Association of ultrasound-based measures of fetal body composition with newborn adiposity.

BACKGROUND: Newborns exhibit substantial variation in gestational age-adjusted and sex-adjusted fat mass proportion. The antecedent characteristics of fetal body composition that are associated with newborn fat mass proportion are poorly understood. OBJECTIVE: The aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity. METHODS: In a longitudinal study of 109 low-risk pregnancies, fetal ultrasonography was performed at approximately 12, 20 and 30 weeks gestation. Estimated fetal adiposity (EFA) was derived by integrating cross-sectional arm and thigh per cent fat area and anterior abdominal wall thickness. Newborn per cent body fat was quantified by Dual Energy X-Ray Absorptiometry. The association between EFA and newborn per cent body fat was determined by multiple linear regression. RESULTS: After controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent body fat (standardized ß = 0.41, p < 0.001) and explained 24.0% of its variance, which was substantially higher than that explained by estimated fetal weight (8.1%). The observed effect was driven primarily by arm per cent fat area. CONCLUSIONS: A composite measure of fetal adiposity at 30 weeks gestation may constitute a better predictor of newborn per cent body fat than estimated fetal weight by conventional fetal biometry. Fetal arm fat deposition may represent an early indicator of newborn adiposity. After replication, these findings may provide a basis for an improved understanding of the ontogeny of fetal fat deposition, thereby contributing to a better understanding of its intrauterine determinants and the development of potential interventions.

Effect of prenatal glucocorticoid treatment on size at birth among infants born at term gestation.

OBJECTIVE: To determine whether prenatal treatment with a single course of glucocorticoids (GCs) affects size at birth among full-term infants independent of fetal size before GC administration or exposure to preterm labor (PTL). STUDY DESIGN: In all, 105 full-term infants were recruited into three study groups (30 GC treated; 60 controls matched for gestational age (GA) at birth and sex; and 15 PTL controls without GC exposure). Size of the infants was estimated before treatment using two-dimensional (2D) ultrasound and by direct measurement at birth. RESULTS: Length, weight and head circumference at birth were smaller among GC-treated infants compared with matched controls (P's<0.01), although fetal size did not differ before treatment (P's>0.2). Exposure to PTL did not account for this effect. CONCLUSIONS: Prenatal treatment with a single course of GCs was associated with a reduction in size at birth among infants born at term gestation. This effect cannot be explained by differences in fetal size before treatment or exposure to PTL.

Focal neurological manifestations following aberrant central venous catheter placement.

An infant developed focal tonic clonic movements of both lower limbs while receiving total parenteral nutrition through a left saphenous percutaneous central venous catheter. Radiographic studies using a contrast confirmed that the catheter tip was located in the ascending lumbar vein in close proximity to the epidural space. Withdrawal of the catheter abated all clinical symptoms. This case emphasizes the need to confirm central venous catheter placement and illustrates yet another risk associated with the infusion of parenteral alimentation.

Delayed repair of congenital diaphragmatic hernia with early high-frequency oscillatory ventilation during preoperative stabilization.

PURPOSE: The authors reviewed their experience in the management of CDH after the introduction of early high-frequency oscillatory ventilation (HFOV) during the preoperative stabilization period and delayed CDH repair. METHODS: This is a retrospective analysis of 24 consecutive infants with CDH treated at University of California, Irvine Medical Center (UCIMC) during a 36-month period from January 1993 to December 1996. RESULTS: Two patients were excluded from the study: one fetus with a prenatal diagnosis was referred for fetal surgery; one infant received CDH repair at another institution 2 weeks before transfer to UCIMC. Eight (36%) infants were inborn, and nine (41%) had a prenatal diagnosis of CDH. Median gestational age was 40 weeks (range, 29 to 42 weeks). Median birth weight was 3,019 g (range, 1,205 to 4,337 g). The defect was left sided in 18 infants (86%). Twenty-one infants were intubated within 5 hours of life, 15 had an AaDO2 greater than 610, 11 had an oxygenation index greater than 40, and 11 had a pH of less than 7.2. The median ratio of pulmonary artery pressure to systemic blood pressure was 0.93 (range, 0.51 to 1.15) in 12 infants. Eighteen infants were placed on HFOV within a median of 1 hour of life. Nitric oxide was given to six infants and surfactant to eight. Four infants were referred for extracorporeal membrane oxygenation (ECMO). Repair of CDH was performed on infants at a median age of 33.5 hours (range, 5.5 to 322). Six (30%) received a prosthetic patch. Overall 18 of 22 infants survived (81%); three survivors received ECMO. Two infants of the survivor group had congenital heart anomalies: one ventricular septal defect (VSD) and one double-outlet right ventricle with a VSD. Of the four nonsurvivors, one had lethal cardiac anomalies and bilateral CDH, two had severe bilateral pulmonary hypoplasia (one received ECMO), and one infant was a 29-week premature baby who did not qualify for ECMO. CONCLUSION: We report a survival rate of 81% (18 of 22) with the management of CDH by delayed surgical repair, early postnatal HFOV, and selective referral for ECMO.

Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure.

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide: preliminary hearing outcomes.

The hearing of 28 children, born with a diagnosis of persistent pulmonary hypertension of the newborn (PPHN) and treated with inhaled nitric oxide, was followed. The latest test for the children varied from 5 to 30 months. Of this group, three children had mild conductive hearing losses; no child had a significant sensorineural hearing loss.

Echocardiographic evidence of improved hemodynamics during inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn.

To evaluate the cardiovascular effects of inhaled nitric oxide (NO) on the systemic and pulmonary circulations, 25 consecutive infants with severe persistent pulmonary hypertension of the newborn (PPHN) underwent serial echocardiographic evaluations before and during inhaled NO therapy. Estimation of the systolic pulmonary artery pressure (SPAP) was derived from measurement of a tricuspid regurgitant jet using Bernoulli's equation. We also derived a pulmonary/systemic pressure ratio to evaluate overall cardiopulmonary effects. Paired measurements of estimated SPAP decreased from 62.0 +/- 3.8 mmHg to 44.7 +/- 4.3 mmHg (p < 0.01) during inhaled NO therapy. The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.06 to 0.59 +/- 0.04 during NO therapy (p < 0.01), indicating a significant decline in the vascular resistance between the two circulations. These changes also correlated with changes in the extrapulmonary shunt patterns at the ductus arteriosus and foramen ovale seen during inhaled NO therapy. The decreased right-to-left shunting was accompanied by a parallel (64%) improvement in systemic oxygenation, with the alveolar-arterial oxygen gradient (A-a DO2) falling from 591 +/- 14 mmHg to 380 +/- 33 mmHg (p < 0.01). We found echocardiography to be a useful clinical tool for evaluating and monitoring pulmonary artery pressure in infants with PPHN. Measurement of the SPAP and the pulmonary/systemic pressure ratio gave a quantitative estimation of the severity of PPHN, and the extrapulmonary shunt flow patterns at the ductus arteriosus and foramen ovale gave qualitative estimates of its severity. Inhaled NO increased pulmonary blood flow and oxygenation and improved the systemic cardiopulmonary hemodynamics in this group of infants.

Granulocyte-macrophage colony-stimulating factor in amniotic fluid and in airway specimens of newborn infants.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes white cell maturation, participates in the metabolism of pulmonary surfactant. Little is known on the production of GM-CSF during pregnancy or the neonatal period. We studied how the concentrations of GM-CSF in amniotic fluid (AF) or in tracheal aspirates (TA) of newborn infants are influenced by length of gestation, postnatal age, as well as conditions affecting the mother or the fetus. One hundred and forty-three AF samples from 143 pregnant patients (gestational age range, 28-42 wk) and 202 TA samples from 82 neonates (gestational age, 24-42.5 wk, postnatal age 0.2 d to 4 wk) were analyzed for GM-CSF using ELISA. In patients with intact membranes, AF GM-CSF increased as a function of gestational age; the concentrations were below 7.5 ng/L (detection limit of the assay) (n = 5), 18.6 +/- 2.3 ng/L (n = 56), and 56.7 +/- 7.9 ng/L (n = 58) at gestational ages between 28 and 32 wk, between 32 and 37 wk, and in term patients, respectively (linear regression: r = 0.404, p = 0.001). Among patients at less than 33 wk of gestation, those with intact membranes had a median AF GM-CSF concentration under the detection limit (n = 7), whereas in those with preterm premature rupture of membranes, the concentration was 50.1 +/- 22.2 ng/L (n = 16) (p = 0.002). Among term patients, those in labor had higher AF GM-CSF than those without signs of labor. TA GM-CSF at less than 12 h of age correlated with gestational age (r = 0.654, p = 0.0002, n = 28); thereafter, TA GM-CSF increased, and gestation dependence disappeared. We conclude that GM-CSF in AF and in fetal lung liquid is developmentally regulated and GM-CSF production increases in inflammatory conditions during pregnancy.

Surfactant dysfunction after inhalation of nitric oxide.

To study whether nitric oxide (NO) affects surfactant function, 36 young rats inhaled one of the following humidified environments for 24 h: 1) air; 2) 95% O2; 3) air and 100 parts/million (ppm) NO; and 4) 95% O2 and 100 ppm NO. The treatments did not change the recovery of phospholipid from bronchoalveolar lavage (BAL). Exposure to NO of animals that breathed either air or 95% O2 increased the minimum surface tension of surfactant from BAL at low (1.5 mumol/ml), but not at high (4 mumol/ml), phosphatidylcholine concentration. After inhaled NO, the nonsedimentable protein of BAL decreased the surface activity of surfactant (1 mumol phosphatidylcholine/ml) more than the protein from the controls. NO treatment of animals that breathed either air or 95% O2 affected neither the quantity nor the molecular weight distribution of nonsedimentable protein. Hyperoxia increased the amount of the nonsedimentable protein, whereas NO increased the iron saturation of transferrin. The surfactant fraction and the nonsedimentable protein from BAL were separately exposed to 80 ppm NO in vitro. NO exposure had no effect on the surface activity of surfactant fraction. NO exposure of nonsedimentable protein from the control animals (no NO) increased the inhibition of the surface activity and changed the adsorption spectrum of the protein, suggesting conversion of hemoglobin to methemoglobin. Nonsedimentable protein from NO-exposed animals contained methemoglobin. We propose that surfactant dysfunction caused by inhaled NO is in part due to alteration of protein(s) in epithelial lining fluid that in turn inactivates surfactant.

Silicone-rubber catheter fracture and embolization in a very low birth weight infant.

A 28-week preterm infant had a percutaneous silicone-rubber central venous catheter placed for parenteral nutritional support. The catheter was later found to have fractured, and a 5.5 cm piece of catheter was lodged in the patient's right atrium. It was retrieved percutaneously by fluoroscopically guided cardiac catheterization without complications. Fracture and embolization of a catheter is a rare but serious complication of central venous catheters, and we report our experience as the only known case of a silicone-rubber catheter fracture and embolization in a premature infant, in which the catheter fragment was retrieved via a percutaneous endovascular approach.

Variable oxygenation response to inhaled nitric oxide in severe persistent pulmonary hypertension of the newborn.

The causes of variable responsiveness to inhaled nitric oxide (NO) in Persistent Pulmonary Hypertension of the Newborn (PPHN) are unknown. The changes in the severity of respiratory failure after the onset of inhaled NO (maximal dose 20 ppm) were studied in 13 consecutive neonates with severe PPHN. Response was defined as a sustained decrease of alveolar-arterial oxygen gradient (AaDO2) by > 20%, or a decrease in oxygenation index (OI) by > 40%. Six neonates had a rapid response within 30 min, three had an intermediate response within 8 h, and three had a delayed response within 12 h after the onset of NO. Three infants with birth asphyxia responded rapidly to inhaled NO. One infant with sepsis did not respond, and two with suspected sepsis had a delayed response. The infants with Meconium Aspiration Syndrome and idiopathic PPHN had a variable response time. Twelve neonates required 4 to 14 days of mechanical ventilation and survived. Infants with PPHN may benefit from a trial of inhaled NO therapy that exceeds 30 min. The variability of the response time to inhaled NO is likely to be multifactorial and dependent on the disease process associated with PPHN.

Interleukin-1 receptor antagonist in the fetomaternal compartment.

Interleukin-1 (IL-1) is a major mediator in infections and inflammation. Interleukin-1 receptor antagonist (IL-1ra) opposes the actions of IL-1. IL-1ra is present in exceptionally high concentrations in third trimester amniotic fluid. We studied IL-1ra in amniotic fluid, fetal serum and newborn urine. The concentrations of IL-1ra in amniotic fluid at mid-trimester and at 25-41 gestational weeks were 6.6 +/- 0.5 ng/ml (n = 30) and 100 +/- 4 ng/ml (n = 202), respectively. At mid-trimester, amniotic fluid IL-1ra was not dependent on fetal gender, whereas during the third trimester IL-1ra was higher in female- than in male-bearing gestations. Urine of normal term newborns during the first day of life contained a very high concentration of IL-1ra (125 +/- 16 ng/ml, n = 50). Urinary concentration in female newborns was significantly higher than that in male newborns (202 +/- 19 ng/ml, n = 25 versus 49 +/- 14 ng/ml, n = 25). IL-1ra concentration in fetal serum at 22-36 gestational weeks was 0.50 +/- 0.07 ng/ml (n = 31) and at term 1.5 +/- 0.3 ng/ml (n = 17). Serum concentrations were not gender-dependent. The gender differences in IL-1ra concentrations may in part explain the lower susceptibility of female fetuses to infection.

Focal intestinal perforation in the extremely-low-birth-weight infant.

The purposes of this report were to (1) document the clinical and laboratory features of 11 extremely-low-birth-weight (ELBW) infants with focal intestinal perforation and (2) investigate the clinical events possibly associated with these perforations by examining matched pairs of infants with and without focal intestinal perforation. During the study period 173 infants with birth weights between 600 and 1000 gm were admitted to the neonatal intensive care nursery. Eleven of these ELBW infants had focal intestinal perforations and formed the study group. These infants were matched with 11 ELBW infants who did not have intestinal perforations or signs of inflammatory bowel disease. The matched pairs were similar in all respects except for a significantly higher percent increase in blood urea nitrogen level after treatment with indomethacin (Wilcoxon signed-rank test, p < 0.02) in infants with intestinal perforation. At laparotomy the perforations were noted to be focal, often multiple, and on the antimesenteric border of the distal ileum. None of the infants showed clinical, radiographic, or intraoperative findings that were consistent with classifications for necrotizing enterocolitis (NEC). The incidence of focal intestinal perforation in ELBW infants was 6% versus 2% for typical NEC. In addition, four of the 11 infants with intestinal perforation had positive cultures for either Staphylococcus epidermidis or Candida albicans, whereas none of the infants without perforation had positive cultures during the study period (Fisher's exact test, p < 0.09). We conclude that the clinical presentation and the characteristic intestinal lesions in this group of ELBW infants are distinct from those in typical cases of NEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of fetal gender on the concentration of interleukin-1 receptor antagonist in amniotic fluid and in newborn urine.

IL-1 receptor antagonist (IL-1ra) is a cytokine that blocks the effects of IL-1 by binding to IL-1 receptors without inducing signal transduction. Amniotic fluid contains high concentrations of IL-1ra. The purpose of this study was 1) to analyze whether factors related to the mother or the fetus influence amniotic fluid IL-1ra concentration, and 2) to study whether the fetus is a source of IL-1ra. Two hundred two specimens of amniotic fluid, as well as 21 urine samples from newborn infants, were analyzed. Women carrying a female fetus had a higher concentration of amniotic fluid IL-1ra than those carrying a male fetus (female 136.4 +/- 6.1 micrograms/L, n = 83; male 74.7 +/- 3.7 micrograms/L, n = 119; p < 0.0001, unpaired two-sided t test). Length of gestation, presence or absence of labor signs, or elevated IL-1 beta in amniotic fluid did not affect the concentration of IL-1ra in amniotic fluid. Urine of infants taken during the first 48 h of life contained a high concentration of IL-1ra (91.1 +/- 17.5 micrograms/L). The urinary IL-1ra concentration was higher in female newborns than in male newborns (females 124.0 +/- 25.2 micrograms/L, n = 11; males 54.9 +/- 19.1 micrograms/L, n = 10; p = 0.04). We conclude that 1) the concentration of IL-1ra in amniotic fluid and newborn urine is dependent on the gender of the fetus and of the newborn and 2) fetal urine is a major source of amniotic fluid IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary mechanics generated by positive end-expiratory and continuous negative pressure.

Pulmonary function measurements were studied on equivalent levels of positive end-expiratory pressure (PEEP) and continuous negative pressure (CNP) while controlling for transpulmonary pressure (TPP). Four adult rabbits were anesthetized, instrumented, and ventilated with intermittent mandatory ventilation by using peak inspiratory pressure (PIP) of 16 cm H2O, PEEP 0 cm H2O, CNP 0 cm H2O, inspiratory time 0.3 seconds, rate 20/min, and fraction of inspired oxygen of 0.3. Subsequently, equal amounts of PEEP and CNP were alternated for 15-minute ventilation periods. PIP was changed to approximate the TPP in each PEEP/CNP pair. There was a significant decrease in PCO2 and increase in pH, mechanical tidal volume, minute ventilation, functional residual capacity, and total dynamic compliance on CNP. These differences could not be explained by changes in TPP.

Continuous negative pressure and intermittent mandatory ventilation in the management of pulmonary interstitial emphysema: a preliminary study.

We reviewed the clinical courses of 12 prematurely born newborns who were placed in continuous negative pressure (CNP) in an Isolette negative pressure ventilator for refractory hypoxemia while receiving intermittent positive pressure mandatory ventilation. All patients had severe lung disease as documented by an increased oxygenation index and bilateral pulmonary interstitial emphysema on x-ray examination. Patients were separated into two groups--survivors and nonsurvivors, with six patients in each group. Initiation of CNP resulted in a significant initial improvement in oxygenation in both groups seen as a 52% decrease in the oxygenation index in survivors and a 57% decrease in the oxygenation index in nonsurvivors (P less than .05). The survivors characterized themselves by showing a further sustained improvement in the oxygenation index--31.4 +/- 9.1 to 6.9 +/- 5.0 (P less than .01)--and a significant decrease in the mean airway pressure--11.6 +/- 4.6 cm H2O to 5.0 +/- 1.9 cm H2O (P less than .05). Four of the six survivors showed radiographic resolution of pulmonary interstitial emphysema. CNP was initiated at a mean age of 68.3 hours in the survivors. Nonsurvivors were initiated in CNP at a mean age of 134.3 hours, but went on to clinically deteriorate owing to irreversible hypoxemia and acidosis. Both oxygenation index and mean airway pressures were virtually unchanged compared with their initial values. The exact mechanisms by which CNP improves pulmonary function in this group of infants is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute changes in hematocrit: their effect on flows in the great arteries of newborns].

To study the effect of acute hematocrit changes on the central circulation of human neonates, pulsed Doppler echocardiography was performed to evaluate flow velocities in the main pulmonary artery (PA) and the ascending aorta (Ao) five and seven hours of age in 16 polycythemic neonates (mean hematocrit of 68.1%), and in 12 normal neonates (mean hematocrit of 57.1%). All the polycythemic neonates were asymptomatic and underwent isovolumic partial exchange transfusion between five and seven hours of age to lower their mean hematocrit to 51.3%. Flow velocity integral per min (FVI/min) (cm/min), acceleration time (AT) (ms), and the ratio of pre-ejection period to ejection time (PEP/ET) were measured on the PA and Ao flow velocity tracings. Despite the significant differences in hematocrit, no significant difference was observed in any of their flow velocity indices at five hours age between the normal and polycythemic neonates. All flow velocity indices remained unchanged between five and seven hours of age in normal neonates. In polycythemic neonates, PA FVI/min and Ao FVI/min increased significantly between five and seven hours of age, reflecting increases in flow in both great arteries, while the difference between Ao FVI/min and PA FVI/min decreased, suggesting a reduction in a left-to-right shunt via the ductus arteriosus. Moreover, PA-AT increased and PA-PEP/ET decreased significantly, suggesting a decrease in pulmonary vascular resistance. These changes caused by an acute decrease in hematocrit resembled the changes in the central circulation previously reported to occur in normal neonates during the postnatal period. In conclusion, an acute decrease in hematocrit transiently accelerates physiological changes in the central circulation during the neonatal period.

Acute hemorrhagic hypotension and its effect on the pulmonary clearance of helium instilled into the rabbit colon.

The study investigates the effect of acute and incremental posthemorrhagic hypotension on pulmonary clearance of helium (CHe) introduced into the colon. Eighteen New Zealand White rabbits were cannulated and connected to a respirator at constant minute ventilation. A helium mass spectrometer was used to monitor airway gas. After 30 min stabilization, 10 ml/kg of helium were injected rectally while CHe and mean aortic blood pressure (BPm) were continuously monitored. Control animals (group 1, n = 5) achieved constant CHe (0.8-3.0 microliter/kg/min) by 20 min, with CHe and BPm continuing unchanged over a 90-min period. Group 2 animals (n = 5) underwent acute blood loss of 12 ml/kg with reinfusion after 30 min. Group 3 animals (n = 8) underwent incremental blood loss of 4 ml/kg up to a maximum of 28 ml/kg without reinfusion. Two animals in group 3 had electromagnetic flow probes placed around their distal abdominal aortae. At 12 ml/kg blood loss, group 2 and 3 animals experienced falls in BPm of 46 and 58% along with simultaneous falls in CHe of 33 and 53%, respectively. These changes were statistically significant (p less than 0.05). Reinfusion (group 2) caused initial parallel increases in CHe and BPm. However, CHe remained elevated as BPm returned to baseline, a finding consistent with colonic reperfusion hyperemia. At blood loss of more then 12 ml/kg (group 3), BPm and electromagnetic flow stabilized while CHe continued to decrease. Under these conditions CHe appeared to reflect shunting of intestinal blood flow away from the mesenteric bed.(ABSTRACT TRUNCATED AT 250 WORDS)