PEDIATRICS Vol. 117 No. 2 February 2006, pp. 357-366 (doi:10.1542/peds.2005-0236)
Factors Associated With Neurodevelopmental Outcome at 2 Years After Very Preterm Birth: The Population-Based Nord-Pas-de-Calais EPIPAGE Cohort
a Service de Médecine Néonatale, Hôpital Jeanne de Flandre, Lille, France
b Unité 149 Institut National de la Santé et de la Recherche Médicale, Paris, France
c Centre d'Action Médico-Sociale Précoce, Villeneuve d'Ascq, France
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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OBJECTIVE. We sought to (1) evaluate at 2 years the postsurfactant era developmental outcome of children who were born before 33 weeks of gestational age (GA) in the Nord-Pas-de-Calais area in France in 1997 and (2) identify risk factors of poor developmental quotient (DQ). Children were part of the EPIPAGE study, which included all of these births in 9 French regions.
METHODS. A prospective observational study was conducted of all births before 33 weeks in 1997. Risk factors of poor DQ were obtained from a multiple linear regression, and results were expressed as DQ differences with 95% confidence intervals.
RESULTS. A total of 546 births were included in the study. A total of 461 (84.4%) had a clinical evaluation at 2 years of age, and 380 (69.6%) had an assessment with the use of the Brunet-Lezine scale of infant development. Their mean GA was 29.9 weeks (29.7–30.1 weeks), and mean birth weight was 1378 g (1338–1418 g). A total of 9% had a recognizable pattern of cerebral palsy, 0.2% were blind, and 0.8% required hearing aids. The mean DQ was 94 ± 11 and decreased from 97 at 32 weeks to 86 at 24 to 25 weeks. After multivariate analysis, children who were born at 24 to 25 weeks had a mean DQ reduction of 11 points (–20 to –1) compared with those who were born at 32 weeks, but minor differences were found from 26 to 32 weeks. Boys had a DQ 4 points lower than girls (–7 to –1).
CONCLUSIONS. In this study, the outcome of extremely preterm infants was poor. After 25 weeks, outcome was related mainly to the sociocultural level of the family and to the presence of severe cerebral ultrasound abnormalities. Consequently, in the postsurfactant era, we have to propose follow-up programs to children who are born extremely preterm and to concentrate our efforts on children with less-than-optimal social and family setting.
Key Words: very preterm infant • outcome • developmental disability • developmental quotient
Abbreviations: GA—gestational age • CP—cerebral palsy • DQ—developmental quotient • SGA—small for gestational age
Over the past 20 years, improvements in the perinatal management of very premature newborns have substantially reduced their mortality.1 These improvements involve the widespread use of prenatal corticosteroid therapy, surfactant, and advanced ventilation techniques. Simultaneously, the development of regionalization policies has helped to decrease mortality by reducing the number of very premature children who are born in hospitals that are unable to provide them with optimum care.2
Very premature children are at risk for multiple neonatal diseases related to their immaturity, and these may leave long-lasting sequelae. Given the continuing debate about the appropriateness of offering neonatal intensive care for extremely preterm infants, it is essential that we have a continuing audit of outcomes for these infants. Neurologic sequelae and psychomotor developmental disorders are among the complications with the greatest influence on long-term quality of life.3 Screening for these developmental anomalies therefore must be a major objective in the follow-up of these infants, and care after discharge is now considered as a critical part of the neonatal intensive care service.4 However, these follow-up programs are costly, time-consuming, and might cause unnecessary anxiety to parents and children. Therefore, there is a need to identify precisely which children have to be included in such programs. Many authors have examined the factors that are associated with psychomotor development in premature children, but most of the very low birth weight children included in population-based follow-up programs were born in the 1980s5 and recent cohorts have focused on extremely premature children without results after 25 weeks.6
In France, a large population-based cohort study of very preterm neonates, the EPIPAGE study, was initiated in 1997 in 9 regions, including the Nord-Pas-de-Calais. Neonates who were born at a gestational age (GA) of <33 weeks represented 1.1% of the live births during that period. Ninety-six percent of those who were born alive were admitted in a NICU, and among these children, 89% survived to discharge.7 Neonates who were included in this cohort were followed from birth through 5 years of age, but a formal psychomotor development assessment was performed at the age of 2 years only in 1 region, the Nord-Pas-de-Calais. The aims of this study were (1) to describe the psychomotor development at 2 years of age of children who were born in this area, when prenatal corticosteroid therapy, surfactant, and prenatal transfer for the highest risk pregnancies all had become widespread, and (2) to analyze, in a multivariate analysis, factors that are associated with this development. We were especially interested in assessing the role of GA on outcome.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Population
Our study population was identified in the EPIPAGE survey.7 All of the children who were born in 1997 in Nord-Pas-de-Calais area in France at a GA of <33 weeks and survived to discharge were included in this study. They represented 22% of the national cohort.8 The Nord-Pas-de-Calais area is a region of 4000000 inhabitants. The rate of prematurity in 1998 was 5.4%, similar to the national rate (6.2%).9 Health insurance is nearly in our study population universal as it is in the French system. The level of education is low: 29.9% of the mothers who deliver in this area have a high school diploma compared with 38.7% in France.9 In 1997, the area was served by 49 delivery units; and among them, 5 were perinatal centers. There were 6 level III NICUs. Inclusion was done in the delivery room. Cross-checking between sources helps to ensure a complete register.10 We checked that our sample was complete by crossing birth ward logs with data files in 10 randomly chosen maternity hospitals, questionnaires we had received, and the birth log kept in delivery room. No case had been omitted.
Data Collection
Data around birth and at the evaluation at 2 years were collected prospectively by questionnaires. The first questionnaire was completed by midwives in the delivery unit and included information from the medical records about surveillance during pregnancy, diseases identified during screening, treatments, delivery, child's condition at birth, and immediate management. The neonatal questionnaire, completed by the staff in the NICU to which the child was transferred, collected the principal complications and treatment during hospitalization, as well as the child's condition at discharge. The study involved no intervention. Care provided for mothers and infants was at the discretion of the hospital staff.
Children then were evaluated at a corrected age of 2 years by pediatricians from the neonatal teams; this included a general clinical and standardized neurologic examination. It was a simple form of examination. elaborated for the study, that analyzed how the child was able to stand, to walk, to run, to squat down, and to climb stairs. All of the pediatricians who were involved in the assessment at 2 years of age participated in the elaboration of this examination to ensure reliability. Cerebral palsy (CP) was defined according to Hagberg and Olow.11 Severe impairments of hearing and vision were assessed systematically. An evaluation of psychomotor development with the revised Brunet-Lézine test12 was also performed, and a developmental quotient (DQ) was calculated. It was corrected for prematurity. The psychologists who tested the children were not blinded.
The study received the approval of the "Commission Nationale de l'Informatique et des Libertés." All families for whom outcome is reported gave written informed consent for the study.
Revised Brunet-Lézine Test
This early childhood psychomotor development scale, inspired by Gesell's scale, was developed in France from 1943 onward. It is intended to enable 4 developmental age subscores to be calculated for children who are aged 2 to 30 months. These subscores cover 4 domains: movement and posture, coordination, language, and socialization. The evaluation is based on the child's performance during the test and on questions to the mother about behavior that can be evaluated objectively but are extremely important for judging development. These subscores allow the calculation of 4 separate DQs that, combined, yield a global DQ. The test was modified in 1965 and revised between 1994 and 1996 on a sample of 1032 French children from 6 French regions, including ours.12 This group of children had a mean DQ of 100, with an SD of 14. The objectives of the revision were to refine the evaluation of language development, to limit the number of questions to the parents, and to recalibrate the scoring, because the initial standards do not reflect the capabilities of contemporary children. The development of the initial Brunet-Lézine test and its revision followed rigorous methods, including the evaluation of test-retest reliability and internal reliability, both of which were high. The 
assessing concordance between 2 examiners was 0.85.12 In our study, 8 experienced psychologists performed the Brunet-Lézine examination after discussions to verify the consistency of their scoring. The assessments were always conducted in the hospital.
Study Variables
We studied 51 variables characterizing the mother, the pregnancy, the child, and the neonatal history. A full list of the items that we analyzed, along with their definitions, is provided in the Appendix. The original EPIPAGE database collected information about family characteristics and medical history of mother and child. Because no special training was provided to midwives and neonatal staff who collected the data, we selected variables precisely defined and known to have an impact on outcome.
Analytic Strategy
Data were encoded for computer analysis using double entry and comparison of files for accuracy. All analyses were performed using Stata 7.0 (Stata Corp, College Station, TX).
We first studied the overall DQ distribution. Then, an analysis was conducted following 3 steps: univariate, intermediate, and multivariate. In the univariate analysis, we looked for associations between the variables above and the DQ (by comparing the means), and we selected those that were associated with the DQ at a P < .20. We then classified these significant variables into the following 7 frames: mothers' psychosocial and demographic characteristics, educational level and parents' occupation, mothers' obstetric history, neonatal characteristics including general severity of illness, respiratory and neurologic conditions, and finally breastfeeding at discharge. Our aim was to find in each of these frames the variables that were associated independently with the DQ. Three variables (GA, gender, and small for GA [SGA]) were included in each frame because they are essential characteristics of the child and strong contributors to later development. The intermediate forward stepwise regression was performed for each thematic group. For each intermediate regression, the initial model included only the 3 forced variables, and then the variable whose association was the strongest in univariate analysis was first introduced into the model. For the next variable, the association with DQ was searched after adjustment on the first one. Finally, we performed a multivariate analysis with forward stepwise linear regression. The 3 forced variables and the variables that were associated with DQ in the intermediate model at P < .05 were included in the model. At the end of the analysis, we compared the children who were assessed at 2 years of age with the children who were not assessed for the variables associated with DQ in the intermediate models.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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During the study period, 634 children were born alive at a GA of <33 weeks in the Nord-Pas-de-Calais area. Antenatal characteristics of mothers are reported in Table 1. Sixty-six percent of births occurred in tertiary care centers, and 80% of the children received their initial care in a NICU. Among them, 72.9% were exposed to antenatal corticosteroids, and 47% received surfactant.
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Thirty-seven neonates died in delivery room, and 49 died in NICUs. Survival rates according to GA are shown in Table 2. A total of 548 children (86.4% of the live births) survived to discharge. Two had congenital anomalies that usually result in developmental retardation (1 child with Down syndrome and another with agenesis of the corpus callosum) and were excluded from the study. Thus, 546 neonates were included in our study population. Among these 546 children, 461 (84.4%) had a clinical examination at the age of 2 years, and 42 (9.1%) of these had a recognizable pattern of CP that was classified as moderate or severe in 27 (5.9%) children. We were able to perform a Brunet-Lezine scale in 380 (69.6%) of the 546 children. In 81 children, the test was not performed either because the child's impairment was too severe (n = 8), the child refused, or the psychologist was not available. These 380 children had a mean GA of 29.9 weeks (29.7–30.1 weeks) and a mean birth weight of 1378 g (1338–418 g). Thirty-four of these children had a form of CP, 1 was blind, and 3 had a hearing loss that was corrected with hearing aids.
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Overall Distribution of the Brunet-Lézine Scores for the 380 Children
Children were assessed at mean corrected age of 23 months. Figure 1 shows the distribution of the global Brunet-Lézine scores. The global DQ ranged from 8 to 123 for a mean of 94 ± 11 and a median of 94; the 10th percentile was 77, and the 90th percentile was 110. DQ was <70 in 18 (4.7%) children. After exclusion of children with CP, the mean DQ was 95 ± 10 (10th percentile at 80 and 90th percentile at 111).
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Univariate Analysis
Univariate analysis identified maternal and neonatal factors, including the 3 forced variables, that were associated with DQ (Tables 3 and 4). DQ was associated with GA and decreased progressively as prematurity increased, from 97 at 32 weeks of GA to 87 at 24 to 25 weeks (P = .02). Boys had a mean DQ 3 points lower than girls (P = .08). Being SGA was not significantly associated with the DQ (P = .83).
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Multivariate Analysis
After the univariate step, 23 variables were associated with DQ. Nine were still associated with the DQ after intermediate analysis: "living as a couple," "smoking at the end of pregnancy," "parental occupation," "antenatal steroids," "hypertension during pregnancy," "shock requiring fluid replacement or inotropic agents," "mechanical ventilation," "severe cerebral ultrasound abnormalities," and "breastfeeding at discharge." We then conducted a forward stepwise linear regression with the 3 forced variables and these 9 significant variables. These 12 variables were available for 342 children, who therefore entered the final analysis group (Table 5).
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DQ was only slightly associated with GA between 32 and 26 to 27 weeks of GA. However, for the children who were born at 24 to 25 weeks, DQ was 11 points lower compared with the children who were born at 32 weeks (P = .03). Girls' mean DQs were 4 points higher than boys' DQs (P < .01). The highest parental occupation of the couple was closely associated with outcome. Compared with the DQ of children who were born from parents with a high or intermediate occupation, the mean DQ was 7 points lower for infants of workers or employees (P < .01) and 14 points lower when both parents were unemployed (P < .01). Severe cerebral ultrasound abnormalities during the neonatal period were associated with a DQ 14 points lower than those of children without such abnormalities (P < .01). The other factors that were associated with a higher score were hypertension during pregnancy (4 points; P = .04), absence of mechanical ventilation (4 points; P < .01), and breastfeeding at discharge (4 points; P = .02).
Comparison Between Children Who Were Assessed by the Brunet-Lézine Test and the Others
The Brunet-Lézine's assessment was not performed in 166 (30.4%) of the 546 children who met the inclusion criteria. We compared the 2 groups according to the 3 forced variables and the 9 variables that were associated with the DQ in the intermediate models. The groups differed for 3 of these variables. The children who were lost to follow-up were more often boys (P < .01). Their mothers smoked more often at the end of pregnancy (P = .01). This group also included more children whose parents both were unemployed at the time of the child's birth (P < .01).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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This is 1 of the first large population-based studies to assess the outcome of very preterm infants who were born during the postsurfactant era. For professionals who work with parents and plan follow-up programs for children who are born very preterm, contemporary data for this population are crucial. The aim of this study was to describe the psychomotor development at 2 years of age of children who were born before 33 weeks and to examine the factors that are associated independently with this development. Inclusion was based on GA rather than birth weight and gave the opportunity to evaluate the prognosis of appropriately grown and SGA infants. We were especially interested in assessing the role of GA in the outcome. This study was based in the Nord-Pas-de-Calais area in France, a densely populated region with a high level of unemployment and a poor level of education. This was confirmed in our group as only 24% of the mothers had a diploma beyond high school, which was 1 of the lowest rates in the 9 regions involved in the EPIPAGE study.8 Organization of perinatal care was not yet fully effective with regard to recommendations: 60% of the neonates were born in a tertiary care center, and 72.9% received antenatal steroids. For the most immature infants, the survival rate at discharge was comparable to the EPICure cohort, a contemporary European cohort.13
To provide reliable, valid, and generalizable information, the ideal study should be prospective, based on large populations, include full-term control groups, have few infants lost to follow-up, be long term, include differential reports of subpopulations, and be conducted by independent psychology researchers.14 We did not have the financial support to evaluate the psychomotor development in a full-term control group and to have independent psychology researchers. Other recommendations were fully followed to give strength to this study. Our results come from the prospective analysis of a regional cohort of 546 children. A total of 84.4% of the survivors were examined at 2 years of age, and nearly 70% had a psychometric evaluation. We were not able to evaluate the DQ in 30% of the initial population. Fortunately, not all of them were lost to follow-up, and only 15.6% had no neurologic evaluation at the age of 2 years. The comparison between tested and untested patients showed significant differences between the groups: the first group included fewer boys, fewer children whose mother smoked at the end of pregnancy, and fewer unemployed parents. These 3 variables all were associated with a higher risk for developmental retardation. Furthermore, the group of children whose DQ was unknown included children whose impairment was too severe to perform a test and children who refused the test, and all of this led to an overestimation of the outcome in the global population.
The rate of CP (9%) was consistent with reports from other centers4 and was not different from the rate observed in the national cohort.15 We used the Brunet-Lézine test to assess development, although it is rarely used in the international literature.16 Unfortunately, there is no reference test or gold standard. A meta-analysis found 80 studies that used 25 different tests to assess the development of low birth weight children.5 The Brunet-Lézine test was the test that was known best by the psychologists who performed the assessments, thus facilitating a homogeneous scoring. Moreover, the scales of Bayley, McCarthy, and Griffith, all frequently used, have not been calibrated on a French sample.
The mean DQ at 2 years of age corrected for prematurity was 94 ± 11, lower than that of the general population even after exclusion of children with CP. The recent standardization of the test that we used is in favor of a lower DQ in very preterm infants compared with the general population. We chose to consider as a reference children who were born at 32 weeks of gestation. Unfortunately, we were not able to compare our group of children who were born at 32 weeks with other groups in the literature as we did not find data considering this group of children as a whole. They are usually included in the group of very low birth weight neonates,17 but the most recent reports tend to include them in the group of low birth weight infants.18, 19 As expected, the DQ decreased with GA from 97 at 32 weeks to 86 at 24 to 25 weeks. This is in accordance with the mean scores of 84 ± 12 and 87 ± 13 on the Bayley Mental and Psychomotor Developmental indexes observed at 30 months' corrected for GA in the EPICURE group.6 After multivariate analysis, DQs were only slightly different from 31 to 26 weeks compared with 32 weeks of GA. This huge difference in development between children who were born at 24 to 25 weeks and children who were born at higher GA is in favor of a true pathologic developmental delay rather than the consequence of the failure to correct for GA. In the EPICURE group, it was interesting to note that the Bayley scores did not differ with GA and were stable between 23 and 25 weeks.6 The results of other earlier works that studied the association between GA and development are contradictory.17, 20, 21 They usually include very few neonates who were born before 26 weeks. Analysis of IQ at 5 years of age is in progress and will provide the opportunity to analyze the correlation between the DQ at 2 years of age and later cognitive outcome.
The disadvantage of male gender was observed in most of the studies that examined neurodevelopmental outcome in preterm children6, 22, 23 and was confirmed recently in extremely preterm birth.24 During the revision of the Brunet-Lézine test on a sample of 1032 children who were born at term, gender was not associated with the test results.12 In our cohort, too, boys were more likely to have impairments than girls with a mean DQ 4 points lower, which is usually considered to be clinically significant. This could be viewed as a particular vulnerability of boys toward prematurity that persists despite improvements in neonatal care.
There now is strong evidence that intrauterine growth restriction is associated with significant neurodevelopmental disabilities and school failure.7, 21 Furthermore, alteration of structural and functional brain development in premature infants who were born with intrauterine growth restriction was described recently.25 However, we were not able to demonstrate that being SGA was a risk factor for a lower DQ at 2 years of age. At that age, posture and motor functions have a great impact on global DQ, and it is possible that this measure is not predictive of later cognitive outcome in this particular group of children. Analysis of the different subtests could be more informative, and, indeed, in the national cohort, being SGA was associated with more difficulties in the social domain at 1 year of age (B. Larroque, M. Kaminski, A. Burguet, et al, unpublished data, 2005). This represents an important area for continuing research, because elaboration of prevention programs in this high-risk group of infants could have implications for practice.
Apart from GA and gender, we found a strong association between a lower psychomotor development and parental unemployment. Parental occupation has always been found to be a powerful indicator of outcome,20–23, 26–29 even in children who are born at term.12 It was interesting to note that in the multivariate analysis, the magnitude of difference in the DQ between 32 weeks and 25 weeks was similar to the difference observed between children whose parents were of intellectual or intermediate sociocultural level and children whose parents both were unemployed. The observed impact of environment on outcome could lead to concentrate educational resources in the group of infants with the highest risk. It has been shown that a stimulating early environment might prevent later cognitive disability,30 even with a complicated perinatal history.28 However, persisting benefits at 8 years of age are modest and observed mainly in the heavier premature infants.30 Another early approach to improve long-term outcome could be found in developmental care.31
The complications of pregnancy and prematurity were selected because they were considered to be objective and easily defined and would be reported reliably. The most powerful obstetric marker of a good outcome was maternal hypertension. It was associated with a mean DQ score 4 points higher than in the group without maternal hypertension. Two hypotheses can be drawn from the association that we found: hypertension has a protective effect toward developmental outcome, or the other factors that are associated with prematurity have a negative impact on outcome. In the recent literature, premature rupture of membranes and chorioamnionitis have been shown to be associated with developmental delay.32 Few studies have assessed the effect of maternal hypertension on psychomotor development, and results were contradictory 23, 33–35 Greenwood et al36 recently reported a modifying effect of GA on risk factors for CP and suggested that the apparent reduced risk for CP associated with preeclampsia in very preterm infants is driven by the characteristics of the gestation-matched control group. In this context, she suggested that the term "protective" for preeclampsia should be abandoned and encouraged to clarify sources of bias in epidemiologic studies of CP risk in preterm infants.
In the final model, only 2 neonatal variables were associated with a lower DQ: the presence of severe cerebral ultrasound abnormalities and mechanical ventilation. The association between severe intracerebral lesions and later outcome was confirmed recently in a vast cohort from a level III neonatal unit.37 Respiratory morbidity has always been studied in relation to outcome. In our cohort, neither oxygen dependence at 28 postnatal days nor oxygen dependence at 36 weeks' GA was associated with a lower DQ. This association was often found in the literature but usually in hospital-based study.23, 29, 38 The criteria that were used in the different units to determine the need for oxygen supplementation were not requested, and it has already been shown that the mode of oxygen delivery varies greatly among centers.39 The adverse effect of postnatal steroids on short- and long-term neonatal morbidity is now well documented,36 and a strong association between duration of treatment and adverse motor outcome was confirmed recently in the EPICure cohort.24 We did not find this association, but these findings must be viewed with caution given that the number of infants who were born before 28 weeks was too low to identify the risk and that no data were available on the formulation, cumulative dosage, or rate of withdrawal. The best criterion of respiratory morbidity associated with outcome was mechanical ventilation. One can assume that the way to give support to the infants with mechanical ventilation is much more consistent across centers than the way to deliver oxygen or to give postnatal steroids.
Finally, we found a positive association between DQ and breastfeeding at discharge, and this association persisted after the multivariate analysis. This link was already highlighted by many authors.40 However, the rate of breastfeeding at discharge was low in this population and reflects the low level of breastfeeding in France. The question of the link between this association and nutritional or socioenvironmental factors that are usually optimal in women who breastfeed their child for a long time is still open.41 Nevertheless, supporting parents to breastfeed preterm infants may maximize the potential advantages of early nutrition in the neurodevelopmental outcome of very low birth weight infants, and a more active policy to help these mothers is particularly needed.
In this study, as in other countries, the outcome of extremely premature infants was poor and questions the active management of extremely small children regardless of the circumstances around birth. After 25 weeks, outcome was much more related to environment and obstetric and neonatal morbidity than to GA. However, even in the postsurfactant era, the risk for developmental disorders is high in very preterm neonates. Some of the risk factors identified are important area of research and give the potential for improving outcome. We certainly have to propose follow-up programs to children who are born very preterm and to concentrate our efforts on children with a less-than-optimal social and family setting. Additional assessment at 5 years of age could help us to identify other factors to individualize follow-up programs with regard to the risk for later disabilities.
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APPENDIX |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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The following data items were included in the analysis and recorded from a standardized form for all infants who were included in the study. Items that required a yes or no answer are indicated yes-no, and ranges of options are given between parentheses. Throughout the record, there were opportunities for the information to be amplified with free text.
Maternity hospital level (I, II, III)
Mother's psychosocial and demographic characteristics
Mother's nationality (French, other)
Lives with partner (yes-no)
Help from partner, assessed by the mother (yes-no)
Help from family circle, assessed by the mother (yes-no)
Number of children at home (0, 1–2, 
3)
Smoking at the beginning and at the end of pregnancy (0, <10, 10 cigarettes per day)
Alcohol consumption at the beginning and at the end of pregnancy (0, 1, 2 glasses per day)
Mood before and during pregnancy, assessed by mother (very good, satisfactory, fairly bad, very bad)
Use of tranquilizers, sleeping pills, or antidepressants before and during pregnancy (yes-no)
Educational level and parents' occupation
Highest educational level in the couple (university level or not)
Highest occupation in the couple (intellectual or intermediate occupation, employee or worker, unemployed)
Mothers' obstetric characteristics
Height and weight before pregnancy (<25th, 25th–75th, >75th percentile)
Parity (0, 1–2, 3)
Maternal age (<21, 21–36, >36 years)
Singleton or multiple pregnancy
Hypertension during pregnancy, regardless of whether it first appeared during pregnancy (yes-no)
HELLP syndrome (yes-no)
Premature rupture of membranes (yes-no)
Chorioamnionitis defined by the obstetrician (yes-no)
Third-stage hemorrhage (yes-no)
Amniotic fluid volume (oligoamnios, normal volume, hydramnios)
Type of delivery (vaginal or cesarean)
Prenatal corticosteroid therapy (yes-no)
Neonatal characteristics
GA (24–25, 26–27, 28–29, 30–31, 32 weeks)
Gender (male or female)
Birth weight (
750, 751–1000, 1001–1250, 1251–1500, >1500 g)
SGA, defined as fetal growth rate <0.75 (yes-no)
Birth rank (in multiple births)
Variables assessing respiratory function
Hyaline membrane disease (yes-no)
Mechanical ventilation (yes-no)
High-frequency ventilation (yes-no)
Refractory hypoxemia defined as PO2 <50 mm Hg under 100% fraction of inspired oxygen (yes-no)
Oxygen dependence at 28 days (yes-no)
Oxygen dependence at 36 weeks (yes-no)
Postnatal corticosteroid therapy (yes-no)
Variables assessing general severity of illness
Acute fetal distress (yes-no)
Clinical Risk Index for Children score (<5, 5–10, >10)
Shock during hospitalization that requires fluid replacement or inotropic agents (yes-no)
Cardiopulmonary arrest during hospitalization (yes-no)
Confirmed maternal–fetal infection (yes-no)
Confirmed neonatal septicemia (yes-no)
Necrotizing enterocolitis stage 2 or 3 according to Bell42 (yes-no)
Variables assessing neurologic severity
Neonatal clinical or electric convulsions (yes-no)
Severe cerebral ultrasound abnormalities including leukomalacia and severe intraventricular hemorrhages defined as Papile's grade III or IV43 (yes-no)
Breastfeeding at discharge (yes-no)
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ACKNOWLEDGMENTS |
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We are very grateful to all of the maternity units and neonatal teams in the Nord-Pas-de-Calais who contributed to collect data and whose help was invaluable: CH Armentières: S. Enchéry; CH Arras: S. Lucidarme; CH Boulogne: A.M. Gournay; CH Calais: M. Poher; CH Douai: S. Racoussot; CH Dunkerque: E. Robin; CH Lens: A. Djebarra; CH Lille St Antoine: A. Bourlet; CH Maubeuge: G. Delebarre; CH Roubaix: S. Rousseau; CH Tourcoing: M. Chenaud; CH Valenciennes: B. Pindi. We also acknowledge Dr B. Carpentier (Arras) and Dr N. Haouari (Lens) for the acquisition of the data. We thank the psychologists for the Brunet-Lézine examinations: Mrs Decoopman, Delfosse, Haleze, Hallosserie, Leblond, Lorthioir, Poulain, and Soulignac. We thank C. Leignel and Dr A. Liska (Arras), who entered all the data. We also thank all of the children and their families who were so enthusiastic to participate in the study.
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FOOTNOTES |
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Accepted Jun 16, 2005.
Address correspondence to Antoine Fily, MD, Service de Médecine Néonatale, Hôpital Jeanne de Flandre, Ave Eugène Avinée, 59037 Lille cedex, France. E-mail: a-fily{at}chru-lille.fr
The authors have indicated they have no financial relationships relevant to this article to disclose.
Dr Fily had primary responsibility for preliminary data analysis and writing the manuscript; Prof Truffert helped with the statistical analysis and elaborated the protocol for the Nord- Pas-de-Calais area; Dr Pierrat participated in the protocol development and performed the final writing of the manuscript; Mrs Delporte was the referent psychologist for the Brunet-Lézine examination; Prof Breart supervised the design and execution of the study.
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