Oxygenation Instability during Bolus versus Continuous Feeding among Very Low Birth Weight Premature Infants, Supported by Noninvasive Ventilation: A Randomized Prospective Study.

OBJECTIVE: This study aimed to compare oxygenation instability, as documented by the oxygen saturation (SpO2) histograms, during bolus (over 30 minutes) versus continuous (over 2 hours) feeding among very low birth weight (VLBW) premature infants, supported with noninvasive ventilation (NIV). STUDY DESIGN: This was a randomized prospective study. VLBW infants supported with NIV received three consecutive feeds in a random order of bolus-continuous-bolus or continuous-bolus-continuous. During each feed, 30 minutes and 2 hours histograms were documented. RESULTS: Twenty-four infants (birth weight [mean ± standard deviation, SD] 820 ± 168 g, gestational age [mean ± SD] 27.0 ± 1.6 weeks) were included in our study (12 infants started with bolus feeding and 12 with continuous feeding) and 72 histograms were obtained (36 during bolus feeding and 36 during continuous feeding). No differences in mean fraction of inspired oxygen (FiO2), and number of apnea events were observed between the two feeding modes. Oxygenation instability as assessed by time spent in different SpO2 ranges and histogram types (stable or unstable) was comparable during bolus and continuous feedings. Changing feeding mode from bolus to continuous or vice versa did not significantly change the oxygenation instability of the group, though individual infants did show a consistence response to feeding length changes. CONCLUSION: Among VLBW infants supported with NIV, oxygenation instability, as documented by SpO2 histograms, was comparable between bolus and continuous feedings. Individual infants may benefit from specific feeding length, and this can be easily demonstrated by the SpO2 histograms. KEY POINTS: · Feeding length did not affect oxygenation instability of preterm infants on noninvasive respiratory Support.. · Oxygen saturation histograms allow objective quantification of oxygenation instability at the bedside.. · Individual infants benefit from specific feeding length, as demonstrated by SpO2 histograms..

Same baby, different care: variations in practice between neonatologists and pediatric intensivists.

The aim of the study was to identify and explore areas in neonatal care in which significant differences in clinical care exist, among neonatal intensive care (NICU) and pediatric intensive care (PICU) physicians. A questionnaire presenting three common scenarios in neonatal critical care-severe pneumonia, post-cardiac-surgery care, and congenital diaphragmatic hernia (CDH) was electronically sent to all PICU and NICU physicians in Israel. The survey was completed by 110 physicians. Significant differences were noted between NICU and PICU physicians' treatment choices. A non-cuffed endotracheal tube, initial high-frequency ventilation, and lower tidal volumes when applying synchronized-intermittent-mechanical-ventilation were selected more often by NICU physicians. For sedation/analgesia, NICU physicians treated as needed or by continuous infusion of a single agent, while PICU physicians more often chose to continuously infuse ≥ 2 medications. Fentanyl, midazolam, and muscle relaxants were chosen more often by PICU physicians. Morphine administration was similar for both groups. Treating CDH with pulmonary hypertension and systemic hypotension, NICU physicians more often began treatment with high dose dopamine and/or dobutamine, while PICU physicians chose low-dose adrenalin and/or milrinone. For vascular access NICU physicians chose umbilical lines most often, while PICU physicians preferred other central sites. CONCLUSION: Our study identified major differences in respiratory and hemodynamic care, sedation and analgesia, and vascular access between NICU and PICU physicians, resulting from field-specific consensus guidelines and practice traditions. We suggest to establish joint committees from both professions, aimed at finding the optimal treatment for this vulnerable population - be it in the NICU or in the PICU. WHAT IS KNOWN: • Variability in neonatal care between the neonatal and the pediatric intensive care units has been previously described. WHAT IS NEW: • This scenario-based survey study identified major differences in respiratory and hemodynamic care, sedation and analgesia, and vascular access between neonatologists and pediatric intensivists, resulting from lack of evidence-based literature to guide neonatal care, field-specific consensus guidelines, and practice traditions. • These findings indicate a need for joint committees, combining the unique skills and literature from both professions, to conduct clinical trials focusing on these specific areas of care, aimed at finding the optimal treatment for this vulnerable population - be it in the neonatal or the pediatric intensive care unit.

Continuous versus Bolus Gastric Tube Feeding in Very Low Birth Weight Infants Supported with Noninvasive Respiratory Support: A Randomized, Pilot Study.

OBJECTIVES: This study aimed to compare time to full feeding (TFF) between continuous gastric feeding (CGF) and bolus feeding (BF) in very low birth weight (VLBW) infants supported with noninvasive ventilation (NIV) and to evaluate feasibility and identify methodological pitfalls for future large-scale studies. STUDY DESIGN: This study is a randomized controlled, prospective, pilot study. VLBW premature infants, supported with NIV, were randomized while still on trophic feeding <20 mL/kg/day to receive feeding over 2 hours of CGF or over 15- to 30-minute BF. The primary outcome was TFF. Analysis was done by intention to treat. RESULTS: Overall, 32 infants were included in this analysis, 17 in the CGF group and 15 in the BF group. Infants in the CGF group were significantly younger than the BF group (mean ± standard deviation [SD] gestational age [GA] 26.9 ± 1.2 vs. 28.9 ± 1.5 weeks, respectively). TFF was comparable with median (interquartile range [IQR]) for the two groups, 10.0 (10.0, 19.0) days in the BF group versus 12.0 (9.0, 13.0) days in the CGF group (p = 0.59). Feeding length was not found to significantly affect TFF in multivariate analysis correcting for GA. Groups were comparable in weight gain, gastrointestinal complications, length of NIV, bronchopulmonary dysplasia incidence, and age at discharge. Most infants from both groups (60% of BF and 70% of CGF) required changes in feeding length. CONCLUSION: In this pilot study, among VLBW infants supported with NIV, TFF was comparable between the BF and CGF groups. These results should be interpreted with caution due to the small sample size and despite the multivariate analysis correcting for the different GA. Interestingly, most infants required changes in feeding length regardless of their allocation. This feasibility study emphasizes the need for careful attention to randomization and strict feeding protocols including criteria for switching allocation in future large-scale studies aimed at determining the preferred feeding length during NIV in VLBW infants. KEY POINTS: · Among infants supported with NIV, length of feeding affects gastric venting.. · BF might increase gastrointestinal reflux, while continuous feeding hinders gastric decompression.. · Among infants supported by NIV, feeding tolerance was comparable between bolus and continuous groups..

Evaluation of audio-voice guided application for neonatal resuscitation: a prospective, randomized, pilot study.

OBJECTIVES: To examine whether audio-voice guidance application improves adherence to resuscitation sequence and recommended time frames during neonatal resuscitation. METHODS: A prospective, randomized, pilot study examining the use of an audio-voice application for guiding resuscitation on newborn mannequins, based on the Neonatal Resuscitation Program (NRP) algorithm. Two different scenarios, with and without voice guidance, were presented to 20 medical personnel (2 midwives, 8 nurses, and 10 physicians) in random order, and their performance videotaped. RESULTS: Audio-voice guided resuscitation compared with non-guided resuscitation, resulted in significantly better compliance with NRP order sequence (p<0.01), correct use of oxygen supplementation (p<0.01) and performance of MR SOPA (Mask, reposition, suction, open mouth, pressure, airway) (p<0.01), and shortened the time to "positive pressure ventilation" (p<0.01). CONCLUSIONS: In this pilot study, audio-voice guidance application for newborn resuscitation simulation on mannequins, based on the NRP algorithm, improved adherence and performance of NRP guidelines.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+), cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+) spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+) release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.

L1 cell adhesion molecule signaling is inhibited by ethanol in vivo.

BACKGROUND: Fetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L1 cell adhesion molecule (L1) is a target for ethanol (EtOH) developmental neurotoxicity. L1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L1 is also dependent on trafficking through lipid rafts (LRs). Our hypothesis is that L1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L1 phosphorylation/dephosphorylation and LR association in vivo. METHODS: Rat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LRs are isolated by sucrose density gradient, and the distribution of L1 in LRs is determined. RESULTS: EtOH at all doses reduced the relative amount of Y1176 dephosphorylation as well as the relative amount of L1 phosphorylated on other tyrosines. The proportion of L1 present in LRs is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls. CONCLUSIONS: L1 is a target for EtOH developmental neurotoxicity in vivo.

The effect of changing respiratory rate settings on CO2 levels during nasal intermittent positive pressure ventilation (NIPPV) in premature infants.

OBJECTIVE: To examine the change in CO2, when applying NIPPV with either a low or a high rate in stable premature infants. STUDY DESIGN: Prospective, controlled, crossover study. Preterm infants on NIPPV were monitored by tcCO2 during two rate changes switching every hour between high (30 bpm) and low (10 bpm) set rates. RESULTS: Fifty premature infants (mean ± SD: 28.3 ± 2.4 weeks' gestation) were enrolled. Each infant had two rate changes; therefore, a hundred rate changes were studied. The mean change in tcCO2, i.e., ΔtcCO2 (95% confidence-interval), was -1.1 (-2.3 to 0.1) mmHg for increasing rate from low to high, and 0.46 (-0.49 to 1.41) mmHg for decreasing rate from high to low. CONCLUSION: Multiplying or dividing the rate settings by three did not significantly change the tcCO2 readings an hour after the change. These findings could affect the management of ventilation settings of NIPPV in premature infants. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov ID: NCT04836689 , The name of the trial registry: "Influence of Respiratory Rate Settings on CO2 Levels During Nasal Intermittent Positive Pressure Ventilation (NIPPV)."

Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts.

Fetal alcohol spectrum disorder is estimated to affect 1% of live births. The similarities between children with fetal alcohol syndrome and those with mutations in the gene encoding L1 cell adhesion molecule (L1) implicates L1 as a target of ethanol developmental neurotoxicity. Ethanol specifically inhibits the neurite outgrowth promoting function of L1 at pharmacologic concentrations. Emerging evidence shows that localized disruption of the lipid rafts reduces L1-mediated neurite outgrowth. We hypothesize that ethanol impairment of the association of L1 with lipid rafts is a mechanism underlying ethanol's inhibition of L1-mediated neurite outgrowth. In this study, we examine the effects of ethanol on the association of L1 and lipid rafts. We show that, in vitro, L1 but not N-cadherin shifts into lipid rafts following treatment with 25 mM ethanol. The ethanol concentrations causing this effect are similar to those inhibiting L1-mediated neurite outgrowth. Increasing chain length of the alcohol demonstrates the same cutoff as that previously shown for inhibition of L1-L1 binding. In addition, in cerebellar granule neurons in which lipid rafts are disrupted with methyl-beta-cyclodextrin, the rate of L1-mediated neurite outgrowth on L1-Fc is reduced to background rate and that this background rate is not ethanol sensitive. These data indicate that ethanol may inhibit L1-mediated neurite outgrowth by retarding L1 trafficking through a lipid raft compartment.

Respiratory morbidity in very low birth weight infants through childhood and adolescence.

OBJECTIVE: To describe the long-term (up to 18 years of age) respiratory outcomes of children and adolescents born at very low birth weight (VLBW; ≤1500 g) in comparison with that of children born >1500 g. METHODS: An observational, longitudinal, retrospective study comparing VLBW infants with matched controls, registered at a large health maintenance organization in Israel. Pulmonary outcomes collected anonymously from the electronic medical files included respiratory illness diagnoses, purchased medications for respiratory problems, office visits with either a pediatric pulmonologist or cardiologist and composite respiratory morbidity combining all these parameters. RESULTS: Our study included 5793 VLBW infants and 11,590 matched controls born between 1998 and 2012. The majority (99%) of VLBW infants were premature (born < 37 weeks' gestation), while 93% of controls were born at term. The composite respiratory morbidity was significantly higher in VLBW infants compared with controls in all age groups (relative risk [95% confidence interval]: 1 year: 1.22 [1.19-1.26], <2 years: 1.30 [1.27-1.34], 2-6 years: 1.29 [1.27-1.32], 6-12 years: 1.53 [1.47-1.59], 12-18 years: 1.46 [1.35-1.56]; respectively). Both VLBW infants and controls demonstrated a steady decline in the composite respiratory morbidity with aging. In VLBW infants, lower gestational age was associated with higher respiratory morbidity only until 2 years of age and the morbidity declined in each gestational age group until adolescence. CONCLUSION: Our study confirmed a strong association between VLBW and pulmonary morbidity. The higher prevalence of respiratory composite morbidity in VLBW infants persists over the years until adolescence. The respiratory morbidity is most evident in the first year of life and declines afterward.

Cannula With Long and Narrow Tubing vs Short Binasal Prongs for Noninvasive Ventilation in Preterm Infants: Noninferiority Randomized Clinical Trial.

Importance: Use of cannulas with long and narrow tubing (CLNT) has gained increasing popularity for applying noninvasive respiratory support for newborn infants thanks to ease of use, perceived patient comfort, and reduced nasal trauma. However, there is concern that this interface delivers reduced and suboptimal support. Objective: To determine whether CLNT is noninferior to short binasal prongs and masks (SPM) when providing nasal intermittent positive pressure ventilation (NIPPV) in preterm infants. Design, Setting, and Participants: This randomized controlled, unblinded, prospective noninferiority trial was conducted between December 2017 and December 2019 at 2 tertiary neonatal intensive care units. Preterm infants born between 24 weeks' and 33 weeks and 6 days' gestation were eligible if presented with respiratory distress syndrome with the need for noninvasive ventilatory support either as initial treatment after birth or after first extubation. Analysis was performed by intention to treat. Interventions: Randomization to NIPPV with either CLNT or SPM interface. Main Outcomes and Measures: The primary outcome was the need for intubation within 72 hours after NIPPV treatment began. Noninferiority margin was defined as 15% or less absolute difference. Results: Overall, 166 infants were included in this analysis, and infant characteristics and clinical condition (including fraction of inspired oxygen, Pco2, and pH level) were comparable at recruitment in the CLNT group (n = 83) and SPM group (n = 83). The mean (SD) gestational age was 29.3 (2.2) weeks vs 29.2 (2.5) weeks, and the mean (SD) birth weight was 1237 (414) g vs 1254 (448) g in the CLNT and SPM groups, respectively. Intubation within 72 hours occurred in 12 of 83 infants (14%) in the CLNT group and in 15 of 83 infants (18%) in the SPM group (risk difference, -3.6%; 95% CI, -14.8 to 7.6 [within the noninferiority margin], χ2 P = .53). Moderate to severe nasal trauma was significantly less common in the CLNT group compared with the SPM group (4 [5%] vs 14 [17%]; P = .01). There were no differences in other adverse events or in the course during hospitalization. Conclusions and Relevance: In this study, CLNT was noninferior to SPM in providing NIPPV for preterm infants, while causing significantly less nasal trauma. Trial Registration: ClinicalTrials.gov Identifier: NCT03081611.

Detection of alcohol consumption during pregnancy--current and future biomarkers.

Alcohol, one of the most frequently reported addictions, is a significant public health problem in the USA. Early identification is important and would aid in intervention for the pregnant woman who continues to drink and for the affected infant. To date, there isn't a definitive test which identifies either alcohol abuse during pregnancy or newborns exposed to alcohol prenatally. The existing biomarkers can detect varying degrees of alcohol exposure but further research is needed to improve sensitivity/specificity and to validate these markers.

Negative results and impact factor: a lesson from neonatology.

OBJECTIVE: To test the hypothesis that articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor. DESIGN AND SETTING: We selected all of the randomized, placebo-controlled trials conducted during the neonatal period between October 1, 1998, and October 1, 2003. Trials were classified as having positive results or negative results (significant or no significant difference, respectively). Only studies dealing with primary outcomes (efficacy) were included. MAIN OUTCOME MEASURES: The impact factor of each journal was determined, and the sample size for each study was noted. RESULTS: There were 233 articles that fulfilled the inclusion criteria. There was a significant difference between the 2 groups in terms of impact factor (P = .03) but not sample size (P = .30). Impact factor correlated with both sample size and the type of study results (positive results vs negative results; P<.05). CONCLUSION: Articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor.

Effect of hematocrit on exhaled carbon monoxide in healthy newborn infants.

OBJECTIVE: We tested the hypothesis that, the red blood cell (RBC) mass, estimated by hematocrit (HCT) or hemoglobin (Hb) level, influences the carbon monoxide (CO) production rate. STUDY DESIGN: The relationship between end tidal CO corrected for ambient carbon monoxide level (ETCOc) and the RBC mass have been studied in 58 full-term infants at the mean age 4.9 hours. RESULTS: Mean ETCOc was 1.88 ppm (1.3 to 3.4 ppm). ETCOc correlated significantly with HCT (R 2=10.1%, p=0.015) and with Hb (R 2=11%, p=0.011). Infants with a capillary HCT >65% had significantly higher ETCOc (mean 1.99+/-0.49 ppm) than infants with a capillary HCT <65% (1.74+/-0.39 ppm), p=0.035. When CO production was corrected for HCT (ETCOc/HCT), this difference did not longer exist. CONCLUSIONS: In newborn infants ETCOc significantly correlates with RBC mass. Comparing different infant's CO generation rate one should take into consideration their initial RBC level. In order to adjust for the existing differences in RBC, we suggest the use of the ETCOc/HCT index.

The effect of prolonged rupture of membranes on circulating neonatal nucleated red blood cells.

OBJECTIVES: To test the hypothesis that absolute nucleated red blood cells (ANRBC) counts are higher at birth in infants who were born after prolonged rupture of membranes (PROM, >24 hours). STUDY DESIGN: Retrospective study of 31 infants admitted to the neonatal intensive care unit who were born after PROM, and pair matched for gestational age and Apgar scores with 31 no PROM controls. Venous ANRBC counts were obtained within 1 hour of life. RESULTS: Groups did not differ in birthweight, gestational age, Apgar scores, and platelets counts. The ANRBC counts and hematocrit were significantly higher in infants who were born after PROM than in controls. CONCLUSIONS: Infants born after PROM have higher ANRBC counts at birth than control infants. We suggest that increased fetal erythropoiesis exists in infants who are delivered after PROM. If correct, our interpretation supports the theory that fetal hypoxia and/or ischemia may result from PROM.

Bone ultrasound velocity of infants born small for gestational age.

BACKGROUND: Quantitative ultrasound is increasingly used to assess bone status. Bone speed of sound (SOS), a biophysical property of bone, has been used to predict bone breakability. While decreased bone mineral content and delayed epiphyseal growth have been reported in small for gestational age (SGA) infants, there are no data on bone SOS in this group of infants. OBJECTIVE: To test the hypothesis that SGA infants have lower bone SOS than appropriate for gestational age (AGA) infants. METHODS: Bone SOS was measured within the first 96 hours of life at the right tibial midshaft in 22 singleton SGA infants. We compared these data with data obtained in 73 AGA controls. We used the Omnisense instrument which measures axially transmitted SOS. Infants ranged in gestational age (GA) from 25 to 42 weeks and in birth weight (BW) from 500 to 2,585 g. Statistical analyses included paired t-tests between the actual value obtained in every child and the theoretical, computed average normal value for GA, BW, or knee-sole length (KSL) based on our curves for AGA singletons. A p value < 0.05 was considered significant. RESULTS: Bone SOS measured in SGA infants was higher than the predicted computed average SOS of AGA singletons with significant differences in all of the parameters studied. CONCLUSIONS: Contrary to our hypothesis, SGA infants have higher bone SOS than AGA controls. Since bone mineral density is reported to be low in these infants, we speculate that intrauterine growth restriction may affect bone mineral density and bone protein matrix in opposite directions.

Decreased bone ultrasound velocity in large-for-gestational-age infants.

BACKGROUND: Bone speed of sound is a measure of bone breakability. There are few reports on bone mineral content in large for gestational age infants; most of them in infants of diabetic mothers. There are no data on bone speed of sound in large for gestational age infants of nondiabetic mothers. OBJECTIVE: To test the hypothesis that large for gestational age infants of nondiabetic mothers have lower bone speed of sound than appropriate for gestational age infants. DESIGN/METHODS: Bone speed of sound was measured within the first 96 hours of life at the right tibial midshaft in 25 singleton large for gestational age infants of non diabetic mothers and compared to appropriate for gestational age controls. RESULTS: Bone speed of sound measured in large for gestational age infants of nondiabetic mothers was lower than in controls. CONCLUSIONS: Large for gestational age infants of nondiabetic mothers have lower bone speed of sound than controls.

Bone ultrasound velocity curves of newly born term and preterm infants.

BACKGROUND: Ultrasound velocity (speed-of-sound [SOS]) has been proposed as a non-invasive method of evaluation of bone status in infants. We hypothesized that SOS correlates with both gestational age and birth weight. METHODS: We measured SOS within the first 96 hours of life at the right tibial midshaft location in 73 neonates ranging in gestational age from 25 to 41 weeks, and in birth weight from 825 to 3880 grams. We used the Sunlight Omnisense 7000p device (Tel Aviv, Israel). Results are expressed as meanS +/- 1 SD; statistical analyses included linear regression and computation of 95% CI regression lines; p<0.05 was considered significant. RESULTS: There was, as hypothesized, a significant correlation between gestational age (or birth weight) and SOS. There were no significant differences between males and females. Ninety-five percent confidence intervals were established. CONCLUSIONS: These data may be used as reference ranges for further studies.

Increased serum potassium and intraventricular hemorrhage revisited.

BACKGROUND: Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants. OBJECTIVE: To retrospectively analyze data obtained on infants with severe IVH in relation to blood K+ concentrations. METHODS: We identified all patients with severe IVH bom between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (+/- 1 week) without IVH in terms of head ultrasound findings on day 5 and whole blood K+ on days 3-5. RESULTS: There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K+ than the control group. Blood pH and K+ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K+ and IVH status. CONCLUSIONS: Severe IVH is significantly associated with higher blood K+ concentrations. A causal relationship cannot be ascertained at this point.

Bone mass evaluation in children - comparison between methods.

Peak adult bone mass should be optimized during childhood and adolescence. The physiology of bone mass accretion during these early years of life has been extensively studied, due to the development of reliable, precise, little or noninvasive methods of bone mass assessment. The purpose of this review is briefly to describe quantitative aspects of bone mass accretion during intrauterine life, childhood and adolescence and to describe the methods that have been used to assess bone mass in children in terms of precision, accuracy, ease of use, invasiveness and normative data. In particular, we review major methods such as radiographic methods, photon absorptiometry, dual-energy X-ray absorptiometry, quantitative ultrasound, quantitative computerized tomography and other methods less frequently used.

Elevated fatty acid ethyl esters in meconium of sheep fetuses exposed in utero to ethanol--a new animal model.

Specific fatty acid ethyl esters (FAEE) in meconium of newborns have been shown to correlate with maternal ethanol exposure. An animal model is needed to assess the validity of this biomarker. We hypothesized that the pregnant/fetal sheep is a feasible animal model for validating FAEE as a biomarker of prenatal ethanol exposure. Nine pregnant ewes were treated during the third trimester with different i.v. ethanol doses. The control group consisted of 14 pregnant ewes exposed to similar volumes of saline. On gestational d 133, the fetuses were delivered and meconium samples removed. FAEEs were quantified by gas chromatography-flame ionization detection. FAEEs were found in both control and ethanol exposed fetuses. Ethyl oleate, ethyl linoleate, and ethyl arachidonate levels were significantly higher in the ethanol-exposed sheep. Ethyl oleate was the FAEE that correlated most strongly with alcohol ingestion during pregnancy and had the greatest area under the curve (0.94). Using a cut-off value of 131 ng/g ethyl oleate dry weight, sensitivity was 89% and specificity was 100%. In conclusion, pregnant ewes are a feasible model for validating biomarkers of prenatal ethanol exposure. Ethyl oleate, ethyl linoleate, and ethyl arachidonate may be useful biomarkers of prenatal alcohol exposure.