Ultrasonographic spleen dimensions in preterm infants during the first 3 months of life.

OBJECTIVE: The purpose of this study was to ultrasonographically evaluate spleen dimensions in healthy prematurely born neonates and infants during the first 3 months of life. METHODS: Ninety-six neonates and infants aged from 2 to 90 days, with gestational ages from 25 to 35 weeks, were prospectively examined between 2001 and 2003. None had either infectious or other serious diseases or congenital disorders. The relationships between the ultrasonographically measured spleen size parameters and postmenstrual age, sex, gestational age, and somatometric parameters (height, weight, and body surface area) were studied with linear regression models with backward selection. Spleen dimension growth curves and upper/lower limits defined by the upper/lower 95% confidence interval were presented in graphs by height, weight, and body surface area. In addition, spleen length was compared with recently published data on term peers. RESULTS: All spleen dimensions were positively correlated with postmenstrual age and somatometric parameters. Sex did not influence the variability of spleen dimensions. Spleen length had lower values and a smaller rate of growth in preterm than term neonates and infants. CONCLUSIONS: We have provided ultrasonographic spleen volumetric values in preterm neonates and infants during the first 3 months of life, giving reference standards applicable for clinical practice or research purposes.     

婴幼儿脑发育及外部性脑积水的MRI研究分析

目的揭示发育期婴幼儿脑室及脑外间隙随月龄变化的特征,并探讨外部性脑积水MRI诊断标准。方法选取2009年1月-2013年5月就诊宝鸡市中心医院疑诊脑部疾患小儿,经严格纳入和排除标准选择671例3岁以内没有神经系统疾病的婴幼儿,按月龄分为9组,在T1WI上测量脑室大小,即前角指数、体部指数,计算脑室颅腔横径（VT/ST）比值,在T2WI上测量脑外间隙、前纵裂、外侧裂的宽度;149例外部性脑积水患儿,采用上述相同的测量方法,并动态观察外部性脑积水的变化。结果 1脑室体积随年龄增长而增大,但其前角指数[（0.32±0.05）mm]及VT/ST比值（14.09%±1.56%）较恒定;脑外间隙随年龄增长呈先增宽后变窄的趋势,〉3～6月龄组为这种趋势的转折点。2外部性脑积水患儿额部蛛网膜下腔、前纵裂及外侧裂间隙均超过相应年龄组标准值上限,VT/ST比值〈15%。结论婴幼儿脑室及脑外间隙各年龄组标准值为评价小儿脑发育提供依据,其中前角指数和VT/ST比值是判定脑室大小的可靠指标;蛛网膜下腔和半球间裂宽度及VT/ST比值可作为诊断外部性脑积水的客观指标。对于继发性外部性脑积水,应采取积极临床干预。     

Sonographic depiction of changes in ventricular size associated with repeated ventricular aspirations

Serial real-time cranial sonography was performed on 11 preterm neonates who had demonstrated progressive posthemorrhagic ventricular dilatation and were subjected to repeated ventricular aspirations. Changes in ventricular size were correlated with gestational age, birth weight, and extent and location of the intracranial hemorrhage, as well as the timing, frequency, and location of the ventricular aspirations and the average amount of cerebrospinal fluid removed. The sizes of both lateral ventricles of each neonate were measured and the occurrence of sequelae related to repeated ventricular aspiration was examined. Eleven ventricles diminished in size, eight increased, and there was no change in three. Two neonates had bleeding near the aspiration sites. It is concluded that repeated aspiration can be associated with a diminution in ventricular size in some neonates. It is recommended that alternative methods of treatment, such as serial lumbar puncture or external ventriculostomy, be attempted prior to initiating repeated ventricular aspirations.     

Noncystic "increased" periventricular echogenicity and other mild cranial sonographic abnormalities: predictors of outcome in low birth weight infants

The sonograms of 71 low birth weight infants were retrospectively reviewed and compared with results of neuromotor examinations at 24 months of age to determine whether mild abnormalities commonly detected on cranial sonograms (including milder grades of hemorrhage, ventricular dilation, and noncystic increases in periventricular echogenicity) were correlated with future neurologic handicaps. Of the 71 infants studied, increased periventricular echoes were noted in 20 (28%), Grade 1 or 2 intracranial hemorrhage in 31 (43%), and mild-moderate ventriculomegaly in 28 (39%). Neuromotor handicaps were detected in 15 (21%). No significant correlation was found between the above sonographic abnormalities and the incidence of future neuromotor handicaps. When those neonates with asymmetric mild-moderate ventriculomegaly were separately analyzed, this group was found to have more neuromotor handicaps (p less than 0.05) than those with normal ventricular size, and this finding warrants future study. Importantly, early cranial sonograms were completely normal in 12% of those infants with neuromotor handicaps. We conclude that the presence of mild cranial sonographic abnormalities (including mildly increased periventricular echogenicity) in these infants is not well correlated with neuromotor handicaps detected at 24 months of age.     

Gamma-carboxyglutamic acid in urine of newborn infants

Gamma-Carboxyglutamic acid (GLA) was measured in the urines obtained from 11 full-term infants, 48 pre-term infants appropriate for gestational age (AGA), and 25 small-for-gestational age (SGA) infants. Separation was performed by high resolution anion exchange chromatography. The results were similar in both AGA and SGA infants. During the first 3 days of life, urinary GLA mean (and range) was 1.66 (0.34-4.60) in the low birth weight infants versus 0.88 (0.26-1.38) in the full-term infants and 0.76 (0.62-1.15) mumol . kg-1 X 24 h-1 in the control adults. In the low birth weight infants, urinary GLA fell from 2.79 (0.61-5.75) at age 1-3 days, to 1.55 (0.26-4.04) mumol/24 h at day 8 (p less than 0.01); it then rose again slowly to 2.12 (0.65-3.93) mumol/24 h at day 45. In these infants there was no correlation between urinary GLA excretion and birth weight or gestational age, or urinary hydroxyproline or serum alkaline phosphatase. Despite the well-known reduced blood levels of vitamin K dependent coagulation factors in neonates, these results show that urinary GLA excretion is at least similar to the excretion in adults. These data suggest that these neonates can carboxylate glutamic acid and that the newborn infant has a high bone turnover.     

Foetal growth determines cerebral ventricular volume in infants The Generation R Study

The cerebral ventricular system is a marker of brain development and a predictor of neurodevelopmental outcome. In premature or dysmature neonates, neuroanatomical structures including the ventricular system appear to be altered. The present study aims to provide information on the association between foetal growth and neonatal cerebral ventricular size in the normal population. Within the Generation R Study, a population-based cohort study, we used three-dimensional cranial ultrasound to determine lateral ventricular volume in 778 term infants aged 4-12 weeks. Foetal growth characteristics were repeatedly measured in early, mid- and late pregnancy and analysed in relation to ventricular volume divided by head circumference. Results revealed positive associations between foetal head circumference in late pregnancy and log-transformed ventricular volume (beta=0.077, 95% confidence interval (0.017; 0.136), equivalent to a 7.7% increase in ventricular volume per standard deviation of head circumference). Similarly, in a per week-longer gestational duration, ventricular volume in infancy was 6.0% larger. Multilevel modelling demonstrated that reduced growth of foetal head circumference and biparietal diameter during pregnancy were associated with decreased ventricular volume in infancy. In conclusion, foetal maturation is positively associated to cerebral ventricular size in term infants. Larger ventricular size in term infants needs to be distinguished from ventricular enlargement due to intraventricular haemorrhage or white matter damage in premature or dysmature infants. Moreover, the naturally occurring enlargement of ventricles during infancy should be considered in interpreting reports on increased ventricular volumes in several neuropsychiatric disorders.     

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus

Background

Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out.

Methods

Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in “healthy” (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant.

Results

29 control infants median (range) corrected gestational age at scan 34⁺⁶(31⁺¹-39⁺³) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30⁺³(27⁺³-36⁺¹) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed.

Conclusion

CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained.     

中山地区新生儿先天性甲状腺功能减低症筛查结果分析

目的探讨不同性别、胎龄、出生体质量新生儿与先天性甲状腺功能减低症(CH)患病的关系及其促甲状腺激素(TSH)水平人群分布特点,指导临床筛查工作。方法对2014-2018年中山地区新生儿CH筛查结果进行回顾性分析,采用单因素分析比较不同性别、胎龄、出生体质量新生儿间CH发病率差异及TSH水平人群分布情况。结果筛查239006例新生儿,确诊CH 139例,发病率为0.058%(139/239006)。过期产儿CH发病率高于足月儿,差异有统计学意义(P<0.05)。新生儿TSH水平呈右偏态分布,不同性别、胎龄、出生体质量新生儿TSH水平单侧95%参考值范围均不同,各组人群TSH水平比较,差异均有统计学意义(P<0.001)。结论新生儿疾病筛查能有效帮助CH患儿早期诊断,过期产是CH发病的影响因素,临床医生在实际工作中还可将新生儿TSH水平人群分布特点纳入参考,做好CH的筛查工作。     

Differences in pain expression between male and female newborn infants

The study of neonatal gender differences in pain expression is important since neonatal pain behavior occurs prior to any learned reaction pattern. The objective of this study was to verify the presence of gender differences in pain expression in preterm and term newborn infants. Sixty-five consecutive neonates (37 female and 28 male infants) with gestational age between 28 and 42 weeks and with 25-120 h of life were studied. Healthy term neonates required a capillary puncture for PKU screening and clinically stable premature infants needed a capillary puncture for glucose dosage. The Neonatal Facial Coding System (NFCS) and the Neonatal Infant Pain Scale (NIPS) were evaluated at bedside prior to the puncture, when patients were at rest, during foot heating; during capillary puncture; and at 1, 3, and 5 min after heel lancing. Results were analyzed by repeated-measures ANOVA followed by the Multiple Comparison Method of Bonferroni. A significant difference among the mean NFCS scores during the six study periods was noted for the whole group of neonates (P<0.000001). Also, a significant interaction between the NFCS score profile in female and male neonates at the different study periods was observed (P=0.025). Regarding NIPS, ANOVA showed only a significant difference among the mean NIPS scores during the six study periods for the whole group of neonates (P<0.000001). No significant interactions between gestational age and time, nor between gestational age and gender were noted, for both NFCS and NIPS. In conclusion, recently born female neonates of all gestational ages expressed more facial features of pain than male infants, during the capillary puncture and 1 min afterwards. Maybe differences in pain processing and/or pain expression among genders may explain this finding.     

Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants, and children

The therapeutic and toxic effects of amikacin are known to depend on its concentration in plasma, but the pharmacokinetics of this drug in neonates, infants, and children and the influences of clinical and biological variables have been only partially assessed. Therapeutic drug monitoring data collected from 155 patients (49 neonates, 77 infants, and 29 children) receiving amikacin were analyzed by a nonparametric population-based approach, the nonparametric maximum-likelihood method. We assessed the effects of gestational and postnatal age, weight, Apgar score, and plasma creatinine and urea concentrations on pharmacokinetic parameters. There is no specific formulation of amikacin for neonates and infants. We therefore used an error model to account for errors due to dilution during preparation of the infusion. The covariates that reduced the variance of clearance from plasma and the volume of distribution by more than 10% were postnatal age (43 and 28%, respectively) and body weight (30.4 and 17.4%, respectively). The expected reduction of clearance was about 10% for the plasma creatinine concentration. The other covariates studied (Apgar scores, plasma urea concentration, gestational age, sex) were found to have little effect. Simulations showed that a smaller percentage of patients had a maximum concentration in plasma/MIC ratio greater than 8 with a regimen of 7.5 mg/kg of body weight twice daily than with a regimen of 15 mg/kg once a day for MICs of 1 to 8 mg/liter.     

小于胎龄儿血中胃肠激素水平对其胃肠道营养影响的研究

目的探讨小于胎龄儿生后血中胃肠激素水平变化及其对胃肠道营养的影响。方法应用放射免疫法监测118例小于胎龄儿（其中早产62例;足月52例）生后喂奶前及第7日胃动素（MOT）、胃泌素（GAS）浓度,并与85例正常足月新生儿作为对照组。结果①小于胎龄儿组生后喂奶前及第7d空腹血浆MOT、GAS均明显低于对照组;但随胎龄、日龄、奶量增加而升高,呈正相关;第7d时已超过足月儿对照组生后开奶前水平;②喂养不耐受组小于胎龄儿生后空腹血中MOT、GAS浓度均较喂养正常组低;③早期喂养能改善小于胎龄儿MOT水平和胃肠道动力,提高肠道喂养的耐受性。结论小于胎龄儿消化道机能适应胃肠道营养,在严密观察下早期喂养,将能促进小于胎龄儿胃肠道的发育和成熟。     

足月新生儿早期行为神经评分与出生体质量及胎龄的相关性

目的了解足月新生儿早期行为神经发育水平,探讨行为神经评分与出生体质量及胎龄的相关性。方法 2012年5-9月,采用便利抽样法选取莆田学院附属医院妇产科出生的单胎正常足月儿93例,采用新生儿20项行为神经测定(neonatal behavior neurological assessment,NBNA)法于新生儿出生后48~72h分别检测25例小于胎龄新生儿(small for gestational age,SGA)、35例适于胎龄新生儿(appropriate for gestational age,AGA)和31例大于胎龄新生儿(large for gestational age,LGA)的行为神经能力。结果与AGA组相比,SGA组、LGA组新生儿的NBNA总分、行为能力、主动肌张力、一般反应、对格格声反应、对说话人的反应、红球反应、牵拉反射、活动度评分等均明显降低(P0.05);SGA组新生儿NBNA各项目评分与出生体质量及胎龄呈正相关,而LGA组新生儿NBNA各项目评分则与出生体质量及胎龄呈负相关。结论新生儿早期行为神经评分与出生体质量及胎龄相关;应加强孕妇的孕期保健以减少SGA及LGA的发生,对早期发现有行为神经轻微异常的新生儿,应及早进行干预,以促进其行为神经的正常发育。     

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants.

OBJECTIVE: To study the pharmacokinetics of flunitrazepam (used for sedation in neonates and infants), to determine the influence of both gestational and postnatal age on the pharmacokinetic parameters, and to analyze the relationship between the hemodynamic parameters and flunitrazepam plasma concentration. METHODS: Flunitrazepam was infused for 20 minutes as a single dose (0.2 mg x kg(-1)) and as multiple doses (0.1 mg x kg(-1)). Six to eight 1-mL blood samples were collected per patient. Flunitrazepam plasma concentration was measured by gas chromatography-mass spectrometry. RESULTS: Thirty-one patients (25 neonates and six infants) were included in the study. Only three of them received multiple doses. After the single dose (n = 28), half-life was 22.6 +/- 7.3 hours, clearance was 0.15 +/- 0.14 L x kg x h(-1), and volume of distribution was 4.6 +/- 4.1 L x kg(-1) (mean +/- SD). Plasma clearance and volume of distribution significantly increased with postnatal age (P < .05), but no pharmacokinetic parameter varied significantly with gestational age. Diastolic blood pressure significantly decreased with increasing flunitrazepam plasma concentrations (P < .05). CONCLUSION: Postnatal age but not gestational age influenced flunitrazepam pharmacokinetic parameters in neonates and infants. Diastolic blood pressure was inversely correlated to flunitrazepam plasma concentration.     

Improved birth weight table for neonates developed from gestations dated by early ultrasonography

Most previously published tables of birth weight percentiles as a function of gestational age have been derived from neonates with imprecise gestational dating. In order to improve the accuracy of neonatal birth weight percentiles, we developed a birth weight table based on measurements from a group of neonates who had accurate gestational dating by prenatal first trimester ultrasonography. By matching a database of obstetrical ultrasonograms over a 5 year period to birth records at our institution, 3718 newborn infants with gestational dating by first trimester ultrasonography were identified. Statistical smoothing and regression techniques were applied to gestational age at birth and birth weight data to develop a table for the 10th, 50th, 90th, and other weight percentiles for 25 weeks of gestation onward. The weight table developed from our population has lower 50th and 90th percentile weights, and narrower 10th to 90th percentile ranges, at 25 to 35 weeks than in prior tables. At 39 to 43 weeks, our 10th, 50th, and 90th percentile weights are higher than those in previous tables. Our weight table for newborn infants, based on measurements from neonates with accurate dating, permits improved assignment of weight percentiles for gestational age and more accurate diagnosis of growth disorders in fetuses and neonates.     

Zidovudine Pharmacokinetics in Premature Infants Exposed to Human Immunodeficiency Virus

We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 ± 0.44 ml/min/kg; volume of distribution, 1.59 ± 0.51 liters/kg; and half-life, 7.2 ± 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.     

Assessment of postnatal gestational age using sonographic measurements of femur length.

Assessment of gestational age in the premature newborn infant is both essential and difficult. The purpose of this study is to evaluate a new method for the assessment of gestational age in premature neonates using femur length measurements obtained by ultrasonography and compare these with an established clinical method. Forty-seven newborn infants with true gestational age calculated by reliable last menstrual period, further confirmed by obstetric ultrasonographic estimation performed at <18 weeks, were enrolled within 3 days of birth. Birth weight, length, and head circumference were appropriate for the true gestational age. The modified Ballard maturational scoring system was used to determine gestational age. A trained sonographer imaged the femur and measured the shaft of the femur using electronic calipers. Gestational age was estimated from an average of six femur length measurements by a radiologist blinded to the study using tables of fetal femur length measurements. Results indicate that gestational age assessment by ultrasonography has an excellent correlation with true gestational age (r = 0.93), as does assessment by the Ballard score (r = 0.87), with no statistical difference between both the correlations' coefficients. We conclude that gestational age assessment in newborn infants weighing <1500 g, without intrauterine growth retardation, by sonographic measurement of femur length is an excellent means to estimate true gestational age. Furthermore, the sonographic method is ideal for sick, paralyzed neonates and may be useful in the design of future clinical trials.     

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilmicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 mug/ml were observed 30 min after 3- and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.     

Population pharmacokinetic analysis of netilmicin in neonates and infants with use of a nonparametric method

BACKGROUND: Although the therapeutic and toxic effects of netilmicin are related to its plasma concentration, its pharmacokinetics in neonates and infants and the influence of clinical and biological variables have been only partially assessed. METHODS: Therapeutic drug monitoring data collected from 186 neonates and 95 infants receiving netilmicin were analyzed with a nonparametric population approach. The influence of gestational and postnatal age, weight, Apgar score, and creatinine and urea plasma concentrations on the pharmacokinetic parameters was assessed. The neonate and infant groups were each randomly divided into a learning sample and a validation sample. The population analysis was performed on each learning subgroup with the nonparametric maximum likelihood (NPML) method. In the validation group, the data were used to assess the concentration predictability. Because there is no specific netilmicin formulation for neonates and infants, an error model was proposed to account for errors attributable to dilution processes when preparing the infusion. RESULTS: In neonates, the covariates that reduced expected variance of plasma clearance by more than 10% were postnatal age, body weight, and plasma creatinine, as well as plasma urea and creatinine in infants. Body weight and sex played a significant role in explaining the variability of the volume of distribution. The accuracy of the concentration predictability assessed in the validation samples was satisfactory, and no significant bias was found. CONCLUSION: These findings help explain the large interindividual variability of the pharmacokinetics of netilmicin and the influence of the clinical and laboratory covariates in neonates and infants.     

Biochemical markers in the assessment of protein-calorie malnutrition in premature neonates

We studied 135 premature newborns of 26 to 36 weeks gestation, divided into three groups: the control group, 66 premature infants with uncomplicated course; 51 premature neonates with appropriate birth weight for gestational age (AGA), who suffered from clinical problems that delayed oral feeding; and 18 premature infants with small birth weight for gestational age (SGA). When neonates of the same postnatal age were compared, prealbumin concentrations were the lowest in the SGA group at the third and fourth postnatal week. Although the AGA group had the most infants with serious illnesses and the lowest protein-calorie intakes, their prealbumin concentrations did not differ significantly from those of the control group. But when the infants of each group were subdivided on the basis of intakes and weight gain regardless of postnatal age, those with greater intakes showed significantly higher prealbumin values; however, in all groups, the infants with higher intakes were also significantly older. Total proteins and albumin showed similar changes in all groups. Prealbumin concentrations showed great interindividual variability in infants of the same postnatal age. We conclude that prealbumin, albumin, and serum total proteins are not sufficiently sensitive biochemical markers to assess alterations of the nutritional status of premature infants.     

Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations

Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two-compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug-level monitoring in a well-defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required.