Two-Year Neurodevelopmental Outcome of an Infant Born at 21 Weeks' 4 Days' Gestation.

Recent literature confirms that, at the lower limit of extrauterine survival, substantial intercenter variability exists in resuscitation practice. The reasons for this variability are unclear, but may be related to disagreement on how to apply the best interests standard to extremely premature infants. Currently, both obstetric and pediatric societies recommend against assessing for viability or attempting resuscitation before 22 weeks' gestation. In this context, we report the unimpaired 2-year outcome of a female infant resuscitated after delivery at 21 weeks' 4 days' gestation and 410 g birth weight. She may be the most premature known survivor to date. This infant had multiple risk factors for adverse outcome, including prolonged mechanical ventilation, bronchopulmonary dysplasia, and threshold retinopathy of prematurity. She achieved discharge from the hospital on low-flow oxygen at 39 weeks' 4 days' gestation and 2519 g. At 24 months' and 8 days' chronological age, she achieved cognitive, motor, and language Bayley III scores of 90, 89, and 88, equivalent to 105, 100, and 103 at 20 months 2 days corrected age. It is known that active intervention policies at 22 weeks' gestation improves the outcome for those infants and it may be reasonable to infer that these benefits would extend, if to a lesser degree, into the 21st week. Ultimately, such limited data exist at this gestational age that the time may have arrived for obstetrical centers to begin systematically reporting fetal outcomes in the 21st week.

Intrafamilial variability of noncompaction of the ventricular myocardium.

BACKGROUND: Noncompaction of the ventricular myocardium (NVM) is a relatively uncommon form of cardiomyopathy characterized by a highly trabeculated myocardium. This report describes the clinical and genetic evaluation of a 3-generation kindred. METHODS: Family members were initially evaluated by 2-dimensional echocardiography. Most family members with signs of NVM were further evaluated by magnetic resonance imaging. Genetic analyses included mutational screening of the taffazin (TAZ) and alpha-dystrobrevin (DTNA) genes. RESULTS: Eight family members had signs of NVM. Considerable interindividual variation was noted in terms of spatial distribution and severity of affected regions and ventricular dysfunction. Depending on which of 2 previously proposed quantitative diagnostic criteria were used and where ventricular myocardial measurements were taken, between 4 and 7 of these individuals had findings that were considered diagnostic. Magnetic resonance imaging served as a useful adjunct for confirming or establishing diagnoses in all 8 individuals. No mutation was found in TAZ or DTNA. CONCLUSIONS: This kindred demonstrates the remarkably wide phenotypic spectrum that can be seen in familial cases of NVM, ranging from prenatal/neonatal lethality to a complete lack of symptoms. The fact that all 8 affected individuals either have shown improvement in ventricular function or symptoms during childhood or have been asymptomatic indicates that NVM can have a relatively benign course. The degree and nature of cardiac involvement are also quite varied, and there is a weak correlation with ventricular function and symptoms. Evaluation of families with NVM requires careful assessment that uses a combination of imaging techniques and diagnostic criteria.

Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity.

OBJECTIVE: Necrotizing enterocolitis (NEC), a serious multisystemic inflammatory disease most commonly seen in premature neonates, is often associated with thrombocytopenia. Infants with severe forms of NEC commonly have platelet counts of less than 50,000/mm(3), occasionally less than 10,000/mm(3). Despite an absence of data to support the practice, platelet transfusions are commonly used to maintain a certain arbitrary platelet count in an effort to prevent bleeding. As platelet transfusions contain a variety of bioactive factors including pro-inflammatory cytokines, we hypothesized that a higher number and volume of platelet transfusions would not be associated with an improvement in mortality or morbidity. STUDY DESIGN: A retrospective cohort analysis was conducted of the medical records of all infants between 1997 and 2001 with Bell's Stage 2 or 3 NEC associated with platelet counts of <100,000/mm(3). The medical records were evaluated for the following variables: platelet counts, number and volume of platelet transfusions, symptoms of bleeding, and hospital course. Mortality and development of short bowel syndrome and/or cholestasis were correlated to the total number and volume (total ml and ml/kg) of platelet transfusions. Differences between the outcome groups were compared using the independent t-test, Fisher's exact test and Mann-Whitney tests. RESULTS: A total of 46 infants met the study criteria (gestational age 28+/-4 weeks and birth weight 1166+/-756 g, mean+/-SD). There were a total of 406 platelet transfusions administered to the study population. Of these, 151 (37.2%) were given in the presence of active bleeding, with 62% of these resulting in the cessation of bleeding within 24 hours. Other listed indications for platelet transfusions were hypovolemia and severe thrombocytopenia. On analysis of the entire cohort, there was no statistical improvement in either mortality or morbidity (short bowel syndrome and cholestasis) with greater number and/or volume of platelet transfusions. Furthermore, we found that infants who developed short bowel syndrome and/or cholestasis had been given a significantly higher number and volume of platelet transfusions when compared to those who did not have these adverse outcomes [median (minimum - maximum) - number of transfusions : 9 (0 to 33) vs 1.5 (0 to 20), p=0.010; volume of transfusions (ml/kg): 121.5 (0 to 476.6) vs 33.2 (0 to 224.3), p=0.013]. CONCLUSION: This retrospective analysis suggests that greater number and volume of platelet transfusions in infants with necrotizing enterocolitis are associated with greater morbidity in the form of short bowel syndrome and/or cholestasis without the benefit of lower mortality.

Severe thrombocytopenia predicts outcome in neonates with necrotizing enterocolitis.

OBJECTIVE: Necrotizing enterocolitis (NEC) is a common and serious gastrointestinal disorder that predominately affects premature infants. Few prognostic indices are available to guide physicians through the expected course of the disease. We hypothesized that the degree and timing of onset of severe thrombocytopenia (platelet count <100,000/mm(3)) would be a predictor of adverse outcome and an indication for surgical intervention in infants with NEC. STUDY DESIGN: The clinical presentation and outcome of all infants with Bell stage II or III NEC treated at Texas Children's Hospital between 1997 and 2001 were retrospectively reviewed. Patients were stratified into two groups based on the presence (Group1) or absence (Group 2) of severe thrombocytopenia (platelet count <100,000/mm(3)) within 3 days of a diagnosis of NEC. Differences between groups were compared using logistic regression to estimate adjusted odds ratios. RESULTS: A total of 91 infants met inclusion criteria (average birth weight 1288+/-135 g; average gestational age 29.0+/-3.0 weeks). Compared to infants in Group 2, infants in Group 1 were more premature (28.0+/-4.1 vs 30.0+/-4.2 weeks; p=0.02), more likely to have received postnatal steroids (42.5% vs 20.4%; p=0.02), and more likely to require laparotomy for gangrenous bowel (adjusted OR 16.33; p<0. 001). The presence of severe thrombocytopenia was also a predictor of mortality (adjusted OR 6.39; p=0.002) and NEC-related gastrointestinal complications including cholestatic liver disease and short bowel syndrome (adjusted OR 5.47; p=0.006). CONCLUSION: Severe thrombocytopenia within the first 3 days after a diagnosis of NEC suggests a higher likelihood of bowel gangrene, morbidity, and mortality. Prospective studies of infants with early and severe thrombocytopenia may help determine the optimal timing of laparotomy in infants with NEC.

Isolated left ventricular noncompaction is rarely caused by mutations in G4.5, alpha-dystrobrevin and FK Binding Protein-12.

Isolated left ventricular noncompaction (LVNC) is a form of cardiomyopathy that most commonly presents in infancy with a hypertrophic and dilated left ventricle characterized by deep trabeculations and intertrabecular recesses. Our goal was to determine the frequency of mutations in G4.5, alpha-dystrobrevin, and FK Binding protein-12 in isolated LVNC patients. No mutations were identified in 47 of the 48 patients studied, while a splice site acceptor site mutation of intron 10 of G4.5 was identified in one patient, resulting in the deletion of exon 10 from the mRNA.