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Continuous negative pressure ventilation utilizes subatmospheric pressure around the thorax to improve oxygenation. It has not been routinely used since the mid-1970s. We treated 37 infants with the combination of continuous negative pressure (CNP) and intermittent mandatory ventilation (IMV), after failing to attain a Pa of ≥50 torr on IMV alone. Lung diseases included pulmonary interstitial emphysema (PIE), respiratory distress syndrome (RDS), and pulmonary artery hypertension (PAH) due either to meconium aspiration syndrome (MAS) or other causes (non-MAS). All infants had evidence of severe parenchymal pulmonary disease, or pulmonary artery hypertension resulting in persistent hypoxemia and hypotension. In the PIE group, CNP was started later in the course of the disease, and both positive pressure and oxygen were maintained for a longer period. The group of infants with non-MAS PAH required CNP and positive pressure ventilation for the shortest period of time. The infants with PIE also had a greater incidence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH). In addition, three patients with PIE died. In the non-MAS patients with PAH, no complications and no deaths occurred. The response to CNP was a rapid improvement in oxygenation in all groups with the greatest increase of Pa in the non-MAS PAH infants: from 30 torr prior to the initiation of CNP to 140 torr within 30 minutes. No significant changes in pH or Pa occurred in any group. Significant decreases in ventilator rate, mean airway pressure (Paw) and FI in peak inspiratory pressure were possible by 12 hours of CNP. CNP and Paw were decreased from −5 cm H2O and 12.8 cm H2O prior to initiation of CNP to −1 cm H2O and 5.0 cm H2O at 72 hours of treatment. FI at 72 hours was decreased to a mean of 0.57. Combined CNP and IMV ventilator therapy improved oxygenation with lessened Paw in infants with refractory hypoxemia due to MAS and PAH and in larger infants with RDS. While we cannot advocate the routine use of CNP, it would appear to have a role in the management of infants who have failed conventional ventilator therapy. Pediatr Pulmonol 1990; 8:245-253.

In his preface to Principles of Perinatal-Neonatal Metabolism, the editor, Dr Richard M. Cowett, establishes that there are enough data on fetal and neonatal metabolism to warrant a comprehensive and critical text. He does not warn us, however, how comprehensive this text will be. An incredible amount of information is packed into 774 pages, even more impressive when one considers the small type.True to his word, Dr Cowett has an all-star array of authors, many of whom are academic household names. He has organized the text into four sections that progress logically.The first, "General Principles," is fundamental for the reader and invaluable in elaborating on many of the major modern techniques used for the study of metabolism, including kinetic techniques (eg, mass spectrometry) and animal models.The middle sections, "Maternal Metabolism During Pregnancy" and "Fetal-Placental Metabolism," are outstandingly in-depth, with superb reviews of maternal-fetal glucose metabolism and fetal-placental

Prior to conception, female rabbits were made hyperglycemic by streptozotocin administration. Fetal hyperglycemia and hyperinsulinemia were documented. Although plasma myoinositol concentrations were higher in the fetuses of diabetic mothers, the ratio of lung to plasma myoinositol concentrations in 29-day fetal rabbits were lower than control values. CDP-diglyceride:inositol phosphatidyltransferase was reduced by 70% in the diabetic fetuses and their lung tissue phosphatidylinositol content was decreased.

Hypoxanthine, the end product of purine metabolism, is usually very elevated in body fluids during severe hypoxia. We measured hypoxanthine in the cerebrospinal fluid of hydrocephalic preterm infants (12 with posthemorrhagic, one with congenital hydrocephalus) to determine whether hydrocephalus is associated with anaerobic metabolism of brain tissue. Cerebrospinal fluid hypoxanthine was undetectable in normal infants. In hydrocephalic infants, the concentration of hypoxanthine ranged from 7.5 mumol/L to 28 mumol (means = 14.3 mumol/L). The hypoxanthine concentrations fell from a mean of 12.8 mumol/L to a mean of 2.0 mumol/L (P less than 0.05) with successful treatment of the ventriculomegaly by lumbar puncture or by ventriculoperitoneal shunt. Patients with acute posthemorrhagic hydrocephalus had similar concentrations of hypoxanthine (means = 14.5 mumol/L) as patients with late or with congenital hydrocephalus (means = 13.8 mumol/L), indicating that brain hypoxia is probably a consequence of the ventriculomegaly and not of the hemorrhagic insult.

The lung profile in amniotic fluid was studied in relation to the various classes of diabetes, to prolonged rupture of membranes, and to hypertension in pregnancy. Pregnancy-induced (Class A, gestational) diabetes mellitus showed a statistically significant delay in appearance of PG, thus a delay in maturation not related to lecithin; also PI levels in Class A diabetes remained elevated longer than normal. Other classes of diabetes were no different from normal except for accelerated maturation in F and R diabetes, where PG appeared before L/S ratios were mature (>2.0), but the small numbers of studies from patients with F and R diabetes were obscured when combined with the much larger number from D diabetes, which statisticaUy were no different from normal. Prolonged rupture of membranes by regression analysis showed clear statistically significant acceleration of maturation affecting both the L/S ratio and PG, which appeared early. HypertensiOn in pregnancy included mostly patients with mild terminal pre-eclampsia who were no different from normal; the relatively small number of samples from patients with severe pregnancy-induced hypertension, “chronic” toxemia, showed accelerated maturation (sometimes with L/S ratios >2.0 and early PG) which was obscured by the large number of mild problems. The appearance of PG signals the late (“final”) maturation of surfactant. Diabetic pregnancy of any class can safely be delivered free of ADS after PG appears.

To determine the maturation of pulmonary surfactant at birth, phospholipid patterns in tracheal or pharyngeal aspirates of 54 newborn infants were analyzed by two-dimensional thin-layer chromatography. The compositions of phospholipids and their surface tension-lowering abilities were assessed after gestations with various complications. Preterm infants with respiratory distress syndrome (RDS) lacked phosphatidylglycerol and had lower lecithin/sphingomyelin ratios than infants without RDS. An acceleration of both phosphatidylcholine (lecithin) and phosphatidylglycerol concentrations was observed in 21 preterm infants born after prolonged rupture of the membranes and treatment with isoxuprine. In these infants, the phospholipid pattern of lung effluent was similar to that of term infants even at gestational ages less than or equal to 30 weeks. Biochemical lung maturation was delayed in aneccephalic infants, infants of diabetic mothers, and one infant of a mother with hypothyroidism.

Phosphatidylglycerol (PG) was absent from lung effluent in 41 infants with respiratory distress syndrome of the newborn (RDS), whereas effluent from healthy control subjects of similar gestational age contained this phospholipid (4.9 +/- 2.4% of lipidphosphorus (P), n = 32). Control infants of 28 weeks of gestation or less with various respiratory disturbances other than RDS also had low PG (0.2 +/- 0.2% of lipid-P, n = 5). In RDS surfactant complex often could be isolated from the airways using differential and density gradient centrifugation. The material thus obtained had prominent phosphatidylinositol (PI) (13.6 +/- 2.8% of lipid-P, n = 6), but no PG. Of those 18 infants who had such surfactant even in the early stages of RDS, 13 were 35 weeks of gestation or more, 3 were offspring of diabetic mothers, and 2 had severe perinatal asphyxia. In healthy control subjects PG sometimes appeared first within an hour of birth, but in RDS PG did not appear until recovery from RDS. In RDS type II (transient tachypnea of the newborn) PG in lung effluent also was abnormally low (1.3 +/- 0.6% of lipid-P, n = 5) and PI was correspondingly prominent (9.7 +/- 3.6% of lipid-P, n = 5), indicating immaturity of surfactant similar to RDS. Surfactant with PG and PI has superior surface-active properties compared to that containing PI, but no PG. Surfactant without PG does not seem to stabilize the alveoli of the newborn as well as does surfactant with PG. The failure of PG appearance following birth therefore may precipitate RDS, especially beyond 35 weeks of gestation.

Autopsy findings suggest that lung surfactant is damaged in the adult respiratory distress syndrome. In the present study 225 bronchoalveolar lavage specimens (78 from 36 patients, 1-78 yr old with respiratory failure, 135 from another 128 patients with other respiratory disease, and 12 from healthy controls) were assayed for the lung profile [lecithin/sphingomyelin (L/S) ratio, saturated lecithin, phosphatidylinositol, and phosphatidylglycerol]. Bronchoalveolar lavage fluid was further analyzed for phospholipids and for phosphatidic acid phosphohydrolase, phospholipase A2, and phosphatidylinositol phosphodiesterase activities. A lipid-protein complex was isolated and analyzed for surface activity, and plasma was measured for myoinositol. There were only small differences seen in the recovery of total phospholipid between respiratory failure patients and normal controls. However, in respiratory failure, phospholipids in bronchoalveolar lavage were qualitatively different from those recovered either from normal controls or from patients with other lung disease: the LO/S ratio, phosphatidylglycerol, and disaturated lecithin were low, whereas sphingomyelin and phosphatidylserine were prominent. These abnormalities were present early in respiratory failure and tended to normalize during recovery. Low L/S ratio (less than 2), and low phosphatidylglycerol (1% or less of glycerophospholipids) in bronchoalveolar lavage was always associated with respiratory failure. Abnormal lavage phospholipids were not due to plasma contamination. The phospholipase studies revealed little evidence of increased catabolism of phospholipids. In respiratory failure, the lipid-protein complexes from lung lavage were not surface active, whereas that from healthy controls had surface properties similar to lung surfactant. Phospholipids from patients with respiratory failure were similar to those from respiratory distress syndrome in the newborn. However, the latter condition is characterized by fast recovery of surfactant deficiency and by high plasma myoinositol that suppresses the synthesis of surfactant phosphatidylglycerol and increases phosphatidylinositol (Pediatr. Res. 1981. 15: 720). On the other hand, in adult respiratory distress syndrome, the abnormality in surfactant phospholipids may last for weeks and in most cases is associated with low phosphatidylinositol, low phosphatidylglycerol, and low plasma myoinositol.

A technique to diagnose subependymal hemorrhage (SEH), intraventricular hemorrhage (IVH), intracerebral hemorrhage, and posthemorrhage hydrocephalus in tiny infants, using real time ultrasound studies of the brain ventricular system, is described. This is a bedside technique that visualizes the brain through the fontanelles and the sutures, in three planes: coronal, sagittal, and horizontal. Excellent visualization of the ventricular system, caudate nuclei, the thalamus, the choroid plexus, the corpus callosum, and the foramen of Monro is obtained. This method has good definition using high frequency transducers since there is no bone interference. The ultrasound diagnosis correlated well with computed tomography (CT) and with direct pathologic studies. This technique was more sensitive in diagnosing small IVH/SEH and organized clots than were CT studies. IVH/SEH were found in 90% of 113 infants less than or equal to 34 weeks of gestation; 49% of the hemorrhages were large and 41% were small. Most hemorrhages were found in the first scan, usually shortly after birth. Twenty-one premature infants who never had perinatal asphyxia or respiratory distress syndrome had IVH/SEH. The hemorrhages were followed until disappearance, usually in one to three months in cases of large hemorrhages.

In seven years the nation's first newborn special care unit has succeeded in reducing its infant mortality rate to less than half the national average. The first step was to reject the isolation and fragmentation that conventional concepts of infection control impose on the treatment of problem newborns.

IN the last twenty years, the staphylococcus has replaced the streptococcus as the chief cause of infection in maternity units. Sporadic and epidemic staphylococcal infection among newborn infants now ranks as one of the most serious hazards in the modern nursery (as summarized by Williams et al.1). Previous reports2 3 4 indicate that hexachlorophene-containing compounds applied to newborn infants reduce staphylococcal infections in nurseries and incidentally decrease nasal carriage of staphylococci. The opening of the new Palo Alto—Stanford Hospital Center in the summer of 1959 afforded an opportunity to institute a program centered around the prevention of staphylococcal colonization of the . . .

Determination of the lecithin/sphingomyelin ratio in amniotic fluid and the newborn infant’s own tracheal fluid has proved of significant value in identifying the premature infant whose lungs have not yet matured to the point at which surface-active pulmonary lecithin will be synthesized rapidly enough after birth, and who are thus at risk for respiratory distress, with its high mortality and high percentage of associated neurologic and intellectual deficits.

RECENT studies at the Yale–New Haven Medical Center1 , 2 have demonstrated that properly performed antiseptic skin and umbilical-cord care brings about a striking decrease in colonization of newborn infants by pathogenic staphylococci.§ Gluck and Wood2 suggested that this effect may be due to the interruption of a major epidemiologic route operative in nurseries — namely, staphylococci from all sources first colonize the skin or cord, or both, and are then carried into the nose. They found a 51 per cent overall colonization of nose and cord in a control group of 500 infants on "dry" skin care and a prompt drop . . .

IN 1952 Farquharson et al.1 reported the control of an outbreak of staphylococcal skin lesions in their nurseries by washing all infants with a hexachlorophene-containing preparation twenty-four hours after delivery and every second day thereafter. Since their report other publications have pointed out the usefulness of hexachlorophene-containing preparations in efforts to control outbreaks of staphylococcal skin lesions in nurseries and in reduction of the incidence of both nasal and skin colonization of newborn infants by staphylococci. Studies by Baldwin and his associates2 reported a significantly lower incidence of nasal colonization in hexachlorophene-washed newborn infants than in a comparable "dry"-skin care . . .

Only in normal pregnancy does the lecithin/sphingomyelin (L/S) ratio correlate with gestational age. Abnormalities of pregnancy, including maternal, fetal, and placental conditions, may affect markedly the maturation of the fetal lung. Certain conditions associated, e.g., with maternal hypertension and severe placental problems including retroplacental bleeding and ruptured membranes accelerate L/S ratio maturation and other conditions such as diabetes mellitus (A, B, and C) delay maturation of the L/S ratio. These studies suggest that an association exists between general major organ system maturation of the fetus—“functional maturity”-and the L/S ratio, independent of gestational age or birth weight.

• We report the preschool growth and development of preterm infants with problematic patent ductus arteriosus requiring either surgical ligation or indomethacin treatment in the neonatal period. Of 60 who completed longitudinal growth assessments, no differences in growth to 3 years could be demonstrated except at 18 months, when male infants who underwent surgical ligation were lighter than those treated with indomethacin. There were no significant differences in vision or hearing abnormalities except for four cases of regressed retinopathy of prematurity among the ligated infants. Developmental tests (Bayley Scales of Infant Development and the Peabody Picture Vocabulary Test) showed no group differences at preschool ages. Although psychomotor performance on the Bayley Scales in the first 1½ years was significantly lower among the surgically treated infants, later analysis showed that a similar number in both treatment groups scored within the normal range. No selective short- or long-term adverse effects of indomethacin treatment could be demonstrated. ( Am J Dis Child 1982;136:507-512)

The pregnancies of two subhuman primate species, the monkey (Macaca mulatta) and the baboon ( Papio papio ), were examined to determine if either is a model for human fetal lung development as reflected in amniotic fluid studies. From the data, we suggest that the pregnant rhesus monkey is a model for the study of human lung development. The biochemical pathways for surfactant are the same; the concentrations of lecithin in amniotic fluid correspond closely; there is a parallel rise in L/S ratios which correspond, and the lecithin acyl ester structures and their changes during gestation are very similar. The presence of chronic stress is associated with acceleration of maturation of the surfactant systems of the lung. Although there are some analogies in baboon pregnancy, important differences in lecithin pathway timing and lecithin acyl ester structures make extrapolation to the human subject less tenable. Ligation of the monkey fetal trachea in the second trimester results in oligohydramnios without apparent lung distention. At delivery, the normal changes with age in surfactant biochemistry are not found in the amniotic fluid but are present in lung-bronchial tree washes.

Pregnant rabbits were given continuous intravenous insulin between days 26.7 and 28.7 after conception. The treatment decreased fetal serum glucose, insulin, and myoinositol. Furthermore, maternal insulin decreased fetal growth slightly, and improved the survival of the prematurely delivered fetuses. Analysis of phospholipids recovered by alveolar lavage revealed that the lung surfactant was quantitatively and qualitatively superior to the surfactant from the fetuses of the saline-glucose control animals. This effect on the lung was more striking than that of glucocorticoid. Another group of pregnant rabbits received continuous intravenous glucose between days 27.0 and 29.0 after conception. The hyperinsulinemic fetuses of the glucose-infused does weighed more and had higher serum glucose and myoinositol than did those of the control animals. There was no detectable difference in alveolar lavage phospholipids between hyperinsulinemic and normoinsulinemic fetuses of glucose-infused does. The possible importance of these findings in understanding the mechanism of acceleration of lung maturation is discussed.

Prolonged rupture of the membranes exerts an accelerating effect on fetal lung maturation independent of gestational age or birth weight and resulting in absence of the respiratory distress syndrome (RDS). Sixty-four true-premature infants born of mothers with no complications of pregnancy other than prolonged rupture of the membranes were evaluated for the presence of RDS. In 42 of these infants, membranes were ruptured 24 hours or less prior to delivery, and RDS occurred in 64 per cent. In 22 infants with membranes ruptured more than 24 hours prior to delivery, 31 per cent developed RDS. Lecithin/sphingomyelin ratios showed marked acceleration following membrane rupture, irrespective of gestational age.

In normal pregnancy lecithin/sphingomyelin ratios correlate with gestational age. In complicated pregnancies biochemical maturation of fetal lung may be accelerated or delayed, depending upon maternal, fetal, or placental conditions. Surfactant contains other phospholipids besides lecithin, including phosphatidylglycerol (PG), the second major component of mature surfactant. Ninety phospholipid patterns in amniotic fluid were studied by two-dimensional thin-layer chromatography. In uncomplicated pregnancies PG was absent until 37 weeks' gestation, then increased there after. In complicated pregnancies (pre-eclampsia, diabetes Classes D, F, and R, premature rupture of membranes) PG was identified before 35 (as early as 29 weeks' gestation. These results verify accelerated lung maturation in certain complicated pregnancies. No newborn infant developed respiratory distress syndrome in the presence of PG.

The experience of the Special Care Nursery of the University of California Medical Center, San Diego, in the management of the high risk newborn with progressive ventricular enlargement is reviewed, and the physiopathological basis of progressive ventricular enlargement is analyzed. (Neurosurgery 14:612-618, 1984)

Two studies were done. In the first, 51 infants from high-risk pregnancies were evaluated for accelerated clinical neurological maturation. Eight infants had accelerated neurological maturation 3 or more weeks in excess of gestational age. In the second study, a sample of 25 infants with documented acceleration of pulmonary surfactant (lecithin/sphingomyelin ratio greater than or equal to 2 at gestational age less than or equal to 32 weeks) all infants showed accelerated neurological maturation (range 3 to 8 weeks) with the conditions studied associated with accelerated pulmonary maturation (for instance, retroplacental bleeding, prolonged rupture of membranes, placental infarction, severe toxemia, hypertensive disease, circumvallation, and amnionitis). Chronic retroplacental bleeding was associated with the most dramatic pulmonary and neurological accelerations.

MYOCARDIAL INFARCTION in the neona te usually occurs in association with congeni ta l hear t disease?..2 There have been isolated case reports of myocardial infarct ion occurring dur ing the per inata l period in the absence of recognized predisposing factors. A case is reported here which suggests that embol i sm of systemic vessels via fetal circulatory pathways may occur in complicated deliveries, which predispose the neona te to hypoxia and hemostasis, with resul tant t h rombus formation.

We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome.

Does a high degree of maternal physical fitness benefit the fetus? Fifty-four women, 35 to 37 weeks pregnant, were tested on a bicycle ergometer and given a physical fitness score (PFS). Forty-one women completed the study. None of the following had a significant correlation with the maternal PFS: Length of gestation, complications of pregnancy, length of labor in primiparas, one-minute Apgar score, infant birth weight, infant length, and infant head circumference. The PFS varied inversely with the length of labor in multiparas (p

In this study, 12 infants who received Pancuronium bromide for mechanical ventilation were monitored with continuously recorded EEG's. All were delivered at term with five minute Apgar scores of

Seventy-five infants ≤34 weeks gestation & birthweight ≥1000g had ultrasound brain studies to diagnose IVH and subependymal hemorrhages (SEH) on the first day of life (30′ to 23 hrs. after birth). They were grouped according to delivery (with & without labor). Diagnosis in the first 24 hours after birth & major IVH/SEH (IVH/SEH associated with ventricular enlargement) were considered. Infants born after labor had a higher incidence of major IVH/SEH even if those without RDS, PDA and asphyxia born with labor were compared with sick infants born without labor (2 Rh-hydrops, 14 RDS & PDA, 2 severe asphyxia). Labor seems important in the pathogenesis of large IVH/SEH in infants BW≥1000g.

Six Infants receiving IND for pharmacologic closure of a PDA were followed for 10-13 months. Neurologic, visual, hearing, cardiac, and renal evaluations were performed and compared to 11 infants with PDA matched for gestational age (31±3 wk), birth-weight (1481±558g), and RDS who underwent operative closure of the PDA between July 1975 and October 1976. All 6 IND treated survived; 2 of 11 control infants died. There was no retrolental fibroplasia in either group. Hearing was normal in all but one control infant. Neurologic evaluations were normal in 5 IND infants with global hypertonia in one, while 3 control infants had transient neurologic anomalies including neck extensor hypertonicity in I and asymmetric deep tendon reflexes In 2 Infants. Bayley Scales of infant Development are within ± 2 S.D. for post-conceptual age in 5 of 6 IND infants. Control Bayley Scales are incomplete. Cardiac evaluation: no residual shunt in either group. Both the IND and control infants had normal BUN and creatinines at 6-13 months of age suggesting that renal Impairment with IND (2.5-5.0 mg/kg) was transient as previously reported. These findings indicate that at 10-13 months of life IND neonates are indistinguishable from those requiring surgical II-gation of PDA. Additional follow-up of both methods of ameliorating this physiologically disadvantagous shunt is warranted.

THE USE OF CONSTANT NEGATIVE DISTENDING PRESSURE (CNDP) IN THE TREATMENT OF PULMONARY INTERSTITIAL EMPHYSEMA (PIE)

Thirty-two survivors of major intraventricular & subependymal hemorrhages (IVH/SEH) (associated with ventricular enlargement) were followed with frequent ultrasound studies. Fifteen infants (BW 770g-1640g) had a slight ventricular enlargement. Eight resolved the enlargement completely 3-12 wks after IVH/SEH & 7 were discharged with mild ventricular dilatation. Four of these 7 infants had follow-up studies (4-12 months); 3 were abnormal (large unilateral & mild bilateral hydrocephalus). Seventeen patients (BW 800g-2480g) had progressive hydrocephalus. Fifteen were treated with repeated lumbar punctures (LP) resolving the hydrocephalus in I & arresting it in 3 cases (mean no. LP's 8, mean volume of CSF 46.5 ml). LP's failed in 11 cases (mean no. LP's 8, mean volume CSF 40 ml). These patients had ventriculoperitoneal shunts (VP) between 14-80 days of life (mean age 27 days). VP resolved the hydrocephalus completely in 6 cases (BW 900g-1440g) & partially in 5 (BW 800g-1470g) (4 had intracerebral hemorrhages) Seven infants had shunt complications (1 infection, 2 obstruction & 4 both). Two infants died. Ultrasound was very useful for the early diagnosis of progressive hydrocephalus & for evaluation of the therapy & complications. Infants without progressive hydrocephalus but with slight ventricular enlargement should be followed closely since they may develop significant abnormalities.

Present evidence indicates that phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS), in decreasing order, activate surfactant lecithin synthesis and maintain surface activity. Animal studies indicate that INO suppresses surfactant PG synthesis. We have studied serum INO levels in newborns with RDS and in adults with ARDS. The INO levels have been correlated with phospholipid (PL) levels from tracheal aspirates (newborns) or alveolar lavage (adults). During 1st neonatal day INO levels were significantly higher in RDS (n=7) than in no RDS (n=12) [mean 1004 (530-2830), vs 179(58-345)μM, p

Thirty sick infants (BW≥1200g) without IVH or subependymal hemorrhage (SEH) or with minor IVH/SEH (without ventricular dilation) on the 1st day of life had frequent ultrasound studies during the 1st week to detect changes in IVH/SEH. Eleven infants with RDS & PDA were treated with Indo before 96 hrs. of life. These treated infants were compared with 19 sick infants who did not receive Indo. There was no difference in proportion of infants who increased IVH/SEH size in treated & untreated groups. Early Indo treatment of PDA does not seem to increase the incidence of major IVH/SEH in sick infants with BW ≥1200 g.

In 13 extremely ill neonates, 483 simultaneous TcPco2 (Roche heated TcPco2 monitors) and Pco2 studies were compared. Infants were

The majority of distressed fetuses and infants discovered during labor and delivery occur in seemingly normal pregnancies. Identification of these infants prior to labor was attempted by screening mothers for UPI with an exercise test at 35-37 weeks gestation. In addition, the relationship between maternal physical fitness (PF) and UPI was evaluated. Fetal heart rate was measured prior to and following maternal exercise. A change in the fetal heart rate of more than 16 beats per minute was considered to be a “positive” test. Five fetuses of 54 women tested had positive tests, 4 of whom subsequently developed fetal distress during labor and delivery. Seven additional infants developed fetal distress during labor and delivery; 6 of these, however, had compromised umbilical circulations. PF was unrelated to UPI in the subjects tested. It is suggested that women with “positive” exercise tests be monitored carefully during labor and delivery and perhaps advised to avoid strenuous activity in the interim.

Alterations in tracheal aspirate phospholipids (TAPL) during recovery from respiratory distress syndrome (RDS) previously have been defined (Ped. Res. 10:984, 1976), the appearance of phosphatidylglycerol (PGL) on day 5 indicating lung maturity. In 11 preterm infants (B.W. 1302±357 gm; G.A. 30.6±2 wks) with sequential TAPL, 6 infants followed a characteristic maturational time course while in 5 infants PGL appeared on day 2 indicating “early” lung maturity. In these 5 infants hemodynamically significant PDA (bounding pulses, murmur, hyperactive precordium; LA/Ao ≥.9 pulmonary plethora) occurred at 2.2±.4 days compared to 2.4±3 days in infants showing lung maturation on day 5. Both groups had similar oxygen requirements & duration of ventilation (93.8 hr. vs 118.8 hr.) to maintain Pao2 ≥50 torr & acid-base equilibrium inspite of biochemical evidence of lung maturity in the former. Evidence of pulmonary maturation in infants with pulmonary hyperperfusion due to a large left-to-right ductal shunt suggests that continued & increasing ventilatory requirements are due to ductal shunting rather than surfactant deficiency. Sequential TAPL in infants with RDS offers a basis for predicting ventilatory requirements during the course of RDS whereby maturing TAPL may suggest the timing for ductal closure; this deteriorating pulmonary function is owing to pulmonary edema rather than immature surfactant. Supported by HD-05292; HD-04380

Despite rapid diagnosis, modern surgical technique and intensive pre- and post-operative care, survival of infants with CDH who present within the first 24 hours of life is poor. Some authors suggest that the degree of lung hypoplasia is often the determinant in survival. In our experience almost all infants with CDH can be adequately ventilated following surgery, yet many of these infants subsequently die. After surgery for CDH, 4 infants had blood sampled from pre-and postductal sites. All infants demonstrated R→L shunting suggesting PH. A 5th infant who became progressively hypoxic following surgery underwent cardiac catheterization. No congenital cardiac lesions were found. However, PH with R→L shunting through the foramen ovale and ductus arteriosus (DA) were demonstrated. In addition left pulmonary venous desaturation was present. Both tolazoline (TZL) and chlorpromazine (CPZ) were injected directly into the main pulmonary artery (MPA). Pulmonary artery pressure (PAP) dropped, systemic arterial saturation rose, and pulmonary circulation improved. It was unclear whether the improvement was fortuitous. Subsequently PAP rose and repeat doses of TZL and CPZ administered into the MPA caused little response, 14 hours later the infant died. PH complicating CDH probably occurs frequently. Establish ment of pulmonary normotension may be necessary for survival.

Lung Development: Biological and Clinical Perspectives is a two-volume work edited by Dr Philip Farrell. The 21 sections in volume 1 and the 15 in volume 2 are provided by 33 contributors, many of whom are pioneers in their fields. Volume 1 mainly deals with the biochemistry and physiology of the developing lung, while volume 2 is primarily concerned with the neonatal respiratory distress syndrome. In general, the assignments of chapters are very good. Some chapters are especially noteworthy, including that by Longmore on the isolated perfused lung model for studies of lung metabolism, and the constructive material presented by Dr Robert B. Kotas. There are important chapters on isolation of alveolar type II cells (Robert J. Mason) and lung cell culture systems (W. H. J. Douglas and S. S. Smith). But there is an extremely disproportionate overemphasis on the CDP-choline pathway and on lecithin in general. This overemphasis is

Cukier et al (1972) first noted positive central spike waves in the EEG of infants who died with intraventricular hemorrhages. In 1979 Staudt & Engel noted suppression of EEG background activity in infants with IVH diagnosed by CT scan. The present study was undertaken to investigate further the EEG in infants with major & minor IVH diagnosed by CT scan. Ten infants were enrolled prospectively and had both EEG's & CT scans during the first 13 days. The EEG's and CT scans on another 31 infants were reviewed retrospectively. In the prospective series, 5 infants had normal EEG's; 4 had abnormal CT scans. Three infants had abnormal EEG's; IVH's were present in 2 infants. In the retrospective series, 23 infants had normal EEG's. Eight in the first week were associated also with major & minor IVH's. The remaining 8 infants had abnormal EEG's, and all but one were associated with abnormal CT scans. Outcome has been assessed up to 3½ years and is variable. However, 7 of 10 infants with abnormal EEG's have either expired or are developmentally delayed, while 7 of 23 infants with normal EEG's were abnormal later (p=NS). In conclusion, abnormal EEG's did not accompany IVH's in the majority of the infants studied.

Human gestational diabetic pregnancies are associated with fetal macrosomia & delayed surfactant production, especially phosphatidylglycerol (PG). Excess serum myoinositol is associated with delayed appearance of PG. Three female rabbits, with dated 27 day pregnancies were infused with D15/.2% saline for 48 hours (15 mg glucose/kg/min). Three controls were infused with D4/.2% saline for 48 hours (3 mg glucose/kg/min). Seventy-three fetuses were delivered at 29 days gestation. Although not all D15 treated fetuses were hyperinsulinemic, fetuses were easily divided into low insulin ( 140 μU/ml) groups. Alveolar lavages of fetal lungs with saline were examined for phospholipids, but no differences were found in percentages of sphingomyelin, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, or phosphatidylethanolamine. PG was undetectable in all specimens. Previous animal models for diabetic pregnancy have produced severe diabetes with anti-beta cell compounds administered to the mother. Fetal wastage & growth retardation often result. This model produces a late gestational hyperglycemic state with fetal hyperinsulinemia, macrosomia, & increased serum myoinositol.

• Lung maturity was assessed in nine neonates with early-onset sepsis and/or pneumonia first observed as respiratory distress syndrome (RDS). All but one infant had at least one clinical or laboratory feature in the immediate postnatal period that suggested infection. Five patients had a mature phospholipid pattern in tracheal or gastric secretions, suggesting that RDS was not present; four patients had an immature pattern, suggesting that RDS coexisted with early-onset sepsis and/or pneumonia. Neither clinical nor radiologic features differentiated patients whose surfactant phospholipid patterns were mature from those whose patterns were immature. The presence of a mature surfactant complex in an infant with RDS should suggest the presence of infection. The presence of an immature pattern, however, does not exclude the presence of infection since RDS may coexist with early-onset sepsis and/or pneumonia. ( Am J Dis Child 134:766-768, 1980)

Pourcelot's index of resistance as adapted by Bada into the pulsatility index (PI) (ratio of systolic & diastolic blood velocities) is suggested as a means of identifying changes in neonatal cerebral blood flow. Abnormality of PI in the anterior cerebral arteries, as detected by anterior fontanelle transcutaneous Doppler technique is suggested for anticipating & identifying intraventricular hemorrhage/intracerebral hemorrhage (IVH/ICH). Since PI reflects a ratio of relative flow velocities without absolutes for correlation, a study was done combining simultaneous recordings of flow velocity wave forms from left & right anterior cerebral arteries with direct umbilical artery catheter blood pressure wave forms. Forty-one studies were performed at 1 to 126 hr of life on 21 pre-term infants (Birthwts 880 to 4300 gm; gest. age 27 to 37 weeks). Analysis of tracings showed that near term and pre-term infants systolic and diastolic flow velocities have direct relationship to arterial blood pressure. PI data was obtained by analysis of beat-to-beat simultaneous blood pressure and flow velocity wave forms. PI data produced in this fashion has in all cases had absolute correlation with the presence or absence of IVH/ICH, verified Independently by real time ultrasound brain studies. The technique is a simple, non-invasive bedside procedure.

Thirty-three sick infants (

Progressive expiratory atelectasis of RDS is attributed to deficient surfactant phospholipids. Fetal lung biosynthesis of the principal ones, lecithin (phosphatidyl choline, PC) the most abundant, and phosphatidyl inositol (PI) and phosphatidyl glycerol (PG), the acidic phospholipids, are determined developmentally during gestation. They appear in amniotic fluid and are used to monitor maturity of fetal lung and optimal time for delivery by means of a LUNG PROFILE, utilizing 2-dimensional thin layer chromatography of the extracted amniotic fluid lipids, comparing on a gestational scale L/S ratio, % disaturated PC, % PI and % PG with level of maturity. The leclthin/sphingomyelin (L/S) ratio relates concentrations of PC to sphingomyelin acting as an “internal standard”. With lung maturation PC increases and there is increasing disaturation of its fatty acid esters, measured as acetone precipitable fraction of PC. PI and PG are essential to the stability of PC; PI increases parallel to PC to 35-36 weeks, then declines. At 36-37 weeks, PG appears and increases; by term and in mature surfactant it is the 2d most abundant surfactant phospholipid. RDS is never seen once PG is present. On recovery from RDS increasing PI is seen; PG may not appear until near 36 gest wks. In infants with retained lung fluid, PG is not present in amniotic fluid but appears after birth in tracheal secretions as symptoms disappear. The lung profile greatly enhances both accuracy of prediction and understanding of lung development and eliminates non-diagnostic intermediate values.

The time interval in milliseconds (ms) from the onset of the QRS complex of the EKG to the onset of Korotkoff sounds in the arm at diastolic cuff pressure (Q-Kd) was determined with a microprocessor based instrument (NB-200 Blood Pressure Interval Analyzer; Nicolet Biomedical). The Q-Kd is dependent primarily upon the pre-ejection period & pulse transmission time. A previous study in older patients suggested a shortening of the time with PDA (Am. J. Cardiol. 19: 147, 1967). Forty-one neonates ((wt. 2148 (±835), 700-4000 g; G.A. 34.7 (±3.8), 27-42 wk)) were studied e over 300 Q-Kd determinations obtained. The standard deviation of repeat Q-Kd's in a neonate was within 7% or less of the mean of five repeat determinations. Q-Kd correlated significantly with weight (80 ms 3000 gm) corr. coef. .492, p< .01; y=.0078X + 8.14. The Q-Kd correlated significantly but less well with gestational age. Ten infants treated (Indomethacin or surgery) for a PDA were evaluated serially. There was no correlation of Q-Kd with the PDA open or closed. This negative correlation was probably due to other cardiovascular parameters such as heart failure which also effects Q-Kd. An unexpected finding was that the instrument was extremely accurate in determining systolic & diastolic blood pressure indirectly. In summary, the Q-Kd was not helpful in diagnosing patency or closure of the ductus arteriosus in neonates.

The macrosomia of infants of diabetic mothers (IDM) is believed due to fetal hyperglycemia & hyperinsulinemia. Serum INO, a possible growth factor, is elevated among IDM. Therefore, we studied whether elevated INO is associated with IDM growth stigmata. Pregnant (27-day) rabbits were infused with insulin IV for 48 hrs to maintain blood glucose between 45-90 mg/dl. Group 1 (4 does): continuous INO infusion, 2 gm/kg/day; Group 2 (3 does): no INO. All had free access to water & lab chow. The groups had similar IV total fluid intake/kg maternal serum glucose & insulin/kg/hr. The does were sacrificed on pregnant day 29 and the fetuses studied for growth. Serum INO was significantly higher in Group 1 fetuses than in Group 2 (