Elevated maternal second-trimester serum alpha-fetoprotein as a risk factor for placental abruption

OBJECTIVE: To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSbeta-hCG) levels to placental abruption. METHODS: Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSbeta-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. RESULTS: The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) (p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity >/= 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP >/= 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSbeta-hCG MoM did not differ between the cases and the controls. CONCLUSION: Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate.     

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy

Objective: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. Methods: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. Results: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free β-human chorionic gonadotropin (β-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. Conclusion: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.     

Maternal serum alpha-fetoprotein and fetal triploidy

Fetal triploidy is commonly found in early pregnancy. The majority of these pregnancies spontaneously abort in the first trimester. Occasionally, the pregnancy progresses to the second and third trimesters. We reviewed the maternal serum alpha-fetoprotein (MSAFP), amniotic fluid alpha-fetoprotein (AFP), amniotic fluid acetylcholinesterase (ACHE), fetal pathology, and placental pathology in sex second-trimester pregnancies complicated by fetal triploidy. Four of these patients had MSAFP values greater than 7.5 multiples of the median (MoM). Five of six pregnancies had MSAFP values greater than 2.25 MoM. All five of these patients had a partial mole. Four patients had amniotic fluid AFP values greater than 2.0 MoM. Two fetuses had associated neural tube defects. These were the only patients with positive amniotic fluid ACHE. None of the other patients had fetuses with anomalies that are known to be associated with an elevated MSAFP. The elevated MSAFP appeared to be related to the presence of a partial mole. Two of the five cases with an MSAFP greater than 2.25 MoM did not have sonographic evidence of a significant anomaly. Therefore, karyotyping can be of benefit in evaluating patients with elevated MSAFP.     

Elevated maternal serum alpha-fetoprotein: association with placental sonolucencies, fetomaternal hemorrhage, vaginal bleeding, and pregnancy outcome in the absence of fetal anomalies.

Elevated maternal serum alpha-fetoprotein (MSAFP) levels have been associated with an increased incidence of both placental sonolucencies and pregnancy complications. We designed a prospective study to test the hypothesis that the presence of these sonolucencies or a positive maternal Kleihauer-Betke stain would be associated with an elevated risk of obstetric complications. We enrolled 95 women with singleton pregnancies, elevated MSAFP, and no evidence of fetal anomalies on second-trimester ultrasound evaluation. Placental sonolucencies were documented at the time of ultrasound examination, and a maternal Kleihauer-Betke stain for fetal cells was obtained on the same day. Complications of pregnancy included fetal growth retardation, preterm delivery, late vaginal bleeding (at or after the 20th week of gestation), and fetal death. Women with elevated MSAFP had an increased incidence of placental sonolucencies, positive maternal Kleihauer-Betke stains, first-trimester vaginal bleeding, late vaginal bleeding, preterm delivery, fetal growth retardation, and fetal death compared with controls. Thirty-nine of 95 women with elevated MSAFP (41.1%) had at least one complication. In women with elevated levels, neither the presence of placental sonolucencies nor a positive Kleihauer-Betke stain correlated with first-trimester vaginal bleeding, the MSAFP level, or an increased risk of pregnancy complications. First-trimester vaginal bleeding was associated with an increased risk of preterm delivery in subjects with elevated MSAFP.     

Obstetric outcome after threatened miscarriage with and without a hematoma on ultrasound

OBJECTIVE: To examine the effect of threatened miscarriage on second-trimester maternal serum alpha-fetoprotein (MSAFP) levels and pregnancy outcome; and to study the significance of ultrasound evidence of an intrauterine hematoma on pregnancy outcome in these patients. METHODS: A retrospective, case-control study was performed on 144 women presenting with bleeding in the first trimester and 144 age-matched control subjects who attended for routine dating scans during the same time scale. The presence or absence of an intrauterine hematoma, MSAFP, and pregnancy outcomes were recorded. RESULTS: The incidence of adverse pregnancy outcome was significantly (P=.02) higher in women with a history of first-trimester threatened miscarriage than in the control group. The relative risk (RR) of an adverse pregnancy outcome for the study group was 2.22 (95% confidence interval [CI] 1.12, 4.39) compared with the control group. The RR of delivering a baby of less than 1000 g was 4.43 (95% CI 0.5, 39.2) in women with first-trimester threatened miscarriage. This was independent of the presence of an intrauterine hematoma. The RR of MSAFP being raised to more than 2.5 multiples of the median (MoM) in the study group was 6.25 (95% CI 0.77, 50.6). There was no difference between women with threatened miscarriage who had or did not have ultrasound evidence of an intrauterine hematoma. CONCLUSION: Threatened miscarriage in the first trimester is associated with an increased incidence of adverse pregnancy outcome, independently of the presence of an intrauterine hematoma. Higher MSAFP in threatened miscarriage suggests a direct placental injury even in the absence of a hematoma.     

Perinatal outcome in women with severe pregnancy complications and multiple thrombophilias

Hypercoagulability leading to placental thrombosis has been implicated in severe pregnancy complications. We compared the perinatal outcome in women with severe preeclampsia, intrauterine growth retardation (IUGR) and severe abruptio placentae and multiple acquired and inherited thrombophilias (study group, n=22) to matched women with similar complications and single thrombophilia (control group, n=22). Gestational age at delivery and birth weight were significantly lower in the study group compared to the control group (p<0.01) and among the study women with severe preeclampsia and IUGR. Severe pregnancy complications may occur earlier during pregnancy and more seriously affect perinatal outcome in women with multiple thrombophilias.     

Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the risk for lethal perinatal outcome

OBJECTIVE: To determine whether a combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low unconjugated estriol (E3) concentration identifies pregnancies at particularly high risk for fetal abnormality or poor outcome. METHODS: Pregnancy outcomes were reviewed for women with elevated MSAFP (> or =2.0 MoM) from our database of 50,315 women who had received triple marker testing from 1993-1998. Outcomes for those with low E3 (< or =0.7 MoM) were compared with those with normal E3 (>0.7 MoM). The incidences of fetal death, neural tube defects, chromosome abnormalities, congenital abnormalities, preterm birth, small-for-gestational age (SGA), twins, and inaccurate dates were compared in the two groups using Fisher's exact test with P < 0.05 considered significant. RESULTS: Of the 50,315 women screened, 1,435 (2.85%) had an elevated MSAFP. Pregnancy outcomes were obtained in 94% of those with elevated MSAFP and 70% of all patients screened. Neural tube defects were present in 57 fetuses/infants (21 anencephalic, 29 spina bifida, 7 encephalocele) of which 46 (81%) had an elevated MSAFP. Of the 1,435 women with an elevated MSAFP, 199 (14%) had a low E3. Compared to those women with elevated MSAFP but normal E3, women with elevated MSAFP and low E3 were at significantly increased risk for fetal death (20.6% vs. 2.8%, relative risk (RR) 8.9), anencephaly (9.0% vs. 0.1%, RR 122.8) and chromosome abnormality (2.5% vs. 0.6%, RR 4.0). CONCLUSIONS: Pregnancies complicated by elevated second trimester MSAFP and low E3 are at a particularly high risk (32%) for lethal perinatal outcomes. Twins, while a common cause of elevated MSAFP, are rarely found when an elevated MSAFP is associated with low E3.     

Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein

ObjectiveThe aim of this study was to investigate the overall distribution of pregnancy outcomes in women with elevated second-trimester maternal serum alpha-fetoprotein (MS-AFP), and to determine the risk of adverse pregnancy outcomes (APOs) by MS-AFP level.Materials and methodsWe retrospectively analyzed the clinical data of 429 women with elevated MS-AFP (≥2.5 multiple of the median (MOM)) and 1555 women with normal MS-AFP (0.5–2.49MOM) from a total of 46,741 prenatally screened singleton pregnant women. The overall distribution of APOs of the two groups, the risk of APOs by MS-AFP level, and the predictive value of elevated MS-AFP to APOs were analyzed.ResultsThe incidence rate of APOs in elevated MS-AFP group was significantly higher than that in normal MS-AFP group (42.89 vs. 8.23%). In elevated MS-AFP group, the top three APOs, in term of incidence rate, were structural fetal abnormalities (7.93%), spontaneous abortion (7.46%) and preterm birth (7.23%); regarding to the risk, the top three APOs were stillbirth, spontaneous abortion and early-onset preeclampsia (odds ratio 35.98, 20.81 and 8.58 respectively). For structural fetal abnormalities, MS-AFP had predictive values for fetal open neural tube defects (ONTDs), gastroschisis and multiple malformations.ConclusionElevated MS-AFP is associated with increased risks of APOs. ONTDs complicate merely a small proportion of pregnancies with elevated MS-AFP, and the rest of them have high risks of obstetric complications. MS-AFP can help to identify these women at high risk of APOs in earlier second-trimester.     

Evaluation of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase gene mutations in patients with severe pregnancy complications in northern Finland

BACKGROUND: Thrombosis in placenta may lead to severe pregnancy complications. Most important inherited thrombophilias are factor V Leiden mutation, prothrombin mutation, and methylenetetrahydrofolate reductase mutation. The aim of our research was to evaluate the prevalence of inherited thrombophilias in severe pregnancy complications and in normal pregnancies. MATERIAL AND METHODS: The study subjects with severe preeclampsia, intrauterine growth restriction, placental abruption or fetal death were collected during the period 1999-2004 from Oulu University Hospital. We also collected during the same period voluntary parturients with normal pregnancy outcome as the control group. FVL, FII, and MTHFR gene mutations of the patients and controls were analyzed. RESULTS: We found a significant difference in the prevalence of FVL mutation between the groups. There were 9.5% FVL mutations in the study group compared to 1.8% in the control group; the observed difference between prevalences was 7.7% (95% CI 2.0-13.4). No statistical difference was found in the FII or MTHFR mutations between the groups. All FV and FII mutations were heterozygous and all the MTHFR mutations homozygous. CONCLUSION: Women with thrombophilia have a risk for severe pregnancy complications. Randomized controlled trials are needed to assess the influence of low-molecular-weight heparin in pregnant women with thrombophilia.     

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.     

Inherited thrombophilias

Many inherited thrombophilias have been detected and the pathophysiologic insight has increased tremendously during the last decades. Despite, however, the overwhelming observational evidence on the association between inherited thrombophilia and several women's health issues, including VTE, thus far the implications for clinical practice are uncertain. Although there is firm epidemiologic evidence that is helpful in counseling women who have inherited thrombophilia to prevent a first or recurrent VTE, the uncertainty is particularly present for women who have other pregnancy complications, such as recurrent pregnancy loss and pre-eclampsia. For this group, well-designed placebo-controlled trials to assess the harm-benefit ratio are urgently needed.     

Inherited thrombophilias and adverse pregnancy outcome: screening and management

Inherited thrombophilias are a heterogenous group of conditions which have been implicated in a variety of pregnancy complications. Evidence is mounting that implicates these inherited disorders in a range of pregnancy outcomes, including recurrent miscarriage, late fetal loss, preeclampsia, abruptio placentae, and intrauterine growth restriction. The most commonly identified inherited thrombophilias consist of Factor V Leiden and the prothrombin gene mutation G20210A. Rarer inherited thrombophilic conditions include deficiencies of protein S, C and antithrombin. More recently, deficiency of protein Z has been linked to pregnancy complications, including preterm delivery. Clinical manifestations often are associated with the presence of more than one inherited thrombophilia, consistent with their multigenic nature. Some, but not all, studies investigating the use of heparin to prevent adverse pregnancy outcome have demonstrated a benefit. However, an adequate randomized trial is required to definitively determine whether heparin anticoagulation is the best prevention option in patients who harbor one or more inherited thrombophilias and are at risk for adverse pregnancy outcome. This review will summarize the association of thrombophilic conditions and obstetrical complications.     

Midtrimester triple test levels in women with severe preeclampsia and HELLP syndrome

BACKGROUND: The levels of midtrimester triple test constituents are known to be altered in hypertensive disorders of pregnancy. OBJECTIVE: Our aim was to determine whether midtrimester triple test constituent levels differ in women with severe preeclampsia and those who also develop HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. METHODS: A retrospective chart analysis of 106 women with severe preeclampsia for whom midtrimester triple test data were available was made. None of these patients had fetuses with abnormal karyotype, nor did they deliver infants with malformations. The levels of midtrimester maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (MShCG) and unconjugated estriol (MSuE3) of 74 patients with severe preeclampsia were compared with those of 32 patients who also developed HELLP syndrome. RESULTS: The mean MShCG was significantly higher and the mean MSuE3 was significantly lower in patients with HELLP syndrome than in those with only severe preeclampsia [1.78 multiple of the medians (MoM), standard error (SE) 0.18 vs. 1.27 MoM, SE 0.07, p=0.015 and 0.86 MoM, SE 0.05 vs. 1.04 MoM, SE 0.07; p = 0.03, respectively]. The two groups did not differ significantly with regard to MSAFP levels. CONCLUSION: Unexplained high levels of midtrimester MShCG and low levels of MSuE3 may be associated with the development of HELLP syndrome in women with severe preeclampsia.     

The significance of abnormally high and low maternal serum alpha-fetoprotein levels between 14 and 25 weeks of gestation.

A total of 6,160 gravidas with gestational ages from 14 to 25 weeks were collected to quantify maternal serum alpha-fetoprotein (MSAFP) using an enzyme immunoassay kit. A level over 2.5 MoM (multiples of the median) was defined as high and a level below 0.4 MoM as low. Ninety-eight women (1.59%) had an initially high MSAFP and 88 (1.42%) a low MSAFP. In the low MSAFP group, 80% returned for a further checkup. Among them, 46% had an over-estimation of gestational age based on their last menstrual period (LMP), 28% had a normal MSAFP and 9% still had a low MSAFP level on a repeat test. Pathologic conditions in other pregnancies included a hydatidiform mole, miscarriage and pseudocyesis. One nonresponder had an ectopic pregnancy. After delivery, no major fetal abnormalities, including trisomy syndromes, were noted in pregnancies carried to term. In the high MSAFP group, 84% returned for check-up. Among them, 15% had an under-estimation of gestational age based on LMP, 16% had twin pregnancies, 46% had a normal MSAFP and 12% still had a high MSAFP on a repeat test. Pathologic conditions in the other pregnancies included one anencephaly, one hydrocephaly and 6 miscarriages. Wrong dating by LMP and false positivity were the most frequent causes of abnormal levels of MSAFP. Two gravidas had artificial abortions because of undue anxiety. MSAFP screening in Taiwan for open neural tube defects does not seem appropriate and using 0.4 MoM as a fixed low cut-off point is inadequate for trisomy syndrome screening. Maternal anxiety should be seriously considered and proper genetic counseling implemented in a screening procedure.     

Unexplained elevated midtrimester maternal serum levels of alpha fetoprotein, human chorionic gonadotropin, or low unconjugated estriol: recurrence risk and association with adverse perinatal outcome

OBJECTIVE: To determine if women experiencing an unexplained elevated maternal serum alpha fetoprotein (MSAFP; > or =2.0 MoM) or human chorionic gonadotropin (hCG; > or =2.0 MoM), or low unconjugated estriol (E3; < or =0.5 MoM) in one pregnancy are at increased risk for similar results in a subsequent pregnancy, and to determine if recurrence of these analyte extremes is associated with adverse perinatal outcome. METHODS: We identified all women delivering two consecutive singleton pregnancies at one hospital between 1992-1997 for whom second trimester trisomy 21 serum screen was performed in each pregnancy. All screens were performed in a single laboratory. Each pregnancy delivered after 20 weeks and had gestational age confirmed by ultrasound prior to 24 weeks. Subjects were excluded if a fetal anomaly or aneuploidy was present. Adverse outcomes included abruption, oligohydramnios, preeclampsia, preterm membrane rupture, preterm delivery, stillbirth, birthweight <10th centile, and admission to neonatal intensive care unit (NICU). RESULTS: A total of 538 women had 1,076 pregnancies meeting inclusion criteria; 12/515 (2.3%) of women with a normal MSAFP, 28/470 (6.0%) with a normal hCG, and 11/504 (2.2%) with a normal E3 in the first pregnancy had an anomalous result for the respective analyte in the second pregnancy. In contrast, only 4/23 (17.4%) patients with an elevated MSAFP (P = 0.003), 14/44 (31.8%) with an elevated hCG (P < 0.001), and 2/10 (20.0%) with a low E3 (P < 0.025) in the first pregnancy had the same analyte anomaly recur in the second pregnancy. The odds ratios for recurrent elevated MSAFP, hCG, and low E3 were 7.5, 5.3, and 9.2, respectively. Adverse perinatal outcomes occurred with similar frequency, regardless of MSAFP, hCG, or E3 results in consecutive pregnancies, using women with normal MSAFP, hCG, and E3 results in one or both pregnancies as controls. CONCLUSIONS: Women experiencing an anomalous serum analyte in one pregnancy are at significant risk to experience the same analyte result in a subsequent pregnancy.     

Prenatal Characteristics of Congenital Nephrosis

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid α-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included.

A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained.

Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7–27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47–128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1–38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4–80.9).

MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.     

Unexplained elevated maternal serum beta-HCG concentration and adverse pregnancy outcome

OBJECTIVE: To investigate the association between unexplained elevated maternal serum beta-Human chorionic gonadotrophin (HCG) in the second trimester of pregnancy and adverse pregnancy outcome. METHODS: In a case-controlled study of 3463 women who opted for second-trimester serum screening for Down syndrome, 142 were found to have a serum beta-HCG of > or =3.5 multiples of the median (MoM), 56 of whom had a serum beta-HCG of > or =5.0 MoM. These women were compared with a control group of women with serum beta-HCG within the 95% confidence interval around the median. RESULTS: In the elevated beta-HCG group (> or =5 MoM) significantly more babies required admission to the special care baby unit (p = 0.02) and were small for gestational age (SGA) (p = 0.03). The mean birth weight was also significantly lower in the group with elevated beta-HCG. Women with a serum beta-HCG of > or =5, > or =6, > or =7 or > or =8 MoM were associated with SGA babies in 40, 44, 64 and 86% respectively. All babies born to the six women with beta-HCG of 8.75-24.1 MoM were SGA. CONCLUSION: Increased surveillance is necessary in pregnancies where the maternal serum beta-HCG in the second trimester is inexplicably elevated to > or =5 MoM.     

Diagnostic evaluation of women experiencing repeated in vitro fertilization failure

OBJECTIVE: The aim of the study was to propose a set of tests to clarify the diagnosis of repeated implantation failure in patients undergoing in vitro fertilization (IVF). STUDY DESIGN: Fifty-nine patients with at least two unsuccessful IVF attempts were included in the study. Blood samples were evaluated for the presence of underlying thyroid abnormalities, antiphospholipid antibodies (aPL), increased levels of natural killer cells (NK), inherited thrombophilia and mouse embryo assay factor (MEA-f). The same tests were performed on 20 normal fertile control patients. RESULTS: Seventy-six percent of IVF patients showed at least one abnormal result. This incidence was higher with respect to that found among control patients (45%). The prevalence of thyroid abnormalities, aPL and increased NK level was higher in IVF patients whereas no differences were observed in terms of prevalence of inherited thrombophilias and MEA-f. CONCLUSIONS: A better understanding of reproductive failure mechanisms should allow an effective diagnostic flow chart and a focused therapeutic option for patients experiencing repeated IVF failure. With this objective in mind, our data provide two important results: thyroid abnormalities, aPL and increased NK levels are more prevalent in women experiencing IVF failure. No evidence was found for an association between inherited thrombophilia and MEA-f and failure to achieve pregnancy after IVF.     

Association of maternal serum alpha-fetoprotein with persistent placenta previa.

OBJECTIVE: To evaluate the relationship between maternal serum alpha-fetoprotein (MSAFP) and the risk of persistent placenta previa. METHODS: We conducted a retrospective cohort study of singleton pregnancies with sonographic evidence of placenta previa at 15-20 weeks' gestation, between October 1991 and August 2000. Only pregnancies with MSAFP determination at 15-20 weeks' gestation and non-anomalous live-born infants > or =24 weeks' gestation were included. Pregnancies in which Cesarean delivery was performed for placenta previa were considered persistent; this was the primary outcome. RESULTS: Of 275 women with previa at 15-20 weeks' gestation, 33 (12%) had previa at delivery. Trend analysis revealed a greater likelihood of persistent previa with increasing MSAFP values (p=0.01). Mid-trimester MSAFP <1 multiple of the median (MoM) was associated with a decreased incidence of persistence of 4%, significantly less than the risk at > or =1 MoM (16%; p=0.01). CONCLUSIONS: There is an association between increasing MSAFP values and greater likelihood of persistent placenta previa. An MSAFP value <1 MoM is associated with a reduction in the risk of persistence of previa to delivery.     

Preconception counseling for women with thrombophilia

Inherited thrombophilias are a heterogeneous group of coagulation disorders that predispose individuals to thromboembolic events. This group of conditions is the major risk factor for thromboembolism during pregnancy and the puerperium. In addition, thrombophilias have been associated with several adverse obstetric events, including pregnancy loss, preeclampsia, placental abruption, and intrauterine growth restriction. An increased risk for these obstetric complications has prompted many authorities to recommend screening and treating pregnant women for thrombophilias. Optimal obstetric management, however, is controversial as thrombophilias are common and many affected individuals are asymptomatic. Indeed, pregnancy outcome in most women with thrombophilias is normal. The most commonly identified inherited thrombophilias are the factor V Leiden and prothrombin G20210A gene mutations. More rare thrombophilias include protein C and S deficiencies, antithrombin III deficiency. Although relatively common, the association between hyperhomocysteinemia and associated mutations (such as the C677 T methylenetetrahydro-folate reductase) and obstetric complications is controversial.