Discussion
The study’s objective was to evaluate the pregnancy, delivery and neonatal outcomes in mothers diagnosed with DS.
The medical literature has demonstrated that individuals with DS have higher rates of thyroid dysfunction including congenital hypothyroidism, thyroid autoimmunity such as Hashimoto’s disease or Grave’s disease9–11. In addition, individuals with DS have a 3 to 4 fold increased risk of developing type 1 diabetes mellitus, which occurs at a younger age compared to individuals without DS10–12. Furthermore, DS increased the risk of developing obesity in children and adults 10. Surprisingly, there was no increased prevalence of thyroid disease, pregestational diabetes or obesity in mothers with DS in our cohort. It is possible, that our sample size of mothers with DS was too small to detect the increased risk of these endocrinologic disorders. Another theory is that women with DS and thyroid disease, diabetes or obesity were less likely to conceive and deliver a baby than women with DS without these medical conditions.
Women with DS maintain some level of fertility, since many case reports have described pregnancies to mothers with DS 6–8,17. It is possible that women with DS suffer from subfertility because they have a relatively low risk of fecundity based on the number of case reports in the literature. However, again bias exists with possible family pressure to practice safe birth control applied by family members particularly if the subjected with DS could not care for a child. Subfertility in women with DS, if it exists is hypothesized to be secondary to premature ovarian dysfunction 5,18.
It has been suggested in the literature that one in three to one in two infants born to mothers with DS, have DS themselves5,7,20. Women with trisomy 21 would be expected to produce an equal number of gametes 23 X and gametes 24 X + 216. This should lead to an equal number of infants with DS and with a normal karyotype. However, some evidence in the literature has suggested that the frequency of DS infants born to mothers with DS could be lower. It is possible that this variation is due to the selective advantage of euploid gametes 6.
Women with DS in our cohort had a statistically significant increased risk of having a preterm delivery (p=0.02). Literature suggests that mothers with DS are at increased risk of preterm delivery6. The increased prevalence of PTD could be partially explained by the risk contributed by carrying an infant with DS, as mothers carrying DS infants are known to be at increased risk of PTD21,22. Furthermore, another contributing factor to PTD could the increased risk of comorbidities in mothers with DS.
Our results demonstrated that infants born to mothers with DS, are almost 1000% more likely to have congenital anomalies compared to the control group. This could likely be explained by increased prevalence of DS infants in mothers with DS as well as other abnormalities not related to DS in the offspring 5,20. It has been well recognized in the literature that infants with DS are more likely to have congenital anomalies and approximately 60 to 64% of children with DS have at least one major anomaly, with the most common ones being cardiac anomalies, digestive system anomalies and respiratory system anomalies 22–24. The literature also described that many offspring to women with DS were associated with other malformation and cognitive deficit and no DS 7,20. However, this is a single study and the question remains, whether infants without DS, born to mothers with DS have an increased risk of congenital anomalies?
Furthermore, our study found that infants born to mothers with DS are 1300% more likely to be SGA compared to infants born to mothers without DS. This is likely partially due to the increased risk of having a DS infant in mothers with DS. Although limited, the available data suggests that infants born to mothers with DS have low birth weight6,21,22. However, it is possible that being born to a mother with DS confers an additional risk to being SGA. A study by Rani et al. summarized cases of DS reported in the literature and suggested that babies born to mothers with DS, at term, are at increased risk of having low birth weight, even if they had a normal karyotype6.
Mothers with DS were almost 2100% more likely to have an IUFD compared to mothers without DS. There is an increased likelihood that mothers with DS carry a child with DS which in itself has been associated with an increased risk of IUFD 21–23. A study by Morris and al. demonstrated that in mothers carrying DS fetuses, between the time of chorionic villus sampling and term an estimated 43 % of pregnancies ended in miscarriage or stillbirth, between the time of amniocentesis and birth 23. Furthermore, we can hypothesize that maternal aneuploidy increases the risk of other aneuploidies in the fetus which can lead to an increased risk of IUFD. However, there is no evidence in the literature regarding the genetics of stillborn infants to mother with DS.
Although our study showed that children born to mothers with DS are at increased risk of malformation, it would be interesting to know the type of congenital malformations in the infants born to mothers with DS. Furthermore, It would also be interesting to know if rates of complications differed between mothers with complete and mosaic DS. This data is unavailable in the literature.