Risk factors for preeclampsia in Japanese twin pregnancies: comparison with those in singleton pregnancies

Objective  To identify the factors associated with the increased risk of developing preeclampsia in twin pregnancies compared with those in singleton pregnancies. Methods  We reviewed the obstetric records of all deliveries at ≥22 weeks’ gestation managed at the Japanese Red Cross Katsushika Maternity Hospital between 2001 and 2007. Results  The incidence of preeclampsia in the twin pregnancies (7.6%: 45 in 593) was significantly higher than that in the singleton pregnancies (1.7%: 196 in 11,311; P < 0.01). In singleton pregnancies, the developing preeclampsia was associated with maternal age at ≥35 years, primiparity, maternal BMI ≥25 before pregnancy, history of infertility therapies such as IVF and having a history of previous preeclampsia. In twin pregnancies, however, the developing preeclampsia was not associated with these variables. Conclusions  In Japanese women, the factors reported to be associated with the increased risk of preeclampsia in singleton pregnancies may not alter the increased risk of preeclampsia in twin pregnancies.     

单、双胎妊娠并发子痫前期临床分析

目的探讨单、双胎妊娠并发子痫前期的临床特点及妊娠结局。 方法选取2009年1月至2013年4月在广州医科大学附属第三医院产科住院分娩的43例双胎并发子痫前期的孕妇为研究组,362例单胎并发子痫前期产妇作为对照组,回顾性分析两组患者的临床特点及母婴结局的情况。 结果研究组住院时间(13.28±11.23)d,较对照组(9.48±4.97)d延长,t＝2.20,P<0.05。研究组剖宫产率、胎膜早破、产后出血、心力衰竭的发生率分别为97.67%、13.95%、11.63%、11.63%,明显高于对照组(79.83%、5.25%、5.25%和4.14%),差异有统计学意义(P<0.05)。研究组发生新生儿感染和黄疸分别为25.58%和48.84%,高于对照组15.19%和32.60%,差异有统计学意义(P<0.05)。 结论双胎并发子痫前期与单胎并发子痫前期相比,会增加孕产妇的剖宫产、胎膜早破、产后出血、心力衰竭等发生率,同时延长产妇的住院时间。     

Primiparity, assisted reproduction, and preterm birth in twin pregnancies: a population based study

Objective To determine the prevalence of pregnancy complications among primiparous patients with twin gestation in our population and to investigate the association between the increased rates of assisted reproduction (ART) in twin gestation and preterm birth (PTD). Material and methods A retrospective population based cohort study was designed, including all twin deliveries after 24 weeks gestation (n = 2,601). The study group included 666 primiparous women and the comparison group 1,935 multiparous women. Maternal characteristics and perinatal outcome were evaluated. Women with fetal malformations were excluded. A multiple logistic regressions analysis for independent risk factors was performed including factors that were significantly different between the study groups in the univariate analysis. Patient’s data were obtained from computerized database and analyzed using SPSS statistical package. Results Primiparous women had a significantly higher rate of preeclampsia, chronic hypertension, ART, prelabor rupture of membranes (PROM) preterm deliveries (PTD), labor dystocia, cesarean section (CS) and vacuum extraction of the first twin than the multiparous group. Primiparous patients had a significantly lower gestational age at delivery and neonatal birth weight of the first and second twin. In multiple logistic regressions analysis primiparity and ART were independent risk factors for PTD, (OR 1.45, 95% CI 1.18–1.78; OR 1.36, 95% CI 1.09–1.71, respectively). Conclusions (1) Primiparous patients with twin gestation represent a unique population with high rate of infertility and underlying diseases such as chronic hypertension in comparison to the multiparous women with twin gestation; (2) primiparity is an independent risk factor for prematurity in twin gestations; and (3) although primiparous women had an increased maternal complications, neonatal mortality rates were not significantly different from multiparous women.     

Early prediction of preterm birth for singleton, twin, and triplet pregnancies

OBJECTIVES: To create prediction models of early preterm birth for singletons, twin, and triplet pregnancies. STUDY DESIGN: We used a historical cohort study with the 1996 birth registration data for singletons and the 1995-1997 linked birth/infant death dataset for multiple births of the United States. Preterm birth was defined as gestational age <32 completed weeks. Eligible study subjects were randomly allocated to two groups: one group (80% subjects) for the creation of the prediction models, and the other group (20% subjects) for the validation of the established prediction models. Multivariate logistic regressions were used to establish the prediction models. We further assessed the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the established prediction models with different cut-off values in the validation group. RESULTS: The sensitivity, specificity, PPV, and NPV of the established model were 24.58, 93.54, 5.91, and 98.69%, respectively for singletons, 64.66, 57.04, 16.29, and 92.59%, respectively for twins, and 63.57, 53.58, 42.96, and 72.78%, respectively for triplets. CONCLUSION: The prediction models of early preterm birth for singleton, twin, and triplet pregnancies created by this study could be useful for obstetricians to identify women being at high risk of preterm birth at early gestation.     

Monochorionic monoamniotic twin pregnancies

Monochorionic monoamniotic (MCMA) twin pregnancy is rare and associated with increased complication rates when compared with singletons, dichorionic and monochorionic diamniotic pregnancy in general. Monoamnionicity presents an enormous challenge following its accurate diagnosis, where the absence of an inter-twin membrane subsequently results in cord entanglement and consistently fluctuating foetal position. Furthermore, the detection of twin-twin transfusion syndrome (TTTS) in MCMA pregnancy can be challenging in the absence of amniotic fluid volume discordance without the presence of the inter-twin dividing membrane. Early surveillance of foetal anatomy permits early recognition of foetal structural anomalies, the twin reversed arterial perfusion (TRAP) sequence and conjoined twins. However, the evidence on how best to monitor MCMA pregnancies remains inadequate, though observational studies have demonstrated that once surveillance is initiated, the potential risk of foetal death decreases significantly. In-utero foetal demise can be acute and unpredictable in MCMA pregnancies, despite close surveillance. Elective preterm delivery is usually advocated when the risk of foetal loss upon continuing the pregnancy outweighs the risk of prematurity – around 33 weeks’ gestation by caesarean section. Nevertheless, the optimal prenatal surveillance regimen and prompts for delivery have yet to be defined.     

Delayed interval delivery in twin pregnancies in the United States: Impact on perinatal mortality and morbidity

OBJECTIVE: To estimate the incidence of delayed interval delivery in twin pregnancies in the United States and evaluate the impact of delayed delivery on perinatal outcomes. STUDY DESIGN: A population-based retrospective cohort study was performed using the U.S. "matched multiple birth" file (1995 to 1998), restricting our analysis to twin sets in which the first twin was delivered vaginally at 22 to 28 weeks (n = 4257). Outcomes examined included perinatal and infant mortality and small-for-gestational-age births. Outcomes of second twins in pregnancies that underwent delayed interval delivery of 1, 2, 3, and >/=4 weeks were compared with those in which both twins were delivered contemporaneously. RESULTS: In this cohort, 6.1% (n = 258) of twins had delayed delivery (>/=1 week) of the second twin. Decreases in perinatal and infant mortality were observed only when the first twin was delivered at 22 to 23 weeks and when the delivery interval was /=4 weeks or when the first twin was delivered at 24 to 28 weeks (regardless of delivery interval), there was no benefit in perinatal or infant mortality. Delayed delivery of >/=4 weeks was associated with increased risk of small-for-gestational-age birth in the second twin, regardless of gestational age at delivery of the first. CONCLUSION: When a first twin was delivered at 22 to 23 weeks, delayed delivery of the second twin was associated with reduced perinatal and infant mortality of the second twin if the interval was less than 3 weeks. Delayed delivery of the second twin when the first was delivered at >/=24 weeks had no benefit on mortality.     

双胎妊娠阴道分娩

双胎妊娠孕妇的合并症和新生儿发病率均较高,其分娩方式的选择虽然目前仍有争议,但在临床处理上仍需结合双胎类型、胎方位、胎儿体重、母体情况和接生者经验等进行综合考虑。阴道分娩过程中应加强监护,尤其注意第二产程的管理,以降低双胎第二胎儿发生宫内窘迫和新生儿窒息的风险。     

Cytokine mapping of sera from women with preeclampsia and normal pregnancies

INTRODUCTION: Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N=15) and compare with levels in sera from normal pregnant women (N=15). MATERIAL AND METHODS: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-alpha, IFN-gamma, TNF-alpha, GM-CSF, MIP-lalpha, MIP-1beta, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA). RESULTS: Preeclamptic women had significantly increased levels of circulating IL-6 (p=0.002), IL-8 (p=0.003) and soluble IL-4R (p=0.037), compared to women with normal pregnancies. CONCLUSION: This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.     

Selective fetocide reverses preeclampsia in discordant twins

OBJECTIVE: Preeclampsia occurs in some twin gestations in association with a placental disorder of one but not both fetuses, thereby placing both at risk. We investigated a novel method of treating preeclampsia in these pregnancies. STUDY DESIGN: Three patients with second trimester preeclampsia linked to a lethal condition in one twin were treated with selective fetocide in an effort to reverse preeclampsia. Two patients presented with twins discordant for severe fetal growth restriction, and 1 patient presented with Ballantyne syndrome and twins discordant for fetal hydrops. RESULTS: Preeclampsia resolved in all 3 patients, allowing continuation of the pregnancy for an additional 9 to 23 weeks before delivery of the remaining fetus. Resolution of preeclampsia occurred in a timeframe consistent with placental involution documented in similar clinical circumstances. CONCLUSION: Selective fetocide may be an option for treating preeclampsia in some twin pregnancies, presumably by causing involution of the pathologic placenta. Delivery is not the only cure for preeclampsia.     

Risk for recurrence of preeclampsia and outcome of subsequent pregnancy in women with preeclampsia in their first pregnancy

Objective: To assess subsequent pregnancy outcome and to identify risk factors for recurrence of preeclampsia (PET) in women with PET in their first pregnancy. Methods: A retrospective cohort study of all nulliparous women diagnosed with PET during the years 1996–2008 (PET group, N = 600). Outcome of subsequent pregnancy was compared with a control group of nulliparous women without PET matched by maternal age in a 3:1 ratio (N = 1800). Results: Subsequent pregnancies in the PET group were characterized by a higher rate of preterm delivery at less than 37 and 34 weeks (15.2% vs. 5.7%, p < 0.001 and 3.8% vs. 0.8%, p < 0.001, respectively), placental abruption (1.7% vs. 0.2%, p = 0.004), IUGR (2.8% vs. 0.9%, p = 0.016), and PET (5.9% vs. 0.8%, p < 0.001). Risk factors for PET and adverse outcome in the subsequent pregnancy included: PET complicated by placental abruption in the index pregnancy (OR = 10.8, 95%-CI = 1.8–34.6), PET requiring delivery prior to 34 weeks in the index pregnancy (OR = 6.5, 95%-CI = 1.6–22.5), chronic hypertension (OR = 5.3, 95%-CI = 1.9–12.7), and maternal age > 35 (OR = 4.3, 95%-CI = 1.2–20.5). Conclusion: PET in the first pregnancy is independently associated with an increased risk for adverse pregnancy outcome and recurrence of PET in the subsequent pregnancy in a manner that is related to the severity of PET in the first pregnancy.     

发育不同一性双胎妊娠的并发症临床分析

目的 探讨发育不同一性双胎妊娠的并发症特点及双胎发育不同一性发生的相关因素。方法 以双胎胎儿体重差＞20％为发育不同一性双胎妊娠诊断标准,回顾性分析96例发育不同一性双胎(观察组)和349例发育一致双胎(对照组)的临床资料,比较两组在妊娠并发症、合并症、分娩情况和围产儿预后等方面的差异。结果 (1)观察组晚期流产、羊水过多、双胎输血综合征和胎盘早剥的发生率分别为13．5％(13／96)、22．9％(22／96)、9．4％(9／96)和5．2％(5／96),明显高于对照组的4．3％(15／349)、10．0％(35／349)、1．4％(5／349)和1．1％(4／349),两组比较,差异有统计学意义(P＜0．05)。(2)观察组围产儿死亡和胎儿畸形的发生率分别为22．9％(44／192)和5．2％(10／192),明显高于对照组的4．4％(31／698)和1．3％(9／698),两组比较,差异有统计学意义(P＜0．01)。(3)观察组胎儿体重轻者较体重重者的围产儿死亡率高,分别为30．2％(29／96)和15．6％(15／96),两组比较,差异有统计学意义(P＜0．05);体重差分别为≤20％、20％～30％和≥30％时,围产儿死亡率分别为4．4％、11．0％和41．9％;胎儿畸形发生率分别为1．3％、5．1％和5．4％,3者间分别比较,差异有统计学意义(P＜ 0．05)。结论发育不同一性双胎妊娠主要的并发症为晚期流产、羊水过多、双胎输血综合征、胎盘早剥、围产儿死亡和胎儿畸形。双胎中体重轻者围产儿死亡率高,且随体重差别增大围产儿死亡和胎儿畸形发生率升高。     

Amniocentesis in twin pregnancies

Objective  To describe the experiences in diagnostic amniocentesis in twin pregnancies. Methods  The computerized database and medical records of pregnant women attending Maternal Fetal Medicine Unit of the hospital for diagnostic amniocentesis at 16–20 weeks gestation between January 1992 and December 2006 were retrospectively reviewed. Results  During 15 years of experience, 7,890 amniocenteses at 16–20 weeks gestation were performed for prenatal diagnosis, including 174 procedures in 87 twin pregnancies. The mean gestational age at the time of amniocentesis was 17.13 ± 3.35 weeks. Preterm birth rate defined as the delivery before 36 gestational weeks was 36.24%. The total fetal loss rate was 5.17%, however, the procedure related fetal loss within 2 weeks after the procedure was 1.15%. Conclusion  Based on our limited data and previous studies, we can counsel patients undergoing twin amniocentesis at mid-trimester that the fetal loss rate may be slightly higher than that of singleton amniocentesis.     

Screening and prevention of preterm birth in twin pregnancies

Preterm birth (PTB) is commonest cause of perinatal mortality and morbidity in multiple pregnancies with significant long-term sequelae. The etiology of PTB is multifactorial. Universal screening by a transvaginal assessment of cervical length (CL) at midtrimester scan is recommended for all women with twin pregnancies. Women with CL ≤ 25 mm should be offered prophylactic vaginal progesterone to mitigate the risk of PTB. Other modalities like home uterine activity monitoring, digital cervical examination, fetal fibronectin (FFN) assessment, and screening for infections are not recommended. History-indicated cerclage is not advised in unselected twin pregnancies, but a combination of physical examination-indicated cerclage, tocolytics, and antibiotics may be considered in twin pregnancies with a dilated cervix prior to 24 weeks’ gestation. Routine use of cervical pessary is not advised and should be limited to research settings. Neither transvaginal CL nor FFN assessment is supported by evidence to predict the risk of PTB in symptomatic women with multiple pregnancies. More research is warranted to develop and validate algorithms to predict PTB to provide individualized care to these high-risk pregnancies.     

多胎妊娠孕中期减至双胎与初始双胎妊娠的妊娠结局比较

目的 探讨多胎妊娠孕妇孕中期行减胎术减至双胎后与初始双胎孕妇的妊娠结局比较.方法 选择2007年8月至2010年9月在山东大学附属省立医院妇产科门诊或住院、多胎妊娠孕妇567例,其中双胎妊娠孕妇478例为非减胎组;妊娠12周以后在本院实施孕中期减胎术(在超声引导下经腹的胎心内氯化钾注射法),由初始多胎减至双胎的孕妇89例为减胎组.减胎组孕妇中,初始三胎70例,初始四胎13例,初始五胎及以上6例.观察两组孕妇年龄、分娩孕周、妊娠并发症、新生儿出生体质量及新生儿结局.结果 (1)两组孕妇年龄及分娩孕周:非减胎组与减胎组孕妇平均年龄分别为(29.7±4.5)和(29.9±5.0)岁,两组比较,差异无统计学意义(P=0.755).非减胎组与减胎组孕妇平均分娩孕周分别为(35.3±3.9)和(34.4±6.3)周,两组比较,差异有统计学意义(P＜0.01).分娩孕周＜28周者(即流产)在非减胎组发生率为6.3％( 30/478),在减胎组为15.7％( 14/89),两组比较,差异有统计学意义(P=0.002).(2)两组妊娠并发症:子痫前期发生率在非减胎组及减胎组分别为8.2％ (39/478)和12.4％(11/89),两组比较,差异无统计学意义(P=0.199);妊娠期糖尿病发生率在非减胎组及减胎组分别为1.7％(8/478)和3.4％( 3/89),两组比较,差异无统计学意义(P =0.287).(3)两组新生儿情况:①非减胎组两个胎儿出生体质量差值＞400g的发生率为28.9％(138/478),减胎组为27.0％ (24/89),两组比较,差异无统计学意义(P=0.715).非减胎组两个胎儿出生体质量差值＞100g的发生率为75.1％(359/478),减胎组为75.3％(67/89),两组比较,差异无统计学意义(P =0.972).②非减胎组新生儿平均出生体质量为(2700 ±468)g,明显高于减胎组的(2352 ±602)g,两组比较,差异有统计学意义(P＜0.01).非减胎组＞孕36周+1 分娩的新生儿平均出生体质量为(2809 ±424)g,减胎组为(2707±506)g,两组比较,差异有统计学意义(P＜0.01).③减胎组及非减胎组＞28孕周分娩新生儿的死亡率分别为1.3％( 1/78)和2.2％( 10/448);减胎组及非减胎组新生儿患病率分别为3.8％ (3/78)和4.0％ (18/448),两组＞28孕周分娩的新生儿死亡率及患病率分别比较,差异均无统计学意义(P =0.588、0.943).结论 多胎妊娠减胎至双胎的妊娠结局较初始双胎者差,其流产率较高;多胎妊娠减胎后分娩孕周受初始胎儿数的影响,新生儿出生体重质量低于初始双胎.     

Prediction and Prevention of Preeclampsia

Preeclampsia increases maternal and perinatal morbidity and mortality rates. Much research has been done to identify unique screening tests that would predict the risk of developing preeclampsia before the classic symptoms appear. The possible use of a screening test with high predictive accuracy in patients with high-risk or low-risk of preeclampsia remains to be investigated. At present, the search for additional tests continues. There is growing interest in the use of combinations of tests. Effective primary prevention is not possible because the causes are still unknown, but to identify and to modify susceptible risk factors might decrease the frequency of preeclampsia. A community guideline improves the screening and early detection of preeclampsia, and uniforms the referral thresholds and assessment procedures. Secondary prevention with calcium supplementation and aspirin administration during pregnancy are beneficial in low calcium intake women and in the patient at a very high risk of developing severe early onset disease. Lifestyle choices, dietary nutritional measures (antioxidant as vitamin C, vitamin E, lycopene, selenium, zinc, magnesium and the mitochondrial antioxidants nicotine, coenzyme Q₁₀ and melatonin; and other dietary nutritional measures as low dietary salt, omega 3 fatty acids, folic acid, garlic, nutritional advice, protein and energy supplementation, isocaloric balanced protein and protein and energy restriction for obese women) and others drugs; have not shown benefits or there is insufficient evidence to recommend clinical use. Proper antenatal care and timed delivery are of utmost importance in tertiary prevention.     

Mode of delivery and neonatal outcome in uncomplicated monochorionic twin pregnancies

Objective: The association between of mode of delivery and perinatal morbidity in monochorionic (MC) twins is not clear. Thus there is no agreement regarding the optimal mode of delivery of MC twins. The aim of this study is to determine the impact of the mode of delivery on neonatal outcome of uncomplicated MC twins in a tertiary center with a strict policy of delivering MC twins by 37 weeks’ gestation. Methods: Retrospective analysis of all uncomplicated MC twin deliveries at a tertiary referral hospital during a 5-year period. Complicated MC pregnancies (fetal death, selective reduction, twin to twin transfusion syndrome, fetal growth restriction of one or both twins or major fetal anomalies) were excluded. Induction of labor or planned caesarean sections of uncomplicated MC pregnancies was conducted between 35 and 37 weeks of gestation. Neonatal outcomes of MC twins were compared according to the mode of delivery. Moreover, mode of delivery was compared with a control group of 1934 dichorionic (DC) twin pregnancies delivered during the same period. Results: The rate of Caesarean section was 63.4% in uncomplicated MC/DA twins pregnancies and this was similar to our rate in DC twins (61%, p = 0.65). Multivariate analysis revealed that adverse neonatal outcome was significantly associated with gestational age at delivery, neonatal birth weight discordance and male gender but not with the intended or actual mode of delivery. Conclusion: Delivering MC twin pregnancies by 37 weeks’ gestation is associated with similar rate of vaginal deliveries compared with DC twin pregnancies. The neonatal outcome was not affected by the mode of delivery, and therefore vaginal delivery seems safe in MC twins.     

单、双胎妊娠并发子痫前期不良妊娠结局的荟萃分析

目的探讨单、双胎妊娠并发子痫前期的孕妇与围产儿不良结局发病率差异。 方法检索PubMed、Web of Science、中国生物医学文献数据库、中国学术文献总库、万方和维普中文数据库中2000年1月至2017年12月国内外发表的关于单、双胎妊娠并发子痫前期妊娠结局的研究。采用RevMan 5.3与Stata 12.0软件对资料进行荟萃分析,采用OR值及相应的95%CI评价不良结局与双胎妊娠并发子痫前期的相关性。 结果纳入10篇文献,共692例双胎妊娠合并子痫前期,3101例单胎妊娠合并子痫前期。双胎妊娠合并子痫前期组发病率高于单胎妊娠合并子痫前期：胎盘早剥OR＝2.16,95%CI为1.40～3.36;产后出血OR＝2.90, 95%CI为2.03～4.15;心功能衰竭OR＝3.73, 95%CI为2.10～6.63 ;肺水肿OR＝2.76, 95%CI为1.04～7.27;剖宫产OR＝2.27, 95%CI为1.58～3.26;胎膜早破OR＝2.99, 95%CI为1.64～5.47;早产OR＝6.24,95%CI为4.16～9.38,新生儿重症监护病房转入率OR＝2.33, 95%CI为1.66～3.26。 结论双胎妊娠合并子痫前期的不良妊娠结局包括胎盘早剥、产后出血、心功能衰竭、肺水肿、剖宫产、胎膜早破、早产和新生儿重症监护病房转入的发病率比单胎妊娠合并子痫前期高。