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Influence of Interpregnancy Interval on Uterine Rupture

Oleh :
Ilham Ertandri 2140312133

Preseptor :

dr. Adriswan, Sp.OG

BAGIAN OBSTETRI DAN GINEKOLOGI

RSUD PADANG PANJANG
FAKULTAS KEDOKTERAN
UNIVERSITAS ANDALAS
2021
 The Journal of Maternal-Fetal & Neonatal
Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage:

https://www.tandfonline.com/loi/ijmf20

Influence of interpregnancy interval on

uterine rupture
Sarah Cunningham, C. E. Algeo & E. A. DeFranco

To cite this article: Sarah Cunningham, C. E. Algeo & E. A. DeFranco (2019): Influence
of interpregnancy interval on uterine rupture, The Journal of Maternal-Fetal & Neonatal Medicine,
DOI:
10.1080/14767058.2019.1671343
To link to this article: https://doi.org/10.1080/14767058.2019.1671343

Published online: 01 Oct 2019.

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THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
https://doi.org/10.1080/14767058.2019.167134

ORIGINAL ARTICLE

Influence of interpregnancy interval on uterine rupture

Sarah Cunningham, C. E. Algeo and E. A. DeFranco
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

ABSTRACT
Objective: This study aims to assess the independent influence of interpregnancy interval (IPI) on ARTICLE HISTORY
uterine rupture using a population-based cohort of all Ohio births, regardless of prior cesarean (PCS) Received 11 July 2019
or trial of labor (TOL) status. Revised 14 September 2019
Study design: Population-based retrospective cohort study of all live births in Ohio (2006–2012). Accepted 18 September 2019
Frequency of uterine rupture was quantified and stratified by number of prior cesarean deliveries
KEYWORDS
and IPI. The relative and adjusted risk of IPI on uterine rupture was calculated using multivariate
Birth spacing; interpregnancy
logistic regression.
interval; uterine rupture
Results: Of 1,034,522 live births recorded during the 7-year study period, 249 cases of uterine
the rare occurrence of
rupture were identified for analysis. Two-thirds of uterine rupture cases (n¼ 158) occurred in women
uterine rupture (overall
with one or more PCS and one-third (n¼ 91) had no prior cesarean. IPI 24–59 months had the lowest
rates range from 1 in
frequency of uterine rupture and was used as the referent group. IPI 12–23 and IPI 60 months were
1235–4366) [2], limited
not significantly associated with risk of uterine rupture, p¼ .847, .540 respectively. In women with
cohorts restricted to
PCS, IPI < 12 months was associated with greater than two-fold increased risk of uterine rupture (aRR
women with only prior
2.4, CI 1.5–3.8). No association between IPI < 12 months and uterine rupture was observed in cesareans or trial of labor
women with no PCS, p¼ .696. conditions, and older data
Conclusion: IPI < 12 months is independently associated with uterine rupture in women with prior sets [4,6–8]. However, the
cesarean, but does not appear to influence risk in women with an unscarred uterus. presence of an association
Introduction between short IPI and uterine rupture after cesarean is
Uterine rupture, the disruption of all uterine layers generally agreed upon.
including the serosa, is a rare and devastating Biologically plausible hypotheses have been described
complication of pregnancy [1]. The maternal and neonatal to explain the increased risk of short IPI on rupture of the
outcomes associated with uterine rupture include scarred uterus. Studies indicate that factors such as poor
maternal blood loss and hysterectomy, neonatal maternal nutritional status and reduced wound healing
intraventricular hemorrhage, periventricular time could account for the increased uterine rupture
leukomalacia, seizures, and death [2]. Clinical signs of rates in women with short IPI [4–6]. Less is known about
uterine rupture include vaginal bleeding, abdominal pain, uterine rupture in patients with an unscarred uterus, also
nausea, and fetal bradycardia and decreased fetal heart known as primary uterine rupture. Rupture of the
rate variability [2,3]. unscarred uterus is even more rare than uterine rupture
Interpregnancy interval (IPI) describes the time following a prior cesarean section (PCS) (1 in 16,840–
between delivery and the following conception. Short IPI 19,765 in the developed world) [2]. Short interpregnancy
is associated with low birth weight, preterm birth, interval has been a suspected risk factor for rupture of
PPROM, and placenta accreta [4]. Previous observational the unscarred uterus, but has not been thoroughly
studies have found associations between short IPI and an investigated.

CONTACT Emily A. DeFranco emily.defranco@uc.edu Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine,
Medical Sciences Building, Room 4407, 231 Albert Sabin Way, Cincinnati, OH, USA
2019 Informa UK Limited, trading as Taylor & Francis Group
increased risk of uterine rupture in vaginal birth after Despite the well-established risks associated with short
cesarean (VBAC) patients [5–7]. It is difficult to compare IPI, as many as 1/3 of pregnant women in the USA
the results of these studies due to variation in the specific continue to experience a short IPI [9].
outcomes measured and lack of a universal definition of Unlike other risk factors, interpregnancy interval is a
“short IPI”. Prior studies have several limitations due to
2 S. CUNNINGHAM ET AL.
potentially modifiable factor, and intervention with
optimizing intervals between pregnancies may have the
potential to improve maternal and perinatal outcomes
[9]. Our study uses a large cohort to assess the
independent relationship between short IPI and uterine
rupture in pregnancies with and without prior cesarean.
Materials and methods
We performed a population-based retrospective cohort
study of all live births in Ohio during a 7-year period
(2006–2012) using vital statistics birth records from the
Ohio Department of Health. The protocol for this study
was approved and a deidentified data set was provided
by the Human Subjects Institutional Board Review of the
Ohio Department of Health. This study was exempt from
review by the Institutional Review Board at the University
of Cincinnati,
Cincinnati, OH.
The exposure of interest, IPI, was defined as time from
the most recent prior birth to the subsequent conception
of the index birth. The interval of time between the prior
birth and index (current birth) is recorded in the US birth
certificate, as “interval”. From this, we created the
variable “interpregnancy interval” by converting the
gestational age of the current (index) birth into months
and subtracting it from the interbirth “interval” variable.
Interpregnancy intervals were categorized as follows for
the purposes of this study: <12, 12–23, 24–59, and 60
months.
The primary outcome was uterine rupture. A ruptured
uterus was defined as full-thickness disruption of uterine
wall involving the overlying visceral peritoneum, as
defined in the National Vital Statistics System in the USA
for the variable “ruptured uterus” [10]. Uterine
dehiscence, silent rupture, incomplete rupture, and
asymptomatic separation are not classified as uterine
rupture on the USA certificate of live birth. Birth
certificate information was gathered from the delivery
record and the Operative or Physician progress note.
Uterine rupture cases were stratified by presence or
absence of prior cesarean, and categorized as rupture of
an unscarred uterus (defined as no prior cesarean) N¼ 91,
and rupture of a scarred uterus (one or more prior
cesareans) N¼ 158. Data on other prior uterine surgeries
such as myomectomy or dilation and evacuation is not
available on the USA certificate of live birth, and
therefore was not available for consideration in this
study.
Baseline maternal demographic, behavioral,
socioeconomic, prenatal, and delivery characteristics
were compared between IPI exposure groups and
between outcome (uterine rupture, yes/no) groups. We
also compared data on maternal or neonatal
complications, such as prolonged labor, meconium
stained fluid, maternal blood transfusion, unplanned
hysterectomy, maternal admittance to ICU, and infant
death, between these groups. Maternal characteristics
were counted only once in statistical comparisons for
multifetal births (twins and higher order) so that mothers
would not be counted more than once for the same
delivery. Neonatal characteristic comparisons were
included for each birth, including those of multifetal
gestations. Births to mothers recorded as having parity
>24 were recategorized as missing data for parity analysis
due to concern for potential data entry error (n¼ 19,584).
Comparisons of dichotomous variables were
performed with chi square test and continuous variables
were compared using ANOVA or Kruskal-Wallis test for
nonparametric variables. Multivariate logistic regression
estimated the risk for uterine rupture associated with
short interpregnancy intervals after adjustment for
potential confounding factors including cigarette smoking,
maternal age, race, induction of labor, Medicaid
insurance, gestational age, and number of prior cesarean
deliveries. Stepwise backward selection yielded a final
model with statistically influential and biologically
plausible covariates. The adjusted relative risks (aRR)
were demonstrated in sequential models to show the
relative influence of each final covariate on the primary
outcome of uterine rupture.
Interpregnancy interval of 24–59 months was used as the
referent for comparisons because it was the interval with
the lowest frequency of uterine rupture. Comparisons
were considered statistically significant if probability
value <.05 or 95% confidence interval was not inclusive of
the null value 1.0. Analyses were performed using Stata
Release 12 software (StataCorp, College Station, TX).
Results
In the cohort of 1,034,552 live births, 19,984 births were
identified as second or greater birth order newborns from
multiple gestation deliveries and were excluded so that
each mother’s birth outcome was counted only once. Of
the remaining, 72,788 birth certificates for multiparous
women lacked data on interpregnancy interval and were
excluded. Further, there were 18,873 lacking data on 001. In that same time, the rate of uterine rupture among
uterine rupture women with PCS decreased from 0.18% of deliveries of
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3deliveries in
2008 to 0.12%
in 2012 to
0.12% in 2012
p< .001. The
overall rate of
uterine
rupture in the
entire
population
was
consistently
0.03% across
the 7-year
timeframe (p¼
.94).

Figure 1. Flow diagram of the study population.

Multivariate logistic regression analysis estimated the
association between uterine rupture, IPI, and coexisting
risk factors. After accounting for the influence of
occurrence which were also removed. Ultimately 922,907 induction of labor, number of prior cesarean sections,
live births remained for analysis, including 249 cases of black race, and preterm delivery on uterine rupture risk,
uterine rupture (Figure 1). The frequency of short IPI in the independent risk of short IPI < 12 months on uterine
the cohort, defined as <12 months, was 11.5%, N¼ rupture, among all women in the cohort (those with and
106,163. without prior cesarean) was adjusted relative risk 1.80, CI
1.28, 2.53, compared to IPI of 24–59 months. With
Women who had a live birth following a short IPI were
analyses limited to women with prior cesarean, short IPI
more likely to be younger than age 20 and utilize
increased the adjusted relative risk of uterine rupture to
Medicaid compared to other IPI groups. Mothers with
2.40 (95% CI 1.53, 3.77), Table 2. Within the final model,
short IPI and IPI >60 months were more likely to report
induction of labor was the most significant risk factor for
Black race, experience a preterm birth (defined as <37
uterine rupture among women with PCS (aRR 3.64, 95%
weeks), and smoke cigarettes. Demographic
CI 1.73, 7.65). Preterm delivery was a significant risk
characteristics of the study cohort are detailed in Table 1.
factor in women with PCS (aRR 1.76, 95% CI 1.02, 3.03)
Of 249 uterine rupture cases included in this analysis,
while increasing gestational length was found to be
91 (36.5%) were unscarred uterine ruptures (no prior
protective (aRR 0.89, 95% CI 0.80, 0.99). Among women
cesarean) and 158 (63.4%) were ruptures of a scarred
with PCS, a slightly longer IPI of 12–23 months
uterus (1 prior cesarean, PCS). Frequency of uterine
experienced no increased risk of uterine rupture (aRR
rupture overall was 0.027% (1 in 3655). This prevalence
1.47 95% CI 0.92, 2.35) compared to the 24–59 months
rate is similar to that which has been reported previously
IPI. Additionally, very long IPI >60 months had no
in the medical literature [2]. The rate of cesarean section
steadily increased from 2006 (28.6%) to 2012 (30.2%) p< .
4 S. CUNNINGHAM ET AL.
Table 1. Demographic and clinical characteristics by interpregnancy interval length.
<12 Months 12–23 24–59 N60¼ Nulliparou p-
N¼ 106,163 Months N¼ Months N¼ s N¼ Val
144,931 187,589 88,752Months 395,472 ue
Maternal age <.0
<20 7612 (7.2%) 4909 (3.4%) 2848 (1.5%) 75 (0.1%) 82,564 (20.9%) 01
20–34 89,340 (84.2%) 122,124 (84.3%) 156,068 (83.2%) 62,227 (70.1%) 288,976 (73.1%)

35 9197 (8.7%) 17,874 (12.3%) 28,634 (15.3%) 26,432 (29.8%) 23,865 (6.0%)
Race/ethnicity
Non Hispanic White 78,786 (74.2%) 117,040 (80.8%) 144,852 (77.2%) 63,551 (71.6%) 306,798 (77.6%) <.0
01
Non Hispanic Black 20,252 (19.1%) 19,092 (13.2%) 28,991 (15.4%) 17,899 (20.2%) 60,575 (15.3%)

Hispanic 5197 (4.9%) 5669 (3.9%) 8821 (4.7%) 4954 (5.6%) 15,893 (4.0%)

Other 1928 (1.8%) 3130 (2.2%) 4925 (2.6%) 2348 (2.6%) 12,206 (3.1%)

Parity, Mean(± SD) 2.0 (1.5) 1.9 (1.4) 1.8 (1.2) 1.8 (1.1) 0 <.0
01
Median (IQR) 2 (1, 2) 1 (1, 2) 1 (1, 2) 1 (1, 2)

Number prior <.0

cesareans 0 82,951 (78.1%) 112,148 (77.4%) 144,006 (76.8%) 70,443 (79.4%) N/A 01
1 15,256 (14.4) 22,979 (15.9%) 30,556 (16.3%) 12,814 (14.4%)

2 4580 (4.3%) 6263 (4.3%) 8596 (4.6%) 3407 (3.8%)

3 1279 (1.2%) 1451 (1.0%) 1700 (0.9%) 684 (0.8%)

4 384 (0.3%) 397 (0.3%) 365 (0.2%) 146 (0.2%)

<.0
Gestational age at delivery, 38.5 (2.6) 38.6 (2.3) 38.5 (2.3) 38.3 (2.6) 38.7 (2.7)
01
weeks Mean (±SD)
Preterm birth <37 weeks 13,506 (12.7%) 14,206 (9.8%) 19,582 (10.4%) 11,817 (13.3%) 45,743 (11.6%) <.0
01
Birthweight, grams 3270 (590) 3355 (558) 3322 (572) 3242 (620) 3223 (608) <.0
Mean (±SD) 01
Cigarette use 27,243 (25.7%) 28,858 (20.0%) 45,497 (24.3%) 27,810 (31.3%) 94,255 (23.8%) <.0
01
Medicaid 48,939 (46.1%) 47,973 (33.1%) 67,555 (36.0%) 35,394 (39.9%) 142,823 (36.1%) <.0
01
Unmarried 45,165 (42.5%) 43,003 (29.7%) 65,138 (34.7%) 40,165 (45.3%) 200,385 (50.7%) <.0
01

Table 2. Risk factors associated with uterine rupture in women with or without prior cesarean.
aRR (95% CI) in women with prior cesarean aRR (95% CI) in women without prior cesarean

Short IPI < 12 months 2.40 (1.53, 3.77) 0.96 (0.49, 1.91)
Labor induction 3.64 (1.73, 7.65) 0.96 (0.47, 1.94)
Number of prior cesareans 1.52 (1.25, 1.85) –
Black race 1.49 (0.90, 2.45) 0.74 (0.29, 1.91)
Preterm delivery < 37 weeks 1.76 (1.02, 3.03) 2.31 (1.04, 5.14)
IPI: interpregnancy interval; aRR: adjusted relative risk (95% confidence interval). Referent group IPI 24–59 months; all factors in this table are
adjusted
for other factors listed. 0.49, 1.91) (Table 2).

significant increased risk of uterine rupture (aRR 1.2, 95%

CI 0.70, 2.21) compared to the 24–59 months IPI (Figure
2). Among women without a prior cesarean, the adjusted
relative risk for uterine rupture after short IPI was not
significantly increased (aRR 0.96, 95% CI
Discussion
In this study, we found that a subsequent pregnancy after
cesarean section with IPI <12 months is associated with
greater than 2 the risk of uterine rupture compared to a delivery, that the birth control method available to
women with longer IPI and PCS. them had unwanted side effects, and that their sexual
partner did not want to use birth control. All of these
Additionally, we found that short IPI is not a significant
factors can be targeted through focused interventions
risk factor for rupture of the unscarred uterus.
and would be most effective when tailored to the
Additionally, this study found an association between
woman’s specific combination of barriers to successful
preterm delivery and uterine rupture, both in women
birth spacing.
with and without PCS, indicating that the risk of rupture
Concerning IPI, many studies in the literature agree
begins before the gestation has reached term.
that “short IPI” is associated with increased risk of
In the discourse concerning induction of labor, Huang
rupture after cesarean section [4–7]. However, the
et al. discussed the differences seen with interdelivery
definition of short IPI varied from < 6–24 months in the
interval, VBAC success, and trial of labor. They
literature. Huang et al. found no association between
uterine rupture and IPI < 18 in women with PCS, although
Under 12 they acknowledge a small sample size and their result
12 to 23
deviates from the majority of the literature [8].
The information provided by our study may assist
60 and over
obstetric care providers when counseling their patients
on optimal birth timing following a cesarean delivery. Our
data suggest the lowest risk for uterine rupture after
cesarean is 2 years between delivery and subsequent
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
conception, slightly longer than the Healthy People 2020
Figure 2. Adjusted relative risk for uterine rupture in women recommendation for IPI of greater than 18 months.
with prior cesarean, by IPI category. IPI: interpregnancy Despite the rarity of uterine rupture, we also advise that
interval. Referent group IPI 24–59 months. Relative risk
women who intend a TOLAC should be in a hospital
displayed as point estimate with 95% confidence interval.
Numbers on the X-axis denote relative risk. IPI categories are setting for their delivery to ensure fast response in the
listed in months. event of complications [14].
In discussions of delivery outcomes, it should not be
ignored that globally many women deliver in middle or
low Human Development Index (HDI) countries, which
found higher failure of VBAC after induction than with
has been shown in a WHO multicountry analysis to be a
spontaneous delivery and suggested spontaneous
risk factor for uterine rupture [11].
delivery may be a sign of healed uterine status [8]. In
Additionally, this study found that lower maternal
contradiction to that theory, Motomura et al. found an
education was also a factor, which previously was
increased risk of uterine rupture with spontaneous onset
associated with high incidence of unintentional pregnancy
of delivery [11]. The current study confirms those reports
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 5
that induction of labor is a risk factor for uterine rupture
in women with PCS [7,8,12]. However, we found that
and short IPI [11]. Together, these findings suggest that
induction was not a risk factor for rupture in women
uterine rupture is influenced by a combination of
without PCS.
environmental, social, and healthcare quality factors.
In 2013 Gemmill and Lindberg found that 55% of
Therefore, patients with and without a history of
pregnancies with short IPI were unintended [9]. Similar
cesarean section, but with a high number of previous
results were found in a report from Utah in 2006 where
pregnancies or other risks for a preterm delivery, may
63% of women with the shortest IPIs reported the
warrant education on the signs and symptoms of uterine
pregnancy to be unintended. Most concerningly, 60% of
rupture. While the incidence of rupture is rare, the
those reporting claimed to be using a form of birth
morbidity is high, and a rapid identification and response
control at the time of conception [13]. Additionally in the
is vital for improved outcomes [14]. Future studies aimed
Utah study, women reporting unintended pregnancies
to better understand the risk factors for uterine rupture
were asked for factors that interfered with preventing a
in women living in low HDI countries would be
pregnancy. Factors reported by these women included:
informative.
being unaware they could become pregnant so soon after
6 S. CUNNINGHAM ET AL.
Biological hypotheses exist for rupture of a scarred
uterus, but few have been described for ruptures
occurring in the unscarred uterus. In this study, we could
not identify an interpregnancy interval associated with
primary rupture or any significant risk factors other than
TOL and preterm delivery, the latter of which can be
considered an outcome rather than an exposure. As
Gibbins astutely stated, the specific risk factors for
primary rupture are not established and the symptoms of
primary rupture are common to laboring patients without
rupture [2]. This enhances the challenge of screening for
and treating an already highly morbid event. More
research is needed to prevent this outcome.
The primary finding of this study can have significant
clinical impact for women with PCS because
interpregnancy interval is a modifiable risk factor. In
addition to patient education, access to affordable birth
control, female empowerment in birth spacing
conversations, and improvement in health equity must be
staples in the movement towards reducing short IPI and
thus improving the health of mothers and infants globally.
Strengths and limitations
The population-based cohort design of this study using
vital statistics data allowed us the ability to estimate both
the incidence and relative risk of uterine rupture in our
population. Some data variables including maternal
demographic information and gestational age at birth are
reliably recorded in the US birth certificate [15]. However,
data on pregnancy complications and medical comorbid
conditions are underreported, which limits the ability to
adjust thoroughly for confounding risk factors. Maternal
surgical history other than prior cesarean is not included
on the birth certificate, therefore the contribution of prior
myomectomy or other uterine surgery on subsequent
uterine rupture could not be measured in this study.
IPI for this study was calculated from data provided on
the birth certificate of the current birth as “interval”,
which is calculated from the date of the last live birth
[10]. This variable does not take into account the time
since a previous miscarriage or stillbirth, although the
birth interval following those outcomes may not have the
same significance of risk as short IPI following a live birth
[15]. Therefore, use of “interval” for this study may have
resulted in a lower number of pregnancies available for
analysis with a known IPI. However, those with a
recorded IPI were likely accurately recorded, as they were
generated by direct extraction from the medical record or
recall of the patient, neither of which is likely to be
differentially misclassified.
There were births with missing IPI data, and the
characteristics of those births differed from those with a
recorded IPI. Multiparous women with missing IPI data
had lower socioeconomic status, fewer prenatal visits,
and were predominantly of black race. However those
with missing IPI data only constituted 7.0% of the total
source population.
Disclosure statement
No potential conflict of interest was reported by the
authors.
This study includes data provided by the Ohio
Department of Health which should not be considered an
endorsement of this study or its conclusions.
Funding
Dr. DeFranco received research funding from the Perinatal
Institute, Cincinnati Children’s Hospital Medical Center.
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