Quantitative ultrasound and biochemical parameters for the assessment of osteopenia in preterm infants

Objective. Our study aimed to evaluate the feasibility of quantitative ultrasound (QUS) evaluation in osteopenia of prematurity and to compare the results to biochemical parameters.

Methods. QUS assessment of bone was performed at the end of the first postnatal week and at term-corrected age (CA) in premature infants (N = 30) and within the first week in full-term infants (N = 25). On the same day of measurement of QUS, the serum calcium, phosphorus (inorganic), and alkaline phosphatase (ALP) activity were measured in the preterm infants.

Results. The median of tibia z score at term-CA in premature infants was significantly lower compared to that of first postnatal week (?1 and 0.4, respectively; p < 0.0001) and it was also lower than that of term-matched controls (0.0; p = 0.001). Preterm infants at term-CA had lower weights and lengths in comparison to term infants. The median ALP value was 585 IU/L at the first postnatal week and 703 IU/L at term-CA in preterm infants (p = 0.003). The median tibia z score of infants with ALP ≥900 IU/L was significantly lower than that of the infants with ALP <900 IU/L (?1.4 vs. 0.1; p = 0.001). An inverse correlation was found between ALP levels and tibia z score at term-CA in preterm infants (rho = ?0.61, p = 0.01).

Conclusions. Bone density of preterm infants at term-CA was lower than that at first postnatal week. Serum ALP levels increased during the first postnatal weeks. The tibia z scores were correlated to serum ALP levels. QUS is a good screening tool for the detection of osteopenia.     

Assessment of bone health in preterm infants through quantitative ultrasound and biochemical markers

Abstract

Objective: To assess bone status in preterm infants with quantitative ultrasound and to search for biochemical markers of bone health.

Methods: Metacarpus bone transmission time (mcBTT) was prospectively performed during hospitalization, together with biochemical and clinical outcomes analysis.

Results: 154 patients were studied. At 3rd week of life mcBTT positively correlated with serum phosphate. Urinary excretion of calcium and phosphate were assessed in a subgroup of 55 patients: on day 21 mcBTT positively correlated with phosphaturia, negatively with calciuria. Gestational age (GA), weight and length at 3rd week and at 36 weeks of GA correlated positively with mcBTT. We found negative correlation between mcBTT at 3rd week and days of parenteral nutrition, mechanical ventilation period and days to reach 1800?g.

Conclusions: Serum phosphate, phosphaturia and calciuria correlate most with mcBTT. Further studies are necessary to verify the possible influence of early bone status on future bone health.     

Bone ultrasound velocity in small- versus appropriate-for-gestational age preterm infants.

OBJECTIVE: To compare bone status of small-for-gestational age (SGA) versus appropriate-for-gestational age (AGA) newborn preterm infants. STUDY DESIGN: Tibial speed of sound (SOS) was measured in 144 infants categorized as SGA or AGA using the reference tables of Lubchenco et al. and Alexander et al. RESULTS: By the Lubchenco tables, 22% of infants were SGA and 75% were AGA. The mean gestational ages of SGA and AGA were similar (33.3+/-2.6 and 32.5+/-2.4 weeks, respectively, P = 0.09); however, SGA infant birth weights were lower (1329+/-392 and 1829+/-481 g, respectively, P<0.001). SOS values were higher for SGA versus AGA infants (3098+/-135 and 3003+/-122 m/s, respectively. P<0.001). Use of the Alexander tables yielded a twofold increase in the percent of infants categorized as SGA; SOS values remained significantly greater for SGA infants (P<0.001). CONCLUSION: Higher tibial SOS values in SGA versus AGA infants indicate greater bone strength.     

Quantitative parameters for light microscopic assessment of the tubuli seminiferi.

For quantitative, histologic assessment of the testis tubuli there are four suitable parameters: diameter of tubulus, area of tubulus, number of cell nuclei per tubulus, and area of nuclei of the various cells participating in spermatogenesis. For estimating areas, the integrative method of measurement, either with a grid or with the aid of the manual optical picture-analysis system, is proposed. The tubulus diameter can be determined rapidly and easily, although the tubulus size can be assessed more accurately by area estimation. An assessment of reproductive capacity in detail is possible by means of rather time-consuming determination of cell nucleus number and nuclear area, whereby the stages of the cycle of the seminiferous epithelium must be considered.     

Nutritional assessment and measurement of body composition in preterm infants

To compose an optimal nutrition for preterm infants, it is necessary to assess their body composition and metabolism. Much information on body composition has become known by carcass analysis of stillborn (pre)term infants, but these data do not inform us about the rapid alterations in body composition of surviving preterm infants during the first weeks of life. Many noninvasive nutritional assessment techniques have been developed with special adaptation to preterm infants. With these techniques it is now possible to have an accurate assessment of TBW, extracellular water; total body fat; fat-free mass; bone mineral content; energy expenditure (metabolic rate); and energy substrate turnover. Most of these techniques unfortunately show relatively large intraindividual variations and, in most cases, it is only possible to study and compare groups of preterm infants. Studies of individual patients over a certain period of time are still rather inaccurate.     

早产的脑神经保护

全球每年约有1500万早产儿出生,早产已成为新生儿死亡的首要原因,存活早产儿也面临脑性瘫痪、认知障碍及运动异常等严重脑损伤并发症。这些远期不良预后缺乏有效治疗措施,所以宫内早期预防早产脑损伤变得尤为重要。一些随机对照试验和荟萃分析显示,产前应用硫酸镁能减少早产儿脑瘫发生率。然而,不同早产病因、硫酸镁合适治疗窗、硫酸镁给药剂量等仍须进一步阐明。     

Quantitative ultrasound assessment of bone health in the neonate

For a number of reasons there is a need to explore reliable non-invasive methods for assessing bone health in neonates and young infants. Epidemiological studies suggest that early events in life may predispose the adult to degenerative diseases such as osteoporosis. Preterm infants have an increased risk of low bone mass because of limited bone mass accretion in utero and a greater need for bone nutrients. Despite improvements in neonatal care fractures still occur. The diagnosis of osteopaenia of prematurity remains difficult as there is no screening test which is both sensitive and specific. Biochemical indices are non-diagnostic, and plain X-rays in the absence of fractures are poor at diagnosing bone disease. Although dual energy X-ray absorptiometry is increasingly used to assess bone mineral status in newborn infants, the size and immobility of the scanner, the length of time to perform the scan and use of ionising radiation make it unsuitable for routine use in the setting of the fragile very low birth weight infant. Quantitative ultrasound (QUS) was first developed in 1984, as a non-ionising, portable and low cost method of assessing bone health. The measurements obtained from QUS are thought to be related not only to the mineral density of the bone but also to reflect parameters of bone quality and strength. Preliminary studies suggest that this technique may be a useful method of assessing changes in bone health in preterm infants, but the data need to be interpreted carefully. This review will concentrate on the methodology of QUS and the studies that have already been performed in neonates.     

Neurobehavioral assessment predicts differential outcome between VLBW and ELBW preterm infants.

OBJECTIVE: To evaluate the impact of birth weight on development of very low birth weight (VLBW) infants using the Neurobehavioral Assessment of the Preterm Infant (NAPI) before hospital discharge, and to show the relation to follow-up outcomes at 12, 18 and 30 months of age. STUDY DESIGN: In total, 113 preterm infants were assessed with the NAPI at 36 weeks postmenstrual age. Later, neurodevelopment was examined using the Bayley Infant Neurodevelopmental Screener (BINS) at 12 months and the Bayley Scales of Infant Development, at 18 and 30 months. The cohort was divided into two groups, based on birth weight, extremely low birth weight (ELBW) (<1000 g) and VLBW (1000 to 1500 g). RESULTS: ELBW infants showed significantly lower NAPI scores compared with VLBW infants at 36 weeks. The predischarge NAPI scores correlated with the 12, 18 and 30 months scores when the ELBW infants continue to have lower performance than the VLBW infants. In all, 14 infants developed cerebral palsy. These infants had significantly lower NAPI, BINS and Bayley scores compared with all other preterm infants. CONCLUSION: NAPI before discharge provides clinically meaningful information related to later neurodevelopmental outcome.     

Donor human milk for preterm infants.

As survival rates for preterm infants improve, more attention is being focused on improving the quality of survival through optimal nutritional management. The benefits of human milk for term infants are well recognized, with current research suggesting that human milk may especially benefit the preterm infant. Some mothers are unable or unwilling to provide breastmilk for their infants. Although not as well studied as mother's own milk, pasteurized donor human milk can provide many of the components and benefits of human milk while eliminating the risk of transmission of infectious agents. Pasteurization does affect some of the nutritional and immunologic components of human milk, but many immunoglobulins, enzymes, hormones, and growth factors are unchanged or minimally decreased. In California donor human milk costs approximately $3.00 per ounce to purchase. A reduction in length of stay, necrotizing enterocolitis and sepsis may result in a relative saving of approximately $11 to the NICU or healthcare plan for each $1 spent for pasteurized donor milk.     

Movement, imaging and neurobehavioral assessment as predictors of cerebral palsy in preterm infants.

OBJECTIVE: To study the relative efficacy of three early predictors of cerebral palsy. METHOD: One Hundred and thirty infants with birth weight <1500 g were recruited. Video recordings of spontaneous general movements were made at 36 and 52 weeks postconceptional age. Magnetic resonance imaging and the neurobehavioral assessment of the preterm infant were done at 36 weeks postconceptional age. Follow-up neurological examination and Bayley assessments were made at 18 months corrected age to make early identification of cerebral palsy. RESULTS: Magnetic resonance imaging gave the best specificity and accuracy of 91 and 84% respectively. General movements at 52 weeks showed an improved specificity and accuracy over performance at 36 weeks postconceptional age. The negative predictive value for all methods tested was between 90 and 97%. Combining the results of magnetic resonance imaging and the neurobehavioral assessment improved the sensitivity of prediction to 80%, suggesting that a holistic approach to early detection of cerebral lesions is preferable to a single test. CONCLUSIONS: The majority of infants who appeared to behave within normal limits and exhibit normal brain structure in the newborn period were classified as neurologically intact at follow-up.     

Respiratory development in preterm infants.

OBJECTIVE: This study examined the development of respiration during the preterm and early post-term periods and the effects of other biological and environmental variables, including sleep state, on this development. STUDY DESIGN: Weekly 2-hour sleep observations and respiration recordings were obtained on 134 preterm infants from the time they were no longer critical until hospital discharge; a follow-up observation was conducted 1 to 3 months later. RESULTS: All respiratory variables, except length of respiratory pauses in quiet sleep, decreased although the rate of this decrease slowed after term for four variables. Respiratory variables, except variability of respiratory pauses lengths and periodic respiration, differed by sleep state. Covariates, except methylxanthine treatment, had minor effects. Four variables showed hospital-related differences, but cisapride treatment helped to explain the differences in three variables. CONCLUSIONS: Much development of respiration occurs in the early weeks after birth and reflects both neural maturation and effects of other biological and environmental factors, especially medications.     

Evaluation of cerebrospinal fluid parameters in preterm infants with intraventricular reservoirs

Objective:Intraventricular reservoirs (IVRs) are used to drain cerebrospinal fluid (CSF) in neonates with post-hemorrhagic ventricular dilatation (PHVD). The objectives of this case-control study were to evaluate changes in CSF parameters in serial IVR taps and to compare CSF parameters in culture-positive and -negative specimens.Study Design:Clinical and laboratory data from serial (up to 7) reservoir taps at 5- to 8-day intervals were collected on preterm neonates with PHVD and IVR insertion.Result:The median (range) gestational age and birth weight of our cohort (n=52) was 26 (23 to 33) weeks and 796 (450 to 1620) grams. Significant decreases in percentage of CSF neutrophils and protein were noted in later taps, compared with the first tap at insertion of IVR. Five (9.6%) infants had positive CSF cultures on 10 occasions. Compared with negative specimens (n=266), the mean (s.d.) proportion of neutrophils in CSF (55% (33) vs 26% (23)) was significantly higher and ratio of CSF to serum glucose significantly lower (0.19 (0.08) vs 0.29 (0.13)) in culture-positive specimens (n=10). The area under the curve was 0.82 (95% confidence interval (CI) 0.72 to 0.93) for CSF white blood cell (WBC) count, 0.79 (95% CI 0.68 to 0.90) for CSF protein and 0.75 (95% CI 0.56 to 0.95) for percentage of neutrophils. The sensitivities and specificities for diagnosis of infection was 90 and 63% for CSF WBC count > 42?mm(-3), 89 and 58% for CSF protein at > 250?mg?dl(-1) and 80 and 67% for CSF neutrophil proportion >31.5%.Conclusion:CSF parameters from IVR taps, specifically proportion of neutrophils and proteins are higher at insertion and progressively normalize over time. Although they vary widely, CSF WBC, protein and neutrophil proportion using higher cut-off values have good sensitivity in the diagnosis of infection.     

Quantitative assessment of the degree of ductal steal using celiac artery blood flow to left ventricular output ratio in preterm infants

BACKGROUND: Determining the significance of a patent ductus arteriosus (PDA) remains difficult in preterm neonates and current echocardiographic markers give little information about ductal steal. We hypothesized that the relationship between celiac artery flow (CAF) and left ventricular output (LVO) in the presence of a PDA may determine haemodynamic significance. OBJECTIVES: To examine CAF to LVO ratio (CAF:LVO) in the presence and the absence of a PDA in preterm neonates, and to compare CAF:LVO to current echocardiographic markers of a significant PDA. METHODS: This was a prospective observational study of neonates <1,500 g. Echocardiography was performed at 12 h and day 3. PDA, LVO and CAF were measured by echocardiography. The infants were divided into those who developed a significant PDA (PDA >1.4 mm and left atrial to aortic ratio >1.5 on day 3) and controls. A further assessment was carried out following successful PDA treatment with ibuprofen or surgical ligation. RESULTS: A total of 33 infants were enrolled. 19 infants had a PDA (median gestation 27 weeks, birth weight 915 g), and 14 controls (gestation 28.7 weeks, birth weight 1,110 g). At 12 h, there was no difference in CAF, LVO or CAF:LVO. On day 3, there was a significant difference in CAF:LVO between PDA versus control groups. CAF:LVO significantly correlated with conventional markers of ductal significance. A CAF:LVO value of 0.10 had a sensitivity of 93% and a specificity of 78% for the presence of a significant PDA. Following successful PDA treatment CAF:LVO returned to levels similar to controls. CONCLUSION: CAF:LVO may be used to determine which PDA warrants treatment and serve as a marker of treatment success. Trials are needed to correlate CAF:LVO with outcome and the impact of basing PDA treatment on this ratio.     

Cup-feeding for preterm infants: mechanics and safety.

Cup-feeding is recommended for breastfed preterm infants to avoid artificial nipples. However, the oral mechanisms used in cup-feeding, or its safety and efficacy, have not been described. The authors measured sipping, breathing, SaO2, and volume of intake during 15 cup-feeding sessions for 8 infants (mean gestational age at birth was 30.6 weeks). Mean duration of sipping bursts and pauses was 3.6 seconds and 28.1 seconds, respectively. Mean breathing rate during bursts and pauses was similar (46.2 +/- 24.3 vs 45.7 +/- 17.7, respectively), with SaO2 > or = 90% during all bursts. Mean duration of cup-feedings was 15.2 +/- 3.9 minutes (range, 11.0-23.3), whereas mean volume of intake was only 4.6 +/- 2.2 mL (range, 1.5-8). For the 15 sessions, 38.5% of milk taken from the cup was recovered on the bib. Although infants remain physiologically stable, cup-feeding has questionable efficacy and efficiency. Differentiating between actual intake versus spillage of milk merits attention.     

Evidence for developmental hypopituitarism in ill preterm infants.

OBJECTIVE: The relationship between the concentrations of cortisol and T4 with outcome in the preterm infants has not been well studied. STUDY DESIGN: Mean cortisol (days 2, 4, and 6) and T4 values were correlated to gestational age, illness, and outcome in 210 infants using ANOVA. RESULTS: Cortisol significantly decreased and T4 increased across gestational age. For both hormones, higher values were found in infants on low ventilatory settings. Combined lower cortisol (mean < 5 microg/dl (138 nmol/l)) and T4 concentrations (<4 microg/dl) were found in 20/210 (9.5%) infants; 11/20 in a high-acuity group (22% of total) including 48% (12/25) of the deaths. Lower cortisol values were found in infants who died (p<0.005) in contrast to a lack of relationship with T4. CONCLUSIONS: Lower cortisol values in infants who died are consistent with the role for cortisol in survival. Combined lower cortisol and T4 concentrations in infants who failed to improve clinical status may suggest that these hormones are markers of a poor physiological state. In contrast, we suggest that these results reflect a developmental hypopituitarism, a necessary role for cortisone and T4 in successful early neonatal transition. Treatment of hypothyroidism in the setting of coexistent low cortisol concentrations (central dysfunction of the hypothalamic-pituitary axes) is known to precipitate cortisol crisis in older populations. Therefore, we caution against treatment of low neonatal thyroid concentrations until more is known about the relationship between cortisol and T4 preterm infant population.     

Heat loss prevention for preterm infants in the delivery room.

OBJECTIVE: Preterm infants are prone to hypothermia immediately following birth. Among other factors, excessive evaporative heat loss and the relatively cool ambient temperature of the delivery room may be important contributors. Most infants <29 weeks gestation had temperatures <36.4 degrees C on admission to our neonatal unit (NICU). Therefore we conducted a randomized, controlled trial to evaluate the effect of placing these infants in polyurethane bags in the delivery room to prevent heat loss and reduce the occurrence of hypothermia on admission to the NICU. METHODS: After parental consent was obtained, infants expected to be <29 weeks gestation were randomized to intervention or control groups just prior to their birth. Infants randomized to the intervention group were placed in polyurethane bags up to their necks immediately after delivery before being dried. They were then resuscitated per NRP guidelines, covered with warm blankets, and transported to the NICU, where the bags were removed and rectal temperatures were recorded. Control infants were resuscitated, covered with warm blankets, and transported without being placed in polyurethane bags. Delivery room temperatures were recorded so this potentially confounding variable could be assessed. RESULTS: Intervention patients were less likely than control patients to have temperature < 36.4 degrees C on admission , 44 vs 70% (p<0.01) and the intervention group had a higher mean admission temperature, 36.5 degrees C vs 36.0 degrees C (p<0.003). This effect remained significant (p<0.0001) when delivery room temperature was controlled in analysis. Warmer delivery room temperatures (>/=26 degrees C) were associated with higher admission temperatures in both intervention and control infants, but only the subgroup of intervention patients born in warmer delivery rooms had a mean admission temperature >36.4 degrees C. CONCLUSIONS: Placing infants <29 weeks gestation in polyurethane bags in the delivery room reduced the occurrence of hypothermia and increased their NICU admission temperatures. Maintaining warmer delivery rooms helped but was insufficient in preventing hypothermia in most of these vulnerable patients without the adjunctive use of the polyurethane bags.     

Evaluation of bone metabolism in newborn twins using quantitative ultrasound and biochemical parameters

Metabolic bone disease (MBD) is one of the important complications of prematurity. Early and adequate nutritional interventions may reduce the incidence and potential complications of MBD. The present study aimed to evaluate bone metabolism in twins via biochemical parameters and quantitative ultrasound (QUS) and to compare the results between twin pairs. Moreover, twin infants were evaluated in terms of potential risk factors likely to have impact on MBD. Forty-three pairs of twins were included in the study. Serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were assessed and bone mineral density was measured using QUS (speed of sound, SOS) at postnatal 30?d. Co-twin with the higher birth weight was assigned to Group 1 (n?=?36) and the other twin was assigned to Group 2 (n?=?36). Birth weight and head circumference were significantly higher in the infants of Group 1 compared with Group 2. No significant difference was found among the groups in terms of gender, history of resuscitation, length of stay in intensive care unit (ICU) or in the incubator, duration of total parenteral nutrition (TPN), type of nutrition, vitamin D use, biochemical parameters, and the SOS value. The factors likely to affect SOS, including type of pregnancy, maternal drug use, gender of infant, birth weight, head circumference at birth, gestational week, length of stay at the ICU, duration of TPN, type of nutrition, resuscitation, vitamin D use, and levels of calcium, phosphorus, magnesium, and alkaline phosphatase were entered into the model. The phosphorus level and the maternal drug use were found to be the factors that significantly reduced SOS, whereas pregnancy after assisted reproductive techniques was found to be a significant enhancing factor.     

Predictors of nutritive sucking in preterm infants.

OBJECTIVE: The purposes of this analysis were to determine how select characteristics of nutritive sucking (number of sucks, sucks/burst, and sucks/minute) change over time and to examine the effect of select factors (morbidity, maturity, prefeeding behavior state, and feeding experience) on those changes. STUDY DESIGN: A longitudinal, non-experimental study was conducted in a Level 3 neonatal intensive care unit using a convenience sample of 88 preterm infants. Statistical analyses were performed using a repeated-measures mixed-model in SAS. RESULTS: Sucking activity (number of sucks, sucks/burst, and sucks/minute) was predicted by morbidity, maturity, feeding experience and prefeeding behavior state. Experience at oral feeding had the greatest effect on changes in the number of sucks, suck/burst and sucks/minute. CONCLUSION: Experience at feeding may result in more rapid maturation of sucking characteristics.     

Evaluation of eosinophilia in hospitalized preterm infants.

OBJECTIVE: To characterize changes in eosinophil counts over time, and to draw comparisons across four gestational age groups with respect to the incidence of, and clinical conditions associated with eosinophilia over the first months of life in a single neonatal intensive care unit (NICU). STUDY DESIGN: Weekly complete blood counts (CBCs) were collected from all NICU patients. Eosinophilia was classified as mild, moderate, or severe. Changes in eosinophil counts were examined over time, the incidence of eosinophilia was determined by gestational age group, and clinical correlations sought. RESULTS: Eosinophil data from 1652 CBCs were analyzed from 332 infants. Eosinophilia occurred in 148 infants (45%) during their hospitalization. The prevalence, severity, and timing of eosinophilia varied by gestational age, infection, and red blood cell transfusions. CONCLUSIONS: The incidence and severity of eosinophilia increased with immaturity, and was temporally associated with infection, necrotizing enterocolitis, and packed red blood cell transfusion.     

Three-dimensional ultrasound measurement of the placental volume in early pregnancy: method and correlation with biochemical placenta parameters.

Placental size has been an interesting topic of research for many years. The main aim of this study was to investigate the feasibility of measuring the placental volume at the end of the first trimester using three-dimensional (3D) ultrasound and to correlate these volumes to known placental functional indices and to factors affecting the placenta. Women with singleton pregnancies at the end of the first trimester were included into this study. The volume data of the placentae were correlated to the crown-rump length (CRL), placenta-associated plasma protein A (PAPP-A), free beta-human chroangiogonadotropin (f-beta-hCG) and other factors that may affect the placental size or function. A total of 1462 pregnancies could be evaluated. Comparison between CRL and placental volume proved a significant correlation (r=0.43, P< 0.001). Due to the observed proportional growth of CRL and placental volume, a quotient (placental volume/CRL) was calculated for each case. There were no differences between placenta/CRL-quotients in relation to gravidity, parity or smoking. Correlations could be established between the placental volume and PAPP-A and f-beta-hCG (PAPP-A: r=0.28, P< 0.001, f-beta-hCG: r=0.10, P< 0.001). The measurement of the placenta in the first trimester can be performed in a high percentage of cases. The placenta/CRL quotient represents a simple method to compare placentae from different gestational days. The correlation between placental volume and maternal serum screening parameters might provide a chance to refine first trimester Down's syndrome serum screening. Future studies will be needed to evaluate the possible clinical use of first trimester placental volume measurements.