Two distinct GUCY2C circuits with PMV (hypothalamic) and SN/VTA (midbrain) origin.

Guanylyl cyclase C (GUCY2C) is the afferent central receptor in the gut-brain endocrine axis regulated by the anorexigenic intestinal hormone uroguanylin. GUCY2C mRNA and protein are produced in the hypothalamus, a major center regulating appetite and metabolic homeostasis. Further, GUCY2C mRNA and protein are expressed in the ventral midbrain, a principal structure regulating hedonic reward from behaviors including eating. While GUCY2C is expressed in hypothalamus and midbrain, its precise neuroanatomical organization and relationship with circuits regulating satiety remain unknown. Here, we reveal that hypothalamic GUCY2C mRNA is confined to the ventral premammillary nucleus (PMV), while in midbrain it is produced by neurons in the ventral tegmental area (VTA) and substantia nigra (SN). GUCY2C in the PMV is produced by 46% of neurons expressing anorexigenic leptin receptors, while in the VTA/SN it is produced in most tyrosine hydroxylase-immunoreactive neurons. In contrast to mRNA, GUCY2C protein is widely distributed throughout the brain in canonical sites of PMV and VTA/SN axonal projections. Selective stereotaxic ablation of PMV or VTA/SN neurons eliminated GUCY2C only in their respective canonical projection sites. Conversely, specific anterograde tracer analyses of PMV or VTA/SN neurons confirmed distinct GUCY2C-immunoreactive axons projecting to those canonical locations. Together, these findings reveal two discrete neuronal circuits expressing GUCY2C originating in the PMV in the hypothalamus and in the VTA/SN in midbrain, which separately project to other sites throughout the brain. They suggest a structural basis for a role for the GUCY2C-uroguanylin gut-brain endocrine axis in regulating homeostatic and behavioral components contributing to satiety.

PP179. The influence of prior abortion on rates of gestational hypertension/pre-eclampsia and spontaneous preterm delivery in nulliparous women.

INTRODUCTION: Gestational hypertension/preeclampsia (GH) is clearly a heterogeneous condition of which the pathogenesis could be different in women with various risk factors. Nulliparity is a known risk factor for GH, however a previous abortion (spontaneous or induced) may be associated with a lower risk of GH. OBJECTIVES: To examine the effect of abortion history on rates of GH and spontaneous preterm delivery (SPTD) and in nulliparous women. METHODS: Nulliparous women with an initial prenatal screening at <13 weeks' gestation and a current singleton gestation delivering between 6/2006 and 6/2011 that voluntarily enrolled for risk assessment-case management services were identified from a database of clinical information. Excluded were women reporting a history of both spontaneous (SAB) and induced (IAB) abortions, or with a priori diagnosis of diabetes. Rates of SPTD and GH were compared between women with SAB or IAB history (AB group) and a reference group of primigravid women using Pearson's chi-square, Student's t, Kruskal-Wallis H, and Mann-Whitney U statistics. RESULTS: Of the 75,487 women studied, 5.7% (n=4288) reported a history of IAB and 24.3% (n=18,328) reported a history of SAB. Overall, 301 women (0.4%) experienced a SAB at <20 weeks in the index pregnancy. Of those 75,186 with delivery ⩾20 weeks, the incidence of SPTD was 6.1% in controls vs. 6.0% in the IAB/SAB group (p=0.550). Rates of GH were 10.2% in controls vs. 8.0% (p<0.001) in the AB group despite the AB group having significantly (p<0.001) higher rates of women of African-American race (8.5% vs. 5.5%); age >34years (23.9% vs. 10.0%); and obesity (19.6% vs. 16.6%). For women with >2 AB's significant differences were observed in rates of SPTD vs. controls (8.2% vs. 6.0%, p<0.001), but rates of GH were similar (9.2% vs. 10.2%, p=0.188). (1)p<0.001 vs. 0 AB group. CONCLUSION: In nulliparous women, prior AB is associated with a reduction in risk for GH. Risk for SPTD increases only in those with >2 prior AB's.

Assessment of the greenhouse effect impact of technologies used for energy recovery from municipal waste: a case for England.

Waste management activities contribute to global greenhouse gas emissions approximately by 4%. In particular the disposal of waste in landfills generates methane that has high global warming potential. Effective mitigation of greenhouse gas emissions is important and could provide environmental benefits and sustainable development, as well as reduce adverse impacts on public health. The European and UK waste policy force sustainable waste management and especially diversion from landfill, through reduction, reuse, recycling and composting, and recovery of value from waste. Energy from waste is a waste management option that could provide diversion from landfill and at the same time save a significant amount of greenhouse gas emissions, since it recovers energy from waste which usually replaces an equivalent amount of energy generated from fossil fuels. Energy from waste is a wide definition and includes technologies such as incineration of waste with energy recovery, or combustion of waste-derived fuels for energy production or advanced thermal treatment of waste with technologies such as gasification and pyrolysis, with energy recovery. The present study assessed the greenhouse gas emission impacts of three technologies that could be used for the treatment of Municipal Solid Waste in order to recover energy from it. These technologies are Mass Burn Incineration with energy recovery, Mechanical Biological Treatment via bio-drying and Mechanical Heat Treatment, which is a relatively new and uninvestigated method, compared to the other two. Mechanical Biological Treatment and Mechanical Heat Treatment can turn Municipal Solid Waste into Solid Recovered Fuel that could be combusted for energy production or replace other fuels in various industrial processes. The analysis showed that performance of these two technologies depends strongly on the final use of the produced fuel and they could produce GHG emissions savings only when there is end market for the fuel. On the other hand Mass Burn Incineration generates greenhouse gas emission savings when it recovers electricity and heat. Moreover the study found that the expected increase on the amount of Municipal Solid Waste treated for energy recovery in England by 2020 could save greenhouse gas emission, if certain Energy from Waste technologies would be applied, under certain conditions.

Sources and levels of potentially toxic elements in the biodegradable fraction of autoclaved non-segregated household waste and its compost/digestate.

Waste that reflected the average UK composition of household waste was treated by autoclaving at the three set pressure/temperature levels of 2.7 bar/130 degrees C, 6.2 bar/160 degrees C and 15.5 bar/200 degrees C. The biodegradable fraction of the autoclaved household waste (;floc') was manually separated by screening and underwent characterization for its Cd, Cr, Cu, Pb, Hg, Ni, and Zn content. Autoclaving did not guarantee the production of compost/digestate that met the UK specification for compost, BSi PAS100, without restrictions being made on the composition of the waste feedstock. Results indicate that the levels of Zn and Cd associated with floc materials alone could lead to compost limit values being exceeded. For all other potentially toxic elements (PTEs), the estimated excessive (i.e. above levels of compliance) PTEs levels for compost/digestate were mainly due to external (i.e. non-floc) materials, primarily electronic/electrical waste. Batteries may have also contributed to the high levels of Zn and Hg. In this study, for all PTEs examined, with the exception of Cd and Zn, autoclaving had a performance comparable to that of the most effective mechanical biological treatment systems.

Carbon--making the right choice for waste management in developing countries.

Due to initiatives such as the clean development mechanism (CDM), reducing greenhouse gas emissions for a developing country can offer an important route to attracting investment in a variety of qualifying project areas, including waste management. To date CDM projects have been largely confined to schemes that control emission from landfill, but projects that avoid landfilling are beginning to be submitted. In considering the waste options which might be suitable for developing countries certain ones, such as energy from waste, have been discounted for a range of reasons related primarily to the lack of technical and other support services required for these more sophisticated process trains. The paper focuses on six options: the base case of open dumping; three options for landfill (passive venting, gas capture with flaring, and gas capture with energy production), composting and anaerobic digestion with electricity production and composting of the digestate. A range of assumptions were necessary for making the comparisons based on the effective carbon emissions, and these assumptions will change from project to project. The highest impact in terms of carbon emissions was from using a sanitary landfill without either gas flaring or electricity production; this was worse than the baseline case using open dumpsites. Landfills with either flaring or energy production from the collected gas both produced similar positive carbon emissions, but these were substantially lower than both open dumping and sanitary landfill without flaring or energy production. Composting or anaerobic digestion with energy production and composting of the digestate were the two best options with composting being neutral in terms of carbon emissions and anaerobic digestion being carbon negative. These generic conclusions were tested for sensitivity by modifying the input waste composition and were found to be robust, suggesting that subject to local study to confirm assumptions made, the opportunity for developing CDM projects to attract investment to improved waste management infrastructure is significant. Kyoto credits in excess of 1 tCO2e/t of waste could be realised.

Postinfectious irritable bowel syndrome may occur after non-gastrointestinal and intestinal infection.

Postinfectious functional gastrointestinal disorders (FGIDs) may not be specific to gastroenteritis. This pilot study aimed to ascertain the 3- and 6-month incidence of functional gut disorders in people with non-gastrointestinal (GI) infection, gastroenteritis and healthy controls. This was a prospective study of three cohorts recruited from hospital (non-GI infections) and the community (others). FGIDs were diagnosed using self-completed Rome II modular questionnaires administered at baseline, 3 and 6 months. Thirty-six subjects with non-GI infection, 219 healthy subjects and 108 with bacterial gastroenteritis participated. No difference in incidence of FGID was detected between the GI and non-GI infection cohorts. Any FGID was more frequent in people who had a non-GI infection than in controls at both 3 [odds ratio: 4.34 (95% CI: 3.60-16.45)] and 6 months [4.76 (4.42-27.92)]. Irritable bowel syndrome (IBS) alone was more frequent in people with non-GI infections than in controls at 3 months (6.12 [1.30-29.12]) but did not quite reach statistical significance at 6 months (4.58 [0.79-26.46]). Our findings were unexpected. Postinfectious FGIDs may be related to non-GI and GI infection, although not all potential biases were controlled in study design. Further studies need to explore these preliminary findings and, if confirmed, the underlying mechanisms.

Recycling of an industrial sludge and marine clay as light-weight aggregates.

The geographical limitations of Singapore, its restricted natural resources and voluminous municipal and industrial waste streams, make environmental management a major challenge for the island state. In an attempt to find ways to reduce importation of raw materials and the waste sent to landfill, light weight aggregates were produced from marine clay and a CaF(2)-rich semiconductor industry sludge. Aggregates were produced in a bench-scale rotary kiln with three clay/sludge loadings (90/10, 70/30 and 50/50%). All three mixtures showed good bloating behavior during firing and the ceramic pellets (1-1.5cm diameter) had densities well below that required for light-weight aggregates. In the initial tests, the pore sizes of the aggregates were in general too large resulting in high water absorption. Comparisons between the composition of the two waste products and the aggregates showed a significant loss of fluorine (40-60%) during processing; a problem which may require flue gas treatment. Leach testing showed that the formed aggregates would not pose a human or environmental hazard in terms of fluorine mobilization.

Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study.

BACKGROUND AND AIMS: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. METHODS: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. RESULTS: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3-7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1-12.9)), protein (OR 3.00 (95% CI 1.25-7.19)), and alcohol (OR 2.71 (95% CI 1.1-6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19-6.4)) or sulphate (OR 2.6 (95% CI 1.08-6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. CONCLUSIONS: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.

A comparison of the discriminatory power of the Inflammatory Bowel Disease Questionnaire and the SF-36 in people with ulcerative colitis.

The aim of this study was to compare the discriminatory power of a generic and a condition-specific quality of life measure (the Medical Outcomes Study Short-Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ)) with respect to sub-groups defined by disease-related and other factors, in a sample of patients with ulcerative colitis. Disease activity was generally more highly correlated with IBDQ scores than with SF-36 scores. The only significant differences with respect to disease extent were in the SF-36 energy/vitality and social function domains. Age was negatively and weakly to moderately correlated with the physical domains of the SF-36 but positively though weakly correlated with scores on the IBDQ emotional domain and those domains of the SF-36 related to mental well-being. Co-existing chronic illness, even on controlling for age, was associated with significantly poorer scores on the generic measure, but had little influence on IBDQ scores. In conclusion, generic and disease-specific measures of quality of life appear to be complementary rather than interchangeable. We recommend the use of both types of measure in parallel.

Defining relapse of ulcerative colitis using a symptom-based activity index.

BACKGROUND: Several tools exist to assess disease activity in patients with ulcerative colitis (UC), but a definition of relapse does not exist. The aim of the study was to determine the score in the Simple Clinical Colitis Activity Index (SCCAI) that defined relapse. The reliability and validity of the SCCAI when self-administered was also examined. METHODS: Patients with UC routinely attending hospital completed the SCCAI questionnaire, which was later administered by their clinician blinded to the scoring process. In the absence of a gold standard definition of relapse, a subjective global assessment of disease status was made by the clinician. The SCCAI was evaluated in a separate cohort of patients. RESULTS: Seventy-one presentations were analysed; mean age 48 years, 49% male, 37% relapse rate. The mean patient score was 4.2 (range 0-14) and mean physician score 3.8 (0-14). A score of 5 or more defined relapse with 92% sensitivity, 93% specificity, 88% positive predictive value and 95% negative predictive value. The difference between the scores obtained by the patient and clinician (0.35, 95% CI 0.09-0.62) was small. Correlation with a more complex symptom and laboratory-based activity index was very high (r = 0.79, P < 0.01). The index was quick to use and comparative results for sensitivity and specificity were recorded in the second cohort of patients. CONCLUSIONS: The SCCAI is a simple tool that can be accurately and quickly self-administered, correlates well with a more complex disease activity index, and can be used to define relapse of UC with high specificity and sensitivity.

Methylcellulose gel is a superior contrast agent for ultrasound examination of the cervix in obstetric patients.

OBJECTIVE: To determine the superior contrast agent for cervical sonography: water-soluble methylcellulose gel vs. normal saline. METHODS: Women with an indication for cervical sonography underwent placement of 10 mL water-soluble methylcellulose gel or normal saline. Assessment of cervical dimensions and contour was performed via transperineal sonography prior to and after contrast placement. RESULTS: Twenty-five patients with similar demographic characteristics and indications for ultrasonography were enrolled into each group. Administration of contrast improved the ability to visualize the external os or vaginal fornices in 18 women in the gel group vs. six in the saline group (P = 0.002). In the gel group, 17 patients had easier identification of the external os and visualization of the fornices was enhanced in 13 patients. The assessment of cervical length prior to and after contrast administration was not statistically different with the use of either of these agents. CONCLUSION: Intravaginal soluble gel is superior to normal saline as a cervical contrast agent. Intravaginal contrast may allow for easier identification of cervical anatomy during ultrasonographic examination in selected patients.

The effect of unselected post-operative nutritional supplementation on nutritional status and clinical outcome of orthopaedic patients.

BACKGROUND AND AIMS: Nutritional supplements are widely administered in hospitals and can benefit clinical outcome. The aim here was to determine the effect of routine post-operative nutritional supplementation on the nutritional status and clinical outcome of adult orthopaedic patients. METHODS: A prospective controlled study was conducted on two adult orthopaedic wards. Patients in the study group were prescribed two nutritional supplements/day post-operatively. Nutritional and biochemical indices and incidence of clinical complications were observed. RESULTS: Of 181 patients studied, 14 in the supplemented group and 34 in the control (P=0.005) developed major complications. There were 22 occurrences of major complications in the supplemented group and 55 in the control (P=0.0002). There was no significant difference in the number of minor complications between the two groups (P=0.2). There was no statistical difference in changes in nutritional parameters or in albumin or CRP between the two groups. There were significantly greater reductions in transferrin (P=0.002) and in haemoglobin (P=0.002) in the control group at week 1. The median costs of hospital stay were 2068 UK pounds in the supplemented group and 2199 UK pounds in the control. The median cost of additional treatments was 30.16 UK pounds in the supplemented group and 46.23 UK pounds in the control. CONCLUSION: A significant reduction in major complications and in number and costs of additional treatments was seen in the supplemented group.

Funneling to the stitch: an informative ultrasonographic finding after cervical cerclage.

OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasound surveillance after cerclage placement and to propose a rationale for cervical sonography in this setting. SUBJECTS AND METHODS: This was a retrospective analysis of 53 women undergoing cervical cerclage by a maternal-fetal medicine specialist, regardless of indication, and delivering between January 1999 and April 2001. Transvaginal ultrasonographic assessment of cervical length and the degree of cervical funneling after cerclage were compared to preoperative values and to outcomes including gestational age at delivery. Funneling to the cerclage was defined as membranes prolapsing down the endocervical canal until they reached the plane of the cerclage. RESULTS: Cervical cerclage resulted in a significant increase in cervical length from 2.1 +/- 1.2 cm to 2.9 +/- 0.8 cm after the procedure, P < 0.001; however, this measure was not correlated with gestational age at delivery. Funneling to the level of the cerclage was associated with an earlier gestational age at delivery 31.3 +/- 5.6 weeks vs. 36.8 +/- 2.8 weeks for those cases without this finding, P < 0.001. A statistically significant association between funneling to the cerclage and preterm delivery was identified irrespective of the indication (prophylactic or emergency) for the procedure. When descent of the membranes to the level of the cerclage was noted, it occurred by 28 weeks' gestation in all patients studied. The incidence of premature rupture of the membranes was also significantly greater postcerclage in women with descent of the membranes to the cerclage (52%) compared to those without this finding (9%) P= 0.002. CONCLUSIONS: Funneling to the cerclage is significantly associated with earlier preterm delivery in patients who have undergone cervical cerclage. Serial sonography up to 28 weeks' gestation is useful in identifying patients at higher risk for premature rupture of the membranes and preterm delivery.

Sulphasalazine and lung toxicity.

Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here. All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms "sulphasalazine" and "sulfasalazine" were combined with the terms "lung", "pulmonary disease", "pneumonitis" and "pleuritis" using Medline and PubMed databases. Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.

Maternal benefit of corticosteroid therapy in patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: impact on the rate of regional anesthesia.

OBJECTIVE: Our purpose was to assess the impact of glucocorticoid administration on the rate of regional anesthesia in women with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. STUDY DESIGN: Maternal records of pregnancies with HELLP syndrome managed between April 1994 and December 1999 were analyzed retrospectively. RESULTS: Sixty-nine patients were identified with antepartum HELLP syndrome and 46 (66%) received glucocorticoids. The presence of thrombocytopenia at admission and the interval from presentation to delivery was evaluated to assess the impact of glucocorticoid use. In the 37 women who had platelet counts of <90,000/mm3, 0 in the untreated group (0 of 11) versus 42% in the steroid group (11 of 26) received regional anesthetic, P =.015. Furthermore, the rate of regional anesthesia increased from 0 in the untreated group delivered within 24 hours (n = 10) to 57% (8 of 14) in the glucocorticoid group, in which women attained a 24-hour latency from presentation to delivery, P =.006. The need for general anesthesia also decreased significantly in treated women who attained a 24-hour latency compared to untreated women who did not, 100% (n = 7) versus 22% (n = 9), P =.003. CONCLUSIONS: Administration of glucocorticoids increases the use of regional anesthesia in women with antepartum HELLP syndrome who have thrombocytopenia, particularly in those who achieve a latency of 24 hours before delivery.

The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis.

OBJECTIVE: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a health-related quality of life (HRQoL) tool measuring physical, social, and emotional status (score 10-70, poor to good HRQoL). The SIBDQ has been predominantly used in trials for Crohn's disease, and further validation of the SIBDQ is desirable in ulcerative colitis (UC) patients. The primary objective was to further validate the SIBDQ by examining discriminant ability against measures of disease activity. The secondary objectives were to examine reliability and responsiveness to change. METHODS: UC patients attending hospital completed the SIBDQ and two activity indices. Patients' disease status (remission, mild, moderate, or severe relapse) was determined subjectively by the patients and their physician. RESULTS: Scores were obtained for 69 events in 61 patients. mean age 47.8 yr (range 16-79). All classes of disease extent were represented. The mean SIBDQ score was 48.4 (13-70). The difference between mean score in patients in remission and relapse was -20.1 (95% CI = -25.1 to -15.1). The difference for remission and mild relapse was -14.6 (95% CI = -8.9 to -20.2). The correlation between SIBDQ and the activity indices were good, r = -0.83 and r = -0.61. Eight patients presented twice. Those with unchanged disease status showed no significant difference in the mean SIBDQ score. Patients whose disease status had deteriorated from remission to mild relapse, or from mild to moderate relapse demonstrated a mean reduction of 11.8 points (95% CI = 20.1-3.4). CONCLUSIONS: This study contributes to the validation of the SIBDQ as a HRQoL tool in UC. It is reproducible and responsive to changes in disease activity.

An in vitro model and case report that used gelatin sponge to restore amniotic fluid volume after spontaneous premature rupture of the membranes.

OBJECTIVE: The purpose of this project was to study an in vitro model for plugging membrane defects with gelatin sponge and to develop a method with which to use this material to treat premature rupture of the membranes. STUDY DESIGN: Fetal membranes were fixed over the opening of a flask that was filled with saline solution and gelatin sponge. Defects of various sizes were created, and the usefulness of differing sizes of gelatin sponge to obstruct the defects was observed. This technique was then applied to a case of previable, spontaneous premature rupture of the membranes. RESULTS: Fifteen amniotomies were performed in the in vitro model. The gelatin sponge obstructed all defects less than 7 mm in length, when pieces up to 1 x 1 cm in dimension (n = 8 amniotomies) were used. For larger defects or those defects with a complex shape (such as cruciate), gelatin sponge was not effective at arresting fluid loss (n = 4 amniotomies). An inspection of larger gelatin sponge pieces, after instillation through a 12-gauge angiocatheter, revealed 36% (15 of 42 pieces) of 1 x 1 - cm pieces remained intact. A case of spontaneous, previable premature rupture of the membranes was treated with this material. A favorable outcome was observed. CONCLUSION: Gelatin sponge is successful at arresting the egress of fluid through membrane defects when smaller defects are present. Complex or larger linear defects may not be treated by this method alone and necessitate adjuvant therapies. This therapeutic strategy can be applied to cases of previable, spontaneous premature rupture of the membranes.

Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia.

OBJECTIVE: Thrombotic vascular disease may predispose patients to the development of preeclampsia. The purpose of this study was to determine whether maternal or fetal genotype frequencies of the inherited thrombophilic gene mutations (factor V Leiden, methylenetetrahydrofolate, and prothrombin) are altered in severe preeclampsia. STUDY DESIGN: We performed a prospective cross-sectional study to compare the maternal and fetal genotype frequencies of factor V Leiden, methylenetetrahydrofolate, and prothrombin. One hundred ten patients with severe preeclampsia were matched for gestational age to 97 normotensive pregnancies. Umbilical cord blood was obtained from 92 control patients and 75 patients with preeclampsia. Deoxyribonucleic acid was extracted from leukocytes and polymerase chain reaction was performed. Polymerase chain reaction products were digested with the appropriate restriction enzyme and fractionated by gel electrophoresis. Genotype frequencies were calculated. Statistical significance was determined by the chi(2) test. RESULTS: There were no significant differences between patients with severe preeclampsia and control patients regarding frequency of maternal factor V Leiden G/506/A mutation (4.4% vs 4.3%; P =.96), methylenetetrahydrofolate CC/667/TT mutation (9.6% vs 6.3%; P =.54), or prothrombin G/20210/A mutation (0% vs 1.1%; P =.92). In addition, no statistical difference could be found between fetal thrombophilias and the development of preeclampsia. Findings were similar in both white (n = 47) and African American (n = 63) preeclamptic subsets. Moreover, there was no association between any of the maternal or fetal genetic polymorphisms and the incidence of hemolysis, elevated liver enzymes, and low platelet count syndrome (n = 21); eclampsia (n = 12); or intrauterine growth restriction (n = 9). CONCLUSION: Inherited thrombophilias are not associated with severe preeclampsia.