Partial pulmonary embolization disrupts alveolarization in fetal sheep

BACKGROUND: Although bronchopulmonary dysplasia is closely associated with an arrest of alveolar development and pulmonary capillary dysplasia, it is unknown whether these two features are causally related. To investigate the relationship between pulmonary capillaries and alveolar formation, we partially embolized the pulmonary capillary bed. METHODS: Partial pulmonary embolization (PPE) was induced in chronically catheterized fetal sheep by injection of microspheres into the left pulmonary artery for 1 day (1d PPE; 115d gestational age; GA) or 5 days (5d PPE; 110-115d GA). Control fetuses received vehicle injections. Lung morphology, secondary septal crests, elastin, collagen, myofibroblast, PECAM1 and HIF1 alpha abundance and localization were determined histologically. VEGF-A, Flk-1, PDGF-A and PDGF-R alpha mRNA levels were measured using real-time PCR. RESULTS: At 130d GA (term approximately 147d), in embolized regions of the lung the percentage of lung occupied by tissue was increased from 29 +/- 1% in controls to 35 +/- 1% in 1d PPE and 44 +/- 1% in 5d PPE fetuses (p < 0.001). Secondary septal crest density was reduced from 8 +/- 0% in controls to 5 +/- 0% in 1d PPE and 4 +/- 0% in 5d PPE fetuses (p < 0.05), indicating impaired alveolar formation. The deposition of differentiated myofibroblasts (23 +/- 1% vs 28 +/- 1%; p < 0.001) and elastin fibres (3 +/- 0% vs 4 +/- 0%; p < 0.05) were also impaired in embolized lung regions of PPE fetuses compared to controls. PPE did not alter the deposition of collagen or PECAM1. At 116d GA in 5d PPE fetuses, markers of hypoxia indicated that a small and transient hypoxic event had occurred (hypoxia in 6.7 +/- 1.4% of the tissue within embolized regions of 5d PPE fetuses at 116d compared to 0.8 +/- 0.2% of tissue in control regions). There was no change in the proportion of tissue labelled with HIF1 alpha. There was no change in mRNA levels of the angiogenic factors VEGF and Flk-1, although a small increase in PDGF-R alpha expression at 116d GA, from 1.00 +/- 0.12 in control fetuses to 1.61 +/- 0.18 in 5d PPE fetuses may account for impaired differentiation of alveolar myofibroblasts and alveolar development. CONCLUSIONS: PPE impairs alveolarization without adverse systemic effects and is a novel model for investigating the role of pulmonary capillaries and alveolar myofibroblasts in alveolar formation

Qualitatively and quantitatively similar effects of active and passive maternal tobacco smoke exposure on in utero mutagenesis at the HPRT locus

BACKGROUND: Induced mutagenesis in utero is likely to have life-long repercussions for the exposed fetus, affecting survival, birth weight and susceptibility to both childhood and adult-onset diseases, such as cancer. In the general population, such exposures are likely to be a consequence of the lifestyle choices of the parents, with exposure to tobacco smoke one of the most pervasive and easily documented. Previous studies attempting to establish a direct link between active smoking and levels of somatic mutation have largely discounted the effects of passive or secondary exposure, and have produced contradictory results. METHODS: Data from three studies of possible smoking effects on in utero mutagenesis at the HPRT locus were compiled and reanalyzed, alone and in combination. Where possible, passive exposure to environmental tobacco smoke was considered as a separate category of exposure, rather than being included in the non-smoking controls. Molecular spectra from these studies were reanalyzed after adjustment for reported mutation frequencies from the individual studies and the entire data set. RESULTS: A series of related studies on mutation at the X-linked HPRT locus in human newborn cord blood samples has led to the novel conclusion that only passive maternal exposure to tobacco mutagens has a significant effect on the developing baby. We performed a pooled analysis of the complete data from these studies, at the levels of both induced mutation frequency and the resulting mutational spectrum. CONCLUSION: Our analysis reveals a more commonsensical, yet no less cautionary result: both active maternal smoking and secondary maternal exposure produce quantitatively and qualitatively indistinguishable increases in fetal HPRT mutation. Further, it appears that this effect is not perceptibly ameliorated if the mother adjusts her behavior (i.e. stops smoking) when pregnancy is confirmed, although this conclusion may also be affected by continued passive exposure

Brain development (sulci and gyri) as assessed by early postnatal MR imaging in preterm and term newborn infants.

OBJECTIVE: To investigate fetal brain development in vivo using early postnatal cranial MRI in term and preterm newborn infants. STUDY DESIGN: 51 infants, 1.5-T whole-body system, extremity coil, spin-echo images obtained in all three planes (T1- and T2-weighted). Independent review by two neuroradiologists (blinded for gestational age and medical history) regarding the development of 12 sulci and 10 gyri using a modified scoring system. Gestational age was obtained either by ultrasound or from the first day of the last menstrual period. Exclusion criteria: head circumference &lt;10th or &gt;90th percentile, cerebral malformation, chromosomal/metabolic disorder. RESULTS AND CONCLUSION: Age at study ranged from 23 5/7-43 0/7 postmenstrual weeks. Brain maturation starts in the central area and proceeds towards the parieto-occipital cortex. The frontal cortex develops last. Transition to degrees 1, degrees 2 and, degrees 3 starts at week 25, 32 and 35 in the central cortex and is completed at week 34, 36 and 39, respectively. Our data compare favourably with the two previously published reports about brain maturation. Early MR imaging seems therefore to be suited to study maturation of the fetal brain. This may be of pathophysiological relevance in neonatal intensive care and neurological follow-up studies

Coiling characteristics of umbilical cords in breech vs. vertex presentation

Objective: To compare selected umbilical cord parameters, especially cord coiling, between breech and vertex presentations. Methods: We prospectively collected umbilical cords from uncomplicated breech and vertex obtained during elective term cesarean deliveries. We compared various cord parameters between the two groups as well as data regarding obstetric history and pregnancy outcome. Results: We evaluated 55 umbilical cords from breech and 55 from vertex deliveries. Umbilical cord length (56.93 cm vs. 63.95 cm, P=0.05), number of coils (5.1±0.4 vs. 11.7±0.6, P&#60;0.0001) and umbilical cord index (UCI) (0.09 coils/cm vs. 0.18 coils/cm, P&#60;0.0001) were all significantly lower for breech presentations and remained significant following multivariate analysis. Conclusion: We document significant differences in umbilical coiling and the UCI between breech and vertex presentation. The precise reason for these differences is still unclear.Peer Reviewe