EFFECTS OF SUSTAINED MATERNAL HYPERTENSION ON FŒTAL GROWTH AND SURVIVAL

1214

EFFECTS OF SUSTAINED MATERNAL HYPERTENSION ON FŒTAL GROWTH AND SURVIVAL W. A. W. WALTERS LECTURER IN

M.B. Adel., Ph.D. Lond., M.R.C.O.G. OBSTETRICS AND GYNAECOLOGY, UNIVERSITY

OF

ABERDEEN*

OBSTETRICIANS have long been concerned about the of pregnancy in women with an elevated bloodpressure and from time to time various aspects of this problem have been investigated. One aspect, the incidence of the condition, can be investigated only by course

investigating a complete population. MacGillivray (1961) studied the epidemiology of pre-eclampsia in Aberdeen but did

focus his attention on the women who had a raised blood-pressure throughout pregnancy. The survey described here was undertaken to discover the incidence and the effect of constant hypertension on the outcome of pregnancy in primigravidse and to investigate the prognosis for the foetus in all subsequent pregnancies in the same women. not

consistently

Patients who had sustained hypertension (as defined) were selected for further detailed study, when their entire casenotes were closely scrutinised. Table I shows the total number of all booked married city primigravidae in Aberdeen during the years 1951-1960 inclusive in whom diastolic blood-pressure was elevated to or above 90 mm. Hg on at least two occasions separated by 24 hours. These cases were subdivided into those with proteinuria and those without proteinuria and from these groups a third category was made which included all cases of sustained

hypertension during pregnancy. The above definition of sustained

hypertension was adhered

to rigidly and as a result some women in this category not attend for their first antenatal examination before

who did the 20th week of gestation have been excluded from this survey. Thus the reported incidence of sustained hypertension in all primigravidae may be slightly lower than the true incidence, but this does not detract from the value of studying it as defined.

Results HYPERTENSION

Incidence

90%

of all

primigravidae

in the

city

of Aberdeen

TABLE I-ABERDEEN BOOKED MARRIED CITY PRIMIGRAVIDE

Patients and Methods Sustained Definition of Hypertension Sustained hypertension was defined as a diastolic bloodpressure of 90 mm. Hg or more before the 20th week of pregnancy which remained at or above this level throughout pregnancy, irrespective of the nature and duration of therapy employed. Treatment consisted of rest in bed and sedation in most cases. Hypotensive drugs were not used. Blood-pressure was recorded as casual readings, and in all cases it was measured by doctors on the staff of the Aberdeen Maternity Hospital. Material All primigravidas booked for delivery in the city of Aberdeen in the years 1951-1960, inclusive, were studied. Those with hypertension of any kind were separated from the others and their case-records were carefully hand-sorted and examined. * Present appointment: senior lecturer in obstetrics and gynaecology, Monash University, Melbourne, Australia. DR. VAN DER GELD AND OTHERS: REFERENCES

Ball, J. D., Williams, A. W., Davies, J. N. P. (1954) Lancet, i, 1049. Black, M., Fowler, J. M. (1965) Br. med. J. i, 682. Bulletin of the World Health Organisation (1965) 33, 257. Coelho, E., Cortez Pimentel, J. (1963) Am. J. Med. 35, 569. Correa, P., Restrepo, C., Carcia, C., Quiroz, A. C. (1963) Am. Heart J. 66, 584.

D’Arbela, P. G., Somers, K. (1964) Proceedings of the 3rd Asian-Pacific Congress on Cardiology, Kyoto, 1, 120. Davies, J. N. P. (1948) E. Afr. med. J. 25, 10. Edington, G. M. (1954) Trans. R. Soc. trop. Med. Hyg. 48, 419. Fagundes, L. A. (1963) Revta. Inst. Med. trop. S. Paulo 5, 198. Graham, J. R., Suby, H. I., Le Compte, P. R., Sandowsky, N. L. (1966) New Engl. J. Med. 274, 359. McKinney, B., Crawford, M. V. (1965) Lancet, ii, 880. McNamara, P. J., Jacobs, W. H., Jaffé, R. J. (1959) Ann. intern. Med. 50, 1035.

Nagaratnam, N., Dissanayake, R. V. P. (1959) Br. Heart J. 21, 167. Nakajima, K., Okada, R., Ueda, H. (1961) Jap. Heart J. 2, 265. Peetoom, F (1963) The Agar Precipitation Technique and its Application as a Diagnostic and Analytical Method. Leiden. (1966) Unpublished. Loghem-Langereis, E. van (1965) Vox Sang. 10, 281. Peuchot, G., Latour, H., Puech, P. (1960) Archs Mal. Cœur. 53, 1137. Robbins, J., Stetson, C. A. (1959) J. exp. Med. 109, 1. Shaper, A. G., Coles, R. M. (1965) Br. Heart J. 27, 121. Shillingford, J. P., Somers, K. (1961) ibid. 23, 433. Somers, K., Van der Geld, H., Feltkamp-Vroom, Th.M. (1966) Unpublished. Spatz, M. (1965) Lab. Invest. 13, 288. Taylor, K. B., Roitt, I. M., Doniach, D., Couchman, K. C., Schapland, C. (1962) Br. med. J. ii, 1347. Turner, P. P., Manson-Bahr, P. E. C. (1960) Br. Heart J. 22, 305. van der Geld, H. (1964) Lancet, ii, 617. (1966) Ph.D. thesis, Amsterdam (unpublished). Oosterhuis, H. J. G. H. (1966) Ann. N.Y. Acad. Sci. 135, 631. van Loghem-Langereis, E., Peetoom, F., Hart, M. van der, Loghem, J. J. van, Bosch, E., Goudsmit, R. (1965) Int. Congr. Blood Transf., Stockholm; p. 55. Vassali, P., McCluskey, R. T. (1964) Ann. N.Y. Acad. Sci. 116, 1065. —

—

—

—

booked for hospital confinement. From table i the incidence of all types of hypertension amongst booked, married city primigravidae during the years 1951-1960 was 29-6%, whereas the incidence of sustained hypertension was small—0.58% or approximately five primiare

gravidse per year. Degree in First Pregnancies Table n shows that the systolic blood-pressure ranged from 130 to 189 mm. Hg throughout pregnancy. But forty-five patients at 20 weeks, forty-six patients at 30 weeks, and forty-three patients at 40 weeks had a systolic blood-pressure below 160 mm. Hg. TABLE

II-SYSTOLIC

PREGNANCIES IN

BLOOD-PRESSURE

55 WOMEN

IN

FIRST

AND

SUBSEQUENT

WITH SUSTAINED HYPERTENSION

1215 TABLE III-DIASTOLIC BLOOD-PRESSURE IN FIRST AND SUBSEQUENT PREGNANCIES IN 55 WOMEN WITH SUSTAINED HYPERTENSION

ranging between 140 and 185 mm. Hg (systolic) and 90 and 130 mm. Hg (diastolic) throughout pregnancy. Proteinuria developed at 30 weeks but there was no oedema. Labour commenced prematurely at 32 weeks and early in the first stage intrauterine death of the foetus occurred. She was delivered normally of a stillborn male foetus weighing 879 g. Death was attributed to the maternal disease. Case 4.-This woman, aged 29, had a blood-pressure ranging between 140 and 165 mm. Hg (systolic) and 90 and 110 mm. Hg (diastolic) throughout pregnancy. She developed slight peripheral oedema at 32 weeks but at no stage did protein appear in the urine. At 39 weeks she came into labour during which intrauterine death of the foetus occurred. A stillborn female foetus weighing 2056 g. was delivered normally per vaginam. Death was attributed to the maternal disease and prematurity.

If

Diastolic blood-pressure tended to rise gradually throughout pregnancy in most patients (table III), and whereas there was only one patient with a diastolic pressure above 110 mm. Hg at 20 weeks, there were fourteen patients in this category at 40 weeks, and the number of patients in the 100-109 mm. Hg category increased almost twofold towards the end of pregnancy. Only fourteen out of the fifty-five patients with sustained hypertension had a diastolic pressure at or above 100 mm. Hg at 20 weeks. It is therefore apparent that most of the patients in this series had mild-to-moderate hypertension by general medical standards in their first pregnancies. Few patients could be said to have had severe hypertension. EFFECTS OF SUSTAINED HYPERTENSION IN FIRST

PREGNANCIES

There were fifty-five primigravidx with sustained hypertension amongst 9512 booked married city primigravidx in the ten-year period 1951-1960. Perinatal Mortality and Complications of Pregnancy Of these fifty-five women, three had stillbirths and in one there was a neonatal death, a perinatal mortality of 7’27% or 72-7 per 1000 total births. This figure is notably greater than that for normotensive primigravidx in the same 10-year period (26-5 per 1000 total births). However, from table v it can be seen that the hypertensive

74-5% of patients were delivered after 38 weeks’ gestation. The duration of pregnancy, calculated from the first day of the last menstrual period, was prolonged by 1 week in nine patients, 2 weeks in two patients, and 3 weeks in one patient. The incidence of prematurity, regarded as a birth-weight of less than 2500 g., was 16-3%. Although hypertension is said to predispose to preeclampsia, proteinuria developed in only seven cases out of fifty-five (13-6%), while generalised cedema of varying degree, determined solely by clinical examination, was recorded in seventeen cases (30-9%). The incidence of proteinuria in Aberdeen primigravidae who are normotensive at the beginning of pregnancy is 5% and in those who are hypertensive at the first antenatal visit, 9%, so that with a more strict definition of hypertension a 13-6% incidence of proteinuria is not unduly high when one considers the small numbers involved. There were no of ante-partum haemorrhage in this series. Foetal distress diagnosed by the presence of meconium in the liquor and slowing of the foetal heart-rate below 120 beats per minute occurred in sixteen patients, an incidence of 29% compared with 18-2% in the control population. Ten of these mothers were 29 years of age cases

or more.

Labour .

was

induced surgically in twenty-nine patients,

Babies delivered of mothers with sustained

hypertension Data For babies born of all Aberdeen booked primiparae

primigravidx are considerably older than the population at risk, 327°0 of them being 30 years of age or more compared with 14-1% of the control population. Details of the four perinatal deaths are as follows: Case .?.—Aged 24; blood-pressure ranged between 150 and 185 mm. Hg (systolic) and (diastolic) during pregnancy.

between 100 and 120 mm. Hg Generalised oedema developed at 28 weeks and proteinuria at 33 weeks. She was delivered, by cxsarean section at 34 weeks because of increasing hypertension, cedema, and proteinuria, of a live male baby (birthweight 2977 g.). Respiratory distress developed and the baby died after 4 hours. The death was attributed to the maternal disease and prematurity. Case 2.-This 38-year-old woman had a blood-pressure ranging between 140 and 175 mm. Hg (systolic) and 90 and 110 mm. Hg (diastolic) throughout pregnancy. She had no cedema or proteinuria at any stage and went into spontaneous labour at 37 weeks. Intrauterine death of the foetus occurred early in labour and normal vaginal delivery resulted in a macerated male foetus weighing 2410 g. Death was attributed to the maternal disease. Case 3.-This 21-year-old woman had a blood-pressure

Birth-weights in primiparae in Aberdeen.

1216 TABLE

IV-SUBSEQUENT

abortions between the sixth and twelfth weeks in all

PREGNANCIES

subsequent pregnancies. Birth-weights in subsequent pregnancies were normal for the gestation period as was the case in first pregnancies. Discussion

*

No record of antenatal care in 1 case. t No record of antenatal 2 cases. I No record of antenatal care in 2 cases.

care

in

TABLE V-MATERNAL AGE-DISTRIBUTION IN FIRST PREGNANCIES

and six babies were delivered by cxsarean section, and fourteen by forceps, making a total operative delivery incidence of 38-1%.

Birth-weight In this group of patients, sustained hypertension of a mild to moderate degree did not influence the growth of the foetus as judged by birth-weights, which were normally distributed according to gestational age. The figure illustrates the relation between birth-weight and duration of pregnancy in the hypertensive group under investigation in Aberdeen as described by Baird et al. (1957). SUBSEQUENT

PREGNANCIES

Degree of Maternal Hypertension

Forty-one patients had second pregnancies, of which thirty-four progressed to the stage of viability. Of these patients, thirty at 20 weeks, thirty-one at 30 weeks, and eighteen at 40 weeks had a diastolic blood-pressure below 100 mm. Hg. Seventeen patients had three pregnancies of which thirteen are known to have progressed to the stage of viability. Of these thirteen patients, twelve at 20 weeks, ten at 30 weeks, and nine at 40 weeks had diastolic bloodpressures below 100 mm. Hg. Eight patients had four pregnancies of which five were known to progress to viability. Three of these patients at 20 weeks, four at 30 weeks, and four at 40 weeks had diastolic blood-pressures below 100 mg. Hg. Only two patients had five pregnancies and both of them had diastolic blood-pressures below 100 mm. Hg throughout their pregnancies. Systolic blood-pressures in subsequent pregnancies followed

a

pattern similar

to

that of diastolic blood-

pressures. The range

of time-intervals between pregnancies extended from 1 to 8 years with means of 2-8, 2-3, 3-2, and 2-5 years between first and second, second and third, third and fourth, and fourth and fifth pregnancies,

respectively. The degree of hypertension did not increase in any of these hypertensive women in subsequent pregnancies. Perinatal Mortality and Birth-weight Table Iv shows that the perinatal mortality in all subsequent pregnancies was one out of fifty-nine births or sixty-eight pregnancies. This one case was a stillbirth which occurred in a fourth pregnancy. The perinatal mortality was therefore 1-7%. There were, however, 9

These results show that the incidence of sustained hypertension in Aberdeen primigravidx is very low and is such a small problem relative to other types of hypertension in this part of Britain that cognizance of this fact should be taken into account when attempting to assess the efficacy of various forms of treatment. There were no cases of really severe hypertension in this series. Although the degree of hypertension was mild to moderate in most cases the perinatal mortality was almost three times as high as in normotensive primigravidx. Two of the four perinatal deaths occurred where mothers had proteinuria and the other two intrauterine deaths occurred where the mothers were over the age of 29. Thus, one could postulate that adverse factors other than hypertension per se were contributory causes of foetal death in all four cases. It is important to note that no perinatal deaths occurred in young primigravidx with sustained hypertension in the absence of proteinuria. This observation correlates well with that of Dixon et al. (1963) who found that choriodecidual blood-flow was not significantly reduced in patients with mild to moderate hypertension, providing that there was no proteinuria. Although it is often stated that hypertension causes impaired growth of the foetus, these results do not confirm this. Birth-weights were within the normal range according to the duration of pregnancy. Surprisingly, no increase in the severity of the hypertension developed in those women who embarked upon further pregnancies, and the perinatal-mortality rate in subsequent pregnancies was low. In this context, it is important to appreciate that most of the patients in this series had successive pregnancies within 2 to 3 years of one another, and therefore the chance of benign hypertensive disease progressing in so short a time would be small. Gate (1960) described seventy-one patients who had a blood-pressure of 150/100 mm. Hg or more before the 20th week of pregnancy. The perinatal mortality in his series was 7-0%, which compares well with the Aberdeen of 7-3%. Browne and Dodds (1942) reported a series of two hundred and thirty-nine patients with hypertension in pregnancy. Twenty-five of these patients had a bloodpressure of 150/100 mm. Hg or more before the 20th week and in this group there were seventeen foetal deaths

figure

(68%). The great improvement in foetal survival in hypertensive women since 1942 is almost certainly due to better antenatal care and more frequent use of induction and operative delivery as illustrated by the increased incidence of obstetric interference in this series and that reported by Gate (1960). Kincaid-Smith et al. (1966) reported a perinatal mortality of only 9-3% in a series of thirty-two severely hypertensive women treated with methyldopa for prolonged periods during pregnancy. Twenty-five of these patients had non-pregnant diastolic blood-pressure levels of 110 mm. Hg or more when not on treatment. The good results obtained suggest that a controlled trial of a hypotensive drug such as methyldopa during pregnancy associated with severe sustained hypertension would be

1217 It is doubtful, however, whether hypotensive would be effective in reducing the perinatal agents in pregnant patients with mild to moderate mortality of sustained hypertension, in whom the perinatal degrees is mortality already quite low, as indicated in this Aberdeen series. It is important to realise when assessing the effects of any maternal disease on the fretus that other factors such as age, parity, social class, and previous obstetric performance must be taken into account. The present study demonstrates how one could easily conclude that sustained mild to moderate hypertension in Aberdeen primigravidae was responsible for the perinatal mortality in this group being almost three times that of the normoCloser examination reveals that tensive population. of the 32-7% hypertensive patients were more than 30 of whereas only 14-1% of the control population years age in this were category. This is an important observation since perinatal mortality due to all causes rises with increasing maternal age and it may be this factor alone which is responsible for the increased perinatal mortality in the hypertensive women. It would appear that the amount of trouble in pregnancy encountered by primigravidx with sustained hypertension is surprisingly small, particularly when maternal age is less than 30 years, and even the few who lose the first baby do well in subsequent pregnancies. Trouble arises in the older women and in those who develop proteinuria in association with hypertension.

HÆMODYNAMIC FACTORS IN THE DEVELOPMENT OF ACUTE PULMONARY ŒDEMA IN RENAL FAILURE

profitable.

Summary A survey of all booked city primigravidx in Aberdeen during the years 1951-60 has revealed a low incidence of sustained hypertension in pregnancy (0-58%). In fiftyfive patients with sustained hypertension the perinatal mortality (7-3%) was almost three times as high as it was in normotensive primigravidx (2-6%). Besides hypertension, other adverse factors were present in all four In those cases in which there were perinatal deaths. the only sustained was in whom patients hypertension adverse factor no perinatal deaths occurred. The perinatal mortality in all subsequent pregnancies in patients who had had sustained hypertension in their first pregnancies was low (1-7%). Sustained hypertension of mild to moderate degree did not influence the growth of the foetus. I thank Prof. Sir Dugald Baird and Dr. R. M. Bernard for their advice and Mrs. L. A. Parker for assistance in preparation of the

manuscript.

Requests

for

reprints

should be addressed

to

W. A. W.

W.,

Monash University, Department of Obstetrics and Gynaecology,

Queen Victoria

Memorial

Hospital, Melbourne, Victoria,

Australia.

REFERENCES

Baird, D., Thomson,

A. M., Billewicz, W. Z. (1957) J. Obstet. Gynœc. Br. Emp. 64, 370. Browne, F. J., Dodds, G. (1942) ibid. 49, 1. Dixon, H. G., Browne, J. C. McC., Davey, D. A. (1963) Lancet, ii, 369. Gate, J. M. (1960) ibid. i, 901. Kincaid-Smith, P., Bullen, M., Mills, J. (1966) Br. med. J. i, 274. MacGillivray, I. (1961) J. Obstet. Gynœc. Brit. Cwlth 68, 557.

"... Our forebears, who taught all aspects of medicine according to the traditional doctrines of the ancients, probably were reasonably happy with the medical curriculum. Tamper-

ing with these

doctrines would have been considered heretical, the faculty gave its ordered lectures untroubled by thoughts that they might be altered or improved. The practical approach of the early American practitioner to disease began to dispel this complacency; the present age of experimentation and scientific deduction has destroyed it completely."-LAMAR SOUTTER, M.D., in Medical Care, p. 31. Springfield, Ill., 1966. so

D. G. GIBSON M.A., M.B. Cantab., M.R.C.P. REGISTRAR, MEDICAL UNIT, WESTMINSTER HOSPITAL,

LONDON

S.W.I*

pulmonary oedema has long been recognised complication of renal failure, there is still doubt as to its pathogenesis. Left-ventricular failure (Rendich et al. 1941), increased pulmonary capillary permeability (Bass and Singer 1950), and fluid overload (Alwall et al. 1953) have all been invoked, either singly or in combination. In left-ventricular failure, the pulmonary capillary pressure is notably raised, and may be of the same order as the normal osmotic pressure of the plasma-proteins (Dexter et al. 1950). Increased pulmonary capillary permeability reduces the effective osmotic pressure of the plasmaproteins, and so allows pulmonary oedema to develop at a lower pulmonary capillary pressure. The relative contribution of ultrafiltration and increased capillary permeability to the pathogenesis of pulmonary oedema could therefore be assessed by measurement of the pulmonary capillary pressure during an acute attack. The use of small-bore, flexible nylon catheters has made the measurement of right-heart pressures possible, without disturbance to the patient, in situations where formal cardiac catheterisation would be impossible. Using this technique, observations were made on seven patients in acute pulmonary oedema due to renal failure, and were correlated with the clinical findings. The effects of dehydration by peritoneal dialysis or hsemodialysis were ALTHOUGH

as a

also noted. Patients and Methods The clinical and biochemical data on the patients are summarised in table i. The evidence for acute pulmonary cedema was the presence of severe dyspnoea, orthopnoea, and mental distress, crepitations over the lungs, and, in particular, the radiographic appearances of perihilar or interstitial oedema; these were assessed by a radiologist who had no knowledge of the other clinical details or haemodynamic findings. The patients were extremely ill and so all observations were made in the ward. Right-heart catheterisation was performed with a ’Portex’ 00 nylon catheter, internal diameter 0-5 mm. and external diameter 0-628 mm., which was introduced through an intravenous cannula, and advanced to the pulmonary artery. Pressures were measured with a Statham ’P23Gb ’ straingauge transducer, calibrated directly against a mercury manometer, and a Sanborn direct-writing twin-channel recorder. The position of the catheter tip was confirmed from the character of the pressure pulse. A catheter wedged in the coronary sinus would record a somewhat similar pressure pulse to that of the right ventricle or pulmonary artery but the catheters used float in the direction of blood-flow, and since they remained freely manoeuvrable throughout the procedure it is unlikely that this happened. Cases 1-3 were treated by hypertonic peritoneal dialysis and case 4 was treated by haemodialysis combined with ultrafiltration. In these four cases the pulmonary oedema resolved and measurement of the right-heart pressures was repeated. Because of their orthopnoea the patients were investigated in the position of maximum comfort, rather than supine. Pressures were referred to a point 5 cm. below the sternal angle. Since the relation of this point to the level of the right atrium varies little with position, the present results are comparable with those in other series where the patients were studied supine. The severe dyspnoea was associated with intrathoracic-pressure *

appointment: registrar, National Heart Hospital, Westmoreland Street, London W.1.

Present