Effects of low oxygen saturation limits on the ductus arteriosus in extremely low birth weight infants.

OBJECTIVE: Postnatal increase in oxygen promotes constriction of the patent ductus arteriosus (PDA). According to the findings of prospective observational studies, the clinical practice of targeting lower fractional oxygen saturation between 70 and 90% has been associated with a reduced incidence of severe retinopathy of prematurity (ROP) without affecting survival or neurodevelopmental disability at 1 year of age. Our objective was to investigate the impact of the use of a lower oxygen saturation target range on the incidence of early hemodynamically significant PDA (hsPDA) and the need for ductal ligation in extremely low birth weight (ELBW, <1000 g) infants. STUDY DESIGN: In this retrospective study, we analyzed data from 263 ELBW infants managed 4 years before (episode I: target oxygen saturation 89 to 94%) and after (episode II: target oxygen saturation 83 to 89%) implementation of the use of lower oxygen saturation limits in two neonatal intensive care units. Infants with a birth weight of 1000 to 1500 g were managed with the same oxygen saturation target range (89 to 94%) during both episodes, and they served as controls. Parametric and nonparametric tests were used as appropriate and multivariate logistic regression models were used to correct for confounders. RESULTS: There was an increase in the incidence of hsPDA (63.2 vs 74.8%, P=0.043), without an increase in the need for surgical ligation (24.2 vs 29.9%, P=0.3) after implementation of the lower oxygen saturation target range policy. After adjusting for confounders, there was an increase in the odds of having an hsPDA (odds ratio (OR) 1.77, 95% confidence interval (CI) (1.03 to 3.06), P=0.04) but the odds for ductal ligation did not change in episode II (OR 1.25, 95% CI (0.70 to 2.25), P=0.4). The incidence of ROP > or = stage III (50.7 vs 15.7%; P<0.0001) and the need for laser ablation (33.8% vs 8.7%; P<0.0001) were significantly reduced. There was no change in the incidence of hsPDA or ductal ligation in the control group. CONCLUSION: Targeting lower oxygen saturation limits to minimize periods of hyperoxemia in ELBW infants reduced the incidence of severe ROP and the need for laser ablation. The incidence of early hsPDA was increased; however, final closure rate and the incidence of surgical ligation of the ductus arteriosus were not affected.

Systemic to pulmonary collaterals in very low birth weight infants: color doppler detection of systemic to pulmonary connections during neonatal and early infancy period.

OBJECTIVE: Angiographic visualization of systemic to pulmonary collaterals (SPC) has been documented in premature infants needing prolonged ventilatory support. Noninvasive identification of such communications in premature infants was reported recently. The purpose of this study was to describe: 1) incidence, 2) clinical findings and implications, and 3) short-term follow-up of SPC diagnosed by echocardiography in very low birth weight (VLBW) infants admitted to the neonatal intensive care unit. METHODS: From December 1, 1994 to August 31, 1996, 196 infants with birth weight <1500 g were admitted to the neonatal intensive care unit; 133 of them received serial echocardiographic evaluations at 1 to 2 days, at 2 weeks, and at 1, 2, and 3 months of life. Follow-up echocardiograms were scheduled at 6 months and 1 year of age for patients with SPC persisting at 3 months of age. RESULTS: SPC were demonstrated in 88 patients (66%) at 1 to 90 days of life (mean 28 days). In most cases, the SPC originated at the distal aortic arch or the proximal descending aorta. Ten patients (11%) were treated for congestive heart failure. The symptoms improved and anticongestive therapy was discontinued in 9. One patient with persistent congestive heart failure underwent therapeutic cardiac catheterization and 1 prominent SPC was embolized. CONCLUSIONS: The incidence of SPC in VLBW infants is much higher than previously reported. We postulate that SPC are bronchopulmonary communications that enlarge and/or proliferate in response to a given stimulus. These communications are associated with increased time on positive pressure ventilation and length of stay in the hospital. SPC may lead to pulmonary edema and should be searched for in VLBW infants with a more complicated course. Echocardiographic examination with color Doppler performed in premature infants to evaluate left to right shunts should include careful search for systemic to pulmonary collaterals.echocardiography, systemic to pulmonary collaterals, aortopulmonary collaterals, prematurity, pulmonary edema.

Reverse aortic arch flow secondary to severe pulmonary hypertension in the neonate.

The purpose of this study is to determine the incidence of reverse aortic arch flow in newborn infants with pulmonary hypertension, and no other identifiable cause for flow reversal, being considered for extracorporeal membrane oxygenation (ECMO) 2) compare the left ventricular output, and 3) outcomes, of these infants, with those in the group of patients with normal arch flow. We reviewed the medical records and echocardiograms of all infants referred to our institution for extracorporeal membrane oxygenation support for pulmonary hypertension, between August 1994 and April 1996. Neonates with pulmonary hypertension and reverse aortic arch flow had significantly lower left ventricular output (p = 0.005), and had significantly higher mortality (p = 0.04), than those with normal aortic arch flow. They required significantly higher ventilatory support (p = 0.01) and tended to need more inotropic support. Reverse aortic arch flow in newborn infants with pulmonary hypertension, and no other cause for the reverse flow, indicates significantly decreased left ventricular output, and may be a marker for a more difficult clinical course and poor prognosis. In this group of patients with pulmonary hypertension, the survival was significantly higher in infants with no PDA or with pure left to right shunt across a PDA.

Aneurysm of the ductus arteriosus: a congenital lesion.

The objective of this study was to evaluate the clinical, radiological, and echocardiographic findings in 11 neonates with aneurysm of ductus arteriosus presented in our institutions between 1993 and 1996, and to postulate a new theory for the pathogenesis of this lesion. Medical records, radiographic studies, and echocardiograms were reviewed. All infants underwent follow-up echocardiograms every 2 to 3 days until the aneurysm spontaneously resolved or surgery was performed. The infants were predominantly term males; six had evidence of fetal distress, two were diagnosed prenatally by fetal echocardiogram, chest X ray evidenced mediastinal mass in six patients. The first echocardiogram showed structurally normal heart with an aneurysmal patent ductus arteriosus. In eight patients the aneurysm completely resolved by 5 to 10 days. One infant underwent surgical resection of the aneurysm after observation for 11 days with no change in size. Thrombosis of the aneurysm was noted in two patients; both underwent surgery. Increasing reports of ductal aneurysms in infants may reflect the availability of high-resolution echocardiography and more frequent use of echocardiography in the neonatal intensive care unit. Spontaneous resolution occurred in the majority of cases as in previous reports. We postulate that, at least in some cases, aneurysm of the ductus arteriosus is a congenital lesion that may represent poststenotic dilation of the ductus due to turbulent flow through a stenotic segment at its pulmonary artery end during fetal life. The presence of aneurysm of the ductus arteriosus should be excluded in selected cases of fetal distress, by fetal echocardiography.

Two sibs with Wolf-Hirschhorn and DiGeorge deletions resulting from an unbalanced chromosome rearrangement, 45,XX/XY, der(4)t(4;22) (p16.3;q11.2) mat,-22.

A mother with apparently balanced translocation between chromosomes 4 and 22 gave birth to two children (sib 1 and twin A) with 45,XX,der(4)t(4;22) (p16.3;q11.2)mat,-22 and 45,XY,der(4)t(4; 22(p16.3;q11.2)mat,-22 karyotypes. The mother was a slow learner and required special education. The imbalance in the sibs arose through a 3:1 malsegregation in the mother. The net result was deletions 4p16.3pter and 22q11.2pter. Deletion 4p is associated with Wolf-Hirschhorn syndrome (WHS). The 22q11.2 microdeletion is associated with a wide range of overlapping phenotypes including DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal facial abnormality, and sporadic or familial cardiac defect. Fluorescence in situ hybridisation (FISH) was performed. Cosmid probes D4S96, which maps to 4p16.3, and D22S75, which maps to 22q11.2, were used. In the mother, the translocation breakpoints were proximal to D4S96 on chromosome 4 and distal D22S75 on chromosome 22. The two sibs had deletions of a D4S96 and a D22S75 probe loci. Sib 1, a 2 1/2 year old girl, has multiple congenital abnormalities and profound developmental delay. The craniofacial features were generally of WHS. Hypoplasia of the thymus hypocalcaemia, and seizures in early infancy, which are clinical features of DGS, were also observed. Twin A was one of a pair of dizygotic twins. He had multiple congenital abnormalities and died soon after birth.

Severe retinopathy of prematurity in extremely low birth weight infants after short-term dexamethasone therapy.

With advances in neonatal intensive care survival of extremely low birth weight (< 1 kg) infants has increased significantly over the past decade. Dexamethasone is used increasingly for the prevention and treatment of chronic lung disease in these infants. The impact of dexamethasone therapy on the incidence or severity of retinopathy of prematurity (ROP) remains controversial. We conducted a retrospective study to evaluate the association between short-term dexamethasone treatment and severe ROP in extremely low birth weight infants. From October 1989 to December 1992, 309 very low birth weight infants were admitted to the neonatal intensive care unit. A total of 266 infants (86%) survived until hospital discharge. Of these, 90 weighed less than 1 kg. Thirty-eight of 90 infants received short-term dexamethasone therapy for chronic lung disease and the remaining 52 infants did not. Infants treated with dexamethasone and those not treated with dexamethasone were comparable in birth weight (820 vs 828 gm), gestational age (26.5 vs 26.9 weeks), inborn (11 vs 14), and occurrence of sepsis (13/38 vs 21/52). Infants treated with dexamethasone required longer periods of mechanical ventilation (44 +/- 23 vs 26 +/- 15 days, p < 0.001), had longer duration of supplemental oxygen (57 +/- 28 vs 29 +/- 23 days, p < 0.001), had higher incidence of patent ductus arteriosus (28/38 vs 18/52, p < 0.0003), and required surfactant therapy more often for respiratory distress syndrome (17/38 vs 11/52, p < 0.01), when compared with infants who did not receive dexamethasone. Severe ROP developed in 16 infants (stage III or higher); 12 of these were in the dexamethasone-treated group (p < 0.003). Thirteen infants required cryotherapy; nine were from the dexamethasone-treated group (p < 0.13). This study demonstrates an apparent association between the incidence of severe ROP and dexamethasone therapy. Prospective, randomized, controlled studies are needed to correct for differences in severity of cardiorespiratory illness to establish whether a causal role exists for steroid therapy in ROP. Until such studies are available, careful consideration must be given to indications, dosage, time of initiation, and duration of treatment with dexamethasone in extremely low birth weight infants.

The use of fetal echocardiography for predicting intrapartum fetal heart rate patterns in the post-term pregnancy.

One of the shortcomings of antepartum testing in the post-term pregnancy is that it does not identify the majority of fetuses who develop abnormal intrapartum fetal heart rate changes. The purpose of this study was to determine whether antenatal cardiovascular evaluation could aid in the identification of post-term fetuses at risk for intrapartum heart rate abnormalities. Seventy-five patients with a gestational age greater than 41 weeks underwent a non-stress test, amniotic fluid index and real-time assessment of the heart for the presence or absence of a pericardial effusion. M-mode measurements of the right ventricular inner dimension (RVID), left ventricular inner dimension (LVID), biventricular outer dimension (BVOD) and Doppler velocimetry of the umbilical artery (S/D) were performed. Group I (n = 32) had normal intrapartum heart rate tracings. Group II (n = 20) had abnormal intrapartum fetal heart rate tracings but did not undergo emergency delivery. Group III (n = 23) had abnormal intrapartum fetal heart rate tracings but underwent emergency delivery. When comparing Group I with Group II, the latter had significant differences for abnormal RVID, RVID/LVID ratio, and pericardial effusion. When comparing Groups I and III, there were significant differences for RVID, RVID/LVID ratio, pericardial effusion, BVOD, LVID and amniotic fluid index. Neither the non-stress test nor S/D predicted abnormal intrapartum fetal heart rate patterns. For prediction of abnormal intrapartum heart rate patterns, the sensitivities of the RVID (0.79), LVID (0.33), RVID/LVID ratio (0.72) and BVOD (0.63) were 1.7-4 times greater than the non-stress test (0.19) and the sensitivities of the RVID, RVID/LVID ratio and BVOD were 2 times greater than the amniotic fluid index (0.28). The positive (0.50-0.86) and negative (0.42-0.68) predictive values were similar for all groups. To predict emergency delivery associated with abnormal heart rate tracings, the sensitivities of the RVID (0.83), RVID/LVID ratio (0.70) and BVOD (0.65) were 2.5-3 times greater than the non-stress test (0.26) and 1.5 times greater than the amniotic fluid index (0.39). The positive (0.36-0.56) and negative (0.70-0.86) predictive values were similar. The presence of pericardial effusion had a higher sensitivity than the non-stress test and amniotic fluid index for predicting abnormal intrapartum heart rate patterns but not emergency delivery. Doppler velocimetry of the umbilical artery had a lower sensitivity than the non-stress test and amniotic fluid index for predicting intrapartum heart rate patterns as well as identifying the fetus needing emergency delivery. The results of this study would suggest that there is initially dilatation of the right ventricle which may be associated with abnormal intrapartum fetal heart rate patterns. However, when the left ventricle dilates, leading to cardiomegaly, there is a greater incidence of abnormal intrapartum fetal heart rate changes and associated emergency delivery. The amniotic fluid index appears to be a later finding for predicting abnormal intrapartum fetal heart rate changes.

Cardiovascular changes in infants with beta-hemolytic streptococcus sepsis.

Sequential hemodynamic and biochemical changes were studied in 24 infants with sepsis due to beta-hemolytic streptococcus to define the temporal patterns of physiologic events and to compare them in surviving (n = 11) and nonsurviving (n = 13) infants. Septicemia was documented by positive blood culture in all. Biophysical and biochemical measurements were obtained before and hourly, for 11 h after antibiotic therapy was initiated. Surviving infants had significantly higher Hct and systolic and mean arterial pressures than nonsurvivors. In nonsurvivors, low BP was associated with a concomitant rise in CVP and severe metabolic acidosis refractory to therapy. Although there were no differences in PaO2 or PaCO2 between survivors and nonsurvivors, arterial-alveolar oxygen gradients were significantly greater in nonsurviving infants. These data show cardiorespiratory and metabolic alterations that differentiate surviving and nonsurviving infants with beta-hemolytic streptococcal septicemia.

Pulsed Doppler measurement of left ventricular output as early predictor of symptomatic patent ductus arteriosus in very preterm infants.

High left ventricular output (LVO) values are associated with symptomatic left-to-right ductal shunting in preterm infants. However, LVO data prior to the occurrence of symptomatic patent ductus arteriosus (SPDA) are lacking. To determine whether serial measurements could predict a SPDA, we measured LVO from day 1 until day 10 with pulsed Doppler echocardiography in 25 preterm infants with birth weights of less than 1,250 g and hematocrits of more than 0.40. Eleven infants never developed patent ductus arteriosus symptoms and had LVO values within the normal range (190-310 ml/min/kg) with only minimal daily variations. The remaining 14 infants developed SPDA which required treatment with indomethacin, ductal ligation, or fluid restriction on days 2-5. From day 1 until day 5 their mean LVO values were significantly higher compared to the group without left-to-right ductal shunt and this increase was secondary to higher stroke volume values. An increase in LVO of more than 60 ml/min/kg consistently preceded SPDA by at least 24 h. Serial measurements of LVO using a single-pulsed Doppler approach can be used for early prediction of SPDA.

Fetal echocardiography. VIII. Aortic root dilatation--a marker for tetralogy of Fallot.

Tetralogy of Fallot has increased in incidence during the past decade. Although abnormalities of the four-chamber screening examination of the fetal heart identifies structural anomalies associated with semilunar and atrioventricular valve hypoplasias, the anomalies associated with tetralogy of Fallot are not as readily identifiable from the four-chamber view alone. This study was designed to determine whether aortic root dilatation, commonly observed in the newborn with tetralogy of Fallot, is a marker for tetralogy of Fallot diagnosed in utero. In 45 normal (control) fetuses the biparietal diameter, head circumference, abdominal circumference, and femur length were measured and M-mode measurements were made of the biventricular outer dimension and aortic root dimension. The aortic root dimension from seven fetuses (18, 19, 20, 23, 32, 33, and 34 weeks' gestation) with tetralogy of Fallot was increased in dimension when compared with cardiac (biventricular outer dimension) and noncardiac biparietal diameter, head and abdomen circumferences, and femur length parameters. In conclusion, incorporation of aortic root imaging with the four-chamber view of the fetal heart during a routine screening examination allows for identification of fetuses with tetralogy of Fallot.

Cardiovascular changes in preterm infants nursed under radiant warmers.

Radiant heat is known to increase insensible water loss and, to a certain extent, oxygen consumption. Little is known about its cardiovascular effects. We measured cardiac output, stroke volume, heart rate, and lower limb and skin blood flow in 20 preterm newborn infants nursed in an incubator and under a radiant warmer at an abdominal skin temperature of 36.5 degrees C. Mean (+/- SEM) birth weight was 1.57 (0.06) kg, gestational age 31.7 (0.4) weeks, and weight at examination 1.69 (0.02) kg; median postnatal age was 15 days. Skin and limb blood flow measurements increased by 44% to 55% with radiant heat (P less than .001 and P less than .01, respectively). Cardiac output increased by 5.4% (P less than .02) under the radiant warmer secondary to a small but significant (P less than .05) increase in heart rate. The changes in cardiac output during radiant heat administration are comparable to those reported for oxygen consumption.

Fetal echocardiography: the prenatal diagnosis of tricuspid atresia (type Ic) during the second trimester of pregnancy.

Fetal echocardiography (real-time and M-mode) was used to evaluate a fetus at 20 weeks of gestation because intermittent bradycardia had been auscultated at 14 weeks of gestation. Real-time examination of the four-chamber view suggested ventricular disproportion with the left ventricle larger than the right, absence of the tricuspid valve, atrial and ventricular septal defects, and normal pulmonic and aortic outflow tracts. M-mode quantitation demonstrated a dilated left ventricle, small right ventricle, dilated mitral valve, hypertrophy of the left ventricular wall, and normal outflow tract dimensions. Following the diagnosis of tricuspid atresia (type Ic), genetic amniocentesis was performed (46,XX). Intrauterine death occurred during the 28th week of gestation. Autopsy confirmed the echocardiographic findings.

Fetal echocardiography. VII. Doppler color flow mapping: a new technique for the diagnosis of congenital heart disease.

One of the difficulties for the fetal sonographer is the complete elucidation of structural defects of the cardiovascular system that are associated with intracardiac or great vessel flow disturbances. With the recent introduction of Doppler color flow mapping, in which blood flow is displayed in color superimposed on a real-time image, it has been impossible to identify flow disturbances in the pediatric and adult patient. This study was undertaken to determine whether Doppler color flow mapping could be used in the fetus to identify normal and abnormal cardiovascular anatomy. Thirty-five normal and high-risk fetuses were examined between 16 and 40 weeks of gestation. Doppler color flow mapping identified normal and abnormal anatomy (ventricular septal defect, atrial septal defect, endocardial fibroelastosis, dysplastic pulmonary valve, and tricuspid regurgitation). It appears that Doppler color flow mapping will add a new dimension to fetal cardiovascular imaging.

Effects of metaproterenol on pulmonary mechanics, oxygenation, and ventilation in infants with chronic lung disease.

Changes in pulmonary resistance, dynamic compliance, tidal volume, and transcutaneous PO2 and PCO2 after nebulized administration of metaproterenol were evaluated in eight newborn infants (birth weight 650 to 1060 g, gestational age 25 to 28 weeks) with chronic lung disease receiving mechanical ventilation. The infants were monitored continuously before and for 15 minutes after nebulization of metaproterenol during 3 consecutive days at mean age 34 days. There were significant increases in compliance, tidal volume, and tcPO2, and significant decreases in pulmonary resistance and tcPCO2. These data show that bronchospasm contributes significantly to the high pulmonary resistance in preterm infants with chronic lung disease and that metaproterenol is beneficial in the therapy of infants with chronic lung disease requiring mechanical ventilation.

Cardiac output changes secondary to theophylline therapy in preterm infants.

The cardiovascular effects of theophylline were studied in 11 clinically stable preterm infants. Theophylline was given as aminophylline using a loading dose of 6.8 mg/kg and a maintenance dose of 2 mg/kg every 8 hours intravenously. Cardiac output, stroke volume, and heart rate were measured using a combination of pulsed Doppler ultrasound and M-mode echocardiography. Compared with day 0, an increase was found in both cardiac output (P less than 0.01) and stroke volume (P less than 0.02) on days 1, 2, and 3. By day 7, stroke volume was comparable to pretreatment values, whereas cardiac output was still increased. Heart rate was augmented significantly (P less than 0.01) throughout the treatment period. Mean arterial blood pressure did not change. All but one of the neonates had serum theophylline concentrations between 6 and 13 mg/L. We conclude that both inotropic and chronotropic effects are evident during the first days of theophylline therapy. The metabolic cost of the increased cardiac output in the preterm infant with theophylline therapy deserves further attention.

Echocardiographic measurements in normal preterm and term neonates.

To the purpose of better defining normative data on intracardiac dimensions and systolic time intervals in very low birth weight infants, we collected M-mode echocardiograms from 210 healthy preterm and term neonates with birth weights between 780 and 5,350 g and gestational ages ranging from 26 to 43 weeks. Fifty-nine neonates were less than 24 h, 62 were 25-48 h, and 89 were 48-144 h of age. Diastolic and systolic left ventricular dimensions increased gradually with advancing birth weight (r = +0.84 and 0.78). Left atrial and aortic root dimensions tended to show a parabolic relationship with birth weight, increments were reduced at higher birth weights (r = +0.92 and 0.85). The shortening fraction of the left ventricle (mean +/- SD 33.8 +/- 4.9%) and the left atrial/aortic ratio (1.16 +/- 0.10) were constant throughout all weight subgroups. Pre-ejection periods and ejection times of both ventricles were reduced in preterm infants due to their higher heart rates, but left and right ventricular PEP/ET ratios in preterm and term infants were comparable. Septal thickness in diastole and in systole tended to increase slowly with advancing birth weight, but correlation coefficients were low. This information is currently used as data base for a computer program to interpret M-mode echocardiograms performed in our nursery.

Hemodynamic variables in infants weighing less than 1000 grams.

VVLBW infants pose a challenge in the management of their hemodynamic changes. Data are just accumulating regarding the hemodynamic variables in this very special group. We have described several newly developed methods of monitoring hemodynamic variables in infants less than 1000 gm. In the coming decade, some of these methods may become more refined and routine.