Early physiological development of infants with intrauterine growth retardation

OBJECTIVES: To assess the patterns of early postnatal physiological adaptation and maturation in intrauterine growth retarded (IUGR) infants by measuring changes in sleeping deep body temperature, heart rate, and concentrations of urinary cortisol. SETTING: At home. PATIENTS: Sixty five IUGR babies and 127 controls matched for sex, social class, and levels of parental smoking. RESULTS: Night time sleeping deep body temperature, heart rate, and cortisol excretion fell with age, eventually establishing an adult type diurnal rhythm of physiological function. Minimum overnight temperature showed a linear decline with age (p < 0.001), but the IUGR infants and the controls had significant differences in intercept (p = 0.007) and slope (p = 0.02). The estimated rate of decline per week was 0.020 degrees C for IUGR infants and 0.031 degrees C for controls. Maximum temperature did not show similar changes. IUGR infants had a mean (SE) age adjusted minimum overnight heart rate that was 4.2 (1.5) beats/min (p = 0.005) higher than controls. Overnight cortisol/creatinine ratios declined with age at a rate of 4.1% per week (log ratio -0.421 (0.0165), p = 0.01), but the ratio for IUGR infants was on average 42% higher (log ratio 0.35 (0.11), p = 0.002) than for controls of the same age. Morning cortisol concentrations did not show a similar pattern. CONCLUSIONS: Postnatal physiological adaptation and maturation of IUGR infants is slower than normal and therefore they remain in a physiologically immature state for longer. The higher heart rates and greater cortisol excretion in such infants may be precursors to hypertension and cardiovascular disease seen in adults.     

Metabolic consequences of intrauterine growth retardation in very low birthweight infants

By the combination of energy and macronutrient balances, continuous open circuit computerized indirect calorimetry, and anthropometry, we have compared small for gestational age (SGA) and appropriate for gestational age (AGA) very low birthweight infants with respect to metabolizable energy intake (mean +/- SE: 125.9 +/- 2.5 versus 130.4 +/- 3.5 kcal/kg X day), energy expenditure (67.4 +/- 1.3 versus 62.6 +/- 0.9 kcal/kg X day), storage of energy and macronutrients and growth. Fourteen studies in six SGA infants (gestational age, 33.1 +/- 0.3 weeks; birthweight, 1120 +/- 30 g) and 22 studies in 13 AGA infants (gestational age, 29.3 +/- 0.4 weeks; birthweight, 1155 +/- 40 g) were performed. The SGA infants had a lower absorption of fat (68.7 +/- 3.2 versus 79.7 +/- 1.7%) and protein (69.1 +/- 3.2 versus 83.4 +/- 1.5%) and hence increased (P less than 0.001) energy loss in excreta (29.9 +/- 2.8 versus 18.2 +/- 1.5 kcal/kg X day). The significant hypermetabolism of SGA infants by 4.8 kcal/kg X day was associated with an increased fat oxidation. Despite lower energy storage, SGA infants were gaining weight (19.4 +/- 0.9 g/kg X day), length (1.25 +/- 0.14 cm/week), and head circumference (1.16 +/- 0.9 cm/week) at higher rates than the AGA group. The energy storage per g weight gain was lower (P less than 0.001) in the SGA group (3.0 +/- 0.14 versus 4.26 +/- 0.26 kcal) reflecting higher water, lower fat (22.2 +/- 1.8 versus 33.8 +/- 2.5%; P less than 0.001) and lower protein (7.7 +/- 0.5 versus 12.5 +/- 0.8%; P less than 0.001) contents of weight gain in the SGA group.     

Vancomycin elimination in human infants with intrauterine growth retardation

BACKGROUND: Intrauterine growth retardation (IUGR) results in substantial decrease in nephron number and renal and hepatic organ mass in experimental animals and newborn infants. Because the liver and the kidneys are the major organs for drug biotransformation and elimination, any decrease in their size and function may lead to impaired metabolism and elimination of drugs in newborns with IUGR. Our objective was to test the hypothesis that IUGR results in prolonged renal elimination of vancomycin in newborns. METHODS: Small for gestational age (SGA) infants (n = 20) were matched with appropriate for gestational age (AGA) infants (n = 123). Steady state peak and trough serum concentrations were used to calculate vancomycin clearance (Cl), volume of distribution (Vd) and half-life (t(1/2)) for each subject. Pharmacokinetic profiles were compared between groups. RESULTS: Overall, Cl, Vd and t(1/2) of vancomycin were the same between groups. However, stratification showed decreased Cl in those SGA versus AGA newborns 3-4 weeks old and in those newborns with a postconceptional age of 27-29 weeks. There was no difference in Vd, normalized for weight, between SGA and AGA babies. The half-life of vancomycin was similar across most groups but was prolonged in SGA newborns aged 3-4 weeks. CONCLUSIONS: Vancomycin Cl differs between SGA and AGA newborns. This difference is greatest early in life and normalizes between groups after the fourth week of life or after 29 weeks postconceptionally. Normalized Vd is similar between SGA and AGA newborns. The elimination of vancomycin is comparable between SGA and AGA infants, except before the fifth week of life, when SGA newborns may eliminate the drug more slowly. Specific vancomycin dose recommendations for SGA versus AGA neonates may therefore be justified during the first month of life.     

Early treatment with nasal continuous positive airway pressure in very low-birth-weight infants

During 1988 and 1989, a regional cohort of 81 infants with birth weights less than 1501 g were treated with oxygen only ( n = 11), early continuous positive airway pressure (CPAP) ( n = 68) or mechanical ventilation from birth ( n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO₂. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only 4 survivors (6%) developed prognostically significant bleedings grade 2–4. No survivors had bronchopulmonary dysplasia. Follow-up at 12–39 months of age revealed definite disabilities in 6 (10%) and suspected disabilities in 2 of 62 long-term survivors. The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO₂ may be effective and lenient in most infants more than 25 weeks' gestation.     

Insulin resistance in short children with intrauterine growth retardation

Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development.     

Insulin resistance in short children with intrauterine growth retardation

Chiarelli F, di Ricco L, Mohn A, De Martino M, Verrotti A. Insulin resistance in short children with intrauterine growth retardation. Acta Pædiatr 1999; Suppl 428: 62–5. Stockholm. ISSN 0803–5326
Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non-insulin-dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development. □ Intrauterine growth retardation, insulin resistance, short children     

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。     

Early pregnancy screening for intrauterine growth retardation

In a prospective clinical study from Uppsala County, Sweden, in 1980, all pregnancies were screened early in pregnancy for 15 previously reported risk factors for intrauterine growth retardation (IUGR). This risk group (n = 639) was then compared with a randomly selected control group (n = 539). In the risk group, there were increased risks for the delivery of growth retarded infants, low birthweight infants and infants spontaneously delivered as prematures. 30% of the population exhibited risk factors. Smoking was the most important risk factor, 16% of the mothers smoked at least ten cigarettes per day and smoking was the main risk factor in the majority of cases with IUGR.     

Abnormal cardiac histology in severe intrauterine growth retardation infants

Four infants with severe intrauterine growth retardation (IUGR) weighing less than 1000 g at birth developed heart failure and died in our unit, where heart failure of IUGR infants is the main reason of death in extremely low birth-weight infants. The causes of their heart failure are one of the main themes in current neonatal medicine. The subjects of this study were four small for gestational age infants; all died due to heart failure 5 to 10 days after birth. Microscopic specimens of hearts from autopsies were evaluated with respect to the following characteristics: thickness of myocardial fibers, maturation of nuclei, presence of dysgenesis or necrosis in myocardium, and amount of glycogen in the heart. Neither dysgenesis nor infarction of the heart was found but hypoplasia in myocardial fibers and decreased glycogen levels were observed. Maturation delay in myocytes' nuclei did not appear to be severe. We conclude that these infants' hearts failed to adapt to postnatal hemodynamic changes because of inadequate myocardial function and inadequate glycogen reserves.     

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.     

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。     

宫内生长迟缓早产儿T淋巴细胞亚群水平变化

目的 了解宫内生长迟缓（IUGR）早产儿生后T淋巴细胞亚群水平及变化。方法 67例早产儿中IUGR早产儿29例,适于胎龄（AGA）早产儿38例;另取健康足月儿20例为对照组。采用流式细胞仪测定各组出生24 h内及校正胎龄38周时外周静脉血T淋巴细胞亚群水平;同时测定各时间点外周血白细胞、淋巴细胞及T淋巴细胞绝对计数。结果 24 h内IUGR早产儿CD3+、CD4+百分比低于AGA早产儿和对照组（P<0.05）,IUGR 早产儿CD8+及CD4+/CD8+低于对照组（P<0.05）,AGA早产儿CD3+、CD4+及CD4+/CD8+低于对照组（P<0.05）;IUGR早产儿外周血淋巴细胞低于对照组（P<0.05）,IUGR、AGA早产儿的T淋巴细胞低于对照组（P<0.05）,IUGR早产儿T淋巴细胞低于AGA早产儿（P<0.05）。校正胎龄38周时,IUGR、AGA早产儿CD3+、CD4+及CD4+/CD8+高于出生24 h内（P<0.05）,IUGR早产儿CD3+、CD4+、CD8+及CD4+/CD8+低于AGA早产儿（P<0.05）;IUGR与AGA早产儿外周血白细胞、淋巴细胞、T淋巴细胞比较差异无统计学意义（P >0.05）。结论 IUGR早产儿T淋巴细胞亚群免疫功能低于AGA早产儿及健康足月儿,并且持续至生后一段时间。     

Early enteral feeding in very low birth weight infants

Background/aim

Debate exists about when to initiate enteral feeding (EF) in very low birth weight (VLBW) preterm infants. This retrospective study compared the effectiveness of an education-based quality improvement project and the relationship of time of the first EF to necrotizing enterocolitis (NEC) or death incidence and parenteral nutrition (PN) days in VLBW infants.

Study design/subjects

VLBW infants born in 2 epochs were compared for hour of the first feed, PN days, NEC or death incidence, and feeding type. The 2 epochs were temporally divided by a quality improvement initiative to standardize initiation of EF in postnatal hours 6–24.

Results

603 VLBW infants were included. Median time of feed initiation decreased from 33 (Epoch 1) to 14 h (Epoch 2) (p < 0.0001). Median PN days were 14 vs. 12, respectively (p = 0.07). The incidence of NEC or death was 13.4% vs. 9.5%, respectively (p = 0.14). When controlling for birth weight, gestational age, race, gender, and time period, earlier feed initiation was associated with decreased NEC or death (p = 0.003). Evaluation of the relationship of early EF (defined as within the first 24 h) in Epoch 2 alone showed that early EF was significantly associated with decreased NEC or death (6.3 vs 15.1%) (RR, 95% CI = 0.28, 0.13–0.58) and less PN days (p < 0.0001).

Conclusions

In a VLBW infant cohort, an education-based process improvement initiative decreased time of EF initiation to a median of 14 h with no associated increase in NEC or death. In fact, results suggest that earlier feeding is associated with decreased NEC or death.     

Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation

OBJECTIVE: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants. DESIGN: Randomised controlled trial. METHODS: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth. RESULTS: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance. CONCLUSIONS: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.