A new biological and clinical resource for research into pregnancy complications: The Baby Bio Bank

About 20% of pregnancies are affected by some form of complication. Research has shown that anomalies in implantation, development, and growth of the fetus; ineffective nutrient exchange between mother and fetus due to placental dysfunction; and maternal problems such as hypertension or infection during pregnancy can all lead to adverse pregnancy outcomes. However, the molecular aetiology of such events remains poorly understood. Fetal growth restriction (FGR), recurrent miscarriage (RM), preterm birth (PTB), and pre-eclampsia (PE) are the most common pregnancy complications encountered in the UK and these outcomes can result in an array of morbidities in both mother and baby, and in the most severe cases in mortality. We need to know more about normal pregnancy and where the important triggers are for failure. This prompted us to collect a large set of biological samples with matching clinical data from over 2500 normal and abnormal pregnancies, for use in research into these conditions. This paper outlines the nature of these sample sets and their availability to academia and industry, with the intention that their widespread use in research will make significant contributions to the improvement of maternal and fetal health worldwide (http://www.ucl.ac.uk/tapb/sample-and-data-collections-at-ucl/biobanks-ucl/baby-biobank).     

脂多糖经线粒体途径诱导细胞滋养细胞凋亡

目的:探讨脂多糖(Lipopolysaccharide,LPS)诱导细胞滋养细胞凋亡的机制。方法:从正常早孕绒毛分离细胞滋养细胞,用无血清培养基培养。在培养基中加入不同浓度的LPS,使其终浓度分别为0、25、50、100、200ng/ml。用光镜和透射电镜观察细胞滋养细胞的形态学变化;用Western blot检测Bax、Bcl-2和Caspase-8的表达。结果:LPS作用后24h,光镜和电镜下见细胞滋养细胞出现凋亡的形态学变化;Western blot检测结果表明,LPS抑制Bcl-2表达,促进Bax和Caspase-8表达。结论:LPS能够经线粒体途径诱导细胞滋养细胞凋亡。     

内毒素调节细胞滋养细胞侵入能力的机制

目的:探讨内毒素(lipopolysacchraride,LPS)对细胞滋养细胞侵入能力的影响。方法:留取正常早孕绒毛,分离细胞滋养细胞,用无血清培养基培养。对照组:培养基中不添加内毒素。实验组:培养基中加入不同浓度的内毒素,其终浓度分别为25、50、100、200ng/m l。Transwell小室检测细胞滋养细胞的侵入能力;采用激光共聚焦-免疫荧光技术检测基质金属蛋白酶-2、9(MMP-2、9)蛋白的表达;RT-PCR检测MMP-2、MMP-9 mR-NA表达水平。结果:内毒素降低细胞滋养细胞侵入Transwell小室的能力,在浓度为0、25、50、100、200ng/m l的LPS作用24h后,细胞滋养细胞侵至滤膜下表面的细胞为145.6±20.7、139.6±18.8、123.1±17、76.5±18、47.9±16,差异有统计学意义(P<0.01);内毒素显著抑制细胞滋养细胞MMP-2、MMP-9蛋白和mRNA的表达。结论:内毒素能够抑制细胞滋养细胞的侵入能力,可能是通过抑制基质金属蛋白酶表达来实现。     

Maternal physiology and complications of multiple pregnancy

Approximately 1% to 3% of all pregnancies in the United States are multiple gestations. The vast majority (97-98%) are twin pregnancies. Multiple pregnancies constitute significant risk to both mother and fetuses. Antepartum complications-including preterm labor, preterm premature rupture of the membranes, intrauterine growth restriction, intrauterine fetal demise, gestational diabetes, and preeclampsia-develop in over 80% of multiple pregnancies as compared with approximately 25% of singleton gestations. This article reviews in detail the maternal physiologic adaptations required to support a multiple pregnancy and the maternal complications that develop when these systems fail or are overwhelmed.     

Anal sphincter disruption at vaginal delivery: is recurrence predictable?

Objectives: To evaluate the efficacy of clindamycin vaginal cream 2% once daily for 7 days in prolonging pregnancy. Study design: Randomised clinical trial of 112 women between 14 and 25 weeks of gestation with diagnosis of asymptomatic bacterial vaginosis were enrolled in a multicenter randomised trial and assigned to active or no treatment. A total of 55 women were assigned to clindamycin and 57 to no treatment. Main outcome measure: frequency of pre-term delivery. Results: The rates of pre-term delivery was 12.2% in the clindamycin group and 15.7% in the no treatment group (P=0.78). Birth weight was <2500 g in three and seven babies, respectively, in the two groups (P=0.32). Mean gestational ages at birth were 38.9 and 39.2 (P=0.52), respectively, in the clindamycin and no treatment groups. Conclusions: The results of this study suggest that treating asymptomatic bacterial vaginosis does neither markedly prolong pregnancy nor increase birthweight.     

Association of Periodontal Disease and Pre-term Low Birth Weight Infants

The incidence of pre-term low birth weight still prevails in developed as well as developing countries though the numbers may vary. Periodontitis is a chronic inflammatory process with multifactorial etiology and adversely affects the outcome of pregnancy which becomes a major public health problem. The association of periodontitis as risk factor for pre-term birth has been in extensive research in the past two decades when a number of studies investigated this relationship. However, definite connection has not been proved yet and research is still ongoing. This article describes about the possible relationship that can exist between pre-term low birth weight infants and periodontal disease.     

Association between maternal panic disorders and pregnancy complications and delivery outcomes

BACKGROUND: The objective of the study was to evaluate the possible association between panic disorders during pregnancy and pregnancy complications, as well as birth outcomes: gestational age and birth weight, as well as preterm birth/low birthweight in newborns. METHODOLOGY: Comparison of newborn infants (without any defects) born to mothers with or without panic disorder in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Main outcome measures were medically recorded pregnancy complications, as well as gestational age and birth weight, proportion of preterm birth and low birthweight. PRINCIPAL FINDINGS: Of 38,151 controls, 187 (0.5%) had mothers with panic disorders during pregnancy. Among pregnancy complications, anemia and polyhydramnion showed a higher prevalence in women with panic disorder. There was a higher proportion of males among newborn infants born to mothers with panic diseases compared to newborn infants of mothers without panic disorders. Pregnant women with panic disorders had a shorter (0.4 week) gestational age (adjusted t = 2.3; p = 0.02) and a larger proportion of preterm births (17.1% versus 9.1%) (adjusted POR with 95% CI = 1.9, 1.3-2.8). However, there was no significant difference in the mean birth weight and rate of low birthweight between the two study groups. CONCLUSION: Panic disorders during pregnancy were associated with anemia, a shorter gestational age and a larger proportion of preterm birth. Further studies are needed to confirm and explain or disprove the male excess among newborn infants born to mothers with panic disorders.     

Vascular ultrasound measures before pregnancy and pregnancy complications: A prospective cohort study

Objectives: To examine the relationship between pre-pregnancy indicators of cardiovascular risk and pregnancy complications and outcomes. Study design: Data from 359 female participants in the Cardiovascular Risk in Young Finns Study were linked with the national birth registry. Flow-mediated dilatation (FMD; maximum change in the left brachial artery diameter after rest and hyperemia); carotid intima-media thickness (IMT); Young’s elastic modulus (YEM); and carotid artery distensibility (Cdist) at the visit prior to the pregnancy were examined as predictors of hypertensive disorders, birthweight, and gestational age using multivariable linear regression with adjustment for confounders (age, BMI, smoking, and socioeconomic status). Results: No relations were seen between FMD, IMT, or the stiffness indices, and hypertensive disorders. Higher pre-pregnancy FMD was associated with lower gestational age, while increased Cdist was associated with reduced birthweight-for-gestational-age. Conclusions: Some cardiovascular ultrasound measures of pre-pregnancy may predict pregnancy complications, but the association is likely to be small.     

Human chorionic gonadotropin levels between 16 and 21 weeks of pregnancy and prediction of pre-eclampsia.

OBJECTIVE: To determine whether levels of beta human choriogonadotropin (beta-hCG) during the second trimester are a predictor of pre-eclampsia. METHODS: A prospective study of 784 women was conducted between their 16th and 20th week of pregnancy. Primigravidas and multigravidas were analyzed separately, and the cutoff point was determined using a receiver operating characteristic curve. The accuracy of beta-hCG levels in the prediction of pre-eclampsia was evaluated. The likelihood ratios were calculated for different levels of beta-hCG in both groups. RESULTS: Pre-eclampsia prevalence was 7.1% among primigravidas and 4.6% among multigravidas. The cutoff concentration was 2.0 MoM in both groups. For primigravidas and multigravidas, respectively, the area below the curve was 0.96 and 0.95; sensitivity was 88.5% and 100%; specificity was 92.0% and 85.6%; positive predictive value was 0.46 and 0.25; and negative predictive value was 0.99 and 1.0. With a cutoff concentration of 2.0 MoM of beta-hCG, the positive likelihood ratio was 11.1 in primigravidas and 6.9 in multigravidas. CONCLUSION: This study shows that measuring levels of beta-hCG during the second trimester of pregnancy is useful in clinical practice to identify pregnant women who will develop pre-eclampsia.     

Maternal blood coagulation factor XIII is associated with the development of cytotrophoblastic shell

We analysed the early implantation tissues of normal women and of a patient with congenital factor XIII deficiency in order to study the role of maternal subunit A of factor XIII (XIIIA) in the development of extravillous cytotrophoblast. The patient had received adequate administration of factor XIIIA concentrate only up to 7 weeks of gestation (wG). Her pregnancy was maintained until the latter half of 8 wG, but was terminated by intrauterine fetal death at 9 wG. Immunohistochemical staining of cytokeratin, XIIIA and subunit S of factor XIII was performed in the early implantation tissues of normal women and of this patient. Numerous well-formed cytotrophoblastic shells and Nitabuch's layers were detected in implantation tissues at 7-8 wG in normal women, and XIIIA was present in the intercellular space in well-formed cytotrophoblastic shells, while the cytotrophoblastic shells and Nitabuch's layers in this patient's implantation tissue were poorly-formed. Furthermore, XIIIA was not detected around them. It is suggested that when the maternal plasma activity of factor XIII is low, the concentration of XIIIA at the placental bed is also low, leading to the insufficient formation of cytotrophoblastic shell and therefore an increased probability of miscarriage in patients with congenital factor XIII deficiency.     

Implications of abnormal liver function in pregnancy and non-alcoholic fatty liver disease

Elevated liver enzyme levels can sometimes be encountered in asymptomatic pregnant women. Similar to non-pregnant subjects, women with elevated gamma glutamyltransferase or alanine aminotransferase in early pregnancy have increased risk of subsequent complications, especially gestational diabetes mellitus. In non-pregnant subjects, the commonest cause of abnormal liver function currently is non-alcoholic fatty liver disease. Risk factors include obesity, diabetes, and the metabolic syndrome. It can progress to hepatocellular carcinoma through the development of steatohepatitis, and has become the leading cause for liver transplantation in women. Found in as many as 16–18% of pregnant women, it is associated with an increased risk of pregnancy complications and abnormal foetal growth, which predisposes the offspring to the same problem subsequently. This condition probably explains the majority of the cases of “idiopathic” abnormal liver function in pregnancy, and should be looked out for in high-risk women owing to its implications on their long-term health outcome.     

The reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data

OBJECTIVE: The purpose of this study was to determine the accuracy of live-birth certificates and hospital discharge data that reported of pre-existing maternal medical conditions and complications of pregnancy. STUDY DESIGN: We conducted a population-based validation study in 19 non-federal short-stay hospitals in Washington state with a stratified random sample of 4541 women who had live births between January 1, 2000, and December 31, 2000. True- and false-positive fractions were calculated. RESULTS: Birth certificate and hospital discharge data combined had substantially higher true-positive fractions than did birth certificate data alone for cardiac disease (54% vs 29%), acute or chronic lung disease (24% vs 10%), gestational diabetes mellitus (93% vs 64%), established diabetes mellitus (97% vs 52%), active genital herpes (77% vs 38%), chronic hypertension (70% vs 47%), pregnancy-induced hypertension (74% vs 49%), renal disease (13% vs 2%), and placenta previa (70% vs 33%). For the 2 medical risk factors that are available only on birth certificates, true-positive fractions were 37% for established genital herpes and 68% for being seropositive for hepatitis B surface antigen. CONCLUSION: In Washington, most medical conditions and complications of pregnancy that affect mothers are substantially underreported on birth certificates, but hospital discharge data are accurate in the reporting of gestational and established diabetes mellitus and placenta previa. Together, birth certificate and hospital discharge data are much superior to birth certificates alone in the reporting of gestational diabetes mellitus, active genital herpes, and chronic hypertension.     

正常妊娠与子痫前期患者胎盘组织VEGF和p53的表达与意义

目的:探讨子痫前期(PE)患者胎盘组织血管内皮生长因子(VEGF)和抑癌基因p53的表达变化、相互关系及其在PE发病过程中的作用。方法:采用链酶菌抗生物素蛋白-过氧化物酶连接(SP)法检测35例PE患者(轻度15例和重度20例)和25例正常妊娠(对照组)胎盘组织中VEGF和p53的表达变化。结果:(1)重度PE患者胎盘组织中VEGF表达强度显著低于正常对照组和轻度PE组(P均0.05),而轻度PE组与正常对照组无显著差异(P0.05);(2)PE患者胎盘组织中p53的表达强度较正常对照组均显著升高(P0.05),重度PE组亦显著高于轻度PE组(P0.05);(3)胎盘组织中VEGF和p53的表达呈显著负相关(r=-0.428,P=0.001)。结论:VEGF和p53在PE和正常妊娠胎盘组织中的表达变化预示着其与PE的发生、发展有一定的关系。     

降低子痫前期患者严重并发症的策略

妊娠期高血压疾病是妊娠最常见的并发症之一,尤其是临床表现严重的子痫前期、子痫和HELLP综合征,可使母亲与胎儿的发病率和死亡率增加,如何及时、准确地诊断和处理关系到患者病情的进展和预后。本文从风险预测、诊断标准和处理原则几个方面阐述了降低子痫前期患者严重并发症发生的策略,以期最大程度改善妊娠期高血压疾病患者的母儿预后。     

孕期体重增加与妊娠并发症及妊娠结局的相关性研究

目的:探讨孕期体重增加与妊娠并发症及妊娠结局的相关性。方法:收集2010年6月至2010年12月在我院进行正规产前检查并分娩的孕妇423例进行研究,分析孕期体重增加与妊娠并发症及妊娠结局的关系。结果:C组妊娠期糖尿病与妊娠期高血压疾病的发病率高于A组和B组,两者比较差异均具有统计学意义(P<0.05);C组剖宫产率及巨大儿的发生率高于A组和B组,C组及B组产后出血的发生率高于A组,两者比较差异均具有显著性(P<0.05)。C组胎儿窘迫及新生儿窒息的发生率明显高于A组(P<0.05)。结论:孕期体重增加过高可导致妊娠并发症及不良妊娠结局的发生,适当控制孕期体重增加可改善母婴妊娠结局,提高产科质量。     

妊娠期头痛的管理

头痛是妊娠期妇女常见症状,妊娠期头痛的管理中,应关注头痛的相关病因、相关治疗和预防。     

牙周病与不良妊娠结局关系的研究

随着对牙周病深入研究发现,其可能是不良妊娠结局的危险因素。动物研究表明,牙周感染可导致出生动物低体质量,死亡率高。已有临床病例研究证实,牙周炎与早产儿,低出生体质量儿和子痫前期之间有相关性。微生物学研究为牙周病与妊娠不良结局之间的关系提供了有力的证据。但也有研究认为．牙周病并不是早产儿,低出生体质量儿的危险因素。牙周病与不良妊娠之间的关系仍不十分明确,进一步探讨牙周病与妊娠不良结局之间的作用机制,为预防与临床治疗提供新信息。     

Tea consumption during pregnancy and the risk of pre-eclampsia

Objective

To examine the effects of tea consumption during pregnancy on the risk of pre-eclampsia.

Methods

A case-control study was carried out among nulliparous pregnant women in Quebec between January 2003 and March 2006. Data were collected using a structured study questionnaire. A total of 92 women with pre-eclampsia and 245 controls were analyzed. Univariate analysis and multivariate regression were performed to examine the association between tea consumption and pre-eclampsia.

Results

Compared with non-tea drinking during pregnancy, the crude odds ratio (OR) and adjusted OR (aOR) of pre-eclampsia for tea drinking were 1.34 (95% CI, 0.80-2.25) and 1.39 (95% CI, 0.81-2.41), respectively. The OR and aOR of severe pre-eclampsia for tea drinking were 1.39 (95% CI, 0.78-2.46) and 2.14 (95% CI, 1.01-4.54), respectively. The aORs for persistent tea consumption in pre-eclampsia and severe pre-eclampsia were 1.88 (95% CI, 1.01-3.51) and 1.95 (95% CI, 1.06-3.57), respectively.

Conclusion

Persistent tea drinking during pregnancy may be associated with an increased risk of pre-eclampsia.