Antenatal Steroids-Too Much, Too Little, or Just Nice?

Brain Function Monitoring in Asphyxiated Infants

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing during the evolution of injury is vital for guiding treatments. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in EEG activity, cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion mediated by endogenous metabolic suppression, followed by secondary deterioration with seizures, hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution and injury severity. In this presentation, we will review evidence that changes in EEG, cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.

Therapeutic Drifts in Hypoxic Ischaemic Encephalopathy

Therapeutic hypothermia (TH) is now well established to improve intact survival after neonatal encephalopathy (NE). However, since the completion of the randomized controlled trials there has been substantial therapeutic drift because many specific situation could not included in the trials. Should we cool late preterm newborns with NE? Is cooling beneficial for mild NE? Is cooling for 72 hours optimal, or should we cool for longer? Will either milder or deeper hypothermia be effective? Why was TH not effective in the HELIX trial? In this presentation I will dissect the underlying pathophysiological principles that can guide practice and future research.

Culture Eats Strategy–Building Robust Systems

While leadership plays an important role in setting strategic priorities of the organization, organizational culture plays an extremely important role at executing these priorities at ensuring a reliable safety and quality of care. Organizational culture is a shared way of thinking, feeling and behaving within the institution itself. It can be the culprit leading to downfalls of healthcare organizations. On the other hand, the right organizational culture can be a remedy for learning organizations to improve their safety and quality of care. The recently published Ockenden report highlighted failings in the perinatal services of the Shrewsbury and Telford Hospitals NHS Trust. There was poor antenatal care for vulnerable women, repeated failures to correctly assess fetal growth, reluctance to refer women to tertiary centres to address fetal abnormalities, poor management of multiple pregnancies, poor management of gestational hypertension, failure to recognize sick or deteriorating women, failure to act on abnormal fetal heart patterns and failure to escalate concerns. These were the result of shortcomings within the leadership and teamwork. There was a culture of bullying and concerns raised by staff were taken lightly. This stemmed from poor working relationships, poor risk assessment, grossly inadequate response to adverse incidents, lack of board grip, inadequate clinical governance and emphasis on ‘normal’ birth particularly in high risk pregnancies at the expense of good care. The patients’ voices were ignored leading to a gross lack of empathy in handling poor outcomes, mortalities and bereavement support. As leaders, senior clinicians in the system need to be cognizant of team dynamics and communication among their members. Creating a psychologically safe environment for people to raise concerns and to learn from it for improvement is essential. This should include partnering and hearing the voices of patients. Leadership sets the culture. In turn, the culture determines the direction the organization is heading. A culture that promotes learning would steer away from merely blaming individuals for errors. In a psychologically safe environment, mistakes and errors are viewed as learning opportunities to strengthen the system. Focusing on this will help create robust processes to ensure a highly reliable delivery of care.

Neonatal Resuscitation: What’s New?

Surfactant Delivery – Minimal, Less, and Least Invasive

Targeting the Inflamed Lung & Sepsis-Use of Human Amnion Epithelial Cells

Controversies in Management of Cervical Insufficiency

Stem Cells for HIE

Tinier and Tinier-Moving Targets for Definition of Viability

Massive Pulmonary Haemorrhage

Screening for Inborn Errors of Metabolism - A Cost-Effective Method

Recommendations from World Association of Perinatal Medicine (WAPM)-Clinical management of COVID-19 in pregnancy

Stem Cells for BPD

Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with ventilator and oxygen therapy in very premature infants. Although the number of very preterm infants at high risk of developing BPD has increased due to recent advances in neonatal intensive care, BPD remains a significant cause of death and lifetime morbidities without effective ways to prevent or treat it. Thus, a new treatment modality is urgently needed to improve the prognosis of this intractable disorder. Previous preclinical studies have shown that mesenchymal stem cells (MSCs) attenuate hyperoxic-induced neonatal lung injury in an animal model simulating BPD of human infants. In a first in human phase 1 clinical trial, we have demonstrated that intratracheal transplantation of umbilical cord blood derived MSCs for bronchopulmonary dysplasia (BPD) is safe and feasible in very preterm infants. Then, we performed a randomized, double-blind, placebo-controlled phase II clinical trial to investigate the therapeutic efficacy of MSCs (1× 107 cells/kg) for BPD. It was conducted on 66 preterm infants born at 23 to 28 weeks of gestation and received mechanical ventilator support with respiratory deterioration between 5 and 14 postnatal days. The primary outcome of death or moderate to severe BPD was not significantly different between the control and MSC group. However, subgroup analysis revealed that MSC transplantation decreased secondary outcome of severe BPD in subgroup infants of 23 to 24 weeks, not in 25-28 weeks of gestation. We recently completed 5-year long-term follow-up study for these enrolled patients and the results are pending. Accordingly, we are now conducting an additional larger randomized double-blinded placebo-controlled phase II clinical trial that focuses on extremely preterm infants of 23 to 24 weeks of gestation. (NCT03392467).

Amniotic fluid derived mesenchymal stem cell-Perinatal Treatment

Preventing Prematurity & Stillbirths

Neonatal Transport & Retrieval in Japan

The Littlest Angels–Establishment of Neonatal Organ & Tissue Donation Services

Ensuring Survival of Babies with Severe Congenital Diaphragmatic Hernia

EXIT Procedures-Latest Advances

Clinical Practice of Neurally Adjusted Ventilatory Assist (NAVA) in the NICU

Neurally adjusted ventilatory assist (NAVA) is a new ventilatory mode that allows the patient to synchronize spontaneous respiratory effort via the detection of an electrical signal from the diaphragm muscle. By utilizing the electrical activity of the diaphragm (EAdi), NAVA can synchronize mechanical ventilatory breaths with the patient’s neural respiratory drive and proportionally support this drive. Theoretically, by maintaining spontaneous breathing and improving the patient-ventilator interaction, NAVA may be able to prevent premature lung damage by avoiding high- pressure or high volume support and providing more physiologic mechanical ventilatory support. Neurally adjusted ventilator assist (NAVA) was introduced to our unit via crossover-RCTs to assess its safety and physiological effects. First, mechanically ventilated preterm infants were randomized to crossover ventilation with NAVA and SIMV-PS for 4-hour each to determine the physiologic effects of NAVA (J Pediatr 2012). Peak inspiratory pressure (PIP), work of breathing, and peak-EAdi with NAVA were lower. Calculated TV to peak-EAdi ratio and PIP to peak-EAdi ratio were higher with NAVA. Second, we conducted another crossover-RCT to compare non-invasive NAVA (NI-NAVA) and NI-PS on patient-ventilator synchrony( ADC-F&E 2015). Maximum-Edi, swing-Edi and PIP were lower during NI-NAVA. All types of asynchronies and Asynchrony-index were reduced with NI-NAVA. In our unit, intubated-NAVA has been mainly applied for infants with higher and/or prolonged ventilatory support. Our cohort studies showed NAVA 1) improved ventilator variables and blood gas values in infants with BPD (PCCM. 2016) and 2) reduced cyanotic episodes and sedatives and dexamethasone uses for infants on prolonged mechanical ventilation (Pediatr Int. 2017). We have used NI-NAVA as a weaning mode from intubated ventilation. Our pilot-study suggested that NI-NAVA might have advantages in reducing extubation-failure compared to nCPAP (BMC Pediatr. 2019) and we has conducted an RCT to determine the clinical advantage of NIV-NAVA compared to nCPAP after extubation in preterm infants (NCT02590757).

Can’t Intubate, Can’t Ventilate –What Next?

Intubation is a core skill that allows a neonatal resuscitation provider to control the airway and more effectively oxygenate and ventilate a newborn infant in cardiopulmonary failure. When intubation and ventilation are indicated, but is technically difficult, the time delay can result in rapid deterioration. It is important for resuscitators to have alternative techniques to control a newborn infant’s airway at their disposal. In this lecture these techniques will be discussed.

Lasting Generations: Substance Abuse in Mothers

Neonatal Hypovolaemic Shock: Surviving the plunge

True hypovolemic shock is rare in neonates and is mostly seen early after birth. Causes include peripartum bleeding from the fetal side of the placenta, feto-maternal haemorrhage, feto-fetal hemorrhage or a postpartum hemorrhage of the neonate. With ongoing bleeding, the autonomic sympathetic system is activated with inhibition of the parasympathetic system leading to increased heart rate, cardiac contractility and arterial and venous tone. Blood volume from the non-vital organs and the venous system will be recruited to help preserve blood flow to the brain, heart and adrenal glands. If the bleeding cannot be stopped, severe hypovolemia will finally lead to severe acidosis and myocardial dysfunction, organ failure and death. The optimal approach to hemorrhagic hypovolemia in neonates has not been well studied. Most of what is known about physiology and management has been extrapolated from animal and adult data. Rapid replacement of the type of the fluid lost, most frequently whole blood, is the key approach along with appropriate supportive measures. Noradrenaline is the first line of vasopressor-inotrope used in adults as it induces significant venoconstriction at the level of the splanchnic circulation in particular. Echocardiography can be effectively used to monitor systemic perfusion during hypovolemic shock in neonates and to test fluid responsiveness at the bedside.

Risk Assessment of Unbooked Mothers in Labour

Definition-Unbooked mothers are those who have no antenatal care who delivered within 3 days of initial booking visit. Booked mothers are those who had regular antenatal check up according to WHO criteria or regional criteria (2-8 visits). There are many studies or researches-the results are more or less same-in only one study done in Harare (Zimbabwe)-they showed that fetomaternal complications are more in booked patients because those patients are already with some obstetric comlications-so the pregnancy outcome is more worse than unbooked patients. But in most of the studies-It has shown that in case of unbooked patients-the obstetric condition is unknown to labor staffs- and they ended up with emergency caesarean section, laparotomy due to rupture uterus,worse perinatal outcome and neonatal complications. To achieve the SDG-30-most of the countries implement various programs and projects to improve the maternal and neonatal health and to reduce the maternal and neonatal mortality rates.These programs are mainly Government programs in collaboration with NGO, development partners, professional bodies etc. In many countries- organized antenatal care provided by different organization are exist-but specially in developing countries the number of unbooked mothers vary from 2% to 38%.They are a great burden for the labor room of the tertiary centers . Usually the unbooked mothers are young, healthy, needs more emergency casarean section, operative delivery , sometimes laparotomy for rupture uterus increasing the maternal and neonatal mortality and morbidity. So to reduce the maternal and neonatal mortality-number of unbooked patient should be decreased by awareness, providing quality and organized antenatal check up proper referral, sometimes by giving some incentives for antenatal care.

Teaching Midwifery–From Obstetric Simulation to Real World Practice

Miracle Babies: Providing parental support

Triaging in the Management of Pre-Eclampsia

Dopplers & Monitoring Methods for Fetal Growth Restriction -When to Intervene

Pitfalls in Functional Lung Ultrasound

Innovations in Saving Babies-From the Past to The New World

Tiny yet Mighty-Care of Extremely Preterm Infants

Although the mortality rate among extremely preterm infants has been improving over time, morbidities among them are not reduced to an acceptable level yet. There is also a variation in the limit of viability, use of antenatal corticosteroid, choice of delivery mode, initiation of resuscitation, NICU care, and follow-up of survivors among extremely preterm infants. These variations can be attributable to the lack of a standardized approach in care based on strong evidence proved by well-designed clinical trials. Therapeutic drifts exist there. There are several reasons why clinical trials were not sufficiently performed until recently. The major reason was due to high mortality rate. If the majority of infants enrolled in clinical trials died, it would be very difficult to prove the benefit of new treatment due to high background noise. Therefore, most practices in NICU for extremely preterm infants have been developed by clinical experiences rather than randomized clinical trials. Accumulated realistic experiences from the front line of NICU care have provided in a way strong support for clinicians. In fact, as mentioned above, the current mortality rate among extremely preterm infants has been declining and reached about 10% by virtue of available clinical knowledge. In this sense, we should appreciate of thoughtfulness and tremendous efforts of many predecessors in modern neonatal medicine. However, in order to achieve further improvement in outcomes of extremely preterm infants, basic and translational research which could fill the current knowledge gaps and new drug/device development in neonatal medicine are mandatory. Since 1980 when Prof. Fujiwara introduced pulmonary surfactant therapy for infants with respiratory distress syndrome, only limited interventions were studied and developed for the care of extremely preterm infants. Now when the mortality rate among extremely preterm infants decreased enough, it is the most suitable time for introducing innovative care into our NICU through evidence-based medicine. For this purpose, international collaboration is essential because clinical trials involving tiny infants are not easy, even for countries with advanced neonatal care.

Babies with Hypoxaemic Respiratory Failure

Hypoxemic respiratory failure (HRF) is often associated with persistent pulmonary hypertension of the newborn (PPHN). This combination (HRF + PPHN) is seen in both preterm and term infants. The approximately incidence is around 2 per 1000 live births in the US. Neonates present with respiratory distress, labile hypoxemia and in some cases, differential cyanosis (lower oxygen saturations -SpO2 – in the lower limbs compared to right upper limb). Most cases of HRF/PPHN are secondary to lung disease such as meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), respiratory distress syndrome (RDS), pneumonia, transient tachypnea of the newborn (TTN) and asphyxia. However, some cases are not associated with lung disease and are due to pulmonary vascular remodeling or hyperactivity and are known as idiopathic or “black-lung” PPHN.
The diagnosis of HRF/PPHN is established by echocardiography. Absence of anatomical cardiac defect, right-to-left or bidirectional shunt at the level of the patent foramen ovale (PFO) or patent ductus arteriosus (PDA), right ventricular hypertrophy or dysfunction, bulging of the interventricular septum to the left and tricuspid regurgitation are common echocardiographic features of HRF/PPHN. The management is based on diagnosis. In parenchymal lung disease such as MAS, pneumonia and RDS, optimal lung recruitment with respiratory support to provide adequate mean airway pressure (including mechanical ventilation if needed), surfactant, along with supplemental oxygen is needed. In patients with hypoplastic lungs such as CDH, gentle ventilation with low pressures will minimize volutrauma to the fragile lungs. If these measures are not adequate, pulmonary vasodilator therapy with inhaled nitric oxide (iNO), IV/PO sildenafil and IV milrinone may be considered. Approximately 20-30% of patients with HRF/PPHN may not respond to mechanical ventilation and pulmonary vasodilator therapy. The most common reason for poor response in inadequate lung recruitment. Using adequate PEEP or mean airway pressure to open the lungs to functional residual capacity is crucial to reduce pulmonary vascular resistance (PVR) and optimize delivery of iNO. Managing hemodynamics with appropriate fluid and vasopressor support is needed in 30-40% of patients with HRF/PPHN. If all these measures fail, extracorporeal membrane oxygenation (ECMO) may be warranted.

Rescuing Neonates in Low- & Middle-Income Countries

Towards Zero NEC–Risk Awareness Tools

Expanding the Scope of Non-Invasive Prenatal Testing (NIPT)

Business as Usual?–Breastfeeding & Skin-to-Skin

Our People–Resilience in Academic Medicine

Asian Neonatal Collaborative Network

The reduction of neonatal death is one of the focuses of the Sustainable Development Goals (SDGs) adopted in the United Nations Sustainable Development Summit in 2015. Although the neonatal mortality has been improving, it still remains high in low- and middle-income countries (LMICs). Therefore, how to reduce the neonatal mortality in LMICs is a key issue in global health. The top cause of neonatal death was prematurity followed by asphyxia. Therefore, the improvement in the care of preterm infants as well as birth asphyxia is important to reduce global neonatal death. Many countries or regions developed national neonatal networks, which are the groups of people and facilities who collaborates to improve the quality of care and outcomes of newborn infants in neonatal intensive care units. In Japan, the Neonatal Research Network Japan (NRNJ) was established in 2004. The NRNJ currently includes approximately 190 NICUs across Japan and maintains national neonatal database of very preterm infants. Furthermore, the NRNJ has been collaborating with other national or regional neonatal networks in high-income countries in a project called iNEO. Wide variations in clinical practice and outcomes of preterm infants were found between the countries or regions in the iNEO. The information has been used for benchmarking and quality improvement to improve preterm infants’ outcomes in each country or region in the iNEO. Following the success of the iNEO, we recently launched another new international collaboration in Asia; Asian Neonatal Network Collaboration (AsianNeo). The AsianNeo includes eight countries (Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, and Thailand). The aims of the AsianNeo are (1) to understand the differences in systems, clinical management and outcomes of sick newborn infants, (2) to improve the quality of neonatal care in participating countries or regions by applying the obtained knowledge and adopting methods of quality improvement, (3) to accelerate the communication among Asian neonatal networks, and (4) to educate young pediatricians and neonatologists. The uniqueness of the AsianNeo is the inclusion of both high-income countries and LMICs in Asia to learn from each other. In this presentation, I will introduce the current activities of the AsianNeo and the future perspectives of these collaborations.

Assisted Vaginal Birth for the 21st Century

In-Utero Myelomeningocoele Repair

Preventing Brain Damage from Hypoglycaemia

Neonatal hypoglycaemia is the most common biochemical abnormality occurring in 15-20% newborn infants. About 10% require more intensive treatment and sub-optimal management may cause irreversible neurological sequelae. Persistent and recurrent hypoglycaemia can severely impair brain growth and its function. The duration of hypoglycaemia has a larger effect on brain injury rather than the severity of hypoglycaemia. The blood glucose threshold for neonatal hypoglycaemic brain injury (NHBI) is controversial and remains unclear. The pathological changes of NHBI characteristically involve gray matter of posterior parieto-occipital regions of brain bilaterally. The cerebellum and brainstem are often not involved and haemorrhagic lesions are rare. Hypoglycaemia and cerebral hypoxia synergistically accentuate neuronal injury. MRI and MRS are the more sensitive and specific screening methods for diagnosing NHBI and they are superior to ultrasound and CT. Skin-to-skin care soon after birth and early initiation of breast feeding have shown to improve glucose homeostasis and are the most important factor for the prevention of NHBI. The management of the neonate needs to be based on a feed-centric pathway. The use of buccal glucose gel has markedly reduced the need for parenteral glucose administration and separation of the mother-infant dyad. It is more effective than milk feeds alone in reversing asymptomatic hypoglycaemia in infants ≥35 weeks gestation. The possibility of hyperinsulinemia as the underlying cause in persistent or recurrent hypoglycaemia must be considered particularly in infants after 72 hours of life. The etiologic factors include intra-uterine growth restriction (IUGR), infants of diabetic mothers (IDM) and Beckwith-Wiedemann syndrome, islet cell dysregulation syndrome and metabolic disorders. In these cases, the plasma glucose levels need to be kept above 3.5 mmol/l to prevent brain injury. They may need treatment with Diazoxide, Glucagon and/or Octreotide in addition to parenteral glucose. Genetic studies and DOPA pet scan in refractory cases enable to distinguish between focal & diffuse lesions in the pancreas and optimise therapy. Wide fluctuations of blood glucose and hyperglycaemia may aggravate brain injury, hence avoided. Early intervention programme can promote the functional reorganization of the central nervous system, promote the recovery and regeneration of injured brain cells in these high-risk infants.

Managing PPHN with Continuous Haemodynamic Monitoring

Justice in Providing Maternal Somatic Support

The Distressed Fetus! Timeliness of Intervention

Low Platelets, at Due Date! The Options

Managing thrombocytopenia in pregnancy can be challenging. About 5-10% of pregnant women have documented thrombocytopenia, which is usually defined as platelet counts of < 150x109/L. Most common cause of thrombocytopenia during the third trimester is gestational thrombocytopenia, which usually do not require any treatment and will resolve spontaneously after delivery. Other causes include pre-eclampsia, HELLP syndrome and hematological disorders such as immune thrombocytopenia purpura (ITP) and thrombotic thrombocytopenia purpura (TTP), which is rare but can be life-threatening. In this talk, I will be focusing on ITP and TTP. For ITP, the goal is to reduce the risk of bleeding for both mothers and babies, while minimizing adverse effects from therapy. Treatment options usually depend on the platelet counts. The first line of treatment is usually corticosteroids, with prednisolone being the preferred choice. Intravenous immunoglobulin is also commonly used in patients who are steroid refractory or resistant. Increasingly, there are other therapeutic options such as rituximab, the new TPO agonist such as eltrombopag , which have shown to not cause major adverse effect in pregnancies. Acquired TTP is not common and can occur during 1st pregnancy and postpartum. This is likely due to the fall in ADAMTS13 level and rise of von Willebrand factor. It is crucial to have high index of suspicion especially when patients present with hemolytic anemia and thrombocytopenia. Relevant investigations such as measurement of ADAMTS 13 levels are important to differentiate from other causes. Treatment of choice for TTP is to commence plasmapheresis as soon as possible.

Role of Maternal Nutrition -The DOHaD Hypothesis

At the Peak of COVID Crisis in Pregnant Women–Can it be Worse?

Simulation Training in Perinatal Emergencies: The ICOE Experience

Medicolegal Perspectives of Birth Injuries

Breast Cancer-Dilemmas of Each Trimester

Gestational breast cancer occurs during pregnancy, the first post-partum year, or lactational period. Patients often present with more advanced diseases, as breast cancer is unexpected in the childbearing years and difficulty detecting lumps in pregnant breasts. The management of breast cancer is dependent on the stage of the disease and the gestation of the pregnancy. In the first trimester, surgery can be performed, and chemotherapy can be instituted within 6 to 12 weeks later during the second trimester. Thus, termination of pregnancy(TOP) is rarely required. They are non-therapeutic and do not affect the prognosis of the patient incurable breast cancer. However, TOP can be considered if the prognosis is poor or if there are other social issues on her ability to care for her child. The dilemma occurs in stage 4 cancers, as in every trimester, the primary objective is always to save the mother. In the first trimester, options for TOP must be discussed if there could be a delay in instituting life-saving systemic therapy in high volume life-threatening metastatic disease. Especially when the patient is not fit for systemic treatment, best supportive care to palliate and support the patient as long as possible to reach pulmonary maturity of the fetus. Staging the disease during pregnancy is usually done with a chest x-ray with abdominal shielding and an ultrasound to assess for liver metastases. Non-contrasted MRI of the spine may be used to evaluate for bone metastases. The diagnosis of cancer is fraught with not just physical impacts but psychosocial ones, the patient, must contend with not just the threat of losing her life but her unborn child. Therefore, it would be mandatory for teams managing these patients to provide psychosocial support and not withstanding to assign patients to social workers or counselors to help them and their family to make medical decisions that need to be made in a timely manner. Either breast conserving or mastectomy can be reasonable options for patients depending on suitability and preference of the patients. As mentioned, systemic therapy can be used in the second and third trimesters. The systemic therapy used are chemotherapy, targeted Her2 therapies like trastuzumab and hormonal treatments are contraindicated. The delivery is an electively planned event, the last systemic therapy must be stopped 3 to 4 weeks before delivery to reduce complications related to neutropenia and thrombocytopenia. In utero exposure to systemic therapy has been documented in small case series, showing low complication rates, with IUGR being the most common. Gestational breast cancer patients are often delivered more preterm. Long term outcomes of babies in utero during cancer treatments show that there is no increase in malignancy or long-term problems when compared to non-breast cancer gestational age-matched controls. Gestational breast cancer compared to non-breast cancer pregnant individuals are associated with a higher risk of death, a large meta-analysis found this is limited those diagnosed in the post-delivery period. In another study, this was found to be both diagnosed during pregnancy or the post-partum period. The talk will further discuss the dilemmas in the three trimesters.

Resuscitation of Newborns at Risk of COVID-19

Examination of the Placenta– Training the Trainees

Dilemmas of Perimortem Caesarean Sections

Preventing Shoulder Dystocia

Renal Failure in Pregnancy

Hypothyroidism in Preterm & Ill Babies

Losing to Save-Termination of Pregnancy