The Impact of Vaginal Delivery in Premature Infants
Weighing Less Than 1,251 Grams
Richard Deulofeut, MD, MPH, Augusto Sola, MD, Ben Lee, MD, MPH, Susie Buchter, MD,
Mostafizur Rahman, MBBS, MPH, and Marta Rogido, MD
OBJECTIVE: To evaluate whether mode of delivery is a
predictor of poor short-term outcome at different birth
Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3aNqwZjvBN0dDTnuyd8pyrnBX5xh/GVwGbrcW4DopSYk= on 02/10/2019
weight categories in very low birth weight infants.
METHODS: This study examined a cohort of infants weigh-
ing less than 1,251 g born at 2 perinatal centers from
January 1, 2000, to December 31, 2003. Outborn infants or
those with major anomalies were excluded from the study.
Outcome variables included death, severe intraventricular
hemorrhage, periventricular leukomalacia (PVL), and
combined poor short-term outcomes (death, severe intra-
ventricular hemorrhage, and PVL).
RESULTS: Of the 397 infants who met enrollment criteria,
44% were born vaginally and 56% by cesarean delivery.
The proportion of multiparous, breech presentation and
prolonged rupture of membranes was significantly differ-
ent between groups. For infants weighing less than 751 g,
the risks of severe intraventricular hemorrhage (41% ver-
sus 22%; odds ratio 关OR兴 2.79, 95% confidence interval 关CI兴
1.08 –7.72) and combined poor short-term outcome (67%
versus 41%; OR 2.95, 95% CI 1.25– 6.95) were significantly
higher if delivered vaginally. Among survivors weighing
less than 751 g, the risk of severe intraventricular hemor-
rhage was higher among those delivered vaginally (24%
versus 9%; OR 8.18, 95% CI 1.58 – 42.20). In infants less
1,251 g who survived, vaginal delivery had a strong associ-
ation with PVL (5% versus 1%; OR 11.53, 95% CI
1.66 –125).
CONCLUSION: In infants less than 1,251 g who survived to
discharge, vaginal delivery is associated with higher risk
for PVL. Furthermore, in infants less than 751 g, vaginal
delivery is a predictor for severe intraventricular hemor-
rhage and combined poor short-term outcome. The nega-
tive impact of vaginal delivery mode decreases as birth
weight category increases. (Obstet Gynecol 2005;105:
525–31. © 2005 by The American College of Obstetri-
cians and Gynecologists.)
LEVEL OF EVIDENCE: II-2
Despite ongoing improvements in perinatal care and
neonatal survival, severe intraventricular hemorrhage
From the Department of Pediatrics, Division of Neonatal–Perinatal Medicine,
Emory University, Atlanta, Georgia.
VOL. 105, NO. 3, MARCH 2005
© 2005 by The American College of Obstetricians and Gynecologists.
Published by Lippincott Williams & Wilkins.
and periventricular leukomalacia (PVL) continue to be
major complications of extreme prematurity, associated
with severe morbidity in the postnatal period. The
pathophysiology of severe intraventricular hemorrhage
and PVL is complex and multifactorial,1 and although
the incidence of these outcomes has gradually decreased
over the last few decades,1,2 the trends in rate reduction
seems to have reached a plateau in recent years.3
Decreased gestational age is a known neonatal risk
factor for severe intraventricular hemorrhage, PVL, and
mortality. In addition, other factors like chorioamnioni-
tis4 and preeclampsia5 have been associated with signif-
icant neonatal morbidity and mortality. The use of ante-
natal steroids is the only perinatal intervention that has
been consistently shown to improve neonatal outcome
and decrease the risk for severe intraventricular hemor-
rhage in premature infants.6
Mode of delivery, specifically cesarean delivery, has
been postulated to have a theoretical advantage over
vaginal delivery in premature infants. This benefit may
be the result of the avoidance of prolonged labor, allow-
ing a less traumatic birth.7 However, how to deliver a
very preterm baby has been a controversial topic in the
obstetric and neonatal community for decades, and de-
livery mode depends on the medical judgment of the
obstetrician. Effective care cannot be based on meta-
analysis of well designed randomized controlled trials
because none of the attempts have come to conclusion.8,9
The question of what delivery mode is less harmful for
the fetus is most relevant in those infants with borderline
viability. Hysterotomy at early gestational age is techni-
cally more difficult, and is more likely to be complicated
with injury to the bladder and uterine artery10 and an
overall increased risk for the mother and the unborn
child in their medical future.11–13
In breech presentation, the cesarean mode of delivery
has been supported by the available evidence in very
preterm gestation.14 –16 However, the optimum mode of
delivery of the early preterm fetus even in breech pre-
sentation is also controversial. Several reports do not
0029-7844/05/$30.00 525
doi:10.1097/01.AOG.0000154156.51578.50
advocate a policy of cesarean delivery for early preterm
breech delivery and do not report associations with
increased survival without disability or handicap.17,18
The literature about the impact of mode of delivery in
extremely premature fetuses in a vertex presentation is
equivocal,19,20 and a prospective randomize approach to
answer this question has been unsuccessful.8 Because of
the conflicting evidence in the literature and major
changes in perinatal practice, we decided to investigate
whether vaginal mode of delivery is associated with
greater risk for poor short-term outcome in premature
infants weighing less than 1,251 g. We hypothesized that
vaginal delivery is a predictor of poor short-term out-
come in infants less than 1,251 g at birth, and that the
negative impact is significant in infants less than 751 g at
birth.
MATERIALS AND METHODS
After receiving institutional review board approval, we
performed a historical cohort study of infants less than
1,251 g born at 2 Emory University perinatal centers,
Grady Memorial Hospital and Emory Crawford Long
Hospital in Atlanta, during the last 4 years (January 1,
2000 to December 31, 2003). This study period was
chosen because there was no temporal trend in cesarean
delivery rates and major perinatal practices. There were
no significant hospital-specific trends observed. The data
were obtained from our existing prospectively recorded
perinatal database. The quality of the data was assured
by review of the infants’ charts when available per-
formed in detail by the first author. A total of 429 records
were retrieved and reviewed; these included the 397
records of infants who met the inclusion criteria. We did
not review the information from maternal records. We
excluded those infants with major congenital anomalies,
outborn infants admitted to our neonatal intensive care
units, and those who received only comfort-care mea-
sures until their demise.
Outcome variables measured included death, severe
intraventricular hemorrhage, PVL, and combined poor
short-term outcome. Severe intraventricular hemor-
rhage was defined as grade III or IV based on Papile’s
classification,21 on cranial ultrasonograms read by a
pediatric radiologist who was unaware of the mode of
delivery. Periventricular leukomalacia was also diag-
nosed in the same way at 1 month of age. Combined
poor short-term outcome was defined as the presence of
death, severe intraventricular hemorrhage, or PVL at
any point during the admission to the neonatal intensive
care unit (NICU). We analyzed these outcomes in the
whole cohort (⬍ 1,251 g), and also on infants who
526 Deulofeut et al Vaginal Delivery and Prematurity
survived to discharge. In both groups, data were also
analyzed by birth weight categories at 250-g intervals.
We recorded neonatal demographics such as birth
weight, gestational age, gender, small for gestational age,
race, and Apgar scores at 1 and 5 minutes of age. We also
collected perinatal variables including the use of antena-
tal steroids, multiple gestation, breech presentation, pro-
longed rupture of membranes, presence of chorioamnio-
nitis, use of magnesium sulfate before delivery, and
delivery room cardiopulmonary resuscitation.
Gestational age was assigned by the best obstetric
estimate (last menstrual period and early fetal ultrasono-
gram, when available). If this information was not avail-
able or if there was significant discrepancy among the
parameters, the modified Ballard examination22 was
used for gestational age as recorded in the admission
physical examination. Small for gestational age was de-
fined as birth weight less than the 10th percentile for the
assigned gestational age. We defined prolonged rupture
of membranes as membranes ruptured for more than 18
hours before the time of birth. Clinical chorioamnionitis
was diagnosed by the obstetrical team and transcribed
into our neonatal database. Delivery room cardiopulmo-
nary resuscitation was defined as the need for chest
compression or epinephrine treatment in the delivery
room.
Demographics were summarized as proportions and
means with standard deviations. Univariate analyses
were performed with the ␹2 for categorical variables,
with Fisher exact test when expected cell counts were less
than five, and t test for continuous variables. Multivari-
able logistic regression models were used to obtain ad-
justed odds ratios (ORs) with 95% confidence intervals
(CIs) comparing outcomes between infants born by vag-
inal delivery and those born by cesarean delivery; only
adjusted ORs are reported. This analysis was done using
the entire cohort (⬍ 1,251 g), the surviving cohort, and
250-g birth weight subgroups for the entire and surviving
cohorts. Variables that were statistically different be-
tween vaginal delivery and cesarean delivery groups in
the entire cohort or in any 250-g subgroup were included
as covariates in the models. Statistical significance was set
at P ⬍ .05. Statistical analyses were performed using SAS
8.02 (SAS Institute Inc, Cary, NC).
RESULTS
A total of 529 infants with a birth weight less than 1,251
g were admitted to the two perinatal centers during the
4-year study period. Of them, 95 infants who were
outborn, 32 infants who received comfort-care measures
only, and 5 infants with major congenital anomalies were
excluded. Therefore, 397 infants met inclusion criteria;
OBSTETRICS & GYNECOLOGY
Table 1. Demographic and Delivery Characteristics of Infants Born Weighing Less Than 1,251 Grams
Vaginal Delivery Cesarean Delivery
Parameter (n ⫽ 175) (n ⫽ 222) P
Birth weight (g)* 916 ⫾ 194 884 ⫾ 172 .029
Gestational age (wk) 27 ⫾ 2.14 27 ⫾ 1.86 .110
Male* 83 (47) 104 (47) .908
Small for gestational age 7 (4) 11 (5) .650
Black 155 (89) 193 (87) .623
White 5 (3) 11 (5) .291
Hispanic 14 (8) 18 (8) .969
Apgar score at 1 min 5 (0–9) 4 (0–9) .120
Apgar score at 5 min 8 (0–9) 8 (1–9) .320
Antenatal steroids* 122 (70) 155 (70) .982
Multiple gestation* 13 (7) 44 (20) .001
Breech presentation* 20 (11) 102 (46) ⬍ .001
Prolonged rupture of membranes* 47 (27) 42 (19) .039
Chorioamnionitis 40 (22) 52 (23) .894
Magnesium sulfate use 92 (53) 110 (50) .550
Delivery room resuscitation 23 (13) 30 (14) .914
Discrete data are presented as n (% of cohort); continuous data are presented as mean ⫾ standard deviation or median (range).
* Variable included in the multivariable logistic regression model.
P ⬍ .05 is considered statistically significant.

175 (44%) of whom were born vaginally and 222 (56%)
of whom were born by cesarean delivery. There was
similar distribution of birth weights and gestational ages
between the two groups, around 900 g and 27 weeks,
respectively. The number of males was equally distrib-
uted, and the use of antenatal steroids, magnesium sul-
fate, and delivery room cardiopulmonary resuscitation
was similar between groups. There were significant dif-
ferences in the presence of multiple gestation, breech
presentation, and prolonged rupture of membranes (Ta-
ble 1). The distribution of birth weight by 250-g catego-
ries was similar between the two groups (Fig. 1).
In this cohort, the outcomes studied were related to
previously described risk factors. In the logistic regres-
sion models, gender was a major risk factor for poor
neonatal outcome in infants less than 1,251 g, regardless

Fig. 1. A cohort of 397 infants met the inclusion criteria and were admitted to the 2 perinatal centers during the 4-year
study period. In each box, the data are presented as numbers of infants, with percentages for each cohort or subcohort.
Deulofeut. Vaginal Delivery and Prematurity. Obstet Gynecol 2005.

VOL. 105, NO. 3, MARCH 2005 Deulofeut et al Vaginal Delivery and Prematurity 527
Table 2. Demographic and Delivery Characteristics of Infants Born Weighing Less Than 751 Grams
Vaginal Delivery Cesarean Delivery
Parameter (n ⫽ 47) (n ⫽ 72) P
Birth weight (g)* 628 ⫾ 61 652 ⫾ 72 .110
Gestational age (wk) 24 ⫾ 1.03 25 ⫾ 1.41 .150
Gestational age range 23–31 23–29 ...
Male* 30 (64) 32 (44) .039
Small for gestational age 5 (11) 10 (14) .811
Birth weight (g)
ⱕ 500 3 (6) 5 (7) .905
501–600 31 (66) 52 (72) .467
601–750 13 (28) 15 (21) .391
Delivery room intubation 46 (98) 69 (96) .546
Antenatal steroid use* 27 (57) 55 (76) .029
Multiple gestation* 5 (11) 9 (12) .467
Breech presentation* 9 (19) 32 (44) .008
Prolonged rupture of membranes* 10 (21) 14 (19) .992
Chorioamnionitis 7 (15) 15 (21) .415
Delivery room resuscitation 12 (26) 14 (19) .932
Death on first day of life 6 (12) 7 (10) .603
Discrete data are presented as n (% of cohort); continuous data are presented as mean ⫾ standard deviation or as a range.
* Variable included in the multivariable logistic regression model.
P ⬍ .05 is considered statistically significant.

of mode of delivery. The combined poor short-term
outcome occurred in 35% of males compared with 19%
of females (P ⫽ .006). For all infants less than 1,251 g in
breech presentation, 40% had combined poor short-term
outcome if born vaginally compared with 29% if born by
cesarean delivery (P ⫽ .24). In multiparous deliveries,
23% developed the combined poor short-term outcome
if born vaginally compared with 18% if born by cesarean
delivery (P ⫽ .17). Breech presentation and multiple
gestation births were associated with increased risk for
poor outcomes by stratification analyses. These factors
were adjusted for by multivariable logistic regression
when analyzing the association of mode of delivery to
poor outcomes in the different cohorts reported. All ORs
reported below are adjusted after logistic regression
analysis.
The analysis of all infants less than 1,251 g who were
studied showed no significant differences between
groups in any of the outcome variables; severe intraven-
tricular hemorrhage occurred in 16% of those born
vaginally and in 15% of those born by cesarean delivery,
and PVL occurred in 5% and 2%, respectively. The pro-
portion for mortality (20% versus 18%) and combined poor
short-term outcome (29% versus 25%) were not different
between groups. Demographics and characteristics of
infants less than 1,251 g are shown in Table 1.
In the subcategory of infants between 1,001 and 1,250
g, 3% of those delivered vaginally developed severe
intraventricular hemorrhage compared with 8% of those
born by cesarean delivery. The proportion for PVL,
mortality, and combined poor short-term outcome was
4% versus 0%, 3% versus 7% and 7% versus 14%,
respectively. None of these trends favoring vaginal de-
livery in this birth weight category were significant after
logistic regression analysis.
Among infants between 751 and 1,000 g, the propor-
tion of severe intraventricular hemorrhage was the same
(15% in both groups). The proportions for PVL (6%
versus 3%), mortality (13% versus 11%), and combined
poor short-term outcome (26% versus 20%) were not
significantly different after regression analysis.
In the subcohort of infants less than 751 g, there were
significant differences in the proportion of severe intra-
ventricular hemorrhage and of combined poor short-
term outcome after multivariable logistic regression anal-
yses. Among infants born vaginally, 41% developed
severe intraventricular hemorrhage compared with 22%
in the cesarean delivery group (OR 2.79, 95% CI 1.08 –
7.72). The combined poor short-term outcome occurred
in 67% of those born by vaginal delivery, compared with
41% among those born by cesarean delivery (OR 2.95,
95% CI 1.25– 6.95). There was a statistically nonsignifi-
cant trend toward an increased risk for PVL (5% versus
3%) and mortality (55% versus 35%) in infants born
vaginally, compared with abdominal delivery. Demo-
graphics and characteristics of this subcohort are shown
in Table 2.
In the analysis of infants who survived to discharge
from the NICU the results were different. Among all
survivors less than 1,251 g, PVL occurred more fre-
quently in those delivered vaginally (5% versus 1%; OR
11.53, 95% CI 1.66 –125). In the tiniest of survivors

528 Deulofeut et al Vaginal Delivery and Prematurity OBSTETRICS & GYNECOLOGY

Table 3. Demographic and Delivery Characteristics of Survivors Weighing Less Than 751 Grams
Vaginal Delivery Cesarean Delivery
Parameter (n ⫽ 21) (n ⫽ 47) P
Birth weight (g)* 655 ⫾ 69 658 ⫾ 79 .850
Gestational age (wk) 25 ⫾ 2.01 26 ⫾ 2.05 .056
Gestational age range 23–31 23–33 ...
Male* 11 (52) 17 (36) .210
Small for gestational age 3 (14) 7 (15) .948
Birth weight (g)
ⱕ 500 1 (5) 1 (2) .553
501–600 3 (14) 12 (26) .301
601–750 17 (81) 34 (72) .449
Delivery room intubation 21 (100) 44 (94) .236
Antenatal steroid use* 14 (67) 37 (79) .289
Multiple gestation* 3 (14) 7 (15) .948
Breech presentation* 3 (14) 19 (40) .033
Prolonged rupture of membranes* 7 (33) 9 (19) .203
Chorioamnionitis 4 (19) 10 (21) .834
Delivery room resuscitation 5 (24) 7 (15) .377
Discrete data are presented as n (% of cohort); continuous data are presented as mean ⫾ standard deviation or as a range.
* Variable included in the multivariable logistic regression model.
P ⬍ .05 is considered statistically significant.

(birth weight ⬍ 751 g), 24% of vaginally delivered infants
had severe intraventricular hemorrhage compared with 9%
in the cesarean delivery group (OR 8.18, 95% CI 1.58 –
42.20). Demographics and characteristics of survivors
weighing less than 751 g are shown in Table 3.
DISCUSSION
The question concerning mode of delivery as a predictor
of poor outcome in premature infants has been difficult
to answer. The limited available data on mode of deliv-
ery in extremely small infants provide conflicting evi-
dence, which has fueled a long-lasting controversy.
There have been attempts to answer this question with
prospective randomized studies. However, none has
been completed due to problems with recruiting of pa-
tients, crossover and ethical considerations.8 To date
there has been no specific prospective randomized trial
exclusively for extreme premature infants to assess the
impact of the mode of delivery.
Despite the lack of evidence to support one delivery
mode over the other, hysterotomy rates have increased
consistently in the last decade in premature deliveries.
Cesarean delivery rate at 23 weeks rose from 15.9% in
1995 to 28.2% in 2002 without major changes in demo-
graphic or obstetric factors.23–24 This trend toward ce-
sarean delivery in premature deliveries may have an
impact in neonatal outcomes, because it is known that
obstetric management influences the outcome of ex-
tremely low birth weight infants. Willingness to inter-
vene apparently results in greater likelihood of intact
survival.25,26 We believe that questioning viability be-
fore delivery might influence the obstetric and neonatal
approach toward these vulnerable infants, dooming
them to a self-fulfilled prophecy of poor neonatal out-
come with less neonatal intervention and exclusion of
cesarean delivery.
This large cohort study was designed a priori to
stratify the impact of mode of delivery at different birth
weight categories and assess mode of delivery as a pre-
dictor of poor outcome in infants less than 1,251 g. We
conducted our analysis based on birth weight because of
the objective nature and reliability of this variable in the
context of a retrospective design. However, the distribu-
tion of small-for-gestational-age infants was similar
among groups, and the results were similar when the
logistic model included gestational age instead of birth
weight. The results show that when the whole cohort is
examined, vaginal delivery is not associated with worse
poor short-term outcome. However, after weight strati-
fication there is a consistent trend of poorer outcomes in
those infants with birth weight equal or less than 1,000 g
when delivered vaginally. These differences become sig-
nificant for the tiniest babies at the borderline of viability.
When born vaginally, the extremely premature infants
(⬍ 751 g) have over 2 times the risk to present severe
intraventricular hemorrhage and combined poor short-
term outcome. Furthermore, the survivors in this small-
est birth weight category had a risk of severe intraven-
tricular hemorrhage about 8 times higher if born
vaginally. Periventricular leukomalacia was the short-
term outcome that was most consistently associated with
vaginal delivery; the differences were statistically signif-

VOL. 105, NO. 3, MARCH 2005 Deulofeut et al Vaginal Delivery and Prematurity 529
icant in infants less than 1,251 g who survived to dis-
charge from the NICU, with 11 times higher risk for
developing PVL.
We acknowledge several limitations to our study. One
of them is the retrospective nature of the design. How-
ever, potential confounding variables were identified
(birth weight, gender, antenatal steroid use, multiple
gestation, breech presentation, and prolonged rupture of
membranes) and statistical adjustment was done in the
logistic regression model. Nevertheless, there might be
other important confounders that we were unable to
control for. In addition, we were not able to separate the
patients according to the duration of labor, but exact
determination of labor duration at this gestational age is
elusive. Chorioamnionitis is a known risk factor for poor
neonatal outcomes. In our study, we relied on clinical
diagnosis transcribed to our neonatal database. Clinical
criteria for the diagnosis of chorioamnionitis are some-
what insensitive and not supported by histologic evi-
dence for infection.27 In a recent study, maternal chorio-
amnionitis by histology was detected in 45% of 101
placentas, but only 33% of these had a diagnosis of
clinical chorioamnionitis.28 In our study, the proportion
of mothers with this diagnosis was somewhat lower, at
22%, with no significant differences observed between
the two groups (Tables 1–3).
The results of this study are different from many
previous reports because others have included larger
infants and have lacked the power to analyze differences
among birth weight categories.20 Different from previ-
ous published studies comparing the impact of mode of
delivery and to remove source of bias, we carefully
identified and excluded from the analysis those infants
labeled as not viable and who received comfort care.
Furthermore, in our study population, the rate of intu-
bations and cardiopulmonary resuscitation in the deliv-
ery room was similar between the two groups of infants
less than 751 g (Table 2). Thus, the variability seen
among the infants at the borderline of viability likely
reflects the impact of mode of delivery and not a less
aggressive prenatal and or postnatal management.
The most feared outcome for the practitioners and
families alike is an infant that survives with very poor
quality of life. White matter injury is an ominous sign in
the premature infant that correlates well with cerebral
palsy and poor neurodevelopmental outcome. Fortu-
nately, PVL incidence in the extremely low birth weight
infant is relatively low, about 6%.29 In our study popu-
lation, the increased rate of PVL in survivors less than
1,251 g delivered vaginally was consistent with results
reported in low birth weight twins delivered vaginally.30
To elucidate the true impact of mode of delivery in
preterm infants, a prospective randomized trial should
530 Deulofeut et al Vaginal Delivery and Prematurity
be conducted; however, this trial is likely to present
challenges with recruitment, crossover, and ethical di-
lemmas. Until more evidence is available, it is not clear if
cesarean delivery is the preferable mode of delivery for
the extreme premature infant. However, in future clini-
cal studies, when other interventions are evaluated, it
may be useful to control for mode of delivery, particu-
larly in the tiniest of infants. Long-term consequences of
the differences found in the current study are being
analyzed in the cohort of survivors who are being seen in
our developmental follow-up program.
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Address reprint requests to: Marta Rogido, MD, 2015 Upper-
gate Drive, Atlanta, GA 30322; e-mail: mrogido@emory.edu.
Received August 6, 2004. Received in revised form November 17, 2004.
Accepted December 2, 2004.
Deulofeut et al Vaginal Delivery and Prematurity 531