Longitudinal follow-up of height up to five years of age in infants born preterm small for gestational age; comparison to full-term small for gestational age infants

OBJECTIVE: This aims to conduct a comparative study of the height catch-up rate in preterm small for gestational age (SGA) infants during early childhood by gestational age and identify the factors affecting short stature in comparison to full-term SGA infants. METHODS: 449 SGA infants (214 full-term infants, 73 infants with gestation of less than 32 weeks, and 162 infants with gestation of more than 32 weeks but less than 37 weeks) from 25 institutions in Japan were assessed for catch-up (> or = -2SD) rate in growth by measuring for length/height at 1 year, 3 years and 5 years of age and the risk factors for no catch-up (< -2SD) at 5 years. RESULTS: The overall length/height catch-up rate was 68% at 1 year, 89% at 3 years and 88% at 5 years. The catch-up rate at 3 and 5 years of age in the group with gestation of less than 32 weeks had a rate of 74%, which was significantly less than the other two groups (approximately 90%). A significant factor associated with short stature at 5 years in the group with gestation of less than 32 weeks was the lower length SD score at time of birth, and for preterm infants born more than 32 weeks of gestation and full-term infants, significant factors were the lower maternal height and head circumference at birth. CONCLUSION: SGA infants born less than 32 weeks of gestation had a higher risk of no catch-up and different factors affecting catch-up compared to preterm SGA infants of gestation more than 32 weeks and full-term SGA infants.     

Born small for gestational age: consequences for growth

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.     

Perinatal predictors of growth patterns to 18 months in children born small for gestational age

AIM: To determine factors before or at birth that are predictive of growth patterns to 18 months in children born small for gestational age (SGA). METHODS: Prospective cohort study of 186 SGA babies. Catch-up growth patterns were defined as early (>10th centile at 6 and 18 months), late (<10th centile at 6 months but >10th centile at 18 months), transient (>10th centile at 6 months but <10th centile at 18 months) or none (<10th centile at 6 and 18 months). RESULTS: Most children (75%) showed catch-up growth by 6 months. Of antenatal variables studied, only early gestation at diagnosis of SGA predicted late or failed catch-up. Late or failed catch-up was also associated with short gestation, small absolute and relative size at birth, increased placental weight/birthweight ratio (Pl/BW) and prolonged neonatal hospital stay. On logistic regression, both late and failed catch-up were associated with short birth length. Late catch-up growth was also associated with prolonged hospital stay and male sex. Failed catch-up was associated with increased Pl/BW. No antenatal or perinatal variables distinguished early from transient catch-up groups. CONCLUSION: SGA babies with late onset and less severe growth restriction have a good chance of catch-up growth by 6 months of age. Catch-up growth is likely to be delayed in SGA babies who are short at birth, are boys, and have prolonged hospital stays. However, poor growth over the first 6 months does not predict later growth patterns. Failure of catch-up growth in babies with increased Pl/BW may reflect an intrinsic growth defect. Transient catch-up growth may reflect environmental factors operating after birth.     

Serum lipid concentrations and growth characteristics in 12-year-old children born small for gestational age

According to Barker's hypothesis, children born small for gestational age (SGA) are at increased risk for cardiovascular diseases in adulthood. The aim of our study was to determine whether retarded fetal growth is associated with dyslipidemia in childhood and, if so, to find predictive factors in the growth characteristics of SGA children. We studied the serum lipid concentrations of 55 SGA children and their 55 appropriate for gestational age control subjects at the age of 12 y. Growth variables were recorded at birth, 5 y, and 12 y of age. The study group consisted of all full-term SGA children born at our university hospital during a 22-mo period in 1984-1986. Nearly half of the SGA children (47.3%) were in the highest quartile for serum total cholesterol of the appropriate for gestational age children (p = 0.038). In multiple logistic regression analysis, poor catch-up growth in height (odds ratio, 13. 8; 95% confidence interval, 2.0-97.5), female sex (odds ratio, 8.1; 95% confidence interval, 1.3-48.9), and early stage of puberty (odds ratio, 7.5; 95% confidence interval, 1.2-46.5) predicted high cholesterol level in the SGA children. By the age of 5 y, 20 (36.4%) SGA children showed catch-up growth of > or =2 SD scores in height, and 21 (38.2%) SGA children showed catch-up growth of > or =2 SD scores in weight from birth. At the age of 12 y, the SGA children were still significantly shorter (p<0.001) and lighter (p< 0.05) than the appropriate for gestational age children, even though their pubertal development was similarly advanced. In conclusion, to be born SGA has long-term consequences for later growth and may already influence the level of serum total cholesterol before the teens. SGA children with poor catch-up growth in height may be at the highest risk for hypercholesterolemia.     

Natural growth in children born small for gestational age with and without catch-up growth

This first report from a population-based postnatal growth study of 3650 healthy Swedish subjects born at full term provides new reference values for height and weight and shows that over the last 20 years there has been a small secular trend in height (0.2–0.4 SDS over the whole age range) in Sweden in both boys and girls. Within this cohort, 111 (3.1%) were of low birth weight (below –2 SDS) and 141 (3.5%) were of low birth length (below –2 SDS); 54 (1.5%) were both light and short at birth. Of the children born small for gestational age, 87% showed full catch-up growth within 2 years of life. They attained puberty at a normal or early age and reached a mean final height of –0.7 SDS. The remaining subgroup of 13% born small for gestational age remained below –2 SDS throughout childhood and reached puberty somewhat early. Their mean final height was –1.7 SDS. The current data set is too small to identify possible background factors, but it is being expanded with this objective in mind.     

Fetal size to final height in Hong Kong Chinese children

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.     

Catch-up growth of supine length/height of very low birth weight, small for gestational age preterm infants to adulthood

OBJECTIVE: To analyze linear growth of very low birth weight (VLBW), small for gestational age (SGA; < 10th percentile) preterm infants from birth as to catch-up or no catch-up growth. STUDY DESIGN: VLBW SGA preterm infants (n = 46) with primarily symmetric intrauterine growth restriction from the Bonn Longitudinal Study were compared with 62 appropriate for gestational age (AGA) VLBW preterm and 73 term infants and with their parents. RESULTS: Forty-six percent of VLBW SGA (21 of 46) had complete height catch-up by adult age, and most became taller than target height (TH) (15 of 21; 71%). The others did not catch up; most of them remained shorter than TH (18 of 25; 72%) after initial catch-up followed by catch-down growth. Mean adult height z-score was lower than that for birth length. Mean body mass index was similar in the catch-up and no catch-up groups (21.8 and 21.3, respectively) and lower than in the controls (23.2). Approximately 1/2 of the head circumference (HC) catch-up children achieved height catch-up as well. CONCLUSIONS: Height catch-up extended beyond age 6 years, independent of HC growth. We could not predict height catch-down or successful catch-up.     

Evaluation of the auxological and metabolic status in prepubertal children born small for gestational age

BACKGROUND: Low birth weight (BW) (<2,500 g) is associated with a high risk of impaired postnatal growth and late metabolic consequences. The aim of this study is to describe the postnatal growth pattern and the metabolic status of children born small for gestational age (SGA) and compare them with premature children born with low (1,500-2,500 g) and very low (<1,500 g) BW. CHILDREN AND METHODS: 104 prepubertal children (47 males and 57 females) aged 3.0 to 8.9 years were divided into four groups according to their birth weight adjusted for gestational age (GA): SGA-premature (SGApr): BW < -2 SD, GA <37 wk (n = 17); SGA-full-term (SGAt): BW < -2 SD, GA >37 wk (n = 29); low birth weight (LBW): BW = 1,500-2,500 g, GA <37 wk (n = 35); very low birth weight (VLBW): BW <1,500 g, GA <37 wk (n = 23). The control group consisted of 27 full-term appropriate for gestational age, prepubertal children matched for age. All children had anthropometric and laboratory measurements. The HOMA model was used to estimate insulin resistance (IR). RESULTS: Weight, height and body mass index (BMI) were significantly lower in the SGA groups -- both term and premature -- (p <0.05) and particularly lower in the VLBW children (p <0.01). At the age of 36 months, 99.6% of SGAt and a smaller percentage of SGApr (88.2%) children achieved catch-up growth. IGF-I and IGFBP-3 levels were lower in the children born SGA, both term and premature, compared to the controls (p <0.05) and especially in those who had catch-up after the age of 6 months (p <0.002). VLBW children aged 6-8.9 years had significantly higher HOMA compared to controls of the same age group (p = 0.005), whereas no evidence of IR was found in the SGA children. None of the children had developed premature adrenarche by the day of examination. CONCLUSIONS: Prepubertal children born SGA and VLBW are thinner and shorter than their age-matched controls. A larger percentage of SGA full-term children achieve catch-up growth than SGA premature children by 3 years of age. SGA children and especially those with late catch-up growth have lower IGF-I levels. Children with VLBW show evidence of IR at age 6-8.9 years. None of the girls showed precocious sexual development by the day of examination.     

Intrauterine growth retardation: diagnostic and therapeutic approach

Intrauterine growth retardation (IUGR) refers to the fetal growth pattern and assumes that at least 2 intrauterine growth assessments are performed, indicating a low growth velocity in the fetus. The term "small for gestational age" (SGA) does not refer to fetal growth but to the size of the infant at birth. Infants with SGA have a low weight and/or length for their gestational age at birth below the 10(th) percentile or -2 SD. Approximately 3-5% of all newborns are born SGA. The etiology of SGA/IUGR is not known. The majority (80-85%) of infants born SGA catch-up within the normal range by 2 years of age. SGA has also been associated with increased prevalence of hypertension and dyslipidaemia at a relatively young age. Most controlled trials have shown a beneficial effect of GH treatment. The growth response seems to be due to the cumulative dose received, parenteral adjusted height standard deviation score (SDS) and bone age pretreatment, baseline overnight peak of GH and IGF-I levels. During GH treatment, children born SGA show a significant increase in fasting levels of insulin and proinsulin and a decrease in insulin sensitivity. Fasting glucose levels significantly increase. All these effects are reversible upon interruption of treatment. However, fasting insulin concentrations as well as glucosylated hemoglobin must be carefully monitored during GH treatment. Total cholesterol, LDL cholesterol and the atherogenic index significantly decrease during GH treatment. An acceleration of bone maturation with GH treatment has been reported even though a gain in height SDS for bone age is demonstrated.     

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children ( n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age. GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.     

Small for gestation and growth hormone therapy

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<−2SD) and do not achieve normal adult, height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above-2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.     

Catch-up growth in appropriate- or small-for-gestational age preterm infants

The aim was to evaluate postnatal growth of preterm infants in childhood and to determine factors that have an effect on catch-up growth (CUG). Ninety-six (42F, 54M) preterm born children with a gestational age of 32.6+/-2.9 weeks and birth weight of 1815+/-668 g were evaluated at age 4.7+/-1.1 years. Preterm children with birth weight and/or length below 10th percentile were accepted as small-for-gestational age (SGA) and those above as appropriate-for-gestational age (AGA). Height SDS was similar (-0.5+/-1.0) in preterm AGA and SGA children. Both groups had low body mass index (BMI) SDS (-0.6+/-1.4 and -1.0+/-1.5, respectively). Of the preterm SGA children, 65.8% showed a CUG in height and 3.8% catch- down growth. These rates were 24.6% and 33.5% in preterm AGA children. CUG in height was best explained by birth length and mother's height and CUG in weight by birth weight and mother's weight. In conclusion, although most of the preterm SGA children show CUG, they reach a compromised height in childhood. A number of preterm AGA children show a catch-down growth.     

Fetal growth regulation and intrauterine growth retardation

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.     

Final height in short children born small for gestational age treated with growth hormone

The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below -2) prepubertal children born SGA (below -2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 microg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r=-0.56, p<0.0001), shorter (r=-0.49, p<0.0001), and lighter (r=-0.46, p<0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.     

Time course of catch-up in adiposity influences adult anthropometry in individuals who were born small for gestational age

Although necessary for a normal final height in individuals who were born small for gestational age (SGA), catch-up growth is associated with drastic changes in body composition that have been suspected to favor the later development of the long-term metabolic complications by promoting central adiposity; however, the specific contribution of catch-up itself on these later complications remains unclear. Therefore, the aim of the study was to characterize the dynamic changes in adiposity during childhood in individuals who were born SGA and to investigate their consequences on adulthood. The magnitude and the time course of postnatal changes in body mass index (BMI) relative to birth and their consequences on adult adiposity were investigated in 127 adults who were born SGA and had available serial anthropometric data in childhood (0-6 y) and adulthood. Catch-up in BMI, observed in 91% of individuals who were born SGA, was mostly completed within the first or second year of age. Overall, adult BMI was correlated with the magnitude of gain in BMI during childhood. However, this effect was significant only when this gain persisted after the first year of life. Similarly, the influence of the magnitude in gain in BMI on the risk for adult BMI >25 kg/m(2) was significantly influenced by the age at which the gain in BMI occurred. In summary, although the extent of catch-up in BMI affects adiposity in adulthood, this effect is mostly deleterious when occurring after 1 y of age, suggesting that a rapid catch-up process should be more suitable than a delayed one. Whether this observation holds through regarding the metabolic syndrome remains to be elucidated.     

294例宫内发育迟缓儿出生2年内的身长追长观察

目的：对294例宫内发育迟缓（IUGR）儿童出生2年内的身长追长观察,了解不同性别、不同胎龄、不同出生体重IUGR儿身长追长情况。方法：294例IUGR儿童与300例足月正常儿在出生后4、6、9、12、15、18、21、24月龄随访,测量其身长,计算身长增长值,比较身长增长情况。结果：IUGR儿童身长追长成功率男女分别为72.2%和71.5%（P=0.90）;早产小样儿与足月小样儿追长成功率分别为77.4%、68.6%（P=0.11）;出生体重1500~2499 g者的身长追长成功率较出生体重<1500 g和≥2500 g者高（P<0.01）。IUGR男童在4、6月龄及18、21、24月龄测得的身长增长值明显高于正常儿（P<0.05）;女童在4、6、9、12及21月龄测得的身长增长值明显高于正常儿。男童早产小样儿在6月龄及9月龄身长增长值明显大于足月小样儿,女童早产小样儿在4月龄及18月龄身长增长值明显大于足月小样儿。不论男女,出生体重<1500 g者在4月龄身长增长值均明显大于≥2500 g者;男童1500～2499 g者在4、6、18、21及24月龄身长增长值明显大于≥2500 g者,女童1500～2499 g者在4、6、9、12及21月龄身长增长明显大于≥2500 g者。结论：IUGR女童的追长以出生后第一年为主,而男童除出生半年内追长外,在出生第二年仍追长明显。早产小样儿的追长比足月小样儿好。出生体重<1500 g者及1500～2499 g者的追长比≥2500 g者好。     

Postnatal consequences of intrauterine development: pubertal development in children born small for gestational age

Five to ten percent of all children are born small for gestational age (SGA). SGA children are not only at risk of remaining small as an adult in case of lacking catch-up growth, but may develop several metabolic disturbances which might have a serious impact on the future health of these children. In this context, several studies described abnormalities of the pubertal development in SGA children, especially in SGA children demonstrating rapid postnatal weight gain. This review highlights the current knowledge of the relationship between auxiological birth para-meters and subsequent pubertal course, and the interrelationships between puberty and growth in SGA children with and without growth hormone therapy.