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Neonatal encephalopathy due to a hypoxic-ischemic event is commonly associated with cardiac dysfunction and acute pulmonary hypertension; both therapeutic hypothermia and rewarming modify loading conditions and blood flow. The pathophysiological contributors to disease are complex with a high degree of clinical overlap and traditional bedside measures used to assess circulatory adequacy have multiple confounders. Comprehensive, quantitative echocardiography may be used to delineate the relative contribution of lung parenchymal, pulmonary vascular, and cardiac disease to hypotension and/or hypoxemic respiratory failure. In this review, we provide a detailed overview of the contributors to hemodynamic instability following perinatal hypoxic-ischemic injury. Our proposed approach to therapy focuses on physiopathological considerations with interventions individualized to this potentially complex condition and considers the pharmacological idiosyncrasies, which may occur among neonates with NE presenting with multiorgan dysfunction while undergoing therapeutic hypothermia.
Danielle R. Rios; Anie Lapointe; Georg M. Schmolzer; Khorshid Mohammad; Krisa P. VanMeurs; Roberta L. Keller; Arvind Sehgal; SatyaN Lakshminrusimha; Regan E. Giesinger. Hemodynamic optimization for neonates with neonatal encephalopathy caused by hypoxic ischemic event: Physiological and therapeutic considerations. Seminars in Fetal and Neonatal Medicine 2021, 1 .
AMA StyleDanielle R. Rios, Anie Lapointe, Georg M. Schmolzer, Khorshid Mohammad, Krisa P. VanMeurs, Roberta L. Keller, Arvind Sehgal, SatyaN Lakshminrusimha, Regan E. Giesinger. Hemodynamic optimization for neonates with neonatal encephalopathy caused by hypoxic ischemic event: Physiological and therapeutic considerations. Seminars in Fetal and Neonatal Medicine. 2021; ():1.
Chicago/Turabian StyleDanielle R. Rios; Anie Lapointe; Georg M. Schmolzer; Khorshid Mohammad; Krisa P. VanMeurs; Roberta L. Keller; Arvind Sehgal; SatyaN Lakshminrusimha; Regan E. Giesinger. 2021. "Hemodynamic optimization for neonates with neonatal encephalopathy caused by hypoxic ischemic event: Physiological and therapeutic considerations." Seminars in Fetal and Neonatal Medicine , no. : 1.
Yogen Singh; SatyaN Lakshminrusimha. Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn. Clinics in Perinatology 2021, 48, 595 -618.
AMA StyleYogen Singh, SatyaN Lakshminrusimha. Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn. Clinics in Perinatology. 2021; 48 (3):595-618.
Chicago/Turabian StyleYogen Singh; SatyaN Lakshminrusimha. 2021. "Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn." Clinics in Perinatology 48, no. 3: 595-618.
Neonatal resuscitation (NRP) guidelines suggest targeting 85–95% preductal SpO2 by 10 min after birth. Optimal oxygen saturation (SpO2) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (QPA), carotid (QCA)and ductal (QDA) blood flows between standard (85–94%) and high (95–99%) SpO2 targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85–94%) or high (95–99%) SpO2 targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO2 targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO2 target (7.4 (4.4–10.8) min) compared to standard SpO2 target (31.5 (21–66.2) min, p = 0.03). QPA was significantly higher during the first 10 min after birth with higher SpO2 target. At 60 min after birth, the QPA, QCA and QDA were not different between the groups. To conclude, targeting SpO2 of 95–99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase QPA but no differences were observed at 60 min. Clinical studies comparing low and high SpO2 targets assessing hemodynamics and neurodevelopmental outcomes are warranted.
Amy Lesneski; Payam Vali; Morgan Hardie; SatyaN Lakshminrusimha; Deepika Sankaran. Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension. Children 2021, 8, 594 .
AMA StyleAmy Lesneski, Payam Vali, Morgan Hardie, SatyaN Lakshminrusimha, Deepika Sankaran. Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension. Children. 2021; 8 (7):594.
Chicago/Turabian StyleAmy Lesneski; Payam Vali; Morgan Hardie; SatyaN Lakshminrusimha; Deepika Sankaran. 2021. "Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension." Children 8, no. 7: 594.
Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious immune-mediated condition, seen 3–5 weeks after COVID-19. Maternal SARS-CoV-2 may potentially cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. We reviewed the perinatal history, clinical features, and outcomes of 20 neonates with features consistent with MIS-C related to maternal SARS-CoV-2 in Kolhapur, India, from 1 September 2020 to 30 April 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Fifteen singletons and five twins born to eighteen mothers with a history of COVID-19 disease or exposure during pregnancy presented with features consistent with MIS-C during the first 5 days after birth. Nineteen were positive for anti-SARS-CoV-2 IgG and all were negative for IgM antibodies. All mothers were asymptomatic and therefore not tested by RTPCR-SARS-CoV-2 at delivery. Eighteen neonates (90%) had cardiac involvement with prolonged QTc, 2:1 AV block, cardiogenic shock, or coronary dilatation. Other findings included respiratory failure (40%), fever (10%), feeding intolerance (30%), melena (10%), and renal failure (5%). All infants had elevated inflammatory biomarkers and received steroids and IVIG. Two infants died. We speculate that maternal SARS-CoV-2 and transplacental antibodies cause multisystem inflammatory syndrome in neonates (MIS-N). Immunomodulation may be beneficial in some cases, but further studies are needed.
Ravindra Pawar; Vijay Gavade; Nivedita Patil; Vijay Mali; Amol Girwalkar; Vyankatesh Tarkasband; Sanjog Loya; Amit Chavan; Narendra Nanivadekar; Rahul Shinde; Uday Patil; SatyaN Lakshminrusimha. Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series. Children 2021, 8, 572 .
AMA StyleRavindra Pawar, Vijay Gavade, Nivedita Patil, Vijay Mali, Amol Girwalkar, Vyankatesh Tarkasband, Sanjog Loya, Amit Chavan, Narendra Nanivadekar, Rahul Shinde, Uday Patil, SatyaN Lakshminrusimha. Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series. Children. 2021; 8 (7):572.
Chicago/Turabian StyleRavindra Pawar; Vijay Gavade; Nivedita Patil; Vijay Mali; Amol Girwalkar; Vyankatesh Tarkasband; Sanjog Loya; Amit Chavan; Narendra Nanivadekar; Rahul Shinde; Uday Patil; SatyaN Lakshminrusimha. 2021. "Neonatal Multisystem Inflammatory Syndrome (MIS-N) Associated with Prenatal Maternal SARS-CoV-2: A Case Series." Children 8, no. 7: 572.
Wide fluctuations in partial pressure of carbon dioxide (PaCO2) can potentially be associated with neurological and lung injury in neonates. Blood gas measurement is the gold standard for assessing gas exchange but is intermittent, invasive, and contributes to iatrogenic blood loss. Non-invasive carbon dioxide (CO2) monitoring has become ubiquitous in anesthesia and critical care and is being increasingly used in neonates. Two common methods of non-invasive CO2 monitoring are end-tidal and transcutaneous. A colorimetric CO2 detector (a modified end-tidal CO2 detector) is recommended by the International Liaison Committee on Resuscitation (ILCOR) and the American Academy of Pediatrics to confirm endotracheal tube placement. Continuous CO2 monitoring is helpful in trending PaCO2 in critically ill neonates on respiratory support and can potentially lead to early detection and minimization of fluctuations in PaCO2. This review includes a description of the various types of CO2 monitoring and their applications, benefits, and limitations in neonates.
Deepika Sankaran; Lida Zeinali; Sameeia Iqbal; Praveen Chandrasekharan; SatyaN Lakshminrusimha. Non-invasive carbon dioxide monitoring in neonates: methods, benefits, and pitfalls. Journal of Perinatology 2021, 1 -10.
AMA StyleDeepika Sankaran, Lida Zeinali, Sameeia Iqbal, Praveen Chandrasekharan, SatyaN Lakshminrusimha. Non-invasive carbon dioxide monitoring in neonates: methods, benefits, and pitfalls. Journal of Perinatology. 2021; ():1-10.
Chicago/Turabian StyleDeepika Sankaran; Lida Zeinali; Sameeia Iqbal; Praveen Chandrasekharan; SatyaN Lakshminrusimha. 2021. "Non-invasive carbon dioxide monitoring in neonates: methods, benefits, and pitfalls." Journal of Perinatology , no. : 1-10.
The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.
Deepika Sankaran; Payam Vali; Praveen Chandrasekharan; Peggy Chen; Sylvia Gugino; Carmon Koenigsknecht; Justin Helman; Jayasree Nair; Bobby Mathew; Munmun Rawat; Lori Nielsen; Amy Lesneski; Morgan Hardie; Ziad Alhassen; Houssam Joudi; Evan Giusto; Lida Zeinali; Heather Knych; Gary Weiner; SatyaN Lakshminrusimha. Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest. Children 2021, 8, 464 .
AMA StyleDeepika Sankaran, Payam Vali, Praveen Chandrasekharan, Peggy Chen, Sylvia Gugino, Carmon Koenigsknecht, Justin Helman, Jayasree Nair, Bobby Mathew, Munmun Rawat, Lori Nielsen, Amy Lesneski, Morgan Hardie, Ziad Alhassen, Houssam Joudi, Evan Giusto, Lida Zeinali, Heather Knych, Gary Weiner, SatyaN Lakshminrusimha. Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest. Children. 2021; 8 (6):464.
Chicago/Turabian StyleDeepika Sankaran; Payam Vali; Praveen Chandrasekharan; Peggy Chen; Sylvia Gugino; Carmon Koenigsknecht; Justin Helman; Jayasree Nair; Bobby Mathew; Munmun Rawat; Lori Nielsen; Amy Lesneski; Morgan Hardie; Ziad Alhassen; Houssam Joudi; Evan Giusto; Lida Zeinali; Heather Knych; Gary Weiner; SatyaN Lakshminrusimha. 2021. "Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest." Children 8, no. 6: 464.
Objective Delayed cord clamping (DCC) and 21 to 30% O2 resuscitation is recommended for preterm infants but is commonly associated with low pulmonary blood flow (Qp) and hypoxia. 100% O2 supplementation during DCC for 60 seconds followed by 30% O2 may increase Qp and oxygen saturation (SpO2). Study Design Preterm lambs (125–127 days of gestation) were resuscitated with 100% O2 with immediate cord clamping (ICC, n = 7) or ICC + 30% O2, and titrated to target SpO2 (n = 7) or DCC + 100% O2 for 60 seconds, which followed by cord clamping and 30% O2 titration (n = 7). Seven preterm (23–27 weeks of gestation) human infants received continuous positive airway pressure (CPAP) + 100% O2 for 60 seconds during DCC, cord clamping, and 30% O2 supplementation after cord clamping. Results Preterm lambs in the ICC + 100% O2 group resulted in PaO2 (77 ± 25 mmHg), SpO2 (77 ± 11%), and Qp (27 ± 9 mL/kg/min) at 60 seconds. ICC + 30% O2 led to low Qp (14 ± 3 mL/kg/min), low SpO2 (43 ± 26%), and PaO2 (19 ± 7 mmHg). DCC + 100% O2 led to similar Qp (28 ± 6 mL/kg/min) as ICC + 100% O2 with lower PaO2. In human infants, DCC + CPAP with 100% O2 for 60 seconds, which followed by weaning to 30% resulted in SpO2 of 92 ± 11% with all infants >80% at 5 minutes with 100% survival without severe intraventricular hemorrhage. Conclusion DCC + 100% O2 for 60 seconds increased Qp probably due to transient alveolar hyperoxia with systemic normoxia due to “dilution” by umbilical venous return. Larger translational and clinical studies are warranted to confirm these findings. Key Points
SatyaN Lakshminrusimha; Payam Vali; Praveen Chandrasekharan; Wade Rich; Anup Katheria. Differential Alveolar and Systemic Oxygenation during Preterm Resuscitation with 100% Oxygen during Delayed Cord Clamping. American Journal of Perinatology 2021, 1 .
AMA StyleSatyaN Lakshminrusimha, Payam Vali, Praveen Chandrasekharan, Wade Rich, Anup Katheria. Differential Alveolar and Systemic Oxygenation during Preterm Resuscitation with 100% Oxygen during Delayed Cord Clamping. American Journal of Perinatology. 2021; ():1.
Chicago/Turabian StyleSatyaN Lakshminrusimha; Payam Vali; Praveen Chandrasekharan; Wade Rich; Anup Katheria. 2021. "Differential Alveolar and Systemic Oxygenation during Preterm Resuscitation with 100% Oxygen during Delayed Cord Clamping." American Journal of Perinatology , no. : 1.
Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.
SatyaN Lakshminrusimha; Sylvia Gugino; Krishnamurthy Sekar; Stephen Wedgwood; Carmon Koenigsknecht; Jayasree Nair; Bobby Mathew. Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs. Children 2021, 8, 378 .
AMA StyleSatyaN Lakshminrusimha, Sylvia Gugino, Krishnamurthy Sekar, Stephen Wedgwood, Carmon Koenigsknecht, Jayasree Nair, Bobby Mathew. Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs. Children. 2021; 8 (5):378.
Chicago/Turabian StyleSatyaN Lakshminrusimha; Sylvia Gugino; Krishnamurthy Sekar; Stephen Wedgwood; Carmon Koenigsknecht; Jayasree Nair; Bobby Mathew. 2021. "Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs." Children 8, no. 5: 378.
COVID-19 vaccines have been developed with unprecedented rapidity, deliver the vaccine antigen in a completely different manner than all previous vaccines in widespread use, and are made available outside of the routine Food and Drug Administration (FDA) approval process. Therefore, it is understandable that there is uncertainty about the safety of their administration during pregnancy and lactation, both among clinicians and those who are pregnant or lactating. In this commentary, we review the limited available data as well as theoretical considerations concerning safety of vaccination during pregnancy and lactation. Finally, we discuss guidance in this situation and our perspective in the context of disease severity and transmission. There are several vaccines in development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and three have been approved by the U.S. FDA (at the time of manuscript submission, March 7, 2021) under Emergency Use Authorization (EUA), with additional ones soon to follow. An EUA may be issued to make potentially life-saving medical products available when there is no available approved alternative. Evidence is required that “the product may be effective” and that “its known and potential benefits outweigh the known and potential risks[1].” Specifically to issue an EUA for a COVID-19 vaccine, the FDA requires demonstration that “the vaccine's benefits outweigh its risks based on data from at least one well-designed phase III clinical trial that demonstrates the vaccine's safety and efficacy in a clear and compelling manner,” in addition to careful evaluation of quality and consistency of the manufacturing process.[2] The FDA issued EUAs in December 2020 for vaccines manufactured by Pfizer-BioNTech and Moderna[3] [4] and in February 2021 for Jannsen (Johnson & Johnson)[5] ([Fig. 1]). The Pfizer-BioNTech and Moderna products are lipid-nanoparticle mRNA vaccines and the Janssen product is a replication-incompetent adenovirus vector. All three vaccines encode for the SARS-CoV-2 spike protein, which serves to attach the virus to angiotensin converting enzyme 2 (ACE2) receptors as the initial infection event.[6] The lipid nanoparticle facilitates cell entry.[7] The Janssen adenovirus vector directly infects cells. Once inside dendritic cells, the mRNA is released into the cytoplasm, or for the Janssen adenovirus vaccine the viral DNA is pushed into the nucleus and then transcribed into mRNA. The spike protein mRNA code is located between start and stop signals for translation, and there is further code to increase protein translation. The mRNA is transcribed in the host cell, producing the spike protein, which is subsequently presented on the cell surface to B and T cells, resulting in an immune response to the protein, antibody production, and cell-mediated immunity, respectively ([Fig. 1]). The Pfizer-BioNTech vaccine is recommended for use in those ≥16 years of age, while the Moderna and Janssen vaccines are recommended for those ≥18 years of age. Both the Moderna and Pfizer-BioNTech vaccines are administered in a two-dose series, with an interval of 21 days for the Pfizer-BioNTech vaccine and 28 days for the Moderna vaccine.[3] [4] Both vaccines have more than 90% efficacy in preventing symptomatic laboratory confirmed COVID-19. The Janssen vaccine is administered in a single dose, and has 66% efficacy in preventing symptomatic laboratory confirmed infection, 93% efficacy vs hospitalization, and 100% efficacy versus death.[5] All three vaccines are generally well tolerated. They may cause mild–moderate local and systemic adverse reactions within the first 1 to 2 days, which generally resolve within a few days. Severe reactions such as anaphylaxis are rare. None of these vaccines have been studied in pregnancy, with pregnancy an exclusion criterion for study participation. In addition, women of reproductive age group had to be on some form of “effective' contraception and have negative pregnancy test before administration of each dose. Despite these restrictive eligibility criteria, several pregnancies occurred after study enrolment (or that were not detected during prevaccination screening). In the Pfizer-BioNTech study, 23 pregnancies occurred and 12 in the vaccine group.[8] One spontaneous abortion and one retained products of conception occurred in the placebo group. In the Moderna study, 13 pregnancies were reported and 6 in the vaccine group.[9] One spontaneous and one elective abortion occurred in the placebo group, and one placebo participant was lost to follow-up. Otherwise, pregnancy outcomes are not known. The FDA review of the developmental and perinatal/postnatal reproductive toxicity of the Moderna vaccine concluded that it did “not have any adverse effects on female reproduction, fetal/embryonal development, or postnatal developmental except for skeletal variations which are common and typically resolve postnatally without intervention.[9]” No long-term follow-up on these pregnant women or their children is yet available. In the Janssen study, there were 8 pregnancies, 4 each in the vaccine and placebo groups. There was one spontaneous abortion (vaccine group), 1 incomplete abortion (placebo group), 2 elective abortions (placebo group) and 1 ectopic pregnancy (vaccine group). Outcomes are not known for two ongoing pregnancies. Janssen submitted a developmental and perinatal/postnatal reproductive toxicity study in rabbits receiving two times the human vaccine dose prior to mating and during gestation periods; the FDA review of this study concluded that the vaccine “did not have any adverse effects on female reproduction, fetal/embryonal development, or postnatal development.[9] Certainly, the inclusion of pregnant and lactating women is needed for vaccine trials as described by Maykin.[10] For the mRNA vaccines, the mRNA does not enter cell nuclei and has...
Dean Blumberg; Aparna Sridhar; SatyaN Lakshminrusimha; Rosemary D. Higgins; George Saade. COVID-19 Vaccine Considerations during Pregnancy and Lactation. American Journal of Perinatology 2021, 38, 523 -528.
AMA StyleDean Blumberg, Aparna Sridhar, SatyaN Lakshminrusimha, Rosemary D. Higgins, George Saade. COVID-19 Vaccine Considerations during Pregnancy and Lactation. American Journal of Perinatology. 2021; 38 (06):523-528.
Chicago/Turabian StyleDean Blumberg; Aparna Sridhar; SatyaN Lakshminrusimha; Rosemary D. Higgins; George Saade. 2021. "COVID-19 Vaccine Considerations during Pregnancy and Lactation." American Journal of Perinatology 38, no. 06: 523-528.
The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.
Jayasree Nair; Lauren Davidson; Sylvia Gugino; Carmon Koenigsknecht; Justin Helman; Lori Nielsen; Deepika Sankaran; Vikash Agrawal; Praveen Chandrasekharan; Munmun Rawat; Sara Berkelhamer; SatyaN Lakshminrusimha. Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord. Children 2021, 8, 353 .
AMA StyleJayasree Nair, Lauren Davidson, Sylvia Gugino, Carmon Koenigsknecht, Justin Helman, Lori Nielsen, Deepika Sankaran, Vikash Agrawal, Praveen Chandrasekharan, Munmun Rawat, Sara Berkelhamer, SatyaN Lakshminrusimha. Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord. Children. 2021; 8 (5):353.
Chicago/Turabian StyleJayasree Nair; Lauren Davidson; Sylvia Gugino; Carmon Koenigsknecht; Justin Helman; Lori Nielsen; Deepika Sankaran; Vikash Agrawal; Praveen Chandrasekharan; Munmun Rawat; Sara Berkelhamer; SatyaN Lakshminrusimha. 2021. "Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord." Children 8, no. 5: 353.
(1) Background: Optimal initial oxygen (O2) concentration in preterm neonates is controversial. Our objectives were to compare the effect of delayed cord clamping with ventilation (DCCV) to early cord clamping followed by ventilation (ECCV) on O2 exposure, gas exchange, and hemodynamics in an asphyxiated preterm ovine model. (2) Methods: Asphyxiated preterm lambs (127–128 d) with heart rate <90 bpm were randomly assigned to DCCV or ECCV. In DCCV, positive pressure ventilation (PPV) was initiated with 30–60% O2 and titrated based on preductal saturations (SpO2) with an intact cord for 5 min, followed by clamping. In ECCV, the cord was clamped, and PPV was initiated. (3) Results: Fifteen asphyxiated preterm lambs were randomized to DCCV (N = 7) or ECCV (N = 8). The inspired O2 (40 ± 20% vs. 60 ± 20%, p < 0.05) and oxygen load (520 (IQR 414–530) vs. 775 (IQR 623–868), p-0.03) in the DCCV group were significantly lower than ECCV. Arterial oxygenation and carbon dioxide (PaCO2) levels were significantly lower and peak pulmonary blood flow was higher with DCCV. (4) Conclusion: In asphyxiated preterm lambs, resuscitation with an intact cord decreased O2 exposure load improved ventilation with an increase in peak pulmonary blood flow in the first 5 min.
Praveen Chandrasekharan; Sylvia Gugino; Justin Helman; Carmon Koenigsknecht; Lori Nielsen; Nicole Bradley; Jayasree Nair; Vikash Agrawal; Mausma Bawa; Andreina Mari; Munmun Rawat; SatyaN Lakshminrusimha. Resuscitation with an Intact Cord Enhances Pulmonary Vasodilation and Ventilation with Reduction in Systemic Oxygen Exposure and Oxygen Load in an Asphyxiated Preterm Ovine Model. Children 2021, 8, 307 .
AMA StylePraveen Chandrasekharan, Sylvia Gugino, Justin Helman, Carmon Koenigsknecht, Lori Nielsen, Nicole Bradley, Jayasree Nair, Vikash Agrawal, Mausma Bawa, Andreina Mari, Munmun Rawat, SatyaN Lakshminrusimha. Resuscitation with an Intact Cord Enhances Pulmonary Vasodilation and Ventilation with Reduction in Systemic Oxygen Exposure and Oxygen Load in an Asphyxiated Preterm Ovine Model. Children. 2021; 8 (4):307.
Chicago/Turabian StylePraveen Chandrasekharan; Sylvia Gugino; Justin Helman; Carmon Koenigsknecht; Lori Nielsen; Nicole Bradley; Jayasree Nair; Vikash Agrawal; Mausma Bawa; Andreina Mari; Munmun Rawat; SatyaN Lakshminrusimha. 2021. "Resuscitation with an Intact Cord Enhances Pulmonary Vasodilation and Ventilation with Reduction in Systemic Oxygen Exposure and Oxygen Load in an Asphyxiated Preterm Ovine Model." Children 8, no. 4: 307.
Pulse oximetry oxygen saturation (SpO2)-based critical congenital heart disease (CCHD) screening is effective in detection of cyanotic heart lesions. We report a full-term male infant with normal perfusion who had passed the CCHD screening at approximately 24 hours after birth with preductal SpO2 of 99% and postductal SpO2 of 97%. Detection of a loud systolic cardiac murmur before discharge led to the diagnosis of pulmonary atresia (PA) with ventricular septal defect (PA-VSD) by echocardiogram. The infant was transferred to a tertiary care center after initiation of prostaglandin E1 (PGE1) therapy. Throughout the initial course, he was breathing comfortably without respiratory distress or desaturations on pulse oximetry. We believe that this is the first documented report of PA missed by CCHD screening. Thorough and serial clinical examinations of the newborn infant proved vital in the timely diagnosis of this critical disease. We review the hemodynamics and the recent literature evaluating utility of CCHD screening in the diagnosis of PA-VSD. Pulse oximetry–based CCHD screening should be considered a tool to enhance CCHD detection with an emphasis on detailed serial physical examinations in newborn infants.
Deepika Sankaran; Heather Siefkes; Frank F. Ing; SatyaN Lakshminrusimha; Francis R. Poulain. Critical Congenital Heart Disease Detection in the Screening Era: Do Not Neglect the Examination! American Journal of Perinatology Reports 2021, 11, e84 -e90.
AMA StyleDeepika Sankaran, Heather Siefkes, Frank F. Ing, SatyaN Lakshminrusimha, Francis R. Poulain. Critical Congenital Heart Disease Detection in the Screening Era: Do Not Neglect the Examination! American Journal of Perinatology Reports. 2021; 11 (02):e84-e90.
Chicago/Turabian StyleDeepika Sankaran; Heather Siefkes; Frank F. Ing; SatyaN Lakshminrusimha; Francis R. Poulain. 2021. "Critical Congenital Heart Disease Detection in the Screening Era: Do Not Neglect the Examination!" American Journal of Perinatology Reports 11, no. 02: e84-e90.
Objectives Neonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest. Design Forty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored. Results Ten lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush. Conclusions 0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.
Deepika Sankaran; Praveen K Chandrasekharan; Sylvia F Gugino; Carmon Koenigsknecht; Justin Helman; Jayasree Nair; Bobby Mathew; Munmun Rawat; Payam Vali; Lori Nielsen; Daniel J Tancredi; SatyaN Lakshminrusimha. Randomised trial of epinephrine dose and flush volume in term newborn lambs. Archives of Disease in Childhood - Fetal and Neonatal Edition 2021, 1 -2020.
AMA StyleDeepika Sankaran, Praveen K Chandrasekharan, Sylvia F Gugino, Carmon Koenigsknecht, Justin Helman, Jayasree Nair, Bobby Mathew, Munmun Rawat, Payam Vali, Lori Nielsen, Daniel J Tancredi, SatyaN Lakshminrusimha. Randomised trial of epinephrine dose and flush volume in term newborn lambs. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2021; ():1-2020.
Chicago/Turabian StyleDeepika Sankaran; Praveen K Chandrasekharan; Sylvia F Gugino; Carmon Koenigsknecht; Justin Helman; Jayasree Nair; Bobby Mathew; Munmun Rawat; Payam Vali; Lori Nielsen; Daniel J Tancredi; SatyaN Lakshminrusimha. 2021. "Randomised trial of epinephrine dose and flush volume in term newborn lambs." Archives of Disease in Childhood - Fetal and Neonatal Edition , no. : 1-2020.
SatyaN Lakshminrusimha; Alan H Jobe. Baby’s First Cries and Establishment of Gas Exchange in the Lung. American Journal of Respiratory and Critical Care Medicine 2021, 1 .
AMA StyleSatyaN Lakshminrusimha, Alan H Jobe. Baby’s First Cries and Establishment of Gas Exchange in the Lung. American Journal of Respiratory and Critical Care Medicine. 2021; ():1.
Chicago/Turabian StyleSatyaN Lakshminrusimha; Alan H Jobe. 2021. "Baby’s First Cries and Establishment of Gas Exchange in the Lung." American Journal of Respiratory and Critical Care Medicine , no. : 1.
During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure.
SatyaN Lakshminrusimha. Neonatal and Postneonatal Pulmonary Hypertension. Children 2021, 8, 131 .
AMA StyleSatyaN Lakshminrusimha. Neonatal and Postneonatal Pulmonary Hypertension. Children. 2021; 8 (2):131.
Chicago/Turabian StyleSatyaN Lakshminrusimha. 2021. "Neonatal and Postneonatal Pulmonary Hypertension." Children 8, no. 2: 131.
In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.
Heather M Siefkes; SatyaN Lakshminrusimha. Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review. Archives of Disease in Childhood - Fetal and Neonatal Edition 2021, 106, 446 -455.
AMA StyleHeather M Siefkes, SatyaN Lakshminrusimha. Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2021; 106 (4):446-455.
Chicago/Turabian StyleHeather M Siefkes; SatyaN Lakshminrusimha. 2021. "Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review." Archives of Disease in Childhood - Fetal and Neonatal Edition 106, no. 4: 446-455.
Inhaled nitric oxide (iNO) was approved for use in critically ill term and near-term neonates (>34 weeks gestational age) in 1999 for hypoxic respiratory failure (HRF) with evidence of pulmonary hypertension. In 2011 and 2014, the National Institutes of Health and American Academy of Pediatrics respectively recommended against the use of iNO in preterm infants <34 weeks. However, these guidelines were based on trials conducted with varying inclusion criteria and outcomes. Recent guidelines from the American Thoracic Society/American Heart Association, the Pediatric Pulmonary Hypertension Network (PPHNet) and European Pediatric Pulmonary Vascular Disease Network recommend the use of iNO in preterm neonates with HRF with confirmed pulmonary hypertension. This review discusses the available evidence for off-label use of iNO. Preterm infants with prolonged rupture of membranes and pulmonary hypoplasia appear to respond to iNO. Similarly, preterm infants with physiology of pulmonary hypertension with extrapulmonary right-to-left shunts may potentially have an oxygenation response to iNO. An overview of relative and absolute contraindications for iNO use in neonates is provided. Absolute contraindications to iNO use include a ductal dependent congenital heart disease where systemic circulation is supported by a right-to-left ductal shunt, severe left ventricular dysfunction and severe congenital methemoglobinemia. In preterm infants, we do not recommend the routine use of iNO in HRF due to parenchymal lung disease without pulmonary hypertension and prophylactic use to prevent bronchopulmonary dysplasia. Future randomized trials evaluating iNO in preterm infants with pulmonary hypertension and/or pulmonary hypoplasia are warranted. (233/250 words).
Praveen Chandrasekharan; SatyaN Lakshminrusimha; Steven H. Abman. When to say no to inhaled nitric oxide in neonates? Seminars in Fetal and Neonatal Medicine 2021, 26, 101200 .
AMA StylePraveen Chandrasekharan, SatyaN Lakshminrusimha, Steven H. Abman. When to say no to inhaled nitric oxide in neonates? Seminars in Fetal and Neonatal Medicine. 2021; 26 (2):101200.
Chicago/Turabian StylePraveen Chandrasekharan; SatyaN Lakshminrusimha; Steven H. Abman. 2021. "When to say no to inhaled nitric oxide in neonates?" Seminars in Fetal and Neonatal Medicine 26, no. 2: 101200.
To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, “usual care” arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18–22 months adjusted for severity of HIE, center, and RCT. Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86–3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92–4.53), respectively. PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.
Prashant Agarwal; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; Seetha Shankaran; Abbot R. Laptook; Dhuly Chowdhury; SatyaN Lakshminrusimha; Sonia Lomeli Bonifacio; Girija Natarajan; Sanjay Chawla; Martin Keszler; Roy J. Heyne; Namasivayam Ambalavanan; Michele C. Walsh; Abhik Das; Krisa P. Van Meurs. Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies. Journal of Perinatology 2021, 41, 502 -511.
AMA StylePrashant Agarwal, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, Seetha Shankaran, Abbot R. Laptook, Dhuly Chowdhury, SatyaN Lakshminrusimha, Sonia Lomeli Bonifacio, Girija Natarajan, Sanjay Chawla, Martin Keszler, Roy J. Heyne, Namasivayam Ambalavanan, Michele C. Walsh, Abhik Das, Krisa P. Van Meurs. Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies. Journal of Perinatology. 2021; 41 (3):502-511.
Chicago/Turabian StylePrashant Agarwal; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; Seetha Shankaran; Abbot R. Laptook; Dhuly Chowdhury; SatyaN Lakshminrusimha; Sonia Lomeli Bonifacio; Girija Natarajan; Sanjay Chawla; Martin Keszler; Roy J. Heyne; Namasivayam Ambalavanan; Michele C. Walsh; Abhik Das; Krisa P. Van Meurs. 2021. "Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies." Journal of Perinatology 41, no. 3: 502-511.
We agree with Dekker et al that their small, randomized trial did not show an increase in the risk of hyperoxia with the use of 100% oxygen.1Dekker J. Martherus T. Lopriore E. Giera M. McGillick E.V. Hutten J. et al.The effect of initial high vs low FiO2 on breathing effort in preterm infants at birth: a randomized controlled trial.Front Pediatr. 2019; 7: 504Crossref PubMed Scopus (4) Google Scholar We acknowledge that in this trial, respiratory effort was improved in the 100% oxygen group (as shown in the graphic abstract). We also agree that the gradient between PiO2 (partial pressure of inspired oxygen), PaO2 (partial pressure of alveolar oxygen), and PaO2 (partial pressure of arterial oxygen) is high soon after birth and improves with time and emphasized this in Figure 3 of the commentary. In addition, we want to point out that there is a potential for significant discrepancy in the relationship between PaO2 and preductal oxygen saturation (SpO2) in neonates.2Bachman T.E. Iyer N.P. Newth C.J.L. Ross P.A. Khemani R.G. Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.BMC Pediatr. 2020; 20: 317Crossref PubMed Scopus (1) Google Scholar
Ola Didrik Saugstad; SatyaN Lakshminrusimha; Maximo Vento. Reply. The Journal of Pediatrics 2020, 229, 309 -310.
AMA StyleOla Didrik Saugstad, SatyaN Lakshminrusimha, Maximo Vento. Reply. The Journal of Pediatrics. 2020; 229 ():309-310.
Chicago/Turabian StyleOla Didrik Saugstad; SatyaN Lakshminrusimha; Maximo Vento. 2020. "Reply." The Journal of Pediatrics 229, no. : 309-310.
Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of high pulmonary vascular resistance (PVR) commonly seen all over the world in the immediate newborn period. Several case reports from India have recently described severe pulmonary hypertension among infants in the postneonatal period. These cases typically present with respiratory distress in 1–6-month-old infants, breastfed by mothers on a polished rice-based diet. Predisposing factors include respiratory tract infection such as acute laryngotracheobronchitis with change in voice, leading to pulmonary hypertension, right atrial and ventricular dilation, pulmonary edema and hepatomegaly. Mortality is high without specific therapy. Respiratory support, pulmonary vasodilator therapy, inotropes, diuretics and thiamine infusion have improved the outcome of these infants. This review outlines four typical patients with thiamine-responsive acute pulmonary hypertension of early infancy (TRAPHEI) due to thiamine deficiency and discusses pathophysiology, clinical features, diagnostic criteria and therapeutic options.
Nalinikanta Panigrahy; Dinesh Kumar Chirla; Rakshay Shetty; Farhan A. R. Shaikh; Poddutoor Preetham Kumar; Rajeshwari Madappa; Anand Lingan; SatyaN Lakshminrusimha. Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)—A Case Series and Clinical Review. Children 2020, 7, 199 .
AMA StyleNalinikanta Panigrahy, Dinesh Kumar Chirla, Rakshay Shetty, Farhan A. R. Shaikh, Poddutoor Preetham Kumar, Rajeshwari Madappa, Anand Lingan, SatyaN Lakshminrusimha. Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)—A Case Series and Clinical Review. Children. 2020; 7 (11):199.
Chicago/Turabian StyleNalinikanta Panigrahy; Dinesh Kumar Chirla; Rakshay Shetty; Farhan A. R. Shaikh; Poddutoor Preetham Kumar; Rajeshwari Madappa; Anand Lingan; SatyaN Lakshminrusimha. 2020. "Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)—A Case Series and Clinical Review." Children 7, no. 11: 199.