Preventing adverse obstetric outcomes in women with genetic thrombophilia

OBJECTIVE: To improve fetomaternal outcomes in women with obstetric complications and inherited causes of thrombophilia. DESIGN: Clinical trial. SETTING: Thrombophilic women with previous unexplained adverse outcomes. PATIENT(S): Twenty-five women with previous severe obstetric complications were treated during and after pregnancy. INTERVENTION(S): Low fixed dose of heparin or aspirin. MAIN OUTCOME MEASURE(S): Fetomaternal outcome. RESULT(S): Low fixed dose of heparin were administered to 24 pregnant women, aspirin to 7. Overall, among 31 treated pregnant women, 28 (90.3%) compared to 4 of 58 (6.9%) in previous pregnancies had a good obstetric outcome. Two fetal losses <14 weeks gestation and a fetal growth restriction were registered. All newborns, except one, were in the tenth centile or above. All babies were discharged in good clinical status. In the treated pregnancies, no thrombosis or pharmacological side effect was recorded. CONCLUSION(S): Heparin prophylaxis at fixed low doses and possibly aspirin could be efficacious in preventing adverse outcomes in women carrying inherited thrombophilia with previous poor obstetric outcomes.     

Antiphospholipid Antibodies in Pregnancy

We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options.     

Obstetric performance in patients with the lupus anticoagulant and/or anticardiolipin antibodies.

Antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies, are associated with recurrent fetal wastage, pregnancy complications, and thromboses. Aggressive medical treatment using aspirin and steroids has been recommended. Fifty-one patients with antiphospholipid antibodies, only four with underlying connective tissue disorders, were followed through 53 pregnancies. Aggressive therapy was used in 33 pregnancies, 90.9% of which resulted in successful obstetric outcomes, a highly statistically significant difference compared with previous pregnancies in the same patients. Most pregnancies among nine patients receiving single-agent therapy (aspirin or steroids alone) and eight patients not treated also had successful outcomes. A 48.6% complication rate was found in association with therapy, particularly gestational diabetes mellitus. There was no statistical correlation between dose or duration of therapy and development of treatment-related complications. Although a subgroup of patients with antiphospholipid antibodies will benefit from aggressive therapy, the high complication rate warrants close observation.     

The corse of pregnancy and delivery in patients with surgicaly corrected tetralogy of Fallot

Twenty-eight pregnancies in 16 patients with surgically corrected tetralogy of Fallot between 1997 and 2002 at the SBALAG "Maichin dom", Sofia, were reviewed. Most of the patients were well and asymptomatic after surgery, excluding one patient who was functional class III. The patients had a total of twenty-one successful pregnancies and deliveries. There were seven abortions (33%) and two small-for-date babies (12%). None of the infants had any cardiac anomalies. The pregnancies were relatively well tolerated and there were no life-threatening cardiac complications. For a patient with some residual abnormalities after surgical correction of tetralogy of Fallot, it is important to reassess the cardiac state before pregnancy and, if once pregnant, to anticipate the possible occurrence of complications during labor. Compared to the general obstetric population, more women in the study group underwent instrumental vaginal delivery and probably best option was elective ventouse or forceps. In conclusion despite potential difficulties and complications associated with corrected tetralogy of Fallot, careful cardiac and obstetric management resulted in good maternal and fetal outcomes.     

Low-Molecular-Weight Heparin for the Prevention of Obstetric Complications in Women with Thrombophilias

Objective. To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications.

Methods. The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy.

Results. Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 ± 5.0 weeks and 1175 ± 590 g, respectively, compared to 37.6 ± 2.3 weeks and 2719 ± 526 g, respectively, in the treated pregnancies (p ≤ 0.001).

Conclusions. This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.     

Inheritance and perinatal consequences of inherited thrombophilia in Greece.

OBJECTIVE: To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women. METHOD: A total of 392 women with spontaneous pregnancy were investigated for Factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations. Adverse pregnancy outcomes were recorded. RESULTS: Thrombophilic genotypes were significantly higher in women with placental abruption. Heterozygocity for Factor V Leiden increased the risk for placental abruption 9.1 times. The MTHFR T677T genotype increased the risk for placental abruption 4.8 times despite folate supplements, and normal serum folate and B(12) levels. Women with inherited thrombophilia and previous obstetric complications were at significant risk for complications in a subsequent pregnancy (P<0.05). CONCLUSION: Women with placental abruption should be screened for thrombophilic factors and plasma homocysteine should be measured. Subgroups of women with inherited thrombophilia and obstetric complications might benefit from prophylactic anticoagulation in subsequent pregnancies.     

Obstetric outcomes of elderly primiparous singleton pregnancies conceived by <Emphasis Type="Italic">in vitro</Emphasis> fertilization compared with those conceived spontaneously

Aim:  To examine the obstetric outcomes of elderly primiparous singleton pregnancies conceived by in vitro fertilization (IVF) compared with those conceived spontaneously.
Methods:  Data were collected from primiparous women aged 35 years and older with a singleton pregnancy conceived by IVF ( n  = 89) or spontaneously ( n  = 849). Data included antenatal data, gestational age at delivery, obstetric complications, such as pregnancy-induced hypertension, gestational diabetes, placental previa and placental abruption, mode of delivery, birth weight, fetal demise and the Apgar score at 1 min.
Results:  The elective Cesarean rate in pregnancies following IVF was significantly higher than that in the control group ( P =  0.014). However, there were no significant differences in obstetric outcomes between the two groups.
Conclusions:  The current results did not support the IVF-related risks of elderly primiparous singleton pregnancies. (Reprod Med Biol 2007; 6: 219–222)     

Hypothyroidism complicating pregnancy

Hypothyroidism rarely complicates pregnancy because most affected women are anovulatory. In this report, we describe 28 complicated pregnancies cared for over a ten-year period at Parkland Memorial Hospital. In the group of 16 pregnancies in 14 overtly hypothyroid women, maternal complications were common and included anemia (31%), preeclampsia (44%), placental abruption (19%), postpartum hemorrhage (19%), and cardiac dysfunction. Perinatal morbidity and mortality were also high mainly because of placental abruption, and reflected frequent low birth weight (31%) and fetal death (12%). In a group of 12 women with subclinical hypothyroidism, these complications were less impressive. We speculate that overt thyroid deficiency is associated with adverse pregnancy outcome related to preeclampsia and placental abruption. Thyroxine replacement probably improves these outcomes even if subclinical hypothyroidism persists.     

Obstetric and perinatal outcomes of pregnancy in patients with repeated implantation failure

ObjectiveDespite the great advance of assisted reproductive technology (ART) in recent decades, many IVF patients failed to achieve a pregnancy even after multiple IVF-ET attempts. These patients are considered to have repeated implantation failure (RIF). While exhausting efforts have been devoted to the improvement of pregnancy rate in RIF patients, it is not clear whether RIF patients have aberrant obstetric or perinatal outcomes after they eventually achieved a pregnancy.Materials and methodsTaking advantage of a relatively large database of IVF-ET cycles at the Chang Gung Memorial Hospital, we compared obstetric and perinatal outcomes of RIF patients who have a successful pregnancy after IVF-ET treatment(s) to those of control IVF-ET patients.ResultsBecause multiple pregnancies are associated with a high risk of obstetric complications, we restricted the analysis to patients who had singleton pregnancies. Analysis of a total of 596 control and 46 RIF cases showed the rates of almost all obstetric and perinatal outcomes investigated are not different between the two groups. However, the rate of placental abruption in the RIF group (4.35%) appeared to be significantly higher than that of controls (0.50%; OR = 8.99). This difference is still statistically significant after adjustment with the age (adjusted OR = 8.2).ConclusionWhile the rates of a spectrum of obstetric and perinatal outcomes are normal in RIF patients, these patients could have an enhanced risk of placental abruption. However, investigations with a large sample size are needed to substantiate this inference.     

Outcome of pregnancy following second- or third-trimester intrauterine fetal death

Objective

To investigate the outcomes of a pregnancy after a second- or third-trimester intrauterine fetal death (IUFD).

Methods

A prospective observational study was conducted at Trousseau Hospital (Paris, France) between 1996 and 2011. The first ongoing pregnancy in women who had had a previous IUFD was monitored. Management of their treatment was according to a standardized protocol. Recurrence of fetal death was the main outcome criterion.

Results

The subsequent pregnancies of 87 women who had experienced at least one previous IUFD were followed up. The cause of previous IUFD was placental in 50 (57%) women, unknown in 19 (22%), adnexal in 12 (14%), metabolic in 2 (2%), and malformative in 4 (5%). Three (3%) participants had another stillbirth. Overall, obstetric complications occurred in 34 (39%) pregnancies (including 22 [25%] preterm births, 5 [6%] small for gestational age, and 6 [7%] maternal vascular complications). Obstetric complications were significantly more common among women whose previous stillbirth had been due to placental causes than among those affected by other causes (P = 0.02).

Conclusion

Most pregnancies after IUFD resulted in a live birth; however, adverse obstetric outcomes were more common when the previous stillbirth was due to placental causes.     

Obstetric prognosis after placental abruption

OBJECTIVE: To assess obstetric outcome in women with a history of placental abruption. METHODS: We utilised the population-based birth registry data of Kuopio University Hospital to investigate pregnancy outcome in 59 women with prior placental abruption. The general obstetric population was used as a reference group in logistic regression analysis. RESULTS: Recurrent placental abruption and associated adverse neonatal outcome occurred in 11.9% (7:59) of the women. If the disease did not recur, a history of placental abruption had no significant effects on birth weight, fetal distress or prematurity rate, whereas the incidence of pre-eclampsia was found to be increased. CONCLUSIONS: Women in whom placental abruption does not recur have a good outcome in their subsequent delivery, almost comparable to that in the general obstetric population. However, the recurrence rate of 11.9% is high (OR: 16.9, 95% CI: 8.2-34.9) when compared with the background incidence of placental abruption (0.7%).     

Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin.

OBJECTIVE: To study the obstetric course of women with a history of recurrent miscarriage associated with antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibodies, treated with low dose aspirin and low dose heparin. DESIGN: Prospective observational study. SETTING: University based tertiary referral clinic. POPULATION: One hundred and fifty pregnant women with a history of recurrent miscarriage associated with persistently positive tests for antiphospholipid antibodies. METHODS: Lupus anticoagulant was detected using the dilute Russell's viper venom time together with a platelet neutralisation procedure. IgG and IgM anticardiolipin antibodies were detected using a standardised enzyme linked immunosorbent assay. An IgG anticardiolipin level > or = 5 per litre units and an IgM anticardiolipin level > or = 3 per litre units was considered positive. Aspirin (75 mg daily) was commenced at the time of a positive pregnancy test and heparin (5000 units subcutaneously 12 hourly, or enoxaparin 20 mg daily) was started when fetal heart activity was demonstrated on ultrasound. Treatment was stopped at the time of miscarriage or at 34 weeks of gestation. RESULTS: One hundred and seven pregnancies (71%) resulted in a live birth. Forty-one pregnancies (27%) miscarried, the majority in the first trimester. One woman had a stillbirth, and one a premature baby who died in the neonatal period. One pregnancy was terminated for a fetal anomaly. Gestational hypertension complicated 17% (18/108) of ongoing pregnancies and antepartum haemorrhage 7% (8/108). Twenty-six babies (24%) were delivered before 37 weeks of gestation. Fifty women (46%) were delivered by caesarean section. The median birthweight of all live born infants was 3069 g (range 531-4300); however 15% (16/108) of the infants were small for gestational age. CONCLUSION: Combination treatment with aspirin and heparin leads to a high live birth rate among women with recurrent miscarriage and antiphospholipid antibodies. However, successful pregnancies are prone to a high risk of complications during all trimesters. Close antenatal surveillance and planned delivery of these pregnancies in a unit with specialist obstetric and neonatal intensive care facilities are indicated.     

Dalteparin and Low-Dose Aspirin in the Prevention of Adverse Obstetric Outcomes in Women With Inherited Thrombophilia

ObjectiveTo evaluate the benefit of treatment with dalteparin and low-dose aspirin (ASA) in the prevention of obstetric complications in women with inherited thrombophilia.MethodsA retrospective chart review identified women who had had at least one pregnancy complicated by severe early-onset preeclampsia, placental abruption, fetal growth restriction (FGR), or fetal death. The following inherited thrombophilias were included: deficiencies of antithrombin, protein C, or protein S, and mutations of factor V Leiden (G1691A), factor II (G20210A), or methylenetetrahydrofolate reductase C677T.ResultsThe records of 43 women with 110 pregnancies were included in the study. Anticoagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11. Dalteparin alone and ASA alone showed equivalent effects in preventing preeclampsia and FGR. Combined dalteparin and ASA significantly decreased the risk of preeclampsia (odds ratio [OR] 0.80; 95% confidence intervals [CI] 0.70–0.91, P = 0.001) and FGR (OR 0.70; 95% CI 0.60–0.82, P = 0.001).ConclusionData from this retrospective cohort study suggest that combined treatment with dalteparin and ASA decreases the risk of preeclampsia by 20% and the risk of FGR by 30% in women with inherited thrombophilia.     

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.     

Ambulatory management of chronic hypertension in pregnancy

Chronic hypertension in pregnancy is one of the most common medical diseases affecting pregnancy. It is associated with serious maternal and fetal complications, including superimposed pre-eclampsia, fetal growth restriction, premature delivery, placental abruption, and stillbirth. Baseline evaluation as early as possible is important to differentiate women with essential hypertension from those with severe hypertension, coexisting end-organ damage, and secondary causes of hypertension, as their risks of poor outcomes are increased. An optimal plan for maternal treatment and fetal surveillance can then be formulated. Coordination of care after delivery is important for long-term maternal health and future pregnancies.     

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.     

Obstetric outcome following laparoscopic adjustable gastric banding.

OBJECTIVE: To evaluate obstetric outcomes following laparoscopic adjustable gastric banding (LAGB) in obese women. METHODS: Obstetric outcomes were compared in a retrospective case-control study with 427 obese women, 13 who underwent LABG and 414 who did not. RESULTS: The mean weight gain during pregnancy was significantly lower in the LABG group than among controls (5.5 kg vs. 7.1 kg; P<0.05). The incidence of pre-eclampsia, gestational diabetes mellitus, low birth weight, and fetal macrosomia was less in the LABG group (P<0.05), and the incidence of cesarean deliveries during labor was half in the LAGB group (15.3% vs. 34.4%; P<0.01). Neonatal outcomes were not significantly different in the 2 groups. CONCLUSIONS: Among obese women, the incidence of adverse obstetric outcomes was less in those who underwent LABG than in those who did not. These results suggest that obese women who wish to become pregnant would decrease their risk of obstetric complications if they first underwent LAGB.     

Occasional Review: Systemic Lupus Erythematosus and Pregnancy at the Royal Women''s Hospital, Brisbane 1979–1989

The management and obstetric outcome of 17 patients with systemic lupus erythematosus (SLE) complicating 42 pregnancies is presented. Similar to world figures there was a 14.3% incidence of therapeutic abortion, a 4.8% incidence of ectopic pregnancy, a 16.7% incidence of spontaneous abortion, a 23.8% incidence of prematurity, a 4.8% incidence of fetal death in utero (FDIU) and a 9.5% incidence of intrauterine growth retardation (IUGR). In patients with antiphospholipid antibodies the obstetric outcome was significantly worse. Pregnancies complicated by preexisting renal compromise all concluded with an adverse outcome to the conceptus. In light of the experiences at the Royal Women's Hospital and a review of the world literature, the need for a standardized approach to SLE in pregnancy and more importantly the need for a large, prospective randomized trial of low dose aspirin in these pregnancies is highlighted.     

子宫肌瘤子宫动脉栓塞术后妊娠情况及影响因素分析

目的:探讨子宫肌瘤患者行子宫动脉栓塞术(UAE)后的妊娠结局,以及肌瘤位置对妊娠率和结局的影响。方法:对行子宫动脉栓塞术的84例有生育要求和497例无生育要求的子宫肌瘤患者进行随访,了解其术后妊娠和产科并发症的发生情况。结果:(1)截止2011年4月,本研究中有50例患者60次妊娠。其中有妊娠要求组共30例39次妊娠,无妊娠要求组共20例21次妊娠。(2)有妊娠要求组妊娠结局为分娩26次(自然分娩9次,剖宫产17次),人工流产4次,自然流产5次,异位妊娠1次,宫内死胎3次(同1人);无妊娠要求组均行人工流产;(2)分娩的26例患者中,发现产科并发症7例26.92%(7/26),其中子痫前期1例3.85%(1/26)、胎盘前置状态1例3.85%(1/26)、早产4例15.38%(4/26)、中央性前置胎盘1例3.85%(1/26);(4)有妊娠要求的单发性肌瘤组(黏膜下、肌壁间、浆膜下、不明)和多发性肌瘤组的妊娠率分别为25.00%、59.09%、62.50%、14.29%和27.58%;单发浆膜下肌瘤组无产科并发症发生,黏膜下子宫肌瘤患者的产科并发症发生率高达75%。结论:子宫肌瘤患者在UAE后可正常妊娠,但自然流产率、胎盘异常等的发生率明显增高,特别是黏膜下和多发性子宫肌瘤患者。