Strengths and limitations
The present study had several limitations. First, owing to limited
information regarding the use of ARTs in the database, we could not
adjust the data for the effect of ARTs. Several previous studies have
shown that the incidence of malformations is higher in multiple
pregnancies that are achieved using in vitro fertilization or
intracytoplasmic sperm injection than in singletons. Second, most of the
BDs associated with multiple pregnancies were isolated fetal
abnormalities, because multiple abnormalities may lead to stillbirth or
abortion.25 Because the database does not contain
information regarding spontaneous abortion, artificial abortion, or
stillbirth, this may have skewed the analysis of the BD data. Thus, the
high incidence of BDs associated with multiple pregnancies may have been
at least in part determined by selection bias, because clinicians are
more careful with respect to twin pregnancies and may therefore have
conducted more diagnostic tests to check for fetal defects. These
limitations should be addressed in the design of future studies.