From the Guidelines
The primary risk factor for Down syndrome is advanced maternal age, with women over 35 having a significantly higher chance of having a baby with this condition, as reported in 1 and 1. The risk increases progressively with age, particularly after age 40. Having a previous child with Down syndrome also increases the risk by about 1%, regardless of maternal age, as mentioned in 1. Carriers of the genetic translocation form of Down syndrome (about 3-4% of cases) have an elevated risk that varies depending on which parent carries the translocation, according to 1. Other factors that may influence risk include certain environmental exposures, abnormal folate metabolism, and genetic variations that affect chromosome separation during cell division. While these factors increase probability, it's essential to understand that Down syndrome can occur in pregnancies without any known risk factors, and most babies born to older mothers do not have the condition. The underlying mechanism involves the presence of an extra chromosome 21 (trisomy 21), which typically occurs due to random errors during the formation of reproductive cells, especially eggs, which become more common as women age, as explained in 1.
Some key points to consider:
- Advanced maternal age is the primary risk factor for Down syndrome, with a term risk of about 1:380 for an average 35-year-old woman, as stated in 1.
- The risk of having a child with Down syndrome increases with advancing maternal age, with approximately 95% of cases resulting from sporadic nondisjunction during parental meiosis, according to 1.
- Family history of Down syndrome increases the a priori risk, depending on the degree of relatedness and the mode of inheritance, as mentioned in 1.
- Carriers of the genetic translocation form of Down syndrome have an elevated risk that varies depending on which parent carries the translocation, as reported in 1.
It's crucial to note that while these factors increase the probability of Down syndrome, the condition can occur in pregnancies without any known risk factors, and most babies born to older mothers do not have the condition, highlighting the importance of prenatal screening and genetic counseling, as discussed in 1.
From the Research
Risk Factors for Down Syndrome
- The risk of Down syndrome is directly related to maternal age 2, 3, 4
- Advanced maternal age at conception is a certain risk factor for the birth of a child with Down syndrome 4
- Recombination errors are also a certain risk factor for the birth of a child with Down syndrome 4
- Other potential risk factors that have been suggested to contribute to the birth of a child with Down syndrome include:
- Paternal age can also influence the incidence of Down syndrome, particularly when combined with advanced maternal age 5
- A paternal age effect was seen in association with a maternal age of 35 years and older, and it was most pronounced when maternal age was 40 years and older 5
- In cases where the maternal age is 40 years and older, the paternal contribution to Down syndrome was 50% 5
Maternal Age and Down Syndrome
- The median maternal age in one study was 32 years, with a range of 20-41 years 2
- Women who are 35 years or older on their due date should be offered chorionic villus sampling or second-trimester amniocentesis 3
- Women younger than 35 years should be offered maternal serum screening at 16 to 18 weeks of gestation 3
Prenatal Testing and Diagnosis
- Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis 6
- NIPT approaches involve whole-genome sequencing, targeted sequencing, and assessment of single nucleotide polymorphism (SNP) differences between mother and fetus 6
- Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes, and possibly Patau syndrome, in high-risk women 6