Miscarriage history raises risk for baby chromosome abnormalities
Background
Approximately 10-15% of recognized pregnancies end
in miscarriage. The main cause of miscarriage is attributed to chromosomal
abnormalities in the embryos. Approximately 70-80% of miscarriages occur due to
chromosomal defects in the embryo. Unfortunately, as women age, their eggs age
as well. The older an egg gets, the greater the chance for chromosomal
abnormalities in an embryo formed from that egg. If an embryo has a chromosomal
abnormality, there is a much greater chance the pregnancy will end in
miscarriage. Less than one percent of chromosomally abnormal fetuses are live
born.
Chromosomes come in pairs. Each parent contributes
half of their child's genetic makeup. 23 chromosomes are inherited from each
parent giving the total of 46. During fertilization, some embryos get one too
many of a certain chromosome (trisomy) whereas some embryos may be missing one
chromosome (monosomy). These types of abnormalities are known as aneuploidies.
The most common form of aneuploidy in humans is Down's syndrome. Babies with
Down's Syndrome are born with an extra copy of chromosome 21 (trisomy 21). Next
to Down's Syndrome, the most common abnormalities found are trisomy 13 and
trisomy 18.
Previous research has shown that women who have a
live birth of a baby with an aneuploidy such as Down Syndrome are at an
increased risk for another baby with the same or different aneuploidy. However,
it is not clear if women who has a miscarriage due to an aneuploidy are at
higher risk for another baby with an aneuploidy.
A study performed recently investigated whether a
history of spontaneous miscarriage predicted an increased risk of fetal
aneuploidy.
Pre-Natal Testing
A total of 46,939 pregnant women were included in
this study. Of these, 80.1% were over the age of 35. Older age was the primary
reason that these women were referred for prenatal testing. Patients underwent
invasive prenatal testing using either amniocentesis-removal of fluid from the
amniotic sac surrounding the fetus or Chorionic Villus Sampling (CVS)- removal
of placental tissue to determine the chromosomal make-up (karyotype) of the
fetus.
Women were excluded from the study if they had a
known genetic condition related to aneuploidy, prior pregnancy with aneuploidy,
or previous multiple pregnancies. After the testing was completed, a pregnancy
history for each patient was obtained, including the number of prior
miscarriages.
Researchers determined whether a fetus harbored any
type of aneuploidy, whether an aneuploidy was in one of the three most common
(trisomy 13, trisomy 18 or trisomy 21) and whether
the mother had any previous miscarriages.
Results: Miscarriage increases the risk for
aneuploidy
The rate of trisomy 13, 18, or 21 amongst all women
referred for testing was 1.21% and for any aneuploidy the rate was 1.49%. The
more miscarriages in a woman's history, the more likely she was to be carrying a
fetus with an aneuploidy. Trisomies increased from 1.10% in women with no prior
spontaneous miscarriages to 1.70% in women with 3 or more miscarriages. The rate
of general aneuploidy increased the same way from 1.39% to 2.18%.
For each miscarriage in a woman's history, the
chance for having a baby with an aneuploidy went up by 13%.
Because maternal age and aneuploidy are closely
related, women were separated into groups younger than 35 and women 35 and
older. Analysis revealed that younger women did not seem to be at increased risk.
Stated another way, for a woman with a prior risk of
1 in 300 for Down syndrome, 3 previous spontaneous abortions would increase that
risk by 47% to 1 in 204. For a woman with a prior risk of any aneuploidy of 1 in
280, 3 previous spontaneous miscarriages would increase the risk to 51% to 1 in
185.
Miscarriage Study Limitations
The study suggests that the risk of aneuploidy
increased with an increasing number of prior spontaneous miscarriages in women
35 and over.
This study had several limitations. Firstly,
chromosomal analysis of the mothers themselves was not available. It is possible
that some women had miscarriages because of an unknown genetic pre-disposition
of certain defects related to aneuploidy. They were also limited by the
information collected during the study. For instance, the ages of the fetuses at
the time of the previous miscarriages were not known. Miscarriages earlier in
pregnancy are a greater indication for aneuploidy. Later in pregnancy, the
association of aneuploidy is not as great. Also, the maternal ages at the time
of the previous miscarriages were not known either.
Miscarriage study conclusions
The data from this study supports the theory that
previous miscarriages increase the chances of subsequent fetal chromosomal
abnormalities particularly in pregnancies that occur in women who are 35 years
of age or older.
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