Obgyn 1
Obgyn 1
Obgyn 1
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya, Japan
Bell Research Center for Reproductive Health and Center, Nagoya, Japan
Department of Obstetrics and Gynecology, Kasugai Municipal Hospital, Kasugai-shi, Aichi, Japan
d
Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Japan
b
c
a r t i c l e
i n f o
Article history:
Received 13 June 2013
Received in revised form 27 September 2013
Accepted 23 October 2013
Keywords:
Amniotic uid
Lamellar body
Placenta previa
Respiratory distress syndrome
Transient tachypnea of the newborn
a b s t r a c t
Background: Pregnancies with placenta previa are signicantly associated with preterm delivery and cesarean
section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in
pregnancies with placenta previa.
Aims: The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory
disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to
evaluate the impact of placenta previa on the amniotic lamellar body count (LBC) values.
Methods: We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 3638 weeks of gestation. Amniotic uid samples were analyzed immediately without centrifugation,
and the LBC was measured using a platelet channel on the Sysmex XE-2100.
Results: RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was signicantly
higher and the LBC values were signicantly lower in the placenta previa group than in the control group
(P = 0.002 and P = 0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% condence interval:
6.587.88) among females with placenta previa. In placenta previa, warning bleeding was a signicant factor
protecting against neonatal respiratory disorders (P = 0.046).
Conclusions: Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is
performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal
TTN even at 3638 weeks of gestation.
2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
The incidence of placenta previa ranges from 3.5 to 4.6 per 1000
births [1]. Patients with placenta previa are more likely to receive
blood transfusions (12% with versus 0.8% without placenta previa)
and to undergo a postpartum hysterectomy, uterine/iliac artery ligation,
or embolization of the pelvic vessels to control bleeding (2.5% with
placenta previa versus 0% without) [2]. Placenta previa increases the
risk of antepartum (RR 9.8), intrapartum (RR 2.5) and postpartum
hemorrhage (RR 1.9) [3]. For these reasons, pregnancies with placenta
previa are signicantly associated with preterm delivery and have a
higher risk for neonatal morbidity and mortality compared to those
without [4]. A retrospective cohort study revealed that the neonatal
mortality rate was 10.7 per 1000 live births when the mothers had
placenta previa compared to 2.5 per 1000 live births in non-previa
Corresponding author at: Department of Obstetrics and Gynecology, Nagoya
University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Tel.: +81 52 744 2261; fax: +81 52 744 2268.
E-mail address: hiro-t@med.nagoya-u.ac.jp (H. Tsuda).
0378-3782/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.earlhumdev.2013.10.005
pregnancies (RR 4.3; 95% CI 4.04.8) [5]. Because of the high rates of
preterm labor and cesarean section in such cases, particular attention
should be paid to the incidence of neonatal respiratory disorders in
pregnancies with placenta previa.
The lamellar body count (LBC) in the amniotic uid is widely
recognized as an accurate predictor of fetal lung maturity [68]. The
LBC can be determined quickly and inexpensively, making it a more
cost-effective predictor of respiratory distress syndrome (RDS) than
the lecithin/sphingomyelin (L/S) ratio [8,9]. Besides RDS, transient
tachypnea of the newborn (TTN) is also a common cause of respiratory
distress during the rst days of life. TTN has been attributed to delayed
absorption of fetal lung uid and in response to increased concentrations of catecholamines and other hormones during labor, the mature
lung epithelium switches from actively secreting chloride and liquid
to actively reabsorbing sodium and liquid [10]. However, evidence has
accumulated that TTN results from mild abnormality of the surfactant
system such as deciency, dysfunction, or both [11,12]. We recently
reported that the LBC in neonates with TTN was signicantly lower
than that in non-RDS/TTN infants [11], therefore we believe that the
pathogenesis of TTN is more likely that of a mild surfactant abnormality
52
than a delayed absorption of fetal lung uid. The LBC has been reported
to be potentially useful for predicting and distinguishing between RDS
and TTN in singleton pregnancies [11,13].
Previous studies on the neonatal outcome of placenta previa
pregnancies have reported that placenta previa increases the risk for
neonatal RDS [14,15], but these studies were mainly focused on preterm
deliveries. Few studies have focused on this issue in near-term and term
pregnancies. Therefore, in this study, we extracted the pure cesarean
cases without fetal or maternal complications that were delivered at
3638 weeks of gestation, and examined the relationship between
placenta previa and neonatal respiratory disorders, including both RDS
and TTN. Moreover, we measured the amniotic LBC in this study, and
evaluated the impact of placenta previa on the LBC values.
Table 1
Maternal and fetal characteristics.
Before 36 weeks, 63
After 39 weeks, 33
Twin pregnancy, 52
Fetal growth restriction, 17
Fetal abnormality, 60
Maternal diabetes mellitus, 11
Pregnancy-induced hypertension, 12
Placenta previa
(n=35)
No placenta previa
(n=151)
Fig. 1. The algorithm of the inclusion and exclusion of cases in this study. All infants were
delivered by scheduled cesarean section at 3638 weeks of gestation without labor. In the
gure, contaminated indicates blood and/or meconium.
Previa
(n = 35)
Control
(n = 151)
P-value
34.2 (3.9)
15/35 (42.9%)
20/35 (57.1%)
37.2 (0.6)
2735 (246)
8.7 (2.1)
7.30 (0.08)
10/35 (28.6%)
33.0 (4.8)
57/151 (37.7%)
73/151 (48.3%)
37.6 (0.6)
2814 (335)
9.3 (0.6)
7.26 (0.60)
24/151 (15.9%)
0.174
0.576
0.348
0.002
0.122
0.089
0.696
0.080
TTN was signicantly higher in the previa group than in the control
group (20% vs 3.3%; P = 0.002) (Table 2). The LBC values were
signicantly lower in neonates born to mothers with placenta previa
than in control neonates (P = 0.024). The LBC in infants with TTN
(3.60 104/L) was signicantly lower than that in the no RDS/TTN
infants (6.07 104/L) (P = 0.008) (data not shown). In the logistic regression analysis, placenta previa was also a signicant risk factor in the
multivariate model for neonatal TTN after controlling for the maternal
age, gestational age at delivery, neonatal birth weight and infertility
treatment (P = 0.011).
Next, we calculated the OR for neonatal respiratory outcomes
(Table 3), and the risk of neonatal TTN was 7.9-fold greater (OR, 7.86;
95% CI, 2.3226.7) among those with placenta previa. After controlling
for the inuences of gestational age, the neonatal TTN was still 7.2fold greater (adjusted OR, 7.20; 95% CI, 6.587.88, P b 0.001) among
those with placenta previa.
3.3. Age-specic analysis of TTN and LBC
The rate of TTN and LBC at each gestational age (in weeks) is
shown in Table 4. The rate of TTN was signicantly higher, and the
LBC values were signicantly lower, in neonates with previa than
in controls at 37 weeks of gestation (P = 0.007 and P = 0.018). At
36 and 38 weeks of gestation, there were no signicant differences
between the two groups. In the previa group, the LBC value increased
with advancing gestational ages.
3.4. Characteristics of placenta previa cases
We extracted 35 cases of placenta previa and examined the factors
affecting the neonatal respiratory outcomes (Table 5). The gestational
age, sex distribution and umbilical artery pH of the newborn were not
signicantly associated with the occurrence of neonatal respiratory
disorders. The maternal condition, including blood loss during CS and
transfusion, was also not signicantly different between neonates
with and without respiratory disorders. In this study, we did not administer maternal corticosteroid therapy to any of the cases. The cases who
had warning bleeding due to placenta previa signicantly prevented the
occurrence of neonatal respiratory disorders (P = 0.046), and the
infants were free from neonatal RDS/TTN in all cases.
4. Discussion
A high incidence of RDS in neonates born to mothers with placenta
previa has been reported [1416], but many of these reported targeted
preterm delivery, and few studies have focused on term pregnancies.
Therefore, in this study, we extracted the pure cesarean cases without
fetal or maternal complications that were delivered at 3638 weeks of
gestation, and examined the relationship between placenta previa and
neonatal respiratory disorders, including RDS and TTN. Most cases of
TTN are self-limiting, but some cases require nasal continuous positive
airway pressure or mechanical ventilation [17,18], and these neonates
Table 2
Respiratory outcomes and lamellar body counts.
LBC (104/L)a,b
RDSc
TTNc
RDS and TTNc
53
Table 3
Odds ratios for neonatal respiratory outcomes according to the presence of placenta
previa.
Outcome
Odds ratio
(95% CI)
P-value
RDS (n = 4, 2.2%)
TTN (n = 12, 6.5%)
RDS and TTN (n = 16, 8.6%)
1.54 (0.1615.3)
7.86 (2.3226.7)
5.72 (1.9716.7)
0.96 (0.831.12)
7.20 (6.587.88)
4.55 (4.234.89)
0.613
b0.001
b0.001
RDS, respiratory distress syndrome; TTN, transient tachypnea of the newborn; 95% CI, 95%
condence interval.
Table 4
Age-specic analysis of neonatal TTN and lamellar body counts.
Previa
Previa
(n = 35)
Control
(n = 151)
P-value
4.7 (2.6)
1/35 (2.9%)
7/35 (20%)
8/35 (22.9%)
6.1 (3.3)
3/151 (2.0%)
5/151 (3.3%)
8/151 (5.3%)
0.024
0.749
0.002
0.003
LBC, lamellar body count; RDS, respiratory distress syndrome; TTN, transient tachypnea of
the newborn.
a
Data are presented as the means standard deviation.
b
MannWhitney U test was used.
c
Fisher's exact test was used.
3.6 (1.8)
4.8 (2.8)
6.8 (2.6)
Control
P-value
3/18 (16.7%)
1/89 (1.1%)
1/44 (2.3%)
0.436
0.007
0.125
7.2 (5.4)
6.4 (2.9)
5.5 (2.8)
0.099
0.018
0.426
54
Conict of interest
Table 5
Characteristics of the placenta previa cases.
RDS/TTN
(n = 8)
No RDS/TTN
(n = 27)
P-value
32.8 (4.8)
4/8 (50%)
6/8 (75%)
37.0 (0.9)
2829 (193)
7.27 (0.11)
3.6 (3.3)
0/8 (0%)
1529 (3682451)
1/8 (12.5%)
9.52 (1.6)
1/8 (12.5%)
34.7 (3.5)
11/27 (41%)
14/27 (52%)
37.3 (0.5)
2705 (257)
7.31 (0.06)
5.1 (2.3)
10/27 (33%)
1598 (5193193)
11/27 (41%)
9.54 (1.3)
9/27 (33%)
0.225
0.473
0.228
0.509
0.221
0.240
0.157
0.046
0.888
0.146
0.967
0.250
GA, gestational age; LBC, lamellar body count; CS, cesarean section; Hb, hemoglobin; RDS,
respiratory distress syndrome; TTN, transient tachypnea of the newborn.
a
Data are presented as means standard deviation.
b
Student's t-test was used.
c
Fisher's exact test was used.
d
MannWhitney U test was used.
determine whether this is the case. In the placenta previa group, the lack
of difference in LBC has been indicated between the presence and
absence of RDS/TTN. We think that the small number of the cases may
have been the cause of this nding.
Our study has some limitations. First, the gestational age was significantly lower in the previa cases than in the control cases. A lower gestational age can be associated with neonatal respiratory complications.
Therefore, we performed a logistic regression analysis to control for
the inuences of the gestational age, and placenta previa was still a signicant risk factor for neonatal TTN. Placenta previa has been reported
to possibly be associated with respiratory morbidities independent
of gestational age in preterm infants [14,15]. Second, the number of
placenta previa and RDS and/or TTN cases was small. We extracted
the pure cesarean cases after excluding factors which can affect neonatal respiratory outcomes. Therefore, this study exactly reects the relationship between placenta previa and neonatal respiratory outcomes.
This is the strong point of this study. A larger study may be necessary
to overcome the limitations of the present study. Third, the prevention
of neonatal TTN during pregnancy has not been previously demonstrated. We could not prevent neonatal TTN even if we were able to predict
that the neonates were as high risk for having TTN during pregnancy. In
the present circumstances, the management of neonatal TTN relies solely on the neonatal care. Therefore, we recommend delivering the fetuses
whose mothers have placenta previa at tertiary centers where adequate
neonatal care can be given.
In conclusion, this study revealed that the rate of TTN was signicantly higher and the LBC values were signicantly lower in previa cases than
in control cases. According to our analysis of the age-specic outcomes of
neonatal TTN and LBC, only the ndings at 37 weeks of gestation showed
signicant differences. This is the rst report about the relationship between placenta previa and TTN. Placenta previa in itself, as well as factors
such as preterm labor and CS, which have a high prevalence in patients
with placenta previa, are also risk factors for neonatal respiratory disorders. We hope that these data will aid in the management of placenta
previa.
References
[1] Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview
and meta-analysis of observational studies. J Matern Fetal Neonatal Med
2003;13:17590.
[2] Olive EC, Roberts CL, Algert CS, Morris JM. Placenta praevia: maternal morbidity and
place of birth. Aust N Z J Obstet Gynaecol 2005;45:499504.
[3] Crane JMG, Van den Hof MC, Dodds L, Armson BA, Liston R. Maternal complications
with placenta previa. Am J Perinatol 2000;17:1015.
[4] Zlatnik MG, Cheng YW, Norton ME, Thiet MP, Caughey AB. Placenta previa and the
risk of preterm delivery. J Matern Fetal Neonatal Med 2007;20:71923.
[5] Ananth CV, Smulian JC, Vintzileos AM. The effect of placenta previa on neonatal
mortality: a population-based study in the United States, 1989 through 1997. Am J
Obstet Gynecol 2003;188:1299304.
[6] Piazze JJ, Maranghi L, Cerekja A, Meloni P, Gioia S, Fumian L, et al. Amniotic uid lamellar body counts for the determination of fetal lung maturity: an update. J Perinat
Med 2005;33:15660.
[7] Neerhof MG, Haney EI, Silver RK, Ashwood ER, Lee IS, Piazze JJ. Lamellar body counts
compared with traditional phospholipid analysis as an assay for evaluating fetal lung
maturity. Obstet Gynecol 2001;97:3059.
[8] Wijnberger LDE, Huisjes AJM, Voorbij HAM, Franx A, Bruinse HW, Mol BWJ. The
accuracy of lamellar body count and lecithin/sphingomyelin ratio in the prediction
of neonatal respiratory distress syndrome: a meta-analysis. BJOG 2001;108:5838.
[9] Lewis PS, Lauria MR, Dzieczkowski J, Utter GO, Dombrowski MP. Amniotic uid
lamellar body count: cost-effective screening for fetal lung maturity. Obstet Gynecol
1999;93:38791.
[10] O'Brodovich HM. Immature epithelial Na+ channel expressions is one of the pathogenetic mechanisms leading to human neonatal respiratory distress syndrome. Proc
Assoc Am Physicians 1996;108:34555.
[11] Tsuda H, Takahashi Y, Iwagaki S, Uchida Y, Kawabata I, Hayakawa M, et al. Amniotic
lamellar body counts can predict the occurrence of respiratory distress syndrome as
well as transient tachypnea of the newborn (TTN). J Perinat Med 2011;39:24550.
[12] Machado LU, Fiori HH, Baldisserotto M, Ramos Garcia PC, Vieira AC, Fiori RM. Surfactant deciency in transient tachypnea of the newborn. J Pediatr 2011;159:7504.
[13] Tsuda H, Takahashi Y, Iwagaki S, Kawabata I, Hayakawa H, Kotani T, et al. Intraamniotic infection increases amniotic lamellar body count before 34 weeks of
gestation. J Matern Fetal Neonatal Med 2010;23:12306.
[14] Bekku S, Mitsuda N, Ogita K, Suehara N, Fujimura M, Aono T. High incidence of respiratory distress syndrome (RDS) in infants born to mothers with placenta previa. J
Matern Fetal Med 2000;9:1103.
[15] Lin CH, Wang ST, Hsu YC, Lin YJ, Yeh TF, Chang FM. Risk for respiratory distress
syndrome in preterm infants born to mothers complicated by placenta previa.
Early Hum Dev 2001;60:21524.
[16] Crane JMG, Van den Hof MC, Dodds L, Armson A, Liston R. Neonatal outcomes with
placenta previa. Obstet Gynecol 1999;93:5414.
[17] Tudehope DI, Smyth MH. Is transient tachypnea of the newborn always a benign
disease report of 6 babies requiring mechanical ventilation. Aust Paediatr J
1979;15:1605.
[18] Clark RH. The epidemiology of respiratory failure in neonates born at an estimated
gestational age of 34 weeks or more. J Perinatol 2005;25:2517.
[19] Koivisto M, Marttila R, Saarela T, Pokela ML, Valkama AM, Hallman M. Wheezing
illness and re-hospitalization in the rst two years of life after neonatal respiratory
distress syndrome. J Pediatr 2005;147:48692.
[20] Tita AT, Landon MB, Spong CY, Lai Y, Leveno KJ, Varner MW, et al. Timing of elective
repeat cesarean delivery at term and neonatal outcomes. N Engl J Med 2009;360:
U11129.
[21] Spong CY, Mercer BM, D'Alton M, Kilpatrick S, Blackwell S, Saade G. Timing of indicated late-preterm and early-term birth. Obstet Gynecol 2011;118:32333.
[22] Matsuda Y, Ikenoue T, Hokanishi H. The perinatal factors associated with the development of neonatal RDS in cases of placenta previa. Nihon Sanka Fujinka Gakkai
Zasshi 1986;38:9038 [In Japanese].