Discussion
The principal findings of the current study are as follows: 1) the risk
of preterm birth was higher in EM group compared to ER group; 2)
however, the risk of non-viable pregnancy loss lower in EM group than in
ER group; 3) the rate of cases with at least one alive neonate was
higher in EM group compared to ER group; 4) short- and long-term outcome
of neonates was comparable between ER and EM groups.
The risk of preterm birth had been consistently reported to be lowered
after ER in previous studies, and the result of the current study also
shows increased risk of preterm birth in ER
group.7,10,11 However, the risk of non-viable
pregnancy loss (miscarriage) after ER is controversial. In recent
meta-analysis which analyzed 6 studies, the miscarriage risk was not
different between EM and ER groups.12 In ER group
compared to EM group, two studies [Antsaklis et al, 2004 (n=255);
Chaveeva et al, 2013 (n=494)] showed increased miscarriage rate (2.9%
->8.1%; 3.9%->7.9%
respectively),10,13 two studies [Drugan et al, 2013
(n=82); Shiva et al, 2014 (n=115)] showed similar rate (from 5.6% to
6.5%; from 12.3% to 12.1% respectively),11,14 and
two studies [Ata et al., 2011 (n=65); Skiadas et al., 2011 (n=156)]
showed decreased miscarriage rate (from 17.9% to 7.7%; from 14.5% to
6.9% respectively).15,16 Higher miscarriage rates in
ER group have been observed in studies with larger numbers of
subjects.10,13 Their results are consistent with the
current study. As experience of MFPR increases, it was reported that the
miscarriage risk after MFPR of triplet to twin pregnancies has reached
to the twin’s natural miscarriage rate.17,18 However,
considering that less invasive procedures such as chorionic villi
sampling or amniocentesis has procedure related fetal
loss,19 it is not reasonable that MFPR is innocuous.
And we are concerned that dead fetus may have acute and remote effects
on the other living fetuses.
In the current study, we have shown a statistically significant
difference in the rate of pregnancies with at least one alive neonate in
the EM group (97.7%) compared to the ER group (92.3%) (p=0.013). This
result may be important information for pregnant woman and her family
who consider MFPR. In term of at least one survival, women with keeping
all three fetuses (EM group) have better outcome than women with
sacrificing one fetus (ER group). Ninety-seven percent of at least one
survival seems to be high. However, 94.8% of at least one survival was
already reported in one study which was conducted from 1986 to
201313. Considering that current study was done more
recently, better outcomes of the current study is not unexpected. Even
though one third of fetuses are already sacrificed in ER group, lower
rate of at least one survival in ER may have an effect on the attitude
to MFPR.
What is interesting in this study is that the risk of neonatal sepsis
was significantly higher in the ER group compared with the EM group even
after multivariable analysis. This result suggests that ER itself might
be a risk factor for sepsis. We think that there is a possibility that a
clinical or subclinical inflammatory response to the dead fetal and
placental tissue following embryo reduction might result in release of
cytokines which may affect the survived fetus more fragile to septic
condition.
The results on long-term neurodevelopmental outcomes are the major
strength of the current study. Although prolonged gestation and increase
in birth weight are also meaningful, more critical outcomes are
long-term sequelae such as cerebral palsy (CP) and developmental delay.
We showed rates of developmental delay and cerebral palsy which were not
different between the EM group and ER group even though the rate of
early preterm birth was significantly higher in the EM group. The
incidence of CP in the triplet pregnancy was 28 to 44.8 / 1000, based on
data from the 1980s and, 20-22 but it decreased to
18/1000 on the data from 1990s and early 2000s.23Actually, the risk of cerebral palsy is highest in neonates delivered at
less than 28 weeks of gestation. It was recently reported that the rate
of CP was 5.6% (21/381) in triplets or higher-order births of extremely
low birth weight infants.24 Our study revealed much
lower rates of CP as only 0.44% in EM group and 2.0% in ER group.
Moreover, after introduction of MgSO4 for neuroprotection in threatened
early preterm delivery,25,26 CP incidence will
decrease further in the near future.
Our study had several limitations. First, this was a retrospective
cohort study design. Second, we could not evaluate developmental delays
using an identical method for all patients, due to the wide range of age
at the time of examination.