588 D.K. Vasudev and D. Fielda small number of patterns have been recognized (e.g., alveolar capillarydysplasia), and these are now being linked to speciﬁc geneticabnormalities.II. PathophysiologyThe exact pathophysiology varies with the underlying mechanism.A. Reduced lung size (e.g., secondary to thoracic dystrophy).B. Structural immaturity (e.g., secondary to oligohydramnios).C. Diffusion deﬁcit (e.g., secondary to alveolar capillary dysplasia). The mainfunctional problem that results in all the above is pulmonary insufﬁciency.The main clinical problem tends to be oxygen transfer (lack of adequatepulmonary surface area).III. DiagnosisA. Antenatal. Diagnosis may be anticipated on the basis of maternal antenatalultrasound scan (e.g., severe oligohydramnios, small fetal chest cavity).Magnetic resonance imaging is also being used.B. Postnatal. Diagnosis may be apparent immediately after birth if hypoplasiais severe (i.e., cannot be resuscitated, or severe respiratory distress frombirth), or is part of recognizable syndrome (e.g., oligohydramnios sequence).When the infant presents later with apparently isolated mild to moderaterespiratory distress, the diagnosis may be delayed. Syndromes either pri-marily or secondarily associated with pulmonary hypoplasia should be con-sidered. Similarly, conditions that can mimic these signs (e.g., infection)should be excluded. In all cases where hypoplasia is the possible diagnosis,the following should be considered:1. Genetics consult2. Measurement of lung volumes3. Measurement of pulmonary compliance4. Examination of surfactant genotype5. Lung biopsyC. The choice of investigation will vary with the severity of the child’s prob-lem. In severe respiratory failure, lung biopsy may be performed as a termi-nal event to permit diagnosis and counselling for future pregnancies (seebelow). If more minor respiratory problems (e.g., unexplained persistenttachypnea), assessment of pulmonary mechanics is appropriate.Table 66.1 Factors which can impair lung growth in utero1. Compression of chest (e.g., oligohydramnios—all causes)2. Compression of lung (e.g., effusion, diaphragmatic hernia)3. Reduction in fetal breathing (e.g., neuromuscular disorder)
58966 Pulmonary Hypoplasia/AgenesisIV. ManagementA. Antenatal. If a diagnosis of pulmonary hypoplasia is made in utero, familiesshould be counselled by the obstetrician, neonatologist, clinical geneticist,and surgeon (if appropriate). Potential options will vary according to thefollowing:1. Primary diagnosis and its prognosis2. Degree of diagnostic certainty resulting from the evaluation. Essentiallyparents must decide betweena. Termination of pregnancy (criteria and regulations vary markedlyamong and within countries).b. Continuing the pregnancy with postnatal intervention and“treatment.”c. Antenatal intervention, practiced only in relation to certain condi-tions (e.g., bilateral pleural effusions). Results vary with both thenature and severity of underlying problem. Evidence of beneﬁt forsuch interventions is not established.B. At delivery, standard resuscitation should take place. Where antenatal scansindicate, special measures (e.g., draining pleural effusions) should be per-formed. Vigorous resuscitation of infants with small volume lungs oftenresults in pneumothorax. If dysmorphic features in the child indicate alethal syndrome, or if oxygenation proves impossible, intensive care maybe withdrawn.C. In the NICU1. Establish routine monitoring. Invasive blood pressure/arterial access isessential in the severest cases; central venous pressure monitoring, ifavailable via the umbilical vein, is of great help in ﬂuid management.2. Ensure adequate systemic blood pressure (maintain tissue perfusion andminimize right-to-left shunting). This may require both infusion of ﬂu-ids and inotropes. Take care not to induce ﬂuid overload.3. Provide adequate respiratory support. Infants with mild hypoplasia maynot require ventilation. For those requiring invasive support, local prac-tice usually governs the first choice; both conventional and high-frequency devices can be used with success. Aim to provide stability ofblood gases (i.e., sufﬁcient oxygenation to prevent metabolic acidosis).More aggressive ventilation may induce pulmonary damage and furtherimpair lung function. If blood gas control proves impossible despitemaximum support, the child should be considered nonviable.4. Attempts to “treat” pulmonary hypoplasia using a combination of con-tinuous positive airway pressure (CPAP) with inhaled nitric oxide (iNO)over a prolonged period has shown some promise but requires fullerevaluation.
590 D.K. Vasudev and D. Field5. Introduce pulmonary vasodilators as indicated; pulmonary hypertensionis often a complication. Echocardiography may help conﬁrm the diag-nosis. Inhaled nitric oxide appears to be the agent of choice.6. Surfactant. There is no clear role for surfactant use in this situation(other than treatment of RDS if the baby has it), but it is frequently triedin an attempt to rescue a deteriorating baby.7. Extracorporeal Membrane Oxygenation (ECMO) is clearly able to pro-vide stability, but there is no evidence of beneﬁt over other forms of carein pulmonary hypoplasia.8. A role for the use of partial liquid ventilation is not established.9. Investigate to establish the diagnosis. Where there are no clear featuresto support a diagnosis of pulmonary hypoplasia, routine tests shouldexclude all other causes of respiratory distress.V. PrognosisPulmonary hypoplasia results from a large number of different conditions. Theprognosis is governed mainly by the etiology and any associated anomalies.A. Mild cases often become asymptomatic with growth. Abnormalities offunction can still be measured in later childhood.B. Infants with moderate hypoplasia can survive with intensive care but oftenneed long-term respiratory support. The effect of growth is uncertain anddeath in later childhood can occur.C. Severely affected babies die despite full support. No current intervention isknown to help in such cases.VI. Counselling about future pregnanciesA. Some infants will be affected by conditions that can recur in futurepregnancies.B. A proportion of severely affected cases cannot be diagnosed without exami-nation of lung tissue. Lung biopsy may be impossible to perform safelywhile the child is alive.C. Postmortem study should be obtained whenever possible. If permission forpostmortem examination is not obtained, an open or needle biopsy of thelung obtained soon after death may still allow a tissue diagnosis (in manyareas, consent to do so is required).Suggested ReadingAiton NR, Fox GF, Hannam S, et al. Pulmonary hypoplasia presenting as persistent tachypnea inthe ﬁrst few months of life. Br Med J. 1996;312:1149–50.Bishop NB, Stankiewicz P. Steinhorn RH. Am J Respir Crit Care Med: Alveolar CapillaryDysplasia; 2011. Epub ahead of print.
59166 Pulmonary Hypoplasia/AgenesisCorreia-Pinto J, Gonzaga S, Huang Y, Rottier R. Congenital lung lesions—underlying molecularmechanisms. Semin Pediatr Surg. 2010 Aug;19(3):171–179. Review.DeMello D. Pulmonary pathology. Sem Neonatol. 2004;9:311–29.Kallapur SG, Ikegami M. Physiological consequences of intrauterine insults. Paediatr Respir Rev.2006;7(2):110–116. Epub 2006 May 30.Kilbride HW, Yeast J, Thibeault DW. Deﬁning limits of survival: lethal pulmonary hypoplasia aftermidtrimester premature rupture of membranes. Am J Obstet Gynecol. 1996;175:675–81.Major D, Cadenas M, Cloutier R, et al. Morphometrics of normal and hypoplastic lungs in pretermlambs with gas and partial liquid ventilation. Pediatr Surg Int. 1997;12:121–5.Nogee LM, deMello DE, Dehner LP, Colten HR. Deﬁciency of pulmonary surfactant protein B incongenital pulmonary alveolar proteinosis. N Engl J Med. 1993;328:404–10.Swenson AW, Becker MA, Donn SM, Attar MA. The use of high frequency jet ventilation to treatsuspected pulmonary hypoplasia. J Neonatal Perinatal Med. 2011;4:33–7.Swenson AW, Donn SM. Alveolar capillary dysplasia: a lethal developmental lung malformation.Curr Respir Med Rev. 2009;5:110–4.Welzing L, Bagci S, Abramian A, Bartmann P, Berg C, Mueller A. CPAP combined with inhalednitric oxide for treatment of lung hypoplasia and persistent foetal circulation due to prolongedPPROM. Early Hum Dev. 2011;87(1):17–20.