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J Perinatol. Author manuscript; available in PMC 2016 September 24.
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Published in final edited form as:

J Perinatol. 2016 May ; 36(5): 352–356. doi:10.1038/jp.2016.38.

Impact of Antenatal Steroids on Intraventricular Hemorrhage in

Very Low Birth Weight Infants
Julia C. Wei, MPH1, Ralph Catalano, PhD1, Jochen Profit, MD, MPH2,3, Jeffrey B. Gould, MD,
MPH2,3, and Henry C. Lee, MD2,3
1University of California, Berkeley School of Public Health
2Divisionof Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University,
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Stanford, CA
3California Perinatal Quality Care Collaborative, Palo Alto, CA

Abstract
Objective—To determine the association between antenatal steroids administration and
intraventricular hemorrhage rates.

Methods—We used cross-sectional data from the California Perinatal Quality Care Collaborative
during 2007-2013 for infants ≤ 32 weeks gestational age. Using multivariable logistic regression,
we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by
gestational age.
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Results—In 25,979 very low birth weight infants, antenatal steroid use was associated with a
reduction in incidence of any grade of intraventricular hemorrhage (odds ratio = 0.51, 95%
confidence interval: 0.45, 0.58) and a reduction in incidence of severe intraventricular hemorrhage
(odds ratio = 0.62, 95% confidence interval: 0.57, 0.67). This association was seen across
gestational ages ranging from 22 to 29 weeks.

Conclusions—While current guidelines recommend coverage for preterm birth at 24 to 34

weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even
before 24 weeks of gestational age.

Introduction
Intraventricular hemorrhage (IVH) is a significant cause of preterm morbidity and mortality,
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1
with approximately 12,000 infants developing IVH every year in the United States. Within
the population of very low birth weight (VLBW; < 1500 g) infants, the incidence of IVH has
been estimated at 20%. However, the incidence of IVH among VLBW infants has declined
in the past few decades, from 40-50% in the early 1980s to approximately 20% in the late
2 3 4 5
1980s, then remaining relatively stable for the past two decades. , , , IVH occurs in nearly

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Corresponding Author: Henry C. Lee, MD, MS, Department of Pediatrics, Division of Neonatal and Developmental Medicine, 750
Welch Rd, Suite 315, Stanford, CA 94305, Office: (650) 723-5711 Fax: (650) 723-8351 ; Email: hclee@stanford.edu
Conflict of Interest: None
 Wei et al. Page 2

2 5
half of infants born at extremely low birth weight (500-750 g). , Infants who survive a
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severe IVH (Grade III or IV) may be at higher risk of significant long-term or permanent
neurological injuries/deficits, including cerebral palsy, mental retardation, and post-
6
hemorrhagic hydrocephalus.

Previous studies have shown that treatment of pregnant women with steroids prior to
delivery is associated with a reduced risk of adverse health outcomes, including IVH.
Liggins et al., conducting the first randomized controlled trial of antenatal betamethasone,
showed downward mortality and lower risks of RDS in infants of treated mothers compared
7
to controls and the need for respiratory support. In that study, four of the infants of control
mothers had IVH, compared to none of the infants of steroid-treated mothers. Although this
difference was not statistically significant, this finding raised the possibility that antenatal
steroid use might reduce the incidence of IVH.
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A Cochrane review in 2006 consisting of a meta-analysis of randomized trials demonstrated

a reduced risk of IVH (relative risk 0.54, 95% confidence interval 0.43 to 0.69) when
8
treatment with antenatal steroids occurred. As most of the trials included occurred in the
1990’s or early 2000’s when IVH rates were higher, we were interested to see if this positive
impact of antenatal steroids would still be present. Furthermore, quality improvement efforts
to increase antenatal steroid use, as well as other independent efforts to reduce IVH may
have weakened this beneficial link.

In the present study, we aimed to determine the magnitude of the effect of antenatal steroid
treatment in the prevention of intraventricular hemorrhage in a modern population-based
cohort, and to assess whether there is a difference in effect according to gestational age.
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Subjects and Methods

Study Population and Data Source
Any hospital in California that provides neonatal intensive care is eligible for membership in
the California Perinatal Quality Care Collaborative (CPQCC). Currently, 132 hospitals are
members of the CPQCC, including 100% of all California Department of Public Health
Children’s Services (CCS)-approved intermediate, community, and regional-level NICUs in
California. Member hospitals submit data on newborn infants who require critical care to the
CPQCC data center. Infants in the CPQCC database represent over 90% of VLBW infants
treated in California NICUs.

During the seven-year study period January 1, 2007 - December 31, 2013, 42,904 VLBW
births qualified for entry into the CPQCC database, i.e., a birth weight between 401-1500
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grams or a gestational age between 22-32 weeks. Of these, 39,956 infants were born at ≤ 32
weeks gestational age. We limited our study cohort to infants who were VLBW who had a
gestational age ≤ 32 weeks, as this population of neonates is most at risk for IVH. We
limited our analyses to inborn infants as attributing the influence of more than one NICU’s
care on IVH would not be possible, particularly in the time period immediately surrounding
delivery.

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Infants with missing data on IVH (n = 5,102) or antenatal steroids (n = 228) were excluded.
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Infants who died prior to having brain imaging performed would be considered as having
missing data on IVH. Following the exclusions, 25,979 infants were included in the analysis.

Measures
Intraventricular hemorrhage: CPQCC members are instructed to classify intraventricular
hemorrhage by neural imaging (cranial ultrasound, CT scan, or MRI) according to the
criteria of Papile et al. with the most severe grade of hemorrhage recorded. (11). The
outcome of IVH was recorded as (0) no IVH, (1) grade 1 IVH – subependymal germinal
matrix hemorrhage only (2) grade 2 IVH – intraventricular blood with no ventricular dilation
(3) grade 3 IVH – intraventricular blood with ventricular dilation, and (4) grade 4 IVH –
intraparenchymal hemorrhage. For this analysis, we looked at IVH as a binary outcome in
two ways: 1. Grades 3 and 4 were combined and defined as an infant having severe IVH and
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Grades 1 to 4 were combined into a category of having any IVH.

Variable of Interest: Exposure to antenatal steroids was classified as “yes / no” with any
maternal receipt of betamethasone, dexamethasone, and hydrocortisone during pregnancy at
any time point prior to delivery counting as “yes”. Other independent variables: birth weight,
gestational age, small for gestational age, maternal age, race / ethnicity, prenatal care (any
prenatal care visit vs none), multiple gestation, five-minute Apgar score, delivery mode,
congenital malformations, and hospital level of neonatal care.

Hospital level of neonatal care was designated by the California Children’s Services (CCS)
for NICUs according to their ability to provide varying levels of care. Regional NICUs are
able to provide the most complex medical and surgical care. Community NICUs can provide
unlimited ventilation, but in general, not major neonatal surgery. Intermediate NICUs
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provide care for those infants who do not need assisted ventilation. Hospitals with licensed
NICU beds that do not choose to participate in the CCS program do not receive a CCS level
designation and are classified as non-CCS hospitals.

Hispanic ethnicity with unknown, missing, or other race was considered to be Hispanic
race / ethnicity. Infants below the 10th percentile of weight for their gestational age were
classified as being small for gestational age while those above the 10th percentile were
classified as normal for gestational age. Details for other variables are available in the
9
CPQCC manual of definitions.

Statistical Analysis
The outcomes of IVH were compared according to demographic and medical factors noted
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above. Because grades 3 and 4 are more commonly associated with adverse long-term
neurological consequences, we examined two main outcomes: 1) severe IVH vs. lower
grades of IVH / no IVH, and 2) any grade of IVH vs. no IVH (13). We conducted univariate
analyses to compare infants exposed to antenatal steroids to infants not exposed to antenatal
steroids and to compare infants who developed any or severe IVH to infants who did not
develop any or severe IVH. We conducted a similar comparison for the outcome of in-
hospital mortality, as death may be a competing outcome for severe IVH.

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To test for differences amongst groups, we used the independent t-test for continuous
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variables and the Pearson chi-square test for categorical variables. Tests were two-sided. A
p-value of < 0.05 was considered statistically significant.

Multivariable logistic regression was used to estimate the odds ratio with 95% confidence
intervals as a measure of association between antenatal steroid use and intraventricular
hemorrhage in VLBW infants. We included relevant covariates in our multivariable model to
control for the potential confounding effects of maternal sociodemographic factors, obstetric
factors, and comorbid conditions. These covariates were chosen a priori based on a review of
the existing literature and included all of the variables listed above in the Measures section.

Although birth weight and gestational age of the infant are highly correlated with each other
(r = 0.77), we employed both variables as covariates in our statistical models. We performed
likelihood ratio tests to compare the fit of models that included only birth weight as a
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covariate to the fit of models that included both birth weight and gestational age as
covariates. We found a statistically significant difference between the log likelihoods of the
two models, indicating the models with both birth weight and gestational age included as
covariates fit the data significantly better. We tested the goodness-of-fit of our final models
with the Hosmer-Lemeshow test, which indicated that the final model fit the data optimally.

We did not include gestational age as a covariate in the analyses in which we stratified the
cohort by gestational age. We stratified infants by one week gestational age intervals,
ranging from 22 weeks to 32 weeks. There were six infants under 22 weeks gestational age
that were included with 22 weeks and combined to form one gestational age group.

All data management and analysis was performed using SAS 9.4 for Windows (Cary, NC).
Institutional review board approval was obtained from the Stanford School of Medicine and
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the University of California, Berkeley.

Results
Patient Characteristics
Sociodemographic and obstetric characteristics of infants and mothers are presented in Table
1. Of the infants in the study cohort, most were delivered through Cesarean section (n =
19,464, 74.9%) vs vaginal delivery (n = 6,514, 25.1%). Neonates were primarily cared for at
regional (n = 7,145, 27.5%) and community (n = 16,651, 64.1%) NICUs rather than
intermediate (n = 856, 3.3%) and non-CCS (n = 1,327, 5.1%) NICUs. The mean birth
weight in the cohort was 1050.6 grams, and mean gestational age 27.9 weeks. A large
majority of these infants’ mothers had received prenatal care (n = 25,119, 97.0%).
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Trends of Antenatal Steroid Use throughout the Study Period

During the study interval, 87.2% (n = 22,645) of the women in the analytic cohort delivering
a VLBW infant received antenatal steroids prior to delivery. During the seven year study
period, the use of antenatal steroids gradually increased each year. In 2007, the first year of
the study period, 84.6% of infants’ mothers received treatment with antenatal steroids. In
2013, 89.9% of mothers received antenatal steroids.

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Trends in the Incidence of Intraventricular Hemorrhage During the Study Period

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Of the VLBW infants, 23.7% (n = 6,165) developed any IVH. Among infants with any IVH,
31.6% had severe IVH. Overall, the incidence of any grade of IVH decreased from 25.2% to
22.4% over the seven year study period. The incidence of severe IVH decreased from 8.3%
in 2007 to 7.0% in 2013.

Association Between Antenatal Steroid Use and Intraventricular Hemorrhage

Not receiving antenatal steroids was associated with both any IVH and severe IVH (Table 2).
Infants with any IVH were more likely to have lower birthweight and younger gestational
age. No prenatal care, singleton gestation (compared to multiple), vaginal delivery, low
Apgar score, and male sex were associated with any IVH. Similarly, lower birthweight and
younger gestational age were associated with higher likelihood of severe IVH (Table 2). No
prenatal care, low Apgar score, and male sex were also associated with severe IVH.
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Figure 1 shows the distribution of IVH grade by receipt of antenatal steroids. The most
prominent difference was the higher likelihood of grade 4 IVH in infants whose mothers did
not receive antenatal steroids (8.9%) compared to those who did receive steroids (3.6%).

After adjusting for maternal sociodemographic and medical risk factors in multivariable
logistic regression, receiving antenatal steroids was significantly associated with no IVH
(adjusted odds ratio 0.68, 95% confidence interval 0.62, 0.75), and with not having severe
IVH (adjusted odds ratio 0.51, 95% confidence interval 0.45, 0.58)

Stratified Analysis by Gestational Age

Adjusted odds ratios and 95% confidence intervals for the association between receipt of
antenatal steroids and any IVH within gestational age subsets are shown in Table 3. Infants
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in gestational age groups encompassing 20 0/7 weeks to 29 6/7 weeks whose mothers
received antenatal steroids had a significantly lower odds of developing any IVH, and groups
encompassing 23 0/7 weeks to 29 6/7 weeks had lower odds of developing severe IVH. For
infants above 30 weeks gestational age, there was not a significant reduction in IVH seen.
As mortality may be a competing outcome for severe IVH, we examined mortality rates
according to receipt of antenatal steroids and found that across all gestational age groups,
those infants whose mothers received antenatal steroids had lower risk of in-hospital death.

Discussion
This large population-based study affirms current scientific knowledge showing a significant
relationship between receipt of antenatal steroids and decreased risk of IVH. Both in crude
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assessment and risk adjusted analyses, infants exposed to antenatal steroids were less likely
to develop any IVH or severe IVH. Adding to prior knowledge however, we found that the
association between ANS use and IVH is limited to gestational age groups from 22 to 30
weeks.

Prior studies have shown that exposure to antenatal steroids was associated with a decrease
in the risk of IVH in neonates born between 29-34 weeks gestational age when examined as
8
an overall combined cohort. While our stratified analysis showed no significant differences

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in infants > 30 weeks gestational age, this is likely in part due to the overall lower risk of
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IVH in this group, which has continued to decrease over time.

Overall though, our findings are consistent with previous studies on historic cohorts.
Shankaran et al. reported an unadjusted odds ratio of 0.39 (95% CI: 0.27, 0.57) for the
association of a complete course of steroids with the development of grades 3 and 4 IVH in
10
a large cohort of singleton VLBW infants (i.e. birthweight 501-1500 g). Wright et al.
examined the association between partial, complete, and any course of antenatal steroids and
the outcomes of any or severe IVH in 9,949 VLBW infants in 14 NICUs with diverse
populations and management strategies. Receipt of complete or any antenatal steroid
treatment was found to be associated with a statistically significant reduction in the risk of
10
IVH (any IVH or severe IVH). A meta-analysis of placebo-controlled randomized trials by
Crowley et al. found that steroid therapy reduces the odds of periventricular hemorrhage,
11
with an odds ratio of 0.38 (95% CI: 0.23, 0.94). The evidence from these studies led the
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NIH Consensus Development Panel to publish a statement that antenatal steroids reduce
mortality and the incidence of IVH in infants born at 29-34 weeks of gestation and
recommended that mothers at risk for preterm delivery between 24-34 weeks gestation be
12
candidates for treatment.

Previous data concerning the association between use of antenatal steroids and the incidence
of IVH in infants delivered at <29 weeks gestational age had been conflicting. A systematic
review of 21 studies by Roberts et al. reported that antenatal steroids reduce the incidence of
8
IVH in infants born before 28 weeks. In contrast, a systematic review of nine randomized
trials by Onland et al. concluded that there was no evidence to support or refute
recommending treatment with antenatal steroids to women at risk of preterm birth at <26
13
weeks of gestation. Since these reviews were published, Mori et al. found that exposure to
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antenatal steroids was associated with a significant decrease in the risk of IVH and severe
14
IVH incidence in infants born between 24-29 weeks of gestational age. Similarly, a
retrospective cohort study in Australia by Wong et al. found a significantly lower incidence
of severe IVH in infants of 24-28 weeks of gestational age who received a complete course
15
of antenatal steroids. Our findings are consistent with these more recent cohort studies.

Studies on this question in infants born at ≤24 weeks of gestational age are scarce. In a study
of 117 neonates, Abbasi et al. reported that mothers of infants < 24 weeks of gestational age
given antenatal steroids had a significantly lower incidence of grade 3 and 4 IVH (16.7%
16
versus 36%, p < 0.05, relative risk = 0.46). However, Hayes et al. found that in neonates
born at 23 weeks gestation, the occurrence of severe IVH in infants exposed to antenatal
steroids was not significantly different compared to the occurrence of IVH in infants not
17
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exposed to antenatal steroids (23.1% compared with 57.1%, p = 0.17). The odds ratio for
the association between antenatal steroids and the outcomes of IVH and severe IVH found
14
by Mori et al. in infants 22-23 weeks gestational age was also found to be not significant.
Due to our large sample size, we were able to detect significant differences even at these
youngest gestational age groups.

Our study is limited in its observational nature, and therefore causal inference cannot be
assumed. Although we attempted to account for confounding factors, there may be potential

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confounding from unobserved variables. A limitation of our study was lack of detailed
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information in our dataset on antenatal steroids, including full, partial, or repeated courses,
and dosage or timing. Another limitation of our study was a lack of imaging data on 5,102
VLBW infants that were excluded from our analyses due to missing information on whether
or not the infant developed IVH. This could result in selection bias that could influence the
estimate in either direction. Some infants may have not received a head ultrasound because
they were very healthy and were not assessed to have risk. Others may not have had a head
ultrasound due to very severe clinical status and subsequent death prior to ability to receive
an ultrasound. However, in either case, we would not expect antenatal steroids to cause bias
in either direction. Characteristics of infants with missing data on antenatal steroids or IVH
status are presented in Table S2. These patients tended to have lower birth weight and
gestational age, and more likely to have been delivered vaginally.
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Conclusion
We confirm the association between antenatal steroids and decreased risk of IVH. Our study
goes further to demonstrate an association between antenatal steroids and decreased IVH in
infants of gestational age ranging from 22-29 weeks. Currently the NIH recommends
mothers at risk of preterm birth at 24-34 weeks gestational age be treated with antenatal
steroids. Our analysis suggest that antenatal steroids could be beneficial in reduction of IVH
incidence in infants < 24 weeks gestational age, and mothers at risk for preterm birth at 22
or 23 weeks gestational age may also be good candidates for treatment with antenatal
steroids.

Supplementary Material
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Refer to Web version on PubMed Central for supplementary material.

Acknowledgements
The project was supported by grant number K23HD068400, Eunice Kennedy Shriver National Institute of Child
Health & Human Development (NICHD). The content is solely the responsibility of the authors and does not
necessarily represent the official views of the Eunice Kennedy Shriver NICHD, or NIH.

Financial Disclosure: This project was funded by grant number K23HD068400, Eunice Kennedy Shriver National
Institute of Child Health & Human Development (NICHD). Dr. Profit’s effort was supported in part by a grant from
NICHD 1 R01 HD083368-01A1 (PI Profit).

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Figure 1.
Distribution of intraventricular hemorrhage grade by receipt of antenatal steroids
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Table 1

Maternal, infant, and delivery characteristics, California Perinatal Quality Care Collaborative, Stanford, CA,
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2007-2013

Mean Standard
deviation
Birth weight 1050.6 282.6
Gestational age 27.9 2.4
Maternal age 29.5 6.8

N (%)

Antenatal Steroids
Yes 22645 (87.2)
No 3334 (12.8)
Intraventricular Hemorrhage
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None 19814 (76.3)

Grade 1 2898 (11.2)
Grade 2 1317 (5.1)
Grade 3 850 (3.3)
Grade 4 1100 (4.2)
Maternal race / ethnicity
Black 3667 (14.2)
Hispanic 11278 (43.8)
Non-Hispanic White 6954 (27.0)
Asian/Pacific Islander 3175 (12.3)
American Indian or Alaska Native 160 (0.6)
Other 512 (2.0)
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Prenatal Care
Yes 25119 (97.0)
No 778 (3.0)
Multiple gestation
Singleton 18777 (72.3)
Multiple 7201 (27.7)
Mode of delivery
Vaginal 6514 (25.1)
Cesarean 19464 (74.9)
Neonatal unit level
Regional 7145 (27.5)
Community 16651 (64.1)
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Intermediate 856 (3.3)

Non-CCS 1327 (5.1)
Congenital malformation
Yes 2397 (9.2)
No 23571 (90.8)

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Mean Standard
deviation
Small for gestational age
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Yes 3224 (12.4)

No 22752 (87.6)
Apgar score – 5 minute
0-3 1187 (4.6)
4-6 4330 (16.7)
7-10 20417 (78.7)
Sex
Male 13343 (51.4)
Female 12632 (48.6)

(N) number of records were missing for the following variables: gestational age (3), maternal age (14), maternal race / ethnicity (233), prenatal care
(82), multiple gestation (1), mode of delivery (1), congenital malformation (11), small for gestational age (11), Apgar score (45), sex (4)
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Table 2

Characteristics of infants with any intraventricular hemorrhage or severe intraventricular hemorrhage

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No Intraventricular Grade 3, 4
intraventricular Hemorrhage Intraventricular
hemorrhage (Any Grade) Hemorrhage
n = 19,814 n = 6,165 n = 1,950
(76.3%) (23.7%) (7.5%)
Antenatal steroids, n (%)
Yes 17,548 (77.5%) 5,097 (22.5%) 1,473 (6.5%)
No 2,266 (68.0%) 1,068 (32.0%) 477 (14.3%)

Birthweight (mean ± SD) 1,087.8 ± 270.8 930.9 ± 286.3 821.0 ± 248.9

Gestational age (mean ± SD) 28.3 ± 2.3 26.6 ± 2.5 25.4 ± 2.0
Maternal age (mean ± SD) 29.7 ± 6.8 29.0 ± 6.9 28.6 ± 6.9
Maternal Race, n (%)
Black 2,708 (73.8%)
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959 (26.2%) 327 (8.9%)

Hispanic 8,514 (75.6%) 2,754 (24.4%) 944 (8.4%)
Non-Hispanic White 5,420 (77.9%) 1,534 (22.1%) 454 (6.5%)
Asian/Pacific Islander 2,459 (77.4%) 716 (22.6%) 161 (5.1%)
American Indian or Alaska Native 133 (83.1%) 27 (16.9%) 7 (4.4%)
Other 402 (78.5%) 110 (21.5%) 34 (6.6%)
Prenatal Care, n (%)
Yes 19,206 (76.5%) 5,913 (23.5%) 1,842 (7.3%)
No 546 (70.2%) 232 (29.8%) 101 (13.0%)
Multiple births or gestation, n (%)
Singleton 14,193 (75.6%) 4,584 (24.4%) 1,417 (7.5%)
Multiple 5,620 (78.0%) 1,581 (22.0%) 533 (7.4%)
Mode of delivery, n (%)
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Vaginal 4,442 (68.2%) 2,072 (31.8%) 657 (10.1%)

Cesarean 15,372 (79.0%) 4,092 (21.0%) 1,293 (6.6%)
Neonatal unit level, n (%)
Regional 5,220 (73.1%) 1,925 (26.9%) 570 (8.0%)
Community 12,760 (76.6%) 3,891 (23.4%) 1,280 (7.7%)
Intermediate 724 (84.6%) 132 (15.4%) 33 (3.9%)
Non-CCS 1,110 (83.6%) 217 (16.4%) 67 (5.0%)
Congenital malformation, n (%)
Yes 1,762 (73.5%) 635 (26.5%) 207 (8.6%)
No 18,043 (76.5%) 5,528 (23.5%) 1,741 (7.4%)
Small for gestational age, n (%)
Yes 2,704 (83.9%) 520 (16.1%) 98 (3.0%)
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No 17,107 (75.2%) 5,645 (24.8%) 1,852 (8.1%)

Apgar score – 5 minute, n (%)
0-3 634 (53.4%) 553 (46.6%) 280 (23.6%)
4-6 2,719 (62.8%) 1,611 (37.2%) 671 (15.5%)

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 Wei et al. Page 13

No Intraventricular Grade 3, 4
intraventricular Hemorrhage Intraventricular
hemorrhage (Any Grade) Hemorrhage
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n = 19,814 n = 6,165 n = 1,950

(76.3%) (23.7%) (7.5%)
7-10 16,434 (80.5%) 3,983 (19.5%) 991 (4.9%)
Sex, n (%)
Male 9,919 (74.3%) 3,424 (25.7%) 1,127 (8.4%)
Female 9,891 (78.3%) 2,741 (21.7%) 823 (6.5%)

Numbers in bold indicate increased risk, p < 0.05 – any intraventricular hemorrhage compared to no intraventricular hemorrhage, and grade 3, 4
intraventricular hemorrhage compared to no or grade 1, 2 intraventricular hemorrhage.
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 Wei et al. Page 14

Table 3

Adjusted risk of any intraventricular hemorrhage stratified by gestational age according to antenatal steroid
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administration

Adjusted OR for Adjusted OR for

Gestational age Total Any IVH antenatal steroids Severe IVH antenatal steroids
(Weeks) n n (95% CI) n (95% CI)
Any IVH Severe IVH
<= 22 6/7 123 81 0.23 (0.09, 0.63)* 50 0.54 (0.23, 1.30)

23 0/7 – 23 6/7 809 483 0.66 (0.47, 0.92)* 260 0.55 (0.39, 0.77)*
24 0/7 – 24 6/7 1884 923 0.58 (0.43, 0.77)* 461 0.47 (0.35, 0.63)*
25 0/7 – 25 6/7 2256 884 0.58 (0.44, 0.76)* 344 0.50 (0.36, 0.69)*
26 0/7 – 26 6/7 2663 818 0.70 (0.54, 0.91)* 281 0.52 (0.37, 0.74)*
27 0/7 – 27 6/7 3073 787 0.73 (0.57, 0.94)* 236 0.54 (0.38, 0.78)*
28 0/7 – 28 6/7 3603 687 0.65 (0.51, 0.84)* 156 0.47 (0.31, 0.72)*
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29 0/7 – 29 6/7 3903 639 0.67 (0.52, 0.86)* 91 0.31 (0.19, 0.51)*
30 0/7 – 30 6/7 3543 425 0.74 (0.55, 1.00) 35 0.47 (0.22, 1.05)
31 0/7 – 31 6/7 2494 273 1.14 (0.75, 1.72) 25 0.86 (0.28, 2.66)
32 0/7 – 32 6/7 1625 165 0.75 (0.48, 1.15) 11 0.49 (0.11, 2.10)

Any intraventricular hemorrhage (IVH) indicates grades 1-4; severe IVH indicates grades 3 and 4. Odds ratios (ORs) are adjusted for maternal
socio-demographic and medical risk factors as noted in Methods, with corresponding 95% confidence intervals (Cis).
*
p < 0.05
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J Perinatol. Author manuscript; available in PMC 2016 September 24.