Discussion
Main findings
The aim of this study was to assess the risk of recurrent preterm birth
following spontaneous preterm birth between
16+0-27+6 weeks. We found that, at
all gestational ages, patients with previous sPTB from 16 weeks onwards
are at high risk for recurrent preterm birth.
A short interpregnancy interval of 0-3 months was associated with an
increased risk of subsequent preterm birth < 37 and
< 32 weeks. Short intervals were more common in patients with
prior sPTB < 24 weeks. Since in the Netherlands no active
support is offered to neonates born before 24 weeks, these births
inevitably end in perinatal death. Therefore, parents might pursue a
subsequent pregnancy shortly after the immature birth.
Interpretation
Multiple studies assessed the association between obstetric history and
the risk for subsequent PTB and found higher risks of PTB following
recurrent miscarriage or prior PTB < 37
weeks.6,11–18 Limited research assessed the
subsequent risk after birth between 16-24 weeks and a cohort comparison
is complicated by international differences in terminology and
registration. One study by Goldenberg et al. (‘93) found a recurrent PTB
rate of 39% in women who gave birth between 13-24 weeks, which
increased to 62% if the prior birth was between 19-22
weeks.12 Edlow et. al. (’07) found that women with
prior birth between 14-24 weeks were 10.8 times more likely to
experience subsequent second-trimester loss or PTB compared to those
with previous full-term delivery.13 A third study from
Denmark (’17) reported a recurrence rate of 7.3% following birth
between 16 and 28 weeks, but this rate varied significantly depending on
the characteristics of the previous birth (fetal anomaly, multiple
gestation, or intrauterine fetal demise), complicating a comparison with
our findings.11
Our results confirm that sPTB between 16-28 weeks is associated with a
high risk for subsequent PTB, with an emphasis that the risk is also
high in women with prior sPTB between
16+0-19+6 weeks. Women with prior
birth at 16+0-19+6 weeks of
gestation had a recurrent risk for PTB < 32 and < 37
weeks of respectively 5.8% and 11.7%, which is high compared to 1.0%
and 5.5% in a general Dutch population of multiparous women with
singleton and multiple pregnancies in 2021
(www.peristat.nl). Therefore, the
obstetric history of women with prior birth between
16+0-19+6 weeks might deserve equal
consideration in a risk assessment for subsequent PTB. Labelling
spontaneous birth at this gestational age range as a miscarriage, may
underestimate the risk for subsequent PTB. Using terminology that
acknowledges the increased risk, by classifying birth between 16-20
weeks as PTB instead of miscarriage, could enhance the recognition,
approach and preventive treatment of patients at risk.
The high recurrent risk after births at low gestational ages raises
questions whether the subsequent risk may also be increased after birth
at gestational ages below 16 weeks. If so, women with a previous
miscarriages just below 16 weeks might be misidentified as patients at
at-risk for subsequent PTB. Accurate national registration is vital to
assess PTB risk following births at 13-15 weeks. All pregnant women in
the Netherlands are advised to contact a midwife or general practitioner
before 10 weeks of pregnancy, allowing for precise gestational age
determination via ultrasound. Therefore, gestational age at which a
(late) miscarriage might occur should be easy to determine. Registering
these pregnancy outcomes will help PTB risk evaluation. If an increased
PTB risk is found, further research is needed to assess whether and
which preventive measures improve subsequent pregnancy outcomes.
Strengths and limitations
This study used data from the perinatal registry in the Netherlands,
covering >97% of births.10 The large
sample size with data from multiple consecutive years enabled a detailed
assessment on subsequent PTB risk by gestational age and allowed for
analysis on the interpregnancy interval. However, due to non-mandatory
registration for births until 24 weeks, underrepresentation is likely
for prior births between 16-24 weeks and also for the recurrence risk in
that range.
In the index pregnancy selection, we excluded induced births, focusing
on spontaneous and unknown start of labor. Excluding pregnancies
complicated by congenital abnormalities or IUFD in the index pregnancy,
likely removed inaccurately registered induced deliveries. However, we
cannot rule out the possibility that the index pregnancy cohort might
still include induced births, potentially underestimating the risk of
subsequent PTB after sPTB. Our subsequent cohort lacks distinction for
high initial PTB risk (e.g., multiples, congenital issues, IUFD).
Therefore, the risk is most likely lower for uncomplicated singletons.
Still, our PTB rates remain notably high, even compared to national
figures encompassing all pregnancies.
No data were available regarding the use of preventive measures in the
subsequent pregnancy. In the Netherlands, patients with previous sPTB
< 34 weeks of gestation are typically offered preventive
progesterone treatment, additional cervical length screening and
potentially receive interventions such as a cervical
cerclage.19 Therefore, it is plausible that a
significant portion of our study population received preventive
treatment in the subsequent pregnancy, which could underestimate the
actual risk faced by patients. However, there may be limited awareness
regarding the increased risk following PTB around 16 weeks, resulting in
fewer or no preventive measures and therefore providing a representative
risk estimate for this subgroup.
No core outcome set (COS) could be used in the design of this study
because of limited availability of the required outcome measures in the
national perinatal registry.
Out of 2,294 women with prior sPTB, we successfully linked 1,285
nulliparous women to a subsequent pregnancy in a primiparous cohort. No
linkage could be established in 1009 women, possibly due to insufficient
matching variables. For example, if the birth record of the subsequent
pregnancy did not include the date of the prior birth and if ZIP code
changed over time, there would insufficient matching variables to
establish a linkage. Other reasons could include no subsequent pregnancy
within the 5-year timeframe, cases where the only pregnancy within the
5-year timeframe resulted in a miscarriage or termination before 16
weeks, or misreported subsequent births as nulliparous births. Also, 172
patients from the index cohort were excluded due to the antenatal
diagnosis of IUFD, which might involve cases of IUFD due to fetal
distress from extreme preterm labor. Given its likelier occurrence
before 24 weeks, the group of patients with prior birth between 16-24
weeks may not be entirely represented.