Late Pregnancy Complications Research Articles

Antithrombotic therapy to prevent miscarriages

Since the original publications on the relation between thrombophilias and adverse pregnancy outcome in the mid-1990s, more and more obstetricians and gynaecologists started to use heparin and/or low-molecular weight heparin (LMWH) empirically for secondary prevention of late pregnancy complications and the prevention of miscarriages in couples presenting with recurrent pregnancy loss.

Inherited Antithrombin Deficiency and Pregnancy: Maternal and Fetal Outcomes

The risk of a venous thromboembolism (VTE) is 4 to 5 times higher among pregnant women than nonpregnant women. Although studies have shown an association between different thrombophilias and pregnancy complications, several extensive reviews and meta-analyses published in the last decade did not find a relationship between inherited thrombophilias and adverse pregnancy outcomes. Antithrombin (AT) deficiency is uncommon among the inherited thrombophilias, and published data on its influence on pregnancy outcome are limited and controversial. This descriptive retrospective study investigated the effects of inherited AT deficiency on pregnancy outcomes among women with this condition. The participants were 9 women with known inherited AT deficiency and at least one pregnancy who have been managed at the study site, a university hospital in Spain. Data on maternal thrombotic complications and pregnancy outcomes among women with AT deficiency were obtained from the hospital medical records. Relatives with known AT deficiency who had no pregnancies managed at the study site were excluded. During the study period, the 9 women with inherited AT deficiency had 18 spontaneous gestations. In 12 (66.7%) of the 18 pregnancies, the women received anticoagulant therapy with low-molecular weight heparin. However, the other 6 (33.3%) were not given anticoagulants because AT deficiency was unknown at that time. During pregnancy and the puerperium, 3 (16.7%) episodes of VTE were recorded; none occurred while the woman was taking heparin. Ten adverse outcomes occurred in 6 of the 18 spontaneous pregnancies (33%), including 5 (33.3%) with intrauterine growth restriction, 2 (11.1%) with spontaneous abortion, 2 (11.1%) with stillbirth, 1 each (6.7%) with placental abruption and preeclampsia, and 3 (23.1%) with intrapartum fetal distress; 2 of these events occurred in one pregnancy and 3 events occurred in another. In 4 of the affected pregnancies, the woman was taking heparin. There was no association between AT activity and pregnancy complications. Fewer pregnancy complications were found among women who had received anticoagulant treatment. These findings show a high incidence of late pregnancy complications and poor pregnancy outcomes among AT-deficient women. A high risk of VTE during pregnancy and the puerperium was found in these women. The study is limited by its small sample size owing to the low prevalence of AT deficiency.

Early fetal growth: concepts and pitfalls

Early fetal growth: concepts and pitfalls

First-Trimester Determination of Complications of Late Pregnancy

THE TERM HARELIP, USED TO DESCRIBE FACIAL CLEFTS, arose from a belief that the defect originated from the mother being startled by a hare during her pregnancy. Theconcept that congenital structural abnormalities of the fetus developed from events during pregnancy is called maternal impression and it continued to be seriously discussedwell intothe19thcentury. However, it isnowknown that the vast majority of congenital structural fetal malformationsareaconsequenceofaneuploidyorabnormalembryonic development in the first 8 weeks postconception. A series of studies suggest that other complications of pregnancy, such as intrauterinegrowthrestriction,pretermbirth,andstillbirth, alsohave theirorigins, at least inpart, inveryearlypregnancy. These observations raise the possibility that women who are at increased risk of adverse outcome in late pregnancy may be identifiable in the first trimester of pregnancy, with the potential for trials of screening and early intervention. The study in this issue of JAMA by Mook-Kanamori et al presents important new information about first-trimester determination of growth restriction. The authors measured the difference between the expected size of the fetus in the first trimester, based on menstrual history, and the actual size of the fetus, assessed by ultrasound. They demonstrated that when the fetus was smaller than expected in the first trimester, there was an increased risk of preterm birth, delivery of a small-for-gestational age (SGA) infant, and delivery of a low-birth-weight infant. The associations were independent of other maternal characteristics and the risk of these outcomes was increased 2 to 3 fold among fetuses in the lowest quintile of first-trimester growth. One of the problems in assessing fetal growth is to differentiate between infants who are growth restricted (grew to less than their genetically determined potential) from infants who are constitutionally small. The study by MookKanamori et al suggests that the associations between firsttrimester growth and the risk of delivering an SGA infant are due to growth restriction because smaller than expected size of the fetus in the first trimester was unrelated to maternal weight and height. Moreover, smaller size in the first trimester was associated with more rapid growth in infancy, suggesting ex utero catch-up growth to compensate for true growth restriction in utero. The findings of Mook-Kanamori et al confirm a previous study thatdemonstratedan increased riskof lowbirthweight, delivery of an SGA infant, and preterm birth among spontaneousconceptionsinwhichthefetuswassmallerthanexpected in the first trimester. The relative weakness of both studies is their reliance on menstrual data to establish the expected size of the fetus inearlypregnancy.Theseanalysesassumethat fertilization took place on day 14 of the menstrual cycle and the first day of the last menstrual period is taken as day 1. It is possible that fertilizationat laterdays in themenstrual cyclecould be associated with adverse outcomes and this would also be associated with smaller than expected size of the fetus in the first trimester. However, secondary analysis of a large-scale, multicenter cohort study of Down syndrome screening conducted in the United States analyzed the associations between early pregnancy growth measurements and the risk of delivering an SGA infant among approximately 1000 women who conceived after use of assisted reproductive technology, and for whom the date of conception was known. This study confirmeda linearrelationshipbetweensmaller thanexpectedsize in the first trimester and both lower birth weight and the proportionofSGAinfants.Hence, theassociation is still observed when the timing of conception is known. The analysis reported by Mook-Kanamori et al also described the maternal characteristics associated with reduced growth in the first trimester. After taking into account multiple comparisons, multivariate analyses demonstrated a significant positive relationship between crown to rump length and maternal age and a significant negative relationship between crown to rump length and hematocrit. The association between poor first-trimester growth and a high hematocrit level is of particular interest. Hematocrit normally declines in early pregnancy and higher hematocrit in early pregnancy is associated with increased perinatal mortality. The association could reflect a direct influence of high hematocrit levels on pregnancy (eg, through alteration in uterine blood flow). Alternatively, it could indicate that the absence of the normal decrease in hematocrit is a marker of some other determi-

James Willocks and the Innovation of Fetal Cephalometry

James Willocks (1928-2004), a Glasgow obstetrician, was an important pioneer of obstetric ultrasound and the originator of the first clinically useful technique of fetal cephalometry. He collaborated with Tom Duggan, an engineer, who designed and built an electronic cephalometer to be used in conjunction with a Kelvin Hughes industrial flaw detector. Working in the Royal Maternity Hospital, Willocks was able to measure the biparietal diameter to an accuracy of better than 2mm. This major innovation enabled fetal growth in the third trimester to be accurately charted and thus greatly improved the detection of placental insufficiency, as well as the management of antepartum haemorrhage, hypertension and other complications of late pregnancy.

Does Continuous Use of Metformin Throughout Pregnancy Improve Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome?

Aim: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. Methods: This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. Results: All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4–16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P < 0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P < 0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P < 0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. Conclusion: In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.

P2 Tissue factor pathway inhibitor (TFPI) in normal and complicated pregnancy

s selected for Poster Presentation P1 Reduced fibrinolytic activity in women after delivery in Benin City, Nigeria J.O. Osakue, O.I. Ajayi, A. Ande. Department of Physiology and Obstetrics/Gynecology, University of Benin and University of Benin Teaching Hospital, Nigeria Abstract: Fibrinolytic activity (using ELT) and plasma fibrinogen concentration in 50 mothers just after delivery were assessed (giving 50 mothers and 50 cord samples). Also 50 healthy women without delivery were used as controls. All these were to ascertain if there is any change in fibrinolytic activity in women after delivery. Methodology: Fifty women (22 35 years) with normal delivery were used for this study (150 samples). Blood samples were collected and investigations were performed before noon. ELT (fibrinolytic activity) was carried out using the method of Cecil Hougie (1986) and plasma fibrinogen concentration (PFC) was estimated using Ingram clot weight method (1961). The t-distribution test was used to test for level of significance between mean of both test and controls, P< 0.05 was significant. Results: The results show significantly lower fibrinolytic activity in mothers and significantly higher fibrinogen concentration than controls (P< 0.05). Maternal PFC and ELT values were also significantly higher than cord samples. Conclusion: There is reduced fibrinolytic activity and increased fibrinogen concentration in mothers immediately after delivery. This may be a proctective coagulative mechanism against excessive post partum haemorhage. Fibrinolytic activity (using ELT) and plasma fibrinogen concentration in 50 mothers just after delivery were assessed (giving 50 mothers and 50 cord samples). Also 50 healthy women without delivery were used as controls. All these were to ascertain if there is any change in fibrinolytic activity in women after delivery. Methodology: Fifty women (22 35 years) with normal delivery were used for this study (150 samples). Blood samples were collected and investigations were performed before noon. ELT (fibrinolytic activity) was carried out using the method of Cecil Hougie (1986) and plasma fibrinogen concentration (PFC) was estimated using Ingram clot weight method (1961). The t-distribution test was used to test for level of significance between mean of both test and controls, P< 0.05 was significant. Results: The results show significantly lower fibrinolytic activity in mothers and significantly higher fibrinogen concentration than controls (P< 0.05). Maternal PFC and ELT values were also significantly higher than cord samples. Conclusion: There is reduced fibrinolytic activity and increased fibrinogen concentration in mothers immediately after delivery. This may be a proctective coagulative mechanism against excessive post partum haemorhage. P2 Tissue factor pathway inhibitor (TFPI) in normal and complicated pregnancy A. Ittel1, F. Bretelle2, M.A. Coulomb2, L. Boubli2, G. Sebahoun1, D. Arnoux1. Departments of 1Hematology and 2Obstetrics, CHU Nord, Marseille, France TFPI plays a crucial role in haemostatic balance by regulating the initial step of blood coagulation. Since it is expressed by both endothelial and trophoblastic cells; TFPI could be of particular importance at the placental level. In this study, we measured free TFPI antigen (elisa method; Diagnostica Stago) in 4 groups of women: (1) 35 healthy nonpregnant women with no oral contraception and no history of pregnancy complications; (2) 47 women at the beginning (<12 weeks) and (3) 103 women at the end of a normal pregnancy; (4) women with late pregnancy complications (IUFD, IUFGR, PE) at the time of obstetrical event (n = 75) and/or at distance of pregnancy (n = 66). In normal pregnancy, mean TFPI level at delivery was significantly higher than in the first trimester (7.5 vs 5.2 ng /ml; p < 0.001) but lower than in non-pregnant controls (9.1 ng /ml; p = 0.002). In patients, TFPI levels varied widely at the time of the adverse event but were found significantly lower than in non-pregnant controls when measured at distance of pregnancy. (mean 6.6 vs 9.1 ng/ml, p < 0.001), TFPI level being below the lowest value of controls in 23% of patients. Among other pro-thrombotic abnormalities, low TFPI levels could play a role in the occurrence of placental vascular complications. P3 A score based prevention strategy of venous thromboembolism in pregnant women Y. Dargaud1, L. Rugeri1, M.C. Vergnes2, B. Arnutti3, P. Amaranto4, C. Negrier1, J. Ninet5, P. Gaucherand6, M.C. Trzeciak1. 1Unite d’Hemostase Clinique, CHU de Lyon, France, 2Laboratoire d’Hemostase, CHU de Bordeaux, France, 3Service d’Hemostase et d’Hemovigilance, CH de Valence, France, 4Service de Medecine Interne, CH de Roanne, France, 5Service de Medecine Interne, CHU de Lyon, France, 6Service de Gynecologie Obstetrique, CHU de Lyon, France Objective: To evaluate the usefulness of score based management of pregnancies with high risk of venous thromboembolism (VTE). Table 1. VTE risk prediction score

The Association Between Antiphospholipid Antibodies and Adverse Pregnancy Outcomes: A Metaanalysis.

BACKGROUND: The Sapporo criteria for the diagnosis of the antiphospholipid syndrome (APS) are based on the presence of antiphospholipid antibodies (APLA) and clinical criteria. Although pre-eclampsia, intra-uterine growth restriction (IUGR), late fetal loss and placental abruption, collectively termed “placenta mediated complications”, are recognized as clinical criteria for the APS, their association with APLA remains controversial.OBJECTIVE: This review was conducted to evaluate the association between APLA (anticardiolipin antibodies, lupus anticoagulant, anti B2 glycoprotein 1 antibodies) and placenta mediated complications in untreated women without autoimmune diseases.METHODS: We performed a systematic review of published case-control, cohort and cross sectional studies using MEDLINE (1975 to October week 2 2007), EMBASE 16 (1980 to 2007 week 42) and all EBM Reviews (3rd quarter of 2007). For eligible studies, the rates of adverse pregnancy outcomes were compared between patients with and without specific APLA. Pooled odds ratios with 95% CI were generated using random-effects models.RESULTS: Our search strategy identified 1204 potentially relevant studies. Twenty five were included in the final analysis. Results are outlined in table 1.CONCLUSION: The association between various APLA and pregnancy complications is for the most part weak and inconsistent. There is currently insufficient data to support a significant link between anti-B2 glycoprotein 1 antibodies and pregnancy morbidity. Caution should be used when establishing a diagnosis of APS based on the presence of any APLA, particularly anti-B2 glycoprotein 1 antibodies, in the setting of late pregnancy complications. Table 1 Association Between APLA and Adverse Pregnancy OutcomesPre-eclampsia OR (95%CI) # studies / participantsIUGR OR (95%CI) # studies / participantsPlacental abruption OR (95%CI) # studies / participantsLate fetal loss OR (95%CI) # studies / participantsLA2.88 (1.42, 5.87) 11 / 60853.51 (1.38, 8.93) 4 / 32320.78 (0.13, 4.80) 2 / 2263.56 (0.12, 106.05) 3 / 3870aCL (IgG/IgM)1.71 (1.09, 2.70) 21 / 97222.31 (0.74, 7.17) 6 / 57531.35 (0.45, 4.02) 4 / 12743.86 (1.14, 13.07) 7 / 5963aCL IgG1.65 (0.84, 3.22) 15 / 36276.16 (2.50, 15.18) 2 / 10061.87 (0.21, 16.83) 2 / 50010.06 (0.88, 114.96) 2 / 1006aCL IgM1.36 (0.93, 1.97) 13 / 53970.75 (0.19, 2.93) 2 / 30020.96 (0.24, 3.85) 2 / 5001.37 (0.42, 4.46) 3 / 3212anti- B2GP1 (IgG/IgM)2.97 (0.47, 18.69) 4 / 222520.03 (4.59, 87.43) 1 / 11082.64 (0.14, 50.63) 1 / 5106.74 (0.24, 191.23) 3 / 1828anti- B2GP1 IgG0.87 (0.38, 2.01) 2 / 607N/A 0 / 0N/A 0 / 00.52 (0.02, 11.02) 1 / 212anti- B2GP1 IgM0.37 (0.16, 0.85) 1 / 400N/A 0 / 0N/A 0 / 01.32 (0.24, 7.42) 1 / 210LA: Lupus anticoagulant; aCL: Anticardiolipin antibodies; Anti-B2 GP1 antibodies: Anti-B2 glycoprotein 1 antibodiesitalic characters indicate statistically significant associations

Association of Elevated Soluble P-Selectin Levels and Fetal Loss in Women with a History of Venous Thromboembolism.

Pregnancy is a hypercoagulable state with an increased risk of venous thromboembolism (VTE). Furthermore, accumulating evidence support the hypothesis that pregnancy complications such as fetal loss are associated with both inherited and acquired thrombophilic defects which may predispose to thrombosis of the placental vasculature and lead to subsequent fetal loss. In recent studies the cell adhesion molecule P-selectin has been identified to be a strong risk factor for VTE. Interestingly, soluble P-selectin (sP-selectin) plasma levels were previously reported to increase during pregnancy. Whether P-selectin is also associated with fetal loss in women with a history of venous thromboembolism, is not known yet. Therefore, the aim of our present study was to investigate the significance of elevated sP-selectin levels for fetal loss (e.g. miscarriage or stillbirth) in women with a history of VTE. We retrospectively evaluated data on pregnancy-associated complications in 304 women (mean age [+/-SD]: 45.6 [+/-11.5] yrs) with a history of VTE. sP-selectin plasma levels were measured using a sensitive ELISA (sP-selectin Immunoassay, R&D Systems®, Minneapolis, MN, USA). At the time of measurement of sP-selectin none of the women was pregnant and did not have an acute event of VTE. The mean age (±SD) of patients at the time of the VTE event was 31.3 (+/- 8.4) yrs. The prevalence of miscarriage (defined as intrauterine fetal death before the 24th week of gestation or when fetus weighed <500 g) in our study population was 21.8% and the prevalence of stillbirth (defined as intrauterine fetal death at or after the 24th week of gestation) was 4.3%. Median (interquartile range [IQR]) sP-selectin level of the total study population was 38.0 [21.7-44.4] ng/mL. The cut-off point for elevated sP-selectin was set at 44.4 ng/mL, which represents the 75th percentile of sP-selectin levels of the study population. The prevalence of stillbirth was significantly higher in subjects with elevated sP-selectin levels compared to those with lower levels (10.5% vs. 2.6%, p=0.008), whereas no statistically significant difference in prevalence of miscarriage was observed between women with and without elevated sP-selectin (17.1% vs. 22.9%, p=0.303). The odds ratio [95% CI] of elevated sP-selectin for stillbirth was 4.2 [1.5-12.7] and for miscarriage 0.7 [0.4-1.3]. In summary, elevated sP-selectin plasma levels were associated with a 4-fold risk for stillbirth in women with a history of VTE. Our data support a possible role of P-selectin in the aetiology of late pregnancy complications.

Pregnancy Outcome in Women with Antiphospholipid Antibodies: Report on a Retrospective Study

Antiphospholipid syndrome (APS) represents a serious risk factor in pregnancy resulting in several complications, leading to fetal loss and hemostatic complications. In this dedicated report, we describe our experiences in the treatment of pregnancies in patients with APS. The retrospective data from 140 pregnant women were investigated, and the treatment results of 121 patients were recorded. We studied two groups of patients receiving different treatment. The first group (N = 78) received the standard therapy with low-weight-molecular heparin (dalteparin 5000 U or certoparin 3000 U daily) and aspirin (100 mg daily) and in the second group (N = 43) an additional 0.2 g/kg intravenous immunoglobulin (IVIG). Outcomes were 74.3% and 83.7% live births in the first group and in the second group, respectively. The abortion rate was similar in both groups (11.5% vs. 11.6%). The late complication rate was lower in the second group (5.8% vs. 14.1%, P < 0.05) than in the group with standard therapy. Interestingly, we found a trend to higher percentage (> 12%) of natural killer (NK) cells in patients with pregnancy complications (60% vs. 12%, P < 0.05). Our retrospective data shows an improvement of late pregnancy complications by additional use of IVIG. It is possible that IVIG influences higher NK cell activity in patients with previous pregnancy complications.

Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome?

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4-16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P<0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P<0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P<0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.

Plasma levels of microparticles at 24 weeks of gestation do not predict subsequent pregnancy complications

To discern whether plasma levels of microparticles (MPs) measured at 24 weeks of gestation predict late complications of pregnancy. Secondary analysis of samples obtained prospectively. Large academic medical center. Two hundred sixty-two healthy women selected from 642 nulliparous women with singleton pregnancies. Sampling for blood cell MPs and thrombophilias at 24 weeks of gestation and measurements of blood flow resistance in uterine, placental, and umbilical arteries at 24 and 31 to 33 weeks of gestation. Relationship between levels of MPs and late pregnancy complications, thrombophilias, and blood flow resistance. Flow cytometry only detected MPs derived from endothelial cells (CD31(+)) and platelet (CD41(+)). No statistically significant correlation was found between levels of CD31(+) or CD41(+) MPs and subsequent occurrence of pregnancy-induced hypertension, preeclampsia, intrauterine growth restriction, or small for gestational age infants. Nor was there a statistically significant correlation with blood flow resistance parameters at 24 weeks of gestation (except for the left uterine artery) or at 31 to 33 weeks of gestation. Levels of these MPs in thrombophilic and nonthrombophilic women were similar. Levels of circulating MPs at 24 weeks of gestation had no predictive value for subsequent development of pregnancy-induced hypertension, preeclampsia, intrauterine growth restriction, or small for gestational age infants.

Stress and reproductive failure: past notions, present insights and future directions.

Maternal stress perception is frequently alleged as a cause of infertility, miscarriages, late pregnancy complications or impaired fetal development. The purpose of the present review is to critically assess the biological and epidemiological evidence that considers the plausibility of a stress link to human reproductive failure. All epidemiological studies published between 1980 and 2007 that tested the link between stress exposure and impaired reproductive success in humans were identified. Study outcomes were evaluated on the basis of how associations were predicted, tested and integrated with theories of etiology arising from recent scientific developments in the basic sciences. Further, published evidence arising from basic science research has been assessed in order to provide a mechanistic concept and biological evidence for the link between stress perception and reproductive success. Biological evidence points to an immune-endocrine disequilibrium in response to stress and describes a hierarchy of biological mediators involved in a stress trigger to reproductive failure. Epidemiological evidence presents positive correlations between various pregnancy failure outcomes with pre-conception negative life events and elevated daily urinary cortisol. Strikingly, a relatively new conceptual approach integrating the two strands of evidence suggests the programming of stress susceptibility in mother and fetus via a so-called pregnancy stress syndrome. An increasing specificity of knowledge is available about the types and impact of biological and social pathways involved in maternal stress responses. The present evidence is sufficient to warrant a reconsideration of conventional views on the etiology of reproductive failure. Physicians and patients will benefit from the adaptation of this integrated evidence to daily clinical practice.

Pregnancy-related acute renal failure: A single-center experience.

Pregnancy-related acute renal failure (ARF) is a common occurrence and is associated with substantial maternal and fetal mortality. It also bears a high risk of bilateral renal cortical necrosis. We conducted this study to evaluate the contributing factors and to assess the frequency of cortical necrosis. In this prospective study, of the 772 patients with ARF admitted at our institute between January 2004 and May 2006, 70 had ARF associated with pregnancy complications. ARF was diagnosed by documenting oliguria (urine output <400 ml/d) or mounting azotemia in the presence of normal urine output. (serum creatinine >2 mg%). Renal biopsy was performed if a patient was found to be oliguric or required dialysis support at the end of three weeks. The incidence of pregnancy-related ARF was 9.06%. Approximately 20% cases occurred due to postabortal complications in early pregnancy and 80% following complications in late pregnancy. Puerperal sepsis was the most common etiological factor in 61.42% of the patients. Preeclampsia accounted for 28.57% of ARF. Two-thirds of patients recovered with dialysis and supportive care. The incidence of biopsy proven renal cortical necrosis was 14.8% (10 of the 70 patients). The incidence of renal cortical necrosis was 28.57% in the early pregnancy group and 10.71% in the late pregnancy group. Postabortal sepsis was the most common precipitating event for renal cortical necrosis. Maternal mortality was 18.57%. Sepsis accounted for a majority of deaths (61.53%). Pregnancy-related ARF is common in western India. Puerperal sepsis is the most frequent etiological factor. Renal cortical necrosis is common and postabortal sepsis was the most common precipitating event. Sepsis accounted for a majority of maternal mortality.

Neumomediastino y enfisema subcutáneo extenso tras parto eutócico

Spontaneous pneumomediastinum associated with subcutaneous emphysema is a rare, though life-threatening, complication of late pregnancy and labor. We report the case of a primipara who, after undergoing normal labor and delivery of a normal-weight baby, developed pneumomediastinum and extensive subcutaneous emphysema with significant symptoms within minutes of delivery. This peripartum complication is usually self-limiting when the aggravating factors are no louguer present. Management includes strict monitoring of the patient and conservative treatment of symptoms.

Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes

Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD). Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM. The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A, ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224-288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-restricted fragment length polymorphism or sequence specific primer assays. For all loci, genotype distribution was in agreement with Hardy-Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls). Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50% vs. 40% in controls). Physically unlinked genes involved in RAS segregate independently. The AGT 174-235 region is associated with PD-PRM in this population.

Fetal Growth in Early Pregnancy and Risk of Delivering Low Birth Weight Infant: Prospective Cohort Study

Placental function in early pregnancy reportedly is associated with a risk of low birth weight. This study was planned to learn whether fetal growth in the first trimester is associated with the duration of pregnancy, birth weight, and/or the risk of having a small for gestational age (SGA) infant. Among more than 38,000 women taking part in a prospective multicenter study in the years 1999-2003 were 976 who conceived by assisted reproductive technology, had crown-rump length measured by ultrasound in the first trimester, and delivered a live singleton infant with no evidence of congenital or chromosomal abnormality. The difference between actual and predicted crown-rump length or the difference in days of gestation (AGA) was the postconceptional age as estimated by crown-rump length minus the actual days since conception. Birth weight varied linearly with AGA; a 1-day increase in AGA correlated with a 28-g increase in birth weight. Adjusting for maternal characteristics and pregnancy complications did not significantly alter this association, but it was significantly attenuated by adjusting for duration of pregnancy. The duration of pregnancy also was proportional to AGA; a 1-day increase in AGA was associated with a 0.4-day increase in duration. Again, neither maternal features nor pregnancy complications significantly altered this association. The AGA explained about 2% of variation in birth weight. The rate of SGA infants was 11.5%. The risk varied inversely with fetal growth in the first trimester; a 1-day increase in AGA was associated with a 13% reduction in risk. Adjusting for maternal characteristics and pregnancy complications did not significantly alter the likelihood of delivering a SGA infant. Gestational age at the time of ultrasonography did not significantly influence either the association between AGA and birth weight or the risk of having a SGA infant. These findings show that fetal size in the first trimester of pregnancy is associated with birth weight They add to growing evidence that conditions in very early pregnancy ultimately influence the duration of pregnancy and the risk of late-pregnancy complications.

EVALUATION OF THROMBOPHILIA SCREENING IN WOMEN WITH OBSTETRICAL COMPLICATIONS: A “REAL WORLD” EXPERIENCE

Introduction: Growing evidence suggests that thrombophilia is associated with adverse pregnancy outcomes. As a result, thrombophilia screening is increasingly requested for women with obstetrical complications. Methods: We evaluated the utilization of thrombophilia screening at a large academic tertiary centre requested by obstetricians for women with either early or late pregnancy complications. The indications, appropriateness and results of 199 thrombophilia screenings performed between July 2003 and June 2006 for adverse pregnancy outcomes were retrospectively examined. Results: Of the screenings, 89 were ordered for early miscarriages and 122 for late pregnancy complications (intra-uterine foetal death, intra-uterine growth retardation, abruptio placentae, preeclampsia and/or hellp syndrome). Only 77 patients reported at least three successive early foetal losses. In the whole population, 56 (28.1%) women were pregnant and 27 (13.6%) on oral contraception at time of referral. In many patients screening was requested before completion of the routine work-up. Despite these limitations, a thrombophilic abnormality was documented in 26% women referred for early recurrent miscarriages. In this subgroup, factor V Leiden was the most prevalent thrombophilia (n=8, 10.4%). For women with late complications, 19.7% had a thrombophilic trait. The subgroup referred for third trimester foetal loss showed the highest prevalence of positive screening (41.7%), mostly Factor V Leiden (n=10, 8.2%). Conclusions: In spite of the growing awareness of the negative impact of thrombophilia on pregnancy outcomes, screening is frequently ordered sub-optimally. When indicated, screening should preferably be performed in the absence of confounding clinical variables (pregnancy, oral contraception) for women with appropriate indications and after completion of the routine work-up.

Maternal Obesity in Early Pregnancy and Risk of Spontaneous and Elective Preterm Deliveries: A Retrospective Cohort Study

Maternal obesity is associated with an increased risk of late pregnancy complications such as stillbirth, gestational diabetes, and cesarean delivery. A low body mass index (BMI), however, has been reported to correlate with an increased risk of preterm delivery, and in some studies a BMI above the “normal” range is associated with decreased rate of spontaneous preterm birth. This study, based on the Scottish Morbidity Record, examined the association between maternal BMI and the risk of preterm delivery in 187,290 women. Preterm delivery was defined as childbirth before 37 weeks’ gestation. With increasing BMI, the risk of spontaneous preterm delivery decreased while the risk of elective preterm delivery increased. Elective preterm delivery was associated with a reduced risk of neonatal death (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55–0.94), and an increased risk of delivering an ELBW infant who survived for 12 months (RR, 1.92; 95% CI, 1.49–2.47). However, the net effect of BMI on these adverse outcomes varied by parity. Nulliparous women with a BMI ≥35 had an increased risk of overall preterm birth (OR, 1.34; 95% CI, 1.15–1.56) and elective preterm birth (OR, 2.13; 95% CI, 1.75–2.58), of which 40% were due to preeclampsia. They were also at increased risk of neonatal death (OR, 2.77; 95% CI, 1.54–4.99) and an ELBW infant still alive at one year (OR, 3.31; 95% CI, 2.13–5.14). In contrast, multiparous women with a BMI ≥35 were not at increased risk of overall preterm birth, neonatal death, or ELBW infant alive at one year. They were at increased risk of elective preterm birth, although to a lesser degree than nulliparas (OR, 1.45; 95% CI, 1.21–1.75) and only 18% of their elective preterm deliveries were due to preeclampsia. These findings show that maternal obesity is associated with an increased risk of preterm delivery. Nulliparous obese women are at highest risk of elective preterm delivery, probably reflecting their increased risk of preeclampsia, as well as increased perinatal mortality and long-term disability in surviving offspring.

Acute fatty liver of pregnancy; three cases and discussion of analgesia and anaesthesia

Acute fatty liver of pregnancy is a rare, potentially fatal, complication of late pregnancy. The incidence is estimated at 1:7000-1:15000 pregnancies. Presentation is classically with malaise, nausea and vomiting, abdominal pain and rarely encephalopathy. Prolongation of laboratory clotting tests is an early feature. Ultrasound examination of the liver is performed to exclude biliary stasis. Rapid clinical deterioration may occur and urgent delivery should be organised. Anaesthetists form part of a multidisciplinary approach before, during and after delivery but there are few reports of anaesthetic involvement. One dilemma facing an anaesthetist called to assist in these cases is the potentially negative effect of general anaesthesia on hepatic encephalopathy versus the risks associated with regional anaesthesia in the presence of coagulopathy. Postoperative analgesia may also be complicated by impaired renal and hepatic function. We present three cases that occurred in our unit in a 6-month period illustrating the spectrum of disease severity and the successful use of different anaesthetic techniques to facilitate management including delivery.