The human lung is a complex and highly specialized organ with over 40 differentiated cell types. Optimal lung function is determined prenatally and an in utero adverse event may interfere with the delicate lung development process and lead to variable degrees of pulmonary hypoplasia.
Fetal lung underdevelopment is a major concern for obstetricians and pediatricians since pulmonary hypoplasia (PH) may lead to severe respiratory distress immediately after birth and even to neonatal death or potential long-term morbidity. During a five year period, the author had the opportunity to conduct in experienced teams several studies on different fetal malformations that dealt with multiple aspects in the wide spectrum of PH: gastroschisis (GAS), giant omphalocele (GO), low obstructive uropathies (LUTO) and congenital diaphragmatic hernia (CDH). The thesis, which focuses on four papers published as first author, reviews important features of PH for a fetal medicine specialist. Three other publications as co-author are presented at the end of the manuscript as "additional contributions".
CHAPTER 1:
Introduction
1.1 Normal fetal lung development 11
1.2 Fetal lung growth regulation 16
1.3 Purpose of the thesis 18
1.4 Content of the thesis 19
CHAPTER 2:
Pulmonary Hypoplasia (PH)
2.1 Definition 21
2.2 Epidemiology 23
2.3 Factors adversely affecting lung growth leading to PH 24
2.3.1 Reduction in intrathoracic space 25
2.3.1.1 Congenital diaphragmatic hernia (CDH) 25
2.3.1.2 Congenital cystic adenomatoid malformation
(CPAM) 32
2.3.1.3 Bronchopulmonary sequestration (BPS) 37
2.3.1.4 Fetal pleural effusions 39
2.3.1.5 Skeletal disorders 41
2.3.2 Reduction in fetal breathing movements (FBM) 43
2.3.2.1 Anterior abdominal wall defects (AWD) 44
2.3.2.2 Reduction in amniotic and lung fluid volume 61
CHAPTER 3:
Prenatal management of pulmonary hypoplasia and potential
therapeutic approach
3.1 Pulmonary hypoplasia: prenatal diagnosis and evaluation 65
3.2 Pulmonary hypoplasia in lower obstructive uropathies
(LUTO) 69
3.3 Pulmonary hypoplasia in CDH 85
3.3.1 Role of left main bronchus occlusion
in the prenatal treatment of CDH 85
CHAPTER 4:
Summary, general discussion and perspectives 117
REFERENCES 125
ADDITIONAL CONTRIBUTIONS 143