Neonatal neuropalliative care

Abstract

Neonatal neuropalliative care is directed toward patients and families impacted by serious, life limiting, or debilitating neurologic illness in the antenatal and newborn period. This chapter will outline key considerations for clinicians hoping to provide a neuropalliative care approach antenatally, at birth, and in the neonatal intensive care unit. We focus on three core domains:(1)family-centered communication and care, (2) prognostication and decision-making, and (3) pain and symptom management. In each domain, we outline key considerations in the antenatal period, at birth, and in the neonatal intensive care unit. We also address special considerations in care at the end of life and in varied cultural and practice contexts. We conclude with suggestions for future research and key considerations for neonatal clinicians who wish to incorporate a neuropalliative approach to care into their practice.

INTRODUCTION

Neuropalliative care bridges core neurology teaching and practice patterns central to palliative care. Palliative care itself represents an approach to the medical care of patients with serious, life-limiting, or debilitating illness that focuses on pain and symptom management, psychosocial support, effective communication, and partnership between families and the medical care team. Neuropalliative care has recently been defined as “care that focuses on the specific needs of patients with neurologic illness and their families, including both primary and specialist palliative care.” (Creutzfeldt et al., 2018). Such care is considered appropriate as soon as a serious neurologic diagnosis is made, regardless of prognostic certainty (Lemmon et al., 2016a). For many fetal and neonatal neurology patients, a neuropalliative care approach offers an extra layer of support to help families navigate communication, decision-making, and symptom management.

Specialist palliative care teams are by nature interdisciplinary and consist of physicians, nurses, social workers, psychologists, chaplains, and others (Lemmon et al., 2016a). However, palliative care itself is a way of providing care and approaching the management of complex patients that can be practiced by all providers (also known as primary palliative care) (Quill and Abernethy, 2013) and “palliative care” should not be seen strictly as a classification of certain team members. Building upon this foundation, trained palliative care specialists can provide expertise as members of a neonatal neurointensive care team for those patients with more medically complex problems, symptom challenges, as well as conflict resolution or additional psychosocial or communication needs. Dedicated palliative care teams can often help bridge care needs between the inpatient and outpatient setting. Additionally, such teams may recognize and manage moral distress among members of a complex child’s medical care team (Rushton et al., 2013). Alongside the primary and subspecialty teams, providers with advanced training in palliative care can help facilitate difficult care conversations and provide additional support for both parents and providers.

The following core palliative care skills were identified in the 2017 Neuropalliative Care Summit as important for medical providers delivering care to neurologically complex patients: identify common palliative care needs associated with specific neurologic disorders, detect and manage whole body pain, provide basic psychosocial and spiritual support, acquire communication skills including empathetic listening, effectively estimate and communicate prognosis and uncertainty, master shared decision-making for common preference sensitive decisions, master shared decision-making and support for patient and families around tragic choices, be aware of palliative care potions of last resort, and recognize and manage caregiver distress and needs (Creutzfeldt et al., 2018). All neurologists, regardless of their stage of training, should be able to provide primary palliative care to patients with neurologically devastating conditions (Creutzfeldt et al., 2016).

Many life-limiting and life-altering neurologic diagnoses present prenatally or in the neonatal intensive care unit(NICU)(Table 11.1). The perinatal period, therefore, offers a unique opportunity to prepare and empower families who may be embarking on a lifetime of interacting with the healthcare system. Technological advances have made it easier for providers to detect life-limiting or life-threatening neurologic problems earlier in pregnancy, allowing for earlier contact between neuropalliative teams and families. A central aspect of palliative care, including neuropalliative care, is establishing a trusting relationship between providers and families that will help facilitate effective continuity of care across a patient’s care course. While some aspects of neuropalliative care will be specific to the time point in which care is delivered—antenatally, at the time of birth, in the NICU, or following discharge—other facets of care will transcend this framework. Skills such as communication, shared decision-making, and the provision of collaborative interdisciplinary care are essential at every stage. Several models of care have been developed to provide perinatal palliative care to infants with neurologic conditions. Some programs provide dedicated medical and support services for infants after discharge from the NICU, such as Transitional Medical Home Programs (Mago-Shah et al., 2021), while others incorporate palliative care clinicians and approaches into neonatal neurointensive care teams.

Table 11.1.

Common fetal and neonatal neurologic diagnoses

Time period	Common diagnoses	Interdisciplinary team members
Antenatal	Hydranencephaly	Obstetrics
	Holoprosencephaly	Fetal neurology
	Congenital hydrocephalus	Perinatal palliative care
	Trisomies	Neurosurgery
	Myelomeningocele	Pastoral care
	Encephalocele	Social work
		Genetic counselors
Post-natal	Intraventricular hemorrhage	Neonatology
	Posthemorrhagic hydrocephalus	Neonatal neurology
	Hypoxic ischemic encephalopathy	Palliative care
	Neuromuscular conditions	Pastoral care
	Neonatal epileptic encephalopathy	Social work
	Perinatal arterial ischemic stroke

In this chapter, we will describe the three core aspects of neonatal neuropalliative care: (1) family-centered communication,(2) prognostication and decision-making, and (3) pain and symptom management. We will address these topics in relation to specific care time points spanning the antenatal consult, delivery, time in the NICU, and ongoing needs following discharge. We will discuss specific issues related to the withdrawal of life-sustaining interventions for infants, bereavement support, and additional considerations related to culture and area of practice. We will conclude with key practice points for the neurology clinician who wishes to incorporate a neuropalliative care approach into their practice.

FAMILY-CENTERED COMMUNICATION

For infants with neurologic injury, multiple subspecialists are typically involved in their care starting before or at birth and intensifying during their first hospital admission(Glass et al., 2014). This multidisciplinary care is a feature of care for both patients with primary neurodevelopmental conditions, such as structural anomalies or genetic syndromes, and for those who have suffered neurologic injury secondary to an underlying cardiopulmonary, hematologic, infectious, or other condition. A patient’s team may be comprised of neonatologists, obstetricians, neurologists, neurosurgeons, general surgeons, palliative care clinicians, geneticists, and any number of other relevant subspecialists. This interdisciplinary team also consists of dedicated nurses, social workers, chaplains, and other disciplines. Given the number of providers engaged in a patient’s care, ensuring timely and accurate communication between team members and with families is essential. Communication must be empathetic and personalized, recognizing families may be at different stages in their ability to receive and process complex information. Sharing of information and providing counseling is often necessary at several points throughout a patient’s clinical course, including antenatally and following discharge.

One commonly used approach to ensuring consistency in messaging between provider groups and accurate family counseling for patients with neurologic injury is having regular joint perinatal conferences that include neonatology, neurology, palliative care, and any other relevant specialties. Postnatally, this translates into having frequent joint care meetings, ideally with families, to discuss changes in clinical status or goals of care. Many neurocritical patients will have prolonged hospitalizations, which may, paradoxically, lead to parents feeling less and less informed over time (Nelson et al., 2007). It is therefore the responsibility of the hospital care providers to engage parents both with routine happenings and at critical decision points in their infant’s care.

In addition to communication and support around physical illness, many families value when clinicians address spiritual and emotional needs (Robinson et al., 2006). Most families appreciate the opportunity to discuss spiritual beliefs with pastoral care; some would welcome discussing spirituality directly with clinicians (Arutyunyan et al., 2018).

Antenatal counseling

A provider’s first encounter with a neonatal neuropalliative care patient may be before that infant is born, through meeting with the infant’s parents in an antenatal counseling session. The parents may have only recently found out about their infant’s neurologic condition or they may have been aware of the condition for some time. Families will have varied levels of medical knowledge, including between parenting couples, and may have done their own research prior to meeting with the neurology team. The consulting specialists should be aware of all diagnostic studies and imaging that have already been performed, what information has been shared with the family, as well as any other relevant medical history including any challenges in past pregnancies or in older siblings.

During the antenatal counseling session, the primary objective is establishing a provider-patient relationship and engaging in shared goal setting for the affected fetus. Antenatal palliative care consultation can be helpful in cases where the infant is unlikely to survive much beyond the delivery and for families of patients with congenital conditions that are not immediately life threatening but are associated with significant neurologic impairment (Sumner et al., 2006). In cases of known severe fetal anomalies, such as neurologic malformations or genetic conditions with neurologic implications, a small but increasing number of women are choosing to continue pregnancy, citing the availability of perinatal palliative care options for their infant (Madeuf et al., 2016; Hostalery and Tosello, 2017). Despite this, only a minority of pregnant mothers carrying fetuses with “uncertain, likely poor” or “nonsurvivable” complications receive prenatal palliative counseling (Kukora et al., 2017). Families of such infants are more likely to make a delivery plan focused on comfort than those who did not receive antenatal palliative care consultation. Existing data suggest that early antenatal counseling of high-risk pregnancies improves family knowledge and satisfaction without increasing parental anxiety (Fish et al., 2021).

For all children with suspected neurologic disorders, it is important to introduce palliative care concepts early as part of the care plan, regardless of mortality risk (Bidegain and Younge, 2015). Clearly describing the role of palliative care in medically complex patients, including maximizing quality of life, optimizing communication, management of pain and distress, and multidisciplinary family support, may help families better receive these interventions after delivery. Some families find comfort elaborating a palliative care birth plan that provides a sense of control and honors their wishes for their baby (Kenner et al., 2015). These plans should be followed at the time of birth regardless of which health providers are present for the delivery, making it essential that antenatal consults and delivery plans for neuropalliative patients be clearly documented and accessible to the newborn care team (Bidegain and Younge, 2015).

At birth

Around the time of delivery, the neonatology providers will be primarily focused on the immediate resuscitation or stabilization needs of the infant. For infants receiving active resuscitation, this will include ensuring that the patient has a patent and secured airway if they are not breathing on their own, monitoring for signs of cardiac or hemodynamic instability, and assessing for any anticipated or unanticipated anomalies. For infants prenatally diagnosed with neurologic conditions, this assessment may include the presence or degree of associated anomalies. As the clinical status of medically complex children can change rapidly, or vary significantly from what was anticipated prenatally, ongoing sharing of information with parents is encouraged. During the resuscitation, such updates will likely come from the neonatology team and maternal clinicians; however, neurology providers may be asked to assess a baby shortly after birth and help provide updates to parents regarding the postnatal neurologic status of their infant.

Parents may differ on how much information they want during the resuscitation and on if they wish to be present at bedside during this initial stabilization period. Hospitals may also differ in if they allow the nonbirthing parent, or support person, to be present during the entirety of the newborn’s resuscitation. While studies support family presence during neonatal resuscitation (Sawyer et al. 2015), this is balanced by recognition of the stress experienced watching one’s child be resuscitated, especially when patient acuity limits the feasibility of real-time communication (Harvey and Pattison, 2012). Many centers bring parents in once the infant is stable or if it seems that the child will not survive the resuscitation. Addressing expectations both on the part of the parents and the provider team well before delivery is important, given the time constraints and urgency of communication at the time of delivery.

Some neonatal neurologic conditions are unanticipated and become apparent at the time of birth. In neonatal encephalopathy, existing data suggest a predictable pattern of communication challenges. For most parents, pregnancy was uncomplicated, until a maternal crisis resulted in an urgent delivery. Mothers describe this experience as traumatic, and many grieve the loss of the typical birth experience (Lemmon et al., 2016b). Fragmented communication between teams, partners, and family members can amplify these challenges (Lemmon et al., 2016b).

In the neonatal ICU

As many as one-quarter of infants in the NICU have a neurologic condition (Glass et al., 2010). Nearly all infants in the NICU are at risk of neurodevelopmental impairment. Effective communication between the neonatology and neurology teams is essential; existing data suggest that lack of consensus among teams is a source of parent distress (Lemmon et al., 2020). Neurology should be actively engaged in care-coordination meetings early in a patient’s course and help guide families with complex decision-making throughout an infant’s admission.

Parents in the NICU are tasked with making critical decisions while integrating new medical information. With parents as the de-facto decision makers for their infants, ensuring parents understand their child’s condition is important. Certain populations in the NICU, such as adolescent parents, may need added enhanced support to process the critical nature of their child’s illness (Boss et al., 2010). Studies of adult patients admitted to ICUs have shown that about 50% of family members have poor understanding of their family member’s illness and experience inadequate communication with physicians (Azoulay et al., 2000). This gap in comprehension is likely multifactorial, impacted by the complexity of a patient’s condition, time spent by the physician with family, and the provision of written materials for family members. Specific to the NICU population, families have shared that effective communication between providers and families includes healthcare workers introducing themselves and their role on the medical team, referring to hospitalized children by name not by their diagnosis, providing consistency of care, recognizing the family’s role, personalizing how information is communicated and tailoring language to meet each family’s needs (Janvier et al., 2014).

Engaging families in rounds is a common and effective way of improving provider–family communication. Joint rounds between subspecialists can also help alleviate the risk of inconsistent information and help ensure family inclusion in the care of their child. Supporting a dedicated NICU palliative care team, that is available to round on patients independently or alongside the neonatal team, can also have a positive impact and has been associated with increased family conferences (Younge et al., 2015). Ideally, a family conference that includes relevant subspecialty providers will occur within the first 72h of a patient’s stay in the ICU (Lilly et al., 2003). During all provider–family encounters, it is important to recognize that a family’s understanding of their infant’s condition may vary depending on what information has been previously shared with them, their baseline level of medical knowledge, their anxiety level, and their past experiences with loss (Kenner et al., 2015). Clinicians should not assume that just because information has been shared with a family, that that family has perceived that information in a similar way as the medical team. Additionally, parents and providers may focus on different aspects of neurologic prognosis in children with neurologic injury. Existing data suggest that parents and clinicians may weigh aspects of outcome differently from one another. While clinicians may focus on neurologic outcome and the potential for neurodevelopmental delays, parents may focus more concretely on infant survival (Lemmon et al., 2019). Parent discussion of outcome is often rooted in language about hope (Kaye et al., 2020); this may be misinterpreted by clinicians as denial, unrealistic expectations, or poor understanding (Lemmon et al., 2019). Indeed, data from parents of seriously ill infants and children suggest that parents often hold hope and prognostic awareness together with one another (Kaye et al., 2020). Lastly, it is important to recognize that in the majority of cases medical information is shared only with one parent or family member, placing a burden upon them to relay important information to the rest of the family (Lemmon et al., 2016b). When possible, it is important to include both parents and any key support people the parents would like present for recurring care meetings.

Ongoing discussions about goals of care are essential. Scheduled check-ins can help provide structure to when families can anticipate routine updates about how their child’s clinical course is progressing. Additional meetings should be held before any major decision points, such as the need for a ventriculoperitoneal shunt, a tracheostomy, a gastrostomy-tube, or other invasive procedure. Some centers have employed the model of a “primary physician,” while others rely on care coordination teams, such as a palliative care service, to provide continuity. Commonly, chronic NICU patients will have several primary nurses who are longitudinally involved in their bedside care. Primary nurses often form relationships with the families and can be an asset at routine or critical care meetings. Indeed, many families feel that their bedside nurse is their primary source of information (Lemmon et al., 2016b), underscoring the importance of including nursing in ongoing care meetings. Neurology teams can also consider a longitudinal attending model to enhance consensus and continuity.

After discharge

Around the time of discharge, it is important for the family and the interdisciplinary provider team to discuss any remaining concerns or questions the parents may have surrounding discharge. This is true regardless of if the patient is being discharged with plans for routine active follow-up or if the child will be going home under a hospice care model with an anticipated short period prior to death. For all families, it is important for providers to understand the family goals around discharge.

One of the key components of predischarge care meetings is to support parents as they take on a more active caretaker role, regardless of how involved they were while the child was in the NICU and regardless of the planned presence of home nursing support. Even the most engaged NICU families can struggle during the transition home. Beyond the care of this child, families may be worried about how the medically complex infant will fit in with older siblings, how to balance working and caretaking, and the potential financial strain of lost wages and accumulating costs (Lemmon et al., 2020).

Clinicians should ensure that follow-up with all necessary services has been arranged and that families understand, and are comfortable with, the follow-up plan. The precise nature and frequency of medical follow-up will be dictated both by the child’s clinical status and by the family’s goals of care. Depending on the availability of local resources, children with congenital or acquired neurologic injury may follow with a series of individual subspecialty clinics, hospice services, in-home therapists, or obtain all of their follow-up through an integrated care model. While location and insurance coverage may limit options for families, it is helpful if inpatient provider teams are aware of locally available options for follow-up care and therapy so that the discharge plan can best meet the family’s needs. Neurologists serve a key role in the longitudinal care of infants with neurologic conditions. Given the communication challenges present in the NICU period, it is critical to revisit key information in follow-up visits. For many families, goals of care will evolve as they transition away from the hospital setting. Neurologists and other clinicians should revisit goals longitudinally.

PROGNOSTICATION AND DECISION-MAKING

For infants with known or suspected neurologic anomalies, both neurology and palliative care providers are instrumental in working with the neonatology service to help guide decision-making. Despite the relative abundance of diagnostic tools, prognostic uncertainty remains for many patients in the neonatal ICU with neurologic injury. In some cases, this is because the timing or cause of the insult is not precisely known. Other times, prognostic uncertainty arises as clinicians try to extrapolate individual risk from population-level estimates (Smith et al., 2013). While a thorough clinical exam, electrophysiological data and neuroimaging can be informative, there is currently no definitive biomarker for injury severity to help guide prognostic efforts (Ferriero and Bonifacio, 2014).Families and providers alike seek early clinical or diagnostic signs that will indicate prognosis, but it often takes days to weeks for a clear picture to arise. Importantly, an infant’s clinical exam may evolve over time, making it challenging to infer long-term outcomes based on a single early physical exam (Bonifacio et al., 2015). Despite prognostic uncertainty, it is recommended that care teams incorporate a neuropalliative care approach early in order to provide an extra later of support for families and clinicians (Lemmon et al., 2016a). This approach should include normalizing the uncertainty of prognosis and being open about the limitations of current forms of diagnostic inquiry, addressing the family’s questions about uncertainty, and helping families manage the effects of uncertainty on their ability to live in the present (Smith et al., 2013). The ouR-HOPE (reflection, humility, open-mindedness, partnership, and engagement) framework offers a self-assessment tool for clinicians who frequently discuss neurologic prognosis with families and encourages clinicians to consider their practice of communicating prognosis (Racine et al., 2017; Bracken-Roche et al., 2019).

A shared decision-making approach is preferred in high-stakes decision-making for infants with neurologic conditions (Peerzada et al., 2004; Kukora and Boss, 2018). This process begins during antenatal discussions about resuscitation at the threshold of viability or for infants with known neurologic injury who are anticipated to have significant life-limiting conditions. For infants in the NICU, decisions may include considerations of whether to provide, withhold, or withdraw life-sustaining treatments. As infants approach discharge, common decisions might include considering home health services, discharge to hospice, or discharge to a long-term care facility. A neuropalliative care approach includes eliciting a family’s decision-relevant values, understanding of long-term outcome, and helping families envision what life may look like upon discharge. Existing data suggest that families often prioritize religious or spiritual beliefs, rather than morbidity and mortality predictions presented by their clinical team as they make high-stakes decisions (Boss et al., 2008). An integrative, multidisciplinary palliative care model including palliative care providers, chaplains, and social workers, can help families clarify and voice decision-relevant values and preferences (Younge et al., 2015).

Antenatal diagnoses

Fetal neurologic diagnoses often become apparent at the fetal anatomy screen, which typically occurs between 18 and 22 weeks gestation (Timor-Tritsch et al., 2009). If abnormalities are identified via ultrasound, prenatal MRI is often used to clarify diagnoses and facilitate planning for birth. Common conditions that can be identified via prenatal imaging are include structural malformations of the brain or spine, hemorrhages, and other vascular malformations or areas of injury. In many cases of antenatally diagnosed neurologic conditions, parents and clinicians will consider additional genetic screening with cell-free DNA testing, chorionic villus sampling, or amniocentesis(NorwitzandLevy,2013;Giletal.,2015).

In some fetal neurologic conditions, in utero intervention may be feasible. For example, some infants with myelomeningocele may be appropriate for in-utero repair undergoing surgery between 19.0 and 25.9 weeks gestation (Adzick et al., 2011). Fetal surgery often requires the balancing of fetal and maternal health risks. In the face of fetal myelomeningocele, repair reduces the need for shunting and leads to improved motor outcomes at 30 months; however, carries a higher risk of preterm delivery and maternal complications. Fetal surgery, via fetoscopic or open approaches, carries pregnancy-associated risks such as chorioamniotic membrane separation, preterm delivery, and fetal loss (Sacco et al., 2019). When exploring the option of fetal surgery, multidisciplinary care is required to ensure the appropriate selection of maternal fetal candidates to allow fora lifesaving or morbidity-reducing fetal outcome without imposing undue risk on the mother (Teefey et al., 2020).

Some families use information about infant diagnosis and prognosis to inform high-stakes decisions about care, including pregnancy termination, location of birth, and plans at the time of birth. Fetal neurologists can help families understand key information about prognosis, as well as the role of prognostic uncertainty, to help them understand what life might look like after birth. When possible, fetal neurologists should partner with perinatal palliative care clinicians to help guide discussions about diagnosis, prognosis, and decision-making.

At birth

For those conditions known prenatally, perinatal palliative care and maternal clinicians should develop a birth plan, including the location of birth and planned resuscitation measures. For those infants receiving active resuscitation, initial assessment of tone, activity level, suck, alertness, and respiratory drive should be performed as part of a complete physical exam. Early labs such as a blood gas may indicate alternations in pH or suggest underlying metabolic disorders in infants presenting with poor neurologic exams.

One of the most common neurologic conditions occurring around the time of delivery is hypoxic ischemic encephalopathy, which occurs when there is decreased blood perfusion and/or oxygenation to the infant. Hypoxic ischemic encephalopathy can be precipitated by maternal conditions, including placental abruption, cord accidents, cord compression, or uterine rupture. Most infants are transferred immediately to the NICU for initiation of therapeutic hypothermia, in which the infant undergoes whole-body cooling for 72h (Natarajan et al., 2018). While this treatment is standard of care and has been demonstrated to improve neurodevelopmental outcome, existing data suggest parents often view the initiation of hypothermia as a choice (Craig et al., 2018; Lemmon et al., 2020).

In the neonatal ICU

Many infants with prenatally diagnosed neurologic conditions are admitted to the NICU. For many other children, diagnoses are apparent at the time of birth. Parents may face a variety of high-stakes decisions in the NICU period. Some parents may face choices about whether to initiate, withhold, or withdraw life-sustaining treatment. Indeed, withdrawal of life-sustaining treatment is the most common mode of death for infants with neonatal seizures or hypoxic ischemic encephalopathy (Lemmon et al., 2017a; Natarajan et al., 2019).

Common conditions diagnosed after birth include perinatal arterial ischemic stroke, neuromuscular conditions, inborn errors of metabolism, intraventricular hemorrhage, and periventricular leukomalacia. Neonatal neurology teams typically use a combination of laboratory, imaging, electroencephalographic, and clinical data to guide diagnostic testing. For neurologic conditions where there is concern for an underlying genetic anomaly, targeted genetic screening, microarrays, and whole exome or genome sequencing may be offered to families. Despite the increased availability of such tests, results may be inconclusive or lead to a diagnosis with unclear prognosis (Lemmon et al., 2016a). Many genetic tests currently have turnaround times that preclude inclusion in real-time decision-making; however, as technology improves, rapid testing may become increasingly available, and facilitate clinical decision-making in critically ill infants (van Diemen et al., 2017).

In the case of hypoxic ischemic encephalopathy, most centers obtain an MRI in the days immediately after cooling to assess for the presence and degree of brain injury. Prognostication in hypoxic ischemic encephalopathy is complex. Due to the evolving nature of the condition, the predictive ability of bedside tools is time dependent. An evaluation typically relies on a combination of infant examination, EEG background, and neuroimaging findings. Seizures are one of the most common symptoms of neurologic compromise in the NICU. Conventional EEG is the gold standard for diagnosis, though amplitude-integrated EEG is often used to augment seizure detection at the bedside (Sewell et al., 2018).

Regardless of etiology, many parents of infants with neurologic conditions must navigate prognostic uncertainty. Existing data from parents of children with neonatal seizures and hypoxic ischemic encephalopathy suggest that uncertainty about long-term outcome is a source of acute and long-term distress (Lemmon et al., 2017b; Lemmon et al., 2020). Clinicians can mitigate that distress by helping families draw boundaries about what outcomes are possible, using a best case, worst case, and most likely approach (Taylor et al., 2017).

After discharge

Many patients with neuropalliative care needs will follow with neurologists and an interdisciplinary team after discharge from the NICU. For these patients, parents may face new decisions or revisit previous ones as they adapt to caring for a child with significant medical needs. Family values may evolve as the infant develops relationships with the community and their family, and as parents become more aware of their day-to-day needs. Primary care providers and subspecialty teams that follow patients longitudinally after discharge may be tasked with helping families navigate decisions about readmission to the hospital, intensive care interventions, and the need for additional therapeutic procedures.

Existing data suggest that prognostic uncertainty remains a cause of longitudinal distress for families after discharge and that parents may experience recurrent grief as children do not meet typical developmental milestones (Lemmon et al., 2017b). Clinicians should revisit prognosis as the infant’s developmental trajectory becomes clear.

PAIN AND SYMPTOM MANAGEMENT

A variety of symptoms can arise in the care of infants with neurologic conditions. A key role for neuropalliative care teams is the management of pain and other symptoms in order to ensure the infant’s comfort and reduce parent distress (Bidegain and Younge, 2015). When possible, clinicians should prioritize nonpharmacological measures such as non-nutritive sucking, swaddling and rocking/holding when managing pain and other distressing symptoms (Pillai Riddell et al., 2011). Clinicians should work to minimize painful procedures, while clustering care and maximizing uninterrupted sleep. If necessary, there is a wide range of pharmacological interventions to treat pain and other distressing symptoms. Symptom management needs will likely vary and evolve throughout a patient’s hospital stay and an interdisciplinary approach is helpful in reaching a balance between symptom management and minimizing medication side effects.

At birth

Some infants are diagnosed antenatally with significant brain malformations or genetic disorders believed to not be consistent with prolonged extrauterine life. Parents and clinicians may construct a birth plan for these infants that prioritizes comfort and minimizes suffering. The primary goal of these birth plans is often to minimize infant pain and distress and facilitate bonding time with the family. Providing non-nutritive feedings or noninvasive oxygen support can allow for memory making and bonding. Hospitals may differ on what interventions are permissible within this context. When possible, clinicians should allow infants to stay in the mother’s room to maximize the time the family has with their infant before death. To ensure the timely and adequate provision of medications to control symptoms, teams should develop processes to ensure the availability of medications in the delivery suite. Since many infants will lack the ability to swallow and not have intravenous access, teams should consider alternate routes of administration, such as intranasal or sublingual (Table 11.2).

Table 11.2.

Pharmacologic pain and symptom management^a

Pain	Morphine Starting dose: 0.02–0.1 mg/kg IV or 0.2–0.4 mg/kg PO/SL q2–4h PRN Infusion: 0.02–0.1 mg/kg/h IV
	Fentanyl Starting dose: 1–3 mcg/kg IV/Intranasal q1–2h PRN Infusion: 1–3 mcg/kg/h IV
	Methadone Starting dose: 0.05–0.2 mg/kg IV/PO q4–24h
	Oxycodone Starting dose: 0.05–0.1 mg/kg PO q4–6h
	Acetaminophen 10–15mg/kg PO/IV or 20 mg/kg PR q6h
	Oral sucrose 24% 0.1–2 mL PO PRN
Pain and Sedation	Clonidine Starting dose: 1–3 mcg/kg PO q6–8h Clonidine patch 1/4–1/2 of a 0.1 mg/24h patch (do not exceed 12mcg/kg/day) Dexmedetomidine Starting dose: 0.5–1 mcg/kg IV or 2–4 mcg/kg PO/SL/buccal/intranasal q1–4h PRN Infusion: 0.2–1 mcg/kg/h IV Gabapentin 5–10 mg/kg PO q8–12h Recommended for use in older infants, starting with the lowest dose; avoid in premature infants
Sedation	Midazolam Starting dose: 0.05–0.1 mg/kg IV or 0.2 mg/kg PO/SL/Intranasal q1h PRN Infusion: 1–2 mcg/kg/min IV Lorazepam Starting dose: 0.05–0.1 mg/kg IV/PO/SL q2–4h Diazepam Starting dose: 0.05–0.25 mg/kg PO/PR q4–12h
Secretion Management	Glycopyrrolate 2–10 mcg/kg IV/SC or 20–100mcg/kg PO q6h Atropine 1 drop of 1% ophthalmic solution SL q4–6h PRN
Hypertonia	Baclofen Starting dose: 0.1 mg/kg PO q8–12h, can increase to maximum of 0.5 mg/kg/dose
Sleep disturbance	Melatonin 0.5–1 mg PO daily

^aPharmacokinetics, safety, and efficacy for many of these agents have not been well established. Acknowledgment: Dr. Chi Dang Hornik for her expert review.

In the neonatal ICU

Neonatal patients with neurologic disease are at risk for the under-recognition of pain and irritability (Lemmon et al., 2016a), with providers believing that such patients experience less pain than patients without neurologic impairment (Breau et al., 2006). Many scales that assess infant pain rely on changes in behavior or expressions of pain (Van Dijk et al., 2000; Holsti and Grunau, 2007; Hummel et al., 2010; Stevens et al., 2014). One of the most frequently used scales in the NICU is the N-PASS (neonatal pain, agitation, and sedation scale) score, which address both pain and sedation in the neonatal population through a standardized assessment of an infant’s clinical state (Hummeletal.,2010). The N-PASS scoring system is beneficial in assessing pain across several domains, namely crying, behavior, facial expression, extremity tone, and vital signs (Hummel et al., 2008). However, N-PASS scoring has not been shown to be reliable for measuring prolonged pain and sedation in nonmechanically ventilated infants nor for assessing acute pain in postoperative infants (Morgan et al., 2020). Assessing prolonged pain and sedation are critical aspects of ongoing management of patients with neurologic conditions, which may limit the use of N-PASS in this population.

Infants with neurologic disorders will also have symptom management needs beyond pain control, including the management of irritability, withdrawal symptoms, secretion management, seizure control, shivering in the setting of therapeutic hypothermia, and challenges related to sleep disturbance (Lemmon et al., 2016a; Garten and Bührer, 2019). Neuropalliative care providers need to be aware of the various forms treatments available to manage each of these conditions, including appropriate dosing and weaning schedules. Medication pharmacokinetics may be altered by certain interventions, including therapeutic hypothermia and extracorporeal membrane oxygenation (ECMO). Additionally, providers need to be aware of any synergistic or competing effects of pharmacotherapy administered to their patients and monitor for signs of overdose or tolerance development. Slow weaning schedules with close monitoring for signs of withdrawal is important with any long-term pharmacotherapy used to manage symptoms in patients with neurologic injury. Basic dosing strategies for common pharmacologic treatments are shown in Table 11.2. For infants in need of ongoing secretion management exceeding the capacity of anticholinergic medications, botulinum toxin injection into the salivary gland can be a helpful temporary therapy (Hockstein et al., 2004). In extreme or persistent cases of sialorrhea, surgical excision of the salivary gland or salivary duct ligation can be considered.

Unexplained irritability is a common finding in infants with a history of neurologic injury. This condition can be especially difficult to manage and often requires a combination of pharmacotherapy and nonpharmacological management strategies. Gabapentin is a common pharmacologic treatment available for use in both term and preterm infants that can modulate the use of opioids and benzodiazepines and improve feeding tolerance (Edwards et al., 2016).

Seizures are a frequent clinical finding in NICU patients receiving neuropalliative care. Importantly, neuropalliative care providers must be aware that many infants have seizures while dying, often acutely. These seizures can be accompanied by gasping, myoclonus, or apnea and are frequently distressing for families (Lemmon et al., 2016a, 2016b; Lemmon et al., 2020). Appropriate counseling about the possibility of seizures at end of life is essential and management should be readily available.

Symptom management of neonatal patients often requires an interdisciplinary approach with input from neonatology, neurology, and palliative care teams. Some practices and scenarios may have systematic protocols to address symptom management needs (e.g., for shivering management during therapeutic hypothermia). Care teams must recognize the negative impact of pain on cognitive, motor, and neurodevelopmental outcomes in all neonatal patients (Montirosso et al., 2012; Vinall and Grunau, 2014) and on postnatal growth for preterm infants (Vinall et al., 2012).

After discharge

Many NICU patients will have ongoing symptom management needs beyond hospitalization. Many patients will be on long-term medications with infrequent drug level or toxicity monitoring. It is therefore important that safe and effective dosing regimens are determined prior to discharge, especially in cases of polypharmacy. Clinicians should help parents understand the need for any necessary drug level monitoring following discharge, as well as clinical signs of mediation toxicity. Parents should receive hands-on education on medication dosing and administration. Parents should have practice drawing up medications and giving them to their child while the child is still admitted to the NICU.

After discharge, longitudinal developmental clinics or palliative care clinicians typically assume care of medication regimens. Outpatient providers should review medication dosing schedules, with an emphasis on practical home administration strategies. Due to rapid weight gain in the first years of life, neurologists and other clinicians should consider weight-based dosing adjustments as appropriate.

CARE AT THE END OF LIFE

Withdrawal of life-sustaining interventions

Withdrawal of life support or the decision to no longer escalate life-sustaining interventions in the NICU are challenging decisions for both families and clinicians. Despite this, many deaths in the NICU, including of infants with severe neurologic injury, occur after withdrawal of life-sustaining interventions in infants that are otherwise physiologically stable (Lemmon et al., 2016a). While professional bodies have stated that critical care decisions for neonates should not differ from those made for older children or adults, some have raised concern that there are differences in decision-making and ethical assessments associated with treatment or non-treatment decisions for newborns compared to other patient populations (Janvier et al., 2007). Parents and providers may be more likely to choose care focused on comfort for neonates at risk of long-term neurodevelopmental impairment than for older children with pre-existing disability (Fontana et al., 2013).

In the setting of withdrawal of life-sustaining treatment, clinicians should prepare families for the possibility that their child may survive for a period after life-sustaining interventions are discontinued. Cases of unexpected survival beyond the NICU period have been reported, and neurologists and palliative care teams are uniquely positioned to provide longitudinal care to families and infants in this context (Pal et al., 2016).

Grief and bereavement

Along with grieving the physical death of their child, many families may experience the compounding grief of loss of their role as parents, as NICU parents, or as parents to a child with medical complexity. Parents may grieve the loss of the NICU support network they have developed and the loss of the envisioned future of a healthy child (Dyer, 2005). While each family will process their grief differently, providers should be aware of differences between how mothers and their partners process grief, with some studies demonstrating that fathers may be faster to move away from a state of acute grief that mothers, with some attributing this to a lack of a physical connection with the infant throughout pregnancy (Côté-Arsenault and Denney-Koelsch, 2016).

Clinical care teams should be available to offer ongoing support of the family at the time of death. Palliative care teams can be instrumental in ensuring that families have appropriate spiritual support before, during, and after the child’s death and that important family death rituals are facilitated. Together the care teams can offer memory making options for families, such as footprints, heartbeat recordings, and photographs. If withdrawal of life-sustaining interventions is planned, providers can ask parents if there are rituals that are important to them culturally, spiritually, within their belief system, or that they wish to see happen, while realizing that many parents may not know what they want or what to ask for in these situations (Kenner et al., 2015). Bereavement activities may be more limited in the setting of visitor and ancillary staff restrictions to the NICU; for example, during the COVID-19 pandemic. Teams should balance safety with family values and traditions and, when feasible, obtain exceptions to visitor restrictions at the end of life.

In the case of fetal loss, stillbirth evaluation should be offered and could include fetal autopsy, placental pathology, and additional genetic testing. Using such investigative tools to determine the cause of fetal death can facilitate emotional closure for parents and can help with future pregnancy planning (Page and Silver, 2020). Parents grieving a fetal loss should receive significant bereavement support as well, and may be facing unique challenges. For example, mothers may continue to appear pregnant for some time after fetal loss, which can serve as a physical reminder of their grief. In the unique case of planned withdrawal of care for children with limited end-organ injury, organ donation after cardiac death can be considered and may offer some families a sense of legacy and purpose after their child’s death (Lechner, 2018). Bereavement processes should include longitudinal contact with the family, and facilitate appropriate referral to parent mental health clinicians as appropriate.

CONSIDERATIONS OF CULTURE, SPIRITUALITY, AND PRACTICE LOCATION

Families of NICU infants come from a wide range of social, cultural, ethnic, and spiritual backgrounds. Family centered and culturally driven clinical and palliative care approaches are recommended to ensure that a family’s beliefs and goals of care are respected. At the same time, individual parents may have personal preferences regarding the care of their child, especially if that child is expected to have a shortened or limited life, and medical staff should not assume that all of a family’s requests or reactions are culture based.(Kenner et al., 2015) Similarly, individual families may identify with a certain culture or religion but not ascribe to all of the presumed belief patterns of that group. Each family must therefore be approached as individuals, navigating their way through making challenging decisions regarding their child’s care.

Many parents draw on their spirituality for guidance when making end-of-life decisions, searching for meaning in loss, and sustaining themselves emotionally through a difficult time for their child (Robinson et al., 2006). While many parents experience their child’s death in spiritual ways, they do not always feel comfortable sharing these beliefs with their providers (Ellis and Campbell, 2004). Often a family’s willingness to share their spiritual views depends upon their sense of the provider’s respect for their views and for spiritual health. This may be especially true for families with less well-represented religious beliefs. For example, Jewish law simultaneously forbids active withdrawal of life-sustaining treatments—such as discontinuing mechanical ventilation—while also forbidding impeding the departure of a dying soul, such as starting new therapies not thought to be helpful (Shinwell and Shinwell, 2008). Within the Muslim tradition, for anomalies where there is no prospect of independent life, such as anencephaly, abortion is permitted before 120 days of pregnancy, even in the most orthodox circles (Husain, 2008). Once in the NICU, many Muslims ascribe to the belief that premature termination of life, through acts of commission or acts of omission, violates the teachings of the Quran, and issues around withdrawal of life-sustaining interventions must be approached with awareness of the ethical and religious considerations at play for these families (Gatrad et al., 2008). Having a Chaplain or other spiritual counselor as an integrated member of the care team can be an asset in identifying and acknowledging a family’s spiritual practices or religious traditions. Even when a spiritually trained team member is available to help guide clinicians, all providers should work to understand, inquire, and respect the spiritual wishes of their patients.

In the United States, the neonatal mortality rate for African-American infants is more than double that of white infants and women of color are more likely to deliver preterm than their white counterparts (Ely and Driscoll, 2019). There are therefore more infants of color in neonatal ICUs and more of these families struggling through the death of their newborn child. Neuropalliative care providers need to be aware of these unbalanced outcome rates and of how these alarming statistics reflect a larger societal issue of structural racism that contributes, directly and indirectly, to an imbalance in neonatal deaths among the African American and Latinx population in the United States. Beyond knowing that genetics is not the driver of these poor birth outcomes (David and Collins, 2007), it is essential that clinicians recognize the systematic burden of loss that may be experienced by families of color.

Neuropalliative care providers should also be aware that patients and families from different cultural backgrounds have unique challenges when navigating the healthcare system and engaging with care providers. This is especially true for those families who are not fluent in English. Language and cultural differences create barriers to effective information sharing between providers and patients (Davies et al., 2010). For those families of infants in need of palliative care, poor information sharing can lead to frustration, anger, and ongoing sadness long after an infant’s death. Additionally, parents describe increased feelings of guilt well after a child’s death if they felt that they were not kept informed in a dignified way or if they were unable to adequately discuss their child’s condition beforehand (Surkan et al., 2006). It is important that providers strive to connect with and adequately inform all parents about the status of their child throughout the hospital stay and especially at critical decision points and when approaching the end of life.

The World Health Organization (WHO)’s 2020 statement on Palliative Care asserts “Palliative Care is explicitly recognized under the human right to health.” While data on the global need for neonatal–perinatal palliative care services is scarce, data on pediatric palliative care needs show that 98% of children with unmet palliative care needs live in low- and middle-income countries, representing as many as 21 million children Connor et al., 2017; World Health Organization, 2020). Despite this burden, almost two-thirds of countries worldwide lack pediatric palliative care services (Knapp et al., 2011). Palliative care that is well integrated into the health system is present in just 21 countries, which represents less than 10% of the world’s children (Clelland et al., 2020). The care needs of newborn infants due to congenital anomalies, complications of prematurity, or birth trauma make up approximately one-third of childhood palliative care needs (Connor et al., 2020). Many of these conditions are associated with long-term neurologic challenges, with different implications of care in different counties. Where pediatric palliative care programs do exist in low- and middle-income countries, they are often external to the mainstream health system. Key barriers to global palliative care coverage, as noted by the WHO, include insufficient training on palliative care for health professionals, cultural and social barriers, and misconceptions about the goals and breadth of palliative care services. These are all important concepts for neurology providers to be aware of when working abroad. Whether at home or abroad, considerations of cultural, socioeconomic, and resource barriers must be considered when engaging with families and providers of children who have congenital or acquired neurologic injury.

RESEARCH GAPS AND PRIORITIES

Despite the growing body of literature surrounding neonatal neuropalliative care, gaps remain in our current understanding and management of these conditions. Here, we outlined key research priorities.

Family centered communication

1. Adaptation of communication training curricula to the NICU context

2. Focused efforts to address the impact of antenatal and neonatal counseling on maternal mental health, including post-partum depression and anxiety

3. Expansion of current counseling and communication practices to better meet the needs and preferences of families of varied cultural and religious backgrounds

4. Review of the feasibility and acceptability of telemedicine or video counseling during antenatal or post-natal consults

Prognostication and decision-making

1. Development and implementation of parent-informed outcomes

2. Ongoing study of biomarkers to support prognostication

3. Dedicated study of antenatal prognostic counseling

4. Tools to support shared decision-making, including decision aids tailored to the NICU context

Symptom management

1. Development and validation of pain measurement tools that accurately reflect symptoms in infants with neurologic condition

2. Dedicated study of the identification and treatment of neuroirritability

3. Expanded guidance for families about symptom management following discharge

As life-sustaining technology allows for increased fetal and neonatal survival, and more options for fetal surgery become available, the field must concurrently define best practices for previously nonsurvivable conditions. These guidelines will need to be clinically and ethically informed, ensuring that the best interest of the affected children remains paramount. Further research is warranted into how palliative care is delivered around the world, especially in resource-constrained settings. Scholars must consider how local access to care, resources, training, and policy inform the ability to provide palliative care to infants with neurologic conditions and their families.

SUMMARY

Neonatal neuropalliative care is an emerging field that can support infants, parents, and clinicians impacted by fetal and neonatal neurologic conditions. As life-sustaining medical technologies continue to advance for the sickest infants, the role of neuropalliative care is likely to increase and broaden.

Family centered communication is the foundation of a neuropalliative care approach. Clinicians should work to ensure that communication is consistent within and between teams, and that parents have longitudinal providers throughout the antenatal and neonatal period. Families face a variety of high-stakes decisions throughout their infant’s life course. Clinicians must work to elicit, clarify, and revisit parental values, recognizing that these decisions are often made and remade over time. Prognostic uncertainty is a reality of care for many infants and families. Clinicians must work to reduce prognostic uncertainty when feasible and acknowledge that this uncertainty can result in parent distress and increased decisional burden. Infants with neurologic conditions may require unique pain and symptom management strategies, and pain may be more difficult to identify and treat than infants in other contexts. The antenatal and neonatal period represents a critical opportunity for clinicians to prepare families for complex decision-making throughout a child’s life. A neuropalliative care approach can support all infants and families impacted by neurologic disease.