The authors report on a neonate with gastroschisis repaired at birth who later had abdominal distension, emesis, feeding intolerance, and an abnormal stooling pattern. Total colon and partial small bowel aganglionosis (TCAS), or Hirschsprung's disease, was diagnosed subsequently. This is the first report of this combination of gastrointestinal anomalies. J Pediatr Surg 36:638-640. Copyright © 2001 by W.B. Saunders Company.

Fractal and non-fractal theories predict universal designs for biological branching transport networks whereby energy dissipation is minimized. However, they are inadequate to account for adaptation via designs that appear sub-optimal. Therefore we have evaluated another theory in the developing lung which is based on bifurcation design and the principle of self-organized criticality. The latter is a universal physical theory whereby fractal and multifractal patterns of branching complexity self-organize into meta-stable states poised between order and disorder. We find bifurcation design in the lung manifests an adaptable fractal dimension, with spatial scaling properties implicating structural origins of airway and vascular disease susceptibility.

Part 1: Medical Care. Prenatal Diagnosis.Premature Delivery. Assessment of Fetal Well-Being. Resuscitation of the New born. Assessment of Gestational Age. Temperature Regulation. Fluid And Electrolyte Balance.Nutrition. Parenteral Nutrition. Infectious Diseases.Acid Base Problems.Shock and Hypoperfusion. Cardiac. Pulmonary.Neonatal Apnea. Neurological Disorders. Drug Abstinence Syndrome. Renal Disorders. Gastrointestinal Disorders. Hematologic Problems. Jaundice. Hypoglycemia, Calcium, Endocrine and Related Problems. Newborn Screening For Genetic and Metabolic Disorders. Serious Inherited Metabolic Disease. Transient Immunologic Disorders. Birth Defects and Genetic Disorders. Common Surgical Problems. Part II: Techniques and Procedures. Oxygen Therapy. Endotracheal Intubation. Continuous Positive Airway Pressure. Ventilatory Assistance. Exogenous Surfactant Administration for RDS. Extracorporeal Membrane Oxygenation. Toracostomy Pericardiocentesis for Pneumopericardium. Adjuncts to Mechanical Ventilation. Analgesics, Sedatives, and Muscle Relaxants. Flexible Fiberoptic Bronchoscopy. Blood Sampling Techniques. Placement and Management of Intravascular Catheters. Continuous Monitoring of Oxygenation and Ventilation. Obtaining Spinal Fluid. Suprapubic Bladder Aspiration. Administration of Blood and Blood Components Exchange Transfusion. Peritoneal Dialysis. Infant Transport PART III: Formulary. Neonatal Drugs. GLOSSARY. APPENDIX. INDEX

Anatomical closure of the ductus arteriosus requires normally quiescent luminal endothelial cells and medial smooth muscle cells to migrate into the subendothelial space forming intimal mounds that eventually coalesce and occlude the vessel's lumen. The migration of endothelial cells and smooth muscle cells requires the presence of integrin receptors that interact with the surrounding matrix. We used immunohistochemical staining to examine the repertoires of integrins expressed by endothelial cells and smooth muscle cells during postnatal closure of the ductus arteriosus in full-term and preterm rhesus monkeys. In the fetal ductus, luminal endothelial cells have a limited repertoire of integrins. During postnatal ductus closure, luminal endothelial cells, of both term and preterm monkeys, change their phenotype and express the full repertoire of integrins found on growing capillary endothelial cells (α1β1,α2β1, α3β1,α6β1, αvβ1,α6β4, and αvβ5). Similarly, during ductus closure, smooth muscle cells of both term and preterm monkeys expand their integrin repertoire to include the α5β1 and αvβ3 integrins; these two integrins have been shown to be essential for smooth muscle cell migration in vitro. These changes in integrin profile occur at the same time the endothelial and smooth muscle cells invade their neighboring compartments. In contrast, preterm monkeys with a persistently patent ductus lumen fail to develop these changes in integrin expression and fail to develop neointimal mounds. No evidence of intimal thickening occurs in the absence of changes in integrin expression. Therefore, endothelial cells and smooth muscle cells change phenotypes to produce the intimal thickening required for ductus closure.

Following muscular constriction of the ductus arteriosus in the first hours after delivery, extensive neointimal thickening is required to produce permanent occlusion of the ductus lumen. In premature infants, despite, smooth muscle constriction, neointimal mounds frequently fail to develop, resulting in vessel reopening. Neointimal mounds are formed by luminal endothelial cells(ECs) and medial smooth muscle cells (SMCs) that migrate into the subendothelial space. The migration of ECs and SMCs requires the presence of cell surface receptors (integrins) that interact with the surrounding extracellular matrix (ECM). The ability of the integrin receptors to bind to different ECM molecules is determined by the combination of α and β subunits that make up the integrin receptor. Using immunohistochemical techniques, we examined ductus arteriosus obtained from 4 fetal and 11 four-day-old newborn (3 full-term and 8 preterm [78% gestation]) rhesus monkeys to determine the effects of gestational age on postnatal integrin expression and ductus remodeling. In the fetal ductus, ECs lining the vessel's lumen have a limited repertoire of integrins (weak expression ofα1β1 and minimal to negligible expression of otherβ1, β3, β4, β5, andβ6 integrins). In contrast, ECs of capillaries invading the ductus adventitial layer strongly express several integrins(α1β1, α2β1,α3β1, α6β1,αVβ5, α6β4). During postnatal closure, luminal ECs of the full-term ductus change their phenotype and express the identical repertoire of integrins found on migrating capillary endothelial cells. Similarly, after birth, SMCs in the closing ductus change their phenotype and express 2 additional integrins(α5β1 and αVβ3) that we have previously shown to be necessary for SMC migration in vitro. Among the 8 preterm ductus, 3 had lumens that were occluded by neointimal formation; the integrin profiles of the ECs and SMCs of these 3 ductus were identical to those expressed by cells of the full-term postnatal closed ductus. In contrast, 5 preterm newborns with persistently patent ductus lumen failed to develop these postnatal changes in integrin expression and failed to develop neointimal mounds. No evidence of intimal thickening occurred in the absence of changes in integrin expression. These findings show that during ductus closure, ECs and SMCs change their phenotype and express integrins found on migrating cells; this enables them to produce the neointimal mounds necessary for permanent closure.

Circulating platelets have been implicated in the hypoxic pulmonary pressor response. This study was undertaken to assess the effects of acute hypoxia-induced pulmonary hypertension on platelet volume and number across the pulmonary circulation in anesthetized newborn lambs. Seven animals were instrumented for measurement of pulmonary vascular resistance. All measurements were made during normoxia and after 5 and 30 minutes of hypoxia (10 to 12% oxygen breathing). Hypoxia caused a doubling of the pulmonary vascular resistance. During hypoxic vasoconstriction, platelet volume decreased rapidly while traversing the lung but was not affected on return to the lung after traversing the systemic circulation. Platelet numbers were unchanged on leaving the lung but were decreased on entering the lung during hypoxia. Our data are consistent with the release of platelet contents in the lung during hypoxic pulmonary hypertension.

We describe seven infants who developed renal calcification and bone de‐mineralization following furosemide therapy with average daily doses of as little as 0.75 mg/kg per day. Renal calcifications were present in all seven cases and were more readily detected with ultrasonography than with plain films. Renal calculi were seen in four patients, sonographically demonstrated as echogenic foci in the dependent portion of the collecting system, usually accompanied by acoustic shadowing. One patient developed nephrocalcinosis, sonographically observed as echogenic medullary pyramids plus punctate, shadowing parenchymal calcifications. In two patients the location of the calcification could not be determined.

Interpretation of the change in pulmonary vascular resistance at birth ignores the hemodynamic consequences of pulsatile pressure and flow. Whereas, impedance analysis can account for such changes. We studied changes of input impedance (Zin) in the left pulmonary arterial circulation (LPAC) before and immediately after birth in four near-term lambs. Epochs of pressure and flow in the LPAC were obtained from a micromanometer and an electromagnetic flowmeter. A computerized spectral analysis program provided Zin in terms of a modulus spectrum [Zin] and phase spectrum (Oin). The [Zin] spectra of the fetus and newborn are qualitatively similar to those obtained by others in adult vascular beds, ie, as a consequence of a pulsatile flow at a given heart rate, the effective circulatory load at the entrance of the LPAC is less than Rp, the resistance of the arteriolar bed("decoupling" phenomena). We interpret this as the LPAC presenting a similar hydraulic load to pulsatile potential hydraulic power. We conclude that the fetal and neonatal LPAC may not differ markedly in how it accomodates pulsatile hydraulic power at harmonics equal to heart rate.

The timing of brain injury which leads to neurologic handicap in infants is difficult to establish. However, in infants who die it is possible to estimate the duration of injury by neuropathologic assessment of the state of necrosis, gliosis, alteration of extravascular red cells and calcification. We reviewed the neuropathologic findings, birth history, and clinical course of neonates autopsied at our center during 1982. Five of the 6 term infants and 10 of the 25 premature infants who died at less than 7 days of age were shown to have brain lesions which predated their time of delivery. Two of the 5 term infants and 7 of the 10 preterm infants had Apgar scores of <3 at 1 min and <5 at 5 min of age. Fetal distress was usually unrecognized and only 1 term and 3 preterm infants were delivered by C-section. Clinical characteristics observed did not suggest a recognizable syndrome of prenatal brain injury. However, the gut and lungs had also been affected prenatally in several cases. Respiratory failure was the usual cause of death. We conclude that a number of infants dying at less than one week of age have evidence of prenatal brain injury. Birth asphyxia is frequently associated with this finding and this suggests that such infants do not tolerate labor. The probability of prenatal brain injury in surviving neurologically damaged infants with similar birth histories seems high. The medicolegal implications are important and we recommend careful neuropathological evaluation of all such infants who die.

In order to assess the mechanism of hyperventilation induced pulmonary vasodilation, 8 newborn lambs were chronically instrumented for measuring pressures in the aorta (PAo), pulmonary artery (PPa), left atrium, and superior vena cava, and pulmonary blood flow (Qp). Two-five days following surgery, the lambs were paralyzed and ventilated with a hypoxic gas mixture in order to raise PPa. They were then mechanically hyperventilated. Without changing the ventilator settings, normocarbia was reproduced by adding CO2 to the inspired gas.Results are reported as means (ranges). Alveolar hypoxia increased pulmonary vascular resistance (PVR) by 78% (9-237%) and the pulmonary/systemic resistance ratio (PVR/SVR) by 67% (6-133%). During hyperventilation, PaCO2 decreased by 15.5 torr (6-34 torr), and PPa fell by 5.6 mmHg (2-9 mmHg). Interestingly, the effects of hyperventilation on PAo, Qp, PVR, and PVR/SVR were variable, and both increases and decreases were seen. The addition of CO2 to the inspired gas during the hypoxic hyperventilated state elevated PaCO2 by 15.6 torr (7-24 torr), and elevated PAo by 10.8 mmHg (0-22 mmHg), PPa by 11 mmHg (8-17 mmHg), SVR by 20.7% (4-35%), PVR by 56% (14-170%), and PVR/SVR by 28% (9-102%). The effect on Qp was variable.We conclude that the newborn's pulmonary bed is very sensitive to changes in PaCO2, and that the reduction of hypoxia induced pulmonary hypertension in newborn lambs by hyperventilation is not due to a direct mechanical effect on the lung.

We studied hydraulic input power and input impedance changes in the left pulmonary arterial circulation (LPAC) before and after birth because they account for the relative importance of pulsatile and steady power and provide insight into the physiologic mechanisms of accomodating to each. Pulsatile pressure and flow were measured by a Millar micromanometer and electromagnetic flowmeter in 5 near term fetal lambs. Instantaneous power (IP) was calculated as the product of pressure and flow with time. The apparent power was calculated as the root mean square (RMS) of IP after the steady power was subtracted. Input impedance analysis allowed partitioning of pulsatile apparent power into average and reactive (RMS) components. Power values were calculated from 4 epochs of 48 seconds before and after birth in each animal. The calculated Potential Hydraulic Input Power (milliwatts) was: Although the steady component of power increased 3 fold after birth, the magnitude of apparent power remained unchanged and was greater than that due to steady power. When apparent power was partitioned, in the fetal state, reactive power was greater than average power while it was less in the newborn. Hemodynamic transmission line theory suggests that average power is the portion of the apparent power dissipated into heat by the viscous properties of the blood and vessel walls, whereas reactive power is given to elastic wall expansion. Since the apparent power associated with pulsatile blood pressure and flow represents a substantial magnitude of the total power delivered to the LPAC, especially in the fetus, how it is partitioned may play a role in normal or abnormal pulmonary vascular development.

Some investigators do not consider smaller primates a reasonable model for chronic problems of VLBW infants by because of mechanical difficulties in life support. We evaluated the premature rhesus monkey as a feasible model of long term complications of prematurity.We delivered, by hysterotomy, three M. Mulatta primates at 74-87% of gestation. Weights ranged from 313-467 gms. Two infants had radiograpahic evidence of HMD. All animals had tracheal intubation immediately after delivery and required continuous medical support until resolution of their lung disease, which had occured in 2 animals by day 5. The infants were ventilated with a Baby Bird ventilator, and temperature was maintained under a radiant warmer. Periodic sampling was done through an umbilical artery catheter for blood gas, hematology, and chemistry values. Blood was replaced from an adult rhesus donor. Infant monkeys required similar ventilator management to VLBW human infants. Except for increased glucose requirements, metabolic needs appeared similar to those of human infants, as were hematologic and serum chemical values. During the first four days of management, we successfully assessed auditory evoked potentials during bilirubin infusion, pulmonary macrophage function, and cord blood neutrophil function. Thus, the premature rhesus monkey appears to be a feasible and useful homologue for a variety of postnatal problems of VLBW infants.

We assessed lung collagen in human infants at risk for chronic lung disease (CLD) because Type I collagen is increased in adult RDS, and idiopathic or experimental pulmonary fibrosis. We determined collagen Types I and III in the lungs from 15 human infants who died while receiving mechanical ventilation, and in 3 stillborn infants. We analyzed lung tissue by CNBr digestion, column chromatography and index polypeptide separation by poly-acrylamide gel electrophoresis. To decrease the influence of measurement error of Type I collagen, we calculated ratios of Type I to III collagen. We then compared infants with clinical and/or pathological CLD to those without CLD using pooled variance techniques and one tailed t-tests. We observed a significant increase in Type I/III collagen with CLD. No general relationship between total ventilator time and collagen I/III ratios existed, but bacterial pneumonia may have been contributory to rapidly developing CLD. All infants with pathologic CLD had increased Type I collagen. Two infants dying early with very high I/III ratios had evidence of prenatal brain damage, suggesting that some increased collagen synthesis may be the result of prenatal lung injury.

Circulatory adaptations to spontaneous hypoxemia were assessed with the microsphere method at 119–123 days gestation in ovine fetuses who were subsequently found to be growth retarded. Combined ventricular output tended to be increased and it was redistributed so that oxygen delivery to the heart was increased by over 50%, oxygen delivery to the lung and placenta were decreased, and that to other organs, including the brain, were maintained. Maternal oxygen breathing for 1 h not only reversed these adaptations, but also produced an augmented lung blood flow. Umbilical blood flow was not affected. These findings have clinical implications for the growth-retarded fetus about to undergo the stress of labor.

The effect of reducing hemoglobin affinity for O2 on fetal oxygenation was assessed in seven fetal lambs in which fetal blood was almost completely replaced by maternal blood 2-3 days postoperatively. Measurements of fetal blood gases and organ blood flow (radionuclide-labeled microsphere technique) were obtained before and 1 h after the exchange transfusion. Umbilical venous blood PO2 increased from 29 +/- 5 to 35 +/- 6 (SD) Torr (P less than 0.001) but hemoglobin O2 saturation decreased from 78.2 +/- 10.3 to 39.8 +/- 8.8% (P less than 0.001), resulting in a 46% decrease in umbilical venous blood O2 content. Since umbilical-placental blood flow also decreased (P less than 0.002), O2 delivery to the fetus decreased by 64% (P less than 0.002). Although O2 extraction increased from 32.5 +/- 6.8 to 50.9 +/- 9.0% (P less than 0.002), fetal O2 consumption fell from 7.28 +/- 1.97 to 4.10 +/- 1.20 ml X min-1 X kg-1 (P less than 0.02), and metabolic acidemia developed. No significant change in fetal cardiac output was observed. Blood flow increased significantly to the myocardium and adrenals but fell in the placenta, carcass, and lungs and was maintained in other organs. This resulted in a significant decrease in the amount of O2 delivered to all fetal organs except to the myocardium in which it was maintained. In the sheep the higher affinity of fetal blood hemoglobin for O2 helps maintain normal oxygenation during fetal life by facilitating O2 uptake at the placenta and unloading O2 in the tissues.