PEDIATRICS Vol. 100 No. 2 August 1997,
p. e4
Copyright ©1997 by the American Academy of Pediatrics
ELECTRONIC ARTICLE:
Outcome of Small-for-Gestational Age and
Appropriate-for-Gestational Age Infants Born Before 27 Weeks of
Gestation
, and
From the * Department of Neonatology and the
Department of
Psychiatry, Sir Mortimer B. Davis Jewish General Hospital: McGill
University, Montreal, Quebec, Canada.
Objective. To evaluate the consequences of being small-for-gestational age at extremely low gestational age.
Methodology. Comparison of two historical cohorts of small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) infants born between 24 and 26 6/7 weeks of gestation (gestational age estimated by early ultrasound at 16 to 18 weeks). Data were collected retrospectively on 191 successive admissions to the neonatal intensive care unit between January 1, 1983, and December 31, 1992. These included: demographic and maternal information, delivery mode and condition at birth, mortality, neonatal intensive care unit morbidities (respiratory distress syndrome, intraventricular hemorrhage, patent ductus arteriosis [PDA], chronic lung disease [CLD], retinopathy of prematurity [ROP], necrotizing enterocolitis, infection), nutrition, and length of hospitalization.
Results. Forty-one (21%) of the 191 infants were
classified as SGA. Those with congenital anomalies (10% in the SGA and
2% in the AGA group) were excluded from further analysis. Despite a
similar rate of respiratory distress syndrome (50%), the SGA infants
had a greater rate of failure of indomethacin treatment for PDA closure
(54% vs 32% for AGA), a higher risk for CLD defined as a need for
supplementary oxygen at 36 weeks (65% vs 32% for AGA), a more
prolonged need for oxygen supplementation and ventilatory support (94 days vs 68 days for AGA and 58 days vs 40 days for AGA, respectively).
SGA infants were also at greater risk for developing severe ROP (stage
III) (65% vs 12% for AGA).
Conclusions. For infants born before 27 weeks, being small-for-gestational age confers additional risks for severe morbidity, ie, PDA ligation, CLD, and ROP.
Key words: extreme prematurity, small for gestational age, mortality, morbidity.Small-for-gestational age (SGA) infants represent a significant percentage of infants admitted to neonatal intensive care units (NICU). There is abundant literature on the neonatal course and long-term outcome of SGA infants born at or near term.1 For those born prematurely, comparisons between SGA and appropriate-for-gestational age (AGA) infants have generally shown that SGA infants have fewer respiratory difficulties in the neonatal period than AGA infants.6 However, these conclusions were drawn when the birth weight rather than the gestational age served as the basis for comparison.9,10 The limited number of studies comparing premature AGA and SGA infants of similar gestational age have shown inconclusive outcomes.11 Furthermore, there is a paucity of information regarding the outcome of infants born at extremely low gestational age (ELGA).
The present study addresses the issue of outcome of SGA infants born between 24 and 26 6/7 weeks of gestation, an age group which was very difficult to study earlier. Nowadays, with the routine use of ultrasound between 16 and 20 weeks of gestation in the province of Quebec, it is possible to accurately date a pregnancy. Furthermore, the survival rate of infants of extremely low birth weight (ELBW) and ELGA has increased in the last decade. This permits the evaluation of the impact of early intrauterine growth retardation on the outcome of infants born before 27 weeks of gestation.
Patient Population
The 191 infants enrolled in the study were born at the Sir Mortimer B. Davis Jewish General Hospital, Montreal, between January 1, 1983 and December 31, 1992. Their gestational age, calculated by ultrasonography performed between 16 and 20 weeks of gestation and LMP, ranged from 24 to 26 6/7 weeks. If there was a discrepancy greater than 1 week between last menstrual (LMP) and ultrasound dating, the gestational age determined by ultrasound was taken as reference. An infant was classified as SGA if the birth weight was at or below the third percentile, using the Usher and McLean grids of intrauterine growth, constructed from patients born in the province of Quebec15 and extrapolated to 24 weeks.Outcome Variables
The following clinical conditions were evaluated:- Early neonatal course describes the infant's condition upon admission to the NICU.
- Respiratory distress syndrome (RDS): The diagnosis of RDS was made on the basis of clinical and radiologic criteria. Surfactant replacement therapy became available in our NICU in 1990 and has been used early in the treatment of infants with RDS in respiratory failure.
- Intraventricular hemorrhage (IVH): Ultrasonographic evaluation of the ventricular system was routinely done in the first week of life and repeated 1 week later. If pathology was present, ongoing evaluation would proceed on a weekly basis. The ultrasounds were evaluated by the same ultrasonographer who was unaware of the SGA/AGA status of the infant. IVH was reported according to Papile's classification.16
- Periventricular leukomalacia: A head ultrasound was done between 36 and 40 weeks of gestation for the diagnosis of periventricular leukomalacia.
- Patent ductus arteriosis (PDA): PDA was diagnosed clinically and by echocardiography. In the absence of contraindications (active bleeding or renal failure), indomethacin was the treatment of choice for ductuses with clinical signs of failure. Two to three courses of indomethacin were attempted before surgery was considered.
- Sepsis: Infection was diagnosed either by a positive blood culture or an abnormal white blood cell count and differential in the presence of obvious clinical signs of infection. Infections were classified as early (occurring during the first week of life) or late.
- Chronic lung disease (CLD): CLD was defined as an oxygen need beyond 36 weeks of gestation.
- Retinopathy of prematurity (ROP): Each infant's retina was assessed by an ophthalmologist 4 to 6 weeks after admission to the NICU with repeat examinations until maturity of the retina. The diagnosis and staging of ROP was done according to the International Classification.17
- Time of discharge: Infants were discharged home when they reached a weight of 2200 g and were free of medical problems.
Statistical Analysis
The data were analyzed by the SPSS statistical program. Between group differences on categorical variables were analyzed with
2 statistics or Fisher's exact test if cell sizes
were less than 5. Student's t test was used to compare the
groups on continuous variables. A P value of <.05 was
considered significant.
Perinatal Outcome
Pregnancy complications, mode of delivery, and the infant's condition at birth are described in Table 1. Except for an increased incidence of preeclampsia in the mothers of SGA infants, all other parameters were similar in the two groups. The percentages of SGA and AGA infants born after prolonged rupture of membranes (greater than 24 hours) were comparable (40% and 30%, respectively). At birth, more SGA infants were depressed as indicated by the greater percentage of SGA infants with an Apgar score of
5 at 5 minutes (32% vs 19%)
(P = .05). The distribution of SGA and AGA
infants by gestational age was as follows: at 24 weeks, 19 SGA and 42 AGA; at 25 weeks, 11 SGA and 50 AGA; and at 26 weeks, 7 SGA and 55 AGA.
The distribution of infants according to gender was similar.
|
Table 1. Perinatal Data |
Early Neonatal Course
Table 2 presents data on neonatal morbidity after admission to the NICU. The incidence of RDS was similar in the two groups (50%). Surfactant replacement therapy was given to 12% of SGA and 14% of AGA infants. The incidence of IVH of any grade was 22% for SGA and 30% for AGA infants. There was a trend for severe IVH (grade III or IV) to occur more frequently among the AGA infants (23% vs 12%).|
Table 2. Early NICU Course |
Mortality
Mortality to discharge home was somewhat higher for the SGA group, although not statistically significant (46% vs 35%). The mean birth weight and gestational age of the 17 deceased SGA infants were 556 g and 25.4 weeks, and for the 52 AGA infants, 773 g and 25.3 weeks. The causes of death were not different for SGA and AGA infants (Table 3). Causes other than respiratory or infectious included intractable hyperkalemia, massive IVH, and renal failure. The median age at death was 7 days for the SGA and 2.5 days for the AGA infants.|
Table 3. Mortality |
Neonatal Complications Among the Survivors
The outcome of the surviving infants (20 SGA, 95 AGA) is described in Tables 4 and 5. Although the incidence of RDS and need for oxygen were similar in AGA and SGA infants, appropriate oxygenation and ventilation were achieved with significantly higher peak inspiratory pressure at 48 and 72 hours for the SGA infants (Table 5). A clinically significant PDA was diagnosed more frequently in the SGA group. Indomethacin treatment was unsuccessful in 7/13 (54%) SGA infants and 14/44 (32%); these infants subsequently required surgical ligation of the ductus arteriosus. Infection was suspected or confirmed more frequently in SGA infants, especially during the first week of life. The number of positive blood cultures was 2 (10%) for SGA and 2 (2%) for AGA infants during the first week of life, and 7 (38%) for SGA and 11 (12%) for AGA infants after 7 days of life.|
Table 4. NICU Outcome, Survivors |
|
Table 5. Respiratory Outcome, Survivors |
The prognosis of SGA infants with chromosomal anomalies, genetic syndromes, or congenital infections is relatively predictable. However, for the others, the outcome is much less certain. Furthermore, very little information is available concerning SGA infants who are born extremely premature. In view of the increasing survival of ELBW infants, a better knowledge of the consequences of the combination of severe prematurity and intrauterine growth retardation becomes imperative for proper parental counseling and decision making.
Received for publication Dec 16, 1996; accepted Feb 24, 1997.
Presented in part at the annual meeting of the Society for Pediatric Research, Seattle, Washington, May, 1994.
Reprint requests to (C.B.) The SMBD-Jewish General Hospital, 3755 Cote St Catherine Road, Room A-209, Montreal, Quebec H3T 1E2, Canada.
SGA, small-for-gestational age. NICU, neonatal intensive care unit. AGA, appropriate-for-gestational age. ELGA, extremely low gestational age. ELBW, extremely low birth weight. LMP, last menstrual period. RDS, respiratory distress syndrome. IVH, intraventricular hemorrhage. PDA, patent ductus arteriosus. CLD, chronic lung disease. ROP, retinopathy of prematurity.
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Pediatrics (ISSN 0031 4005). Copyright ©1997 by the American Academy of Pediatrics
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