妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。     

Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy

OBJECTIVE: To evaluate the value of maternal serum CA125 and CA15-3 concentrations for discriminating pathological from normal pregnancies. METHODS: Serum samples from 120 women, in whom pregnancy outcome was pathological, i.e. spontaneous abortion, fetal death, intrauterine growth retardation, chromosomal and structural abnormalities, and (pre)eclampsia, were assessed for CA125 and CA15-3 and compared with levels found in 350 women with a normal pregnancy outcome matched for age and duration of pregnancy. RESULTS: Maternal CA125 serum values were significantly higher in the first and the third trimester of pregnancy (median 23.0 and 21.0 U/ml; p < 0.00001 and p < 0.001, respectively), compared to those in the second trimester (median 14.0 U/ml), but not significantly different from those obtained in pathological pregnancies. Maternal serum CA15-3 values were significantly higher during the third trimester (median 26.0 U/ml) compared to the first and second trimester of pregnancy (median 14.0 and 15.0 U/ml; p < 0.0001); CA15-3 serum levels in normal and pathological pregnancies showed no significant difference. CONCLUSION: Maternal serum levels of CA125 are higher during the first and third trimester of pregnancy. CA15-3 maternal serum levels are higher during the third trimester compared to the first and second trimester. Maternal CA125 and CA15-3 serum levels showed no relation with a pathological outcome of pregnancy.     

The utility of detailed first trimester ultrasound examination in abnormal fetal nuchal translucency

OBJECTIVE: To determine the value of a first trimester fetal ultrasound examination in cases of an increased nuchal translucency (NT). METHOD: A detailed fetal ultrasound examination was performed within 4 days of a detection of a first trimester increased NT. RESULTS: As many as 23 fetuses were evaluated. Severe anomalies were detected in eight and mild anomalies were detected in six fetuses. Two fetuses had trisomy 13, one had trisomy 21, and 16 fetuses had a normal karyotype. A chromosomal analysis was not available in four fetuses with major anomalies due to parental decision. In one fetus, craniosynostosis was detected only at 24 weeks' gestation. CONCLUSIONS: The current study shows that a first trimester targeted scan of fetuses with an increased NT in an experienced center can shorten the parental decision-making process and spare parents a prolonged period of diagnostic uncertainty and anxiety, particularly when a structural anomaly is clearly diagnosed in the first trimester.     

Transvaginal ultrasonographic detection of congenital anomalies in the first trimester

Transvaginal ultrasonography enables detailed visualization of the first-trimester pregnancy. Thirty-three structural anomalies have been diagnosed in the first trimester of pregnancy during a 2-year study period. An understanding of normal embryonic development is essential before attempting diagnosis in this gestational period.     

Notch1蛋白在正常妊娠早中晚期胎盘绒毛中的表达变化及其意义

目的:检测Notch1蛋白在正常妊娠早、中、晚期胎盘绒毛中的表达水平变化,探讨Notch1在胎盘形成中的作用及意义。方法:采用免疫组织化学SP法、Real-timePCR、Western blot分别检测20例正常早期绒毛组织、15例中期妊娠和20例晚期妊娠胎盘组织中Notch1 mRNA及蛋白的表达水平。结果:Notch1蛋白在正常早、中、晚期妊娠过程中均有不同程度的表达,随着妊娠的进展其表达水平呈下调趋势,但无统计学差异(P>0.05)。正常早期绒毛组织中Notch1 mRNA的表达水平显著高于妊娠中、晚期胎盘组织(P<0.05)。结论:Notch1蛋白可能参与正常妊娠早期绒毛的分化及胎盘的形成过程,有利于维持妊娠的正常发展。     

Increased nuchal translucency at 11-14 weeks of gestation in congenital heart disease, genetic syndromes and adverse pregnancy outcome

Nuchal translucency (NT) measurement between 11-14 weeks of gestation is an'effective method of ultrasound screening for chromosomal fetal anomalies, congenital heart disease, some other structural abnormalities, rare genetic syndromes, skeletal dysplasia and adverse pregnancy outcome (spontaneous abortion and intrauterine fetal demise). The aim of the present study is to assess the prognostic value of increased first trimester NT in fetuses with normal karyotype in relation to pregnancy outcome.     

Cavum velum interpositum cysts in normal and anomalous fetuses in second trimester of pregnancy: Comparison of its size and prevalence

ObjectiveCavum veli interpositi (CVI) is a potential space below the splenium of corpus callosum and sometimes presents as a cyst.Materials and methodsIn this prospective cross-sectional study, 360 fetuses with normal second trimester scan and 152 s trimester fetuses with structural abnormalities were included.ResultsThe CVI cysts were more common in fetuses with brain anomaly compared to normal fetuses and fetuses with extra-central nervous system (CNS) anomalies (23% vs 18.3% and 18% respectively; p value < 0.01). The mean size of cysts in normal fetuses, fetuses with extra-CNS anomalies and fetuses with brain abnormalities was 4.6 mm, 5.8 mm and 9.2 mm respectively. There was a significant difference between cysts size in normal fetuses and fetuses with brain anomalies (p value < 0.01) and the cut-point was 7.1 mm.ConclusionThe prevalence of CVI cysts is more in fetuses with brain anomaly. Fetuses with a cyst size >7.1 mm need a more detailed brain examination.     

Nucleic acids and protein changes in normal and pre-eclamptic placentae.

DNA and RNA assayed in the placentae of three groups of pregnant women: normal second trimester (16-28), normal third trimester (28 weeks up to term) and in preeclampsia. The protein level in the placentae of the three groups was also assayed. The proteins, DNA and RNA all decreased after 28 weeks and up to term in normal pregnancy. In pre-eclampsia DNA and RNA showed a significant increase compared with cases of normal third trimester pregnancy. Whereas the proteins also showed an increased level, this was still less than its concentration during the second trimester of pregnancy. Protein/DNA and RNA/DNA ratios were calculated for the three groups. These ratios showed a gradual decrease during normal pregnancy from 16 weeks up to term, but with a sharper decrease in pre-eclampsia.     

First trimester ultrasonographic diagnosis of fetal structural abnormalities in a low risk population

Objectives Ultrasonographic screening between 12⁺⁰¹ and 13⁺⁶ weeks for fetal structural abnormalities using transab dominal sonography and, where necessary, transvaginal sonography in a low risk population.
Design A prospective observational study
Setting London teaching hospital
Methods Pregnant women with a total of 1632 low risk viable fetuses between 12⁺⁰ and 13⁺⁶ weeks of gestation were scanned using transabdominal and, where necessary, transvaginal sonography (40%). If the anatomical survey was normal, the women underwent routine 18-20 week anomaly scans. Pregnancy outcomes were obtained from radiological and neonatal computerised databases, and postal or telephone patient enquiry.
Results Seventeen (1.0%) major structural abnormalities were diagnosed in the study group. Of these, 11 (64.7%) were diagnosed at the 12-13 week scan, three diagnosed in the mid-trimester and three postnatally. Of the fetal abnormalities diagnosed antenatally, 78.6% were diagnosed in the first trimester. The sensitivity of abnormality detection by the combination of both first and second trimester scans was 82.3%. In addition, a significant number of missed abortions (   n = 36  ) were also diagnosed by the first trimester scan.
Conclusion This study has demonstrated the potential of screening a low risk population for fetal abnormalities at 12-13 weeks of gestation using transabdominal sonography and, where necessary, transvaginal sonography. Larger studies are required to establish the clinical value of the first trimester scan.     

早期自然流产患者绒毛Notch受体mRNA和蛋白表达及与妊娠关系的初步探讨

目的:初步探讨早期自然流产患者绒毛Notch受体(Notch1、Notch2、Notch3、Notch4)mRNA及蛋白表达及对滋养细胞的调控作用。方法:用实时荧光定量逆转录聚合酶链反应技术和免疫印迹法检测6例自然难免流产患者和12例正常早期妊娠妇女绒毛Notch1、Notch2、Notch3、Notch4的mRNA和蛋白的表达水平。结果:(1)自然流产组绒毛Notch1和Notch3 mRNA表达水平高于正常早期妊娠组(P<0.05);(2)Western-blot检测显示早期自然流产患者绒毛中Notch1、Notch2、Notch3受体蛋白的表达水平高于正常早期妊娠组(P<0.05)。结论:Notch受体蛋白在早期自然流产患者绒毛中表达上调,可能与自然流产的发病原因有关。     

Abnormal first-trimester fetal nuchal translucency and Cornelia De Lange syndrome

BACKGROUND:Cornelia de Lange syndrome is a genetic disorder associated with delayed growth and characteristic facial features. There is no definitive biochemical or chromosomal marker for the prenatal diagnosis of this syndrome. We describe a case of Cornelia de Lange syndrome associated with an increased nuchal translucency in the first trimester.CASE:A large nuchal translucency was identified in a fetus during a first trimester ultrasound. Subsequent second- and third-trimester sonograms demonstrated severe fetal growth restriction, limb shortening, and abnormal facial features, despite normal fetal karyotype per chorionic villus sampling. Neonatal evaluation confirmed the diagnosis of Cornelia de Lange syndrome.CONCLUSION:Sonographic finding of an increased nuchal translucency in early pregnancy is associated with fetal aneuploidy and various structural and genetic abnormalities. Increased nuchal translucency may identify fetuses that require vigilant assessment, especially when found in association with other abnormalities.     

南昌地区正常孕产妇血清免疫球蛋白与补体3水平的观察

目的 了解正常妊娠孕产妇血清ＩｇＧ、ＩｇＡ、ＩｇＭ及Ｃ３水平。方法 采用单相免疫扩散法对２７３例正常孕产妇三种血清免疫球蛋白（Ｉｇ）和补体３（Ｃ３）水平进行了测定,并与２１例非妊娠妇女作比较。结果 正常妊娠组与非妊娠组比较,血清ＩｇＧ水平降低明显,差异有显著性（Ｐ〈０．０１）。早、中、晚孕及产后分别下降４４．０３％、１８．４６％、３５．４５％和３５．７７％。除中孕组外,其它各组差异均有显著性（Ｐ〈     

Fetal karyotyping after 28 weeks of gestation for late ultrasound findings in a low risk population

OBJECTIVE: To analyze the indications and the results of invasive testing for fetal karyotyping for ultrasound abnormality in the third trimester of pregnancy, when first- and second-trimester screening tests were negative. METHODS: Retrospective study of 171 consecutive pregnancies that underwent invasive testing after 28 weeks of gestation in 2 institutions between January 1999 and December 2001. Forty-one patients did not have any form of screening for fetal aneuploidy beforehand. One hundred and thirty of them had a normal first-trimester scan and a low risk of fetal aneuploidy by nuchal translucency and/or maternal serum screening and were included in the statistical analysis. RESULTS: Mean maternal age, gestational age at diagnosis and at invasive testing were 30.5 years; 29.3 weeks and 32.5 weeks respectively. Amniocentesis and fetal blood sampling were performed in 97 and 33 cases respectively.The most frequent indications for invasive testing in the third trimester were major fetal malformations (51%) and intrauterine growth restriction (19%) detected on routine second- or third-trimester ultrasound examination. Ultrasound markers of aneuploidy and polyhydramnios accounted for 17 and 11% of the indications respectively.Fetal karyotype was normal in 121/130 cases. A gene mutation was found in one case. The karyotype was abnormal in nine cases, including seven cases of aneuploidy (one Turner syndrome, three trisomy 18, and three trisomy 21) and two cases of structural chromosomal abnormalities (46,XX, del 4 p16.1 and 46,XX, dup1).One hundred cases resulted in the delivery of a normal baby. Thirty cases led to termination of pregnancy or intrauterine death due to major fetal malformations (N = 25), abnormal karyotype in six of these, and severe IUGR (N = 5) with normal karyotype. Fetal US markers of aneuploidy and isolated polyhydramnios were associated with a favorable outcome in all cases.A significant increase in the risk of chromosomal anomaly was seen when two or more anomalies were found, rising from 2% with one anomaly to 21% when two or more anomalies were present. CONCLUSION: In low risk patients, fetal karyotyping in the third trimester may be justified when the diagnosis of fetal malformation is made in the third trimester of pregnancy. Two or more anomalies increase the risk of fetal aneuploidy even with a negative-screening test in the first and second trimester of pregnancy.     

Repeated hematocrit measurements in low-risk pregnant women

OBJECTIVE: To determine the incidence of anemia in the third trimester among women with normal hematocrits early in pregnancy. STUDY DESIGN: Low-risk women seeking prenatal care were identified. Patients with a hematocrit >33% in the first or second trimester and a hematocrit drawn in the third trimester were included. Rates of anemia; hematocrit <33%; and severe anemia, hematocrit < 30%; were determined. The primary outcome was the development of anemia in the third trimester. RESULTS: A total of 1,604 women met inclusion criteria; 16.2% of women became anemic, and 4.5% became severely anemic in the third trimester. Using a starting hematocrit value of 39% as a cutoff, only 66% of women would need to be rescreened in the third trimester in order to detect 78.5% of anemias (sensitivity 78.5%, specificity 39.7%, negative predictive value 90.5%). CONCLUSION: The percent of women with normal hematocrits in the first trimester who become anemic in the third trimester is 16.2. Hematocrit screening in the third trimester may be unnecessary for low-risk women with starting hematocrits > 39%.     

妊娠期糖尿病患者与正常孕妇妊娠中晚期胰岛素抵抗及胰岛B细胞功能观察

目的前瞻性纵向观察中期妊娠诊断为妊娠期糖尿病(GDM)患者及血糖正常孕妇在妊娠中晚期胰岛素抵抗及胰岛B细胞功能变化,并比较两者之间的差别。方法 2009年2月至2010年3月在中山大学孙逸仙纪念医院产前检查的82例孕妇于妊娠20～24周行葡萄糖耐量试验(OGTT)及胰岛素释放试验,诊断为GDM43例为GDM组,血糖正常的39例为对照组。于32～36周复查OGTT及胰岛素释放试验,纵向观察两组孕妇胰岛素抵抗及胰岛B细胞功能的变化。结果两组的胰岛B细胞分泌指数(HOMA-β)晚期妊娠均高于中期妊娠,时间主效应有统计学意义(F=7.863,P=0.007);GDM组的早期胰岛素分泌指数(△I30/△G30)中期妊娠及晚期妊娠均低于对照组,组间主效应差异有统计学意义(F=6.052,P=0.018),但GDM组从中期妊娠到晚期妊娠有所升高,而对照组逐渐下降。GDM组的血糖曲线下面积(AUCG)在中期妊娠及晚期妊娠均大于对照组(分别为P<0.0001,P=0.001),同时对照组的AUCG晚期妊娠显著高于中期妊娠(P=0.001);稳态模式胰岛素抵抗指数(HOMA-IR)及混合胰岛素敏感度的时间及组间主效应差异均无统计学意义。结论中晚期妊娠正常孕妇及GDM患者胰岛素抵抗均增加,后者胰岛素抵抗程度高于前者,胰岛B细胞代偿功能两者均增强;GDM组的早期胰岛素分泌功能较正常妊娠组下降。胰岛素抵抗和胰岛素分泌代偿不足是GDM发生、发展的重要机制。     

The Concentrations of Markers of Bone Turnover in Normal Pregnancy and Preeclampsia

Background. The purpose of our study was to investigate the concentrations of markers of bone turnover in normal pregnancy and preeclampsia. Material and Methods. Forty-five pregnant patients with preeclampsia, 78 healthy pregnant women (26 in first, 26 in the second, and 26 in third trimester of pregnancy), and 20 nonpregnant women were included in the study. Serum concentrations of osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps—degradation products of type I collagen, were determined using the ELISA method. Statistical analysis was performed using Mann–Whitney U-test. Results. The concentrations of sRANKL and OPG were significantly higher in the second trimester of normal pregnancy when compared to the first and the third trimesters and to nonpregnant controls. The concentrations of osteocalcin were significantly higher in the first trimester of physiological pregnancy in comparison with nonpregnant women and with second and third trimesters of pregnancy. The concentrations of CrossLaps were significantly higher in the second trimester of normal pregnancy when compared to the first and third trimester. In preeclampsia, the sera concentrations of osteocalcin and CrossLaps were significantly higher when compared to the third trimester of normal pregnancy. Conclusion. The results suggest that the bone formation is increased in the first trimester, whereas the bone resorption is increased in the second trimester of normal pregnancy. Furthermore, the results suggest that the bone turnover is increased in patients with preeclampsia when compared to healthy normotensive pregnant women.     

Evaluation of a two-step ultrasound examination protocol for the detection of major fetal structural defects

Objective: To evaluate a two-step screening protocol of ultrasound examinations (11–14 and 20–24 weeks) for the detection of major fetal structural defects. Methods: Retrospective study in a private maternity hospital. Women with viable singleton pregnancies having both first trimester scan and anomaly scan at our department and subsequently delivered at our hospital were included. Major fetal structural defects were defined as those requiring medical or surgical treatment or those causing mental handicap. Results: A total of 3,902 pregnancies included 61 fetuses with structural defects (1.56%). Twenty-six (42.6%) were diagnosed in the first trimester and 29 (47.5%) in the second. Six anomalies were detected in the third trimester or after birth. Overall detection rate of the two-step program was 90.2%. Conclusions: Detailed examination of fetal anatomy at 11–14 weeks resulted in the early diagnosis of about 40% of major structural defects     

Fetal heart scanning in the first trimester

The detailed study of the fetal cardiac anatomy in the first trimester of pregnancy by means of ultrasound, transvaginally or transabdominally, is feasible and remains a safe procedure provided thermal and mechanical indices are taken into account. Optimal time for successful imaging of the four chambers and great arteries in early gestation appears to be between 13 to 14 weeks. In experienced hands, first-trimester fetal echocardiography is accurate in detecting major structural cardiac abnormalities and yields a high negative predictive value. Thus, in a clinical setting, it can be offered to families considered to be 'at risk' of cardiac defects (e.g. those with previous family history or when fetal nuchal translucency is increased) and can be a powerful tool to reassure families regarding normality of major cardiac structures and connections. However, the early detection of an important structural abnormality (chromosomally normal or not) may be associated with a high termination rate if this is an acceptable option. The high prevalence of associated chromosomal and extracardiac abnormalities for many of the high-risk families, who may benefit from this approach, cannot be ignored. Therefore, fetal heart scanning in the first trimester should be performed in conjunction with detailed first-trimester obstetric scanning.     

Maternal hemoglobin concentration is closely related to birth weight in normal pregnancies

Maternal Hb levels during the third trimester were studied in relation to certain maternal and fetal parameters in 877 apparently normal pregnancies. Low Hb levels at term were closely associated with increased frequency of newborns in the heavy weight-for-date group. Conversely, high maternal Hb levels were closely associated with an increased frequency of newborns in the light weight-for-date group. The maternal Hb levels both in the early third trimester and at term were significantly higher in mothers of small-for-date newborns than in those with newborns of normal weight. In both groups the maternal Hb levels increased significantly during the third trimester of pregnancy. High maternal Hb levels both early and late in the third trimester of pregnancy should be a matter of concern rather than of reassurance.     

人类白细胞抗原G、E在人胎盘组织中的表达及其意义

目的:探讨人类白细胞抗原G、E(HLA-G、E)在人胎盘组织中的表达及意义。方法:用原位杂交及免疫组化法分别检测HLA-G、E mRNA及蛋白质在人正常早孕绒毛组织、晚孕胎盘组织中的表达。结果:在人正常早孕绒毛组织中的绒毛细胞滋养细胞、合体滋养细胞及绒毛外滋养细胞(EVCT)内均有HLA-G、E mRNA及HLA-E蛋白质表达,而HLA-G蛋白质仅在EVCT内表达;晚孕胎盘组织中HLA-G、E mRNA及蛋白质表达于蜕膜板内的EVCT及羊膜上皮细胞。结论:HLA-E表达于人正常早孕绒毛组织中所有类型的滋养细胞及晚孕胎盘组织中的EVCT和羊膜上皮细胞。抗人HLA-G单克隆抗体4H84仅能检测出人胎盘组织中EVCT及羊膜上皮细胞内的HLA-G蛋白。