Neonatal intensive care unit: predictive models for length of stay.

OBJECTIVE: Hospital length of stay (LOS) is important to administrators and families of neonates admitted to the neonatal intensive care unit (NICU). A prediction model for NICU LOS was developed using predictors birth weight, gestational age and two severity of illness tools, the score for neonatal acute physiology, perinatal extension (SNAPPE) and the morbidity assessment index for newborns (MAIN). STUDY DESIGN: Consecutive admissions (n=293) to a New England regional level III NICU were retrospectively collected. Multiple predictive models were compared for complexity and goodness-of-fit, coefficient of determination (R (2)) and predictive error. The optimal model was validated prospectively with consecutive admissions (n=615). Observed and expected LOS was compared. RESULT: The MAIN models had best Akaike's information criterion, highest R (2) (0.786) and lowest predictive error. The best SNAPPE model underestimated LOS, with substantial variability, yet was fairly well calibrated by birthweight category. LOS was longer in the prospective cohort than the retrospective cohort, without differences in birth weight, gestational age, MAIN or SNAPPE. CONCLUSION: LOS prediction is improved by accounting for severity of illness in the first week of life, beyond factors known at birth. Prospective validation of both MAIN and SNAPPE models is warranted.

Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants.

OBJECTIVE: Dietary carotenoids (lutein, lycopene and ß-carotene) may be important in preventing or ameliorating prematurity complications. Little is known about carotenoid status or effects of supplementation. STUDY DESIGN: This randomized controlled multicenter trial compared plasma carotenoid levels among preterm infants (n=203, <33 weeks gestational age) fed diets with and without added lutein, lycopene and ß-carotene with human milk (HM)-fed term infants. We assessed safety and health. RESULT: Plasma carotenoid levels were higher in the supplemented group at all time points (P<0.0001) and were similar to those of term HM-fed infants. Supplemented infants had lower plasma C-reactive protein (P<0.001). Plasma lutein levels correlated with the full field electroretinogram-saturated response amplitude in rod photoreceptors (r=0.361, P=0.05). The supplemented group also showed greater rod photoreceptor sensitivity (least squares means 6.1 vs 4.1; P<0.05). CONCLUSION: Carotenoid supplementation for preterm infants raises plasma concentrations to those observed in HM-fed term infants. Carotenoid supplementation may decrease inflammation. Our results point to protective effects of lutein on preterm retina health and maturation.

Experience with a multidisciplinary antenatal diagnosis and management model in fetal medicine.

BACKGROUND: Fetal medicine is a new and evolving specialty. Complex fetal conditions may require the multidisciplinary input of clinicians from many different specialties. METHODS: Referral of fetal patients was made to a multidisciplinary antenatal diagnosis and management (MADAM) board if more than one specialty (in addition to maternal-fetal medicine) needed to be intimately involved in the evaluation or care of the fetus; consultation would probably lead to alterations in fetal or perinatal management; or development or revision of management guidelines was anticipated. The case log of the MADAM conferences was reviewed retrospectively for number and type of fetal anomalies, and outcome of the presentation to the MADAM board. RESULTS: During a 5-year period, 1% of 25654 pregnant women who were evaluated required consultations with individual pediatric and pediatric surgical specialists. Of these, 114 patients were referred to one of 77 MADAM conferences for consensus recommendation. Of these 77 discussions, 32 (42%) led to an alteration in prenatal management, 14 (18%) led to co-ordination of postnatal management and 12 (16%) led to the establishment of a new treatment guideline, or the modification of an existing one. In all, perinatal management was altered in 75% of cases. CONCLUSION: The MADAM model functions as a forum for exchange of up-to-date scientific information, development of evidence-based treatment protocols and continuity of care through the pre-, peri- and postnatal periods.

Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation.

Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling "loop." This hypothesized mechanism is supported by the following experimental data: 1) leptin stimulates the de novo synthesis of surfactant phospholipid by both fetal rat type II cells (400% x 100 ng(-1) x ml(-1) x 24 h(-1)) and adult human airway epithelial cells (85% x 100 ng(-1) x 24 h(-1)); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions such as parathyroid hormone-related protein (PTHrP), PGE(2), and dexamethasone stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP receptor antagonist inhibits the expression of leptin mRNA by explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by lipofibroblasts. This is the first demonstration of a paracrine loop that functionally cooperates to induce alveolar acinar lung development.

Inhibition of placental 11beta-hydroxysteroid dehydrogenase type 2 by catecholamines via alpha-adrenergic signaling.

The placenta expresses high levels of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) that converts cortisol into inactive 11-keto metabolites and effectively protects the developing fetus from maternal cortisol during pregnancy. Impairment of this glucocorticoid barrier has adverse effects on fetal outcomes. A similar spectrum of adverse fetal effects is induced by antenatal stress during pregnancy. To examine the hypothesis that physiological stress may regulate placental 11betaHSD2 gene expression, we examined the effects of the catecholamines norepinephrine (NE) and epinephrine (E) on 11betaHSD2 expression in human trophoblastic cells. With the use of Northern blotting and semiquantitative RT-PCR, we determined that NE and E rapidly downregulate 11betaHSD2 steady-state mRNA levels in early- and late-gestation human trophoblasts and BeWo trophoblastic cells. Experiments using different adrenoceptor subtype-selective agonists and antagonists demonstrated that this catecholamine suppression of 11betaHSD2 mRNA expression is mediated via both alpha(1)- and alpha(2)-adrenoceptors and is independent of beta-adrenergic stimulation. To examine transcriptional regulation, BeWo cells were transiently transfected with a reporter construct in which an 11betaHSD2 human promoter sequence was inserted upstream of the luciferase gene. Treatment with 10(-7) M NE decreased luciferase activity by ~60% (n = 3, P < 0.01). These results suggest the NE/E-mediated decrease in placental 11betaHSD2 gene expression is an instance of alpha-adrenoceptor-specific rapid transcriptional inhibition of an adrenergic target gene. This molecular mechanism may be involved in the deleterious effects of antenatal physiological stress on fetoplacental growth and development.

Diaphragm dimensions of the healthy preterm infant.

BACKGROUND: The diaphragm is the major inspiratory muscle in the neonate; however, human neonatal diaphragm development has not been extensively studied. We hypothesized that diaphragm thickness (t(di)) would be positively related to postmenstrual age (PMA), body weight, body length, head circumference, and nutritional intake. OBJECTIVES: To evaluate the evolution of diaphragm growth and motion in the healthy, preterm infant. METHODS: We used ultrasound to measure t(di) at the zone of apposition to the rib cage and diaphragm excursion (e(di)) during inspiration. Thirty-four stable, preterm infants (16 males and 18 females) between 26 and 37 weeks' PMA were studied during quiet sleep at weekly intervals until the time of discharge or transfer from the neonatal intensive care unit. All infants were clinically stable and not receiving ventilatory support. RESULTS: We found that 1) t(di) increased from 1.2 +/- 0.1 to 1.7 +/- 0.05 mm between 26 to 28 and 35 to 37 weeks' PMA; 2) t(di) was positively correlated with PMA (r = 0.40), body weight (r = 0.52), body length (r = 0.53), and head circumference (0.49), but not with postnatal nutritional intake (r = 0.09); and 3) e(di) decreased with increasing PMA. CONCLUSIONS: Our findings suggest that diaphragm development in premature infants scales with body dimensions. We speculate that the increase in t(di) with age is likely attributable to increased diaphragm muscle mass, and the reduced e(di) with age may be resulting from a reduction in chest wall compliance.

Variations in prevalence of hypotension, hypertension, and vasopressor use in NICUs.

OBJECTIVE: Very low birth weight infants are vulnerable to hypotension and its associated complications. Vasopressors are used to raise blood pressure (BP), but indications for use are uncertain. Our objectives were (1) to study variations in BP stability among NICUs, (2) to investigate inter-NICU differences in vasopressor use, and (3) to address the association between intraventricular hemorrhage (IVH) and abnormal BPs. STUDY DESIGN: A total of 1288 infants with birth weight <1500 g were admitted to six NICUs in Massachusetts and Rhode Island over 21 months. The lowest and highest mean BPs were collected within the first 12 hours. Also recorded were the use of vasopressors within the first 24 hours and the occurrence of IVH. Logistic regressions were used to model outcomes, controlling for gestational age and illness severity using the Score for Neonatal Acute Physiology. RESULTS: Two of the six NICUs had significantly higher percentages of infants with at least one hypotensive BP, with prevalences of 24% to 45%. Percentages of infants treated with vasopressors ranged from 4% to 39%. This range of vasopressor use could not be explained by inter-NICU differences in birth weight, illness severity, or rates of hypotension. We found a borderline association between severe IVH and hypotension (odds ratio 1.6, p=0.055), but not between severe IVH and hypertension. CONCLUSION: Wide differences exist in the prevalence of hypotension, hypertension, and vasopressor use among NICUs. We also found an association between hypotension and IVH, but not between hypertension and IVH.

Mechanical stretch promotes alveolar epithelial type II cell differentiation.

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial interactions play important roles in this process. We hypothesized that mechanical stretch simulating fetal breathing movements is an important regulator of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we analyzed effects of stretch on primary cultures of type II cells and cocultures of epithelial and mesenchymal cells isolated from fetal rat lungs during late development. Cyclic stretch of isolated type II cells increased surfactant protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and 270 +/- 40%, respectively, compared with unstretched cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% (P < 0.003). Unlike SP-C, addition of fibroblasts did not produce significant additional effects on SP-B mRNA levels. Under these conditions, we observed only modest increases in cellular immunoreactive SP-B, but secreted saturated phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial cell function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.

Effect of lung fluid composition on type II cellular activity after tracheal occlusion in the fetal lamb.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) causes accelerated lung growth. However, prolonged TO is associated with a decline in the type II cell number. Type II cell function after TO is unclear. Herein, the authors examine type II cell function after TO and the role of tracheal fluid. METHODS: Fetal lambs (term, 145 days) underwent TO at 122 days. Tracheal pressure was recorded daily. In one group of animals (TF; n = 6), lung fluid was aspirated, measured, and reinfused daily. In their respective twins, NS group, lung fluid was replaced milliliter per milliliter with normal saline (NS; n = 6). At death near term, lung weight was obtained, and tissues were processed for stereologic volumetry. Type II cells were quantitated using antisurfactant protein B immunohistochemistry. Surfactant protein B-mRNA expression was studied by Northern analysis. Wilcoxon signed rank test and single factor analysis of variance (ANOVA) were used for statistical analysis (P<.05 was significant). RESULTS: In both experimental groups, intratracheal pressure rose from 1.9+/-1.0 torr to 3.7 to 4.8 torr by day 1, and remained constant thereafter. Lung fluid volume increased from 11.9+/-4.2 on day 0 to 36.8+/-8.0 mL/kg in TF, and to 28.4+/-9.3 mL/kg in NS by day 1 (P<.05). At death, lung weight/body weight ratio was higher in TF (5.45% +/- 0.91%) than in NS (4.40% +/- 0. 67%) or control (3.83%+/-0.58%; P<.05). Type II numerical density was substantially reduced after TO: 57.7+/-12.8 x 10(6)/mL (TF) and 45.0 +/-25.9 x 10(6)/mL (NS), versus 82.3+/-13.6 x 10(6)/mL in controls. Ultrastructurally, remaining type II cells in TF were enlarged and engorged with lamellar bodies; in NS, they were smaller and contained fewer lamellar bodies. Surfactant protein B mRNA expression was significantly decreased in NS, but not in TF, compared with controls. CONCLUSIONS: Type II cell function as well as overall lung growth are stimulated by TO. Lung growth after TO is therefore not unavoidably detrimental to type II cells. After isobaric saline exchange of lung fluid, type II cell function is severely inhibited, confirming the role of tracheal fluid composition in type II stimulating type II cell function.

Fas ligand expression coincides with alveolar cell apoptosis in late-gestation fetal lung development.

Apoptosis plays a central role in the cellular remodeling of the developing lung. We determined the spatiotemporal patterns of the cell death regulators Fas and Fas ligand (FasL) during rabbit lung development and correlated their expression with pulmonary and type II cell apoptosis. Fetal rabbit lungs (25-31 days gestation) were assayed for apoptotic activity by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and DNA size analysis. Fas and FasL expression were analyzed by RT-PCR, immunoblot, and immunohistochemistry. Type II cell apoptosis increased significantly on gestational day 28; the type II cell apoptotic index increased from 0.54 +/- 0.34% on gestational day 27 to 3.34 +/- 1.24% on day 28, P < 0.01 (ANOVA). This corresponded with the transition from the canalicular to the terminal sac stage of development. The day 28 rise in epithelial apoptosis was synchronous with a robust if transient 20-fold increase in FasL mRNA and a threefold increase in FasL protein levels. In contrast, Fas mRNA levels remained constant, suggestive of constitutive expression. Fas and FasL proteins were immunolocalized to alveolar type II cells and bronchiolar Clara cells. The correlation of this highly specific pattern of FasL expression with alveolar epithelial apoptosis and remodeling implicates the Fas/FasL system as a potentially important regulatory pathway in the control of postcanalicular alveolar cytodifferentiation.

Effects of the supine and prone position on diaphragm thickness in healthy term infants.

BACKGROUND: The physiological basis underlying the decline in the incidence of sudden infant death syndrome (SIDS) associated with changing the sleep position from prone to supine remains unknown. AIMS: To evaluate diaphragm thickness (t(di)) and shortening in healthy term infants in the prone and supine positions in order to determine whether changes in body position would affect diaphragm resting length and the degree of diaphragm shortening during inspiration. METHODS: In 16 healthy term infants, diaphragm thickness at the level of the zone of apposition on the right side was measured using ultrasonography. Heart rate (HR), breathing frequency (f), and transcutaneous oxyhaemoglobin saturation (SaO(2)) were recorded simultaneously during diaphragm imaging with the infants in the supine and prone positions during quiet sleep. RESULTS: At end expiratory (EEV) and at end inspiratory lung volumes (EIV), t(di) increased significantly in the prone position. The change in t(di) during tidal breathing was also greater when the infant was prone. SaO(2), HR, and f were not significantly different at EEV and at EIV in both positions. CONCLUSION: In healthy term infants, placed in the prone position, the diaphragm is significantly thicker and, therefore, shorter, both at EEV and EIV. Diaphragm shortening during tidal breathing is greater when the infant is prone. In the prone position, the decreased diaphragm resting length would impair diaphragm strength, and the additional diaphragm shortening during tidal breathing represents added work performed by the diaphragm. This may compromise an infant's capacity to respond to stressful situations when placed in the prone position and may contribute to the association of SIDS with prone position.

The use of inhaled glucocorticosteroids and recovery from adrenal suppression after systemic steroid use in a VLBW premature infant with BPD: case report and literature discussion.

Despite development of many prevention and treatment modalities for bronchopulmonary dysplasia (BPD), a form of chronic respiratory insufficiency in premature infants recovering from respiratory distress syndrome, BPD remains a treatment challenge and a significant cause of long-term morbidity. A ventilator-dependent very low birth weight infant in our newborn special care unit was receiving multiple courses of systemic dexamethasone for severe respiratory failure. The infant demonstrated adrenal suppression manifested by a baseline cortisol concentration below reported levels in infants of similar birth weight and postnatal age. We hypothesized that he had developed adrenal insufficiency as a result of the prolonged systemic steroid administration used to treat his respiratory problems. We further hypothesized that inhaled beclomethasone therapy would aid in the infant's recovery phase during relative adrenal insufficiency--and so substituted inhaled for systemic steroids. Inhaled corticosteroid treatment improved the clinical respiratory course and postnatal growth of this premature infant with BPD without inhibiting his recovery from adrenal insufficiency.

Perinatal risk and severity of illness in newborns at 6 neonatal intensive care units.

OBJECTIVES: This multisite study sought to identify (1) any differences in admission risk (defined by gestational age and illness severity) among neonatal intensive care units (NICUs) and (2) obstetric antecedents of newborn illness severity. METHODS: Data on 1476 babies born at a gestational age of less than 32 weeks in 6 perinatal centers were abstracted prospectively. Newborn illness severity was measured with the Score for Neonatal Acute Physiology. Regression models were constructed to predict scores as a function of perinatal risk factors. RESULTS: The sites differed by several obstetric case-mix characteristics. Of these, only gestational age, small for gestational age. White race, and severe congenital anomalies were associated with higher scores. Antenatal corticosteroids, low Apgar scores, and neonatal hypothermia also affected illness severity. At 2 sites, higher mean severity could not be explained by case mix. CONCLUSIONS: Obstetric events and perinatal practices affect newborn illness severity. These risk factors differ among perinatal centers and are associated with elevated illness severity at some sites. Outcomes of NICU care may be affected by antecedent events and perinatal practices.

Variations in blood transfusions among newborn intensive care units. SNAP II Study Group.

OBJECTIVES: Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. STUDY DESIGN: In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs. RESULTS: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay. CONCLUSIONS: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

Effects of mechanical forces on lung-specific gene expression.

Fetal breathing movements (FBM) are necessary for fetal lung growth and maturation. The authors analyzed fetal rat lungs cultured with or without lung distension and tracheal ligation, and examined the effects of mechanical stretch on a human pulmonary epithelial cell line (NCI-H441) that shows regulated expression of surfactant proteins (SP-A, SP-B). Cells were grown on silastic membranes and mounted in a Flexercell Strain Unit. Cyclic deformation simulating FBM was achieved by applying a vacuum of 22 kPa (5%-15% radial deformation) at 50 cycles per minute for 2 to 24 hours. Results indicate that static distension for as little as 4 hours decreased steady-state SP-A and SP-B mRNA levels in whole lung (n = 5-6, P < .01). In contrast, cyclic stretching of H441 cells for 24 hours increased SP-B and SP-A expression 2- to 4-fold over controls. Cyclic deformation also significantly enhanced 3H-choline incorporation into saturated phosphatidylcholine. Dynamic mechanodeformation may be a critical stimulus for fetal lung development.

Paracrine mediators of mechanotransduction in lung development.

The process of normal fetal lung development is dependent on "mild" tissue distension (approximately 3 mm Hg) by fluid, resulting in the production of pulmonary surfactant which is necessary for survival at the time of birth. The mechanical "stretching" of lung tissue triggers a cellular differentiation cycle, in part by stimulating the expression and production of cell phenotype-specific soluble cytokines. Pulmonary cytokines regulate differentiation and metabolic function of neighboring cells. For example, tonic stretching of type II alveolar epithelial cells in monolayer culture stimulates the expression and production of the differentiation factor parathyroid hormone-related peptide (PTHrP), which is released by type II cells and specifically binds to its receptor on contiguous fibroblasts, stimulating the "second messenger" cyclic AMP. Tonic distension of cultured type II cells increases PTHrP production, and distension of fibroblasts in monolayer culture increases their PTHrP responsiveness, suggesting that stretching couples and coordinates the production and receptor-mediated action of PTHrP. These data provide a mechanistic basis for the previously observed hand-in-glove spatial pattern of PTHrP and the PTHrP receptor (PTHrPR) in developing terminal airways. PTHrP stimulates specific differentiated functions of fetal lung fibroblasts by: 1) augmenting glucocorticoid binding; 2) increasing metabolic activities directly related to surfactant synthesis, such as lipoprotein lipase elaboration and triglyceride uptake rate; 3) stimulating cytokines, such as interleukins 6 and 11, that can act in a retrograde fashion on epithelial cells; 4) thereby increasing the synthesis of surfactant phospholipids and surfactant-associated proteins, closing this stretch-mediated cell-cell interactive loop. Experimental interruption of this mechanism at any of these steps blocks the spontaneous maturation of the lung in vitro, as evidenced by the inhibition of surfactant production.

Variation among neonatal intensive care units in narcotic administration.

OBJECTIVES: To compare rates of narcotic administration for medically treated neonates in different neonatal intensive care units (NICUs) and to compare treated and untreated neonates to assess whether narcotics provided advantages or disadvantages for short-term outcomes, such as cardiovascular stability (ie, blood pressure and heart rate), hyperbilirubinemia, duration of respiratory support, growth, and the incidence of intraventricular hemorrhage. STUDY DESIGN: The medical charts of neonates weighing less than 1500 g, admitted to 6 NICUs (A-F), were abstracted. Neonates who had a chest tube or who had undergone surgery were excluded from the study, leaving the records of 1171 neonates. We modeled outcomes by linear or logistic regression, controlling for birth weight (<750, 750-999, and 1000-1499 g) and illness severity (low, 0-9; medium, 10-19; high, > or =20) using the Score for Neonatal Acute Physiology (SNAP), and adjusted for NICU. RESULTS: Narcotic use varied by birth weight (<750 g, 21%; 750-999 g, 13%; and 1000-1499 g, 8%), illness severity (low, 9%; medium, 19%; and high, 37%), day (1, 11%; 3, 6%; and 14, 2%), and NICU. We restricted analyses to the 1018 neonates who received mechanical ventilation on day 1. Logistic regression, adjusting for birth weight and SNAP, confirmed a 28.6-fold variation in narcotic administration (odds ratios, 4.1-28.6 vs NICU A). Several short-term outcomes also were associated with narcotic use, including more than 33 g of fluid retention on day 3 and a higher direct bilirubin level (6.8 micromol/L higher [0.4 mg/dL higher], P = .03). There were no differences in weight gain at 14 and 28 days or mechanical ventilatory support on days 14 and 28. Narcotic use was not associated with differences in worst blood pressure or heart rate or with increased length of hospital stay. CONCLUSIONS: Our study found a 28.6-fold variation among NICUs in narcotic administration in very low-birth-weight neonates. We were unable to detect any major advantages or disadvantages of narcotic use. We did not assess iatrogenic abstinence syndrome or long-term outcomes. These results indicate the need for randomized trials to rationalize these widely differing practices.

Prenatal ultrasound diagnosis of abdominal aortic aneurysm with fibrotic occlusion in aortic branch vessels.

In a 35-year-old multiparous patient, an ultrasound scan performed at 32 weeks' gestational age for size less than dates revealed an appropriately grown fetus with a two-vessel umbilical cord. Also noted were dilated, tortuous abdominal and pelvic vessels. A scan at 33.5 weeks confirmed the two-vessel cord and noted a widely dilated abdominal aorta and a left foot 2 cm shorter than the right. Delivery at 36 weeks was followed by a neonatal course complicated by thromboses, renovascular hypertension, and a newly patent ductus with pulmonary hypertension. Successful ligation was followed by acute pulmonary hypertension, cardiac dysfunction and death. Autopsy findings included aneurysmal dilation of the abdominal aorta without evidence of arterial wall pathology.

Limb defects and congenital anomalies of the genitalia in an infant with homozygous alpha-thalassemia.

We describe an infant with homozygous alpha-thalassemia, genital abnormalities, and terminal transverse limb defects, whose limbs demonstrate evidence of loss of tissue and abnormal morphogenesis. We propose these defects were due to either severe fetal anemia or to vascular occlusion by abnormal erythrocytes, resulting in hypoxia of the developing distal limbs and genitalia.