子痫前期患者胎盘早剥发病危险因素分析

目的 探讨子痫前期患者胎盘早剥发病的危险因素.方法 对1994年1月至2008年12月的15年间,在北京大学第三医院住院并分娩的219例患者的临床资料进行回顾性分析,根据病情分为3组:子痫前期早剥组,52例,为重度子痫前期发生胎盘早剥的患者;子痫前期组,130例,为重度子痫前期未发生胎盘早剥的患者;原因不明早剥组,37例,为非子痫前期发生胎盘早剥的患者.选择同期无并发症的正常分娩产妇178例为对照组(按1∶2病例对照研究方法选择).采用单因素及多因素回归分析方法,分析子痫前期患者胎盘早剥的发病危险因素.结果 (1)与对照组比较,单因素分析结果显示,孕次、产次、子痫前期病史、中晚期妊娠丢失史、自身免疫性疾病史、慢性高血压病史、此次孕期无规律产前检查、胎儿生长受限(FGR)及脐动脉收缩期最大血流速度(S)与舒张末期血流速度(D)的比值(S/D)异常是子痫前期患者胎盘早剥发病的危险因素;多因素回归分析显示,孕期无规律产前检查(OR=45.348,95%CI为17.096～120.288,P=0.000)、FGR(OR=27.087,95%CI为5.585～131.363,P=0.000)及中晚期妊娠丢失史(OR=16.068,95% CI为1.698～152.029,P=0.015)是子痫前期患者胎盘早剥发病的独立危险因素.(2)与子痫前期组比较,子痫前期病史(OR=3.715,95% CI为1.096～12.596,P=0.035)及孕期无规律产前检查(OR=2.509,95%CI为1.173～5.370,P=0.018)是子痫前期患者胎盘早剥发病的独立危险因素.结论 孕期无规律产前检查、子痫前期病史、中晚期妊娠丢失史及FGR是影响子痫前期患者胎盘早剥发病的危险因素.     

Thrombophilia and women's health: An overview

Thrombophilia, whether inherited or acquired, is one of the hot topics in women's health. Several factors, some of which are specific to the female patient, enhance thrombus formation in the presence of thrombophilia and include oral contraception, hormone replacement therapy, pregnancy, and puerperium. Thrombotic events are not only restricted to venous thromboembolism but also are believed to cause repeated embryonic loss, fetal loss, placental abruption, intrauterine growth restriction, and severe pre-eclampsia. It seems that some thrombophilias, and a combination of thrombophilic factors, carry a greater risk than others for a given adverse outcome. The addition of LMWH to the armamentarium was associated with conceptual change in the practice of anticoagulation. Care should be exercised in the interpretation of various risks and the potential of anticoagulation as a remedy to reduce that risk.     

Thrombophilia and pregnancy complications

OBJECTIVE: This systematic review examines the strength of the association between thrombophilia and recurrent pregnancy loss and other serious obstetric complications.Study design Electronic databases and manual bibliography searches were used to identify studies evaluating the association between thrombophilia and pregnancy loss, preeclampsia, fetal growth retardation, and placental abruption. RESULTS: Thrombophilic disorders are associated with an increased risk of fetal loss in the majority of case control and cohort studies. The risk is increased throughout pregnancy, but may be higher in the second and third trimester. The common pathologic finding of placental infarction suggests unexplained fetal loss may result from uteroplacental insufficiency and thrombosis. Thrombophilic disorders are not consistently associated with preeclampsia, fetal growth retardation, or placental abruption. Preliminary data suggest prophylactic anticoagulation may improve outcome in thrombophilic women with unexplained recurrent fetal loss. CONCLUSION: Women with thrombophilia have an increased risk of pregnancy loss and possibly other serious obstetric complications, although definition of the magnitude of risk will require prospective longitudinal studies. Preliminary data suggesting prophylactic anticoagulation may improve gestational outcome provide a rationale for prospective randomized trials in thrombophilic women with unexplained recurrent fetal loss.     

Thrombophilia and adverse pregnancy outcome

PURPOSE OF REVIEW: Recent case-control studies and metaanalyses have attempted to quantify the risks associated with individual thrombophilic defects and adverse clinical events in pregnancy, including fetal loss, preeclampsia, placental abruption and intrauterine growth restriction. This review has examined the evidence. RECENT FINDINGS: The literature is in general agreement that thrombophilia increases the risk of venous thromboembolism and adverse pregnancy outcomes, including pregnancy loss, preeclampsia, placental abruption and intrauterine growth restriction in pregnancy. However, the size of the estimated risks varies between individual studies due to heterogeneity in study design. Low-molecular-weight heparin has been shown to be the superior choice, on the grounds of safety and effectiveness, in preventing venous thromboembolism and improving pregnancy loss. Large-scale, randomized controlled studies are required, however, to confirm these findings. Although selective thrombophilia screening based on prior venous thromboembolism history has been shown to be marginally more cost-effective than universal screening in pregnancy, the overall clinical and economic benefit of universal and selective screening is unsupported. SUMMARY: Despite the growing evidence in the literature, there are still gaps in our knowledge of thrombophilia and pregnancy. In particular, accurate estimates are required of the risks of venous thromboembolism and adverse pregnancy outcomes associated with some thrombophilias and the relative clinical and cost-effectiveness of different anticoagulation therapies in the prevention of venous thromboembolism and pregnancy loss. More large-scale studies are required to better inform clinicians and help determine optimum management and prevention strategies of thrombophilia and associated adverse clinical events in pregnancy.     

Incidence,obstetric risk factors and pregnancy outcome of preterm placental abruption: a retrospective analysis

Objective: To determine obstetric risk factors for the occurrence of preterm placental abruption and to investigate its subsequent perinatal outcome. Study design: A retrospective comparison of all singleton preterm deliveries complicated with placental abruption, between the years 1990-1998, to all singleton preterm deliveries without placental abruption, in the Soroka University Medical Center. Results: Placental abruption complicated 300 (5.1%) of all preterm deliveries (n = 5934). A back-step multivariable analysis found the following factors to be independently correlated with the occurrence of preterm placental abruption: grandmultiparity (more than five deliveries), early gestational age, severe pregnancy-induced hypertension, previous second-trimester bleeding and non-vertex presentation. These pregnancies had a significantly lower rate of preterm premature rupture of membranes than preterm pregnancies without placental abruption. Pregnancies complicated with preterm placental abruption had significantly higher rates of cord prolapse, non-reassuring fetal heart rate patterns, congenital malformations, Cesarean deliveries, perinatal mortality, Apgar scores lower than 7 at 5 min, postpartum anemia and delayed discharge from the hospital than did preterm deliveries without placental abruption. In order to assess whether the increased risk for perinatal mortality was due to the placental abruption, or due to its significant association with other risk factors, a multivariable analysis was constructed with perinatal mortality as the outcome variable. Placental abruption (OR 3.0, 95% CI 2.1-4.1) as well as cord prolapse, previous perinatal death, low birth weight and congenital malformations were found to be independent risk factors for perinatal mortality. Conclusion: Preterm placental abruption is an unpredictable severe complication associated with significant perinatal morbidity and mortality. Factors found to be independently associated with placental abruption were grandmultiparity, severe pregnancy-induced hypertension, malpresentation, earlier gestational age and a history of second-trimester vaginal bleeding.     

Factor V Leiden mutation: the most commonly inherited risk factor for venous thromboembolism

Factor V Leiden mutation is a common genetic risk factor for venous thrombosis. It has been documented in up to 65% of patients with unexplained venous thromboembolism. This genetic mutation is now known to be the most common inherited cause of activated protein C (APC) resistance. Recently, FV Leiden mutation has been associated with adverse pregnancy outcomes (including recurrent fetal loss, severe preeclampsia, placental abruption, intrauterine growth restriction and stillbirth), in addition to venous thromboembolic disorders. In this article, we discuss the genetic basis, diagnosis and clinical significance of FV Leiden mutation. Awareness of the clinical manifestations associated with FV Leiden mutation should ensure screening of appropriate populations and prophylaxis against thromboembolic disease when indicated.     

Risk factors for placental abruption in an Asian population

The objective of this study was to identify risk factors for placental abruption in an Asian population. The authors conducted a retrospective review of 37 245 Taiwanese women who delivered between July 1990 and December 2003. Pregnancies complicated by placenta previa, multiple gestation, and fetal anomalies were excluded. Multivariable logistic regression was used to adjust for potentially confounding variables and to identify independent risk factors for placental abruption. Three hundred thirty-two women had placental abruption (9 per 1000 singleton deliveries). Women who smoked during pregnancy (adjusted odds ratio [OR] = 8.4; 95% confidence interval [CI] = 3.0-23.9), had gestational hypertensive diseases (adjusted OR = 4.9; 95% CI = 3.3-7.3), pregnancies complicated by oligohydramnios (adjusted OR = 4.2; 95% CI = 2.7-6.7), polyhydramnios (adjusted OR = 3.3; 95% CI = 1.4-7.7), preterm premature rupture of membranes (adjusted OR = 1.9; 95% CI = 1.1-3.1), entanglement of umbilical cord (adjusted OR = 1.6; 95% CI = 1.2-2.1), were of or more than 35 years of age (adjusted OR = 1.5; 95% CI = 1.1-2.0), and had a low prepregnancy body mass index (adjusted OR = 1.3; 95% CI = 1.0-1.6) were at increased risk for placental abruption. Some risk factors for placental abruption among Taiwanese women are the same as those of other ethnic groups, whereas some of the risk factors are different.     

Placement of a vena cava filter in term pregnancy: case report and review of the literature

During pregnancy there are hemostatic changes that may result in a hypercoagulable state producing thrombotic consequences. This condition may be aggravated in women who are carriers of congenital thrombophilic factors. These factors may increase obstetric complications such as miscarriages, fetal growth restriction, placental abruption and preeclampsia. Trombophilic factors may also cause venous thromboembolism, which is the leading cause of maternal morbidity and mortality. We report a case of a 22-year-old woman with factor V Leiden mutation, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter.     

Prepregnancy risk factors for placental abruption

BACKGROUND: To define the prepregnancy risk factors for placental abruption. METHODS: One hundred and ninety-eight women with placental abruption and 396 control women without placental abruption were retrospectively identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Relevant historical and clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. RESULTS: The overall incidence of placental abruption was 0.42%. Placental abruption recurred in 8.8% of the cases. The independent risk factors were smoking (OR 1.7; 95% CI 1.1, 2.7), uterine malformation (OR 8.1; 1.7, 40), previous cesarean section (OR 1.7; 1.1, 2.8), and history of placental abruption (OR 4.5; 1.1, 18). CONCLUSIONS: Although univariate analysis identified many risk factors, only smoking, uterine malformation, previous cesarean section, and history of placental abruption remained significant after multivariate analysis, increasing the risk of placental abruption in subsequent pregnancy. It may be possible to approximate the risk for placental abruption based on these simple prepregnancy risk factors.     

Risk of Fetal Death Associated With Maternal Drug Dependence and Placental Abruption: A Population-Based Study

ObjectiveSubstance use in pregnancy is associated with placental abruption, but the risk of fetal death independent of abruption remains undetermined. Our objective was to examine the effect of maternal drug dependence on placental abruption and on fetal death in association with abruption and independent of it.MethodsTo examine placental abruption and fetal death, we performed a retrospective population-based study of 1 854 463 consecutive deliveries of liveborn and stillborn infants occurring between January 1, 1995 and March 31, 2001, using the Canadian Institute for Health Information Discharge Abstract Database.ResultsMaternal drug dependence was associated with a tripling of the risk of placental abruption in singleton pregnancies (adjusted odds ratio [OR] 3.1; 95% confidence intervals [CI] 2.6–3.7), but not in multiple gestations (adjusted OR 0.88; 95% CI 0.12–6.4). Maternal drug dependence was associated with an increased risk of fetal death independent of abruption (adjusted OR 1.6: 95% CI 1.1–2.2) in singleton pregnancies, but not in multiples. Risk of fetal death was increased with placental abruption in both singleton and multiple gestations, even after controlling for drug dependence adjusted OR 11.4 in singleton pregnancy; 95% CI 10.6–12.2, and 3.4 in multiple pregnancy; 95% CI 2.4–4.9).ConclusionMaternal drug use is associated with an increased risk of intrauterine fetal death independent of placental abruption. In singleton pregnancies, maternal drug dependence is associated with an increased risk of placental abruption.     

血栓性疾病史女性孕前系统管理

既往血栓性疾病史是妊娠女性发生静脉栓塞的首要高危因素,其造成的肺栓塞是危及孕妇生命的主要原因,同时血栓性疾病史孕妇也是子痫前期、死胎、胎盘早剥等不良妊娠并发症的高危人群。对这些人群进行系统孕前管理是减少或杜绝此类恶性事件发生的关键。     

Clinical presentation and risk factors of placental abruption

BACKGROUND: To study the risk factors of placental abruption during the index pregnancy. METHODS: One hundred and ninety-eight women with placental abruption and 396 control women were identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. The clinical manifestations of placental abruption were also studied. RESULTS: The overall incidence of placental abruption was 0.42%. The independent risk factors were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), pre-eclampsia (2.7; 1.3, 5.6), and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%), and fetal heart rate abnormalities (69%) were the most common manifestations. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% had preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). Retroplacental blood clot was seen by ultrasound in 15% of the cases. CONCLUSIONS: Maternal alcohol consumption and smoking, and smoking by the partner turned out to be independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption.     

Obstetric history and the risk of placenta previa

OBJECTIVE: To evaluate secular trends in the occurrence of placenta previa and whether placenta previa is associated with the outcome of previous pregnancies, cesarean section, and sociodemographic factors. DESIGN: A cohort study based on the Medical Birth Registry of Norway. Placenta previa in the second pregnancy was investigated for associations with outcomes in the first pregnancy and sociodemographic factors. RESULTS: In birth orders 1 and 2 the occurrence of placenta previa was 1.2 and 2.2 per 1,000, respectively, with no secular trend. The occurrence increased with maternal age and was lowest in women aged 20-29 years. The recurrence rate was 23 per 1,000 (adjusted odds ratio (OR) of recurrence=9.7). In women with prior delivery at < or =25 gestational weeks the risk of placenta previa was 6.7 per 1,000 (adjusted OR=3.0). In women with prior placental abruption the risk was 5.8 per 1,000 (OR=2.6). In women with prior perinatal death the risk was 4.4 per 1,000 (adjusted OR= 1.8). No independent relationship emerged with socio-economic factors, previous birthweight, and a history of pregnancy induced hypertension. Cesarean section was associated with subsequent development of placenta previa (adjusted OR= 1.3). CONCLUSIONS: We found no secular trends in the occurrence of placenta previa. Placenta previa is associated with previously described risk factors for placental abruption. The increased risk of placenta previa subsequent to placental abruption supports the theory of a shared etiologic factor. However, placenta previa and placental abruption do not share a common etiology in relation to a history of pregnancy induced hypertension, fetal growth retardation, and socio-economic factors.     

Risk factors for placental abruption in a socio-economically disadvantaged region.

OBJECTIVE: This study was undertaken in order to determine the risk factors for pregnancies complicated by placental abruption in a socio-economically disadvantaged region in metropolitan Adelaide. METHODS: This was a retrospective case-control study including all singleton pregnancies resulting in placental abruption between 2001 and 2005. RESULTS: The overall incidence of placental abruption was 1.0%; the overall perinatal mortality among the births with abruption was 13%. Univariate analyses showed the following significant risk factors for placental abruption: preterm pre-labor rupture of the membranes (PRE-PROM; odds ratio (OR) 4.79, 95% confidence interval (CI) 1.52-15.08), non-compliance with antenatal care (OR 2.93, 95% CI 1.06-8.90), severe intrauterine growth restriction (IUGR), and elevated homocysteine levels (OR 45.55, 95% CI 7.05-458.93). Severe IUGR was significantly more common in the abruption group compared with the control group (p = 0.032). In the multivariate analysis, PRE-PROM remained a significant independent risk factor for placental abruption. Marijuana use, domestic violence, and mental health problems were more common (borderline significance) in the abruption group. Smoking and preeclampsia were not found to be associated with placental abruption in this study. CONCLUSIONS: In this high-risk population, PRE-PROM and elevated homocysteine levels appear to represent the major risk factors for placental abruption.     

Frequency of selected thrombophilias in women with placental abruption

OBJECTIVE: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. METHODS: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20,175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. RESULTS: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). CONCLUSIONS: We found that factor V Leiden is a significant risk factor for placental abruption.     

Abruptio placentae in the setting of an atypical presentation of acute appendicitis: a case report

BACKGROUND: Causes of placental abruption include traumatic events, cocaine use, hypertension, cigarette smoking and advanced maternal age. Recent studies also implicate inflammatory precursors, such as preterm premature rupture of membranes and chorioamnionitis. Clear precipitating events are often not identified, and precise etiologic determinants are still being determined. CASE: A 25-year-old woman, grayida 4, para 2012, presented with acute onset of severe abdominal pain; frequent, low-amplitude contractions; and a nonreassuring fetal heart tracing. While performing an urgent cesarean section for acute placental abruption, a ruptured appendicitis was identified. CONCLUSION: This case suggests that appendicitis in the third trimester may be a risk factor for placental abruption.     

The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus

OBJECTIVE: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. METHODS: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. RESULTS: One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). CONCLUSION: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated. LEVEL OF EVIDENCE: II-2.     

Two successful pregnancies following eight miscarriages in a patient with antithrombin deficiency

Inherited thrombophilias are associated with an increased risk of maternal thromboembolism and certain adverse pregnancy outcomes, including second- and third-trimester fetal loss, placental abruption, severe intrauterine growth restriction, and early-onset, severe preeclampsia. Pregnant patients with severe thrombophilias, especially antithrombinopathies are at very high risk for both thromboembolism and adverse pregnancy outcomes. A case of a patient with antithrombin deficiency is reported, who had two successful pregnancies after eight miscarriages. Our case shows that a combined treatment with antithrombin substitution and a prophylactic, body-weight-adjusted dose of low-molecular-weight heparin may be successful in preventing pregnancy loss and thromboembolism in antithrombin deficiency during pregnancy, although other complications, such as preeclampsia and intrauterine growth restriction cannot always be prevented.     

Doppler blood flow changes and placental morphology in pregnancies with third trimester hemorrhage.

Combined real-time ultrasound and pulsed Doppler ultrasound examinations were performed in 67 patients with third trimester hemorrhage and other symptoms related to placental abruption, starting from the onset of symptoms to delivery. In 52 of the cases, placental morphology was investigated by light microscopy. Thirteen patients were ultimately given the diagnosis abruptio placentae. None of the morphological placental changes considered had any statistical relationship to placental abruption. Patients with placental centrocotyledon hemorrhages and infarction more often had abnormal umbilical artery flow velocity waveforms at the onset of symptoms, and more frequent abnormal arcuate artery flow velocity waveforms were found among those with placental infarction alone. Abnormal flow velocity waveforms in the umbilical and arcuate arteries were associated with placental abruption, both at the onset of symptoms and at the final examination before delivery. The results indicate an increased risk for placental abruption if the arcuate and/or umbilical artery flow velocity waveforms are abnormal in patients with third trimester hemorrhage.     

Reproductive risk factors,Doppler findings,and outcome of affected births in placental abruption: a population-based analysis

Placental abruption complicates about 1% of all singleton pregnancies and the aim of this study is to assess the reproductive maternal risk factors associated with placental abruption, and the outcome of affected births. We analyze 170 women with singleton pregnancies complicated by placental abruption who gave birth at Kuopio University Hospital from March 1989 to December 1999. The general obstetric population ( n = 22,905) was selected as the reference group and logistic regression analysis was used to identify independent reproductive risk factors. Furthermore, Doppler ultrasonographic results and pregnancy outcome measures in the two groups were also recorded. The incidence of placental abruption was 0.57% in the referral area. Preeclampsia, grand multiparity, velamentous umbilical cord insertion, cigarette smoking, prior fetal demise, advanced maternal age (>35 years), and previous miscarriage were independent risk factors of placental abruption, with adjusted relative risks of 4.39, 3.60, 2.53, 2.46, 2.02, 1.62, and 1.55, respectively. Most cases of placental abruption occur before the onset of labor in low-risk pregnancies and are not predictable with regard to maternal reproductive risk factors. Current antepartum methods of detecting uteroplacental problems, including Doppler ultrasonography, are not effective in prenatal prediction of placental abruption. The outcome of affected births is still poor.