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.     

Acquired and inherited thrombophilia disorders in pregnancy

Thromboembolism is the leading cause of antepartum and postpartum maternal mortality. The presence of antiphospholipid antibodies is responsible for many pregnancy losses and other morbidities in pregnant women, and is the most prevalent and treatable cause of acquired thrombophilia in pregnancy. There is also evidence that women with thrombophilia are at increased risk not only of pregnancy-related venous thromboembolism but other vascular pregnancy complications. Many studies have examined the association between thrombophilia and pregnancy complications. This article reviews the most up-to-date knowledge of prevalence, pathogenesis, and diagnosis of acquired and inherited thrombophilias and their relationship and association with pregnancy complications.     

Study of the frequency of occurrence of genetic and acquired thrombophilia in infertile women prior IVF

Abstract

This study of infertile women prior in vitro fertilization (IVF) is focused at the genetic and acquired thrombophilia before the IVF program, the identification of the frequency of occurrence of thrombophilia in them, the impact of thrombophilia of the offensive, the course and outcome of pregnancies, to improve the quality of cycles in terms of a pregnancy and childbirth. Forty-five women with infertility were examined. Thirty-two (71%) were identified thrombophilia: genetic thrombophilia in 32 cases (100%), among them a combination of several forms of genetic thrombophilia – 21 (63%) of them, other forms of thrombophilia (genetic and acquired) – in 5 of them (16%). In IVF 23 (72%) women became pregnant. In 87% of pregnancies ended in spontaneous birth, in 13% of cases of preterm birth.     

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.     

Association of thrombophilia and polycystic ovarian syndrome in women with history of recurrent pregnancy loss

Purpose: To evaluate the prevalence of thrombophilic disorders in polycystic ovarian syndrome (PCOS) women with history of recurrent pregnancy loss (RPL). Materials and methods: This study was carried out in 184 women with history of RPL, of which 92 of them were diagnosed with PCOS and 92 patients were without known PCOS. The prevalence of thrombophilic disorders was compared between the two mentioned groups. Results: According to the findings, 70.7% of PCOS women with history of RPL had thrombophilic disorders. The prevalence of protein C deficiency was significantly higher in PCOS group compared to the non-PCOS group (21.7% vs. 10.9%, p = 0.04). There was a trend toward higher prevalence of protein S deficiency in PCOS group compared to the control group, but the difference did not reach statistical significance (23.9% vs. 13%, p = 0.05). The prevalence of other thrombophilic disorders such as antithrombin III deficiency, homocysteine elevation, antiphospholipid antibody and Factor V Leiden was comparable between groups. Conclusion: The prevalence of thrombophilic disorders was more common in PCOS women than the normal group. The protein C deficiency is associated with PCOS in women with history of RPL. There was a trend toward higher prevalence of protein S deficiency in PCOS women, which needs further study.     

Perinatal outcomes and complications of pregnancy in women with immune thrombocytopenic purpura

Objective.?To investigate pregnancy and perinatal outcomes in women with immune thrombocytopenic purpura (ITP).

Methods. A retrospective study comparing all singleton pregnancies of women with and without ITP was conducted. Deliveries occurred between the years 1988 and 2007. Multiple logistic regression models were performed to control for confounders.

Results.?During the study period, 186,602 deliveries were recorded, out of which 104 (0.06%) occurred in patients with ITP. In a multivariable analysis, we found the following conditions to be significantly and independently associated with ITP: hypertensive disorders, diabetes mellitus, and preterm delivery (<34 weeks gestation). Patients with ITP had significantly higher rates of preterm delivery (<34 weeks gestation; 6.7%vs. 2.2%; p < 0.001) and perinatal mortality (4.8%vs. 1.3%; p = 0.011) when compared with patients without ITP. Two multivariable logistic regression models were constructed with perinatal mortality and preterm delivery (<34 weeks gestation) as the outcome variables to control for possible confounders such as congenital malformations, hypertension, diabetes mellitus, and maternal age. In these models, ITP was found to be an independent risk factor for perinatal mortality (OR = 3.77; 95% CI 1.32–10.78, p = 0.013), as well as for preterm delivery before 34 weeks gestation (OR = 3.01; 95% CI 1.39–6.52, p = 0.005).

Conclusion.?ITP is significantly and independently associated with preterm delivery before 34 weeks gestation and with perinatal mortality.     

Management of pregnancy complications in women of advanced maternal age

The average age of women at childbirth in high resource obstetric settings has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (>40 years) should be given low dose aspirin in the presence of an additional risk factor for pre-eclampsia and offered serial ultrasounds for fetal growth and wellbeing. Given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with woman.     

Prevalence of post-traumatic stress disorder in pregnant women with prior pregnancy complications

Objective. To assess the prevalence of post-traumatic stress disorder (PTSD) in pregnant women with prior pregnancy complications.

Methods. Seventy-six pregnant women at a maternal–fetal medicine referral clinic were asked to complete an anonymous questionnaire. Fifty-six women had a prior pregnancy complication (study group), and the remaining 20 had none (comparison group). Subjects were assessed with a questionnaire consisting of a modified patient-rated version of the Clinician Administered PTSD Scale (CAPS). The modified CAPS was used to approximate the prevalence of full or partial PTSD related to a prior pregnancy complication using two scoring rules, the rule-of-3 (original rule) and rule-of-4 (more stringent rule).

Results. The prevalence of full PTSD among women with prior pregnancy complications was 12.5% and 8.9% based on the rule-of-3 and rule-of-4, respectively. For partial PTSD, the prevalence was 28.6% based on the rule-of-3 versus 17.9% based on the rule-of-4. The most common type of complication was miscarriage, accounting for 73.5% of the reported complications. None of the women in the comparison group met criteria for full or partial PTSD.

Conclusions. The prevalence of PTSD in pregnant women with a prior pregnancy-related complication is considerable. These findings provide additional evidence that pregnancy complications can be experienced as traumatic, and as such lead to partial or full PTSD symptoms.     

The risk of maternal and placental complications in pregnant women with asthma: a systematic review and meta-analysis

Abstract

Objective: To investigate if maternal asthma is associated with an increased risk of maternal and placental complications in pregnancy.

Methods: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between January 1975 and March 2012 were considered for inclusion. Forty publications met the inclusion criteria, reporting at least one maternal or placental complication in pregnant women with and without asthma. Relative risk (RR) with 95% confidence intervals (CIs) was calculated.

Results: Maternal asthma was associated with a significantly increased risk of cesarean section (RR?=?1.31, 95%CI?=?[1.22–1.39]), gestational diabetes (RR?=?1.39, 95%CI?=?[1.17–1.66]), hemorrhage (antepartum: RR?=?1.25, 95%CI?=?[1.10–1.42]; postpartum: RR?=?1.29, 95%CI?=?[1.18–1.41]), placenta previa (RR?=?1.23, 95%CI?=?[1.07–1.40]), placental abruption (RR?=?1.29, 95%CI?=?[1.14–1.47]) and premature rupture of membranes (RR?=?1.21, 95%CI?=?1.07–1.37). Moderate to severe asthma significantly increased the risk of cesarean section (RR?=?1.19, 95%CI?=?[1.09–1.31]) and gestational diabetes (RR?=?1.19, 95%CI?=?[1.06–1.33]) compared to mild asthma. Bronchodilator use was associated with a significantly lowered risk of gestational diabetes (RR?=?0.64, 95%CI?=?[0.57–0.72]).

Conclusions: Pregnant women with asthma are at increased risk of maternal and placental complications, and women with moderate/severe asthma may be at particular risk. Further studies are required to elucidate whether adequate control of asthma during pregnancy reduces these risks.     

Uterine prolapse in pregnancy: risk factors,complications and management

Abstract

Presentation of uterine prolapse is a rare event in a pregnant woman, which can be pre-existent or else manifest in the course of pregnancy. Complications resulting from prolapse of the uterus in pregnancy vary from minor cervical infection to spontaneous abortion, and include preterm labor and maternal and fetal mortality as well as acute urinary retention and urinary tract infection. Moreover, affected women may be at particular risk of dystocia during labor that could necessitate emergency intervention for delivery. Recommendations regarding the management of this infrequent but potentially harmful condition are scarce and outdated. This review will examine the causative factors of uterine prolapse and the antepartum, intrapartum and puerperal complications that may arise from this condition as well as therapeutic options available to the obstetrician. While early recognition and appropriate prenatal management of uterine prolapse during pregnancy is imperative, implementation of conservative treatment modalities throughout pregnancy, these applied in accordance with the severity of the uterus prolapse and the patient’s preference, may be sufficient to achieve uneventful pregnancy and normal, spontaneous delivery.     

Late pregnancy complications can affect risk estimates of elective induction of labor

Objective.?Multiple observational studies have emphasized the increased risk of elective induction versus spontaneous labor. We estimated the risks of elective induction before 39 weeks compared to expectant management.

Methods.?Using a single institution's delivery data (1996–2004), we identified women with uncomplicated term gestations who underwent elective induction before 39 weeks (Early Induction Group). A comparison group of women eligible for elective induction before 39 weeks but who were managed expectantly was created by identifying the remaining deliveries ≥39 weeks and excluding women with “established” pregnancy complications such as diabetes or heart disease (Expectant Management Group), but retaining women with complications that may have developed while waiting, e.g. gestational hypertension or abruption.

Results.?Pregnancies in the Early Induction Group were generally not at increased risk for morbidity when compared to the entire Expectant Management Group, in whom 49% developed pregnancy complications or went postdates. These pregnancies had poorer maternal and neonatal outcomes when compared to patients who remained uncomplicated with spontaneous labor onset, thus reducing the overall benefit of expectant management.

Conclusions.?Failure to account for the large proportion of women who develop late pregnancy complications can falsely elevate the estimated risk of elective induction prior to 39 weeks.     

Maternal and perinatal complications in triplet compared with twin pregnancy

Objective: To compare maternal and perinatal complications in triplet and twin pregnancies. Study design: Case-controlled study in the setting of a University Hospital. Each pregnancy of a consecutive series of 40 triplet pregnancies of 20 weeks or more was matched for parity and maternal age with two sets of twins delivered in the same year. Primary end points of the analysis were maternal complications and perinatal outcome. Results: Of the triplets 82% and of the twins 36% were a result of assisted reproduction. Pre-term labor occurred significantly more often in triplet than in twin gestation. Triplets had a significantly lower median birth-weight (1478 vs. 2030 g) and gestational age at delivery (32 vs. 35.5 weeks). The mean neonatal hospital stay was significantly longer in triplets, mainly related to the lower birth-weight, but there was no significant difference between triplets and twins in the incidence of major neonatal complications. Conclusion: This data of the anticipated perinatal outcome in triplet and twin pregnancies may be used to counsel women with a triplet pregnancy considering selective reduction to twins. All methods of assisted reproduction should aim at prevention of multifetal gestation.     

ACE gene in pregnancy complications: Insights into future vascular risk

Objective: A history of placenta-mediated pregnancy complications (PMPCs) increases the risk of cardiovascular disease later in life, possibly related to the persistence of endothelial dysfunction. We performed this study in order to search for a common genetic background shared by women with a history of PMPC and vascular disorders, due to their common pathophysiologic pathway of endothelial dysfunction.

Methods: We analyzed the prevalence of seven polymorphisms in ACE, AGTR1, AGT, and eNOS genes, endothelial-function related, in 290 women with a history of premature cardiovascular events (CVDs), and in 367 women with a history of PMPC (preeclampsia (PE), stillbirth (SB), and small for gestational age (SGA)), compared with 300 healthy women (HW) who delivered after uneventful pregnancy (HW).

Results: ACE D allele frequency was similar between women with history of CVD and PMPC, and significantly higher than that observed in HW [OR (95% CI) 1.91, p = 0.002, and OR (95% CI) 2.18, p < 0.0001, respectively]. In women carrying ACE-240T or eNOS-786C allele, a two-fold increase in SB susceptibility was evidenced (p = 0.004 and p = 0.005, respectively). Women with a history of SB and premature CVD exhibited a significantly higher unfavorable allelic burden ≥ 3 in comparison to that observed in HW (p < 0.0001 and p = 0.002, respectively).

Conclusions: Our findings demonstrate a common genetic background shared by women with a history of vascular disorders and PMPCs; pregnancy may be considered a window to future cardiovascular risk; therefore, “non-classic” genetic biomarkers of endothelial dysfunction might allow one to identify women who could have a greater benefit for an early cardiovascular screening and prevention.     

Predictors of obstetric complications in women with heart disease

Objectives: The objective of this study is to evaluate obstetric outcomes in women with heart disease and determine whether current multidisciplinary management approaches adversely affect the mother, the neonate, or both. Also to compare the accuracy of several risk scores (RS) including the modified World Health Organization classification (mWHO) and CARPREG to predict obstetric and neonatal complications and to study the addition value of Uteroplacental-Doppler flow (UDF) parameters to predict obstetric complications.

Methods: A prospective cohort study examined outcomes in women with heart disease (HD), the majority of whom had corrective surgery and delivered between January 2007 and March 2012.

Results: One hundred and seventy-four patients with 179 pregnancies were included in the study. Obstetric complications, including premature labor, arose in 87 patients (48.6%). Neonatal complications were observed in 11 cases (7%). On multivariate analysis, maternal heart disease was predictive of adverse perinatal events (46 cases, 25.7%) and mode of delivery (Thierry’s spatula) of third- or fourth-degree perineal tears (six cases, 3.2%). mWHO classification predicted obstetric complications (p?=?0.0001) better than the CARPREG study. Impaired UDF (uterine artery pulsatility index-20 weeks and umbilical artery pulsatility index-32 weeks in HD versus healthy women: 20w 1.12 versus 1.34, p?=?0.005; 32w 0.87 versus 1.09, p?=?0.008) was associated with adverse obstetric and offspring outcome in the group of HD pregnant women.

Conclusions: Nearly 50% of pregnancies were associated with an adverse obstetric outcome, particularly IUGR. mWHO was better at predicting obstetric and neonatal complications that CARPREG in all cathegories. Furthermore, compromised UDF combined with mWHO improved the prediction of obstetric and offspring complications in this population.     

Maternal appraisals of risk,coping and prenatal attachment among women hospitalised with pregnancy complications

One goal of pregnancy is the development of maternal emotional attachment to the unborn baby, and this attachment has been shown to be related to later relationships and development. There are many factors which may hinder the development of prenatal attachment, including the presence of complications, hospitalisation, and anxiety. However, women's appraisals of risk may not be congruent with medical assessments of risk. The current study sought to model the relationships between risk (maternal perceptions and medical ratings), coping, psychological well‐being, and maternal–foetal attachment among 87 women hospitalised for pregnancy‐related complications. Analysis indicated that positive appraisal as a coping strategy mediates the relationship between maternal appraisals of risk and maternal–foetal attachment, and that medical ratings of risk were not predictive of maternal–foetal attachment. Awareness of the potential incongruence between patients' and health professionals' perceptions of risk is important within the clinical environment. The potential benefits of promoting positive appraisal in high‐risk pregnancy merit further research.     

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.     

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia.

OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.