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Biomedical subjects

D Mahieu-Caputo

Publications and source records attributed to D Mahieu-Caputo.

At least 19 recordsLinked to original sources
PubMed2006

The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. OBJECTIVES: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. PATIENTS AND METHODS: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. RESULTS: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurrence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL(-1) decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL(-1) was 79% and the positive predictive value of a concentration <or=2 gL(-1) was 100%. CONCLUSION: These findings indicate that a simple fibrinogen measurement can anticipate the risk of severe bleeding in PPH.

Adult↗
PubMed2005

[Neurological outcome of children from twin pregnancies].

The neurological outcome is an important issue regarding twin pregnancies. In fact, twin pregnancy is clearly associated with an important neurological morbidity, roughly 4 times higher than singleton pregnancy. It is possible to distinguish some high-risk situations, making it possible to calculate more accurately the individual risk. The different aetiologies are analysed: hypotrophy, prematurity, malformations, prenatal occurrence of anoxic and ischemic lesions, and particularly the link with monochorionicity. The neurological outcome is mainly depending on hypotrophy and prematurity. However, the rate of long-term neurological complications is not different between twins and singletons after adjustment for term and birth weight. An increased risk of malformation is associated with twin pregnancies, essentially a high rate of abnormal neural tube closing (RR=2). Monochorionic pregnancies have a specific morbidity, not related to these aetiologies, with characteristic anoxic and ischemic lesions. Cerebral palsy is observed in 10-20% of the monochorionic pregnancies, vs 3.7% of the bichorionic ones. These complications are linked to the constant vascular anastomoses, between the circulations of the two monochorionic twins. When the twin-to-twin transfusion syndrome is severe, a poor neurological outcome is observed in 4 to 18% of the surviving children. However, this rate depends on studies, treatments, and methods of neurological evaluation. The laser destruction of anastomoses could decrease this morbidity. The stillbirth rate, either associated or not with twin to twin transfusion syndrome, is increased by monochorionicity. The death of one of the twins is associated with a 20% higher risk of neurological sequelae for the surviving co-twin.

Congenital Abnormalities↗
PubMed2003

Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome.

OBJECTIVES: To investigate if systemic hypertension occurs in fetuses with twin-to-twin transfusion syndrome (TTTS). METHODS: We conducted an observational cohort study in a tertiary care centre in 23 pregnant women with TTTS. Polyhydramnios stuck twin sequence occurred at a median gestational age of 22 weeks (range 15-27). Biventricular myocardial hypertrophy was diagnosed in 22/23 recipient fetuses. In cases with atrioventricular valve regurgitation (AVR), it was possible to estimate the fetal systolic systemic blood pressure by ultrasound, on the basis of the simplified Bernouilli equation. The diagnosis of fetal hypertension (FHT) was made when the estimated systolic arterial pressure was equal to or above 1.6-fold the expected value. RESULTS: In 10 pregnancies (group A), fetal blood pressure could be assessed in recipients with AVR. The maximum velocities ranged from 2.9 to 5 m/s, leading to estimates of systemic fetal arterial pressure from 37 to 104 mmHg, that is, 1.6- to 2.8-fold the expected values. In 13 pregnancies (group B), fetal blood pressure could not be assessed in the absence of AVR. In group A, perinatal death (16/20) and hydrops (7/20) were significantly more frequent than in group B (8/26 and 1/26 respectively). CONCLUSION: Fetal systemic hypertension may occur in recipient twins and could play a role in the pathophysiology of TTTS.

Cohort Studies↗
PubMed2002

[What's new in fetal medicine?].

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.

Adult↗
PubMed2001

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

Animals↗
PubMed2001

Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia.

OBJECTIVE: To study the potential for prenatal magnetic resonance imaging to predict pulmonary hypoplasia in congenital diaphragmatic hernia. DESIGN: Prospective observational study. SETTING: Tertiary care centre. PARTICIPANTS: Thirteen cases of congenital diaphragmatic hernia (11 left, 2 right) without associated anomalies and 74 controls. METHODS: Measurements by magnetic resonance imaging of fetal lung volume were achieved. In the control fetuses, a regression analysis was performed to associate fetal lung volume with gestational age. This yielded a formula allowing calculation of the expected fetal lung volume as a function of gestational age. In the cases with congenital diaphragmatic hernia, the observed/expected fetal lung volume ratio was compared with perinatal outcome. MAIN OUTCOME MEASURES: Neonatal mortality and pulmonary hypoplasia, which was defined as lung/body weight ratios less than 0.012. RESULTS: The expected fetal lung volume was derived from the following formula: Fetal lung volume (mL) = exp (1.24722 + 0.08939 x gestational age in weeks). The observed/expected fetal lung volume ratio was significantly lower in congenital diaphragmatic hernia (median: 0.31, range: 0.06-0.63), than in controls (median: 0.99, range: 0.42-1.94). This ratio was significantly less in the infants with congenital diaphragmatic hernia who died (median: 0.26, range: 0.06-0.63) compared with those who survived (median: 0.46, range: 0.35-0.56). The observed: expected fetal lung volume ratio was significantly correlated with the post mortem lung: body weight ratio. CONCLUSION: In isolated congenital diaphragmatic hernia, fetal lung volume measurement by magnetic resonance imaging is a potential predictor of pulmonary hypoplasia and postnatal outcome. Further studies are required to establish the clinical value of magnetic resonance imaging for the prenatal assessment of fetal lungs.

Case-Control Studies↗
PubMed2001

[Allotransplantation in utero and immortalization of primate fetal hepatocytes].

We are developing cell therapy approaches on non-human primates as a preclinical model for the treatment of hepatic metabolic diseases. In foetuses, the tissues, including liver, are in expansion, which should facilitate hepatocytes engraftment, and the immune system becomes fully mature only after birth. We have set out conditions for isolation of fetal hepatocytes from macaca mulatta at the end of the 2nd trimester of gestation (90-100 days), their cryopreservation and retroviral transduction. Two different routes of administration of hepatocytes were evaluated: the umbilical vein which was deleterious for the foetuses, and the intraparenchymatous injection which was well tolerated by the animals. Administration of hepatocytes into the hepatic parenchyma resulted in microchimerism and allogenic cells were visualized 9 days after transplantation. Another approach has been to immortalize simian foetal hepatocytes using a retroviral vector expressing SV40 Large T flanked by lox sites. A cell line has been established for 2 years, which is not tumorigenic when injected subcutaneously into nude mice and display characteristics of bipotent hepatoblasts, precursors of hepatocytes and biliary cells. After orthotopic transplantation into nude mice via the portal vein, these cells expressed albumin until the sacrifice of the animals (17 days). The next steps will be to define conditions for transplantation of retrovirally transduced fetal primary and/or immortalized hepatocytes into young foetuses (60 days of gestation) and post-natally.

Animals↗
PubMed2000

[Fetal pain].

IN UTERO CARE: The definition of pain proposed by the International Association for the Study of Pain is not adapted to the newborn or to the fetus because it assumes recognition and verbal expression of an unpleasant experience. Neonatologists have however demonstrated that full term and highly premature infants experience pain. In addition, the health of these infants improves with proper management. Such an approach is indispensable, not only from an obvious humane point of view, but also because treatment of pain in utero could have a beneficial effect for the fetus. PRENATAL PAIN AND ITS CONSEQUENCES: As it is impossible to resolve the question of conscious perception of pain by the fetus, we use experimental or clinical arguments favoring sensitivity to pain to assess pain during fetal life. We have also investigated the deleterious consequences of antenatal pain and how to evaluate them clinically in order to propose therapeutic care. It can be accepted that the fetus is able to perceive pain as early as 26 weeks gestation, possibly from 20 weeks. In the short-term, fetal pain causes changes in behavior, hemodynamics and hormonal functions but the long-term consequences remain unknown. ANTENATAL ANALGESIA: As no validated data on assessment of pain in the fetus are available, prevention becomes primordial in all at risk situations (pregnancy termination beyond 24 weeks gestation, in utero interventions). Morphine derivatives (sufentanil) would be the analgesic of choice for antenatal pain.

Animals↗
PubMed2000

Bipolar coagulation of the umbilical cord in complicated monochorionic twin pregnancy.

OBJECTIVES: In monochorionic twin pregnancy in which one twin is a nonviable fetus, selective feticide may be considered. We aimed to occlude the umbilical cord with a bipolar forceps for doing so. STUDY DESIGN: This was a multicenter experience in 10 consecutive patients either with twin-to-twin transfusion syndrome and one fetus affected by a condition not compatible with normal extrauterine life or with acardiac twinning. RESULTS: There were no intraoperative problems, and the mean procedure time was 17.5 minutes. The flow was stopped in all 10 cases. Two cases were complicated by rupture of the fetal membranes within 2 days, and the pregnancies were terminated. The other 8 pregnancies resulted in the live birth of a healthy baby. The mean interval between procedure and birth was 15.1 weeks (range, 7-20 weeks). In one patient emergency cesarean delivery for abruptio placentae was done at 26 weeks, 7 weeks after the procedure. The other 7 patients were delivered beyond the 36th week of gestation. All 8 children are alive and well, with a mean follow-up of at least 1 year. CONCLUSION: Bipolar coagulation is a safe, effective, and simple procedure for cord coagulation that is feasible through a single port and can be performed solely under ultrasonographic guidance.

Female↗
PubMed2000

Twin-to-twin transfusion syndrome. Role of the fetal renin-angiotensin system.

The twin-to-twin transfusion syndrome (TTS) results from an unbalanced blood supply through placental anastomoses in monochorionic twins. It induces growth restriction, renal tubular dysgenesis, and oliguria in the donor and visceromegaly and polyuria in the recipient. A better understanding of its pathophysiology could contribute to improving the management of TTS, which still carries a high perinatal mortality in both twins. As well as several other candidates, the renin-angiotensin system might be involved in TTS. To evaluate its role in the pathogenesis of the syndrome, we studied the kidneys of 21 twin pairs who died from TTS at 19 to 30 weeks, compared with 39 individuals in a control group, using light microscopy, immunohistochemistry, and in situ hybridization. The overexpression of the renin protein and transcript with frequent evidence of renin synthesis by mesangial cells was observed in the donor kidneys, presumably as a consequence of chronic renal hypoperfusion. This upregulation of renin synthesis might be beneficial to restore euvolemia. In severe cases of TTS, however, angiotensin-II-induced vasoconstriction acts as an additional deleterious factor by further reducing the renal blood flow in donors. In recipients, renin expression was virtually absent, possibly because it was down-regulated by hypervolemia. However, in addition to congestion and hemorrhagic infarction, there were severe glomerular and arterial lesions resembling those observed in polycythemia- or hypertension-induced microangiopathy. We speculate that fetal hypertension in the recipient might be partly mediated by the transfer of circulating renin produced by the donor, through the placental vascular shunts.

Female↗
PubMed2000

Fetal serum beta2-microglobulin predicts postnatal renal function in bilateral uropathies.

BACKGROUND: Predicting postnatal renal function is crucial for the prenatal evaluation of fetal bilateral uropathies. Prenatal ultrasound can identify intrauterine terminal renal failure, but is not sensitive enough to identify those infants who would survive with an impaired renal function. Because it reflects fetal glomerular filtration, fetal serum beta2-microglobulin is a potential predictor of postnatal renal function. METHODS: Fetal serum beta2-microglobulin (beta2m) was assayed in 61 cases of bilateral or low obstructive uropathy, 74 controls, and 17 cases of bilateral renal agenesis, and was correlated with renal function. RESULTS: Fetal serum beta2m was 3.2 mg/L (range 1.5 to 4.7) in controls (N = 74), 9.5 mg/L (range 6.7 to 11.3) in bilateral renal agenesis (N = 17), 7 mg/L (5.1 to 10.6) in uropathy in which terminal renal failure resulted in termination of pregnancy (N = 26), and 3.7 mg/L (range 2.3 to 11.2) in live births with uropathy (N = 35). In the latter subgroup, fetal serum beta2m was significantly and positively correlated (r2 = 0.91) with postnatal serum creatinine. All survivors with a postnatal serum creatinine < or =50 micromol/L ha a fetal serum beta2m lower than 5 mg/L. Four of 6 survivors with a postnatal serum creatinine> 50 micromol/L had a fetal serum beta2m greater than 5 mg/L. CONCLUSION: Fetal serum beta2-microglobulin is a marker for renal function and predicts postnatal serum creatinine in bilateral or low fetal obstructive uropathy.

Biomarkers↗
PubMed1998

Diagnosis and management of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) is associated with significant perinatal morbidity and mortality. This condition can be a sign of genetic disorders, fetal infection, uteroplacental insufficiency, or constitutionally small fetuses. Correct determination of gestational age is the first step in prenatal screening of growth-retarded fetuses. The discovery of a small-for-gestational age fetus necessitates fetal assessment for the evaluation of the etiology and prognosis, and for the determination of the optimal timing for delivery of these fetuses at risk of perinatal asphyxia. IUGR is more frequent in multiple-gestation pregnancies (23-34%) and will be discussed separately. There is no medical treatment for IUGR. Early aspirin treatment reduces the incidence of IUGR in a high-risk population but should not be used routinely in all pregnant women.

Female↗
PubMed1996

Fetal serum interferon-alpha suggests viral infection as the aetiology of unexplained lateral cerebral ventriculomegaly.

We assayed fetal serum interferon-alpha (IFNA), a cytokine produced by leukocytes as a response to viral infection, in a series of 59 consecutive cases of ventriculomegaly diagnosed in utero and in 89 controls. Results were correlated with other findings including karyotype, maternal-fetal screening for serum antibodies to specific infectious pathogens, viral cultures of amniotic fluid, and neuropathological examination or postnatal follow-up. Fetal serum IFNA assay was negative in the five ventriculomegalies associated with a genetic anomaly and positive in the three cases with documented cytomegalovirus infections. In addition, fetal serum IFNA was detected significantly more often in the cases of ventriculomegaly with unexplained pathogenesis (15/51, 29.4 per cent) than in controls (1/89, 1.1 per cent). Detection of IFNA suggestive of viral infection in fetuses with otherwise unexplained ventriculomegaly underscores the need for more extensive viral screening in such cases.

Cerebral Ventricles↗