Methods:
Study design and data
sources
In this nationwide population-based cohort study, we used data from the
Swedish Medical Birth Register (MBR), covering about 99% of all births
in Sweden, and we included women with singleton births between
January 1, 1982, and December 31,
2012.
The obstetric history of each woman, including data on comorbidity (such
as diabetes, hypertension, and cardiovascular diseases), was obtained
from the MBR and the Swedish National Patient Register (NPR). Data from
these registers were linked using a unique Swedish personal
identification number20. All diagnoses and
complications during pregnancy or delivery are classified according to
the Swedish version of the International Classification of Diseases
(ICD), using the ICD-8 until 1986, the ICD-9 (1987 to 1996), and the
ICD-10 since 1997. This study is reported as per the Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE) guideline
(S1 Table).
Study population
The study cohort consisted of women who had their first two births
between 1982 and 2012. Women who had singleton birth with available data
on the mode of delivery on the 1st delivery were
included. We excluded records where the first pregnancy was a multiple
gestation or resulted in stillbirth. Ethical approval was obtained from
Regional Ethical Review Board in Stockholm.
Mode of delivery
Mode of birth was categorised into VB and CD. We further subclassified
this as follows: (1) spontaneous VB [reference group], (2) assisted
delivery (vacuum/forceps), (3) pre-labour CD (before the onset of
labour), (4) in-labour CD (after the onset of labour), and (5)
unspecified CD, where data on the type of CD were not available. The
variable was defined this way to assess the effect of specific types of
mode of birth in the 1st birth on the risk of
stillbirth in the second pregnancy.
Then we considered mode of birth in both first and second births in
order to assess the impact of VBAC on the risk of stillbirth, in which
mode of delivery was grouped as follows: (1) repeat CD (CD in both
pregnancies, [reference group]), (2) VBAC, (3) first VB and
subsequent CD, and (4) VB in both pregnancies. It should be noted that
mode of delivery recorded in the MBR is the ’final’ mode of delivery,
which may differ from the woman’s intended mode of delivery. For
example, a woman may attempt a trial of labour after a CD and fail,
ending up with an in-labour CD. Thus, our study groups represent a good
reflection of what happens in ’real-world’ situations.
Outcome
The outcome of interest was stillbirth (antepartum and intrapartum fetal
death). We used data from the Swedish MBR to identify stillbirths in the
second pregnancy. This was defined as fetal death
after 28 completed weeks (until
June 2008) and fetal death after 22 completed weeks since July 2008.
We classified stillbirth into explained and unexplained stillbirth using
an adapted version of the ReCoDe (RElevant COndition at DEath)
classification system. The ReCoDe classification system is designed in a
hierarchical manner to organise relevant clinical conditions associated
with death in utero. It contains nine main categories, starting fromA (conditions affecting the fetus) to I(unclassified), and each category is divided into several
subgroups22. These categories include a wide range of
clinical conditions related to the fetus, the placenta, the mother, and
intrapartum conditions. On the other hand, unexplained cases are divided
into two subcategories; cases with irrelevant conditions despite
information or cases lacking available information22.
We used the diagnosis variables from the MBR and NPR to classify
stillbirth according to the underlying conditions of the ReCoDe
classification system. All diseases and complications during pregnancy
or delivery were classified according to the Swedish version of ICD
codes. In addition, small for gestational age (SGA) was defined as a
birthweight below 2 standard deviations (SDs) of the population mean
birthweight adjusted for sex-specific and gestational age distributions
or according to ICD codes (codes are shown in Table S2).
Statistical analysis
Maternal and birth characteristics are presented according to stillbirth
and mode of delivery (Tables S3-S5) using frequency and percentages.
Logistic regression models were performed to evaluate all associations
using crude ORs and aORs, along with 95% CIs. First, we estimated the
odds of stillbirth in the second birth following a CD in the first
delivery, compared with the outcome of second deliveries following a
prior VB. Second, we expanded the exposure variable to evaluate the
impact of specific types of mode of delivery, specifically pre-labour CD
and in-labour CD, on the associations. Finally, in a third model, we
considered the mode of delivery in the first and second births to
estimate the odds of stillbirth in women with a VBAC compared to women
with a repeat CD. For completeness, we report the results for all the
mode of delivery combinations in the first and second births.
Adjusted models included maternal age, BMI, smoking, education, country
of origin, year of delivery, comorbidities (diabetes, chronic
hypertension, cardiovascular disease), and pregnancy-related disorders
(gestational diabetes, gestational hypertension, and preeclampsia) in
the first pregnancy. We added a missing data category to control for
missing data on BMI and smoking.
We undertook subgroup analysis based on ReCoDe classification
categories, including a specific cause of stillbirth for explained
stillbirths (cases with a known condition for death). We conducted
separate analyses for causes of death restricted to stillbirths caused
by: (a) lethal congenital anomaly, (b) SGA\fetal growth
restriction, (c) any cord issue, (d) placental abruption, (e) any
placental abnormalities, (f) any maternal conditions, (g) uterine
rupture, (h) intrapartum asphyxia/birth trauma. We additionally
evaluated the association between a previous CD and explained stillbirth
(including any relevant condition), unexplained stillbirth (including
cases without relevant condition), and finally relevant versus no
relevant condition (Table S7).
We did sensitivity analyses according to birth defects, preeclampsia,
gestational diabetes, preterm birth, SGA, and time period. We also
calculated the population attributable fraction (AF) (details are shown
in Appendix page 2).
Statistical analyses were performed using Stata version 16.1 (StataCorp,
Texas, USA), and all tests were two-sided with a 5% significance level.