Patrice Poulain

Paracetamol, Aspirin, and Indomethacin Induce Endocrine Disturbances in the Human Fetal Testis Capable of Interfering With Testicular Descent

CONTEXT Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol and/or to other mild analgesics is associated with an increased risk of cryptorchidism. OBJECTIVE We aimed to determine whether mild analgesics disrupted the morphology and endocrine function of the human testis. DESIGN We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite N-(4-hydroxyphenyl)-arachidonoylethanolamide (AM404), aspirin, indomethacin, and ketoconazole at 10(-4) to 10(-7) M. SETTING The study was conducted at the University of Rennes I. PATIENTS/PARTICIPANTS Human fetal testes were from pregnant women after induced abortion, between 7 and 12 weeks of gestation (GW). MAIN OUTCOME MEASURES Testosterone (RIA), anti-Müllerian hormone (ELISA), insulin-like factor 3 (RIA), and prostaglandin (PG) D2 and PGE2 (ELISA) were assayed in the medium. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen, androgen, and peroxisome proliferator-activated γ receptors. RESULTS Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404, and ketoconazole decreased insulin-like factor 3 levels. Aspirin stimulated whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol and aspirin in the 7 to 12 GW testes and by indomethacin but only in 7 to 9.86 GW testes. The inhibitory trends seen for PGD2 were not statistically significant. CONCLUSIONS Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin, and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.

Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: A multicenter case–control study†

Neural tube defects (NTDs) are severe congenital malformations due to failure of neural tube formation in early pregnancy. The proof that folic acid prevents NTDs raises the question of whether other parts of homocysteine (Hcy) metabolism may affect rates of NTDs. This French case‐control study covered: 77 women aged 17–42 years sampled prior to elective abortion for a severe NTDs (cases) and 61 women aged 20–43 years with a normal pregnancy. Plasma and erythrocyte folate, plasma B6, B12 and Hcy were tested as five polymorphisms MTHFR 677 C → T, MTHFR 1298 A → C, MTR 2756 A → G, MTTR 66 A → G and TCN2 776 C → G. Cases had significantly lower erythrocyte folate, plasma folate, B12 and B6 concentrations than the controls, and higher Hcy concentration. The odds ratio was 2.15 (95% CI: 1.00–4.59) for women with the MTRR 66 A → G allele and it was decreased for mothers carrying the MTHFR 1298 A → C allele. In multivariate analysis, only the erythrocyte folate concentration (P = 0.005) and plasma B6 concentration (P = 0.020) were predictors. Red cell folate is the main determinant of NTDs in France. Folic acid supplement or flour fortification would prevent most cases. Increased consumption of vitamins B12 and B6 could contribute to the prevention of NTDs. Genetic polymorphisms played only a small role. Until folic acid fortification becomes mandatory, all women of reproductive age should consume folic acid in a multivitamin that also contains B12 and B6.

Short Communication. Prenatal detection of a congenital pancreatic cyst and Beckwith–Wiedemann Syndrome

We report a case of congenital pancreatic cyst detected prenatally by ultrasound in a fetus with evidence for a diagnosis of Beckwith–Wiedemann syndrome (BWS). Neonatal hypoglycaemia was prevented. The cyst was managed by internal drainage. This is the second reported case of BWS associated with pancreatic cystic dysplasia and the first time that this association has been detected prenatally. Differential diagnosis of cystic abdominal lesions occurring in utero should take pancreatic cysts into consideration. This case suggests that pancreatic cysts should be included in the BWS phenotype.

Perinatal morbidity and mortality in twin pregnancies with dichorionic placentas following assisted reproductive techniques or ovarian induction alone: a comparative study

OBJECTIVE To compare maternal and perinatal outcome in non-spontaneously and spontaneously conceived dichorionic twin pregnancies. STUDY DESIGN We report a retrospective study of all 350 twin pregnancies delivered ≥22 weeks of gestation between January 1, 2001 and December 31, 2005 in a tertiary maternity unit. We compared maternal outcome, perinatal morbidity and neonatal mortality between spontaneous and non-spontaneous dichorionic twin pregnancies, with a subgroup analysis separating pregnancies following assisted reproduction technology (ART group) from those following ovarian induction alone (OI group). Generalized linear model and multivariate analysis were performed. RESULTS The proportion of primiparous women and the mean maternal age were higher in the non-spontaneously conceived dichorionic twin pregnancy group as expected (70.2% vs. 38.2%, p<0.001 and 32.1 ± 3.8 vs. 30.7 ± 4.6 years, p<0.01). Multivariate analysis, adjusted for maternal age and parity, revealed that non-spontaneously conceived dichorionic twin pregnancies were associated with a higher risk of very preterm birth (OR 2.20, 95% confidence interval 1.02-4.77, p<0.05), low birth weight (1.77, 1.21-2.61, p<0.01), very low birth weight (1.99, 1.13-3.49, p<0.05), NICU admission (1.66, 1.14-2.43, p<0.01), and fetal or neonatal death (3.21, 1.30-7.95, p<0.05). Multivariate analysis confirmed that the mean gestational age (p<0.01) and mean birth weight of the first (p<0.05) and second twins (p<0.01) were lower in the non-spontaneously conceived dichorionic twin pregnancy group. These associations were confirmed in the OI group analysis (n=39) but not in the ART group (n=65). Ovarian induction was associated with an increase in the risk of preterm and very preterm births (2.25, 1.06-4.75, p<0.05 and 3.47, 1.42-8.49, p<0.01, respectively), low and very low birth weights (2.87, 1.63-5.05, p<0.001 and 2.59, 1.33-5.07, p<0.01, respectively), NICU admission (2.92, 1.67-5.11, p<0.001) and fetal or neonatal death (4.20, 1.40-12.56, p<0.05). The mean gestational age (p<0.001) and mean birth weight of the first (p<0.01) and second twins (p<0.001) were also lower in the OI group. CONCLUSIONS Twin pregnancies with dichorionic placentation following non-spontaneously conceived pregnancy are associated with a higher risk of adverse perinatal outcome compared with dichorionic spontaneously conceived twin pregnancies especially in case of ovarian induction alone.

Selective intrapartum anti-bioprophylaxy of group B streptococci infection of neonates: a prospective study in 2454 subsequent deliveries

OBJECTIVE To investigate the efficacy of a selective intrapartum prophylaxy of group B streptococci (GBS) infection of the neonates. STUDY DESIGN A prospective protocol of universal antepartum screening of GBS and selective intrapartum treatment from the 1st February 1994 to the 31st December 1995, on 2454 subsequent deliveries was designed. Our policy included: (1) antepartum screening as soon as possible after 28 weeks by a single vaginal and perianal sample for culture; (2) intrapartum recognition of one condition of high risk of fetal contamination during labor (these conditions included: a temperature of 38 degrees C during labor, rupture of membranes for more than 12 h or prolonged labor for more than 12 h with rupture of membranes, prematurity, twins, maternal diabetes, previous pregnancy with GBS infection of the neonate); and (3) intrapartum anti-bioprophylaxy (amoxicillin) for women with positive screening during pregnancy and one condition of high risk of fetal contamination during labor. We studied the outcome of neonates during this period to look for immediate GBS severe infection of the neonates in the form of bacteraemia or meningitis and compared the results with the rate of neonatal infection before this protocol (4.5/1000 live births in 1993). RESULTS We noted that 11% of pregnant women were carriers, 25% of which led to antibiotic chemoprophylaxis during the labor. We noticed four cases of neonatal bacteraemia of GBS. One case arose from the group of carriers (but no condition of risk of fetal contamination during the labor and no chemoprophylaxy). The three other cases were from women with a negative antepartum screening. There was no case of meningitis and all four babies were in good health at day 10 of life. Comparing with results prior to the study, we noticed that the rate of neonatal bacteraemia dropped from 4.5 to 1.6 per 1000 livebirths (P < 0.0001). CONCLUSION This protocol of intrapartum anti-bioprophylaxy significantly decreases the rate of GBS neonatal sepsis. We propose to improve the efficacy of this prevention program, especially with regard to the method of antepartum screening of pregnant women colonized with GBS.

Diagnosis of post-partum ovarian vein thrombophlebitis by color Doppler ultrasonography: about 10 cases

Background. Post‐partum ovarian vein thrombosis is often overlooked or mistaken for other complications such as endometritis. Color Doppler ultrasonography is a very good diagnostic method when properly indicated and correctly interpreted according to clinical data.

Screening for Chlamydia trachomatis using self-collected vaginal swabs at a public pregnancy termination clinic in France: results of a screen-and-treat policy.

Objective: To assess the prevalence of Chlamydia trachomatis (CT) infection and the risk factors for CT infection among women presenting for abortion at a clinic in France. Methods: Women seeking surgically induced abortions were systematically screened by PCR on self-collected vaginal swabs between January 1, 2010, and September 30, 2010. CT-positive women were treated with oral azithromycin (1 g) before the surgical procedure. Results: Of the 978 women included in the study, 66 were CT positive. The prevalence was 6.7% (95% confidence intervals [CI] 5.1%–8.3%). The risk factors for CT infection were the following: age <30 years (Odds ratio [OR]: 2.0 [95% CI: 1.2–3.5]), a relationship status of single (OR: 2.2 [95% CI: 1.2–4.0]), having 0 or 1 child (OR: 5.2 [95% CI: 2.0–13.0]), not using contraception (OR: 2.4 [95% CI: 1.4–4.1]), and completing 11 weeks or more of gestation (OR: 2.1 [95% CI: 1.3–3.6]). Multiple logistic regression indicated that 4 factors—having 0 or 1 child, a single relationship status, no contraceptive use, and a gestation of 11 weeks or more—were independently associated with CT infection. The rate of postabortion infection among all patients was 0.4% (4/978). Conclusions: These results reveal a high prevalence (6.7%) of CT-positive patients among French women seeking induced abortions. Because it is not common practice to screen the general population for CT, screening before induced abortions seems relevant. A cost-effectiveness study is required to evaluate this screen-and-treat policy.

Remarks about the prognosis in case of antenatal diagnosis of gastroschisis

We report our experience of 15 cases of gastroschisis which occurred between 1981 and 1993. All but one were diagnosed antenatally by ultrasound between 16 and 32 weeks of pregnancy. We made a termination of the pregnancy in 3 cases, for multiple malformations in 2 cases and one case of very early premature rupture of the membranes (PROM). When checked (11 cases), the karyotype was normal. We made a cesarean section in 11 cases: the indication was a complication for 6 (fetal distress, PROM, polyhydramnios, large dilatation of the gut). We noted growth retardation in 7 newborns and prematurity in 5/12 (mean gestational age of 36.8 weeks). The preoperative study of the gut noted 5 cases with intestinal damage and one case of complete necrosis of the gut. The global prognosis is not as good as usual, with a perinatal mortality of 41.6% (5/12). We discuss this latter point and examine the literature.

Diagnosis of fetal urinary tract malformations: prenatal management and postnatal outcome.

To evaluate prenatal management and to define the criteria of gravity for accurate assessment of the renal and overall prognosis of fetuses presenting malformations of the urinary tract.

Diagnostic anténatal d’une sirénomélie

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 35 - N° 2 - p. 181-185