Double versus single thrombophilias during pregnancy

Objective: The primary objective of this study was to evaluate whether women with double thrombophilias have a greater risk for obstetric complications as compared with women who have single thrombophilias.

Study design: This is a retrospective cohort study of all patients in a single practice with a clinically significant inherited thrombophilia and treated with anticoagulation between 2005 and 2013. Thrombophilias evaluated include: factor V Leiden, prothrombin G20210A gene mutation, protein S deficiency, protein C deficiency, and antithrombin III deficiency. Double thrombophilia was defined as the presence of two thrombophilias or homozygosity for factor V Leiden or prothrombin Gene Mutation. Demographic and obstetrical outcome data were collected. Data on all patients with double thrombophilias who met inclusion criteria was reported. Data was then compared between the patients with double thrombophilias and single thrombophilias with singleton gestations. The data was analyzed with Pearson’s chi-squared or Student’s t-test as appropriate with p value <.05 used for significance.

Results: Eighteen patients with clinically significant double thrombophilias who met inclusion criteria were identified. Most patients delivered full term (88.9%) and appropriate for gestational age (77.8%) infants. One hundred thirty-two patients with single thrombophilias and 14 patients with double thrombophilias with singleton gestations were then compared. Demographic characteristics were not significantly different between the two groups. There were no significant differences in obstetrical outcomes between patients.

Conclusions: There were no significant differences in obstetrical outcomes for patients with clinically significant double thrombophilias versus single thrombophilias when treated with anticoagulation.     

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.     

妊娠期单纯疱疹病毒感染与不良妊娠结局

单纯疱疹病毒(HSV)能引起生殖器官感染,妊娠合并HSV感染可造成胎儿宫内感染,引发流产、死胎、畸形、胎儿生长受限和新生儿感染等不良妊娠结局。此外,HSV感染还与输卵管妊娠及不孕等密切相关。文章阐述了妊娠合并HSV感染的流行病学、发病机制、临床特征、不良妊娠结局、诊断、预防和治疗的研究概况。     

Maternal asthma: pregnancy course and outcome

Objective: To evaluate the association between maternal asthma and perinatal outcome.

Study design: In this retrospective population-based cohort study, all pregnancies between 1991 and 2014 in a tertiary medical center, were included. Multiple pregnancies and congenital malformations were excluded. Pregnancy course and outcomes were compared between women with and without asthma, and multivariable generalized estimating equations were used to control for confounders.

Results: During the study period, 243,363 deliveries met the inclusion criteria, 1.35% of which (n?=?3283) occurred in women diagnosed with asthma. Multiple perinatal complications were found to be associated with maternal asthma, including hypertensive disorders, preterm delivery, and cesarean delivery. However, no significant differences between the groups were noted in neonatal outcomes, including perinatal mortality rates and low Apgar scores. In the regression model, maternal asthma was noted as an independent risk factor for preterm delivery, hypertensive disorders of pregnancy, and cesarean delivery (aOR?=?1.21, 95%CI 1.1–1.4, p?=?.007; aOR?=?1.35, 95%CI 1.2–1.6, p?p?Conclusions: Maternal asthma is associated with an increased risk for adverse pregnancy outcome. This association remains significant while controlling for variables considered to coexist with maternal asthma. Nevertheless, perinatal outcome is generally favorable.     

Isolated low second-trimester maternal serum beta-human chorionic gonadotropin is not associated with adverse pregnancy outcome

OBJECTIVE: We investigated whether low human chorionic gonadotropin from maternal serum screening is associated with adverse pregnancy outcome. STUDY DESIGN: Women between 15 and 20 completed weeks of gestation who had a maternal serum screen performed from June 1999 to November 2001 were studied. Cases included women with human chorionic gonadotropin values of 0.5 and <2.0 multiples of the median, and estriol values of >0.6 and <2.0 multiples of the median. Control subjects were selected randomly from the population of women with normal values for all three analytes. RESULTS: There were 146 case subjects and 292 control subjects. There was no increased risk in the study group compared with the control subjects for preterm delivery, intrauterine fetal death, low birth weight, abruptio placentae, preeclampsia, or preterm premature rupture of membranes. CONCLUSION: An isolated low human chorionic gonadotropin level from second-trimester maternal serum screening is not associated with adverse pregnancy outcome.     

Screening and management of inherited thrombophilias in the setting of adverse pregnancy outcome

Inherited thrombophilic conditions are associated with adverse pregnancy outcomes, including severe pre-eclampsia, fetal loss, abruptio placentae, and intauterine growth restriction. Although the prevalence of these complications is approximately 8% in the general population, their presence is associated with a significantly increased recurrence risk. Thrombophilic conditions most strongly associated with adverse pregnancy outcome include factor V Leiden, prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin. Other thrombophilic conditions, such as protein Z deficiency, also appear to be associated with an increased risk of pregnancy complications. Antenatal administration of heparin to prevent pregnancy complications has shown promise in small studies, but a randomized, placebo-controlled trial is necessary to determine whether heparin administration is beneficial in preventing adverse pregnancy outcome.     

Inherited thrombophilias and anticoagulation in pregnancy

Thromboprophylaxis, primary or secondary, should be considered in selected pregnant women with inherited thrombophilias; such women may be divided into high-, medium- and low-risk categories on the basis of the specific thrombophilic defect and any personal or family history of venous thromboembolism (VTE). Women at high risk of VTE should receive treatment doses of low-molecular-weight heparin (LMWH) throughout pregnancy and should remain on anticoagulation for 6 weeks postpartum, or, where appropriate, long-term. Women at moderate risk should be treated with prophylactic fixed-dose LMWH throughout pregnancy and for 6 weeks postpartum. Women at low risk should receive prophylactic fixed-dose LMWH for 6 weeks postpartum, and low-dose aspirin LDA should be considered during pregnancy. LWMH offers important advantages over unfractionated heparin (UFH); heparin-induced thrombocytopaenia (HIT) and osteopaenia are rarely seen. For treatment doses of LMWH, dosage adjustment based on anti-Xa levels is usually required as pregnancy progresses. Warfarin should be avoided throughout pregnancy. LMWH, UFH and warfarin are safe for breast-feeding mothers.     

First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome

Purpose: Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome.

Materials and methods: Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery.

Results: Four thousand five hundred and four women were included in the final analysis – 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500?g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0–3.28 for TSH 2.5–4.0 mIU/L and OR 2.33, 95% CI 1.11–4.42 for those with TSH?>?4 4.0 mIU/L).

Conclusions: Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome – low birth weight and placental abruption – although this needs to be further explored.     

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.     

Hypertension during pregnancy in South Australia, part 2: risk factors for adverse maternal and/or perinatal outcome - results of multivariable analysis

OBJECTIVE: To identify factors associated with adverse pregnancy outcomes among women with hypertension during pregnancy. DESIGN: A population-based retrospective multivariable analysis using the South Australian perinatal data collection. METHODS: Perinatal data on 70,386 singleton births in 1998-2001 were used in multivariable analyses on three groups: all women combined, all hypertensive women and women with pregnancy hypertension only, in order to identify independent risk factors for requirement for level II/III care, preterm birth, small for gestational age (SGA) birth and maternal length of stay greater than 7 days. RESULTS: The risks for the four morbidities were all increased among women with hypertension compared with normotensive women. Those with pre-existing hypertension had the lowest risk (with odds ratios (OR) 1.26-2.90). Pregnancy hypertension held the intermediate position (OR 1.52-5.70), while superimposed pre-eclampsia was associated with the highest risk (OR 2.00-8.75). Among women with hypertension, Aboriginality, older maternal age, nulliparity and pre-existing or gestational diabetes increased the risk for level II/III nursery care, preterm birth and prolonged hospital stay. Smokers had shorter stays, which may be related to their decreased risk of having a Caesarean section or operative vaginal delivery. Asian women, Aboriginal women, smokers and unemployed women had an increased risk for having an SGA baby, while women with pre-existing or gestational diabetes had a reduced risk. CONCLUSIONS: Among hypertensive pregnant women, nulliparity, older maternal age, Aboriginality, unemployment and diabetes are independent risk factors for one or more major adverse pregnancy outcomes. Smoking does not always worsen the outcome for hypertensive women except for SGA births.     

Diagnosis and management of tubal pregnancy: effect on fertility outcome

We analysed 188 ectopic pregnancies seen during a 2-year period. They represented 2.2% of the live births that occurred during the same time interval. Overall, 53% of the tubal pregnancies had ruptured at the time of examination. Location was ampullary in 51% of the cases, isthmic in 28%, and 10% had aborted. Sixty-nine (38%) patients had an IUD. Diagnostic sensitivity was 58%-93% for pregnancy tests, 79% for culdocentesis, 41% for ultrasound examination, 43% for dilatation and curettage, and 100% for laparoscopy. Salpingectomy was performed in 47% of the cases, salpingotomy in 27%, and tubal resection in 19%. During a follow-up of 116 women (mean 1.5 years, range 0.5-3 years) 49% delivered, 10% had repeat ectopic pregnancy, 10% had abortion, 17% were infertile and 15% practised birth control. Among those who delivered no difference was found between those who underwent salpingectomy and those who underwent conservative surgery.     

Women with endometriosis at first pregnancy have an increased risk of adverse obstetric outcome

Objective: To evaluate pregnancy, delivery and neonatal outcome in singleton primiparous versus multiparous women with/without endometriosis.

Methods: Multicentric, observational and cohort study on a group of Caucasian pregnant women (n?=?2239) interviewed during their hospitalization for delivery in five Italian Gynecologic and Obstetric Units (Siena, Rome, Padua, Varese and Florence).

Results: Primiparous women with endometriosis (n?=?219) showed significantly higher risk of small for gestational age fetuses (OR: 2.72, 95% CI 1.46–5.06), gestational diabetes (OR: 2.13, 95% CI 1.32–3.44), preterm premature rupture of membranes (OR: 2.93, 95% CI 1.24–6.87) and preterm birth (OR: 2.24, 95% CI 1.46–3.44), and were hospitalized for a longer period of time (p?n?=?1331). Multiparous women with endometriosis (n?=?97) delivered significantly more often small for gestational age fetuses (OR: 2.93, 95% CI 1.28–6.67) than control group (n?=?592). Newborns of primiparous women with endometriosis needed more frequently intensive care (p?=?0.05) and were hospitalized for a longer period of time (p?Conclusions: Women with endometriosis at first pregnancy have an increased risk of impaired obstetric outcome, while a reduced number of complications occur in the successive gestation. Therefore, it is worthy for obstetricians to increase the surveillance in nulliparous women with endometriosis during pregnancy.