Prescription of drugs during pregnancy: a study using EFEMERIS, the new French database.

BACKGROUND: Because of the limited data concerning drug risks in pregnancy, health professionals are often deprived of relevant and sufficient information related to prescribing or dispensing during pregnancy. However, previous studies have emphasised the widespread French prescription of several drugs (sometimes "typically French") which have not been assessed in pregnant women. OBJECTIVES: The aim of the present study was to create the first French database of drugs prescribed and dispensed during pregnancy and the outcome of these pregnancies. METHODS: This feasibility study concerns pregnant women who gave birth to a baby between 1 July 2004 to 30 June 2005 in Haute-Garonne and who are registered in the French Health Insurance Service. Data sources include (1) the French Health Insurance Database (drugs prescribed during pregnancy), (2) the Mother and Child Protection Centre Database (newborn health at birth and 9 months after) and (3) the Antenatal Diagnostic Centre Database (medical pregnancy interruptions). RESULTS: The database is composed of 10,174 "mother-outcome" pairs. The prevalence rate of congenital anomalies was 2.2%. Pregnant women were prescribed 11.3 +/- 8.2 different drugs. Among the 20 most frequently prescribed drugs, around half of them have not been evaluated in pregnant women. CONCLUSIONS: The first results of this study show that implementation of a French database on prescription of drugs and pregnancy outcomes is feasible. Compared with several databases available in other countries, EFEMERIS provides exact data on period of exposure to drugs, pregnancy terminations, and follow up of the baby 9 months after birth. Recording these data would make it possible to assess the risk of malformations due to a greater number of drugs and would contribute to international drug evaluation studies.

Sonographic measurement of nuchal skinfold thickness for detection of Down syndrome in the second-trimester fetus: a multicenter prospective study. The AFDPHE Study Group. Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant.

OBJECTIVE: To determine the sensitivity and specificity of soft-tissue nuchal-fold measurement in the second-trimester fetus for the detection of trisomy 21. METHOD: Thirty-six investigators in 12 centers measured nuchal skinfold thickness in 3308 fetuses of 14-24 weeks' gestation. All mothers were referred for amniocentesis because of age, history of genetic disorder, or laboratory findings. Those referred with an ultrasound indication for amniocentesis, including nuchal-fold thickening, were excluded. RESULTS: Overall, nuchal skinfold was 6 mm or more in 8.5% of chromosomally normal fetuses and in 38% of those with trisomy 21. A false-positive rate below 5% was obtained by 81% of the investigators. Raising the cutoff of normality to 7 mm after 18 weeks' gestation improved specificity. CONCLUSION: Although the diagnostic value of this sign in skilled hands could allow its use as an indication for genetic amniocentesis at the second trimester, the method does not appear suitable for population screening because of the high variability in the results among the investigators.

Randomized trial of two media used for in vitro fertilization.

Culture media are important components of IVF. Their selection must meet the need for efficiency, and also economic and practical requirements. From these standpoints, we compared two widely used media: Ham's F10 supplemented with cord serum and Menezo B2 used without serum. The test followed a randomized protocol using two series of 159 and 162 oocytes. Since no difference was seen in efficiency assessed from cleavage rate, the discussion focuses on cost and ease of use.

Choice of an ovarian stimulation protocol according to the follicular puncture method in an in vitro fertilization programme.

In order to ascertain the adequacy of ovarian stimulation protocols with a type of follicular puncture, 126 women undergoing in vitro fertilization received either combination clomiphene/hMG or hMG alone according to a randomized test protocol. Within both groups patients for whom a pelvic examination was required had laparoscopies, while others had transvaginal ultrasonically guided punctures as far as possible. Clomiphene/hMG was more efficient than hMG alone as assessed from the cleavage rate (68% vs. 54%; p less than 0.01) and the pregnancy per attempt rate (16% vs. 5%; p less than 0.05). Laparoscopic punctures were more efficient than ultrasonically guided punctures (mean number of recovered oocytes: 4.8 +/- 2.6 vs. 3 +/- 2.5; p less than 0.001), but slightly better results were achieved by this latter method in ongoing pregnancy per puncture rate (18% vs. 8%; NS). With ultrasonically guided punctures, stimulation by clomiphene/hMG allowed better oocyte recoveries (3.8 +/- 2.5 vs. 2.3 +/- 1.9, p less than 0.05). Such results constitute an argument for preferential use of the clomiphene/hMG stimulation protocol with ultrasonically guided punctures.

Familial cystic hygroma. Report of 8 cases in 3 families.

The authors report 8 cases of familial cystic hygroma concerning 3 families. In the first family, the two affected fetuses with normal karyotypes showed cystic hygroma of the neck associated with campomelic long bone disease. No other fetal anomalies in the two fetuses were found in the second family, and only one of the four abortuses revealed associated malformations (meningomyelocoele, cleft palate) in the third family. In all these cases, parental consanguinity is found, supporting an autosomal recessive mode of inheritance.

Antenatal detection of subdiaphragmatic pulmonary sequestration: a case report.

Extralobar pulmonary sequestration is part of the spectrum of bronchopulmonary foregut malformations. Usually found in the thorax, it may be located in the retroperitoneum. We report one case of subdiaphragmatic pulmonary sequestration detected by prenatal ultrasound, and diagnosed at surgery after birth. This case illustrates the diagnostic and therapeutic problems occurring during pregnancy and the neonatal period.

[Nuchal translucency: technical measurement and value]. / La clarté nucale: technique de mesure et signification.

Nuchal translucency measurement is a very powerful screening test to detect chromosomal anomalies or other malformations. The technique for measurement is based on strict guidelines that will be described in this paper. Training is mandatory. Risk calculation for chromosomal anomalies (trisomy 21) must also consider maternal age and gestational age. In France, in 1999 the predictive positive value of nuchal translucency for chromosomal anomalies was about 1/7. Other ultrasound markers such as the absence of nasal bone combined with nuchal translucency increase detection. A higher performance will be achieved when ultrasound will be combined with first-trimester maternal serum markers.

[Value of MR imaging of the fetal kidney]. / Apport de l'IRM dans l'étude du rein foetal.

Sonography is the imaging modality of choice for initial evaluation of the fetus. However, the role of MR imaging for fetal evaluation is expanding. Based on a review of seven cases, the role of MRI to further characterize renal abnormalities detected at US, especially hyperechoic kidneys, is demonstrated.

[Screening for trisomy 21 by measuring nuchal translucency during the first trimester of pregnancy]. / Dépistage de la trisomie 21 par mesure de la clarté nucale au premier trimestre de la grossesse.

The purpose of the present literature review is to assess the screening value of trisomy 21 by measurement of fetal nuchal translucency (NT) thickness in the first trimester. NT is a subcutaneous translucency between the skin and the soft tissues overlying the cervical spine, which disappears in the second trimester. Ultrasound examination was used to image a sagittal section of the fetus to measure the maximum thickness of the subcutaneous translucency. NT is physiological for a measurement < 3 mm but the incidence of chromosomal abnormalities (essentially trisomies 21, 18 and 13) increases when NT > or = 3 mm. Differential diagnoses include cystic hygroma and fetal hydrops. For screening purposes, a cut-off threshold value of > or = 3 mm, with a standardized technique, gave a sensitivity > or = 50%, a false positive rate < 5% and a positive predictive value > 1%. In the chromosomally normal group, prognosis was good, but incidence of structural defects and fetal loss increased, with a sharp rise in these complications for fetal translucency thickness > or = 5 mm.

[Prenatal diagnosis of holoprosencephaly. A series of twelve cases]. / Diagnostic anténatal de l'holoprosencéphalie. A propos d'une série de 12 cas.

OBJECTIVE OF THE STUDY: To determine the prenatal ultrasound criteria of holoprosencephaly and their correlation with embryogenesis. MATERIAL AND METHODS: We report 12 cases of holoprosencephaly that have been discovered between January 1990 and June 1996 (eleven alobar holoprosencephalies and one semilobar holoprosencephaly) at La Grave Hospital, Toulouse. RESULTS: In all cases, severe facial anomalies have been (cyclopia, cebocephaly or ethmocephaly). Prenatal ultrasound diagnosis was based on the association of brain anomalies (wide monoventricular cavity, thalami fusion, lacking of median structures) and facial dysmorphia (hypotelorism, orbital anomalies, median cleft lip ...). Finding microcephaly was a frequent sign of holoprosencephaly (64% of all cases). Chromosomal abnormalities have been found in 36% of the fetuses (Trisomy 13 is the most common). All patients underwent therapeutic abortions. CONCLUSION: Transvaginal sonography diagnosis can be made around the 14th to 16th week amenorrhea. An early diagnosis allows an easier pregnancy termination, when such severe anomalies are found. In order to provide genetic counseling, a cytogenetic study of the fetus is necessary.

[Evaluation of the economic burden in the respective indications of in vitro fertilization and tubal microsurgery at a regional hospital center]. / Evaluation du poids économique dans les indications respectives de la fécondation in vitro et de la microchirurgie tubaire dans un Centre Hospitalier Régional.

The authors have calculated the cost of obtaining and maintaining an intrauterine pregnancy to term by IVF and by tubal surgery according to the four classical indications. They have worked this out from local experience. The indications are: reversal of sterilization, surgery on proximal lesions, surgery on distal lesions and multifocal lesions. IVF is superior to surgery where the lesions are multifocal and possibly also in proximal blocks. But surgery is indicated in a large number of distal blocks and particularly in reversal of sterilization. The authors point out how difficult it is to extrapolate from national or international statistics. The choice must depend particularly on the experience of the local teams.

[Ultrasonic control immediately after voluntary interruption of pregnancy. Apropos of 144 cases]. / Le contrôle échographique en post interruption volontaire de grossesse immédiat. A propos de 144 cas.

This study has led to two conclusions: the first is that ultrasound examinations of the pelvis are often asked for immediately after termination of pregnancy because clinicians suspect there may be complications. On the other hand these ultrasound pictures are difficult to interpret and so often, therefore, curettage is carried out which in fact is not necessary. The authors describe a prospective study carried out on 144 cases of termination of pregnancy for which pelvic ultrasound was routinely carried out following termination of pregnancy. The results of this study show that there are several types of ultrasound pictures found immediately after termination of pregnancy; these contain some that can be considered to be reassuring and others that are doubtful. The conclusion depends on the answer to several questions: is it correct to carry out routine ultrasound immediately after termination of pregnancy and has it a real practical purpose? From this can one say that it is necessary to do an ultrasound after every termination of pregnancy? If not, are there special indications for the procedure?

[From failure to success? A case of reduction of the number of embryos in a septuplet pregnancy]. / De l'échec au succès? Un cas de réduction embryonnaire d'une grossesse septuple.

The authors report a case of septuplet pregnancy that occurred after stimulation of ovulation using h.M.G.-h.C.G. This multiple pregnancy occurred because of failure of the triple surveillance using clinical, biological and ultrasound techniques. The number of embryos was reduced by needling through the abdominal wall. Two procedures were necessary. The technique that was used is described in detail and illustrated. The twin pregnancy that was left carried on successfully. This describes a technique that should be used rarely and should not in any way modify the strict rules for monitoring ovulation.

[Predictive value of non-specific signs of fetal infection in congenital toxoplasmosis]. / Valeur prédictive des signes non spécifiques d'infection foetale dans la toxoplasmose congénitale.

AIMS: To study the predictive value of 9 non-specific signs for congenital toxoplasmosis. METHOD: The work was carried out as a prospective study comparing non-specific signs in 22 fetuses infected with toxoplasmosis and 59 fetuses free of the disease. RESULTS: Four of the nine parameters were found to be statistically higher in the group of infected fetuses. These are the level of leucocytes (p < 0.05) gamma glutamyl transferase (p < 0.001) total M immunoglobulin (p < 0.0001) and C4 fraction of complement (p < 0.0001). This last sign which is non-specific for infection has never been looked at until now in congenital toxoplasmosis but is seems to be of great importance because its sensitivity is much greater than of all the other parameters that have been used up till now (81%) and the positive predictive value is excellent (72%). On the other hand the value of a raised leucocyte count is a matter for discussion. CONCLUSION: The presence of even one abnormally raised feature in the fetal blood of these non-specific signs is enough to screen for a population which is of high risk for congenital toxoplasmosis and sufficient to change our attitude to treating the condition.

[Antenatal treatment of fetal urinary tract malformations. Apropos of the treatment of a case of posterior urethral valves]. / Traitement anté-natal des malformations urinaires foetales. A propos du traitement d'un cas de valves de l'urèthre postérieur.

Palliative in utero treatments of certain malformations of the fetal urinary tract are now possible. The most important of these is urethral obstruction by valves. A case of in utero treatment of such a disease is reported, with a six month follow-up of the infant. In utero diversion of urine was performed by means of a catheter placed in the bladder using a technique derived from intra-uterine transfusions. The purpose is to permit drainage of urine from the kidneys into the liquor to prevent permanent damage to the kidneys because of back pressure. The technical problems included deciding the correct size of catheter and the technique of localising the bladder and inserting the catheter under ultrasound control. The ethical problems are raised partly because there is no central ethical committee to make decisions and partly because of the need to evaluate and to inform the patients of the various risks. The patients take the risk on behalf of their children and the mother takes a small risk for her own health.

[Parametrial pregnancy. Report of a case of "paracervical" pregnancy treated by medico-surgical management]. / Grossesse paramétriale. A propos d'un cas de grossesse "paracervicale" traitée par association médico-chirurgicale.

We report an exceptional case of para-cervical pregnancy. Ultrasonography enabled accurate diagnosis after explorative laparoscopy. Treatment was conservative involving methotrexate and surgical ablation of the pregnancy by vaginal approach with a successful outcome.

[Antenatal diagnosis of toxoplasmosis. 176 case reports]. / Diagnostic anténatal de la toxoplasmose. A propos de 176 observations.

OBJECTIVE: To determine the value of antenatal diagnosis of congenital toxoplasmosis by ultrasound guided aspiration of cord blood for testing. MATERIAL: This is a prospective study of 176 cases. As well as obtaining fetal blood and amniotic fluid the searched for specific IgM and A as well as culturing for the parasites on human fibroblasts and inoculation of mice, as well as researching them for non-specific signs of fetal infection. 149 children were able to be followed up one year after birth. RESULTS: 15% of the children (22/149) were infected with toxoplasmosis. 11 out of these were diagnosed positive antenatally. For the 11 others the diagnosis of fetal infection could only be made after birth, but the non-specific signs made it possible to expect early that they had been contaminated. 59% (13/22) had latent toxoplasmosis which only showed up after a mean interval of 34 months after birth. 41% (9/22) had clinical and/or paraclinical signs of toxoplasmosis (mainly unilateral non-macular chorioretinitis and intracranial calcifications) but they are well after a follow-up period averaging 30 months. COMMENTARY: Ultrasound alone, when it shows up fetal abnormalities, can make the diagnosis of the severity of the condition. The role of taking fetal specimens is to make clear those infants that are infected because of specific signs, and to find those fetuses which are at high risk because of non-specific signs in order to improve the management of the cases. This development has made it possible to avoid carrying out a large number of unnecessary terminations of pregnancy and has resulted in the birth of affected infants that had no functional sequelae from the infection.

[Biological reference values in the human fetus. 106 cord blood sampling in utero]. / Valeurs biologiques de référence chez le foetus humain. A propos de 106 ponctions de cordon in utero.

The authors give biological reference figures obtained from 106 fetuses that were sampled in utero between the 20th and 34th week of amenorrhoea. These fetuses were considered to be normal because there was no clinical or ultrasound evidence of an abnormality. Furthermore the biological values sought in antenatal testing and the absence of all pathology in the first year of life, confirmed that these were normal fetuses. The result has been expressed as a global figure for all 106 fetuses; then they have been divided up according to the gestational age groups (20-23, 24-27, and 28-34 weeks of amenorrhoea). These biological reference values and their changes as the age of the fetuses advanced are discussed and compared with the figures reported in the literature.

[Maternofetal infection with human parvovirus B19. Apropos of 2 cases]. / Infection materno-foetale à parvovirus humain B19. A propos de deux observations.

Two cases of maternal-fetal human parvovirus B19 infection are reported. The first case involved a feto-placental anasarca occurring during the third trimester and complicated by in-utero death with expulsion of a fetus with multiple malformations. The second case involved meconial peritonitis during the second trimester with favourable outcome after cesarean section and resolution of the digestive syndrome. Proof of PV B19 infection was obtained by identifying M specific immunoglobulins and viral DNA. After a review of the clinical situations most often encountered and the particular features of these two cases, therapeutic attitudes are proposed for this infection of major gravity during pregnancy.

[Fetal blood sampling under ultrasonic control]. / Prélèvement de sang du cordon foetal sous contrôle échographique.

Withdrawing foetal blood from the umbilical cord under ultrasonic control requires close co-ordination between obstetricians and echographists. The most important indications for this procedure are infections and foetal karyotype determination.