Materials and Methods
We performed a retrospective cohort study from January 2006 to August
2017. We identified all triplet pregnancies which underwent first
trimester ultrasonography to measure the fetal crown-rump length and to
determine amnionicity and chronicity. Only trichorionic triamniotic
triplet pregnancies were included, and were divided into two groups
according to their decisions after counseling on the MFPR; expectant
management (EM) group consisting of women who declined MFPR and embryo
reduction (ER) group consisting of women who chose MFPR from triplet to
twin pregnancy. Women who decided to reduce to singleton pregnancy from
triplet pregnancy were excluded. The institutional review boards of
Seoul National University Hospital Clinical Research Institute (IRB No.;
H-1311-045-533) and CHA Bundang Medical Center approved this study (IRB
No.; C 2016-10-007).
MFPR were performed with transvaginal or transabdominal intrathoracic
potassium chloride injection before 14 weeks of gestation. We reviewed
the clinical records of the mothers and babies for information
concerning maternal demographics, clinical presentation, laboratory
examinations, ultrasound assessments, and birth outcome. The two groups
were compared for the rates of non-viable pregnancy loss before 23
weeks, the rates of preterm birth, and the number of surviving fetuses.
Maternal obstetric complications, such as preeclampsia and gestational
diabetes, were also evaluated.
To evaluate the short-term birth outcome, we investigated neonatal
survival and composite morbidity, which was defined as the occurrence of
at least one of the followings: neonatal sepsis, intracranial hemorrhage
(ICH), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA),
pulmonary hypertension, respiratory distress syndrome (RDS),
bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC).
We evaluated SGA using the standard described in the previous
report.8 We investigated the long-term
neurodevelopment outcomes after one year of corrected age. Developmental
delay and cerebral palsy were evaluated by the Korean Ages and Stages
Questionnaire (K-ASQ), or Gross Motor Function Measure (GMFM) or chart
review. Because the K-ASQ is useful only for young children (4-60 months
of age), older children (preschool or elementary school age) were
instead evaluated by pediatric charts regarding their ability to perform
daily activities or learning ability in school. We considered
development to be normal in children described with no difficulties in
fulfilling their normal academic obligations; those who attended special
schools for mentally retarded children were categorized as cases of
developmental delay.
Statistical analysis was performed using SPSS version 23.0 (SPSS
Institute, Chicago, IL, USA) and R, version 3.3.1 software (R Foundation
for Statistical Computing, Vienna, Austria; http://www.r-project.org).
We analyzed discrete data using Fisher’s exact test and comparisons of
continuous variables were performed with Mann-Whitney U test, as
appropriate. A generalized estimating equation (GEE) was used to assess
which variables were associated with neonatal outcomes, accounting for
the familial correlation in the model, because the study population
consisted of twin or triplet pairs within a single
mother.9 We also performed a multivariable analysis
including maternal age, BMI and method of conception as covariates,
which were selected with p < 0.2 in univariate analysis when
comparing cases with neonatal survival or those with neonatal death. A P
value <0.05 was considered statistically significant.