Short- and long-term outcome following thoracoamniotic shunting for fetal hydrothorax.

OBJECTIVES: To assess short- and long-term outcome in a cohort of fetuses diagnosed with hydrothorax (FHT) which underwent thoracoamniotic shunting in utero, and to examine the antenatal predictors of survival and of survival with normal neurodevelopmental outcome. METHODS: This was a retrospective analysis of 132 fetuses that underwent thoracoamniotic shunting at our center between 1991 and 2014. Data were extracted from hospital obstetric and relevant neonatal intensive care and neonatal developmental follow-up databases. Outcomes included survival to discharge and survival with normal neurodevelopmental outcome beyond 18 months. Information on malformations, syndromes and genetic abnormalities were obtained from antenatal, postnatal and pediatric hospital records or by parent report. We compared pregnancy characteristics among those who survived vs non-survivors and among those with normal neurodevelopmental outcome vs those who were abnormal or died. We explored whether there was a trend in survival over the study period. RESULTS: The mean gestational age at diagnosis of FHT was 25.6 weeks. The fetus was hydropic at diagnosis in 61% of cases, 69% had bilateral effusions and 55% had bilateral shunts inserted. Other diagnoses were present in 24% of cases, two-thirds of which were discovered only postnatally. There were 16 intrauterine and 30 neonatal deaths, with a 65% survival rate overall. The mean gestational age at delivery of liveborns was 35.4 (range, 26.9-41.6) weeks, and 88/116 (76%) were preterm (< 37 weeks). Of 87 liveborn at the treatment center, 75% experienced some respiratory and/or cardiovascular morbidity after birth, many with a lengthy hospital stay (mean, 36 (range, 1-249) days). Overall, 84% of survivors were developmentally normal beyond 18 months and outcomes were better when pleural effusions were isolated, 92% of these cases being neurodevelopmentally normal. There was no trend in survival or neurodevelopmental outcome over time. Despite the presence of FHT and neonatal respiratory issues, most (89%) of the 55 survivors with relevant follow-up had no long-term pulmonary complications. Gestational age at delivery was the only factor independently predictive of both survival and survival with normal neurodevelopmental outcome. CONCLUSIONS: FHT is associated with other pathologies in a quarter of cases and carries a significant risk of prematurity, mortality and neonatal morbidity. The outcome is good in survivors but is best in isolated cases. Predictors of outcome at diagnosis are poor. Future improvement in diagnostics at time of identification of FHT may help to identify those that would benefit most from thoracoamniotic shunting. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal anti-Ro antibody exposure, congenital complete atrioventricular heart block, and high-dose steroid therapy: impact on neurocognitive outcome in school-age children.

OBJECTIVE: To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate, and/or prolonged dexamethasone therapy for immune-mediated congenital atrioventricular heart block (CAVB) on the cognitive and academic performance of these children at school age. METHODS: We performed a prospective, blinded assessment of the cognitive functioning of 3 cohorts of children ages 6-16 years with in utero exposure to maternal anti-Ro antibodies in the following groups: no CAVB and no prenatal dexamethasone treatment (n = 14), CAVB without prenatal treatment (n = 10), and CAVB with prenatal dexamethasone treatment (n = 16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function, and behavior. RESULTS: All cohorts scored within the normal range and were not significantly different in terms of intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For children with CAVB who were treated prenatally, there were no significant associations between the neurocognitive function scores, the minimal fetal heart rate (range 47-80 beats per minute), and either the duration (range 2-15 weeks) or dosage (range 56-824 mg) of dexamethasone therapy. CONCLUSION: CAVB and transplacental treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers of children are needed to validate our observation, and assessment of other cognitive abilities is warranted.

Fetal thoracoamniotic shunting for large macrocystic congenital cystic adenomatoid malformations of the lung.

OBJECTIVE: To evaluate fetal thoracoamniotic shunting for isolated large macrocystic congenital cystic adenomatoid malformations (CCAM) of the lung. METHODS: This was a retrospective study of 11 fetuses with macrocystic CCAM who underwent thoracoamniotic shunting. This procedure was offered if fetal hydrops or signs of evolving hydrops (such as ascites or polyhydramnios) were present, or when there were very large lesions or lesions rapidly increasing in size. If there were multiple large cysts within the lesion, a single shunt was used, aiming to traverse several cysts. RESULTS: Shunts were inserted at a mean gestational age of 24.6 (range, 17-32) weeks. Marked mediastinal shift was present in all cases. Six fetuses were hydropic and, of the remaining five, one had severe polyhydramnios, three had lesions that were rapidly increasing in size and one had a very large lesion at initial presentation. In total, four cases had polyhydramnios. Shunting one cyst always decompressed the entire lesion and hydrops and/or polyhydramnios resolved in all surviving fetuses. One hydropic fetus that underwent the procedure at 17 weeks died 1 day later. The shunt dislodged in one case and the lesion did not re-expand. No mother went into labor or had ruptured membranes before 35.6 weeks. Mean gestational age at delivery was 38.2 weeks (n = 10). All pregnancies were delivered vaginally, with no maternal complications. All newborns had uneventful lobectomies, and pathology confirmed CCAM in all cases. CONCLUSION: Fetal thoracoamniotic shunting for large macrocystic CCAM is associated with favorable outcome in most cases, and should be considered in severe cases even before hydrops develops.

Early intrauterine transfusion in severe red blood cell alloimmunization.

OBJECTIVE: To determine perinatal outcome in pregnancies with early severe red blood cell (RBC) alloimmunization. METHODS: This was a retrospective analysis of 30 patients requiring their first intrauterine transfusion (IUT) at < 22 weeks of gestation. Timing of the first IUT was based on evaluation of either the middle cerebral artery peak systolic velocity (MCA-PSV) or development of ascites. RESULTS: Thirty-three per cent of the patients had experienced a previous intrauterine fetal death as a result of RBC alloimmunization. Of these alloimmunized pregnancies, 26 (87%) were associated with anti-D, four (13%) with anti-Kell and 12 had more than one antibody type involved. The antibody titers before the first IUT ranged from 1:128 to 1:8024. All fetuses were severely anemic before the first IUT with a median hemoglobin (Hb) level of 37 (range, 3-81) g/L. The nine hydropic fetuses had a lower Hb level compared with non-hydropic fetuses (median 15 g/L vs. 42 g/L, P = 0.016). However, 15 (71%) non-hydropic fetuses had an Hb level of < 50 g/L before the first IUT. The median gestational age at the first IUT was 20.4 (range, 16-22) weeks, and between one and nine transfusions were needed during pregnancy. Transfusion was via the intrahepatic vein (IHV) (n = 19), umbilical vein (n = 6) or umbilical artery (n = 2), or was intracardiac (n = 2) or intraperitoneal (n = 1). Overall perinatal survival rate was 80% and did not differ between hydropic and non-hydropic fetuses. Median gestation at delivery, after exclusion of six intrauterine fetal deaths, was 36.7 (range, 27.8-38.4) weeks. CONCLUSIONS: In early severe RBC alloimmunization, fetuses can be severely anemic without hydrops, and prognosis cannot be predicted by the presence or absence of hydrops. Early IUT followed by serial transfusions is associated with a perinatal survival rate of about 80%.

Perinatal outcome following fetal chest shunt insertion for pleural effusion.

OBJECTIVE: To evaluate perinatal outcome of fetuses with primary pleural effusions following pleuroamniotic shunting. METHODS: This was a retrospective study of 88 fetuses with large pleural effusions referred to a tertiary fetal medicine unit between 1991 and 2008 which, after a thorough work-up, underwent pleuroamniotic shunting. RESULTS: At presentation, 59 (67.0%) fetuses were hydropic and 67 (76.1%) had bilateral effusions. In 17 (19.3%) fetuses, pleural fluid was aspirated prior to shunting and in 71 (80.7%), shunts were inserted directly as the first procedure. Mean gestational age at shunting was 27.6 (range, 18-37) weeks and at delivery 34.2 (range, 19-42) weeks. Seventy-four (84.1%) babies were born alive, of whom 52 (70.3%) survived the neonatal period. Of 59 hydropic fetuses, 10 (16.9%) died @ in utero and 18 neonates (30.5%) died, resulting in perinatal survival of 52.5%, whereas of 29 non-hydropic fetuses, perinatal survival was 72.4%. Hydrops resolved following shunting in 28 fetuses, of whom 71% survived, compared to 35% survival in 31 fetuses where hydrops persisted (P = 0.006). Of 22 neonatal deaths, seven were related to pulmonary hypoplasia, five to genetic syndromes, two to aneuploidy and one to a congenital anomaly (truncus arteriosus). Overall 13 (14.8%) were diagnosed with a chromosomal, genetic or other condition, several of which could not have been diagnosed antenatally. CONCLUSION: Carefully selected fetuses with primary pleural effusions can benefit from pleuroamniotic shunting, allowing hydrops to resolve with a survival rate of almost 60%.

Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants.

OBJECTIVE: To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of

Maternal ABO-mismatched blood for intrauterine transfusion of severe hemolytic disease of the newborn due to anti-Rh17.

BACKGROUND: Clinically significant antibodies to high-incident antigens present a challenge in hemolytic disease of the newborn. Antigen-negative blood may be difficult to obtain for intrauterine transfusion (IUT). In these instances, maternal blood is de facto compatible regardless of an ABO mismatch. CASE REPORT: A group B/D-- woman with a history of hemolytic disease of the newborn due to anti-Rh17 (titer 256) presented to the obstetrical clinic at 12 weeks gestation for management of her third pregnancy. She consented to donate blood for possible IUT. STUDY DESIGN AND METHODS: Washed maternal packed cells were suspended in saline to 75 percent Hct and irradiated before transfusion. The fetus was transfused via the intrahepatic vein. RESULTS: Ultrasound examination at 19 weeks indicated a hydropic fetus. The fetal blood group was O Rh+, direct antiglobulin test 4+, and hemoglobin 22 g per L. A total of 368 mL of maternal blood was transfused during seven procedures. Labor was induced at 38 weeks, and a 2560-g male infant was delivered by Caesarian-section due to fetal distress. The infant grouped as B Rh+, direct antiglobulin test negative. No group O red blood cells were detected. The hemoglobin level was 143 g per L rising to 209 g per L at discharge 3 days later. The indirect bilirubin was 55 micromol/L and remained stable during the hospital stay. Phototherapy was discontinued after 1 day, and the infant was discharged without an exchange or top-up transfusion. CONCLUSIONS: Maternal ABO-mismatched blood is an alternate source for IUT in instances when antigen-compatible allogenic blood is unavailable.

Outcome of infants 23-26 weeks' gestation pre and post surfactant.

To describe mortality and neurodevelopmental outcome before and after the introduction of rescue therapy with natural surfactant in two neonatal units in Toronto, Canada, a retrospective cohort study of 891 liveborn 23-26 wk gestational age infants, 421 presurfactant (1982-1987) and 470 postsurfactant (1990-1994) was performed. Overall mortality was stable over time (41% vs 35%, p = 0.077), but declined for inborn 24 (71% vs 43%, p = 0.03) and 26 wk (26% vs 13%, p = 0.01) gestational age infants and was higher in surfactant-treated infants (p < 0.0001). Chronic lung disease (61% vs 34%, p < 0.0001) and bilateral blindness (8% vs 4%, p = 0.004) declined over time, with stable rates of cerebral palsy (12% vs 15%), cognitive deficit (27% vs 26%) and aided sensorineural hearing loss (5% vs 4%). Sixty-five percent of surviving infants in both eras were free from neurodevelopmental impairment, and severe impairment declined over time (p = 0.035). This study shows no secular change in overall mortality in a large cohort of 23-26 wk gestational age infants since the introduction of rescue therapy with natural surfactant. However, it does suggest that maternal transfer to and delivery of all extremely preterm infants in high risk perinatal centres is justified.

Mid-trimester thoracoamniotic shunting for the treatment of fetal primary pleural effusions in a twin pregnancy. a case report.

Thoracoamniotic shunting has been described as having a beneficial role in the antenatal management of primary pleural effusions in singleton pregnancies. We report a case of a twin pregnancy in which progressive pleural effusions and hydrops were diagnosed in one of the fetuses at 16 weeks of gestation. An initial evaluation ruled out underlying genetic and anatomic abnormalities in both twins. At 19 weeks gestation, the first procedure of bilateral thoracoamniotic shunting was performed in the affected fetus, subsequent to which the lungs re-expanded and the hydrops resolved. Three additional shunt replacements and one therapeutic amniocentesis were required on follow-up. At 35 weeks, labor was induced. The first fetus (healthy) was delivered vaginally and the second fetus (affected) was delivered by cesarean section. Both neonates are healthy at one year follow-up.

Juvenile myelomonocytic leukemia and Noonan syndrome.

A case of juvenile myelomonocytic leukemia (JMML, previously referred to as JCML) in a neonate with Noonan syndrome (NS) is described. The boy presented with bilateral congenital hydrothoraces, nonimmune hydrops, dysmorphic facies, persistent thrombocytopenia, and leukocytosis. The diagnosis of JMML was made on bone marrow cell culture studies. Review of the literature reveals an unusual preponderance of hematologic malignancies, in particular JMML, among patients with NS. Of 40 NS patients admitted to the authors' institution during a 10-year period, there were 4 (10%) with evidence of a monocytic proliferation, which resolved spontaneously. The authors postulate that patients with NS may have an increased incidence of myeloproliferative disorders, which in most cases appears to be benign but may be preleukemic or even lethal.

Functional and antigenic concentrations of alpha-1-proteinase inhibitor after administration for the prevention of chronic lung disease of prematurity.

OBJECTIVE AND METHODS: Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficiency to impede the development of emphysema. A1PI supplementation may also be useful for protecting premature neonates who receive mechanical ventilation from the development of chronic lung disease (CLD). However, the pharmacokinetics of exogenous A1PI in this population are unknown. We attempted to determine the disposition of A1PI in premature infants with birth weight 600-1,250 g who received 60 mg/kg on days 0, 4, 7 and 14 in a randomized, placebo-controlled, double-blind trial. Functional and antigenic plasma concentrations of A1PI were measured at specified time points. RESULTS: On both functional and antigenic assays, concentrations began in the normal adult range and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the treatment and placebo groups. CONCLUSIONS: The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the adult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maintain A1PI plasma concentrations above baseline.

Reducing neutrophil elastase-induced lung injury.

The first trial of alpha1-proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity was recently completed. Receipt of four intravenous doses of the medication was associated with a trend towards a reduction in respiratory morbidity. A dose-ranging trial is in progress.

Congenital chylothorax in siblings.

We describe two cases of congenital chylothorax in siblings with important differences from previously described familial cases. Our findings support the likelihood of an autosomal recessive inheritance in some cases of this condition, rather than X-linked recessive inheritance, which has also been suggested. Autopsy findings from one of these cases and others previously described suggest that the pathophysiological mechanisms involved may be variable.

alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial.

BACKGROUND: An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD. DESIGN: A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28. RESULTS: A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups. CONCLUSIONS: In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely.

The outcome after perinatal management of infants with potential airway obstruction.

Masses in the head and neck are being detected prenatally with increasing frequency, necessitating the need for management of potential upper airway obstruction at delivery. Establishment of the airway at delivery and its maintenance thereafter are critical. This should optimally be performed with the baby still attached to the placental circulation. The importance of multidisciplinary team management, including a high risk obstetrician, neonatologist, pediatric otolaryngologist, pediatric thoracic surgeon, and an anesthetist, cannot be overemphasized. Endotracheal intubation is attempted first, if unsuccessful then is followed by insertion of a rigid bronchoscope. Tracheotomy should be reserved for airway obstructions, which are not amenable to endotracheal intubation or in babies in whom exchange from a bronchoscope to endotracheal tube cannot be safely performed. The management of six infants with prenatally diagnosed potential airway obstruction is presented. Morbidity and mortality still ultimately depend on the severity of the existent anomalies.

Surfactant replacement in neonates with early chronic lung disease.

OBJECTIVE: To study the effect of a single dose of exogenous bovine surfactant on oxygen and ventilatory requirements of neonates with early chronic lung disease. STUDY DESIGN: Prospective pilot study. SETTING: Three regional neonatal intensive care units. METHODS: Infants 7 to 30 days old with birth weights less than 1500 g were eligible if they required a fraction of inspired oxygen (FIO2) of more than 0.4, had stable ventilatory requirements for 24 hours before study entry, and showed diffuse haziness on chest radiographs. Those with patent ductus arteriosus or active infection or those receiving steroid therapy were excluded. After treatment with the surfactant, differences in FIO2 and the ventilator efficiency index were analyzed using the Wilcoxon signed rank test. RESULTS: Ten patients were recruited. Median values (range): birth weight, 693 g (530 to 1100 g); gestation, 25 weeks (24 to 27 weeks); and postnatal age at study entry, 13 days (9 to 30 days). The FIO2 decreased significantly between 0 and 1 hour after surfactant administration, from a median (range) of 0.67 (0.47 to 0.88) to 0.39 (0.28 to 0.63). This effect was sustained for 24 hours (median FIO2, 0.36). Although the FIO2 subsequently increased to 0.49 (range, 0.35 to 0.88) at 72 hours, it was significantly lower than that entry before the study. There was a trend toward an increase in the ventilator efficiency index at 24 and 48 hours. CONCLUSIONS: A single dose of surfactant is effective in reducing oxygen requirements in neonates with early chronic lung disease. Surfactant replacement may be useful adjunctive therapy in these neonates.

The premature infant: anesthesia for cesarean delivery.

The influence of anesthetic technique (general [GA] versus epidural [EPI]) on neonatal outcome was assessed for singleton infants of gestational age 32 wk or less, delivered by cesarean section. Neonates were identified from a prospectively collected perinatal database from 1986 to 1991. The independent effect of anesthetic technique on low 1-min Apgar scores after controlling for other risk factors was assessed by ordinal logistic regression. Among the 509 infants studied, 30% had Apgar scores of 0 to 3 at 1 min and 5.9% at 5 min. Among infants delivered with GA, 46.4% had low 1-min and 10.1% had low 5-min Apgar scores as compared to 22.0% and 3.8% for EPI. GA as compared to EPI was associated with higher risk of low (0-3) 1-min score after controlling for confounding factors (relative odds = 2.92, [1.99, 4.27 95% confidence intervals]). Other factors significantly related to low 1-min Apgar scores included malpresentation, maternal diabetes, primiparity, low gestational age, and associated neonatal outcomes (presence of respiratory distress syndrome and intraventricular hemorrhage). When there is a choice to be made in cesarean delivery of the premature infant, EPI is associated with higher 1- and 5-min Apgar scores compared to GA.

Absent end-diastolic flow velocity waveforms in the umbilical artery--the subsequent pregnancy.

OBJECTIVE: Our purpose was to assess the recurrence risk, course, and outcome of subsequent pregnancies in women with absent umbilical end-diastolic velocity. STUDY DESIGN: Absent umbilical end-diastolic velocity was detected in 88 women. Sixteen of them were prospectively followed up in their 19 subsequent pregnancies. These pregnancies were compared with their index pregnancies. RESULTS: The index pregnancy was invariably complicated with a perinatal mortality of 56%, growth restriction in 94% (15/16), and prematurity in 100% (75% < 32 weeks' gestation). In contrast, the outcome of the subsequent pregnancies was much better, and 74% (14/19) were uncomplicated. No perinatal deaths occurred, and none were delivered before 32 weeks' gestation. Absent umbilical end-diastolic velocity recurred in only two pregnancies, both of which were complicated. Six women had autoantibodies; these accounted for 80% (4/5) of subsequent complicated pregnancies. CONCLUSION: After an index pregnancy with absent umbilical end-diastolic velocity, subsequent pregnancies had favorable outcomes. Recurrence of absent umbilical end-diastolic velocity was low. The absence of autoantibodies and normal Doppler studies were associated with improved outcome.

Importance of vagal afferents in determining ventilation in newborn rats.

We studied the effect of acute bilateral vagotomy on ventilation and ventilatory pattern in rats. In 1- to 6-day-old unanesthetized rats, vagotomy resulted in a substantial decrease (38%) in ventilation during air breathing. After vagotomy there was a threefold increase in tidal volume (VT), inspiratory time (TI) doubled, and expiratory time (TE) was six times longer. When studied under isoflurane anesthesia, newborn rats showed decreases in ventilation similar to that observed without anesthesia, whereas anesthetized adult rats had no consistent changes in ventilation. Adult and newborn rats had nearly identical proportionate increases in VT and TI after vagotomy, but TE lengthened to a greater extent in the newborns. Additionally, we demonstrated a significant decrease in ventilation when 100% O2 rather than air was supplied to nonvagotomized unanesthetized newborn rats. Ventilation decreased by 19% after vagotomy under hyperoxic conditions. We conclude that vagal afferent input, probably of pulmonary mechanoreceptor origin, provides positive feedback to respiration in newborn rats and that newborn rats greater than 24 h old also have a degree of peripheral chemoreceptor drive during air breathing.