superimposed on the diabetic state in pregnancy. Another excellent example of the semi-quantitative assessment of fetal risk is provided by the use of amniocentesis data in the manage ment of Rh iso-immunized preg nancies.9 In a broader approach, certain perinatal units have applied blanket screening to all patients entering the antenatal clinic using such para
the for

drops. 5. Very few of these deaths had any significant adverse event in labour (prolongation, cord accident, delivery trauma) which would have contributed to the total risk to the infant. An important exception to this observation is the fact that in the group of infants with low Apgar scores (less than 4) there was a higher incidence of delivery compli

whidh has been attained. The preg nancy may in fact go on to greater maturity and in this event the score

scoring assumes the worst risk pos sible for the stage in the gestation

conditions in well-circumscribed geographic areas.11

cluded emotional and socioeconomic assessment, the influence of which is controversial and difficult to score in any reproducible way. Prechtl13 has devised a tally of 42 prenatal and perinatal adverse factors which have been positively correlated with significant neuro logical findings in the first 10 days of life. This relatively simple addi tive system apparently permits identification of the high-risk preg nancy with respect to sub-lethal brain damage in the neonate. Prechtl concluded that so-called "non-optimal" or adverse conditions tended to occur in association with each other, which in effect gives support to the concept of cumulative fetal risk. Larks and Larks14 have produced multivariate linear regression equa tions which correlate prenatal and perinatal adverse factors in an at tempt to predict the risk to the unborn infant. Feldstein and Butler15 have recently published a mathematical validation for the concept of cumulative fetal risk by a multi variate regression analysis. We would hope that a simple scoring technique would provide the basis for a mental tally of adverse factors by the attending physician to be applied to the potential highrisk pregnancy, both at the initial antenatal visit and throughout the pregnancy. A simple technique, such as the one presented here, migfht be of real value in the train ing of resident obstetricians. The ultimate aim would be almost instinctive application of such a

Recently Nesbitt and Aubry12 presented a semi-objective grading system based on arbitrary scores given to eight categories of adverse factors considered at the first prenatal visit in their clinic. This technique obviously allows but one opportunity for scoring or grad ing the potential high-risk preg nancy and is equivalent to our socalled baseline data. Study of 1001 consecutive patients allowed division into low, moderate and high-risk pregnancies. The latter group repre sented approximately 30% of their total and was found to be respon sible for 60% of all pathological outcomes. As in our technique, individual scores for adverse factors were arbitrarily assigned. They in
have

tally to every antenatal pa disadvantages of more complex scoring techniques, by virtue of the number of parameters considered together with the time and personnel necessary to gather the data, are obvious. What the simple technique loses in relative precision is redeemed by
score or

tient. The

its

ease

of

application.

RESUME Simple methode de cotation pour deceler ante partum le danger que court le fetus
Nous avons mis au point une methode de cotation d'une grande simplicite permettant de deceler avant Vaccouchement le danger auquel le fetus est expose. Nous Vavons appliquee a 936 parturientes qui ont accouche au Women's Col lege Hospital de Toronto. Cette methode tient compte des conditions defavorables generalement admises et part du principe que le fetus est soumis a un risque cumulatif. Le systeme de cotation lui-meme est base sur trois cate gories de renseignements: les donnees de l'etat pregravidique, les con ditions pendant la presente gros sesse avant le declenchement du travail et la longueur de la gestation au moment de I'application de la methode. La marque 0 designe le risque le plus faible pour le fetus et la marque 10 le risque le plus eleve. Dans aucun des 144 deces survenus dans la periode perinatale, on n'a note la cote 0 et chez les 792 survivants, la cote n'a jamais depasse 6. Cette methode se compare favorablement a une methode plus compliquee et a celle consistant d mesurer Vexcretion d'estriol comme cela a ete pratique dans 85 cas. II s'agit, selon nous, d'un moyen d'evaluer rapidement par un simple calcul mental, les facteurs de risque auxquels est soumis le fetus et de choisir les cas de grossesse a risque

potentiellement elevi, lesquels pour ront ainsi etre traites energiquement avant, pendant et apres le
travail.

(Continued on page 67)

65

Canad. Med. Ass. J., Oct. 18, 1969, vol. 101.463

indications: HYDROPRES* tablets are indicated in mild to severe hypertension. The combined use of hydrochlorothiazide and reserpine will sometimes reduce the blood pressure when either compound alone is without effect. Particularly in patients with sodium and water retention. HYDROPRES* helps to correct fluid imbalance. It produces mild sedation that is tranquilizing but not hypnotic, thus helping to control emotional fluctuations of blood pressure. It counteracts tachycardia that may accompany high blood pressure, permits less rigid dietary salt restriction, and when the anginal syndrome accompanies high blood pressure, it may become less severe or even disappear with control of the hypertension. In many cases, even ot severe degree. HYDROPRES* alone may control the blood pressure. If a greater antihypertensive effect is required, more potent drugs can be added in comparatively small dosage and with smoother control. Dosage Summary: The usual adult starting dosage ranges from 25 mg. od. to 50 mg. b.i.d.. per os. increased or decreased according to the blood pressure response of the patient. Contraindications: Anuria; discontinue if increasing azotemia and oliguria occur during treatment of severe progressive renal disease; electroshock therapy; at least seven days should elapse between discontinuance of reserpine and initiation of electroshock therapy; in persons known to be sensitive to hydrochlorothiazide. Warnings: Special caution is necessary in patients with impaired renal function to avoid cumulative or toxic effects. Use caution in hepatic cirrhosis. Dosage of other antihypertensive agents. especially the ganglion blockers, must be reduced by at least 50 per cent as soon as hydrochlorothiazide is added to the regimen. A probable association exists between the use of coated tablets containing potassium salts, with or without thiazide diuretics, and the incidence of serious small bowel ulceration. Such preparations should be used only when adequate dietary supplementation is not practical, and should be discontinued if gastrointestinal disturbances occur.

(Continued from page 65) ANTEPARTUM IDENTIFICATION OF THE FETUS AT RISK

REFERENCES

1. Canada Bureau of Statistics, Vital Statistics Section, Infant mortality, 1950-1964, Queen's Printer, Ottawa 1967. 2. Ontario Perinatal Study Committee: Second report of the permatal mortality study, in ten university teaching hospitals, Ontario, Canada 1959 Toronto 1967. 3. Perinatal .4ortaiity: The first report of the 1958 British perinatal mortality survey, under the auspices of the National Birthday Trust Fund, edited by N. R. Butler and D. G. Bonhani, E. & S. .Livingstone Ltd., Edinburgh. 1963 4. BROWNE, J. C.: Proc. Roy. Soc. Med. (London), 45: 532, 1952. 5. GOODWIN, 3. W. AND REID, D. E.: Amer. J. Obstet. Gynec., 85: 209, 1963. 6. APGAR, V.: Anesth. Anaig., 32: 260, 1953. 7. EFFER, S. B.: Personal communication. 8. WHITE, P.: Pregnancy complicating diabetes. in: Treatment of diabetes mellitus, edited by E. P. Joslin, H. F. Root, P. White and A. Marble, Lea & Febiger, Philadelphia, 1959, p. 690. 9. BOWMAN, 3. M. AND POLLOCK, 3. M.: Pediatrics, 35: 815, 1965. 10. Lirrut, A. B.: Personal communication. 11. ANDERSON, U. M. et al.: New Eng. 3. Med., 273: 308, 1965. 12. Nasarrr, R. B. AND Ausay, R. H.: Amer. J. Obstet. Gynec., 103: 972, 1969. 13. PaacHm, H. F.: Brit. Med. 3., 4: 763, 1967. 14. LAsics, S. D. AND LARKs, G. G.: Mathematical Biosciences, 3: 135, 1968. 15. FELDSTEIN. M. S. AND BUTLER, N. R.: Brit. 3. Prey. Soc. Med., 19: 128, 1965.

Precautions and Side Effects: Hydrochiorothiazide: Check

carefully for signs of fluid and electrolyte imbalance. Serum and urine electrolyte determinations are important when patient vomits excessively or is receiving parenteral fluids or electrolyte intake is inadequate. Although potassiumloss usually is not excessive. hypokalemia may develop, especially with brisk diuresis, in severe cirrhosis, or concomitant corticosteroid or ACTH administration. Hepatic coma may be precipitated. Hypokalemia may precipitate digitalis toxicity. Hypochloremic alkalosis occurs infrequently and is rarely severe. Unduly restricted dietary salt may complicate thiazide therapy. Hypokalemia may be avoided or treated by use of potassium chloride or foods high in potassium content; similarly chloride deficit by ammonium chloride or near normal salt intake. or both (except in cirrhotics). Discontinue 48 hours before elective surgery. Hyperuricemia may occur and gout. In diabetics, insulin requirements may be increased, decreased or unchanged. Hyperglycemia and glycosuria may result. Thiazide diuretics have reportedly precipitated a cutaneous vasculitis in elderly patients with a history of repeated and continuing exposure to several drugs. Thrombocytopenia. leukopenia. agranulocytosis. aplastic anemia, and jaundice have been reported as rare side reactions, Nausea. vomiting, diarrhea, dizziness. and paresthesias may occur. Purpura. rash.-photosensitivity, or other hypersensitivity reactions have been reported in a small percentage of cases. There have been scattered reports of pancreatitis, xanthopsia. neonatal thrombocytopenia, and neonatal jaundice, but data is insufficient to establish a causal relationship. Since thiazides cross the placental barrier and appear in breast milk, it is possible that side effects seen in the adult may also occur in the newborn. Reserpine. With continued use side effects often disappear and most can be controlled by reducing dosage. The need to discontinue therapy is rare. Reactions most often reported include excessive sedation, nightmares, nasal congestion. conjunctival injection, enhanced susceptibility to colds, muscular aches, headache. dizziness, dyspnea. anorexia. nausea, increased intestinal motility. diarrhea, weight gain, dryness of the mouth. blurred vision. flushing of the skin, pruritus. skin rash. dysuria, syncope. impotence or decreased libido. bradycardia. angina pectoris and other direct cardiac effects, and central nervous system (including ocular) sensitization. Should be used cautiously in the presence of coronary disease and in patients with a history of peptic ulcer. ulcerative colitis, or other gastrointestinal disorders. May precipitate biliary colic in patients with gallstones, or bronchial asthma in susceptible persons. May cause hypotension. including orthostatic. Should be discontinued two weeks before giving anesthesia. In some patients a syndrome similar to Parkinsons disease has been produced. but is usually reversible with decreased dosage or discontinuance. Anxiety or depression, as well as psychosis. may develop. If depression is present when therapy is begun, it may be aggravated. Dejailed information on dosage. administration, precautions and bibliography is available on request. Flow Supplied: Tablets HYDROPRES*.25 and HYDROPRES*,50. 25 or 50 mg. each of hydrochlorothiazide and 0.125 mg. of reserpine. are supplied in bottles of 100 and 1000. *Trademark
MEMBER

Yesterday's Medicine
THE RESOLUTIONS PASSED AT THE QUEBEC MEETING The usual number of resolutions were submitted to the annual meeting of the Association. It was a pleasure to commend the Government for at last establishing a Department of Public Health. The members also went on record as being willing to assist the Government in the choice of the Deputy Minister. That the Government has since chosen wisely in this connection is obvious to all. A committee was appointed to consider the whole question of medical research in Canada. Its members have a large undertaking ahead of them if they devise some adequate scheme for encouraging this work in Canada. The great problem would seem to be to provide the funds necessary for maintaining a body of workers in such a way that they will not have to build up a private practice. The conclusion of the War called for a resolution commending the members of the profession for the good work they accomplished while in uniform. Suggestions for malntalning a permanent military medical organization were also made. These included the teaching of military subjects at the universities and the establishing of research fellowships by the Militia Department. This would seem to be the cheapest and at the same time the best method of tralning physicians for the duties they might be called on to perform in the event of another war. The splendid record made 'by militia medical officers in the senior positions would suggest the possibility of training the officers at the universities by means of post-graduate courses. They should be compelled, however, to maintain their efficiency as medical men by the struggle for existence in private practice.-Editorial: Canad. Med. Ass. J., 9: 937 (October), 1919.
67

O MERCK SHARP&DOHME I
OF CANADA LIMITED MONTREAL

Where today's research is tomorrow's therapy.

Canad. Med. Ass. 3., Oct. 18, 1969, vol. 101-464