Ultrasonographic analysis of fetal gastrointestinal motility during the peripartum period in the dog.

The aim of this study was to investigate fetal gastrointestinal motility (FGM) of dogs using ultrasonic imaging and its association with vaginal and rectal temperature, serum progesterone concentrations and fetal heart rate. Pregnant bitches were examined after day 54 of gestation and there were determinations of vaginal and rectal temperature and serum progesterone concentrations. The fetal abdomen was evaluated for 30 s using longitudinal and transversal assessments, and FGM was scored as 0 (no peristalsis) or 1 (evident peristalsis). Number of fetuses with a 1 or 0 score were determined for each bitch (number and the percentage of fetuses with FGM). A total of 135 FGM measurements were recorded. There was FGM in 0/3, 0/6, 1/6 (16.7 %), 3/20 (15 %), 5/18 (27.3 %), 18/28 (64.3 %), 12/17 (70.6 %), 14/22 (63.6 %), 6/9 (66.7 %), 4/6 (66.7 %) fetuses from day -9 until 0 preceding parturition, respectively. In the last 5 days before parturition, 63.3 % of fetuses had FGM. Vaginal and rectal temperature were strongly and positively correlated (P < 0.001). Vaginal temperature was positively correlated with progesterone concentrations and fetal heart rate (P < 0.01), and there was a small negative correlation with FGM (r = -0.331, P < 0.05). Due to ease of data collection, the assessment of FGM is a valuable procedure for evaluation of fetal maturity in dogs. Vaginal and rectal temperatures are reliable variables to be assessed during the last week of pregnancy for estimating the time of parturition.

Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a fetal defect comprising an incomplete diaphragm and the herniation of abdominal organs into the chest cavity that interfere with fetal pulmonary development. Though the most promising treatment for CDH is via interventional fetoscopic tracheal occlusion (TO) surgery in-utero, it has produced mixed results due to the static nature of the inserted occlusion. We hypothesize that a suitable noninvasively-actuatable, cyclic-release tracheal occlusion device can be developed to enable dynamic tracheal occlusion (dTO) implementation. OBJECTIVE: To conduct an in-vitro proof-of-concept investigation of the construction of thermo-responsive polymer valves designed for targeted activation within a physiologically realizable temperature range as a first step towards potential development of a noninvasively-actuatable implantable device to facilitate dynamic tracheal occlusion (dTO) therapy. METHODS: Six thermo-responsive polymer valves, with a critical solution temperature slightly higher than normal physiological body temperature of 37°C, were fabricated using a copolymer of n-isopropylacrylamide (NIPAM) and dimethylacrylamide (DMAA). Three of the valves underwent ethylene oxide (EtO) sterilization while the other three served as controls for EtO-processing compatibility testing. Thermal response actuation of the valves and their steady-state flow performances were evaluated using water and caprine amniotic fluid. RESULTS: All six valves consisting of 0.3-mole fraction of DMAA were tested for thermal actuation of caprine amniotic fluid flow at temperatures ranging from 30-44°C. They all exhibited initiation of valve actuation opening at ~40°C with full completion at ~44°C. The overall average coefficient of variation (CV) for the day-to-day flow performance of the valves tested was less than 12%. Based on a Student t-test, there was no significant difference in the operational characteristics for the EtO processed versus the non-EtO processed valves tested. CONCLUSIONS: We successfully fabricated and demonstrated physiological realizable temperature range operation of thermo-responsive polymer valves in-vitro and their suitability for standard EtO sterilization processing, a prerequisite for future in-vivo surgical implantation testing.

Cystatin C in newborns: a promising renal biomarker in search for standardization and validation.

OBJECTIVE: Neonatologists still commonly use creatinine as a proxy for renal clearance, despite issues related to neonatal (patho)physiology and methodology (assay variability). Cystatin C (CysC) has been suggested to be a more reliable biomarker, but assay related differences have also been reported in children and adults. We are unaware of any review on the assay related impact on CysC reference values in newborns. METHODS: A structured literature search was performed on published CysC values in (pre)term neonates. RESULTS: The extensive range (>5-fold) in serum CysC observations in neonates in part relates to the fact that CysC concentrations are higher at birth with subsequent decrease and that CysC concentrations are higher in preterm compared to term neonates. The CysC assay matters while disease characteristics also affect CysC values, but not always in the predicted direction. CONCLUSIONS: Similar to creatinine, the extensive CysC range in neonates is only in part explained by renal (patho)physiology. Its applicability in neonatal medicine can be further improved by use of assay specific reference values, adapted to neonatal renal physiology (e.g. weight, age) and should be compared to a gold standard such as inulin clearance.

Conceitos atuais sobre avaliação da maturidade pulmonar fetal / Current concepts on the assessment of fetal lung maturity

A Síndrome do Desconforto Respiratório (SDR), também conhecida como Doença da Membrana Hialina, é uma das principais causas de morbidade e mortalidade neonatal. O principal fator associado à SDR é a produção insuficiente de surfactante pulmonar, o que geralmente está associada à prematuridade. Alguns protocolos internacionais recomendam que a confirmação da maturidade pulmonar fetal seja realizada em partos eletivos antes de 39 semanas de gestação. Diversos são os métodos capazes de avaliar a maturidade pulmonar fetal, como a Relação Lecitina/Esfingomielina,a Pesquisa de Corpos Lamelares, a Relação Surfactante/Albumina, o percentual deFosfatidilglicerol, o Índice de Estabilidade da Espuma e o Shake Test ou Teste de Clements. Este estudo visa apresentar os principais métodos disponíveis e as recomendações atuais sobre quando realizar a avaliação da maturidade pulmonar fetal.(AU)

The Respiratory Distress Syndrome (RDS), also known as hyaline membrane disease, is a major cause of neonatal morbidity and mortality. The main factor associated with RDS is the insufficient production of pulmonary surfactant, which is usually associated with prematurity. Some international guidelines recommend that the confirmation of fetal lung maturity is performed in elective deliveries before 39 weeks of gestation. There are several methods to assess fetal lung maturity, such as the Lecithin/Sphingomyelin ratio, the Lamellar Body Count, the Surfactant/Albumin ratio, the percentage of phosphatidylglycerol, the Foam Stability Index and the Shake Test or Clements test. This study aims to present the main available methods and current recommendations on when to conduct the evaluation of fetal lung maturity.(AU)

The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS.

OBJECTIVE: We measured vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1(sVEGFR-1) concentrations in cord blood and tracheal aspirate fluid (TAF) in order to investigate the role of them in lung maturation and the severity of respiratory distress syndrome (RDS) in preterm newborns, born to preeclamptic mothers. METHODS: Newborns were divided into two groups as preterms born to preeclamptic mothers and preterms born to healthy mothers. They were also divided into two groups as severe RDS (sRDS) and mild RDS (mRDS) according to the need of surfactant and extent or type of ventilatory support. The concentrations of VEGF and sVEGFR-1 in cord blood and TAF (only in preterms with sRDS) were assayed by standardized enzyme-linked immunosorbent assay. RESULTS: When the patients were evaluated as sRDS and mRDS, cord blood VEGF and VEGF/sVEGFR-1 concentrations of preterms with sRDS were significantly lower than the concentrations of preterms with mRDS. Conversely, cord blood sVEGFR-1 concentrations of preterms with sRDS were significantly higher than the concentrations of preterms with mRDS. VEGF and sVEGFR-1 concentrations in TAF could be compared only between sRDS preterms, born to preeclampsia (+) and (-) mothers. No statistical significance was detected between the two groups when sVEGFR-1, VEGF and VEGF/sVEGFR-1 concentrations in TAF were compared. CONCLUSION: Preeclampsia seems not to have an important effect on VEGF and sVEGFR-1 concentrations of preterm newborns both in cord blood and in TAF. Low VEGF and high sVEGFR-1 concentrations seem to be associated with the severity of RDS irrespective of preeclampsia, suggesting that VEGF may be one of the main components of lung maturation.

Intraluminal tracheal occlusion using a modified 8-mm Z-stent in a sheep model of left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate pulmonary growth and development after fetoscopic intraluminal tracheal occlusion (FITO) using a modified 8-mm Z-stent in an ovine model of congenital left-sided diaphragmatic hernia (CDH). METHODS: Thirty-three time-dated ewes were studied: Group I: healthy controls; Group II: CDH controls (untreated); Group III: CDH treated with FITO. CDH was created in Groups II and III at 70-80 days' gestation. FITO was performed at 100-110 days. Left lung histological, morphometric, immunohistochemical and biochemical studies were conducted after delivery and euthanasia at 138 days. RESULTS: Fifteen (45%) animals (Group I: 3; Group II: 5; Group III: 7) were available for analysis. The left lung parenchymal volume to fetal weight ratios were similar between Groups I and III (p = 0.24), and higher than Group II (p < 0.05III (79 versus 75%, p = 0.26), compared to 41% in Group II (p < 0.05). Pulmonary hypoplasia occurred in 1/7 (16%) in the FITO group, compared to 100% in Group II and 0% in Group I (p = .003). DNA and protein were significantly increased in Group III (p < 0.001). The concentration of type II pneumocytes was similar between healthy controls and the FITO group, and was paradoxically increased in untreated hernia fetuses. There was no histological evidence of tracheal injury. CONCLUSION: FITO with a modified 8-mm Z-stent is associated with lung growth and maturation similar to controls without obvious deleterious effects. A phase I clinical trial of FITO with the modified 8-mm Z-stent in severe CDH patients seems warranted.

Maternal smoking and fetal lung signals--an in utero MRI investigation.

OBJECTIVE: To investigate whether fetal lung signals and fetal lung signal progression over gestation observed on magnetic resonance imaging are different in mothers who reported smoking during pregnancy compared with nonsmoking controls. METHOD: Cross-sectional retrospective study of 100 consecutive singleton pregnancies that underwent magnetic resonance imaging. Fetal lung-liver signal intensity ratios of 18 fetuses of mothers who reported smoking during pregnancy were compared with 82 fetuses of nonsmoking controls. RESULTS: Average gestational age at magnetic resonance imaging was 26.4 ± 5.2 weeks (Range 18.4-38.2 weeks). Cases reported smoking between 2 and 15 cigarettes per day. The mean number of cigarettes per day for cases was 9.2 ± 3.4. Mean fetal lung-liver signal intensity ratios did not differ significantly between the two groups (p = 0.8). They showed a linear increase with gestational age (r(2) = 0.3). Multiple regression analysis of lung-liver signal intensity ratios using gestational age and smoking status as predictors revealed a significant influence of gestational age (p < 0.0001) but not maternal smoking status (p = 0.8) on fetal lung-liver signal intensity ratios. CONCLUSIONS: Fetuses of mothers who reported smoking during pregnancy show similar lung signals and lung signal progression over gestation on magnetic resonance imaging as nonsmoking controls.

VEGF levels in humans and animal models with RDS and BPD: temporal relationships.

Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) contribute significantly to neonatal morbidity and mortality. Pulmonary function depends on the interaction between alveolar microvasculature and airspace development. While it has been shown in various animal models that vascular endothelial growth factor (VEGF) and its receptors increase in normal animal lung development, its pathophysiological role in neonatal respiratory failure is not yet entirely clear. Current animal and human studies exhibit controversial results. Though animal models are invaluable tools in the study of human lung disease, inherent differences in physiology mandate clarification of the timing of these studies to ensure that they appropriately correlate with the human stages of lung development. The purpose of this review article is to highlight the importance of considering the temporal relationship of VEGF and lung development in human neonates and developmentally-appropriate animal models with RDS and BPD.

Inflammation and lung maturation from stretch injury in preterm fetal sheep.

Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7-8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating V(T) to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH(2)O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high V(T) ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA.

Effect of cytomegalovirus infection on temporal lobe development in utero: quantitative MRI studies.

Several environmental factors, including viral infections during fetal development, are known to increase the risk of schizophrenia. Cytomegalovirus (CMV) is the main cause of viral congenital infection. Since changes in temporal lobe structures are a consistent finding in imaging studies of adult schizophrenics, we investigated possible derangement in temporal lobe development in CMV infected fetuses. Abdominal MRI (1.5 T) was performed using a single-shot fast spin echo T2-weighted sequence. MRI volumetry was employed to measure brain and temporal lobe size in 27 CMV infected fetuses and 52 gestational age matched controls in utero. The ratio of temporal lobe to whole brain was computed for each fetus and group comparisons were performed using Student's t-test or ANOVA. Temporal lobe volumes, normalized to whole brain and co-varied with gestational age; were significantly smaller in fetuses infected with CMV compared to uninfected fetuses. (Infected group mean ± SEM: 0.086 ± 0.006, controls: 0.113 ± 0.003, p<0.0001). Infection during the 1st and 2nd trimester had a more pronounced effect than infection during the 3rd trimester. Infected fetuses with no MRI findings had significantly lower temporal lobe/whole brain ratios than controls (0.092 ± 0.008, p<0.01, N=11) and the lowest ratios were observed in fetuses with overt findings such as cysts or gray matter heterotopy (0.067 ± 0.015). These results demonstrate the ability of quantitative fetal brain MRI to detect previously unreported, specific deficits in brain development in CMV infected fetuses, which, in conjunction with other genetic and environmental factors, may contribute to the risk of developing schizophrenia later in life.

Antenatal fetal VEGF therapy to promote pulmonary maturation in a preterm rabbit model.

AIM: To assess the effects of fetal tracheal administration of VEGF on pulmonary maturation in a preterm rabbit model. METHODS: On day 26 (term=31days), fetal rabbits received recombinant rat VEGF (30microg in 70microL normal saline) or placebo (normal saline 70microL) intratracheally, with or without subsequent tracheal occlusion. Non-operated littermates served as internal controls. Fetuses were harvested on day 28 for morphometric study of the lungs or for mechanical ventilation and measurement of lung mechanics. In total, 96 fetuses from 42 does were used, 47 for ventilation and 49 for morphometry. RESULTS: In fetuses receiving intratracheal VEGF, an increase in immunoreactivity for Flk-1 was observed throughout the lung parenchyma. Tracheal occlusion (TO) adversely affected pulmonary mechanics as compared to un-occluded controls. That effect is partly reversed by intratracheal VEGF. Intratracheal injection of VEGF without tracheal occlusion improves lung mechanics but no more than what was observed in placebo injected controls. CONCLUSION: Antenatal intratracheal VEGF administration was associated with an increase in Flk-1 immunoreactivity. It also improves lung mechanics, however more so when the trachea is occluded. Without TO, the effects were comparable to placebo controls.

Hidden in plain sight: the mammary line in males may be the missing link regulating inguinoscrotal testicular descent.

BACKGROUND/PURPOSE: Inguinoscrotal testicular descent is controlled by androgens and the genitofemoral nerve, but the trigger for what makes the gubernaculum become a migratory organ like a limb bud remains unknown. Recent observations in the flutamide-treated rat suggested a link with the mammary line. We aimed, therefore, to reassess histologic anatomy in 2 different rodent models of androgen blockade, the testicular feminisation mouse (TFM) and the flutamide-treated rat. METHODS: Neonatal TFM mice and fetal and neonatal rats after pretreatment of dams with an antiandrogen, flutamide (75 mg/kg; sunflower oil; days 16-19), were prepared for histologic analysis of the inguinal region and compared with fetal and neonatal controls. RESULTS: Fetal control rats (E15.5 days) showed a mammary bud just outside the future inguinal canal adjacent to the gubernaculum. Neonatal TFM mice showed persistence of the inguinal breast bud supplied by the genitofemoral nerve. Flutamide-treated rats (D2) showed the gubernaculum surrounded by a persisting breast bud. CONCLUSIONS: The inguinal mammary line is adjacent to the gubernaculum in fetal rodents, and after androgen blockade, the gubernaculum becomes connected to the breast. The male mammary line, which is hidden in plain sight outside the inguinal canal, is made visible by androgen blockade. It may be the missing link in testicular descent, regulating gubernacular migration.

In utero iron status and auditory neural maturation in premature infants as evaluated by auditory brainstem response.

OBJECTIVE: To determine whether cord ferritin (CF) concentration, an index of in utero iron status, is associated with auditory neural maturation in premature infants. STUDY DESIGN: A prospective cohort study was performed to compare auditory neural maturation in infants with latent iron deficiency (CF 11-75 ng/mL) and infants with normal iron status (CF > 75 ng/mL) at birth. Our inclusion criteria were infants of 27-33 weeks gestational age who were admitted to the neonatal intensive care unit between July 2007 and November 2008 within 12 hours after birth and had cord blood collected. Infants with TORCH infections (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex), chromosomal disorders, craniofacial anomalies, culture-proven sepsis, and/or unstable conditions were excluded. CF level was measured using a chemiluminescence immunoassay method. Bilateral monaural auditory brainstem evoked response (ABR) was assessed using 80-dB nHL click stimuli at a repetition rate of 29.9/seconds within 48 hours after birth. RESULTS: Of the 80 infants studied, 35 had latent iron deficiency. After controlling for confounders, the infants with latent iron deficiency had significantly prolonged absolute wave latencies I, III, and V and decreased frequency of mature ABR waveforms compared with the infants with normal iron status. CONCLUSION: Premature infants with in utero latent iron deficiency have abnormal auditory neural maturation compared with infants with normal in utero iron status.

[Fetoscopic surgery as prenatal intervention for isolated congenital diaphragmatic hernia]. / Die fetoskopische Chirurgie als Möglichkeit der pränatalen Intervention bei der isolierten angeborenen Zwerchfellhernie.

Congenital diaphragmatic hernia (CDH) occurs sporadically with an incidence of 1:2,500 live births. Despite the progress in neonatal intensive care, CDH remains associated with a mortality of at least 30 % in isolated cases. The in essence surgically correctable defect of the diaphragm enables the prenatal herniation of abdominal organs into the thoracic cavity. The resulting abnormal development of the airways and pulmonary vessels causes neonatal respiratory insufficiency and persistent pulmonary hypertension. The condition can be diagnosed prenatally and the degree of pulmonary hypoplasia, which determines the postnatal course, can be measured to make an -individual prognosis. In severely affected patients, prenatal surgery may improve neonatal outcome by reversing pulmonary hypoplasia. This is currently implemented by percutaneous fetoscopic endoluminal tracheal occlusion (FETO) to trigger fetal lung growth. Although there are no maternal complications, preterm rupture of the membranes remains the major drawback of the procedure (20 % < 34 weeks). However, as compared to historical controls of a similar severity, survival as well as early neonatal morbidity are significantly improved by FETO. As a consequence, a multicentre randomised-controlled trial in fetuses with moderate hypoplasia on FETO compared to expectant management has been started ( www.totaltrial.eu). Primary outcome measure is survival without chronic lung disease (i. e., with-out bronchopulmonary dysplasia). A trial in severely affected -fetuses with survival as main outcome is currently under review by ethics committee. A standardised neonatal management enables optimal treatment and multicentre compatibility. It remains to be proven if fetoscopic surgery can maintain a solid position in the prenatal treatment of CDH to improve both mortality and morbidity of the affected children.

Surfactant in the preterm infant: what's going on.

Surfactant treatment has been demonstrated to decrease pneumothorax and mortality in preterm infants. Natural surfactants are better than synthetic surfactants. Early rescue treatment with surfactant is better than late treatment, whereas the role of surfactant prophylaxis is under re-evaluation due to the actual large diffusion of antenatal steroid and nasal continuous positive airway pressure treatment which have changed the clinical characteristics of preterm infants with respiratory distress syndrome. It is possible that in the next future anti-inflammatory and anti-oxidant properties of exogenous natural surfactants may be improved through their combination with adequate agents with the aim of counteracting the pathogenetic role of inflammatory and oxidative lung injury injuries in the development of brochopulmonary dysplasia.

Delayed lung maturation of foetus of diabetic mother rats develop with a diminish, but without changes in the proportion of type I and II pneumocytes, and decreased expression of protein D-associated surfactant factor.

Newborn children of diabetic mothers have an increased morbidity and mortality because of respiratory distress syndrome. We study lung histogenesis during intrauterine development of offspring of diabetic Sprague-Dawley rats at 18, 19 and 21 days of gestation (DG). Pregnant rats were grouped into diabetic (streptozotocin-induced), citrate, and control groups; five female and five male offspring were selected randomly from each group at 18, 19 and 21 DG, and a biopsy of the lung was taken and processed in paraffin for histological examination. The biopsy for the transmission electron microscopy (TEM) analysis was taken at 21 days. A delay in alveolization of the offspring at 18, 19 and 21 days of the diabetic group was observed, which was confirmed at TEM level, and also less quantity of protein D associated to surfactant in diabetic group was detected (P < 0.001). The foetuses of the diabetic group presented a delay in lung histogenesis and in differentiation of the type II pneumocytes cells, but conserved the proportion with a decrease in 50% of pneumocytes, accompanied by a diminish of protein D associated to surfactant factor.

Antenatal inflammation and lung injury: prenatal origin of neonatal disease.

INTRODUCTION: Antenatal inflammation in utero may be associated with lung injury and subsequent aberrant lung development resulting in bronchopulmonary dysplasia (BPD). BPD has become a developmental disease with a uniform arrest in lung development. STUDY DESIGN: The role of antenatal inflammation in the induction of lung injury was explored in a sheep model suitable for the study of lung development with respect to human development. Chorioamnionitis was induced by a single injection of endotoxin into the amniotic cavity under ultrasound guidance. RESULT: Endotoxin-induced chorioamnionitis caused a cascade of lung injury, pulmonary inflammation and remodeling in the fetal lung similar to lung injury previously described in adult animal models. The structural changes in the fetal lung after chorioamnionitis showed little to no fibrosis and alveolar/microvascular simplification similar to new BPD. The identified cytokine networks and regulators may explain the absence of fibrosis and lung simplification after strictly intra-uterine inflammation. CONCLUSION: The mechanisms of antenatal inflammation in the fetal lung were multifactorial and could be antenatally modulated. Fetal pulmonary inflammation was temporarily suppressed by maternal glucocorticoid therapy. However, pulmonary inflammation could be augmented postnatally by resuscitation, oxygen toxicity, mechanical ventilation and pulmonary and systemic infection, which opens a broad window of clinical options.

Magnetic resonance imaging assessment of brain maturation in preterm neonates with punctate white matter lesions.

INTRODUCTION: Early white matter (WM) injury affects brain maturation in preterm infants as revealed by diffusion tensor imaging and volumetric magnetic resonance (MR) imaging at term postmenstrual age (PMA). The aim of the study was to assess quantitatively brain maturation in preterm infants with and without milder forms of WM damage (punctate WM lesions, PWML) using conventional MRI. METHODS: Brain development was quantitatively assessed using a previously validated scoring system (total maturation score, TMS) which utilizes four parameters (progressive myelination and cortical infolding, progressive involution of glial cell migration bands and germinal matrix tissue). PWML were defined as foci of increased signal on T1-weighted images and decreased signal on T2-weighted images with no evidence of cystic degeneration. A group of 22 preterm infants with PWML at term PMA (PWML group) were compared with 22 matched controls with a normal MR appearance. RESULTS: The two groups were comparable concerning gestational age, birth weight and PMA. TMS was significantly lower in the PWML group than in the control group (mean TMS 12.44 +/- 2.31 vs 14.00 +/- 1.44; P = 0.011). Myelination (mean 2.76 +/- 0.42 PWML group vs 3.32 +/- 0.55 control group, P = 0.003) and cortical folding (3.64 +/- 0.79 vs 4.09 +/- 0.43, P = 0.027) appeared to be significantly delayed in babies with PWML. CONCLUSION: Conventional MRI appears able to quantify morphological changes in brain maturation of preterm babies with PWML; delayed myelination and reduced cortical infolding seem to be the most significant aspects.

Role of platelet-derived growth factor-B, vascular endothelial growth factor, insulin-like growth factor-II, mitogen-activated protein kinase and transforming growth factor-beta1 in expansion-induced lung growth in fetal sheep.

Increased fetal lung expansion induces lung growth, cell differentiation and extracellular matrix remodelling, although the mechanisms involved are unknown. Platelet-derived growth factor (PDGF)-B, vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-II are mitogens activating the mitogen-activated protein kinase (MAPK) pathway, whereas transforming growth factor (TGF)-beta1 induces differentiation and extracellular matrix remodelling. In the present study, we investigated the mRNA levels of PDGF-B, VEGF, IGF-II and TGF-beta1, as well as active MAPK levels, during increased fetal lung expansion induced by tracheal obstruction (TO) in sheep for 0 (controls), 36 h or 2, 4, or 10 days (n = 5 in each group). The 3.7-kb VEGF transcript increased by 30% (P < 0.05) at 36 h TO. The expression of PDGF-B decreased by approximately 25% (P < 0.01) at 2-10 days TO. In contrast, TGF-beta1 mRNA increased by 96% (P < 0.05) at 10 days TO, when bioactive TGF-beta1 decreased by 55% (P < 0.05). Insulin-like growth factor-II mRNA tended to increase at 10 days TO (37% above controls; P = 0.07), whereas mRNA for its receptor, IGF1R, was reduced by TO. There was no change in active MAPK levels preceding or at the time of a TO-induced 800% increase in cell proliferation. We conclude that VEGF is likely to promote expansion-induced endothelial cell proliferation, but the mechanisms underlying expansion-induced proliferation of fibroblasts and alveolar epithelial cells are unlikely to be mediated by increases in PDGF-B or IGF-II expression or activation of the MAPK pathway.