The impact of optimal dating on the assessment of fetal growth.

BACKGROUND: The impact of using the Intergrowth (IG) dating formulae in comparison to the commonly used Robinson dating on the evaluation of biometrics and estimated fetal weight (EFW) has not been evaluated. METHODS: Nationwide cross-sectional study of routine fetal ultrasound biometry in low-risk pregnant women whose gestational age (GA) had been previously assessed by a first trimester CRL measurement. We compared the CRL-based GA according to the Robinson formula and the IG formula. We evaluated the fetal biometric measurements as well as the EFW taken later in pregnancy depending on the dating formula used. Mean and standard deviation of the Z scores as well as the number and percentage of cases classified as <3rd, < 10th, >90th and > 97th percentile were compared. RESULTS: Three thousand five hundred twenty-two low-risk women with scans carried out after 18 weeks were included. There were differences of zero, one and 2 days in 642 (18.2%), 2700 (76.7%) and 180 (5%) when GA was estimated based on the Robinson or the IG formula, respectively. The biometry Z scores assessed later in pregnancy were all statistically significantly lower when the Intergrowth-based dating formula was used (p < 10- 4). Likewise, the number and percentage of foetuses classified as <3rd, < 10th, >90th and > 97th percentile demonstrated significant differences. As an example, the proportion of SGA foetuses varied from 3.46 to 4.57% (p = 0.02) and that of LGA foetuses from 17.86 to 13.4% (p < 10- 4). CONCLUSION: The dating formula used has a quite significant impact on the subsequent evaluation of biometry and EFW. We suggest that the combined and homogeneous use of a recent dating standard, together with prescriptive growth standards established on the same low-risk pregnancies, allows an optimal assessment of fetal growth.

Implementing the INTERGROWTH-21st fetal growth standards in France: a 'flash study' of the College Français d'Echographie Foetale (CFEF).

OBJECTIVES: To assess potential differences in fetal size between the French population and the international population from the INTERGROWTH-21st (IG-21st ) Project and to measure the impact of switching to the IG-21st reference standards for fetal size. METHODS: This was a nationwide cross-sectional study of fetal ultrasound biometry. Low-risk singleton pregnancies were recruited prospectively within the network of the national French College of Fetal Ultrasound, CFEF, over a 6-week period. Further selection was performed based on the criteria of the IG-21st Project in order to obtain a comparable population. Head circumference (HC) was used as the main fat-free skeletal measure of growth for comparison of French fetal size with that of the IG-21st population. The impact of switching to the IG-21st fetal growth standards was quantified by comparing Z-scores calculated using the IG-21st standards with those calculated using locally derived reference ranges for HC, abdominal circumference (AC) and femur length (FL). RESULTS: Following selection, 4858 cases were analyzed. The distribution of HC demonstrated clear similarity between our French population and the IG-21st population: our observed centile curves closely matched those of IG-21st and the Z-scores were close to 0 across gestational age. The IG-21st standards performed as well as did locally derived charts in terms of screening for small-for-gestational age by AC, while they identified significantly fewer small FL values than were expected and than did the locally derived charts. CONCLUSIONS: Under strict selection criteria, fetal size in France is similar to that of the international population used in the IG-21st Project. The discrepancies in FL are unlikely to impact on prenatal management. Therefore, switching from locally derived reference ranges to the IG-21st standards appears to be a safe option. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[A simple self-assessment tool for the first-trimester ultrasound images]. / Une auto-évaluation simplifiée des images échographiques du premier trimestre.

OBJECTIVES: The objective of this study was to establish a minimum subset of simple criteria for the self-assessment of the quality of first-trimester ultrasound images of nuchal translucency (NT) and crown-rump length (CRL). METHODS: We designed 162 simplified image-scoring methods (ISM) based on 1, 2, 3 or 4 binary criteria derived from the 8 criteria of the original image scoring method of the French College of Fetal Ultrasound (CFEF). These ISM were assessed on 68,250 consecutive scans of the French national audit conducted by the CFEF on NT and CRL images. The ISM associated with the best precision to identify excellent/reasonable quality scans were selected. RESULTS: Simplified ISM based on 1, 2, 3 and 4 criteria showed maximum positive predictive values of 95.3% (95.11-95.50) 98.0% (97.87-98.14), 99.3% (99.17-99.35) and 99.7% (99.68-99.79), respectively, to identify excellent/reasonable quality scans. The proportion of excellent/reasonable scans was 2.8 to 16.7% when three criteria among the 8 were insufficient, and 0.17 to 3.95% when four criteria were insufficient. CONCLUSIONS: The best performing ISM was based on the following four quality criteria: (i) sagittal plane of the NT, (ii) calipers placement for measuring the NT, (iii) image magnification of NT images and (iv) CRL measurement. This score might be the most relevant in clinical practice in the first-trimester screening.

[Fetal abdominal cysts at the first trimester scan]. / Images kystiques abdominales fœtales du premier trimestre.

OBJECTIVES: Abdominal cysts are seldom detected at the first trimester scan. The aim of this study is to ascertain their outcome, which is currently not established. METHODS: The French College of Fetal Ultrasound conducted a prospective observational study of 24months, collecting all cases of abdominal cysts discovered during the first trimester ultrasound. Cases of megacystis were excluded from the study. Ultrasound images, prenatal diagnosis expert reports and pregnancy outcomes were collected by sonographers after patient consent. RESULTS: Ten cases of abdominal cysts were collected. The cysts had a mean diameter of 15mm. They were anechoic in 5 cases, hyperechoic in 2 cases and mixed in 3 cases. In 6 of 10 cases, complete resolution was observed at 18WG with a good post-natal outcome; the five cases with anechoic images were associated with normal pediatric examination at birth and in the case of the resolved hyperechoic image, an isolated imperforate anus was observed. In the four cases of hyperechoic or mixed images that had not resolved, the outcome was poor with four termination of pregnancies, including two cases of cloacal dysgenesis. CONCLUSIONS: Abdominal cysts are rare at the first trimester scan. They resolve in two thirds of cases and are then associated with good outcome. When they do not resolve or when they are not strictly anechoic, they require a referral ultrasound examination at 18 and 22WG.

Monitoring of ovulation induction with human menopausal gonadotropin and human chorionic gonadotropin by ultrasound.

Ovarian follicular growth was monitored by ultrasound and plasma estradiol levels in 43 cycles of 27 patients. These women were treated with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) for anovulation or poor cervical mucus. Ultrasonography can help to prevent multiple pregnancies by allowing the withholding of the ovulatory injection of hCG if the number of mature follicles is too great. Nevertheless, mild to moderate hyperstimulation cannot always be prevented; it is sometimes the price one has to pay to obtain a pregnancy. Giving a direct view of follicular maturation, this method can be helpful in the determination of the best time for the induction of ovulation.

Vascular resistance of uterine arteries: physiological effects of estradiol and progesterone.

To determine if reproductive hormones played a role at physiological levels on vascular resistance of uterine arteries, we studied young women having inactive ovaries who received exogenous estradiol (E2) and progesterone (P). Six women, ages 27 to 36 with absent or nonfunctioning ovaries, received transdermal E2 and vaginal P after a 28-day replacement regimen duplicating E2 and P levels seen in the menstrual cycle. Vascular resistance of uterine arteries was evaluated before treatment (baseline), on days 13 to 14 and on days 26 to 27, using transvaginal pulsed Doppler combined with real-time imaging. Doppler waveforms were analyzed by the pulsatility index (PI). Baseline evaluation showed narrow systolic Doppler flow waves with a PI of 5.2 +/- 0.4, mean +/- SEM. On cycle day 13, Doppler waveforms showed a marked broadening with uninterrupted diastolic flow indicative of a profound decrease in vascular resistance. This was reflected by a significant decrease in PI to 1.3 +/- 0.3, mean +/- SEM. Doppler measurements made on days 26 to 27 showed no significant change. Our results indicate that at physiological levels, E2 affects vascular resistance of uterine arteries. This represents a new parameter of estrogen action, readily measurable by a noninvasive technique that, in the future, may help for assessing the efficacy of various estrogenic treatments.

Resveratrol Oxidation in Botrytis cinerea Conidia.

ABSTRACT Observations using light microscopy showed that approximately 30% of Botrytis cinerea conidia treated with semi-lethal concentrations (i.e., 60 mug/ml) of the grapevine phytoalexin resveratrol possessed intracellular brown coloration. This coloration was never observed in the absence of resveratrol or in conidia treated with resveratrol together with sulfur dioxide (antioxidant compound) or sodium diethyldithiocarbamate (inhibitor of laccase action), suggesting that discoloration resulted from the laccase-mediated oxidation of resveratrol. Further studies using transmission electron microscopy enabled the observation of particular intravacuolar spherical vesicles and of granular material deposits along the tonoplast. These observations are likely to be related to the oxidation of resveratrol by an intracellular laccase-like stilbene oxidase of B. cinerea.

Characterization of a Pterostilbene Dehydrodimer Produced by Laccase of Botrytis cinerea.

ABSTRACT In the interaction between grapevines and Botrytis cinerea, one of the main aspects of pathogenicity is fungal ability to degrade phytoalexins synthesized by the plant in response to infection. Laccase-like stilbene oxidase activity in liquid cultures of B. cinerea has been shown to be related to the decrease of phytoalexin concentrations. Recent research and results presented in this paper determined the chemical structure of a pterostilbene metabolite produced by B. cinerea. Study of degradation of pterostilbene that has just one free hydroxy phenyl group function allowed us to determine the oxidative dimerization process undergone by grapevine phytoalexins after B. cinerea infection. The phytopathological significance of this degradation process in the B. cinerea interaction has also been discussed.

Changes in the phytoalexin content of various Vitis spp. in response to ultraviolet C elicitation.

The phytoalexin production potential of three American Vitis species and that of three cultivars of Vitis vinifera were evaluated in response to UV-C irradiation. Time course changes in resveratrol, piceid, epsilon-viniferin, and pterostilbene contents were studied within 3 days after a short UV-C irradiation. Results show that the two major stilbenes accumulated as a response to UV-C elicitation are resveratrol and epsilon-viniferin, a resveratrol dehydrodimer, the concentration of both compounds usually reaching quantities >100 microgram/g of fresh weight. In contrast, piceid and pterostilbene were constantly produced in low quantities. Owing to the results obtained, the role of stilbene phytoalexins in the resistance of grapevines to diseases is discussed.

Stilbene content of mature Vitis vinifera berries in response to UV-C elicitation.

A method using HPLC analysis has been used to compare the level of resveratrol and its derivatives, piceid, pterostilbene and epsilon-viniferin, in grapevine berries of three Vitis vinifera varieties. The concentration of these compounds has been evaluated in healthy and Botrytis cinerea infected grape clusters, both in natural vineyard conditions and in response to UV elicitation.

[Accidental ultrasonographic disclosure of isolated intra-abdominal fetal hyperechogenicity. Apropos of a series of 87 cases]. / Découverte fortuite à l'échographie d'une hyperéchogénicité intra-abdominale foetale isolée. A propos d'une série de 87 cas.

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyperechogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

[What's new in fetal medicine?]. / Quoi de neuf en médecine foetale?

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.

[Nul telediastolic flux. Prognostic value]. / Flux télédiastolique nul. Valeur pronostique.

42 fetuses over a period of 2 1/2 years have presented with absent end-diastolic velocity. In 6 of these cases the measurements that had been carried out before the 22nd week of pregnancy with later normalisation of the Doppler velocities did not constitute a poor prognostic sign. On the other hand, absent end-diastolic velocity after the 22nd week (36 fetuses) was a sign of chronic fetal distress. The fetal mortality was 33.2%. 19.45% of the infants had chromosome abnormalities and only 58% of these children were alive and healthy. 74% of the live infants were delivered by caesarean section. With these results we think that absent end-diastolic velocity is a simple diagnostic sign, but it warns us that we should carry out tests for the fetal karyotype.

[Fortuitous discovery in echography of an isolated fetal intra-abdominal hyperechogenic mass. 87 cases]. / Découverte fortuite à l'échographie d'une hyperéchogénicité intra-abdominale foetal isolée. A propos d'une série de 87 cas.

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyper-echogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

[Combined hydramnios with fetal ascites due to intra-uterine meconium peritonitis (authors' transl)]. / Une association hydramnios-ascite foetale relevant d'une péritonite méconiale intra-utérine.

It is possible with echotomography to make out fetal ascites in the last months of pregnancy. One of the causes of combined fetal ascites and hydramnios among several other possible ones is primary meconium peritonitis, which diagnosis can be confirmed after birth.

[Prenatal diagnosis and genetic diseases of the lung]. / Diagnostic anténatal et maladies génétiques pneumologiques.

Currently two genetic pulmonary disorders can be diagnosed before birth: alpha-1-antitrypsin deficiency and mucoviscidosis. For the latter there are two possible diagnostic techniques: first a study of the intestinal enzymes of the amniotic fluid, a reliable method only at the 18th week, and also a study of DNA markers (ADN) of the trophoblastic cells using molecular biological techniques: this can be performed from the 10th to 11th week of pregnancy but presupposes a family study in which there is already a subject suffering from the disorder. Foetal echocardiography enables various pulmonary abnormalities to be detected: pleural effusion, cyst, pulmonary hypoplasia and other disorders. This technique however has some limits, at least at present. Most often these severe malformations are revealed at birth such as respiratory distress or stillbirth. Adenomatous cystic malformations or congenital lobar emphysema, a posterior diaphragmatic hernia, and oesophageal atresia with oesophagotracheal fistula are the most frequent and are curable surgically.

[Report of the French Comité national technique de l'échographie de dépistage prénatal (CNTEDP)--Recommendations for second line prenatal ultrasound]. / Rapport du Comité national technique de l'échographie de dépistage prénatal (CNTEDP): recommandations pour l'échographie de diagnostic.

OBJECTIVES: The committee has among its functions, to promote a quality assurance policy for obstetrics and foetal ultrasound scans by participating in the development of an information strategy for the professionals and the public on the interest and limits of these techniques, and in the development of rules for good practice. Thus, the committee produced in 2005 a good practice's recommendations report concerning the screening ultrasound scans. It pursued its work with a similar report concerning this time the "diagnostic" prenatal ultrasound or second line prenatal ultrasound. The present report has set its objective to define as precisely as possible the content of a "diagnostic" ultrasound scan and what should be expected from it. MATERIALS AND METHODS: A group of experts from the committee members has functioned as a task team that met on a regular basis. First, in the context of a professional consensus and a review of the literature, it determined the clinical goals in regard to the indication of the "diagnostic" ultrasound scan. After discussing different formats of the scan test procedure, some intuitive hypotheses on the content of the test were developed. Each criteria was validated by the group of experts with a statistics' definition and a diagnosis' capacity. The hypotheses were finally validated or discarded after confrontation with the data of the literature. Finally, the content of the report was discussed during the plenary sessions of the CNTEDP, the National Committee on the Technical aspect for PreNatal Ultrasound Screening. All the items validated in format document have been the subject of a consensus with a right to veto. The preliminary report was reviewed by a group of six readers not members of the CNTEPD. RESULTS: The "diagnostic" ultrasound scan test is organized in two parts: one common part made of the content of the screening test, to which is added the study of the anatomic structures and taking some additional pictures. The sonologist must then do a specific scan study for the organ suspected or diagnosed with an anomaly. Subsequently, a series of ten format documents per anomaly is proposed to guide the examiner (i.e., abdomen, chest, heart, genitourinary, cerebrospinal, skeletal and limbs, IUGR, polyhydramnios, infection, twin pregnancy). These documents suggest a check-list of items to study during the scan, specific pictures to take, and, give some comments on the management plan. DISCUSSION AND CONCLUSION: The CPDPN, the Multidisciplinary Committee for PreNatal Diagnosis, since it was established in 1994, has contributed to structure most of the activity of the prenatal diagnosis, but did not answer the question of the quality of the second line prenatal ultrasound. Screening ultrasound, and focused ultrasound scan are not "levels" in the scan procedure, but different and supplementary studies contributing to the quality of the mother and her foetus follow-up. This report of the CNTEDP, in defining the content of this scan test, clarifies the objectives of the diagnostic test compared to the screening test, and subsequently gives the public a better understanding of what is expected or due in regard to our prenatal screening strategy. A reliable second level scan, affordable and consistent, is a label of good quality for our prenatal strategy. The recommendations of the committee should be understood in a large perspective of quality assurance, that includes an initial and a continuous medical education, a quality control system for the echograph, and a procedure to inform the public.