Preterm birth at 23 to 26 weeks' gestation: Is active obstetric management justified?

Preterm birth at 23 to 26 weeks' gestation: Is active obstetric management justified? Chukwuma G. Nwaesei, M.D., David C. Young, M.D., Joseph M. Byrne, Ph.D., Michael J. Vincer, M.D., Doris Sampson, R.N., Jacquelyn R. Evans, M.D., Alexander C. Allen, M.D., and Dora A. Stinson, M.D.

Halifax, Nova Scotia, Canada To determine if active perinatal management was justified in preterm deliveries at .s26 weeks' gestation, the outcome (survival and short- and long-term morbidity) of 43 infants (group I) born between 23 and 26 weeks' gestation was compared with that of 17 infants (group II) born at 27 weeks' gestation. Of the 12 surviving infants in group I (survival 28%), 11 were ventilated (median = 50 days), eight had moderate to severe bronchopulmonary dysplasia, and four had mild retrolental fibroplasia. At follow-up, two infants had physical disabilities with moderate to severe functional impairment, one had a minor disability, and nine had normal neurodevelopment. In contrast, of the 13 surviving infants in group II (survival 76%), nine were ventilated (median = 8 days), six had moderate to severe bronchopulmonary dysplasia, and six had mild RLF. At follow-up, one infant had a physical disability with moderate to severe functional impairment, four had minor disabilities, and eight had normal development. Perinatal factors that positively influenced survival in the two groups combined included active perinatal management, antenatal steroids, female sex, and absence of clinical chorioamnionitis and asphyxia. Although group I infants had a significantly higher mortality rate (p < 0.05) and required a longer duration of ventilation (p < 0.05), no differences in the incidence of postnatal complications or long-term morbidity at 2 to 4 years of age were evident between the two groups. (AM J 0BSTET GYNECOL 1987;157:890-7.)

Key words: Preterm delivery, active obstetric management, survival, neurodevelopmental outcome

Advances in obstetric and neonatal care and the improvement in survival rates and quality of outcome for very low birth weight infants in recent years have led to a reevaluation in the management of premature deliveries. More specifically, the management of deliveries between 23 and 26 weeks of gestation when the fetus has traditionally been regarded as nonviable, previable, or borderline viable has received increasing attention.'·5 For perinatologists in tertiary care settings who must deal with these issues regularly and for primary care physicians who must decide whether to transfer such cases to tertiary care centers for further management, the crucial question is, what is the lowest gestational age that justifies active perinatal care? Below what gestational age should there be a hands-off approach by the perinatal team? In other words, how premature is too premature?

From the Department of Neonatal Pediatrics and the Department of Obstetrics and Gynecology, Dalhousie University, the Department of Psychology, IWK Hospital for Children, and the Perinatal Follow-Up Program, Grace Maternity Hospital. Received for publication July 22, 1986; revised January 21, 1987 and April21, 1987; accepted May 19, 1987. Reprint requests: Chukwuma Nwaesei, M.D., Perinatal Follow-Up Program, Grace Maternity Hospital, 5821 University Ave., Halifax, Nova Scotia, Canada BJH 1W3.

890

At the Grace Maternity Hospital in Halifax, Nova Scotia, Canada (the major high-risk maternal referral center in Nova Scotia with 1000 high-risk deliveries out of 5400 annual deliveries), the approach has been to assume fetal viability and provide active perinatal management for pregnancies terminating at 27 weeks' gestation and above. With deliveries occurring at 26 weeks' gestation or less, there is no clear consensus. Most are treated passively, with regard primarily for maternal considerations. Such an attitude is supported by previous reports on the outcome of infants born at 26 weeks' gestation or less, which indicate very high mortality rates and uniformly poor long-term neurodevelopment. 6 · 7 Because more recent reports have demonstrated an improvement in survival rates and increasing numbers of intact survivors among these extremely preterm infants, I. 2 • 4 it has been suggested that the gestational age limit for active intervention on behalf of the fetus should be lowered even further-from the currently accepted 27 weeks to 24 weeks.' We have reviewed our experience with this group of infants to determine if a change in approach is indicated. We reviewed the outcome of infants born between 23 and 26 weeks' gestation for: (1) survival, (2) short-term morbidity and (3) long-term neurodevel-

Volume 157 Number 4, Part I

opmental status and compared it with that of infants born at 27 weeks' gestation during the same period. Material and methods

The study population consisted of all liveborn infants delivered between 23 and 27 weeks of gestation within the Grace Maternity Hospital during the 3-year period from Jan. 1, 1980 to Dec. 31, 1982. Gestational age was based on: (1) firm dates-a firsttrimester history with known last normal menstrual period, regular periods, and no birth control pills used in the preceding 6 months and one or both of the following: (2) ultrasound examination in the first trimester with crown rump length agreeing with dates and (3) ultrasound examination between 18 and 20 weeks' gestation with biparietal diameter agreeing with dates, within 6 days. Inclusion of patients into this study was made exclusively on the basis of assignment of prenatal gestational age. In cases in which there was a discrepancy between prenatal and postnatal assessments, prenatal gestational-age assessment prevailed. One infant with congenital anomalies incompatible with long-term survival has also been excluded from the study. Gestational age was assigned as the last completed week. The obstetric managment of these patients varied. A key feature in the different approaches was the obstetrician's perception of fetal viability and the decision as to whether cesarean section would be considered evidence of fetal distress in labor or malpresentation (breech). When the fetus was thought to be nonviable by the obstetric staff, a hands-off approach was instituted. Many obstetricians who have made this decision would use no form of fetal monitoring; maternal wellbeing was the only consideration, with no intervention on behalf of the fetus (passive management). Those obstetricians who considered the fetus viable would attempt to deliver the fetus in the best possible condition, with electronic fetal monitoring used as a guide to timely operative vaginal delivery; others would perform a cesarean section for malpresentation or for fetal distress diagnosed by continuous electronic fetal heart rate monitoring, supplemented by fetal scalp blood pH (active management). Other management decisions such as the use of tocolytics and/or steroids were largely based on the advancement of labor as indicated by dilatation of the cervix and whether amniotic membranes were ruptured, with gestational age not a crucial factor. Patients were classified as having received steroids if at least 24 hours had elapsed from the first dose to delivery. All obstetric management decisions were carried out under the direct supervision of attending obstetricians. Neonatal staff attended all deliveries. Resuscitation was with bag and mask and oxygen or more commonly

Preterm birth at 23 to 26 weeks' gestation

891

with endotracheal intubation. Each newborn infant was cared for in the special neonatal care nursery under direct supervision of a neonatologist. Follow-up protocol

An appointment for assessment was offered to all surviving infants at the ages of 2, 3, or 4 years. All were seen at the Perinatal Follow-Up Clinic at the Grace Maternity Hospital, at which time an interim history was obtained and assessment of growth and physical and neurodevelopmental examinations were then carried out. Evidence of hydrocephalus, cerebral palsy, or minor changes in tone was noted. Psychometric assessment was performed by a clinical child psychologist who administered the Bayley Scales of Infant Development to the 2 year olds, and the McCarthy Scales of Children's Abilities to the 3 and 4 year olds, respectively. All scores and physical measurements were corrected for the infant's gestational age. Audiologic assessments were performed by the Nova Scotia Hearing and Speech Clinic, and if the child had not been seen recently by an ophthalmologist, an appointment was offered. None of the medical personnel participating in the follow-up protocol had participated in the perinatal management of these infants. Definition of terms

Neonatal survival was defined as alive at discharge from the nursery. Clinical asphyxia was defined as depression at birth that required positive pressure resuscitation for longer than 2 minutes, skin pallor, and abnormal neurologic signs (e.g., marked alteration of muscle tone or seizures). Clinical chorioamnionitis was defined as malodorous vaginal discharge and/or fever (temperature >37.5° C), with lower abdominal tenderness before delivery. All cases of clinical chorioamnionitis were confirmed by histopathologic evidence of inflammation of the chorionic plate. Bronchopulmonary dysplasia" was defined as follows: ( 1) respiratory distress beyond 2 weeks of age not otherwise explained and/or Pco 2 >60 mm Hg on two or more occasions beyond 1 week of age and (2) chest radiographic changes typical of bronchopulmonary dysplasia. 8 Retrolental fibroplasia was graded as mild (grades 1 or 2) or moderate to severe (grades 3 and 4). Physical disability was defined as cerebral palsy and visual or hearing deficits. Cerebral palsy was graded according to motor disabilities. Mild cerebral palsy was defined as a disability in ambulant children that interfered only slightly with normal daily functioning. Such children had hyperreflexia and hypertonicity, and if both lower limbs were affected, a positive Babinski re-

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October 1987 Am J Obstet Gynecol

Results

,-77%---,

(/)

16 14

40%

I-

z 12 10 ~

<( LL

LL

8

a: w

6 4

0

CD

::2!

:::>

z

2 0

~

1 hr 2-24 hr

1-7 2nd 3rd 4th ~ 5 days week week week weeks POSTNATAL AGE

Fig. 1. Age at death.

flex. Moderate cerebral palsy included those children who attempted to walk at 2 years old. Severe cerebral palsy included those children who were likely to remain permanently nonambulant. 9 Overall neurodevelopmental status was classified as normal or functionally handicap. An infant was considered normal if intellectual potential as measured by either the Bayley Mental Developmental Index or the McCarthy General Cognitive Index was in the normal range (i.e., above 84), and both gross motor and fine motor performances were qualitatively and quantitatively appropriate for the age. Functional handicap was classified according to the degree imposed by single or multiple physical disabilities (severe cerebral palsy, sensory impairment, and cognitive deficits). Severe functional handicap was considered to be present in children who had one or more of the following disabilities: moderate or severe cerebral palsy, a mental developmental index or a general cognitive index <69, and sensorineural deafness that required the use of hearing aids or bilateral blindness. A moderate functional handicap was diagnosed in children with a mental developmental index or a general cognitive index of 69 to 84 and one or more of the following: mild cerebral palsy, sensorineural deafness not requiring amplification, severe myopia, strabismus, or retrolental fibroplasia. Children were classified as having a mild functional handicap if they had either a mental developmental index or a general cognitive index score between 69 and 84 or mild cerebral palsy with a mental developmental index or a general cognitive index score >84. Statistics

Continuous variables were analyzed by t test; discontinuous variables were analyzed by X2 test with the Yates correction or Fisher's exact test as needed. p Values <0.05 were considered statistically significant.

Of the 14,776 infants delivered during the study period, 60 met the study criteria. All 60 mothers had a prenatal ultrasound examination in the first trimester and/or between 18 and 20 weeks' gestation. In 17 cases (28%), the crown rump length agreed with maternal dates, and in the remaining 43 cases (72%), the biparietal diameter agreed with the dates within 6 days. The birth weights of the 60 infants ranged from 450 to 1360 gm (mean ± SD = 746 ± 168 gm). Overall survival was 42% (25/60). The mean birth weight ( ± SD) of the 25 surviving infants was 810 ± 112 gm; for those who died it was 710 ± 187 gm (p < 0.007). The number and percentage of surviving infants and the birth weight distribution of the dead and surviving infants at each completed week of gestational age are shown in Table I. As expected, newborn survival at each week of gestation improved with increasing gestational age and was highest for infants at 27 weeks' gestation. The earliest survival was at 24 weeks' gestation (740 gm male). Of the 35 deaths, 13 deaths (37%) occurred within 1 hour of delivery (Fig. 1). An additional 14 infants (40%) died by 24 hours of age. The m~or causes of death were hyaline membrane disease (8/35, or 23%), extreme immaturity (6/35, or 17%), intrapartum asphyxia (6/35, or 17%), and infection (5/35, or 14%). Of the four infants who died after the first week of age, one infant (930 gm male born at 27 weeks) died at 15 days of age of massive pulmonary hemorrhage after a fulminant course of hyaline membrane disease. Two infants (a 780 gm female infant at 24 weeks and an 800 gm male at 27 weeks) died at 62 days and 168 days of age, respectively, of severe cystic bronchopulmonary dysplasia with pulmonary hypertension. The fourth infant (795 gm male at 25 weeks) died at 76 days of age from overwhelming sepsis, disseminated intravascular coagulopathy, and shock. Survival

The survival rate in the infants who were 23 to 26 weeks' gestation (group I) was 28% compared with the 76% rate among infants who were 27 weeks' gestation (group II) (Table I). The birth weight and gestational age distribution of study infants in relation to mode of obstetric management is shown in Table II. Only 14 of the 43 infants (33%) in group I were born to mothers who had active obstetric management compared with 15 of 17 infants (88%) in group II. The earliest gestational age at which a cesarean section was performed was 25 weeks. Five patients (12%) received antenatal steroids at least 24 hours before delivery in group I compared with seven patients (41%) in group II. Of the perinatal factors evaluated for their influence on survival in group I infants, only female sex was positively correlated. However, when all study infants

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893

Table I. Newborn survival and birth weight distribution at each completed week of gestation Birth weight (gm) (mean ± SD)

Survivors Wkof gestation

Total live births

No.

23 24 25 26 27 Total

7 10 13 13 17 60

0 1 5 6 13 25

I

% 0 10 38 46 76 42

Dead

560 460 780 735 865 710

± ± ± ± ± ±

I

54 99 274 185 75 187

Survived

740*:j: 704 ± 148* 813 ± 113* 854 ± 72* 810 ± 112t

T

Total

560 650 751 771 857 746

± ± ± ± ± ±

54 98 230 155 72 168

*Not significantly different from those who died. tSignificantly different from those who died. :j:Lone survivor.

Table II. Birth weight and gestational age distribution in relation to mode of obstetric management Obstetric management

Whole group Gestational age (mean Birth weight (mean ± .;;26 wk infants* Gestational age (mean Birth weight (mean ±

± SD) SD)

Active

Passive

(n = 29)

(n = 31)

26.2 ± 0.9 794 ± 136

± SD) SD)

Passive Active (n = 14)

(n = 22)

24 ± 1.3 ( p < 0.0001) 701 ± 184 ( p < 0.03) 25.3 ± 0.6 728 ± 160

24.9 ± 0.8 731 ± 191

NS NS

*Twenty-four to 26 weeks' gestational age infants only.

(groups I and II combined) were considered, antenatal steroids, active obstetric management, absence of clinical chorioamnionitis or clinical asphyxia, and female sex were found to be positively correlated with neonatal survival (Table III). Short-term morbidity

Table IV shows the frequency of postnatal complications in surviving infants born at 23 to 36 weeks and at 27 weeks' gestation. Major postnatal complications among surviving infants were bronchopulmonary dysplasia and retrolental fibroplasia. Group I (infants 23 to 26 weeks' gestation). Of the 12 surviving infants born between 23 and 26 weeks' gestation, seven had idiopathic respiratory distress syndrome and required ventilatory support. Four additional infants in this group who had severe recurrent apnea also required ventilatory assistance. Not all infants were evaluated for intracranial hemorrhage by real-time ultrasonography, since this technique was not used routinely in our nursery until 1981. Of the nine infants in this group who had serial cranial ultrasound evaluation, five had no hemorrhage, two had hemorrhage into the germinal matrix, one had intraventricular hemorrhage with arrested ventriculomegaly, and one infant had bilateral intraparenchymal hemorrhage with hydrocephalus requiring ventriculoperito-

neal shunt. Eight infants had moderate to severe bronchopulmonary dysplasia that required prolonged ventilation. Of the five infants in this group with patent ductus arteriosus, three required surgical ligation. All four infants with retrolental fibroplasia had only mild disease (grades 1 and 2). Group II (infants 27 weeks' gestation). Of the 13 surviving infants born at 27 weeks' gestation, nine developed respiratory distress syndrome and required ventilatory support. Of the nine infants screened for intraventricular hemorrhage, only one infant had evidence of hemorrhage (germinal matrix hemorrhage only). Eight infants in this group had varying degrees of bronchopulmonary dysplasia, and all six infants with retrolental fibroplasia had only mild forms of the disease. Five of the nine infants with patent ductus arteriosus required surgical ligation of the duct. There was no difference in the mean duration of hospital stay among the two groups of gestational-age infants. Long-term follow-up (groups I and II)

All surviving infants were between 2 and 4 years of age at the time of developmental evaluation. Of the 12 survivors, in group I, six were two years old, five were 3 years old, and one was 4 years old, respectively, at the time of assessment. Of the 13 survivors in

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Table III. Correlation of perinatal factors with neonatal survival Percent survivor Whole group

l

l

p Value

%

p

18/29 7/31

62 23

<0.005

7/14* 5/22*

50 23

NS

5/15 2/4

33 50

NS

3/13 112

23 50

NS

8112 17/48

67 35

<0.05

2/5 10/38

40 26

NS

7/27 18/33

26 54

<0.025

4/22 8/21

18 38

NS

12/41 13/19

24 68

<0.005

8/33 4/10

24 40

NS

9/36 16/24

33 67

<0.005

3/26 9/17

12 53

<0.005

Characteristic

Obstetric management Active Passive Mode delivery (malpresentation) Vaginal Cesarean section Antenatal steroids (>24 hr before delivery) Yes No Clinical chorioamnionitis Yes No Clinical asphyxia Yes No Sex Male Female

,;;26 wk only

n

n

%

*Twenty-four to 26 weeks' gestational age infants only.

Table IV. Comparison of postnatal morbidity in surviving infants born at :;;:;26 weeks' and 27 weeks' gestation ,;;26 wk (n = 12) (%)

Hyaline membrane disease Patent ductus arteriosus Clinical sepsis Ventilatory support (IMV only) Seizures Duration of IMV (median days) Age birth weight regained (days)* Length of hospital stay (days)* Retrolental fibroplasia grades l and 2 Bronchopulmonary dysplasia Mild Moderate to severe Intra/periventricular hemorrhage Mild Moderate to severe

7 5 10 ll

(58) (42) (83) (92)

l (8)

50 14.6 ± 4.36 135 ± 52 4 (33) 0 8 (n = 9)t 2

2

27 wk (n = 13) (%)

9 10 8 9 l 8 14.9 132 6

(69) (77) (61) (69) (8) ± 6 ± 89 (46)

3 5 (n = 9)t l 0

p Value

NS NS NS NS NS <0.05 NS NS NS NS NS

IMV = Intermittent mandatory ventilation. *Mean± SD. tNumber screened by cranial ultrasound examination.

group II, seven were two years old, three were 3 years old, and three were 4 years old. Table V compares the long-term neurodevelopmental outcome in the two groups of infants. There was no statistically significant difference in the incidence of functional handicap or physical disabilities among the two groups of surviving infants. Two of 12 (17%) surviving infants in group I and one of 13 (7%) surviving infants in group II had physical disabilities. The nature and severity of physical and functional handicap of affected infants are shown in Table VI.

Comment

For many decades, birth weight has been used as a convenient characteristic against which to measure survival prospects of premature infants. It was readily available, objective, and served to circumvent the difficulties of accurate determination of gestational age because of the uncertainties of the last normal menstrual period. Survival statistics based on birth weights largely served the interest of the neonatologist and had limited value to the obstetrician who must make the critical management decision before delivery. Although

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Table V. Comparison of long-term outcome at ages 2 to 4 years between surviving infants born at ,;26 weeks' and 27 weeks' gestation ,;;26 wk (n = 12) (%)

Neurodevelopmental status Normal Minor functional handicap Moderate functional handicap Severe functional handicap Physical disability (CP, blindness, deafness) CP

=

9 (75) I (8)

27 wk (n = 13) (%)

p Value

8 (62)

NS NS NS NS NS

4 (31) I (7)

2 (17) 2 (17)

I (7)

Cerebral palsy.

Table VI. Survivors with functional ± physical disabilities Birth weight Gestation (wk)

,;:;26 wk (n = 3) 25 25 25 27 wk (n = 5) 27 27 27 27 27

Functional handicap

Sensorineural deafness

Cerebral palsy

(gm)

680 760 460

F F

Spastic quadriplegia

M

750

F

870 770 880 940

Mild spastic diplegia

F F

Bilateral

M M

Severe

Untestable 50 83

Severe Severe Mild

80

Moderate

75 70 70 80

Mild Mild Mild Mild

MDI = Mental Development Index. GCI = General Cognitive Index.

birth weight and gestational age have been shown to be major determinants of neonatal survival, 10 gestational age better reflects fetal maturation and is therefore more likely to be a better predictor of outcome. In a study of the survival of infants born at 24 to 28 weeks' gestation that used multivariate analysis, Herschel et al. 2 showed that gestational age made the most significant contribution to outcome; birth weight did not add to the discrimination. More recently, in a cohort of 1338 very premature and/or very low birth weight infants representing 94% of all liveborn infants at 32 weeks' gestation or less, Verloove-Vanhorick et al. 10 found that gestational age was a better predictor of neonatal survival than was birth weight. Therefore future studies on preterm infants are encouraged to place greater emphasis on gestational age, and not postnatal birth weight as the crucial independent variable affecting neonatal survival. Our neonatal survival rate at each completed week of gestation is comparable with that reported by others. 2· 6 The survival of preterm infants partly depends on whether the obstetrician believes that the fetus is viable.11· 12 Our aim was to determine if the nature of obstetric management (active or passive) at 23 to 26 weeks' gestation influenced neonatal survival. This was a difficult task, since the obstetrician's attitude does not readily lend itself to experimental investigation. Our definition of active obstetric management in-

eluded all cases of assumed fetal viability in which the ultimate goal of management was to avoid fetal hypoxia and acidosis. This did not necessarily imply cesarean section. Other management maneuvers considered equally important included careful positioning of mother, generous use of oxygen in cases of suspected fetal distress, and avoidance of depressant drugs as much as possible during labor. In our institution during the review period, no delivery occurring earlier than 24 weeks was actively managed. Of the 14 deliveries between 24 and 26 weeks' gestation that had active obstetric management, seven infants (50%) survived. In contrast, only five of 22 infants (23%) born at 24 to 26 weeks' gestation whose mothers had not been actively managed in labor survived. Although this difference did not achieve statistical significance, there certainly was a trend for infants delivered to mothers who had been actively managed in labor to do better. However, when infants born at 27 weeks' gestation were included in the analysis, active intervention was clearly beneficial. Because many more infants were actively managed at 27 weeks' gestation (15117, or 88%) than at ,;26 weeks (14/43, or 32%), the apparent difference observed in the analysis of the whole group may very well reflect the influence of gestational age and the mode of obstetric management. Because very few mothers (5/43) received steroids at 26 weeks' gestation or less, the possible influence of this

896

Nwaesei et al.

management decision on neonatal survival at these gestations is difficult to determine. The optimal mode of delivery for malpresentation in preterm infants remains controversial. Although some reports strongly favor the abdominal route,'· 12 others are unable to show any impact of delivery method on neonatal survival."· 14 In a recent review of the impact of cesarean birth on preterm breech presentation, Bodmer et al. 15 concluded that although cesarean section was performed least often among extremely premature infants (25 to 28 weeks' gestation), these cases may prove most beneficial. During the period of our review, of 15 infants who were in breech presentations or with transverse lie at ~26 weeks' gestation, only two (13%) were delivered by cesarean section. In contrast, two of four infants (50%) with malpresentation at 27 weeks' gestation were delivered by cesarean section. Because delivery by cesarean section for malpresentation was used more frequently when the infant was more mature, the improved survival advantage may only reflect gestational maturation. The advantage that was due to the method of delivery was unclear. Thus no conclusions can be drawn about abdominal delivery of infants at ~26 weeks' gestation from this report because the numbers were too small. It has recently been suggested that occult antepartum infection of the genital tract could be an important cause of preterm delivery. 16 Our data show a negative impact of clinical chorioamnionitis on neonatal survival for the whole group. The trend is similar for the infants born at ~26 weeks' gestation but is not statistically significant (Table III). Except for differences in the duration of ventilation, we were unable to demonstrate any other significant differences in postnatal morbidity (Table IV) between surviving infants born at ~26 weeks' gestation and those born at 27 weeks. in this regard, our results contrast with those of Gilstrap et al., 13 who reported significantly more serious postnatal morbidity among surviving infants born between 23 and 26 weeks' gestational age. Earlier reports of long-term neurodevelopmental status of extremely premature infants showed uniformly poor outcome. 6 • 7 Bennett-Britton et al. 6 reviewed the outcome of 158 infants weighing ~800 gm at birth in a referral neonatal intensive care unit and found no intact survivors with gestational age ~26 weeks or birth weight ~700 gm. Our study population differs from that of Bennett-Britton et al. 6 in that it was inborn but is similar to that of Yu et al.,< who have recently reported more encouraging findings in gestational age groups identical to ours. Of 35 survivors born between 24 and 26 weeks' gestation, these investigators reported a 74% satisfactory outcome at 2 years of age. The present report has the advantage of a much longer period of follow-up and represents a 100%

October 1987 Am J Obstet Gynecol

follow-up, with every survivor undergoing developmental assessment (Table V). In summary, we have reviewed the outcome of infants born between 23 and 26 weeks' gestation (group I) in comparison with infants born at 27 weeks' gestation (group II). Group I infants had a significantly higher mortality rate, most notably at 23 and 24 weeks' gestation, and required a longer duration of ventilatory support. No other differences were evident between the two groups. Analysis of perinatal factors showed that for groups I and II combined, active obstetric management, antenatal steroids, and female sex were associated with increased survival, whereas the presence of clinical chorioamnionitis and asphyxia resulted in increased death. When infants born at ~26 weeks' gestation (group I) were analyzed separately, there was a trend for infants whose mothers had been actively managed in labor to have a better outcome, but this trend did not reach statistical significance. It could be argued that intensive perinatal care should be widely extended to all deliveries occurring between 23 and 26 weeks' gestation, with the expectation that sooner or later perinatologists would become sufficiently adept to allow even the 'youngest infant to survive without major impairment. A prospective study designed with such an approach would have greater validity in addressing the gestational-age threshold question. However, the ethical, psychological, and economic implications of such an approach must also be addressed. Our data suggest a favorable long-term outcome for surviving infants born between 24 and 26 weeks' gestation but does not answer the question whether active perinatal management of these deliveries should become a standard practice. Further study is required to address this question. The high neonatal loss among deliveries occurring between 23 and 26 weeks' gestations dictates that efforts aimed primarily at postponing deliveries beyond 26 weeks, or better still, eliminating premature delivery, should remain the mainstay of therapy. Until this is achievable, obstetric management decisions involving these deliveries will have to be made on an individual basis, keeping in mind that very preterm infants can have a favorable long-term outcome.

REFERENCES 1. Dillon WP, Egan EA. Aggressive obstetric management in late second-trimester deliveries. Obstet Gynecol 1981;58: 685-90. 2. Herschel M, Kennedy JL, Kayne HL, Henry M, Cetrulo C. Survival of infants born at 24 to 28 weeks' gestation. Obstet Gynecol 1982;60; 154-8. 3. Buckwald S, Zorn WA, Egan EA. Mortality and follow-up data for neonates weighing 500 to 800 g at birth. Am J Dis Child 1984; 138:779-82. 4. Yu VYH, Orgill AA, Bajuk B, Astbury J. Survival and

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5. 6. 7. 8. 9.

10.

2 year outcome of extremely preterm infants. Br J Obstet Gynaecol 1984;91 ;640-6. Yu VYH, Loke HL, Bajuk B, Szymonowicz W, Orgill AA, Astbury J. Prognosis for infants born at 23 to 28 weeks' gestation. Br Med J 1986;293: 1200-3. Bennett-Britton S, Fitzhardinge PM, Ashby S. Is intensive care justified for infants weighing less than 801 gm at birth? J Pediatr 1981;99:937-43. Schechner S. For the 1980's; how small is too small? Clin Perinatal 1980;7; 135-43. Northway Jr WH, Rosan RC, Porter DY. Pulmonary disease following respirator therapy. N Eng! J Med 1967; 276:357-68. Kitchen WH, Yu VYH, Orgill AA, et a!. Collaborative study of very-low-birth-weight infants. Correlation of handicap with risk factors. Am J Dis Child 1983;137: 555-9. Verloove-Vanhorick SP, Verwey RA, Brand R, eta!. Neonatal mortality risk in relation to gestational age and birth weight; results of a national survey of preterm and verylow-birth weight infants in the Netherlands. Lancet 1986; 2:55-7.

11. Paul RH, Koh KS, Monfared AH. Obstetric factors influencing outcome in infants weighing from 1,001 to 1,500 grams. AMJ 0BSTET GYNECOL 1979;133:503-8. 12. Bowes Jr WA, Halgrimson M, Simmons MA. Results of the intensive perinatal management of very-lowbirthweight infants (501 to 1500 grams). J Reprod Med 1979;23:245-50. 13. Gilstrap LC, HauthJC, Bell RE, Ackermanjr NB, Yoder BA, Delemos R. Survival and short-term morbidity of the premature neonate. Obstet Gynecol 1985;65:37-41. 14. Effer SB, Saigal S, Rand C, eta!. Effect of delivery method on outcomes in the very low birth weight breech infants; is the improved survival related to cesarean section or other perinatal care maneuvers? AM J 0BSTET GYNECOL 1983;145:123-8. 15. Bodmer B, Benjamin A, McLean FH, Usher RH. Has use of cesarean section reduced the risk of delivery in the preterm breech presentation? AM J OBSTET GYNECOL 1986;154:244-50. 16. Guzick DS, Winn K. The association of chorioamnionitis with preterm delivery. Obstet Gynecol1985;65:11-6.

Inhibitory effect of quinidine on plasma pseudocholinesterase activity in pregnant women J. Reddy Kambam, M.D., John J. Franks, M.D., and Bradley E. Smith, M.D. Nashville, Tennessee The effect of quinidine at therapeutic and subtherapeutic concentrations on pseudocholinesterase activity in the plasma of 16 normal pregnant women was studied. The mean plasma pseudocholinesterase activity in the absence of quinidine (control) was 0.67 ± 0.11 U/ml. The mean pseudocholinesterase activity in the presence of quinidine at concentrations of 0.5, 1.0, 2.0, and 5.0 f.Lg/ml was 0.48 ± 0.09, 0.38 ± 0.09, 0.29 ± 0.1 0, and 0.19 ± 0.09 U/ml, respectively. At therapeutic concentrations needed to treat cardiac arrhythmias (2 to 5 f.Lg/ml), quinidine inhibited pseudocholinesterase activity by 60% to 70%. All the plasma samples had a normal dibucaine number (78 to 85). We recommend caution when succinylcholine and/or ester-type local anesthetics are used in pregnant women receiving quinidine. (AM J OssTET GYNECOL 1987;157:897-9.)

Key words: Pregnancy, quinidine sulfate, plasma pseudocholinesterase Pregnancy is associated with a significant decrease in plasma pseudocholinesterase activity. 1• 2 Pseudocholinesterase is responsible for the rapid metabolism of succinylcholine, a depolarizing muscle relaxant. Succinylcholine is still the most popular muscle relaxant used for rapid sequence intubation of the trachea in pregnant patients. Pseudocholinesterase is also responsible for hydrolysis of ester-type local anesthetics including

From the Department of Anesthesiology, Vanderbilt University Medical Center. Supported by the Study Center for Anesthesia Toxicology, Vanderbilt University. Received for publication March 10, 1987; accepted May 19, 1987. Reprint requests:]. Reddy Kambam, M.D., Department of Anesthesiology, Vanderbilt University Hospital, Nashville, TN 37232.

procaine, tetracaine, cocaine, and chloroprocaine. Several pharmacologic agents interfere with the metabolism of these ester-type drugs by depressing pseudocholinesterase activity."·' Quinidine, a potent antiarrhythmic agent, is known to prolong the muscle paralysis caused by succinylcholine. 6 The mechanism for prolongation of action of succinylcholine caused by quinidine is not well understood. Furthermore, the effect of quinidine at therapeutic concentrations (2 to 5 1-Lg/ml) on pseudocholinesterase activity in pregnant women has not been reported. Recently we observed two cases of prolongation of succinylcholine duration of action in patients receiving quinidine. We also documented desensitization block after succinylcholine administration in a patient receiving quinidine sulfate. When measured after surgery pseudocholinesterase ac897