Effect of antenatal growth on brain white matter maturation in preterm infants at term using tract-based spatial statistics

Background

White matter maturation of infants can be studied using diffusion tensor imaging (DTI). DTI of the white matter of the infant brain provides the best available clinical measures of brain tissue organisation and integrity.

Objective

The purpose of this study was to compare white matter maturation between preterm infants born small for gestational age (SGA) and preterms with weight appropriate for gestational age (AGA) at birth.

Materials and methods

A total of 36 preterm infants were enrolled in the study (SGA, n?=?9). A rater-independent method called tract-based spatial statistics (TBSS) was used to assess white matter maturation.

Results

When measured by TBSS, the AGA infants showed higher fractional anisotrophy values in several white matter tracts than the SGA infants. Areas with significant differences included anterior thalamic radiation, corticospinal tract, forceps major and minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and superior longitudinal fasciculus (temporal part). No significant difference was found for mean diffusivity.

Conclusion

As an objective and user-independent method, TBSS confirmed that preterm infants with impaired antenatal growth have impaired white matter maturation compared to preterm infants with normal antenatal growth. The differences were mainly detected in radiations that are myelinated first.     

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.     

Weight loss and bronchopulmonary dysplasia in very low birth weight infants

Our objective was to evaluate the extent of weight loss in very low birth weight (VLBW) preterm infants and to discover how weight loss and other variables correlate with bronchopulmonary dysplasia (BPD). We conducted an observational study of 387 VLBW preterms, gestational age (GA) < 33 weeks, in a single institution over a period of 5 years. The mean weight loss of AGA infants was significantly greater than that of SGA infants. In AGA infants, GA, z-score, weight loss, and male sex were found to correlate with BPD. After adjustments were made for GA and birth weight, each 10% loss of body weight increased the risk for developing BPD by a factor of 2.7. We concluded that excessive weight loss does not prevent BPD in VLBW preterms and presumably should be prevented. Controlled fluid restriction resulting in milder weight loss is probably the right choice.     

Factors associated with weaning in full term and preterm infants

BACKGROUND: The optimal age for the introduction of solid foods (weaning) in infants is poorly researched yet may have implications for both short and longer term health. Many parents do not comply with current guidelines. OBJECTIVE: To determine and compare the age at weaning in term appropriate size for gestational age (AGA), small for gestational age (SGA), and preterm infants, and factors associated with weaning age in these groups. DESIGN: Data from > 2000 infants from seven prospective randomised trails conducted between 1990 and 1997 were used to address the objectives. RESULTS: Most infants, term AGA, SGA, or preterm, received solids before 4 months of age. Only 2% of term infants were exclusively breast fed to 6 months of age. Formula fed infants received solids on average two weeks earlier than breast fed infants. Preterm infants were significantly more likely, and term SGA infants less likely, to receive solids at both 6 and 12 weeks after term than term AGA infants. Weight at 6 weeks of age was a stronger predictor of earlier weaning than either birth weight or weight gain from birth to 6 weeks in term infants. In preterm infants, formula feeding and maternal smoking were associated with earlier weaning. CONCLUSIONS: Infants born in the mid 1990s were weaned on average earlier than the 4 months recommended by the Department of Health. Earlier weaning was associated with less positive health behaviours. Further research is required to provide evidence based weaning guidelines, including specific advice for SGA and preterm infants, and to investigate longer term consequences of weaning practices.     

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.     

34 周以下适于胎龄及小于胎龄早产儿出生 2 周内 蛋白质、能量摄入及体质量变化

目的了解34周以下早产适于胎龄儿(AGA)和小于胎龄儿(SGA)生后蛋白质、能量摄入量以及体质量z评分的变化情况。方法回顾收集2012年1月至2014年12月入院的314例早产儿,比较268例AGA和46例SGA早产儿生后2周内蛋白质、能量摄入情况和体质量变化。结果 SGA组住院时间、肠外联合肠内营养时间、全肠内营养时间、达足量喂养时间均较AGA早产儿长,差异有统计学意义(P??0.05);SGA组生后第4、8、12天能量摄入量明显低于AGA组,SGA组生后第6、8天总蛋白质摄入量明显低于AGA组,差异均有统计学意义(P??0.05);SGA组日平均体质量增长量大于AGA组,差异有统计学意义(P??0.05);AGA组与SGA组生后2周内体质量z评分均逐渐远离中位水平,且SGA组2周时体质量z评分低于AGA组(P??0.05)。结论胎龄??34周的SGA早产儿恢复出生体质量后的生长速率快于AGA早产儿,存在一定的追赶生长;但SGA、AGA早产儿的生长均有待提高。     

TRANSEPIDERMAL WATER LOSS IN NEWBORN INFANTS

ABSTRACT. In 68 appropriate for gestational age (AGA) and 33 small for gestational age (SGA) infants, transepidermal water loss was studied during the first four weeks after birth. The method used to measure evaporation rate is based on measurement of the water vapour pressure gradient close to the skin surface. All measurements were made at an ambient humidity of 50% and with the infants calm and quiet. At all the investigated post-natal ages in both AGA and SGA infants, an exponential relationship was found between transepidermal water loss (g/m² h) and gestational age, this loss being much higher in the pre-term infants than in those born at term. The transepidermal water loss was generally lower in SGA than in AGA infants during the first week of post-natal life, irrespective of gestational age at birth. There was a gradual decrease in transepidermal water loss with increasing post-natal age in both pre-term AGA and pre-term SGA infants. Three weeks after birth this water loss tended to be higher in pre-term SGA infants than in pre-term AGA infants of corresponding gestational age.     

The contribution of preterm birth and intrauterine growth restriction to childhood undernutrition in Tanzania

Objectives were to examine the growth patterns of preterm and growth‐restricted infants and to evaluate the associations of prematurity and intrauterine growth restriction (IUGR) with risk of stunting, wasting and underweight. Data from a cohort of HIV‐negative pregnant women–infant pairs were collected prospectively in Tanzania. Small for gestational age [SGA, birthweight (BW) <10th percentile] was used as proxy for IUGR. Anthropometry was measured monthly until 18 months. Length‐for‐age (LAZ), weight‐for‐length (WLZ), and weight‐for‐age (WAZ) z‐scores were calculated using the 2006 World Health Organization (WHO) Child Growth Standards. Stunting, wasting and underweight were defined as binary outcomes using a cut‐off of z‐scores. Multivariate Cox proportional hazard models were used to assess the associations between preterm and SGA to time to stunting, wasting and underweight. The study included 6664 singletons. Preterm and appropriate for gestational age (AGA) infants had slightly better nutritional status than term‐SGA infants and despite some catch‐up growth, preterm‐SGA infants had the poorest nutritional status. The gap in LAZ and WAZ z‐scores among the groups remained similar throughout the follow‐up. Compared with term‐AGA babies, relative risk (RR) of stunting among preterm‐AGA babies was 2.13 (95% confidence interval (CI) 1.93–2.36), RR among term‐SGA was 2.21 (95% CI 2.02–2.41) and the highest risk was among the babies who were both preterm and SGA (RR = 7.58, 95% CI 5.41–10.64). Similar magnitude of RR of underweight was observed among the three groups. Preterm and SGA infants should be closely monitored for growth failure. Intervention to reduce preterm and SGA birth may lower risk of undernutrition in resource‐limited settings.     

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。     

Transepidermal water loss in newborn infants. VIII. Relation to gestational age and post-natal age in appropriate and small for gestational age infants

In 68 appropriate for gestational age (AGA) and 33 small for gestational age (SGA) infants, transepidermal water loss was studied during the first four weeks after birth. The method used to measure evaporation rate is based on measurement of the water vapour pressure gradient close to the skin surface. All measurements were made at an ambient humidity of 50% and with the infants calm and quiet. At all the investigated post-natal ages in both AGA and SGA infants, an exponential relationship was found between transepidermal water loss (g/m2 h) and gestational age, this loss being much higher in the pre-term infants than in those born at term. The transepidermal water loss was generally lower in SGA than in AGA infants during the first week of post-natal life, irrespective of gestational age at birth. There was a gradual decrease in transepidermal water loss with increasing post-natal age in both pre-term AGA and pre-term SGA infants. Three weeks after birth this water loss tended to be higher in pre-term SGA infants than in pre-term AGA infants of corresponding gestational age.     

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.     

Body water content of extremely preterm infants at birth

BACKGROUND: Preterm birth is often associated with impaired growth. Small for gestational age status confers additional risk. AIM: To determine the body water content of appropriately grown (AGA) and small for gestational age (SGA) preterm infants in order to provide a baseline for longitudinal studies of growth after preterm birth. METHODS: All infants born at the Hammersmith and Queen Charlotte's Hospitals between 25 and 30 weeks gestational age were eligible for entry into the study. Informed parental consent was obtained as soon after delivery as possible, after which the extracellular fluid content was determined by bromide dilution and total body water by H(2)(18)O dilution. RESULTS: Forty two preterm infants were studied. SGA infants had a significantly higher body water content than AGA infants (906 (833-954) and 844 (637-958) ml/kg respectively; median (range); p = 0.019). There were no differences in extracellular and intracellular fluid volumes, nor in the ratio of extracellular to intracellular fluid. Estimates of relative adiposity suggest a body fat content of about 7% in AGA infants, assuming negligible fat content in SGA infants and lean body tissue hydration to be equivalent in the two groups. CONCLUSIONS: Novel values for the body water composition of the SGA preterm infant at 25-30 weeks gestation are presented. The data do not support the view that SGA infants have extracellular dehydration, nor is their regulation of body water impaired.     

Growth and development are similar in VLBW children born appropriate and small for gestational age: an interim report on 97 preschool children

AIM: To investigate growth and development in a cohort of children born with very low birth weight (VLBW) treated at a single tertiary neonatal unit. METHODS: We studied 97 children born between January 1995 and July 1997 with BW <1,500 g. At follow-up (mean age 3.7 years) anthropometric data and data on neurological status, motor, speech and language development were collected. Small for gestational age (SGA) was defined as weight and/or length at birth <10th percentile; shortness at follow-up was defined as height <10th percentile. RESULTS: Comparison was made between the appropriate for gestational age (AGA) (n = 46) and SGA (n = 51) groups. At follow-up, 23 AGA and 35 SGA children were short, had a smaller head circumference (-1.9 vs -0.8 SDS), were lighter at birth (BW -1.3 vs -0.7 SDS), and had a higher rate of broncho-pulmonary dysplasia (BPD) (28 vs 12); no differences in neonatal characteristics or neurological status were evident. A higher frequency of motor delay occurred in the 'short' group. Short children also had a smaller head circumference (HC) (-1.6 vs -0.7). Short SGA children had a higher frequency of BPD, smaller HC (-2.1 vs -1.0), and a slightly higher proportion of suspicious neurological findings, motor delay, and speech and language delay (n.s.). CONCLUSIONS: Preterm VLBW infants, whether AGA or SGA at birth, face the risk of being short at preschool age. Height outcome is probably influenced by postnatal factors. Our data also suggest that short stature is associated with developmental difficulties in this population.     

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.     

Longitudinal growth of head circumference in term symmetric and asymmetric small for gestational age infants

Aims

To study longitudinal growth pattern of head circumference of full-term symmetric and asymmetric small for gestational age (SGA) infants of the two sexes during first year of life.

Study Design

Mixed-longitudinal growth research design.

Subjects

Head circumference amongst full-term 100 symmetric, 100 asymmetric as well as 100 appropriate for gestational age (AGA) infants was measured at birth, 1, 3, 6, 9 and 12 months of age using standardized technique and instrument.

Results

The mean head circumference of male symmetric SGA infants measured significantly (p ≤ 0.001) smaller than asymmetric SGA infants while, in female symmetric SGA infants it measured shorter beyond 6 months. As compared to AGA infants, head circumference in symmetric and asymmetric SGA infants measured significantly smaller in size. Growth velocity for head circumference amongst symmetric and asymmetric SGA male infants did not show statistically significant differences. Rate of head circumference growth remained significantly higher amongst female asymmetric SGA infants than the symmetric ones between 3 and 6 months while, a reversal of trend was observed between 9 and 12 months.

Conclusion

The better growth attainments for head circumference of male and female asymmetric SGA infants than their symmetric SGA counterparts during first postnatal year of life may be attributed to the continuation of influence of “head sparing” experienced by asymmetric SGA babies during prenatal life.     

Underlying maternal and pregnancy‐related conditions account for a substantial proportion of neonatal morbidity in late preterm infants

Aim

We studied the impact of maternal and pregnancy‐related conditions and the effect of gestational age itself, on the health of infants born late preterm.

Methods

Singletons born in gestational weeks 34 + 0 to 41 + 6 in 1995–2013 in the southern region of Sweden were identified from a perinatal register. We found 14 030 infants born late preterm and 294 814 born at term. A hierarchical system was developed to examine the impact of pregnancy complications. The outcomes studied were as follows: neonatal death, central nervous system (CNS) or respiratory disease, infection, neonatal admission and respiratory support. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained using logistic regression analyses.

Results

Late preterm infants were at increased risk for all outcomes compared to term infants, with adjusted ORs from 13.1 (95% CI: 12.7–13.6) for neonatal admission to 2.3 (95% CI: 1.8–2.9) for infections. Late preterm birth after preterm prelabour rupture of membranes was associated with an overall lower risk compared to late preterm births due to other causes. Exposure to antepartum haemorrhage or maternal diabetes increased the risk for CNS and respiratory morbidity.

Conclusion

Morbidity decreased in late preterm infants with increasing gestational age. Underlying conditions accounted for a substantial part of the morbidity.     

Peripheral nerve conduction velocity and brainstem auditory evoked responses in small for gestational age preterm infants

Ulnar nerve conduction velocity (NCV) and brainstem auditory evoked responses (BAER) were measured in each of 11 preterm small for gestational age (SGA) infants born at less than 35 weeks gestation. The mean motor NCV in the SGA infants was similar to that reported for infants who were appropriately grown for their gestational age (AGA). However, the mean central conduction time of the BAER in SGA infants was significantly shorter than that of AGA infants of the same post-menstrual age. Thus, the precocious development of auditory brainstem neural function in preterm SGA infants is not accompanied by changes in functional maturation of the peripheral motor nerves.     

Low‐birthweight rates higher among Bangladeshi neonates measured during active birth surveillance compared to national survey data

Birth size is an important gauge of fetal and neonatal health. Birth size measurements were collected within 72 h of life for 16 290 live born, singleton infants in rural Bangladesh from 2004 to 2007. Gestational age was calculated based on the date of last menstrual period. Newborns were classified as small‐for‐gestational age (SGA) based on a birthweight below the 10th percentile for gestational age, using three sets of US reference data. Birth size distributions were explored based on raw values as well as after z‐score standardisation in reference to World Health Organization (WHO) 2006 growth standards. Mean (SD) birthweight (g), length (cm) and head circumference (cm) measurements, completed within [median (25th, 75th percentile)] 15 (8, 23) h of life, were 2433 (425), 46.4 (2.4) and 32.4 (1.6), respectively. Twenty‐two per cent were born preterm. Over one‐half (55.3%) of infants were born low birthweight; 46.6%, 37.0% and 33.6% had a weight, length and head circumference below ?2 z‐scores of the WHO growth standard at birth; and 70.9%, 72.2% and 59.8% were SGA for weight based on Alexander et al., Oken et al. and Olsen et al. references, respectively. Infants in this typical rural Bangladesh setting were commonly born small, reflecting a high burden of fetal growth restriction and preterm birth. Our findings, produced by active birth surveillance, suggest that low birthweight is far more common than suggested by cross‐sectional survey estimates. Interventions that improve fetal growth during pregnancy may have the largest impact on reducing SGA rates.     

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.     

Decreased bone mineral content in small-for-gestational-age infants compared with appropriate-for-gestational-age infants: normal serum 25-hydroxyvitamin D and decreasing parathyroid hormone

Bone mineral content was determined by photon absorptiometry, adapted for use in neonates, in 23 small-for-gestational-age (SGA) infants of 31 to 42 weeks of gestational age, for 12 weeks. At birth, term SGA infants had lower bone mineral content than term appropriate-for-gestational-age (AGA) infants; postnatal increase in bone mineral content was slow and lagged significantly behind that of term AGA infants. Preterm SGA infants had bone mineral content that was similar to that of preterm AGA infants at birth; postnatal bone mineral content was similar to that of preterm AGA infants, but was decreased compared with the expected intrauterine bone mineral content. Serum 25-hydroxyvitamin D concentrations and parathyroid hormone levels were the same for SGA and AGA infants. Serum 25-hydroxyvitamin D concentrations decreased slightly with postnatal age and remained within normal limits. Serum parathyroid hormone concentrations decreased in both SGA and AGA infants and reached undetectable levels at 10 to 12 weeks of age.