Perinatal intensive care: Where and how to draw the line

J. E. Milligan, M.D., F.R.C.S.(C), F.A.C.O.G., A. T. Shennan, M.B., M.R.C.P.(U.K.), F.R.C.P.(C), and E. M. Hoskins, M.D., F.R.C.P.(C)

Toronto, Ontario, Canada

With the rapid advances in perinatal intensive care and resultant changes in neonatal prognosis, it is often

difficult for the medical personnel involved to know where application of such care is justified, whether major intervention for fetal reasons is warranted, or what information to give parents as to probable

outcome. To aid in developing guidelines for these areas of concerns, 730 consecutive live births that occurred in a perinatal unit between 23 and 32 weeks' gestation were analyzed for mortality and long-term morbidity by gestational age at birth. Probability of a normal outcome varies considerably according to which method of analyzing outcome is used. With a greater than 50% probability of intact survival from 25 weeks' gestation and above, intervention for fetal reasons seems to be justified if indicated on purely

medical grounds, although prolonged use of restricted resources at or below 25 weeks remains a concern. (AM. J. OBSTET. GVNECOL. 148:499, 1984.)

Obstetric decision-making in the management of preterm delivery has become increasingly difficult as neonatal outcome, especially for the preterm infant, has changed with the rapid advances in perinatal in­tensive care. 1-5 The difficulties are compounded by the

fact that most reports on mortality and morbidity are related to infants of known weight rather than the less objectively certain gestational age.

Some of the decisions relate to concerns (both medi­cal and legal) as to when it is appropriate to start con­sidering use of the tertiary perinatal unit, and when, purely on the basis of medical outcome, it is appro­priate to consider intervention for fetal reasons. Fi­nally, in discussions with parents during the decision­making process, there is the issue of what they should be told in regard to the probable neonatal outcome and the likelihood of their being able to take hOqle from the neonatal intensive care unit a normal infant.

To help address these very valid obstetric concerns, data on mortality and morbidity by week of gestational age have been derived and analyzed.

Material and methods

All live-born infants, between 23 and 32 weeks' ges­tation, born in the Regional Perinatal Unit, Women's College Hospital, between January 1, 1979, and De­cember 31, 1982, were included for analysis. The ges­tational age accepted was that noted by the obstetrician

From the Regional Perinatal Unit, Women's College Hospital, Uni­versity of Toronto Perinatal Complex.

Presented at the Thirty-ninth Annual Meeting of The Society of Obste­tricians and Gynaecologists of Canada, Vancouver, British Co­lumbia, Canada, june 14-18,1983.

Reprint requests: Dr. J. E. Milligan, Obstetrical Director, Regional Perinatal Unit, Women's College Hospital, 76 Grenville St., To­ronto, Ontario, Canada M5S 1B2.

prior to delivery. If there was a difference of 3 or more weeks on neonatal evaluation (by Dubowitz score) in the neonatal intensive care unit, then the neonatal as­sessment was substituted (less than 1.0% of cases).

All infants were inborn, delivered by obstetricians, and had immediate neonatal resuscitation and inten­sive care. This approach has been described in detail elsewhere.6

Mortality data were derived from the permanent hospital records. A few infants were transferred to the regional pediatric hospital (Hospital for Sick Children) for operations, and are also included if death occurred prior to discharge. Data with respect to morbidity, in­cluding routine ultrasound (since 1981 f and ophthal­mologic examination, were obtained from the neonatal intensive care unit course, as well as from follow-up assessments at 3, 6, 9, 12, and 18 months from ex­

pected date of confinement, as outlined by Hoskins and associates.8

The follow-up program, which included psycho­metric testing at 12 and 18 months after term, is rou­tinely provided for (1) any infant who weighs less than 1,500 gm at birth, and (2) infants over 1,500 gm in whom a problem has been suspected during their course in the neonatal intensive care unit or on exami­nation at discharge. In the denoting of major devel­opmental handicap, some degree of judgmental deci­

sion is involved. The criteria used in this instance were those which would cause a significant interference with what is usually considered to be normal lifestyle.

Follow-up data were noted only if the infant was seen in the follow-up clinic and discharged from hospital at least 6 months prior; thus, several infants who were

discharged during the last few months of 1982, could not be included, since they had not yet been seen at the time this report was prepared. An exception to this rule

499

500 Milligan, Shennan, and Hoskins March 1, 1984 Am. J. Obstet. Gynecol.

Table I. Distribution of 730 consecutive live births at 23 to 32 weeks' gestation

Number of live births Mean weight (gm ± I SD) Mean duration of stay in neonatal

intensive care unit for survivors (days ± I SD)

Table II. Mortality by week of gestation

(a)

23

7 542.9 ± 67.6

124.0

(b)

Gestation (wk)

24

23 620.9 ± 89.9 105.0 ± 1.5

25

44 761.8 ± 92.3

97.2 ± 34.8

(c)

26

45 880.0 ± 158.3

74.2 ± 21.6

Total first week deaths Congenital anomalies incompatible with life

Week of % Incidence gestation No. Mortality No. %

23 6 85.7 24 II 47.8 I 4.4 25 12 27.3 2 4.6 26 II 24.4 2 4.4 27 13 21.7 2 3.3 28 16 18.2 7 8.0 29 9 9.1 3 3.0 30 8 8.8 4 4.4 31 7 6.3 6 5.4 32 7 4.4 5 3.1

was made if the handicap that caused morbidity was diagnosed prior to discharge. In such instances, both the handicap and the patient have been included in the follow-up data. If more than one abnormality was present, only the more major handicapping condition is shown; mental retardation was considered to be present if the Bayley developmental score was less than

80.9

Results

There were 730 live-born infants delivered in the Unit at 23 to 32 weeks' gestation, during the 4-year period from January, 1979, to December, 1982. Their distribution by week of gestation, mean weight, and length of stay in the neonatal intensive care unit until discharge from the hospital is shown in Table I.

In Table II, data are presented relative to mortality in the various ways it can be, and is, calculated. The most common ways of presenting mortality data are presented in columns a, b, and c. Column a: Shown are

total first week deaths (early neonatal mortality) as ab­solute numbers and as a percentage of the original

admitted group. Column b: Shown are deaths due to congenital anomalies incompatible with life, their inci­dence in the original admitted group, and the resultant

Corrected first Deaths Uncorrected week mortality > 1 week prior mortality to discharge

(%) to discharge (%)

85.7 85.7 45.5 3 60.9 23.3 4 36.4 20.9 24.4 19.0 2 25.0 Il.l I 19.3 6.3 I 10.1 4.6 2 11.0 0.9 0 6.3 1.3 I 5.0

mortality rate if corrected for such congenital anoma­lies. The incidence of these anomalies does not sig­nificantly alter with lower gestational age in the range studied. The diagnoses included in this category are listed in Table III. Column c: Table II shows the addi­tional deaths that occurred after the first week but prior to discharge, and the resultant higher mortality rate obtained if total mortality to discharge is calcu­lated. Unlike deaths due to congenital anomalies, this rate and frequency do increase with lower gestational age.

The type and number of the handicaps are shown in Table IV, and their occurrence by week of gestation in Table V. This latter table shows a lower incidence of follow-up than would be the case if only patients from 1979 to 1981 were included, since many infants were

not yet discharged long enough to have been evaluated in the follow-up clinic.

In fact, in all groups below 30 weeks, the follow-up rate was over 90% in the first 3 years of the study popu­lation. The overall incidence of major developmental handicap in the total 1979 to 1982 group was 53 of 730 patients (7.3%), whereas in the 1979 to 1981 subgroup, it was 40 of 533 (7.5%) (all with follow-up over 16 months).

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Perinatal intensive care 501

Gestation (wk)

27

60 968.4 ± 161.2

72.2 ± 18.3

28

88 1,046.3 ± 194.9

59.4 ± 2l.l

29

99 1,163.8 ± 214.3

47.3 ± 24.8

Thus, it does not appear that many infants with a major handicap have not been identified in the total 4-year group.

Even though the likelihood of missing a handicap appears to be low (if there is a normal neonatal inten­sive care unit course and ultrasound), especially in in­fants who weighed more than 1,500 gm (this group accounts for the large number without follow-up at 30 to 32 weeks), the last column in Table V indicates the potential incidence of major developmental handicap, if one adds a correcting factor for this missing segment. Correction is made by assuming a similar rate of major developmental handicap in those lost to follow-up (or not yet seen) as was found in those actually followed, and probably causes a bias toward a higher rate.

Comment

It is easy to understand why most results relate to the absolute and exact measurement of infant birth weight, rather than the uncertainties of last menstrual period, unknown ovulation time, and even ultrasound mea­

surements, all of which make uncertain gestational age the bane of most obstetricians' existence. Nonetheless, from weight curves, length of stay, and progressive and increased survival, it would appear that careful obstet­ric evaluation by present-day techniques does, indeed, bear a close relationship to actual outcome parameters.

Mortality is probably the easiest outcome marker to use, since it can be measured so readily. It is apparent, though, that the most common mortality measurement (first week mortality) may be misleading. First, congeni­tal anomalies incompatible with life will considerably lower (or improve) this rate. It is apparent, however, that up to 56% of these anomalies would probably not be diagnosed antenatally (unless for some other reason, genetic amniocentesis had been carried out). Thus, this correction should probably not be considered in the obstetric decision-making. Since the uncorrected mor­

tality to discharge does include the increasing effect of lower gestational age and ignores the, as yet unknown, condition of the infant on admission to the neonatal intensive care unit, it is probably a more realistic obstetric standard.

30 31 32

91 1,325.7 ± 248.2

40.8 ± 26.8

112 1,547.9 ± 300.8

31.8 ± 21.7

161 1,708.8 ± 313.3

24.4 ± 18.0

Table Ill. Deaths due to congenital anomalies incompatible with life

Not diagnosed antenatally Likely to be

diagnosed antenatally

Trisomy 2 Nonimmune hydrops Pulmonary hypoplasia 4 Anencephaly

(crush syndrome) Multiple anomalies Cardiac disease Diaphragmatic hernia Metabolic abnormality Arthrogryposis

6 Potter's syndrome 2 Hydrocephalus 2 I I

Table IV. Number and type of major developmental handicaps

Mental retardation Spastic diplegia Quadriplegia Hemiplegia Blind Hydrocephalus Hypotonia Periventricular leukomalacia

15 15 9 7 3 2 I

3 3

7 I

The problems inherent in using morbidity or devel­opmental handicap as a marker reflecting perinatal care are even greater. The initial problems are moral or judgmental. Who is to judge the quality of life of an individual with mild spastic diplegia and normal intel­ligence, or a blind person who is otherwise perfectly normal? In this evaluation, all were considered equally

as having major developmental handicaps. The more practical problem is at what age the mea­

surement of handicap should be made and whether more minor degrees of handicap should be included. 10

In this series, since the incidence of major devel­opmental handicap was almost the same at 6 months after discharge as at 18 months, this former time frame was accepted and minor degrees of handicap were excluded.

Finally, the most thorny problem is what to do in the

502 Milligan, Shennan, and Hoskins

Worst % probability of taking home a normal Infant D Corrected occurrence of MDH % _

Uncorrected mortality to dllchar\Je % _

Fig. 1. Worst potential probability of taking home a normal infant. Obstetric predelivery prediction. MDH, Major devel­opmental handicap.

Table V. Occurrence of major developmental handicaps

Neonatal intensive care unit Follow-up

I No. I Week of Admissions Discharges gestation (No.) (No.) %

23 7 I I 100 24 23 9 8 88.9 25 44 28 27 96.4 26 45 34 27 79.4 27 60 45 35 77.8 28 88 71 61 85.9 29 99 89 81 91.0 30 91 81 58 71.6 31 112 105 62 59.1 32 161 153 68 44.4

March 1, 1984 Am. J. Obstet. Gynecol.

Best % probability of taking home a normal Infant D Actual Incidence MDH % _

1.t week mortality corrected for con\Jenltal anomalle. % _ 100%

68

98

72 66 73 94 89 86

Fig. 2. Best potential probability of taking home a normal infant. Neonatal postresuscitation prediction. MDH, Major developmental handicap.

Actual occurrence of handicap Corrected* occurrence of

I major developmental

% Those I % Admitted handicap: percentage of No. followed group admitted group

0 0 0 0 3 37.5 13.0 14.8 4 14.8 9.1 9.6 3 11.1 6.7 8.4 9 25.7 15.0 19.3

14 23.0 15.9 18.5 5 6.2 5.1 5.6 8 13.8 8.8 10.8 5 8.1 4.5 7.6 2 2.9 1.2 2.8

*Corrected by assuming same occurrence of major developmental handicap in those lost to follow-up as in those followed.

calculations with those lost to follow-up. Is the infant with a normal neonatal intensive care unit course, normal ultrasound, and normal examination at 3 months, whose parents leave the country at 4 months, to be considered abnormal? Conversely, is the child who dies of sudden infant death syndrome (SIDS) to be considered normal. The difficulty is compounded in the 30- to 32-week gestation, with an increasing num­ber of infants weighing more than 1,500 gm at birth, who with a normal neonatal intensive care unit course have such a low incidence of major developmental handicap that, because of volume and low rate of iden­tified problems, cannot be routinely included in most follow-up programs. 1O

The answers to these problems are arbitrary, and the two extremes are reflected in the somewhat optimistic rates of actual major developmental handicap and the unduly pessimistic rates of corrected incidence of major developmental handicap.

The bottom line in medical practice may well be to know what the probability is of death or damage. From the informed patient's point of view, in this particular instance, the bottom line must surely be the probability

of taking home a normal infant. The two extremes of probability, related to our unit over these particular 4 years, are shown in Figs. 1 and 2. The worst potential outcome (Fig. 1) may well be the most valid obstetric predelivery probability. The best potential outcome (Fig. 2) might well be considered to be the postresusci­tation prediction that the neonatologist can give once congenital anomalies are ruled out and the state of the infant is known. Since there is such a wide range of outcomes when different units and time frames are compared,ll it is recommended that each unit involved in this type of care should develop, in an ongoing fash­ion, its own outcome curves for use in decision-making.

Although differences in the two curves are of practi­cal interest and use, the similarities are of concern. The progressive fall of mortality to 26 weeks is not surpris­ing, although the mortality rates are lower than have been reported even recently by others. 12• 13 It is reassur­ing to note that the falling mortality is not at the ex­pense of the increased morbidity, which Kitchen and associates13 reported as increasing at lower gestational age. It is almost as though, if perinatal insult occurs at 26 weeks and below, then the fragility of the organism

Volume 148 Number 5

is such that death, not damage, will result. It is of clini­

cal concern, and biologic fascination, however, to note

that at 27 to 28 weeks, there is minimal change in mor­

tality but an increase in morbidity. One must query

whether the tolerance of the developing biologic sys­

tems is such that an insult no longer causes death but

does result in damage. The changing responses of such

systems during fetal development at this stage of gesta­

tion must, obviously, be an area of high priority in basic research.

Finally, it is reassuring to know that no matter how

one visualizes potential outcome, the odds of a favor­

able result in this study were greater than 50% at 25

weeks' gestation and above. By any medical standards,

this has to be considered worthwhile. The only philo­

sophic concern must be when the resources required

for this result are restricted in availability. In such a case, with the use of resources, as reflected in length of

stay required at 25 weeks and below, is one justified in

using the facility for this result, when the result is posi­tive in over 84% of cases at 29 weeks? This concern is

compounded, since the requirements of resources are

only half as much at 29 weeks, thus allowing twice as

many patients to be looked after. This latter problem is

one of the areas the physician, as a member of society

and as a health care planner, must consider and is but

one of the increasing number of moral and ethical con­

cerns related to medicine in general, and perinatology

in particular. 14 It is doubtful, however, whether any

practicing physician, whose main aim should be the well-being of his patient, should ever have to answer

this dilemma on the basis of individual patients.

REFERENCES

1. Hack, M., Fanaroff, A. A., and Merkatz, I. R.: The low birthweight infant-Evolution of a changing outlook, N. Engl. J. Med. 301:1162, 1979.

Perinatal intensive care 503

2. Shennan, A. T., and Milligan, J. E.: The growth and de­velopment of infants weighing 1,000-2,000 grams at birth and delivered in a perinatal unit, AM. J. OBSTET. GYNECOL. 136:273, 1980.

3. Driscoll, J. M., Driscoll, Y. T., Steir, M. E., Stark, R. I., Dangman, B. c., Perez, A., Wung, J.-T., and Kritz, P.: Mortality and morbidity in infants less than 1001 grams birthweight, Pediatrics 69:31, 1982.

4. Ruiz, M. P. D., LaFever, J. A., Hakanson, D.O., Clark, D. A., and Williams, M. L.: Early development of infants of birthweights less than 1000 grams, with reference to mechanical ventilation in newborn period, Pediatrics 68:330, 1981.

5. Stewart, A. L., Turcan, D. M., Rawlings, G., and Reyn­olds, E. O. R.: Prognosis of infants weighing 1000 grams or less at birth, Arch. Dis. Child. 52:97, 1977.

6. Milligan, J. E., and Shennan, A. T.: Perinatal manage­ment and outcome in the infant weighing 1,000 to 2,000 grams, AM. J. OBSTET. GYNECOL. 136:269, 1980.

7. Dolfin, T., Skidmore, M. B., Fong, K. W., Hoskins, E. M., and Shennan, A. T.: Incidence, severity and timing of subependymal and intraventricular hemorrhages in pre­term infants born in a perinatal unit as detected by serial real-time ultrasound, Pediatrics 71:541, 1983.

8. Hoskins, E. M., Elliot, E., Shennan, A. T., Skidmore, M. B., and Keith, E.: Outcome of very low-birth weight infants born at a perinatal center, AM. J. OBSTET. GYNECOL. 145:135, 1983.

9. Bayley, N.: Bayley Scales of Infant Development, New York, 1969, The Psychological Corporation.

10. Fitzhardinge, P. M., and Pape, K. E.: Follow-up studies of the high risk newborn, in Neonatology: Pathophysiology and Management of the Newborn, ed. 2, Philadelphia and Toronto, 1981,J. B. Lippincott Co.

11. Schechner, S.: For the 1980's: How small is too small? Clin. Perinatol. 7:135, 1980.

12. Lamont, R. F., Dunlop, P. D. M., Crowley, P., and Elder M. G.: Spontaneous preterm labour and delivery at under 34 weeks' gestation, Br. Med. J. 286:454, 1983.

13. Kitchen, W. H., Yui, V. G. H., Orgik, A. A., Ford, G., Rickards, A., Astbury, J., Ryan, M. M., Russo, W., Lissen­der, J. V., and Bajuk, B.: Infants born before 29 weeks' gestation: Survival and morbidity at 2 years of age, Br. J. Obstet Gynaecol. 89:887, 1982.

14. Avery, G. B.: The mortality of drastic intervention, in Neonatology: Pathophysiology and Management of the Newborn, ed. 2, Philadelphia and Toronto, 1981, J. B. Lippincott Co.