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Objective: To assess the impact of time of birth on infant mortality and early neonatal mortality in full term and preterm births., Design: Analysis of data from the Swedish birth register, 1973-95., Participants: 2 102 324 spontaneous live births of infants without congenital malformation., Outcome Measurements: Absolute and relative risk of infant mortality, early neonatal mortality, and early neonatal mortality related to asphyxia., Results: Infant mortality, early neonatal mortality, and early neonatal mortality related to asphyxia were higher in infants who were born during the night (9 pm to 9 am) compared with those born during the day for 1973-9, 1980-9, and 1990-5. The difference was more dramatic for preterm infants. The largest difference was observed during 1990-5, when there was a 30% increase in early neonatal mortality (relative risk 1.31, 95% confidence interval 1.10 to 1.57) and a 70% increase in early neonatal mortality related to asphyxia (1.70, 1.22 to 2.38) in preterm infants born during the night compared with rates for preterm infants born during the day. A detailed analysis over 24 hours revealed two "high risk" periods: between 5 pm and 1 am and around 9 am., Conclusions: Infants born during the night have a greater risk of infant and early neonatal mortality and early neonatal mortality related to asphyxia than those born during the day. There has been no improvement over the past two decades. The problem is more serious for preterm births and was even worse in the 1990s. Shift changes and the hours immediately after such changes are high risk periods for neonatal care.

Unlabelled: Body mass index (BMI) is an important indicator of nutritional status. Many studies have been done to present BMI reference values in centile values rather than mean and SD values since its statistical distribution is positively skewed. Both height and weight growth charts are usually available in terms of mean and 1, 2 and 3 SD around the means; it would be of clinical value to produce BMI reference charts in a similar way. The aim of this work was to derive the mean and +/- 1, 2 and 3 SD BMI reference ranges as a supplement to the BMI centile reference values published previously for the same group of Swedish children. The method was based on an age-dependent Box transformation, and the beta-value was given as a third-degree polynomial function over the paediatric age. The BMI reference values can be given from mathematical functions in addition to values for specific ages., Conclusion: The BMI reference values and charts derived as described effectively reflect the nature of the variant age-dependent positive skewed statistical distribution of BMI values in the population, and can serve as a valid supplementary tool in the evaluation of growth and nutrition during paediatric years.

Forty-eight normal full-term Chinese babies (25 boys and 23 girls) were followed up every 2 mo in the first year and every 3 mo during the second year of life for anthropometric measurements. Blood samples were taken at birth and at 6, 10, 12, and 18 mo after birth for serum GH-binding protein, IGF-I, and IGF-binding protein 3 analysis. Onset of the childhood phase of growth in the infants was determined from the growth data plotted on Infancy-Childhood-Puberty growth charts. The serum GH-binding protein concentrations were low in cord blood but rose significantly at 6 mo, with slower rises in late infancy and early childhood. However, a significant rise in serum IGF-I and IGF-binding protein 3 levels was only observed from 10 mo of life onward. The change in IGF-I between birth and 6 mo was significantly correlated with length gain (r(2) = 0.35, p < 0.05) and body mass index gain (r(2) = 0.41, p < 0.01) during the same period. The 34 infants with onset of childhood phase of growth between 6 and 10 mo had a higher mean serum IGF-I value at 10 mo (8.8 +/- 5.8 nM versus 4.9 +/- 3.1 nM; p < 0.05) and higher length velocity between 10 and 12 mo (16.3 +/- 4.7 cm/y versus 8.8 +/- 4.3 cm/y; p < 0.001) compared with the 14 infants with a later onset after 10 mo of age. A significant correlation between a change in serum IGF-I and IGF-binding protein 3 levels was observed during the three 6-mo periods between birth and 18 mo, but a significant correlation between a change in serum GH-binding protein and a change in serum IGF-I or IGF-binding protein 3 levels was only seen between 12 and 18 mo of age. The multiple regression analysis (r(2) = 0.43, p = 0.0002) revealed that the change in serum GH-binding protein and IGF-I concentrations between 6 and 12 mo of age and the age of onset of childhood phase of growth could explain 43% of the length gain between 6 and 12 mo of age in our babies. The results of our study support the hypothesis that the onset of the childhood phase of growth is associated with the onset of significant GH action on growth.

We consider the estimation of sources of variation for panel data with repeated measurements. With no repeated measurements and known measurement error, models for variation decomposition have been proposed when there are one or more types of measurements. Estimation was performed using the EM algorithm accompanied by model augmentation that demands more computational efforts. In this article we extend previous variation models and modify the estimation methods in order to estimate various variation components after eliminating the unknown effects of measurement error. Specifically, methods that dispense with model augmentation and estimation of time-dependent covariates are considered. A set of lower leg length data from Chinese infants is analysed by using the proposed model. Interestingly, our results are consistent with the well-accepted three-phase (infancy-childhood-puberty) growth transition proposition for human growth. Moreover, gender effect is found to be time-varying., (Copyright 2001 John Wiley & Sons, Ltd.)

Objective: To describe the seasonal growth patterns in Shanghai infants, to explore seasonal time lag between weight gain and length gain, and to investigate the long-term effect of birth season on early postnatal growth., Design: Community-based longitudinal study., Setting: Shanghai, People's Republic of China., Method: Children were followed up monthly from 1 to 6 months, 3 monthly from 6 to 12 months, and 6 monthly from 12 to 24 months., Subjects: A total of 6018 children born between 1 January 1980 and 31 December 1990., Main Outcome Measures: Weight gain, length gain and change in body mass index (BMI) over the seasons of the year., Results: The infants tended to grow faster in height in spring and summer, and faster in weight and BMI in autumn and winter. The seasonal effect on weight gain and length gain is largely independent. The mean length value at 1 month of age was about 2.0 cm higher in infants born in May to July than in those born in November to February. At 24 months of age this difference was reduced to about 0.7 cm., Conclusions: There is a clear and consistent seasonality in growth in Shanghai infants. The seasonality seems to act independently on weight and length. Birth month has some association with attained size, but this is reduced during the first 2 y of life.

Objectives: This study was designed to explore whether the influence of subnormal growth in fetal, infancy, childhood and pubertal phases on adult short stature was the same when comparing privileged and underprivileged populations., Methods: Data came from two longitudinal growth studies: 1) Hong Kong Chinese children who were born in 1967 (n = 132), and 2) the comparatively more privileged Swedish children who were born in 1973-1975 (n = 2,850)., Results: 68% of Hong Kong Chinese children had two or more growth phases subnormal, much higher than the 12.4% for Swedish children. 42.4% of Hong Kong Chinese were short at final height, much higher than the 2.2% for Swedish children. Subnormal growth in any growth phase was associated with an increased risk of adult short stature in both series (p<0.01). After adjustment for mid-parental height, the place of residence (Hong Kong/Sweden) was not significant for adult shortness (p>0.05) in the pooled data., Conclusions: The impact of subnormal growth in any phase on adult shortness is similar in privileged and underprivileged populations. The much higher prevalence of subnormal growth and consequently adult short stature in developing countries is likely mainly attributable to adverse extrinsic or environmental influences.

No large population-based study has addressed the question of how overnutrition is related to subsequent height gain in childhood, timing of puberty, and final height. The present data represent a large Swedish population-based longitudinal growth study. Height gain in childhood, timing of reaching peak height velocity and height gain during adolescence, and final height were regarded as the short-term, interim, and long-term outcomes of childhood nutritional status, i.e. body mass index (BMI) change between 2 and 8 y. Midparental height was adjusted as the genetic influence on linear growth of the child. Childhood BMI gain was related to an increased height gain during the same period, i.e. an increase of 1 BMI unit was associated with an increase in height of 0.23 cm in boys and 0.29 cm in girls. A higher BMI gain in childhood was related to an earlier onset of puberty; the impact on the timing of puberty was 0.6 y in boys and 0.7 y in girls. Each increased unit of BMI gain in childhood also reduced the height gain in adolescence, 0.88 cm for boys and 0.51 cm for girls. No direct correlation was shown between childhood BMI gain and final height. We conclude that overnutrition between 2 and 8 y of age will not be beneficial from a final height point of view, as the temporary increase in height gain in childhood will be compensated by an earlier pubertal maturity and a subnormal height gain in adolescence.

This study used data from the Swedish Medical Birth Registry between 1982 and 1995 to address the question of whether there is higher mortality in twins in relation to singletons of the same gestational age and to examine the optimal gestational age range for twins. A "varying-coefficient approach" was adopted to estimate the gestational age-specific relative and absolute risks of mortality in twins and singletons, adjusting for size at birth and risk factors of short gestational duration. The models showed that twins born between 29 and 37 weeks of gestation had lower mortality than did singletons of the same gestational age. Twins born at older gestational age had higher mortality than did their singleton counterparts, because longer gestational duration was more advantageous to singletons than to twins. Without adjustment for size at birth, there was an upturn of mortality in twins born after 38 weeks. It is postulated that twins have better health than singletons initially, but they could not enjoy the benefit of a longer gestational duration as much as singletons could. The optimal gestational age for twins appeared to be 37-39 weeks according to neonatal and infant mortality.

Objective: To identify the risk factors of obesity in preschool children in China., Design: A nationwide case-control study in eight cities in China., Subjects: A total of 748 boys and 574 girls (age 0.1 - 6.9 y), including the obese and non-obese. One obese child was matched with one non-obese child by sex and age., Measurements: Weight, height and other measurements were taken for all the subjects. The information on child activity, feeding pattern and family background was collected by our study team from the parents and the kindergarten teacher., Results: Birth weight > or =4.0 kg, high eating speed, obesity among the child's relatives > or =25%, mother's body mass index (BMI) > 25 kg/m2 and father's BMI > 25 kg/m2 were identified as the major significant (P < 0.05) risk factors of obesity in preschool children in China., Conclusion: Family history of obesity, high birth weight and eating speed were identified as the risk factors of obesity in preschool children in China. Our results show the need for family therapy as part of an intervention program for childhood obesity, which includes behavior modification.

It is commonly agreed that birth weight is associated with blood pressure in adults. However, not much is known about birth length, ponderal index, and early postnatal growth, whose effects on adult blood pressure, if any, can affect the interpretation of the birth weight-blood pressure association. This study examined the association between fetal growth, early postnatal growth, and blood pressure in Chinese adults. One hundred twenty-two subjects born in Hong Kong in 1967 were followed from birth to age 30 years. Multiple linear regression was used to analyze the association between size at birth, postnatal changes in body size, and systolic and diastolic blood pressure at age 30 years. Having adjusted for potential confounders and each other explanatory variable, it is found that birth length standard deviation score (regression coefficient or beta=-3.2), ponderal index at birth (beta=-1.8), and postnatal changes in ponderal index from age 6 months to 18 months (beta=-2.2) were inversely associated with systolic blood pressure (each P<0.05). Postnatal changes in length standard deviation score were not significantly associated with systolic blood pressure. Birth length standard deviation score was inversely associated with diastolic blood pressure at age 30 years (beta=-2.6; P<0.05). Other anthropometric variables were not associated with diastolic blood pressure. The results support the hypotheses that both fetal growth and early postnatal growth may have a long-term impact on blood pressure in adults. It also highlights the importance of differentiating length and weight for length.

Obesity is associated with elevated blood pressure (BP) both in adults and children. Childhood obesity has become a severe health problem, especially during the last few decades. So far there has not been any large-scale study specifically focusing on the association between obesity and BP in early life. The aim of this study is to examine systematically the association between obesity and BP in preschool Chinese children in mainland China. In 1996, measurements of weight, height, and BP values were collected in a nationwide, case-control study of 748 boys and 574 girls who ranged in age from 0.1 to 6.9 years in 8 cities in mainland China. One obese child and 1 nonobese child were matched for gender and age. The BP differences of the mean-matched pair were approximately 5 mm Hg for systolic blood pressure (SBP) and approximately 4 mm Hg for diastolic blood pressure (DBP) (P<0.05); a higher value was noted in obese children. The BP value of 19.4% children in the obese group and 7.0% children in the nonobese group was higher than the 95th percentile value (P<0.0001), which is defined as high BP by the Task Force on Blood Pressure Control in Children. Both SBP and DBP were significantly (P<0.05) positively related to body mass index (BMI) values (P<0.05) for children in obese and nonobese groups after adjustment for age, gender, and height. To be specific, an increase of 1 BMI unit was associated with, on average, an increase of 0.56 mm Hg and 0.54 mm Hg in SBP and DBP, respectively, for obese children. In nonobese children, the increase in SBP and DBP was 1.22 mm Hg and 1.20 mm Hg, respectively. An increase in the BMI is conclusively associated with elevated SBP and DBP in nonobese children. Furthermore, an increase in the adjusted BMI was associated with an increase in SBP and DBP in obese and nonobese children.

Previous growth studies have not explored how different growth phases-the fetal, infancy, childhood, and puberty phases-interact with each other in the development of adult shortness. In this paper, the authors attempt to describe the importance of each growth phase for adult shortness and the effect of growth in one phase on other, subsequent phases. The authors analyzed data from a longitudinal population-based growth study of 2,850 healthy, full term Swedish children born between 1973 and 1975. The height values were transformed into a centimeter score (CMS) by subtracting the raw values from the reference mean values for a particular age and sex. Subnormal growth in any growth phase, as defined by a decrease of 3 CMS or more during a growth phase, was associated with significant increased risk for final heights below 0, -6, and -12 CMS. For children with subnormal growth during one, two, and three phases, the percentages for final height below -12 CMS (a standard deviation score of approximately -2) were 0.5%, 9.4%, and 75%, respectively. Most children (57/62) with a final height below -12 CMS had subnormal growth in two or three phases. Height gains during the four growth phases were interdependent. The infancy phase was negatively associated with fetal growth (r = -0.33, p < 0.01); the childhood phase was positively associated with infancy growth (r = 0.21, p < 0.01); and the puberty phase was negatively associated with childhood growth (r = -0.10, p < 0.01).

Unlabelled: The objectives of the present work were to present a new reference for the age at childhood onset of growth and to investigate the secular trend in the timing of puberty in a community-based normal population in Sweden. A total of 2,432 children with longitudinal length/height data from birth to adulthood were used to determine the two measures by visual inspection of the measured attained length/height and the change in growth velocity displayed on a computer-generated infancy-childhood-puberty (ICP) based growth chart. The series represents a sample of normal full-term children born around 1974 in Göteborg, Sweden. We found about 10% of children were delayed (>12 mo of age) in the childhood onset of growth based on the previous reported normal range, i.e. 14% in boys and 8% in girls. Distribution of the age at childhood onset of growth was skewed. The medians were 10 and 9 mo for boys and girls, respectively. After natural logarithmic transformation, the mean and standard deviation (SD) were 2.29 (anti-log 9.9 mo) and 0.226 for boys, 2.23 (anti-log 9.3 mo) and 0.220 for girls, respectively. The 95% normal ranges were 6.3-15.4 and 6.0-14.3 for boys and girls, respectively. The distribution of the timing of PHV was close to the normal distribution. The mean values were 13.5 y for boys and 11.6 y for girls with 1 y SD for both sexes., Conclusion: A downward secular trend in the onset of puberty was clearly shown in the population. The age at childhood onset of growth did not correlate with the timing of puberty (r = -0.01 and 0.05, p > 0.7 and 0.1 in boys and girls, respectively). Normal ranges of the age at childhood onset of growth are in need of revise, as this study indicates. The new reference presented here could be a reliable indicator in further studies.

Unlabelled: It is well known that some adult diseases, such as cardiovascular diseases, may be programmed during foetal life. It is not clear, however, whether final height may be predicted from foetal growth. A longitudinal cohort of full-term healthy Swedish babies (n = 3,650) was followed up from birth to maturity in a population-based growth study. Length or height and its changes were analysed from birth to 18 y of age; 2,807 children, with data available on birth length, final height and parental height, were included in this analysis. The result clearly shows that length at birth relates to final height. In terms of standard deviation scores (SDS), the mean difference in length at birth from the mean was greatly decreased in final height, but retained the same order as was seen at birth. In terms of centimeter difference from the reference mean values, the difference in length at birth remained roughly stable into final height. For instance, babies 5 cm above or below the mean birth length will end up approximately 5 cm above or below the mean in final height. Parental height-a surrogate value of the genetic final height potential of an individual-is shown to influence postnatal growth in height strongly. However, the difference from the mean in length at birth remained into adulthood within the same midparental height group., Conclusion: This study reveals that trends in foetal linear growth continue into maturity. Foetal growth is a significant predictor of postnatal growth. Final height is dependent on both the magnitude of foetal growth and the genetic potential in stature, and appears to some extent to be programmed from foetal growth.

Unlabelled: The body mass index or BMI (weight/height2) is a somewhat crude estimate of nutritional status. However, due to its simplicity and high correlation with total body fat, it has been the method of choice in both paediatric clinics and research over the years. Since BMI is not an equivalent measure of the percentage of body fat in different ethnic groups and in the two sexes, population-specific BMI reference data is needed. Several BMI reference values have been published for French, American, British and Hong Kong children in recent years. In Sweden, weight-for-age and height-for-age reference values, which were published in 1976, are still used as the current national growth reference values. Updated growth reference values are needed for assessing nutritional status due to the secular trend toward and increasing prevalence of childhood obesity. The aim of this study was to produce BMI reference values for Swedish children of paediatric age. The series came from a large Swedish population-based longitudinal growth study of 3650 full-term babies followed from birth to 18 y of age. The children in this data set were born in the early 1970s. The pattern and level of 50th centile BMI values presented here are quite similar to those of the Swedish cohort study in the 1950s. In comparison with the US BMI reference values, the Swedish values are much lower, especially for the higher centile values., Conclusion: The new Swedish BMI chart from our study may provide a useful tool for paediatricians to assess body fat, and consequently nutritional status, in Swedish children.

Objective: To assess the prevalence of asthma and other allergies in children in Urumqi and Beijing, compared with that in Hong Kong., Methods: A total of 7754 primary school students were randomly selected to participate in the study. Data were collected in 1995-96 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol for 6- and 7-year-olds. The study design and data quality assurance in all aspects followed the protocol, including the double entry of data., Results: The questionnaire response rate was high (98.9%). Beijing children reported significantly more asthma than those living in Urumqi in three categories: wheezing or whistling in the chest in the past year (6.0%, 95% confidence interval (CI): 5.1-6.9% vs 2.9%, 2.3-3.5%, P < 0.001), sleeping disturbed due to wheezing (1.3%, 0.9-1.7% vs 0.6%, 0.3-0.9%, P < 0. 03) and having experienced asthma ever (10.7%, 9.6-11.8% vs 7.6%, 6. 6-8.6%, P < 0.001). The prevalence of allergic rhinitis (30.0% vs 31. 1% estimated as 12-month nasal symptoms in Beijing and Urumqi, respectively) and eczema (2.8% vs 2.0% recorded as 12-month itchy rash) in the two cities were not significantly different. A similar study was also performed in Hong Kong in 1995 using the same ISAAC protocol. The children in Urumqi and Beijing had fewer (P < 0.05) allergic symptoms compared to those living in Hong Kong (n = 3618). The 12-month prevalence of wheezing, nasal symptoms and itchy rash found in Hong Kong were 9.2% (95% CI: 8.2-10.2%), 35.1% (33.5-36.7%) and 4.2% (3.5-4.9%), respectively., Conclusion: : Urumqi, Beijing and Hong Kong represent communities at different stages of westernization and the results from these three cities reflect a worldwide trend for an increasing prevalence of allergies along with westernization. These three cities could assist in identifying risk factors involved in the increase in asthma, allergic rhinitis and eczema.

Linear growth retardation (stunting) is prevalent (10-80%) in developing countries. It takes place between 6 and 18 mo of age and can be characterized by the delayed onset of the childhood phase of growth. The objective of this work was to study the existence of stunting in early life and, when present, its lifelong effects on final height in a normal healthy population in a developed country. A total of 2432 children with longitudinal height data from birth to adulthood were analyzed. The series represents a normal healthy population-based sample of full-term children born around 1974 in Göteborg, Sweden. We found the incidence of stunting to be about 10% as indicated by delayed onset of the childhood phase of growth (>12 mo of age): 14% in boys and 8% in girls. In a multiple linear regression model, final height was described by length at 6 mo of age, age at onset of the childhood phase of growth, and age at peak height velocity during puberty. All three measures contributed significantly (p < 0.05) to final height with a total R2 of 0.33. A final height difference of 5.0 cm could be explained by abnormal onset of the childhood phase of growth in this normal population. The timing of the childhood onset of growth did not correlate with the timing of puberty. For the first time, we can conclude that stunting in early life is not only a problem in developing countries. Its importance on final height achieved is clearly shown, even after controlling for the timing of puberty.

Racial group studies have identified differences in the occurrence of congenital heart disease (CHD) among ethnic populations. The aim of this study was to characterize the proportionate frequency and clinical profile of children with symptomatic cardiac abnormalities in Hong Kong. The hospital records of 666, mainly Southern Chinese children with symptomatic CHD, who were 4 years of age or younger and who were admitted to Grantham Hospital, Hong Kong, in 1994 and 1995 were analyzed retrospectively. Left-to-right shunting (45.0%) and pulmonary outflow obstruction (34.4%) were the most frequently diagnosed categories, followed by left ventricular outflow obstruction (8.3%), transposition of the great arteries (4.2%), conditions with intracardiac mixing (3.9%), and other cardiac lesions (4.2%). Compared with Western studies, pulmonary outflow obstruction (p<0.0001), particularly tetralogy of Fallot and critical pulmonary stenosis, were more frequent in Chinese children. In contrast with previous reports, coarctation of the aorta (5%) does not seem to be uncommon in Chinese patients. Conversely, aortic stenosis and hypoplastic left ventricle may be rare in these children (1% vs 3% and 3-7%). Other cardiac lesions showed no consistent racial difference in the frequency of occurrence. Chinese patients with Down's syndrome had ventricular septal defect (38%) as the predominant lesion followed by atrioventricular septal defect (25%). Western studies usually report a reverse pattern for these two lesions. The mortality rate for the total cohort was 7.5%. However, of those with conditions with intracardiac mixing and left ventricular outflow tract obstruction many did not survive childhood (20% and 21%, respectively).

Objectives: It has been known that size at birth is important for postnatal growth and final height. However, there are few data in the literature on the difference in height growth patterns from fetal size to final height between less privileged and more privileged populations. The aim of this study was to describe the important features in height growth from birth to maturity in an underprivileged Hong Kong Chinese cohort in comparison to a more privileged Swedish cohort., Methods: The longitudinal height growth data from birth to maturity in full-term healthy Hong Kong Chinese children (n=132) who were born in 1967 were analyzed, and compared with those for Swedish children who were born in 1973-75 (n=3650)., Results: Children with longer birth length achieved taller adult stature with respect to their target height. The mean final height retained the same order as that of the mean length at birth for various birth length groups. All children in the Hong Kong Chinese series showed catch-down height growth during the first 2 years of life, in contrast to the catch-up in smaller babies and catch-down in larger babies for the Swedish series. The growth deficit for the Hong Kong Chinese was -0.9 SDS at birth, -1.8 SDS at 2.0 years of age, -2.1 SDS at 8 years of age, and -1.7 SDS at final height., Conclusions: Fetal size is important for postnatal growth and attained final height with respect to a child's familial genetic potential in stature, not only for privileged populations, but also for underprivileged populations. However, children in underprivileged populations experience a persistent increasing growth deficit during infancy and childhood. Special attention should be given to monitor their growth status in early years and to institute appropriate intervention programs.

Obesity in adults is associated with an increased mortality rate from various diseases. Childhood overweight or obesity may persist into adulthood, and for this reason it is important to identify such children at risk. The data were taken from a larger longitudinal growth study of 3650 full-term and healthy Swedish babies followed from birth to 18 y of age. Body mass index (BMI) was used to estimate (during the pediatric years) the risk of obesity at 18 y of age. A probability chart for becoming overweight (>25 kg/m2) by 18 y of age was constructed, For example, in girls, a BMI of 16 kg/m2 at 4 y of age is associated with a 20% risk of attaining a BMI value over 25 kg/m2 at 18 y, and in boys at 4 y of age, a BMI of 19 kg/m2 leads to a 60% risk that they will have a BMI value over 25 kg/m2 at 18 y. The probability risk charts for adult overweight developed here is the first one presented. They provide an easy and novel instrument to use to identify those children who are at high risk of becoming obese adults, so that they may have clinical intervention at younger ages.

Objectives: The objectives of this study were to investigate early linear growth retardation and to identify potential risk factors for it., Methodology: A community-based prospective study was performed in Chongqing, China, with infants being examined at 12 and 15 months of age. A total of 101 infants were examined twice. Supine length, bodyweight, lower leg length, head circumference, middle upper arm circumference and biceps skinfold thickness were measured., Results: The prevalence of short stature (length-for-age standard deviation score, < -2) was 22% and 23% at 12 and 15 months of age, respectively, while the incidence of growth stunting (low growth velocity) between 12 and 15 months of age was 24%, using the stunting screening method. A mother having a history of abortion and infants having current episodes of diarrhoea were identified as risk factors for growth stunting., Conclusions: We conclude that both short stature and growth stunting are common in the population studied. The stunting screening method used is applicable in developing communities.

Target height, the genetic potential in stature, is commonly estimated by the corrected midparental height (CMH) method. A new model for estimating target height has recently been introduced based on a large, Swedish, population-based study. The aim of this study was to compare the validity of the two methods for estimating target height in Hong Kong Chinese children. The Hong Kong Chinese were more than 10 cm shorter than the Swedes in stature. The secular increase in height over the two generations, however, was 4.2-4.8 cm for the Hong Kong Chinese, much larger than that of the Swedes (0.7-1.0 cm). The two populations are thus at different stages in the secular trend. The new model derived from Swedish population for estimating target height was shown to be applicable to Hong Kong Chinese children; the mean of residual final height values was close to zero (-0.15 cm, p = 0.74). However, the mean of residual final height was significantly above the expected value of zero (4.5 cm, p<0.0001) when the CMH method was applied to the data, which implies an underestimation bias of 4.5 cm. Consequently, if the CMH method is used to estimate target height and evaluate growth hormone treatment responses in short children, it may inflate the treatment response by 4.5 cm. In conclusion, the recently proposed model for target height estimation offers a better alternative for estimating target height in Hong Kong Chinese children and for assessing growth-promoting treatments.

Objective: Previous growth studies on children born small for gestational age (SGA) indicate that birth length, weight, and target height are important predictors for postnatal catch-up growth in SGA. Their influences on different phases of catch-up growth are still not described. The aim of this study was to clarify the influences of target height, length, and nutritional status at birth on different phases of postnatal catch-up growth (infancy, childhood, puberty) in SGA and the long-term consequences., Methods: Data were obtained from a longitudinal population-based growth study on Swedish children (N = 2815). Primary outcome measurements include heights, the changes in height standard deviation scores (SDS) during various phases of growth and relative risk for adult shortness., Results: The difference in final height in children born SGA was attributable to their difference in target height and the magnitude of catch-up growth during the first 6 months of life, rather than the difference in length or body mass index (BMI) at birth. Length at birth showed negative influence on catch-up growth during infancy (0 to 2 years of age), but no significant influence thereafter. The BMI or weight for length SDS at birth showed no significant influence on catch-up growth during any growth phase. Target height showed positive influence on catch-up growth from the onset of childhood. Neither target height nor length and BMI at birth showed any significant influence on catch-up growth during puberty. The magnitude of catch-up growth during infancy, especially the first 6 months of life, is most critical in decreasing risk at adult shortness. We confirmed that the SGA group had a sevenfold greater risk for adult shortness than the non-SGA group (relative risk = 7.31; 95% confidence interval: 3.96-13.52). However, approximately 40% of children who were below -2 in height SDS at 2 years of age remained short at final height in both SGA and non-SGA groups. The mean height SDS of children born SGA increased by 1.65 from birth to final height, but the length deficit in centimeters at birth (-5.4 cm) persisted into adulthood (-5.9 cm)., Conclusions: BMI at birth is not related to postnatal catch-up growth in infants born SGA, but birth length and target height are important. The genetic influence on catch-up growth appears to start from the onset of childhood. Being born short or becoming short during the first 2 years of life is similar in terms of risk for adult short stature.

The prevalence of asthma among schoolchildren in Costa Rica is very high -- at the level of 20-30% -- and the reason is still unknown. A group of children from our previous epidemiologic study was randomly selected in order to establish the relation between asthma symptoms and allergy sensitization to common allergens. Serum samples from children with and without asthma were analyzed for the presence of IgE antibodies to 36 different allergens, for the presence of IgE antibodies to a pool of 10 common allergens, and for total serum IgE. The most prevalent IgE antibodies were those to mite, cockroach, dog, and house-dust allergens with MAST pipettes for the serologic measurements. Positive reactions to house dust, mite, cat, and the two molds (Alternaria and Cladosporium), and food allergens such as egg white, peanut, and shellfish were significantly more prevalent among the asthmatics than the nonasthmatics. Sensitization was equally prevalent at different ages, but the house-dust, mite, cat, dog, cockroach, Alternaria, and egg-white allergens had sensitized boys more often than girls (P < 0.01). The result of the analysis of IgE antibodies to a pool of 10 common allergens by Phadiatop supported the MAST pipette results, showing allergen sensitization in 57.7% of the asthmatic children and 42.3% in the nonasthmatic group. The concentration of IgE was significantly higher among the asthmatic children (372.2 kU/l) than among the nonasthmatic children (249.1 kU/l) (P < 0.00001). Parasitic infestations were not examined in this study, but in most of Costa Rica these have largely been eliminated and could not explain the high total IgE levels. Our data indicate that the very high prevalence of bronchial asthma in Costa Rican schoolchildren can be related to sensitization, especially to airborne indoor allergens such as those of mites, cockroaches, and dogs.

The corrected midparental height method was introduced by Tanner in 1970 (Tanner method) and is commonly used to estimate target height in children to evaluate the effectiveness of growth-promoting therapies. It has not been established if the equation used to compute target height should be the same for children with short, normal, or tall parents. In this study, we examined the predicted target height values by parental heights in a large population-based study (n = 2402). A simple linear function of midparental height (x) was proposed to estimate target height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95% predicted interval of about +/-10 cm. The prediction model was similar for boys and girls in SD scores (SDS), and was not affected by assortative mating or difference in parental heights. The model may underestimate the potential stature by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In comparison, the Tanner method may lead to a 6-cm error in underestimating target height for these children. The function would be a better choice than the Tanner method for estimating target height in the clinical evaluation of growth promotion treatments because it is common that short children also have short parents. Children with very short parents will usually be much taller than their parents in adult stature, and we believe that a different function should be developed. The results support the proposed nondominant, non-sex-linked, polygenic inheritance in stature. The estimated heritability values were 0.75-0.78 in cm or 0.55-0.60 in SDS.

Helicobacter pylori causes chronic inflammation of the gastric mucosa and has been identified in tracheobronchial secretions. Serum IgG against H. pylori was therefore measured prospectively in consecutive subjects with bronchiectasis (n = 100; mean age +/- SD 55.1 +/- 16.7 yr), active pulmonary tuberculosis (n = 87; age, 57.3 +/- 19.1 yr), and healthy volunteers (n = 94; age, 54.6 +/- 7.6 yr). Seropositivity was found in 76.0% of bronchiectatic subjects, which was significantly higher than that of the control (54.3%, p = 0.001) and tuberculous (52.9%, p = 0.0001) groups. Multiple logistic regression, adjusted for age, sex, occupational social class, and number of persons living in the household, showed that H. pylori IgG levels of the bronchiectatic group were still significantly higher than that of the control (p = 0.0014) and tuberculous (p = 0.0154) groups. Multiple regression analysis revealed associations between H. pylori serology and sputum volume (p = 0.03) and age (p = 0.001) in the bronchiectatic patients, but not lung function indices or causes of bronchiectasis. The H. pylori seroprevalence in bronchiectasis was significantly (p = 0.0002) higher in patients who produced more (83.1%) than those who produced less than 5 ml sputum/24 h (58.6%). This is the first report of a high H. pylori seroprevalence in bronchiectasis which appears to be specific. Further studies are indicated to evaluate the possible pathogenic role of H. pylori in bronchiectasis.

The aims of this study were to determine the number of randomised clinical trials where the correspondence address included the words 'Hong Kong' for the years of publication between January 1987 and December 1996, and to study their characteristics: year of publication, disease area, sample size, and correspondence address of the department and institute; MEDLINE EXPRESS was used for the search. A total of 5605 publications were identified, of which only 170 (3.0%) were found to be randomised clinical trials. No significant increase in the proportion of randomised clinical trials could be seen during the decade of publication (P>0.05). Approximatley 50% of the trials had a small sample size (fewer than 75 subjects) and most randomised clinical trials were performed in the field of internal medicine, followed by surgery, and obstetrics and gynaecology (total, 69%). The predominant research area was gastrointestinal disease (34%). Despite a relatively high academic output from Hong Kong, the number of randomised clinical trials has not increased much during the decade.

Objective: To study the effect of the body proportion and pubertal growth spurt on the stature of children with beta-thalassaemia major., Methods: The height, sitting height, upper to lower segment (U:L) ratio and pubertal development were determined in 71 Chinese children (38 girls and 33 boys) with beta-thalassaemia. The growth patterns of 20 patients with complete growth data between 3 years and final height, were analyzed according to whether they underwent a pubertal growth spurt or not., Results: 27% of the boys and 32% of the girls had a height below the 3rd percentile. About 60% of all the children had a U:L ratio below the 10th percentile for age. Abnormal body proportion was found in patients with or without growth retardation. 34% of the 41 children over the age of 14 years underwent spontaneous puberty. In 28 patients over the age of 16 years, a growth spurt was observed in 46% of the children during spontaneous or induced puberty. The retrospective analysis showed that the height deviation from the mean in adulthood was significantly higher in patients without pubertal growth acceleration than in those with a growth spurt (x = -11.8 cm, s = 7.6 cm vs x = -4.4 cm, s = 4.4 cm; P = 0.02)., Conclusions: An abnormal U:L ratio was commonly observed in patients with beta-thalassaemia major and may be one factor contributing to the short stature of these patients. Abnormal puberty was present in a significant proportion of children and the lack of a pubertal growth spurt was found to be detrimental to adult height.

Background: We propose a modification of the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method to study the cytotoxicity of bilirubin. The original method involves reading the intensity of a purplish blue color resulting from the conversion of MTT to formazan crystals by the mitochondria of viable cells. We have found that when the method is applied to study the effect of bilirubin on growing cells, precipitation of the yellow bilirubin pigment interferes with the colorimetric reading., Methods: A human liver cell line was used. The interference of bilirubin deposition on the MTT assay was investigated by comparing the value of optical density of the MTT solution in the presence and absence of bilirubin. The effect of 0.04 mol/L HCL-isopropanol on the bilirubin precipitate was tested by recovering the amount of bilirubin from the wells after the isopropanol treatment., Results: Bilirubin deposition increases MTT reading by 10-24%. Hydrochloride-isopropanol (0.04 mol/L) dissolves MTT formazan only without disturbing the bilirubin precipitates. The bilirubin extracted into the supernatant was less than 5% of the total bilirubin deposited., Discussion: This indirect MTT assay, as developed in this study, could eliminate the interference of bilirubin deposits and serve as a good method for the study of bilirubin cytotoxicity.

Evidence-based medicine shifts the basis for clinical decision making from intuition and unsystematic clinical experience to the examination of evidence resulting from clinical research. Evidence-based medicine is the same as good clinical research. The selection of a proper study design for a specific study objective is the most important cornerstone of good clinical research. Evidence-based medicine places great importance on the design of a study, with optimum evidence being obtained from the randomised, controlled clinical trial. However, various study designs are equally important-if properly used-in the process of searching for solid and important evidence for use in clinical practice. There should be an emphasis on a quality improvement shift in research design from retrospective to prospective, cross-sectional to longitudinal, uncontrolled to controlled, and non-randomised to randomised. The reasons for using suboptimal study designs in clinical research are the lack of formal research training and the pressure to obtain academic output without being motivated. Research design is one of the most important aspects to study and practice, and there are four simple rules: (1) avoid retrospective studies; (2) focus on prospective studies; (3) use controls, randomisation, and blinding; and (4) always discuss the research design with an experienced researcher or statistician before commencing the study.

Training courses in the concepts of clinical trials research methodology that include rules in good clinical practice have not yet been extensively implemented in Hong Kong. This study aims to define the current knowledge of rules in good clinical practice and identify any need for such training programmes. Between May and August 1996, 161 clinical research staff were asked non-randomly to fill in a questionnaire about their knowledge of research methodology and their interest in specific courses. The median number of correctly answered questions (maximum score, 20) was 5 and the mode was 4, which was the expected score if questions had been answered randomly. Only minor differences in score were detected between doctors, research staff, and industry employees. Many researchers were keen, however, to further their knowledge by attending future courses; on average, each person showed an interest in three of the eight proposed courses. The study shows that the knowledge of rules in good clinical practice among clinical research staff in Hong Kong is poor, but there is nevertheless a demand for training programmes.

A difference in length or height growth is observed between populations in developing and developed countries and, within a country, between well-off and poor subpopulations. The aim of this community-based study was to identify possible risk factors for growth stunting in early life using the infancy-childhood-puberty (ICP) growth model. A periurban slum, a village and an urban slum, plus a local control group in Lahore, Pakistan, were investigated. In total, there were 425 infants born from September 1984 to March 1987 in the study. Children were followed from birth to 24 months and anthropometric data were recorded at each examination. A well-designed questionnaire was used to collect background information to identify risk factors for growth faltering over this period. The age at onset of the childhood component was determined individually using the ICP growth model. A late onset was defined as onset after 12 months. Univariate odds ratio analysis identified 20 significant risk factors for a delayed childhood onset in the total sample. Backward logistical analysis showed that only six variables were significant, i.e. small number of rooms in a household, episode(s) of diarrhoeal diseases, poor house structure, low body mass index, early end of breastfeeding and birth in warm season. Stratified analysis showed that episode(s) of diarrhoeal diseases and birth in warm season were the only significant risk factors in the two poor areas. This study also found that the impact of diarrhoeal diseases on length growth persisted after allowing for birth season. Seasonal variation in length growth was seen in the age at onset of the childhood component. General socioeconomic status was found to be a risk factor for growth faltering in early life. Diarrhoeal diseases and being born in a warm season are particular risk factors for growth faltering in early life.

Aims: Growth stunting is prevalent in developing countries. The prevalence of stunting ranges from 10-80% or more. The critical period for growth faltering in length is between six and 18 months. The aims of this study were 1) to investigate the association between the age at onset of the childhood component and growth stunting in early life; 2) to develop a screening method for identifying any individual infant subject to stunting in early life., Materials & Methods: This community-based longitudinal study was carried out in Lahore, Pakistan. Three studied areas and one local control group were included in the study. There were 425 subjects for whom data were available for determining the age at onset of the childhood component. The onset was defined as an abrupt increase in length velocity. It was determined individually using the infancy-childhood-puberty growth model., Results: The medians of the age at onset of childhood component were 15, 13, 10 and 9 months in the periurban, village, urban and control groups, respectively. The onset was significantly related to both length and length velocity during the critical period of stunting. Based on the distribution of individual length increment from 12 to 15 months, 2.0 and 3.0 cm were chosen as the cut-off points to identify a stunting infant. In the normal onset group, 84% of the children were identified as growing normally; in the delayed onset group, 61% were identified as stunting. Using this screening method, 97% of children have a delayed onset if their length increase is below 2 cm from 12 to 15 months; 99% of them have a normal onset if the increase is above 3 cm over the same period., Conclusions: The age at onset of the childhood component can significantly explain the variations in both length and length velocity in early life. The stunting screening method reported here is simple. It can be used in almost any situation, such as a pediatric clinic or community-based survey.

Objective: To assess the prevalence and risk factors of childhood asthma and allergies in Hong Kong and compare with that in Singapore and Great Britain., Methodology: Parents of 3618 randomly selected 6- to 7-year-old children responded to a questionnaire prepared by the International Study of Asthma and Allergies in Childhood (ISAAC) together with supplementary questions on risk factors., Results: The 12-month prevalences of wheezing, rhinitis symptoms and itchy rash were 9.2%, 35.1% and 4.2%, respectively. Wheezing in the past year was significantly associated with rhinitis symptoms in the past year, itchy rash in the past year, rhinitis interfering with daily activities moderately or severely, kept awake by itchy rash in the past year, parental wheezing (one or both parents), frequent upper respiratory tract infections (URTI), born in Hong Kong and male sex. For girls, the prevalence of wheezing in the past year was lowest when they were born in July/August and highest when born in January/February., Conclusions: The prevalence of allergic disorders in Hong Kong was comparable to that in Singapore and Great Britain. Several potential risk factors such as parental wheezing, frequent URTI, born in Hong Kong, male sex and month of birth in girls were identified.

A large, population-based representative study (n = 3656) has shown that the vast majority of healthy, full-term, singleton infants born small for gestational age (SGA) achieve catch-up growth during the first 2 years of life. Indeed, most of the increase in height SDS occurs by 2 months of age. Children born SGA who do not show postnatal catch-up growth and so remain short at 2 years of age, have a higher risk of short stature (< -2 SDS) in later life, with a relative risk at 18 years of age of 5.2 if born light and of 7.1 if born short.

As Northern Europeans are currently the tallest people in the world, specific growth charts for girls with Turner's Syndrome from this area are needed. Based on height and weight measurements from 598 girls with Turner's Syndrome (372 from the Netherlands, 108 from Denmark, 118 from Sweden) not treated with growth-promoting substances and without signs of spontaneous puberty, we constructed growth charts for height-for-age, height-velocity-for-age, weight-for-age, weight-for-height and Body Mass Index for age. Reference tables and regression equations for mean and standard deviation are provided allowing calculation of Standard Deviation Scores. The height and height velocity curves show a low birth length, gradual deviation from the normal percentile curves without pubertal growth spurt, and a prolonged growth until the early 20s. Mean adult height was 146.9 +/- 7.8 cm. Mean weight-for-age was lower than in normal reference children but height-adjusted weight was higher, except in infancy and early childhood. Further studies are required on the factors influencing the weight-height relationship in Turner's Syndrome.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

The pretreatment mixed cross-sectional and longitudinal height measurements of 203 patients with Turner's syndrome (TS) were analysed. Only one observation was included per year per child and a total of 858 observations formed the basis of the growth study. The mean and SD values were fitted separately by a second-degree polynomial function, giving smoothed growth curves. The spontaneous growth pattern of Chinese girls with TS runs parallel to published Caucasian TS growth curves. The mean final height of Chinese patients with TS was 142 cm compared to 147 cm and 139 cm observed in Northern European and Japanese patients, respectively. Patients with the 46, X, i(Xq) karyotype were found to be significantly shorter, whereas children with the 45, X/46, XY and 46, X, del(Xq) karyotypes were significantly taller among this group of patients. Patients with TS who were disomic for Xp are significantly taller than patients who were monosomic for Xp. Our results suggest that karyotype can have a significant effect on the growth of children with TS.

This short communication discusses the possible influence of final height prediction on the estimation of the growth response to therapy. These influences are illustrated in terms of height at 8 and 18 years of age for 28 prepubertally short boys. On the basis of several treatment simulations and assumptions, we conclude that the mean residual final height; that is, the mean of individual differences between final height and predicted final height, is a robust outcome measure in growth-promoting studies. However, the treatment residual final height (the difference between final height and predicted final height following growth-promoting treatment) was only partially correlated (r2 = 0.27) with the gain due to treatment, but was highly correlated (r2 = 0.75) with the residual final height; thus, growth-response estimations made on the basis of treatment residual final height may be more dependent on the predicted interval, or confidence interval, of final height than on the effect of growth-promoting treatment.

A large number of studies have documented a strong correlation between size at birth and subsequent height, although the reported incidence of catch-up growth and consequently the impact on final height has varied with time and between countries. These variations may be real, but could also be related to a number of methodological problems. The aim of this study was to explore two important aspects related to postnatal growth after disturbed fetal growth: first, the definition of small for gestational age (SGA), including the selection of cut-off points in defining shortness; and, secondly, the importance of the general socio-economic status of the population with regard to the incidence of growth faltering in early life. Data were analysed from two longitudinal population-based studies, one from Sweden and one from Hong Kong. Of the Swedish cohort, 3.8% had a birth length below -2 SD scores; in the Hong Kong population the corresponding value was 11.9% (Swedish reference values were used in both studies). The following conclusions were made. Size at birth is important for postnatal growth, and the difference in length at birth of 9-10 cm between the two extreme birth length subgroups remains, on average, until maturity. This seems to be true for the two study populations with different degrees of socio-economic development. However, the rate of catch-up growth is highly dependent on the definition of SGA, on the rate of catch-up growth in early life and on the incidence of growth faltering between 6 and 18 months of age.

Growth in 110 children with Legg-Calve-Perthes' disease (LCPD) was longitudinally followed throughout the growth period. The infancy childhood puberty (ICP) growth model, which has the advantage that reference values can be adjusted for the individual age at pubertal maturation, was used. On the average, the children were slightly shorter at birth and they remained short throughout the entire growth period to maturity. At maturity, the boys were 4.4 cm and the girls were 2.5 cm below the reference mean. The growth velocity was normal at the time of diagnosis, prepubertally, and during puberty. Boys and girls differed only in that the boys were more overweight.

We report early linear growth in 73 children (51 boys, 22 girls) with early onset of chronic renal failure (CRF). The inclusion criteria was onset of CRF before 6 months of age, two or more height measurements during the 1st year of life, follow-up for at least 3 years and continuously impaired renal function with a glomerular filtration rate below 50 ml/min per 1.73 m2 at 1 year or later. Only height measurements taken during conservative treatment or dialysis were included. The data were analysed in terms of the infancy-childhood-puberty growth model. There was an age-dependent growth failure in early life leading to an attained height of -3 standard deviation score (SDS) at 3 years of age. Approximately one-third of the reduction in height occurred during fetal life and one-third during the first postnatal months. Between 0.75 and 1.5 years of age height also decreased by 1 SD as a consequence of a delayed onset of the second, the 'childhood', phase of growth in 36% of the patients and by an 'offset childhood' growth pattern--i.e. a return to the infancy phase pattern after onset of the childhood phase--in 60% of the patients. Growth between 0.25-0.75 and 1.5-5 years of age was generally percentile parallel and thus less likely to be affected in CRF with early disease onset. The glomerular filtration rate was not related to the height gain in early life. We speculate that the growth failure during fetal life and the first postnatal months reflects metabolic and/or nutritional influences and the impaired growth at 0.75-1.5 years of age is related to a partial insensitivity to growth hormone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

The aim of this study was to determine the developmental profile of mannose-binding protein (MBP) in preterm infants. MBP was measured in 885 longitudinally collected serum samples from 168 preterm infants, and 63 were genotyped with respect to the codon 54 mutation in the MBP gene. MBP level/codon 54 genotyping were also determined on the cord blood of 146/123 term infants and 138/123 adults, respectively. The best cut-off values of MBP for dividing preterm, term infants and adults into 'low' and 'high' MBP groups were 400 ng/ml (55 low, 113 high), 700 ng/ml (35 low, 111 high) and 750 ng/ml (33 low, 105 high), respectively, by achieving the least number of misclassifications according to the codon 54 mutation. The relative risk of the 'low' groups for presence of the codon 54 mutation compared with 'high' groups were 42.4, 67.9 and 22.9 for preterm, term infants and adults, respectively (P < 0.00001). The gestational age and birth weight of the 'low' (n = 55) and 'high' (n = 113) MBP groups of the 168 preterm infants were 29.5 +/- 2.8 weeks, 30.5 +/- 2.8 weeks (P = 0.03) and 1230 +/- 317 g, 1277 +/- 289 g (P = 0.35), respectively. The mean MBP levels of these two groups of preterm infants were different (P < 0.001) at all ages measured. As a whole group, the MBP level rose from a mean of 500 ng/ml at 25 weeks gestation to 1700 ng/ml at 20 weeks post full-term. The mortality rates of 'low' and 'high' MBP groups of preterm infants were 22% and 12%, respectively (P = 0.113). This difference in mortality was due to gestational age and birth weight standard deviation score (SDS) after adjusting for length of gestation and gender (P = 0.0001) rather than to low MBP levels (P = 0.65). MBP levels were not related to birthweight SDS score (P = 0.26). The mean +/- s.d. MBP levels for preterm, term infants and adults without the codon 54 mutation were 1225 +/- 701 ng/ml (n = 45), 2064 +/- 829 ng/ml (n = 88) and 2473 +/- 1395 ng/ml (n = 95), respectively; the corresponding values for those with the codon 54 mutation were 130 +/- 275 ng/ml (n = 18), 533 +/- 665 ng/ml (n = 35) and 330 +/- 225 ng/ml (n = 28), respectively. Intra-uterine growth retardation in preterm infants does not influence MBP levels. For those without the codon 54 mutation, there is a significant difference in MBP level between the three age groups. For those with the codon 54 mutation, there is a significant difference between preterm and term infants, but not between term infants and adults. We conclude that there is a maturation in MBP levels for preterm infants, and that a moderately low MBP phenotype does not affect survival. We cannot exclude an effect of profoundly reduced MBP levels (characteristic of individuals homozygous for the codon 54 mutation), since no such preterm infant was identified in this study.