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Perinatal/Neonatal Case Presentation Pulmonary Hypertension and Right Ventricular Dysfunction in Growth-Restricted, Extremely Low Birth Weight Neonates

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Perinatal/Neonatal Case Presentation Pulmonary Hypertension and Right Ventricular Dysfunction in Growth-Restricted, Extremely Low Birth Weight Neonates Perinatal/Neonatal Case Presentation Pulmonary Hypertension and Right Ventricular Dysfunction in Growth-Restricted, Extremely Low Birth Weight Neonates Olivier Danhaive, MD hypotensive episode. The echocardiograms, performed during the Rene´e Margossian, MD acute episode as part of the work-up, showed severe pulmonary Tal Geva, MD hypertension and right ventricle (RV) dysfunction. The goals of this Stella Kourembanas, MD report are to describe the clinical and hemodynamic features of these patients, and to discuss the pathophysiology and the therapeutic implications of this condition. This case series reports an acute episode of hypoxemia and systemic PATIENTS AND METHODS hypotension in seven infants under 1 kg, taking place several hours or days after birth, after a period of stability and in the absence of significant lung These cases were observed between December 1998 and December disease. These patients were growth-restricted at birth and had a history of 2000 in two Harvard University-affiliated teaching centers in chronic fetal hypoxia and oligohydramnios. Pulmonary hypertension and Boston, MA, USA. During that period, a total of 153 newborns right ventricular dysfunction were found by echocadiography. Right <1 kg had been hospitalized, 49 of which had a birth weight 2 ventricular ejection fraction was significantly depressed during the acute <10th percentile for gestational age (32%). Echocardiograms episode, compared to baseline values measured after recovery. The timing of were performed with a Hewlett Packard Sonos 5500 cardiac scanner symptoms seemed related to ductus arteriosus closure or constriction. using transducers appropriate for patient size. The diagnosis of Oxygenation and right ventricular function improvement occurred within a pulmonary hypertension was established on the basis of tricuspid few days under ventilatory and inotropic support, while milrinone was regurgitant jet velocity or, when impossible, on the systolic administered in five cases. In conclusion, pulmonary hypertension is a rare configuration of the ventricular septum. RV pressure greater than but significant cause of hypoxemia in preterm infants, and pulmonary half-systemic or a flattened septum were reported as ‘‘moderate’’, vasodilator therapy should be considered in the presence of right ventricular whereas RV pressure equal or superior to systemic or a septum 3 dysfunction. bulging into the left ventricle were reported as ‘‘severe’’. RV Journal of Perinatology (2005) 25, 495–499. doi:10.1038/sj.jp.7211299 dysfunction was assessed qualitatively as ‘‘mild’’, ‘‘moderate’’ or Published online 14 April 2005 ‘‘severe’’. RV ejection fraction was determined using a previously described technique based on standard two-dimensional echocardiograms, in which RV systolic and diastolic volumes are calculated using the formula: volume ¼ 2/3 area  maximum length.4 All ultrasound scans were reviewed by a single cardiologist INTRODUCTION (R.M.), who performed the morphological analyses and Idiopathic pulmonary hypertension in the absence of significant measurements. Each patient was used as his/her own control, by lung disease is a rare finding in very low birth weight infants, in comparing data obtained during the acute episode with those after which hypoxemia typically results of surfactant deficiency, clinical improvement. Medical chart review was approved by the increased alveolar–arterial gradient, ventilation–perfusion institutional review boards of the two hospitals. mismatch and intrapulmonary shunting. 1 We report a series of seven premature infants with an extremely low birth weight who presented initially with a mild form of respiratory distress syndrome RESULTS or no lung disease visible on chest radiograms, then, following a Pre- and Perinatal History (Table 1) period of cardio-respiratory stability, had an acute hypoxemic and Three of the pregnancies were multiple. Routine fetal infection screenings were unremarkable, and there was no evidence of fetal malformations on morphological ultrasonograms. Signs of fetal distress, such as intrauterine growth restriction, decreased Department of Neonatology (O.D.), Bambino Gesu` Children’s Hospital, Rome, Italy; Division of movements, nonreassuring heart rhythm or low 1-minute Apgar Newborn Medicine (O.D., S.K.), Children’s Hospital, Boston, MA, USA; and Department of Cardiology (R.M., T.G.), Children’s Hospital, Boston, MA, USA. score were present in all cases. Pregnancy-induced hypertension, Address correspondence and reprint requests to Olivier Danhaive, MD, Department of pre-eclampsia, oligohydramnios or reversed placental end-diastolic Neonatology, Bambino Gesu` Children’s Hospital, 4 Piazza Sant’Onofrio, Rome 00165, Italy. flow were reported in most, suggesting placental insufficiency as an Journal of Perinatology 2005; 25:495–499 r 2005 Nature Publishing Group All rights reserved. 0743-8346/05 $30 www.nature.com/jp 495 Danhaive et al. Pulmonary Hypertension in Growth-Restricted ELBW Infants Table 1 Pre- and Perinatal Data Case Sex GA BW Apgar Pre- and perinatal history Placenta 1 M 29 weeks 650 g 2–6 Pre-eclampsia, moderate oligohydramnios since 28 140 g (<10th p), hypermature placenta, decidual <10th p weeks, IUGR, reversed EDPF, absent fetal movements vasculopathy, two infacts (3 and 1.5 cm) 2 F 26 weeks 450 g 1–5 PIH, vaginal bleeding, IUGR since 24 weeks, severe 235 g (50th p), hypermature placenta, <5th p oligohydramnios, reversed EDPF, absent fetal circumvallate insertion, single umbilical artery, movements chronic abruptio and retroplacental hematoma 3 F 32 weeks 490 g 8–9 Quadruplet reduced to twin, pre-eclampsia, extreme 390 g fused twin placenta, marginal cord insertion <3rd p IUGR and absent EDPF since 24w, oligohydramnios; decreased fetal movements 4 F 25 weeks 750 g 5–7 Placental hematoma since 12 weeks, fetal growth 230 g (50th p) circumvallate insertion, chronic 25th p arrest and absent EDPF since 23 weeks abruptio and subchorionic hematoma 5 M 29 weeks 655 g 6–8 Dizygotic twin, discordant IUGR Not available <3rd p 6 M 29 weeks 790 g 7–7 Vaginal bleeding, placenta previa, prolonged 186 g (<10th p) hypermature placenta, <10th p premature rupture of membranes since 28 weeks, velamentous cord insertion, multiple infarcts oligohydramnios 7 F 29 weeks 450 g 5–7 Dizygotic twin 2nd born, PIH, discordant IUGR, severe Single umbilical artery <3rd p oligohydramnios, absent fetal movements M: male; F: female; p: percentile; Apgar: scores at 1 and 5 minutes; PIH: pregnancy-induced hypertension; IUGR: intrauterine growth restriction; EDPF: end-diastolic placental flow; percentiles of BW are expressed for gestational age; percentiles of placental weight are expressed for BW.9 etiology. All the infants were delivered by cesarean section. Five therapy for 4 and 6 months, respectively. Two babies died: patient 6 mothers (patients 3 to 7) had been treated with betamethasone at 5 months of age, out of respiratory syncytial virus infection, and prior to delivery. The median gestational age was 29±2.1 weeks, patient 7 at 10 days after a brain hemorrhage. and the birth weight 655±132 g (median±SD). In the five cases where the placenta was examined, structural anomalies were Echocardiography Results (Table 2) noted. Prior to the hypoxemic event, between day 1 and 6 (median: 3), five infants had been examined by echocardiography because of a Postnatal Clinical Course (Table 2) heart murmur, and had shown a PDA with either a bidirectional or Six of the patients were intubated at birth and received surfactant left-to-right (L-R) shunt. At the onset of hypoxemia, all patients within 6 hours. At 48 hours, four were extubated, while three were had evidence of pulmonary hypertension and global RV still receiving mild mechanical ventilation; all had a FiO2r30%. dysfunction. The RV ejection fraction was 13 to 40%, median: 28 At this stage, despite echocardiographic signs of mild pulmonary (normal: 58 to 715). The ductus was closed in three of the five hypertension, patients 1, 3 and 5 received indomethacin given patients with a previous PDA, and had become restrictive with an the large size of the patent ductus arteriosus (PDA) and a inverted, right-to-left (R-L) shunt in two. In the two cases not predominantly left-to-right shunt. After a variable interval of checked before (2 and 6), the ductus was also closed. On follow-up stability (2 to 12 days from birth), all patients became abruptly echocardiograms performed 2 to 8 days after the onset of hypoxemic and hypotensive. The PaO2/FiO2 ratio decreased symptoms, signs of RV hypertension had disappeared in all cases significantly (minus 40 to 76%). Chest radiograms at that time except patient 3, and the RV ejection fraction had increased 1.2- to showed only minimal or no lung disease. Echocardiography was 3.6-fold. In patient 3, after 7 days the ductus was still patent, but performed then (see below). Mechanical ventilation needed to be with a reversed, L-R shunt, and was ultimately ligated at the age of resumed or intensified, and vasopressors (dopamine, dobutamine) 3 months; mild pulmonary hypertension persisted until 6 months. were used for a duration of 3 to 10 days (median: 4). Milrinone, a RV hypertrophy developed on patients 3 and 6, who were also found phosphodiesterase-III inhibitor, was used in five of the infants at a to have restricted pulmonary artery branches. dosage of 0.25 to 0.75 mg/kg/min for a duration of 3 to 10 days, based on the presence of RV dysfunction. All patients improved DISCUSSION substantially within 2 to 5 days. The PaO2/FiO2 index increased
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