Prophylactic dosing adjustment in pregnancy based upon measurements of anti-factor Xa levels.

OBJECTIVE: To determine the necessity for monitoring of anti-factor Xa levels in pregnant women taking low molecular weight heparin (LMWH). STUDY DESIGN: A review of a hematological database with chart review was undertaken to identify patients on LMWH. Levels were drawn monthly. They were considered suboptimal if prophylactic and therapeutic doses of LMWH had an anti-Xa value <0.2 U/mL and 0.6 U/mL, respectively. Variables of interest included age, parity, thrombophilias, and antiphospholipid antibody syndrome. RESULTS: Of 30 patients, three required therapeutic-dose LMWH and 27 were on prophylaxis. Sixty-six percent on a therapeutic dose required a dose change, whereas 11% on a prophylactic dose were changed (p = 0.013). None of the variables were predictive of a need for change. One thromboembolic event was noted while on prophylactic-dose LMWH. CONCLUSIONS: No single variable is predictive of a need for dose change. Patients on a therapeutic dose were more likely to need change.     

Thrombosis prophylaxis in pregnancy with use of subcutaneous heparin adjusted by monitoring heparin concentration in plasma

Twenty-six pregnant women were given prophylactic heparin treatment because of previous thromboembolic complications. The mean duration of treatment was 25 weeks (range, 6 to 32 weeks). The amount of heparin was adjusted to a plasma concentration of 0.08 to 0.15 IU/ml, measured as anti-factor Xa activity. This effect was compared with that on activated partial thromboplastin time. The average dose was 16,400 IU/24 hours or 225 IU/kg of body weight per 24 hours. When the plasma concentration was within the stipulated range, the dose was 234 IU/kg of body weight/24 hours. No significant prolongation of activated partial thromboplastin time was found in two thirds of the samples. Blood coagulation was either not activated or only slightly activated, as verified by a low level of fibrinopeptide A. Platelet counts and antithrombin III levels were generally not depressed. No thromboembolic complications occurred during the pregnancies or puerperium. Bleeding during delivery was not increased. No fractures of the spine caused by osteoporosis were found on radiologic examination post partum.     

Management and outcome of pregnancy in women with thrombophylic disorders and past cerebrovascular events

OBJECTIVE: To evaluate the maternal and fetal outcome in a cohort of women undergoing a subsequent pregnancy after a previous cerebrovascular event in the presence of thrombophilia. PATIENTS: Fifteen pregnancies were followed up in 12 women with past cerebrovascular events and thrombophilic disorders. The cerebrovascular events occurred during a previous pregnancy in five patients. Six patients had a bad obstetric history including intrauterine fetal death in four cases, early onset of severe preeclampsia in two cases and one infant that was small for gestational age. THE THROMBOPHILIC DISORDERS INCLUDED: anti-phospholipid syndrome, protein C, S or antithrombin III deficiencies, mutations of the methyltetrahydrofolate reductase (MTHFR). All patients received prophylactic treatment with low molecular weight heparin and low dose aspirin. RESULTS: Thromboembolic complications occurred in four pregnancies. Postpartum complications occurred in one patient; deep vein thrombosis and pulmonary emboli after stopping anticoagulation treatment. No patient had long-term neurologic damage. All pregnancies except one resulted in live births. (mean gestational age at delivery 36 +/- 3. 7 weeks, mean birth weight 2656 +/- 811 g). The one remaining pregnancy was electively terminated. There was one neonatal death due to the complications of severe prematurity in a woman with severe HELLP syndrome. CONCLUSION: This preliminary data suggests that women with a history of cerebrovascular events and thrombophilic disorders receiving prophylactic treatment, have a relatively favorable pregnancy outcome; however, they remain at significant risk during pregnancy. Further studies are necessary to determine the optimal prophylactic treatment.     

Short-term low-dose heparin plus bedrest impairs bone metabolism in pregnant women

OBJECTIVE: To assess the osteoporotic risk of short-term low-dose heparin plus bedrest in pregnancy. STUDY DESIGN: In a prospective case-control study, 10 pregnant women on bedrest receiving prophylactic unfractionated heparin 10,000 IU per day for 7-46 days pre-study and 28 days per-study were compared with 6 normal pregnant controls of similar maternal and gestational age and 10 nonpregnant women of similar age. Serum ionised calcium, 1,25-dihydroxyvitamin D(3), osteocalcin, and urinary calcium/creatinine ratio were determined three times at 2-week intervals. RESULTS: 1,25-Dihydroxyvitamin D(3) was lower in the treated group than in pregnant controls throughout (P<0.03). Osteocalcin was lower at study start than end in both pregnant groups (P<0.05), and lower in the treated group than in either pregnant (n.s.) or nonpregnant controls (P<0.005). Calcium/creatinine ratio differences were non significant (n.s.). CONCLUSION: Short-term low-dose heparin plus bedrest suppresses 1,25-dihydroxyvitamin D(3) and osteocalcin levels in pregnancy.     

Preference and compliance in postoperative thromboembolism prophylaxis among gynecologic oncology patients

OBJECTIVE: To compare low molecular weight heparin and external pneumatic compression in terms of patient preference and compliance to determine if either of these two methods is superior in postoperative thromboembolism prophylaxis of gynecologic oncology patients. METHODS: A total of 211 patients undergoing major surgery for a suspected gynecologic malignancy were randomized to receive thromboembolism prophylaxis with either external pneumatic compression or low molecular weight heparin. Surveys regarding thromboembolism prophylaxis were completed by patients before surgery and approximately 7 days postoperatively. Patient preferences as well as reasons for patient dissatisfaction with prophylactic methods were elicited in the questionnaires. In addition, patient compliance with prophylaxis was recorded twice a day during hospitalization. Patients were not considered to be compliant with prophylaxis if the external pneumatic compression device was not functioning properly or if the administration of low molecular weight heparin was not given in a timely manner. RESULTS: The majority of patients were satisfied with the prophylactic method that they received to the extent that they would prefer the treatment they received to one they had not necessarily experienced. The postoperative preferences of 78% of patients receiving low molecular weight heparin and 74% of those wearing external pneumatic compression corresponded to what the patients actually received as a method of thromboembolism prevention. Patient compliance with prophylaxis was noted to be inadequate in ten of 104 (9.6%) patients receiving external pneumatic compression and seven of 103 (6.8%) patients receiving low molecular weight heparin. CONCLUSION: Pneumatic compression and low molecular weight heparin are similar both in terms of patient preference and compliance among gynecologic oncology patients receiving postoperative thromboembolism prophylaxis.     

Management of thromboembolism in pregnancy

The incidence of venous thromboembolism is increased during pregnancy and the postpartum period. This risk is high for women with documented hereditary or acquired risk factors who have experienced a prior thrombotic event. These individuals require a minimum of prophylactic dose anticoagulation with unfractionated or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum. Women receiving therapeutic dose anticoagulation with warfarin before pregnancy for a hereditary or acquired condition should be transitioned to therapeutic doses of unfractionated heparin or low molecular weight heparin before or within 6 weeks of becoming pregnant, and can then resume warfarin postpartum. Women experiencing a thromboembolic event during pregnancy should receive therapeutic treatment with unfractionated heparin or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum, and for a total of at least 6 months.     

Adverse pregnancy outcome, the uteroplacental interface, and preventive strategies

Adverse pregnancy outcome (APO), includes fetal loss > or =20 weeks' gestation (fetal death), severe preeclampsia <36 weeks, or severe intrauterine growth restriction (severe IUGR) defined as birth weight < or =5th percentile or < or =10th percentile for gestational age. APO affects 8% of pregnant women (320,000 annually) and collectively contributes to the largest proportion of maternal/fetal mortality and morbidity. Women with prior APO in antecedent pregnancy are at high risk of an adverse maternal or fetal outcome in the subsequent pregnancy. Maternal serum markers and Doppler ultrasound can be used to predict adverse pregnancy outcome. There are no adequate, completed randomized trials for prophylactic measures; the roles of aspirin, calcium, and low molecular weight heparin need to be evaluated.     

Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy

Objective To assess the safety and efficacy of enoxaparin use for thromboprophylaxis or treatment of venous thromboembolism during pregnancy.
Design Retrospective review of casenotes of women who received enoxaparin during pregnancy.
Setting Obstetric Medicine Unit at Glasgow Royal Maternity Hospital.
Sample Data were obtained on 57 pregnancies in 50 women over six years.
Methods Information was obtained from case records in relation to outcome measures, the presence of underlying thrombophilia and indication for anticoagulation.
Main outcome measures Incidences of venous thromboembolism, haemorrhage, thrombocytopenia, peak plasma anti-factor Xa levels and symptomatic osteoporosis.
Results There were no thromboembolic events in the thromboprophylaxis group. There were no incidences of heparin-induced thrombocytopenia. Twenty-two women had spinal or epidural anaesthesia and no complications were encountered. There was one instance of antepartum haemorrhage following attempted amniotomy in a woman with previously unknown vasa praevia. Two women sustained postpartum haemorrhage, both secondary to vaginal lacerations, resulting in blood loss > 1000 mL. Blood loss following caesarean section was not excessive. No instances of vertebral or hip fracture were encountered. The median peak plasma anti-factor Xa level on a dose of 40 mg once daily was 0.235 U/mL; peak plasma anti-factor Xa levels were not affected by gestational age.
Conclusions The use of enoxaparin in pregnancy is associated with a low incidence of complications and a dose of 40 mg once daily throughout pregnancy provides satisfactory anti-factor Xa levels and appears effective in preventing venous thromboembolism.     

Assessment of the effectiveness of using low molecular weight heparin in the prophylaxis of venous thrombo-embolic diseases in obstetrics

OBJECTIVES: Assessment of the effectiveness of using low molecular weight heparin in the prophylaxis of venous thrombo-embolic diseases in pregnant women, parturients and puerperants. MATERIAL AND METHODS: 14,106 female patients were retrospectively analysed in the period between 1990-1999. The patients were divided into 4 groups: I--142 pregnant patients with crural varices, II--10 pregnant patients who had suffered from deep venous thrombosis, III--5 patients with implanted artificial cardiac valves, IV--13,949 patients without any risk factors. In the patients in groups I-III low molecular weight heparin was used prophylactically. RESULTS: In the studied groups no cases of pulmonary embolism were observed. Superficial venous thrombosis occurred in 10 women (3 in group I and 7 in group IV). Deep venous thrombosis occurred in 5 patients (2 in group I and 3 in group IV). In patients who received low molecular weight heparin over a long period of time, no excessive bleeding during delivery was observed. Other complications in the form of osteoporosis and thrombocytopenia were also not observed. CONCLUSIONS: 1. Administering of low molecular weight heparin during pregnancy, labour and puerperium has no influence on the increase of maternal et fetal complications. 2. Administering of low molecular weight heparin in pregnant women, in labour and in puerperium with increase risk of thrombo-embolic disease allows to avoid pulmonary arteries embolism. 3. Pregnant women and women in puerperium with increased risk of venous thrombo-embolic disease should be under control of experienced obstetrician in cooperation with vascular surgeon and hematologist.     

Body mass index, provider advice, and target gestational weight gain

OBJECTIVE: To study the relationships among prepregnancy body mass index (BMI), women's target gestational weight gain, and provider weight gain advice. METHODS: Project WISH, the acronym for Women and Infants Starting Healthy, is a longitudinal cohort study of pregnant women in the San Francisco Bay area. We excluded subjects with preterm birth, multiple gestation, or maternal diabetes. RESULTS: Among overweight women (prepregnancy BMI 26.1-29.0), 24.1% reported a target weight gain above the Institute of Medicine (IOM) guidelines, compared with 4.3% of normal weight women (P < .001). Among women with a low prepregnancy BMI (< 19.8), 51.2% reported a target weight gain below the guidelines, compared with 10.4% of normal weight women (P < .001). These patterns persisted in a multivariate analysis. Latina ethnicity, lower maternal education, low prepregnancy BMI (< 19.8), lack of provider advice about weight gain, and provider advice to gain below guidelines were all independently associated with a target weight gain below IOM guidelines. Prepregnancy BMI more than 26, multiparity, lower age, and provider advice to gain above guidelines were all associated with a target gain above IOM guidelines. CONCLUSION: Women's beliefs about the proper amount of weight gain and provider recommendations for weight gain vary significantly by maternal prepregnancy BMI. Many women report incorrect advice about gestational weight gain, and women with high or low prepregnancy BMI are more likely to have an incorrect target weight gain. New approaches to provider education are needed to implement the IOM guidelines for gestational weight gain.     

Anticoagulación en gestantes portadoras de prótesis mecánicas

Objective

To study distinct anticoagulation regimens in pregnant women with prosthetic heart valves.

Subjects and methods

We performed a systematic review of the literature to determine the required levels of anticoagulation prophylaxis, timing of the introduction of oral anticoagulation and its substitution by heparins, and the maternal and fetal risks associated with different anticoagulation regimens.

Results

A target international normalized ratio (INR) of 2.5-3.5 should be achieved. Although consensus on the heparin of choice is lacking, heparin dose requirements should be based on anti-factor Xa levels (around 1.0 U/mL) or activated partial thromboplastin time (aPTT) (2-3 times control value). The risk of thrombosis in heparin-treated patients is approximately 7%, while the incidence of heparin embryopathy ranges from 1.6-7.4%. The switch from oral anticoagulation to heparin should be made no later than at weeks 35-36 of pregnancy.

Conclusions

The nticoagulation therapy of choice in the first trimester of pregnancy cannot currently be established. Prospective and randomized studies are required to determine the advisability of one treatment over the other     

Obstetric and perinatal complications in HIV-infected women. Analysis of a cohort of 167 pregnancies between 1997 and 2003

BACKGROUND: The unquestionable benefit of antiretroviral therapy in reducing the rate of mother-to-child transmission can be lessened by potential maternal or neonatal toxicity. OBJECTIVE: To analyze obstetric and perinatal complications in a cohort of HIV-infected pregnant women and their relationship with maternal antiretroviral therapy. POPULATION: One hundred and sixty-seven HIV-infected pregnant women who delivered at Hospital Universitario La Paz, Madrid, Spain between January 1997 and December 2003. METHODS: Data on the clinical and epidemiological characteristics of HIV-infected patients, previous and current antiretroviral therapy, gestational diabetes mellitus, length of pregnancy, mode of delivery, and weight of the newborn were collected. Pregnancy outcomes were compared with those of all the pregnant women attended at our hospital. MAIN OUTCOME MEASURES: Gestational diabetes mellitus, premature delivery, and low birth weight. RESULTS: Gestational diabetes mellitus was diagnosed in 8.9% of patients. All the cases of gestational diabetes were in the combined antiretroviral therapy group, and the majority were receiving triple antiretroviral therapy with a protease inhibitor. The risk of developing this pathology was greater among women receiving antiretroviral therapy prior to pregnancy. The premature delivery rate was 29% and the low birth weight rate was 28%. CONCLUSION: Gestational diabetes mellitus is more common in HIV-infected women than in the general population and is related to combined antiretroviral therapy, especially the use of protease inhibitors, which suggests the need for close follow-up during pregnancy in HIV-infected patients. Nevertheless, the adverse perinatal consequences observed were more related to maternal factors than to antiretroviral therapy.     

Risk of preeclampsia in HIV-positive pregnant women receiving HAART: a matched cohort study

Objective: We sought to determine whether HIV-positive women receiving highly active anti-retroviral therapy (HAART) are at higher risk for preeclampsia than HIV-negative women. Secondary outcomes included comparing the risks of preterm birth, low birth weight, and small for gestational age birth in these women. Methods: In this retrospective matched cohort study, we compared the pregnancy outcomes of HIV-positive women treated with HAART with those of HIV-negative women who gave birth at Mount Sinai Hospital, Toronto, Ontario. Data were ascertained through chart review. Univariate and multivariate logistic regression models were used to compare pregnancy outcomes between the two groups. Results: Ninety-one HIV-positive pregnant women receiving HAART and 273 HIV-negative pregnant women were identified. After adjusting for confounding factors, there was no difference between HIV-positive and HIV-negative women in the odds of preeclampsia (3.3% vs. 5.1%; adjusted odds ratio [aOR] 0.59; 95% CI 0.11 to 3.08), preterm birth (15.6% vs. 11.4%; aOR 1.70, 95% CI 0.79 to 3.66) or small for gestational age infants (20.2% vs. 8.8%; aOR 2.08, 95% CI 0.89 to 5.24). HIV-positive women treated with HAART had increased odds of giving birth to a low birth weight infant compared to HIV-negative women (20.2% vs. 9.9%; aOR 2.91; 95% CI 1.47 to 5.78). Conclusion: In this cohort, HIV-positive women on HAART did not demonstrate a higher risk of preeclampsia, preterm birth, or small for gestational age infants; however, they did have a higher risk of having low birth weight infants.     

Heritable coagulopathies in pregnancy

Heritable coagulopathies are leading causes of maternal thromboembolism and are associated with an increased risk of maternal and perinatal morbidity and mortality. The most common of these disorders are antithrombin III deficiency, protein C deficiency, protein S deficiency, activated protein C resistance resulting from the factor V Leiden mutation, elevated prothrombin activity associated with a mutation in the prothrombin gene, and hyperhomocystinemia. The maternal risk of a thromboembolic episode is increased by a factor of eight in the presence of any of these heritable states. In addition, the relative risk for a stillbirth in the presence of one of these disorders is 3.6. These conditions are also associated with intrauterine growth retardation and preeclampsia. Proper management of heritable coagulopathies during pregnancy is essential to reduce the risk of these serious sequelae. Patients with newly diagnosed deep-vein thromboses or pulmonary emboli should be treated with therapeutic levels of unfractionated or low molecular weight heparin, followed by subsequent prophylactic heparin therapy. All patients with a history of thromboembolism before pregnancy or evidence of any of these coagulopathies may be offered prophylactic therapy with low molecular weight heparin. Patients with antithrombin III deficiency should receive full therapeutic heparin therapy for the entire pregnancy, irrespective of their thromboembolic history. Postpartum therapy with either heparin or warfarin is required in all cases. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the various heritable coagulopathies that can complicate pregnancy, to state the potential adverse effects of heritable coagulopathies in pregnancy, and to explain the management of heritable coagulopathies during pregnancy.     

Leptin and gestational weight gain: relation of maternal and cord blood leptin to birth weight

OBJECTIVES: To determine maternal serum leptin concentrations throughout normal pregnancy, as well as cord blood leptin concentration, and to correlate serum and cord blood leptin levels with gestational weight gain and birth weight, respectively. METHODS: This study comprised 52 normal pregnant women, including 11 in the first, 19 in the second, and 22 in the third trimester, in addition to 30 healthy, fertile nonpregnant women of comparable age and with normal body mass index (BMI). Maternal blood and fetal cord blood samples were withdrawn from the normal, healthy pregnant women and the nonpregnant controls for the determination of serum leptin by a specific radioimmunoassay. RESULTS: Maternal serum leptin concentrations in the first trimester did not differ significantly from those of healthy nonpregnant control subjects, whereas leptin concentrations in the second and third trimesters were elevated significantly. There were significant positive correlations between maternal serum leptin concentration and gestational age, gestational weight, and BMI. Cord blood leptin concentration correlated positively with birth weight and third trimester maternal serum leptin. CONCLUSION: Elevated serum leptin is associated with maternal adiposity and risk of developing large for gestational age infants.     

肝素治疗胎儿生长受限的临床观察

目的探讨肝素用于治疗胎儿生长受限(FGR)的临床疗效及安全性.方法将107例FGR患者分为3组,标准肝素治疗组37例,将标准肝素50～75 mg溶于5%葡萄糖氯化钠注射液500 ml中静脉滴注,6～8 h滴完;低分子肝素治疗组31例,给予低分子肝素(商品名速避凝)0.2～0.4 ml皮下注射;对照组39例,给予低分子右旋糖酐500 ml加复方丹参注射液20 ml静脉滴注. 治疗前后及终止妊娠前,行彩色超声(彩超)检查,监测胎儿生长情况和脐血流变化,并进行生物物理评分,同时监测血小板计数(PLT)、凝血酶原时间(PT)、部分凝血活酶时间(APTT);记录新生儿情况并进行随访.结果 (1)标准肝素治疗组、低分子肝素治疗组,平均每周宫高均增长(0.7±0.6) cm,高于对照组的 (0.5±0.4) cm,差异有显著性(P＜0.05);平均每周双顶径分别增长[(2.4±0.7) mm、(2.5±0.8) mm,显著高于对照组的(1.7±0.6) mm,差异也有显著性(P＜0.05).(2)标准肝素治疗组、低分子肝素治疗组、对照组胎儿生物物理评分别为(9.7±0.8) 分、(9.6±0.6) 分、(8.9±0.7)分,差异有显著性(P＜0.05).(3)标准肝素治疗组及低分子肝素治疗组,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比值)分别为2.5±0.5、2.4±0.5,显著低于对照组的2.9±0.6,差异有显著性(P＜0.05);搏动指数(PI)、阻力指数(RI)也显著低于对照组,差异也有显著性(P＜0.05).(4)标准肝素治疗组、低分子肝素治疗组新生儿出生后1分钟Apgar评分8～10分者分别占86%、87%,显著高于对照组的74%(P＜0.05);新生儿出生体重分别为(3100±256)g、(3080±225)g,显著高于对照组的(2580±304)g,差异有显著性(P＜0.05);胎龄均为(38±4)周,也显著长于对照组的(37±4)周,差异均有显著性(P＜0.05).(5)标准肝素治疗组及低分子肝素治疗组足月小样儿均为2例(分别占5%、6%),显著低于对照组的7例(18%),差异均有显著性(P＜0.05).(6)各组孕妇治疗前后PLT、PT、APTT比较,差异均无显著性(P＞0.05).(7)标准肝素治疗组及低分子肝素治疗组,治疗后孕妇的宫高、胎儿的股骨长度、头围、腹围、脐血流各指标、新生儿出生体重、胎龄等变化比较,差异均无显著性(P＞0.05).结论肝素可改善胎盘血流,使胎儿体重增加,减少足月小样儿的发生率,改善围产儿的预后,且肝素治疗FGR对母、儿都较安全.     

The "pregnancy zone" protein and fetal welfare

The frequency of women with demonstrable "pregnancy zone" protein (assumed to be a steroid-induced alpha-2-globulin) at term of pregnancy was determined in order to investigate whether lack of this protein in maternal serum was in any way related to maternal age, parity, abortion history, or some factors reflecting fetal maturity (birth weight, placental weight, and gestational age). 311 (88.9%) out of 350 pregnant women demonstrated "pregnancy zone" protein in their sera. Birth weight was significantly lower (p less than .05) among infants of women lacking this protein. No apparent correlation was found between lack of "pregnancy zone" protein in maternal serum and maternal age, parity, previous abortion, placental age, or gestational age. The results indicated that lack of or low levels of this protein in the maternal circulation at term is a phenomenon compatible with normal pregnancy, although some slight effect on fetal development cannot be excluded.     

Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial.

OBJECTIVE: To compare the efficacy and treatment-related complications of low molecular weight heparin and external pneumatic compression in the prevention of venous thromboembolism of postoperative gynecologic oncology patients. METHODS: A total of 211 patients over age 40 years, undergoing a major operative procedure for gynecologic malignancy, were randomized to receive perioperative thromboembolism prophylaxis with either low molecular weight heparin (n = 105) or external pneumatic compression (n = 106). Demographic data and clinical outcome were recorded for each patient. All patients underwent bilateral Doppler ultrasound of the lower extremities on postoperative days 3-5 to evaluate for the presence of occult deep vein thrombosis. A follow-up interview 30 days after surgery sought to detect patients who developed deep vein thrombosis or pulmonary embolism after hospital discharge. RESULTS: Venous thrombosis was diagnosed in two patients receiving low molecular weight heparin and in one patient receiving external pneumatic compression. The frequency of bleeding complications, measured by the number of required perioperative transfusions, and estimated intraoperative blood loss was similar between the two groups. CONCLUSION: Low molecular weight heparin and external pneumatic compression are similarly effective in the postoperative prophylaxis of thromboembolism. The use of low molecular weight heparin is not associated with an increased risk of bleeding complications when compared with external pneumatic compression. We believe that both modalities are reasonable choices for prophylaxis in this high-risk group of patients.     

Recurrence and severity of abnormal pregnancy outcome in patients treated by low-molecular-weight heparin: a prospective pilot study

Objective: This prospective pilot study assesses the recurrence rate and severity of abnormal pregnancy outcome (APO), excluding early pregnancy complications, in pregnant patients, without acquired thrombophilia, treated by prophylactic doses of low-molecular-weight heparin (LMWH), independently from their congenital thrombophilic condition. Methods: We recruited a cohort of 128 pregnant patients with previous APO; 100 of whom with APO and intrauterine growth restriction (IUGR) and 28 with maternal APO only. LMWH treatment was started at recruitment. Composite cross-over recurrence rate IUGR, gestational hypertension, preeclampsia, help syndrome, abruptio placenta were analyzed. The main outcome measure was severe APOs with iatrogenic delivery ≤ 32 weeks of gestation. Results: Median gestational age at LMWH treatment was 20 weeks. Severe APO decreased in treated pregnancies from 45% to 4% (relative risk = 0.3, confidence interval 95% = 0.2–0.8). This value was not significantly different in thrombophilic and nonthrombophilic patients. When severe and minor complications were analyzed altogether, the recurrence rate was 28%. In patients with APO and fetal growth restriction (FGR) in the index pregnancy, newborn weights were significantly better in the treated pregnancy: 1090 g (1035–1145) vs. 850 g (535–1200), p < 0.01. Conclusions: Prophylactic regimen of LMWH significantly reduced the recurrence rate of severe composite APO in pregnancies affected in the index pregnancy by APO and FGR or small for gestational age newborns. This result was independent from the patients’ inherited thrombophilic conditions.