Applicability of first‐trimester combined screening for fetal trisomy 21 in a resource‐limited setting in mainland China

Li, B; Sahota, Daljit Singh; Lao, Terence T.; Xu, Jing; Hu, SQ; Zhang, L; Liu, QY; Sun, Qiang; Tang, D; Ma, Rong

doi:10.1111/1471-0528.14004

Cited by 11 publications

(15 citation statements)

References 19 publications

(45 reference statements)

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“…The actual total risk of the fetus being affected by one of the autosomal and sex chromosome aneuploidies, four microdeletion syndromes and 50 single gene diseases is 1 in 65 (Additional file 3). Based on the above estimates, all pregnancies matching the characteristics of our cohort [28,29], a first tier NIPT such as the one presented herein should be integrated as part of standard health care. Accordingly, being aware of the fetal risk, couples can take informed decisions regarding the clinical management of their pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases

Koumbaris¹,

Achilleos²,

Nicolaou³

et al. 2019

Mol Cytogenet

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Background: Non-invasive prenatal testing (NIPT) has been widely adopted for the detection of fetal aneuploidies and microdeletion syndromes, nevertheless, limited clinical utilization has been reported for the non-invasive prenatal screening of monogenic diseases. In this study, we present the development and validation of a single comprehensive NIPT for prenatal screening of chromosomal aneuploidies, microdeletions and 50 autosomal recessive disorders associated with severe or moderate clinical phenotype. Results: We employed a targeted capture enrichment technology powered by custom TArget Capture Sequences (TACS) and multi-engine bioinformatics analysis pipeline to develop and validate a novel NIPT test. This test was validated using 2033 cell-fee DNA (cfDNA) samples from maternal plasma of pregnant women referred for NIPT and paternal genomic DNA. Additionally, 200 amniotic fluid and CVS samples were used for validation purposes. All NIPT samples were correctly classified exhibiting 100% sensitivity (CI 89.7-100%) and 100% specificity (CI 99.8-100%) for chromosomal aneuploidies and microdeletions. Furthermore, 613 targeted causative mutations, of which 87 were unique, corresponding to 21 monogenic diseases, were identified. For the validation of the assay for prenatal diagnosis purposes, all aneuploidies, microdeletions and point mutations were correctly detected in all 200 amniotic fluid and CVS samples. Conclusions: We present a NIPT for aneuploidies, microdeletions, and monogenic disorders. To our knowledge this is the first time that such a comprehensive NIPT is available for clinical implementation.

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Section: Discussionmentioning

confidence: 99%

Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases

Koumbaris¹,

Achilleos²,

Nicolaou³

et al. 2019

Mol Cytogenet

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“…Studies assessing the cost-effectiveness of the FMF 'screen-and-treat' strategy concluded that routine aspirin administration is the optimal cost-effective approach, compared both with no aspirin administration for prevention and with aspirin administration based on serum biomarker and ultrasound measurements or clinical risk factors 45,46 . However, these studies did not take into account that PE screening can be incorporated alongside first-trimester trisomy screening, which has been validated as cost-effective in both developed and developing countries, including China 47,48 . The relatively low positive predictive value of the preterm PE screening test (e.g.…”

Section: Implications For Clinical Applicationmentioning

confidence: 99%

Prospective evaluation of first‐trimester screening strategy for preterm pre‐eclampsia and its clinical applicability in China

Gao

Liu

et al. 2021

Ultrasound in Obstet & Gyne

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Objectives To evaluate, in a Chinese population, the performance of a screening strategy for preterm pre‐eclampsia (PE) using The Fetal Medicine Foundation (FMF)'s competing‐risks model and to explore its clinical applicability in mainland China. Methods This was a prospective, multicenter, observational cohort study including 10 899 women with singleton pregnancy who sought prenatal care at one of 13 hospitals, located in seven cities in mainland China, between 1 December 2017 and 30 December 2019. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI) and maternal serum levels of placental growth factor (PlGF) and pregnancy‐associated plasma protein‐A (PAPP‐A) at 11 + 0 to 13 + 6 weeks’ gestation were measured and converted into multiples of the median using Chinese reference ranges. Individualized risk for preterm PE was calculated using the FMF algorithm. Prior risk was calculated based on maternal demographic characteristics and obstetric history. We evaluated the efficiency of the screening strategy using various combinations of biomarkers and analyzed its predictive performance for a composite of placenta‐associated adverse pregnancy outcomes, including PE, placental abruption, small‐for‐gestational age (SGA) and preterm birth, at fixed false‐positive rates for preterm PE. Results We identified 312 pregnancies that developed PE, of which 117 cases were diagnosed as preterm PE (< 37 weeks' gestation). There were 386 pregnancies complicated by severe composite placenta‐associated adverse outcome, including preterm PE, 146 cases of severe SGA (birth weight < 3rd percentile) neonate, 61 cases with placental abruption and 109 cases of early preterm birth < 34 gestational weeks. The triple‐marker model containing biomarkers MAP, UtA‐PI and PAPP‐A achieved, at fixed false‐positive rates of 10%, 15% and 20%, detection rates for preterm PE of 65.0%, 72.7% and 76.1%, respectively, and detection rates for severe composite placenta‐associated adverse outcome of 34.7%, 41.7% and 46.4%, respectively. Replacing PAPP‐A with PlGF or adding PlGF to the model did not improve the performance. Of women screening positive for preterm PE at a fixed 5% false‐positive rate, an estimated 30% developed at least one placenta‐associated adverse pregnancy outcome, including PE, placental abruption, SGA (birth weight < 10th percentile) and preterm birth < 37 weeks. Conclusions The FMF competing‐risks model for preterm PE was found to be effective in screening a mainland Chinese population. Women who screened positive for preterm PE had increased risk for other placenta‐associated pregnancy complications. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

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“…Human chorionic gonadotropin (hCG) is routinely used for first trimester Down's syndrome screening programs worldwide (11,12). hCG could be a determinant of GDM risk as it has been shown to stimulate placental glycogenolysis through activation of adenylate cyclase and its immunomodulatory effects could ameliorate pancreatic autoimmunity (13,14).…”

Section: Introductionmentioning

confidence: 99%

Associations between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus

Liu

Guo

Maraka

et al. 2021

Thyroid

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Background: Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones. Methods: This study included 18,683 pregnant women presenting at a tertiary hospital in Shanghai, China, between January 2015 and December 2016. GDM was diagnosed using a 2-hour, 75-g, oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines. Multivariable logistic or linear regression models were used to identify associations, adjusting for maternal age, education level, family history of diabetes, parity, fetal sex, thyroperoxidase antibody (TPOAb) status, and prepregnancy body-mass index. Results: Higher hCG concentrations were associated with a lower plasma glucose level during the OGTT, but not with fasting plasma glucose or hemoglobin A1c concentrations tested during early pregnancy. hCG in early pregnancy was negatively associated with GDM risk ( p = 0.027). Mediation analysis identified that an estimated 21.4% of the association of hCG-associated GDM risk was mediated through changes in free thyroxine (fT4) concentrations ( p < 0.05). In the sensitivity analysis restricted to TPOAb-positive women, hCG was not associated with GDM ( p = 0.452). Conclusions: Higher hCG levels in early pregnancy are associated with a lower risk of GDM. Maternal fT4 may act as an important mediator in this association.

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Applicability of first‐trimester combined screening for fetal trisomy 21 in a resource‐limited setting in mainland China

Cited by 11 publications

References 19 publications

Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases

Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases

Prospective evaluation of first‐trimester screening strategy for preterm pre‐eclampsia and its clinical applicability in China

Associations between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus

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