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Neonatal survival and disability rate at age 18 months for infants born between 23 and 28 weeks of gestation
Neonatal survival and disability rate at age 18 months for infants born between 23 and 28 weeks of gestation Francine Lefebvre, MD, Jacqueline Glorieux, LPs, and Thérèse St-Laurent-Gagnon, MD Montreal, Quebec, Canada OBJECTIVE: Our purpose was to determine gestationN age-specific outcomes of infants born in a period of surfactant use. STUDY DESlGN: All 465 consecutive births between 23 and 28 weeks' gestation in a tertiary center from 1987 to 1992 were analyzed prospectively. At 18 months' corrected age, 217 of 254 (85%) survivors were evaluated. RESULTS: From 1987 and 1988 to 1991 and 1992 there was an increase in survivai for infants bom at 24 weeks (from 0% to 33%, p = 0.17), 25 to 26 weeks (38% to 71%, p < 0.005), and 27 to 28 weeks (66% to 84%, p < 0.05). At each weekly interval from 24 to 28 weeks of gestation the respective incidence of normality was 44%, 71%, 57%, 76%, and 72% (not significant) and the respective mean developmental quotient was 91 _+17, 89 _+25, 90 + 24, 96 + 15, and 96 _+14 (not significant). CONCLUSIONS: Gestational age was strongly associated with outcome in terms of survival. Overall, 70% of children followed up were developing within the normal range. (AMJ OüSTETGYNECOL 1996;174:833-8.)
Key words: Extremely low gestational age, neonatal outcome, premamre infants, ver y-low-birth-weight infants
Studies about neurodevelopmental profiles ofvery premature infants usually classify children by birth weight, generally focusing on very-low-birth-weight (<1500 gm) infants. However, several crucial decisions are based not on birth weight but on gestational age. These are prenatal transfer, tocolysis, steroid use, fetal monitoring, cesarean section, and neonatal resuscitation. These decisions are based on the perceived outcome at the lower spectrum of prematurity) Until the general availability of obstetric ultrasonography to help date pregnancies, it was difficult to measure gestational age with some certainty. Few studies have reported on the outcomes of chihtren born at extremely early gestational ages with gestational age used to classify the children. The early studies are based on infants born >10 years ago. 2-7 More recently, three large series were published on babies born before surfactant therapy was used. ~-~° There is only one tbllow-up report to date on a group of very early gestational age From the Neonagal Service and Research Cent~ Hôpita; Ste-Justine, and the Department of Pediatrics, Universitéde Montréal. Funded by Université de Montréal (CAF[R) and H@ital Ste-Justine Presented in part at the Sixty-second Annual Meeting of the So«ielyfor Pediatric Research, Washington, D.C., May 1993, and in part at the Annual Meeting of the American Academy of Cerebral Pals~ and Developmental Medicine, Nashville, Tennesse¢ October1993. Receivedfor publication April 6, 1995; revisedJuly 26, 1995; accepted Bly 31, 1995. Reprim requests: Francine Lefeövre, MD, FIôpital SteJustine, 3175 Chemin Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5. Copyright © 1996 by Mosby-YearBook, Inc. 0002-9378/96 $5.00+ 0 6/1/68367
infants horn at _<26 weeks after having received surfactant. 1 The purpose of this study is to provide 18-month outcome data stratified by gestational age of children born at extremely early gestations mostly during a rescue surfactant therapy period. Methods
Population, All infants were born at Hôpital Ste-Justine, a pediatric University Hospital with a referral center for high-risk pregnancies and with a tertiary care neonatal intensive care unit. Charts were reviewed of all consecutive births occurring between 23 and 29 weeks' gestation from 1987 to 1992. Inclusion criteria in the study were a live fems on admission of the mother to the hospital and a gestational age of 23 to 28 weeks at birth. For uniformity, gestauonal age at birth was calculated from the age attributed at the first ultrasonography that had to be performed before 24 weeks. Gestational age was expressed in completed weeks of pregnancy. There were 465 infants born between 23 and 28 weeks' gestation during the sm@ period. For 395 infants (85%), the results of obstetrie ultrasonography done at 16.4 _+4,1 weeks (mean + SD) were used to determine gestational age. The ultrasonography gestational age varied only by a mean of 3 days less than the ages by maternal dates, Gestational age was calculated according to mother's dates for 70 infants whose nltrasonographic data either were not available or were not existent. Decisions about prenatal management such as fetal 833
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monitoring, steroid use, or indication for cesarean section and about neonatal management such as initiation of resuscitation and neonatal care were discussed among obstetricians, neonatologists, and parents. Cesarean section for fetal reasons was generally avoided for extremely preterm infants (23 to 24 weeks). At delivery, resuscitation was performed by the neonatal team. In the neonatal intensive care unit, for infantsjudged nonviable, assisted ventilation was not initiated and they were provided comfort care. For some infants with a condition carrying a poor prognosis, respirator care therapy was withdrawn with the consent of the parents. An artificial surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) was introduced in the unit i n J u n e 1988 according to a multicenter double-blind placebo protocol. Infants with radiographically proven respiratory distress syndrome, moderately severe to severe according to the blood gas values, within the first 24 hours after birth, were randomly allocated to receive either air or surfactant in two doses. 12 This study ended i n J u n e 1989 for infants >1249 gm, in July 1989 for infants 750 to 1249 gm, and in September 1990 for infants 500 to 749 gm. Thereafter, the same protocol of surfactant administration was kept during the open investigative new drug period and when the drug was licensed. An occasional third dose was given to very sick infants. Thus there were three distinct periods: the era before surfactant (1987 to mid-1988), the surfactant protocol (mid1988 until mid-1989 for infants >750 gm or mid-1990 for infants 500 to 749 gin), and the surfactant era when the drug could be given to any infant in need (mid-1989 for infants _>750 gm or mid-1990 for infants 500 to 749 gm to 1992). Surfactant was never used prophylactically. Neurodevelopmental profile. All 254 survivors were prospectively enrolled in follow-up. A complete follow-up protocol unti118.5 _+ 1.0 months' corrected age (fange 16 to 25 months) was carried out for 217 children (85%). In the neonatal intensive care unit 216 infants with complete follow-up had at least orte cerebral ultrasonography (211 in the first month of life, 169 after 1 month of life). Intraventricular hemorrhage was graded 1 to 4 according to the classification by Papile. All 217 children had an ophthalmologic examination either in the neonatal intensive care unit (202 children) or in the outpatient clinic in the first 5 months of life (140 children). Retinopathy of prematurity was defined as stage 1 to 4 according to the international classification. With the approval of the ethics committee and signed parental consent, all 217 children had a psychometric and a neurologic evaluation and 205 had an audiologic evaluation at 18 months. Socioeconomic status ~3 of the family was coded for 207 children. The Griffiths Mental Developmental Scales ~4including locomotor, social, language, coordination, and performance scales were administered to the children by a psychologist unaware of their medical or social history. Premature children were compared with a control group
of 41 heahhy children of the same ethnic origin, seen at 18 months by the same psychologist, in the same setting as part of another project. ~5 Neurologic evaluation 16 was performed by the same neonatologist. Free field audiologic evaluation was done by an audiologist in a soundproof chamber. Cerebral palsy was diagnosed as spastic quadriplegia if the child had eqnally increased torte in both upper and lower extremities along with marked motor delay, spastic diplegia if the child had increased tone mainly in the lower extremities, hemiplegia if the child had an increased torte of both upper and lower extremities on orte side, and hypotonia if the tone was markedly decreased along with delayed motor milestones. In an attempt to identify children most likely to remain nonambulant, cerebral palsy was considered severe if the Griffiths locomotor quotient was _<50 (test mean 100). All children with quadriplegia fell into the category of severe cerebral palsy. Children with cerebral palsy were engaged in rehabilitation programs under the supervision of neurologists, occupational therapists, physiotherapists, speech therapists, and rehabilitation physicians. Outcome variables were defined as minor to moderate disabilities, major disabilities, and normality. Children with minor to moderate disabilities had a developmental quotient between 80 and 89 a n d / o r minor or moderate cerebral palsy. Children with major disabilities had a developmental quotient < 80, severe cerebral palsy, unilateral blindness, and hearing loss requiring amplification. All those children were identified as having impairments. Children free of any of the disabilities mentioned were considered normal. Because of the young age of the children, we did not attempt a classification of handicaps that requires a j u d g m e n t on the basis of whether the disability interferes with Ieading a normal life. Statistieal methods. Continuous variables were analyzed by unpaired Student's t test and analysis of variance for muhiple comparisons. Dichotomous variables were analyzed by X2 with continuity correction for small numbers. Data are expressed as mean _+SD where applicable.
Results Between 1987 and 1992, 465 infants were born at 23 to 28 weeks' gestation. Birth weight was between 500 and 1500 gm for 451 infants. Six infants weighed <500 gm and all died. Eight infants weighed >1500 gin, including two infants with sacrococcygeal teratoma and one with a complex heart anomaly among the heaviest neonates. In the whole cohort 40 infants (8.6%) were small for gestational age (_<10th percentile). A significant congenital anomaly occurred in 2 of the 45 stillborn infants, 9 of the 166 infants who died, and 6 of the 254 survivors. There was a proportional decrease in the percentage of fetal deaths and delivery room deaths along with an increase in the percentage of survivors with increasing ges-
Lefebvre, Glorieux, and St-Laurent-Gagnon 835
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rational age (Table ~[). Fetal death occurred in 45 cases. There were 44 infants who died soon after birth in the delivery room. All were severely depressed with an Apgar score of _<3 at 1 minute, and resuscitation was attempted in only four infants. Among infants born alive there has been an increase in the use of antenatal betamethasone from 10% in the presurfactant period to, 26% in the period of routine surfactant use (p = 0.00ä), with an increase of two treatment doses from :)% to 20% (p < 0.00ä). Admitted to the neonatal intensive care unit were 376 infhnts, 122 of whom died. Mean age at death of infants admitted to the neonatal intensive care unit was 11.7_+ 27.9 days (range 0.01 to 176 days). From 23 to 28 weeks the respecfive ages were 0.8_+0.7, 4.0_+7.7, 13.6 _+38.6, 12.2 _+20.9, 17.7 _+33.3, and 13.6 _+28.7 days (analysis ofvariance, p = 0.49; not significant). Among the 122 infants admitted to the neonatal intensive care unit who died, 101 (83%) were intubated and ventilated whereas 21 (17%) died without intervention. Even if they did not survive, more infants born alive at 23 weeks were admitted to the neonata] intensive care unJt in the last period of regular surfactant use than before (12/19 vs 0/6, p < 0.05). Improvement of survival from 1987 to 1992 for infants born alive at 24, 25 to 26, and 27 to 28 weekd gestation is clear at each gestational age range (Fig. 1). The increase in survival at 24 weeks from 0% to 33% was clinically important, although not statisfically significan t (p = 0.17). Surfactant use was gradually introduced among infants admitted to the neonatal intensive eare unit: beforeJune 1988 (0/76 infants), during the double-blind, placebocontrolled protocol (14/71 or 20% of infants), and during regular surfaetant use (105/229 or 46% of infants). During this last period, surfactant use from 23 to 28 weeks was as follows: 6 of 12 infants (50%), 9 of 15 (60%), 20 of 34 (59%), 22 of 35 (63%), 23 of 69 (33%), and 25 of 64 (39%). There were 254 infants who survived to be discharged. One survivor of 27 weeks' gestation died at home of sudden infant death syndrome. Thirty-six ehildren had an incomplete or no follow-up. Complete follow-up was obtained for 107 boys and 110 girls. There were 191 (88%) white and 26 (ä2%) nonwhite ehildren. Children belonged to families of the following socioeconomie status: 35 (17%) in higher classes (I and II), 40 (19%) in class III, 84 (41%) in elass W, and 48 (23%) in the lower class (V). Between each week of gestation from 24 to 28 weeks, no demographic difference in sex, Face, or socioeeonomie status was found. Howeve~; there were large differences in the neonatal characteristics reflecting the degree of immaturity of the infants (Table II). The differenee in ineidence of cesarean section may be explained by a certain degree of reluctanee of the obstetrician to perform surgery on the mother of the most immature infants. Incidences of sur-
100= 80-
27-28 w e e k s + 25-26 w e e k s ÷ 24 w e e k s
-"~84t"
60-
% 40-
~
200
1987-88
~°33
1989-90
1991-92
Fig. t. Survivaltrend Ihr 408 int~mtsborn alive at 24 to 28 weeks of gestaLion. Ast~ish, p < 0.05, 1989 m 1990 versus 1987 to 1988; dagg-~ p< 0.05, 1991 to 1992 versus 1987 to 1988; doubledagg~; p< 0.005, 1991 to 1992 versus 1987 m 1988.
factant use represent all 6 years, inciuding those when ~.3o surfactant was avaiIable. All stages of retinopathy of premamrity are inc]uded in the table. RefinopatEy of prematurity stage 3 or 4 was found at all gestational ages in a totaT of eight infants, and cryotherapy was performed in two. Overall, the incidence of normality among survivors followed up to 18 months was 70% (Table III). Probably because of the smal] numbers involved in the most immature gestations, we could not find statistical evidence for more disabilifies at lower gestations. ChiIdren of 24 m 26 weeks had a tendency to have more developmental quotients <80 compared wirb children of 27 to 28 weeks (17/73 [23%] vs 18/144 [12%]; p = 0.06, Z2 with continuity correction). The finding of 12% (9/73) of children at 24 to 26 weeks wi th severe cerebral palsy compared with 5 % (8/144) at 27 to 28 weeks was not statistically signifieant. The mean developmental quotient for the 217 children studied was 94 ± 18 without significant difference between the different gestationaI ages (analysis of varianee, p = 0.16; not significant). However, mean developmental quotient at eaeh gestafional age was signifieantly different (analysis of variance, p = 0.0001) from that of the eontrol group of 41 healthy children who obtained a mean developmental quofient of 110 -+ 6. When presurfaetant and routine surfaetant periods were compared, the survival rate increased and the disability and normality rates remained stable (Table B/).
Comment Attempts at clinica! estimates of gestationa] age from physieal examination of infants may be misleading by >2 weeks from mothers' dates.t7 There is, however, no gold standard method of determining gestational age with certainty. ~sWe tried to have the best estimate by reviewing
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Lefebvre, GIorieux, and St-Laurent-Gagnon
March 1996 AmJ Obstet Gynecol
T a b l e I. P r o g n o s i s for fetuses alive o n a d m i s s i o n of t h e i r m o t h e r s to t h e delivery r o o m I
Gestation (wk)
No. of births
Birth weight (gm)
Fetal deaths
23 24 25 26 27 28 23-28
38 47 69 72 125 114 465
631 -+ 140 702-+ 144 811 -+133 910-+145 1013-+204 1167-+293 942 -+268
13 8 7 3 8 6 45
] I
(34%) (17%) (10%) (4%) (6%) (5%) (10%)
Delivery room deaths 13 14 11 5 1 0 44
(34%) (30%) (16%) (7%) (1%) (0%) (9%)
NICU deaths 12, 16 20 20 25 29 122
Survivors
(32%) (34%) (29%) (28%) (20%) (25%) (26%)
0 9 31 44 91 79 254
(0%) (19%) (45%) (61%) (73%) (69%) (55%)
NICU, Neonatal intensive care unit. Resuhs are expressed as number and percent or mean ± SD. Differences between gestations are significant with analysis of variance for birth weight except for 23 versus 24 weeks. Differences between gestations are significant with Z~ for fetal deaths (23 vs 25, 26, 27, and 28 weeks; 24 vs 26 and 28 weeks), delivery room deaths (23, 24, 25, and 26 vs 27 and 28 weeks; 23 and 24 vs 26 weeks), and survivors (23, 24, and 25 vs 27 and 28 weeks; 23 and 24 weeks vs 25 and 26 weeks; 23 weeks vs 24 weeks).
T a b l e II. N e o n a t a l data of c h i l d r e n with follow-up to 18 m o n t h s
~7:r ?cA 24 25 26 27 28 24-28
9 24 40 72 72 217
Birth weight (gvn)
BOTIt by cesargan section
748-+ 121 1 829+82 5 935-+105 12 1002-+151 40 1167+_209 42 1015-+202 100
Grade 3 of 4 1 Retinopathy I intraven- I Perivenof tricular I tricular prematurity hemorrhage leukomalacia
[
Assisted ventilation
(11%) 9 (21%) 21 (30%) 36 (56%) 53 (58%) 50 (46%) 169
(100%) (87%) (90%) (74%) (69%) (78%)
Ventilation (days) Surfactant 55-+ 12 38-+25 27-+23 18-+19 11 -+20 2l-+23
3 10 18 18 20 69
(33% (42% (45% (25% (28%) (32%)
Oxygen >-36wk 8 17 23 24 19 91
(89%) 6 (71%) 7 (57%) 9 (33%) 7 (26%) 6 (42%) 35
(67%) 2 (29%) 5 (22%) ! (10%) 5 (8%) 2 (16%) 15
(22%) (21%) (2%) (7%) (3%) (7%)
0 4 1 3 4 12
(0%) (17%) (2%) (4%) (5%) (5%)
Length of stay (days) 170+_166 106-+27 101_+41 91-+63 73-+38 92-+60
Results are expressed as number and percent or mean ± SD, Differences between gestafions are significant with analysis ofvariance for days ofventilaüon and, except between 24 weeks versus 25 weeks, for birth weight. Differences are significant for length of stay for 24 weeks versus 25, 26, 27, and 28 weeks and for 25 and 26 weeks versus 28 weeks. Differences between gestations are significant with Z2 for cesarean secüon and oxygen >-36weeks (24, 25, and 26 weeks vs 27 and 28 weeks), assisted ventilation (26 weeks vs 28 weeks), retinopathy of prematurity (24 and 25 weeks vs 27 and 28 weeks; 24 vs 26 weeks), and grade 3 or 4 intraventricular hemorrhage (25 weeks vs 26 and 28 weeks).
all m o t h e r s ' charts to calculate gestafional age f r o m t h e
d a t a c o n c e r n i n g these infants b e m a d e available rapidly.
original early obstetric u l t r a s o n o g r a p h y
However, while t h e infants are d e v e l o p i n g a n d e n o u g h p a t i e n t s are b e i n g a c c u m n l a t e d , significant c h a n g e s in n e o n a t a l care o f i n f a n t s may occur. T h e i n t r o d u c t i o n o f s u r f a c t a n t is a g o o d r e c e n t e x a m p l e of such a m a j o r c h a n g e . Only o n e s t u d y " r e p o r t e d follow-up of surfact a n t - t r e a t e d infants o f extremely early gestational age, h o r n at 23 to 26 weeks. It d e s c r i b e d a n i m p a i r m e n t rate of 35% at 23 m o n t h s . This c o m p a r e s with o u r rate o f i m p a i r m e n t of 20 of 51 (39%) at 18 m o n t h s for survivors h o r n b e t w e e n 24 a n d 26 weeks in t h e m o s t r e c e n t p e r i o d of o p e n access to surfactant. A n o t h e r study 2~ of surfactantt r e a t e d infants of 23, 24, a n d 25 weeks p r o g n o s t i c a t e d a possible p o o r o u t c o m e at 6 m o n t h s of life, o n t h e basis of d e a t h o r severe i n t r a c r a n i a l a b n o r m a l i t i e s , for 98%, 79%, a n d 31% of infants, respectively. Studies o f infants b o r n at <29 weeks b e f o r e s u r f a c t a n t use have r e p o r t e d i m p a i r m e n t rates f r o m 17% to 39% d u r i n g infancy a n d c h i l d h o o d f -°' 9, ,0. z3, 2~ O n e s t u d y ~ o f c h i l d r e n h o r n at <29 weeks d u r i n g t h e mid-1980s rep o r t e d a h i g h rate o f i m p a i r m e n t o f 65% at 4 years. However, it is at school age t h a t a c a d e m i c p e r f o r m a n c e gives the full p i c t u r e o f the f n n c t i o n i n g o f c h i l d r e n . In a
report,
this
m e t h o d b e i n g u s e d for 85% of t h e infants. O n average, this gave a m e a n d i f f e r e n c e o f only 3 days less t h a n t h e m o t h e r s ' dates, c o n f i r m i n g it to b e a g o o d choice. We gave o u r p r e f e r e n c e to u l t r a s o n o g r a p h y d a t i n g b e c a u s e it prevails i n case of discrepancy, a n d for u n i f o r m i t y we u s e d it for all infants. It h a s b e e n r e p o r t e d t h a t t h e p e r c e p t i o n of viability of very-low-birth-weight infants by physicians may affect survival of i n f a n t s in t h e sense t h a t m a n a g e m e n t decisions may b e b a s e d o n i n c o r r e c t i n f o r m a t i o n a b o u t n e o n a t a l survival) 9" 20 I n o u r n n i t discussions b e t w e e n n e o natologists a n d obstetricians t h a t were b a s e d o n t h e suggested m a n a g e m e n t 2~ o f w o m e n with t h r e a t e n e d b i r t h o f a n i n f a n t of e x t r e m e l y low gestational age, have h a d a n impact. In t h e last years o f t h e study m o r e infants have b e e n b o r n after b e t a m e t h a s o n e , have b e e n a d m i t t e d to t h e n e o n a t a l intensive care u n i t at 23 weeks a n d t r e a t e d with surfactant, a n d have survived at 24 weeks. Since p r o g n o s i s c h a n g e s rapidly for infants of very low b i r t h w e i g h t or very early gestations, it is i m p e r a t i v e t h a t
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Table III. O u t c o m e o f c h i l d r e n with follow-up until 18 m o n t h s Psychomotor mardation
Neurologic disorder-Cerebralpalsy
Sensory disorder
Total disab
c~f)qth~ All Gestation No. of Developmental (wh) children Quotient (DQ <90)
24 25 26 27 28 24-28
9 24 40 72 7'2 217
91-+17 89-+25 90-+24 96-+15 96-+14 94-+18
4 6 14 17 15 56
Severe (DQ <80)
(44%) 3 (25%) 5 (35%) 9 (24%) 9 (21%) 9 (26%) 35
All
Severe
(33%) 1 (11%) 0 (21%) 6 (25%) 4 (22%) 11 (27%) 5 (12%) 7 (10%) 3 (12%) 12 (17%) 5 (16%) 37 (17%) 17
(0%) (I7%) (12%) (4%) (7%) (8%)
Blind
1 0 0 0 1 1
(11%) (0%) (0%) (0%) (1%) (0.5%)
Deaf
1 0 0 0 1 1
Major
A r,
(11%) 4 (44%) 1 (0%) 5 (21%) 2 (0%) 9 (22%) 8 (0%) 9 (12%) 8 (1%) 11 (15%) 9 (0.5%) 38 (17%) 28
Normal
(11%) 4 (8%) 17 (20%) 23 (11%) 55 (12%) 52 (13%) 151
(44%) (71%) (57%) (76%) (72%) (70%)
DQ,, Developmental Quodent. Results are expressed as number and percent or mean -+.SD. There are no statisticaI differences between the gestational age groups. Table Ig. O u t c o m e d u r i n g three consecutive periods 27-28 weeks' gestation
24-26 weehs'gestation I
Disabilities
Disabilities
S,arvirJoTs
P«iod
Presurfactant Surfactant-Protocol Surfactant-Routine
Year (approximate)
(No./NICU admission)
Major
Minor or moderate Normal
: (11%) 2 (22%) 4 (31%) 2 (15%)
6 (67%) 7 (54%)
Survivors (No./NICU admission)
32/50 (64%) 28/41 (68%)
Major
Normal
1987-1988 1988-1989
12/26 (46%) 15/30 (50%)
5 (17%) 4 (14%) 20 (69%) 3 (12%) 4 (17%) t7 (71%)
1989-1992
57/84 (68%)* 13 (25%) 7 (14%) 31 (61%) 110/133 (83%)J" 12 (13%) 9 (10%) 70 (77%)
Results are expressed as number and percent. *Z2, p = 0.077 (not significant), compared with presurfactant period tZ 2, p = 0.01, compared with presurfactant period
g r o u p of 5-year-old children b o r n at <29 weeks Msall et al. 7 f o u n d that 9% n e e d e d intensive special education, and 48% r e q u i r e d some special education resources. A l o n g with an increased incidence of slow intelligence and m o r e limited academic skills, Hack et al. 2~ r e p o r t e d an increased risk that school-age child{en who weighed <750 g m would require special e d u c a t i o n placement, c o m p a r e d with low-birth-weight (750 to 1499 gm) and t e r m controls (45% vs 25% vs 14%). T h e question o f w h e t h e r aggressive efforts or new technologies a u g m e n t the p r o p o r t i o n of i m p a i r e d children seems to find a r e p e a t e d answer that it is n o t so. TM 25 We f o u n d no increase in the p r o p o r t i o n of i m p a i r e d children w h e n the presurfactant p e r i o d was c o m p a r e d with the routine surfactant period. However, a stable disability rate in the presence of an increasing survival rate means m o r e disabled survivors as an absolute number. Within a g r o u p of very p r e m a t u r e children the question of whether the handicap rate increases with decreasing gestational age remains unanswered. ~ In contrast to mortality, handicap was not related to gestational age (or birth weight) in a very large c o h o r t o f p r e t e r m infants <32 weeks. 4 O n the contrary, in a similar but rauch smaller c o h o r t of infants b o r n at <32 weeks, severe disabilities were described in survivors b o r n at 24 to 27 weeks m o r e offen than at 28 to 31 weeks. ~ Also in an extremely pre-
m a t u r e g r o u p p r o f o u n d cognitive i m p a i r m e n t increased with decreasing gestation. 9 In o u r c o h o r t we could n o t find statisticat support for such a difference. In this study, in spite of the c o n c e r n that m i g h t arise a r o u n d 24 weeks of gestation, the o u t c o m e of surviving children b o r n at an extremely early gestational age followed up to 18 m o n t h s was generally e n c o u r a g i n g with 70% of the children developing within the n o r m a l range. Gestational age was strongly associated with o u t c o m e in terms of mortality. While survival bas increased over the years, the p r o p o r t i o n of i m p a i r e d survivors has r e m a i n e d stable. We r e c o m m e n d the use of gestational age in future fotlow-up studies because it is the most i m p o r t a n t parameter known before birth that influences decisions with a direct impact on the o u t c o m e of the infant. We are very grateful to Dr. H a r r y Bard for reviewing this manuscript. We thank Jocelyne Vallée, research nurse, for h e r dedicated work in data collection, Monique Grisé, clinic nurse, for h e r supportive care of patients, and Marie-Claude Vinay, psychology student, for her work with patients. REFERENCES
1. Effer SB, Lopes LM, Whitfield MF. When does ontcomejustify heroic interventions? Univariate analysis of gestational
838 Lefebvre,Glorieux, and St-Laurent-Gagnon
age-specific neonatal mortalip/and morbidip/. J Soc Obstet Gynecol Can 1992;14:39-49. 2. Milligan JE, Shennan AT, Hoskins EM. Perinatal intensive care: where and how to draw the line. AMJ OBSTETG~Ecoe 1984;148:499-503. 3. Doyle LW, Kitchen WH. Do neurological impairments and disabilities increase with decreasing gestational age in survivors of borderline viabilip/at birth? Aust PaediatrJ 1987;23: 211-2. 4. vanZeben-van der Aa TM, Verloove-Vanhorick SP, Brand R, Ruys JH. Morbidity of very low birthweight infants at corrected age of two years in a geographically defined population. Lancet 1989;1:253-5. 5. Wariyar U, Richmond S, Hey E. Pregnancy outcome at 24-31 weeks' gestation: neonatal survivors. Arch Dis Child 1989;64: 678-86. 6. Nwaesei CG, Young DC, ByrneJM, et al. Preterm birth at 23 to 26 weeks' gestation: is active obstetric management justified? AMJ OBSTEXGWECOL 1987;157:890-7. 7. Msall ME, Buck GM, Rogers BT, Merke D, Catanzaro NL, Zorn WA. Risk factors for major neurodevelopmental impairments and need for special education resources in extremely premature infants. J Pediatr 1991 ;119:606-14. 8. Johnson A, Townshend P, Yudkin P, Bull D, Wilkinson AR. Functional abilities at age 4 years of children born before 29 weeks of gestation. BMJ 1993;306:1715-8. 9. Whyte HE, Fitzhardinge PM, Shennan AT, Lennox K, Smith L, LacyJ. Extreme immaturip/: outcome of 568 pregnancies of 23-26 weeks' gestation. Obstet Gynecol 1993;82:1-7. lô. Synnes AR, Ling EWY, Whitfield ME et al. Perinatal outcomes of a large cohort of extremely low gestational age infants (twenp/-three to twenty-eight completed weeks of gestation). J Pediatr 1994; 125:952-60. 11. Ferrara TB, Hoekstra RE, Couser RJ, et al. Survival and follow-up of infants born at 23 to 26 weeks of gestational age: effects of surfactant therapy. J Pediatr 1994;124:119-24. 12. Long W, Thompson T, Sundell H, et al. Effects oftwo rescue doses of a synthetic surfactant on mortalip/rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome. J Pediatr 1991; 118:595-605. 13. Hollingshead AB. Two factor index of social position. New Haven, Connecticut: AB Hollingshead, 1957. 14. Griffiths R. The abilifies of young children. Child development research centre. London: Young and Son, 1970.
March 1996 Am J Obstet Gynecol
15. Glorieux J, Dussault JH, Letarte J, Guyda H, Morissette J. Preliminary results on the mental development of hypothyroid infants detected by the Quebec Screening Program. J Pediatr 1983;102:19-22. 16. Amiel-Tison C, Stewart A. Follow-up studies during the first five years of life: a pervasive assessment of neurological function. Arch Dis Child 1989;64:496-502. 17. SpinnatoJA, Sibai BM, Shaver DC, Anderson GD. Inaccuracy of Dubowitz gestational age in low birth weight infants. Obstet Gynecol 1984;63:491-5. 18. DiPietro JA, Allen MC. Esfimation of gestational age: implications for developmental research. Child Dev 1991;62: 1184-99. 19. Goldenberg RL, Nelson KG, Dyer RL, WayneJ. The variabilip/of viabilip/: the effects of physicians' percepfions of viability on the survival of very low-birth weight infants. AM J OBSTETGYNECOL1982;143:678-84. 20. Fenton AC, Field DJ, Mason E, Clarke M. Attimdes to viability of preterm infants and their effect on figures for perinatal mortalip/. BMJ 1990;300:434-6. 21. Fetus and Newborn Committee, Canadian Paediatric Society; Maternal-Fetal Medicine Committee, Society of Obstetricians and Gynaecologists of Canada. Management of the woman with threatened birth of ma infant of extremely low gestational age. Can Med Assoc J 1994;151:547-53. 22. Allen MC, Donohue PK, Dusman AE. The limit of viability-neonatal outcome of infants born at 22 to 25 weeks' gestation. N EnglJ Med 1993;329:1597-601. 23. Eg-Andersen G. Predicfion of outcome in 164 infants born after 24 to 28 weeks gestafion. Acta Paediatr Scand Suppl 1989;360:56-61. 24. Msall ME, Rogers BT, Buck GM, Mallen S, Catanzaro NL, Duffy LC. Funcfional status of extremely preterm infants at kindergarten entry. Dev Med Child Neurol 1993;35:31220. 25. Hack M, Taylor HG, Klein N, Eiben R, Schatschneider C, Mercuri-Minich N. School-age outcomes in children with birth weights under 750 g. N EnglJ Med t994;331:753-9. 26. Robertson CMT, Hrynchyshyn GJ, Etches PC, Pain KS. Populafion-based study of the incidence, complexity, and severity of neurologic disability among survivors weighing 500 through 1250 grams at birth: a comparison of two birth cohorts. Pediatrics 1992;90:750-5.
Key words: Extremely low gestational age, neonatal outcome, premamre infants, ver y-low-birth-weight infants
Studies about neurodevelopmental profiles ofvery premature infants usually classify children by birth weight, generally focusing on very-low-birth-weight (<1500 gm) infants. However, several crucial decisions are based not on birth weight but on gestational age. These are prenatal transfer, tocolysis, steroid use, fetal monitoring, cesarean section, and neonatal resuscitation. These decisions are based on the perceived outcome at the lower spectrum of prematurity) Until the general availability of obstetric ultrasonography to help date pregnancies, it was difficult to measure gestational age with some certainty. Few studies have reported on the outcomes of chihtren born at extremely early gestational ages with gestational age used to classify the children. The early studies are based on infants born >10 years ago. 2-7 More recently, three large series were published on babies born before surfactant therapy was used. ~-~° There is only one tbllow-up report to date on a group of very early gestational age From the Neonagal Service and Research Cent~ Hôpita; Ste-Justine, and the Department of Pediatrics, Universitéde Montréal. Funded by Université de Montréal (CAF[R) and H@ital Ste-Justine Presented in part at the Sixty-second Annual Meeting of the So«ielyfor Pediatric Research, Washington, D.C., May 1993, and in part at the Annual Meeting of the American Academy of Cerebral Pals~ and Developmental Medicine, Nashville, Tennesse¢ October1993. Receivedfor publication April 6, 1995; revisedJuly 26, 1995; accepted Bly 31, 1995. Reprim requests: Francine Lefeövre, MD, FIôpital SteJustine, 3175 Chemin Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5. Copyright © 1996 by Mosby-YearBook, Inc. 0002-9378/96 $5.00+ 0 6/1/68367
infants horn at _<26 weeks after having received surfactant. 1 The purpose of this study is to provide 18-month outcome data stratified by gestational age of children born at extremely early gestations mostly during a rescue surfactant therapy period. Methods
Population, All infants were born at Hôpital Ste-Justine, a pediatric University Hospital with a referral center for high-risk pregnancies and with a tertiary care neonatal intensive care unit. Charts were reviewed of all consecutive births occurring between 23 and 29 weeks' gestation from 1987 to 1992. Inclusion criteria in the study were a live fems on admission of the mother to the hospital and a gestational age of 23 to 28 weeks at birth. For uniformity, gestauonal age at birth was calculated from the age attributed at the first ultrasonography that had to be performed before 24 weeks. Gestational age was expressed in completed weeks of pregnancy. There were 465 infants born between 23 and 28 weeks' gestation during the sm@ period. For 395 infants (85%), the results of obstetrie ultrasonography done at 16.4 _+4,1 weeks (mean + SD) were used to determine gestational age. The ultrasonography gestational age varied only by a mean of 3 days less than the ages by maternal dates, Gestational age was calculated according to mother's dates for 70 infants whose nltrasonographic data either were not available or were not existent. Decisions about prenatal management such as fetal 833
834
Lefebvre, Glorieux, and St-Laurent-Gagnon
March 1996
AmJ Obstet Gynecol
monitoring, steroid use, or indication for cesarean section and about neonatal management such as initiation of resuscitation and neonatal care were discussed among obstetricians, neonatologists, and parents. Cesarean section for fetal reasons was generally avoided for extremely preterm infants (23 to 24 weeks). At delivery, resuscitation was performed by the neonatal team. In the neonatal intensive care unit, for infantsjudged nonviable, assisted ventilation was not initiated and they were provided comfort care. For some infants with a condition carrying a poor prognosis, respirator care therapy was withdrawn with the consent of the parents. An artificial surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) was introduced in the unit i n J u n e 1988 according to a multicenter double-blind placebo protocol. Infants with radiographically proven respiratory distress syndrome, moderately severe to severe according to the blood gas values, within the first 24 hours after birth, were randomly allocated to receive either air or surfactant in two doses. 12 This study ended i n J u n e 1989 for infants >1249 gm, in July 1989 for infants 750 to 1249 gm, and in September 1990 for infants 500 to 749 gm. Thereafter, the same protocol of surfactant administration was kept during the open investigative new drug period and when the drug was licensed. An occasional third dose was given to very sick infants. Thus there were three distinct periods: the era before surfactant (1987 to mid-1988), the surfactant protocol (mid1988 until mid-1989 for infants >750 gm or mid-1990 for infants 500 to 749 gin), and the surfactant era when the drug could be given to any infant in need (mid-1989 for infants _>750 gm or mid-1990 for infants 500 to 749 gm to 1992). Surfactant was never used prophylactically. Neurodevelopmental profile. All 254 survivors were prospectively enrolled in follow-up. A complete follow-up protocol unti118.5 _+ 1.0 months' corrected age (fange 16 to 25 months) was carried out for 217 children (85%). In the neonatal intensive care unit 216 infants with complete follow-up had at least orte cerebral ultrasonography (211 in the first month of life, 169 after 1 month of life). Intraventricular hemorrhage was graded 1 to 4 according to the classification by Papile. All 217 children had an ophthalmologic examination either in the neonatal intensive care unit (202 children) or in the outpatient clinic in the first 5 months of life (140 children). Retinopathy of prematurity was defined as stage 1 to 4 according to the international classification. With the approval of the ethics committee and signed parental consent, all 217 children had a psychometric and a neurologic evaluation and 205 had an audiologic evaluation at 18 months. Socioeconomic status ~3 of the family was coded for 207 children. The Griffiths Mental Developmental Scales ~4including locomotor, social, language, coordination, and performance scales were administered to the children by a psychologist unaware of their medical or social history. Premature children were compared with a control group
of 41 heahhy children of the same ethnic origin, seen at 18 months by the same psychologist, in the same setting as part of another project. ~5 Neurologic evaluation 16 was performed by the same neonatologist. Free field audiologic evaluation was done by an audiologist in a soundproof chamber. Cerebral palsy was diagnosed as spastic quadriplegia if the child had eqnally increased torte in both upper and lower extremities along with marked motor delay, spastic diplegia if the child had increased tone mainly in the lower extremities, hemiplegia if the child had an increased torte of both upper and lower extremities on orte side, and hypotonia if the tone was markedly decreased along with delayed motor milestones. In an attempt to identify children most likely to remain nonambulant, cerebral palsy was considered severe if the Griffiths locomotor quotient was _<50 (test mean 100). All children with quadriplegia fell into the category of severe cerebral palsy. Children with cerebral palsy were engaged in rehabilitation programs under the supervision of neurologists, occupational therapists, physiotherapists, speech therapists, and rehabilitation physicians. Outcome variables were defined as minor to moderate disabilities, major disabilities, and normality. Children with minor to moderate disabilities had a developmental quotient between 80 and 89 a n d / o r minor or moderate cerebral palsy. Children with major disabilities had a developmental quotient < 80, severe cerebral palsy, unilateral blindness, and hearing loss requiring amplification. All those children were identified as having impairments. Children free of any of the disabilities mentioned were considered normal. Because of the young age of the children, we did not attempt a classification of handicaps that requires a j u d g m e n t on the basis of whether the disability interferes with Ieading a normal life. Statistieal methods. Continuous variables were analyzed by unpaired Student's t test and analysis of variance for muhiple comparisons. Dichotomous variables were analyzed by X2 with continuity correction for small numbers. Data are expressed as mean _+SD where applicable.
Results Between 1987 and 1992, 465 infants were born at 23 to 28 weeks' gestation. Birth weight was between 500 and 1500 gm for 451 infants. Six infants weighed <500 gm and all died. Eight infants weighed >1500 gin, including two infants with sacrococcygeal teratoma and one with a complex heart anomaly among the heaviest neonates. In the whole cohort 40 infants (8.6%) were small for gestational age (_<10th percentile). A significant congenital anomaly occurred in 2 of the 45 stillborn infants, 9 of the 166 infants who died, and 6 of the 254 survivors. There was a proportional decrease in the percentage of fetal deaths and delivery room deaths along with an increase in the percentage of survivors with increasing ges-
Lefebvre, Glorieux, and St-Laurent-Gagnon 835
Volume 174, Number 3 Ami Obstet Gynecol
rational age (Table ~[). Fetal death occurred in 45 cases. There were 44 infants who died soon after birth in the delivery room. All were severely depressed with an Apgar score of _<3 at 1 minute, and resuscitation was attempted in only four infants. Among infants born alive there has been an increase in the use of antenatal betamethasone from 10% in the presurfactant period to, 26% in the period of routine surfactant use (p = 0.00ä), with an increase of two treatment doses from :)% to 20% (p < 0.00ä). Admitted to the neonatal intensive care unit were 376 infhnts, 122 of whom died. Mean age at death of infants admitted to the neonatal intensive care unit was 11.7_+ 27.9 days (range 0.01 to 176 days). From 23 to 28 weeks the respecfive ages were 0.8_+0.7, 4.0_+7.7, 13.6 _+38.6, 12.2 _+20.9, 17.7 _+33.3, and 13.6 _+28.7 days (analysis ofvariance, p = 0.49; not significant). Among the 122 infants admitted to the neonatal intensive care unit who died, 101 (83%) were intubated and ventilated whereas 21 (17%) died without intervention. Even if they did not survive, more infants born alive at 23 weeks were admitted to the neonata] intensive care unJt in the last period of regular surfactant use than before (12/19 vs 0/6, p < 0.05). Improvement of survival from 1987 to 1992 for infants born alive at 24, 25 to 26, and 27 to 28 weekd gestation is clear at each gestational age range (Fig. 1). The increase in survival at 24 weeks from 0% to 33% was clinically important, although not statisfically significan t (p = 0.17). Surfactant use was gradually introduced among infants admitted to the neonatal intensive eare unit: beforeJune 1988 (0/76 infants), during the double-blind, placebocontrolled protocol (14/71 or 20% of infants), and during regular surfaetant use (105/229 or 46% of infants). During this last period, surfactant use from 23 to 28 weeks was as follows: 6 of 12 infants (50%), 9 of 15 (60%), 20 of 34 (59%), 22 of 35 (63%), 23 of 69 (33%), and 25 of 64 (39%). There were 254 infants who survived to be discharged. One survivor of 27 weeks' gestation died at home of sudden infant death syndrome. Thirty-six ehildren had an incomplete or no follow-up. Complete follow-up was obtained for 107 boys and 110 girls. There were 191 (88%) white and 26 (ä2%) nonwhite ehildren. Children belonged to families of the following socioeconomie status: 35 (17%) in higher classes (I and II), 40 (19%) in class III, 84 (41%) in elass W, and 48 (23%) in the lower class (V). Between each week of gestation from 24 to 28 weeks, no demographic difference in sex, Face, or socioeeonomie status was found. Howeve~; there were large differences in the neonatal characteristics reflecting the degree of immaturity of the infants (Table II). The differenee in ineidence of cesarean section may be explained by a certain degree of reluctanee of the obstetrician to perform surgery on the mother of the most immature infants. Incidences of sur-
100= 80-
27-28 w e e k s + 25-26 w e e k s ÷ 24 w e e k s
-"~84t"
60-
% 40-
~
200
1987-88
~°33
1989-90
1991-92
Fig. t. Survivaltrend Ihr 408 int~mtsborn alive at 24 to 28 weeks of gestaLion. Ast~ish, p < 0.05, 1989 m 1990 versus 1987 to 1988; dagg-~ p< 0.05, 1991 to 1992 versus 1987 to 1988; doubledagg~; p< 0.005, 1991 to 1992 versus 1987 m 1988.
factant use represent all 6 years, inciuding those when ~.3o surfactant was avaiIable. All stages of retinopathy of premamrity are inc]uded in the table. RefinopatEy of prematurity stage 3 or 4 was found at all gestational ages in a totaT of eight infants, and cryotherapy was performed in two. Overall, the incidence of normality among survivors followed up to 18 months was 70% (Table III). Probably because of the smal] numbers involved in the most immature gestations, we could not find statistical evidence for more disabilifies at lower gestations. ChiIdren of 24 m 26 weeks had a tendency to have more developmental quotients <80 compared wirb children of 27 to 28 weeks (17/73 [23%] vs 18/144 [12%]; p = 0.06, Z2 with continuity correction). The finding of 12% (9/73) of children at 24 to 26 weeks wi th severe cerebral palsy compared with 5 % (8/144) at 27 to 28 weeks was not statistically signifieant. The mean developmental quotient for the 217 children studied was 94 ± 18 without significant difference between the different gestationaI ages (analysis of varianee, p = 0.16; not significant). However, mean developmental quotient at eaeh gestafional age was signifieantly different (analysis of variance, p = 0.0001) from that of the eontrol group of 41 healthy children who obtained a mean developmental quofient of 110 -+ 6. When presurfaetant and routine surfaetant periods were compared, the survival rate increased and the disability and normality rates remained stable (Table B/).
Comment Attempts at clinica! estimates of gestationa] age from physieal examination of infants may be misleading by >2 weeks from mothers' dates.t7 There is, however, no gold standard method of determining gestational age with certainty. ~sWe tried to have the best estimate by reviewing
836
Lefebvre, GIorieux, and St-Laurent-Gagnon
March 1996 AmJ Obstet Gynecol
T a b l e I. P r o g n o s i s for fetuses alive o n a d m i s s i o n of t h e i r m o t h e r s to t h e delivery r o o m I
Gestation (wk)
No. of births
Birth weight (gm)
Fetal deaths
23 24 25 26 27 28 23-28
38 47 69 72 125 114 465
631 -+ 140 702-+ 144 811 -+133 910-+145 1013-+204 1167-+293 942 -+268
13 8 7 3 8 6 45
] I
(34%) (17%) (10%) (4%) (6%) (5%) (10%)
Delivery room deaths 13 14 11 5 1 0 44
(34%) (30%) (16%) (7%) (1%) (0%) (9%)
NICU deaths 12, 16 20 20 25 29 122
Survivors
(32%) (34%) (29%) (28%) (20%) (25%) (26%)
0 9 31 44 91 79 254
(0%) (19%) (45%) (61%) (73%) (69%) (55%)
NICU, Neonatal intensive care unit. Resuhs are expressed as number and percent or mean ± SD. Differences between gestations are significant with analysis of variance for birth weight except for 23 versus 24 weeks. Differences between gestations are significant with Z~ for fetal deaths (23 vs 25, 26, 27, and 28 weeks; 24 vs 26 and 28 weeks), delivery room deaths (23, 24, 25, and 26 vs 27 and 28 weeks; 23 and 24 vs 26 weeks), and survivors (23, 24, and 25 vs 27 and 28 weeks; 23 and 24 weeks vs 25 and 26 weeks; 23 weeks vs 24 weeks).
T a b l e II. N e o n a t a l data of c h i l d r e n with follow-up to 18 m o n t h s
~7:r ?cA 24 25 26 27 28 24-28
9 24 40 72 72 217
Birth weight (gvn)
BOTIt by cesargan section
748-+ 121 1 829+82 5 935-+105 12 1002-+151 40 1167+_209 42 1015-+202 100
Grade 3 of 4 1 Retinopathy I intraven- I Perivenof tricular I tricular prematurity hemorrhage leukomalacia
[
Assisted ventilation
(11%) 9 (21%) 21 (30%) 36 (56%) 53 (58%) 50 (46%) 169
(100%) (87%) (90%) (74%) (69%) (78%)
Ventilation (days) Surfactant 55-+ 12 38-+25 27-+23 18-+19 11 -+20 2l-+23
3 10 18 18 20 69
(33% (42% (45% (25% (28%) (32%)
Oxygen >-36wk 8 17 23 24 19 91
(89%) 6 (71%) 7 (57%) 9 (33%) 7 (26%) 6 (42%) 35
(67%) 2 (29%) 5 (22%) ! (10%) 5 (8%) 2 (16%) 15
(22%) (21%) (2%) (7%) (3%) (7%)
0 4 1 3 4 12
(0%) (17%) (2%) (4%) (5%) (5%)
Length of stay (days) 170+_166 106-+27 101_+41 91-+63 73-+38 92-+60
Results are expressed as number and percent or mean ± SD, Differences between gestafions are significant with analysis ofvariance for days ofventilaüon and, except between 24 weeks versus 25 weeks, for birth weight. Differences are significant for length of stay for 24 weeks versus 25, 26, 27, and 28 weeks and for 25 and 26 weeks versus 28 weeks. Differences between gestations are significant with Z2 for cesarean secüon and oxygen >-36weeks (24, 25, and 26 weeks vs 27 and 28 weeks), assisted ventilation (26 weeks vs 28 weeks), retinopathy of prematurity (24 and 25 weeks vs 27 and 28 weeks; 24 vs 26 weeks), and grade 3 or 4 intraventricular hemorrhage (25 weeks vs 26 and 28 weeks).
all m o t h e r s ' charts to calculate gestafional age f r o m t h e
d a t a c o n c e r n i n g these infants b e m a d e available rapidly.
original early obstetric u l t r a s o n o g r a p h y
However, while t h e infants are d e v e l o p i n g a n d e n o u g h p a t i e n t s are b e i n g a c c u m n l a t e d , significant c h a n g e s in n e o n a t a l care o f i n f a n t s may occur. T h e i n t r o d u c t i o n o f s u r f a c t a n t is a g o o d r e c e n t e x a m p l e of such a m a j o r c h a n g e . Only o n e s t u d y " r e p o r t e d follow-up of surfact a n t - t r e a t e d infants o f extremely early gestational age, h o r n at 23 to 26 weeks. It d e s c r i b e d a n i m p a i r m e n t rate of 35% at 23 m o n t h s . This c o m p a r e s with o u r rate o f i m p a i r m e n t of 20 of 51 (39%) at 18 m o n t h s for survivors h o r n b e t w e e n 24 a n d 26 weeks in t h e m o s t r e c e n t p e r i o d of o p e n access to surfactant. A n o t h e r study 2~ of surfactantt r e a t e d infants of 23, 24, a n d 25 weeks p r o g n o s t i c a t e d a possible p o o r o u t c o m e at 6 m o n t h s of life, o n t h e basis of d e a t h o r severe i n t r a c r a n i a l a b n o r m a l i t i e s , for 98%, 79%, a n d 31% of infants, respectively. Studies o f infants b o r n at <29 weeks b e f o r e s u r f a c t a n t use have r e p o r t e d i m p a i r m e n t rates f r o m 17% to 39% d u r i n g infancy a n d c h i l d h o o d f -°' 9, ,0. z3, 2~ O n e s t u d y ~ o f c h i l d r e n h o r n at <29 weeks d u r i n g t h e mid-1980s rep o r t e d a h i g h rate o f i m p a i r m e n t o f 65% at 4 years. However, it is at school age t h a t a c a d e m i c p e r f o r m a n c e gives the full p i c t u r e o f the f n n c t i o n i n g o f c h i l d r e n . In a
report,
this
m e t h o d b e i n g u s e d for 85% of t h e infants. O n average, this gave a m e a n d i f f e r e n c e o f only 3 days less t h a n t h e m o t h e r s ' dates, c o n f i r m i n g it to b e a g o o d choice. We gave o u r p r e f e r e n c e to u l t r a s o n o g r a p h y d a t i n g b e c a u s e it prevails i n case of discrepancy, a n d for u n i f o r m i t y we u s e d it for all infants. It h a s b e e n r e p o r t e d t h a t t h e p e r c e p t i o n of viability of very-low-birth-weight infants by physicians may affect survival of i n f a n t s in t h e sense t h a t m a n a g e m e n t decisions may b e b a s e d o n i n c o r r e c t i n f o r m a t i o n a b o u t n e o n a t a l survival) 9" 20 I n o u r n n i t discussions b e t w e e n n e o natologists a n d obstetricians t h a t were b a s e d o n t h e suggested m a n a g e m e n t 2~ o f w o m e n with t h r e a t e n e d b i r t h o f a n i n f a n t of e x t r e m e l y low gestational age, have h a d a n impact. In t h e last years o f t h e study m o r e infants have b e e n b o r n after b e t a m e t h a s o n e , have b e e n a d m i t t e d to t h e n e o n a t a l intensive care u n i t at 23 weeks a n d t r e a t e d with surfactant, a n d have survived at 24 weeks. Since p r o g n o s i s c h a n g e s rapidly for infants of very low b i r t h w e i g h t or very early gestations, it is i m p e r a t i v e t h a t
Lefebvre, Glorieux, and St-Laurent-Gagnon 837
Volume 174, Number 3 AmJ Obstet Gynecol
Table III. O u t c o m e o f c h i l d r e n with follow-up until 18 m o n t h s Psychomotor mardation
Neurologic disorder-Cerebralpalsy
Sensory disorder
Total disab
c~f)qth~ All Gestation No. of Developmental (wh) children Quotient (DQ <90)
24 25 26 27 28 24-28
9 24 40 72 7'2 217
91-+17 89-+25 90-+24 96-+15 96-+14 94-+18
4 6 14 17 15 56
Severe (DQ <80)
(44%) 3 (25%) 5 (35%) 9 (24%) 9 (21%) 9 (26%) 35
All
Severe
(33%) 1 (11%) 0 (21%) 6 (25%) 4 (22%) 11 (27%) 5 (12%) 7 (10%) 3 (12%) 12 (17%) 5 (16%) 37 (17%) 17
(0%) (I7%) (12%) (4%) (7%) (8%)
Blind
1 0 0 0 1 1
(11%) (0%) (0%) (0%) (1%) (0.5%)
Deaf
1 0 0 0 1 1
Major
A r,
(11%) 4 (44%) 1 (0%) 5 (21%) 2 (0%) 9 (22%) 8 (0%) 9 (12%) 8 (1%) 11 (15%) 9 (0.5%) 38 (17%) 28
Normal
(11%) 4 (8%) 17 (20%) 23 (11%) 55 (12%) 52 (13%) 151
(44%) (71%) (57%) (76%) (72%) (70%)
DQ,, Developmental Quodent. Results are expressed as number and percent or mean -+.SD. There are no statisticaI differences between the gestational age groups. Table Ig. O u t c o m e d u r i n g three consecutive periods 27-28 weeks' gestation
24-26 weehs'gestation I
Disabilities
Disabilities
S,arvirJoTs
P«iod
Presurfactant Surfactant-Protocol Surfactant-Routine
Year (approximate)
(No./NICU admission)
Major
Minor or moderate Normal
: (11%) 2 (22%) 4 (31%) 2 (15%)
6 (67%) 7 (54%)
Survivors (No./NICU admission)
32/50 (64%) 28/41 (68%)
Major
Normal
1987-1988 1988-1989
12/26 (46%) 15/30 (50%)
5 (17%) 4 (14%) 20 (69%) 3 (12%) 4 (17%) t7 (71%)
1989-1992
57/84 (68%)* 13 (25%) 7 (14%) 31 (61%) 110/133 (83%)J" 12 (13%) 9 (10%) 70 (77%)
Results are expressed as number and percent. *Z2, p = 0.077 (not significant), compared with presurfactant period tZ 2, p = 0.01, compared with presurfactant period
g r o u p of 5-year-old children b o r n at <29 weeks Msall et al. 7 f o u n d that 9% n e e d e d intensive special education, and 48% r e q u i r e d some special education resources. A l o n g with an increased incidence of slow intelligence and m o r e limited academic skills, Hack et al. 2~ r e p o r t e d an increased risk that school-age child{en who weighed <750 g m would require special e d u c a t i o n placement, c o m p a r e d with low-birth-weight (750 to 1499 gm) and t e r m controls (45% vs 25% vs 14%). T h e question o f w h e t h e r aggressive efforts or new technologies a u g m e n t the p r o p o r t i o n of i m p a i r e d children seems to find a r e p e a t e d answer that it is n o t so. TM 25 We f o u n d no increase in the p r o p o r t i o n of i m p a i r e d children w h e n the presurfactant p e r i o d was c o m p a r e d with the routine surfactant period. However, a stable disability rate in the presence of an increasing survival rate means m o r e disabled survivors as an absolute number. Within a g r o u p of very p r e m a t u r e children the question of whether the handicap rate increases with decreasing gestational age remains unanswered. ~ In contrast to mortality, handicap was not related to gestational age (or birth weight) in a very large c o h o r t o f p r e t e r m infants <32 weeks. 4 O n the contrary, in a similar but rauch smaller c o h o r t of infants b o r n at <32 weeks, severe disabilities were described in survivors b o r n at 24 to 27 weeks m o r e offen than at 28 to 31 weeks. ~ Also in an extremely pre-
m a t u r e g r o u p p r o f o u n d cognitive i m p a i r m e n t increased with decreasing gestation. 9 In o u r c o h o r t we could n o t find statisticat support for such a difference. In this study, in spite of the c o n c e r n that m i g h t arise a r o u n d 24 weeks of gestation, the o u t c o m e of surviving children b o r n at an extremely early gestational age followed up to 18 m o n t h s was generally e n c o u r a g i n g with 70% of the children developing within the n o r m a l range. Gestational age was strongly associated with o u t c o m e in terms of mortality. While survival bas increased over the years, the p r o p o r t i o n of i m p a i r e d survivors has r e m a i n e d stable. We r e c o m m e n d the use of gestational age in future fotlow-up studies because it is the most i m p o r t a n t parameter known before birth that influences decisions with a direct impact on the o u t c o m e of the infant. We are very grateful to Dr. H a r r y Bard for reviewing this manuscript. We thank Jocelyne Vallée, research nurse, for h e r dedicated work in data collection, Monique Grisé, clinic nurse, for h e r supportive care of patients, and Marie-Claude Vinay, psychology student, for her work with patients. REFERENCES
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