Growth and development of term disproportionate small-for-gestational age infants at the age of 7 years

Twenty-four term infants with disproportionate intrauterine growth retardation (SGA group) and 24 normally grown term infants matched for age, sex, birth rank and social class were followed from birth until 7 years of age. Both groups were free from perinatal complications and chronic diseases. The children in the SGA group continued to be underweight-for-height with a low ponderal index and a relatively small head circumference at the age of 7 years. Only minor shifts occurred in the individual growth curves since the age of 3 years. In 12 SGA children and 1 control multiple 'soft' neurological signs were found. Their grammar school teachers observed problematic behavior (hyperactivity, poor concentration and clumsiness) in 9 and academic problems in 5 of the 12 SGA children with neurological dysfunction. These findings indicate that disproportionate intrauterine growth retardation at term can have long-term effects on growth and development.     

Aetiology and classification of small for gestational age infants

Objective: To determine important aetiological factors in small gestational age (SGA) infants and the effectiveness of anthropometric indexes in identifying patterns of growth retardation.
Methodology: Eighty-four SGA infants and 81 controls were enrolled. Maternal biological, lifestyle and psychosocial factors were compared for the total group and the term Caucasian subset. Anthropometric indexes were also examined in relation to growth patterns.
Results: Decreased maternal size, poor weight gain, previous SGA infant and smoking were significantly associated with SGA status. Poor parental education and unemployment was increased in the study group. Mothers of SGA infants, especially the term Caucasian group, had a greater prevalence of hypertension and depressive and stress symptomatology. Ponderal index failed to identify discreet patterns of disproportionate/proportionate growth retardation.
Conclusion: Biological, lifestyle and psychosocial differences remain important aetiological factors of intrauterine growth retardation. Identification of specific patterns of growth retardation by ponderal index remains controversial.     

Serum insulin-like growth factor 1 and serum growth-promoting activity during the first postnatal year in infants with intrauterine growth retardation

Follow-up from birth to age 12 months was obtained in 21 infants born with intrauterine growth retardation. Serum insulin-like growth factor 1 was measured by radioimmunoassay. The bioassayable growth-promoting activity of the serum was measured as the "thymidine activity" on lectin-activated lymphocytes at 5 days and 1, 3, 6, 9, and 12 months, and was compared with control values. Depending on their length at age 12 months, the intrauterine growth retardation infants were divided into three groups: at or above the average (n = 8, group A), between the mean and -2 SD (n = 7, group B), or less than -2 SD (n = 6, group C). No differences in nutritional indexes or in head circumference were found between the three groups. Insulin-like growth factor 1 was significantly lower at age 5 days in intrauterine growth retardation than in control infants. It increased slowly in groups A and B to reach the control values at age 9 and 12 months. In group C it remained significantly subnormal at 1 yr of age. Thymidine activity was also significantly lower at age 5 days in intrauterine growth retardation compared with control infants. It increased sharply at age 1-3 months in groups A and B but remained significantly lower in group C up to 1 yr of age. Although individual values of insulin-like growth factor 1 and thymidine activity were closely correlated, the increase of length during the first postnatal year correlated significantly with the thymidine activity levels at 1 and 3 months but not with the insulin-like growth factor 1 levels at 1, 3, and 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

THE CLINICAL GROWTH OF INFANTS AND CHILDREN WITH VENTRICULAR SEPTAL DEFECTS1

A study was undertaken of the relationship of the haemodynamic disturbance of ventricular septal defects to the growth of affected subjects. Stunting was observed, particularly with respect to weight, and occurred mainly but not exclusively in subjects with a large defect. Some subjects already exhibited stunting at birth with evidence of intrauterine growth retardation. By 3 to 12 months of age, the differences in growth between the subjects became marked. There was some improvement subsequently, related in part to improvement in the haemodynamic disturbance. The pertinent literature is reviewed and the possible mechanisms of the multiple factors involved in the growth retardation are discussed.     

Classification schemes of small-for-gestational age and type of intrauterine growth retardation and its implications to early neonatal mortality

Classification of small-for-gestational age (SGA) and pattern of intrauterine growth retardation (IUGR) and their relationship to early neonatal mortality (first 3 days) were studied in a population of 9201 full-term infants in a maternal and child center in Mexico City. SGA infants were classified on the basis of two methods: one, using the tenth percentile of a birth weight (BW) by gestational age reference growth distribution, and the other, using a cut-off point of birth weight of 2900 g. Crown-heel length (CHL) and Rohrer's ponderal index (PI = BW/CHL3) were used to classify patterns of proportionate and disproportionate IUGR. Overall, infants classified as SGA and type of IUGR had an increased risk of death in comparison to full-term appropriate-weight infants. IUGR proportionate infants with short CHL had a significantly greater mortality than disproportionate IUGR infants with normal CHL. A slightly but not significantly greater mortality was observed for IUGR disproportionate versus proportionate using PI regardless of the method of SGA used. The combination of misclassification for SGA and for type of IUGR were examined relative to the availability of gestational age and the uses of data for clinical management versus research. It is concluded that hospitals may tolerate misclassification of SGA but should pay close attention in assessing the pattern of IUGR when evaluating the mortality of newborn term infants.     

Low birth weight and intrauterine growth retardation in Filipino infants

Low birth weight, prematurity, and intrauterine growth retardation represent important health tasks for neonates. Pregnancy outcome risk categories based on combinations of these variables and a measure of body proportions were developed and tested with respect to how well they predict poor growth during infancy. Data were collected during a prospective community-based survey of births representative of the Cebu region of the Philippines. In the sample of 2139 births for which there were available birth weight and gestational age data, 20% of infants were classified as growth retarded and 12% were low birth weight. Low birth weight, the more conservative category, was a better predictor of small infant size at 12 months of age than intrauterine growth retardation. Rohrer's index, which captures information about patterns of intrauterine growth, improves the positive predictive value of categories based either on intrauterine growth retardation or low birth weight. Infants who had an adequate Rohrer's index, ie, were well proportioned at birth, were smaller at 12 months of age than infants who had a low Rohrer's index, ie, had weight deficits relative to their lengths at birth. Important questions about the value of the intrauterine growth retardation classification are raised by the results.     

Investigation of Growth Hormone Secretion in Patients with Intrauterine Growth Retardation

Rochiccioli, P., Tauher, M., Moisan, V. and Pienkowski C. (Department of Paediatrics, CHU Rangneil, Toulonse Cedex, France). Investigations of growth hormone secretion in patients with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 42, 1989.
Growth hormone (GH) deficiencies have rarely been reported in intrauterine growth retardation (IUGR). This study has investigated GH secretion using GH provocation tests, 24-hour GH secretory profiles, and insulin-like growth factor I (IGF-I) measurements in 24 children with intrauterine growth retardation. The criteria for diagnosis were a birth length and weight below the 10th percentile for gestational age. The average age at investigation was 5.5 years, and the average growth retardation was -3.3 SD. Twenty children had shown catch-up growth between the ages of 6 months and 3 years, followed by varying decreases in growth velocity. Studies of GH secretion demonstrated GH deficiency in 16 patients, with neurosecretory dysfunction in six. Treatment with pituitary GH in nine children increased mean growth velocity from 3.5 cm/year to 7 cm/year. GH therapy should thus be effective in improving the height prognosis of children with intrauterine growth retardation.     

Language development in preschool children born after asymmetrical intrauterine growth retardation

BackgroundAfter intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions.AimThe assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation.MethodsExaminees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed.ResultsThere were statistically significant differences (p < 0.05) in language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference ? head circumference at birth)/(Body weight ? birth weight)] and language outcome. Children with neonatal complications had lower results (p < 0.05) in language comprehension and total expressive language.ConclusionIntrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language.     

Neurology and behaviour of growth-retarded neonates. Relation to biochemical placental function tests in late pregnancy

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.     

Activities of lipase and trypsin in duodenal juice of infants small for gestational age

In 18 low birth weight infants, small for gestational age, with different degrees of intrauterine growth retardation the activities of pancreatic lipase and trypsin and the concentrations of bile acids were measured in preprandially aspirated duodenal juice. The results were compared to those of 24 low birth weight infants, appropriate for gestational age, with comparable birth weights and postnatal ages. The activities of both measured pancreatic enzymes were negatively correlated with the degree of intrauterine growth retardation, expressed as the difference between the individual birth weight and the weight of the 10th percentile of the intrauterine growth curve (lipase: r = -0.697, p less than 0.001; trypsin: r = -0.739, p less than 0.001). The activity of trypsin in the small for gestational age infants was within the range of that found in the infants appropriate for gestational age. However, the lipase activity was decreased in infants who presented with growth retardation of greater than 400 g/kg birthweight. The concentrations of bile acids were similar in both groups (4.60 +/- 2.51 and 4.55 +/- 2.26 mmol/L, respectively) and sufficient for activating the bile salt stimulated lipase in human milk. The data suggest that in intrauterine growth retarded infants the lipase activity in the duodenal juice can be a limiting factor for optimal fat digestion. This should be considered in the nutritional management of such infants.     

Birth weight and adult lung function: a within-pair analysis of twins followed up from birth

Background  The aim of the study was to evaluate whether there is any association between intrauterine growth and later lung function or bronchial reactivity in early adulthood in line with Barker’s hypothesis. Methods  Nineteen twin pairs with disproportionate intrauterine growth pattern were followed up from birth: either one of the pairs had intrauterine growth retardation (birth weight <2 SD) or the within-pair birth weight difference was >1.3 SD. Flow-volume spirometry, followed by isocapnic hyperventilation of cold air, was performed at the ages of 8–16 and 14–22 years in 1993 and 1999. Wilcoxon’s matched-pairs analysis was used to compare smaller and larger twin pairs. Results  In 1993, there were no significant differences between the groups in either spirometry or cold air challenge. In 1999, such a difference was found in forced expiratory volume % (FEV%) and forced expiratory flow (FEF) at 25%–75%, the smaller twin pairs having lower values. In 1993, nine subjects reacted to cold air (>9% decrease in FEV in 1 second). In 1999, only four subjects reacted to cold air, and they all belonged to the group of smaller twins (P=0.04). Conclusion  Lung function evaluated by FEV% and FEF25–75 was lower and responses to cold air were more common at the median age of 16 years in twins with impaired intrauterine growth.     

Alcohol drinking and intrauterine dystrophia. Effects and significance in infancy]

In a prospective study intrauterine growth retardation (IUGR) (less than 10. growth percentile at birth) was used as a predictor to diagnose intrauterine alcohol exposure. An interview about maternal alcohol consumption was performed prenatally--when IUGR was diagnosed by ultrasound--or postnatally. The children were followed up to 18 months of age. In 6/47 children we diagnosed various degrees of the Fetal Alcohol Syndrome FAS, with only one patient showing a full blown syndrome at birth. 5 patients could not be identified until the pediatric reexamination at the age of 8-18 months. IUGR and a maternal history of even moderate drinking during pregnancy should emphasize the possibility of an intrauterine alcohol damage, even in a normal child at birth.     

Is intrauterine growth retardation a risk factor for child abuse?

A case-control study was conducted to determine whether infants with intrauterine growth retardation are at an increased risk of child abuse. Case children were those who had been born at Yale-New Haven Hospital and were reported to the hospital's child abuse committee because they had been physically abused. For each case, one control child was chosen from the hospital's log of births and matched to the case child by age, gender, race of the mother, method of payment for the hospitalization, and the provider of the child's health care at the time of birth. Infants were defined as having intrauterine growth retardation if they had either a ponderal index or a birth weight that was less than the tenth percentile for gestational age using the Kansas City or Denver growth standards. We identified 117 case-control pairs that met those criteria. The matched odds ratios for each of the four definitions of intrauterine growth retardation were less than one, indicating that infants with intrauterine growth retardation are at a decreased risk of abuse. The matched odds ratio for a low ponderal index according to the Kansas City standard was 0.4 (95% confidence interval 0.19, 0.83). This result was not affected by such possible confounding factors as the mother's age. We conclude that infants with intrauterine growth retardation are not at an increased risk and may be at a decreased risk of physical abuse.     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白的关系

目的 检测宫内发育迟缓(IUGR)儿脐血胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,分析这些指标的变化程度与胎儿期生长的关系。方法 将86例脐血标本分为IUGR(即小于胎龄儿)组和适于胎龄儿(AGA)组。采用竞争性放射免疫分析法(RIA)测定IGF-1水平,非竞争性免疫放射分析法测定IGFBP-3水平。两组间比较用t检验,两变量之间的关系采用相关回归分析。结果 与AGA组相比,IUGR组脐血IGF-1和IGFBP-3水平显著降低(P均<0.01);IGF-1、IGFBP-3均随胎龄及出生体重增加而增加(P均<0.01);IGFBP-3与IGF-1呈正相关(P<0.01)。结论 脐血IGF-1和IGFBP-3的含量可作为判断新生儿生长发育程度的一项客观生化指标。     

Aortic vessel wall characteristics and blood pressure in children with intrauterine growth retardation and abnormal foetal aortic blood flow

Blood pressure and pulsatile diameter changes of the abdominal aorta were measured in 68 children (mean age 9 years), with varying degrees of intrauterine growth retardation who were previously examined in their intrauterine life with Doppler velocimetry of the thoracic descending aorta. Diastolic blood pressure was lower ( p < 0.05) and pulse pressure was increased ( p < 0.01) in children with a birthweight small for gestational age as compared to those with a birthweight appropriate for gestational age. Systolic blood pressure was positively associated with relative increase in weight from birth up to the time of examination ( p < 0.01), but not to early catch-up growth. Aortic vessel wall diameters were smaller in children born small for gestational age, both before and after correction for current body surface area ( p < 0.01). Blood pressure and aortic vessel wall characteristics exhibited no relationship to the foetal aortic Doppler wave-form. Changes in foetal haemodynamics associated with intrauterine growth retardation do not appear to contribute to a later increase in blood pressure. Within a group of foetuses with suspected growth retardation, increasing foetal weight deviation and a birthweight small for gestational age is associated with lower diastolic blood pressure at 9 years of age.     

Hypotonia at six years in prematurely-born or small-for-gestational-age children

A neurological follow up study was done of 143 full-term infants who were small for gestational age based on intrauterine growth retardation and of 49 preterm appropriate-for-gestational-age (PTAGA) infants at the age of 6 years. Findings were compared with those of a reference group of 192 full-term appropriate-for-gestational-age (FTAGA) children. In 11% of the children of both study groups, hypotonia was found without any other neurological deviancy. This type of hypotonia was absent in the reference group, whereas minor neurological dysfunction consisting of hypotonia with other neurological signs was found in all the three groups of children. No relation was found with obstetrical or neonatal variables, including severity of growth retardation and gestational age, or with weight, body height or head circumference at 6 years. The possible interference of preterm birth or intrauterine growth retardation with, and the role of placental mechanisms in, fetal and early postnatal muscle development is discussed.     

广州和佛山地区早产低出生体重儿出院时宫外生长迟缓发生情况调查

目的评价早产低出生体重儿出生时宫内生长受限(IUGR)和出院时宫外生长迟缓(EUGR)的发生情况。方法广州市、佛山市10家医院新生儿科出院的早产低出生体重儿(胎龄<37周,体重<2500g),分别以出生时、出院时生长发育指标在相应宫内生长速率期望值的第10百分位水平以下定义为IUGR、EUGR,分别计算各胎龄组、各体重组IUGR、EUGR发生率及总的发生率,并计算各胎龄组、各体重组EUGR发生率比IUGR发生率增加的比例。结果共595例早产低出生体重儿,出生时以体重、身长、头围为指标的IUGR发生率分别为20.2%、16.5%和24.4%,出院时以体重、身长、头围为指标的EUGR发生率分别为42.2%、28.1%和34.3%。不同出生胎龄(<31周、31～32周、33～34周、≥35周)出院时EUGR发生率较出生时IUGR发生率变化的情况:以体重为指标,EURG发生率各组分别增加36.8%、24.8%、19.1%、18.3%;以身长为指标,EUGR发生率各组分别增加26.5%、17.4%、8.2%、6.5%;以头围为指标,各组分别增加26.5%、14.0%、8.2%、3.2%,胎龄越小,增加率越高,组间比较差异有统计学意义(P<0.05)。不同出生体重(<1500g、1500～1999g、≥2000g)出院时EUGR发生率较出生时IUGR发生率变化的情况:以体重为指标,EUGR发生率分别增加45.3%、21.2%、17.4%;以身长为指标,EUGR发生率分别增加29.7%、14.8%、4.6%;以头围为指标,EUGR发生率分别增加26.6%、12.0%、4.3%,体重越低,增加率越高,组间比较差异有统计学意义(P<0.05)。结论早产低出生体重儿IUGR发生率较高,出院时EUGR发生率较IUGR发生率增高,且出院时EUGR发生率较出生时IUGR发生率的增加随出生胎龄和出生体重的降低而升高。     

Abnormal fetal aortic velocity waveform and postnatal growth

Postnatal growth from birth up to 7 y of age was evaluated in 151 children with varying degrees of intrauterine growth retardation who were previously examined in their intrauterine life with Doppler velocimetry of the thoracic descending aorta. The children with abnormal fetal aortic blood flow class (BFC), of which 39/46 (85%) had a birthweight > or = 2 SD below the mean of the population, were lean at birth and had a high rate of catch-up growth in weight and length during the first 3 and 6 mo, respectively. After the initial phases of rapid catch-up in weight and length, mean values of SD scores for weight and height remained relatively unchanged up until 2 y of age, thereafter increasing gradually up to 7 y of age, leaving 4/46 (8%) and 4/46 (8%) below -2 SD for weight and height, respectively. The pattern of changes in length/height and weight over time did not differ between those infants with abnormal BFC and those with normal BFC. The abnormal fetal aortic waveform was not related to rate of early catch-up growth or to height or weight at 7 y of age after adjustment for deviation in growth at birth. The magnitude of deficit in weight and length at birth was more predictive of subsequent growth.     

Body proportionality and head and length 'sparing' in growth-retarded neonates: a critical reappraisal

Despite the popular current distinction between "proportional" and "disproportional" intrauterine growth retardation, it has never been shown that variation in body proportions is greater among growth-retarded than nongrowth-retarded infants of the same birth weight, nor that proportionality is distributed bimodally among growth-retarded infants. Based on a cohort of 8719 neonates born between 1980 and 1986 of mothers with concordant (+/- 7 days) menstrual dating and early ultrasound estimates of gestational age, we used a continuous measure of birth weight for gestational age to define four study groups: nongrowth retarded (n = 5163) and mild (n = 411), moderate (n = 226), and severe (n = 147) intrauterine growth retardation. Compared with non-growth-retarded infants of the same gestational age, growth-retarded infants had substantially lower lengths, head circumferences, and proportionality ratios, and the magnitude of the deficits increased significantly with increasing degrees of growth retardation. When the comparison was based on birth weight rather than gestational age, however, growth-retarded infants had slightly but significantly greater lengths and head circumferences, with increased variability in body proportions, but no evidence of the bimodality that would characterize two distinct subtypes. The analysis suggests that proportionality among intrauterine growth-retarded infants represents a continuum, with progressive disproportionality as severity of growth retardation increases. Moreover, despite evidence of some "sparing," the absolute magnitudes of the deficits in length and head growth remain substantial.     

Intrauterine growth of twins

In a retrospective study of 150 twins born between 1970–1977, birth weight, length, and head circumference was plotted against gestational age. In comparison to singletons, all 3 parameters were low normal. While length and head circumference values follow the growth pattern of singletons, prenatal birth weight shows a progressive decline toward maturity.The intrauterine growth pattern of twins resembles that of intrauterine growth retardation of singletons.Dedicated to Prof. Dr.H.-R. Wiedemann on the occasion of his 65th birthday