Effects of an early transfer from incubator to a warming crib in very low birthweight preterm infants

doi:10.21203/rs.3.rs-3005359/v1

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Effects of an early transfer from incubator to a warming crib in very low birthweight preterm infants

https://doi.org/10.21203/rs.3.rs-3005359/v1

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Purpose: Very low birth weight infants are cared for postnatally in the incubator because of adverse consequences of hypothermia. Data on the optimal weight of transfer to a warming crib are rare. The aim of this study was to determine the course of temperature and body weight during a standardized transfer to a warming crib at a set weight.

Methods: Prospective intervention study in very low birthweight infants who were transferred from the incubator to a warming crib at a current weight between 1500g and 1650g.

Results: No infant had to be transferred back to an incubator. Length of hospital stay was equal compared to a historical cohort from the two years directly before the intervention. The intervention group showed an increase in the volume fed orally on the day after transfer to the warming crib, although this did not translate into an earlier discontinuation of gavage feedings. Compared to the historical group, infants in the intervention group could be transferred to an unheated crib at an earlier postmenstrual age and weight.

Conclusions: Early transfer from the incubator to a warming crib between 1500 g and 1650 g is feasible and not associated with adverse short-term events or outcomes.

preterm infant

thermoregulation

incubator

warming crib

length of stay

Eight percent of infants in Germany in 2020 were born prematurely. According to data from the German Institut für Qualitätssicherung [5] 0.66% of all infants were born at a very low birthweight below 1500 g (VLBW). A lack of subcutaneous adipose tissue causes increased energy expenditure to maintain the body temperature especially in VLBW infants. Hypothermia can lead to hypoglycemia, respiratory distress and ultimately tissue hypoxia. Therefore, the primary goal for these infants is to provide thermoneutral care. In an incubator, heat loss due to conduction, convection, radiation, and evaporation are reduced to a minimum. During the hospital stay infants are gradually weaned from incubator conditions to an open crib with warming mattress (warming crib). From there the heat is gradually reduced until the infant tolerates an open unheated crib, which is one of the conditions necessary for discharge.

Clinical practice regarding weight limits at which preterm infants are transferred from the incubator to the warming bed varies widely between different countries and centers. [2, 6, 7, 9–12]. Several studies [1, 6, 7, 10, 12] showed that preterm infants can maintain stable body temperature when removed from the incubator at a body weight as low as 1600g. In three studies, earlier transfer to the warming crib was associated with a shorter hospital stay [1, 9, 12]

The aim of this monocentric prospective study was to determine the course of temperature and body weight during a standardized transfer of 42 VLBW infants from the incubator to a warming crib at a current weight between 1500g and 1650g. Infants were compared to a historical control group that did not differ in in birth weight and gestational age but were transferred to the warming crib at a higher body weight (1710g ± 126). Furthermore, feeding behavior, weight development, and length of hospital stay were compared between the two groups.

This is a prospective intervention study in very low birthweight infants who were transferred from the incubator to a warming crib at a current weight between 1500g and 1650g. A general change in management with a tendency to lower weight at change from incubator to warming crib has been seen. To evaluate safety of this we conducted a study with standardized weight at transfer.

Eligibility

Infants born at the University Hospital Essen between 12/2012 and 09/2014 with a birthweight < 1500 g regardless of gestational age (GA) were eligible for the study when they reached a current weight between 1500 and 1650g. Patient characteristics are shown at Table 1.

Table 1

Patient characteristics of intervention (IV) and historical control (HC) group
	IV n = 42	HC n = 42	p-value
male, n (%)	23 (54.7%)	21 (50.0%)
birth weight [g]	1008 ± 275	1102 ± 294	0.252
birth weight [g]	[530–1450]	[460–1540]	0.252
PMA at birth	28.2 ± 2.3	28.6 ± 2.1	0.498
PMA at birth	]23.9–32.3]	]23.3–32.1]	0.498
weight [g] at transfer	1558 ± 46	1710 ± 126	< 0.001
weight [g] at transfer	[1490–1650]	[1540–1990]	< 0.001
PMA at transfer	33.1 ± 1	33.9 ± 2	0.005
PMA at transfer	[30.7–36.1]	[31.6–39.4]	0.005
Notes. Data are presented as mean ± standard deviation [range], if not indicated otherwise.
g = gramm, PMA = postmenstrual age.

The infant had to be clinically stable, not requiring observation in the incubator. Exclusion criteria were invasive mechanical ventilation or noninvasive respiratory support like binasal continuous positive airway pressure (CPAP) with an additional oxygen requirement of > 0.25, failure to regain birth weight at the time of screening, ongoing phototherapy or indwelling central venous catheter /umbilical catheter.

Termination criteria

Inability to maintain body temperature above 36.5°C, was an indication to transfer back to the incubator, as was clinical instability, e.g., increased episodes of apnea and bradycardia, clinical or laboratory signs of infection or need for phototherapy according to the standard of care at our center.

Patient recruitment

Parents of VLBW infants were approached when the infant reached 1400 g of body weight, and written informed consent was obtained (Table 1).

Outcomes

The primary outcome was successful transfer to a warming bed without hypothermia during the first 72 hours following transfer in the intervention group (IV group).

Secondary outcomes were length of hospital stay, the PMA at transfer to a normal bed (± 2 days), at discharge (± 2 days), and when reaching full oral feedings as well as body weight at several time points (before and after transfer to the warming bed, at a postmenstrual age (PMA) of 36.0 weeks (± 2 days), at transfer to a normal bed, at the time of discharge (± 2 days), at term equivalent age (± 2 days) (Table 2). If infants were discharged before term equivalent age, data were collected at readmission, which was routinely scheduled for vaccination and MRI at term equivalent age. Additional secondary outcomes in the IV group were stability of vital signs within the first 72 hours after transfer and amount of oral feeding.

Table 2

results of intervention (IV) and historical control (HC) group
		IV n = 42 mean (95% CI)	HC n = 42 mean (95% CI)
Weight gain	48h before (g/kg/d)	24 ± 17² (18–29)	18 ± 11¹¹ (14–22)
	48h after (g/kg/d)	20 ± 16⁹ (15–26)	16 ± 14¹⁰ (11–21)
end caffeine medication	DOL	51 ± 28¹ (42–59)	48 ± 28² (38–57)
	PMA weeks	35.6 ± 3¹	35.0 ± 3²
unheated crib	PMA weeks	35.5 ± 1³ (35.0–35.9)	36.3 ± 2⁴ (35.6–36.9)
	weight (g)	2057 ± 211³ (1988–2124)	2233 ± 251¹ (2153–2313)
weight	PMA 36.0 (g)	2130 ± 293⁵ (2025–2236)	2189 ± 251⁶ (2105–2272)
	PMA 40.0 (g)	3250 ± 518⁶ (3076–3421)	3133 ± 452⁷ (2980–3286)
	discharge (g)	2768 ± 604¹ (2575–2961)	2747 ± 740¹ (2511–2983)
length of stay	days	73 ± 33⁸ (63–84)	71 ± 36 (60–82)
end of gavage feeding	PMA in weeks	35.5 ± 2⁶ (34.7–36.2)	34.7 ± 4 (33.4–35.9)
Notes. Data are presented as mean ± standard deviation (95% confidence interval).
IV mean = intervention group mean, HC mean = historical group, DOL = day of life, PMA = postmentrual age, g = gramm; 95% CI = 95% confidence interval; ¹ n = 40, ² n = 35, ³ n = 39, ⁴ n = 41, ⁵ n = 32, ⁶ n = 37, ⁷ n = 36; ⁸ n = 41, ⁹ n = 38, ¹⁰ n = 29, ¹¹ n = 31

Intervention

After reaching a weight above 1500 g, the infant was moved to the warming crib on the same day. The observation period for the primary outcome covered the period 48 h before to 72 h after transfer. Weaning from incubator (Isolette 8000, Draeger, Germany) heat was not performed in the 48 hours before the transfer. Infants were transferred to a warming crib (Babytherm 8000, Draeger, Germany; Lifetherm, Loewenstein medical, Germany) set at 37.0°C on a gel mattress with a canopy. All infants were dressed in a bodysuit, a sweater, a romper and a wool cap and socks and covered with two towels. The standard room temperature was 24°C with a humidity of 45%. Skin temperature was continuously measured via a sternal and axillary probe (target temperature > 36.0°C), rectal temperature was measured six times daily according to the clinical routine in our NICU (target temperature: > 36.5°C). When the skin temperature was below the target, a rectal measurement was performed. When a rectal temperature < 36.5°C was confirmed, the mattress temperature in the warming crib was increased by 0.5°C up to a maximum of 38.0°C. When the skin temperature increased to > 36.5°C after this intervention, the warming crib was kept at the elevated temperature for 24 hours. In case the temperature was still < 36.5°C one hour after elevation or if maximum temperature was reached, the infant was transferred back to the incubator. Kangaroo care was not limited by study participation. The time span of kangaroo care was excluded from continuous temperature analyses.

Monitoring

Vital signs were recorded using TrendFaceSolo 1.2-0 software (ixellence GmbH, Wildau, Germany) from 48 hours before to 72 hours after transfer on a laptop and exported as Microsoft Office Excel (Microsoft Corporation, Redmond, USA) spreadsheets. Body weight was measured daily before feeding from 48 hours before to 72 hours after transfer. The volume of feeding received via nasogastric tube or orally was documented daily.

Data collection for the historical cohort

In the historical comparison group (HC group) data of 42 VLBW - preterm infants were evaluated retrospectively. These were born between 12/2010 and 10/2011 in the UK Essen and were transferred to the warming crib with a weight of 1700g or more (Table 1).

In HC group, the weight was evaluated at birth, at time of transfer from incubator to warming crib, at a PMA of 36.0, at term equivalent age (± two days), and at the time when the infant was transferred from to an unheated crib. Postmenstrual age was noted at birth, at transfer to the warming crib, at transfer to the unheated crib and at discharge.

Ethical approval

An ethics approval was obtained from the ethics committee of the Medical Faculty of the University of Duisburg-Essen (12-5087-BO).

Statistics

Sample size calculation

Due to lack of reliable evidence from the literature on the target outcomes between early and late transfer and very little concerns regarding the danger level of the intervention, the study was conducted as a pragmatic pilot trial. Thus, all eligible infants born between 12/2012 and 09/2014 whose parents had signed informed consent were assigned to the intervention. From admissions in previous years, we extrapolated that 60 eligible infants would be born during the study period, of which we aimed to include 42 (70 %).

Statistical analyses

The t-test for normally distributed and chi-square test were used to compare continuous and non-continuous data, respectively. The significance level was set at p = 0.05. Since this is a prospective study with a HC group, the 95% confidence intervals (95% CI interval) were also given for better interpretation.

Software

Statistical analysis was performed using Microsoft® Excel® for MAC 2011 and IBM® SPSS Statistics Version 24.

During the study period, 117 infants below 1500 g were born at our center, of which 42 were recruited for the intervention (Figure 1). PMA at birth and birthweight did not differ between the IV and the HC group (Table 1). The mean weight at transfer to the warming crib was 1558 ± 46g in the IV and 1710 ± 126g in the HC group.

Primary outcome IV group:

In the IV group, one infant showed hypothermia (rectal temperature 36.3°C), which was measured as part of routine care. Consequently, the temperature of the warming crib was raised to 38.0 °C without need for a transfer back to the incubator.

Secondary outcomes IV group:

The volume of oral feeding significantly increased on the day after transfer (24 ± 40 ml/kg/d before vs. 40 ± 48 ml/kg/d after transfer; p = 0.003) while the volume via gavage feeding significantly decreased from 126 ± 41 ml/kg/d to 112 ± 44 ml/kg/d (p = 0.008). The total volume of enteral feeding thus remained stable (p = 0.765). We observed no significant differences for daily weight gain before and after the transfer (Table 2).

Secondary outcomes in comparison between the IV and HC:

The mean body weight at the time of transfer to an unheated crib, was significantly lower in the IV group (2057 ± 211 g vs 2233 ± 251 g, p = 0.001). The mean PMA, at this time point was also significantly lower in the IV group than in the HC group (35.3 ± 1 weeks vs. 36.2 ± 2 weeks, p=0.024) (Table 2).

We observed no significant differences between the two groups for body weight at a PMA of 36.0 weeks, at a PMA of 40.0 weeks and at discharge, discontinuation of caffeine medication, discontinuation of gavage feedings, PMA at discharge and length of hospital stay (Table 2).

Protocol violations

In the IV group 20 patients had a protocol violation because body weight was not measured daily during the test phase. In HC group, the children were weighed only every two days according to the ward routine. Thus, in eight cases weight was not available exactly on the transfer. Even though the mean weight at transfer in the HC group was significantly higher than in the IV group (1558g ± 46 IV group vs.1710g ± 126 HC group), 15 children had weights overlapping the study group between 1500 and 1650g.

The optimal timepoint of moving a preterm infant from the incubator is a frequent subject of debate. Clinical practice regarding the transfer highly depends on the individual judgment of the attending nurses and physicians. Typically, weight limits between 1500g and 1800g have been studied, because at this weight the amount of subcutaneous adipose tissue is assumed to be sufficient to maintain the body temperature. One infant showed hypothermia, but a transfer back to the incubator was not necessary. The volume of oral feeding increased on the day after transfer. We saw comparable weight development of both groups at 36.0 PMA, 40.0 PMA and at discharge.

Due to the different methodologies, the comparability of the studies is limited. Studies showed considerable variation regarding type of crib (with or without warming mattress or radiant heat), clothing, environmental conditions used (ambient temperatures ranged between 22 and 26°C) [1, 2, 7, 9, 10, 12]. In our study, the room temperature was in the middle of the range at 24°C. Weaning from respiratory support also varied in previous studies from any respiratory support to CPAP and may occur significantly later than at a current weight of 1500g [1, 7, 10, 12]. This is why we included 12 infants with non-invasive respiratory support and a FiO2 < 0.25 in our study. The method of temperature measurement also differed between studies. The majority used intermittent axillary measurements.The timing of measuring also varied, between initially hourly [1] or every three hours [12] and varied over time. Continuous skin temperature monitoring was not used by any of the studies.

Hypothermia and additional heat requirement

In our study, no infant in the study group had to be transferred back to the incubator due to hypothermia. Infants were transferred to the warming crib with standardized clothing and blankets. This method is used in the majority of NICUs in Germany. Previous studies transferred to an unheated crib, where radiant heat could be applied in the event of hypothermia [7, 10, 12]. Although some studies showed the safety of this method [9–12], the study by New et al. showed higher rates of hypothermia compared to ours [7].

The PMA at which additional heat by mattress was no longer necessary was significantly lower in the IV group than in HC group. This is in concurrence with the study by Barone et al. who showed a reduced total duration of external heat requirement [1].

Length of hospital stay

Some previous studies demonstrated a reduction of the length of hospital stay [1, 9, 12]. In concurrence with the study by New et al. our study could not confirm this [7]. PMA at discharge did not differ significantly between the IV and HC group. These findings are confirmed by West et al. [11], who compared a transfer weight of 1600g and 1500 g and achieved a comparable PMA at discharge to our IV group (38.3°C (West) vs 38.4°C (IV) weeks). This may be explained by the fact, that reasons other than temperature stability also influence length of hospital stay like feeding behavior, resolution of apnea of prematurity or social factors. As an indication of this, our study shows a lack of influence of the timing of transfer to the warming crib on the time to full oral feeds.

Weight development

Dollberg et al. found an increased energy demand due to the transfer from the incubator [3], therefore the weight development before and after transfer is an important safety aspect. Berger et al. compared metabolic rates at a transfer weight of 1500 g vs. 1600 g via indirect calorimetry. They showed no significant differences in energy expenditure (2.9 ± 6.8 versus 1.1 ± 4.8 kcal/kg/d, p = 0.7) [2]. Influence of transfer on weight gain was not examined by other studies.

Our study demonstrated no significant difference in weight gain in the 48 hours after transfer when comparing the IV and the HC group. Although 19% of infants in the IV group (4/42) vs only 3.8% of infants the HC group (1/42) did not gain any weight in the 48 hours after transfer to the warming crib, there was no significant difference in weight gain when comparing the periods 48 hours before and after transfer to the warming crib in the IV group. In contrast, Barone et al. showed that infants transferred from incubator to warming crib at 1700 g compared to 1600g gained significantly more weight (17.5 ± 4.8 vs. 11.1 ± 7.3 g/kg/d, p = <0.001) [1]. Both groups in this study achieved less weight gain both before and after transfer compared to our study (24 ± 17 g/kg/d before, 20 ± 16 g/kg/d after).

Weight at a PMA of 36.0 weeks (± 2 days), at discharge (± 2 days) and at term equivalent age (PMA 40.0 weeks ± 2 days) did not differ significantly between IV and HC groups.

In the study of West et al. [11] infants with transfer weights of 1600 g and comparable PMA at discharge had a lower weight at that time point compared to our IV group (West: 2320 ± 336 g vs. IV: 2768 ± 604 g). This study practiced transfer from an incubator to an unheated crib. The additional heat provided by the warming crib in our study may have resulted in a higher weight gain until discharge due to lower energy consumption. However, better weight gain may have been achieved even before transferring due to different nutritional management, as the pre-transfer weight gain in the 1600g group in the study from West et al. (15.9 g/kg/d) compared with the IV group from this study (24 ± 17 g/kg/d) implies. The weight gain in our study is also above the average weight gain of 16 g/kg/d in preterm infants with a current weight of 1000 - 1499 g [8].

Enteral nutrition

Discontinuation of gavage feeding is a second major factor in determining discharge timing for infants. The volume of oral feeds increased significantly the day after transfer compared to before (p = 0.003) with equal total volume. Nursing and parental handling for feeding may be improved by easier access to the infant in a warming crib. However, this effect did not translate into a faster weaning from gavage feeding in the IV group compared to the HC group. Schneiderman et al. showed that there was a negative correlation between increased weight at the time of transfer to the warming crib and the time to full oral feeds. They showed that each 100 g increase in body weight resulted in a prolonged time on gavage feeds of 0.8 days [9]. Maturity of the child thus has more influence than weight. As Griffith et al. has shown, there is a significant negative correlation between duration of gavage feeding and oral feeding success [4].

Limitations

We performed a monocentric study because the results would have been poorly comparable due to structural differences. Due to the low birth rate of children under 1500g, we did not randomize. Because only one study monitor and laptop were available, only one infant at a time could be included for the duration of the intervention phase (24 h before to 72 h after transfer). There was a protocol violation in 20 patients of the IV group, as body weight was not measured daily during the intervention phase. In the HC group, infants were weighed every two days according to the ward routine at that time. This resulted in a missing weight in 8 cases in the HC on the day of transfer to the warming crib. In the IV group one case does not receive a weight at transfer. Although the mean weight at transfer in the HC group was significantly higher than in the IV group, 15 children in the HC group had weights between 1500 and 1650 g at time of transfer, which was within the limits that were intended for the intervention A bias in patient selection could exist for the following reasons: parents had to be proficient in the German language for informed consent, therefore children of parents with migration background were often excluded. If isolation or barrier precautions were required in accordance with hygienic guidelines in case of certain bacterial or viral colonization of the infants, these patients could also not be included.

This study showed that an early transfer from the incubator to a warming crib between 1500 g and 1650 g is feasible and not associated with adverse short-term events or outcomes. No infant in the IV group had to be transferred back to an incubator. Length of hospital stay was equal compared to a historical cohort from the two years directly before the intervention. The IV group showed an increase in the volume fed orally on the day after transfer to the warming crib, although this did not translate into an earlier discontinuation of gavage feedings. Compared to the HC group, infants in the IV group could be transferred to an unheated crib at an earlier PMA and weight.

DOL day of life

GA gestational age

HC group historical group

IV group intervention group

PMA post menstrual age

VLBW very low birth weight

The authors declare no conflict of interest.

Ethics statement

The studies involving human participants were reviewed and approved by Ethics Committee of the Medical Faculty of the University of Duisburg-Essen. Written informed consent from

the participants’ legal guardian was obtained in accordance with the national legislation and the institutional requirements.

Author contributions

SG conceptualized the study, collected and analyzed the data, drafted the initial manuscript, and revised the manuscript. AS collected and interpreted data and participated in the drafting of the initial manuscript. AKD and MS helped to conceptualize analyses and interpret data. NB and UF-M critically reviewed and edited the manuscript. All authors critically revised the manuscript for important intellectual content, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

Funding

The study received no funding.

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No competing interests reported.

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Effects of an early transfer from incubator to a warming crib in very low birthweight preterm infants

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