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 Table of Contents  
Year : 2022  |  Volume : 5  |  Issue : 2  |  Page : 65-69

Measuring what matters: Respiratory archetypes in extreme preterm neonates

Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India

Date of Submission07-Apr-2022
Date of Acceptance11-May-2022
Date of Web Publication07-Jun-2022

Correspondence Address:
Dr. Femitha Pournami
Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram - 695 029, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/arwy.arwy_11_22

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Background: Descriptions of course of illness during prolonged intensive care is as essential as studying outcomes in extremely low gestational age neonates (ELGANs). Understanding the expected trajectory of respiratory illness aids in the recognition of risk factors followed by appropriate counselling and resource allocation. We studied the patterns of respiratory illness in ELGAN over the first 2 weeks and its association with bronchopulmonary dysplasia (BPD). Methodology: Levels of respiratory care in ELGAN from 2017 to 2021 were analysed. They were classified into four groups (pragmatically at the bedside) based on oxygen requirements as Category 1: persistent low needs (PL) – FIO2 <0.3 on day 3, and FIO2 <0.3 at 2 weeks, Category 2: progressive worsening (PW) – FIO2 <0.3 on day 3, worsening to >0.3 at 2 weeks, Category 3: persistent high needs (PH) – FIO2 >0.3 on day 3, continuing to need >0.3 at 2 weeks and Category 4: progressive improvement (PI) – FIO2 >0.3 on day 3, improving to <0.3 at 2 weeks. The proportion of infants in each group who developed BPD was also determined. Results: Seventy-four survivors of 91 live-born ELGAN were included, of whom 29.7% developed BPD. Most infants were in PL category (83.8%). Those in the worse categories (PW and PH) constituted only 4.05%. The association of classification as worse patterns (PW or PH) with BPD was not statistically significant, but the numbers were very small. Conclusions: Major proportion of ELGAN were categorised into reassuring archetypes of respiratory requirements. Drawing conclusions about the association with BPD may need analysis of a larger number of infants.

Keywords: Bronchopulmonary dysplasia, extreme preterm, extremely low gestational age neonates, respiratory patterns

How to cite this article:
Kolisambeevi AA, Pournami F, Prithvi AK, Nandakumar A, Prabhakar J, Jain N. Measuring what matters: Respiratory archetypes in extreme preterm neonates. Airway 2022;5:65-9

How to cite this URL:
Kolisambeevi AA, Pournami F, Prithvi AK, Nandakumar A, Prabhakar J, Jain N. Measuring what matters: Respiratory archetypes in extreme preterm neonates. Airway [serial online] 2022 [cited 2023 Feb 1];5:65-9. Available from: https://www.arwy.org/text.asp?2022/5/2/65/346894

  Introduction Top

Premature birth often hits like a bolt from the blue. Families and clinicians are expected to face the maelstrom of intensive care at its highest for weeks. Their classification as bronchopulmonary dysplasia (BPD) may determine long hospital stay, home oxygen needs, readmissions and subsequent risk of reactive respiratory illnesses.[1] Although scientific literature predominantly focuses on immediate and long-term outcomes of extremely low gestational age neonates (ELGAN); studying the course of illness during intensive care should be an integral part. If the expected respiratory course can be reasonably predicted in the beginning, it would aid decision-making on various fronts.

The aim of our study was to classify ELGAN based on their requirements of respiratory support into four archetypes using a modification of a previously described method that is pragmatic by the bedside.[2] We also sought to analyse the proportions of clinically relevant short-term outcomes in each group.

  Methodology Top

This retrospective observational study was conducted in a 33-bedded Level IIIB (National Neonatology Forum, India) accredited unit of a multispeciality referral centre in South India. The unit has five consultants and 10 registrars (postdoctoral subspeciality trainees in neonatology), of whom at least one consultant and two registrars are available on the floor round the clock by rotation. We are associated with a high-risk obstetric and perinatology unit. All infants ≥24 weeks gestation or >400 g birth weight born with signs of life are offered standard care. The unit has in place written protocols for the assessment of gestational age by the first-trimester ultrasound, antenatal steroids and magnesium sulphate administration, ultrasound and clinically-based timing of delivery, delayed cord clamping, delivery room continuous positive airway pressure (CPAP), surfactant, pulse oximetry-targeted oxygen therapy, synchronised intermittent mandatory ventilation, rescue high-frequency ventilation, early extubation to CPAP/noninvasive nasal ventilation, early caffeine citrate, aggressive nutrition strategy,[3] preferred use of breast milk,[3],[4] treatment of haemodynamically significant patent ductus arteriosus (hsPDA), asepsis routines, and nursing and doctor documentation templates. We practice early parent participation.[5] The unit prefers to discharge based on physiological stability when certain predefined criteria are fulfilled.[6]

A convenience sample of all neonates who were delivered at ≤28 weeks gestation (ELGAN) between January 2017 and October 2021 (inborn or outborn admitted within 24 h of life) and who survived till 36 weeks postmenstrual age were included in the study. The relevant clinical specifics, risk factors, details of course of illness, evaluations and outcomes were obtained from electronic medical records.

They were classified into one of four groups based on their respiratory care requirements:

Category 1: persistent low needs (PL) – FIO2 <0.3 on day 3 and FIO2 <0.3 at 2 weeks

Category 2: progressive worsening (PW) – FIO2 <0.3 on day 3 and worsening to >0.3 at 2 weeks

Category 3: persistent high needs (PH) – FIO2 >0.3 on day 3 and continuing to need >0.3 at 2 weeks.

Category 4: progressive improvement (PI) – FIO2 >0.3 on day 3 and improving to <0.3 at 2 weeks.

The 'FIO2 need' noted was that which was documented for at least 12 h of the particular day of life. As long durations of respiratory care pose a significant strain on hospital resources as well as parental coping, we measured the proportions in each group – rates of BPD,[7] culture positive sepsis and treated for hsPDA. For the purpose of risk factor and outcome examinations, the 'better' categories 1 and 4 were analysed as one group (Group 1); and categories 2 and 3 as another group (Group 2).

As this was a retrospective descriptive study, de-identification of patient details retrieved from medical records was done and no patient/family interview was planned. We, therefore, did not seek ethical clearance or informed consent.

  Results Top

Ninety-one live-born ELGAN received standard intensive care support. Of these, 74 completed care in the unit [Figure 1]. The median birth weight was 875 g, and the median interquartile range gestation at birth was 27 (26 and 28) weeks [Table 1]. It is noteworthy that 48.6% did not require intubation in the delivery room and 29.7% continued to require noninvasive supports at the end of 24 h. Survival rates increased with higher gestational ages at birth (23 weeks: 0%, 24 weeks: 50%, 25 weeks: 80%, 26 weeks: 76%, 27 weeks: 89% and 28 weeks: 100%).
Figure 1: Study flow diagram (BPD = Bronchopulmonary dysplasia; ELGAN = Extremely low gestational age neonates; FIO2 = Fraction of inspired oxygen)

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Table 1: Characteristics of extremely low gestational age neonates who survived till discharge (n=74)

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The proportions of infants in each of the predefined archetypes of respiratory support requirements are presented in [Figure 1] and [Table 2]. Most infants (83.8%) were in category 1, where the FIO2 need continued to remain below 0.3 even at the end of 2 weeks of life. There was no significant association of the worse patterns (categories 2 and 3: Group 2) with respect to risk factors [Table 3] or with the outcome of BPD (Group 1 [categories 1 and 4]: 28.2% vs. Group 2: 66.7%). The numbers are, however, too small to make meaningful conclusions in this regard.
Table 2: Archetypes of respiratory requirements as dictated by FIO2 requirements on day 3 and subsequently at 2 weeks of life (see text for details of categorisation) and association with bronchopulmonary dysplasia (n=74)

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Table 3: Comparison of risk factors between 2 groups based on the severity of respiratory morbidity (Group 1 [Category 1 or 4] and Group 2 [Category 2 or 3])

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  Discussion Top

Our study included ELGAN with a median gestation of 27 weeks and birth weight of 875 g. It was heartening to note that most (83.8%) infants had low-oxygen requirements in the immediate neonatal period and continued to remain that way even at 2 weeks of age. The main task of the neonatal intensivist is the prevention and management of BPD in ELGAN which continues to remain unacceptably high. Definitions of BPD have evolved with the intention of establishing uniformity in reporting and negating the influence of practice variations.[8] Our finding of 29.7% BPD is comparable to the reported incidence of 25%–40%.[1]

Several strategies have been suggested and tested to minimise therapy-associated lung injury.[9] More than half of the neonates could be managed in the delivery room with CPAP, although half of these infants subsequently required intubation in the neonatal intensive care unit (NICU). Landmark trials such as COIN, SUPPORT and VON report that a good fraction of even those <1000 g did not require intubation at birth.[10] They also reported a small but statistically significant reduction in the risk for death or BPD in the CPAP-treated infants.[10]

Descriptions of the evolution of respiratory illness in ELGAN are few. Laughon et al. suggested classification into three patterns in the first 2 weeks of life and reported that chronic lung disease was related to the severity and need for higher oxygen supplementation.[2] They further went on to identify the antecedents of BPD with regard to various patterns.[11] We did not find an association between the classification of respiratory support requirements and BPD. It is important to emphasise that our modification of the classification was somewhat broader as we considered an FIO2 of 0.23–0.25 too narrow a window for making bedside distinctions. We chose an FIO2 of 0.3 as a cutoff. An earlier study conducted in our unit identified FIO2 >0.3 on day 3 as a significant risk factor for continued need for respiratory support at 2 weeks of age.[12]

Other authors have improvised on the original definitions. In 2017, Nobile et al. used a narrow width of FIO2 needs (between 0.23 and 0.25) but suggested the addition of a fourth category of pulmonary improvement to the Laughon classification.[13] We used this category too and similar to these authors, grouped the PL and PI together for risk factor and outcome analysis.

The intention to study patterns of respiratory support requirement and classify them into archetypes stemmed from the need to establish regional baseline data of the expected course of illness.

Our study has some notable strengths. Up to one-fourth of the study, infants were <26 weeks and maybe representative of small sick neonates who warrant care in the current NICUs. Prespecified definitions, documentation methods and strict unit protocols help to negate the obvious drawbacks of a retrospective analysis. Finding a larger proportion of infants to be in Group 1 (low requirements at 2 weeks of life) was reassuring. However, we must admit that our study had some important limitations. As the number of infants in Group 2 (PW and PH) was very low, meaningful comparisons and statistical tests of association with outcomes and risks may require a larger database that can be obtained from a multicentric study. Moreover, the inherent drawbacks of a retrospective study also need to be kept in mind.

  Conclusions Top

A major proportion (83.8%) of ELGAN required low FIO2 at 3 days of life and continued to need low oxygen even at 2 weeks. Nearly, 95.9% were categorised into groups that required low level of respiratory supports. We fully understand that meaningful conclusions about the association with BPD would require the study of a larger number of infants.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Zysman-Colman Z, Tremblay GM, Bandeali S, Landry JS. Bronchopulmonary dysplasia – Trends over three decades. Paediatr Child Health 2013;18:86-90.  Back to cited text no. 1
Laughon M, Allred EN, Bose C, O'Shea TM, Van Marter LJ, Ehrenkranz RA, et al. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics 2009;123:1124-31.  Back to cited text no. 2
Upadhyay S, Pournami F, Nandakumar A, Prabhakar J, Nair PMC, Jain N. Outcome of very preterm infants with early optimal nutrition strategy: A comparative cohort study. Nutr Clin Pract 2020;35:708-14.  Back to cited text no. 3
Nandakumar A, Pournami F, Prabhakar J, Nair PMC, Jain N. Exclusive breast milk versus hybrid milk feeding for preterm babies-a randomized controlled trial comparing time to full feeds. J Trop Pediatr 2020;66:38-45.  Back to cited text no. 4
Pillai A, Pournami F, Prabhakar J, Nair P, Jain N. Effect of early parent participation program on physiological stability in preterm infants: A randomized controlled trial. Am J Perinatol 2021. doi: 10.1055/s-0041-1726126.  Back to cited text no. 5
Prakash R, Pournami F, Prabhakar J, Nandakumar A, Nair PM, Jain N. Duration of caffeine for apnea of prematurity – A randomized controlled trial. Indian J Pediatr 2021;88:1174-9.  Back to cited text no. 6
Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9.  Back to cited text no. 7
Ibrahim J, Bhandari V. The definition of bronchopulmonary dysplasia: An evolving dilemma. Pediatr Res 2018;84:586-8.  Back to cited text no. 8
Davidson LM, Berkelhamer SK. Bronchopulmonary dysplasia: Chronic lung disease of infancy and long-term pulmonary outcomes. J Clin Med 2017;6:4.  Back to cited text no. 9
Kennedy KA, Cotten CM, Watterberg KL, Carlo WA. Prevention and management of bronchopulmonary dysplasia: Lessons learned from the neonatal research network. Semin Perinatol 2016;40:348-55.  Back to cited text no. 10
Laughon M, Bose C, Allred EN, O'Shea TM, Ehrenkranz RA, Van Marter LJ, et al. Antecedents of chronic lung disease following three patterns of early respiratory disease in preterm infants. Arch Dis Child Fetal Neonatal Ed 2011;96:F114-20.  Back to cited text no. 11
Alok Kumar MK, Pournami F, Gurram Venkata SK, Nandakumar A, Prabhakar J, Jain N. Can early clinical status predict outcomes in extremely low birth weight neonates? J Child Sci 2020;10:e32-7.  Back to cited text no. 12
Nobile S, Marchionni P, Vento G, Vendettuoli V, Marabini C, Lio A, et al. New insights on early patterns of respiratory disease among extremely low gestational age newborns. Neonatology 2017;112:53-9.  Back to cited text no. 13


  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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