Introduction
Hypoxic ischemic encephalopathy (HIE) is one of the most serious birth complications that affect full-term neonates, and despite medical advances such as therapeutic hypothermia, it remains a major cause of life-long disability and mortality worldwide (Cetinkaya, 2024). In South Africa (SA), intrapartum-related complications, including intrapartum hypoxia and subsequent HIE, are reported as the second most prevalent causes of neonatal deaths (Masaba & Mmusi-Phetoe, 2020). The reported incidence of HIE in SA ranges from 1.5 to 13.3 per 1000 live births (Bruckmann & Velaphi, 2015; Horn et al., 2013; Lambey Nakwa et al., 2023), similar to the range of 1.5–20.3 reported in other low- and middle-income countries (LMICs) (Kukka et al., 2022) and compared with the 1.5 per 1000 live births in high-income countries (Acun et al., 2022).
Factors such as a high burden of disease, widespread poverty, limited healthcare resources and facilities, inadequate ambulance services and a shortage of healthcare workers, typical of LMICs, predispose SA to higher prevalence rates of HIE (Ballot et al., 2020). Limited access to therapeutic hypothermia treatment in SA – the standard of care for neonates with moderate to severe HIE – further compounds the risk of poor neurodevelopmental outcomes in affected neonates (Ballot et al., 2021; Kukka et al., 2022). These challenges not only contribute to the incidence of HIE but may also lead to adverse long-term outcomes (Tagin et al., 2012), further straining the healthcare system of SA.
While it is universally agreed that HIE is an important cause of neonatal mortality, for survivors, it is associated with a substantial burden of impairment (Ballot et al., 2020; Krüger et al., 2017, 2019; Malan et al., 2022). Although dependent on the extent of the cerebral injury, neonates with HIE are likely to present with varying degrees of encephalopathy, including depressed levels of consciousness, difficulty initiating and maintaining respiration, hypotonia, seizures and weakened reflexes, including delayed or absent feeding and swallowing responses (Gillam-Krakauer & Gowen, 2022). Thus, HIE has been referred to as a potential neurological cause of oropharyngeal dysphagia (OPD) (Da Costa et al., 2019; Krüger et al., 2017, 2019; Martinez-Biarge et al., 2012).
Injuries to areas such as the basal ganglia, thalamus and brainstem are frequently reported in neonates with HIE and can disrupt oral-motor function (Martinez-Biarge et al., 2012; Quattrocchi et al., 2010), leading to oral phase dysphagia (Krüger et al., 2017, 2019; Malan et al., 2022; Martinez-Biarge et al., 2012; Quattrocchi et al., 2010). As a result, neonates with HIE often present with shallow latching, poor suction, single sucks, short sucking bursts and reduced feeding endurance (Krüger et al., 2017, 2019; Malan et al., 2022), which may delay the attainment of full oral feeding, increase aspiration risk and prolong hospitalisation (Arvedson et al., 2020; Jadcherla, 2016). In addition, a disrupted pharyngeal swallow, particularly affecting suck–swallow–breathe (SSB) coordination and the initiation of an effective swallow reflex, may be observed (Malan et al., 2022), further increasing the risk for desaturation, bradycardia (Thoyre & Carlson, 2003) and aspiration (Viswanathan & Jadcherla, 2020).
Clinical signs such as coughing, choking and wet respiration have been observed in neonates with HIE and suggested laryngeal penetration or aspiration (Krüger et al., 2019). Importantly, Malan et al. (2022) found that 31% of neonates with HIE showed penetration or aspiration on the videofluoroscopic swallow study (VFSS), with 60% of the aspiration events occurring silently. While some improvement of swallowing may occur with maturation, many neonates with HIE remain at risk for persistent feeding difficulties at discharge (Jensen et al., 2017; Malan et al., 2022), potentially requiring long-term support and monitoring (Martinez-Biarge et al., 2012).
Evidence-based early intervention may assist in reducing the negative sequelae associated with OPD (Jadcherla, 2016), such as aspiration-associated respiratory disease (Durvasula et al., 2014), interrupted feeding interactions, psychological distress symptoms in the caregiver (Jonsdottir et al., 2021; Zanardo et al., 2017) and the length of hospitalisation (American Academy of Pediatrics, 2008).
There is a small but growing body of local research on neonates with HIE. Considering the prevalence of HIE in SA and the negative consequences associated with OPD, more dysphagia-specific research is justified to provide context-specific feeding and swallowing characteristics to further guide neonatal intervention.
The aim of this study was to describe the feeding and swallowing profile of neonates with HIE in a neonatal unit in Cape Town, South Africa, including characteristics of oral feeding readiness, time taken to reach full oral feeds, feeding method at discharge from the neonatal unit and clinical signs and symptoms of OPD.
Discussion
This study found that while most neonates with HIE were deemed medically stable for oral feeding by the fourth day of life, their physiological stability, behavioural state organisation and their ability to self-regulate during feeding were influential in determining their oral feeding success during the initial feeding assessment. Oral feeding is a complex developmental process that requires stable physiological, motor and behavioural functioning (Viswanathan & Jadcherla, 2020). The findings reinforce the importance of a cue-based, behavioural approach to assessing oral feeding readiness. Recognising and responding to self-regulation cues allows caregivers and healthcare professionals to support neonates in achieving feeding success safely while also fostering a more positive and responsive feeding experience (Gulati et al., 2020).
Physiological instability – such as tachycardia, abnormal respiratory patterns and uncoordinated SSB rhythms – was common among participants with feeding and swallowing difficulties in this study, likely indicating a lack of readiness for oral feeding (Wahyuni et al., 2022). These findings align with literature linking autonomic instability to impaired feeding and swallowing function, possibly because of delayed skill development (Viswanathan & Jadcherla, 2020) or inappropriately timed oral feeding (Ross & Philbin, 2011). Similarly, difficulties in behavioural state organisation, particularly in neonates with non-optimal alertness (e.g. drowsiness, agitation), were observed among the participants with OPD (n = 4; 57.1%). These behavioural states indicate difficulties with state regulation, likely because of neurological impairment (Volpe, 2012) or the effects of medication (Mutanana et al., 2020). Notably, none of the neonates in optimal alert states were diagnosed with OPD, reinforcing the importance of behavioural readiness for safe and effective oral feeding (Gulati et al., 2020).
All neonates showing stress cues and poor self-regulation were diagnosed with OPD, suggesting that the feeding situation exceeded their capacity to self-regulate (Maltese et al., 2017; Wahyuni et al., 2022), thus underscoring the critical role of the self-regulatory subsystem in feeding success. Instability during feeding can lead to fatigue, poor endurance, disorganised behaviour, motor instability and ultimately unsafe and inadequate oral intake leading to a prolonged period of enteral feeding and hospitalisation (Arvedson et al., 2020). These findings suggest that instability across these interrelated subsystems compromises oral feeding readiness and success, emphasising the need for clinicians to observe behavioural and physiological cues when assessing oral feeding readiness to reduce aspiration risk and support better feeding outcomes.
The study highlights the variability in feeding among neonates with HIE with 44.2% (n = 23) requiring supplemental enteral feeds and 11.5% (n = 6) full enteral support at the initiation of oral feeding attempts – largely because of signs of oral phase dysfunction. Despite early challenges, most participants (96.2%; n = 50) achieved full oral feeds within a median of 5 days, likely because of neurological recovery (Medoff-Cooper et al., 2009), improved endurance (Lau & Smith, 2011), improved subsystem functioning and interaction (Jones, 2012) and intervention by the resident SLT for some participants.
Feeding outcomes such as oral feeding readiness, need for enteral support, time to full oral feeds and discharge feeding methods varied according to HIE severity, as indicated by aEEG patterns and whether or not therapeutic hypothermia was initiated. Neonates with a normal initial aEEG, indicating mild HIE, showed early oral feeding readiness and full oral feeding within 1 day, despite some signs of OPD. The participants who underwent therapeutic hypothermia treatment – those with moderately and severely abnormal initial aEEG – presented similarly with respect to the time taken to oral feeding readiness (4 and 5 days, respectively) and the time taken to full oral feeds (5 and 6 days, respectively). However, those with severely abnormal aEEG patterns who did not receive therapeutic hypothermia experienced the longest median time to oral feeding readiness (12.5 days) and the longest median time to the establishment of full oral feeds (13.5 days) with two participants requiring gastrostomy placement at the time of discharge.
Therapeutic hypothermia appeared to mitigate feeding difficulties in neonates with moderate to severe HIE, likely contributing to better feeding outcomes. These findings, while limited, support the neuroprotective role of therapeutic hypothermia (Bonifacio et al., 2022). Studies with larger sample sizes across multiple centres will, however, enable more accurate statistical comparisons of aEEG patterns, therapeutic hypothermia treatment and feeding and swallowing outcomes.
This study confirmed that neonates with HIE – regardless of severity – are at increased risk for feeding and swallowing difficulties, reinforcing HIE as a significant risk factor for OPD and its associated complications (Gulati et al., 2015; Jadcherla, 2016; Krüger et al., 2017, 2019; Malan et al., 2022). Oral phase signs and symptoms of dysphagia were observed in the majority (78.9%; n = 15) of participants in this study, though fewer (63.2%; n = 12) met the diagnostic criteria for OPD, possibly because of timing differences in assessments allowing for neurological recovery and skill development (Shandley et al., 2021). The most frequently reported oral feeding difficulties were short sucking bursts and reduced endurance, both of which are consistent with prior findings in neonates with HIE (Krüger et al., 2017, 2019; Malan et al., 2022). These challenges are linked to swallowing difficulties (Arora et al., 2022), fatigue and disorganised behavioural states (Vandenberg, 2007), potentially increasing the risk for aspiration, poor oral intake and prolonged enteral feeding and hospitalisation (American Academy of Pediatrics, 2008).
Weak sucking responses (42.1%; n = 8) and inadequate lip closure during breastfeeding also emerged as difficulties, suggesting latching and milk extraction problems (Lau, 2015), possibly because of abnormal muscle tone (Arvedson et al., 2020) associated with neurological impairment (Da Costa et al., 2019; Straathof et al., 2022). Although anterior spillage was not observed, despite reports of inadequate lip closure (26.3%; n = 5) during breastfeeding, weak sucking responses (42.1%; n = 8) likely resulted in an insufficient bolus size and therefore an insufficient bolus mass for an ‘excessive’ loss of liquid. Poor tongue cupping/grooving and anterior–posterior movement (52.6%; n = 10), which are crucial for effective bolus control and safe swallow initiation, were also noted. These impairments increase the risk for anterior spillage, premature spillage, penetration, aspiration and suboptimal nutritional intake (Arvedson et al., 2020).
In neonates, the acts of latching, sucking and swallowing are regulated by central pattern generators in the brainstem (Viswanathan & Jadcherla, 2020). However, effective feeding involves a coordinated effort from multiple brain regions. As such, hypoxic-ischemic injuries, which may affect several neural structures, can significantly disrupt these feeding functions (Jadcherla, 2016; Krüger et al., 2017, 2019; Malan et al., 2022; Martinez-Biarge et al., 2012; Quattrocchi et al., 2010; Shandley et al., 2021). The findings of this study – including poorly coordinated SSB sequences and other oral phase difficulties – likely reflect the impact of neurological injury commonly seen in HIE.
As hypoxic-ischemic injuries do not affect all brain structures at the same time and in the same way, brain regions with higher energy demands, such as the brainstem tegmentum (Miller et al., 2005), basal ganglia and thalamus (Martinez-Biarge et al., 2012; Miller et al., 2005; Quattrocchi et al., 2010), are particularly vulnerable to hypoxic-ischemic insults (Huang & Castillo, 2008) and play critical roles in feeding coordination. Damage to these areas, specifically the brainstem, has been strongly associated with oral-motor dysfunction in neonates with HIE (Quattrocchi et al., 2010). As the basal ganglia modulate the final motor output via the thalamus (Mistry & Hamdy, 2008), an impairment in the organisation and execution of the oral phase of swallowing in neonates with HIE has been associated with basal ganglia, thalamic and mesencephalic lesions (Martinez-Biarge et al., 2012), which could explain the oral phase difficulties observed in the present study.
Hypoxic ischemic encephalopathy may also adversely affect the pharyngeal phase of swallowing (Gulati et al., 2015; Jensen et al., 2017), though this cannot be confirmed clinically because of limitations in bedside assessments (Cordier et al., 2023). In this study, 26.3% (n = 5) of participants demonstrated clinical signs of pharyngeal dysphagia, but the absence of instrumental evaluations such as VFSS may have led to under-identification. Given the high number of oral phase difficulties and previous findings of abnormal pharyngoesophageal reflexes in neonates with HIE (Gulati et al., 2015; Jensen et al., 2017; Malan et al., 2022), it is likely that more participants presented with undetected pharyngeal phase impairments.
Only 10.5% of neonates were suspected of delayed pharyngeal swallows based on the clinical evaluation, whereas prior studies found higher prevalence rates on the VFSS than were identified on the NFAS (Malan et al., 2022). Delayed pharyngeal swallows can result in pooling of the milk bolus and increase aspiration risk (Jadcherla, 2016; Viswanathan & Jadcherla, 2020). Clinical signs of aspiration such as gurgling (10.5%; n = 2) and coughing (5.3%; n = 1) were rare. However, silent aspiration appears to occur more frequently in neonates and children who are neurologically compromised, making clinical inference more difficult (Freitag et al., 2021; Malan et al., 2022). Research indicates that impaired laryngeal sensation and reduced swallow reflex sensitivity in HIE may contribute to this silent risk (Freitag et al., 2021; Jensen et al., 2017); however, this relationship requires further investigation.
Overall, the study reaffirms that neonates with HIE commonly present with oral phase difficulties and possibly under-recognised pharyngeal phase impairments reinforcing the need for instrumental evaluations as part of routine care where clinically indicated. These findings are consistent with previous research showing that feeding and swallowing difficulties in HIE can span across the phases of swallowing (Gulati et al., 2015; Jensen et al., 2017; Krüger et al., 2017, 2019; Malan et al., 2022).
Clinical implications
Neonates with HIE, regardless of severity, are at an increased risk for feeding and swallowing difficulties and should be screened for feeding difficulties and referred to SLTs once medically stable. Given South Africa’s high HIE incidence, dysphagia services should be accessible in all paediatric facilities. As neonates with HIE are at an increased risk for silent aspiration particularly, an instrumental assessment of swallowing – such as VFSS and fiberoptic endoscopic evaluation of swallowing (FEES) – may be required for the accurate diagnosis of aspiration and subsequent management (Malan et al., 2022). However, because of limited access to instrumental assessments, clinicians must remain vigilant and collaborate with specialised centres. Considering the increased risk for neurodevelopmental consequences such as cerebral palsy (Kukka et al., 2022), long-term follow-up of infants with HIE is recommended to ensure early intervention, reduce adverse outcomes and inform training for SLTs and healthcare professionals. This research informs current clinical practice and may contribute to education and training in the field of paediatric dysphagia.
Limitations
This study has several limitations. While aEEG is an established prognostic tool for selecting neonates for therapeutic hypothermia (Horn et al., 2013), its application in dysphagia research is novel, limiting comparisons with studies using traditional HIE classifications. Additionally, while the NFAS is a valid tool for the South African context, it is limited in assessing the pharyngeal phase of swallowing, which cannot be fully explored. The tool may also not fully reflect clinical practice, as a diagnosis of OPD required multiple positive indicators within the assessment, potentially under-identifying difficulties. The retrospective nature of part of the study introduced inconsistencies and missing data with feeding difficulties likely under-reported because of limited SLT staffing and referral practices. Finally, the small sample with unequal subgroups and the use of a novel HIE classification limit generalisability and comparison with existing literature. Nonetheless, emerging patterns in feeding development offer valuable direction for future research.