Inherited thrombophilias and adverse pregnancy outcome: screening and management

Inherited thrombophilias are a heterogenous group of conditions which have been implicated in a variety of pregnancy complications. Evidence is mounting that implicates these inherited disorders in a range of pregnancy outcomes, including recurrent miscarriage, late fetal loss, preeclampsia, abruptio placentae, and intrauterine growth restriction. The most commonly identified inherited thrombophilias consist of Factor V Leiden and the prothrombin gene mutation G20210A. Rarer inherited thrombophilic conditions include deficiencies of protein S, C and antithrombin. More recently, deficiency of protein Z has been linked to pregnancy complications, including preterm delivery. Clinical manifestations often are associated with the presence of more than one inherited thrombophilia, consistent with their multigenic nature. Some, but not all, studies investigating the use of heparin to prevent adverse pregnancy outcome have demonstrated a benefit. However, an adequate randomized trial is required to definitively determine whether heparin anticoagulation is the best prevention option in patients who harbor one or more inherited thrombophilias and are at risk for adverse pregnancy outcome. This review will summarize the association of thrombophilic conditions and obstetrical complications.     

Prehypertension in early versus late pregnancy

Introduction: Hypertensive disorders play a significant role in maternal morbidity and mortality. Limited data on prehypertension (preHTN) in pregnancy exist. We examine the risk of adverse outcomes in patients with preHTN in early (<20 weeks) versus late pregnancy (>20 weeks).

Materials and methods: Retrospective cohort study of singleton gestations between August 2013 and June 2014. Patients were divided based on when they had the highest blood pressure in pregnancy, as defined per the Joint National Committee 7 (JNC-7). Groups were compared using χ², Fisher’s exact, Student’s t-test, and Mann–Whitney U test with p?Results: There were 125 control, 95 early preHTN, 136 late preHTN, and 21 chronic hypertension (CHTN). Early preHTN had an increased risk of pregnancy-related hypertension (PRH) (OR 12.26, p?p?p?=?.02) compared with normotensive and decreased risk for PRH (OR 0.26, p?=?.02), and composite adverse outcomes (OR 0.379, p?=?.04) compared with CHTN. Compared with late preHTN, early preHTN had more PRH (OR 2.85, p?p?=?.04).

Conclusions: Early prehypertension increases the risk of adverse obstetrical outcomes. Other than an increased risk of PRH, patients with late prehypertension have outcomes similar to normotensive women.     

遗传性易栓症的妊娠期筛查与抗凝治疗评价

汉族人群遗传性易栓症以蛋白C或蛋白S缺乏为主,抗凝血酶缺乏少见,罕见凝血因子ⅤLeiden(FⅤL)突变及PGM突变。遗传性易栓症增加妊娠期血栓栓塞性疾病的风险,是胎盘介导的妊娠并发症的协同性促进因素,而不是主要病因。如果已经明确具有进行治疗的指征,没有必要再行遗传性易栓症的筛查;如果病因不明,而遗传性易栓症筛查的阳性结果可能会影响治疗决策时,筛查或许是有用的。现有证据仅表明,预防性应用低剂量阿司匹林可以减少子痫前期复发。低分子肝素是否能改善胎盘介导的妊娠并发症的再发风险,单中心和多中心研究的结论并不一致。虽然缺乏有力的证据支持,目前仍建议对具有胎盘介导的妊娠并发症病史的遗传性易栓症患者进行选择性、个体化抗凝治疗。     

Single inherited thrombophilias and adverse pregnancy outcomes

INTRODUCTION: Inherited thrombophilia is believed to be a multiple gene disease with more than one defect. We aimed to determine the association between single thrombophilic patterns and a variety of pregnancy diseases. METHODS: 284 pregnant women were recruited for the present study and were divided in two groups: A group (176 controls) and B group (108 cases). Patients belonging to the B group had one of the following: severe pre-eclampsia, hemolysis, hepatic enzymes increase, hypertension and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction, intrauterine death, abruptio placentae and disseminated intravascular coagulopathy. To detect methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, an inverse hybridization technology was used. Plasma homocysteine, antithrombin (AT) III and protein S were determined. A modified functional activated protein C resistance was detected. RESULTS: MTHFR C677T and hyperhomocysteinemia were more prevalent than other thrombophilias. Deficiency in AT III was significantly linked with pre-eclampsia (relative risk 0.88; 95% CI 0.83-0.94). Activated protein C resistance (APCR) was significantly related to the abruptio placentae (relative risk 0.71; 95% CI 0.61-0.82). COMMENTS: Apart from the linkage between AT III deficiency and the occurrence of pre-eclampsia, and apart from the increased risk of abruptio placentae in pregnant women with altered APCR, we obtained findings in contrast with some of the published literature. In our case series, no association of pre-eclampsia with factor V Leiden or with prothrombin gene mutation was found.     

Risks and guidelines for the consumption of alcohol during pregnancy

Daily average intake of alcohol during pregnancy has consistently been associated with short term adverse outcomes such as miscarriage, preterm birth and intrauterine growth restriction, a large variety of malformations, as well as long term adverse outcomes such as foetal alcohol syndrome, mental retardation and general impairment of cognitive functions including intelligence, attention, learning abilities as well as social and behavioural functions. Weekly average consumption and alcohol binge drinking (usually defined as ≥ 5 drinks on a single occasion) independently of high daily average intake has not been consistently associated with short and long term adverse outcomes. Health authorities in most countries recommend that pregnant women completely abstain from alcohol. Even so, many health professionals including doctors, midwives and nurses do not provide information to pregnant women in accordance with the official recommendations, although a large proportion of women of child bearing age and pregnant women drink alcohol, especially before recognition of pregnancy. The discrepancy between guidelines and the information practice of health personnel is likely to continue to exist because guidelines of abstinence are not clearly evidence-based and not in line with current focus on autonomy and informed choice for patients, and because guidelines do not consider the everyday clinical communication situation.     

Pregnancy complications in women with inherited thrombophilia

Objective: The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications. Methods: All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000–2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Results: Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9–10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5–16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3–10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4–15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90–10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age. Conclusion: Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.     

妊娠合并急性脑出血的临床分析

目的研究妊娠合并急性脑出血的临床特点及其对母婴的影响,探讨合并急性脑出血的孕妇的妊娠结局。方法对1990年1月至2012年9月,12例妊娠合并急性脑出血患者的临床资料进行回顾性分析。结果 12例妊娠急性脑出血的孕产妇死亡7例,存活5例;新生儿存活7例。结论妊娠期脑出血多发生在晚期妊娠及分娩过程,妊娠合并急性脑出血应先行终止妊娠,依患者情况适时行开颅手术,分娩以剖宫产为宜,尽量同时行绝育术。不宜采取母乳喂养。妊娠合并急性脑出血以全麻下剖宫产为宜,并同时做好新生儿抢救的准备,母婴多可获得较好的结局。     

Hereditary thrombophilias are not associated with a decreased live birth rate in women with recurrent miscarriage

OBJECTIVE: To assesses the live birth rate without treatment in women with hereditary thrombophilia who have recurrent miscarriage and women without thrombophilia who have recurrent miscarriage. DESIGN: Prospective observational study. SETTING: Tertiary referral unit in university hospital. PATIENT(S): One hundred twenty women with thrombophilia and 65 women without thrombophilia. MAIN OUTCOME MEASURE(S): Number of live births or repeated miscarriages. RESULTS: Of the 185 patients, 44 with thrombophilia and 26 without thrombophilia have conceived. Nineteen of the 44 pregnancies (43.2%) in thrombophilia patients have terminated in live births, compared with 8 of 26 pregnancies (30.8%) in patients without thrombophilia. This difference is not statistically significant. CONCLUSIONS: Hereditary thrombophilia did not seem to affect the live birth rate in women with recurrent miscarriage.     

复苏周期中单/双囊胚移植患者的临床结局比较

目的:探讨复苏周期单囊胚和双囊胚移植对患者妊娠结局的影响。方法:回顾性分析行囊胚冷冻-复苏患者2 021例,其中单囊胚复苏移植组(A组)326例,双囊胚复苏移植组(B组)1 695例。比较单/双囊胚复苏移植对患者临床结局的影响及新生儿情况分析。结果:A组胚胎着床率、临床妊娠率、早产率、多胎率、低体质量儿率分别显著低于B组(P0.05);A组早期流产率、新生儿体质量、身长以及Apgar评分均显著高于B组(P0.05)。结论:单囊胚移植能够明显降低多胎率及产科风险。     

Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes

Venous thromboembolism and adverse pregnancy outcomes are potential complications of pregnancy. Numerous studies have evaluated both the risk factors for and the prevention and management of these outcomes in pregnant patients. This consensus group was convened to provide concise recommendations, based on the currently available literature, regarding the use of antithrombotic therapy in pregnant patients at risk for venous thromboembolic events and adverse pregnancy outcomes.     

Maternal and neonatal outcomes among pregnant women with fibromyalgia: a population-based study of 12 million births

Purpose: Fibromyalgia (FM) is a rheumatologic disorder marked by chronic, widespread pain and associated comorbid conditions. The purpose of our study was to evaluate the effect of FM on maternal and neonatal outcomes.

Methods: Using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1999 to 2013, we conducted a population-based retrospective cohort study consisting of women who delivered during that period. Logistic regression was used to compare maternal and neonatal outcomes among pregnancies in women with and without FM.

Results: Of 12 584 918 births during the 15-year study period, 7758 (0.06%) were to women with FM with rates increasing over the study period. Women with FM were more commonly older in age, overweight or obese, and users of alcohol, tobacco, and illicit drugs. They were more likely to experience anxiety, depression, and bipolar disorder. Women with FM were at greater risk of gestational diabetes, preterm premature rupture of membranes, and placental abruption. Women with FM more commonly had cesarean deliveries (odds ratios (OR): 1.11, 95% CI: 1.05–1.16) and births complicated by venous thromboembolism (OR: 2.34, 95% CI: 1.91–2.86). Infants of women with FM were more likely to be premature (OR: 1.35, 95% CI: 1.25–1.46) and have intrauterine growth restriction (OR: 1.48, 95% CI: 1.30–1.68).

Conclusions: The prevalence of FM in pregnancy is rising in the US. FM is a high-risk pregnancy condition associated with adverse maternal and newborn outcomes.     

多囊卵巢综合征孕期代谢特点及其管理

多囊卵巢综合征（PCOS）是育龄女性内分泌和代谢紊乱性疾病,对孕期与非孕期育龄妇女均可能产生不利影响。近年来,随着对PCOS孕妇的相关研究不断深入,发现其妊娠期母儿并发症的发生率升高,且与胰岛素抵抗、肥胖、糖脂代谢、高雄激素血症等相关,做好孕前、孕期及产后的管理对近远期并发症的预防可能均有重要作用。文章对PCOS孕期代谢特点及其管理等内容进行阐述。     

548例妊娠期甲状腺功能筛查指征及亚临床甲减对妊娠结局影响的分析

目的回顾性分析妊娠期甲状腺功能的筛查指征及阳性率;阐明妊娠合并亚临床甲减对妊娠结局的影响。方法 2008年1月至2010年12月在北京大学第一医院产科分娩的孕妇行甲状腺功能检测者548例,对其筛查指征进行比较;对TSH水平正常孕妇的FT4水平按妊娠时期分类,取妊娠特异性FT4水平的95%可信区间作为本研究FT4的正常参考值,分组比较亚临床甲减组和对照组孕妇不良妊娠结局的差异。结果 548例孕妇中发现高TSH血症111例,应用高危因素筛查策略仅能检出49例（44.1%）;TSH正常组FT4水平行妊娠周期特异性分组,妊娠早、中、晚期FT4的水平呈下降趋势,组间P值均〈0.001;得出的FT4的频率分布95%可信区间作为参考值,对两组（亚临床甲减组和对照组）孕妇不良妊娠结局进行比较,两组间差异无统计学意义（P〉0.05）。结论实施高危因素的甲状腺功能筛查策略甲状腺功能异常漏诊率较高;尚未发现亚临床甲减与孕妇不良妊娠结局之间的相关性。     

Cardiovascular risk factors in women with inheritable thrombophilia a decade after single or recurrent hypertensive disorder of pregnancy

Objective: To described cardiovascular risk factors in women with inheritable thrombophilia 8–19 years after early-onset hypertensive disorders of pregnancy (HD) with or without recurrent HD. Methods: Women with recurrent HD were compared with women with single HD, for physical examination and cardiovascular parameters in serum. Results: Systolic blood pressure, diastolic blood pressure, and albumin: creatinine ratio were higher in women with recurrent HD compared with women with single HD (p = 0.046, p = 0.029, and p = 0.008, respectively). In both groups 72.7% had an increased cardiovascular risk. Conclusion: Women with inheritable thrombophilia after single or recurrent HD have a high cardiovascular risk.     

Double versus single cervical cerclage for the prevention of preterm births

Objective: To evaluate the effectiveness double cervical cerclage in reducing antenatal complications and improve perinatal outcomes.

Methods: We searched Medline, Scopus, Clinicaltrials.org, The Cochrane Central Register of Controlled Trials and Google Scholar search engines.

Results: Six studies were included that involved 880 women. Double cerclage was significantly superior to single cerclage in reducing preterm births <34?weeks (734 cases, OR 0.59, 95% CI 0.40, 0.86) and preterm births <28?weeks (645 cases, OR 0.43, 95% CI 0.26–0.73). It also significantly increased the gestational age (380 cases, MD 2.63, 95% CI 0.87, 4.39). However, as a technique, it failed to improve the rates of preterm births <37?weeks (740 cases, OR 0.98, 95% CI 0.72, 1.34) the incidence of chorioamnionitis (740 cases, OR 0.83, 95% CI 0.51, 1.36) and the occurrence of preterm premature rupture of the membranes (796 cases, OR 1.32, 95% CI 0.95, 1.82).

Conclusions: It seems that double cerclage effectively increases the gestational age at delivery and decreases the rates of extremely premature births. However, as a procedure, it does not reduce the incidence of antenatal morbidity or the neonatal death rates. Further research is needed in the field as our meta-analysis is limited by the small number of enrolled studies.     

Hypertension during pregnancy in South Australia, part 1: pregnancy outcomes

BACKGROUND: There have been conflicting reports about pregnancy outcome in the hypertensive disorders of pregnancy. The present study was undertaken to examine outcomes using a population database. AIMS: To examine for differences in a range of pregnancy outcomes between three different groups of hypertensive women and normotensive women in South Australia. METHODS: Nine pregnancy outcomes were compared for 70,386 singleton pregnancies in the South Australian perinatal data collection in 1998-2001, consisting of 639 women with pre-existing hypertension, 5356 women with pregnancy hypertension, 448 women with superimposed pre-eclampsia and 63 943 normotensive women. Means for the four groups were calculated for birthweight, gestational age, the baby's and mother's length of stay. The groups were also compared for perinatal deaths with an earlier period, 1991-1997. RESULTS: While all three hypertensive groups had high incidences of induction of labour and emergency Caesarean, only pre-existing hypertension and superimposed pre-eclampsia were significantly associated with elective Caesarean section. All hypertensive groups had increased risks for low birthweight and preterm birth and special and neonatal intensive care. Uncomplicated pre-existing hypertension was not associated with small for gestational age infants, but with preterm delivery between 32 and 36 weeks' gestation. Superimposed pre-eclampsia had the worst prognosis for perinatal and maternal morbidity. While pregnancy hypertension held the intermediate position, it was not associated with an increase in perinatal mortality. The perinatal mortality rate for women with hypertensive disorders in 1998-2001 was significantly lower than that of an earlier period and equivalent to that for normotensive women. CONCLUSIONS: Superimposed pre-eclampsia occurs in approximately 40% of pregnancies of women with pre-existing hypertension and has the most severe outcomes. The hypertensive disorders are associated with high levels of morbidity and intervention, but the high perinatal mortality associated with these disorders has fallen significantly.     

Index pregnancy versus post-index pregnancy in patients with recurrent pregnancy loss

Objective: To compare pregnancy outcomes of two consecutive pregnancies in a cohort of women with recurrent pregnancy loss (RPL), in order to determine the long-term prognosis of women with RPL managed in a dedicated RPL clinic.

Methods: A retrospective cohort study including 262 patients with two or more consecutive pregnancy losses followed by two subsequent pregnancies – index pregnancy (IP) and post-index pregnancy (PIP). All patients were evaluated and treated in the RPL clinic in the Soroka University Medical Center.

Results: Comparing IP with PIP, no significant difference in perinatal outcome was observed. The perinatal outcome remained encouraging with approximately 73% birth rate (73.7% versus 72.5%; p?=?0.83). Only 11% of the women with RPL continued to experience pregnancy losses for two subsequent pregnancies. In a multivariate logistic regression analysis, number of miscarriages pre-Index was the only factor independently associated with birth in the PIP.

Conclusion: There is no significant difference between IP and PIP regarding perinatal outcome. Appropriate management in the RPL clinic conferred a significant beneficial effect on long-term pregnancy outcome of a cohort of women with RPL.