表皮生长因子及其受体与胎儿出生体重的关系

目的探讨表皮生长因子（ＥＧＦ）及其受体与胎儿出生体重的关系。方法采用酶联免疫吸附测定法对正常非孕妇女１５例（对照组）、足月正常体重儿４０例（正常体重儿组）、ＩＵＧＲ儿４０例（ＩＵＧＲ儿组）、巨大儿２５例（巨大儿组）的母血清、脐血清及羊水中ＥＧＦ浓度进行测定,同时采用免疫组化方法对以上各组胎盘及胎膜上ＥＧＦ受体（ＥＧＦＲ）进行测定。结果各组母血、脐血及羊水中ＥＧＦ浓度明显高于对照组（Ｐ＜００５）。ＩＵＧＲ儿组母血、脐血及羊水中ＥＧＦ浓度低于正常体重儿组,差异有显著性。巨大儿组母血、脐血及羊水中ＥＧＦ浓度与正常体重儿组比较,差异无显著性。在ＩＵＧＲ儿组胎盘及胎膜上ＥＧＦＲ表达明显低于正常体重儿组（Ｐ＜０．０１）,巨大儿组胎盘上ＥＧＦＲ表达高于正常体重儿组。结论ＥＧＦ及其受体与ＩＵＧＲ的发生有关,在妊娠后期测定母血及羊水中ＥＧＦ浓度,对评价胎儿的生长发育具有重要意义。     

Aplastic anemia associated with pregnancy: maternal and fetal complications

Objective: To analyze obstetric complications associated with aplastic anemia (AA) among pregnant women and analyze the underlying factors.

Methods: A retrospective analysis of 60 pregnancies with AA. Thirty four of these patients were grouped as complicated group having obstetric complications and the rest 26 without complications as the control group. Comparative analysis was conducted to access the related risk factors, which may affect the maternal and fetal complications.

Results: The major maternal complications in this study were premature labor, gestational diabetes, pre-eclampsia, acute heart failure, postpartum hemorrhage, and severe postpartum infection. Premature birth, fetal growth restriction and stillbirths accounted for 27.3%, 5.0% and 6.7% of prenatal mortality. Twenty six of patients had uncomplicated pregnancies. Patients without complications had higher mean hemoglobin concentration (75.38?±?16.19?g/L) and platelet counts (23.92?±?14.82?×?10⁹ cells/L) than did women with complications (mean hemoglobin concentration, 61.47?±?15.15?g/L, p?=?0.001; mean platelet counts, 12.11?±?7.87?×?10⁹ cells/L, p?<?0.001).

Conclusion: Pregnancies associated with AA can carry the risk of multiple maternal and fetal complications. Low hemoglobin concentration and platelet counts may be the primary risk factors for obstetric complications in pregnancies associated with AA.     

Genetic factors and fetal growth sex constitution and birthweight in twins

Fetal growth is considered a multifactorially-influenced characteristic. Genetic factors were found to play the main role in fetal growth determination, and it is the polygenic inheritance. The paper reviews the birthweights of 360 unlike-sexed two-egg twins, born at the Clinic of Gynecology and Obstetrics, Faculty of Medicine in Beograd, from January 1, 1970 through June 30, 1984. The mean birthweight differences between the male (2954.94 +/- 704.28 g) and female (2313.19 +/- 651.32 g) fetuses, amounted to 141.75 g. The difference is highly significant (P less than 0.01); variation coefficient shows that the examined groups were homogenous (VC was below 30%). The results were discussed from the genetic point of view, and particularly from the point of view of sex constitution, with special respect to the effect of Y chromosome on fetal growth. It has been known that human somatic development, body weight, bone maturation and teeth development are influenced by variety of factors. In addition to nutritional and other factors of the external environment, genetic and humoral factors are leading. The fact that fetuses with XY male constitution are heavier at birth than female fetuses with XX constitution, made us consider the correlation between genotype-phenotype, and the mentioned characteristics. This study was aimed at finding out the role of genetic factors in fetal growth, with respect to sex constitution, particularly to chromosome effect on fetal growth in unlike-sexed two-egg twins.     

Placental growth factor (PlGF): a key to optimizing fetal growth

Abstract

The needs of the uterus and the fetus for the provision of nutrients and oxygen, supplied by the blood flow, are understandably extremely high, with the circulatory system playing the most important role in this action. Abnormal vascular growth and transformation that create a high vessel resistance network have been associated with various pregnancy pathologies, including miscarriage, small for gestational age (SGA) fetuses with or without preeclampsia and intrauterine growth restriction (IUGR). Placental growth factor (PlGF) has a major role in vasculogenesis and angiogenesis in human placenta. Low concentrations of PlGF and high concentrations of its inhibitor-soluble Fms-like tyrosine kinase-1 (sFlt-1) are linked with impaired angiogenesis and placental development, leading to the above pregnancy complications. The activity of vascular endothelial growth factor (VEGF), which is the most potent of all angiogenic mediators, is partly modulated by PlGF. Although the mechanisms via which PlGF exerts its various effects are still under investigation, we herein discuss the known actions exerted by this major mediator together with its results on fetal growth.     

孕妇血清表皮生长因子在判断胎儿成熟度中的价值

目的了解正常孕妇在妊娠各期血清中表皮生长因子（ＥＧＦ）及孕激素（Ｐ）,与羊水中ＥＧＦ、Ｐ、淀粉酶（Ａｍｓ）、肌酐（Ｃｒ）、间接胆红素（ＴＢ）的浓度变化在判断胎儿成熟度中的价值。方法用放射免疫法测定正常孕妇１８１例（早孕３５例,中孕６９例,晚孕７７例）血清及其中８７例孕妇（中孕４４例,晚孕４３例）羊水中的ＥＧＦ、Ｐ浓度变化;用生化分析仪测定此８７例孕妇羊水中Ａｍｓ、Ｃｒ、ＴＢ浓度变化。同时还对其中２３例足月分娩的新生儿的脐静脉、脐动脉血清中ＥＧＦ及Ｐ的浓度进行测定。结果孕妇血清中ＥＧＦ和Ｐ的浓度均随孕周增长而增加。羊水中ＥＧＦ浓度与羊水中Ａｍｓ、Ｃｒ浓度呈正相关。孕３２周以后,当ＥＧＦ≥４．５μｇ／Ｌ时,胎儿成熟率为７０．５９％。结论妊娠期孕妇血清中ＥＧＦ的浓度变化可用于判断胎儿成熟度     

类胰岛素生长因子与胎儿生长发育关系的研究

目的 探讨类胰岛类生长因子（insulin-like growth factor-1,IGF-1)与胎儿生长发育的关系。方法 对38例正常儿、20例母体糖尿病新生和15例巨大儿的足月分娩前母及脐血进行IGF－1测定,明确IGF－1与新生儿体重和身长的关系。结果 正常足月分娩的脐血IGF－1值平均为70μg/L,脐血IGF－1和新生儿体重和身长均呈正相关。母血IGF－1是脐血IGF－1的2．87倍,母血IGF－1和脐血IGF－1呈明显正相关。糖尿病组母血和脐血的IGF－1均高于正常组,巨大儿组的母血IGF－1高于正常组。结论 IGF－1是促进胎儿生长发育的一种细胞因子。孕期母血IGF－1监测可以预测胎儿生长发育情况。     

Unexplained fetal death is associated with increased concentrations of anti-angiogenic factors in amniotic fluid

Objective.?Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors.

Study design.?This cross-sectional study included patients with fetal death (n?=?35) and controls (n?=?129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n?=?25); (2) preeclampsia and/or placental abruption (n?=?5); and (3) chromosomal/congenital anomalies (n?=?5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n?=?92) and women at term not in labor (n?=?37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results.?(1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p?<?0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p?<?0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR?=?10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively).

Conclusion.?Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations.     

胎儿脑电图及其定量分析用于产时胎儿窘迫诊断的研究

目的探讨胎儿脑电图(fetal electroencephalogram,FEEG)波形及其定量分析用于产时诊断胎儿窘迫及判断新生儿预后的价值。方法采用自制的经阴道胎儿脑电电极对65例产妇在第一产程末至胎儿娩出前进行FEEG监测,观察脑电图波形变化并进行定量分析;并将胎儿窘迫组(22例)和非胎儿窘迫组(43例)的脑电图波形及定量分析结果进行比较。同时比较胎儿酸中毒组和血气正常组两组的脑电图波形,分析新生儿近期预后与产时FEEG关系。结果(1)应用经阴道直接接触胎儿头皮的脑电电极记录的脑电图与新生儿脑电图特点相似;(2)胎儿窘迫组产时脑电图波形异常率明显高于非胎儿窘迫组(72·7%和9·0%,P<0·05),前者双频指数(bispectral index,BIS)明显降低、95%边缘频率(spectral edge frequency,SEF)明显升高;(3)胎儿酸中毒组与血气正常组相比产时脑电图及其定量分析有显著异常(BIS:48·23±1·98和70·18±0·76,P<0·05;95%SEF:29·02±1·09和14·02±1·69,P<0·01);(4)产时FEEG异常与新生儿不良预后有关。结论(1)自制的经阴道胎儿脑电电极可准确地采集胎儿脑电信号,且不损伤胎儿头皮,是安全、可行的;(2)胎儿脑电波异常可较早的反映胎儿宫内缺氧及酸中毒的状况,并可做为产时胎儿监测的直观指标;(3)产时胎儿脑电图定量分析BIS、95%SEF是反映胎儿和新生儿缺氧及酸中毒的敏感指标。     

The outcomes and risk factors of fetal bradycardia associated with external cephalic version

Objective: The objective of this study is to assess the outcomes and risk factors of fetal bradycardia after external cephalic version (ECV).

Methods: We performed a retrospective study of women who underwent ECV after 35 weeks of gestation in 2010–2016. We assessed the birth outcomes, including umbilical cord artery pH, according to the duration of fetal bradycardia and the risk factors for bradycardia.

Results: Among 390 cases, 189 (48.5%) cases showed fetal bradycardia during or immediately after ECV. The duration of fetal bradycardia was <1?min (n?=?82, 43.4%), <5?min (n?=?168, 88.9%); and <10?min (n?=?186, 98.4%). All cases showed a good prognosis. Fetal bradycardia lasting >10?min occurred in three cases; emergency cesarean section was performed in each case, with delivery after 12–4?min of bradycardia. Two of three cases showed low Apgar scores at 5?min, with an umbilical cord arterial pH of <7.1. Lower maternal BMI and a prolonged ECV procedure were significantly associated with bradycardia (p for trend: .016 and .015, respectively).

Conclusions: Fetal bradycardia lasting >10?min after ECV was a risk factor for asphyxia. Thus, delivery should be completed within 10?min after bradycardia. A low maternal BMI and a prolonged ECV procedure were risk factors for bradycardia after ECV.     

Amniotic fluid insulin-like growth factor binding protein 3 concentration as early indicator of fetal growth restriction

Objective

Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth.

Study design

Amniotic fluid samples (14–18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR.

Results

Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P = 0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P = 0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P = 0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR = 0.289, 95%CI = 0.1–0.9, P = 0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups.

Conclusions

High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.     

孕鼠补充牛磺酸减少胎儿生长受限胎鼠脑细胞凋亡

目的 通过建立胎儿生长受限(fetal growth restriction,FGR)大鼠模型,探讨孕鼠补充牛磺酸对FGR胎鼠脑细胞凋亡以及胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)和半胱氨酸蛋白酶-3(caspase 3)表达的影响. 方法 将15只Sprague-Dawley (SD)孕鼠随机分为对照组、FGR模型组(模型组)、FGR+孕鼠补充牛磺酸组(牛磺酸组),每组5只.通过低蛋白饮食法建立FGR模型,牛磺酸组自妊娠第12天开始于饲料中添加牛磺酸300 mg/(kg·d)直至自然分娩.对照组每窝随机取2只适于胎龄胎鼠,牛磺酸组与模型组每窝随机取2只FGR胎鼠,应用原位末端脱氧核苷酸转移酶标记(terminal deoxynucleotidyl transferase mediated nick end labeling,TUNEL)法检测各组胎鼠脑神经细胞凋亡情况.用免疫组织化学方法检测GDNF和caspase-3表达情况.统计学方法采用单因素方差分析、Kruskal-Wallis秩和检验、SNK检验和Tamhane's检验. 结果 (1)对照组、模型组及牛磺酸组胎鼠总数分别为65、60和59只,胎鼠平均体重为(6.36±0.44)、(4.55±0.45)和(5.11±0.67)g.模型组胎鼠均发生FGR,牛磺酸组胎鼠FGR发生率为76.3％ (45/59),成功建立FGR模型.(2)对照组胎鼠脑组织内偶见TUNEL阳性细胞;模型组明显增多,在大脑皮质、海马、白质区均有分布;牛磺酸组较模型组则明显减少.3组TUNEL阳性细胞数分别为(0.46±0.11)、(14.76±3.42)和(6.78±1.93)个(H＝429.80,P＝0.000).(3)对照组胎鼠大脑皮质内仅有少量GDNF阳性细胞分布,模型组明显增多,牛磺酸组则进一步增多.3组GDNF阳性细胞数分别为(93.56±6.73)、(120.36±6.23)和(139.56±5.28)个(H=715.17,P＝0.000).(4)对照组胎鼠大脑皮质内仅见少数caspase 3阳性细胞分布,模型组明显增多,牛磺酸组较模型组显著减少,但仍多于对照组.3组caspase 3阳性细胞数分别为(7.50±2.31)、(151.32±24.43)和(37.28±11.21)个(F=132.54,P＝0.000). 结论 FGR胎鼠脑细胞凋亡显著增多.孕鼠补充牛磺酸可以显著减少FGR胎鼠脑细胞凋亡,其机制可能与牛磺酸能够促进GDNF表达和减少caspase-3表达有关.     

Antepartum fetal evaluation by assessment of fetal heart rate and fetal movements

Three antenatal monitoring tests--fetal movement acceleration test (FMAC-test), fetal heart rate-nonstress test (FHR-NST), and daily fetal movement recording (DFMR) were evaluated in 212 high risk pregnant women. While in 196 cases all three tests were normal, in 16 patients one to three tests showed pathological results. In the latter group, there was a significantly higher incidence of perinatal mortality, low Apgar score and growth retardation. Since false positives are known to occur in these tests, at least two should be pathological to warrant delivery in am attempt to prevent fetal death in utero. The sequence in which the pathology appears in the deteriorating fetus is as follows: the first to become non-reactive is the FMAC-test, followed by decreased fetal movements till cessation, and, finally, severe changes in the FHR-NST take place. The importance of this sequence of events is discussed.     

Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction

IntroductionDiscriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity.MethodsPlasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference <10th percentile for gestational age) at sites in Canada, New Zealand and the United Kingdom. When available, placenta tissue underwent histopathological examination for lesions indicating placental dysfunction, blinded to PlGF and clinical outcome. Lesions were evaluated according to pre-specified severity criteria and an overall severity grade was assigned (0–3, absent to severe). Low PlGF (concentration <5th percentile for gestational age) to identify placental FGR (severity grade ≥ 2) was assessed and compared with routine parameters for fetal assessment. For all cases, the relationship between PlGF and the sampling-to-delivery interval was determined.ResultsLow PlGF identified placental FGR with an area under the receiver-operator characteristic curve of 0.96 [95% CI 0.93–0.98], 98.2% [95% CI 90.5–99.9] sensitivity and 75.1% [95% CI 67.6–81.7] specificity. Negative and positive predictive values were 99.2% [95% CI 95.4–99.9] and 58.5% [95% CI 47.9–68.6], respectively. Low PlGF outperformed gestational age, abdominal circumference and umbilical artery resistance index in predicting placental FGR. Very low PlGF (<12 pg/mL) was associated with shorter sampling-to-delivery intervals than normal PlGF (13 vs. 29.5 days, P < 0.0001).DiscussionLow PlGF identifies small fetuses with significant underlying placental pathology and is a promising tool for antenatal discrimination of FGR from fetuses who are constitutionally-small.     

Pravastatin to prevent recurrent fetal death in massive perivillous fibrin deposition of the placenta (MPFD)

Massive perivillous fibrin deposition of the placenta (MPFD) or maternal floor infarction (MFI) is a serious condition associated with recurrent complications including fetal death and severe fetal growth restriction. There is no method to evaluate the risk of adverse outcome in subsequent pregnancies, or effective prevention. Recent observations suggest that MFI is characterized by an imbalance in angiogenic/anti-angiogenic factors in early pregnancy; therefore, determination of these biomarkers may identify the patient at risk for recurrence. We report the case of a pregnant woman with a history of four consecutive pregnancy losses, the last of which was affected by MFI. Abnormalities of the anti-angiogenic factor, sVEGFR-1, and soluble endoglin (sEng) were detected early in the index pregnancy, and treatment with pravastatin corrected the abnormalities. Treatment resulted in a live birth infant at 34 weeks of gestation who had normal biometric parameters and developmental milestones at the age of 2. This is the first reported successful use of pravastatin to reverse an angiogenic/anti-angiogenic imbalance and prevent fetal death.     

Open fetal surgery for life-threatening fetal malformations

After more than two decades of experimental and clinical work, fetal surgery has become an accepted treatment modality for selected fetuses with life-threatening anomalies. Color Doppler ultrasound and ultrafast fetal magnetic resonance imaging have enhanced the accuracy of prenatal evaluation traditionally made by ultrasound alone. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with liver herniation and a sonographic right lung to head circumference ratio (LHR) of less than one may benefit from fetal tracheal occlusion. Fetal sacrococcygeal teratoma complicated with placentomegaly, hydrops, or progressive high output heart failure may benefit from in utero resection of the tumor. Although preterm labor still remains the Achilles heel of open fetal surgery, effective tocolysis may, in the future, expand the scope of fetal surgery.     

Decreased fetal activity and fetal heart rate changes after amniocentesis complicated by fetal hemorrhage

A case is described in which amniocentesis caused placental injury, abruptic placenta, and fetal hemorrhage which caused fetal distress. This was primarily manifested by reduction of fetal movements and later by fetal heart rate deceleration. Emergency cesarean section was performed of monitoring the fetus after amniocentesis by assessment of fetal movements is stressed.