Cases Of Persistent Pulmonary Hypertension Research Articles

Increased incidence of Persistent Pulmonary Hypertension of the Newborn following third trimester maternal COVID-19 infection

Abstract Background Novel coronavirus (COVID-19) has been a world concern since December 2019. The knowledge about vertical transmission and fetal morbidity and mortality from maternal COVID-19 infection is limited. We detected an increase in the number of cases of term and near-term neonates with persistent pulmonary hypertension (PPHN) during the COVID-19 pandemic in 2020. Methods and results We collected data on all newborns with PPHN born between 2018 and 2020. We excluded premature infants (<34+0 weeks) and infants with other significant pathology or genetic syndromes. Compared to 5 cases of PPHN of 22930 live births in 2018, and 6 cases of PPHN of 22270 live births in 2019 (2-year average 0.02%, 95% CI 0.013%-0.043%), there were 16 PPHN cases from 22323 live births in 2020 (0.07%, 95% CI 0.044%-0.12%), a 3 fold increase (p<0.01). We report 5 cases of term and near-term neonates born to mothers who had highly suspected (2) and PCR proven (3) COVID-19 infection during the third trimester of pregnancy, who presented with PPHN during COVID-19 pandemic in 2020. All had otherwise unexplained pulmonary hypertension, right ventricular hypertrophy (RVH) and dilatation. Two patients needed endotracheal intubation, one was supported by nasal continuous positive airway pressure (CPAP) without intubation, two needed O2 support by nasal cannula only ant two newborns (one of them was intubated) needed Nitric oxide (NO) as pulmonary vasodilator therapy. No patient required Extracorporeal membrane oxygenation (ECMO) or died, and no prolonged residual cardiovascular or pulmonary morbidity was recorded during a median follow up of 4.8 months (range 4–6 months). Conclusions The increase in the incidence of PPHN during the COVID-19 pandemic, and the cases presented, suggest an intrauterine effect of maternal COVID-19 infection on the fetal pulmonary circulation. It is possible that the maternal infection affected the fetal pulmonary vascular resistance, or altered the normal decline in the resistance after birth. The right ventricular hypertrophy and dilatation with reduced function may be secondary to this hypothetical increased afterload or a direct effect of the infection. Further studies are warranted to elucidate the pathogenesis and clinical implications of this phenomenon. Funding Acknowledgement Type of funding sources: None.

Vein of galen malformation presenting as severe persistent pulmonary hypertension in neonate

Vein of Galen malformation (VOGM) is a rare type of arteriovenous malformation with majority presenting in neonatal period. The most common presentation is high output cardiac failure and association with persistent pulmonary hypertension (PPHN) is rarely reported. If left untreated mortality rate is very high. Endovascular embolization is the preferred treatment modality at present. We describe a full-term male baby presented at 1 h of life with respiratory distress, eventually diagnosed to have PPHN on echocardiography. Ultrasonography cranium done in view of cranial bruit revealed VOGM which later confirmed with magnetic resonance (MR) imaging brain and MR angio and venography. All supportive measures were provided. But because of hemodynamic instability endovascular embolization could not be attempted and baby succumbed due to severe refractory PPHN. We should consider the possibility of VOGM in all refractory cases of PPHN even though the association is very rare.

Outcomes of 'one-day trial of vaginal delivery of twins' at 36-37 weeks' gestation in Japan.

ObjectiveThe lack of obstetricians in Japan has prevented the implementation of a 24–hour delivery monitoring system for high-risk deliveries such as twin vaginal delivery at many obstetric facilities. To examine the outcomes of a 1-day trial of the vaginal delivery of twins at 36–37 weeks' gestation.MethodsWe induced the vaginal delivery of twins at 36–37 weeks' gestation of 256 women who provided consent between January 2007 and December 2016 using the following protocol: 1) administration of 0.5 mg oral prostaglandin E2 every 1 hour (maximum: 1.5 mg) in the morning; 2) intravenous administration of oxytocin and amniotomy in the afternoon; and 3) selection of caesarean delivery when vaginal delivery was not expected by evening. We examined their perinatal outcomes in a chart review.ResultsThe completion rates of vaginal delivery in total, nulliparous, and multiparous women were 79%, 72%, and 84%, respectively. There were no cases of neonatal asphyxia. The total incidence of neonatal respiratory disorders was 2.1%, but there were no cases of persistent pulmonary hypertension. The total incidence of postpartum hemorrhage requiring transfusion was 2.7%.ConclusionThe 1-day planned vaginal delivery of twins at 36–37 weeks' gestation appears valid and safe, and our findings suggest that it can be an option for the delivery of twins.

Prenatal Exposure to Antidepressants and Persistent Pulmonary Hypertension of the Newborn

Objective To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants. Design Systematic review and meta-analysis. Data sources Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012. Eligibility English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article. Results Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn. Conclusions The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.

Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis

Objective To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants.Design Systematic review and meta-analysis.Data sources Embase, Medline, PsycINFO, and CINAHL from inception...

Severe airway obstruction during surfactant administration using a standardized protocol: a prospective, observational study

The objective of this study was to evaluate the occurrence of adverse effects during surfactant delivery, using a standardized protocol for administration and management of complications. The protocol was developed, implemented and used for 6 months. Vital signs and ventilatory parameters were prospectively recorded during the procedure. Infants were classified into three groups, based on the occurrence and severity of complications: no, minor or major. A total of 39 infants received surfactant and 19 presented some complication: 11 minor and 8 major. Six of the major complications were episodes of severe airway obstruction (SAO) and five occurred in extreme low birth weight (ELBW) infants that had more severe lung disease before surfactant delivery. Two cases of persistent pulmonary hypertension occurred in infants with birth weight>1000 g. This study identified a high rate of SAO and provides data to support changes in the protocol, which should include faster and more robust increases in positive inspiratory pressures in ELBW infants presenting with SAO.

Congenital Cytomegalovirus Infection Manifesting as Neonatal Persistent Pulmonary Hypertension: Report of Two Cases

Various neonatal symptoms can lead to a diagnosis of congenital CMV infection. We report two cases of persistent pulmonary hypertension in relation with congenital CMV infection following maternal primary infection and reinfection, respectively. Both infants had severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support. One of them required extracorporeal membrane oxygenation for five days. Ganciclovir therapy was attempted in the two cases on day 12 postnatal. One of the infant died on day 15 postnatal. The other survived and is developing uneventfully at 15 months of age. Conclusion: Neonatal persistent pulmonary hypertension can be the consequence of congenital CMV infection. Intensive respiratory support and IV ganciclovir are indicated in case of life-threatening condition.

IDIOPATHIC PERSISTENT PULMONARY HYPERTENSION IN AN INFANT WITH SMITH-LEMLI-OPITZ SYNDROME

Persistent pulmonary hypertension (PPHN) of the newborn remains a challenging condition to diagnose and treat. It has been reported in infants with Smith-Lemli-Opitz syndrome (SLOS), a rare defect in cholesterol synthesis. Typically, there is evidence of pulmonary hypoplasia. We report the first case of PPHN in the absence of pulmonary hypoplasia or other parenchymal diseases in an infant with SLOS. Perturbations in cholesterol metabolism interrupt key signaling pathways that participate in the normal maintenance of pulmonary vascular tone. We found that caveolae-dependent signaling may be involved in this process since our patient had altered expression of caveolin-1.

A case of persistent pulmonary hypertension of the newborn: Treatment with inhaled iloprost

= Abstract = We report a case of a full-term neonate with persistent pulmonary hypertension who developed asphyxia after birth and was treated with iloprost. The neonate had persistent hypoxia and did not respond to supportive treatment. Because inhaled nitric oxide (iNO) was not available in our hospital, inhaled iloprost was administered via an endotracheal tube. This resulted in an immediate elevation of oxygen saturation. Echocardiography revealed the conversion of the rightto-left ductal shunt to the left-to-right one and a decrease of the right ventricular pressure. The use of inhaled iloprost did not cause any significant side effects. Here, we describe our experience where iloprost was used in a neonate with persistent pulmonary hypertension because the standard therapy with inhaled nitric oxide was not available. (Korean J Pediatr 2009;52:1175-1180)

A case of persistent pulmonary hypertension in a newborn with Costello syndrome

A case of persistent pulmonary hypertension in a newborn with Costello syndrome

A novel association of alveolar capillary dysplasia and duodenal atresia with paradoxical dilatation of the duodenum

Background/purpose The authors experienced 3 cases of persistent pulmonary hypertension of the neonate (PPHN) associated with duodenal atresia with paradoxical dilatation of the distal blind end of the duodenum. The aim of this study was to clarify the characteristics of this novel association. Methods The medical charts of the patients were reviewed retrospectively. Results Case 1 was a 2,862-g male infant with a prenatal diagnosis of duodenal atresia. The dilated intestine was identified as the distal blind end of the duodenum during duodeno- duodenostomy. PPHN developed after surgery, and the patient died despite treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Lung biopsy results showed alveolar capillary dysplasia (ACD) with misalignment of pulmonary vessels. Case 2 was a 2,244-g female infant with duodenal atresia. Surgery could not be performed because of refractory PPHN, which resulted in death. Autopsy results showed ACD with misalignment of pulmonary vessels and duodenal atresia associated with dilatation of the distal blind end. Case 3 was a 2,462-g female infant with a prenatal diagnosis of duodenal atresia associated with dilatation of the distal blind end. Enlarged echogenic fetal lungs were noted antenatally. PPHN developed after surgery, and she was extubated successfully under combined therapy with iNO and intravenous prostacyclin. Unfortunately, she finally died of refractory PPHN. A retrospective review of the prenatal ultrasonographic findings showed enlarged echogenic fetal lungs as in the first 2 cases. Conclusions The characteristics of this novel association are enlarged echogenic fetal lungs, duodenal atresia associated with paradoxical dilatation of the distal blind end, and refractory PPHN resistant to iNO.

Abdominal wall defects and congenital heart disease.

To determine the incidence of cardiac disease associated with abdominal wall defects of fetuses and associated parameters including maternal age, sex, gestational age at delivery, outcome, karyotypes, Apgar scores and associated congenital anomalies. This was a retrospective study of fetuses with a prenatal diagnosis of gastroschisis or omphalocele. The Maternal-Fetal Medicine Fetal Therapy (MFM) database was reviewed for all fetuses with abdominal wall defects identified prenatally. All available MFM records, fetal echocardiograms, neonatal echocardiograms and neonatal charts were reviewed for the types of abdominal wall defects and associated cardiac disease identified by ultrasound. Other parameters reviewed included: maternal age, sex, gestational age at delivery, outcome, karyotypes (when available), Apgar scores and associated congenital abnormalities. Forty-eight fetuses with an abdominal wall defect and cardiac disease findings were identified. Of these fetuses 26 had gastroschisis and 22 had omphalocele. The mean maternal age was 24.0 +/- 5.40 years in the gastroschisis and 29.2 +/- 7.23 years in the omphalocele group (P < 0.01). Differences in mean gestational age at delivery, mean birth weight and median Apgar scores at 1 and 5 min were not statistically significant. Abnormal cardiac findings were seen in 4/26 (15%) cases of gastroschisis and included one case of peripheral pulmonary stenosis, two cases of supraventricular tachycardia and one case of persistent pulmonary hypertension (PPHN) of the newborn. Abnormal cardiac findings were seen in 10/22 (45%) cases of omphalocele and included one muscular ventricular septal defect, two atrial septal defects of the secundum variety, one ectopia cordis, one coarctation of the aorta, one dysplasia of the tricuspid valve, one large pericardial effusion and four cases of PPHN. Fetuses with omphalocele appear to have an increased risk not only of congenital heart disease (CHD) but also of perinatal cardiac abnormalities, especially PPHN. A prenatal maternal hyperoxia test may be of predictive value in determining which patients may develop PPHN. The fact that both CHD and PPHN are increased in fetuses with abdominal wall defects may be of value in counseling parents prenatally, and stresses the importance of performing echocardiography both prenatally and postnatally in these cases.

Mode of delivery and risk of respiratory diseases in newborns

Objective: To determine whether there is an increased incidence of persistent pulmonary hypertension in neonates delivered by cesarean, with or without labor, compared with those delivered vaginally. Methods: We did a computerized retrospective review of 29,669 consecutive deliveries over 7 years (1992–1999). The incidences of persistent pulmonary hypertension of the newborn, transient tachypnea of the newborn, and respiratory distress syndrome (RDS) were tabulated for each delivery mode. Cases of persistent pulmonary hypertension were reviewed individually to determine delivery method and whether labor had occurred. The three groups defined were all cesarean deliveries, all elective cesareans, and all vaginal deliveries. Results: Among 4301 cesareans done, 17 neonates had persistent pulmonary hypertension (four per 1000 live births). Among 1889 elective cesarean deliveries, seven neonates had persistent pulmonary hypertension (3.7 per 1000 live births). Among 21,017 vaginal deliveries, 17 neonates had persistent pulmonary hypertension (0.8 per 1000 live births). χ 2 analysis showed an odds ratio 4.6 and P < .001 for comparison of elective cesarean and vaginal delivery for that outcome. Conclusion: The incidence of persistent pulmonary hypertension of the newborn was approximately 0.37% among neonates delivered by elective cesarean, almost fivefold higher than those delivered vaginally. The findings have implications for informed consent before cesarean and increased surveillance of neonates after cesarean.

Histological Study of Pulmonary Vasculature in Fatal Cases of Persistent Pulmonary Hypertension of the Newborn.

Using our own morphometric technique, we examined pulmonary vasculature in eight neonates who died of persistent pulmonary hypertension of the newborn (PPHN). PPHN was judged to be idiopathic in three neonates and was associated with fatal meconium aspiration in the other five. Two characteristic structural features of PPHN were revealed in this study. First, medial thickening of the normally fully-muscularized pulmonary vessels occurred in the smaller and more peripherally located arteries. Second, fully-muscularized vessels extended as far as the intraacinar arteries, which are normally non-muscular vessels at this age. This structural abnormality appears not to merely represent a failure of the fetal pattern to regress, and it is suggested that PPHN is due to a structural abnormality of the pulmonary microcirculation in fatal cases.

An autopsy case of persistent pulmonary hypertension of newborn with tricuspid insufficiency

An autopsy case of persistent pulmonary hypertension of newborn with tricuspid insufficiency

Effects of Chronic in Utero Hypoxia on the Pulmonary Vasculature of the Newborn Guinea Pig

This report analyzes the effect on pulmonary vascular structure and function in the newborn guinea pig of chronic fetal hypoxemia, induced by maternal hypobaric hypoxia (380-420 torr) without direct interference with the utero-placental blood flow. Six pregnant guinea pigs were maintained in hypobaric chambers, 10 newborns from their litters being the hypoxic group. Twenty newborns from the litters of 10 pregnant guinea pigs maintained in air were the control group. After spontaneous delivery catheters were placed in the left carotid and the main pulmonary arteries of the newborns. Oxygen consumption was measured, pressures recorded from the pulmonary artery, right ventricle, and right atrium, oxygen saturation and hemoglobin concentration estimated on blood from systemic arteries, pulmonary artery, and right atrium, and cardiac output calculated (Fick principle). All data were normalized per kilogram body weight. Morphometric analysis of the pulmonary vasculature after injection of the pulmonary arteries showed no difference between the groups. Contrary to expectation chronic hypoxemia in utero did not cause pulmonary hypertension or the precocious muscularization of the precapillary unit found in human cases of persistent pulmonary hypertension: it caused growth retardation, a feature not typical of the human syndrome.

Association of elective repeat cesarean delivery and persistent pulmonary hypertension of the newborn

Seventy-one cases of persistent pulmonary hypertension of the newborn have been reviewed in an attempt to identify possibly preventable causes. Three groups of infants were identified. The first group consisted of 36 infants with evidence of perinatal asphyxia. The second group was made up of 23 infants who exhibited a variety of associated factors including pneumonia, septic shock, and congenital diaphragmatic hernia. A third group included 12 infants delivered by elective repeat cesarean section. Infants in the third group did not have evidence of perinatal asphyxia, meconium aspiration, or infection. Chest roentgenograms revealed amniotic fluid aspiration in seven cases, retained lung fluid in three cases, and normal findings in two cases. All 12 infants in the third group developed respiratory distress which eventually progressed to respiratory failure and persistent pulmonary hypertension of the newborn. These data suggest that infants of elective repeat cesarean deliveries are at risk for developing persistent pulmonary hypertension of the newborn and constitute a group of patients with a potentially preventable course of events.