Biomedical subjects

H Valensise

Publications and source records attributed to H Valensise.

At least 19 recordsLinked to original sources

PubMed2006

Maternal total vascular resistance and concentric geometry: a key to identify uncomplicated gestational hypertension.

OBJECTIVE: To evaluate the prognostic impact of elevated total vascular resistance (TVR) on the outcome of pregnancy in early mild gestational hypertension (EMGH). DESIGN: Prospective observational study. SETTING: Data collected from women with EMGH referred to the obstetrics outpatient clinic of Tor Vergata University from June 2003 to June 2005. POPULATION: A total of 268 women with EMGH (systolic and diastolic blood pressure [BP] 140-150 mmHg and 90-99 mmHg, respectively, without significant proteinuria). METHODS: Women had a maternal echocardiographic examination and BP examination within 24 hours of diagnosis. From this, the TVR was calculated and the geometric pattern of the left ventricle assessed. MAIN OUTCOME MEASURES: Fetal/maternal adverse outcomes (pre-eclampsia, preterm delivery, placental abruption, other maternal medical problems, fetal distress, neonatal low birthweight, admittance to neonatal intensive care unit and perinatal death). RESULTS: Ninety-two out of the 268 pregnancies showed adverse outcomes (34.3%). The best independent predictor for the composite of maternal and fetal complications was TVR (OR 64.4, 95% CI 25.9-160.1). The cutoff value was 1340 dyn seconds/cm(5) with a sensitivity and a specificity of 90 and 91%, respectively. Concentric geometry of the left ventricle was also an independent predictor (OR 4.72, 95% CI 1.85-12.04). CONCLUSIONS: Echocardiography could help in identifying women with EMGH who subsequently develop maternal and fetal complications, allowing a classification in high-risk (TVR > 1340 dyn seconds/cm(5), concentric geometry of the left ventricle) and low-risk women (TVR < 1340 dyn seconds/cm(5), nonconcentric geometry of the left ventricle) for adverse outcomes of pregnancy.

Abruptio Placentae↗

PubMed2005

Intrauterine growth restriction and fetal body composition.

OBJECTIVE: To assess the differences in fetal body compartments between fetuses with normal growth and those with reduced intrauterine growth, during the third trimester, through ultrasonographic determination of subcutaneous tissue thickness (SCTT). METHODS: Twenty-eight patients were enrolled into this case control study carried out at 30-31 weeks' gestation. Two study groups were matched for maternal age and pregestational body mass index: controls (n = 14) and intrauterine growth-restricted (IUGR) fetuses (n = 14). Routine ultrasound-derived biometric parameters (head circumference, abdominal circumference, femur length and humerus length) were measured. Additionally, the mid-arm fat mass and lean mass (MAFM and MALM), the mid-thigh fat mass and lean mass (MTFM and MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were measured. The Mann-Whitney U-test and Student's t-test were used to compare the two groups. RESULTS: The abdominal circumference and the humerus were significantly smaller in IUGR fetuses than in controls. Most of the SCTT values were different in the two groups. The SSFM (3.6 +/- 1.1 vs. 2.6 +/- 0.7 mm; P = 0.011), the AFM (5.1 +/- 0.7 vs. 4 +/- 1 mm; P = 0.01), the MAFM (3.5 +/- 0.9 vs. 2.2 +/- 0.8 cm2; P < 0.01) and MALM (2.1 +/- 0.4 vs. 1.7 +/- 0.5 cm2; P = 0.029) were all significantly greater in fetuses with normal development compared to those with growth restriction. CONCLUSIONS: During the third trimester, SCTT (with the exception of MTFM and MTLM) is reduced in fetuses with IUGR. Furthermore, MALM is lower in growth-restricted fetuses, confirming that the parameters measured in this study are affected in IUGR fetuses. Our findings indicate that specific changes in fetal body compartments occur as a result of chronic metabolic impairment.

Abdomen↗

PubMed2005

Postpartum cerebellar infarction and haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome.

Pregnancy is considered to be a hypercoagulable state per se with an increased risk for cerebrovascular events, however cerebellar infarction has been rarely described in pregnant women. A nulliparous pre-eclamptic woman at 25 weeks' gestation was submitted to an echocardiographic exam that showed an impaired cardiac structure and function. After 2 h, the patient underwent caesarean section for diagnosis of haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. Afterwards her platelet count raised, and eight days later she developed nystagmus, ataxia, dysmetria and motor deficit in the right limbs and sensory impairment in the right side of the face and in the left limbs. Cerebral magnetic resonance imaging (MRI) demonstrated a right cerebellar and median posterior bulbar infarction. Colour-coded sonography of cerebral vessels showed an occlusion of the right vertebral artery. Coagulation pattern analysis evidenced double heterozygosis of the methylenetetrahydrofolate reductase (MTHFR) gene and single mutation of the prothrombin gene. This case report gives evidence of the importance of considering the different risk factors involved in stroke occurrence during pregnancy.

Adult↗

PubMed2004

Abnormal maternal cardiac function precedes the clinical manifestation of fetal growth restriction.

OBJECTIVE: To compare maternal hemodynamics in women whose fetuses are small-for-gestational age (SGA) with those in women with fetal growth restriction (FGR) before manifestation of the clinical disease. METHODS: Thirty-five normotensive pregnant women with fetal abdominal circumference < 10th centile, normal fetal anatomy and normal umbilical artery pulsatility index (PI) underwent maternal echocardiographic examinations between 27 and 30 weeks of gestation. Pregnancies were followed until delivery and fetuses were retrospectively classified as either SGA or FGR and the maternal hemodynamic data were compared. RESULTS: Nineteen SGA and 16 FGR patients were retrospectively identified after delivery. Heart rate, stroke volume, cardiac output, left atrial function and left ventricular mass index were higher, while mean blood pressure and total vascular resistance were lower in the SGA group compared with the FGR group. A significant inverse linear correlation was found between total vascular resistance and weight centile (r = 0.83; P < 0.0001). CONCLUSIONS: Mothers of SGA fetuses show hemodynamic features similar to those with physiological pregnancies suggesting that their fetuses are likely to be constitutionally small and not pathologically growth-restricted.

Adult↗

PubMed2004

Fluctuations of fatty acid amide hydrolase and anandamide levels during the human ovulatory cycle.

Implantation is possible within a defined period of the menstrual cycle, referred to as the 'implantation window'. It is during this critical period that proper dialog can be established between the blastocyst and a receptive endometrium. If for any reason this dialog is not established or is altered, the embryo is aborted. The factors responsible for the interaction between the embryo and the mother at the moment of implantation remain poorly understood. Recent studies indicate that endocannabinoids may contribute to the development of an adequate milieu at the implantation site. Here we show that the levels of anandamide and of its degrading enzyme, the fatty acid amide hydrolase, in peripheral lymphocytes undergo specific variations during the various phases of the human ovulatory cycle. In particular, we found the highest levels of fatty acid amide hydrolase activity and protein content, paralleled by the lowest anandamide concentrations, in the period that temporally coincides with the putative window of implantation in humans. On the other hand, the anandamide-synthesizing phospholipase D, the anandamide membrane transporter and the anandamide-binding cannabinoid receptors of lymphocytes did not change during the menstrual cycle. This study indicates that high fatty acid amide hydrolase activity and low anandamide levels may be among the factors that co-operate in the success of implantation. This would add to our understanding of the pathophysiological and therapeutic implications of the endocannabinoid system in human fertility.

Adult↗

PubMed2003

Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies.

OBJECTIVE: To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. METHODS: Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. RESULTS: Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37-40 weeks' gestation for MTFM, at 20-22 and 26-28 weeks for MTLM, at 31-34 and 35-37 weeks for MAFM, at 26-28 and 38-40 weeks for SSFM, and at 39-40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. CONCLUSIONS: We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state.

Adult↗

PubMed2003

The fetal body compartments and their detection during pregnancy. A review.

The recent efforts in the study of fetal compartments could help us to a better recognition of the proper fetal growth and well being. Fat content correlates directly with energy stores. Fat mass and lean body mass is often used in the nutritional assessment of the individual. Moreover chromosomal abnormalities may be detected by studying the fetal soft tissues of the neck, thus providing further proofs of the importance of evaluating the fetal body compartments. To obtain fat mass and lean mass, several measurements were proposed. We report a review of the literature on that topic.

Embryonic and Fetal Development↗

PubMed2003

Maternal cardiac systolic function and total body water estimation in normal and gestational hypertensive women.

We assessed total body water (TBW) content and cardiac function in 25 normotensive (N) and 22 gestational hypertensive (GH) women matched for age, gestational age, and prepregnancy body mass index (BMI) during the third trimester of gestation. Patients underwent maternal echocardiography, bioelectrical impedance analysis (BIA), and hematocrit (Hct %) evaluation. The TBW:Hct ratio (water balance index, WBI) was calculated. Hct was significantly lower in N vs. GH women (31.9+/-2.2% vs. 36.2+/-2.5; p<0.001). There was no difference in TBW between the two groups. WBI was higher in N vs. GH women (1.35+/-0.20 l.kg(-1) x m(-2) vs. 1.19+/-0.18; p<0.001). N subjects showed a higher stroke volume than GH patients (78.0+/-9.7 ml vs. 67.9+/-10.2; p=0.001). Atrial function was higher in N vs. GH women (left atrial fractional area change 57.4+/-5.1% vs. 42.5+/-7.5; p<0.001). A correlation was found between stroke volume and WBI ( r=0.93, p<0.0001). Maternal cardiac function and WBI are strongly related and might help in understanding the mechanisms of adaptation in normal and hypertensive pregnancy.

Adult↗

PubMed2003

Maternal body composition at term gestation and birth weight: is there a link?

To assess the relative influence of maternal body composition at late gestation on birth weight, we examined maternal body composition near term (36.50+/-2.67 weeks gestation) in a group of 29 women, aged 20-39 years. The women came to the laboratory after an overnight fast. After anthropometric measurements, bioelectrical impedance analysis (BIA) was performed, determining resistance (R) and reactance (Xc), with a Tefal scale at 50 kHz. Fat mass (FM, kg) and fat-free mass (FFM, kg) were determined with the total body water (TBW) equation of Siri. The correlation between BIA parameters and birth weights was examined by linear regression analysis. All subjects delivered between 37 and 41 weeks' gestation. The mean+/-SD values of the studied parameters were: Xc=490.00+/-77.34 ohm, R=55.71+/-8.71 ohm, FM=24.18+/-6.51 kg, FFM=45.82+/-2.65 kg, maternal weight gain=9.51+/-6.43 kg, birth weight=3.43+/-0.36 kg. A direct significant correlation was found between FFM, maternal weight gain, and birth weight. It is known that in late pregnancy, maternal weight gain over gestation is linked to birth weight. We observed that FFM was the most important maternal body component associated with the newborn weight at term gestation, and we believe that this finding might be elucidated by fluid retention. In fact, resistance seemed to be inversely related to birth weight and we do not overlook the link between resistance and TBW. The implementation of our study could shed more light on the influence of maternal body composition on birth weight.

Adult↗

PubMed2003

Body composition during normal pregnancy: reference ranges.

Maternal body composition undergoes a deep adaptative change during the course of pregnancy. Fat mass, fat-free mass, and total body water (TBW) increase in different ways and their effects on pregnancy outcome represent a field of major interest in perinatal medicine. The aim of this study was to evaluate the changes in maternal body composition [maternal weight, TBW, intracellular water (ICW) and extracellular water (ECW)] during healthy pregnancy by using bioimpedance analysis (BIA). A total of 170 healthy pregnant women, aged 22-44 years, volunteered to participate in our study. The BIA measurements were carried out with a Tefal BIA scale determining resistance and reactance. Lukaski's multiple-regression equation was used to estimate TBW and ICW and ECW were computed using the prediction formula of Segal. The evaluations were performed at 10-38 weeks' gestation, every 3-4 weeks, and hematocrit was determined at every time interval. Analysis of variance and multiple comparisons of Bonferroni were performed to compare variables among the different study intervals. Second-order polynomial interpolation was used to obtain percentile values for each bioimpedance parameter. Percentile bioimpedance values of the healthy population are provided at each study time, by showing the mean value and the 5th, 25th, 75th, 95th percentiles. Moreover, normal reference ranges for TBW are provided for each gestational age, in relation to maternal weight gain. Reactance, TBW, and ICW enhance slightly during the course of gestation. Tetrapolar BIA could be an easy and practical tool for evaluating changes of maternal body components during pregnancy. It could also provide indirect proof of the normal hemodilution occurring in normal pregnancies. Moreover, fat mass deposition, and not only fluid retention, seems to be responsible for the mother's gestational weight gain, since reactance is an indirect parameter in estimating fat mass amount.

Adipose Tissue↗

PubMed2003

Postpartum thyroiditis is associated with fluctuations in transforming growth factor-beta1 serum levels.

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFbeta1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity. The aim of this study was to assess serum concentrations of TGFbeta1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFbeta1 (aTGFbeta1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA(+), and 29 were ATA(-). Twenty of the 34 ATA(+) women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFbeta1 in 50% of ATA(+) pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFbeta1 activation; and 2) decreased total TGFbeta1 and increased aTGFbeta1 serum levels during the active phase of PPT in ATA(+) women. This seems to suggest that inflammation may be responsible for TGFbeta1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFbeta1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.

Adult↗

PubMed2002

Abnormal maternal cardiac function and morphology in pregnancies complicated by intrauterine fetal growth restriction.

OBJECTIVE: To explore maternal cardiac function through an echocardiographic evaluation, in a group of nulliparous patients with intrauterine fetal growth restriction during the third trimester of pregnancy. METHODS: Twenty-one consecutive nulliparous pregnant women who had fetuses with intrauterine growth restriction (IUGR) and abnormal umbilical artery Doppler pulsatility index (PI) underwent maternal echocardiographic examination during the third trimester of gestation. The data were then compared with those obtained from 21 normal nulliparous women who had fetuses with an estimated fetal weight > 10th percentile and a normal umbilical artery Doppler PI who were considered as the control group. RESULTS: Heart rate was slightly lower in the IUGR group, whereas blood pressure and total vascular resistance were higher compared with the control subjects. End-diastolic volume, stroke volume and cardiac output were lower in the IUGR patients compared with normal patients. The IUGR group had smaller left atrial maximal dimensions and greater left atrial minimal areas compared with the control subjects. Left atrial function was depressed in the IUGR group. A smaller left ventricular mass was present in the IUGR patients compared with the control subjects. Isovolumetric relaxation time (IVRT) was prolonged in the IUGR patients compared with the controls. CONCLUSIONS: The absence of a 'correct' maternal cardiovascular compensatory response to abnormal trophoblastic invasion, might be one of the factors that slowly determine the conditions of reduced placental perfusion and eventually of the development of fetal growth restriction.

Adult↗

PubMed2001

Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility.

Physiological concentrations of progesterone stimulate the activity of the endocannabinoid-degrading enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH) in human lymphocytes. At the same concentrations, the membrane-impermeant conjugate of progesterone with BSA was ineffective, suggesting that binding to an intracellular receptor was needed for progesterone activity. Stimulation of FAAH occurred through up-regulation of gene expression at transcriptional and translational level, and was partly mediated by the Th2 cytokines. In fact, lymphocyte treatment with IL-4 or with IL-10 had a stimulating effect on FAAH, whereas the Th1 cytokines IL-12 and IFN-gamma reduced the activity and the protein expression of FAAH. Human chorionic gonadotropin or cortisol had no effect on FAAH activity. At variance with FAAH, the lymphocyte anandamide transporter and cannabinoid receptors were not affected by treatment with progesterone or cytokines. Good FAAH substrates such as anandamide and 2-arachidonoylglycerol inhibited the release of leukemia-inhibitory factor from human lymphocytes, but N-palmitoylethanolamine, a poor substrate, did not. A clinical study performed on 100 healthy women showed that a low FAAH activity in lymphocytes correlates with spontaneous abortion, whereas anandamide transporter and cannabinoid receptors in these cells remain unchanged. These results add the endocannabinoids to the hormone-cytokine array involved in the control of human pregnancy.

Adult↗

PubMed2001

Maternal diastolic function in asymptomatic pregnant women with bilateral notching of the uterine artery waveform at 24 weeks' gestation: a pilot study.

OBJECTIVE: To study second-trimester maternal cardiac adaptation in asymptomatic patients at risk, on the basis of abnormal uterine artery Doppler, for the development of gestational hypertension or having a small-for-gestational age fetus. Fetal and maternal outcomes were verified at the end of pregnancy. METHODS: Thirty-six normotensive women with abnormal uterine artery waveforms underwent maternal echocardiographic examination at 24 weeks' gestation. RESULTS: Twenty-one women (58.3%) subsequently showed normal outcome; 12 patients developed gestational hypertension (33.3%) and three (8.3%) had small-for-gestational age newborns. Left ventricular outflow tract, left ventricular diastolic dimensions and atrial and ventricular function were significantly lower in the pathological outcome group. Diastolic function parameters were significantly different between the two groups: peak mitral E-wave and A-wave and A-wave duration showed lower values in the pathological outcome group. Isovolumetric relaxation time of the left ventricle was significantly longer in the pathological outcome group. The prevalence of an altered geometric pattern was 14.3% (3/21) in the normal and 80% (12/15) in the pathological outcome groups (P < 0.001). CONCLUSIONS: Women who subsequently develop a complication of pregnancy tend to display abnormal cardiac adaptation. An abnormal placentation process, expressed by an elevated resistance index and the presence of notches in the uterine artery waveform, are likely to cause an adaptative mechanism involving the whole cardiovascular system. A pathological outcome of pregnancy is associated with the failure of this process.

Adult↗

PubMed2001

Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin.

PROBLEM: To compare the use of intravenous immunoglobulins (IVIG) with prednisone plus low-dose aspirin (LDA) in treating pregnant women with a history of recurrent fetal loss having the antiphospholipid antibody (aPL), in terms of live-birth rate and maternal and perinatal morbidity. METHOD: A prospective, two-centers trial study included 82 recurrent aborters with aPL syndrome. Twenty-nine were treated with prednisone and LDA in one center, 53 received IVIG in the other center. Maternal and fetal outcomes and pregnancy complications were compared between groups. RESULTS: Live-birth rates were equivalent between groups (78 vs 76%). Mean birth weight was higher in the IVIG group than in the prednisone plus LDA group. In the prednisone- plus LDA-treated patients, gestational hypertension and gestational diabetes were found significantly more often than in the IVIG-treated group (14 vs 5% and 14 vs 5%, respectively). CONCLUSION: In patients with aPL syndrome, IVIG treatment improved pregnancy outcome, with significantly lower pregnancy complication rates, when compared with prednisone plus LDA therapy.

Abortion, Habitual↗

PubMed2001

Maternal diastolic dysfunction and left ventricular geometry in gestational hypertension.

The objective of this study was to evaluate diastolic parameters and left ventricular geometry in gestational hypertension. Twenty-one consecutive pregnant women with gestational hypertension and 21 normotensive women matched for age and gestational age were enrolled in the third trimester of gestation. Echocardiographic and uterine color Doppler evaluations were performed. Systolic, diastolic, and mean blood pressure, total vascular resistance (TVR), and uterine resistance index were higher in hypertensive women than in control subjects (P<0.01). Left atrial function and cardiac output were significantly lower in gestational hypertension (P<0.01). Patients with gestational hypertension had longer left ventricular isovolumetric relaxation time (IVRT) (P<0.0001); lower velocity-time integral of the A wave (P<0.05) and of the diastolic pulmonary vein flow (P<0.05); and higher velocity-time integral of the reverse pulmonary vein flow (P<0.05). Systolic fraction of the pulmonary vein flow was higher in women with gestational hypertension than in control subjects (P<0.01); the difference in duration of pulmonary vein flow and A wave was closer to 0 in gestational hypertension (P<0.0001). Altered left ventricular geometry was found in 100% of hypertensive patients and in 19.05% of normotensive patients (P<0.001). IVRT, left ventricular end-systolic volume, atrial function, and uterine resistance index were directly related to TVR (P<0.01); deceleration time of the E wave showed a quadratic correlation with TVR (P<0.01). Gestational hypertension is characterized by an altered cardiac geometric pattern of concentric hypertrophy. The altered geometric pattern assessed during gestational hypertension is associated, in our study, with depressed systolic function, high TVR, altered diastolic function, and left atrial dysfunction. Deceleration time of the E wave, IVRT, and left atrial fractional area change, found in concomitance with the highest TVR, may be useful in the evaluation of cardiac function and hemodynamics present in pregnancy-induced hypertension.

Adult↗

PubMed2001

Proposal for a novel and inexpensive surgical instrument to perform the tension-free vaginal tape procedure in women with genuine stress incontinence.

The tension-free vaginal tape (TVT) technique is now commonly used in the management of female genuine stress incontinence. Short operation time, small amount of local anesthetic, fast postoperative mobilization, brief hospital stay, little residual urinary volume and little need for sick leave make TVT a simple and well-accepted minimal invasive surgery for the treatment of stress incontinence. We became suspicious of the procedure due to the very expensive cost of the instrumentation. Moreover we think that this "blind" procedure may be less dangerous by using a more familiar instrument than a large and gross steel needle. We propose the use of an unmodified procedure with a new, cheaper and easy-to-use steel clamp-like-instrument.

Humans↗

PubMed2000

Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage.

BACKGROUND: Endocannabinoids such as anandamide are thought to have adverse effects on pregnancy and embryonic development. The activity of the degradative enzyme anandamide hydrolase may therefore be crucial for prevention of excessive concentrations of anandamide in the uterus, and thus prevention of pregnancy failure or female infertility. We tested this hypothesis in a preliminary study, and then used the results to find out whether anandamide hydrolase activity could predict miscarriage in a group of pregnant women. METHODS: We assessed anandamide hydrolase activity in peripheral lymphocytes from 50 healthy, pregnant women at weeks 6-11 of gestation by a specific radiochromatographic method. The expression of the enzyme at the protein level was measured by ELISA with specific polyclonal antibodies. In a further study, we measured anandamide hydrolase concentration in 120 women who were 7-8 weeks pregnant and compared these findings with subsequent pregnancy outcome. FINDINGS: In the first study, seven of the 50 women had a miscarriage. Anandamide hydrolase activity was lower in the seven women who miscarried than in the 43 who did not (60.43 pmol/min per mg protein [SD 29.34] vs 169.60 pmol/min per mg protein [30.20]; difference 109.17 pmol/min per mg protein [95% CI 26.64-191.70]; p<0.0001 by the Mann-Whitney test). Enzyme activity correlated with enzyme concentration, and a threshold concentration represented by an optical density (after ELISA) of 0.15 absorbance units at 450 nm separated the women who had miscarriages from those who did not. In the second study, 15 women had anandamide hydrolase concentrations below the threshold, and 105 had concentrations at or above the threshold. All 15 women in the low anandamide hydrolase group had miscarriages, compared with one of the 105 women with high concentrations (p<0.0001 by Fisher's exact test). INTERPRETATION: Decreased anandamide hydrolase activity and expression in peripheral lymphocytes is an early (<8 weeks of gestation) marker of spontaneous abortion, and may prove useful as a diagnostic tool for large-scale, routine monitoring of gestation. Our results also suggest that endocannabinoids might be critical in regulating the lymphocyte-dependent cytokine network associated with human fertility and successful pregnancy.

Abortion, Habitual↗