Structural aspects of postnatal lung development - alveolar formation and growth

The human lung is born with a fraction of the adult complement of alveoli. The postnatal stages of human lung development comprise an alveolar stage, a stage of microvascular maturation, and very likely a stage of late alveolarization. The characteristic structural features of the alveolar stage are well known; they are very alike in human and rat lungs. The bases for alveolar formation are represented by immature inter-airspace walls with two capillary layers with a central sheet of connective tissue. Interalveolar septa are formed by folding up of one of the two capillary layers. In the alveolar stage, alveolar formation occurs rapidly and is typically very conspicuous in both species; it has therefore been termed 'bulk alveolarization'. During and after alveolarization the septa with double capillary networks are restructured to the mature form with a single network. This happens in the stage of microvascular maturation. After these steps the lung proceeds to a phase of growth during which capillary growth by intussusception plays an important role in supporting gas exchange. In view of reports that alveoli are added after the stage of microvascular maturation, the question arises whether the present concept of alveolar formation needs revision. On the basis of morphological and experimental findings we can state that mature lungs contain all the features needed for 'late alveolarization' by the classical septation process. Because of the high plasticity of the lung tissues, late alveolarization or some forms of compensatory alveolar formation may be considered for the human lung.     

Developmental changes in endothelial vasoactive and angiogenic growth factors in the human perinatal lung

Little is known of the mechanisms underlying the marked fall in pulmonary vascular resistance that occurs at birth, but changes in the expression of endothelial vasoactive and angiogenic factors during lung development might play a key role. Nitric oxide, endothelin-1, and vascular endothelial growth factor have critical effects on vascular tone and cell growth. Here, we investigated the protein expression of endothelial nitric oxide synthase, endothelin-1 and its receptors, and vascular endothelial growth factor in pulmonary necropsy samples from 14 fetuses of different gestational ages and from 5 infants. Expression of endothelin-1 and its receptor endothelin-A was strong and stable. In contrast, expression of the endothelin-B receptor was weak in early gestation, then increased markedly in mid-gestation and remained high thereafter. The expression of endothelial nitric oxide synthase and vascular endothelial growth factor fell markedly after mid-gestation and remained low thereafter. These data point to a discrepancy between maturational and functional changes in human pulmonary vascular structures. The weak perinatal expression of endothelial nitric oxide could suggest that other potent vasodilatory mediators are responsible for the marked vasodilation observed at birth.     

Cyclooxygenase-2 in human perinatal lung

Cyclooxygenases-1 and -2 are the key enzymes in the conversion of arachidonic acid to prostanoids. Cyclooxygenase-2 (COX-2) takes part both in inflammation and in control of cell growth. COX-2 immunohistochemistry was performed on lung tissues from autopsies, with four groups included: fetuses (n = 4, GA = 16.0 to 32.0 wk), preterm infants (n = 10, GA = 23.0 to 29.9 wk), term infants (n = 6, GA = 38.7 to 42.0 wk), and infants with bronchopulmonary dysplasia (BPD) (n = 4, GA = 28.9 to 30.7 wk). COX-2 staining occurred exclusively in the epithelial cells resembling type II pneumocytes in the alveolae, and in ciliated epithelial cells in the bronchi. In fetuses, moderate intensity alveolar staining was seen in 90-100% cells lining the alveolar epithelium. In preterm infants, high intensity alveolar staining was seen in a scattered pattern. In term infants, the alveolar staining was also scattered, but with a lower proportion of positive cells. In BPD no staining appeared in alveolar epithelial cells. The most intense bronchial staining was found in fetuses and the least intense in term infants; staining was also seen in BPD. COX-2 is present in human perinatal lung from the gestational age of 16 wk, in a changing pattern. We suggest that COX-2 may, in addition to participating in inflammation, also play a developmental role in the perinatal lung.     

Information in perinatal medicine: ethical aspects]

Besides the undeniable need to respect parental autonomy, providing information is a legal and moral obligation, to be informed a basic right. The act of informing should be considered as an exchange and necessarily begins by listening to the other. According to the jurisprudence of the Court of Cassation that draws on Article 35 of the Deontological Code, information has to be clear (implying an educational effort, availability and to check that the information has been well understood), appropriate (adapted to each situation and person) and honest (which supposes a moral contract between parents and physicians). Loyalty implies a consideration of the uncertainty underlying medical practice, and of the limitations in arriving at a prognosis. Indeed, caution needs to be exercised in conveying information, taking into account the risk of its becoming self-fulfilling, which could modify the way in which parents take care of their child. The information given has to be coherent, both within the spatial dimension (coherence of information between the different maternity services in the perinatal network) and the temporal dimension (coherence of information between pre- and postnatal stages). It must be acknowledged that information is essentially subjective. There is a fundamental difference between coherence and uniformity, and as regards information, uniformity is neither possible nor desirable. In each situation, priority must be given to oral information delivered in an appropriate material context. The principle of establishing, in the medical file, a written trace of the information given at various stages is one way to guarantee its coherence.     

Glucocorticoids,inflammation and the perinatal lung

Many women delivering preterm infants at less than 30 weeks gestation have subclinical chorioamnionitis. Based on current guidelines, maternal glucocorticoid treatment is given to induce lung maturation. Fetal exposure to proinflammation can cause acute and chronic injury, but inflammation also can induce fetal lung maturation. Both antenatal glucocorticoids and inflammation modulate lung development, by inducing the surfactant system, inducing structural maturation, and inhibiting alveolarization. The opportunities for the future are to develop new safer strategies to mature the preterm foetus, and the risks are potential adverse interactions of repetitive glucocorticoid exposures and unrecognized fetal exposure to inflammation.     

Velocity of head growth during the perinatal period

Growth velocity of head circumference was studied longitudinally in different gestational age groups of 222 appropriate-weight-for-dates (AFD) and 94 small-for-dates (SFD) healthy infants during the first 5 months of life. Term AFD and SFD infants showed a steady slowing of growth rate of head circumference from birth. In contrast, preterm AFD infants of less than 36 weeks' gestation showed an increasing velocity of growth followed by slowing, with maximum velocity occurring between 30 and 40 days after birth. The shorter the postconceptional age at birth the later maximum velocity occurred. However, those preterm AFD infants of between 30 and 33 weeks' gestation who were given a high caloric feed showed a similar velocity curve to that of infants of 34-37 weeks of gestation. Cross-sectional data were used to estimate growth velocity of head circumference in the fetus. Two conclusions emerged. First, there is a slowing of head growth velocity from 31 weeks' gestation in utero, and second, term infants show a marked increase in volocity after birth. Though the occurrence of maximum velocity of head growth is delayed in the preterm infant, the net effect is such that at a given postconceptional age his head circumference is greater than that of the term infant, at least within the first 5 postnatal months.     

Prediction and perinatal outcomes of fetal growth restriction

Assessment of fetal growth and wellbeing is one of the major purposes of antenatal care. Some fetuses have smaller than expected growth in utero and while some of these fetuses are constitutionally small, others have failed to meet their growth potential, that is they are growth restricted. While severe growth restriction is uncommon, the consequences of it being undetected may include perinatal death or severe morbidity. It is, therefore, important to have strategies in place to detect the fetus at risk of growth restriction. These would include an assessment of 'prior risk' from maternal history and examination combined with the results of biochemical and ultrasound investigations, the most promising of which are uterine artery Doppler and biochemistry. We discuss some of the factors to consider when stratifying the obstetric population into degrees of likelihood for growth restriction, and discuss aspects of the management and outcome of pregnancies complicated by growth restriction.     

Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia

Moderate hypothermia is a novel neuroprotective therapy for full term neonates with severe perinatal asphyxia. Although the therapy appears to be safe, admission to a level III neonatal intensive care unit of these patients is justified. Potential complications include hypotension, tube obstruction due to sticky secretions, severe bradycardia, and thrombocytopenia. Furthermore, doses of commonly used drugs such as sedatives, anticonvulsants and antibiotics should be adjusted during hypothermia and on rewarming, and should be monitored carefully. Further studies aiming at optimizing onset, duration, and depth of hypothermia in neonates are necessary. Combination of hypothermia with drugs may further improve neuroprotection in asphyxiated full term neonates.     

Effects of maternal hypervitaminosis A on perinatal rat lung histology

Retinyl acetate (160,000 USP/day in corn oil) was administered orally to pregnant Long-Evans rats during the last third of gestation. Postnatal evaluation of this treatment was assessed by examination of histologic sections of lung taken from stillborns and from pups that survived several hours. In all sections from treated litters, expansion of lung either did not appear to have occurred, or was not uniform. Control lung sections were uniformly expanded in all cases. It appears that hypervitaminosis A during the fetal period alters normal lung maturation. These data provide additional supporting evidence that the fetal period is susceptible to teratogens.