Neonatal infants lose heat immediately after birth through mechanisms such as radiation, convection, evaporation, and conduction [1,2]. Preterm infants are more vulnerable to reduced temperatures because of their higher ratio of skin surface area to weight, highly permeable skin, decreased subcutaneous fat, and less-developed stores of brown fat [3,4]. The association between admission temperature and neonatal mortality and morbidity in preterm infants has been studied using data from multiple centers [5-9]. However, despite large sample sizes, such studies are often biased when investigating outcomes because of differences in neonatal care and temperature management among centers. Moreover, it is unclear whether a low temperature at admission is only associated with short-term outcomes, or if it influences long-term outcomes. This study aimed to investigate whether low admission temperatures in extremely low birth weight (ELBW) infants are associated with short- and long-term outcomes.

This study investigated the association between short- and long-term outcomes and admission hypothermia in ELBW infants at a single center. ELBW infants with moderate hypothermia at admission were born at a younger gestational age with lower body weights and higher vaginal delivery rates. The incidence of hsPDA and the rate of BSID-II MDI <70 were associated with moderate hypothermia, indicating that hypothermia at admission may affect both short- and long-term outcomes in ELBW infants.

Previous multicenter studies have shown an association between admission temperature and mortality in preterm infants [5-8]. In addition, the Korean Neonatal Network study on very low birth weight infants consistently demonstrated that infants with lower admission temperatures had increased odds of mortality [14]. However, our data did not reveal any differences in mortality rates between the moderate hypothermia and control groups. This may be due to the small sample size and high overall survival. Short-term neonatal morbidities such as BPD, IVH, NEC, retinopathy of prematurity (ROP), and sepsis are associated with a low admission temperature [5,6,8]. In the present study, the incidence of hsPDA was higher in the moderate hypothermia group compared with the control. Other morbidities such as RDS, severe IVH, pulmonary hypertension, BPD, and ROP requiring surgery seemed to be more prevalent in moderately hypothermic infants, but the difference was not statistically significant. Hypothermia may negatively affect the smooth fetal-to-neonatal transition, resulting in increased respiratory distress and persistent pulmonary hypertension [5]. Hypothermia in newborn infants increases oxygen and energy consumption, metabolic acidosis, and hypoglycemia, which may lead to hemodynamic instability [15,16]. Postnatal ductal closure is facilitated by increased alveolar oxygen content [17]. The series of clinical conditions of admission hypothermia leading to hypoxia and hemodynamic instability may have contributed to the increased incidence of hsPDA in hypothermic infants.

To date, a small number of studies have investigated the correlation between admission temperature and long-term neurodevelopmental outcomes. According to a Canadian Neonatal Network study on extremely low-gestational-age neonates, hypothermic infants compared to normothermic infants showed increased odds of death or neurodevelopmental impairment at a corrected age of 18 to 21 months [18]. Another recent study demonstrated that a higher admission temperature was associated with a lower incidence of death and neurodevelopmental impairment at 3 years of age in VLBW infants [19]. In our study, hypothermic ELBW infants showed a higher prevalence of BSIDII MDI scores <70; however, due to follow-up losses and missed BSID-II examinations in relatively well-growing infants, the incidence of neurodevelopmental impairment in our study may not be accurate. The mechanisms underlying the adverse long-term outcomes associated with hypothermia remain unclear. Hypothermia in preterm infants increases neonatal morbidity. Neonatal morbidities, such as IVH, BPD, and NEC, are correlated with long-term neurodevelopmental impairment [20]. Prolonged hospital stays due to such morbidities may correlate with worse neurodevelopmental outcomes. Moreover, the medical or surgical treatment for patent ductus arteriosus is associated with increased odds of neurodevelopmental impairment and low MDI scores [21]. The increased incidence of hsPDA in hypothermic infants may have affected the long-term outcomes in this study.

Previous studies in developed countries have shown that 36% to 53% of preterm infants (<32 to 33 weeks born) show admission hypothermia [8,9]. According to the Korean Neonatal Network study, admission hypothermia occurs in 74.1% of VLBW and in preterm infants less than 33 weeks, which is greater than the rate seen in developed nations [14]. In this study, the proportion of moderate hypothermia was 25.7%, which is higher than the 11.9% to 22.3% reported in other studies [8,9]. Standard thermal care strategies, such as maintaining an adequate delivery room temperature and using plastic bags, radiant warmers, and preheated transport incubators, should be emphasized.

This study showed that ELBW infants with moderate hypothermia had higher vaginal delivery rates. In such cases, admission hypothermia may occur because the delivery is often unplanned. A recent report demonstrated higher survival rates in ELBW infants with cesarean births than in those with vaginal birth [22]. We speculate that admission hypothermia may have affected survival in this study.

This study had several limitations. First, it was a retrospective observational study with a small sample size. Second, the followup rate at the corrected age of 18 to 24 months was low, resulting in an even smaller sample size for assessing long-term outcomes. Third, BSID-II tests were not routinely performed in all patients. Lastly, axillary temperature measured at admission may be lower than rectal temperature, and thus may not fully represent core body temperature [23]. The main strength of this study is that it is the first in Korea to assess long-term neurodevelopmental outcomes associated with admission temperature.

In summary, this study demonstrated that moderate hypothermia was associated with an increased incidence of hsPDA and an increased rate of BSID-II MDI <70. Our study suggests that the effects of moderate hypothermia upon admission may persist after discharge. Therefore, adequate thermoregulation should be reinforced in ELBW infants.