Effects of intra-uterine growth restriction on the control of breathing and lung development after birth

1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweig ht can increase the risk for airway dysfunction in children and adults, Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and p rogressive hypercapnia during the first weeks after birth in postnatal lamb s in which IUGR was induced by chronic placental insufficiency. It was foun d that the postnatal increase in ventilatory sensitivity to hypoxia observe d in control lambs was diminished in low birthweight lambs; in contrast, th e sensitivity to hypercapnia was not affected, In other studies, we found t hat IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings sggest that the prenatal development of the brain-stem or r espiratory chemoreceptors may be affected by intra-uterine factors associat ed with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possib le that the structure of respiratory muscles and, hence, their ability to m aintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, i n particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liqui d secretion and volume, in relation to bodyweight, were unaffected; however , there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after b irth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in Foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung functi on, to determine mechanisns underlying these effects and to determine the c apacity for postnatal recovery.