Inhaled Nitric Oxide for Oligohydramnios-Induced Pulmonary Hypoplasia: A Report of Two Cases and Review of the Literature
Divisions of Neonatology and Pulmonary Biology, Children's Hospital Medical Center and Good Samaritan Hospital, Cincinnati, OH 45229-3039, USA. Journal of Perinatology
(Impact Factor: 2.07).
02/2002; 22(1):82-5. DOI: 10.1038/sj.jp.7210580
We describe the clinical courses of two premature infants, a male born at 29(4/7) weeks' gestational age after an 8-week period of rupture of membranes (ROM) and severe oligohydramnios, and a female infant born at 31 weeks' gestational age after an 18-week period of ROM and severe oligohydramnios. Within hours after birth, despite intubation and aggressive ventilation, both infants developed fulminant hypoxic respiratory failure. Their clinical courses were consistent with pulmonary hypertension and both infants were transferred for trials of inhaled nitric oxide (iNO). Both infants had dramatic responses to iNO, suggesting that the pulmonary disease seen after prolonged oligohydramnios may have a component of nitric oxide-sensitive pulmonary hypertension. The goals of this article are to (1) review oligohydramnios-induced pulmonary hypoplasia, (2) discuss patients at highest mortality risk, and (3) describe the effects of iNO on pulmonary hypertension in infants with hypoxemia following prolonged ROM and severe oligohydramnios.
Available from: David P Van der Ham
- "Histological findings form the basis of the diagnosis pulmonary hypoplasia, however complete autopsy data were often not available . An international recognized definition of pulmonary hypoplasia is lacking, and it rather is a diagnosis by exclusion . Congenital pneumonia, infant respiratory distress syndrome (IRDS) and pulmonary hypoplasia sometimes occur simultaneously, and have overlapping symptoms . "
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ABSTRACT: Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome.Methods/design: Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. Intervention: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, Ss-error 0.2 and alpha-error 0.05).
This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure.Trial registration: NTR 3492 Dutch Trial Register (www.trialregister.nl).
Available from: Christoph Berg
- "Gestational age at PPROM and the latency period between rupture of membranes and delivery are significant risk factors for the development of pulmonary hypoplasia, which is associated with a poor neonatal outcome . However, it is increasingly recognised, that many infants with pulmonary hypoplasia have an element of reversible pulmonary hypertension that is sensitive to inhaled nitric oxide (iNO) therapy   . Furthermore, animal data suggest that iNO therapy enhances distal lung growth and promotes pulmonary vascular angiogenesis . "
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ABSTRACT: Second trimester preterm premature rupture of the membranes (PPROM) before 24 weeks of gestation is associated with a high morbidity and mortality rate.
To demonstrate the efficacy of early continuous positive airway pressure (CPAP) combined with inhaled nitric oxide (iNO) for treatment of preterm infants with lung hypoplasia and persistent foetal circulation (PFC) due to very early PPROM and prolonged severe oligohydramnios.
Seven infants with prolonged PPROM, lung hypoplasia, respiratory distress and persistent foetal circulation were intubated in the delivery room for subsequent surfactant and iNO application. As our new treatment strategy was to keep the period of mechanical ventilation as short as possible, all infants were switched on nasal CPAP combined with iNO within the first 24 hours.
Mean gestational age at PPROM was 19+6 weeks (range 14+2 to 23+6 weeks) and the average latency period between rupture of membranes and delivery was 10+3 weeks (7+3 to 16+4 weeks). Infants were born at 30+3 weeks of gestation (28+3 to 33+1 weeks) with an average birth weight of 1468g (884 to 2200g). In all neonates CPAP combined with iNO reversed PFC and 6 patients stabilised without the need for reintubation and mechanical ventilation. One infant had to be reintubated following 12 hours of CPAP combined with iNO due to respiratory insufficiency. All seven infants survived to discharge.
CPAP combined with iNO might be a promising approach for therapy of preterm infants with lung hypoplasia and persistent foetal circulation due to very early PPROM.
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ABSTRACT: In summary, infants born after midtrimester PPROM are at high risk for significant pulmonary complications. These complications should be anticipated and clinical management should be based on the unique pathophysiologic changes. We agree with Geary and Whitsett that nitric oxide should be used cautiously in preterm infants until more data are available regarding long-term implications. However, its use in early midtrimester PPROM patients with severe oligohydramnios is reasonable based on the high mortality rate and underlying pathophysiology.
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