超声诊断的短股骨胎儿产前诊断结果和随访研究

Prenatal diagnosis and follow-up of fetuses with short femur detected by ultrasonography

摘要

目的 对胎儿股骨发育小于两个标准差及以上(≤-2SD)孕妇的产前诊断结果、妊娠结局及胎儿出生后生长水平情况进行分析,从而更好地促进短股骨(SF)胎儿的产前优生咨询。方法 选取2018年12月至2022年12月期间因超声诊断股骨发育≤-2SD,就诊于淮安市妇幼保健院产前诊断中心行介入性产前诊断的35例孕妇为研究对象.依据胎儿超声表现分为单纯SF组和SF合并其他超声异常组.对两组产前诊断结果包括染色体微阵列(CMA)和家系全外显子组测序(Trio-WES)、妊娠结局、生长水平进行随访和比较分析。结果 SF胎儿致病性染色体异常诊断率为5.71%(2/35),其中单纯SF组和SF合并超声异常组分别为4.76%(1/21)和7.14%(1/14).SF胎儿Trio-WES总体诊断率为26.32%(5/19),其中单纯SF组和SF合并超声异常组分别为33.33%(4/12)和14.29%(1/7).孕有SF胎儿的孕妇引产率22.86%(8/35)、妊娠丢失率17.14%(6/35)、活产率54.29%(19/35).两组之间引产率、妊娠丢失率、活产率均无统计学差异(P>0.05).SF胎儿出生后成功随访19例,为3~48月龄,均未见其他异常,身高水平处于下等和中下等的频率为57.89%(11/19),其中单纯SF组和SF合并超声异常组分别为63.64%(7/11)和50.00%(4/8),两组差异无统计学意义(P>0.05)。结论 SF胎儿染色体异常诊断率5.71%,Trio-WES诊断率26.32%,二者联合应用是SF遗传学病因诊断的优化组合.排除遗传学原因后SF胎儿相关孕妇仍有较高的丢失率.SF胎儿出生后、身高水平位于中下等的频率较高.

Abstract

Objective To promote and benefit prenatal consultation for families with fetuses affected by short femur (SF) (≤-2SD), the prenatal diagnosis results and pregnancy outcomes of pregnant women with fetuses with SF and postnatal growth levels of SF fetus were analyzed. Methods A total of 35 pregnant women who were diagnosed with femoral development ≤-2SD through ultrasound and received invasive prenatal diagnosis at the department of prenatal diagnosis of Huai'an Maternal and Child Health-Care Center between December 2018 and December 2022 were selected for the study. According to the fetal ultrasound findings, the fetus was divided into the isolated SF group and the SF with other abnormal ultrasound findings group. The prenatal diagnosis results including chromosomal microarrays (CMA) and trio whole exome sequencing (Trio-WES), pregnancy outcomes, and growth levels between the two groups were followed up and compared. Results The pathogenic chromosomal abnormality diagnosis rate for SF fetuses was 5.71% (2/35), with 4.76% (1/21) in the isolated SF group and 7.14% (1/14) in the SF with other ultrasound abnormalities group. The overall Trio-WES diagnostic rate for SF fetuses was 26.32% (5/19), with 33.33% (4/12) in the isolated SF group and 14.29% (1/7) in the SF with other ultrasound abnormalities group. The induction rate for pregnant women with SF fetuses was 22.86% (8/35), the pregnancy loss rate was 17.14% (6/35), and the live birth rate was 54.29% (19/35). There were no statistically significant differences between the two groups in terms of induction rate, pregnancy loss rate, or live birth rate (P>0.05). After birth, 19 SF fetuses were successfully followed up, aged 3 to 48 months, and no other abnormalities were observed. The height level was in the lower and lower-middle range in 57.89% (11/19), with 63.64% (7/11) in the isolated SF group and 50.00% (4/8) in the SF with other ultrasound abnormalities group. There was no statistically significant difference between the two groups (P>0.05). Conclusion The chromosomal abnormality diagnosis rate for SF fetuses was 5.71%, and the Trio-WES diagnostic rate was 26.32%. The combination of both methods is an optimized approach for genetic etiology diagnosis of SF. After excluding genetic causes, pregnant women carrying SF fetuses still have a relatively high pregnancy loss rate. After birth, the frequency of SF fetuses with height levels in the lower-middle range was relatively high.

关键词

短股骨 / 产前诊断 / 妊娠结局 / 生长水平 / 随访

Key words

short femur / prenatal diagnosis / pregnancy outcome / growth level / follow-up

参考文献

[1] 中华医学会围产医学分会胎儿医学学组, 中华医学会妇产科学分会产科学组. 胎儿生长受限专家共识(2019版)[J]. 中华围产医学杂志, 2019, 22(6): 361-380.

[2] 张倩雯, 龚云辉, 周容, 等. 胎儿短股骨诊治的临床进展[J]. 中国计划生育和妇产科, 2019, 11(1): 27-29,40.

[3] Mohr-Sasson A, Toussia-Cohen S, Shapira M, et al. Long-term follow-up on fetuses with isolated sonographic finding of short long bones: a cohort study[J]. Arch Gynecol Obstet, 2020, 301(2): 459-463.

[4] Saccone G, Berghella V, Maruotti G M, et al. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study[J]. Am J Obstet Gynecol, 2017, 216(5): 525.e1-525.e12.

[5] Borrell A, Grande M, Meler E, et al. Genomic microarray in fetuses with early growth restriction: a multicenter study[J]. Fetal Diagn Ther, 2017, 42(3): 174-180.

[6] Zhu H, Lin S, Huang L, et al. Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction[J]. Prenat Diagn, 2016, 36(7): 686-692.

[7] Mustafa H J, Tessier K M, Reagan L A, et al. Fetal growth standards for Somali population[J]. J Matern Fetal Neonatal Med, 2021, 34(15): 2440-2453.

[8] 陈佩文, 陈欣林. 国际妇产科超声协会2022年更新版«中孕期常规胎儿超声检查»临床指南解读[J]. 中国产前诊断杂志:电子版, 2023, 15(2): 34-46.

[9] Riggs E R, Andersen E F, Cherry A M, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J]. Genet Med, 2020, 22(2): 245-257.

[10] 王秋菊, 沈亦平, 邬玲仟, 等. 遗传变异分类标准与指南[J]. 中国科学:生命科学, 2017, 47(6): 668-688.

[11] 国家卫生健康委. 关于发布推荐性卫生行业标准«7岁以下儿童生长标准»的通告[DB/OL]. http://www.nhc.gov.cn/fzs/s7848/202211/8b94606198e8457dafb3f8355135f1a3.shtml, 2022-09-19/2023-04-20.

[12] Huang Y, Liu C, Ding H, et al. Exome sequencing in fetuses with short long bones detected by ultrasonography: a retrospective cohort study[J]. Front Genet, 2023, 14: 1032346.

[13] Liu J, Huang L, He Z, et al. Clinical value of genetic analysis in prenatal diagnosis of short femur[J]. Mol Genet Genomic Med, 2019, 7(11): e978.

[14] Hu T, Tian T, Zhang Z, et al. Prenatal chromosomal microarray analysis in 2466 fetuses with ultrasonographic soft markers: a prospective cohort study[J]. Am J Obstet Gynecol, 2021, 224(5): 516.e1-516.e16.

[15] Woodbury-Smith M, D'Abate L, Stavropoulos D J, et al. The phenotypic variability of 16p11.2 distal BP2-BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples[J]. J Med Genet, 2023, 60(12): 1153-1160.

[16] Yue F, Hao M, Jiang D, et al. Prenatal phenotypes and pregnancy outcomes of fetuses with 16p11.2 microdeletion/microduplication[J]. BMC Pregnancy Childbirth, 2024, 24(1): 494.

[17] Li M, Liu L, Wu Y, et al. Prenatal diagnosis and molecular cytogenetic characterization of an inherited microdeletion of chromosome 16p11.2[J]. J Int Med Res, 2022, 50(7): 3000605221109400.

[18] Mortier G R, Cohn D H, Cormier-Daire V, et al. Nosology and classification of genetic skeletal disorders: 2019 revision[J]. Am J Med Genet A, 2019, 179(12): 2393-2419.

[19] 任远, 游艳琴, 周红辉, 等. 妊娠晚期股骨短小胎儿21例临床分析[J]. 中华妇产科杂志, 2017, 52(2): 86-92.

[20] Zhou X, Chandler N, Deng L, et al. Prenatal diagnosis of skeletal dysplasias using a targeted skeletal gene panel[J]. Prenat Diagn, 2018, 38(9): 692-699.

[21] 王影, 樊阳阳, 胡盈, 等. 妊娠期高血压疾病伴发胎儿生长受限的研究[J]. 中国妇幼健康研究, 2020, 31(1): 104-108.

基金资助

江苏省妇幼健康项目(F201714)

江苏省妇幼健康项目(F201707)

江苏省新药研究与临床药学重点实验室(XZSYSKF2020024)

淮安市自然科学研究计划(HAB202217)