Hypothermia in Very Low Birth Weight Infants: Distribution, Risk Factors and Outcomes

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Journal of Perinatology (2011) 31, S49–S56 r 2011 Nature America, Inc. All rights reserved. 0743-8346/11 www.nature.com/jp ORIGINAL ARTICLE Hypothermia in very low birth weight infants: distribution, risk factors and outcomes

SS Miller1, HC Lee2 and JB Gould1 1Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA and 2Department of Pediatrics, Division of Neonatology, University of California, San Francisco, CA, USA

hypothermia: 32.0 to 35.9 1C (89.6 to 96.61 F); and (3) severe Objective: The objective of this study was to study the epidemiology of hypothermia: below 32 1C (<89.61 F). The purpose of this study neonatal hypothermia in preterm infants using World Health Organization was to assess the validity of the WHO classifications in the context (WHO) temperature criteria. of a contemporary neonatal intensive care setting. Specifically, we Study Design: A population-based cohort of 8782 very low birth weight wanted to (1) determine the distribution of neonatal hypothermia (VLBW) infants born in California neonatal intensive care units in 2006 as defined by WHO in a population-based cohort of VLBW infants; and 2007. Associations between admission hypothermia and maternal and (2) identify the clinical associations and risk factors for these neonatal characteristics and outcomes were determined using logistic classifications; and (3) assess the degree to which neonatal regression. morbidities and mortalities were independently associated with the WHO hypothermia classifications. A better understanding of the risk Result: In all, 56.2% of infants were hypothermic. Low birth weight, factors for and the mortality and morbidities associated with cold cesarean delivery and a low Apgar score were associated with stress, moderate and severe hypothermia in this fragile population hypothermia. Spontaneous labor, prolonged rupture of membranes and is critical to designing appropriate advocacy and neonatal practice antenatal steroid administration were associated with decreased risk of interventions to promote normothermia. hypothermia. Moderate hypothermia was associated with higher risk of intraventricular hemorrhage (IVH). Moderate and severe hypothermic conditions were associated with risk of death.

Conclusion: Hypothermia by WHO criteria is prevalent in VLBW infants Patients and methods and is associated with IVH and mortality. Use of WHO criteria could guide The California Perinatal Quality Care Collaborative (CPQCC) the need for quality improvement projects targeted toward the most collects clinical data in a prospective manner for infants born in vulnerable infants. 127 member hospitals. Membership is offered to any hospital in Journal of Perinatology (2011) 31, S49–S56; doi:10.1038/jp.2010.177 California that provides neonatal intensive care. In the study period from 1 January 2006 to 31 December 2007, greater than 90% of Keywords: prematurity; neonatal intensive care units; risk assessment California’s very low birth weight (VLBW) infants were cared for in CPQCC hospitals, creating a unique data set. This study was approved by the Stanford University Institutional Review Board. Introduction The CPQCC conducts yearly data abstractor trainings at In both developed and developing countries, hypothermia is an locations throughout California. Each record has a variety of range important risk factor for morbidity and mortality in newborns.1–5 and logic checks both at the time of data collection and before data The World Health Organization (WHO) established criteria for closeout, and records with excessive missing data are audited. assessing hypothermia and published a guidebook on the thermal During the study period, there were 11 664 VLBW infants born protection of newborns in 1997, indicating that this issue is a with birth weight less than 1500 g. Of them, infants with a worldwide problem even for term infants, particularly in developing gestational age (GA) less than 23 weeks (n ¼ 492) or unknown nations.6 WHO classifications of hypothermia are (1) cold stress or GA (n ¼ 13) or born with a birth weight less than 400 g (n ¼ 37) mild hypothermia: 36.0 to 36.4 1C (96.8 to 97.51 F); (2) moderate were excluded. Patients born at non-CPQCC hospitals and subsequently transferred to a CPQCC member hospital were Correspondence: Dr SS Miller, Department of Pediatrics, Division of Neonatal and excluded (n ¼ 1522). Infants with neurological or gastrointestinal Developmental Medicine, Stanford University, 750 Welch Road, Suite 315, Palo Alto, CA 94304, USA. congenital anomalies such as anencephaly, meningomyelocele, E-mail: [email protected] encephalocele, gastroschisis or omphalocele (n ¼ 34) were Hypothermia in very low birth weight infants SS Miller et al S50 excluded because of the risk for increased evaporative losses. Also culture-positive bacterial sepsis, severe intraventricular hemorrhage excluded were infants who had no temperature recorded in the first (IVH grade 3 or 4 determined by any modality used to image the hour (n ¼ 482) or who died in the delivery room and had no brain on or before day 28 of life) and ultimate disposition temperature recorded (n ¼ 302). There were 8782 infants in the (discharge home or death). Necrotizing enterocolitis was defined as final analytical cohort. one or more clinical signs (bilious gastric aspirate or emesis, The first temperature on admission was standardized by the abdominal distention or occult or gross blood in stool with CPQCC guidelines. The infant’s core body temperature was no apparent rectal fissure) and one or more radiographic measured and recorded within the first hour after admission to findings (pneumatosis intestinalis, hepatobiliary gas or the neonatal intensive care unit. The temperature in degrees pneumoperitoneum). ROP stage 3 was defined as the presence of a Centigrade to the nearest tenth of a degree was recorded. If the ridge with extraretinal fibrovascular proliferation and stage 4 was infant’s temperature was measured several times within the first defined as partial retinal detachment. Grade 3 IVH was defined as hour after admission, the first temperature measurement value was intraventricular blood with ventricular dilation and Grade 4 was entered into the database. For centers that measure temperature in defined as intraparenchymal hemorrhage. degrees Fahrenheit, a Fahrenheit-to-Centigrade conversion table Associations between predictor variables and hypothermia was provided. Rectal temperature was the preferred value; however, were tested in a bivariate analysis, followed by stepwise logistic if unavailable, esophageal, tympanic or axillary temperature was regression. Separate models were constructed for combined severe recorded. and moderate, mild and severe hypothermia. We then studied the The admission temperature and outcomes described below were potential contribution of hypothermia to neonatal outcomes. recorded at the hospital of birth. If an infant was subsequently Separate models were constructed for neonatal outcomes in which transferred within the first 28 days after birth, the outcomes that severe, moderate or mild hypothermia was the independent occurred at the transfer hospital were recorded and included in our variable. Relevant factors were entered into forward stepwise analyses. If an infant was transported after 28 days, the majority of multivariable logistic regression models with an entry criteria whom would have been transported for convalescent care, any a-level of 0.05 to give odds ratios and 95% confidence limits for outcomes that occurred during the period at this second hospital those variables associated with hypothermia. Statistical analyses were not recorded, with the exception of the outcome of death, were computed using SAS 9.1 (SAS, Cary, NC, USA). which was reported regardless of transport status. If an infant transported after 28 days developed morbidity that was serious enough to warrant readmission, these outcomes were recorded and Results included in the analysis. The cohort of 8782 infants had a mean (±s.d.) birth weight and A cross-sectional data analysis was conducted to examine the GA of 1072±278 g and 28.4±2.8 weeks, respectively. The mean distribution, predictors and outcomes associated with neonatal admission temperature was 36.3 1C (s.d. 0.8), with a range of 26.1 hypothermia. Temperature criteria were based on the WHO to 39.6 1C; 30.5% were mildly hypothermic, 25.6% were moderately classifications of hypothermia and are defined as follows: (1) cold hypothermic, 0.1% were severely hypothermic, 43.0% were stress or mild hypothermia, 36.0 to 36.4 1C (96.8 to 97.51 F); normothermic and 0.8% were noted to have a temperature (2) moderate hypothermia, 32.0 to 35.9 1C (89.6 to 96.61 F); and X38.0 1C (Figure 1). (3) severe hypothermia, below 32 1C (<89.61 F). Temperatures The incidence of hypothermia was greatest and the mean X38.0 1C were considered as fever. Because of the low number of admission temperature lowest with decreasing GA and birth weight. In infants with temperature <32 1C(n ¼ 9), severe and moderate all, 78.7% of infants born at 23 weeks and 82.8% of infants with a hypothermia were combined into one category. Predictor variables birth weight of 400 to 499 g were hypothermic. As GA and birth weight were as follows: maternal and intrapartum variables (age, race/ increased, there was a decrease in the percentage of moderate ethnicity, prenatal care, antenatal steroids, spontaneous labor, hypothermia and an increase in the percentage of cold stress. The multiple births, delivery mode, maternal or uterine infection, mean admission temperature also increased with birth weight and prolonged rupture of membranes (PROM) and hypertension); gestational age, with stabilization occurring after 26 weeks and infant characteristics (gender, birth weight, gestational age) and between 800 and 899 g gestation (Appendix Tables A1 and A2). delivery room variables (Apgar scores, resuscitation including Descriptive characteristics for the total study cohort, with oxygen administration, CPAP, bag-mask ventilation, chest division into normothermic, mild and moderate/severe compressions and epinephrine administration). Low Apgar scores hypothermic infants, are listed in Table 1. were defined as an assigned value <7. Neonatal outcome measures included necrotizing enterocolitis, severe retinopathy of prematurity Risk factors for hypothermia (ROP stage 3 or 4), oxygen dependence at 36-week-corrected On bivariate analysis, black (P ¼ 0.0001) Hispanic (P ¼ 0.0025) gestational age, early (on or before day 3) and late (after day 3) and other/unknown (P ¼ 0.04) races were associated with

Journal of Perinatology Hypothermia in very low birth weight infants SS Miller et al S51

Normal Severe Moderate 32-35.9° * Fever 25 <32° 36.5- ≥38° 37.9°

Percent 15

0 31 31.5 32 32.5 33 33.5 34 34.5 35 35.5 36 36.5 37 37.5 38 38.5 39 39.5 40 Temperature at Admission to NICU (degrees centigrade) * Cold Stress 36.0-36.5°

Figure 1 Distribution of admission temperatures from the delivery room for 8782 very low birth weight infants born in California neonatal intensive care units. hypothermia, as were maternal hypertension, Cesarean section and sepsis, oxygen use at 36-week-corrected gestational age, IVH, death low 1- and 5-min Apgar scores (P<0.0001). Antenatal steroid use and the combined outcome of grades 3 to 4 IVH and death. (P<0.001), PROM (P<0.001), spontaneous labor (P<0.001), Table 3 shows the frequency of these morbidities across WHO multiple births (P ¼ 0.006) and uterine infection (P<0.001) were temperature criteria. Although there were significant bivariate associated with normothermia. There were no associations associations between hypothermia and ROP, late-onset sepsis, found with Asian race, maternal age, gender, prenatal care or oxygen at 36 weeks, IVH and death, many of these relationships maternal infection. Similar risk factors were seen for cold stress were not statistically significant after risk adjustment. After risk (details on request). adjustment, we found no association between mild hypothermia Using forward stepwise logistic regression, models were created and any of the morbidities or death. Moderate hypothermia was for the combined category of moderate/severe hypothermia, associated with higher odds of IVH (odds ratio 1.3, 95% confidence for cold stress and for any hypothermia as compared with limit 1.1 to 1.6) and death (odds ratio 1.5, 95% confidence limit normothermia (Table 2). For the outcome of moderate/severe 1.3 to 1.9). Severe hypothermia, although seen in only nine hypothermia, the most notable effect came from birth weight, with infants, was also associated with higher odds of death (odds ratio increasing odds of hypothermia associated with decreasing birth 5.6, 95% confidence limit 1.1 to 28.1). weight between 400 and 999 g. Cesarean mode of delivery, low 1- and 5-min Apgar scores, maternal hypertension and Black race carried higher odds of moderate/severe hypothermia. Discussion Spontaneous labor, PROM and antenatal steroid administration This study evaluated transitional hypothermia in a population- were associated with lower odds of moderate-to-severe hypothermia, based cohort of VLBW infants born in California neonatal intensive independent of birth weight. care units using the WHO classifications of hypothermia: cold stress Factors associated with the development of cold stress were or mild hypothermia, 36.0 to 36.4 1C (96.8 to 97.5 1F); moderate similar to those of moderate/severe hypothermia. The model for hypothermia, 32.0 to 35.9 1C (89.6 to 96.6 1F); and severe severe/moderate hypothermia showed decreasing odds with hypothermia, below 32 1C (<89.6 1F). We found that cold stress increasing birth weight, whereas the cold stress model had and moderate hypothermia on admission were very common (30.5 statistically stable odds across birth weight categories. and 25.6%, respectively), whereas severe hypothermia was seen in only 0.1% of VLBWs. Both cold stress and moderate/severe Neonatal outcomes hypothermia were associated with various maternal and infant We evaluated the relationship between hypothermia and stage 3 characteristics. Cold stress did not increase the odds of morbidity or or 4 ROP, necrotizing enterocolitis, early-onset sepsis, late-onset death. Moderate hypothermia was associated with increased odds of

Journal of Perinatology Hypothermia in very low birth weight infants SS Miller et al S52

Table 1 Descriptive characteristics and study demographics

Characteristic N % of total cohort Normothermic (%) Cold stress (%) Moderate/severe (%)

Maternal age (in years) <20 837 9.5 8.5 9.6 11.2 20–29 3655 41.7 42.6 40.5 41.5 30–39 3727 42.5 42.7 43.1 41.4 X40 554 6.3 6.2 6.8 5.9

Race Black 1181 13.5 12.1 14.3 14.8 Hispanic White 2537 28.9 29.3 28.9 28.7 Non-Hispanic White 2412 27.5 28.9 27.3 24.8 Asian 948 10.8 10.3 11.2 11.1 Other/unknown 1704 19.4 19.4 18.3 20.5 No prenatal care 375 4.3 4.1 4.4 4.5 Maternal hypertension 2425 28.7 24.6 31.9 32.4 Maternal infection 418 6.0 4.7 5.0 4.9 Uterine infection 505 6.0 7.1 4.9 4.4 Vaginal delivery 2142 24.5 27.2 22.0 22.5 Cesarean section 6603 75.5 72.8 78.0 77.5 Singleton birth 6216 70.8 68.9 72.4 72.2 Multiple birth 2561 29.2 31.1 27.6 27.8

Gender Female 4452 50.7 50.6 49.3 52.3 Male 4327 49.3 49.4 50.7 47.7

Apgar score: 1 min 0–6 4478 51.1 46.5 49.8 59.6 7–10 4289 48.9 53.5 50.2 40.4

Apgar score: 5 min 0–6 1558 17.8 14.3 15.4 26.3 7–10 7208 82.2 85.7 84.6 73.7

Resuscitation 0 (None) 560 6.4 6.7 6.5 5.9

1 (Blow by O2) 1316 15.0 15.7 17.6 10.9 2 (Continuous positive airway pressure) 1034 11.8 13.7 12.2 8.1 3 (Bag-mask ventilation) 1370 15.6 15.4 17.0 14.4 4 (Endotracheal intubation) 3901 44.4 44.9 41.6 48.1 5 (Chest compressions) 293 3.3 2.5 3.1 4.9 6 (Epinephrine given) 308 3.5 2.1 2.0 7.7 Antenatal steroids 6966 80.1 82.6 79.9 76.3 Spontaneous labor 5278 60.5 63.7 57.5 58.2 Prolonged rupture of membranes 1382 16.3 18.6 15.0 13.6

IVH and death, and severe hypothermia was associated with Maintaining infant normothermia has been shown to improve increased odds of death. Severe hypothermia may in fact have a survival and outcomes for decades.7–9 In previous studies, greater impact on morbidity; however, given the small number of hypothermia has been associated with increased neonatal infants with severe hypothermia (n ¼ 9), these associations may morbidity and mortality, such as IVH and death, and to have an not have been detected. increased association with lower GA in premature infants at the

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Table 2 Risk factors for WHO criteria of moderate/severe hypothermia, cold stress and any hypothermia as determined by logistic regression models

Moderate/severe (95% CL) Cold stress (95% CL) Any low temperature (95% CL)

Birth weight (vs 1400–1499) 1000–1099 g NS 1.3 (1.0–1.6) 1.3 (1.0–1.5) 900–999 g 1.6 (1.3–2.0) 1.3 (1.1–1.6) 1.5 (1.2–1.8) 800–899 g 1.7 (1.3–2.1) NS 1.4 (1.1–1.7) 700–799 g 2.2 (1.7–2.8) 1.3 (1.1–1.7) 1.7 (1.4–2.1) 600–699 g 3.8 (2.9–4.9) 1.6 (1.2–2.1) 2.5 (2.0–3.2) 500–599 g 4.2 (3.1–5.9) 1.8 (1.2–2.5) 2.9 (2.1–3.8) 400–499 g 8.0 (4.2–15.3) 2.6 (1.3–5.3) 5.0 (2.7–9.3) Delivery mode (Cesarean vs vaginal) 1.2 (1.0–1.4) 1.3 (1.1–1.5) 1.2 (1.1–1.4) Spontaneous labor 0.8 (0.7–0.9)a 0.9 (0.8–1.0)a 0.8 (0.8–0.9)a Prolonged rupture of membranes 0.7 (0.6–0.9)a 0.8 (0.7–0.9)a 0.8 (0.7–0.9)a Antenatal steroids 0.7 (0.6–0.8)a 0.9 (0.8–1.0)a 0.8 (0.7–0.9)a Maternal hypertension 1.1 (1.0–1.1) NS NS 1 min Apgar (0–6 vs 7–10) 1.1 (1.0–1.3) 1.1 (1.0–1.3) 1.1 (1.0–1.3) 5 min Apgar (0–6 vs 7–10) 1.5 (1.3–1.7) NS 1.3 (1.1–1.4) Resuscitation (none vs any in delivery room) NS 0.8 (0.7–0.9)a 0.8 (0.7–0.9)a Multiple gestation NS 0.8 (0.7–0.9)a 0.9 (0.8–1.0)a

Race Black 1.3 (1.1–1.5) NS 1.2 (1.1–1.4) Asian NS NS 1.2 (1.0–1.4)

Abbreviations: CL, conﬁdence limits; NS, not statistically signiﬁcant; WHO, World Health Organization. aRepresents factors associated with lower risk of hypothermia. All odds ratios listed in the table have P<0.05.

Table 3 Neonatal outcomes evaluated according to WHO criteria for reviews have been carried out to evaluate interventions that may hypothermia using bivariate analyses be valuable in decreasing post-birth heat loss in very preterm 11–13 Morbidity Normal (%) Cold stress (%) Severe/moderate (%) P-value infants, and currently the latest guidelines for newborn (N ¼ 2233)a (N ¼ 2639)a (N ¼ 3740)a resuscitation from the American Academy of Pediatrics emphasize the goal of preventing hypothermia in premature Stage 3 or 4 6.5 6.5 11.2 <0.0001 infants.14 Despite the emphasis placed on maintaining ROP normothermia, no population-based investigation of the NEC 7.3 7.2 8.8 0.11 distribution and predictors of initial temperatures using WHO Sepsis (early) 2.4 2.0 2.3 0.46 criteria in VLBW infants born in contemporary neonatal intensive Sepsis (late) 11.4 10.9 15.0 <0.0002 Oxygen at 36 8.4 6.5 7.0 <0.0001 care units and their relationship to morbidity and mortality has weeks been published. IVH 6.8 7.0 13.0 <0.0001 The WHO divides hypothermia into three major categories: Death 6.7 8.5 17.0 <0.0001 severe (<32 1C), moderate (32.0 to 35.9 1C) and mild/cold stress 6 Death + IVH 11.1 12.3 22.8 <0.0001 (36.0 to 36.4 1C). We used the WHO criteria as it was considered 3–4 to provide more clinically relevant benchmarks than defining Abbreviations: IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; hypothermia as a dichotomous variable or in single-degree ROP, retinopathy of prematurity; WHO, World Health Organization. increments. For example, if one defines hypothermia as a single aInfants excluded if they died and did not have the condition. cutoff point of <36.5 1C, one combines cold-stressed infants who The independent variable is hypothermia. The (%) is the percent of infants in each are not at risk for short-term morbidity or death with moderately subcohort that have the condition. and severely hypothermic infants whose risk for IVH and death is significantly increased. In addition, the WHO categories are used threshold of viability.3,10 Following an initial period of stabilization, worldwide. LBW infants born in the United States are routinely maintained in Our study using WHO categories also suggests that there is a a variety of thermoneutral environments. Several studies and maturational difference between severe/moderate hypothermia and

Journal of Perinatology Hypothermia in very low birth weight infants SS Miller et al S54 cold stress. As an infant matures in size and gestation, the odds of hypothermia was not a significant risk factor, likely representing being severely/moderately cold and at high risk for IVH and death the confounding effect of factors such as birth weight. decreased, whereas the risk for being cold stressed without an A study by Laptook et al.18 in 2007 evaluated admission increased risk for death or short-term morbidity increased. At temperature of LBW infants to determine predictors and associated around 26 weeks of gestation and/or at 900 to 1000 g, the odds for morbidities. The distribution of temperatures was similar to that hypothermia stabilized, indicating that perhaps a critical point in found in our study. Using multivariate analysis, they concluded the ability to thermoregulate had been reached (Appendix Figures that birth weight alone had a relatively small effect on A1 and A2). hypothermia. This was in contrast to our results. Their outcome Maternal factors such as Cesarean delivery and hypertension analyses revealed an association of admission temperature with carried higher odds of moderate/severe hypothermia, whereas death and late-onset sepsis, but not with severe IVH. spontaneous labor, PROM and antenatal steroid administration There were several limitations to our study. The exact timing showed decreased odds of developing moderate/severe hypothermia, that the temperature was obtained within the first hour of independent of birth weight. Cesarean delivery may contribute to admission is unknown. A longer time between birth and first hypothermia as operating rooms are often kept at cooler recorded temperature may result in lower initial temperatures; temperatures for the physician’s comfort. The WHO has however, a study by Loughead et al.19 found no significant recommended that delivery or resuscitation room temperatures be difference in the time passed between delivery and initial set at a minimum of 25 1C (771 F), with a suggested range of 25 to temperature with a range of less than 10 min to greater than 28 1C (77 to 82.4 1F),6 which anecdotally is often not the case. 31 min. The method by which temperature was obtained was also Infant characteristics that were associated with hypothermia most unknown (rectal, axillary or skin), which may lead to differences notably included decreasing birth weight and low Apgar scores. in reported temperatures. Prematurity and LBW are associated with a large surface area-to- Insights gained from this study have the potential to facilitate body mass ratio, decreased subcutaneous fat, greater body water quality improvement efforts both in California and nationwide. content, immature skin leading to increased evaporative water and This study revealed that using the WHO criteria for hypothermia is heat losses, a poorly developed metabolic mechanism for a valuable method for evaluating infants at the greatest risk for responding to thermal stress and delayed development of skin developing low temperatures and for those at greatest risk for poor blood-flow control reducing the ability to maintain heat by outcomes because of hypothermia. In our California cohort, 25.8% vasoconstriction,15–17 all of which may lead to hypothermia. Low of VLBW infants were at increased risk of mortality because of Apgar scores may be associated with increased resuscitative efforts moderate/severe hypothermia following birth. A review of the rates or increased inherent illness in the infant at birth, of which of moderate/severe hypothermia by the CPQCC center shows a wide hypothermia may be a marker or result. variation in the percentage of VLBW infants found to be Cold stress was also associated with LBW, Cesarean hypothermic, ranging from less than 5% to greater than 70% section and a low 1-min Apgar score. Decreased odds of (details available on request). We suspect that this high variability hypothermia were found for spontaneous labor, PROM and may be widespread in developed countries, making reduction in the antenatal steroid use, as well as for no resuscitative efforts in the percentage of infants with moderate-to-severe hypothermia a delivery room and multiple gestation. We speculate that high priority for quality improvement initiatives. A variety of the reason for no resuscitative effort being associated with interventions, such as polyethylene bags, heating mattresses or normothermia may be due to the likelihood that a lack of increasing the delivery room temperature, have been shown to resuscitation may indicate that the infant was relatively healthier reduce hypothermia in premature infants, both in randomized and therefore was able to better maintain core body temperature. trials and in quality improvement projects.20–22 Because of its In addition, in the midst of resuscitation, measures to keep infants relationship to IVH and neonatal mortality, we believe that change warm may be difficult to maintain or neglected altogether. in the percentage of moderate/severe hypothermia as defined by Although cold stress was not found to be associated with short-term WHO may serve as an important indicator of the effectiveness of morbidities, the long-term consequences of mild hypothermia one’s interventions. Future studies could then focus on comparison remain unknown. data before and after any recommended practice changes are Neonatal outcomes were evaluated and support previous studies implemented to evaluate for effectiveness in improving neonatal that showed an association between hypothermia and IVH and hypothermia and outcomes. death.1–3 Our study revealed higher odds of IVH with moderate hypothermia and higher odds of death with both severe and moderate hypothermia. Despite the association of ROP, oxygen use at 36-week-corrected age and late sepsis with hypothermia on Conflict of interest bivariate analyses, in risk adjusted logistic regression models, The authors declare no conflict of interest.

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Acknowledgments 10 Dincsoy MY, Siddiq F, Kim YM. Intracranial hemorrhage in hypothermic low-birth- weight neonates. Child’s Nerv Syst. 1990; 6: 245–248; discussion 248. This project was supported in part by NIH/NCRR/OD UCSF-CTSI Grant Number 11 Watkinson M. Temperature control of premature infants in the delivery room. Clin KL2 RR024130. Its contents are solely the responsibility of the authors and do not Perinatol 2006; 33: 43–53, vi. necessarily represent the official views of the NIH. 12 Vohra S, Roberts RS, Zhang B, Janes M, Schmidt B. Heat Loss Prevention (HeLP) in the delivery room: a randomized controlled trial of polyethylene occlusive skin wrapping in very preterm infants. JPediatr 2004; 145: 750–753. References 13 Sedin G. To avoid heat loss in very preterm infants. J Pediatr 2004; 145: 720–722. 14 Pediatrics AAP. Textbook of Neonatal Resuscitation. 2006: 8–6. 1 Mathur NB, Krishnamurthy S, Mishra TK. Evaluation of WHO classification of 15 Aylott M. The neonatal energy triangle. Part2: thermoregulatory and respiratory hypothermia in sick extramural neonates as predictor of fatality. J Trop Pediatr 2005; adaption. Paediatr Nurs 2006; 18: 38–42. 51: 341–345. 16 Hammarlund K, Sedin G. Transepidermal water loss in newborn infants. VI. Heat 2 Daga AS, Daga SR, Patole SK. Determinants of death among admissions to intensive exchange with the environment in relation to gestational age. Acta Paediatr Scand care unit for newborns. J Trop Pediatr 1991; 37: 53–56. 1982; 71: 191–196. 3 Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: 17 Costarino A, Baumgart S. Modern fluid and electrolyte management of the critically ill outcomes to discharge from hospital for infants born at the threshold of viability. premature infant. Pediatr Clin North Am 1986; 33: 153–178. Pediatrics 2000; 106: 659–671. 18 Laptook AR, Salhab W, Bhaskar B. Admission temperature of low birth weight infants: 4 Yu VY, Joseph R, Bajuk B, Orgill A, Astbury J. Perinatal risk factors for necrotizing predictors and associated morbidities. Pediatrics 2007; 119: e643–e649. enterocolitis. Arch Dis Child 1984; 59: 430–434. 19 Loughead MK, Loughead JL, Reinhart MJ. Incidence and physiologic 5 Szymonowicz W, Yu VY, Wilson FE. Antecedents of periventricular haemorrhage in characteristics of hypothermia in the very low birth weight infant. Pediatr Nurs 1997; infants weighing 1250 g or less at birth. Arch Dis Child 1984; 59: 13–17. 23: 11–15. 6 Organization WH. Thermal Protection of the Newborn: A Practical Guide. Geneva: 20 Bhatt DR, White R, Martin G, Van Marter LJ, Finer N, Goldsmith JP et al. Transitional Switzerland, 1993. hypothermia in preterm newborns. J Perinatol 2007; 27(Suppl 2): S45–S47. 7 Silverman WA, Balnc WA. The effect of humidity on survival of newly born premature 21 McCall EM, Alderdice FA, Halliday HL, Jenkins JG, Vohra S. Interventions to prevent infants. Pediatrics 1957; 20: 477–486. hypothermia at birth in preterm and/or low birth weight infants. Cochrane Database 8 Silverman WA, Fertig JW, Berger AP. The influence of the thermal environment upon Syst Rev 2008; (2): CD004210. the survival of newly born premature infants. Pediatrics 1958; 22: 876–886. 22 Lee HC, Ho QT, Rhine WD. A quality improvement project to improve 9 Buetow KC, Klein SW. Effect of maintenance of ‘normal’ skin temperature on survival admission temperatures in very low birth weight infants. J Perinatol 2008; 28: of infants of low birth weight. Pediatrics 1964; 34: 163–170. 754–758.

Appendix Table A1 Admission temperature for infants <32 weeks gestational age with Table A2 Admission temperature for infants <32 weeks gestational age with birth weight <1500 g by gestational age birth weight <1500 g by birth weight

Gestational N Mean BW Mean temp Range Birth weight (g) N Mean GA (s.d.) Mean temp (s.d.) Range age (weeks) (s.d.) (s.d.) 400–499 87 24.7 (1.7) 35.4 (1.3) 32.0–39.1 23 263 606 (90) 35.3 (1.3) 31.0–38.4 500–599 343 24.5 (1.6) 35.6 (1.1) 31.7–38.3 24 572 672 (103 35.8 (1.2) 26.1–39.0 600–699 622 25.0 (1.8) 35.8 (1.1) 30.5–39.0 25 732 762 (128) 36.1 (0.9) 32.8–39.5 700–799 793 25.7 (1.8) 36.1 (1.0) 26.1–39.5 26 820 876 (160) 36.3 (0.8) 32.2–39.2 800–899 800 26.6 (1.8) 36.3 (0.7) 33.1–38.5 27 993 978 (180) 36.3 (0.7) 32.3–39.1 900–999 792 27.4 (1.8) 36.2 (0.7) 32.9–39.0 28 1120 1097 (204) 36.4 (0.8) 27.0–39.2 1000–1099 905 28.2 (1.9) 36.4 (0.8) 26.7–39.2 29 1311 1195 (198) 36.4 (0.7) 26.1–38.6 1100–1199 973 29.1 (1.9) 36.4 (0.7) 33.2–38.6 30 1022 1245 (185) 36.4 (0.7) 33.4–39.1 1200–1299 1076 29.8 (1.9) 36.4 (0.7) 27.0–39.1 31 413 1295 (169) 36.3 (0.6) 33.0–37.9 1300–1399 1159 30.4 (1.9) 36.4 (0.6) 33.5–38.4 32 235 1310 (149) 36.3 (0.6) 34.8–38.0 1400–1499 1232 31.1 (1.9) 36.4 (0.7) 26.1–39.6

Abbreviation: BW, birth weight. Abbreviation: GA, gestational age.

Journal of Perinatology Hypothermia in very low birth weight infants SS Miller et al S56

90.0 Moderate/Severe 80.0 Cold Stress Total Cold 70.0

60.0

50.0

40.0 Percentage

30.0

20.0

10.0

0.0 23 24 25 26 27 28 29 30 31 32 Gestational Age (weeks) Figure A1 Percentage of hypothermia by gestational age. The total number of cold infants is divided into WHO temperature categories of moderate/severe hypothermia and cold stress.

Percentage of Hypothermia by Birth Weight 90 Moderate/Severe 80 Cold stress Total cold 70

40 Percentage

Birth weight (grams) Figure A2 Percentage of hypothermia by birth weight. The total number of cold infants is divided into WHO temperature categories of moderate/severe hypothermia and cold stress.

Journal of Perinatology