Outcome of Continuous Positive Airway Pressure (CPAP) Administration in Delivery Room for Neonates with ≧35 Weeks of Gestational Age with Respiratory Distress: A Randomized Control Trial in a Tertiary Care Hospital

Background

The sixth edition of neonatal resuscitation program (NRP 2011) introduced Continuous Positive Airway Pressure (CPAP) via T-piece resuscitator as a mode of intervention for spontaneously breathing neonates without apnea or gasping; presenting with labored breathing or persistent cyanosis and heart rate of > 100/min, regardless of gestational age (GA). ¹

Over the years the use of delivery room CPAP (DR CPAP) became the norm for preterm neonates, with multiple studies reporting a reduced need of surfactant and endotracheal intubation.^2–6 However, there is inconclusive evidence for the use of CPAP in the late preterm and term neonates with recent retrospective studies reporting significant increased incidence of pressure leak syndromes amongst this group.^7–9.

The aim of the study was to compare the outcome of DR CPAP and DR FFO in late preterm and term neonates presenting with respiratory distress (spontaneously breathing neonates without apnea or gasping; presenting with labored breathing or persistent cyanosis and heart rate of > 100/min). The objective was to study early neonatal outcome in the DR and after NICU admission amongst this group of neonates.

Methodology

The study was conducted at a tertiary care center in North Karnataka, India, from January 2021 to April 2022. Ethical clearance was obtained from the Institutional Ethics Committee (JNMC Institutional Committee on Human Subjects Research, J.N. Medical College, Belagavi: Ref:MDC/DOME/149).

The inclusion criteria were neonates delivered with GA ≧ 35 weeks by normal vaginal delivery (NVD)/lower segment Caesarean section (LSCS) who developed labored breathing in the delivery room or required free flow oxygen to maintain SPO₂ in target range. Neonates with antenatally or postnatally detected life threatening congenital anomalies, those needing prolonged positive pressure ventilation (PPV) or intubation as per NRP algorithm were excluded from the study. ¹⁰

A written consent was obtained from the parents prior to the delivery. Neonates who met the inclusion criteria were randomized into 2 groups by a computer spawned sequence, which was kept ready in the resuscitation corner of the delivery room.

Group 1 (DR CPAP) received CPAP via a T-piece resuscitator (Fisher Paykel Neopuff^TM) and group 2 (DR FFO) received only free flow oxygen via face mask, set as per NRP 2020 recommendations. Randomization was done only for neonates delivered in presence of the physicians certified in the latest NRP (2020). ¹⁰ Neonates were enrolled as per the flow diagram depicted in Figure 1.

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Figure 1.

Consort Flow Diagram.

Neonates from both the groups who had worsening of the distress at any point of time or with persistent respiratory distress in the form of labored breathing or unable to maintain

target saturation at the end of one hour of resuscitation, were shifted to neonatal intensive care unit (NICU) for further management. Modified Downes score was documented for each neonate at the point of admission to NICU (Table 3). ¹¹ Those neonates who improved in the delivery room (respiratory rate between 40-60/minute, no retractions, and maintaining oxygen saturation above 95%) were shifted to the mother and received routine neonatal care.

All the maternal and neonatal data including resuscitation details were documented in a standardized proforma. Outcome of the neonates shifted to the NICU was recorded at the end of one week.

A sample size of 130 neonates was calculated based on the systematic review of the effects of interventions in the term and late preterm infants experiencing delayed respiratory transition based on the following formula n = f(α/2, β) × [p1 × (100 − p1) + p2 × (100 − p2)] / (p2 − p1) ² ]. ¹²

Data were analyzed using R software version 4.2.1 and Excel. Categorical variables were presented in the form of a frequency table and Continuous variables as Mean±SD/Median (Min, Max) form. Chi-square test was applied to find the association of attributes. Mann-Whitney U test was used to compare distributions of variables over groups. P-value less than equal to.05 was considered statistically significant.

Results

131 neonates were enrolled in the study; 62 randomized to DR CPAP and 69 to DR FFO.

Table 1 gives the demographic data of the mothers and neonates enrolled into the study. The mean GA was of 38.44±1.4 weeks in the DR CPAP group, while 38.27±1.35 weeks in the DR FFO group.

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Table 1.

Demographic Data of the Mothers and Neonates.

Variables	SubCategory	CPAP	FFO	Total	P Value
Maternal Details
Age of mother	Mean±SD Median (Min, Max)	24.91±4.97 24 (18, 42)	24.88±4.33 24 (19, 42)	24.9±4.65 24 (18, 42)	.8156MW
Neonatal Details
Gestational age (weeks)	Late preterm (< 37 weeks)	6(9.52%)	5(7.46%)	11(8.46%)	.673C
	Term (≥ 37 weeks)	57(90.48%)	62(92.54%)	119(91.54%)
	Mean±SD Median (Min, Max)	38.44±1.4 38 (36, 42)	38.27±1.35 38 (35, 41)	38.35±1.37 38 (35, 42)	5623MW
Birth weight (Kg)	Mean±SD Median (Min, Max)	2.8±0.49 2.7 (2, 4)	2.78±0.49 2.8 (1.6, 4.5)	2.79±0.49 2.8 (1.6, 4.5)	.951MW
Gender	Female	31(48.39%)	27(38.81%)	58(44.27%)	.2727C
	Male	32(51.61%)	41(61.19%)	73(55.72%)
Mode of delivery	AVD	1(1.59%)	3(4.48%)	4(3.05%)	.2694MC
	LSCS	34(53.97%)	43(64.18%)	78(59.54%)
	NVD	28(44.44%)	21(31.34%)	49(37.40%)
Liquor	Clear	47(74.6%)	54(80.6%)	101(77.69%)	.412C
	MSL	16(25.4%)	13(19.4%)	29(22.31%)

Abbreviation: C, chi-square test; MC, chi-square test with Monte Carlo simulation; MW, Mann-Whitney U test.

As shown in Table 2; 69 (52.67%) out of the total 131 subjects were randomized to DR FFO while 62 (47.32 %) to DR CPAP. A total of 58 (84.05 %) neonates from DR FFO group improved while 11 (15.94 %) were shifted to NICU. And 55 neonates (87.3 %) of the DR CPAP group improved while 7 (12.7 %) neonates were shifted to NICU.

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Table 2.

Comparisons of Delivery Room Outcome.

Variable	Subcategory	CPAP	FFO	Total	P Value
DR outcome	Improved	55(87.3%)	58(84.05%)	113(86.25%)	.5485C
	Shifted to NICU	7(12.7%)	11(15.94%)	18(13.74%)
Variables	Mean±SD		Median (Min, Max)		P Value
DR CPAP duration (min)	12.34±5.02		10 (5, 30)		.802MW
DR FFO duration (min)	12.34±5.02		10 (5, 30)

Abbreviation: C, chi-square test; MC, chi-square test with Monte Carlo simulation; MW, Mann-Whitney U test.

Table 3 shows a comparison of Modified Downe’s score between the 2 groups, with no statistically significant difference among them.

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Table 3.

Comparison of Modified Downe’s Score.

Modified Downe’s Score	CPAP	FFO	Total	P Value
0	1(14.29%)	3(27.27%)	4(22.22%)	.3938MC
1	1(14.29%)	5(45.45%)	6(33.33%)
2	3(42.86%)	2(18.18%)	5(27.78%)
3	2(28.57%)	1(9.09%)	3(16.67%)

Abbreviation: C, chi-square test; MC, chi-square test with Monte Carlo simulation; MW, Mann-Whitney U test.

Only 3 neonates required nasal CPAP in the NICU while none of the neonates from the study required intubation after shifting to NICU. Table 4 shows a comparison of the respiratory support required in the NICU from both the groups. No significant difference was observed in the neonatal outcome in the NICU amongst both the groups. By the end of 1 week, 8 neonates were discharged from NICU and no neonate required any kind of respiratory support for more than 4 days.

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Table 4.

Comparison of Respiratory Support in NICU

Respiratory Support inNICU	CPAP	FFO	Total	P Value
Nasal CPAP	2(28.57%)	1(9.09%)	3(16.67%)	.5392MC
O2 by nasal prongs	4(57.14%)	8(66.66%)	12(61.11%)	1MC

Abbreviation: C, chi-square test; MC, chi-square test with Monte Carlo simulation; MW, Mann-Whitney U test.

Various perinatal factors including mode of delivery known to alter the transitional adaptation of the neonate were recorded in the proforma and analyzed. A total of 77 (59.23%) were delivered via LSCS, 49 (37.69%) via vaginal delivery and 4 were assisted vaginal deliveries (Table 1). As shown in Table 5 there was no significant statistical difference in the improvement of the neonates in the delivery room and NICU amongst both the groups (P value:.548)

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Table 5.

Comparison of Outcome Based on Mode of Delivery, Liquor, and Gestational Age.

Variables	Subcategory	CPAP	FFO	P Value
Mode of delivery	LSCS	31 (91.18%)	36 (83.72%)	.5212MC
	NVD	24 (85.71%)	17 (80.95%)	.7226MC
Liquor	Clear	43 (91.49%)	46 (85.19%)	.3893MC
	MSL	12 (75%)	10 (76.92%)	1MC
Gestational age(weeks)	Late preterm (< 37 weeks)	4 (66.67%)	2 (40%)	.5732MC
	Term (≥ 37 weeks)	51 (89.47%)	54 (87.1%)	.7956MC

Abbreviation: C, chi-square test; MC, chi-square test with Monte Carlo simulation; MW, Mann-Whitney U test.

Discussion

With over 2 decades since its inception, the NRP has had to evolve perpetually to stay valid and provide an optimal resuscitation to the neonates in the delivery room. ¹³

In this study conducted at a tertiary care hospital in North Karnataka we studied the outcome in neonates with ≧ 35 weeks of GA, who received CPAP or FFO in the delivery room.

In our study 119 (91.4 %) neonates were term, and 12 (8.46 %) late preterm who developed respiratory distress but no difference was observed in outcome of these neonates after randomization to either of the groups (P value:.57).

The application of DR CPAP in term and late preterm neonates with optimal or suboptimal levels of surfactant, well prepared for the change from in-utero to external air exchange transition; cannot be justified. These neonates with ≧ 35 weeks of GA require a relatively low pressure to distend the alveoli, and are therefore predisposed to acute injury when CPAP is applied. ¹⁴

The data is thus lacking and inconclusive for the use of CPAP on late-preterm and term neonates in the delivery room.

In our study the mean time required to resolve respiratory distress in neonates who received DR CPAP was 12.34±5.02 mins while DR FFO required 13.82±8.56 mins (P value =.802), with no statistical advantage in supporting the neonatal transition.

Modified Downes score provided an objective assessment of the severity of respiratory distress amongst the 2 group of neonates who required NICU admission and as shown in Table 3 there was no significant difference in outcome amongst both the groups (P value:.39). In our study, though none of the babies had a modified Downes score of more than 3 at the point of admission to NICU, 3 babies received nasal CPAP as per the advice of the attending physician.

Yilmaz et al reported that NICU admission rates can be reduced with the use of prophylactic CPAP in the late preterm and term neonates delivered via elective caesarean section without any side-effects. ¹⁶ However, Srinivasan et al reported no adverse or beneficial effects of providing prophylactic CPAP for the similar group of neonates in the delivery room. ¹⁷ There was no statistically significant benefit of DR CPAP over DR FFO in these neonates delivered via LSCS in our study (P value:.5).

Meconium aspirated in-utero or postnatally can have direct toxic effects on the lung parenchyma and the resulting meconium aspiration syndrome may result in the requirement of a considerable respiratory support. In this study, out of the 22 neonates born out of meconium stained liquor, 12 (75 %) were subjected to DR CPAP and 10 (76.92 %) to DR FFO with no statistical significance observed in the outcome (p value: 1).

Literature review shows no significant benefit recorded of DR CPAP in neonates with ≧ 35 weeks of GA while some studies have reported the possibility of adverse effects.^7–9

Though we did not document pneumothorax among any of the neonates from DR CPAP group, retrospective birth cohort study of newborns conducted by Smithhart et al found an increased incidence of pneumothorax after the application of 2011 NRP guidelines, from 0.4% to 0.6%. ⁷

Interestingly, in a recent publication by the same group, a reduced incidence of pneumothorax was reported when DR CPAP was de-implemented for neonates with gestation ≧ 35 weeks. ¹⁸

Similarly, Spillane et al reported an increased risk of NICU admissions as well as an increased duration of hospital stay in neonates receiving DR CPAP with a gestation of 35 week as compared to neonates receiving PPV or no resuscitation in the DR. ¹⁹

A major limitation of this study is that it was conducted in a single tertiary care center with a small sample size. Large multicenter trials with larger sample size and at various levels of health care need to be conducted to evaluate the benefit of DR CPAP and DR FFO among late preterm and term neonates before any recommendations can be made for a developing nation like India. Whether to let a late preterm or term neonate presenting with respiratory distress pave its own way through the transitory period or to intervene with DR CPAP will be understood with these trials.

Conclusion

This randomized control trial shows no significant difference in the delivery room or early neonatal outcome of neonates after the administration of DR CPAP or DR FFO amongst neonates with GA ≧ 35 weeks, presenting with respiratory distress.

No significant difference was seen in the requirement of respiratory support in the NICU between the 2 groups of neonates shifted for NICU care or at the end of the delivery room resuscitation. Robust evidence needs to be generated to support the current recommendation of administering DR CPAP irrespective of gestation age.