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Article |

Prevalence and Associated Factors of Minor Neuromotor Dysfunctions at Age 5 Years in Prematurely Born Children:  The EPIPAGE Study FREE

Catherine Arnaud, MD; Laetitia Daubisse-Marliac, MD; Mélanie White-Koning, PhD; Véronique Pierrat, MD; Béatrice Larroque, MD, PhD; Hélène Grandjean, MD, PhD; Corine Alberge, MD; Stéphane Marret, MD, PhD; Antoine Burguet, MD, PhD; Pierre-Yves Ancel, MD, PhD; Karine Supernant, DUT; Monique Kaminski, MSc
[+] Author Affiliations

Author Affiliations: Institut National de la Santé et de la Recherche Médicale Unit 558, Research Unit on Perinatal Epidemiology, Child Health, and Development, University Toulouse III (Drs Arnaud, Daubisse-Marliac, White-Koning, and Grandjean) and Neonatal Care Unit, Children Hospital (Dr Alberge), Toulouse, France; Jeanne de Flandre Hospital, Lille, France (Dr Pierrat); Institut National de la Santé et de la Recherche Médicale Unit 149, Institut Fédératif de Recherche 169, Epidemiological Research on Perinatal Health and Women's Health, Villejuif, France (Drs Larroque, Burguet, and Ancel and Mss Supernant and Kaminski); Charles Nicolle Hospital, Rouen, France (Dr Marret); and Pediatric Unit, University Hospital, Poitiers, France (Dr Burguet).


Arch Pediatr Adolesc Med. 2007;161(11):1053-1061. doi:10.1001/archpedi.161.11.1053.
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Objectives  To assess the frequency of minor neuromotor dysfunctions (MNDs) at age 5 years according to gestational age, to test their association with behavioral and learning difficulties, and to find determining neonatal factors.

Design  Prospective population-based cohort study of children born in 1997 and followed up from birth to age 5 years.

Setting  All maternity wards in 9 regions of France.

Participants  A total of 1662 children born before 33 completed weeks of gestation and 2 control groups including 245 children born at 33 to 34 weeks and 332 children born at 39 to 40 weeks.

Main Exposure  Birth before 33 weeks.

Main Outcome Measure  Short version of the Touwen neurological examination classifying children as healthy, having mild MND (MND-1), or having moderate MND (MND-2) depending on the number of abnormal neuromotor signs found.

Results  Of children born before 33 weeks, 41.4% had MND-1 and 3.0% had MND-2. These proportions were 30.8% and 0.5%, respectively, for children born at 33 to 34 weeks and 22.0% and 0.7%, respectively, for children born at 39 to 40 weeks. Minor neuromotor dysfunction was independently associated with learning difficulties at age 5 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). In very preterm children, factors associated with MND-1 were postnatal corticotherapy (OR, 1.8; 95% CI, 1.3-2.6), multiple births (OR, 0.7; 95% CI, 0.6-0.9), and, in singletons, breastfeeding (OR, 0.8; 95% CI, 0.6-0.99). Being a boy (OR, 3.1; 95% CI, 1.5-6.4), having had acute fetal distress (OR, 2.8; 95% CI, 1.4-5.5) or severe abnormalities on early cranial ultrasonography (OR, 2.7; 95% CI, 1.2-6.2), and having had postnatal corticotherapy (OR, 2.7; 95% CI, 1.2-6.1) increased the risk of MND-2.

Conclusions  The high rate of MNDs and their association with an increased risk for learning difficulties justify their screening in case of (even moderate) prematurity.

Important progress in obstetric and neonatal care in recent decades has improved the survival of increasingly premature infants, but the prevalence of the most severe neurodevelopmental sequelae, such as cerebral palsy,13 cognitive impairment, or behavioral problems,4 remains high. Research has focused on children born extremely preterm or with extremely low birth weights and mostly on the severe long-term neurodevelopmental outcomes.58 However, in children without obvious neurological deficits, subtle abnormalities such as difficulties with fine motor function, coordination, and learning may occur.9 These minor neuromotor dysfunctions (MNDs), which may have adverse effects on family life and require specific social, educational, and health care resources, can also be found in children born less prematurely.1013

In early childhood (ages 4-6 years), these MNDs can reliably be observed using a detailed and standardized neurological examination such as the one described by Touwen.14 Some studies have indicated that the quality of general movements and the presence of neurological soft signs in early childhood are related to the type and severity of later neurological and behavioral developmental difficulties1517 as well as the presence of learning disorders.18

We analyzed the results of the Touwen examination at age 5 years in a cohort of children born very preterm and in 2 control groups of children born at 33 to 34 and 39 to 40 weeks of gestation followed up from birth with the same methods. Our aims were to assess the frequency of MND according to gestational age (GA), to describe their association with behavioral problems and learning difficulties, and to determine which sociodemographic or neonatal factors are associated with such dysfunctions in the very preterm group.

POPULATION

The children included are from the EPIPAGE (Etude Epidémiologique sur les Petits Ages Gestationnels) project,19 which is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. Three groups of children were included: all of the children born before 33 completed weeks of gestation and 2 control groups, including all of the children born at 33 to 34 weeks during April and October and 1 in 4 children born at 39 to 40 weeks during 1 week. Ethics approval was sought from the appropriate body and parental informed consent was obtained.

All of the children whose parents agreed to participate were enrolled in the study. In 2 regions, half of the infants born at 32 weeks were randomly excluded from the follow-up to reduce the workload. At age 5 years, each child was seen both by a pediatrician who undertook a detailed and standardized physical and neurological examination and by a psychologist who performed a test of cognitive abilities. All of the pediatricians and psychologists were trained to administer these tests. They were not informed of the child's perinatal history at the time of examination. Parents were also asked to fill in a questionnaire on the health, development, and behavior of their child.

MEASURE OF MND AT AGE 5 YEARS

The neurological examination was a shorter version of the Touwen examination previously validated in a population of 5-year-old children born very preterm.20 A neurological profile is derived from 16 items grouped into 4 subsystems representing a subset of the neurological repertoire: posture and muscle tone, reflexes, coordination and balance, and motor behavior of the face and eyes. Each of these 4 subsystems is rated as optimal or nonoptimal according to specific criteria based on the presence of a number of dysfunctional signs. The children are then classified as healthy (MND-0) if the 4 subsystems are optimal or as having mild MND (MND-1) or moderate MND (MND-2) if up to 2 subsystems or more than 2 subsystems, respectively, show dysfunctional neuromotor signs. Available information suggests that the reliability of this pediatric neuromotor assessment is fairly good (κ values of interrater agreement for various subsystems, > 0.7).17,21 As the examination aims to detect minor abnormalities, it is not applicable to children with cerebral palsy, cannot be carried out when severe mental (IQ < 50) or sensory impairment is present, and can only be interpreted if the children perform all of the required tests.

FACTORS STUDIED IN RELATION TO MND IN THE VERY PRETERM GROUP

The following social and demographic characteristics were recorded at birth and included in the analysis: mother's nationality (French or other), marital status (mother living alone, yes or no), parity (0, 1-2, or ≥ 3), maternal educational level (university level or not), and mother's age (< 21, 21-34, or > 34 years).

Neonatal characteristics were determined from medical records: GA (defined as completed weeks of amenorrhea based on the date of the last menstrual period and results of early prenatal ultrasonography), sex, multiple births, antenatal steroids, birth weight, small for GA (defined as a birth weight below the 10th percentile of the live births in the EPIPAGE study for a given GA and sex), acute fetal distress, Apgar score less than 7 (5 minutes after birth), Clinical Risk Index for Babies score (validated tool for assessing the initial neonatal risk and severity of illness of the preterm infant, based on birth weight, GA, oxygen requirement, base excess in the first 12 hours of life, and presence of congenital abnormalities, and categorized as < 5, 5-10, or > 10 [with higher scores indicating high mortality and morbidity]),22 confirmed maternal-fetal infection, persistent patent ductus arteriosus, postnatal corticosteroid therapy, bronchodysplasia (defined as oxygen dependence at 36 weeks23), and breastfeeding at discharge. Furthermore, the results of cranial ultrasonographic examinations (1-3 per child) were grouped into 3 levels: infants with consistently normal examination results, those with subependymal hemorrhage or intraventricular hemorrhage (IVH) without intraparenchymal involvement (ie, grade I-II IVH), and those with grade III IVH, white matter abnormalities (persisting echodensities, ventricular dilatation, or unilateral or bilateral cystic periventricular leukomalacia), or intraparenchymal hemorrhage.2426

Cognitive development was assessed using the French version of the Kaufman Assessment Battery for Children,27 which gives a global intelligence scale (equivalent to IQ).

The following parent-reported items were used to assess the children's learning difficulties at age 5 years: learning difficulties at school (numerous or none/few), language impairment (yes or no), and speech therapy (yes or no). Child behavior was assessed using the parent form of the Strengths and Difficulties Questionnaire28,29 (designed for children aged 4-16 years), which contains 25 items yielding 4 symptom scales (conduct, hyperactivity, emotion, and peer problems) combined into a total difficulties score. An additional domain, the prosocial scale, assesses social competence. The 90th percentiles in a large sample of British children from the general population have been defined as thresholds identifying high risk of psychological problems29 but are not validated for the French version. Therefore, we defined thresholds such that 10% of the children in the EPIPAGE control group (born at 39-40 weeks) were considered at high risk for having a psychological problem: conduct problem, score of 5 or greater; hyperactivity, score of 7 or greater; emotional symptoms, score of 5 or greater; peer problems, score of 4 or greater; total difficulties, score of 16 or greater; and prosocial behavior, score of 6 or less.

STATISTICAL ANALYSIS

For the children who completed all of the 16 items, the results of the Touwen examination were described and compared for each GA group using a trend analysis for proportions. The statistical analyses were weighted to take into account the differences in the proportions of children born at 32 weeks' GA who underwent follow-up in some regions. The Pearson χ² statistic was corrected for survey design.30

To determine the factors associated with MNDs in the group of very preterm children, 2 separate multivariate logistic regression analyses with the same reference group (equivalent to multinomial regression) were carried out: the first compared children with MND-1 with children without MND, and the second compared children with MND-2 with the same children without MND. We tested for interactions between the significant variables in the final model.

We also compared the characteristics of the children with missing items in the neurological examination with those of the children who completed all of the items for the variables that we found to be associated with MND.

The statistical analyses were performed using STATA statistical software version 9.31

In total, 2239 children underwent a pediatric examination. Their mean (SD) chronological age was 5.1 (0.2) years, with no difference according to GA at birth. Of these children, the Touwen examination was not applicable to 154 children with a severe disability (Table 1).

DESCRIPTION OF MND AT AGE 5 YEARS

Of the 367 children who did not complete the Touwen examination, 275 were born very preterm (18.2% of the children of similar GA to whom the examination was applicable), 47 were born at 33 to 34 weeks (19.4% of the children of similar GA to whom the examination was applicable), and 45 were born at 39 to 40 weeks (13.6% of the children of similar GA to whom the examination was applicable) (Table 1). There was no statistically significant difference in the proportions of unclassified children according to GA (P = .09).

In total, 1237 children born before 33 weeks, 195 children born at 33 to 34 weeks, and 287 children born at 39 to 40 weeks were included in the analysis. The characteristics of this sample according to GA are given in Table 2. Table 3 gives the results of the Touwen examination in terms of the frequencies of nonoptimal items, nonoptimal subsystems, and the neuromotor profile (MND status). Across all of the GA groups, the tests that the children failed the most were those assessing coordination and balance. In total, 41.4% (95% confidence interval [CI], 38.6%-44.2%) of children born very preterm (before 33 weeks) had MND-1 and 3.0% (95% CI, 2.1%-4.1%) had MND-2. These proportions were 30.8% (95% CI, 24.4%-37.8%) and 0.5% (95% CI, 0.01%-2.8%), respectively, for children born at 33 to 34 weeks and 22.0% (95% CI, 17.3%-27.2%) and 0.7% (95% CI, 0.1%-2.5%), respectively, for children born at 39 to 40 weeks. Among the children with MND-1, the proportion of children with 2 suboptimal subsystems decreased with increasing GA (from 37.6% [35 of 93 children] for the children born before 28 weeks to 14.3% [9 of 63 children] for the children born at 39-40 weeks).

Table Graphic Jump LocationTable 2. Comparison of the Characteristics Between Gestational Age Groups
Table Graphic Jump LocationTable 3. Frequencies of Nonoptimal Performance of Items and Subsystems of the Touwen Examination According to Gestational Age
ASSOCIATION BETWEEN MND AND LEARNING OR BEHAVIORAL DIFFICULTIES AT AGE 5 YEARS IN CHILDREN BORN VERY PRETERM

Whatever their GA at birth, all of the children went to school at age 5 years. Table 4 shows that MNDs were associated with cognitive development (psychologist's assessment), learning difficulties at school, and behavioral problems (parent-reported) in the very preterm group. After adjusting for maternal sociodemographic characteristics, the presence of MND was found to be independently associated with cognitive impairment (odds ratio [OR], 2.1; 95% CI, 1.4-3.3), learning difficulties (OR, 1.6; 95% CI, 1.1-2.2), and behavioral problems (total difficulties score: OR, 1.4; 95% CI, 1.02-1.9; and emotional problems: OR, 1.4; 95% CI, 1.1-1.9).

Table Graphic Jump LocationTable 4. Relationship Between Learning and Behavioral Difficulties, IQ, and Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm
FACTORS ASSOCIATED WITH MND AT AGE 5 YEARS IN CHILDREN BORN VERY PRETERM

We determined which of the maternal sociodemographic or neonatal factors were associated with MND in the very preterm group. None of the mothers' social and demographic characteristics (as recorded at birth) were found to be significantly associated with MND-1 or MND-2. Table 5 and Table 6 show the univariate analyses and the final multivariate models that explain the relationships between neonatal factors and the presence of MND-1 and MND-2. Postnatal corticotherapy was independently associated with an increased risk of MND-1 at age 5 years. On the contrary, children from multiple births and breastfed children had a decreased risk of MND-1. In this model, a significant interaction between breastfeeding and multiple births was found. In singletons, breastfeeding was significantly associated with a decreased risk of MND-1 (OR, 0.8; 95% CI, 0.6-0.99), whereas this effect was not significant in children from multiple births (P = .59). However, in all of the children, postnatal corticotherapy doubled the risk of MND-1 (even after adjusting for bronchodysplasia).

Table Graphic Jump LocationTable 5. Neonatal Characteristics Associated With Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm, With Multivariate Analysis Comparing Mild vs No Minor Neuromotor Dysfunction
Table Graphic Jump LocationTable 6. Neonatal Characteristics Associated With Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm, With Multivariate Analysis Comparing Moderate vs No Minor Neuromotor Dysfunction

Concerning the risk of MND-2 in the very preterm population, the adjusted analysis of neonatal characteristics showed that being a boy, having had acute fetal distress, having had grade III IVH, white matter abnormalities, or intraparenchymal hemorrhage (on early cranial ultrasonography), and having had postnatal corticotherapy were independent risk factors.

CHARACTERISTICS OF VERY PRETERM CHILDREN UNCLASSIFIED FOLLOWING THE TOUWEN EXAMINATION

The comparison of the group of unclassified very preterm children who did not complete the Touwen examination with the group of classified children who did complete it showed that 4 of the tested characteristics were significantly more frequent in the unclassified group: being from multiple births (36.7% vs 29.9%, respectively; P = .03), associated intellectual impairment (14.9% vs 9.1%, respectively; P = .008), learning difficulties (19.7% vs 14.7%, respectively; P = .05), and behavioral problems (as measured by the Strengths and Difficulties Questionnaire) (26.0% vs 19.3%, respectively; P = .02).

SUMMARY OF MAIN FINDINGS

Our study shows that almost half (44.4%) of the children born very preterm and significant proportions of children born at 33 to 34 weeks (31.3%) and 39 to 40 weeks (22.6%) have mild MND at age 5 years. Furthermore, as GA decreases, the proportion of children classified as having MND-1 with 2 suboptimal subsystems increases. Moderate MNDs are much less frequent (3.0% of children born before 33 weeks).

In the very preterm group, parents of children with MND more frequently report behavioral and learning difficulties than parents of children with no neuromotor problems.

The multivariate model for these children shows that postnatal corticotherapy doubles the risk of MND-1 at age 5 years, whereas children from multiple births and children breastfed at discharge have a decreased risk. The independent risk factors for MND-2 are being a boy, having had acute fetal distress, having had severe abnormalities on cerebral ultrasonography, and having had postnatal corticotherapy.

STRENGTHS AND WEAKNESSES OF THE STUDY

The population of the EPIPAGE study was defined on a geographical basis, thus avoiding potential recruitment bias. Another strength of this study was that it included 2 control groups of different GAs. Previous studies have shown that GA is a better predictor of mortality and morbidity than birth weight,32 as recruitment based on birth weight leads to overrepresentation of more-mature children with restricted growth.33 All of the 3 groups and not just the very preterm children were followed up until age 5 years.

At this age, 69.6% of the children who were followed up were examined by a pediatrician. Among the children to whom the Touwen examination was applicable, 17.6% did not perform all of the tests. The circumstances of the examination (distance from home, succession of medical examinations, or unfamiliar environment) may partly explain some children's lack of cooperation. However, refusal to cooperate may also reflect a disability in 1 or several aspects of development. In our study, children who were unclassified following the Touwen examination more often had associated intellectual impairments, learning difficulties at school, and behavioral problems than the classified children. Therefore, it is likely that the true prevalence of MND is underestimated. Wocadlo and Rieger34 found that, compared with cooperative children of a similar GA, a greater proportion of the prematurely born children who refused to cooperate for an examination at age 3 years had minor motor and cognitive difficulties at age 5 years. Another study35 also showed that children monitored with difficulty are more likely to have severe neuromotor disability than those monitored without difficulty.

COMPARISON WITH OTHER STUDIES

Our results confirmed that MNDs are more frequent in very premature children than in children born at term and showed an increased risk with decreasing GA as previously described.3638 The frequencies found for children born at 33 to 34 and 39 to 40 weeks are close to those published by Hadders-Algra et al36 using the original version of the Touwen examination. The relatively high proportion of MND-1 among children born at 39 to 40 weeks (more than 1 in 5 children) could partly be due to the high sensitivity of the Touwen classification, which is mainly designed for descriptive purposes.14 However, because this examination has prognostic significance,16 the children classified as having MND-1 are more likely to have later difficulties than the others. The examination results must obviously be interpreted according to the type and extent of nonoptimal signs and with the child's full history. It should be noted that only 3.2% of the children born at 39 to 40 weeks had at least 2 dysfunctional subsystems. In a study of children born in 1992 and 1993,20 the proportions of MNDs at age 5 years in premature children were lower than the frequencies found in our study. A possible explanation might be that the former study was hospital-based; therefore, the children included may have benefited from closer health surveillance.

The neonatal parameters associated with the existence of MND-2 at age 5 years were mostly the same as the known risk factors for cerebral palsy and could justify the term cerebral palsy a minima sometimes used to describe moderate MND. As has been reported for cerebral palsy,1,3942 we found that being a boy and having had postnatal corticotherapy were significantly associated with MND-2. The factors most significantly associated with MND-2 were acute fetal distress and ultrasonographic examination results showing grade III or IV IVH or white matter abnormalities. A study by Jongmans et al13 confirmed that there exists an association between neonatal cerebral lesions visible using cranial ultrasonography and having MND at age 6 years. Kutschera et al43 have shown that transient periventricular echodensities in very low-birth-weight infants seem to lead to MND in children without major neurological impairment.

Our results show a significantly lower risk of mild MND for children from multiple births than for singletons. Twins are generally considered to be at higher risk than singletons in terms of mortality and morbidity. However, this is mostly due to differences in weight and GA, and the excess risk usually disappears after adjusting for these 2 factors. Few long-term studies on multiple births separately consider children born prematurely. A recent study44 compared a cohort of 6- to 12-year-old twins born between 27 and 36 weeks with a control group of singletons of the same age and born at the same GA and found that the twins had a higher risk of minimal brain dysfunction. In another study45 of 2-year-old children born before 31 weeks' GA, no significant difference in the incidence of death or severe disability was observed between twins and singletons. However, 2 studies observed as we did that twins were less severely affected than singletons. Bonellie et al46 found that the prevalence of cerebral palsy was lower for twins born at 28 to 31 weeks than for singletons of the same GA. Draper et al47 studied survival in children born prematurely according to different age groups and weight at birth and found that infants from multiple births had a greater chance of survival. These differences may be explained by the higher rate of pathological maternal complications during pregnancy leading to premature birth in single pregnancies compared with multiple pregnancies.48 Also, the frequency of incomplete Touwen examinations in our study was higher in multiple births than in singletons, and these children had similar 5-year characteristics as the children with MND. This potential selection bias could be partly responsible for the relationship between multiple births and lack of MND.

Beneficial effects of breast milk on cognitive skills, behavior, and neuromotor development in very preterm children have been widely demonstrated,4951 even though some studies found no effect on neurodevelopmental outcomes.52 It has been postulated that the act of feeding at the breast as well as the interaction between mother and child account for more optimal outcomes.53 In our study, breastfeeding was significantly associated with a decreased risk of MND only for singletons. However, a weakness of our study was that the only information we had was breastfeeding at discharge from the neonatal unit without any information on the duration of breastfeeding. Consistent with previous studies,54 our findings showed that breastfeeding was significantly less frequent in twins (17.3%) than in singletons (24.7%) (P = .002). It is also likely that the duration of breastfeeding was shorter for multiple births.

The association between MND at age 5 years and parent-reported learning and behavioral difficulties at the same age was particularly strong in this population and even more so for moderate MND. These results are in agreement with previous studies. Children with mild motor delay have lower academic achievement scores at age 8 years.55 Batstra et al56 reported that 5- to 11-year-old children with MND had poorer school results than others. Behavioral problems at school, especially signs of attention deficit, were also reported in children born prematurely. These children usually are more socially isolated, have less concentration, and are more hyperactive compared with children born at term, and this effect seemed to be mediated by intellectual and neuromotor delays in this population.57

IMPLICATIONS FOR PRACTICE AND RESEARCH

Our results show the importance of a close assessment of all children born preterm, whatever their GA. The neuromotor dysfunctions should be tracked through a detailed and systematic examination that requires training58 but can be performed in general practice. Owing to their consequences on school learning, it is important to detect these MNDs through screening before school age to offer adapted early intervention. Research should be carried out to identify the type of interventions needed and to assess their efficiency. Furthermore, the relatively high frequency of MND-1 in children born at term requires further investigation.

Birth characteristics, minor abnormalities on neonatal ultrasonography of the brain, and motor milestones have only limited value in the early detection of neuromotor dysfunctions.59 It is necessary to investigate whether other early factors could be predictive of dysfunctional neuromotor and behavioral development at school age. Furthermore, it is essential to regularly set up new cohorts as screening methods and health practices are constantly changing.

Correspondence: Catherine Arnaud, MD, Institut National de la Santé et de la Recherche Médicale Unit 558, Faculté de Médecine, 37 allées Jules Guesde, 31073 Toulouse CEDEX, France (carnaud@cict.fr).

Accepted for Publication: May 2, 2007.

Author Contributions: Dr Arnaud had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Arnaud, Grandjean, and Kaminski. Acquisition of data: Pierrat, Larroque, Alberge, Marret, Burguet, Ancel, and Supernant. Analysis and interpretation of data: Arnaud, Daubisse-Marliac, White-Koning, Pierrat, Larroque, Grandjean, and Kaminski. Drafting of the manuscript: Arnaud, Daubisse-Marliac, and White-Koning. Critical revision of the manuscript for important intellectual content: Pierrat, Larroque, Grandjean, Alberge, Marret, Burguet, Ancel, Supernant, and Kaminski. Statistical analysis: Arnaud, Daubisse-Marliac, and White-Koning. Obtained funding: Larroque, Marret, Ancel, and Kaminski. Administrative, technical, and material support: Larroque and Supernant. Study supervision: Grandjean and Kaminski.

EPIPAGE Study Group: Béatrice Larroque, MD, PhD, Pierre-Yves Ancel, MD, PhD, Béatrice Blondel, PhD, Gérard Bréart, MD, PhD, Michel Dehan, MD, PhD, Micheline Garel, MsC, Monique Kaminski, MsC, Françoise Maillard, DUT, Christiane du Mazaubrun, MsC, Pascale Missy, PhD, Fadila Sehili, MD, Karine Supernant, DUT, Institut National de la Santé et de la Recherche Médicale Unit 149, Paris, France; Myriam Durant, DUT, Jacqueline Matis, MD, Jean Messer, MD, Alain Treisser, MD, Hautepierre Hospital, Strasbourg, France; Antoine Burguet, MD, PhD, Laurence Abraham-Lerat, DUT, Alain Menget, MD, Gérard Thiriez, MD, St. Jacques Hospital, Besançon, France; Catherine Lévêque, DUT, Stéphane Marret, MD, PhD, Loic Marpeau, MD, PhD, Charles Nicolle Hospital, Rouen, France; Pierre Boulot, MD, PhD, Jean-Charles Picaud, MD, Arnaud de Villeneuve Hospital, Montpellier, France; Anne-Marie Donadio, DUT, Bernard Ledésert, MD, PhD, Observatoire Régional de la Santé, Montpellier; Monique André, MD, Jean-Louis Boutroy, MD, Jeanne Fresson, MD, PhD, Jean-Marie Hascoët, MD, Maternity Hospital, Nancy, France; Catherine Arnaud, MD, Sylvie Bourdet-Loubère, PhD, Hélène Grandjean, MD, PhD, Institut National de la Santé et de la Recherche Médicale Unit 558, Paul Sabatier University, Toulouse, France; Michel Rolland, MD, PhD, Alain Fournié, MD, PhD, Children and Maternity Hospital, Toulouse; Catherine Leignel, DUT, Pierre Lequien, MD, PhD, Véronique Pierrat, MD, PhD, Francis Puech, MD, PhD, Damien Subtil, MD, PhD, Patrick Truffert, MD, PhD, Jeanne de Flandre Hospital, Lille, France; Georges Boog, MD, PhD, Valérie Rouger-Bureau, DUT, Jean-Christophe Rozé, MD, PhD, Maternity and Children Hospital, Nantes, France; Michel Dehan, MD, Véronique Zupan, MD, Antoine Béclère Hospital, Clamart, France; Michel Vodovar, MD, Marcel Voyer, MD, Institut de Puériculture, Paris.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grants from Institut National de la Santé et de la Recherche Médicale (French National Institute of Health and Medical Research), Merck-Sharp, Dohme-Chibret, Medical Research Foundation, Directorate General for Health of the French Ministry for Social Affairs, and the French Hospital Program of Clinical Research, Paris, France.

Role of the Sponsors: The sponsors of the study had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Previous Presentation: This study was presented in part at the XX European Congress of Perinatal Medicine; May 26, 2006; Prague, Czech Republic.

Hack  MFanaroff  AA Outcomes of children of extremely low birthweight and gestational age in the 1990s. Semin Neonatol 2000;5 (2) 89- 106
PubMed Link to Article
Colvin  MMcGuire  WFowlie  PW Neurodevelopmental outcomes after preterm birth. BMJ 2004;329 (7479) 1390- 1393
PubMed Link to Article
Vincer  MJAllen  ACJoseph  KSStinson  DAScott  HWood  E Increasing prevalence of cerebral palsy among very preterm infants: a population-based study. Pediatrics 2006;118 (6) e1621- e1626
PubMed Link to Article
Bhutta  ATCleves  MACasey  PHCradock  MMAnand  KJ Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288 (6) 728- 737
PubMed Link to Article
Wood  NSMarlow  NCosteloe  KGibson  ATWilkinson  AREPICure Study Group, Neurologic and developmental disability after extremely preterm birth. N Engl J Med 2000;343 (6) 378- 384
PubMed Link to Article
Doyle  LWAnderson  PJ Improved neurosensory outcome at 8 years of age of extremely low birthweight children born in Victoria over three distinct eras. Arch Dis Child Fetal Neonatal Ed 2005;90 (6) F484- F488
PubMed Link to Article
Anderson  PDoyle  LW Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA 2003;289 (24) 3264- 3272
PubMed Link to Article
Hille  ETden Ouden  ALSaigal  S  et al.  Behavioural problems in children who weigh 1000 g or less at birth in four countries. Lancet 2001;357 (9269) 1641- 1643
PubMed Link to Article
Mikkola  KRitari  NTommiska  V  et al.  Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997. Pediatrics 2005;116 (6) 1391- 1400
PubMed Link to Article
Hadders-Algra  MHuisjes  HJTouwen  BC Perinatal correlates of major and minor neurological dysfunction at school age: a multivariate analysis. Dev Med Child Neurol 1988;30 (4) 472- 481
PubMed Link to Article
Marlow  NRoberts  LCooke  R Outcome at 8 years for children with birth weights of 1250 g or less. Arch Dis Child 1993;68 (3, spec No.) 286- 290
PubMed Link to Article
Hille  ETden Ouden  ALBauer  Lvan den Oudenrijn  CBrand  RVerloove-Vanhorick  SPCollaborative Project on Preterm and Small for Gestational Age (POPS) Infants in The Netherlands, School performance at nine years of age in very premature and very low birth weight infants: perinatal risk factors and predictors at five years of age. J Pediatr 1994;125 (3) 426- 434
PubMed Link to Article
Jongmans  MMercuri  Ede Vries  LDubowitz  LHenderson  SE Minor neurological signs and perceptual-motor difficulties in prematurely born children. Arch Dis Child Fetal Neonatal Ed 1997;76 (1) F9- F14
PubMed Link to Article
Touwen  BC Examination of the Child With Minor Neurological Dysfunction.  Philadelphia, PA JB Lippincott & Co1979;
Groen  SEde Blecourt  ACPostema  KHadders-Algra  M General movements in early infancy predict neuromotor development at 9 to 12 years of age. Dev Med Child Neurol 2005;47 (11) 731- 738
PubMed Link to Article
Hadders-Algra  M The neuromotor examination of the preschool child and its prognostic significance. Ment Retard Dev Disabil Res Rev 2005;11 (3) 180- 188
PubMed Link to Article
Hadders-Algra  MGroothuis  AM Quality of general movements in infancy is related to neurological dysfunction, ADHD, and aggressive behaviour. Dev Med Child Neurol 1999;41 (6) 381- 391
PubMed Link to Article
Breslau  NChilcoat  HDJohnson  EOAndreski  PLucia  VC Neurologic soft signs and low birthweight: their association and neuropsychiatric implications. Biol Psychiatry 2000;47 (1) 71- 79
PubMed Link to Article
Larroque  BBreart  GKaminski  M  et al. Epipage Study Group, Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed 2004;89 (2) F139- F144
PubMed Link to Article
Fily  ATruffert  PEgo  ADepoortere  MHHaquin  CPierrat  V Neurological assessment at five years of age in infants born preterm. Acta Paediatr 2003;92 (12) 1433- 1437
PubMed Link to Article
Kakebeeke  THJongmans  MJDubowitz  LMSchoemaker  MMHenderson  SE Some aspects of the reliability of Touwen's examination of the child with minor neurological dysfunction. Dev Med Child Neurol 1993;35 (12) 1097- 1105
PubMed Link to Article
International Neonatal Network, The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993;342 (8865) 193- 198[published correction appears in Lancet. 1993;342(8871):626].
PubMed Link to Article
Bancalari  EClaure  NSosenko  IR Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol 2003;8 (1) 63- 71
PubMed Link to Article
Volpe  JJ Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol 1998;5 (3) 135- 151
PubMed Link to Article
Kuban  KC White-matter disease of prematurity, periventricular leukomalacia, and ischemic lesions. Dev Med Child Neurol 1998;40 (8) 571- 573
PubMed Link to Article
Paneth  N Classifying brain damage in preterm infants. J Pediatr 1999;134 (5) 527- 529
PubMed Link to Article
Kaufman  AKaufman  N K ABC Batterie pour l'examen psychologique de l'enfant.  Paris, France Editions du Centre de Psychologie Appliqué e1993;
Goodman  R The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 1997;38 (5) 581- 586
PubMed Link to Article
Goodman  R Psychometric properties of the strengths and difficulties questionnaire. J Am Acad Child Adolesc Psychiatry 2001;40 (11) 1337- 1345
PubMed Link to Article
Rao  JScott  A On chi-squared tests for multiway contingency tables with cell proportions estimated from survey data. Ann Stat 1984;12 (1) 46- 60
Link to Article
 Intercooled STATA [computer program].  Version 9.0. College Station, TX Stata Corp1999;
Tin  WWariyar  UHey  ENorthern Neonatal Network, Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. BMJ 1997;314 (7074) 107- 111
PubMed Link to Article
Arnold  CCKramer  MSHobbs  CAMcLean  FHUsher  RH Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates. Am J Epidemiol 1991;134 (6) 604- 613
PubMed
Wocadlo  CRieger  I Very preterm children who do not cooperate with assessments at three years of age: skill differences at five years. J Dev Behav Pediatr 2000;21 (2) 107- 113
PubMed Link to Article
Tin  WFritz  SWariyar  UHey  E Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty. Arch Dis Child Fetal Neonatal Ed 1998;79 (2) F83- F87
PubMed Link to Article
Hadders-Algra  MHuisjes  HJTouwen  BC Preterm or small-for-gestational-age infants: neurological and behavioural development at the age of 6 years. Eur J Pediatr 1988;147 (5) 460- 467
PubMed Link to Article
Forslund  MBjerre  I Follow-up of preterm children, I: neurological assessment at 4 years of age. Early Hum Dev 1989;20 (1) 45- 66
PubMed Link to Article
Soorani-Lunsing  RJHadders-Algra  MHuisjes  HJTouwen  BC Minor neurological dysfunction after the onset of puberty: association with perinatal events. Early Hum Dev 1993;33 (1) 71- 80
PubMed Link to Article
O'Shea  TMDoyle  LW Perinatal glucocorticoid therapy and neurodevelopmental outcome: an epidemiologic perspective. Semin Neonatol 2001;6 (4) 293- 307
PubMed Link to Article
Felderhoff-Mueser  UBuhrer  C Clinical measures to preserve cerebral integrity in preterm infants. Early Hum Dev 2005;81 (3) 237- 244
PubMed Link to Article
Stoelhorst  GMRijken  MMartens  SE  et al.  Developmental outcome at 18 and 24 months of age in very preterm children: a cohort study from 1996 to 1997. Early Hum Dev 2003;72 (2) 83- 95
PubMed Link to Article
Wood  NSCosteloe  KGibson  ATHennessy  EMMarlow  NWilkinson  AR The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth. Arch Dis Child Fetal Neonatal Ed 2005;90 (2) F134- F140
PubMed Link to Article
Kutschera  JTomaselli  JMaurer  UPichler  GSchwantzer  GUrlesberger  B Minor neurological dysfunction, cognitive development and somatic development at the age of 3 to 11 years in very-low-birthweight infants with transient periventricular echodensities. Acta Paediatr 2006;95 (12) 1577- 1581
PubMed Link to Article
Iannone  GTripaldi  CChindemi  A  et al.  Long-term neuropsychological outcome in preterm twins. ScientificWorldJournal 2006;6899- 907
PubMed Link to Article
Asztalos  EBarrett  JFLacy  MLuther  M Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience. Twin Res 2001;4 (6) 431- 438
PubMed Link to Article
Bonellie  SRCurrie  DChalmers  J Comparison of risk factors for cerebral palsy in twins and singletons. Dev Med Child Neurol 2005;47 (9) 587- 591
PubMed Link to Article
Draper  ESManktelow  BField  DJJames  D Prediction of survival for preterm births by weight and gestational age: retrospective population based study. BMJ 1999;319 (7217) 1093- 1097
PubMed Link to Article
Mizrahi  MFurman  BShoham-Vardi  IVardi  HMaymon  EMazor  M Perinatal outcome and peripartum complications in preterm singleton and twins deliveries: a comparative study. Eur J Obstet Gynecol Reprod Biol 1999;87 (1) 55- 61
PubMed Link to Article
Pinelli  JSaigal  SAtkinson  SA Effect of breastmilk consumption on neurodevelopmental outcomes at 6 and 12 months of age in VLBW infants. Adv Neonatal Care 2003;3 (2) 76- 87
PubMed Link to Article
Vohr  BRPoindexter  BBDusick  AM  et al.  Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics 2006;118 (1) e115- e123
PubMed Link to Article
Callen  JPinelli  J A review of the literature examining the benefits and challenges, incidence and duration, and barriers to breastfeeding in preterm infants. Adv Neonatal Care 2005;5 (2) 72- 92
PubMed Link to Article
Furman  LWilson-Costello  DFriedman  HTaylor  HGMinich  NHack  M The effect of neonatal maternal milk feeding on the neurodevelopmental outcome of very low birth weight infants. J Dev Behav Pediatr 2004;25 (4) 247- 253
PubMed Link to Article
Britton  JRBritton  HLGronwaldt  V Breastfeeding, sensitivity, and attachment. Pediatrics 2006;118 (5) e1436- e1443
PubMed Link to Article
Yokoyama  YWada  SSugimoto  MKatayama  MSaito  MSono  J Breastfeeding rates among singletons, twins and triplets in Japan: a population-based study. Twin Res Hum Genet 2006;9 (2) 298- 302
PubMed Link to Article
Sullivan  MCMargaret  MM Perinatal morbidity, mild motor delay, and later school outcomes. Dev Med Child Neurol 2003;45 (2) 104- 112
PubMed Link to Article
Batstra  LNeeleman  JHadders-Algra  M The neurology of learning and behavioural problems in pre-adolescent children. Acta Psychiatr Scand 2003;108 (2) 92- 100
PubMed Link to Article
Nadeau  LBoivin  MTessier  RLefebvre  FRobaey  P Mediators of behavioral problems in 7-year-old children born after 24 to 28 weeks of gestation. J Dev Behav Pediatr 2001;22 (1) 1- 10
PubMed Link to Article
De Kleine  MJNijhuis-Van Der Sanden  MWLya Den Ouden  A Is paediatric assessment of motor development of very preterm and low-birthweight children appropriate? Acta Paediatr 2006;95 (10) 1202- 1208
PubMed Link to Article
Fallang  BOien  IHellem  ESaugstad  ODHadders-Algra  M Quality of reaching and postural control in young preterm infants is related to neuromotor outcome at 6 years. Pediatr Res 2005;58 (2) 347- 353
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 2. Comparison of the Characteristics Between Gestational Age Groups
Table Graphic Jump LocationTable 3. Frequencies of Nonoptimal Performance of Items and Subsystems of the Touwen Examination According to Gestational Age
Table Graphic Jump LocationTable 4. Relationship Between Learning and Behavioral Difficulties, IQ, and Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm
Table Graphic Jump LocationTable 5. Neonatal Characteristics Associated With Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm, With Multivariate Analysis Comparing Mild vs No Minor Neuromotor Dysfunction
Table Graphic Jump LocationTable 6. Neonatal Characteristics Associated With Minor Neuromotor Dysfunction in 5-Year-Old Children Born Very Preterm, With Multivariate Analysis Comparing Moderate vs No Minor Neuromotor Dysfunction

References

Hack  MFanaroff  AA Outcomes of children of extremely low birthweight and gestational age in the 1990s. Semin Neonatol 2000;5 (2) 89- 106
PubMed Link to Article
Colvin  MMcGuire  WFowlie  PW Neurodevelopmental outcomes after preterm birth. BMJ 2004;329 (7479) 1390- 1393
PubMed Link to Article
Vincer  MJAllen  ACJoseph  KSStinson  DAScott  HWood  E Increasing prevalence of cerebral palsy among very preterm infants: a population-based study. Pediatrics 2006;118 (6) e1621- e1626
PubMed Link to Article
Bhutta  ATCleves  MACasey  PHCradock  MMAnand  KJ Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288 (6) 728- 737
PubMed Link to Article
Wood  NSMarlow  NCosteloe  KGibson  ATWilkinson  AREPICure Study Group, Neurologic and developmental disability after extremely preterm birth. N Engl J Med 2000;343 (6) 378- 384
PubMed Link to Article
Doyle  LWAnderson  PJ Improved neurosensory outcome at 8 years of age of extremely low birthweight children born in Victoria over three distinct eras. Arch Dis Child Fetal Neonatal Ed 2005;90 (6) F484- F488
PubMed Link to Article
Anderson  PDoyle  LW Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA 2003;289 (24) 3264- 3272
PubMed Link to Article
Hille  ETden Ouden  ALSaigal  S  et al.  Behavioural problems in children who weigh 1000 g or less at birth in four countries. Lancet 2001;357 (9269) 1641- 1643
PubMed Link to Article
Mikkola  KRitari  NTommiska  V  et al.  Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997. Pediatrics 2005;116 (6) 1391- 1400
PubMed Link to Article
Hadders-Algra  MHuisjes  HJTouwen  BC Perinatal correlates of major and minor neurological dysfunction at school age: a multivariate analysis. Dev Med Child Neurol 1988;30 (4) 472- 481
PubMed Link to Article
Marlow  NRoberts  LCooke  R Outcome at 8 years for children with birth weights of 1250 g or less. Arch Dis Child 1993;68 (3, spec No.) 286- 290
PubMed Link to Article
Hille  ETden Ouden  ALBauer  Lvan den Oudenrijn  CBrand  RVerloove-Vanhorick  SPCollaborative Project on Preterm and Small for Gestational Age (POPS) Infants in The Netherlands, School performance at nine years of age in very premature and very low birth weight infants: perinatal risk factors and predictors at five years of age. J Pediatr 1994;125 (3) 426- 434
PubMed Link to Article
Jongmans  MMercuri  Ede Vries  LDubowitz  LHenderson  SE Minor neurological signs and perceptual-motor difficulties in prematurely born children. Arch Dis Child Fetal Neonatal Ed 1997;76 (1) F9- F14
PubMed Link to Article
Touwen  BC Examination of the Child With Minor Neurological Dysfunction.  Philadelphia, PA JB Lippincott & Co1979;
Groen  SEde Blecourt  ACPostema  KHadders-Algra  M General movements in early infancy predict neuromotor development at 9 to 12 years of age. Dev Med Child Neurol 2005;47 (11) 731- 738
PubMed Link to Article
Hadders-Algra  M The neuromotor examination of the preschool child and its prognostic significance. Ment Retard Dev Disabil Res Rev 2005;11 (3) 180- 188
PubMed Link to Article
Hadders-Algra  MGroothuis  AM Quality of general movements in infancy is related to neurological dysfunction, ADHD, and aggressive behaviour. Dev Med Child Neurol 1999;41 (6) 381- 391
PubMed Link to Article
Breslau  NChilcoat  HDJohnson  EOAndreski  PLucia  VC Neurologic soft signs and low birthweight: their association and neuropsychiatric implications. Biol Psychiatry 2000;47 (1) 71- 79
PubMed Link to Article
Larroque  BBreart  GKaminski  M  et al. Epipage Study Group, Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed 2004;89 (2) F139- F144
PubMed Link to Article
Fily  ATruffert  PEgo  ADepoortere  MHHaquin  CPierrat  V Neurological assessment at five years of age in infants born preterm. Acta Paediatr 2003;92 (12) 1433- 1437
PubMed Link to Article
Kakebeeke  THJongmans  MJDubowitz  LMSchoemaker  MMHenderson  SE Some aspects of the reliability of Touwen's examination of the child with minor neurological dysfunction. Dev Med Child Neurol 1993;35 (12) 1097- 1105
PubMed Link to Article
International Neonatal Network, The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993;342 (8865) 193- 198[published correction appears in Lancet. 1993;342(8871):626].
PubMed Link to Article
Bancalari  EClaure  NSosenko  IR Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol 2003;8 (1) 63- 71
PubMed Link to Article
Volpe  JJ Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol 1998;5 (3) 135- 151
PubMed Link to Article
Kuban  KC White-matter disease of prematurity, periventricular leukomalacia, and ischemic lesions. Dev Med Child Neurol 1998;40 (8) 571- 573
PubMed Link to Article
Paneth  N Classifying brain damage in preterm infants. J Pediatr 1999;134 (5) 527- 529
PubMed Link to Article
Kaufman  AKaufman  N K ABC Batterie pour l'examen psychologique de l'enfant.  Paris, France Editions du Centre de Psychologie Appliqué e1993;
Goodman  R The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry 1997;38 (5) 581- 586
PubMed Link to Article
Goodman  R Psychometric properties of the strengths and difficulties questionnaire. J Am Acad Child Adolesc Psychiatry 2001;40 (11) 1337- 1345
PubMed Link to Article
Rao  JScott  A On chi-squared tests for multiway contingency tables with cell proportions estimated from survey data. Ann Stat 1984;12 (1) 46- 60
Link to Article
 Intercooled STATA [computer program].  Version 9.0. College Station, TX Stata Corp1999;
Tin  WWariyar  UHey  ENorthern Neonatal Network, Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. BMJ 1997;314 (7074) 107- 111
PubMed Link to Article
Arnold  CCKramer  MSHobbs  CAMcLean  FHUsher  RH Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates. Am J Epidemiol 1991;134 (6) 604- 613
PubMed
Wocadlo  CRieger  I Very preterm children who do not cooperate with assessments at three years of age: skill differences at five years. J Dev Behav Pediatr 2000;21 (2) 107- 113
PubMed Link to Article
Tin  WFritz  SWariyar  UHey  E Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty. Arch Dis Child Fetal Neonatal Ed 1998;79 (2) F83- F87
PubMed Link to Article
Hadders-Algra  MHuisjes  HJTouwen  BC Preterm or small-for-gestational-age infants: neurological and behavioural development at the age of 6 years. Eur J Pediatr 1988;147 (5) 460- 467
PubMed Link to Article
Forslund  MBjerre  I Follow-up of preterm children, I: neurological assessment at 4 years of age. Early Hum Dev 1989;20 (1) 45- 66
PubMed Link to Article
Soorani-Lunsing  RJHadders-Algra  MHuisjes  HJTouwen  BC Minor neurological dysfunction after the onset of puberty: association with perinatal events. Early Hum Dev 1993;33 (1) 71- 80
PubMed Link to Article
O'Shea  TMDoyle  LW Perinatal glucocorticoid therapy and neurodevelopmental outcome: an epidemiologic perspective. Semin Neonatol 2001;6 (4) 293- 307
PubMed Link to Article
Felderhoff-Mueser  UBuhrer  C Clinical measures to preserve cerebral integrity in preterm infants. Early Hum Dev 2005;81 (3) 237- 244
PubMed Link to Article
Stoelhorst  GMRijken  MMartens  SE  et al.  Developmental outcome at 18 and 24 months of age in very preterm children: a cohort study from 1996 to 1997. Early Hum Dev 2003;72 (2) 83- 95
PubMed Link to Article
Wood  NSCosteloe  KGibson  ATHennessy  EMMarlow  NWilkinson  AR The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth. Arch Dis Child Fetal Neonatal Ed 2005;90 (2) F134- F140
PubMed Link to Article
Kutschera  JTomaselli  JMaurer  UPichler  GSchwantzer  GUrlesberger  B Minor neurological dysfunction, cognitive development and somatic development at the age of 3 to 11 years in very-low-birthweight infants with transient periventricular echodensities. Acta Paediatr 2006;95 (12) 1577- 1581
PubMed Link to Article
Iannone  GTripaldi  CChindemi  A  et al.  Long-term neuropsychological outcome in preterm twins. ScientificWorldJournal 2006;6899- 907
PubMed Link to Article
Asztalos  EBarrett  JFLacy  MLuther  M Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience. Twin Res 2001;4 (6) 431- 438
PubMed Link to Article
Bonellie  SRCurrie  DChalmers  J Comparison of risk factors for cerebral palsy in twins and singletons. Dev Med Child Neurol 2005;47 (9) 587- 591
PubMed Link to Article
Draper  ESManktelow  BField  DJJames  D Prediction of survival for preterm births by weight and gestational age: retrospective population based study. BMJ 1999;319 (7217) 1093- 1097
PubMed Link to Article
Mizrahi  MFurman  BShoham-Vardi  IVardi  HMaymon  EMazor  M Perinatal outcome and peripartum complications in preterm singleton and twins deliveries: a comparative study. Eur J Obstet Gynecol Reprod Biol 1999;87 (1) 55- 61
PubMed Link to Article
Pinelli  JSaigal  SAtkinson  SA Effect of breastmilk consumption on neurodevelopmental outcomes at 6 and 12 months of age in VLBW infants. Adv Neonatal Care 2003;3 (2) 76- 87
PubMed Link to Article
Vohr  BRPoindexter  BBDusick  AM  et al.  Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics 2006;118 (1) e115- e123
PubMed Link to Article
Callen  JPinelli  J A review of the literature examining the benefits and challenges, incidence and duration, and barriers to breastfeeding in preterm infants. Adv Neonatal Care 2005;5 (2) 72- 92
PubMed Link to Article
Furman  LWilson-Costello  DFriedman  HTaylor  HGMinich  NHack  M The effect of neonatal maternal milk feeding on the neurodevelopmental outcome of very low birth weight infants. J Dev Behav Pediatr 2004;25 (4) 247- 253
PubMed Link to Article
Britton  JRBritton  HLGronwaldt  V Breastfeeding, sensitivity, and attachment. Pediatrics 2006;118 (5) e1436- e1443
PubMed Link to Article
Yokoyama  YWada  SSugimoto  MKatayama  MSaito  MSono  J Breastfeeding rates among singletons, twins and triplets in Japan: a population-based study. Twin Res Hum Genet 2006;9 (2) 298- 302
PubMed Link to Article
Sullivan  MCMargaret  MM Perinatal morbidity, mild motor delay, and later school outcomes. Dev Med Child Neurol 2003;45 (2) 104- 112
PubMed Link to Article
Batstra  LNeeleman  JHadders-Algra  M The neurology of learning and behavioural problems in pre-adolescent children. Acta Psychiatr Scand 2003;108 (2) 92- 100
PubMed Link to Article
Nadeau  LBoivin  MTessier  RLefebvre  FRobaey  P Mediators of behavioral problems in 7-year-old children born after 24 to 28 weeks of gestation. J Dev Behav Pediatr 2001;22 (1) 1- 10
PubMed Link to Article
De Kleine  MJNijhuis-Van Der Sanden  MWLya Den Ouden  A Is paediatric assessment of motor development of very preterm and low-birthweight children appropriate? Acta Paediatr 2006;95 (10) 1202- 1208
PubMed Link to Article
Fallang  BOien  IHellem  ESaugstad  ODHadders-Algra  M Quality of reaching and postural control in young preterm infants is related to neuromotor outcome at 6 years. Pediatr Res 2005;58 (2) 347- 353
PubMed Link to Article

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