Joram Glaser

Indomethacin Tocolysis Increases Postnatal Patent Ductus Arteriosus Severity

Postnatally, therapeutic indomethacin administration is usually effective in mediating patent ductus arteriosus (PDA) constriction in premature infants. There are infants, however, who remain resistant to indomethacin and require more aggressive surgical intervention to facilitate ductal closure. Indomethacin tocolysis has been reported to increase the incidence of persistent PDA in premature infants. It was our impression that infants exposed to antenatal indomethacin not only suffered from an increased incidence of PDA, but that they were more symptomatic from PDA and that for them, PDA was more resistant to medical closure. It is this observation that we sought to examine in this study. Methods. Medical records of all mothers and premature neonates with birth weight ≤1500 g, admitted to the neonatal intensive care unit of the Shaare Zedek Medical Center during 1996 and 1997, who survived for at least 1 week, were reviewed retrospectively. Data on maternal indomethacin and steroid exposure, birth weight and gestational age, and ductus status and treatment were analyzed. In our obstetrics department, indomethacin is the medication of choice to inhibit premature labor. Mothers who arrive in premature labor are started on indomethacin therapy, if delivery is not imminent. All infants ≤1500 g were studied by a pediatric cardiologist between 24 and 72 hours of life using two-dimensional echocardiography with color flow mapping to assess ductal patency. Decisions to treat were based on echocardiographic evidence of PDA, along with any of the following clinical signs: bounding pulses, diastolic pressure of ≤25 mm Hg, pulmonary plethora and/or cardiomegaly on chest x-ray, or increasing oxygen requirement with no other explanation. Initial treatment is with indomethacin, if there are no contraindications. Our general approach is to begin therapy with a continuous indomethacin infusion, followed by a course of bolus indomethacin if the infant does not respond. However, each attending neonatologist may treat according to his/her preference (ie, bolus vs continuous). All infants with PDA are followed with serial echocardiographic examinations until the ductus is closed. Results. A total of 105 premature infants met the above criteria. Thirty-six of these 105 infants had echocardiographic signs of a PDA (34.3%). Those with PDA were less mature (gestational age, 28.9 ± 2.6 vs 30.3 ± 2.6 weeks, respectively) and tended to be smaller (1060 ± 270 vs 1166 ± 261 g). Of the 36 infants with PDA, 15 (42%) resolved spontaneously and 21 (58%) were symptomatic and required treatment with indomethacin. There were no differences in gestational age or birth weight between infants whose PDA resolved spontaneously and those requiring indomethacin therapy. Four of the 21 (19%) treated infants remained unresponsive to indomethacin and required ductal ligation. Of 17 infants with PDA who responded to indomethacin therapy, 1 (6%) was treated with a single course of bolus indomethacin, to which he responded, and 16 (94%) were treated with continuous indomethacin and responded promptly. The differences in therapeutic responsiveness to initial treatment with continuous vs bolus indomethacin were not significant. Of the 105 infants, 29 were exposed to indomethacin tocolysis. Those who were exposed to antenatal indomethacin and those who were not were well-matched with respect to birth weight and gestational age. Fifteen (52%) of the 29 exposed infants versus 18 (24%) of the 76 infants not exposed to antenatal indomethacin developed a PDA postnatally (relative risk = 2.1; 95% confidence interval: 1.22–3.74), and 45% of the antenatally exposed infants versus 12% of the nonexposed infants were symptomatic and required indomethacin (relative risk = 1.9; 95% confidence interval: 1.17–3.20). Four of the exposed infants versus none of the unexposed infants required surgical ligation. Among the indomethacin-exposed infants, the nonresponsive and responsive infants were well-matched with regard to birth weight, gestational age, antenatal steroid exposure, and day of life on which indomethacin therapy was initiated. Multiple regression analyses found prenatal indomethacin exposure to be the most significant antecedent variable associated with both the incidence and the severity of PDA, as indicated by the need for indomethacin treatment. Conclusions. We have demonstrated that prenatal indomethacin exposure increases both the incidence and the clinical severity of postnatal PDA, as manifested by increased need for therapeutic indomethacin and surgical ligation. Furthermore, we have shown it to be a more significant risk factor than gestational age, birth weight, or antenatal steroid exposure in both the development and the severity of postnatal PDA. These data should be considered in considerations as to choice of tocolytic therapy.

Buschke’s Scleredema with Right-Sided Heart Failure

Heart failure as a complication of Buschkes scleredema was not reported in the literature on this rare disease. A young girl with a severe form of Buschkes disease is described. She developed severe right-sided heart failure--proven by the typical clinical, auscultatory, electrocardiographic and echocardiographic findings; was treated successfully with penicillin, anticongestive measures and steroids, and showed a remarkable complete recovery.

Outcome of ten years’ echocardiographic follow-up in children with Gaucher disease

The non-neuronopathic form Gaucher disease, the most prevalent lysosomal storage disorder, is marked by tremendous phenotypic heterogeneity; cardio-pulmonary involvement is distinctly rare except in the most severely affected patients. With the advent of enzyme replacement therapy, most symptomatic patients will not suffer from lung disease. However, because of concern about pulmonary hypertension among adult patients exposed to enzyme replacement therapy, echocardiography has been recommended as an early warning system for routine follow-up of all patients, including children. The purpose of this study was to review the results of more than a decade of echocardiographic findings in children followed semi-annually in a large referral clinic in order to ascertain whether echocardiography as an early signal of pulmonary hypertension in children is appropriate. 330 echocardiographic examinations were performed in 71 children (276 patient follow-up years). Only four patients receiving enzyme therapy each had a single abnormal examination that upon repeat examination six months later reverted to within normal limits. There were no abnormal results among the untreated patients. Therefore, we feel comfortable with rescinding our recommendation with regard to routine echocardiographic examinations in children. At the present time we believe that a baseline examination to rule out abnormalities would be sufficient.

Familial Membranous Subaortic Stenosis

Familial occurrence of membranous subaortic stenosis (MSS) is described in three families. The defect was found in 2 siblings in two of these families, and in 3 siblings of the third family. The importance of early diagnosis and treatment of MSS is emphasized. We suggest early evaluation of first-degree relatives of patients with MSS for the possibility of this defect.

Echocardiographic Diagnosis of Anatomically Corrected Malposition of the Great Arteries

In anatomically corrected malposition of the great arteries, the great arteries are abnormally related to one another and to the ventricles but arise from their normal ventricles. We present here a case in which this diagnosis was made by echocardiography and confirmed by cardiac catheterization.

Accelerated weight gain by infants with pulmonic stenosis.

Retrospectively we compared the weight gain of infants who had significant valvular pulmonic stenosis with the growth of infants who had mild pulmonic stenosis and small ventricular septal defects. Our results indicate that the infants with significant pulmonic stenosis gained weight exceptionally well in comparison with others.

Acquired Obstruction of the Ventricular Septal Defect in Tetralogy of Fallot

The interventricular septal defect in patients with tetralogy of Fallot is, in most cases, a nonrestrictive malalignment type of defect. Rare examples of a restrictive defect have been described. We report a case of tetralogy of Fallot with pulmonic atresia in which the interventricular septal defect was found to be nonrestrictive at birth. The obstruction of the defect developed gradually, until, at the age of 6 years, a gradient of 55 mm Hg across the defect was found at repeat cardiac catheterization. Echocardiography proved that the acquired obstruction was due to excessive tricuspid valve tissue, while Doppler studies suggested a similar gradient between the right ventricle and the ascending aorta. This rare case should alert the clinician to the possibility of an acquired obstruction of the ventricular septal defect, with suprasystemic right ventricular pressure, in cases of tetralogy of Fallot, even if an early study suggested a nonobstructive defect. The diagnosis of this situation is of importance because of the poor prognosis which it carries.

An Unusual Case of Double-Outlet Left Ventricle

The first case of a double-outlet anterior left ventricle with normal relationships of the great vessels is reported (S.L.D.). This case is associated with a chromosomal trisomy--the exact nature of which is not yet clear. The clinical, electrocardiographic, echocardiographic and angiographic features are described.

Early cardiac evaluation of thoracically conjoined twins.

Thoracopagus conjoined twins were delivered at 31 weeks gestation by cesarean section. Although there was a single heart, the possibility of salvaging one twin only was contemplated. Echocardiography revealed an A-V canal and suspected transposition of the great vessels. To determine the possibility of surgery, cardiac catheterization was performed to rule out other congenital cardiac malformations incompatible with life, and also to delineate the exact anatomy of the great vessels of the heart. Unfortunately, complex congenital abnormalities were found, thus excluding the possibility of surgery. Newly delivered conjoined twins should be regarded as potentially correctable and should be promptly investigated while they are yet in good clinical condition.

Pregnancy and delivery by caesarean section in a patient with transposition of the great arteries and single ventricle. Case report

Dear Sir, In their study of natural killer (NK) cells in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection, Dr Tay and his colleagues [BrJ Obstet Gynaecol(1987) 94,9019061 detected NK cells in the subepithelial stroma of most cases of HPV infection and CIN. In contrast, there were few intraepithelial NK cells in HPV infection and CIN. They suggest that this may be due to poor tumour antigenicity or a direct tumour effect or an effect of seminal plasma. We believe the most likely explanation is that exposure of the cervix to seminal plasma inhibits NK activity in cervical epithelium. In general, human seminal plasma contains various agents which inhibit the normal immune response (Alexander & Anderson 1987), including the response of lymphocytes to a viral infection (Turner et al. 1987). More specifically, human seminal plasma has been shown to suppress NK cell activity (James & Szymaniec 1985; Tarter et al. 1986). The inhibition of NK activity in cervical epithelium by repeated exposure to seminal plasma may promote both neoplasia and viral infections of the cervix. This is consistent with the documented epidemiological associations between cervical neoplasia and sexual behaviour (Kessler