The Journal of Maternal-Fetal and Neonatal Medicine, May 2010; 23(5): 389392

Early-onset preeclampsia and neonatal outcomes

ANGIE C. JELIN1, YVONNE W. CHENG1, BRIAN L. SHAFFER1, ANJALI J. KAIMAL1, SARAH E. LITTLE2, &
AARON B. CAUGHEY1
1
Division of Perinatal Medicine and Genetics, Department of Obstetrics, Gynecology and Reproductive Sciences, University of
California, San Francisco, USA, and 2Brigham and Womens Hospital, Massachusetts General Hospital, Boston, Massachusetts,
USA
(Received 26 March 2009; revised 23 June 2009; accepted 2 July 2009)
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Abstract
Objective. To evaluate the neonatal outcomes of infants delivered to mothers with early-onset preeclampsia.
Study design. This is a retrospective cohort of 1709 infants delivered at 24 0/7 to 29 6/7 weeks gestation was examined.
Neonatal outcomes of 235 infants delivered prematurely because of preeclampsia were compared with 1474 infants delivered
preterm because of other etiologies. Primary outcomes examined included: small for gestational age (SGA), respiratory
distress syndrome (RDS), and neonatal death (NND). Multivariable logistic regression was used to analyze the association
between preeclampsia and the neonatal outcomes, controlling for potential confounders.
Results. Infants of women with preeclampsia were more likely to be SGA (17.8% vs. 5.6%, AOR 3.9, CI 2.56.2) and have
RDS (70.6% vs. 60.7%, AOR 1.5, 95% CI 1.12.2); however, they were less likely to suffer a NND (11.1% vs. 18.1%, AOR
0.6, 95% CI 0.40.9).
Conclusion. Compared with neonates delivered prematurely because of other etiologies, neonates born to preeclamptic
For personal use only.

mothers were more likely to be SGA and have RDS, but had a decrease in mortality. This may be a reflection of the
differences in the underlying pathophysiology behind indicated preterm birth due to preeclampsia.

Keywords: Early-onset preeclampsia, neonatal outcomes, preterm delivery

Introduction specific gestational-age based risks of either continuing or

The rate of preterm delivery in the United States, 1213%,
is higher than in other developed countries [1]. Preventa-
tive efforts to combat the rate of preterm delivery in the
United States have generally focused on the overall
incidence of preterm delivery without taking into account
the distinct pathophysiology leading to delivery in specific
subpopulations [2]. The percentage of preterm deliveries
for medical indications is rising at a steeper rate than
deliveries for other indications [3]. Medically indicated
deliveries may decrease both maternal and neonatal
mortality, this should be taken into account when
considering strategies to reduce the incidence of preterm
birth [4].
Early-onset preeclampsia, a medical indication for
preterm birth, poses a management dilemma. Abundant
research has failed to adequately prevent, predict, or treat
this progressive condition and delivery remains the only
cure [5]. Management decisions are driven by severity of
disease measured by both maternal and fetal status.
Randomized controlled trials indicate neonates benefit
from expectant management of mild preeclampsia up to 37
weeks [6] and severe preeclampsia up to 3234 weeks
[7,8]. Indications for delivery prior to these thresholds have
been suggested, but no clear consensus has emerged
[9,10]. As such, management decisions are based upon the
delivering the pregnancy.
The neonatal outcomes of infants born to mothers with
preeclampsia may differ from those born to nonpreeclamp-
tic women, adding to the complexity of weighing the
maternal and fetal consequences for delivery [11]. In-
formation regarding neonatal outcomes may be helpful to
optimize management and to help elucidate differences in
the intrauterine environment in preterm pregnancies of
varying etiologies. This study examines the neonatal
outcomes of infants born to mothers with early-onset
preeclampsia compared with other etiologies for preterm
birth.
Methods
This is a retrospective cohort of preterm infants (24 0/7
to 29 6/7 weeks of gestation) delivered at the University
of California San Francisco. Infants delivered with
congenital abnormalities were excluded. The primary
predictor of interest was preeclampsia at the time of
delivery. The institutional definition for mild preeclamp-
sia is either systolic blood pressure 4140 mmHg or
diastolic blood pressure 490 mmHg on two readings at
least 6 h apart along with a 24 h urine collection of
4300 mg protein.

Correspondence: Aaron B. Caughey, Department of Obstetrics and Gynecology, University of California, San Francisco, 505 Parnassus Avenue, Box 0132, San
Francisco, CA 94143, USA. Tel: 650-829-1920 (H), 415-719-4301 (P). E-mail: abcmd@berkeley.edu
This work was previously presented as a poster (abstract #0473) at the annual meeting for Society of Maternal Fetal Medicine, Dallas, TX on February 1, 2008.
ISSN 1476-7058 print/ISSN 1476-4954 online 2010 Informa UK Ltd.
DOI: 10.3109/14767050903168416
 390 A. C. Jelin et al.

Institutional guidelines for management of preeclampsia
include expectant management of mild preeclampsia
before 37 weeks and severe preeclampsia before 34 weeks
gestation if stable. Guidelines for delivery in the period
under examination (19802001) differed by attending and
include, but are not limited to doubling of liver enzymes,
HELLP syndrome, severe range blood pressures un-
controllable with two agents, unrelenting headache or
epigastric pain, pulmonary edema, acute renal failure,
DIC, thrombocytopenia, non-reassuring fetal status, or
IUGR with reversed diastolic flow in umbilical artery
Dopplers.
Maternal and neonatal outcomes were analyzed using
Stata v.9 (Stata Corporation, College Station, TX). Out-
comes for preeclamptic mothers and their infants were
compared with mothers without preeclampsia and infants
delivered preterm for other indications. The outcomes
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CI 2.56.2), and RDS (aOR 1.5, 95% CI 1.12.2), but
decreased risk of NND (aOR 0.6, 95% CI 0.40.9; Table
II). After controlling for mode of delivery, the infants
delivered to mothers with preeclampsia were still at
increased risk for SGA (aOR 4.2, 95% CI 2.67.0) and
decreased risk for NND (aOR 0.6, 95% CI 0.30.9).
However, these infants were no longer at a statistically
significant increased risk for RDS (aOR 1.3, 95% 0.91.9;
Table II).
The risk of NND was further evaluated by gestational
age. Although not statistically significant, infants delivered
to mothers with preeclampsia had a lower likelihood
of NND in each gestational age group. In the 24 0/7 and
25 0/7 gestational age group, NND was 18.4% in infants
delivered to mothers with preeclampsia compared with
30.3% for deliveries because of other etiologies. In
the remaining gestational age groups 26 0/7 to 27 0/7

analyzed included: neonatal death (NND), small for and 28 0/7 to 29 0/7 NND rates were lower in pregnancies
gestational age (SGA), respiratory distress syndrome complicated by preeclampsia compared with other etiolo-
(RDS), acidemia, necrotizing enterocolitis (NEC), intra- gies: 12.5% vs. 17.1% and 8.0% vs. 10.1%, respectively
cerebral hemorrhage, and jaundice. (Table III).
Dichotomous outcomes were compared with the w2
test followed by multivariable logistic regression analysis
to control for potential confounders. Covariates included
in the multivariable regression models were maternal age,
race/ethnicity, parity, insurance status, gestational age at Table II. Neonatal outcomes.
delivery, year of delivery, betamethasone administration,
and birth weight. An additional multivariable logistic OR (95%) CI P-value
regression analysis was performed to control for mode of
delivery as an additional confounder. A P-value 50.05 Multivariable regression*
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was considered statistically significant. Jaundice 0.93 0.661.31 0.66

NEC 0.57 0.231.40 0.22
SGA{ 3.94 2.516.18 50.001
Neonatal death 0.61 0.370.99 0.049
Results Acidemia 2.07 0.984.35 0.055
The cohort included 1709 births meeting study criteria for RDS 1.54 1.072.23 0.021
analysis; a total of 235 (14%) of these women carried a ICH 0.90 0.611.34 0.18
diagnosis of preeclampsia. Infants born to mothers with Multivariable regression controlling for mode of delivery{
preeclampsia had a significantly increased incidence of Jaundice 0.90 0.641.28 0.58
SGA (17.8% vs. 5.6%, P 5 0.001) and RDS (70.6% vs. NEC 0.53 0.221.31 0.17
60.7%. P 0.004), but NND (11.1% vs.18.1%, P 0.008) SGAx 4.19 2.626.69 50.001
was significantly lower for these infants (Table I). There Neonatal death 0.55 0.330.90 0.018
was a trend toward an increased rate of acidemia. There Acidemia 1.99 0.934.26 0.075
were no significant differences in NEC, intracerebral RDS 1.28 0.881.87 0.198
hemorrhage, or jaundice. ICH 0.91 0.611.35 0.64
Multivariable logistic regression analysis was preformed
to control for potential confounders. After controlling for *Controlling for fetal birth weight, steroid administration,
confounding factors aside from mode of delivery, the maternal race/ethnicity, parity, year of delivery, maternal age,
infants delivered after pregnancies complicated by pre- and gestational age at delivery.
{
eclampsia remained at higher risk for SGA (aOR 3.9, 95% Not controlled for birth weight.
{
Controlling for fetal birth weight, steroid administration, mater-
nal race/ethnicity, parity, year of delivery, maternal age, mode of
delivery, and gestational age at delivery.
Table I. Neonatal outcomes: preeclampsia compared with other x
Not controlled for birth weight.
preterm deliveries.

Other preterm
Preeclampsia delivery
(n 235) (n 1474) Table III. Neonatal death stratified by gestational age: preeclamp-
(13.8%) (86.2%) w2 P-value sia compared with other preterm deliveries.

Jaundice 34.87 36.60 0.26 0.61 Other

NEC 2.55 4.68 2.19 0.14 Gestational preterm
SGA 17.83 5.63 43.67 50.001 age (weeks) Preeclampsia delivery w2 P-value
Neonatal death 11.06 18.05 6.98 0.008
Acidemia 9.09 5.52 2.69 0.10 2425 (n 453) 18.4% 30.4% 2.39 0.12
RDS 70.64 60.72 8.47 0.004 2627 (n 539) 12.5% 17.1% 0.97 0.33
ICH 19.57 20.56 0.12 0.73 2829 (n 717) 8.0% 10.1% 0.53 0.47

Comment
The inverse relationship between neonatal morbidity and
gestational age at delivery [12,13] makes preterm birth the
greatest contributor to both neonatal morbidity and
mortality. Preterm delivery due to early-onset preeclampsia
is iatrogenic and, thus, differs in etiology from spontaneous
preterm birth. Currently, expectant management is the only
means to prolong gestational age. Until further prevention
or treatment of preeclampsia become available, both
maternal and fetal morbidity and mortality may occur in
absence of delivery. This study demonstrates that neonate
outcomes in pregnancies complicated by preeclampsia differ
from outcomes in pregnancies delivered because of other
etiologies: these neonates have an increased risk of SGA and
RDS, but decreased risk for neonatal mortality.
The 17.8% increased rate of SGA in the infants
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by CDL-UC Davis on 11/21/14
delivered to mothers with preeclampsia compared with
5.6% in other infants is consistent with previous studies
[14]. Placental insufficiency due to preeclampsia likely
inhibits fetal growth leading to SGA and/or intrauterine
growth restriction (IUGR). The degree of IUGR is often
inversely proportional to gestational age [15,16]. Despite
evidence suggesting that preterm induction of labor in the
setting of growth restriction does not improve neonatal
outcomes [14,15], IUGR may have been a contributing
indication to deliver these infants at an earlier gestational
age [17]. IUGR is a marker of chronic placental
insufficiency associated with markers of acute deteriorat-
ing neonatal status such as a non-reassuring fetal heart
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rate or abnormal biophysical profile [14]. In the absence
of these more acute markers, its utilization in the decision
to proceed with an induction of labor is controversial
[18]. The presence of SGA in the cohort of neonates
delivered secondary to preeclampsia was not associated
with increased mortality in this study.
Infants delivered to mothers with preeclampsia were
more likely to experience RDS, with 70.6% of infants
affected vs. 60.7% in the control group. Historically, it was
believed that infants delivered under preeclamptic condi-
tions exhibited a stress response, expediting lung develop-
ment, and decreasing the rate of RDS [19]. Recent studies
have refuted this notion [20]. Our study demonstrates that
the increased risk of RDS is at least partially related to the
higher frequency of cesarean delivery after a medically
indicated induction of labor in women with preeclampsia.
This finding is supported by the multivariable analysis
suggesting that these infants are no longer at a statistically
significant increased risk for RDS after controlling for
mode of delivery [21]. A decreased rate of NND observed
in pregnancies complicated by preeclampsia, 11% vs. 18%
in the control group, refutes previous studies that demon-
strated no survival advantage [19,22]. In 1990, Odendaal
reported a decrease in neonatal mortality from 25% to 11%
with expectant management between 28 and 34 weeks, the
same as that experienced in our cohort of a lower
gestational age, but greatly improved from the 20%
mortality rate described in 1989 by Derham et al. [13] in
infants delivered between 26 and 30 weeks gestational age.
Likely, with improved neonatal care, infants survive at
earlier gestational ages; additionally, expectant manage-
ment of preeclampsia further reduces neonatal mortality.
This is supported by the trending decrease in mortality
found in the subgroup analysis by gestational age. The
decrease in NND in the study cohort is incongruent with
the increased rate of SGA and RDS. Unexplained by the
pathophysiology of preeclampsia, this may be attributed
to the etiologies of preterm delivery in the control group.
Preeclampsia outcomes 391
Preterm premature rupture of membranes carries the
highest neonatal morbidity of all etiologies of preterm
labor, increasing the neonatal mortality of the control
group when compared with the infants delivered for
preeclampsia indications [23].
There are several limitations to our study. The study
design is retrospective and nonrandomized, thus is prone
to confounding. Although many confounders such as
demographics and ethnicity were controlled for by utiliza-
tion of logistic regression analysis, there may be unmea-
sured confounders which we were unable to take into
account. Further, although expectant management of
preeclampsia is institutionally accepted, specific practice
management may differ by physician; of note patient care
in our institution is subject to weekly intra- and inter-
departmental review for quality assurance which decreases
the likelihood of wide variation in practices. Additionally,
neonatal outcomes were diagnosed by pediatricians and
could be affected by diagnostic bias. For example, RDS
could be over diagnosed in neonates following a delivery
complicated by preeclampsia. However, because the
prevailing wisdom is that RDS may actually be lower in
women with preeclampsia, such a bias would be in the
opposite direction of the findings of our study. It could,
however, be over diagnosed in infants following a cesarean
delivery. Another limitation was the long-time period for
which we included subjects in the study. We did this to
allow for adequate power in the examination of rare
outcomes and the ability to stratify the analyses. Further,
we controlled for year of delivery in the multivariable
analyses and the overall findings persisted.
This study provides information about the neonatal
outcomes following delivery because of early-onset pre-
eclampsia. The information gained is likely applicable to
other tertiary care centers and can be utilized to counsel
women experiencing early preterm births of different
etiologies. Additional studies are needed to further explore
the pathophysiology behind the increases in RDS and SGA
as well as the paradoxical survival advantage of infants born
to mothers with preeclampsia.
Acknowledgment
Aaron B. Caughey is supported by the Robert Wood
Johnson Foundation as a Physician Faculty Scholar.
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