Factors affecting development: similarities and differences among children who were small, average, and large for gestational age at birth

The development of 118 small-for-gestational age (SGA), 137 average-for-gestational age (AGA), and 118 large-for-gestational age (LGA) children was assessed at 7 years. The contributions of different factors to the variance in developmental scores were investigated by multiple regression analyses. All three groups showed the powerful influence of social class on intellectual ability at this age; and in the SGA and AGA groups the gross and fine-motor skills of girls were superior to boys. Smoking had a small effect in the AGA group, and in the two extreme groups first-born children did slightly better than later-born. Hypertension was associated with reduced scores in the SGA group, and LGA children who had spontaneous vaginal deliveries had higher scores than those delivered instrumentally or by caesarean section. There was a significant positive correlation between gestational age and developmental scores in the AGA group; but in the SGA group the relationship was in the reverse direction. Social class and sex affect the development of most children aged 7 years. Other factors seem to manifest an effect only under specified conditions.     

早产和低出生体重及小于胎龄儿与脑性瘫痪发病的关系

目的 明确早产、低出生体重及小于胎龄儿(SGA)与脑性瘫痪(简称脑瘫)的关联程度。方法 1997年5—7月对江苏省7个市的1～6岁儿童进行了现况普查,共查305263名,并对其胎龄、出生体重及胎龄别出生体重与脑瘫的关系进行了分析。结果 本组儿童共发现脑瘫484例,发生率为1．59‰。早产儿及过期产儿脑瘫发生率相对危险性(RR)分别为足月儿的25．16倍及2．40倍;低出生体重及巨大儿的脑瘫发生率RR分别为正常出生体重儿的19．63倍及1．34倍;SGA及大于胎龄儿(LGA)脑瘫发生率RR为适于胎龄儿(AGA)的4．34倍及0．84倍。先按胎龄别出生体重分层再按胎龄分组,发现各层内早产儿脑瘫发生率均较足月儿高,RR最高AGA层为28．34倍,其次LGA层为21．41倍,最低SGA层为9．29倍,各层内过期产儿脑瘫发生率也较足月儿高,RR最高AGA层为2．63倍,其次SGA层为1．90倍,最低LGA层为1．55倍;先按胎龄分层再按胎龄别出生体重分组发现各层内SGA脑瘫发生率均较AGA高,RR最高足月儿层为4．41倍,其次过期产儿层为3．19倍,最低早产儿层为1．45倍,各层内LGA脑瘫发生率均不比AGA高,除足月儿层相近为0．98倍外,早产儿及过期产儿层均较AGA低,RR分别为0．74倍和0．58倍。按胎龄大小及胎龄别出生体重大小联合分成9组进行比较,发现多数组脑瘫发生率均较足月AGA组高,RR按次序为早产SGA40．99倍、早产AGA28．34倍、早产LGA21．08倍、过期SGA8．39倍、足月SGA4．41倍、过期AGA2．63倍、过期LGA1．53倍、足月LGA0．98倍;前6组差异均有显著性,后2组倍数接近1．0,差异无显著性。结论 早产及SGA两种因素均与小儿脑瘫发生率增加关联,这两个因素分别为小儿脑瘫独立的危险因素;过期产与脑瘫的关联很弱,LGA则与脑瘫的发生率增加无关。     

Head circumference and developmental ability at the age of seven years

Data on 365 children who had been small (SGA) average (AGA) or large (LGA) for gestational age at birth were analysed at the age of seven years. Significant positive correlations were found between head circumference and developmental scores in the SGA and LGA groups. These were mainly due to associations between relatively small heads and low scores. Familial factors, social class and sex affect both head circumference and developmental ability at this age. Their influences on these two parameters differ in degree; and in the case of sex, in direction. When account was taken of these other factors the contribution of birth-weight group to the variance in head circumference remained high; but its contribution to developmental scores was reduced.     

Head Circumference and Developmental Ability at the Age of Seven Years

ABSTRACT. Data on 365 children who had been small (SGA) average (AGA) or large (LGA) for gestational age at birth were analysed at the age of seven years. Significant positive correlations were found between head circumference and developmental scores in the SGA and LGA groups. These were mainly due to associations between relatively small heads and low scores. Familial factors, social class and sex affect both head circumference and developmental ability at this age. Their influences on these two parameters differ in degree; and in the case of sex, in direction. When account was taken of these other factors the contribution of birth-weight group to the variance in head circumference remained high; but its contribution to developmental scores was reduced.     

成都市9~15岁儿童出生情况与体格指标流行病学调查

目的：宫内环境可能对儿童生长发育产生影响,通过流行病学调查研究四川省成都市9~15岁儿童出生胎龄、体重与体格发育指标的关系。方法：调查9~15岁的中小学学生共7194名,根据出生胎龄及体重对儿童进行分类（包括小于胎龄儿、适于胎龄儿、大于胎龄儿）,测量身高、体重,并对其家长进行问卷调查。结果：被调查人群小于胎龄儿发生率为6.23%（448例）,其中身高未出现“追赶生长”（低于均值两个标准差）为5.13%,且多个年龄段儿童平均身高低于适于胎龄儿（P<0.05）。大于胎龄儿发生率为18.06% (1299例),大于胎龄儿中超重发生率为13.78% (179 例),肥胖发生率为4.39%（57例）,且多个年龄段儿童平均体重大于适于胎龄儿（P<0.05）。结论：出生时为小于胎龄儿、大于胎龄儿的儿童在远期生长发育中,可以出现身高和体重异于正常儿童,应关注这类孩子在学龄期的身高体重发育情况。     

Children of Deviant Birthweight: the Influence of Genetic and Other Factors on Size at Seven Years

ABSTRACT. 138 small-for-gestational age (SGA), 138 average-for-gestational age (AGA) and 136 large-for-gestational age (LGA) children who had been followed up from birth were measured at the age of seven years. Parental measurements were also obtained. Significant differences for weight, height and head circumference of the children and their parents were found between the three groups. There were highly significant parent-child correlations for most somatic measures in all groups. Within each group the parental contribution to the variance in children's somatic measures was large; so also was the effect of sex on head circumference. Other biological and pathological factors made only a small contribution in any group.     

Children of deviant birthweight: the influence of genetic and other factors on size at seven years

138 small-for-gestational age (SGA), 138 average-for-gestational age (AGA) and 136 large-for-gestational age (LGA) children who had been followed up from birth were measured at the age of seven years. Parental measurements were also obtained. Significant differences for weight, height and head circumference of the children and their parents were found between the three groups. There were highly significant parent-child correlations for most somatic measures in all groups. Within each group the parental contribution to the variance in children's somatic measures was large; so also was the effect of sex on head circumference. Other biological and pathological factors made only a small contribution in any group.     

胎龄联合出生体重对新生儿遗传代谢病相关代谢物的影响

目的 探讨胎龄联合出生体重对遗传代谢病（IMD）相关代谢物的影响。方法 从2014~2016年间参加IMD筛查的38 931名新生儿中,随机抽取3381例经随访排除IMD疾病的新生儿样本,按胎龄联合出生体重分为极早产适于胎龄儿组（n=12）、早产小于胎龄儿组（n=18）、早产适于胎龄儿组（n=219）、早产大于胎龄儿组（n=18）、足月小于胎龄儿组（n=206）、足月适于胎龄儿组（n=2 677）、足月大于胎龄儿组（n=231）。采集各组新生儿出生3~7 d充分哺乳后的足跟血,采用串联质谱检测干血斑中17种IMD关键代谢指标水平。利用Spearman秩相关分析各影响因素与代谢指标的相关性,采用协方差分析各组代谢指标水平差异。结果 在控制了新生儿生理及病理状态等相关因素后,与足月适于胎龄儿组相比,亮氨酸\异亮氨酸\羟基脯氨酸、缬氨酸在极早产适于胎龄儿、早产小于胎龄儿、早产适于胎龄儿组,鸟氨酸在早产适于胎龄儿组,脯氨酸在极早产、早产适于胎龄儿组中水平明显下降（P < 0.05）;苯丙氨酸在极早产、早产适于胎龄儿组,甲硫氨酸在早产小于胎龄儿组,酪氨酸在早产适于胎龄儿组中水平则明显升高（P < 0.05）;游离肉碱、乙酰肉碱、丙酰肉碱在早产小于胎龄儿、早产适于胎龄儿组,十八碳烯酰肉碱在早产小于胎龄儿组中水平明显升高（P < 0.05）。大部分肉碱指标在早产和足月的小于胎龄儿分别与适于胎龄儿、大于胎龄儿组间比较中差异有统计学意义（P < 0.05）。结论 胎龄不足和低出生体重均会造成IMD筛查指标异常,故在判读IMD筛查指标异常时应结合胎龄和体重情况综合判断。     

小于胎龄儿青春前期女孩硫化脱氢表雄酮和胰岛素水平的研究

目的探讨小于胎龄儿(SGA)青春前期女孩肾上腺机能初现及是否具有肾上腺机能早现、高肾上腺雄激素血症、高胰岛素血症和胰岛素抵抗现象。方法以符合纳入标准的SGA 39例为研究对象,年龄(7.4±1.7)岁,42例适于胎龄儿(AGA)为对照组,年龄(7.4±1.7)岁。在隔夜空腹12 h后,行身体检查,并抽血检测空腹血糖、胰岛素、硫化脱氢表雄酮(DHEAS)、皮质醇和雌二醇。胰岛素敏感性用空腹血糖与胰岛素乘积的倒数再取自然对数来评价。结果两组中未发现肾上腺机能早现的临床表现,两组间孕母孕龄、年龄、体重指数、空腹血糖、皮质醇、雌二醇和胰岛素敏感性指数差异无统计学意义。SGA组出生体重、研究时的身高和体重均低于AGA组,SGA血清胰岛素和DHEAS水平均高于AGA组(对数转换值:1.076±0.041vs.1.050±0.051,P<0.05;2.637±0.271vs.2.514±0.250,P<0.05)。AGA组DHEAS值在7岁以后出现明显增加,SGA组DHEAS值出现增加的趋势与AGA组比较有所提前。结论AGA女孩肾上腺机能初现的年龄约为7岁,而SGA女孩肾上腺机能初现有始动提前的趋势,青春前期SGA女孩有高肾上腺雄激素血症和胰岛素水平升高的现象,但以胰岛素敏感性指数来评价,尚未发现胰岛素抵抗现象。     

Proportionality at birth. Associations with weight, gestational age and sex

501 small (SGA), 330 average (AGA) and 460 large for gestational age (LGA) babies were measured at birth. Head-chest, head-crown-rump length, and chest-crown-rump length ratios were used to evaluate the changing patterns of proportionality with increasing gestational age. The SGA group showed strong negative correlations for head-chest and head-length ratios, and positive correlations for chest-length ratios. The patterns were similar in the AGA group, only less evident. For all three measures of proportionality, correlations with gestational age in the LGA group were close to zero. In each group boys had higher head-chest ratios than girls.     

Physical and developmental status of preschool small-for-gestational-age children: A comparative study

This study aimed to assess the current developmental and physical status of preschool children identified from hospital records as being small-for-gestational-age (SGA) at birth. Sixty-seven children were compared with a matched group of appropriately grown (AGA) children. Mothers of SGA children were more likely to have smoked during pregnancy, to have suffered pre-eclamptic toxaemia (PET), and to have had shorter labours than the AGA group. They were less likely to have breast-fed their babies, and reported higher incidences of eating problems and visits to the general practitioner. On physical and developmental parameters the AGA group was significantly ahead of the SGA group. For all subjects breast feeding was correlated with higher Stanford Binet scores, and environmental factors appeared more salient for the progress of the SGA children at this age than biological factors. The results are discussed with regard to possible amelioration of the effects of being born small for gestational age.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

Pubertal development in children born small for gestational age

Reduced fetal growth appears to be associated with precocious adrenarche, early puberty and polycystic ovary syndrome with subsequent fertility problems. We investigated pubertal development and DHEAS levels in children born small for gestational age (SGA) and children born appropriate for gestational age (AGA). Physical examination was carried out twice. Mean age (+/-SD) at the first visit: SGA group, 9.1+/-1.1 yr; AGA group, 9.0+/-1.1 yr. AT FOLLOW-UP: SGA group, 11.6+/-1.0 yr; AGA group, 11.6 +/-1.1 yr. Pubertal stages of the children were assessed. Pubic hair was recorded as a measure of androgenization. Chronological age (CA) was expressed as a percentage of the age corresponding to the pubertal stage (CA/pubertal age [PA] x 100%). Estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) were measured in all children. FIRST VISIT: All children were prepubertal without signs of pubarche. DHEAS concentrations were higher in SGA children than in AGA children (p = 0.004). FOLLOW UP: Twenty SGA children and 15 AGA children were pubertal. CA/PA x 100% was lower in SGA girls than in AGA girls (p = 0.004). Since 2.5 years earlier all girls had been prepubertal, this means a more rapid progression in the SGA girls. CA/PA x 100% was similar in SGA and AGA boys (p = 0.1). DHEAS levels tended to be higher in SGA children than in AGA children (p = 0.06). These data support that a low birth weight may have long-lasting effects on pubertal development, as observed in a more rapid progression in SGA girls. In prepubertal SGA children, an exaggerated adrenarche is observed compared to AGA children, which tended to persist through puberty.     

Proportionality at Birth

ABSTRACT. 501 small (SGA), 330 average (AGA) and 460 large for gestational age (LGA) babies were measured at birth. Head-chest, head-crown-rump length, and chest-crown-rump length ratios were used to evaluate the changing patterns of proportionality with increasing gestational age. The SGA group showed strong negative correlations for head-chest and head-length ratios, and positive correlations for chest-length ratios. The patterns were similar in the AGA group, only less evident. For all three measures of proportionality, correlations with gestational age in the LGA group were close to zero. In each group boys had higher head-chest ratios than girls.     

Effect of maternal lipid profile,C-peptide,insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns

Background

Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA_1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA_1c during late pregnancy on LGA newborns.

Methods

This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA_1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns.

Results

Maternal TG, C-peptide, insulin and HbA_1c levels were significantly higher in the LGA group than in the AGA group (P<0.05). The LGA group had significantly lower levels of maternal TC, HDL-C and LDL-C than the AGA group (P<0.05). After adjustment for confounding variables, including maternal age, pre-pregnancy body mass index, education, smoking, annual household income, amniotic fluid volume, gestational hypertension, newborn gender and gestational age at blood collection, high maternal TG levels remained significantly associated with LGA newborns (P<0.05).

Conclusion

High maternal TG level during late pregnancy is significantly associated with LGA newborns.     

The influence of gestational age, size for dates, and prenatal steroids on cord transferrin levels in newborn infants

Serum transferrin levels assess protein status in older children and adults. To generate standards for its use in newborn infants, we measured umbilical cord serum transferrin levels in 161 appropriate (AGA), 25 large (LGA) and 16 small (SGA) for gestational age infants between 25 and 43 weeks' gestation. We also assessed the effects of intrauterine growth, exposure to prenatal steroids, and presence of pulmonary maturity on neonatal transferrin levels. Cord transferrin levels in AGA infants were significantly correlated with increasing gestational age (r = 0.60; p less than 0.001). Infants born before 37 weeks' gestation had significantly lower transferrin levels, when compared with those born at term (p less than 0.001). LGA infants had significantly higher levels than age-matched AGA infants (253 +/- 75 vs. 214 +/- 53 mg/dl; p less than 0.025). Despite significantly lower mean birth weights (p less than 0.001), SGA infants also had significantly higher levels than gestational age-matched AGA controls (227 +/- 63 vs. 167 +/- 40 mg/dl; p less than 0.005). For infants less than 35 weeks' gestation, neither the 20 preterm infants with exposure to prenatal steroids (maternal betamethasone), nor the 26 infants with pulmonary maturity had significantly elevated transferrin levels, when compared with gestational age-matched control infants. Newborn transferrin levels correlate well with gestational age and are significantly affected by size for dates, but not by a brief course of prenatal steroids or by pulmonary maturity.     

Cognitive development of term small for gestational age children at five years of age.

AIM: To assess the relative significance for cognitive development of small for gestational age, parental demographic factors, and factors related to the child rearing environment. METHODS: IQ of a population based cohort of 338 term infants who were small for gestational age (SGA) and without major handicap, and a random control sample of 335 appropriate for gestational age (AGA) infants were compared at 5 years of age. RESULTS: The mean non-verbal IQ was four points lower, while the mean verbal IQ was three points lower for the children in the SGA group. The results were not confounded by parental demographic or child rearing factors. However, parental factors, including maternal non-verbal problem solving abilities, and child rearing style, accounted for 20% of the variance in non-verbal IQ, while SGA versus AGA status accounted for only 2%. The comparable numbers for verbal IQ were 30 and 1%. Furthermore, we found no evidence that the cognitive development of SGA children was more sensitive to a non-optimal child rearing environment than that of AGA children. Maternal smoking at conception was associated with a reduction in mean IQ comparable to that found for SGA status, and this effect was the same for SGA and AGA children. The cognitive function of asymmetric SGA was comparable to that of symmetric SGA children. CONCLUSIONS: Our findings indicate that child cognitive development is strongly associated with parental factors, but only marginally associated with intrauterine growth retardation.     

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.     

小于胎龄儿幼儿期生活质量及其影响因素的研究

目的 了解小于胎龄儿(SGA)幼儿期的生活质量与适于胎龄儿(AGA)比较是否存在差异,并调查影响SGA 生活质量的因素.方法 采用婴幼儿生活质量问卷表(ITQOL SF-47)对儿保门诊就诊的出生时为SGA 和AGA 的1~3 岁幼儿进行生活质量调查,分别比较SGA 组(n=203)与AGA 组(n=130)、SGA 追赶组(n=119)与无追赶组(n=84)、SGA 首次儿保随访组(n=144)与多次儿保随访组(n=59)的生活质量.采用广义线性模型分析法调查影响SGA 生活质量的因素.结果 SGA 组ITQOL 总分低于AGA 组(630±99 vs 716±84,PPPP结论 SGA 幼儿期的生活质量低于同龄正常儿童.适当促进追赶生长及定期儿童保健对提高SGA 的生活质量有益;儿童性别、居住地、母亲文化程度对SGA 幼儿期的生活质量也有影响.     

Cognitive development of term small for gestational age children at five years of age

AIM—To assess the relative significance for cognitive development of small for gestational age, parental demographic factors, and factors related to the child rearing environment.METHODS—IQ of a population based cohort of 338 term infants who were small for gestational age (SGA) and without major handicap, and a random control sample of 335 appropriate for gestational age (AGA) infants were compared at 5 years of age.RESULTS—The mean non-verbal IQ was four points lower, while the mean verbal IQ was three points lower for the children in the SGA group. The results were not confounded by parental demographic or child rearing factors. However, parental factors, including maternal non-verbal problem solving abilities, and child rearing style, accounted for 20% of the variance in non-verbal IQ, while SGA versus AGA status accounted for only 2%. The comparable numbers for verbal IQ were 30 and 1%. Furthermore, we found no evidence that the cognitive development of SGA children was more sensitive to a non-optimal child rearing environment than that of AGA children. Maternal smoking at conception was associated with a reduction in mean IQ comparable to that found for SGA status, and this effect was the same for SGA and AGA children. The cognitive function of asymmetric SGA was comparable to that of symmetric SGA children.CONCLUSIONS—Our findings indicate that child cognitive development is strongly associated with parental factors, but only marginally associated with intrauterine growth retardation.