Non-invasive prenatal testing reveals copy number variations related to pregnancy complications

Abstract

Background Pregnancy complications could lead to maternal and fetal morbidity and mortality. Early diagnosing and managing complications have been associated with good outcomes. The placenta was an important organ for development of pregnancy complications. Thus, non-invasive prenatal testing technologies could detect genetic variations, such as aneuploidies and sub-chromosomal copy number variations, reflecting defective placenta by maternal plasma cffDNAs. Maternal cffDNAs had been proved to derive from trophoblast cells of placenta. Results In order to find out the relationship between genetic variations and pregnancy complications, we reviewed NIPT results for subchromosomal copy number variations in a cohort of 3890 pregnancies without complications and 441 pregnancies with pregnancy complications including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm prelabor rupture of membranes (PPROM) and placenta implantation abnormalities (PIA). For GDMs, we identified three CNV regions containing some members of alpha- and beta-defensins, such as DEFA1, DEFA3, DEFB1. For PIHs, we found three duplication and one deletion region including Pcdhα, Pcdhβ, and Pcdhγ, known as protocadherins, which were complicated by hypertensive disorders. For PPROMs and PIAs, we identified one and two CNV regions, respectively. SFTPA2, SFTPD and SFTPA1, belonging to surfactant protein, was considered to moderated the inflammatory activation within the fetal extra-embryonic compartment, associated to duration of preterm prelabor rupture of fetal membranes, while MEF2C and TM6SF1 could be involved in trophoblast invasion and differentiation. Conclusions Our findings gave a clue to correlation between genetic variations of maternal cell-free DNAs and pregnancy complications. Electronic supplementary material The online version of this article (10.1186/s13039-019-0451-3) contains supplementary material, which is available to authorized users.

Identify gestational diabetes mellitus by deep learning model from cell-free DNA at the early gestation stage

“…We annotated 2190 genes in the window regions ( Supplementary Table 2 ). The previously discovered alpha- and beta-defensin genes, DEFA1, DEFA3 and DEFB1 [ 22 ], also occurred in our gene list.…”

“…A study with cfDNA had identified CNVs in three chromosome regions related to a high risk of GDM. Gene enrichment analysis reveals that the genes in these regions contain some alpha- and beta-defensin family members, such as DEFA1, DEFA3 and DEFB1, copy number variations of which are associated with type I and II diabetes [ 22 ]. However, there are no existing methods for early prediction of GDM based on the CNV markers.…”

Translation and cross-cultural validation of the non-invasive prenatal testing questionnaire in Arabic

“… 13 The questionnaire contains demographic information related to age, native language, educational level, gestational week, parity and previous miscarriages as well as multiple choice and Likert scale questions related to their attitudes, knowledge, choice of information related to risk and decision-making of prenatal testing including the NIPT. 7 The attitudes regarding delivering a baby with a chromosomal defect, and the self-estimated probability of the event, was included in the assessment items.…”

“… 6 Non-invasive prenatal testing is a cell-free DNA test involving the isolation of fetal DNA from a maternal plasma sample. 7 The cell-free DNA is from a placental origin, released in the maternal circulation from the fetal apoptotic trophoblasts. 8 The release of fetal DNA fragments in maternal circulation increases with gestational age and the reliability of testing is more than 10% as early as 10 weeks gestation.…”

Counselling for prenatal anomaly screening—A plea for integration of existential life questions

“…Therefore, it is important to provide health education regarding the aim of prenatal anomaly screening and its possibilities through medical expertise. In countries offering prenatal anomaly screening, medical counsellors are easily interpreted as exponents of (medical) society, usually focusing primarily on the advantage of screening to detect an anomaly to manage or monitor pregnancy outcomes [11,[16][17][18][19]. However, parents might have other motivations for both attending counselling and/or entering prenatal screening programmes [20].…”