Estimating RSV Hospitalization Among Premature Infants

Abstract and Introduction

Abstract

Background: Prophylaxis against respiratory syncytial virus-associated hospitalization (RSV-H) with anti-RSV monoclonal antibody is not considered cost-effective for routine use in most jurisdictions. The aim of this study was to develop a scoring tool to estimate local risk of RSV-H in the first year of life among moderately premature infants to assist in prophylaxis decision making.

Methods: A retrospective cohort was constructed from population-based databases in Nova Scotia, Canada, to follow 32- to 35-week gestation infants from the prenatal period to <12 months of age, from 1998 to 2008. Potential risk factors were entered into the logistic regression model, where the dependent variable was RSV-H. Receiver operator characteristic analysis demonstrated cutoff scores producing the highest predictive accuracy, and the likelihood ratio test was used to select the final set of variables for the predictive tool.

Results: In 2811 eligible infants, the overall RSV-H rate was 3.1% (88/2811). Of 17 variables considered, 3 were used to create the scoring tool: birth during December to February, household smoke exposure and household crowding. The positive likelihood ratios of predictive tool scores for high, moderate and low of RSV-H were 3.57, 3.38 and 1.95, whereas posttest probabilities (risk of RSV-H) were 11.4%, 10.8% and 1.6%, respectively.

Conclusions: While able to predict infants at low risk of RSV-H, the tool did not discriminate high from moderate risk infants. The tool could be used in anticipatory care to help educate families about reducing risk of serious RSV illness in their newborn.

Introduction

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants and young children;^[1,2] worldwide, up to 199,000 deaths and 33 million episodes occur each year.^[3] There are no vaccines available and treatment is symptomatic. In 2 randomized controlled clinical trials, the RSV-specific monoclonal antibody palivizumab reduced the risk of RSV-associated hospitalization (RSV-H) in premature infants and those with certain cardiac and lung disorders.^[4] In most jurisdictions, this passive prophylaxis is not considered cost-effective for routine use and is recommended only for those considered at highest risk of severe RSV-associated illness, such as those born at ≤29 weeks of gestation.^[5–7] Given the high cost of prophylaxis, several research groups have studied local RSV epidemiology and developed predictive indices to identify a subset of moderately premature children who could be offered palivizumab.^[8–13]

The purpose of this study was to determine if a subset of infants 32- to 35-weeks gestational age (wGA) could be identified, based on risk factors present at the time of birth, to be at higher risk of RSV-H. Access to a maternal–perinatal population-based database used comprehensively throughout our province, and a universal healthcare system capturing all hospital admissions allowed creation of a retrospective cohort of children that was followed from the perinatal period through the first year of life for RSV-H.

Table 1. Characteristic of the Study Cohort at Baseline (n = 2811)
Characteristic	n	%
Born in December, January and February	652	23.0
Weeks gestational age
32	257	9.1
33	422	15.0
34	762	27.1
35	1370	48.7
Low birth weight (≤2500 g)	729	26.0
Female	1508	53.6
Twin	623	22.2
Premature preterm rupture of membranes	992	35.3
Received antenatal steroid	995	35.4
Living in a household with
Passive household smoke exposure*	643	24.3
Among smokers 0.5 pack pack/d (1 to <12 cigarettes)	307	47.7
Single/divorced/separated parent	802	30.0
≥5 individuals per household (including subject)	497	18.3
≥2 siblings ≤5 years of age (preschool aged siblings)	337	13.6
Breast-feeding 1765 63.8
Low Apgar score at 1 min (0–6)	658	23.5
Cesarean section delivery	1162	41.3
Advanced maternal age (≥35 years)	501	17.8
RSV-associated hospitalization (ICD-CM code; N = 88)
ICD-9-CM 007.9 (viral infection)	1	1.1
ICD-9-CM 466.1 (acute bronchiolitis)	13	14.8
ICD-9-CM 480.1 (pneumonia caused by RSV)	2	2.3
ICD-10-CM B97.4 (RSV)	6	6.8
ICD-10-CM J12.1 (RSV pneumonia)	2	2.3
ICD-10-CM J21.0 (acute bronchiolitis caused by RSV)	64	72.2

Table 1. Characteristic of the Study Cohort at Baseline (n = 2811)

Characteristic

Born in December, January and February

652

23.0

Weeks gestational age

257

9.1

422

15.0

762

27.1

1370

48.7

Low birth weight (≤2500 g)

729

26.0

Female

1508

53.6

Twin

623

22.2

Premature preterm rupture of membranes

992

35.3

Received antenatal steroid

995

35.4

Living in a household with

Passive household smoke exposure*

643

24.3

Among smokers 0.5 pack pack/d (1 to <12 cigarettes)

307

47.7

Single/divorced/separated parent

802

30.0

≥5 individuals per household (including subject)

497

18.3

≥2 siblings ≤5 years of age (preschool aged siblings)

337

13.6

Breast-feeding 1765 63.8

Low Apgar score at 1 min (0–6)

658

23.5

Cesarean section delivery

1162

41.3

Advanced maternal age (≥35 years)

501

17.8

RSV-associated hospitalization (ICD-CM code; N = 88)

ICD-9-CM 007.9 (viral infection)

1.1

ICD-9-CM 466.1 (acute bronchiolitis)

14.8

ICD-9-CM 480.1 (pneumonia caused by RSV)

2.3

ICD-10-CM B97.4 (RSV)

6.8

ICD-10-CM J12.1 (RSV pneumonia)

2.3

ICD-10-CM J21.0 (acute bronchiolitis caused by RSV)

72.2

Predictive Variable	RSV-H, β Coefficient	Relative RSV-H, β Coefficient	Score
Household crowding (≥5 individuals)	0.255	0.224	22
Born in December, January or February	0.474	0.417	42
Passive household smoke exposure	0.408	0.359	36
Total	—	1	100

Risk Group	Total, n	RSV-H, n (%)	Score Range
Low risk	1517	23 (1.5)	0–41
Moderate risk	831	43 (5.2)	42–64
Highest risk	208	12 (5.8)	65–100

Predicted RSV-H risk	RSV-H (+)	No RSV-H (−)	Total
High vs. low predicted RSV-H scores
High (+)	12	196	208
Low (−)	23	1842	1865
Total	35	2038	2073
Sensitivity	34.3%
Specificity	90.4%
PPV	5.8%
NPV	98.8%
LR+	3.57
Positive posttest probability	11.4%
Moderate vs. low predicted RSV-H scores
Moderate (+)	43	440	483
Low (−)	23	1842	1865
Total	66	2282	2348
Sensitivity	65.0%
Specificity	80.7%
PPV	8.9	%
NPV	78.4%
LR+	3.38
Positive posttest probability	10.8%

Estimating Respiratory Syncytial Virus-associated Hospitalization in the First Year of Life Among Infants Born at 32–35 Weeks of Gestation

Abstract and Introduction

Abstract

Introduction

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Authors and Disclosures

Authors and Disclosures

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