Frequency, causes and avoidability of outborn births in a French regional perinatal network.

OBJECTIVES: To evaluate the rate and circumstances of outborn deliveries within a French perinatal network, and to determine their avoidability. STUDY DESIGN: Cohort study including preterm infants <33 weeks gestation and/or weighing <1500g born outside a level III maternity unit in Lower Normandy region, France, in 2008-2010. In 2008 and 2009, only neonates transferred to the Caen University Teaching Hospital (CHU) were included. In 2010, all outborn neonates in the region were included by means of a medical information system program. A panel of 7 experts was set up to determine the avoidability of each outborn case using a two-stage modified Delphi procedure. Inter-expert agreement was evaluated using the kappa index. RESULTS: Sixty-four cases (71 neonates) were included. The outborn rate in 2010 was 16.1% (40/248, 95% CI (116-207%)). The most common reason for delivery was spontaneous onset of labour (57.8%). In 12 cases, the place of birth (level 2b maternity unit) was considered to be appropriate by the experts (term ≥32WG), but 8 cases involved infants of low birth weight (<1500g). For the 52 cases born in inappropriate sites, 9.6% were considered to be avoidable (kappa index=0.42 (p<10-3)). CONCLUSION: Our outborn rate meets regionalisation targets. Our method of expert evaluation identified a small percentage of avoidable births in inappropriate sites. Regular reassessment of obstetric practices and good coordination between network actors are crucial to improve the management of pregnancies at risk of outborn delivery.

The reported in vitro anti-estrogen pentachloronitrobenzene enhances the estrogenic activity of estradiol in vivo in the rat.

Pentachloronitrobenzene (PCNB) has been shown to inhibit foci-formation for MCF-7 cells in vitro (Zou, E., Hatakeyama, M., Matsumra, F., 2002. Foci-formation of MCF-7 cells as an in vitro screening method for estrogenic chemicals. Environ. Toxicol. Pharmacol. 11, 71) This effect was referred to as representing an anti-estrogenic property of PCNB. However, we have found no evidence that PCNB acts as either an estrogen or an anti-estrogen, either in vitro or in vivo. The assays conducted were binding to human and rat estrogen receptors (ER), a hER yeast trans-activation assay, the immature rat uterotrophic assay and a pubertal female rat assay. Nonetheless, when PCNB was evaluated as a possible anti-estrogen against estradiol in the immature rat uterotrophic assay, it enhanced, rather than reduced the activity of estradiol. Absence of an effect by PCNB on the uterotrophic activity of diethylstilbestrol suggests that the effect with estradiol was related to alteration of its metabolism. However, PCNB was not hepatotoxic and failed to inhibit cytochrome P450 or estradiol sulphotransferase. Pentachlorophenol, a major metabolite of PCNB, was inactive as an estrogen and failed to enhance the uterotrophic activity of estradiol.

Natural variability and the influence of concurrent control values on the detection and interpretation of low-dose or weak endocrine toxicities.

While defining the no effect level for the 5 alpha-reductase inhibitor finasteride in the Hershberger assay, we encountered an inverted-U low-dose trophic effect on the prostate gland of the rat. Two attempts to confirm this observation were unsuccessful, and we concluded that the positive effect initially observed was associated with normal biologic variability. During the same period we attempted, unsuccessfully, to repeat our own observation of weak uterotrophic activity in the rat for the sunscreen 3-(4-methylbenzylidene)camphor (4MBC). Further evaluation led us to conclude that 4MBC is uterotrophic only when the control uterine weights are at the low end of their normally encountered range. This led us to reevaluate our earlier mouse uterotrophic assay data for bisphenol A (BPA). Originally we had concluded that BPA gave irreproducible evidence of weak uterotrophic activity, but upon ordering the eight experiments we had conducted, according to decreasing control uterine weight, we confirmed reproducible weak uterotrophic activity for BPA when the control uteri were at the low end of their normal range. In this article, we describe these observations, together with a reanalysis of the data associated with several reported instances of weak or low-dose endocrine effects that have proven difficult to confirm in independent laboratories. These include the activity of BPA on the CF1 mouse prostate; the activities of BPA, octylphenol, and nonylphenol on the rat testis; and the effect of polycarbonate caging on control mouse uterine weight. In all of these cases, variability among controls provides a major obstacle to data interpretation and confirmation. Our recommendations on experimental design are also presented, with a view to ending the current impasse on the reality, or otherwise, of low-dose or weak endocrine toxicities.

Confirmation of uterotrophic activity of 3-(4-methylbenzylidine)camphor in the immature rat.

In this study we found that the ultraviolet sunscreen component 3-(4-methylbenzylidine)camphor (4MBC) is uterotrophic in immature rats when administered by either subcutaneous injection or oral gavage. These data confirm earlier reports of uterotrophic activity for this agent when administered to immature rats in the diet or by whole-body immersion; however, they are in contrast to negative unpublished immature rat uterotrophic assay results. Data also indicate that 4MBC binds to isolated rat uterine estrogen receptors and shows activity in a human estrogen receptor yeast transactivation assay; however, we considered both of these effects equivocal. In this study, we confirmed the original observation that 4MBC was active as a mitogen to MCF-7 breast cancer cells. We evaluated and discounted the possibility that the estrogenic activity of 4MBC is related to its bulky camphor group, which is of similar molecular dimensions to that of the weak estrogen kepone. Uncertainty remains regarding the mechanism of the uterotrophic activity of 4MBC.

[Current legal status of contraception]. / Les dispositions légales actuelles de la contraception

PIP: Current French legislation on contraception is a result of the law of December 18, 1967, which liberalized the previous repressive code, and is being applied in a series of steps. As of 1967, contraceptive propaganda was permitted. In 1969 regulations for production, importing, marketing and prescribing contraceptives were formulated. In July 1973, the regulations were defined for Establishments for Information and Family Counseling, giving information, consultation and counseling only, and for Centers for Family Planning and Education, providing medical and social services. About 200 Establishments and 100 Centers have been recognized. Certain other proposals are being considered to liberalize contraception for minors, to simplify prescriptions and to reimburse recipients of social security for contraceptive devices and drugs.^ieng