Discussion
In this large cross-sectional study based on US births, we evaluated the
impact of gestational age on delivery mode for pregnancies complicated
by SGA. Because the gestational age when delivery becomes indicated may
influence labour outcomes, we performed a causal mediation analysis to
quantify the mediating and interaction effects of gestational age on
exposure to SGA and delivery mode. The principal finding of this study
is that the risk for caesarean delivery with TOL at term gestations and
caesarean delivery without TOL across all gestations for SGA births is
primarily attributable to exposure to SGA rather than mediation or
interaction effects of gestational age.
The caesarean delivery without TOL outcome includes women who had
prelabour caesareans. The intent of performing a prelabour caesarean for
some obstetricians is to avoid impending complications as a consequence
of labour, including category 2 fetal heart rate tracings that may
precipitate an emergent caesarean delivery. In this analysis, caesarean
rates without TOL were higher for SGA births at each gestational age
strata except for 39-40 weeks’ gestation. The decomposition analysis
revealed that exposure to SGA by itself (and independent of gestational
age) was the driver of this risk.
The caesarean delivery after TOL outcome includes those who required
caesarean deliveries for abnormal fetal heart rate patterns and labour
complications. The rates of caesarean delivery after TOL were higher for
SGA births across gestational age strata, but the highest rates were
observed ≥41 weeks’ gestation. When these rates were highest at term
gestations, exposure to SGA was the dominant driver of caesarean
delivery risk.
Prior studies have shown high rates of caesarean delivery for SGA
pregnancies. For example, in a study of 2885 non-anomalous, singleton,
cephalic presenting SGA fetuses at 25-34 weeks in New York (1995-2003),
the overall caesarean delivery rate was 57.9% (26). That study was
limited by small size, but also did not stratify the analyses by
gestational age ranges, caesarean history, or caesarean indications. As
a result, a picture emerges of caesarean risk for SGA pregnancies that
may fuel concerns about high rates of emergent deliveries. While the
results of this study also found higher overall caesarean delivery rates
from 22-44 weeks’ gestation for SGA versus AGA pregnancies (34.3% for
SGA <5th percentile and 36.4% for SGA
<3rd percentile versus 29.6% for AGA), a
more nuanced picture emerges when caesarean rates are broken into
gestational age ranges. For example, there were extremely high rates
<32 weeks’ gestation (over 80%), but the rates improved as
gestational age advanced. This breakdown by gestational age provides
improved insight into the caesarean risk for SGA pregnancies.
The results of this analysis also demonstrated that labour outcomes for
SGA pregnancies are impacted by indication for delivery. The overall
high caesarean rates for SGA fetuses in the US were largely driven by
prelabour procedures. Approximately two-thirds of all Caesareans were
classified as prelabour procedures, but the risk was highest
<32 weeks’ gestation. Further, Caesarean delivery rates
without TOL were considerably higher at each gestational age strata
compared to rates with TOL, except at ≥41 weeks’ gestation. These
findings give credence to apprehensions raised by the NIH Consensus
statement “Preventing the First Caesarean Delivery,” that
“concern[s] about vaginal delivery coupled with relative
indifference regarding the risks of Caesarean may lead to a decision
that is not based on clinical evidence” (1). The results of this
analysis suggest that too many patients in the US are not given the
opportunity to have TOL and spontaneous vaginal delivery.
In fact, while the rates of Caesarean delivery after TOL are higher for
SGA versus AGA pregnancies, the magnitude of risk is less than some
providers may recognize. Overall rates of caesarean with TOL were 9.1%
for SGA <5th percentile and 10.2% for SGA
<3rd percentile versus 5.9% for AGA births.
The caesarean with TOL risks were notably highest for SGA and AGA births
after 41 weeks gestation. Also, the risks of caesarean delivery with TOL
was lowest for SGA versus AGA births at 39-40 weeks’ gestation and with
the smallest risk difference at this gestation age range. These
observations corroborate the main findings of the ARRIVE trial (27) that
induction of labour in the 39th week reduces Caesarean
delivery rates.
The results of this mediation analysis suggest that different mechanisms
drive the risk of caesarean delivery after TOL at preterm versus term
gestations. At preterm gestations, interaction of SGA with gestational
age has a larger effect on the risk, whereas exposure to SGA itself has
a large effect at term gestations. Unfortunately, this dataset cannot
explain how the interaction affect contributes to caesarean delivery
after TOL rates in preterm gestations. It is possible that the fetal
heart rate monitoring profile of preterm SGA fetuses could provide
insight, but this has not been elucidated. A 2010 Cochrane review that
sought to assess the effects of a policy of elective caesarean delivery
versus expectant management for growth restricted fetuses could only
identify 6 trials with 122 patients (28). The included studies were
marred by recruitment problems, which limited the conclusions of the
systematic review. The manifestation of gestational age-SGA interaction
as it relates to fetal tolerance of labour at preterm gestations
requires further evaluation.
Exposure to SGA alone (i.e., the CDE) explains increased risks of
caesarean delivery after TOL for term and late-term SGA births. In this
case, it is likely that the impact of pathologic growth restriction
drives the risk and likely reflects underlying ischemic placental
disease (IPD) (6, 29). IPD, which also includes preeclampsia and
placental abruption, has been implicated in over 50% of all
clinician-initiated preterm deliveries and may play a more substantial
role in term gestations (6, 29).
The main strength of the study is the application of a causal mediation
approach, a cutting edge statistical methodology (30), to evaluate the
individual contribution of SGA and the impact of gestational age on
caesarean risk. Many studies in the obstetrical literature
inappropriately attempt to adjust for gestational age as a confounder,
leading to biased associations since gestational age may be on the
causal pathway for many adverse perinatal outcomes (31, 32). Using
causal mediation analysis, the study results clarify the impact of
gestational age as an intermediate on the SGA-labour outcome paradigm to
elucidate the causal relationship between exposure and outcome.
We explicitly outlined the assumptions that we used to make causal
claims in this mediation analysis (12). Further, these assumptions were
assessed by a sensitivity analysis that evaluated the extent unmeasured
confounding could bias our results. The E-values were 2-3 fold larger
than the observed effect estimates, suggesting that it would take very
large effect sizes of unmeasured confounders to nullify the
associations, a situation that is unlikely. This methodological approach
strengthens the study, and suggests robustness of the findings.
The study has some limitations. The data could not provide insight into
spontaneous versus clinician-initiated preterm deliveries. We wanted to
assess labour outcomes, including abnormal fetal heart rate patterns,
but this information is not readily available from the data source. In
order to capture women who had caesarean deliveries for fetal
indications after unsuccessful TOL, we had to include all women who were
coded as having caesarean delivery after TOL. Some of these patients
required caesarean delivery for labour dystocia as well as maternal
indications. Although we were able to avoid confounding due to prior
caesarean delivery by limiting the analytic cohort to women of live
birth parity 2, we recognize that our primary outcome has some
limitations.