The Journal of Visualized Experiments (JoVE) is a peer reviewed, PubMed-indexed video journal. Our mission is to increase the productivity of scientific research.

Recommend to Librarian

In JoVE (1)

Other Publications (111)

Articles by Frans J. Walther in JoVE

 JoVE Clinical and Translational Medicine

Accurate and Simple Evaluation of Vascular Anastomoses in Monochorionic Placenta using Colored Dye


JoVE 3208 9/05/2011

1Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, 2Division of Fetal Therapy, Department of Obstetrics, Leiden University Medical Center, 3Department of Obstetrics, Leiden University Medical Center

Twin-to-twin transfusion syndrome and twin anemia polycythemia sequence are two potentially devastating problems in perinatal medicine. Both disorders occur only in monochorionic twins and result from unbalanced blood flow through placental vascular anastomoses. We provide a simple protocol to accurately evaluate the presence of vascular anastomoses using colored dye injection of placental vessels after birth.

Other articles by Frans J. Walther on PubMed

Transepidermal Water Loss During Halogen Spotlight Phototherapy in Preterm Infants

Among preterm infants there is a relationship between skin blood flow and transepidermal water loss (TEWL). The aim of this study was to assess whether halogen spotlight phototherapy without significant heat stress increases TEWL and affects maintenance fluid requirements in preterm infants. TEWL was measured noninvasively before the start and after 1 h of halogen spotlight phototherapy in a group of preterm infants, nursed in double-walled incubators with moderately high relative humidity. Relative humidity and ambient temperature in the incubator were tightly controlled. Mean +/- SD birth weight of the 18 infants was 1412 +/- 256 g, gestational age 30.6 +/- 1.6 wk, and age at measurement 5 +/- 3 d. Nine infants received ventilatory assistance. Relative humidity was 40-80% (mean 52%). Average TEWL increased from 13.6 to 16.5 g/m(2)/h during phototherapy. These data show that TEWL increases by approximately 20% during phototherapy despite constant skin temperature and relative humidity. Maintenance fluids of preterm infants should be increased by 0.35 mL/kg/h during exposure to halogen spotlight phototherapy.

Multilayer Formation Upon Compression of Surfactant Monolayers Depends on Protein Concentration As Well As Lipid Composition. An Atomic Force Microscopy Study

The determinants for the formation of multilayers upon compression of surfactant monolayers were investigated by compressing films, beyond the squeeze-out plateau, to a surface tension of 22 millinewtons/m. Atomic force microscopy was used to visualize the topography of lipid films containing varying amounts of native surfactant protein B (SP-B). These films were compared with films containing synthetic peptides based on the N terminus of human SP-B: monomeric mSP-B-(1-25) or dimeric dSP-B-(1-25). The formation of typical hexagonal network structures as well as the height of protrusions were shown to depend on the concentration of SP-B. Protrusions of bilayer height were formed from physiologically relevant concentrations of 0.2-0.4 mol % (4.5-8.5 wt %) SP-B upwards. Much higher concentrations of SP-B-(1-25) peptides were needed to obtain network structures, and protrusion heights were not equal to those found for films with native SP-B. A striking observation was that while protrusions formed in films of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dipalmitoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (DPPG) (80/20) had single bilayer thickness, those formed in DPPC/1-palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (80/20) had various heights of multilayers, whereas those seen in DPPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/DPPG (60/20/20) were mainly of bilayer height. For the first time direct observations by atomic force microscopy show (i) that a certain minimal concentration of SP-B is required for the formation of layered protrusions upon film compression, (ii) that protrusion height depends on whether the phospholipids contain an unsaturated fatty acyl chain, and (iii) that protrusion height also depends on whether the unsaturated acyl chain is present in phosphatidylcholine or in phosphatidylglycerol.

Surfactant with SP-B and SP-C Analogues Improves Lung Function in Surfactant-deficient Rats

The use of mammalian lung surfactant extracts has sharply reduced mortality and morbidity from respiratory distress syndrome in premature infants. Synthesis of surfactant protein B and C (SP-B and SP-C) analogues may lead the way to a synthetic surfactant preparation. Dimeric SP-B(1-25) (dSP-B(1-25)) is based on the N-terminal domain of human SP-B and SP-Cfc is a modified human SP-C in which a single phenylalanine is substituted for a palmitoylated cysteine residue in the N-terminal segment (Phe-4 > Cys-4 variant). We tested the effects of synthetic surfactants with 1 or 2% dSP-B(1-25) and 1% SP-Cfc on lung function in surfactant-deficient rats. Four experimental surfactant preparations were prepared by mixing 1% dSP-B(1-25), 2% dSP-B(1-25), 1% dSP-B(1-25) +1% SP-Cfc, and 2% dSP-B(1-25) +1% SP-Cfc with phospholipids (PL). PL and Survanta, a bovine lung extract, were controls. Groups of 8 rats were ventilated, lavaged until surfactant deficiency, and treated with 100 mg/kg surfactant. Arterial blood gas values and dynamic compliance were measured every 15 min and after 2 h of ventilation, the rats were killed and pressure-volume curves performed. Oxygenation improved quickly after instillation of surfactant with synthetic peptides and Survanta. Oxygenation and lung volumes were consistently higher in the 2% than in the 1% dSP-B(1-25) groups. Addition of 1% SP-Cfc to the synthetic surfactants further improved oxygenation and lung volume, but to a lesser extent than increasing the dSP-B(1-25) content from 1 to 2%. These data indicate that improvements in oxygenation and lung volume in lavaged rats are dependent on the concentration of dSP-B(1-25) in the surfactant preparation and that the presence of SP-Cfc has a relative minor effect on these parameters.

Dimeric Surfactant Protein B Peptide Sp-b(1-25) in Neonatal and Acute Respiratory Distress Syndrome

Surfactant protein B (SP-B) is a constituent surfactant protein critical for normal lung function. Monomeric SP-B(1-25) (mSP-B(1-25)), a peptide based on the N-terminal domain of human SP-B, mixed in phospholipids partially restores lung function in surfactant-deficient animals. Because native SP-B is a homodimer, we synthesized and tested dimeric SP-B(1-25) (dSP-B(1-25)). Circular dichroism (CD) and Fourier Transform Infrared (FTIR) spectroscopy indicated that the secondary conformation of SP-B(1-25) was not significantly perturbed by dimerization. The effects on lung function were compared to phospholipids and Survanta in models of neonatal respiratory distress syndrome (RDS) and acute RDS (ARDS). Preterm rabbits born at 27 days of gestation received 100 mg surfactant / kg at birth and were ventilated for 1 hour with a tidal volume of 10 mL / kg. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured. Adult rats were lavaged to induce surfactant deficiency, treated with 100 mg surfactant / kg, and ventilated for 2 hours. Lung function was assessed using arterial blood gases and dynamic compliance every 15 minutes and postmortem pressure-volume curves. Lung volumes in both models and oxygenation in the lavaged rats were consistently higher in the dSP-B(1-25) than in the Survanta and mSP-B(1-25) surfactant groups. The data suggest that dSP-B(1-25) is more efficient in restoring lung function in neonatal RDS and ARDS than mSP-B(1-25) surfactant.

Adrenal Suppression and Extubation Rate After Moderately Early Low-dose Dexamethasone Therapy in Very Preterm Infants

A short course of moderately early dexamethasone therapy with a starting dose of 0.5 mg/kg/day improves lung compliance and shortens the duration of ventilatory support in preterm infants with respiratory distress syndrome (RDS). We conducted a double-blind, randomized study to evaluate whether a moderately early 14-day weaning course of low-dose dexamethasone affects adrenal function and facilitates weaning from the ventilator.

Long-term Neurodevelopmental Outcome in Twin-to-twin Transfusion Syndrome

The purpose of this study was to determine the long-term neurodevelopmental outcome in children after twin-to-twin transfusion syndrome.

Gene Expression Profile and Histopathology of Experimental Bronchopulmonary Dysplasia Induced by Prolonged Oxidative Stress

Oxidative stress is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants characterized by arrested alveolar and vascular development of the immature lung. We investigated differential gene expression with DNA microarray analysis in premature rat lungs exposed to prolonged hyperoxia during the saccular stage of development, which closely resembles the development of the lungs of premature infants receiving neonatal intensive care. Expression profiles were largely confirmed by real-time RT-PCR (27 genes) and in line with histopathology and fibrin deposition studied by Western blotting. Oxidative stress affected a complex orchestra of genes involved in inflammation, coagulation, fibrinolysis, extracellular matrix turnover, cell cycle, signal transduction, and alveolar enlargement and explains, at least in part, the pathological alterations that occur in lungs developing BPD. Exciting findings were the magnitude of fibrin deposition; the upregulation of chemokine-induced neutrophilic chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), amphiregulin, plasminogen activator inhibitor-1 (PAI-1), secretory leukocyte proteinase inhibitor (SLPI), matrix metalloproteinase-12 (MMP12), p21, metallothionein, and heme oxygenase (HO); and the downregulation of fibroblast growth factor receptor-4 (FGFR4) and vascular endothelial growth factor (VEGF) receptor-2 (Flk-1). These findings are not only of fundamental importance in the understanding of the pathophysiology of BPD, but also essential for the development of new therapeutic strategies.

Correct Use of the Apgar Score for Resuscitated and Intubated Newborn Babies: Questionnaire Study

Pentoxifylline Reduces Fibrin Deposition and Prolongs Survival in Neonatal Hyperoxic Lung Injury

Bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment modalities. Pentoxifylline, a phosphodiesterase inhibitor, inhibits multiple processes that lead to neonatal hyperoxic lung injury, including inflammation, coagulation, and edema. Using a preterm rat model, we investigated the effects of pentoxifylline on hyperoxia-induced lung injury and survival. Preterm rat pups were exposed to 100% oxygen and injected subcutaneously with 0.9% saline or 75 mg/kg pentoxifylline twice a day. On day 10, lung tissue was harvested for histology, fibrin deposition, and mRNA expression, and bronchoalveolar lavage fluid was collected for total protein concentration. Pentoxifylline treatment increased mean survival by 3 days (P = 0.0018) and reduced fibrin deposition by 66% (P < 0.001) in lung homogenates compared with untreated hyperoxia-exposed controls. Monocyte chemoattractant protein-1 expression in lung homogenates was decreased, but the expressions of TNF-alpha, IL-6, matrix metalloproteinase-12, tissue factor, and plasminogen activator inhibitor-1 were similar in both groups. Total protein concentration in bronchoalveolar lavage fluid was decreased by 33% (P = 0.029) in the pentoxifylline group. Pentoxifylline treatment attenuates alveolar fibrin deposition and prolongs survival in preterm rat pups with neonatal hyperoxic lung injury, probably by reducing capillary-alveolar protein leakage.

NMR Structures of the C-terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. SP-B's biophysical functions can be partially mimicked by subfragments of the protein, including the C-terminus. We have used NMR to determine the structure of a C-terminal fragment of human SP-B that includes residues 63-78. Structure determination was performed both in the fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical structure, in agreement with predictions made by comparison to homologous saposin family proteins. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Differences in helical residue side chain positioning between the two solvents were also found, with better agreement between the structures for the hydrophobic face than the hydrophilic face. A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the alpha-helix. Interactions of basic residues of SP-B with anionic lipid headgroups are known to have an impact on function, and these studies demonstrate structural ramifications of such interactions via the differences observed between the peptide structures determined in HFIP and SDS.

Structure and Properties of Phospholipid-peptide Monolayers Containing Monomeric SP-B(1-25) II. Peptide Conformation by Infrared Spectroscopy

The conformation and orientation of synthetic monomeric human sequence SP-B(1-25) (mSP-B(1-25)) was studied in films with phospholipids at the air-water (A/W) interface by polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS). Modified two-dimensional infrared (2D IR) correlation analysis was applied to PM-IRRAS spectra to define changes in the secondary structure and rates of reorientation of mSP-B(1-25) in the monolayer during compression. PM-IRRAS spectra and 2D IR correlation analysis showed that, in pure films, mSP-B(1-25) had a major alpha-helical conformation plus regions of beta-sheet structure. These alpha-helical regions reoriented later during film compression than beta structural regions, and became oriented normal to the A/W interface as surface pressure increased. In mixed films with 4:1 mol:mol acyl chain perdeuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPC-d(62):DOPG), the IR spectra of mSP-B(1-25) showed that a significant, concentration-dependent conformational change occurred when mSP-B(1-25) was incorporated into a DPPC-d(62):DOPG monolayer. At an mSP-B(1-25) concentration of 10 wt.%, the peptide assumed a predominantly beta-sheet conformation with no contribution from alpha-helical structures. At lower, more physiological peptide concentrations, 2D IR correlation analysis showed that the propensity of mSP-B(1-25) to form alpha-helical structures was increased. In phospholipid films containing 5 wt.% mSP-B(1-25), a substantial alpha-helical peptide structural component was observed, but regions of alpha and beta structure reoriented together rather than independently during compression. In films containing 1 wt.% mSP-B(1-25), peptide conformation was predominantly alpha-helical and the helical regions reoriented later during compression than the remaining beta structural components. The increased alpha-helical structure of mSP-B(1-25) demonstrated here by PM-IRRAS and 2D IR correlation analysis in monolayers of 4:1 DPPC:DOPG containing 1 wt.% (and, to a lesser extent, 5 wt.%) peptide may be relevant for the formation of the intermediate order 'dendritic' surface phase observed in similar surface films by epi-fluorescence.

Parainfluenza Virus 4 Detection in Infants

Comparison of Three Lipid Formulations for Synthetic Surfactant with a Surfactant Protein B Analog

Surfactant protein B (SP-B) is an essential component of pulmonary surfactant. Synthetic dimeric SP-B(1-25) (SP-B(1-25)), a peptide based on the N-terminal domain of human SP-B, efficiently mimics the functional properties of SP-B. The authors investigated the optimum lipid composition for SP-B(1-25) by comparing the effects of natural lung lavage lipids (NLL), a synthetic equivalent of NLL (synthetic lavage lipids SLL), and a standard lipid mixture (TL) on the activities of SP-B(1-25). Surfactant preparations were formulated by mixing 2 mol% SP-B(1-25) in NNL, SLL, and TL. Calfactant, a calf lung lavage extract with SP-B and SP-C, was a positive control and lipids without peptide were negative controls. Minimum surface tension measured on a captive bubble surfactometer was similar for the three SP-B(1-25) surfactant preparations and calfactant. The effects on lung function were compared in ventilated, lavaged, surfactant-deficient rats. Oxygenation and lung volumes were consistently higher in rats treated with calfactant and SP-B(1-25) in NLL or SLL than in rats treated with SP-B(1-25) in TL. Fourier transform infrared spectra observed abnormal secondary conformations for SP-B(1-25) in TL as a possible cause for the reduced lung function. Lipid composition plays a crucial role in the in vitro and in vivo functions of SP-B(1-25) in surfactant preparations.

Haemoglobin Differences at Birth in Monochorionic Twins Without Chronic Twin-to-twin Transfusion Syndrome

To determine the haemoglobin (Hb) differences at birth in monochorionic (MC) twins without chronic twin-to-twin transfusion syndrome (TTTS) in relation to birth order and placental vascular anatomy.

Withholding Treatment, Withdrawing Treatment, and Palliative Care in the Neonatal Intensive Care Unit

Advances in pharmacology and technology have sharply reduced mortality of extremely preterm infants at the expense of an increasing number of survivors with handicaps and disabilities. The EURONIC study among neonatal intensive care units across Europe demonstrates that treatment of infants born at the limits of viability raises challenging ethical, moral, legal, and emotional dilemmas among neonatologists, nurses, and parents alike. When is it wise to withhold or withdraw intensive care and, if so, what are the needs of the nonviable or dying infant, family, and neonatal staff to provide a humane and compassionate death? This process begins with a thorough determination of diagnosis and prognosis, followed by decision making on the basis of futility of treatment or quality-of-life issues, and counseling of parents. Withholding or withdrawing of intensive care should be synonymous with palliative care. Perinatal audit and after-care of the family complete the process. The Dutch viewpoint and practice guidelines on withholding and withdrawing of neonatal intensive care are presented.

Neonatal Outcome in Twin-to-twin Transfusion Syndrome Treated with Fetoscopic Laser Occlusion of Vascular Anastomoses

To determine neonatal mortality and morbidity rates in monochorionic twins with chronic twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser occlusion of vascular anastomoses.

Preoperative Cranial Ultrasound Findings in Infants with Major Congenital Heart Disease

Advances in diagnostic testing and surgical techniques have resulted in reduced mortality in neonates with congenital heart disease (CHD) and a major concern for neurological morbidity in the presence of preoperative neurological injury.

Intravenous Immunoglobulins Without Initial and Follow-up Cordocentesis in Alloimmune Fetal and Neonatal Thrombocytopenia at High Risk for Intracranial Hemorrhage

To report on a less invasive treatment strategy in alloimmune fetal and neonatal thrombocytopenia (FNAIT) at high risk for either in utero or neonatal intracranial hemorrhage (ICH).

Parvovirus B19 Infection in Pregnancy

Parvovirus B19 is a small single-stranded DNA virus and a potent inhibitor of erythropoiesis, due to its cytotoxicity to erythroid progenitor cells. Infection with parvovirus B19 during pregnancy can cause several serious complications in the fetus, such as fetal anemia, neurological anomalies, hydrops fetalis, and fetal death. Early diagnosis and treatment of intrauterine parvovirus B19 infection is essential in preventing these fetal complications. Testing maternal serum for IgM antibodies against parvovirus B19 and DNA detection by PCR can confirm maternal infection. If maternal infection has occurred, ultrasound investigation of the fetus and measurement of the peak systolic flow velocity of the middle cerebral artery are sensitive non-invasive procedures to diagnose fetal anemia and hydrops. Intrauterine transfusion is currently the only effective treatment to alleviate fetal anemia, but if the fetus is (near) term, induction of delivery should be considered. Most maternal infections with parvovirus B19 occur through contact with infected children at home. Individual counseling of susceptible pregnant women will reduce unnecessary fetal deaths.

Spatial and Temporal Expression of Surfactant Proteins in Hyperoxia-induced Neonatal Rat Lung Injury

Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in which oxidative stress and surfactant deficiency play a crucial role, is characterized by arrested alveolar and vascular development of the immature lung. The spatial and temporal patterns of expression of surfactant proteins are not yet fully established in newborn infants and animal models suffering from BPD.

Incidence, Origin, and Character of Cerebral Injury in Twin-to-twin Transfusion Syndrome Treated with Fetoscopic Laser Surgery

The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

Potential Use of Autologous Umbilical Cord Blood Red Blood Cells for Early Transfusion Needs of Premature Infants

This prospective study investigated whether the odds of receiving a red blood cell (RBC) transfusion in premature infants can be predicted at birth and for whom of these infants harvesting of umbilical cord blood (UCB) for autologous transfusion within 30 days after birth would be worthwhile.

Fetal Stroke and Congenital Parvovirus B19 Infection Complicated by Activated Protein C Resistance

Parvovirus B19 infection in gestation has been associated with severe fetal complications such as anaemia, hydrops and fetal demise. Fetal infection in the first trimester poses the greatest risk for these complications, but infection during the third trimester is more common than previously appreciated and can be associated with severe complications, i.e. fetal death, in the absence of hydrops or classical clinical symptoms. Parvovirus B19 infection has been associated with vasculitis and pathological changes in the central nervous system, which may cause stroke. We report a newborn infant with a rare combination of a recent central nervous system infection with parvovirus B19 and a factor V Leiden mutation, who developed fetal stroke. Conclusion: Factor V Leiden mutation leads to activated protein C resistance and increases the risk of thromboembolism. Thromboembolism occurs rarely in newborns with activated protein C resistance, but can be precipitated by dehydration, asphyxia and infection. Although parvovirus B19 infection of the central nervous system may be a precipitant in neonatal and/or fetal stroke, it can also cause stroke independent of a thrombophilic mutation. In this case, both causative factors may have coincided.

Neurodevelopmental Outcome After Laser Therapy for Twin-twin Transfusion Syndrome

Parvovirus B19 Infection in Pregnancy Studied by Maternal Viral Load and Immune Responses

Facilitate risk assessment of vital complications in fetuses of pregnancies affected by acute parvovirus B19 (B19V) infection.

Polymicrogyria in a Neonate with Severe Autoimmune Thrombocytopenia: Rare Coincidence or Related Disorder?

Parvovirus B19 Infection in Pregnancy: Maternal and Fetal Viral Load Measurements Related to Clinical Parameters

To correlate quantitative maternal and fetal parvovirus B19 (B19V) viral loads and antibody levels at intrauterine transfusion (IUT) as a predictor of fetal morbidity.

Postnatal Management of Fetal and Neonatal Alloimmune Thrombocytopenia: the Role of Matched Platelet Transfusion and IVIG

We evaluated the effects of platelet transfusions and intravenous immunoglobulin (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT) with and without antenatal treatment with IVIG. Records of neonates with FNAIT admitted between January 2000 and November 2005 were reviewed. The patients were divided into group I, treated antenatally with IVIG for known FNAIT, and group II, postnatally diagnosed with FNAIT. The primary outcome was the time interval to reach a platelet level above 100 x 10(9)/L in relation to the type of treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in group II. In group I, four children were born with a platelet count above 100 x 10(9)/L and never needed treatment, and four received a single matched platelet transfusion at birth with a maintained response. Five neonates received IVIG and one matched transfusion, with all but one rapidly responding. In antenatally treated cases, postnatal IVIG had no apparent effect on the platelet count. In group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of the four other patients responded to a number of unmatched platelet transfusions, with one neonate rapidly responding after one matched transfusion, while another needed nine matched transfusions before a persistent adequate platelet count was reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet count in any of our cases. In neonates with FNAIT treated antenatally with IVIG, neonatal management using a single matched platelet transfusion was adequate in all cases. In neonatally diagnosed cases not treated before birth, multiple matched platelet transfusions may be required. We found no evidence to support the use of IVIG in neonates with FNAIT.

Long-term Outcome After Fetal Transfusion for Hydrops Associated with Parvovirus B19 Infection

To evaluate neurodevelopmental status of children treated with intrauterine red blood cell and platelet transfusion for fetal hydrops caused by parvovirus B19.

Early Respiratory Management of Respiratory Distress Syndrome in Very Preterm Infants and Bronchopulmonary Dysplasia: a Case-control Study

In the period immediately after birth, preterm infants are highly susceptible to lung injury. Early nasal continuous positive airway pressure (ENCPAP) is an attempt to avoid intubation and may minimize lung injury. In contrast, ENCPAP can fail, and at that time surfactant rescue can be less effective.

Velamentous Cord Insertion and Unequal Placental Territories in Monochorionic Twins with and Without Twin-to-twin-transfusion Syndrome

The objective of this study was to determine the incidence of velamentous cord insertion and placental territory discordancy in monochorionic twins with and without twin-to-twin transfusion syndrome (TTTS).

Long-term Neurodevelopmental Outcome in Twin-to-twin Transfusion Syndrome Treated with Fetoscopic Laser Surgery

This study was undertaken to determine the long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome treated with laser.

Structure and Conformation of the Disulfide Bond in Dimeric Lung Surfactant Peptides SP-B1-25 and SP-B8-25

Raman spectroscopy was used to determine the conformation of the disulfide linkage between cysteine residues in the homodimeric construct of the N-terminal alpha helical domain of surfactant protein B (dSP-B(1-25)). The conformation of the disulfide bond between cysteine residues in position 8 of the homodimer of dSP-B(1-25) was compared with that of a truncated homodimer (dSP-B(8-25)) of the peptide having a disulfide linkage at the same position in the alpha helix. Temperature-dependent Raman spectra of the S-S stretching region centered at approximately 500 cm(-1) indicated a stable, although highly strained disulfide conformation with a chi(CS-SC) dihedral angle of +/-10 degrees for the dSP-B(1-25) dimer. In contrast, the truncated dimer dSP-B(8-25) exhibited a series of disulfide conformations with the chi(CS-SC) dihedral angle taking on values of either +/-30 degrees or 85+/-20 degrees . For conformations with chi(CS-SC) close to the +/-90 degrees value, the Raman spectra of the 8-25 truncated dimers exhibited chi(SS-CC) dihedral angles of 90/180 degrees and 20-30 degrees . In the presence of a lipid mixture, both constructs showed a nu(S-S) band at approximately 488 cm(-1), corresponding to a chi(CS-SC) dihedral angle of +/-10 degrees . Polarized infrared spectroscopy was also used to determine the orientation of the helix and beta-sheet portion of both synthetic peptides. These calculations indicated that the helix was oriented primarily in the plane of the surface, at an angle of approximately 60-70 degrees to the surface normal, while the beta structure had approximately 40 degrees tilt. This orientation direction did not change in the presence of a lipid mixture or with temperature. These observations suggest that: (i) the conformational flexibility of the disulfide linkage is dependent on the amino acid residues that flank the cysteine disulfide bond, and (ii) in both constructs, the presence of a lipid matrix locks the disulfide bond into a preferred conformation.

Matched Follow-up Study of 5-8 Year Old ICSI-singletons: Comparison of Their Neuromotor Development to IVF and Naturally Conceived Singletons

Intracytoplasmic sperm injection (ICSI) is an invasive technique of artificial reproduction. We investigated the effect of ICSI on neuromotor development in 5-8 year old singletons.

Inhaled Nitric Oxide Attenuates Pulmonary Inflammation and Fibrin Deposition and Prolongs Survival in Neonatal Hyperoxic Lung Injury

Administration of inhaled nitric oxide (iNO) is a potential therapeutic strategy to prevent bronchopulmonary dysplasia (BPD) in premature newborns with respiratory distress syndrome. We evaluated this approach in a rat model, in which premature pups were exposed to room air, hyperoxia, or a combination of hyperoxia and NO (8.5 and 17 ppm). We investigated the anti-inflammatory effects of prolonged iNO therapy by studying survival, histopathology, fibrin deposition, and differential mRNA expression (real-time RT-PCR) of key genes involved in the development of BPD. iNO therapy prolonged median survival 1.5 days (P = 0.0003), reduced fibrin deposition in a dosage-dependent way up to 4.3-fold (P < 0.001), improved alveolar development by reducing septal thickness, and reduced the influx of leukocytes. Analysis of mRNA expression revealed an iNO-induced downregulation of genes involved in inflammation (IL-6, cytokine-induced neutrophilic chemoattractant-1, and amphiregulin), coagulation, fibrinolysis (plasminogen activator inhibitor 1 and urokinase-type plasminogen activator receptor), cell cycle regulation (p21), and an upregulation of fibroblast growth factor receptor-4 (alveolar formation). We conclude that iNO therapy improves lung pathology and prolongs survival by reducing septum thickness, inhibiting inflammation, and reducing alveolar fibrin deposition in premature rat pups with neonatal hyperoxic lung injury.

Risk of Persistent Pulmonary Hypertension of the Neonate in Twin-to-twin Transfusion Syndrome

Chronic twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin gestations and is associated with high perinatal mortality and increased neurological, cardiovascular and renal morbidity.

Reading Preterm Infants' Behavioral Cues: an Intervention Study with Parents of Premature Infants Born <32 Weeks

The effect of a short-term intervention with parents in the Neonatal Intensive Care Unit (NICU) on their knowledge of infant behavioral cues and confidence in caregiving was examined. Ten sets of parents with a total of 22 premature infants born <32 weeks gestational age admitted to a NICU were enrolled in a time-lag control trial over an 8-month period. The intervention group was given 4 sessions of instructions on preterm infant behavior for a period of 2 weeks. The control group did not receive the instructions. All parents completed two subscales of the Mother and Baby Scale (MABS) at weeks 1 and 3 and a short questionnaire concerning nursing support at week 3. Intervention parents completed a pre- and post-test on knowledge of preterm infant behavioral cues at weeks 1 and 3. There was a significant improvement in the post-test scores concerning knowledge of preterm infant behavioral cues and a higher nursing support score for mothers in the intervention group. Intervention mothers showed no significant improvement in confidence in caregiving. Only half of the intervention group fathers participated in the sessions and there were no significant differences in fathers' scores. While the intervention significantly increased maternal knowledge of infant behavioral cues, there was no significant effect on mothers' confidence in caregiving. Very few fathers participated in the entire intervention. A longer, more intensive program with a larger sample size and finding ways of incorporating more participation from fathers is recommended.

Staff Opinions Regarding the Newborn Individualized Developmental Care and Assessment Program (NIDCAP)

This study explored the opinions of (para)medical and nursing staff in two Dutch Neonatal Intensive Care Units (NICU's). A questionnaire was used that measured: a) the perceived impact of NIDCAP on several NICU conditions, b) attitudes, subjective norm, perceived behavioral control, knowledge and abilities of using the NIDCAP method (based on the Theory of Planned Behavior) and c) training interest, requirements, information sources and the relevance of the NIDCAP method for different groups of NICU patients. Respondents were positive about NIDCAP and felt that using NIDCAP is fulfilling and leads to improvement of the infant's development, health and well-being. However, NIDCAP was also thought to be time-consuming and might worsen job conditions. The nursing staff, compared to the medical staff, had a more positive attitude (p=.004), higher perceived behavioral control (p=.004) and perceived a more positive impact of NIDCAP on NICU conditions (p=.008).

Hydrophobic Surfactant Proteins and Their Analogues

Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments.

On the Pathogenesis of Recipient Twin Limb Ischemia

A Randomized, Controlled Trial of Delivery-room Respiratory Management in Very Preterm Infants

Initial ventilation strategy may play an important role in the development of bronchopulmonary dysplasia in very preterm infants. Early nasal continuous positive airway pressure is an accepted approach, but randomized clinical trials are lacking. Our aim was to determine whether early nasal continuous positive airway pressure, preceded by a sustained inflation, is more effective and less injurious in very preterm infants than conventional intervention.

Structure of Mini-B, a Functional Fragment of Surfactant Protein B, in Detergent Micelles

Surfactant protein B (SP-B) is essential for normal lung surfactant function, which is in itself essential to life. However, the molecular basis for SP-B's activity is not understood and a high-resolution structure for SP-B has not been determined. Mini-B is a 34-residue peptide with internal disulfide linkages that is composed of the N- and C-terminal helical regions of SP-B. It has been shown to retain similar activity to full-length SP-B in certain in vitro and in vivo studies. We have used solution NMR to determine the structure of Mini-B in the presence of micelles composed of the anionic detergent sodium dodecyl sulfate (SDS). Under these conditions, Mini-B forms two alpha-helices connected by an unstructured loop. Mini-B possesses a strikingly amphipathic surface with a large positively charged patch on one face of the peptide and a large hydrophobic patch on the opposite face. A tryptophan side chain extends outward from the peptide in a position to interact with lipids at the polar/apolar interface. Interhelix interactions are stabilized by both disulfide bonds and by interleaving of hydrophobic side chains from the two helices.

Dynamic Surface Activity of a Fully Synthetic Phospholipase-resistant Lipid/peptide Lung Surfactant

This study examines the surface activity and resistance to phospholipase degradation of a fully-synthetic lung surfactant containing a novel diether phosphonolipid (DEPN-8) plus a 34 amino acid peptide (Mini-B) related to native surfactant protein (SP)-B. Activity studies used adsorption, pulsating bubble, and captive bubble methods to assess a range of surface behaviors, supplemented by molecular studies using Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and plasmon resonance. Calf lung surfactant extract (CLSE) was used as a positive control.

Congenital Heart Disease in Twin-to-twin Transfusion Syndrome Treated with Fetoscopic Laser Surgery

To determine the incidence of congenital heart disease (CHD) and right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery and evaluate the role of increased afterload by determining the difference in blood pressure and endothelin-1 at birth between donor and recipient twins.

Twins with Cardiomyopathy and Complete Heart Block Born to an HIV-infected Mother Treated with HAART

Pediatric Outcome in Rhesus Hemolytic Disease Treated with and Without Intrauterine Transfusion

To study the short-term morbidity in Rhesus hemolytic disease of infants treated either with or without intrauterine transfusions (IUT).

Measurement of the 'shoulder-umbilical' Distance for Insertion of Umbilical Catheters in Newborn Babies: Questionnaire Study

Approximately 40 years ago, Dr. Peter Dunn introduced a simple method to determine the insertion length of umbilical catheters in neonates, by using the 'shoulder-umbilical' (S-U) length. Since then, various studies have reported a high rate of malposition of umbilical catheters. One of the possible reasons is that the method used to determine the S-U length varies among paediatric professionals. We performed a questionnaire study among 101 paediatric professionals in the Netherlands and found that the method used by the participants to measure the S-U length was highly inconsistent. Placement of an umbilical venous catheter in a too deep position may lead to potentially life-threatening complications. Therefore, uniformity in measurement is paramount for clinical and teaching purposes. Paediatric professionals using Dunn's definition to place umbilical catheters should adhere more strictly to the original description of the measurement of the S-U length.

Perinatal Outcome, Health, Growth, and Medical Care Utilization of 5- to 8-year-old Intracytoplasmic Sperm Injection Singletons

To evaluate short- and long-term health in intracytoplasmic sperm injection (ICSI) singletons.

Effects of Basic Developmental Care on Neonatal Morbidity, Neuromotor Development, and Growth at Term Age of Infants Who Were Born at <32 Weeks

The goal of this study was to investigate the effect of basic elements of developmental care (incubator covers and positioning aids) on days of respiratory support and intensive care, growth, and neuromotor development at term age in infants who were born at <32 weeks' gestation.

Early Nasal Continuous Positive Airway Pressure and Low Threshold for Intubation in Very Preterm Infants

To determine if selective intubation, use of early nasal continuous positive airway pressure (NCPAP) at birth with a low threshold for early surfactant treatment, reduces the need for intubation in very preterm infants in the first days after birth.

A Clinical Study on the Feasibility of Autologous Cord Blood Transfusion for Anemia of Prematurity

The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbilical cord blood (UCB), as an alternative for allogeneic transfusions in premature infants admitted to a tertiary neonatal center.

Cord Blood Clara Cell Protein CC16 Predicts the Development of Bronchopulmonary Dysplasia

Clara cell protein (CC16) is an anti-inflammatory protein and a biomarker of pulmonary epithelial cells and alveolocapillary membrane injury in adults. We investigated whether low cord blood concentrations of CC16 are associated with the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants and the relationship between CC16 and its pro-inflammatory counterpart, the secretory phospholipase A(2) (sPLA(2)) enzyme. CC16 concentration, sPLA(2) activity and IL-6 concentration were measured in cord blood plasma from 79 preterm infants (25 controls, 37 infants who developed RDS and 17 infants who developed BPD). After adjustment for gestational age and Apgar score at 5 min, the CC16 concentration was lower in BPD infants than in preterm controls (p<0.01). sPLA(2) activity was similar in all groups and the IL-6 concentrations were increased in both RDS and BPD infants (p<0.01 and p<0.05, respectively, vs. controls). We conclude that low cord blood CC16 concentrations in preterm infants independently predict the development of BPD. Low CC16 levels may reflect early lung injury, which contributes to the severity of RDS and progress towards BPD. Future studies are needed to assess whether the early administration of recombinant human CC16 in preterm infants with low cord blood CC16 prevents the development of BPD.

Comparing Brain White Matter on Sequential Cranial Ultrasound and MRI in Very Preterm Infants

Periventricular white matter (WM) echodensities, frequently seen in preterm infants, can be associated with suboptimal neurodevelopment. Major WM injury is well detected on cranial ultrasound (cUS). cUS seems less sensitive for diffuse or more subtle WM injury. Our aim was to assess the value of cUS and magnetic resonance imaging (MRI) for evaluating WM changes and the predictive value of cUS and/or MRI findings for neurodevelopmental outcome in very preterm infants with normal to severely abnormal WM on sequential high-quality cUS.

In Utero Acquired Limb Ischemia in Monochorionic Twins with and Without Twin-to-twin Transfusion Syndrome

To report on the occurrence of in utero acquired limb ischemia in two referral institutions managing monochorionic (MC) twins with and without twin-to-twin transfusion syndrome (TTTS) and estimate its prevalence.

Cerebral Injury in Monochorionic Twins with Selective Intrauterine Growth Restriction And/or Birthweight Discordance

The objective of the study was to study the incidence of severe cerebral injury in monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) and/or birthweight discordance.

Lateral Stress Relaxation and Collapse in Lipid Monolayers

Surfactants at air/water interfaces are often subjected to mechanical stresses as the interfaces they occupy are reduced in area. The most well characterized forms of stress relaxation in these systems are first order phase transitions from lower density to higher density phases. Here we study stress relaxation in lipid monolayers that occurs once chemical phase transitions have been exhausted. At these highly compressed states, the monolayer undergoes global mechanical relaxations termed collapse. By studying four different types of monolayers, we determine that collapse modes are most closely linked to in-plane rigidity. We characterize the rigidity of the monolayer by analyzing in-plane morphology on numerous length scales. More rigid monolayers collapse out-of-plane via a hard elastic mode similar to an elastic membrane, while softer monolayers relax in-plane by shearing.

Cognitive Development of Singletons Born After Intracytoplasmic Sperm Injection Compared with in Vitro Fertilization and Natural Conception

To investigate cognitive development of singletons conceived by intracytoplasmic sperm injection (ICSI) at 5-8 years of age.

Effects of Individualized Developmental Care in a Randomized Trial of Preterm Infants <32 Weeks

The goal was to investigate the effects of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) on days of respiratory support and intensive care, growth, and neuromotor development at term age for infants born at <32 weeks.

No Short-term Benefits of Antenatal Corticosteroid Treatment in Severely Preterm Growth Restricted Fetuses: a Case-control Study

Antenatal corticosteroid administration to premature, growth restricted fetuses may not be beneficial and even have adverse effects on neonatal outcome.

Brain Imaging Findings in Very Preterm Infants Throughout the Neonatal Period: Part II. Relation with Perinatal Clinical Data

This study describes the relation between frequent and clinically relevant brain imaging findings in very preterm infants (GA<32 weeks), assessed with sequential cranial ultrasonography throughout the neonatal period and MRI around term age, and several potential perinatal risk factors. For ultrasound findings during admission the following independent risk factors were identified: male gender for periventricular echodensities and intraventricular haemorrhage, postnatal corticosteroid treatment for cystic white matter lesions, and lower gestational age for post-haemorrhagic ventricular dilatation. For MRI findings around term age, including punctate white matter lesions, ventricular dilatation, decreased cortical complexity, and diffuse and excessive high signal intensity, no independent risk factors were found. In very preterm infants, the risk factors for frequently found changes on cranial ultrasound have largely remained unchanged over the last decades, while no risk factors could be identified for subtle and diffuse white matter injury as seen on MRI around term age.

Neonatal Brain Injury: Imaging, Monitoring and Protection

Magnetic Resonance Imaging of the Brain in Newborn Infants: Practical Aspects

Magnetic Resonance Imaging is becoming more widely available and increasingly important for imaging the neonatal brain. In newborn infants it poses challenges regarding patient preparation, safety, optimal timing, and sequence optimization. These issues are addressed in this paper and indications for performing neonatal Magnetic Resonance Imaging are presented.

Brain Imaging Findings in Very Preterm Infants Throughout the Neonatal Period: Part I. Incidences and Evolution of Lesions, Comparison Between Ultrasound and MRI

This study describes the incidence and evolution of brain imaging findings in very preterm infants (GA<32 weeks), assessed with sequential cranial ultrasound (cUS) throughout the neonatal period and MRI around term age. The accuracy of both tools is compared for findings obtained around term. Periventricular echodensities and intraventricular haemorrhage were the most frequent cUS findings during admission. Frequent findings on both cUS and MRI around term included ventricular dilatation, widened extracerebral spaces, and decreased cortical complexity. MRI additionally showed punctate white matter lesions and diffuse and excessive high signal intensity, but did not depict lenticulostriate vasculopathy and calcifications, and was less reliable for germinolytic and plexus cysts. cUS detected most abnormalities that have been associated with abnormal neurodevelopmental outcome.

Neonatal Cranial Ultrasonography: How to Optimize Its Performance

Cranial ultrasonography (CUS) is an excellent and non invasive tool for brain imaging during the neonatal period. It is traditionally performed through the anterior fontanel. Although the advantages of CUS are numerous, there are also diagnostic limitations. Alternative imaging techniques including the use of different transducer types and frequencies and of additional acoustic windows can improve image quality and the diagnostic accuracy of CUS. This review will focus on techniques to be applied for optimizing the performance of CUS in the newborn infant.

Risk Factors for Neurodevelopment Impairment in Twin-twin Transfusion Syndrome Treated with Fetoscopic Laser Surgery

To estimate the risk factors for adverse long-term neurodevelopment outcome in twin-twin transfusion syndrome treated with laser surgery.

Follow-up Outcomes at 1 and 2 Years of Infants Born Less Than 32 Weeks After Newborn Individualized Developmental Care and Assessment Program

This was a randomized, controlled trial to investigate the effect of Newborn Individualized Developmental Care and Assessment Program on growth, cognitive, psychomotor, and neuromotor development at 1 and 2 years in infants born at <32 weeks' gestational age.

The Pregnancy and Long-term Neurodevelopmental Outcome of Monochorionic Diamniotic Twin Gestations: a Multicenter Prospective Cohort Study from the First Trimester Onward

We sought to document the pregnancy and neurodevelopmental outcome in monochorionic diamniotic twin pregnancies and to identify risk factors for death and impairment.

Sildenafil Attenuates Pulmonary Inflammation and Fibrin Deposition, Mortality and Right Ventricular Hypertrophy in Neonatal Hyperoxic Lung Injury

Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome.

Cerebellar Injury in Preterm Infants: Incidence and Findings on US and MR Images

To investigate the incidence and characteristics of cerebellar injury in a cohort of very preterm infants by using the mastoid fontanelle (MF) and posterior fontanelle (PF) approach in addition to routine cranial ultrasonography (US) through the anterior fontanelle (AF), with magnetic resonance (MR) imaging as the reference standard.

Pulmonary Secretory Phospholipase A2 in Infants with Respiratory Distress Syndrome Stimulates in Vitro Neutrophil Migration

The massive pulmonary neutrophil influx in respiratory distress syndrome (RDS) in preterm infants has been ascribed to the effect of leukotriene B(4) (LTB(4)).

Functional Importance of the NH2-terminal Insertion Sequence of Lung Surfactant Protein B

Lung surfactant protein B (SP-B) is required for proper surface activity of pulmonary surfactant. In model lung surfactant lipid systems composed of saturated and unsaturated lipids, the unsaturated lipids are removed from the film at high compression. It is thought that SP-B helps anchor these lipids closely to the monolayer in three-dimensional cylindrical structures termed "nanosilos" seen by atomic force microscopy imaging of deposited monolayers at high surface pressures. Here we explore the role of the SP-B NH(2) terminus in the formation and stability of these cylindrical structures, specifically the distribution of lipid stack height, width, and density with four SP-B truncation peptides: SP-B 1-25, SP-B 9-25, SP-B 11-25, and SP-B 1-25Nflex (prolines 2 and 4 substituted with alanine). The first nine amino acids, termed the insertion sequence and the interface seeking tryptophan residue 9, are shown to stabilize the formation of nanosilos while an increase in the insertion sequence flexibility (SP-B 1-25Nflex) may improve peptide functionality. This provides a functional understanding of the insertion sequence beyond anchoring the protein to the two-dimensional membrane lining the lung, as it also stabilizes formation of nanosilos, creating reversible repositories for fluid lipids at high compression. In lavaged, surfactant-deficient rats, instillation of a mixture of SP-B 1-25 (as a monomer or dimer) and synthetic lung lavage lipids quickly improved oxygenation and dynamic compliance, whereas SP-B 11-25 surfactants showed oxygenation and dynamic compliance values similar to that of lipids alone, demonstrating a positive correlation between formation of stable, but reversible, nanosilos and in vivo efficacy.

Critical Structural and Functional Roles for the N-terminal Insertion Sequence in Surfactant Protein B Analogs

Surfactant protein B (SP-B; 79 residues) belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78), confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7) attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity.

Synthetic Surfactant Based on Analogues of SP-B and SP-C is Superior to Single-peptide Surfactants in Ventilated Premature Rabbits

Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure.

Does Parenteral Nutrition Influence Electrolyte and Fluid Balance in Preterm Infants in the First Days After Birth?

New national guidelines recommend more restricted fluid intake and early initiation of total parenteral nutrition (TPN) in very preterm infants. The aim was study the effect of these guidelines on serum sodium and potassium levels and fluid balance in the first three days after birth.

Monitoring of Neonatal Haemodynamics: Light Shining at the End of the Tunnel?

Is Sequential Cranial Ultrasound Reliable for Detection of White Matter Injury in Very Preterm Infants?

Cranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (WM) injury. Our aim was to assess in very preterm infants the reliability of a classification system for WM injury on sequential cUS throughout the neonatal period, using magnetic resonance imaging (MRI) as reference standard.

Clinical Outcome in Neonates with Twin Anemia-polycythemia Sequence

The purpose of this study was to evaluate neonatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS).

Humidified and Heated Air During Stabilization at Birth Improves Temperature in Preterm Infants

Neonatal resuscitation guidelines recommend techniques to minimize heat loss in the delivery room. The use of humidified and heated gas is standard of care for preterm infants who need respiratory support in the NICU, but international resuscitation guidelines do not stipulate use of this therapy during stabilization at birth. We aimed to investigate the effect of humidified and heated gas on admission temperature in preterm infants who require respiratory support at birth.

Poor Accuracy of Methods Currently Used to Determine Umbilical Catheter Insertion Length

This study compares the methods of Dunn and Shukla in determining the appropriate insertion length of umbilical catheters. In July 2007, we changed our policy for umbilical catheter insertions from the method of Dunn to the method of Shukla. We report our percentage of inaccurate placement of umbilical-vein catheters (UVCs) and umbilical-artery catheters (UACs) before and after the change of policy. In the Dunn-group, 41% (28/69) of UVCs were placed directly in the correct position against 24% (20/84) in the Shukla-group. The position of the catheter-tip of UVCs in the Dunn-group and the Shukla-group was too high in 57% (39/69) and 75% (63/84) of neonates, respectively. UACs in the Dunn-group were placed directly in the correct position in 63% (24/38) compared to the 87% (39/45) of cases in Shukla-group. The position of the catheter-tip of UACs in the Dunn-group and the Shukla-group was too high in 34% (13/38) and 13% (6/45) of neonates, respectively. In conclusion, the Dunn-method is more accurate than the Shukla-method in predicting the insertion length for UVCs, whereas the Shukla-method is more accurate for UACs.

Leak and Obstruction with Mask Ventilation During Simulated Neonatal Resuscitation

To evaluate mask technique during simulated neonatal resuscitation and test the effectiveness of training in optimal mask handling.

[A Neonate with Increased Joint Laxity]

A neonate presented with increased laxity and dislocations of several joints, a loose skin and criss-cross lines in the palms of her hands. She was diagnosed with the arthrochalasia type of Ehlers-Danlos syndrome.

Apelin Attenuates Hyperoxic Lung and Heart Injury in Neonatal Rats

Apelin, a potent vasodilator and angiogenic factor, may be a novel therapeutic agent in neonatal chronic lung disease, including bronchopulmonary dysplasia.

Short and Long Term Outcome of Neonatal Hyperglycemia in Very Preterm Infants: a Retrospective Follow-up Study

Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose > or = 10 mmol/l, treated with insulin for > or = 12 hours) on growth and neurobehavioral outcome at 2 years of age.

Growth-restricted Preterm Newborns Are Predisposed to Functional Adrenal Hyperandrogenism in Adult Life

The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain.

Discordance for Schimmelpenning-Feuerstein-Mims Syndrome in Monochorionic Twins Supports the Concept of a Postzygotic Mutation

The Schimmelpenning-Feuerstein-Mims (SFM) syndrome comprises a craniofacial nevus sebaceus, seizures, developmental delay, ocular and skeletal abnormalities. It is a sporadic condition and hypothesized to result from mosaicism involving a lethal autosomal dominant gene. We report a second occurrence of discordant monozygotic (MZ) twins with severe SFM, supporting the concept of a postzygotic mutation.

Use of Rifampin in Persistent Coagulase Negative Staphylococcal Bacteremia in Neonates

Coagulase negative staphylococci (CoNS) are the most common cause of neonatal sepsis in the Neonatal Intensive Care Unit (NICU). A minority of neonates does not respond to vancomycin therapy and develops persistent bacteremia, which may be treated with rifampin. We evaluated the use of rifampin in persistent CoNS bacteremia.

Long-Term Follow Up After Intra-Uterine TransfusionS; the LOTUS Study

The Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children.

[Practice Guideline 'Perinatal Management of Extremely Preterm Delivery']

At the request of the State Secretary of the Dutch Ministry of Health, Welfare and Sport a national multidisciplinary workgroup developed an evidence-based practice guideline for the management of pregnant women with an imminent preterm delivery after a pregnancy of less than 26 weeks duration and for extremely preterm neonates. Active care measures are advised for neonates from a gestational age of 24 0/7 weeks onwards, unless there are serious arguments that justify a conservative management. In cases of imminent preterm delivery, intrauterine transport to a perinatological care centre is advised from a gestational age of 23 4/7 weeks onwards. In cases of imminent preterm delivery, glucocorticoids to enhance fetal lung maturity should be administered from a gestational age of 23 5/7 weeks onwards. From a gestational age of 24 0/7 weeks onwards a caesarean section may be considered if the fetal condition during spontaneous labour justifies this.

Long-term Outcome in Relationship to Neonatal Transfusion Volume in Extremely Premature Infants: a Comparative Cohort Study

In premature born infants red blood cell (RBC) transfusions have been associated with both beneficial and detrimental sequels. Upon RBC transfusion, improvement in cerebral blood flow and oxygenation have been observed, while a more liberal transfusion policy may be associated with a better developmental outcome. The effect of the transfusion volume on long-term outcome is not known.

Long-term Neurodevelopmental Outcome in TTTS in the Eurofoetus Trial

Neonatal Morbidity in Twin-twin Transfusion Syndrome

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins which are often born prematurely and may suffer from typical conditions associated with prematurity. In addition, surviving twins with TTTS are at increased risk for other complications including neurological, cardiovascular, renal and hematologic morbidity. Rare complications such as hypoxic-ischemic lesions to limbs or intestines and amniotic band syndrome have also been reported in TTTS survivors. This review focuses on the neonatal and pediatric mortality and morbidity in TTTS survivors, with special emphasis on the long-term neurodevelopmental outcome.

Hematological Morbidity and Management in Neonates with Hemolytic Disease Due to Red Cell Alloimmunization

Treatment of severe anemia with intrauterine red cell transfusions in fetuses with red cell alloimmunization has led to a dramatic increase in perinatal survival. Due to this increased survival focus is nowadays shifting towards improving postnatal treatment options. Phototherapy, exchange transfusions and intravenous immunoglobulin are used to treat hyperbilirubinemia and prevent kernicterus. Postnatal treatment of anemia consists of top-up transfusions, supplements to support erythropoiesis such as folic acid and iron, and occasionally erythropoietin treatment. In addition to anemia, other hematological complications such as thrombocytopenia, coagulation disturbances, leucopenia and iron overload have been reported. This review focuses on the hematological morbidity in neonates with red cell alloimmunization and summarizes the current evidence on management options.

Neonatal Outcome After Prenatal Interventions for Congenital Lung Lesions

Congenital lung lesions, mostly congenital cystic adenomatoid malformations (CCAMs) and bronchopulmonary sequestrations (BPSs), are uncommon disorders. Prenatal intervention in severely affected (hydropic) fetuses has drastically improved perinatal survival. Not much is known, however, on the short-term and long-term respiratory and neurodevelopmental outcome. Several small case series have been reported and suggest an increased incidence of neonatal morbidity, mainly associated with prematurity and respiratory failure at birth. Overall, neonatal mortality and morbidity after prenatal interventions for CCAM seems to be worse than for BPS. This review focuses on the neonatal outcome after prenatal intervention for congenital lung lesions and summarizes the results reported in the literature.

Outcome After Fetal Intervention

Long-term Neurodevelopmental Outcome in Monochorionic Twins After Fetal Therapy

Monochorionic (MC) twins are at risk for several disorders, including twin-twin transfusion syndrome (TTTS), Twin Reverse Arterial Perfusion (TRAP) and selective intrauterine growth restriction (sIUGR). Several fetal interventions, such as serial amnioreduction (AR), fetoscopic laser coagulation of placental anastomoses (FLC) and selective feticide have lead to improved perinatal morbidity and mortality rates. Nevertheless, the rate of cerebral lesions in MC twins after fetal therapy appears to be high. Follow-up studies show a high incidence of cerebral palsy (CP) and neurodevelopmental impairment (NDI). We performed a systematic review on the long-term neurodevelopmental outcome in MC twins with TTTS following AR and FLC and MC twins following selective feticide of the co-twin due to TTTS, TRAP, sIUGR and congenital anomalies.

Long-term Neurodevelopmental Outcome After Intrauterine Transfusion for Fetal Anemia

The long-term neurodevelopmental outcome of children born after intrauterine blood transfusion (IUT) for red cell alloimmunization is considered favorable. Severe hydrops has been identified as a strong predictor for neurodevelopmental impairment. However, the long-term outcome of survivors of IUT for congenital Parvovirus B19 infection and fetomaternal hemorrhage is not well known. Limitations of the follow-up studies to date are small sample size, lack of controls, unclear criteria for impairment and lack of standardized developmental tests. Future research should take into account more subtle impairments, since cognitive functioning <-1 SD, behavioral and learning problems already have a significant impact on care requirements and future socio-economic potential. A better understanding of the effect of IUT and fetal anemia on child development over time will allow more accurate parental counseling and targeted interventions to optimize child development when needed.

Abdominal Fat Accumulation in Adults Born Preterm Exposed Antenatally to Maternal Glucocorticoid Treatment is Dependent on Glucocorticoid Receptor Gene Variation

Preterm birth is associated with short stature, abdominal adiposity, insulin resistance, and hypertension, resembling effects of increased glucocorticoid bioactivity. Although antenatal glucocorticoid treatment does not substantially contribute to these associations, it is unknown whether genetic variants in the glucocorticoid receptor gene could modulate the effects of antenatal glucocorticoid treatment on the above phenotype.

Ultrasound Detection of Posterior Fossa Abnormalities in Full-term Neonates

Routine cranial ultrasonography, using the anterior fontanelle as acoustic window enables visualization of the supratentorial brain structures in neonates and young infants. The mastoid fontanelle enables a better view of the infratentorial structures, especially cerebellar hemorrhage in preterm infants. Reports on the usefulness and reliability of cranial ultrasonography using the mastoid fontanelle approach for the detection of posterior fossa abnormalities, focusing only on full-term neonates are limited. This article describes the technique of mastoid fontanelle ultrasonography in full-term neonates and the features of posterior fossa abnormalities that may be encountered in various neonatal disorders and conditions, combined with subsequent MRI in the same patients. Cranial ultrasound through the mastoid fontanelle plays a pivotal role in the early detection of posterior fossa pathology and selection of neonates with an indication for MRI.

Diffuse Hyperechogenicity of Basal Ganglia and Thalami in Preterm Neonates: a Physiologic Finding?

To elucidate whether echogenicity (EG) of the basal ganglia and thalami (BGT) represents a physiologic phenomenon in preterm neonates (<32 weeks gestation).

Thrombocytopenia in Neonates and the Risk of Intraventricular Hemorrhage: a Retrospective Cohort Study

The overall prevalence of thrombocytopenia in neonates admitted to neonatal intensive care units ranges from 22 to 35%. There are only a few small studies that outline the relationship between the severity of thrombocytopenia and the risk of bleeding. This makes it difficult to form an evidence-based threshold for platelet transfusions in neonatal patients. The aim of this study was to determine the prevalence of thrombocytopenia in a tertiary neonatal intensive care unit and to study the relation between thrombocytopenia and the risk of intraventricular hemorrhage (IVH).

Intravenous Immunoglobulin in Neonates with Rhesus Hemolytic Disease: a Randomized Controlled Trial

Despite limited data, international guidelines recommend the use of intravenous immunoglobulin (IVIg) in neonates with rhesus hemolytic disease.

Compressive Force Applied to a Manikin's Head During Mask Ventilation

ObjectiveTo investigate the compressive force applied to the head during mask ventilation and determine whether this force increases in response to an attempt to correct the mask leak.MethodsThe authors asked 24 participants (consultants, fellows and nurses) to administer positive pressure ventilation to a modified leak-free, term newborn manikin using a self-inflating bag (SIB) and a Neopuff T-piece device. Recordings were made before and after the participants were informed about their percentage of mask leak and asked to correct this. Airway pressure and flow were measured using a Florian monitor, and the force applied to the head was measured using a concealed custom-made load cell weighing scale.ResultsThere were no differences in the mean (SD) force applied to the head between devices used and before or after the attempt to correct the mask leak (SIB before 2215 (892) and after 2195 (989) g; Neopuff before 1949 (957) and after 2028 (909) g). There was a large variation in force with both devices before and after the attempt (coefficient of variation: SIB before 40% and after 45%; Neopuff before 50% and after 45%). There was no correlation between mask leak and the difference in force used before and after the attempt to correct the mask leak using both devices.ConclusionDuring mask ventilation of a manikin, the authors observed that large forces were exerted on the head with either an SIB or a Neopuff, but these forces did not increase during the attempt to minimise the mask leak.

KL₄ Peptide Induces Reversible Collapse Structures on Multiple Length Scales in Model Lung Surfactant

We investigated the effects of KL₄, a 21-residue amphipathic peptide approximating the overall ratio of positively charged to hydrophobic amino acids in surfactant protein B (SP-B), on the structure and collapse of dipalmitoylphosphatidylcholine and palmitoyl-oleoyl-phosphatidylglycerol monolayers. As reported in prior work on model lung surfactant phospholipid films containing SP-B and SP-B peptides, our experiments show that KL₄ improves surfactant film reversibility during repetitive interfacial cycling in association with the formation of reversible collapse structures on multiple length scales. Emphasis is on exploring a general mechanistic connection between peptide-induced nano- and microscale reversible collapse structures (silos and folds).

Fetal, Neonatal and Developmental Outcomes of Lithium-exposed Pregnancies

INTRODUCTION: Many women with a bipolar disorder are of reproductive age and will need to continue lithium treatment during pregnancy. The teratogenic and perinatal effects of lithium are known, but not the long-term effects of lithium on neurodevelopment of the children. This study investigates growth, neurological, cognitive and behavioral development of children exposed to lithium in utero. METHOD: In an observational retrospective cohort study 15 children who were exposed to lithium in utero were investigated at 3-15years of age. Neurological development was tested using the Hempel or Touwen examination. Cognitive development was assessed with the Bayley Scales of Infant Development III, Wechsler Preschool and Primary Scale of Intelligence or the Wechsler Intelligence Scale for Children. Parents completed the Child Behavior Checklist to assess behavioral development and a standard questionnaire about general development of the child since birth. RESULTS: One child had signs of a minor neurological dysfunction, but without further clinical implications. The results of the cognitive tests were within normal limits, although most children had lower scores on the performance IQ subtest. Growth, behavior and general development were within the normal range. CONCLUSIONS: Continuing lithium therapy during pregnancy did not cause adverse effects on growth, neurological, cognitive and behavioral development of exposed children.

Low Versus High Gas Flow Rate for Respiratory Support of Infants at Birth: a Manikin Study

Neonatal resuscitation guidelines do not specify the gas flow rate during mask ventilation. Aim: Investigating the effect of gas flow rates on pressures, volumes delivered and mask leak.

A ToF-SIMS Study of the Lateral Organization of Lipids and Proteins in Pulmonary Surfactant Systems

Pulmonary surfactant is a complex lipid-protein mixture whose main function is to reduce the surface tension at the air-liquid interface of alveoli to minimize the work of breathing. The exact mechanism by which surfactant monolayers and multilayers are formed and how they lower surface tension to very low values during lateral compression remains uncertain. We used time-of-flight secondary ion mass spectrometry to study the lateral organization of lipids and peptide in surfactant preparations ranging in complexity. We show that we can successfully determine the location of phospholipids, cholesterol and a peptide in surfactant Langmuir-Blodgett films and we can determine the effect of cholesterol and peptide addition. A thorough understanding of the lateral organization of PS interfacial films will aid in our understanding of the role of each component as well as different lipid-lipid and lipid-protein interactions. This may further our understanding of pulmonary surfactant function.

Long-term Neurodevelopmental Outcome After Intrauterine Transfusion for Hemolytic Disease of the Fetus/newborn: the LOTUS Study

To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT).

Parvovirus B19 in Pregnancy: Prenatal Diagnosis and Management of Fetal Complications

PURPOSE OF REVIEW: Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical importance. This review aims to raise awareness of recently discovered potentially devastating consequences of this infection in pregnancy, and provides updated guidelines on diagnosis and management. RECENT FINDINGS: In contrast to previous beliefs, parvovirus B19 infection during any stage of pregnancy may not only cause fetal death, but may also result in severe and irreversible neurological sequelae in survivors. Improved diagnostic techniques allow more reliable and earlier diagnosis of fetal disease. SUMMARY: Clinicians need to be aware of the risk of adverse outcome of parvovirus B19 infection in pregnancy, and sometimes the long interval between exposure and fetal symptoms. Accurate diagnosis using PCR and weekly ultrasound checks ups with Doppler measurement of middle cerebral artery flow velocity up to 20 weeks postexposure may improve detection of fetal disease. More timely treatment likely results in improved outcome.

Thrombocytopaenia and Intraventricular Haemorrhage in Very Premature Infants: a Tale of Two Cities

ObjectiveTo study whether the incidence of intraventricular haemorrhage (IVH) in very premature infants (<32 weeks gestation) with thrombocytopaenia is lower when using a liberal platelet-transfusion guideline compared with a restrictive guideline.Study designA retrospective cohort study comparing the incidence of IVH in very premature infants with thrombocytopaenia (platelet count <150×10(9)/l) admitted between 2007 and 2008 to two neonatal intensive care unit in The Netherlands. The restrictive platelet-transfusion unit (N=353 infants <32 weeks gestation) transfused only in case of active haemorrhage and a platelet count <50×10(9)/l. The liberal-transfusion unit (N=326 infants <32 weeks gestation) transfused according to predefined platelet count thresholds. Primary outcome was the incidence and severity of IVH in infants with thrombocytopaenia in both units.ResultsThe number of infants with thrombocytopaenia that received a platelet transfusion was significantly lower in the restrictive-transfusion unit compared with the liberal-transfusion unit, 15% (21/145) versus 31% (41/141), (p<0.001). The incidence of IVH in infants with thrombocytopaenia in the restrictive-transfusion and liberal-transfusion units was 30% (44/145) and 29% (41/141), respectively (p=0.81). The incidence of severe IVH (grade 3 or 4) in the restrictive-transfusion and liberal-transfusion units was 8% (12/145) and 11% (16/141), respectively (p=0.38).ConclusionIn the restrictive-transfusion unit, the rate of platelet transfusions was significantly lower, but the incidence and severity of IVH was similar to the liberal-transfusion unit.

Auditing Resuscitation of Preterm Infants at Birth by Recording Video and Physiological Parameters

OBJECTIVE: To evaluate compliance with neonatal resuscitation guidelines during resuscitation of preterm infants by video recording of delivery room management and monitoring physiologic parameters. METHODS: The delivery room management of preterm infants at birth was recorded by an independent researcher. Physiological parameters (airway pressures, gas flow, tidal volume, heart rate and oxygen saturation) were measured, use of supplemental oxygen was noted and a video of the resuscitation was recorded. All signals were digitised and recorded using specially designed software. The delivery room management was then evaluated and compared with the local resuscitation guidelines. RESULTS: Thirty-four infants were included with a mean (SD) gestational age of 30.6 (3.2) weeks and birth weight of 1292 (570) grams. Time from birth to initial evaluation was longer than recommended (65 (15) seconds). Respiratory support was started at 70 (23) seconds. In 7/34 infants (21%), interventions were performed according to guidelines. In 25/34 infants (74%), one or more respiratory interventions were not performed according to guidelines. In 10/34 infants (29%), one or more non-respiratory interventions (mainly related to the prevention of heat loss) were not performed according to guidelines. The presence and adequacy of spontaneous breathing was difficult to judge clinically. In almost all occasions (96%) the information from the respiratory function monitor was not used. CONCLUSIONS: Neonatal caregivers often deviate from resuscitation guidelines. Respiratory function monitoring parameters were often not used during resuscitation. A difficult part of neonatal resuscitation is subjectively assessing spontaneous breathing.

Phosphodiesterase 4 Inhibition Attenuates Persistent Heart and Lung Injury by Neonatal Hyperoxia in Rats

Phosphodiesterase (PDE) 4 inhibitors are potent anti-inflammatory drugs with antihypertensive properties, and their therapeutic role in bronchopulmonary dysplasia (BPD) is still controversial. We studied the role of PDE4 inhibition with piclamilast on normal lung development and its therapeutic value on pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in neonatal rats with hyperoxia-induced lung injury, a valuable model for premature infants with severe BPD. The cardiopulmonary effects of piclamilast treatment (5 mg·kg(-1)·day(-1)) were investigated in two models of experimental BPD: 1) daily treatment during continuous exposure to hyperoxia for 10 days; and 2) late treatment and injury-recovery in which pups were exposed to hyperoxia or room air for 9 days, followed by 9 or 42 days of recovery in room air combined with treatment started on day 6 of oxygen exposure until day 18. Prophylactic piclamilast treatment reduced pulmonary fibrin deposition, septum thickness, arteriolar wall thickness, arteriolar vascular smooth muscle cell proliferation and RVH, and prolonged survival. In the late treatment and injury-recovery model, hyperoxia caused persistent aberrant alveolar and vascular development, PH, and RVH. Treatment with piclamilast in both models reduced arteriolar wall thickness, attenuated RVH, and improved right ventricular function in the injury recovery model, but did not restore alveolarization or angiogenesis. Treatment with piclamilast did not show adverse cardiopulmonary effects in room air controls in both models. In conclusion, PDE4 inhibition attenuated and partially reversed PH and RVH, but did not advance alveolar development in neonatal rats with hyperoxic lung injury or affect normal lung and heart development.

Waiting
simple hit counter