An infant with Netherton syndrome and persistent pulmonary hypertension requiring extracorporeal membrane oxygenation.

Netherton syndrome is a rare genodermatosis characterized by ichthyosiform scaling, hair shaft abnormalities, and atopic features. Affected infants typically have delayed growth and development, immune abnormalities with recurrent infections, and intermittent aminoaciduria. We report a 23-day-old girl who presented with severe primary pulmonary hypertension, exfoliative erythroderma, and trichorrhexis invaginata. Genetic studies confirmed a premature termination mutation R350X in exon 12 of SPINK5. This mutation further supports the genotypic-phenotypic prediction that severe sequela result from premature termination mutations. To our knowledge, this is the first instance of Netherton syndrome associated with primary pulmonary hypertension to be reported. Further postulated is a possible link between excessive desquamation of fetal skin and respiratory failure in a neonate with Netherton syndrome.

Incidence of low free T4 values in premature infants as determined by direct equilibrium dialysis.

BACKGROUND: The incidence of transient reductions in serum free T(4) (FT(4)) in premature infants may be overestimated because certain FT(4) analytical methods underestimate FT(4) concentrations. Transient reductions of FT(4) measurements have been reported in the majority of premature newborn infants. Direct equilibrium dialysis (DED) does not underestimate FT(4) concentrations and is the best available technique to measure serum FT(4) in the premature infant. OBJECTIVE: To evaluate the incidence of low FT(4) concentrations in premature infants using DED to measure FT(4). DESIGN/METHOD: We measured FT(4) by DED in infants with birth weight <1500 g. Infants were excluded if the following conditions were present: congenital anomalies or maternal thyroid disorders. Free T(4) was measured at 14 days of life. Low FT(4) was defined using a statistical definition of FT(4) measurements <10.3 pmol/l (0.8 ng/dl). RESULTS: Free T(4) was measured by DED in 114 infants. Low FT(4) levels were seen in nine infants (7.9%). CONCLUSION: The incidence of low FT(4) was much lower than previously reported when FT(4) was measured using DED indicating that methodological issues are involved in the variability among estimates of the frequency of transient reduction in FT(4).

Identifying potential heart donors among newborns undergoing circulatory determination of death.

BACKGROUND: Infants younger than 1 year old have the highest heart transplant wait-list mortality. Transplantation from donors after circulatory determination of death (DCDD) is an innovative new option for these patients. We examined the potential for heart donation in neonatal intensive care unit (NICU) patients undergoing elective withdrawal of life support. METHODS: Medical records of all patients who died between June 2003 and June 2008 in our 84-bed NICU were reviewed. The mode of death among potential organ donors (weight > 2.5 kg) was categorized into 4 groups: Died despite cardiopulmonary resuscitation (CPR), do not resuscitate (DNR) status, brain death, or withdrawal of life support. Patients undergoing planned life-support withdrawal were evaluated for DCDD potential. RESULTS: Of 266 NICU deaths during the study period, 117 patients weighed more than 2.5 kg at the time of death, of whom 15 (13%) died despite CPR, and 33 (28%) were DNR. No brain deaths occurred; consequently, no conventional organ donation resulted. Of 69 infants (59%) who died after withdrawal, 53 were excluded as potential donors due to active infection, cardiac dysfunction, or congenital heart disease. Among the remaining 16, median time from withdrawal to death was 31 minutes (range, < 1-310 minutes). Five infants (4.3% of deaths in babies > 2.5 kg) died within 30 minutes, had good cardiac function, and could have been potential DCDD heart donors. CONCLUSIONS: Among NICU patients withdrawn from life support during a 5-year period, 4.3% would have been suitable heart donors after circulatory determination of death. Implementing a NICU DCDD program could markedly expand the donor pool and reduce short-term wait-list mortality for infant heart transplantation.

An open label, pilot study of Aerosurf® combined with nCPAP to prevent RDS in preterm neonates.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) is an accepted mode of respiratory support for preterm infants with respiratory insufficiency. To avoid potential sequelae of endotracheal (ET) intubation and mechanical ventilation, prophylactic aerosolization of surfactant delivered via nCPAP has been attempted with limited success. METHODS: To determine the feasibility and safety of prophylactic aerosolization of a peptide-containing synthetic surfactant, Aerosurf® (lucinactant for inhalation) was delivered by nCPAP to preterm infants at risk for respiratory distress syndrome (RDS). Neonates were enrolled into treatment group 1 (Aerosurf retreatment separated by at least 3 h) or treatment group 2 (Aerosurf retreatment separated by at least 1 h). A vibrating membrane nebulizer Aeroneb Pro® was used to aerosolize 20 mg/mL Aerosurf. All neonates received the initial 3-h treatment, and three retreatments were permitted within 48 h based on clinical response. RESULTS: Seventeen infants were enrolled. Aerosurf was well tolerated, with transient desaturations observed during dosing without bradycardia or hypotension. Variability in output rates of the Aeroneb Pro was observed leading to different average dispensed drug volumes per treatment per patient. All infants survived; 29.4% required subsequent ET surfactant replacement therapy, 23.5% were diagnosed with RDS at 24 h, and 11.8% with bronchopulmonary dysplasia (BPD) at 28 days of life. Mean FiO2 was 0.4 at baseline, and 0.32 at 4 h posttreatment. CONCLUSIONS: Aerosurf can be safely administered via nCPAP in preterm infants at risk for RDS and may provide an alternative to surfactant administration via an ET tube. Further studies are required to evaluate this delivery approach.

Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome.

Walker-Warburg syndrome (WWS) is an autosomal recessive disorder of infancy characterized by hydrocephalus, agyria, retinal dysplasia, congenital muscular dystrophy, and over migration of neurons through a disrupted pial surface resulting in leptomeningeal heterotopia. Although previous work identified mutations in the o-mannosyl transferase, POMT1, in 6 out of 30 WWS families [Beltran-Valero de Bernabe et al., 2002], the incidence of POMT1 mutations in WWS is not known. We sequenced the entire coding region of POMT1 in 30 consecutive, unselected patients with classic WWS. Two novel heterozygous mutations were found in two patients from non-consanguineous parents, whereas 28 other patients failed to show any POMT1 mutations. One patient was found to be heterozygous for a transition, g.1233T > A, which predicts p.Y352X. A second patient was found also to be heterozygous for a transition g.1790C > G, which predicts p.S537R. As an additional determination of the frequency of the POMT1 mutations in WWS, we tested for linkage of WWS to POMT1 in six consanguineous families. All six demonstrated heterozygosity and negative LOD scores at the POMT1 locus. From these data we show that POMT1 is an uncommon cause of WWS, the incidence of coding region mutations in this population of WWS being less than 7%. We conclude that while the incidence of POMT1 mutations in WWS can be as high as 20% as reported by Beltran-Valero de Bernabe et al. [2002] and it can be as low as approximately 7%, as reported here.