Growth of 519 Small for Gestational Age Infants during the First Two Years of Life

ABSTRACT. The physical growth of 519 small for gestational age infants (SGA), with a birth weight below the 10th percentile on our own growth curve, born in the region of University Central Hospital of Turku during the period June 1,1981-May 31, 1982, was studied. The study population consists of 4 517 term, appropriate for gestational age (AGA) infants, 488 term SGA infants, 320 preterm AGA infants and 31 preterm SGA infants. The degree of intrauterine growth retardation (IUGR) seemed to have an effect on physical growth in term SGA infants. Those term SGA infants with a low Ponderal Index (PI) (type II) were taller and had a larger head circumference at the age of 24 months than term SGA infants with adequate PI (type I). Among the preterm SGA infants the degree of IUGR seemed to have no effect on later growth. Smoking is still one of the main risk factors associated with poor intrauterine growth. In this study we also found that smoking has an effect on later growth; the children of smoking mothers were smaller than those of non-smoking mothers in the AGA group. Among the SGA infants the infants of non-smoking mothers were bigger than those of smoking mothers. This difference could be explained by other factors associated with SGA. We found that in spite of the catch-up growth during the first months, 26% of the severely SGA infants (birth weight below the 2.5th percentile) still had a weight below the 2.5th percentile at the age of 24 months.     

Whole blood fatty acid composition differs in term versus mildly preterm infants: small versus matched appropriate for gestational age

To investigate the associations between whole blood fatty acid (FA) profile and restricted intrauterine growth, any small for gestational age (SGA) infant born in our maternity ward through 1 y was matched with two appropriate for gestational age (AGA), of the same GA +/- 0.5 wk, infants, further subdivided into term and preterm. Whole blood was collected at d 4 on a strip and FA % composition assessed by means of gas chromatography. The whole sample consisted of 28 SGA versus 56 AGA born at term and 20 SGA versus 40 AGA born preterm at around 35 wks. Parent FA of the n-6 and n-3 FA families were higher in preterm groups, whereas docosahexaenoic acid was higher in term AGA (median % values, 3.9 versus 3.7 in term SGA, 2.8 in preterm AGA, and 2.5 in preterm SGA, p < 0.001). Term AGA had markedly higher values for the docosahexaenoic acid/alpha-linolenic acid ratio (median value: 91, versus 18 in term SGA, 12 in preterm AGA, and 10 in preterm SGA, p < 0.001). Term SGA had significantly lower levels of total monounsaturated FA and higher levels of eicosapentaenoic acid. Therefore, the 4-d whole blood FA pattern is associated with both GA and birth weight.     

Lung function in children born after foetal growth restriction and very preterm birth

Aims: To assess lung function at early school age in children delivered at very early gestation owing to intrauterine growth restriction and abnormal foetal blood flow (IUGR). Methods: Spirometry was performed at median age 8.4 (range 6.5–10.7) years in 31 children born preterm with IUGR (PT‐IUGR) with a median (range) birth weight (BW) of 650 (395–976) g and median (range) gestational age 27 (24–29) weeks. Control groups were matched for gender and age and had BW appropriate for gestational age (AGA); 31 children born preterm (PT‐AGA) with BW of 1010 (660–1790) g matched for gestational age at birth, and 31 children born at term (T‐AGA) with BW of 3530 (3000–4390) g. Results: The PT‐IUGR group had lower mean (SD) values of z‐scores for FEV₁, FEV₁/FVC and forced mid‐expiratory flow rate (FEF_25–75%) compared to the T‐AGA group, p = 0.003, p = 0.032 and p < 0.001, respectively, but did not differ from the PT‐AGA group. PT‐IUGR children delivered at ≥26 gestational weeks (GW) had lower FEF_25–75% than PT‐AGA children of corresponding GA, p = 0.014. Conclusion: Lung function was reduced in the PT‐IUGR group at early school age compared to controls born at term. The influence of IUGR on later lung function was only apparent in children born preterm after 26 GW.     

Effects of intrauterine growth retardation and its subtypes on the development of the preterm infant.

The aim of this prospective study was to examine the neurological development of preterm children with asymmetric (A-SGA) or symmetric (S-SGA) intrauterine growth retardation (IUGR). Twenty-six A-SGA preterm children, 27 S-SGA preterm children and 131 appropriate for gestational age (AGA) preterm children were compared with 121 full-term AGA children. They were assessed by one author at the corrected age of 18 months +/- 2 weeks using the modified Denver Developmental Screening Test. Development was evaluated in terms of scores for fine motor and gross motor performance, for visuo-auditory perception, for speech and for social abilities. In the A-SGA group there were more children with low visuo-auditory perception scores and social abilities scores than in the control group. The S-SGA group differed from the other groups in all developmental sectors except visuo-auditory perception. Numbers of neurologically abnormal or suspect children in both SGA groups were twice the number in the control group. IUGR and sex were the only factors that correlated with slow neurological development. These results show that there will be a significant possibility of slow neurological development if a preterm baby has been subject to IUGR, especially symmetric IUGR.     

High risk appropriate for gestational age (AGA) and small for gestational age (SGA) preterm infants. Neurological handicap and developmental abnormalities at five years of age

Outcome at five years of age of 110 high risk AGA, 71 high risk SGA preterm infants with similar birth weight and 102 term control infants was studied. Mean IQ in the 3 groups was not statistically different. Major handicaps were found in 16.3% of the AGA and in 8.5% of the SGA preterms. There was no major handicap among the controls. Minor neurodevelopmental abnormalities were present in 25.6% of AGA, 28.2% of SGA and 19.6% of controls. The types of neurodevelopmental handicaps were different in the 3 groups and generally more severe in the AGA group. All the major handicaps among AGA preterms were found in children with severe neonatal complications. In the SGA preterm group, only 1/3 of the major handicaps can be related to perinatal complications. Affective and behavior disorders were probably related in some way to neurodevelopmental achievement. This study showed that preterm infants with GA less than or equal to 32 weeks are more at risk than more mature SGA preterms with similar birth weight.     

Neurodevelopmental screening of in utero growth-retarded prematurely born children before school age

As part of a prospective follow-up study of two premature cohorts (gestational age 36 weeks) born between 1976 and 1977, designed to evaluate the effects of IUGR on morbidity, mortality and neurological development in prematurely born children, 71 prematurely born children (48 AGA, 23 IUGR) without major neurological handicaps were subjected to detailed assessment of their neurological and psychological status at the age of 4 years. Thirty-six healthy full-term children formed a control group. The socioeconomic status of the families of the premature groups was similar to that of the families of the control group. The assessment consisted of a neurodevelopmental screening test and four psychological tests. Validation of the NDS test in relation to proven cognitive problems (sensitivity 96%, specificity 64%, relative risk 16.74) and determination of normal ranges were based on findings in the control group. There were significantly more children with moderate to high risk scores (10) among the IUGR group than among the AGA group. The neurodevelopmental profile of the preterm IUGR group was characterized by complex deviations of motor, visual and perceptual functions from normal. Preterm AGA children had only slightly higher risk scores in relation to fine motor, upper motor and perceptive functions than control children. Of the various perinatal factors studied, IUGR (especially in relation to boys who needed respirator therapy) was the most likely to be associated with abnormal NDS scores before school age.Abbreviations AGA adequate for gestational age - IUGR intrauterine growth retardation - IQ intelligence quotient - NDS neurodevelopmental screening - PI ponderal index     

Macromolecular absorption in small-for-gestational-age infants

Using human alpha-lactalbumin as a marker protein, macromolecular absorption was studied in 40 preterm infants, appropriate for gestational age (AGA), in 12 AGA term infants and in 18 preterm infants, small for gestational age (SGA). The absorption of alpha-lactalbumin was measured as concentration in serum after a human milk feed and expressed as micrograms alpha-lactalbumin/l serum/l human milk/kg body weight on day 7, 14, 21 and 42 after delivery. The serum concentration of alpha-lactalbumin was correlated negatively with maturity and postnatal age. In the SGA infants, the concentration of alpha-lactalbumin was significantly higher than in the AGA infants of similar gestational age. The data show that intrauterine growth retardation causes a delayed postnatal decrease in macromolecular absorption. This may indicate delayed intestinal maturation.     

Lean body mass in small for gestational age and appropriate for gestational age infants

Dual photon absorptiometry using 153Gd in a whole-body scanner was used to measure lean body mass (LBM) in 51 newborn infants. LBM% decreased exponentially with increasing gestational age in both small for gestational age (SGA) and appropriate for gestational age (AGA) infants. In preterm SGA and AGA infants LBM was 104% and 103%, respectively, indicating that no fat was detectable. In term SGA infants LBM was 98%, which corresponded to 48 gm fat on average, and in term AGA infants LBM was 87%, which corresponded to 452 gm fat on average. The LBM%, ponderal index, and skinfold thickness were significantly different between AGA and SGA infants. Infants with clinical signs of intrauterine wastage had significantly higher LBM% than did infants without signs of weight loss. Our results on LBM% by dual photon absorptiometry agree with earlier dissection data; the clinically applicable methods of (1) height combined with weight (i.e., ponderal index), (2) skinfold thickness, and (3) scoring by clinical observations are useful for the estimation of lack of fat as an indicator of intrauterine growth retardation.     

Children born small for gestational age are not at special risk for preschool emotion and behaviour problems

Despite the wealth of literature examining long term outcomes of preterm low birthweight children, few studies have directly assessed the developmental impact of being born full term but small for gestational age (SGA). We aim to determine whether (i) being SGA increases preschool behavioural problems and (ii) other risk factors operate differently in SGA and appropriate for gestational age (AGA) controls. 550 New Zealand European mothers and their 3.5 year old children participated in this study. All children were born at full term (>37 weeks' gestation) and approximately half were SGA (≤sex specific 10th percentile for gestation) the remainder were AGA controls. Extensive data were collected at the child's birth, 1 year and 3.5 years. Behavioural problems were measured when children were 3.5 years, using the Strengths and Difficulties Questionnaire (SDQ). Multiple regression analyses were used to examine the associations between risk factors and behavioural problems; statistical weighting was used for analyses of the total study group. There was no significant difference in behavioural problems between SGA and AGA groups. In the total sample the significant predictors of behavioural problems included: mothers' school leaving age; smoking during pregnancy; maternal alcohol use during pregnancy; and absence of the father. Predictors of behavioural problems were found to be the same for SGA and AGA groups. These results do not support the view that SGA is a risk for behavioural preschool difficulties or that SGA children are sensitised to risks known to be associated with such difficulties in the preschool years.     

Developmental assessment of intrauterine growth retarded babies of varying maternal etiology

Head circumference was measured serially and developmental performance assessed at the age of 9 months in 41 full-term intrauterine growth retarded babies of varying maternal etiologies. 18 full term and 12 preterm babies who were appropriate for gestational age (AGA) served as controls. The IUGR babies of undernourished mothers had maximum retardation in head circumference.The IUGR babies of small sized mothers had head circumference equal to that of fullterm AGA babies. The IUGR babies of mothers with toxemia of pregnancy and idiopathic group also reached very close to that of fullterm AGA babies for head circumference demonstrating catch up growth. 19.5 per cent of IUGR (as homogenous group) babies were found to have delayed development compared to 16.7 per cent of preterm and 5.6 per cent of fullterm AGA babies. Amongst IUGR groups, babies of undernourished mothers were found to suffer most, followed by babies of mothers with toxemia of pregnancy. None of the babies in the idiopathic group and only one out of 12 in small maternal size group were found to have delayed development.     

Body measurements, neurological and behavioural development in six-year-old children born preterm and/or small-for-gestational-age

In three groups of low birth weight (LBW) infants: full term, small-for-gestational-age (FT-SGA, N = 142); preterm, appropriate-for-gestational-age (PT-AGA, N = 47); preterm, small-for-gestational-age (PT-SGA, N = 20); and a reference group of FT-AGA infants (N = 185) the relationship between body weight, body length and head circumference and the presence of minor neurological dysfunction (MND) was studied. Non-caucasian and handicapped children were excluded from the analysis. Data were collected on behaviour and school achievement. The parameters of physical growth in the three LBW groups were reduced significantly compared to the FT-AGA group. In both preterms and full-terms body measurements were related to weight at term age; in the preterm groups no relation with gestational age at birth was found. MND was not related to body weight or length. In the group of FT severely growth retarded infants a relation was found between a skull circumference below the third centile and the presence of MND. Body measurements, behaviour at home and at school and school achievement were not related. The significance of severe intrauterine growth retardation for developmental disorders is emphasized. The data suggest a different aetiology and clinical significance of small head size for AGA and SGA born children.     

Neurodevelopmental consequences of being born SGA

Fetal growth retardation is associated with postnatal growth retardation and cardio-vascular and metabolic problems later on in life. Less well described are the consequences of neurodevelopmental outcome. The term SGA is associated with mild to moderate school problems, still present in late puberty and with lower psychological and intellectual performance in young adulthood as compared with AGA controls. Also after preterm SGA birth, neurodevelopmental sequelae are more complex than after preterm AGA birth. Recent volumetric MRI studies of the brain show reduced cortical grey matter volume as one of the most important features of fetal growth retardation. In addition, the hippocampus appears to be especially susceptible to the effects of placental insufficiency. Although growth hormone treatment of children with short stature after SGA birth has been shown to increase head circumference, no clinically significant psychological improvement has been demonstrated after growth hormone treatment to date.     

宫内发育迟缓早产儿生后生长迟缓对早期神经发育的影响

目的 探讨宫内发育迟缓(IUGR)早产儿生后生长迟缓对早期神经发育的影响。方法 回顾性分析2008 年5 月至2012 年5 月出生并定期随访至校正胎龄6 个月的171例早产儿的临床资料,其中IUGR早产儿40 例,早产适于胎龄儿(AGA)131 例。比较两组校正胎龄40 周、3个月、6个月的生长迟缓率及校正胎龄3 个月、6 个月时的神经发育情况。神经发育采用Gesell发育量表评估。结果 IUGR 组校正胎龄40 周、3个月、6个月的生长迟缓率均明显高于AGA 组;校正胎龄3 个月时Gesell 各项发育商(大运动、精细动作、语言、适应性及个人社交)均低于AGA 组;校正胎龄6 个月时,IUGR组精细动作及语言发育商低于AGA组,但两组大运动、适应性及个人社交发育商比较差异已无统计学意义。IUGR组6月龄时体重追赶落后的患儿各项发育商均明显低于追赶理想的IUGR 和AGA 患儿。结论 IUGR早产儿生后早期的生长迟缓可对早期神经发育产生不良影响。     

Effects of prematurity and dysmaturity on growth at age 5 years

Forty-two term and 106 preterm appropriate for gestational age (AGA), and 43 term and 31 preterm small for gestational age (SGA) children were observed from birth to age 5 years. Parents' weight and height were also measured in 193 subjects including 97 couples. The percentage of short children was higher in SGA (17%) than in AGA (3.4%) children (P less than 0.01). This difference was significant in the preterm but not in the term children, suggesting that early failure of growth in utero can result in reduced growth in children. The findings were similar for weight and head circumference, but microcephaly was more frequent in term SGA (30%) than in preterm SGA (6.4%) children (P less than 0.05), suggesting that late impaired growth in utero can result in poor growth of the head. Height at the age of 5 years correlated with the parents' height only in AGA children, and with length at birth in SGA children. Weight of the 5-year-old children correlated with the mother's weight only in AGA children. Multivariate analysis in 66 couples and their children confirmed a greater tendency toward the influence of parental factors in AGA children and a more significant relationship with perinatal factors in SGA children.     

Preterm birth and carotid diameter and stiffness in childhood

BACKGROUND AND AIM: Low birthweight, either as a result of poor foetal growth or preterm birth, is a risk factor for stroke in adult life. Carotid stiffening, an early marker of atheromatous disease, has been found in low-birthweight children born at term. We hypothesized that carotid artery growth and dynamic properties are permanently affected by preterm birth. METHODS: Carotid artery stiffness and dimensions in 56 school children, 39 born very preterm (mean gestational age [GA] 29 weeks) and 17 controls born at term, were studied by ultrasonic measurements of the pulsatile movements of the vessel wall. RESULTS: The carotid artery diameter was 6.4 mm both in children born preterm and at term (p=0.99). No difference in carotid stiffness was found. Within the preterm group, no differences could be seen between those born small for gestational age (SGA) or appropriate for gestational age (AGA). CONCLUSIONS: Carotid artery elasticity and structure are not altered after preterm birth. The mechanisms behind the increased stroke risk in adults born preterm remain unresolved.     

Normal thyroid function in young adults who were born very preterm

There is some evidence for elevated thyrotropin (TSH) levels in children born preterm, but follow-up studies into adulthood are lacking. We tested whether thyroid function in young adults born at a gestational age < 32 weeks, with either an appropriate (appropriate for gestational age, AGA) or low birth weight for gestational age (small for gestational age, SGA), differed from that in age-matched controls. We made our measurements when the study participants reached 21 years of age. Serum concentrations of TSH and free T4 (fT4) and body composition were measured in subjects born preterm and AGA (n = 29) or SGA (n = 28), and in non-preterm controls (n = 30). The TSH and fT4 concentrations of participants were within normal limits. Free T4 levels in subjects born preterm were slightly higher than those in controls: 17.0 +/- 2.4 (AGA) and 17.2 +/- 1.7 (SGA) vs. 16.1 +/- 1.9 pmo/L (p = 0.04). TSH concentrations did not differ between groups. From these preliminary data, we conclude that young adults born preterm have a normal thyroid function.     

Prematurity-associated morbidity during the first two years of life. A population-based study

Two-year patterns of postneonatal morbidity, both chronic and non-chronic, reported for all liveborn preterm infants (n = 612; malformations excluded) delivered in the province of Kuopio, Finland, between 1978 and 1982. The overall readmission rate was 30%, the commonest cause being respiratory infections, surgical disorders (inguinal hernias) and neurological problems. The higher readmission rate in preterms born at less than or equal to 33 weeks of gestation was due to a large proportion of children being admitted with chronic prematurity-associated conditions; preterms without chronic disabilities had similar rates of readmission irrespective of gestational age. Neonatal treatment variables were of little help in the identification of children requiring readmission after neonatal care. Instead, intrauterine growth retardation (IUGR) or being of the male sex significantly increased the risk of subsequent readmission.     

Normal visual evoked potentials in preschool children born small for gestational age

Aim: Previous studies have shown visual evoked potential (VEP) abnormalities in infants and animals born small for gestational age (SGA) compared with controls. The current exploratory study aims to investigate whether VEP abnormalities persist in older ages. Methods: Pattern VEP latencies were obtained in 21 children (11 girls, 10 boys), born SGA and moderately preterm, at an average age of 5 years and 8 months. Fifty‐one children (24 girls, 27 boys, mean age of 5 years and 7 months), also born moderately preterm but with normal height and weight at birth, served as controls Results: Visual evoked potential results showed no significant differences in latency between children born SGA and controls born appropriate for gestational age (AGA) for either binocular stimulation, right eye or left eye stimulation. Conclusions: Our findings do not indicate any differences in VEP latency at preschool age for children born SGA compared with children born AGA. The results may support previous studies, suggesting that children born SGA show accelerated neurophysiologic maturation during their first year of life and that previously delayed VEP latencies after catch‐up stay unchanged compared with controls.     

Prematurity-Associated Morbidity during the First Two Years of Life

ABSTRACT. Two-year patterns of postneonatal morbidity, both chronic and non-chronic, are reported for all liveborn preterm infants (n=612; malformations excluded) delivered in the province of Kuopio, Finland, between 1978 and 1982. The overall readmission rate was 30%, the commonest causes being respiratory infections, surgical disorders (inguinal hernias) and neurological problems. The higher readmission rate in preterms born at ≦33 weeks of gestation was due to a larger proportion of children being admitted with chronic prematurity-associated conditions; preterms without chronic disabilities had similar rates of readmission irrespective of gestational age. Neonatal treatment variables were of little help in the identification of children requiring readmission after neonatal care. Instead, intrauterine growth retardation (IUGR) or being of the male sex significantly increased the risk of subsequent read-mission.     

Effect of breastfeeding on cognitive development of infants born small for gestational age

Breastfeeding during infancy appears to result in enhanced cognitive development during childhood, but it is not known whether breastfeeding should be encouraged for infants born small for gestational age (SGA) whose growth might otherwise benefit from nutritional supplementation. To address this issue, duration of exclusive breastfeeding and cognitive development were evaluated prospectively for 220 term children born SGA and 299 term children born appropriate for gestational age (AGA). Cognitive development was assessed using the Bayley Scale of Infant Development at 13 mo and Wechsler Preschool and Primary Scales of Intelligence at 5 y of age. Infants born SGA were given supplemental foods significantly earlier than those born AGA. Growth of infants born SGA was not related to early nutritional supplementation. The salutary effect of exclusive breastfeeding on cognitive development was greater for children born SGA than for those born AGA. Based on a linear association between duration of exclusive breastfeeding and intelligence quotient (IQ), children born SGA and exclusively breastfed for 24 wk were predicted to have an 11-point IQ advantage over those breastfed for 12 wk, as opposed to a 3-point advantage for children born AGA with similar durations of breastfeeding. The IQ distribution of children born SGA and exclusively breastfed for more than 12 wk was not different from that of all children born AGA.

Conclusion : Duration of exclusive breastfeeding has a significant impact on cognitive development without compromising growth among children born SGA. These data suggest that mothers should breastfeed exclusively for 24 wk to enhance cognitive development.