Materials and Methods
Study setting and cohort
This retrospective cohort study included parturients with CHD who gave
birth via caesarean section from 1994 to 2019 and whose information was
in a database maintained by the Department of Obstetrics and Gynaecology
at the National Cerebral and Cardiovascular Centre, in Suita, Osaka,
Japan. Parturients with simple congenital arrhythmias or cardiomyopathy
were excluded. The institutional ethics committee waived the need for
patient consent and approved the study before medical record review
began (R19094).
Outcomes
Cardiovascular events were defined based on the existing
literature.14-17 The primary outcome was a postpartum
cardiovascular event consisting of a composite of all-cause death, new
onset or worsening heart failure, pulmonary hypertension, sustained or
non-sustained arrhythmia, and thromboembolic complications (myocardial
infarction, mechanical valve thrombosis, venous thromboembolism, or
cerebrovascular event) that required treatment with intravenous or oral
medication or electrical defibrillation. Heart failure that required
treatment with only oral diuretics and cardiovascular events that
occurred during pregnancy and continued into the postpartum period were
not considered primary outcomes.
Secondary outcomes consisted of maternal respiratory events, neonatal
all-cause death, neonatal intubation, Apgar score, and umbilical
arterial pH. Low Apgar score was defined as Apgar score < 7 at
1 minute or 5 minutes after delivery.18 When a patient
was multiple pregnancy, only data on the first newborn was analysed.
Composite neonatal outcomes included neonatal intubation and low Apgar
score. Primary or secondary outcomes could include events that occurred
up to 1 week after caesarean section.
Exposure variables
Anaesthetic technique was analysed as general or neuraxial anaesthesia.
We categorized spinal, epidural, or the combination of spinal and
epidural anaesthesia as neuraxial anaesthesia and general anaesthesia or
the combination of general and epidural anaesthesia as general
anaesthesia. Parturients who converted from neuraxial to general
anaesthesia were excluded because the aim of the study was to clarify
the association between these 2 anaesthetic techniques and outcomes.
Potential confounders
Maternal demographic characteristics included age, multiparity, multiple
pregnancy, and body mass index (BMI). BMI was divided into 4 categories
based on the existing literature.19 Obstetrics
characteristics included multiparity, date of caesarean delivery in
periods of approximately 5 years to adjust for technical advances in
caesarean sections (1994–1999, 2000–2004, 2005–2009, 2010–2014, and
2015–2019), gestational age at delivery categorized into 3 groups based
on existing literature: age <31 years, age of 32–36 years,
and age ≥37 years to adjust for the risk of older
age,20 type of indication for caesarean section
(maternal cardiovascular indication or obstetric
indication),21 and emergency caesarean delivery
status.
Maternal cardiac demographics included New York Heart Association (NYHA)
classification before pregnancy and modified World Health Organization
(mWHO) classification for maternal cardiovascular
risk.22 Two certified experts, an adult cardiologist
specializing in caring for obstetric patients and a paediatric
cardiologist at our institution, assessed mWHO class for maternal
cardiovascular risk, which is the best available assessment model for
estimating cardiovascular risk in pregnant women with
CHD.23
Systemic ventricular ejection fraction (EF) values from the most recent
echocardiographic examination before caesarean section were collected.
Cardiovascular events during pregnancy included any of the following:
heart failure, pulmonary hypertension, sustained or non-sustained
arrhythmia, and thromboembolic complications (myocardial infarction,
mechanical valve thrombosis, venous thromboembolism, or cerebrovascular
event) that required treatment with intravenous or oral medication,
electrical defibrillation, or caesarean delivery.
Statistical Analysis
Stata version 15 (College Station, TX, USA) was used for analysis. For
baseline patient characteristics, continuous variables are presented as
means with standard deviation for normally distributed variables and
were compared using the t-test. Non-normally distributed variables are
presented as medians (interquartile range) and were compared using the
Mann-Whitney U test. Categorical baseline variables were compared using
Fisher’s exact test.
To account for the heterogeneity of CHD, the association between
anaesthetic technique and composite postpartum cardiovascular events was
analysed using generalized linear mixed models assuming a binomial
distribution (i.e., mixed-effects logistic regression) with a random
intercept for each mWHO class for maternal cardiovascular risk.
Confounding factors included cardiovascular events during pregnancy,
gestational age at delivery, and emergency caesarean section status. The
association between anaesthetic technique and composite neonatal
outcomes was also analysed using mixed-effects logistic regression with
a random intercept for each mWHO classification for maternal
cardiovascular risk. Confounding factors included cardiovascular events
during pregnancy, gestational age at delivery, birth weight, and
emergency caesarean section status. Confounding factors considered to be
relevant to primary or secondary outcomes were selected based on
existing clinical knowledge. Only parturients with complete information
available were included in the analysis.
We also performed sensitivity
analyses. First, we added date of caesarean delivery as a confounding
factor for both composite maternal and neonatal outcomes. Second, we
replaced emergency caesarean status with gestational weeks at delivery
or type of indication for caesarean section as potential confounding
factors for composite maternal or neonatal outcomes, respectively.
Third, we applied inverse probability of treatment weighting (IPTW) to
analyse whether anaesthetic technique is associated with composite
postpartum cardiovascular events. We used multivariate logistic
regression to estimate propensity scores using the following factors:
age, BMI, multiparity, multiparous, cardiac events during pregnancy,
gestational weeks at delivery, emergency caesarean section status,
systemic ventricular EF, date of caesarean delivery, NYHA class before
pregnancy and mWHO class for maternal cardiovascular disease. To reduce
bias and the amount of missing data, 2 authors abstracted data from
electronic medical records from 2008 to 2019 and paper charts from 1994
to 2007.