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.
