The Persisting Value of Autopsies on Extremely Preterm Infants in the 21st Century

An autopsy is performed with the primary objective of finding the definitive cause of death. Historically, it was done to know more about the anatomical details and pathological findings of the diseases. Extremely preterm (EP) infants are infants born at less than 28 weeks of gestation.1 According to the World Health Organization, more than 90% of EP babies born in low-income countries die within the first few days of life compared with less than 10% of EP babies in high-income settings.2 In addition to the high mortality, the EP infants had poor neurodevelopmental outcome.3 Among the causes of in-hospital mortality, necrotizing enterocolitis (NEC), respiratory distress syndrome, intraventricular hemorrhage (IVH), infections, and gastrointestinal causes are among the top.4 Autopsy (postmortem) of preterm infants can provide vital information about the cause of death and the accuracy of antemortem clinical diagnosis. In the preterm infant, because clinical manifestations are often nonspecific, diagnostic errors like unintentionally delayed, wrong, or missed diagnoses could occur. An autopsy could help in these scenarios. It has been reported that frequently classical autopsies have revised the initial diagnosis.5,6 However, conventional autopsy might have religious, social, and cultural reservations. Additionally, with technological advancement, an alternative could be offered to families. An autopsy could provide valuable information and contribute to determining the definitive cause of death (COD) in preterm infants. In a series of reports regarding the timing of death, 66% to 73% of preterm infants had died in less than 28 days of life.5,6 Hoffsten et al.5 looked at the incidence of autopsy in preterm infants between 2002 and 2018 and found that in 34.9% of the cases, CODs were revised by these autopsies. Interestingly, the revised CODs after autopsy included the expected problems of EP infants (NEC, IVH, etc.). Except for congenital anomalies and chromosomal abnormities (5.0%–9.9%),5 most of the diagnoses (pneumothorax, IVH, NEC) are known to occur in EP infants. Similarly, Elder and Zuccollo6 studied 74 extremely EP infants, of which 29 died in less than 28 days and had autopsies. The reported new diagnoses on autopsy included hemorrhages (pulmonary, IVH, cerebral), asphyxia, congenital malformations, heart defects, and iatrogenic cause—long line perforation of the right atrium and traumatic perforation of the stomach. The study was done in 2005; with the advent of technological advances, an echocardiogram is readily available to diagnose cardiac conditions earlier. A fetal echocardiogram is an integral part of antenatal ultrasound. Postnatal ultrasound screening for IVH is routine in neonatal intensive care unit. There has been a decrease in autopsy rate globally. Xiao et al.7 reported a decline in autopsy rates in Western countries, including United States. Swinton et al.8 and Brodlie et al. 9 reported rates of autopsies from Kansas, Missouri, and southeast of Scotland to be approximately 33% to 67%, respectively. Similarly, the autopsy rates are lower in underdeveloped countries from southern Asia and sub-Saharan Africa.10 Mostly, an autopsy is offered for free, but a fee is attached to the procedure in certain cases.11 The Centers for Medicare and Medicaid Services eliminated the autopsy requirement in 2019,12 but some private insurance plans could cost between $3000 and $5000 for an autopsy. The death of a preterm infant is stressful to the family, especially when it is sudden. Although EP infants have a higher risk of mortality, the rate of unexpected, unexplained death is a traumatic experience. While the family is mourning the loss, it is difficult for the neonatal intensive care unit team to talk about the option of an autopsy. A compassionate approach to discussing the importance and need for an autopsy is advisable. Some families are very approachable and want to pursue an autopsy to alleviate their anxiety, while others cannot decide in the moment of stress. When approaching parents, ethical principles should be followed. The details of ethical and legal aspects of the autopsy are reported earlier.13,14 The ethical principles of justice, beneficence, and nonmaleficence should be considered, as highlighted by Sarnaik.15 An autopsy in EP infants is essential in finding rare anomalies or genetic diseases. It may also help find accidental/incidental injuries. Among the techniques of autopsies, minimally invasive autopsy (MIA) is another option over the complete diagnostic autopsy. 16 MIA needles to collect samples from key organs and body fluids instead of opening the cadaver.17 The caveat with MIA is the missing important information about the gross appearance of the organs. In pediatric practice, the role of postmortem computed tomography and postmortem magnetic resonance imaging (MRI) has been examined. Some institutions reported reimbursement for postmortem imaging. However, the significant barriers were the lack of funding. de Sévaux et al.18 compared the autopsy findings of 298 infants with the findings on postmortem MRI. They observed that 56.3% of autopsy findings were not detected using postmortem MRI. Understandably postmortem MRI has limitations in detecting infections and infarctions at the tissue or cellular level; a conventional autopsy is more precise, but MRI is noninvasive. The benefits and limitations of postmortem computed tomography and postmortem-MRI should be discussed with the parents. In conclusion, an autopsy on an EP infant has pros and cons (Table 1). It should be conducted when an iatrogenic COD is suspected, examples include tracheal perforation during intubation, traumatic esophageal or gastric perforation secondary to nasogastric tube or central line–related arrhythmias or cardiac tamponade, sudden deterioration during a procedure, or procedure-related complications. A few factors and potential alternatives should be considered when making the autopsy decision in EP infants (Figure 1). Routine autopsies in EP infants should be examined through the lens of ethical understanding and parental concerns. In instances where parents insist or there are medicolegal implications, an autopsy should be obtained by the least invasive method. Table 1 - Pros and cons of autopsy in extremely preterm infants. Pros Cons Provide information on rare congenital anomalies and chromosomal abnormalities Parental stress (they have to decide while they are still mourning over their loss) May help/confirm finding the cause of death Ethical issues (justice, nonmaleficence) Detect incidental or accidental injuries Invasive (cutting of the deceased body) May help improve future outcomes Religious, social, cultural reservations More informative than postmortem imaging Cost Informing future genetic counseling of parents and other family members Figure 1: Factors influencing the autopsy decision and alternative in extreme preterm infants. MIA: Minimally invasive autopsy; PM-CT: Postmortem computed tomography; PM-MRI: Postmortem magnetic resonance imaging.