高龄孕妇对2种不同唐氏产前诊断方案的需求及经济学评价

目的:探讨高龄孕妇对2种不同唐氏产前诊断方案的需求,并对这2种方案进行经济学评价。方法:选择2015年3月1日至2016年3月31日孕20+6周前在深圳市妇幼保健院产科就诊的单胎高龄孕妇4104例,由孕妇自主选择先行无创胎儿DNA检测(NIPT),NIPT高风险再行羊膜腔穿刺(方案1)或直接羊膜腔穿刺(方案2)。比较孕妇对2种方案的需求及其影响因素,并对2种方案进行经济学评价。结果:选择方案1的比率明显高于方案2[51.34%(2107/4104)vs 7.65%(314/4104),χ~2=1883.431,P0.001]。Logistic回归分析显示,孕妇年龄、传统唐氏筛查结果和胎儿颈部透明层厚度(NT)是影响孕妇选择的因素。与方案2相比,方案1可以节省67.21%的总费用。结论:高龄孕妇对NIPT有巨大的需求,且高龄孕妇采用NIPT筛查阳性后再行羊膜腔穿刺术可节省医疗费用,建议在充分知情同意的基础上可将NIPT用于高龄孕妇的一线筛查,尤其是适用于年龄较轻、传统唐氏筛查非高风险、NT正常的高龄孕妇。     

两个BDB1家系基因突变分析和产前诊断

目的:对两个B1型短指(趾)(BDB1)家系进行基因突变分析和产前诊断。方法:提取两家系成员的外周血基因组DNA,应用PCR产物直接测序法对致病基因ROR2的第8外显子和一部分第9外显子进行突变筛查。提取两例孕妇血浆胎儿游离DNA和羊水细胞DNA,对胎儿进行产前诊断,超声检查评估胎儿表型。结果:两家系中发现同一杂合截短突变c.2273CA(p.S758X)。无创产前筛查的结果表明,家系1中的Ⅲ3胎儿不携带c.2273CA杂合突变,家系2中的Ⅲ4胎儿携带c.2273CA杂合突变,该结果与羊水细胞DNA检测、超声检查的结果一致。结论:c.2273CA杂合突变为两个BDB1家系的致病原因,推荐综合使用多个指标进行产前诊断。     

Visual, motor and perceptual abilities at school age in children with isolated mild antenatal ventricular dilatation

Background

The detection of prenatal ventriculomegaly raises anxiety about possible neurological sequelae. A few studies have investigated possible neurodevelopmental sequelae in the first years after birth but no systematic assessment has been performed at school age.

Aims

The aim of this study was to assess minor neurological signs, perceptual and visual function in a cohort of children with isolated mild antenatal ventricular dilatation examined at school age.

Study design

Seventeen children with evidence of mild antenatal ventriculomegaly in the second and third trimester of pregnancy were included in the study.

Outcome measures

Children were assessed at school age (range 5 years 3 months-11 years, 11 months) using a structured neurological examination for minor neurological signs and age specific tests assessing perceptual motor abilities (Developmental Test of Visual-Motor Integration; Movement Assessment Battery for Children).

Results

Only one of the 17 children had abnormal results. The remaining 16 had normal results on all the tests, irrespective of the magnitude and the symmetry of the dilatation or of its evolution on neonatal scan.

Conclusions

Our results suggest that children who had mild isolated prenatal ventricular dilatation are unlikely to develop even minor motor or perceptual difficulties at school age.     

羊水染色体多态性与妊娠结局的关系分析

目的:探讨羊水染色体多态性与妊娠结局的关系,为产前诊断染色体多态性的临床处置提供理论依据。方法:对3960例高危孕妇行羊膜腔穿刺术,抽取羊水经培养后制备染色体核型并进行分析,诊断为染色体多态性的胎儿,其父母接受外周血染色体检查,并对1岁龄婴儿期生长发育情况进行跟踪随访。结果:3960例羊水染色体核型共检出多态性核型116例,其中114例多态性核型来自于父母其中一方,仅1例9qh-和1例22ps+为新生变异。随访发现110例胎儿孕中晚期及出生后1岁以内,未见明显生长发育异常;1例inv(9)于孕29+2周不明原因胎死宫内;1例新生9qh-胎儿,孕晚期B超发现胎儿头围、腹围较实际孕周小2周,出生8个月后随访身高、体重及运动协调能力发育较同龄儿稍低;另一例新生变异22ps+,孕期及出生后随访未见明显异常;4例失访,妊娠结局未知。结论:具有明确遗传来源的染色体多态性变异可参照其父辈的身体智力发育情况予以判断其妊娠结局,新发生的胎儿多态性变异对其妊娠结局及今后的生长发育情况可能造成一定的负面影响,但其影响的具体机制及对应关系还有待进一步研究。     

Pregnancy in Adolescence: Is It an Obstetrical Risk?

Study ObjectiveAdolescent pregnancy is an important public health problem worldwide. It is associated with increased risk of maternal and fetal complications. We aimed to investigate whether adolescent pregnancies have an increased risk for perinatal complications. We focused primarily on the relationship between adolescent pregnancy and preterm delivery.Design, Setting, Participants, Interventions, and Main Outcome MeasuresWe used records of 38,646 women who gave birth at our hospital, between January 2008 and December 2009. Five hundred eighty-two randomly selected pregnant adolescents and 2,920 healthy parity and body mass index matched pregnant women 20-34 years of age were included the study. Perinatal outcomes were compared between the groups.ResultsThe mean gestational ages of the adolescent and control groups at the first prenatal visit were 11.2 (range, 8-31) and 8.5 (range, 7-28) weeks, respectively (P < .001). The risks of preterm delivery (odds ratio, 2.46; 95% confidence interval, 1.80-3.37; P < .001) and preeclampsia (odds ratio, 2.14; 95% confidence interval, 1.30-3.51; P = .002) were significantly greater among the adolescent mothers. In both groups, the most frequent reason was spontaneous preterm delivery.ConclusionAs shown in this study, pregnant adolescents present to hospitals for prenatal care at a much more advanced gestational age compared with adults. At the time they present to the hospital, and particularly in the first trimester, they must be advised to undergo an ultrasound scan to determine the gestational age. As such, it would be reasonable to increase the frequency of examinations after the second trimester, because of the increased risk of preterm labor and preterm birth.     

黏多糖贮积症Ⅰ型二例基因突变检测及产前诊断

目的 对黏多糖贮积症Ⅰ型病例进行基因检测,对再孕母亲进行产前诊断.方法 用酶学检测方法 确诊2例黏多糖贮积症Ⅰ型先证者;采用PCR扩增技术结合序列分析的方法,检测2例先证者血液及其再孕母亲羊水细胞中IDUA基因外显子及其两侧内含子.结果 在2例经酶学检测确诊的先证者中共检测出4种基因突变:p.L238R、c.883InsC、c.531InsT、p.L346R,2种为插入突变,2种为错义突变.在先证者1母亲羊水细胞IDUA基因中未发现致病基因突变,羊水细胞中IDUA酶活性为9.0 nmol/(h·mg蛋白);在先证者2母亲羊水细胞IDUA基因中检测到与先证者相同的两个致病突变,羊水细胞中IDUA酶活性为0.5 mol/(h·mg蛋白).结论 从黏多糖贮积症Ⅰ型先证者发现的4种突变中,p.L346R为已知突变,p.L238R,c.883InsC,c.531InsT为首次发现的新突变.胎儿1未获得与先证者相同致病基因,为正常胎儿.胎儿2获得与先证者相同致病基因,为受累胎儿.产前基因诊断结果 与酶学产前诊断结果 相符合.

Abstract：

Objectiye Mucopolysaccharidosis type Ⅰ(MPS Ⅰ; MIM# 252800)is an autosomal recessive disease that results from the deficiency in the lysosomal enzyme α-L-iduronidase(IDUA).IDUA is one of the enzymes involved in degradation of glycosaminoglycans heparan sulphate and dermatan sulphate.The deficiency of IDUA leads to widespread accumulation of partially degraded mucopolysaccharides inside lysosomes,resulting in progressive cellular and multiorgan dysfunction. Up to now there is no definitely effective treatment for this disorder,therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPS Ⅰ families.This study was conducted to detect IDUA gene mutation in patients with MPS Ⅰ and make a definite diagnosis of homozygote or heterozygote and make first trimester prenatal diagnosis.Method The 2 male probands included in this study were diagnosed as MPS Ⅰ patients in Peking Union Medical College Hospital,case 1 was 2 years old and case 2 was 5 years old.Genomic DNA was extracted from leucocytes in the 2 patients and 2 mothers' cultured amniocytes.IDUA gene DNA sequence was amplified by polymerase chain reaction(PCR)and the PCR products were sequenced directly.Novel mutations were analyzed in 100 normal chromosomes.Result The genotype of case 1 was p.L238R/c.883InsC,while of case 2 was c.531InsT/p.L346R.The fetal case 1 did not inherit the same pathogenic inherited the same pathogenic mutations with the proband,the genotype of fetal 2 was c.531InsT/p.L346R,in 2 MPS Ⅰ patients,p.L238R,c.883InsC,c.531InsT were novel.The fetal case 1 was diagnosed as normal fetus while the fetus 2 was diagnosed as affected.The results of the two kinds of prenatal diagnostic methods were correspondent with each other.     

产前诊断脐膨出胎儿80例结局分析

目的了解80例产前诊断为脐膨出胎儿的结局。方法回顾性分析2004年12月到2010年1月广东省妇幼保健院产前超声检查诊断为“先天性脐膨出”的患儿临床资料,通过医院信息系统和电话随访相结合,记录孕妇和新生儿的诊疗资料。结果80例中,36例脐膨出胎儿伴发结构畸形,其中4例失访,3例行脐带血染色体检查,1例为47XXY,31例终止妊娠,1例死胎;44例单发脐膨出,5例失访,11例行脐带血染色体检查,均正常,28例终止妊娠,11例活产,其中1例出生时未见脐膨出,1例巨大脐膨出患儿一期手术后死亡,1例巨型脐膨出患儿予非手术治疗,8例小型脐膨出患儿均经一期手术治疗,无一例死亡,术后发育良好。结论运用产前超声和染色体检查等仔细甄别胎儿脐膨出,通过宫内转运或新生儿转运开展早期诊治,获产前诊断的单发小型脐膨出可以继续妊娠。     

Prenatal stress and infant affective reactivity at five months of age

Background

Prospective studies concerning prenatal stress and its outcome on children's emotional development postulated a potential influence of prenatal hormonal levels or emotional stressors on child development [1-3]. In a retrospective study, an influence of maternal emotional stress on infant affective reactivity was found [4].

Aims

This study was conducted in order to confirm these findings in a prospective study design.

Study design

A prospective longitudinal study design was conducted with three study waves during pregnancy and one time point five months postnatally.

Subjects

The final sample consisted of n = 104 mother-infant dyads.

Outcome measures

Maternal baseline cortisol levels and emotional stress were assessed in each trimester of pregnancy. Children were examined with the infant reactivity battery according to Kagan & Snidman [5] at the age of five months.

Results

Mothers of children with high affective reactivity (cry score ≥ 7) were significantly less depressed (p < .10) and perceived less stress (p < .05) in mid-pregnancy and were confronted with less external stress factors (p < .10) at the end of pregnancy. Cortisol levels did not differ in both groups in any pregnancy trimenon (p > .05).

Conclusions

These data add a new specific aspect to the ‘fetal programming hypothesis’ and are the first to confirm the speculative data from retrospective studies. Baseline cortisol does not seem to be the ‘hormonal mediator’ of this association. Therefore, cortisol stress reactivity or other neuroendocrine mechanisms should be assessed in future studies.     

胎儿复杂性先天性心脏病产前与出生后诊断处理的价值及预后比较

目的:比较分析胎儿复杂性先天性心脏病(CHD)产前诊断与出生后诊断处理的价值及预后情况。方法:回顾性分析在我院产检诊断为胎儿复杂性CHD,经产前咨询保留胎儿,并在本院分娩,出生后转NICU进一步诊治(产前诊断组)与院外分娩后诊断为复杂性CHD,出生后72小时内转我院NICU诊治(产后转诊组)患儿的分娩结局及预后,并进行比较。结果:产前诊断组共106例,产后转诊组共129例。产前诊断组经产前咨询,30例家属放弃胎儿并引产,76例保留胎儿并在我院分娩。两组分娩孕周、出生体重、早产率和分娩方式比较,差异无统计学意义(P0.05)。两组出生后放弃治疗(6例vs 31例)、小儿心脏外科评估认为无需手术治疗及可随诊(30例vs 14例)、心脏手术后并发症(20例vs 56例)间比较,差异有统计学意义(P0.05);手术后死亡、呼吸机脱机时间和手术后住院天数间比较,差异无统计学意义(P0.05)。结论:产前明确胎儿复杂性CHD的诊断,可减少患儿心脏手术后并发症,改善预后。并且可避免一些无治疗价值的复杂性先天性心脏病新生儿的出生。     

双胎及三胎妊娠地中海贫血产前基因诊断研究

目的:探讨双胎妊娠和三胎妊娠地中海贫血的产前基因诊断情况。方法:对27例双胎妊娠和三胎妊娠患者进行绒毛膜穿刺或羊膜囊穿刺胎儿取样,采取裂隙聚合酶链反应以及聚合酶链反应结合反向点杂交方法进行产前基因诊断。结果:在进行α地中海贫血产前基因诊断的20例双胎妊娠及1例三胎妊娠中,共对43个胎儿进行取材,共检测出6例Bart's水肿胎,3例血红蛋白H病。在进行β地中海贫血产前基因诊断的6例双胎妊娠中,共对9个胎儿进行取材,共检测到3例中重型β地中海贫血。结论:地中海贫血的多胎妊娠孕妇产前基因诊断能较有效检出Bart's水肿胎和中重型β地中海贫血患儿,可预防重型地中海贫血患儿的出生。