MANUSCRIPT CITATION

Shankaran S, Bell EF, Laptook AR, Saha S, Newman NS, Kazzi SNJ, Barks J, Stoll BJ, Bara R, Gabrio J, Childs K, Das A, Higgins RD, Carlo WA, Sánchez PJ, Carlton DP, Pavageau L, Malcolm W, D’Angio CT, Ohls RK, Poindexter BB, Sokol GM, Van Meurs KP, Colaizy TT, Khmour A, Puopolo KM, Garg M, Walsh M for the Eunice Kennedy Shriver National Institute of Child Health, and Human Development Neonatal Research Network . J Pediatr 2019 ;204:96-102. PMID 30337189

REVIEWED BY

Vikas Chowdhary, MD
Assistant Professor of Pediatrics
Arkansas Children’s Hospital
University of Arkansas for Medical Sciences

Ankita Shukla, MD
Assistant Professor of Pediatrics
Arkansas Children’s Hospital
University of Arkansas for Medical Sciences

TYPE OF INVESTIGATION

Prevention

QUESTION

To determine if (P) moderately preterm infants born between 29-33 weeks gestation, (I) weaned from an incubator to an open crib at 1600 grams (C) compared to 1800 grams (O) decreases their length of hospital stay.

METHODS

• Design: Prospective, randomized, multi-center.
• Allocation: Allocation concealed.
• Blinding:
• Follow-up period: Infants were followed until hospital discharge.
• Setting: 17 neonatal intensive care units in US which are a part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Neonatal research network (NRN)
• Patients: Infants with gestational age between 29-33 weeks and birth weight <1600 grams
  • Inclusion Criteria: (a) Moderately preterm infants 29 0/7 -33 6/7 weeks’ gestational age and with birth weight <1600 grams (b) weight <1540 gms at screening (c) age ³ 48hrs (d) in an incubator
  • Exclusion Criteria: (a) phototherapy for hyperbilirubinemia (b) respiratory support (>2L/minute of oxygen therapy or positive pressure support) (c) treatment for hypotension, multiple episodes of apnea (>5 episodes of hour), a major congenital anomaly, or designation for transfer to a referral hospital while in an incubator.
• Intervention: Random assignment to weaning to crib at 1600 or 1800g.
• Outcomes:
  • Primary outcome: Length of hospital stay from birth to discharge.
  • Secondary outcomes: length of stay between random assignment and discharge; postmenstrual age, growth velocity and growth parameters at 36 weeks’ PMA and at discharge
• Analysis and sample size: The targeted effect size was estimated to be 7 days with a standard deviation of 20 days. Selecting a type 1 error of 0.05 and a power of 90%, the sample size was calculated to be 366. Analysis was based on intention-to-treat
• Patient follow-up: Until discharge

MAIN RESULTS

The reported characteristics of the mothers which included age, ethnicity, gravida status, parity, maternal diabetes, hypertension (during or before pregnancy), antepartum hemorrhage, complete course of antenatal steroids, antibiotic administration during this admission, magnesium sulphate before delivery, Cesarean delivery, prolonged rupture of membranes were similar between the two groups.

Of 1565 infants screened, 885 were eligible, of which 366 were enrolled—187 to the 1600-g and 179 to the 1800-g group. Neonatal characteristics were divided into (a) pre-intervention, which included gestational age, birth weight, small for gestational age, sex, Apgar scores, delivery room resuscitation, growth parameters at birth and age at randomization; and (b) Characteristics at intervention (start of the wean) included the weight, axillary and ambient temperature, and post menstrual age. All were similar between groups.

Axillary temperatures and post menstrual ages were lower in Infants in the 1600 gram weaning group compared to the 1800 gram weaning weight group. The incubator temperature was also higher in the 1600 gm weaning weight group.

PRIMARY OUTCOME

For the primary outcome, the length of hospital stay was not significantly different in the 2 groups, with a median of 43 days for the 1600 gram wean group and 41 days for the 1800 gram wean group, with a p value of 0.12

SECONDARY OUTCOMES

Length of stay from randomization assignment to discharge was similar between the 2 groups. Growth velocity was the only parameter that differed and was higher in infants weaned at 1600 grams. Remaining characteristics including time necessary to achieve full enteral feeds, did not differ between the 2 groups.

CONCLUSIONS

The authors conclude that weaning infants at a lower weight from incubator to crib in moderately preterm infants did not affect length of stay. Furthermore, early weaning was well tolerated and associated with higher growth velocity.

COMMENTARY

Preterm newborn infants need to be placed in incubators to maintain stable temperatures in order to prevent cold stress and associated increased mortality (1). However, there is accumulating evidence that compared to current practice, transfer of infants to an open crib at lower body weights is safe and does not lead to increased mortality, temperature instability or poor weight gain (2,3). Due to the limited available data, there is a wide variation in clinical practice for weaning from an incubator. Institutional policies rely mainly on provider comfort or bedside nurses’ perceptions (4). Weaning earlier is considered beneficial in improving maternal- infant bonding, breast-feeding rates and neuro-development (5).

The current study aimed to assess whether weaning from an incubator to a crib at a lower birth weight was associated with decreased length of hospital stay. Infants were randomized at 1500-1540 gms to either group and weaned similarly in both cohorts by 1 to 1.5 ^oC until 28 ^oC in the isolette, maintaining axillary temperatures between 36.5 to 37.4 ^oC. Infants were then weaned to a crib if stable for 8-12 hours at 28 ^oC.

Failure rates at first attempted weaning were higher in the lower weight neonates.  Episodes of moderate and severe cold stress were more frequent in the lower weight group (10 infants out of 13 with moderate cold stress and 4 out of 5 with severe cold stress were in <1600 grams) however these were uncommon and not statistically significant.  A study limitation is that blinding is not possible, which may introduce bias based on physician directive and health care providers perception of an adverse event with this population. Infants at lower weights have a higher likelihood of being moved back into an isolette and evaluated for infection with bradycardias and desaturation which possibly are associated with prematurity as opposed to weaning to a crib. Another limitation was that a large number of infants (~30%) were not included in secondary outcome analysis due to missing data.  Interestingly, 36% of families refused to participate in the trial which was higher than other RCTs and observational studies (7,8)

The strength of this study lies in its focus on a specific population and its likely generalizability. Although the infants were not discharged earlier, the study is consistent with results from earlier and smaller trials (6,7,8). Weaning at 1600g vs 1800g appears safe for these infants, and may improve kangaroo care and parental involvement. Among providers, there was a higher perceived risk of cold stress and temperature instability in the more preterm infants.

However, a small study by Heimler et al demonstrated that weaning at lower weights led to faster deposition of subcutaneous fat which may be advantageous for efficient weight gain and cold resistance (9). The question of whether faster fat deposition leads to slower organ weight gain has not been answered. This RCT adds to the existing data that weaning medically stable infants at lower weight of 1600 grams is feasible and safe but it does not decrease the length of hospital stay.

REFERENCES

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2. West CR, Williams M, Weston PJ. Feasibility and early transfer of premature infants from incubators to cots: a pilot study. J Paediatr Child Health 2005; 41: 659-662.
3. New K, Flenady V, Davies MW. Transfer of preterm infants from incubator to open cot at lower versus higher body weight. Cochrane Database Syst Rev 2008; CD004214.
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5. Conde-Agudelo A, Diaz-Rossello JL. Kangaroo mother care to reduce morbidity and mortality in low birth weight infants. Cochrane Database Syst Rev 2016; CD002771.
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8. West CR, Williams M, Weston PJ.Feasibility and safety of early transfer of premature infants from incubators to cots: a pilot study. J Paediatr Child Health 2005;41:659–62.
9. Heimler R, Sumners JE,  Grausz JP, Kien CL, Glaspey JC. Thermal Environment Change in Growing Premature Infants: Effect on General Somatic Growth and Subcutaneous Fat Accumulation. Pediatrics1981; 68: 82-86.