Timing of initial surfactant treatment in very low birth weight newborns

Rebello, Celso Moura; Nacif, Luciene Ferreira do Amaral; Deutsch, Alice D´Agostini; Paes, Ângela Tavares

doi:10.1590/S1679-45082010AO1758

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Original Article • Einstein (São Paulo) 8 (3) • Jul-Sep 2010 • https://doi.org/10.1590/S1679-45082010AO1758 copy

Timing of initial surfactant treatment in very low birth weight newborns

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To correlate the timing of treatment using exogenous surfactant with the main variables related to respiratory distress syndrome or prematurity.

Methods:

A historic cohort study between January 1, 2004 and June 30, 2007, including very low birth weight newborns (birth weight <1,500 g) admitted to the hospital and who required surfactant therapy. Newborns were divided into three study groups: early (treatment during the first two hours); intermediate (treatment between two and six hours) and late (treatment after six hours). Variables analyzed were: air leak syndrome, mortality, bronchopulmonary dysplasia, intracranial hemorrhage, patent ductus arteriosus, retinopathy of prematurity, duration of oxygen therapy, duration of mechanical ventilation, length of hospital stay and number of surfactant doses.

Results:

A total of 63 newborns were included (Early Group, n = 21; Intermediate Group, n = 26 and Late Group, n = 16), there was a statistical significance between birth weight and gestational age. Multivariate logistic regression analysis was used to compensate the effects of gestational age, birth weight and other possible interferences over the variables. This analysis revealed a greater incidence of air leak syndrome among newborns of the Early Group compared to the Intermediate Group (OR = 6.98; 95%CI = 1.24-39.37; p = 0.028), with no difference compared to the Late Group (OR = 3.72; 95% CI = 0.28-49.76; p = 0.321). There were no differences regarding the other variables analyzed.

Conclusions:

In this retrospective, non-randomized study, surfactant administration during the first two hours of life enhanced the risk of air leak syndrome, compared to the treatment between two and six hours after birth, with no reduction of early or late neonatal mortality or bronchopulmonary dysplasia, compared to later treatment after birth.

Keywords:
Pulmonary surfactants; Infant, premature; Infant, newborn; Pneumothorax

Characteristics	Early Group n = 21	Intermediate Group n = 26	Late Group n = 16	p value
Gestational age (weeks)	26.7 ± 2.0^* * p<0.05 when compared to Late Group;	28.0 ± 2.2^* * p<0.05 when compared to Late Group;	30.2 ± 1.3	< 0.01
Birth weight (g)	837 ± 213^* * p<0.05 when compared to Late Group; ^§ § p<0.05 when compared to Intermediate Group.	1,012 ± 270^* * p<0.05 when compared to Late Group;	1,296 ± 161	< 0.01
C-section (%)	14 (66.7%)^* * p<0.05 when compared to Late Group;	23 (88.5%)	16 (100.0%)	0.017
Multiparous (%)	8 (38.1%)^* * p<0.05 when compared to Late Group;	11 (42.3%)	10 (62.5%)	0.021
Use of prenatal corticoids (%)	12 (57.1%)	15 (57.7%)	12 (75.0%)	0.458
Male	8 (38.1%)	14 (53.8%)	8 (50.0%)	0.548
Multiple gestation	10 (47.6%)^* * p<0.05 when compared to Late Group;	16 (61.5%)	14 (87.5%)	0.043
Apgar 1st minute ≤ 3	6 (28.6%)	4 (15.4%)	0 (0.0%)	0.061
Apgar 5th minute ≤ 3	1 (4.8%)	1 (3.8%)	0 (0.0%)	0.662

Outcomes		Early Group (n = 21)	Intermediate Group (n = 26)	Late Group (n = 16)	p value
Pneumothorax		6 (28.6%)^* * p < 0.05 when compared to Late Group; ^§ § p < 0.05 when compared to the Intermediate Group.	1 (3.8%)	1 (6.3%)	0.033
Pneumomediastinum		3 (14.3%)	1 (3.8%)	0 (0.0%)	0.218
Interstitial emphysema		5 (23.8%)^* * p < 0.05 when compared to Late Group; ^§ § p < 0.05 when compared to the Intermediate Group.	0 (0.0%)	1 (6.3%)	0.019
Early neonatal mortality		4 (19.0%)	6 (23.1%)	0 (0.0%)	0.108
Late neonatal mortality		5 (23.8%)	6 (23.1%)	0 (0.0%)	0.597
Bronchopulmonary dysplasia		9 (42.9%)	6 (23.1%)	2 (12.5%)	0.119
Intracranial hemorrhage (total)		8 (38.1%)	9 (34.6%)	1 (6.3%)	0.067
Patent ductus arteriosus		9 (42.9%)	17 (65.4%)	9 (56.3%)	0.302
Retinopathy of prematurity		12 (57.1%)	11 (42.3%)	3 (18.8%)	0.063
Total oxygen time (days)		48.5 ± 42.5^* * p < 0.05 when compared to Late Group;	30.4 ± 35.2	18.5 ± 15.6	0.032
Mechanical ventilation time (days)		22.3 ± 19.9^* * p < 0.05 when compared to Late Group; ^§ § p < 0.05 when compared to the Intermediate Group.	10.2 ± 17.3	5.1 ± 3.4	0.005
Length of stay (days)		66.2 ± 45.6	57.7 ± 43.2	48.8 ± 19.8	0.414
Number of surfactant doses
	One dose	14 (66.7%)	17 (65.4%)	13 (81.3%)	0.539
	Two doses	7 (33.3%)	9 (34.6%)	3 (18.8%)

Dependent variable	Comparison	Odds ratio (95%CI)	p value
Air leak syndrome^* * OR and contrasts adjusted by: ^h h gestational age;	Early/Intermediate	6.98 (1.23; 39.37)	0.028
	Early/Late	3.72 (0.28; 49.76)	0.321
Early neonatal mortality^* * OR and contrasts adjusted by: ^b b maternal age; ,^e e Apgar 5th minute; ,^f f multiple gestation; ,^h h gestational age; ,ⁱ i birth weight;	Early/Intermediate or Late^‡ ‡ The intermediate and late treatment groups were put together due to the low number of deaths.	0.04 (0.00; 1.13)	0.059
Bronchopulmonary dysplasia^* * OR and contrasts adjusted by: ^a a parity; ,^b b maternal age; ,ⁱ i birth weight;	Early/Intermediate	1.76 (0.39; 8.00)	0.465
	Early/Late	2.27 (0.20; 25.64)	0.509
Intracranial hemorrhage^* * OR and contrasts adjusted by: ^d d use of prenatal corticoids; ,^f f multiple gestation;	Early/Intermediate	1.01 (0.28; 3.69)	0.987
	Early/Late	6.29 (0.62; 62.50)	0.119
Patent ductus arteriosus^* * OR and contrasts adjusted by: ^c c premature rupture of membranes; ,^e e Apgar 5th minute;	Early/Intermediate	0.50 (0.14; 1.79)	0.288
	Early/Late	0.81 (0.19; 3.43)	0.769
Retinopathy of prematurity^* * OR and contrasts adjusted by: ^f f multiple gestation; ,^h h gestational age;	Early/Intermediate	1.73 (0.49; 6.17)	0.397
	Early/Late	4.97 (0.71; 34.87)	0.107
		Difference
Total oxygen time (days)^* * OR and contrasts adjusted by: ^f f multiple gestation;	Early/Intermediate	15.72 (-4.19; 35.63)	0.119
	Early/Late	22.28 (-1.09; 45.65)	0.061
Mechanical ventilation time (days)^* * OR and contrasts adjusted by: ^f f multiple gestation; ,ⁱ i birth weight;	Early/Intermediate	7.04 (-2.31; 16.39)	0.137
	Early/Late	3.67 (-9.44; 16.78)	0.577
Length of stay (days)^* * OR and contrasts adjusted by: ^e e Apgar 5th minute;	Early/Intermediate	13.06 (-10.18; 36.29)	0.265
	Early/Late	25.25 (-1.23; 52.25)	0.061

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[1] Corresponding author: Celso Moura Rebello – Rua Engenheiro Teixeira Soares, 165 – Butantan – CEP 05505-030 – São Paulo (SP), Brasil – Tel.: (11) 3812-2121 – e-mail: celso.rebello@uol.com.br