Published online November 1, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1452-e1465 (doi:10.1542/peds.2006-1069)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farooqi, A.
Right arrow Articles by Serenius, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farooqi, A.
Right arrow Articles by Serenius, F.
Related Collections
Right arrow Premature & Newborn
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

Growth in 10- to 12-Year-Old Children Born at 23 to 25 Weeks' Gestation in the 1990s: A Swedish National Prospective Follow-up Study

Aijaz Farooqi, MDa, Bruno Hägglöf, MD, PhDb, Gunnar Sedin, MD, PhDc, Leif Gothefors, MD, PhDa and Fredrik Serenius, MD, PhDa

a Department of Pediatrics, Institute of Clinical Sciences, University Hospital, Umeå, Sweden
b Department of Child and Adolescent Psychiatry, Institute of Clinical Sciences, University Hospital Umeå
c Department of Women's and Children's Health, Section for Pediatrics, Uppsala University, Uppsala, Sweden


   ABSTRACT
TOP
 ABSTRACT
POPULATION AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
BACKGROUND. Knowledge of long-term growth of extremely preterm infants in relation to gestational age is incomplete, and there are concerns regarding their poor growth in early childhood. As part of a longitudinal study of a national cohort of infants born at <26 weeks' gestation (extremely immature), growth development from birth to the age of 11 years was examined, and correlates of growth attainment were analyzed.

METHODS. Two hundred forty-seven extremely immature children were born alive from April 1990 through March 1992 in the whole of Sweden, and 89 (36%) survived. Growth and neurosensory outcomes of all extremely immature survivors were evaluated at 36 months of age. Eighty-six (97%) extremely immature children were identified and assessed at 11 years of age. In this growth study, 83 extremely immature infants (mean [SD]: birth weight, 772 g [110 g]; gestational age, 24.6 weeks [0.6 weeks]) without severe motor disability were followed up prospectively from birth to 11 years old and compared with a matched group of 83 children born at term. z scores for weight, height, head circumference, and BMI were computed for all children. We also examined gender-specific longitudinal growth measures. Predictors of 11-year growth were studied by multivariate analyses.

RESULTS. Extremely immature children were significantly smaller in all 3 growth parameters than the controls at 11 years. Extremely immature children showed a sharp decline in weight and height z scores up to 3 months' corrected age, followed by catch-up growth in both weight and height up to 11 years. In contrast to weight and height, extremely immature children did not exhibit catch-up growth in head circumference after the first 6 months of life. The mean BMI z scores increased significantly from 1 to 11 years in both groups. The mean BMI change between 1 and 11 years of age was significantly larger in extremely immature than in control participants. Extremely immature girls showed a faster weight increase than extremely immature boys, whereas catch-up growth in height and head circumference was similar in these groups. Multiple-regression analyses revealed that preterm birth and parental height were significant predictors of 11-year height, and group status (prematurity) correlated strongly with head circumference.

CONCLUSIONS. Children born at the limit of viability attain poor growth in early childhood, followed by catch-up growth to age 11 years, but remain smaller than their term-born peers. Strategies that improve early growth might improve the outcome.

Key Words: growth • extremely immature

Abbreviations: EI—extremely immature • VLBW—very low birth weight • ELBW—extremely low birth weight • CVD—cardiovascular disease • NSI—neurosensory impairment • HC—head circumference • EDD—expected date of delivery • SES—socioeconomic status • SGA—small for gestational age • CI—confidence interval • PNS—postnatal steroids

Advances in perinatology and neonatology in the1990s have led to a dramatic increase in the survival of extremely immature (EI; <26 weeks' gestation) infants born at the threshold of viability.1–3 Once the survival is more assured, the concern becomes focused on growth and development of these infants. Very low birth weight (VLBW; <1500 g) or extremely low birth weight (ELBW; <1000 g) children experience significant growth failure in their early childhood.4–8 Growth outcomes of adolescent ELBW children have recently begun to appear in the literature. All of these reports document compensatory catch-up in growth parameters up to adolescence.9–12 However, ELBW adolescents remained significantly shorter and lighter than their control peers in the majority of these studies. In most reports, growth outcomes are presented in relation to the birth weight rather than to gestational age. This raises a possibility of introducing bias, because more mature children with fetal growth restriction are included.13 Incomplete cohorts at later follow-up ages, discrepancies between reference populations, and definitions of growth failure make it difficult to interpret the results.

There are concerns that disturbances of growth in intrauterine and postnatal life of preterm infants may have long-term implications for their adult health. It has been hypothesized that adaptations made by the fetus or infant when undernourished induce alterations in metabolism and hormonal output, possibly increasing the risk for diabetes and cardiovascular disease (CVD) later in life.14 Furthermore, there is accumulating evidence of a risk for the development of CVD later in life in growth-restricted infants who exhibit an accelerated weight gain in childhood.15,16 With the exception of 1 population-based study from the United Kingdom,17 information is lacking on growth outcomes of extremely premature infants born in the 1990s. As part of a longitudinal follow-up study in a national Swedish cohort of EI children (born at <26 weeks' gestation), we examined the growth development from birth to the age of 11 years and analyzed correlates of growth attainment at 11 years.


   POPULATION AND METHODS
TOP
 ABSTRACT
 POPULATION AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The study participants comprised survivors of a national cohort of 247 consecutive live-born EI (<26 weeks' gestation) infants who were born during April 1990 through March 1992 in the whole of Sweden. Of these 247 EI infants, 89 (36%) survived in the neonatal period, and all were alive at the time of this study (mean age: 11 years). All of the 89 EI survivors were assessed in their neonatal period and at 36 months' corrected age when they were enrolled in the "1000-g" national Swedish cohort.18,19 The identification of EI subjects at the present assessment, recruitment of control participants, and other methodologic details have been described elsewhere20 and will be briefly repeated here. Of the 89 EI children, 3 were not assessed (2 refused, 1 was abroad). Thus, 86 EI children (97% of all survivors) were followed up to a mean age of 11 years. Three children with severe motor disability were excluded from this study, which thus comprised 83 children (94% of all survivors). Another 3 were on growth hormone treatment and were included in the study only until the start of that treatment (at 4 years 10 months, 3 years 8 months, and 4 years 9 months). Thus, 83 (94% of all survivors) EI children were assessed up to 4 years of age, and 80 (90%) were assessed from age 4 up to 11 years.

The control participants in our assessment (mean age: 11 years) were recruited by selecting from the national birth register a healthy term child with normal birth weight born at the same hospital, of the same gender, and nearest in birth date (±7 days) to the EI child. Three controls were initially selected for every EI child. Because we aimed to have 1 control for every index child, we initially contacted the first of the control families. If the family did not respond or refused to participate, we then approached the second family and, if necessary, the third. Neurosensory impairment (NSI) at child age of 11 to 12 years was identified by reviewing pediatric case records and records from other specialist health services.20 Information about the child's current health status was obtained by the Nordic Child and Family Health Questionnaire,21 which included responses to the questions regarding chronic medical and psychiatric conditions diagnosed by a medical specialist or child psychologist. Chronic conditions at 11 years of age were defined to include NSI and medical or psychiatric illness with duration of ≥12 months. The Nordic Child and Family Health Questionnaire also provided information about the sociodemographic and socioeconomic backgrounds of the study participants.

Data Collection
The method of data collection in the perinatal period in the EI children has been described previously.18 Fetal ultrasonography performed at 16 to 17 weeks' gestation was used to determine the gestational age at birth in 97% of these children. Trained nurses at the NICU measured the weight at birth of all EI children. Thereafter, weight was measured at repeated intervals up to discharge from the hospital. Measurement of head circumference (HC) and length of the EI children was postponed at birth on many occasions, but between the second and fourth weeks of postnatal age, all surviving EI children had their length and HC measurements performed; subsequently, the 3 growth parameters (weight, length, and HC) were measured at regular intervals up to discharge from the hospital. Data concerning the child's condition at birth, birth weight, birth length, and HC were recorded on a special form that was sent to the child care center at which the child was seen at regular intervals up to the age of 6 years. All children were registered at the child health care center. After the hospital period in the EI children and from birth in the control participants, the length, weight, and HC were measured during health checks either at the hospital or the child health care center up to the age of 6 years. After that age, measurements of length and weight were taken at school by a school nurse at regular intervals (once or more every year). Growth data were collected from the child health care units, hospital records, and school health services until the children reached 11 to 12 years of age. At this assessment (11–12 years), the weight, length, and HC of all the EI and control participants were measured by a trained nurse in a standardized way. The ages at the time of measurement were corrected for gestational age up to the age of 3 years.

Height was measured as supine length until the child could stand up by himself or herself, which is generally at ~2 years of age. After the age of 2 years, height was measured with a stadiometer attached to the wall. All height measurements were made to the last completed 0.5 cm.

Weight in the first 2 years of life was measured to the last completed 0.1 kg while the child was naked on a balance scale or an electronic scale. Children from ages 2 to 11 years were weighed while wearing minimal clothing on a digital scale with an accuracy of 0.1 kg.

HC was measured in the maximum fronto-occipital plane using nonextensible plastic-coated tape. After 4 years of age, HC is not usually measured at routine health checkups; therefore, HC records were not available from 4 years of age to the time of this assessment at 11 years. The average numbers of measurements of weight and height from birth to 11 years in EI and control participants were 34 (range: 15–45) and 18 (range: 10–36), respectively. The corresponding values of HC measurements from birth to 3 years in the 2 groups were 17 (range: 10–32) and 6 (range: 4–9), respectively. Data on parental anthropometry (height and weight), obtained by self-reports, were available for 97% of the study population.

Data Analysis
The growth data for each child were examined before they were combined with the data sets of the 2 previous studies for analysis.18,19 Before the statistical analysis was performed, the raw growth data were inspected for recording errors. This was performed in 2 stages. First, nonpositive age increments were listed and scrutinized. Second, tentative SD scores were established to look for extreme values in either direction. For determining weight/height at exact predefined ages, fourth-degree polynomial-regression22 curves were fitted for each child and variable. Interpolated values were then calculated for the predefined ages in EI and control children.

z scores for weight, height, BMI (kg/m2), and HC were computed relative to Swedish population norms being used in Sweden at the time.23,24 Swedish reference values for the calculation of HC z scores were unavailable from 4 years old onward; therefore, we used the United Kingdom growth chart for computing HC z scores at 11 years of age.25 In EI children, z scores for the growth variables from birth to expected date of delivery (EDD) corresponding to 40 weeks' gestation were computed relative to the Swedish reference data based on estimated fetal weight.26 A z score was calculated by subtracting the expected value for the measurement (weight, height, BMI, or HC) from the child's actual measurement and dividing by the SD for the measurement. A z score of 0 equals the median (50th percentile), a score of +2 SDs approximates the 98th percentile, and a score of –2 SDs approximates the 2nd percentile in normally distributed populations. Subnormal growth was defined as a z score of >2 SDs below the mean for the growth variables. The cutoffs for overweight at different ages in boys and girls were defined as proposed by Cole et al.27 When data were available for both parents, z scores were averaged to obtain a midparental height z score. Otherwise, the measurement from the sole parent was assumed to represent midparental height.

All statistical analyses were performed with SPSS 13.0 for Windows (SPSS Inc, Chicago, IL) except for the calculations of polynomial models, which were conducted with Minitab 14.1 (Minitab, State College, PA). Descriptive statistics such as frequency distributions, means, SDs, and ranges were used. To compare the growth of children relative to the reference population at each age and to compare rates of change in z scores between the consecutive ages, data were analyzed by the single-group t test. Children's heights were compared with their midparental height by using paired t tests. Data were compared between the groups by nonpaired t tests. Multiple-regression analysis was performed to identify correlates of growth at 11 years of age. Two regression models were constructed. In the first model, stepwise regression analyses were conducted to determine if preterm birth was a factor associated with growth at 11 years after controlling for other explanatory variables such as gender, having a chronic condition at 11 years, parental height and weight, and socioeconomic status (SES). In the other model, analyses were repeated in the EI children only to determine if growth was predicted by major neonatal complications (intraventricular hemorrhage grade 3 or 4 or periventricular leukomalacia, retinopathy of prematurity stage ≥3, bronchopulmonary dysplasia, or necrotizing enterocolitis), birth weight, or gestational age after controlling for other explanatory variables such as SES, parental anthropometric measures, and having a chronic condition at this assessment. The study was approved by the regional ethical committee at Umeå University.


   RESULTS
TOP
 ABSTRACT
 POPULATION AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Infant data and sociodemographic characteristics are shown in Table 1. Ninety-two percent of the EI children were born at perinatal tertiary care centers. In the 83 EI subjects, the mean (SD) gestational age and birth weight were 24.6 (0.7) weeks and 765 (110) g, respectively. Seventeen percent of the EI children were from multiple pregnancies. The mean (SD) birth weight z score in the EI infants (–0.57 [0.98]) was significantly below the reference mean and 6 (7%) were small for gestational age (SGA, birth weight less than –2 SDs).


View this table:
[in this window]
[in a new window]

  		TABLE 1 Infant Birth, Neonatal Data, and Chronic Conditions at 11 Years and Sociodemographic Characteristics

 
Sociodemographic characteristics, including maternal education and single-parent families, were similar in the 2 groups. Twelve percent of the children lived in a single-parent family. At 11 years of age, 45% of the EI children versus 22% of the controls (P < .005; odds ratio: 2.6; 95% confidence interval [CI]: 1.3 to 5.2) reported chronic conditions that implied an NSI, a medical or a psychiatric condition lasting for ≥12 months. The children in the control group were 8 months older, on average, than the index children because of the slower recruitment process for control participants.

Growth From Birth to 11 Years
Raw data on weight, length, HC, and BMI at various ages are shown in Table 2, and data on parental anthropometric measures are shown in Table 3.


View this table:
[in this window]
[in a new window]

  		TABLE 2 Raw Growth Data at Each Age

 

View this table:
[in this window]
[in a new window]

  		TABLE 3 Parental Anthropometric Measurements

 
Weight
Weight z scores are shown in Table 4. EI children showed a marked drop in weight z scores in the neonatal period, and the scores continued to decline up to 3 months' corrected age. After 3 months' corrected age, the z scores in the EI children began to increase and continued to do so, reaching the mean of the reference at ~11 years of age. The mean difference in weight z scores between the EI and control participants was significant at all ages (Table 4); however, it decreased from –2.32 at 3 months' corrected age to –0.39 at 11 years of age. The proportion of EI children with subnormal weight (<2 SDs below the mean) increased from 7% at birth to 60% at 3 months' corrected age, after which there was a reduction in this proportion at later ages (Fig 1A). At 11 years, none of the children in the EI cohort or control participants had subnormal weight. Compared with their male controls, EI boys had significantly lower mean weight z scores at all ages from birth to 11 years, whereas between the girls of the 2 groups, this difference disappeared from 7 years of age onward (Fig 2 A and B). At 11 years of age, the EI boys were 5 kg lighter in weight than their control participants (difference in means: EI boys, –4.9 [95% CI –8.2 to –1.6]; P = .003).


View this table:
[in this window]
[in a new window]

  		TABLE 4 Weight z Scores at Each Age

 

Figure 1
View larger version (22K):
[in this window]
[in a new window]

  		FIGURE 1 Percentage of EI (<26 week's gestation) children with subnormal weight for age (A; weight below –2 SDs), height for age (B; height below –2 SDs), and HC for age (C; HC below –2 SDs) at different ages23–26: a comparison with controls (number of children assessed from birth to 4 years: EI, 83; control, 83; 5–11 years: EI, 80; control: 80). Age is corrected for preterm birth up to 3 years of age. a Indicates proportion of EI infants with subnormal weight at birth; b Indicates proportion of EI children at EDD and control participants at birth with subnormal weight, length, or HC.

 

Figure 2
View larger version (28K):
[in this window]
[in a new window]

  		FIGURE 2 A–H, Graphs illustrating mean z scores of weight, height, BMI, and HC at each age in EI (<26 weeks' gestation) boys (number of boys assessed, birth to 4 years: EI, 38; control, 38; 5–11 years: EI, 36; control, 36) and girls (number of girls assessed, birth to 4 years: EI, 45; control, 45; 5–11 years: EI, 44; control, 44): comparison with control participants. Age is corrected for preterm birth up to 3 years of age. az scores at birth in EI children; bz scores at EDD in EI children and birth z scores in control participants. The null line is the z score for the reference group.23–26

 
Length/Height
There were not enough length z scores at birth in EI children to make statistical comparisons worthwhile. Compared with their controls and the reference population, the EI children had significantly lower height z scores at all ages (Table 5). At EDD the mean (SD) height z scores in EI children were –1.79 (0.85), declining sharply to the lowest values in the next few months (Table 5). Like the scores for weight, the height z scores increased after 3 months' corrected age. EI children showed a significant increase in height z scores between the ages of 3 months (corrected for prematurity) and 3 years (mean increase: 1.44 [95% CI: 1.18 to 1.71]) and between ages 7 and 11 years (mean increase: 0.28 [95% CI: 0.20 to 0.36]). Between the ages of 3 and 7 years, the height z scores did not change in the EI children but remained fairly constant and significantly below zero. In the control participants, the height z scores did not change significantly from 0 between any consecutive ages. At this assessment, the mean (SD) height z scores were significantly lower in the EI children than in the control participants (–0.53 [1.08] vs 0.10 [0.93], respectively; P < .001). The proportion of EI children with subnormal height increased from 37% at EDD to 62% at 3 months' corrected age and was subsequently reduced at later ages (Fig 1B). At 11 years, a small and nonsignificant proportion of EI children (EI, 6%; control, 1%; P = .2) remained subnormal in height. A similar pattern of catch-up growth in height z scores was observed in EI boys and girls (Fig 2 C and D). At 11 years of age, the EI girls were 3.1 cm and the EI boys 5.7 cm shorter than their contemporary control participants (difference in means: girls, –3.1 [95% CI: –6.2 to –0.09]; P = .04; boys, –5.7 [95% CI: –8.71 to –2.7]; P < .001).


View this table:
[in this window]
[in a new window]

  		TABLE 5 Height z Scores at Each Age

 
BMI
Compared with their controls the EI children had significantly lower BMI z scores up to 5 years of age, but by 7 years this difference had disappeared (Table 6). There was a significant increase in the mean BMI z scores between ages 1 and 11 years in both groups (mean increase [SD]: EI, 1.5 [1.15]; control, 0.85 [1.4]). The mean gain in BMI between 1 and 11 years of age was significantly greater in the EI cohort than in the control participants (difference in mean gain: 0.64 [95% CI: 0.25 to 1.03]; P = .002). At 11 years of age, EI children as a group were relatively heavy for their height, but their mean BMI z score was not significantly different from 0 (mean difference: 0.29 [95% CI: –0.005 to 0.59]) or from the controls (mean difference: –0.09 [95% CI: –0.5 to 0.31]). Fifteen percent vs 17% of the EI and control participants, respectively, were overweight according to the cutoffs for BMI proposed by Cole et al.27 In an analysis for gender differences in BMI, the mean BMI z scores for EI girls was found to be comparable to those for their controls from ages 2 to 11 years, whereas the mean BMI z scores for EI boys were significantly lower than those for their control participants up to 7 years of age, reaching the mean of the reference at ~9 years (Fig 2 E and F). Compared with EI boys, there was a trend toward an increase in the proportion of overweight EI girls at various ages (at 5 years: EI girls vs boys, 24% vs 3%; P = .005; at 7 years: EI girls vs boys, 20% vs 5%; P = .1; at 11 years: EI girls vs boys, 20% vs 8%; P = .1). In the control participants, no such gender differences were found.


View this table:
[in this window]
[in a new window]

  		TABLE 6 BMI z Scores at Each Age

 
HC
There were not enough HC measurements at birth in EI children to make comparisons. At EDD, the mean HC z scores in EI children were significantly lower than those in their control participants (mean difference: –1.1 [95% CI: –1.33 to –0.87]; P < .0001). These remained significantly lower than those in the control participants and in the reference mean at all ages at which comparison was possible (Table 7). The control participants did not change their z scores from the reference mean between any consecutive ages. A significantly higher proportion of the EI cohort compared with controls had subnormal HC (<2 SDs below the mean) at 11 years of age (EI, 22%; control, 1%; P < .001) (Fig 1C). In addition, there were significant differences between EI and control children by gender at 11 years of age: the mean HC of EI boys was 2 cm lower than that of their control participants, and it was 1.2 cm lower in EI girls than in their controls (P < .001). Unlike the increases in height and weight, the EI children did not show any catch-up growth in HC after the age of 6 months (Fig 2 G and H).


View this table:
[in this window]
[in a new window]

  		TABLE 7 HC z Scores at Each Age

 
SGA, Growth Deficiency, and Chronic Conditions
At this assessment, the mean z scores of weight, height, and HC for 6 EI children who were born SGA were –0.48, –0.96, and –2.6, respectively. The corresponding values in the EI children who were born appropriate for gestational age (n = 74) were –0.12, –0.5, and –0.99, respectively. Of the 6 EI children who were born SGA, at 11 years of age none had weight z scores less than –2 SDs, 1 child had a height z score less than –2 SDs, and 5 had HC z scores less than –2 SDs. The mean (SD) z scores in height, weight, and HC in EI children with (n = 33) and without (n = 47) any chronic condition did not differ significantly at 11 years of age (height z scores: –0.47 [1.03] vs –0.6 [1.1]; weight z scores: –0.13 [1.1] vs –0.17 [1.3]; HC z scores: –1.36 [1.0] vs –1.1 [1.1], respectively). Three children had been investigated earlier in childhood for short stature and had been started on growth hormone therapy at 4 to 5 years of age, although none of the children had growth hormone deficiency. Before starting growth hormone therapy these children had a mean height z score of –3.1 (SD: 0.6) at 4 years of age.

Parental Anthropometry
Midparental height z scores were available for parents of 81 children (98%) in each group (ie, in the EI cohort and control participants). There were no differences in maternal or paternal height or weight between the 2 groups (Table 3).The difference in the mean height z scores between the EI children and their parents (midparental height z score) was significantly below 0 at 11 years old (paired t test, t = –4.99; P < .001; mean difference in height z scores: –0.56 [95% CI –0.79 to –0.34]). The corresponding values in the control participants were not different from 0 (mean difference: –0.09 [95% CI –0.28 to 0.09]). A majority of the EI children (94%) were within 2 SDs of their mean midparental height z scores.

Correlates of Growth
Stepwise regression analyses revealed that the z scores for height and HC at 11 years of age continued to be significantly lower in the EI children than in the control participants after adjustment for midparental height, gender, SES, and having a chronic condition. Midparental height (z score) was a significant predictor of the children's height, explaining 22% of the variance (ß = 0.545; P < .0001), followed by the group status (prematurity), which explained 8% of the variance (ß = 0.528; P < .001). Group status was the major determinant of HC (z score) (R2 = 0.24; ß = 1.0; P < .001), and midparental height (z score) showed a weak but significant correlation with HC, explaining 3% of the variance (ß = 0.25; P = .01). Maternal weight was the only variable that correlated with weight or BMI z scores (for weight z score: R2 = 0.26; ß = 0.042; P < .001; for BMI z score: R2 = 0.17; ß = 0.047; P < .001). In the separate analyses of boys and girls, preterm birth was a significant predictor of weight in boys but not in girls. In the subanalysis of the EI cohort only, midparental height and birth weight z scores correlated with height at 11 years of age (Table 8). As observed in the analyses of both groups, the only variable that correlated with weight and BMI z scores was mother's weight. Birth weight z scores predicted head size. Gender, gestational age, SES, and presence of a chronic condition did not correlate with any of the anthropometric measurements in this assessment.


View this table:
[in this window]
[in a new window]

  		TABLE 8 Multiple-Regression Analysis of Correlates of Weight and Height, BMI, and HC at 11 Years in EI Children (<26 Weeks' Gestation; n = 80)

 

   DISCUSSION
TOP
 ABSTRACT
 POPULATION AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This is the first study (based on gestational age) of long-term growth outcomes in children born EI in the 1990s. We have presented our data on the basis of gestational age, thereby avoiding the confounding bias associated with reporting outcomes in terms of birth weight groupings.13 The data are presented in z scores, which provide a more sensitive estimate of deviation of growth than the use of percentiles or cutoff levels for growth deficiency.28,29 In EI children, growth data from birth to EDD were compared with Swedish gender-specific intrauterine growth standards.26 These latter values are in agreement with reference data currently being developed for Swedish infants born preterm.30 One of the strengths of our study is the large number of measurements at various time points throughout the study period in both EI and control participants. Because the measurements were not made at exact ages, we performed a polynomial-regression analysis to reduce the fluctuation in sample size over various ages,22 and the interpolated values could be used for predefined ages. Other notable strengths of the study are its nationwide composition, prospective follow-up, and high follow-up rate. Furthermore, the racial composition was homogeneous (97% Swedish or Nordic), and the SES was similar in EI children and controls.

Our results reveal that EI children have growth failure in early extrauterine life in comparison with those of normal intrauterine growth during the third trimester. The relative decline in growth parameters continued up to 3 months' corrected age. Growth data are available from a large population-based prospective national follow-up study of 283 infants born at <26 weeks' gestation in 1995 in the United Kingdom, the EPICure study.17 At EDD, their mean z scores for weight, height, and HC were –1.72, –2.49, and –0.86, respectively, compared with –1.6, –1.8, and –1.3 at EDD in our study. These data reveal the similar distributions of growth failure in weight, height, and HC in early extrauterine life. High rates of growth failure were also observed in a recent retrospective study from the United States31 concerning growth outcomes of 24317 infants at discharge who were born between 23 and 34 weeks' gestation in 1997–2001 (reported from 124 NICUs). At discharge home, of their subgroup of infants born at ≤25 weeks' gestation (n = 880), 64%, 84%, and 44% had weight, height, and HC parameters ≤10th percentile, respectively.

At 24 months' corrected age, the proportions of infants with subnormal growth parameters regarding weight, height, and HC in our study were 20%, 13% and 17%, respectively, compared with 13%, 25%, and 38% in the EPICure study at 30 months' corrected age.17 Thus, the findings were similar for weight, but the proportions of infants with subnormal length and HC were considerably higher in the EPICure study. It is possible that the lower disability rate in our cohort of EI children contributed to the better results for growth of HC and height. However, the relatively small sample size in our study limits the comparison of data. Other investigators have also reported increased rates of growth deficiencies in early childhood among VLBW or ELBW children.4–7,10,12

At 11 years of age, the EI children were lighter and shorter than the control participants, and the difference was more marked in boys than in girls. However, a majority of these children (>90%) were within 2 SDs of the reference mean for age. Our EI cohort displayed a fast catch-up growth in weight and length from 3 months' corrected age to 3 years, after which there was a period of late catch-up growth that continued up to this assessment. Catch-up growth in weight was more rapid than the increase in height z scores. Others have reported late catch-up growth in weight and height of ELBW or VLBW children in their early teens and in adolescence.7–9,11,12 In all of these studies,7–9,11,12 preterm children had significantly lower z scores for all anthropometric measures during adolescence compared with their normal birth weight peers, and in some of these cohorts7,12 in which outcomes have been reported at a young adult age, the differences in growth parameters have remained significant.32,33 Saigal et al33 recently reported growth outcomes at a young adult age in 147 (89%) of 166 children with birth weight <1001 g (mean gestational age: 27 weeks) who were assessed in a prospective longitudinal population-based study. Young ELBW adults (males and females) had significantly lower anthropometric measurements than their gender-specific controls.

At 11 years of age, although the EI children had higher mean weight z scores than mean height z scores, with a discrepancy of 0.4 SD, their mean BMI z score was not significantly different from that of the control participants or the reference population. At this assessment, 15% of our EI cohort would be considered overweight according to age- and gender-specific cutoffs for BMI.27 There was a significant increase in BMI over time in both groups, which is consistent with an increase in body fatness as a child grows. However, there were significantly larger childhood gains of BMI in EI children than in the control participants. There are reports that low birth weight in combination with accelerated weight gain during childhood is associated with an increased risk of CVD in adult life.15,16,34 However, these studies did not specifically address children born extremely preterm, a group with a dramatic increase in survival in the past decade,1–3 who exhibit substantial growth failure in early infancy.17,31 In a recent retrospective study35 it was found that the risk of CVD was more strongly related to the speed of childhood gain in BMI than to the BMI attained at any particular age. Thus, it may reasonably be speculated that the pronounced growth restriction in the postnatal period and in early infancy, with accelerated catch-up growth in childhood, may put these immature infants at risk of metabolic and cardiovascular morbidity in later life, a concern that is shared by others.32,33

EI girls showed more pronounced catch-up growth in weight than EI boys, which is compatible with the greater change in BMI in EI girls than in the EI boys. Furthermore, we observed a trend toward an increased prevalence of overweight in the EI girls compared with the EI boys at different ages. A greater increase in BMI in preterm girls at adolescence12 and in young adult VLBW girls32 has also been reported. As speculated by others,32 the gender differences in growth probably have multifactorial causes. The greater susceptibility of VLBW boys to neonatal complications has been well described.36 In our population the rates of major neonatal complications (intraventricular hemorrhage grade 3–4 or periventricular leukomalacia, retinopathy of prematurity stage ≥3, bronchopulmonary dysplasia, and necrotizing enterocolitis) and the length of neonatal hospital stay were similar in the EI boys and EI girls. However, EI girls had lower rates of chronic conditions than EI boys (33% vs 51%; P = .11), but the difference was not significant.

At this assessment, the mean HC z scores in EI boys and girls were 1.3 and 0.89 SDs lower than their contemporary control participants, respectively. These reductions amount to 2 and 1.3 cm in EI boys and girls, respectively. In contrast to the increase in weight and height, our EI cohort did not show any catch-up growth in HC after the first year of life. Our findings are in agreement with others,37–39 which strengthens the evidence that the catch-up growth mostly occurs during the first year of life. Furthermore, 21% of the EI children had a subnormal HC at 3 years' corrected age, and in a similar proportion (22%) HC remained subnormal at 11 years of age. Similar reductions in head-growth attainment have been reported in studies of adolescent growth outcomes in VLBW or ELBW children.8,11,12,40 As in the studies by Peralta-Carcelen et al11 and Peterson et al,41 we found that the HC was significantly lower in EI children who were born SGA than in those who were appropriate for gestational age. Subnormal head size has been associated with poor developmental outcomes in preterm children.39–43

There were no differences in parental height and weight between our EI and control groups, which is in agreement with reports from other investigators.11,12 Although the EI children had significantly lower height z scores compared with their midparental height by age 11 (mean difference: 0.57 SD), a majority of them (>90%) were within 2 SDs of their mean midparental height. The proportion of children with subnormal height decreased from 15% to 6% within a period of 2 years (ie, from 9 to 11 years of age). It is likely that some of our EI children had entered puberty. However, we did not collect data on pubertal development, and bone ages were not measured. Some investigators have found no differences in sexual maturation rates by gender in children who had ELBW8,11 or VLBW,40 in comparison to term control children. A few studies have reported an advanced bone age in VLBW40 and ELBW adolescents11 with reference to their chronological age and speculated that this may contribute to shorter height in adulthood in preterm children. The final adult stature of extremely preterm infants born in the modern era of perinatal care remains to be determined.

Within the multivariate models, differences in height and head size persisted between EI and control participants when controlling was performed for other explanatory variables. Of all the tested variables, midparental height and group status predicted height at 11 years old, whereas the major correlate of HC was the group status. In the subanalysis of EI children only, parental height was the major determinant of height, emphasizing the strong genetic influence on the growth. In the EI cohort, birth weight for age correlated with height, but the association was weak. Head size was influenced by the birth weight scores in EI children. In fact, in the majority of the EI children (83%) who were born SGA, the head size remained subnormal at 11 years of age. However, our study does not provide useful data on long-term growth after intrauterine growth impairment, because only 7% of the EI children were below 2 SDs for the mean weight at birth. A number of studies have identified significant correlates of growth and catch-up growth among VLBW or ELBW infants in childhood and adolescence. Intrauterine growth restriction has a negative effect on the growth and catch-up growth during childhood and into adolescence.7,11,44,45 Neonatal complications have been shown to bear a negative relation to growth during early infancy and childhood,17,46,47 and parental size is positively related to growth parameters in childhood and adolescence.7,10–12,44,48

The detrimental effect of long courses of postnatal steroids (PNS) on linear growth is evident from the published reports on this subject.17,49 In the beginning of the 1990s, administration of PNS for treatment of chronic lung disease of prematurity was not considered to be an important predictor of long-term outcome with regard to growth and NSI. Therefore, information on PNS was not collected prospectively in our longitudinal investigation of preterm infants born from 1990 through 1992. Furthermore, 92% of our immature cohort (survivors) was born in the 7 Swedish tertiary perinatal care facilities of Sweden. In our personal communication with the co-authors of the articles on the neonatal and 3-year follow-up of our EI cohort,18,19 it was brought to our knowledge that PNS treatment of chronic lung disease in preterm infants was not a common practice in Sweden in the beginning of the 1990s. However, we do not possess the exact information in this regard.

As suggested by Karlberg,50 growth from birth to maturity has been described as occurring in 3 additive phases: infancy, childhood, and puberty (ie, the "ICP model"). The infancy component, the mechanism of which is not well understood, seems to onset at approximately midgestation and continues with a decelerating influence up to ~3 to 4 years of age. The childhood component starts during the first year of life, has a continuously slow decelerating course, and does not disappear until adult size is attained. It may reasonably be speculated, as suggested by others,48 that preterm birth disrupts the normal regulation of the infancy growth period, resulting in poor growth in the first years, whereas the childhood growth period remains well preserved. Early growth failure might be the result of disruption from the intrauterine physiologic environment and complications in the neonatal period. Interaction of the nutritional and endocrine factors that govern early growth in infants born prematurely is not perfectly understood. Differences in levels of many circulating hormones between preterm and term infants have been reported,51–54 linking them to the early growth failure in premature infants.54 We need to address the specific issues of whether postnatal growth failure is related to nutritional factors and how fast these infants should grow (including catch-up growth). This might enable us to understand whether the postnatal growth failure and its associated poor developmental performance can be moderated by dietary means.


   CONCLUSIONS
TOP
 ABSTRACT
 POPULATION AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Our group of preterm children who were born at the limit of viability attained poor growth in their postnatal period and early childhood. This was followed by catch-up growth up to the age of 11 years; nevertheless, the children remained smaller than their term-born peers. It is possible that the growth outcomes reported for these children born in the early 1990s may not be relevant for current survivors in view of the significant advances in the intensive care of extremely preterm infants in the past 15 years, which include greater awareness to ensure optimal nutrition in the neonatal period and during infancy. It is not clear whether children born extremely preterm are expected to follow growth trajectories similar to those of their term peers, but the severe growth failure exhibited by the children in our EI cohort in their early postnatal life is unequivocal. We believe that by optimizing nutrition in the neonatal period and in infancy, health and growth outcomes may be improved.


   ACKNOWLEDGMENTS
 
This Study was financially supported by the Oskarfonden Foundation, the Sven-Jerrings Fond Foundation, and the Kempe-Carlgren's Fund.

We thank research nurse Margareta Backmän (Umeå) and project assistant Nighat Farooqi (Umeå) for assistance in collecting data and establishing an invaluable contact with the families. We also thank Dr Hans Stenlund in Umeå for statistical advice. We are indebted to the children and their families for cooperation.


   FOOTNOTES
 
Accepted Jun 8, 2006.

Address correspondence to Aijaz Farooqi, MD, Department of Pediatrics, University Hospital, SE-901 85 Umeå, Sweden. E-mail: aijaz.farooqi{at}pediatri.umu.se

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 POPULATION AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Lorenz J. The outcome of extreme prematurity. Semin Perinatol. 2001;25 :348 –359[CrossRef][Web of Science][Medline]
  2. Serenius F, Ewald O, Farooqi A, Holmgren PÅ, Håkansson S, Sedin G. Short-term outcome after active perinatal management at 23–25 weeks gestation: a study from two Swedish tertiary care centers. Part 2: infant survival. Acta Paediatr. 2004;93 :1081 –1089[CrossRef][Web of Science][Medline]
  3. El-Metwally, Vohr B, Tucker R. Survival and neonatal morbidity at the limits of viability in the mid 90s: 22–25 weeks. J Pediatr. 2000;137 :616 –622[CrossRef][Web of Science][Medline]
  4. Daily DK, Killbride HW, Wheeler R, Hassanein R. Growth patterns of infants weighing less than 801 g at birth to 3 years of age. J Perinatol. 1994;14 :454 –460[Medline]
  5. O'Callaghan MJ, Burns Y, Gray P, et al. Extremely low birth weight infants and controls: a comparison of intellectual abilities, motor performance, growth and health. Early Hum Dev. 1995;40 :115 –125[CrossRef][Web of Science][Medline]
  6. Kitchen WH, Doyle LW, Ford GW, Callanan C. Very low birth weight and growth at 8 years. I: weight and height. Am J Dis Child. 1992;146 :40 –46[Abstract/Free Full Text]
  7. Hack M, Weissman B, Borawski-Clark E. Catch-up growth during childhood among very low-birth-weight children. Arch Pediatr Adolesc Med. 1996;150 :1122 –1129[Abstract/Free Full Text]
  8. Ford GW, Doyle LW, Davis NM, Callanan C. Very low birth weight and growth into adolescence. Arch Pediatr Adolesc Med. 2000;154 :778 –784[Abstract/Free Full Text]
  9. Hirata T, Bosque E. When they grow up: the growth of extremely low birth weight (< or = 1000 g) infants at adolescence. J Pediatr. 1998;132 :1033 –1035[CrossRef][Web of Science][Medline]
  10. Doyle LW. Growth and respiratory health in adolescence of the extremely low-birth weight survivor. Clin Perinatol. 2000;27 :421 –432[CrossRef][Web of Science][Medline]
  11. Peralta-Carcelen M, Jackson DS, Goran MI, Royal SA, Mayo MS, Nelson KG. Growth of adolescents who were born at extremely low birth weight without major disability. J Pediatr. 2000;136 :633 –640[CrossRef][Web of Science][Medline]
  12. Saigal S, Stoskopf BL, Streiner DL, Burrows E. Physical growth and current health status of infants who were of extremely low birth weight and controls at adolescence. Pediatrics. 2001;108 :407 –415[Abstract/Free Full Text]
  13. Arnold CC, Kramer MS, Hobbs CA, McLean FH, Usher RH. Very low birth weight: a problematic cohort for epidemiological studies of very small or immature neonates. Am J Epidemiol. 1991;134 :604 –613[Abstract/Free Full Text]
  14. Barker DJP. Mothers, Babies and Health in Later Life. Edinburgh, Scotland: Churchill Livingstone; 1998
  15. Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJP. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ. 1999;318 :427 –431[Abstract/Free Full Text]
  16. Lucas LA, Fewtrell MS, Cole TJ. Fetal origins of adult disease: hypothesis revisited. BMJ. 1999;319 :245 –249[Free Full Text]
  17. Wood NS, Costello K, Gibson AT, et al. The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less. Arch Dis Child Fetal Neonatal Ed. 2003;88 :F492 –F500[Abstract/Free Full Text]
  18. Finnström O, Otterblad-Olausson P, Sedin G, et al. The Swedish national prospective study on extremely low birth weight (ELBW) infants: incidence, mortality, morbidity and survival in relation to level of care. Acta Paediatr. 1997;86 :503 –511[Web of Science][Medline]
  19. Finnström O, Otterblad-Olausson P, Sedin G, et al. Neurosensory outcome and growth at three years in extremely low birthweight infants: follow-up results from the Swedish national prospective study. Acta Paediatr. 1998;87 :1055 –1060[CrossRef][Web of Science][Medline]
  20. Farooqi A, Hägglöf B, Gothefors L, Sedin G, Serenius F. Chronic conditions, functional limitations, and special health care needs in 10- to 12-year-old children born at 23 to 25 weeks’ gestation in the 1990s: a Swedish national prospective follow-up study. Pediatrics. 2006;118(5) . Available at: www.pediatrics.org/cgi/content/full/118/5/e1466
  21. Berntsson L, Köhler L. Health and Wellbeing of Children in Five Nordic Countries in 1984 and 1996 [doctorial thesis]. Gothenburg, Sweden: Nordic School of Public Health; 2000
  22. Royston P. Constructing time-specific reference ranges. Stat Med. 1991;10 :675 –690[Web of Science][Medline]
  23. Albertsson-Wikland K, Luo ZC, Niklasson A, Karlberg J. Swedish population based longitudinal reference values from birth to 18 years of age for height, weight and head circumference. Acta Paediatr. 2002;91 :739 –754[CrossRef][Web of Science][Medline]
  24. Karlberg J, Luo ZC, Albertsson-Wikland K. Body mass index reference values for Swedish children. Acta Paediatr. 2003;92 :648 –652[CrossRef][Web of Science][Medline]
  25. The Child Growth Foundation. British 1990 Growth Reference for Height, Weight, BMI and Head Circumference. London, United Kingdom: Child Growth Foundation; 1996
  26. Marsal K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr. 1996;85 :843 –848[Web of Science][Medline]
  27. Cole TJ, Mary C, Bellizzi CM, Flegal MK, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320 :1240 –1243[Abstract/Free Full Text]
  28. Physical status: the use and interpretation of anthropometry. Report of a WHO expert committee: World Health Organ Tech Rep Ser. 1995;854 :1 –452[Medline]
  29. Shann F. Nutritional indices: Z, centile or percent? Lancet. 1993;341 :526 –527[Web of Science][Medline]
  30. Niklasson A, Karlberg P. New reference for Swedish infants' size at birth. Horm Res. 1999;51(suppl 2) :1 –153
  31. Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious problem in prematurely born preterm neonates. Pediatrics. 2003;111 :986 –990[Abstract/Free Full Text]
  32. Hack M, Schluchter M, Carter L, Rahman M, Cuttler L, Borawski E. Growth of very low birth weight infants to age 20 years. Pediatrics. 2003;112(1) . Available at: www.pediatrics.org/cgi/content/full/112/1/e30
  33. Saigal S, Pinelli J, Stoskopf B, et al. Comparison of growth of ELBW survivors and NBW from birth to young adulthood. Pediatr Res. 2005;105 :57A
  34. Ivring RJ, Belton NR, Elton RA, Walker BR. Adult cardiovascular risk factors in premature babies [published correction appears in Lancet. 2000;356:514]. Lancet. 2000;355 :2135 –2136[CrossRef][Web of Science][Medline]
  35. Barker DJP, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Trajectory of growth among children who have coronary events as adults. N Engl J Med. 2005;353 :1802 –1809[Abstract/Free Full Text]
  36. Stevenson DK, Verter J, Fanaroff AA, et al. Sex differences in outcomes of very-low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed. 2000;83 :F182 –F185[Abstract/Free Full Text]
  37. Hack M, Breslau N. Very low birth weight infants: effect of brain growth during infancy on intelligent quotient at 3 years of age. Pediatrics. 1986;77 :196 –202[Abstract/Free Full Text]
  38. Hack M, Breslau N, Fanaroff AA. Differential effects of intrauterine and postnatal brain growth failure in infants of very low birth weight. Am J Dis Child. 1989;143 :63 –68[Abstract/Free Full Text]
  39. Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E. Effect of low birth weight and subnormal head size on cognitive abilities at school age. N Engl J Med. 1991;325 :231 –237[Abstract]
  40. Powls A, Botting N, Cook RWI, Pilling D, Marlow N. Growth impairment in very low birthweight children at 12 years: correlation with perinatal and outcome variables. Arch Dis Child Fetal Neonatal Ed. 1996;75 :F152 –F157[Abstract/Free Full Text]
  41. Peterson J, Taylor HG, Minich N, Klein N, Hack M. Subnormal head circumference in very low birth weight children: neonatal correlates and school age consequences. Early Hum Dev. 2006;82 :325 –334[CrossRef][Web of Science][Medline]
  42. Teplin SW, Burchinal M, Johnson-Martin N, Humphry RA, Kraybill EN. Neurodevelopmental, health, and growth status at age 6 years of children with birth weights less than 1001 grams. J Pediatr. 1991;118 (5):768–777
  43. Kitchen WH, Doyle LW, Ford G, Callanan C, Rickards AL, Kelly E. Very low birth weight and growth at 8 years. II: Head dimensions and intelligence. Am J Dis Child. 1992;146 :46 –50[Abstract/Free Full Text]
  44. Fewtrell MS, Cole TJ, Bishop JN, Lucas A. Neonatal factors predicting childhood height in preterm infants: evidence for a persisting effect of early metabolic bone disease. J Pediatr. 2000;137 :668 –673[CrossRef][Web of Science][Medline]
  45. Qvigstad E, Verloove-Vanhorick SP, Ens-Dokkum MH, et al. Prediction of height achievement at five years of age in children born very preterm or with very low birth weight: continuation of catch-up growth after two years of age. Acta Paediatr. 1993;82 :444 –461[Web of Science][Medline]
  46. Ehrencrantz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104 :280 –289[Abstract/Free Full Text]
  47. Hack M, Merkatz IR, McGrath SK, Jones PK, Fanaroff AA. Catch-up growth in very-low-birth-weight infants: clinical correlates. Am J Dis Child. 1984;138 :370 –375[Abstract/Free Full Text]
  48. Niklasson A, Engström E, Hård AL, Albertsson-Wikland K, Hellström A. Growth in very preterm children: a longitudinal study. Pediatr Res. 2003;54 :899 –905[CrossRef][Web of Science][Medline]
  49. Gibson AT, Pearse RG, Wales JK. Growth retardation after dexamethasone administration: assessment of knemometry. Arch Dis Child. 1993;69 :505 –509[Abstract/Free Full Text]
  50. Karlberg J. On the modeling of human growth. Stat Med. 1987;6 :185 –192[Web of Science][Medline]
  51. Rajaram S, Carlson SE, Koo WW, Rangachari A, Kelly DP. Insulin-like growth factor (IGF)-1 and IGF-binding protein 3 during the first year in term and preterm infants. Pediatr Res. 1995;37 :581 –585[Web of Science][Medline]
  52. Wollmann HA. Growth hormone and growth factors during perinatal life. Horm Res. 2002;53 :50 –54[CrossRef]
  53. Yeung MY, Smyth JP. Hormonal factors in the morbidities associated with extreme prematurity and the potential benefits of hormonal supplementation. Biol Neonate. 2002;81 :1 –15[Web of Science][Medline]
  54. Cavazzoni E, Gill M, Wales JKH, Clayton PE, Gibson AT. The relationship between IGF-1, IGFBP-3 and postnatal growth failure in premature infants over the first two months after birth [abstract]. J Endocrinol. 1998;156(suppl) :146
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Arch. Dis. Child. Fetal Neonatal Ed.Home page
M Tan, L Abernethy, and R Cooke
Improving head growth in preterm infants - a randomised controlled trial II: MRI and developmental outcomes in the first year
Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2008; 93(5): F342 - F346.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farooqi, A.
Right arrow Articles by Serenius, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farooqi, A.
Right arrow Articles by Serenius, F.
Related Collections
Right arrow Premature & Newborn
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?