Diagnosis Of Persistent Pulmonary Hypertension Of The Newborn Research Articles

Efficacy of sildenafil in persistent pulmonary hypertension of the newborn.

Objective: To find out efficacy of sildenafil for the treatment of persistent pulmonary hypertension of the newborn (PPHN). Study Design: Observational study. Setting: Department of Neonatology, Sughra Shafi Medical Complex, Sahara Medical College, Narowal. Period: May 2020 to April 2021. Material & Methods: A total of 22 neonates of both genders with diagnosis of PPHN were enrolled during the study period. Demographic characteristic along with information about perinatal and postnatal characteristics were recorded among all neonates at the time of admission. X-ray chest were asked. Oral sildenafil was administered as 2mg/kg per dose thrice a day to all study cases and continued till extubation. Outcome was recorded on the basis of difference in FiO2 need after initiating sildenafil, time required to get ventilator off or mortality. Results: Out of a total of 22 neonates, 13 (59.1%) were male. Majority of the neonates, 15 (68.2%) were term newborns. Mode of delivery was lower segment cesarean section in 17 (77.3%) cases. APGAR score at 5 minutes was between 7 to 10 in 13 (59.1%) newborns. There were 13 (59.1%) newborns who required immediate resuscitation following birth. Meconium aspiration syndrome was the commonest associated condition found among 8 (36.4%) neonates. As per echocardiographic findings, 13 (59.1%) neonates had severe PPHN, 5 (22.7%) moderate and 4 (18.2%) mild. Mean oxygenation index at the time of admission was noted to be 46+14. Inotropic support was administered to 19 (86.4%) cases. Mean length of neonatal intensive care unit was 15+5 days. Mortality was reported among 10 (45.4%) neonates. Conclusion: Oral sildenafil was found to be a promising option for the treatment of neonates having PPHN. Oral sildenafil was found to successfully improve oxygenation among neonates having PPHN.

Acute Kidney Injury in Term Babies with Persistent Pulmonary Hypertension of the Newborn

OBJECTIVE: The study aimed to determine the prevalence of acute kidney injury (AKI) in term neonates with persistent pulmonary hypertension of the newborn (PPHN), to identify the probable risk factors, and to find its relation to mortality.
 
 METHODS: The study recruited 758 term neonates admitted to the neonatal ICU (NICU). Diagnosis of PPHN was established on the basis of clinical and echocardiographic criteria. For diagnosis of AKI, we adopted the modified Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition. This definition has three grades of AKI severity depending on degree of serum creatinine rise and urinary output. Patients were followed until they died or discharged from NICU.
 
 RESULTS: Among the 758 term neonates included in the study, there were 47 babies (6.2 %) fulfilling the criteria of PPHN. AKI was reported in 16 patients (34.0 %) and the reported mortality rate was 31.9 %. Neonates with AKI had significantly higher mortality rate when compared with patients without AKI (75.0 % versus 9.7 %; p = 0.0001). A significant association was noted between severe grades of PPHN and AKI.
 
 CONCLUSIONS: AKI is prevalent in neonates with PPHN. It is significantly associated with mortality. There is suggested link between AKI and severity of PPHN.

Standardization of nitric oxide inhalation in extremely preterm infants in Japan.

In perinatal medicine, inhaled nitric oxide (iNO) has been an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn (PPHN) and hypoxemic respiratory failure (HRF). Its use in more premature infants, however, is controversial. To evaluate the current clinical practices regarding use of acute iNO in extremely preterm infants, a nationwide survey was conducted in Japan. A questionnaire survey was conducted from May to September, 2015. Questionnaires about PPHN and iNO treatment were sent to the doctor in charge of the neonatal care unit in 213 perinatal medical centers (PMC) that possessed iNO equipment in Japan. A total of 143 of the 213 PMC provided responses (67.1%). A diagnosis of PPHN was made exclusively on echocardiography in all PMC. On definitive PPHN diagnosis, iNO was selected in the majority of the PMC (72%) and started from ≤10 p.p.m. in most PMC (49.7%) for extremely preterm infants. During iNO therapy, cardiac function was checked on echocardiography by a neonatologist every ≤8h. iNO weaning was started when differential peripheral oxygen saturation (SpO2 ) disappeared, or when SpO2 reached 100% and so on. After iNO concentration reached 5p.p.m., it was decreased gradually and carefully in five steps, taking 12-24h to go from 5 to 0 p.p.m. Inhaled nitric oxide was predominantly used in extremely preterm infants as early rescue therapy for PPHN based on echocardiography performed by a neonatologist.

An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment and outcome

Objectives: To explore the incidence, etiologies, diagnostic methods, treatment options and outcomes in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to identify mortality risk factors in a study from six Asian countries.Methods: A retrospective chart review of patients with documented PPHN from seven centers in six Asian countries (Japan, Kuwait, India, Pakistan, Singapore, and Thailand) between 1 January, 2014 and 31 December, 2016, was performed.Results: A total of 369 PPHN infants were identified. The incidence of PPHN ranged from 1.2 to 4.6 per 1000 live births. The all-cause mortality rate was 20.6% (76 of 369). Meconium aspiration syndrome was the primary cause of PPHN (24.1%). In most cases (84.8%) echocardiography was used to establish the diagnosis of PPHN. Sildenafil was the most commonly used pulmonary vasodilator (51.2%). Multivariate multiple regression analysis indicated gestational age <34 weeks (adjusted odds ratio (OR) = 3.27; 95% CI 1.56–6.74), congenital diaphragmatic hernia (CDH)/lung hypoplasia (LH) (adjusted OR = 6.13 (95% CI 2.28–16.42)), treatment with high frequency oscillation ventilation (HFOV) with or without inhaled nitric oxide (iNO) (adjusted OR = 3.11 (95% CI 1.52–6.34)), and inotropic agents (adjusted OR = 9.43 (95% CI 2.71–32.83)) were independently associated with increased risk of death.Conclusions: The incidence of PPHN in the current study was higher than in western settings. Birth weight, gestational age, CDH/LH, HFOV/iNO, and inotropic agents were significant mortality risk factors.

Persistent Pulmonary Hypertension of the Newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is often secondary to parenchymal lung disease (such as meconium aspiration syndrome) or lung hypoplasia (with congenital diaphragmatic hernia) but can also be idiopathic. PPHN is characterized by elevated pulmonary vascular resistance, resulting in right-to-left shunting of blood and hypoxemia. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis and confirmed by echocardiography. Lung volume recruitment with optimal use of positive end-expiratory pressure or mean airway pressure and/or surfactant is very important in secondary PPHN due to parenchymal lung disease. Other management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation, and pulmonary vasodilator therapy. Failure of these measures leads to consideration of extracorporeal membrane oxygenation, although this rescue therapy is needed less frequently with advances in medical management. Randomized clinical trials with long-term follow-up are required to evaluate various therapeutic strategies in PPHN.

Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn

Importance The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. Objective To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy. Design and Setting Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010. Participants A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders. Exposures for Observational Studies SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use. Main Outcomes and Measures Recorded diagnosis of PPHN during the first 30 days after delivery. Results A total of 128 950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102 179 (2.7%) used an SSRI and 26 771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10 000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10 000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10 000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74). Conclusions and Relevance Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn.

The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy. Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010. A total of 3,789,330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders. EXPOSURES FOR OBSERVATIONAL STUDIES: SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use. Recorded diagnosis of PPHN during the first 30 days after delivery. A total of 128,950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102,179 (2.7%) used an SSRI and 26,771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10,000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10,000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10,000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74). Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

Persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance resulting in right-to-left shunting of blood and hypoxemia. PPHN is often secondary to parenchymal lung disease (such as meconium aspiration syndrome, pneumonia or respiratory distress syndrome) or lung hypoplasia (with congenital diaphragmatic hernia or oligohydramnios) but can also be idiopathic. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis. The diagnosis is confirmed by the echocardiographic demonstration of – (a) right-to-left or bidirectional shunt at the ductus or foramen ovale and/or, (b) flattening or leftward deviation of the interventricular septum and/or, (c) tricuspid regurgitation, and finally (d) absence of structural heart disease. Management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation and pulmonary vasodilator therapy. Failure of these measures would lead to consideration of extracorporeal membrane oxygenation (ECMO); however decreased need for this rescue therapy has been documented with advances in medical management. While trends also note improved survival, long-term neurodevelopmental disabilities such as deafness and learning disabilities remain a concern in many infants with severe PPHN.Funded by: 1R01HD072929-0 (SL)

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Introduction: Over the last 15 years, there have been changes in the treatment strategies available for the management of persistent pulmonary hypertension of the newborn (PPHN). Methods: Case-based retrospective review of patients admitted to a single tertiary-referral NICU aged 7 days or less between 1998–2012 with a diagnosis of PPHN. Results: 362 patients meeting inclusion criteria were admitted over the study period. Number of patients and baseline patient demographics including: gender, age, gestational age, birth weight, admission diagnosis, paediatric index of mortality (PIM2) score and oxygenation index (OI) at admission have not significantly changed over the last 15 years. Average length of stay remained constant and a decrease in overall mortality rate before discharge was not significant. Rates of referral for ECMO were unchanged but there was a shift over time in the characteristics of those patients that went on to need ECMO support. Almost half (48.1%) of those requiring ECMO support now have a diagnosis of sepsis, in contrast to the earliest period when most (51.7%) had meconium aspiration syndrome. The most common indication for ECMO was previously refractory hypoxaemia, whereas now most (77.7%) of those failing conventional management have more complex air leak or circulatory failure with shock. Those managed with ECMO now have a lower mean OI at admission but higher PIM2 scores. The outcome post ECMO (mean 76.4% survival) has not changed. Conclusions: As strategies for managing meconium aspiration/PPHN have improved, newborns that might previously have been transferred to our institution are now treated in local hospitals and those admitted who might previously have needed ECMO are managed with conventional therapies. Although the number of neonates needing ECMO support has remained constant over the last 15 years, the reasons for failure of conventional management have changed and patients are more likely to have complicating shock/circulatory failure than more straightforward refractory hypoxaemia.

ABO Blood Group Is Associated with Response to Inhaled Nitric Oxide in Neonates with Respiratory Failure

BackgroundInhaled nitric oxide (iNO) reduces death or need for extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). However, the response to iNO is variable and only 50–60% of infants demonstrate a response to iNO. It is not known why only some infants respond to iNO. Adults and children with blood groups B or AB do not respond as well to iNO as those with blood groups O/A.Methods/Principal FindingsTo determine if blood group was associated with iNO response in newborn infants, a retrospective medical record review was done of infants admitted to a regional NICU from 2002-9 with a diagnosis of PPHN. Data were collected during the first twelve hours post-initiation of treatment. Of 86 infants diagnosed with PPHN, 23 infants had blood group A [18 received iNO], 21 had group B [18 with iNO], 40 had group O [36 with iNO], and 2 had group AB [both received iNO]. Change in PaO2/FiO2 was less in infants with blood group A, of whom less than half were responders (ΔPaO2/FiO2>20%) at 12 h versus 90% of infants with either O or B. Race, sex, birth weight, gestational age, Apgar scores at 1 and 5 minutes, and baseline PaO2/FiO2 were similar among groups. Outcomes including need for ECMO, death, length of ventilatory support, length of iNO use, and hospital stay were statistically not different by blood groups.Conclusions/SignificanceOur results indicate that blood group influences iNO response in neonates. We hypothesize that either there is genetic linkage of the ABO gene locus with vasoregulatory genes, or that blood group antigens directly affect vascular reactivity.

Nitric oxide in neonatal transposition of the great arteries

Three newborn infants with transposition of the great arteries (TGA) and intact ventricular septum (IVS) developed postnatal persistent pulmonary hypertension of the newborn (PPHN) and were successfully treated with inhaled nitric oxide (iNO). Intervention with balloon atrial septostomy (BAS) was performed in two of the infants before the iNO treatment, but they continued to be severely hypoxic with metabolic acidosis. However, the iNO immediately improved oxygenation and the clinical condition. The third neonate had a moderately large atrial communication and echocardiographic signs of PPHN. He received iNO before BAS with dramatic clinical improvement, which therefore postponed BAS. Early diagnosis of PPHN and treatment with iNO may improve final outcome in neonates with TGA and IVS. In the presence of moderately large atrial communication and PPHN, treatment with iNO might be considered before BAS.

Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn.

Clinical experience indicates that persistent pulmonary hypertension of the newborn (PPHN) is one of the major causes of death in infants with meconium aspiration syndrome (MAS). We aimed to investigate the risk factors associated with MAS which lead to PPHN in order to search for ways to reduce the mortality associated with MAS. From 1995 to 2003, we conducted a retrospective study of infants with MAS at the China Medical University Hospital. We compared the risk factors associated with MAS, including pattern of fetal heart beat, mode of delivery, apgar score, sex, gestational age, birth body weight, in born or out born infants, resuscitation before admission, first pH at admission, asphyxia, surfactant usage, pneumothorax, pulmonary hemorrhage and shock before the diagnosis of PPHN between PPHN and non PPHN infants. During the nine-year study, 362 infants with MAS were enrolled. There were 64 infants with (17.7%) PPHN and 298 infants without PPHN. According to univariant analysis, the significant risk factors associated with MAS which lead to PPHN were out born infant (p=0.007), change of fetal heart beat pattern (p=0.0001), resuscitation before admission (p=0.0001), low pH (p=0.002), asphyxia (p<0.0001), shock (p<0.0001), pneumothorax (p=0.0004), and pulmonary hemorrhage (p<0.0002). Based on the results of logistic regression analysis, the risk factors were pneumothorax (p=0.04, odds ratio: 2.34), change of fetal heart beat pattern (p=0.02, odds ratio: 2.37) and asphyxia (p=0.001, odds ratio: 5.48). We conclude that pneumothorax, change of fetal heart beat pattern and asphyxia are the most important risk factors associated with MAS which lead to the development of PPHN. Avoidance of asphyxia and pneumothorax might be the key to reduce the incidence of PPNH and mortality rate of MAS.

Three-year follow up of term and near-term infants treated with inhaled nitric oxide.

The present study describes the outcome at 3 years in term and near-term infants treated with inhaled nitric oxide (iNO) for persistent pulmonary hypertension of the newborn (PPHN). The study population consisted of 18 infants delivered at 34 weeks by best obstetric estimate who were admitted to the neonatal intensive care units with a diagnosis of PPHN. Eighteen infants (mean gestational age 38.5 +/- 2.6 weeks, mean birthweight 3015 +/- 587 g) were treated with iNO. The mean oxygenation index before iNO was 27.2 +/- 15.2. Responses to iNO were classified into three groups: (i) early response in eight infants; (ii) late response in two; and (iii) poor response in eight infants. Three infants died within seven postnatal days. Fifteen surviving infants were followed up to 3 years. The mean developmental scale was 98.4 +/- 9.0. One infant was diagnosed with severe neurodevelopmental disability due to cerebral palsy. Another infant was diagnosed with mild neurodevelopmental disability because of a low developmental scale. No infant showed significant hearing loss. Five infants had reactive airway disease (RAD) at 18 months, these infants required a significantly longer duration of mechanical ventilation in their neonatal period than non-RAD infants (P = 0.02). The frequency of survival with normal neurodevelopmental outcome was significantly higher in the early response group than the late or poor response groups (P = 0.03). In iNO-treated PPHN, mortality and neurodevelopmental outcome were associated with response to iNO, and pulmonary outcome was associated with duration of mechanical ventilation.

Analysis of Nonsteroidal Antiinflammatory Drugs in Meconium and Its Relation to Persistent Pulmonary Hypertension of the Newborn

Objective. The objective of this study was to detect fetal exposure to nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to determine the relationship between fetal exposure to NSAIDs and the development of persistent pulmonary hypertension of the newborn (PPHN). Methods. In a case-control study of the inborn and outborn nurseries of a large urban medical center, meconium was collected from 101 newborn infants (40 with the diagnosis of PPHN based on clinical or echocardiographic criteria and 61 randomly selected, healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas chromatography/mass spectrometry. The risk of developing PPHN was determined in infants who were exposed antenatally to NSAID. Results. Infants with PPHN (n = 40) had a mean gestation of 38.9 weeks and birth weight of 3524 g, which were similar to the those of the control group (n = 61). However, the incidence of low Apgar scores (≤6) at 1 minute and 5 minutes was significantly higher in the PPHN group than in the control group. The diagnoses associated with PPHN were primary PPHN (25%), meconium aspiration syndrome (35%), respiratory distress syndrome (20%), low Apgar score/asphyxia (12.5%), and pneumonia/sepsis (8%). Mean duration of ventilator support for the PPHN group was 11 days. Nitric oxide (NO) was given to 19 infants (47.5%) for a mean duration of 25.4 hours. Fourteen of the 19 infants who were treated with NO (74%) required extracorporeal membrane oxygenation, and 2 died. The overall incidence of positive NSAID in meconium in the study population (n = 101) was 49.5%: 22.8% were positive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and 43.6% for aspirin. There was poor agreement (Cohen9s κ = 0.09) between maternal history of NSAID use and NSAID detection in meconium. PPHN was significantly associated with 1) the presence of at least 1 NSAID in meconium (odds ratio [OR] = 21.47; 95% confidence interval [CI] = 7.12–64.71) or 2) the presence in meconium of aspirin (OR = 8.09; 95% CI = 3.27–20.10), ibuprofen (OR = 12.89; 95% CI 3.93–42.32), or naproxen (OR = 3.31; 95% CI = 1.17–9.33). By logistic regression analysis, low Apgar scores at 1 and 5 minutes and the antenatal exposure to aspirin, naproxen, and ibuprofen were significantly associated with PPHN and treatment with inhaled NO or extracorporeal membrane oxygenation. Conclusion. We confirm by meconium analysis the results of previous studies that demonstrated that the use of NSAIDs during pregnancy, particularly aspirin, ibuprofen, and naproxen, is high; is grossly underestimated by maternal history; and is significantly associated with PPHN. Thus, the easy access to over-the-counter NSAIDs of pregnant women should be reevaluated, and the potential dangers of these drugs to the newborn infant should be more effectively promoted.