The study, led by Justin Kotliar of the Children’s Regional Hospital at Cooper University Health Care together with colleagues at New York-Presbyterian-Weill Cornell Medicine, set out with unusually specific targets. The team aimed to reduce moderate-to-severe hypothermia on admission, the time elapsed before antibiotics and intravenous fluids were started, and the use of invasive ventilation, each by 25 percent. They also aimed to reduce bronchopulmonary dysplasia, a chronic lung disease of prematurity, by 10 percent, and to achieve adherence to a Golden Hour bundle in at least half of eligible infants. The population in focus was defined by gestational age below 32 weeks, birth weight at or below 1500 grams, or both, the categories of newborns whose immature physiology leaves them most vulnerable in the delivery room.

The intervention itself was not a new drug or device but a structured bundle of coordinated practices, implemented through seven successive Plan-Do-Study-Act cycles between December 2021 and October 2023. This iterative framework, drawn from the Institute for Healthcare Improvement’s Model for Improvement, treats each change as a small experiment: a proposed modification is introduced, its effects are measured, and the results inform the next cycle. The bundle incorporated standardized admission workflows, improved thermoregulation practices in the delivery room, and optimized early respiratory management. In practical terms, that meant rehearsed team roles, checklists modeled on aviation-style human factors engineering, plastic wrap and warming measures to prevent heat loss, and a deliberate preference for gentler, non-invasive respiratory support where clinically appropriate rather than defaulting to intubation and mechanical ventilation.

The results, tracked with statistical process control charts known as Shewhart charts, were striking. Moderate-to-severe hypothermia on admission fell from 25 percent of infants to zero over the study period. Hypothermia matters enormously in this population: large database analyses, including work from the Canadian Neonatal Network, have linked admission temperatures outside the normal range to increased mortality and major morbidity in infants born before 33 weeks. Because premature infants have thin skin, little subcutaneous fat, and a high surface-area-to-mass ratio, they lose heat rapidly, and cold stress triggers oxygen consumption and metabolic strain that fragile organs can ill afford. Eliminating moderate-to-severe hypothermia entirely represents the kind of outcome that quality improvement science rarely achieves.

Medication and fluid timing improved just as dramatically. The mean time to antibiotic administration dropped from 132 minutes to 77 minutes, a reduction of nearly half. Early-onset sepsis remains a feared diagnosis in preterm infants, and while the decision to start antibiotics is a careful clinical judgment, delays in initiating treatment once the decision is made can allow bacterial infection to progress in babies with limited physiological reserves. Meanwhile, the proportion of infants receiving intravenous fluids within the Golden Hour rose from 30 percent to 86 percent. Fluid and glucose homeostasis in the first hour is a delicate balance, as the neonatal literature on fluid, electrolytes, and nutrition emphasizes, and establishing reliable intravenous access early stabilizes both metabolism and the delivery of critical medications.

Perhaps the most consequential finding concerned the lungs. The rate of grade 2 or grade 3 bronchopulmonary dysplasia, classified using an evidence-based diagnostic approach, fell from 37 percent to 19 percent over the study period. Bronchopulmonary dysplasia is one of the most burdensome long-term complications of extreme prematurity, associated with prolonged oxygen dependence, rehospitalization in infancy, and impaired neurodevelopment. Its pathogenesis involves volutrauma and barotrauma from mechanical ventilation, inflammation, and oxygen toxicity, all of which injure lungs that are still forming alveoli. By shifting early respiratory management away from unnecessary invasive ventilation toward approaches such as nasal continuous positive airway pressure, a strategy supported by randomized trials including the COIN trial, the bundle appears to have protected developing lungs during their most vulnerable period.

Adherence to the full Golden Hour bundle ultimately reached 88 percent, far exceeding the 50 percent goal the team had set. That figure is notable because bundle adherence is often the weak link in quality improvement work. Neonatal resuscitation and stabilization involve large, multidisciplinary teams, including neonatologists, nurses, respiratory therapists, and pharmacists, all performing time-critical tasks in a confined space under stress. Human factors research has shown that in such environments, memory-based protocols fail predictably, and that checklists, role clarity, and positive reinforcement of team behaviors are essential to reliability. The Weill Cornell team’s use of repeated PDSA cycles appears to have embedded the bundle into routine practice rather than leaving it as a paper protocol.

The study’s methodology deserves attention because it illustrates how modern quality improvement research differs from a conventional randomized trial. Outcomes were analyzed using Shewhart P-charts and X-bar/S-charts, statistical process control tools originally developed for manufacturing that distinguish ordinary variation from meaningful, sustained change. A special-cause signal on such a chart, indicated by points beyond control limits or persistent runs on one side of the centerline, provides evidence that an intervention genuinely shifted a process rather than fluctuating by chance. This approach is well suited to sequential implementation, in which every eligible infant receives the intervention and historical baselines serve as the comparison. The initiative was reviewed by the institutional board at Weill Cornell Medicine and deemed exempt as quality improvement, and the authors reported no competing interests and no external funding.

The findings also fit into a growing international literature. Previous single-center initiatives, including projects published in the American Journal of Medical Quality and in the Journal of Perinatology itself, have reported improvements in admission temperature and time to interventions after Golden Hour protocols. A 2024 scoping review in BMC Pediatrics catalogued the expanding range of Golden Hour quality improvement efforts worldwide. What distinguishes the new study is the breadth of outcomes that moved together: thermoregulation, antibiotic timing, fluid initiation, ventilation practice, and ultimately a chronic lung disease diagnosis, all improving in parallel as bundle adherence climbed. That coherence matters, because it suggests the improvements flowed from a genuine system change rather than isolated fixes.

Cautions remain, as they do with any single-center, uncontrolled initiative. Statistical process control can demonstrate that outcomes changed after the intervention, but it cannot fully exclude the influence of concurrent changes in patient mix, staffing, or co-interventions over nearly two years. The diagnosis of bronchopulmonary dysplasia depends in part on survival and on imaging practices, which can shift over time. Still, the magnitude and internal consistency of the changes, from a 25 percent hypothermia rate to zero and a near-halving of severe chronic lung disease, are difficult to dismiss. For neonatal intensive care units everywhere, the message is both humbling and empowering: some of the most powerful medicine delivered to a premature infant is not a new molecule but the disciplined, rehearsed, and human-centered organization of the first sixty minutes of life.

Subject of Research: Quality improvement in Golden Hour neonatal care to reduce morbidity in at-risk preterm infants

Article Title: Sixty golden minutes: a quality improvement bundle reduces morbidities in at-risk preterm infants

Article References: Sixty golden minutes: a quality improvement bundle reduces morbidities in at-risk preterm infants. (n.d.). https://doi.org/10.1038/s41372-026-02925-1

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02925-1

Keywords: Golden Hour, preterm infants, neonatology, quality improvement, hypothermia, bronchopulmonary dysplasia, NICU, Plan-Do-Study-Act, statistical process control, thermoregulation, antibiotic timing, invasive ventilation

The research team, led by Aysheshim Fentu Yeshalem of Jigjiga University’s Department of Pediatrics and Child Health, combed through the medical records of every preterm neonate admitted to the hospital’s neonatal intensive care unit over a two-year window running from February 9, 2024 to February 7, 2026. In total, 440 preterm babies were included in the analysis, a complete enumeration of admissions during the study period rather than a sample. By reconstructing each infant’s clinical course from admission to discharge or death, the investigators were able to calculate the overall mortality rate and, crucially, to identify which characteristics and treatments were statistically linked to survival.

The headline number is sobering: 30.3 percent of the preterm neonates died, with a 95 percent confidence interval of 25.9 to 34.8 percent. In practical terms, for every hundred premature babies wheeled into the unit, roughly thirty did not leave. Preterm birth is defined as delivery before thirty-seven completed weeks of gestation, and babies born early face a cascade of physiological challenges: their lungs may lack sufficient surfactant to stay inflated, their immune systems are immature, their skin is thin and loses heat rapidly, and their digestive systems often cannot coordinate sucking and swallowing. In high-resource settings, incubators, mechanical ventilation, and surfactant therapy have driven preterm mortality down dramatically. In settings like Jigjiga, where such technologies may be limited or unavailable, survival depends far more heavily on basic supportive care.

To untangle which factors mattered most, the researchers used binary logistic regression, a statistical technique that estimates the odds of an outcome, in this case death, while adjusting for the influence of other variables. They screened the candidate variables for multicollinearity, the phenomenon in which predictors overlap so heavily that their individual effects become impossible to separate, using the variance inflation factor, and found all values below four, comfortably under conventional thresholds of concern. They then checked whether the final model fit the observed data using the Hosmer-Lemeshow test, which returned a p-value of 0.53, indicating no significant departure between predicted and actual outcomes. Associations were considered statistically significant at a p-value below 0.05.

Three risk factors stood out as powerful predictors of death. The first was birth weight below 1,500 grams, the threshold clinicians call very low birth weight. Babies in this category faced roughly three times the odds of dying compared with heavier preterm infants, an adjusted odds ratio of 3.23. This makes biological sense: weight at birth is a composite proxy for gestational age, organ maturity, and nutritional reserves in utero, and the lightest babies have the least physiological buffer against complications such as respiratory distress, infection, and feeding intolerance.

The second major risk factor was a low Apgar score at five minutes of life. The Apgar score is a rapid assessment performed at one and five minutes after birth that rates a newborn’s appearance, pulse, grimace, activity, and respiration, each on a scale of zero to two, for a maximum of ten. A score below seven at five minutes signals that the baby has not transitioned smoothly to life outside the womb, often reflecting birth asphyxia or depressed physiological function. In the Jigjiga cohort, a five-minute Apgar below seven nearly quadrupled the odds of death, with an adjusted odds ratio of 4.09, making it the strongest intrinsic risk factor identified in the study.

The third and most striking risk factor was hypothermia during the hospital stay, which more than quintupled the odds of mortality, with an adjusted odds ratio of 5.09. Newborns, and especially preterm newborns, lose heat quickly because of their high surface-area-to-weight ratio, thin skin, and limited subcutaneous fat. Hypothermia is insidious because it worsens nearly every other problem a fragile infant faces: it impairs the ability to breathe, slows metabolism, increases the risk of hypoglycemia, and weakens immune defenses. The World Health Organization has long championed the so-called warm chain, a sequence of simple measures from immediate drying and skin-to-skin contact to delayed bathing and appropriate covering, precisely because maintaining a normal body temperature is one of the cheapest and most effective lifesaving measures in neonatal care.

Just as important as the risk factors, however, were the protective ones, and here the study delivers a genuinely hopeful message. Preterm babies who received kangaroo mother care, the practice of continuous skin-to-skin contact between mother and infant combined with frequent breastfeeding, had 83 percent lower odds of death, with an adjusted odds ratio of 0.17. Kangaroo mother care was pioneered in resource-limited settings and has since been validated in trials worldwide; for stable low-birth-weight babies it can match or exceed the survival benefits of conventional incubator care while also promoting breastfeeding, weight gain, and maternal bonding. Its strong protective association in Jigjiga reinforces calls to make the practice universal in neonatal units across the region.

Two other interventions were also linked to dramatically better survival. Babies who were resuscitated at birth had 72 percent lower odds of dying, an adjusted odds ratio of 0.28, a finding that highlights the life-or-death importance of having trained personnel and functioning resuscitation equipment in every delivery room. And infants who began feeding within twenty-four hours of birth had 81 percent lower odds of death, with an adjusted odds ratio of 0.19. Early feeding, ideally with the mother’s own milk, stabilizes blood sugar, protects the immature gut, reduces the risk of sepsis, and prevents the catabolic weight loss that can spiral into further complications. The fact that resuscitation, kangaroo care, and early feeding all emerged as independent protective factors suggests that the pathway to lower mortality in this setting runs not through expensive technology but through the disciplined, consistent delivery of care that is already known to work.

The authors conclude that mortality among preterm neonates at the hospital was high, and they call for proper labor follow-up, resuscitation at birth, prevention and treatment of hypothermia, kangaroo mother care, and early initiation of feeding to be implemented as standard practice. They also recommend prospective, multicenter studies to build on their findings, noting that a retrospective, single-center design has inherent limits: it can identify associations but cannot fully establish causation, and it reflects the experience of one hospital’s catchment population. Even so, the study fills an important evidence gap for Ethiopia’s Somali region and adds to a growing body of research showing that the global burden of preterm death is concentrated precisely where the simplest interventions are least consistently available. For the roughly one in ten babies born too soon worldwide, the difference between life and death, this study suggests, may come down to warmth, milk, and a pair of trained hands in the first minutes and days of life.

Subject of Research: Neonatal mortality and associated risk and protective factors among preterm neonates in eastern Ethiopia

Article Title: Neonatal mortality and associated factors among preterm neonates admitted to Jigjiga University Sheikh Hassan Yabare Comprehensive Specialized Hospital, Ethiopia: a retrospective cross-sectional study

Article References: Yeshalem, A. F., Alemu, H. G., Roble, A. K., Ahmed, M., Muse, A. I., Eshetu, B. G., Ma,alin, M. S., & Abdulahi, A. A. (2026). Neonatal mortality and associated factors among preterm neonates admitted to Jigjiga University Sheikh Hassan Yabare Comprehensive Specialized Hospital, Ethiopia: a retrospective cross-sectional study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07781-8

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07781-8

Keywords: preterm birth, neonatal mortality, Ethiopia, kangaroo mother care, hypothermia, APGAR score, low birth weight, neonatal intensive care, early feeding, birth asphyxia, resuscitation, BMC Pediatrics

The research, conducted at the Department of Forensic Medicine in Hradec Králové in the Czech Republic, is the first systematic, statistically validated investigation of reactive splenic contraction in human hypothermia deaths. The finding itself is not new to physiology. The spleen acts as a rapidly mobilizable blood reservoir, capable of sequestering up to 200 to 250 milliliters of densely packed erythrocytes. When the sympathetic nervous system fires—during exercise, hypoxia, hemorrhage, or severe stress—the splenic capsule and vessels contract, squeezing stored red blood cells into the circulation and boosting oxygen-carrying capacity within moments. What had never been done before was to rigorously test whether this dramatic physiological response leaves a recognizable and diagnostically reliable footprint at autopsy in people who died of hypothermia.

The study team, led by Lenka Zátopková and Štěpánka Pohlová Kučerová together with senior author Petr Hejna, examined 54 fatalities attributed to accidental hypothermia and compared them against 170 randomly selected control cases representing both natural and non-natural deaths, including heart failure, cardiopulmonary failure, hanging, and suffocation. The researchers defined reactive splenic contraction by a strict macroscopic triad: an apparent reduction in splenic volume or weight relative to the decedent’s body size, wrinkling of the splenic capsule, and anemization of the red pulp on the cut surface, typically accompanied by increased firmness of the tissue. All three components had to be present simultaneously, a deliberately conservative requirement designed to maximize specificity and prevent misclassification based on isolated, nonspecific splenic changes.

The results were unambiguous. The complete contraction triad was identified in 48 of the 54 hypothermia fatalities, a prevalence of 88.9 percent, but in only 2 of the 170 controls, or 1.2 percent. This translates into a sensitivity of 88.9 percent and a specificity of 98.8 percent, with a positive predictive value of 96.0 percent, a negative predictive value of 96.6 percent, and an overall diagnostic accuracy of 96.4 percent. The statistical association between splenic contraction and fatal hypothermia was extraordinarily strong, with an odds ratio of 672.0 and a 95 percent confidence interval stretching from 131.4 to 3437.2, far beyond the threshold of statistical significance. Histological examination of the spleen in every hypothermia case confirmed the macroscopic impression of red-pulp anemization, revealing a depletion of erythrocytes within the red pulp and empty vascular lumina consistent with the wholesale mobilization of the splenic blood store.

Perhaps the most intriguing result concerns how splenic contraction relates to the established markers of hypothermia. Among the classical findings, only Wischnewsky spots showed a statistically significant association with splenic contraction. No significant relationships emerged with cold erythema, the inner knee sign, hemorrhages within core skeletal muscles, or fatty degeneration of renal tubular epithelial cells. In practical terms, this means that splenic contraction does not simply ride along with the other tissue changes of cold death. Among contraction-positive fatalities, cold erythema was absent in more than a quarter of cases, and roughly a third lacked either muscle hemorrhages or renal fatty degeneration; in six cases, both of those deeper findings were missing entirely. Splenic contraction, in other words, appears to carry independent diagnostic information rather than redundant confirmation of what other signs already show.

This independence points toward a compelling pathophysiological interpretation. Hemorrhagic and degenerative lesions such as muscle hemorrhages and renal tubular fatty change generally require prolonged survival and sustained exposure to critical cold before they develop. Splenic contraction, by contrast, reflects an immediate physiological adaptation: acute sympathetic activation, circulatory centralization shunting blood toward vital organs, and the rapid expulsion of the splenic erythrocyte reservoir into the systemic circulation. The authors therefore propose that a contracted spleen may represent one of the earliest morphofunctional responses to lethal cold stress, visible at autopsy even when the slower-developing hemorrhagic and degenerative manifestations have not yet had time to appear. Supporting this view, the mean splenic weight in contraction-positive hypothermia cases was just 76.1 grams, compared with 132.5 grams in contraction-negative hypothermia cases and 175.4 grams in controls, and the difference could not be explained by age differences between the groups.

The scientific groundwork for this conclusion was laid decades ago, though it was largely forgotten. In 1944, the German researcher Wendt demonstrated experimentally in rabbits that whole-body cooling reduced spleen volume by up to one third, with the most pronounced contraction occurring at core temperatures of 24 to 26 degrees Celsius, and that the organ regained its normal size after rewarming. Subsequent animal studies by Varman and Bernshtein corroborated the spleen’s reservoir role under hypothermic conditions, showing decreases in splenic weight and volume accompanied by rising circulating hemoglobin concentrations. Isolated human case reports followed, including Horn’s account of a 49-year-old sailor who died of cold exposure after falling overboard, and retrospective series by Gillner and Waltz and by Schneider and Klug that noted contracted spleens in a minority of hypothermia deaths. Two doctoral dissertations touched on the finding, but neither provided the prospective, controlled evidence needed to establish its diagnostic value, and major forensic textbooks continued to relegate splenic contraction to quotation marks and question marks—or to omit it entirely.

The practical implications for forensic practice are considerable. Hypothermia deaths are frequently misinterpreted at first glance, particularly when the scene suggests sudden natural death, acute intoxication, or even violence. Cold erythema and ecchymosis-like discolorations on the limbs can mimic traumatic injuries, occasionally raising suspicion of assault. In such ambiguous situations, the conditions that mimic hypothermia typically produce a congested, blood-filled spleen, whereas a contracted, pale, wrinkled spleen points decisively in the opposite direction. Because the contracted spleen is readily visible the moment the abdominal cavity is opened—sometimes alongside reverse Wischnewsky spots visible through the gastric wall—its early recognition can redirect the differential diagnosis toward hypothermia and prompt targeted dissection of the back and core musculature, inspection of the knee joints, and supplementary histological and toxicological analyses. The authors also suggest that the finding could support minimally invasive postmortem approaches, such as laparoscopic inspection of body cavities combined with postmortem imaging, where early visual cues carry exceptional value.

Modern imaging may soon extend this diagnostic reach even further. Preliminary work with postmortem computed tomography has reported elevated splenic radiodensity in hypothermia deaths, consistent with a denser, more compact parenchyma produced by contraction, and the present study’s exploratory imaging data showed compatible tendencies, though the small number of cases precluded statistical analysis and will be reported separately. The researchers are careful to emphasize the limits of their work: the study was conducted at a single institution, the macroscopic assessment was not blinded, interobserver agreement was not formally measured, and histological examination of the spleen was performed only in the hypothermia group. Splenic contraction is not pathognomonic and must never be interpreted in isolation. Nevertheless, with nearly nine out of ten hypothermia deaths showing the triad and fewer than two percent of controls doing so, the evidence strongly supports adding routine splenic assessment to the forensic autopsy protocol—transforming an organ long dismissed as morphologically unremarkable into a quiet but eloquent witness to death by cold.

Subject of Research: Validation of reactive splenic contraction as a diagnostic autopsy sign of fatal hypothermia

Article Title: Spleen contraction verified as a supportive autopsy sign of fatal hypothermia

Article References: Zátopková, L., Kučerová, Š. P., Kovařík, D., Pažinová, J., Pitková, R., Bačinová, P., Janík, M., & Hejna, P. (2026). Spleen contraction verified as a supportive autopsy sign of fatal hypothermia. International Journal of Legal Medicine. https://doi.org/10.1007/s00414-026-03984-x

Image Credits: AI Generated

DOI: 10.1007/s00414-026-03984-x

Keywords: hypothermia, forensic pathology, spleen, splenic contraction, autopsy, Wischnewsky spots, cold erythema, postmortem diagnosis, forensic medicine, blood reservoir, postmortem imaging, legal medicine

The research team conducted a narrative review with systematic elements, searching PubMed in November and December 2025 with combinations of pediatric terms such as child, infant, neonate, newborn, and adolescent and maltreatment terms such as abuse, neglect, non-accidental, and battered child, crossed with cold-related terms including hypothermia, cold injury, low body temperature, and frostbite. A supplementary non-systematic search of German-language publications in Google Scholar was added to catch literature not indexed in PubMed. Two reviewers independently screened abstracts against inclusion and exclusion criteria, excluding studies focused exclusively on adults, on clinical or therapeutic hypothermia, and on accidental cold exposure such as winter sports accidents. Out of 192 search results plus four additional German-language publications, only 22 papers ultimately made the cut, a strikingly small body of evidence for a phenomenon the authors describe as a significant threat to affected children.

To understand why cold is so dangerous to young children, the review lays out the underlying physiology in detail. Hypothermia is generally defined as a core body temperature falling below 35 degrees Celsius, although the World Health Organization uses a threshold of 36.5 degrees for newborns. Crucially, hypothermia does not require extreme environments: it can develop at ordinary room temperature if a victim is unable to take self-rescue measures and no help arrives. In water, the danger multiplies, because heat conducts 20 to 25 times faster through water than through air. The body fights back with stress hormone release, shivering, peripheral vasoconstriction, glycogen mobilization, and, in infants, heat production from brown fat tissue. Yet children lose heat faster than adults because of their larger surface-to-volume ratio, narrower range of thermoregulatory responses, and faster metabolic exhaustion. A literature review cited in the paper documented neonatal cooling rates ranging from 1.2 to a staggering 28.5 degrees Celsius per hour.

Local cold injuries follow a different but equally grim pathophysiology. Frostbite results from rapid exposure to extreme cold, producing ice crystals both inside and outside cells, and typically strikes the extremities, nose, and ears. Severity is usually graded clinically into four levels. Non-freezing cold injury develops more slowly and involves no ice crystal formation, but both forms trigger vasoconstriction, ischemia, inflammatory cellular damage, electrolyte shifts that initiate cell death, and thrombosis. The body does mount a defense known as the hunting response, in which blood vessels dilate for five to ten minutes to protect chilled tissue, but if cold exposure continues, circulation to the affected body part is shut down to preserve the core, leading to further ischemia and necrosis. The consequences can range from lasting sensory deficits to amputation and death, and both injury types demand intensive, multidisciplinary treatment.

Against this physiological backdrop, the case reports assembled by the Düsseldorf team paint a disturbing picture of how cold exposure is weaponized or allowed to harm children. Gustavson and Levitt described four cases of abuse-related pediatric hypothermia in 1996, noting that hypothermia without a consistent history should always raise suspicion of abuse. In three of their four cases, the children had been forced into cold water or held under a cold shower, leading the authors to propose inflicted cold-water immersion or near drowning as a recognized mechanism. Other reports lean toward neglect: Bernstein and colleagues described a newborn found in a dumpster, still attached to her placenta, with an initial core temperature of just 20 degrees Celsius. Knight and colleagues, reviewing pediatric neglect deaths, reported a three-year-old boy with patterned contusions found dead at home, in whom autopsy revealed hypothermia as the cause of death.

One of the review’s clearest findings is demographic. Every case of abuse- or neglect-related hypothermia identified in the literature involved infants and children aged six or younger, and only one reported case involved a child older than four, a six-year-old boy tied to a bed with an electrical cord in a cold room, deliberately prevented from escaping. This age pattern almost certainly reflects vulnerability: very young children cannot remove themselves from cold environments, cannot communicate what happened, and depend entirely on caregivers for warmth and shelter. The authors also observed that most of the affected children showed concomitant injuries indicative of physical abuse or pronounced signs of other forms of neglect, suggesting that cold exposure tends to appear in particularly severe cases of maltreatment, where caregivers who inflict one hazard are likely violating the child’s wellbeing in multiple ways at once.

The rarity of published cases, however, may be more apparent than real. The review highlights substantial underreporting: mild hypothermia resulting from abuse or neglect likely goes unrecognized in clinical settings or is deemed too insignificant to publish, and hypothermia is notoriously difficult to detect post mortem, which may allow it to escape forensic notice entirely. Publication bias further skews the record toward the most severe cases. The true extent of unreported cases is therefore likely considerable, the authors conclude, and clear generalizations from 22 publications remain difficult. Outcomes in the documented cases nonetheless span the full spectrum, from children who recovered without lasting physical effects to those requiring amputation of extremities and those who died.

Local cold injuries tell an even sparser story. The review found only isolated reports, including a 2024 case of medical child abuse in which a mother caused what the authors called cold burn injuries by repeatedly spraying her 17-month-old child’s skin with deodorant spray. Neglect-related frostbite is similarly rare in the literature, with the closest cases being newborns left outside in the cold, though the authors note that distinguishing neglect from active abuse is often legally and clinically impossible in such scenarios. A retrospective study of 46 pediatric frostbite cases by Boles and colleagues found that lack of supervision was a major risk factor and the most common cause, with the child unsupervised in 9 of 14 cases involving children up to 12 years old. The review also flags alcohol intoxication as a risk factor for hypothermia in older children and adolescents, raising questions about supervisory neglect depending on age and circumstances.

A particularly subtle finding concerns hypothermia as a secondary phenomenon rather than a direct result of cold exposure. Hypothermia is a well-known sign in severe trauma and can indicate brain injury with impaired central thermoregulation, and it appears regularly in abusive head trauma. Kennedy and colleagues, studying 520 children with traumatic brain injury, of whom 50 had abusive head trauma, found a twofold increase in unfavorable outcomes among children with secondary hypothermia. Lee and colleagues, in a retrospective study of 156 physically abused children admitted to intensive care, found that trauma-induced hypothermia was associated with poor neurological outcomes and was the second strongest risk factor for mortality, with abusive head trauma accounting for 87.1 percent of ICU admissions. This creates a diagnostic trap: secondary hypothermia from abusive head trauma could be mistaken for additional cold-related abuse, and healthcare professionals must be aware of the phenomenon to prevent false allegations.

The review closes with a warning about differential diagnosis and interpretation pitfalls. Cold-induced skin injuries can resemble thermal burns and must be distinguished from them, while cold aerosol burns, sometimes called frosties, are frequently self- or peer-inflicted among adolescents. Accidental hypothermia in newborns, whose limited thermoregulatory reserves put them at risk of pneumonia and sepsis, must also be considered, and the authors note that external factors such as homelessness, forced displacement, or war may prevent parents from protecting their children through no fault of their own. Even bruising demands careful reading, because hypothermia impairs coagulation and can produce more pronounced hematomas, while standard laboratory coagulation tests run at 37 degrees Celsius fail to capture the full extent of the dysregulation. The authors acknowledge that their findings, drawn largely from high-income countries, may not generalize elsewhere, and they call for studies with larger case numbers. Their central message stands: hypothermia and cold injuries, though rare on paper, are severe, potentially fatal manifestations of child maltreatment, and recognizing them could save the youngest and most vulnerable patients.

Subject of Research: Hypothermia and local cold injuries as rare but severe manifestations of child abuse and neglect

Article Title: Hypothermia and cold injuries – rare but severe manifestations of child abuse and neglect

Article References: Küppers, L., Ritz, S., & König, L. M. (2026). Hypothermia and cold injuries – rare but severe manifestations of child abuse and neglect. International Journal of Legal Medicine. https://doi.org/10.1007/s00414-026-03977-w

Image Credits: AI Generated

DOI: 10.1007/s00414-026-03977-w

Keywords: child abuse, child neglect, hypothermia, frostbite, cold injury, cold exposure, forensic medicine, pediatrics, abusive head trauma, thermoregulation, child protection, legal medicine

The story began when the patient was thirteen years old. She visited a local clinic complaining of fatigue and fever, and routine laboratory tests revealed two red flags that pointed away from an ordinary infection: hypothyroidism and abnormally elevated sodium levels in her blood, a condition known as hypernatremia. Both findings suggested a problem with the pituitary gland and the hormonal circuitry it controls. A cranial computed tomography scan then identified a mass in the suprasellar region, the anatomical neighborhood just above the pituitary where the optic chiasm, pituitary stalk, and hypothalamus are packed closely together. She was referred to a pediatric department for further evaluation.

Because the mass sat in a location where surgical biopsy carried a high risk of injuring surrounding brain structures, the medical team did not attempt to obtain tissue for histological examination. Instead, they relied on indirect evidence. Magnetic resonance imaging showed a suprasellar mass extending toward the third ventricle and the pineal region, involving the hypothalamus itself. In addition, the patient’s serum level of beta-human chorionic gonadotropin, a hormone sometimes secreted by certain germ cell tumors, was mildly elevated at 0.3 nanograms per milliliter. Taken together, the imaging findings and the tumor marker were sufficient for a clinical diagnosis of primary intracranial germinoma, a rare germ cell tumor that arises in the midline of the brain and is particularly common in children and adolescents. At the time of diagnosis, she already had panhypopituitarism, meaning near-total loss of pituitary hormone production, and central diabetes insipidus, a condition in which the brain fails to produce the hormone that allows the kidneys to conserve water.

Treatment followed a standard strategy for intracranial germinoma: chemotherapy using the CARE regimen, followed by whole-ventricular irradiation at a total dose of 23.4 Gy delivered in thirteen fractions. The response was excellent. Follow-up magnetic resonance imaging demonstrated marked tumor regression, and the beta-human chorionic gonadotropin level normalized to 0.1 nanograms per milliliter or below. Yet even before treatment, the tumor’s location had already left its signature on her thermoregulation. She suffered persistent hyperthermia, with body temperatures ranging from 37 to 38 degrees Celsius, despite the absence of any clinical or laboratory evidence of infection or inflammation. The team suspected that the tumor’s infiltration of the hypothalamus had disrupted the brain’s thermostat. Roughly one month after therapy ended, her temperature settled into a normal range of 36 to 37 degrees, and for several years she remained clinically stable, with only occasional mild temperature elevations during summer months.

The first sign that something deeper was wrong arrived eight years after the original diagnosis, when the patient was twenty-one. In February of that year, she presented with fatigue, abdominal pain, and poor oral intake. Laboratory tests revealed hyponatremia, a dangerously low blood sodium level of 131 milliequivalents per liter, along with hypoglycemia, a blood glucose of 66 milligrams per deciliter. Her body temperature on arrival was 34.5 degrees Celsius, well below the threshold of clinical hypothermia. Physicians initially interpreted the picture as a sick-day state triggering relative adrenal insufficiency, and they administered stress-dose steroids while admitting her for active external warming. Her symptoms improved and she was discharged after seven days. Notably, however, the serum cortisol level drawn at presentation, which became available only later, was actually elevated at 56.2 micrograms per deciliter, a detail that would prove important.

A year later, the pattern repeated with greater severity. In January, at twenty-two years of age, she arrived with fatigue and was found to be profoundly hypothermic at 33.3 degrees Celsius with a bradycardic heart rate of just 41 beats per minute. In March of the same year she was readmitted with fatigue and decreased responsiveness, her temperature at 35.2 degrees. Once again, stress-dose steroids failed to produce rapid improvement, and once again the later cortisol measurement came back elevated, this time at 42.1 micrograms per deciliter. Brain magnetic resonance imaging showed no tumor recurrence and no new lesions. Hypothermia in the 34-degree range persisted throughout her hospitalization, but with active external warming her general condition gradually recovered, and she was discharged on the eleventh day.

The clinical reasoning that followed is what makes this case instructive. Adrenal crisis, the most feared endocrine emergency in patients with pituitary dysfunction, was initially suspected during both hypothermic episodes. But two observations argued against it: the cortisol levels measured during the episodes were elevated rather than low, and steroid supplementation did not rapidly resolve the symptoms. Combined with the absence of tumor recurrence on imaging, these findings pointed the team toward a different diagnosis: delayed hypothalamic dysfunction, a recognized late complication of cranial radiotherapy that can emerge months to decades after treatment in a dose- and time-dependent manner. The hypothalamus, the report’s authors emphasize, is more radiosensitive than the pituitary gland and may suffer functional impairment even at relatively low radiation doses. The whole-ventricular irradiation this patient received at 23.4 Gy may therefore have contributed to the slow, delayed failure of her brain’s temperature control system.

The metabolic derangements that accompanied her hypothermic episodes also fit this explanation. Hyponatremia and hypoglycemia during such episodes are more plausibly attributable to hypothermia itself than to adrenal failure. Severe cold impairs hepatic gluconeogenesis, the liver’s production of glucose, and blunts the counterregulatory hormonal responses, including glucagon release and sympathetic nervous system activation, that normally defend blood sugar and blood pressure against stress. Reduced oral intake compounds the problem. In other words, the hypothermia was not merely a symptom; it was the primary engine of her clinical deterioration and impaired consciousness, driving the laboratory abnormalities that had initially misled her physicians toward a diagnosis of adrenal insufficiency.

What can be done for a patient whose internal thermostat has failed? The report notes that several pharmacological agents targeting neurotransmitter systems have shown benefit in select cases of hypothermia associated with hypothalamic dysfunction, but no established therapy exists and the supporting evidence remains limited. Active external warming therefore constitutes the mainstay of management, encompassing direct measures such as electric blankets and hot water bottles as well as environmental temperature control with heating devices. Acting on this understanding, the medical team recommended proactive thermal management during the winters when the patient was twenty-three and twenty-four: maintaining room temperature above 20 degrees Celsius, using an electric blanket, and consuming warm beverages as part of daily life. Since these measures were implemented, she has experienced no further episodes of clinical deterioration or decreased consciousness requiring hospitalization, a strikingly simple intervention with apparently decisive results.

The broader lesson of this case extends well beyond one patient. Intracranial germinomas are cured in the great majority of cases, and long-term survival is the expected outcome. But as childhood and adolescent brain tumor survivors live decades beyond their treatment, the late effects of therapy become the dominant medical challenge. Endocrine surveillance for growth hormone deficiency, hypogonadism, and adrenal insufficiency is standard practice, yet thermoregulatory capacity is rarely assessed systematically. This report suggests it should be. A hypothalamic thermostat damaged by tumor infiltration or by radiation may compensate quietly for years before failing, and the failure mode, recurrent profound hypothermia masquerading as adrenal crisis or sepsis, is easy to misdiagnose. For clinicians caring for long-term survivors of suprasellar and hypothalamic tumors, the message is concrete: follow-up should address not only endocrine function but also thermoregulatory function, and practical lifestyle guidance about cold exposure may prevent life-threatening complications years after apparently successful treatment. In an era when cancer survival is increasingly measured in decades, the hypothalamus, that small almond-shaped guardian of the body’s internal climate, deserves a permanent place on the list of structures to watch.

Subject of Research: Delayed hypothalamic thermoregulatory dysfunction causing recurrent hypothermia after treatment of a suprasellar germinoma

Article Title: Delayed Hypothalamic Dysfunction Presenting as Recurrent Hypothermia After Treatment of Suprasellar Germinoma: A Case Report

Article References: Nishimura, A., Kado, T., Fujisaka, S., Kato, M., & Ishiki, M. (2026). Delayed Hypothalamic Dysfunction Presenting as Recurrent Hypothermia After Treatment of Suprasellar Germinoma: A Case Report. Clinical Case Reports, 14(10), Article e73535. https://doi.org/10.1002/ccr3.73535

Image Credits: AI Generated

DOI: 10.1002/ccr3.73535

Keywords: hypothalamus, hypothermia, suprasellar germinoma, cranial radiotherapy, thermoregulation, late complications, pituitary dysfunction, brain tumor survivorship, cortisol, case report, endocrinology, radiation therapy

The research team, led by Purbasha Mishra of Smt. NHL Municipal Medical College in Ahmedabad, India, together with Shrutiprajna Kar and Rajendra Prasad Anne, conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science through November 24, 2025. They included only randomized controlled trials comparing delivery room skin-to-skin contact with standard care in neonates born before 37 weeks of gestation, and they assessed outcomes spanning thermoregulation, cardio-respiratory stability, breastfeeding rates, and critical neonatal morbidities. The question they set out to answer is deceptively simple but clinically profound: when a preterm infant is clinically stable at birth, does the biological norm of immediate maternal contact do harm, or does it help?

The physiology behind the debate is worth unpacking. A newborn preterm infant loses heat rapidly because of a high surface-area-to-mass ratio, thin skin, and limited subcutaneous fat, and cold stress in the first minutes of life is linked to serious consequences including hypoglycemia, respiratory distress, and increased mortality. Incubators and radiant warmers were engineered precisely to solve this problem. Yet the mother’s chest offers something no machine can replicate: a dynamic thermal field that adjusts to the infant’s needs, warming a cold baby and cooling an overheated one, a phenomenon often described as maternal thermal synchrony. Skin-to-skin contact also stabilizes heart rate and breathing, reduces crying and stress hormone levels, and promotes early colonization with maternal skin flora and the release of hormones that support breastfeeding. The concern, however, has always been that preterm infants, unlike full-term babies, might be too unstable to tolerate this arrangement safely in the first minutes and hours of life.

One of the most striking findings of the new analysis concerns overheating, a complication that receives far less attention than hypothermia but carries real risks for newborns, including apnea and metabolic stress. Across three studies encompassing 254 participants, neonates who experienced delivery room skin-to-skin contact had a significantly lower risk of hyperthermia compared with those receiving standard care, with a risk ratio of 0.65 and a 95 percent confidence interval of 0.49 to 0.87, a result the authors graded as being of moderate certainty. This finding aligns with the thermal synchrony hypothesis: the maternal chest appears to be remarkably good at not just warming babies but preventing them from becoming too warm, something radiant warmers in particular can struggle to achieve with precision.

What about the cold, the fear that has driven routine separation for generations? On this question the evidence is more equivocal. Across three studies with 308 participants, there was no statistically significant difference in the incidence of hypothermia, defined as a temperature below 36 degrees Celsius, between the skin-to-skin group and standard care, with a risk ratio of 1.61 and a wide confidence interval of 0.51 to 5.1. The authors graded the certainty of this evidence as very low, meaning the true effect could range from a substantial increase in risk to a meaningful reduction. The wide interval reflects small sample sizes and few events, a persistent challenge in neonatal research where recruiting large numbers of extremely vulnerable infants is ethically and practically difficult. Still, the point estimate and the lack of statistical significance suggest that fears of dramatic cooling during skin-to-skin contact may be overblown, at least for the stable preterm infants studied here.

Perhaps the most clinically consequential finding involves cardio-respiratory stability. The review used the SCRIP score, a validated tool measuring the stability of the cardio-respiratory system in preterm infants, which tracks heart rate, respiratory rate, temperature, and oxygen saturation over time. At 60 and 120 minutes of age, stability scores were similar between the two care approaches. But by 360 minutes, six hours after birth, infants who had received delivery room skin-to-skin contact showed significantly better stability scores, with a mean difference of 0.39 and a confidence interval of 0.25 to 0.52 across three studies involving 222 neonates, graded as moderate certainty. This delayed divergence is intriguing: rather than destabilizing fragile infants, sustained maternal contact appears to confer a physiological advantage that becomes apparent as the newborn continues the transition to extrauterine life.

Critically, the review also looked for evidence of harm and found little. There was no significant difference in the number of neonates who developed cardiorespiratory instability during the intervention itself, with three studies and 197 participants yielding a risk ratio of 3.1 but a very wide confidence interval of 0.44 to 22, graded as low certainty. The wide interval again reflects sparse data, but it does not signal a consistent danger. And in one of the most practical outcomes for families and health systems alike, skin-to-skin contact was associated with higher rates of exclusive breastfeeding at discharge: across three studies with 192 participants, the risk ratio was 1.10 with a confidence interval of 1.01 to 1.19, graded as low certainty. Early maternal contact is thought to prime the breastfeeding relationship by stimulating oxytocin release, encouraging the first latch, and keeping mother and baby together during the sensitive window when feeding behavior is established.

The authors are careful about the limits of their evidence, and those limits matter for how the findings should be applied. None of the included studies enrolled extremely preterm neonates, typically defined as those born before 28 weeks of gestation, nor infants with congenital anomalies, the very patients for whom the risks of separation and of contact are both most contested. Data on critical neonatal outcomes such as mortality, intraventricular hemorrhage, necrotizing enterocolitis, and chronic lung disease were limited, meaning the review cannot speak to whether DR-SSC influences these rare but devastating events. The certainty ratings ranged from moderate to very low across outcomes, a reminder that 562 infants spread across eight trials is a thin evidentiary base for a practice that would touch millions of births worldwide. The meta-analysis followed PRISMA reporting standards and was prospectively registered, lending methodological credibility, but the underlying trials themselves were small.

Even with those caveats, the implications for neonatal practice are substantial. The authors conclude that initiating skin-to-skin contact in the delivery room for clinically stable preterm neonates born at 28 weeks of gestation or beyond probably reduces the risk of hyperthermia and promotes exclusive breastfeeding, while likely not increasing the risk of hypothermia or compromising cardio-respiratory stability. In other words, the traditional justification for routine separation, that the incubator is demonstrably safer, is not supported by the best available evidence for a large group of preterm infants. What emerges instead is a picture of DR-SSC as a promising strategy for selected mother-infant dyads, contingent on clinical stability at birth and the availability of appropriate monitoring. Many neonatal guidelines, including those shaped by the World Health Organization’s embrace of kangaroo mother care, have been gradually moving toward earlier and earlier maternal contact, and this review adds rigorous, if still imperfect, evidence to that trajectory.

The human stakes are hard to overstate. Every year an estimated 13 million babies are born preterm, and the first hour of life, sometimes called the golden hour, shapes trajectories of survival, feeding, and bonding. If the simplest intervention imaginable, a mother holding her baby against her bare chest in the delivery room, can outperform a high-technology incubator on key measures of temperature regulation, six-hour physiological stability, and breastfeeding success, then delivery rooms everywhere may need to rethink their choreography. The next generation of trials will need to test the approach in extremely preterm infants, track long-term neurodevelopmental outcomes, and establish clear protocols for identifying which stable preterm babies can safely go to their mother’s chest instead of a plastic bassinet. For now, the message of this review is quietly revolutionary: for many preterm newborns, the safest place after birth may not be a machine at all, but the mother they were separated from in the first place.

Subject of Research: Delivery room skin-to-skin contact as an alternative to incubator care for clinically stable preterm neonates

Article Title: Delivery room skin-to-skin contact for preterm neonates: a systematic review and meta-analysis

Article References: Mishra, P., Kar, S., & Anne, R. P. (2026). Delivery room skin-to-skin contact for preterm neonates: a systematic review and meta-analysis. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07759-6

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07759-6

Keywords: preterm birth, skin-to-skin contact, delivery room, neonatology, hypothermia, hyperthermia, cardiorespiratory stability, breastfeeding, kangaroo mother care, systematic review, meta-analysis, incubator care

That apparent normality did not last. During his four-week admission he suffered several further episodes of transient hypothermia accompanied by hypertension and sweating, each resolving spontaneously. Over the following four years he was admitted more than a dozen times with the same constellation of symptoms: hypothermia plunging as low as 28 degrees Celsius, profuse diaphoresis, blood pressure disturbance that swung between severe hypertension and profound hypotension, and symptomatic hyponatremia with sodium levels between 119 and 132 mmol/L. On every occasion, repeat testing found no evidence of infection or endocrine disease. This pattern of periodic hypothermia, autonomic instability and low sodium pushed the clinical team toward an entirely different explanation: a thermoregulatory disorder originating in the central nervous system. When the authors re-examined his prior brain imaging, they found something the original report had missed, an abnormality of the corpus callosum together with a cavum veli interpositi, a fluid-filled structure that can accompany callosal malformations.

Those findings were supportive of a diagnosis of Shapiro syndrome, an extraordinarily rare condition first described in 1969 by Shapiro, Williams and Plum in two patients who presented with spontaneous episodic hypothermia and hyperhidrosis alongside radiographic evidence of agenesis of the corpus callosum. The corpus callosum is the thick bundle of nerve fibres connecting the brain’s two hemispheres, and its absence or malformation is the structural hallmark of the syndrome. Since the original description, the recognised phenotype has expanded to include other autonomic disturbances such as hypertension or hypotension, altered consciousness and metabolic derangement. Of the approximately 60 cases reported in the literature, about half had no evidence of callosal dysgenesis at all; these are considered a variant of the syndrome, sometimes called episodic spontaneous hypothermia, and they tend to affect older patients.

Understanding why such a syndrome can exist requires understanding how tightly the human body normally controls its temperature. The evolution of mammals from aquatic to terrestrial life posed a serious thermoregulatory challenge, because land temperatures vary far more than water temperatures. That pressure drove a transition from poikilothermy, in which body temperature drifts with the environment, to homeothermy, the ability to hold internal temperature within a narrow set range. Holding a high, stable temperature maximises enzymatic activity, speeds neural processing and improves healing. Endothermy, the generation of internal heat, gave early mammals a survival edge over ectothermic dinosaurs, which depended on external heat sources, were inactive at night, were more vulnerable to seasonal change and were in some cases restricted to particular latitudes.

In humans, the hypothalamus acts as the thermostat. The pre-optic area of the anterior hypothalamus is chiefly responsible for temperature control, integrating thermal signals arriving from skin and visceral thermoreceptors with direct measurements of hypothalamic temperature. Within this region, distinct populations of neurons perform complementary roles. Warm-sensing neurons increase their activity in response to heat and receive excitatory input from peripheral warm receptors; when they fire, they trigger heat-loss mechanisms such as sweating and peripheral vasodilation. Cold-sensing neurons make up less than 5 percent of the pre-optic population and are normally held in check by tonic inhibition from warm-sensing neurons, balanced against tonic excitation from temperature-insensitive neurons. When that inhibition is lifted, cold-defence mechanisms activate: shivering and non-shivering thermogenesis, peripheral vasoconstriction, activation of brown fat through sympathetic excitation, hypothalamic-pituitary stimulation of thyroxine production to raise basal metabolic rate, and even behavioural responses like huddling. Infection complicates this picture because endogenous pyrogens suppress warm-sensing neurons, raising the set point and producing fever.

Hypothermia itself is defined as a core temperature below 35 degrees Celsius and is graded as mild, between 32 and 35 degrees, moderate, between 28 and 32 degrees, or severe, below 28 degrees. The physiological consequences scale with severity. At the cellular level, cold drives water crystallisation, membrane disruption and protein changes, while secondary ischaemic injury follows vasoconstriction, endothelial damage and thrombosis. Mild hypothermia typically produces a catecholamine surge with tachycardia and hypertension, which may explain the striking blood pressure of 207/176 mmHg in the case described here. As temperature falls further, cardiovascular function degrades into progressive bradycardia and hypotension. Cerebral metabolic rate drops by roughly 6 percent for every 1-degree Celsius decline, producing confusion, behavioural change, ataxia and progressive obtundation. Respiratory drive is depressed, causing respiratory acidosis, while cold diuresis, impaired renal tubular function and occasional shivering-induced rhabdomyolysis disturb electrolytes, a mechanism relevant to the patient’s recurrent hyponatremia. Coagulopathy from platelet and clotting-factor dysfunction is also common.

Because so many conditions can lower body temperature, clinicians must work through a broad differential. Exogenous hypothermia from environmental exposure is compounded by age, intoxication, homelessness, low body fat and immobility. Endogenous causes include sepsis, especially gram-negative bacteraemia, hypovolaemic shock, hypoglycaemia, diabetic ketoacidosis, uremia and hepatic encephalopathy, and endocrinopathies such as hypothyroidism, adrenal failure and hypopituitarism. Drugs matter too: alcohol, opioids, barbiturates and phenothiazines impair thermal perception and cause vasodilation, while at the opposite extreme, neuroleptic malignant syndrome, serotonin syndrome and malignant hyperthermia produce dangerous overheating. Neurological causes form their own category. Peripheral neuropathies rarely cause overt thermoregulatory failure except in rare genetic disorders such as congenital insensitivity to pain with anhidrosis. Spinal cord injuries, particularly high cervical lesions, impair both afferent temperature sensing and efferent responses like shivering and vasomotor control. Focal lesions of the hypothalamus or brainstem, demyelinating disease, autoimmune encephalitis and neurodegenerative conditions such as Parkinson’s disease can all disrupt central temperature control, and episodic hypothermia has been documented in migraine, HIV, Parkinson disease and multiple sclerosis.

The authors argue that a central thermoregulatory disorder should be suspected whenever a patient presents with unexplained hypothermia or hyperthermia, particularly without environmental triggers, infection, endocrinopathy or organ failure. It remains largely a diagnosis of exclusion. Additional neurological signs such as autonomic dysfunction or altered mental status may point toward a central cause, though they can also result directly from the thermal derangement itself. Structural brain imaging is paramount in such cases, precisely because the decisive clue in this patient, callosal dysgenesis with a cavum veli interpositi, was present on an earlier scan but initially overlooked. The case is a striking reminder that radiological findings can hide in plain sight until the clinical pattern demands a second look.

Why the corpus callosum matters in Shapiro syndrome is still unresolved, and dysgenesis alone is clearly insufficient to cause the disorder. Hypothalamic involvement is supported by findings of hypothalamic neuronal loss in some reported cases, although structural imaging is often normal. Shapiro’s original hypothesis of diencephalic epilepsy has not held up: patients rarely show EEG abnormalities and generally do not respond to anticonvulsants. Alternative mechanisms, including neurotransmitter dysfunction and hypermelatoninemia, have been proposed, but the cause-and-effect relationship is difficult to disentangle. Some support for the neurotransmitter hypothesis comes from occasional responses to prophylactic agents such as clonidine, clomipramine and cyproheptadine. The patient in this report briefly received clonidine, but treatment was not continued because of poor response, non-compliance and episodes of hypotension, underscoring how difficult management can be in a condition whose mechanisms remain obscure.

The broader lesson from this case extends beyond one rare syndrome. Virtually any neurological disease affecting cognition, sensation or movement can increase susceptibility to thermal dysregulation, but periodic hypothermia and hyperthermia should prompt consideration of a central disorder once infection and systemic disease have been excluded. Diagnostic precision matters because treatment strategies, both pharmacological and non-pharmacological, differ according to the underlying cause, and misattributing recurrent hypothermia to infection leads to repeated courses of unnecessary antimicrobials, as happened here before the true diagnosis emerged. For a man whose body temperature repeatedly fell to levels that would kill most people within hours, the answer lay not in his blood but in a structure of his brain that no one had looked at carefully enough, until a decade of mysterious admissions finally forced a second reading of the scan.

Subject of Research: Shapiro syndrome, a rare disorder of central thermoregulation associated with agenesis of the corpus callosum

Article Title: Recurrent Hypothermia and Autonomic Dysfunction Secondary to Shapiro Syndrome

Article References: Kumar, N., Johnson, J., Watkins, S., & Mulroy, E. (2026). Recurrent Hypothermia and Autonomic Dysfunction Secondary to Shapiro Syndrome. Annals of Clinical and Translational Neurology, 13(8), 1719-1725. https://doi.org/10.1002/acn3.70419

Image Credits: AI Generated

DOI: 10.1002/acn3.70419

Keywords: Shapiro syndrome, hypothermia, corpus callosum, hypothalamus, thermoregulation, autonomic dysfunction, hyperhidrosis, hyponatremia, neurology, case report, episodic spontaneous hypothermia, diencephalon