Search PubMed⌕ Search

Biomedical subjects

Dick Tibboel

Publications and source records attributed to Dick Tibboel.

At least 55 records · Page 3Linked to original sources
PubMed2005

Fetal lung and diaphragm development in congenital diaphragmatic hernia.

Congenital Diaphragmatic Hernia (CDH) is a congenital disorder with an incidence of 1 in 2500 live births. Respiratory distress of newborns with CDH is the result of pulmonary hypoplasia and pulmonary hypertension. Hypoplastic lungs are characterized by a decreased number of airways with smaller airspaces, whereas the combination of a decreased number of vascular branches and an increased adventitia and medial thickness of the pulmonary arterial walls result in pulmonary hypertension. The appearance of the CDH lungs suggests that its complete formation is stalled during development. Understanding the basic mechanisms of lung development is mandatory to unravel the origin of CDH. Although the histological abnormalities in CDH lungs have been well described, less is known about the underlying molecular mechanisms. In this review we will discuss the current molecular and genetic background of lung formation, as well as a reflection of this knowledge towards CDH.

Diaphragm↗
PubMed2005

Assessment of sedation levels in pediatric intensive care patients can be improved by using the COMFORT "behavior" scale.

OBJECTIVES: The original COMFORT scale, including both observational and physiologic items, has been validated for measuring distress in children admitted to a pediatric intensive care unit. However, physiologic variables are influenced by drugs given in the pediatric intensive care unit setting. The objectives of this study were to assess the usefulness of physiologic variables in judgment of sedation and to determine new cutoff points for the COMFORT "behavioral" scale (COMFORT-B), using only observational items. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: Seventy-eight patients admitted to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: COMFORT scores were obtained in this patient group. Similar to the original COMFORT scale validation, the expert opinion of nurses (Nurse Interpretation Score of Sedation) served to determine optimal cutoff scores for the COMFORT-B scale. A total of 843 combined COMFORT and Nurse Interpretation Score of Sedation scores were obtained in 78 patients. Cronbach's alpha for the COMFORT scale was .78, increasing to .84 when the physiologic items, blood pressure and heart rate, were excluded. COMFORT scores were significantly different for the three Nurse Interpretation Score of Sedation categories (Kruskal-Wallis, p < .001). According to the pediatric intensive care unit nurses, undersedation was present in 11% and oversedation in 3% of all observations. Cutoff points for the COMFORT-B scale were </=10 for oversedation and >/=23 for undersedation. The area in the COMFORT-B score between 11 and 22 does not adequately predict under- or oversedation, pointing to a need for supplemental observation. CONCLUSIONS: The COMFORT-B scale is a reliable alternative to the original COMFORT scale. The cutoff points of the COMFORT-B scale in conjunction with the Nurse Interpretation Score of Sedation facilitate the use of sedation algorithms on the pediatric intensive care unit.

Adolescent↗
PubMed2005

Routine enteral nutrition in neonates on extracorporeal membrane oxygenation.

OBJECTIVES: To evaluate over a 5-yr period the feasibility and tolerance of a protocol of routine enteral nutrition in neonates requiring extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective medical chart review. SETTING: Level III children's hospital, pediatric surgical intensive care unit. PATIENTS: Neonates treated with venoarterial ECMO (VA-ECMO) between January 1997 and January 2002. Patients with congenital diaphragmatic hernia were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Charts of all neonates treated with VA-ECMO were reviewed. Feasibility was evaluated by recording the time period needed for enteral nutrition to reach 40% of total fluid intake; tolerance was evaluated by reviewing data on enteral nutrition related morbidity. Sixty-seven of the 77 eligible patients received enteral feeding during ECMO. Thirty-six of these patients (54%) received 40% of total fluid intake as enteral nutrition within a median of 3 (range, 2-4) days. Over the years there was a trend toward an increasing usage of enteral nutrition from 71% to 94% (p = .07). Enteral nutrition was temporarily discontinued in 16 patients, with 14 showing gastric retentions, one showing discomfort, and one showing aspiration. Symptoms of bilious vomiting, blood-stained stool, or abdominal distention were not present. CONCLUSION: Neonates on ECMO in this series tolerated enteral feeding well and did not show serious adverse effects. Overall, it is our experience that routine use of enteral feeding in critically ill neonates on VA-ECMO is feasible.

Enteral Nutrition↗
PubMed2005

Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial.

OBJECTIVE: To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery. SUMMARY BACKGROUND DATA: Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results. METHODS: Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources. RESULTS: Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects. CONCLUSIONS: In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise.

Analysis of Variance↗
PubMed2005

Survival after non-aggressive obstetric management in cases of severe fetal anomalies: a retrospective study.

OBJECTIVE: Obstetricians may choose to refrain from interventions aimed at sustaining fetal life (i.e., non-aggressive obstetric management) when the fetus has an extremely poor prognosis. However, if the infant is then born alive, crucial neonatal management decisions then have to be made. We sought empirical data concerning such perinatal end-of-life decisions. Firstly, to describe survival during delivery and after birth following non-aggressive obstetric management, and secondly, to describe neonatal management in infants born alive after non-aggressive obstetric management. DESIGN: Retrospective descriptive study. SETTING: Tertiary centre. POPULATION: Eighty-one infants born to women who opted for a non-aggressive obstetric management policy because of sonographically diagnosed severe fetal anomaly. METHODS: Data were collected from obstetric and neonatal records, as well as ultrasound reports. MAIN OUTCOME MEASURES: Survival, neonatal management and health status after birth. RESULTS: Relevant data were available for 78/80 (98%) infants. Six (8%) infants died in utero, 16 (21%) died during delivery (11 from cephalocentesis) and 56 (72%) were born alive. Life-sustaining neonatal treatment was initiated in 29 (52%) of the live-born infants. Twenty-three of these 29 (79%) infants died within six months of birth. Of the 27 live-born infants who did not receive neonatal life-sustaining treatment, 25 (93%) died. Eight infants survived; all with severe health problems. CONCLUSION: Life-sustaining neonatal support after non-aggressive obstetric management in the presence of severe fetal malformation has little impact on survival.

Adolescent↗
PubMed2005

Intra- and interindividual variability of glucuronidation of paracetamol during repeated administration of propacetamol in neonates.

BACKGROUND: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of propacetamol were determined in neonates in whom propacetamol was repeatedly administered. METHODS: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of propacetamol. Spearman rank and linear multiple regression (MedCalc, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP-G to overall urine paracetamol (APAP-G+APAP-S+free paracetamol) elimination (G/T ratio). RESULTS: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T ratio with increasing postnatal (p<0.0001) and postconceptional age (p<0.01), repeated administration (p<0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant (p<0.01) after correction of postnatal and postconceptional age in a multiple regression model. CONCLUSION: Major variability in the ontogeny of UGT activity to overall elimination of paracetamol was documented in neonates. Besides postnatal and postconceptional age, a significant effect of repeated administration on UGT activity was documented.

Acetaminophen↗
PubMed2005

Variability in pain expression characteristics in former preterm infants.

OBJECTIVES: To document pain expression characteristics in former preterm infants in the first year of life in whom systematic evaluation and treatment of pain was provided. METHODS: Data on the Modified Behavioral Pain Scale (MBPS), Visual Analogue Scale (VAS, crying time and heart rate were collected during immunization. The effect of clinical characteristics {postconception and gestational age [PCA], surgery, ventilation, fentanyl, length of stay (LOS)} on bio-behavioral parameters was evaluated. RESULTS: 121 procedures were recorded in 49 infants. GA was 28 (25-32) weeks. PCA was 60 (34-90) weeks. Median MBPS was 8 (2-10), median crying time 44 (0-112) s. Median pre-procedural heart rate was 144 (103-201) and increased to 184 (147-220) afterwards, resulting in a relative increase of 29 (5-99)%. Median VAS score was 7 (1-10). Significant correlations of PCA with pre-procedural heart rate (r=-0.36) and with relative increase in heart rate (r=0.33) were identified. A correlation of LOS on crying time (r=0.37) was observed. CONCLUSIONS: Correlations of PCA with pre-procedural and relative increase in heart rate reflect the maturational decrease in heart rate. LOS had an effect on pain expression, potentially reflecting the impact of cumulative 'minor' procedural pain.

Analgesia↗
PubMed2004

Overexpression of lunatic fringe does not affect epithelial cell differentiation in the developing mouse lung.

The Notch/Notch-ligand pathway regulates cell fate decisions and patterning in various tissues. Several of its components are expressed in the developing lung, suggesting that this pathway is important for airway cellular patterning. Fringe proteins, which modulate Notch signaling, are crucial for defining morphogenic borders in several organs. Their role in controlling cellular differentiation along anterior-posterior axis of the airways is unknown. Herein, we report the temporal-spatial expression patterns of Lunatic fringe (Lfng) and Notch-regulated basic helix-loop-helix factors, Hes1 and Mash-1, during murine lung development. Lfng was only expressed during early development in epithelial cells lining the larger airways. Those epithelial cells also expressed Hes1, but at later gestation Hes1 expression was confined to epithelium lining the terminal bronchioles. Mash-1 displayed a very characteristic expression pattern. It followed neural crest migration in the early lung, whereas at later stages Mash-1 was expressed in lung neuroendocrine cells. To clarify whether Lfng influences airway cell differentiation, Lfng was overexpressed in distal epithelial cells of the developing mouse lung. Overexpression of Lfng did not affect spatial or temporal expression of Hes1 and Mash-1. Neuroendocrine CGRP and protein gene product 9.5 expression was not altered by Lfng overexpression. Expression of proximal ciliated (beta-tubulin IV), nonciliated (CCSP), and distal epithelial cell (SP-C, T1alpha) markers also was not influenced by Lfng excess. Overexpression of Lfng had no effect on mesenchymal cell marker (alpha-sma, vWF, PECAM-1) expression. Collectively, the data suggest that Lunatic fringe does not play a significant role in determining cell fate in fetal airway epithelium.

Animals↗
PubMed2004

Postmortem findings and clinicopathological correlation in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a severe life-threatening disease, with an incidence of 3 per 10,000 births, that can occur as an isolated defect or in combination with other congenital anomalies. We reviewed the clinical and autopsy reports of 39 subjects with CDH that were autopsied between 1988 and 2001 to determine whether autopsy had an additional value in the detection of malformations in patients with CDH. We compared the clinical data (including echographic results in some patients) concerning congenital anomalies with the autopsy results. Before autopsy, 6 structural cardiac defects, 3 anomalies of the urogenital system, and 3 anomalies of the digestive tract were observed in 10 patients (clinical and echographic results). However, with postmortem examination, only 4 structural cardiac defects were confirmed, 2 cases showed another cardiac anomaly, and 7 new cardiac defects were found. In the urogenital system, 1 anomaly was confirmed, 1 was not confirmed, and 1 showed another malformation. In addition, in 7 patients new urogenital malformations were found after autopsy. In the digestive tract, all 3 malformations were confirmed, but we found 3 new malformations after postmortem examination. All clinically established dysmorphic features and anomalies of the skeletal system and central nervous system were confirmed by autopsy, and no additional malformations were found. We concluded that postmortem examination has an important additional role in the detection of structural cardiac defects and malformations of the urogenital system and digestive tract in children with CDH.

Abnormalities, Multiple↗
PubMed2004

Distal angiogenesis: a new concept for lung vascular morphogenesis.

Although several molecular players have been described that play a role during the early phases of lung development, it is still unknown how the vasculature develops in relation to the airways. Two opposing models describe development of lung vasculature: one suggests that both vasculogenesis and angiogenesis are involved, whereas the second describes vasculogenesis as the primary mechanism. Therefore, we examined the development of the murine pulmonary vasculature through a morphological analysis from the onset of lung development [9.5 days postcoital (dpc)] until the pseudoglandular stage (13.5 dpc). We analyzed fetal lungs of Tie2-LacZ transgenic mice as well as serial sections of wild-type lungs stained with endothelial-specific antibodies (Flk-1, Fli-1, and PECAM-1). Embryos were processed with intact blood circulation to maintain the integrity of the vasculature; hence individual vessels could be identified with accuracy through serial section analysis. Furthermore, circulating primitive erythrocytes, formed exclusively by the blood islands in the yolk sac, are trapped in vessels during fixation, which proves the connection with the embryonic circulation. We report that from the first morphological sign of lung development, a clear vascular network exists that is in contact with the embryonic circulation. We propose distal angiogenesis as a new concept for early pulmonary vascular morphogenesis. In this model, capillary networks surround the terminal buds and expand by formation of new capillaries from preexisting vessels as the lung bud grows. The fact that at an early embryonic stage a complete vascular network exists may be important for the general understanding of embryonic development.

Animals↗
PubMed2004

Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung.

Recent investigations have suggested an active role for endothelial cells in organ development, including the lung. Herein, we investigated some of the molecular mechanisms underlying normal pulmonary vascular development and their influence on epithelial branching morphogenesis. Because the lung in utero develops in a relative hypoxic environment, we first investigated the influence of low oxygen on epithelial and vascular branching morphogenesis. Two transgenic mouse models, the C101-LacZ (epithelial-LacZ marker) and the Tie2-LacZ (endothelial-LacZ marker), were used. At embryonic day 11.5, primitive lung buds were dissected and cultured at either 20 or 3% oxygen. At 24-h intervals, epithelial and endothelial LacZ gene expression was visualized by X-galactosidase staining. The rate of branching of both tissue elements was increased in explants cultured at 3% oxygen compared with 20% oxygen. Low oxygen increased expression of VEGF, but not that of the VEGF receptor (Flk-1). Expression of two crucial epithelial branching factors, fibroblast growth factor-10 and bone morphogenetic protein-4, were not affected by low oxygen. Epithelial differentiation was maintained at low oxygen as shown by surfactant protein C in situ hybridization. To explore epithelial-vascular interactions, we inhibited vascular development with antisense oligonucleotides targeted against either hypoxia inducible factor-1 alpha or VEGF. Epithelial branching morphogenesis in vitro was dramatically abrogated when pulmonary vascular development was inhibited. Collectively, the in vitro data show that a low-oxygen environment enhances branching of both distal lung epithelium and vascular tissue and that pulmonary vascular development appears to be rate limiting for epithelial branching morphogenesis.

Animals↗
PubMed2004

Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs.

Maternal hypothyroxinemia during early pregnancy poses an increased risk for poor neuropsychological development of the fetus. We tested the hypothesis that maternal hypothyroidism before the onset of fetal thyroid function also affects postnatal development of heart and lungs. This question was addressed in transgenic mice that express herpes simplex virus thymidine kinase in their thyroidal follicle cells. Treatment with ganciclovir rendered these mice severely hypothyroid because viral thymidine kinase converts ganciclovir into a cytotoxic nucleoside analog. Since ganciclovir crosses the placenta, it also destroyed the thyroid of transgenic embryos while leaving the thyroids of nontransgenic littermates unaffected. Hypothyroidism of both mother and fetus did not affect prenatal heart and lung development. However, the postnatal switch from beta- to alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers. Similarly, postnatal animals of the latter two groups retained elevated surfactant protein (SP) A, B, and C mRNA levels in their alveolar epithelium. In hypothyroid pups from hypothyroid mothers, these changes were accompanied by decreased alveolar septation. Our study shows that these effects of maternal hypothyroidism become manifest after birth and are aggravated by the concomitant existence of neonatal hypothyroidism.

Animals↗
PubMed2004

Expression of angiogenesis-related factors in lungs of patients with congenital diaphragmatic hernia and pulmonary hypoplasia of other causes.

Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplasia (PH) and pulmonary hypertension. Hypoplastic lungs have fewer and smaller airspaces than normal, with thicker interalveolar septa; the adventitia and media of pulmonary arteries are thickened, and the total size of the pulmonary vascular bed is decreased compared to normal. Although histological abnormalities in PH have been described, less is known about the underlying molecular mechanisms. Therefore, we have investigated a series of proteins, known to be involved in angiogenesis, including von Hippel-Lindau protein (pVHL), hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk-1), and endothelial and inducible nitric oxide synthase (eNOS, iNOS) by immunohistochemistry on paraffin-embedded lung tissue of CDH patients ( n = 13), patients with lung hypoplasia due to other causes ( n = 20), and normal controls ( n = 33). pVHL was expressed more frequently in the arterial smooth muscle cells of CDH lungs compared with both other groups. Furthermore, HIF-1a was expressed less frequently in the endothelium of arteries, veins, and capillaries of CDH lungs as compared with both other groups. No differences were observed in the expression patterns of VEGF, Flk-1, eNOS, and iNOS between the different groups. Our data suggest a role for pVHL and HIF-1a in normal and abnormal pulmonary angiogenesis. The differential expression of these proteins may provide a molecular basis for the histological differences observed in the lung vessels of patients with CDH.

Angiogenic Proteins↗
PubMed2004

Morphometric analysis of the lung vasculature after extracorporeal membrane oxygenation treatment for pulmonary hypertension in newborns.

Persistent pulmonary hypertension in the newborn (PPHN) is characterised by increased medial and adventitial thickness in the lung vasculature. This study describes morphometry of lung vasculature after extracorporeal membrane oxygenation (ECMO) in newborns with PPHN, due to meconium aspiration syndrome, sepsis or idiopathic persistent pulmonary hypertension of the newborn (i-PPHN). Three groups were studied: newborns with PPHN treated with ECMO (n=9), newborns with PPHN not treated with ECMO (n=12) and age-matched controls without PPHN (n=11). In pulmonary arteries with an external diameter of less than 150 microm, arterial media, adventitia and total wall thickness, expressed as a percentage of the external diameter, and their cross-sectional areas were calculated. Newborns with PPHN, compared with controls, demonstrated increased percentage of media thickness, adventitia thickness and total wall thickness, and increased medial, adventitial and total wall cross-sectional area. Newborns treated with ECMO, compared with those not treated so, showed a decreased percentage of media thickness and medial cross-sectional area in arteries with an external diameter less than 75 microm, and decreased percentage of media thickness and decreased medial, adventitial and total wall cross-sectional area in arteries with an external diameter of 75-150 microm. ECMO for persistent PPHN, due to meconium aspiration syndrome, sepsis or i-PPHN, reduces the abnormal morphometry of small pulmonary arteries. The underlying mechanisms contributing to this improved morphometry are yet unknown.

Extracorporeal Membrane Oxygenation↗
PubMed2004

Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in term and preterm neonates to suggest dosing regimens. METHODS. A population pharmacokinetic analysis of paracetamol (acetaminophen) time-concentration profiles in 48 neonates was undertaken using non-linear mixed-effects models. Neonates were given either single (n=30) or multiple doses (n=18) of propacetamol infusion over 15 min. Neonates had a median postnatal age of 1 day (range, 1-76 days). Median post-conceptual age (PCA) was 35 weeks (range, 27-42 weeks), and median weight was 2.4 kg (range, 0.51-4 kg). RESULTS: The population volume of distribution estimate and between-subject variability (%) for a one-compartment model with zero-order input and first-order elimination was 70.4 l (30.7%)/70 kg. Clearance increased from 2.85 l/70 kg, CV 40.7% at 27 weeks PCA to reach 7.05 l/h per 70 kg by 42 weeks PCA (standardised to a 70-kg person using allometric "1/4-power" models). Between-occasion variability for volume of distribution and clearance were 17.4% and 26%, respectively. CONCLUSIONS: A mean paracetamol steady-state target concentration above 10 mg/l at trough can be achieved using a loading dose of 40 mg/kg and maintenance doses of 20 mg/kg 6 h in 28-week PCA neonates, 25 mg/kg 6 h at 32 weeks, 30 mg/kg 6 h at 36 weeks and 20 mg/kg 4 h at term (propacetamol doses). Since the role of the oxidative enzyme CYP2E1 and production of the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine still is unknown in premature neonates, lower doses scaled by age-related clearance and centred on a daily dose of 60 mg/kg per day in a child of 6-8 years with a clearance of 0.25 l/h per kg (12.5 l/h per 70 kg) may be more appropriate.

Acetaminophen↗
PubMed2004

The effect of cumulative energy and protein deficiency on anthropometric parameters in a pediatric ICU population.

BACKGROUND AND AIMS: Nutritional support is essential in the care of critically ill children since inadequate feeding increases morbidity and negatively affects growth. We aimed to compare cumulative energy and protein intakes with recommended dietary intakes (RDA) and examine relationships between accumulated balances and anthropometric parameters. METHODS: Prospective, observational study. Total daily energy and protein intakes were determined during a maximum of 14 days in 261 children admitted to our multidisciplinary tertiary pediatric ICU. Actual intakes were subtracted from RDA and cumulative balances were calculated. Relations between cumulative balances, various clinical factors and changes in anthropometry (weight, arm and calf circumference) were analyzed using regression analysis. RESULTS: At 14 days after admission children showed significant cumulative nutritional deficits compared to RDA. These deficits were on average 27, 20, 12 kcal/kg and 0.6, 0.3, and 0.2 g protein/kg per day for preterm neonates (n = 103), term neonates (n = 91) and older children (n = 67), respectively. Age at admission, length of ICU-stay and days on mechanical ventilation were negatively related to cumulative balances. Cumulative energy and protein deficits were associated with declines in SD-scores for weight and arm circumference. CONCLUSIONS: Children admitted to the ICU accumulate substantial energy and protein deficits when compared to RDA. These deficits are related to decreases in anthropometric parameters.

Adolescent↗
PubMed2004

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia.

BACKGROUND: Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH. METHODS: Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated. RESULTS: Five hundred ten infants less than 37 weeks' gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P <.01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P <.07). CONCLUSIONS: Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.

Bias↗