Observational study to compare the clinical efficacy of the natural surfactants Alveofact and Curosurf in the treatment of respiratory distress syndrome in premature infants.

INTRODUCTION: Natural surfactants have been shown to be superior to synthetic surfactants in the treatment of neonatal respiratory distress syndrome (RDS). In Germany, Alveofact (A) and Curosurf (C) are the most frequently used natural surfactant preparations. The aim of this retrospective, observational study was to compare the effects of A and C on gas exchange and outcome in premature infants. METHODS: During a 5-year period in our neonatal intensive care unit (NICU), 187 premature infants were treated with surfactant, with 82 receiving A and 105 receiving C. We recorded F(I)O(2) and gas exchange (PaO(2)/F(I)O(2) ratio, PaCO(2), SaO(2)) during the first 72h after surfactant application and the incidence of outcome parameters at day 28 (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH grade III or IV), patent ductus arteriosus (PDA), pneumothorax, necrotizing enterocolites (NEC) and death). The differences between the patient groups were assessed by ANOVA or the calculation of relative risks. Bonferroni correction was used for multiple comparisons. RESULTS: There were no statistically significant differences between infants treated with A and C in mean gestational age (28.4 vs. 28.4 weeks), birth weight (1210 vs.1258 g) and time of first surfactant application (60 vs. 90 min postnatal). We observed no significant between group differences in course of F(I)O(2) and blood gases, or in incidence at day 28 of BPD (41.7% vs. 42.8%), IVH III/IV (18.3% vs. 14.3%), pneumothorax (9.8% vs. 4.8%), PDA (23.2% vs. 21.9%), PVL (7.3% vs. 9.5%) and death (17% vs. 17.1%). There were also no statistically significant differences in the subgroup of infants <28 weeks. The lower incidence of NEC in A compared with C (1.2% vs. 10.5%, P=0.01) was not statistically significant after Bonferroni correction. CONCLUSION: Independent of gestational age no significant difference in the clinical efficacy of A and C was observed.

Somatostatin or octreotide as treatment options for chylothorax in young children: a systematic review.

OBJECTIVE: Chylothorax is a rare but life-threatening condition in children. To date, there is no commonly accepted treatment protocol. Somatostatin and octreotide have recently been used for treating chylothorax in children. We set out to summarise the evidence on the efficacy and safety of somatostatin and octreotide in treating young children with chylothorax. DESIGN: Systematic review: literature search (Cochrane Library, EMBASE and PubMed databases) and literature hand search of peer reviewed articles on the use of somatostatin and octreotide in childhood chylothorax. PATIENTS: Thirty-five children treated for primary or secondary chylothorax (10/somatostatin, 25/octreotide) were found. RESULTS: Ten of the 35 children had been given somatostatin, as i.v. infusion at a median dose of 204 microg/kg/day, for a median duration of 9.5 days. The remaining 25 children had received octreotide, either as an i.v. infusion at a median dose of 68 microg/kg/day over a median 7 days, or s.c. at a median dose of 40 microg/kg/day and a median duration of 17 days. Side effects such as cutaneous flush, nausea, loose stools, transient hypothyroidism, elevated liver function tests and strangulation-ileus (in a child with asplenia syndrome) were reported for somatostatin; transient abdominal distension, temporary hyperglycaemia and necrotising enterocolitis (in a child with aortic coarctation) for octreotide. CONCLUSIONS: A positive treatment effect was evident for both somatostatin and octreotide in the majority of reports. Minor side effects have been reported, however caution should be exercised in patients with an increased risk of vascular compromise as to avoid serious side effects. Systematic clinical research is needed to establish treatment efficacy and to develop a safe treatment protocol.

A survey of transcutaneous blood gas monitoring among European neonatal intensive care units.

BACKGROUND: PCO2 and PO2 are important monitoring parameters in neonatal intensive care units (NICU). Compared to conventional blood gas measurements that cause significant blood loss in preterms, transcutaneous (tc) measurements allow continuous, non-invasive monitoring of blood gas levels. The aim of the study was to survey the usage and opinions among German speaking NICUs concerning tc blood gas monitoring. METHODS: A questionnaire was developed and sent to 56 head nurses of different NICUs in Germany, Switzerland and Austria. RESULTS: A completely answered questionnaire was obtained from 41 NICUs. In two of these units tc measurements are not performed. In most NICUs (77%), both PtcO2 and PtcCO2 are measured simultaneously. Most units change the sensors every 3 hours; however, the recommended temperature of 44 degrees C is used in only 15% of units. In only 8% of units are arterial blood gases obtained to validate tc values. Large variations were found concerning the targeted level of oxygen saturation [median upper limit: 95% (range 80-100%); median lower limit: 86% (range 75-93%)] and PO2 [median upper limit: 70 mmHg (range 45-90 mmHg); median lower limit: 44 mmHg (range 30-60 mmHg)]. CONCLUSION: Our survey shows that the use of tc monitors remains widespread among German speaking NICUs, despite earlier data suggesting that their use had been abandoned in many NICUs worldwide. In addition, we suggest that the current method of monitoring oxygenation may not prevent hyperoxemia in preterm infants.

Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels.

Interstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels. The female neonate was born at 37 weeks of gestation as the second child to a 31-year-old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double-outlet right-ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium. Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long-term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery.

Immature platelet values indicate impaired megakaryopoietic activity in neonatal early-onset thrombocytopenia.

Newly released platelets, referred to as immature platelets, can be reliably quantified based on their RNA content by flow cytometry in an automated blood analyser. The absolute number of immature platelets (IPF#) and the immature platelet fraction (IPF%) reflect megakaryopoietic activity. We aimed to analyse the implication of these parameters in analysing the pathomechanism of early-onset neonatal thrombocytopenia. Platelet counts and IPF were determined at day 1 to 3 (d1 to d3) in 857 neonates admitted to intensive care. In thrombocytopenic patients (platelet counts<150 x 10(9)/l, n=129), IPF# was significantly lower (8.5 +/- 2.7 x 10(9)/l), than in non-thrombocytopenic neonates (9.5 +/- 3.6 x 10(9)/l, n=682, p<0.05). IPF% was significantly higher in thrombocytopenic (9.3 +/- 7.9%) vs. non-thrombocytopenic neonates (4.1 +/- 1.8%, p<0.001). While neonates with early-onset infection (n=134) had lower platelet counts (199 +/- 75 x 10(9)/l) compared to controls (230 +/- 68 x 10(9)/l, n=574, p<0.01), there were no differences in IPF# or IPF%. Likewise, "small for gestational age" infants (SGA, n=149) had lower platelet counts at d1 (199 +/- 75 x 10(9)/l, p<0.001) than controls, but no differences in IPF. A trend towards lower IPF# was detected if SGA infants with platelet counts <100 x 10(9)/l (5.4 +/- 3.9 x 10(9)/l, n=11) and thrombocytopenic neonates with infection (9.9 +/- 7.3 x 10(9)/l, n=10, p=0.11) were compared. The evaluation of IPF# indicates that thrombocytopenia in neonates is likely due to a combination of increased platelet consumption and inadequate megakaryopoietic response by the neonatal bone marrow. Furthermore, SGA neonates with moderate and severe thrombocytopenia might have a pronounced suppression of megakaryopoiesis compared to neonates with infection.

Is volume and leak monitoring feasible during nasopharyngeal continuous positive airway pressure in neonates?

OBJECTIVE: To investigate tidal volume (VT) and leak measurements during continuous positive airway pressure (CPAP) in neonates using a commercial ventilatory device equipped with a flow sensor at the Y-piece. DESIGN: Randomized cross-over trial. SETTING: Neonatal intensive care unit level III. PATIENTS: Thirty-two infants, median (range) birth weight 1,435 (710-2,730) g, gestational age 30 (24-38) weeks. INTERVENTIONS: During nasopharyngeal CPAP, leak and VT were measured with and without occlusion of the contralateral nostril using the Leoni ventilator (Heinen & Löwenstein, Germany) and a recently developed algorithm to correct measured VT in the presence of leaks. The measuring range of the Leoni is limited to leaks <90%. MAIN RESULTS: Analyzable measurements with leaks <90% could be obtained in 12.5% of the patients with open nostril, and in 65.6% with occluded nostril. Calculated leak flow after nostril occlusion was 23 (3-77) ml min(-1) with closed mouth. Leak flow increased significantly if mouth was opened (548 (0-1,394) ml min(-1), p<0.001), but was probably even higher where leaks exceeded 90%. Mean expiratory volume +/- SD was 5.8 +/- 1.3 ml kg(-1) (corrected VT 5.9 +/-1.2 ml kg(-1)) for leaks <20%, and 3.7 +/-1.4 ml kg(-1) (corrected VT 5.8 +/- 2.2 ml kg(-1)) for leaks between 20 and 69%. CONCLUSIONS: Leak and corrected VT could be determined in the presence of leaks of up to 69%, but leaks during CPAP often exceeded the measuring range. Reliable volume and leak monitoring was not possible with the tested equipment during nasopharyngeal CPAP. Advanced equipment is necessary to further investigate the effects of leaks on neonatal CPAP therapy.

Impaired somatic growth and delayed lung development in infants with congenital diaphragmatic hernia--evidence from a 10-year, single center prospective follow-up study.

PURPOSE: In infants with congenital diaphragmatic hernia (CDH), somatic growth and pulmonary development are key issues beyond the time of intensive care treatment. The aim of the study was to investigate the somatic growth and pulmonary function after discharge and to compare CDH patients with a group of matched controls. METHODS: Anthropometric measurements and lung function tests were performed in 26 infants after surgical repair of CDH and 26 non-CDH intensive care patients, matched for gestational age and birth weight. Spontaneously breathing infants were tested at a mean of 44 weeks postconceptional age (range, 36-58 weeks). Body weight, body length, respiratory rate (RR), tidal volume (V(T)), functional residual capacity by body plethysmography (FRC(pleth)), respiratory compliance (C(rs)), and respiratory resistance (R(rs)) were measured. RESULTS: The mean (SD) weight gain per week in the CDH infants was significantly lower compared to non-CDH infants (89 [39] g vs 141 [49] g; P = .002). The breathing pattern between both groups differed considerably. In CDH infants, V(T) was significantly lower (P < .001) and RR significantly higher (P = .005). The respiratory compliance was also significantly (P < .001) reduced, whereas R(rs) did not differ significantly. No statistically significant differences were seen in FRC(pleth) related to the body weight between CDH and non-CDH infants (20.3 [4.4] mL/kg vs 21.5 [4.9] mL/kg). CONCLUSION: Despite apparently well-inflated lungs after surgery, evidence of early and significantly reduced weight gain and impaired lung function in CHD patients should prompt careful dietary monitoring and regular lung function testing.

Comparison of 2-h versus 3-h enteral feeding in extremely low birth weight infants, commencing after birth.

AIM: Immaturity is associated with problems in enteral nutrition of extremely low birth weight (ELBW) infants. Different time intervals between single feedings are used; however, no data are available to show a benefit of either regime. METHODS: In January 2001 enteral feeding regime was changed from 2-h to 3-h intervals. In a retrospective study charts were analysed for all ELBW infants during a period of 2 years prior (01/99-12/00) and after (08/01-07/03) changing the feeding regime. RESULTS: Forty-two in the 2-h group (gestational age 27 +/- 2.1, birth weight 797 +/-150) and 32 infants in 3-h (GA 26.9 +/- 1.8 weeks, BW 809 +/- 148 g) were included. Median (range) time until complete enteral feeding (26 (7 to 69) vs. 20 (12 to 58) days) was not statistical different. There were no differences with respect to enteral morbidity (NEC, abdominal surgery, feeding intolerance), length of stay (84 +/- 23 vs. 86 +/- 26 days), growth parameters or weight at discharge. Total duration of phototherapy and average length of continuous positive airway pressure (CPAP) support were significantly (p < 0.01) longer in the 3-h feeding group. CONCLUSION: Weight gain and time until complete enteral nutrition are similar in 2-h and 3-h feeding regimes. Data suggest an advantage of 2-h feedings concerning the length of CPAP and phototherapy.

Is unexplained third trimester intrauterine death of fetuses with gastroschisis caused by umbilical cord compression due to acute extra-abdominal bowel dilatation?

We report on a case of gastroschisis in which sudden dilatation of extra-abdominal bowel at 34+1 weeks was followed by an unusual umbilical flow velocity waveform (diastolic notching). The condition was associated with normal umbilical Doppler indices, brain sparing effect and a non-reactive cardiotocograph (CTG). Findings at postnatal surgery strongly suggested severe cord compression by the herniated dilated bowel. The significance of notching in the umbilical artery waveform is discussed, as is the potential importance of this sign in the prepartum management of fetuses with gastroschisis.

Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome).

Clinical, pathological, and X-ray findings of two brothers with features resembling congenital intrauterine infection-like syndrome are presented. Extensive screening for intrauterine infection was performed. Nevertheless all confirmatory tests were normal. Both brothers showed extensive intra- and extra-cranial calcifications, thrombocytopenia, a septum pellucidum cyst, one-sided paresis of the diaphragm, and metaphyseal changes on X-ray scans resembling intrauterine infection. Within the first days of life, they developed seizures and died from severe cerebral hemorrhage. The MRI scan of the brain showed cerebellar hypoplasia in one of the boys, while the cerebellum had normal size in the other. No indication of a metabolic disorder, especially in calcium metabolism, was identified. Due to the clinical overlap with Hoyeraal-Hreidarsson syndrome, mutations in the DKC1 gene (Xq28) and the hTR gene (RNA component of telomerase on chromosome 3q) have been excluded. The parents are non-consanguineous and further family history was unremarkable. The findings in these boys overlap with features described in congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome).

Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g.

OBJECTIVE: To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment. METHODS: In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%. RESULTS: Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta. CONCLUSION: Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants.