Prediction of neonatal outcome of TTTS by fetal heart and Doppler ultrasound parameters before and after laser treatment.

OBJECTIVES: To determine the prognostic value of fetal Doppler and echocardiographic parameters for neonatal survival up to 30 days after laser coagulation in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS). METHODS: Fetal echocardiography and outcome data of consecutive cases of TTTS treated by laser were retrospectively reviewed. Hemodynamic and cardiac function parameters were collected before and after laser. RESULTS: Between February 2006 and January 2015, 106 fetoscopic laser were performed. The final analysis was limited to cases with ultrasound within 2 days before laser (n = 77) and 4 weeks after laser (n = 86). Overall neonatal survival rate was 64.9% (135/208) and 77.9% of pregnancies (81/104) had at least one baby alive. For the recipient twin, the preoperative predictors of neonatal survival were umbilical artery (UA) pulsatility index (PI), cerebro-placental PI ratio, UA end diastolic flow (EDF), ductus venosus a-wave, right ventricular myocardial performance index (RV-MPI) and CHOP score. The postoperative predictors of donor survival were donor RV-MPI and recipient UA EDF, umbilical vein pulsations, tricuspid regurgitation, cardiac hypertrophy and CHOP score. CONCLUSION: The hemodynamic predictors of postnatal survival after laser were preoperative signs of recipient cardiomyopathy and postoperative signs of cardiac overload in both twins. © 2016 John Wiley & Sons, Ltd.

Prevalence of rosacea in the general population of Germany and Russia - The RISE study.

BACKGROUND: There is an unmet need for general population-based epidemiological data on rosacea based on contemporary diagnostic criteria and validated population survey methodology. OBJECTIVE: To evaluate the prevalence of rosacea in the general population of Germany and Russia. METHODS: General population screening was conducted in 9-10 cities per country to ensure adequate geographic representation. In Part I of this two-phase study, screening of a representative sample of the general population (every fifth person or every fifth door using a fixed-step procedure on a random route sample) was expedited with use of a questionnaire and algorithm based on current diagnostic criteria for rosacea. Of the subjects that screened positive in the initial phase, a randomly selected sample (every third subject) t`hen underwent diagnostic confirmation by a dermatologist in Part II. RESULTS: A total of 3052 and 3013 subjects (aged 18-65 years) were screened in Germany and Russia respectively. Rosacea prevalence was 12.3% [95%CI, 10.2-14.4] in Germany and 5.0% [95%CI, 2.8-7.2] in Russia. The profile of subjects with rosacea (75% women; mean age of 40 years; mainly skin phototype II or III, majority of subjects with sensitive facial skin) and subtype distribution were similar. Overall, 18% of subjects diagnosed with rosacea were aged 18-30 years. Over 80% were not previously diagnosed. Within the previous year, 47.5% of subjects had received no rosacea care and 23.7% had received topical and/or systemic drugs. Over one-third (35% Germany, 43% Russia) of rosacea subjects reported a moderate to severe adverse impact on quality of life. CONCLUSION: Rosacea is highly prevalent in Germany (12.3%) and Russia (5.0%). The demographic profile of rosacea subjects was similar between countries and the majority were previously undiagnosed.

[Progesterone and preterm delivery: back to the future?]. / Progestérone et prévention de l'accouchement prématuré: retour vers le future?

Progesterone was widely used in France during the 1980s and 1990s to prevent preterm birth until some published cases of cholestasis suddenly stopped its prescription. Since then, multiple randomized controlled trials have emerged and demonstrated the efficiency of the treatment but also its safety at low doses. In order to clarify its indications, we performed a current literature review. We analyzed literature data according to different categories of risk and different routes of administration. Results confirm that progesterone is an efficient treatment to prevent preterm birth in singleton gestation with short cervical length, and in singleton gestation with prior preterm birth with or without short cervical length. Apart from these indications, progesterone, especially 17-alpha-hydroxyprogesterone (17OHP), should not be used outside research protocols.

[Fellowship in Canada: instructions]. / Fellowship au Canada : mode d'emploi.

In North America, postdoctoral fellowships are proposed to physicians and surgeons after their residency to obtain an expertise in a specific domain of their speciality. In obstetrics and gynecology, three fellowship programs are accredited by the Royal College of Physicians and Surgeons of Canada: maternal fetal medicine, gynaecological oncology and reproductive endocrinology and infertility. A two-year fellowship in Canada provides a great professional and personal experience. We present here the organization of these programs and the conditions to be admitted in a fellowship program in Canada.

Fetal urinoma: two new cases and a review of the literature.

OBJECTIVE: To evaluate the functional prognosis of kidneys affected prenatally by urinomas. METHODS: This was a retrospective review of cases of fetal urinoma reported in the literature, as well as two of our own cases. RESULTS: Twenty-three patients with a prenatal diagnosis of urinoma (five bilateral) were included in the analysis. Postnatal ipsilateral renal function was observed in only six of the 28 renal units (i.e. around 20%). CONCLUSIONS: Although the precise causes of urinomas are still unknown, this review shows that in the event of a fetal urinoma, the probability of a non-functional dysplastic ipsilateral kidney lies at around 80%. In-utero puncture only appears to be justified in cases where fluid accumulation has mass effects on adjacent major structures.

Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of a pure muscular form with variable and early antenatal manifestations in the same family.

We report on a family of three consecutive fetuses affected by type IV glycogen storage disease (GSD IV). In all cases, cervical cystic hygroma was observed on the 12-week-ultrasound examination. During the second trimester, fetal hydrops developed in the first pregnancy whereas fetal akinesia appeared in the second pregnancy. The diagnosis was suggested by microscopic examination of fetal tissues showing characteristic inclusions exclusively in striated fibers, then confirmed by enzymatic studies on frozen muscle. Antenatal diagnosis was performed on the third and fourth pregnancies: cervical cystic hygroma and low glycogen branching enzyme (GBE) activity on chorionic villi sample (CVS) were detected in the third pregnancy whereas ultrasound findings were normal and GBE activity within normal range on CVS in the fourth pregnancy. Molecular analysis showed that the mother was heterozygous for a c.1471G > C mutation in exon 12, leading to the replacement of an alanine by a tyrosine at codon 491 (p.A491T); the father was heterozygous for a c.895G > T mutation in exon 7, leading to the creation of a stop codon at position 299 (p.G299X). GSD IV has to be considered in a context of cervical cystic hygroma with normal karyotype, particularly when second trimester hydrops or akinesia develop. Enzymatic analysis of GBE must be performed on CVS or amniotic cells to confirm the diagnosis. Characteristic intracellular inclusions are specific to the disease and should be recognized, even in macerated tissues after fetal death. Genetic analysis of the GBE gene may help to shed some light on the puzzling diversity of GSD IV phenotypes.

[Myasthenia gravis and pregnancy. Report on 13 cases]. / Myasthénie et grossesse: à propos de 13 grossesses.

OBJECTIVES: To evaluate our experience of myasthenia during pregnancy. MATERIALS AND METHODS: Retrospective study in a tertiary care university hospital including pregnant women affected by myasthenia gravis and who delivered in the obstetrical tertiary center. Medical and delivery reports were analyzed. RESULTS: Between 1994 and 2002, 12 women, age 31 (25-36), delivered 14 children. One women delivered twice, and there was one twin pregnancy. Clinical symptoms of myasthenia worsened in five. One was admitted twice to the intensive care unit during her pregnancy. Two were admitted to intensive care unit during the first month of post-partum. Gestational age at birth was 39.3 weeks (38-40.6), all birth weights were normal: 3329 g (2660-4520). Six women delivered vaginally, two by instrumental extraction and five by cesarean section. Apgar score was normal for all infants: 9/10. The level of anti-acetylcholine receptor antibodies (anti AchR) was high: 36.4 nM/L (0-46.8) (normal below 0.6 nM/L), but was not related to neonatal outcome. Three children presented neonatal myasthenia. CONCLUSION: We recommend obstetrical monitoring in tertiary centers for pregnant women with myasthenia gravis because of the risk of neonatal myasthenia. Measurement of anti-acetylcholine receptor antibodies may be useful. Pediatric and maternal observation is necessary in the first days of post partum.

Periventricular leukomalacia and mode of delivery in twins under 1500 g.

BACKGROUND: The optimal mode of delivery in twin gestations remains undefined, particularly for twins weighing less than 1500 g. OBJECTIVE: To evaluate the impact of the mode of delivery on neonatal outcome in twins below 1500 g. MATERIALS AND METHODS: In this multicenter cohort study during 1999, 66 sets of twins born in hospital and weighing below 1500 g formed our study group. Antenatal and neonatal parameters and their relationship to mode of delivery were studied, based on a factor analysis. Analysis of covariance was used to assess the effect of the mode of delivery on postnatal factors, with antenatal parameters used as covariates. RESULTS: Statistical analysis showed that infants delivered vaginally had significantly more periventricular leukomalacia than those children delivered by Cesarean section (p = 0.03). The estimated odds for leukomalacia were higher in the vaginal than in the Cesarean group when adjusted for covariates (OR = 4.7; 95% CI = 1.0, 25.15). CONCLUSION: Routine Cesarean section should be recommended in twin gestations with infants weighing less than 1500 g, regardless of gestational age or fetal presentation.

Fetal thoracoamniotic shunting as the only treatment for pulmonary sequestration with hydrops: favorable long-term outcome without postnatal surgery.

Although it is established that bronchopulmonary sequestration complicated by fetal hydrops carries a high risk of perinatal mortality, prenatal management remains controversial. Therapeutic options include immediate delivery, medical therapy based on an inotropic regimen, alcohol ablation of the vascular pedicle, open fetal surgery, or thoracoamniotic shunting of fetal pleural effusions. We report a case of pulmonary sequestration with hydrothorax and fetal hydrops which was successfully treated by a single fetal thoracoamniotic catheter drainage. Following emergency catheter placement, hydrothorax and hydrops decreased dramatically. The sequestration gradually disappeared postnatally, and long-term outcome remained normal without any postnatal therapy. Based on this observation, the natural history of pulmonary sequestration and prenatal management options are reviewed.

[Routine cytomegalovirus screening during pregnancy: is it worthwhile?]. / Faut-il proposer un dépistage sérologique de l'infection à cytomégalovirus pendant la grossesse?

The issue of routine antenatal screening for cytomegalovirus (CMV) infection raises a controversy in France. Supporters of a screening policy argue that this frequent congenital infection (about 1% of all newborns) is a known cause of neurological impairment or hearing loss, which could be prevented by the prenatal screening of the infection. However the majority of infected fetuses will be free of any symptom, and there is currently no reliable prognostic marker in the antenatal period. Moreover, no prenatal treatment has proven to be effective and safe. A screening strategy might lead to iatrogenic concerns, including parental anxiety, invasive prenatal testing, and terminations of pregnancies for unaffected fetuses. Based on current knowledge, routine antenatal screening of CMV infection during pregnancy cannot be recommended. Further research should focus on the development of a safe and effective prenatal treatment, and the development of better diagnostic tests.

Pregnancy outcome in fetuses with increased nuchal translucency and normal karyotype.

OBJECTIVE: This study was conducted to evaluate pregnancy outcome and mid- and long-term prognosis of cases with nuchal translucency > or =4 mm and normal karyotype. METHODS: Retrospective analysis of 160 cases who presented with a nuchal translucency > or =4 mm when the CRL was between 45 and 84 mm was undertaken. Cystic hygromas were excluded. When the karyotype was normal a detailed anomaly scan was performed at 20 to 24 weeks followed by serial ultrasound examination. Clinical examination of the neonates was performed by a paediatrician. Long-term follow-up was completed through a questionnaire filled in by parents, GPs and paediatricians. RESULTS: 160 fetuses had an NT > or =4 mm. 44.3% had an abnormal karyotype. Of the 55.7% with normal karyotypes, 74 % did not show any abnormalities on follow-up ultrasound scan. Mid- and long-term outcome was known in 91% of the cases. 6.4% had a malformation diagnosed only at birth. Among the normal neonates, 11.1% are considered to have a significant neurological handicap or orthopaedic problems at 12 to 72 months of age. CONCLUSION: In an unselected population, NT > or =4 mm is associated with a high incidence of chromosomal and non chromosomal abnormalities. Even when the fetal karyotype and serial ultrasound examinations are considered to be normal, the risk of fetal malformation and developmental delay should not be underestimated.

[Accompanying babies to death after late termination of pregnancy]. / Accompagnement au décès postnatal dans le cadre de l'interruption tardive de grossesse.

When feticide, necessary within the framework of late termination of pregnancy, cannot be achieved before delivery for medical reasons or because the act is refused by the parents, we propose as an alternative, to accompany the baby to death in the neonatology unit. This approach can be seen as palliative care despite the ethical and legal issues it raises. It can be an appropriate response to the parents' distress when moral and religious beliefs are contradicted by medical reality. This situation remains exceptional and must be envisaged case by case. The decision to institute the principle of accompanying babies to death was made after open discussion conducted for many years among neonatologists. The final decision cannot however be made until the obstetrical and pediatric teams have reached a sufficient degree of reciprocal confidence.

[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.

Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study.

OBJECTIVES: To compare nuchal translucency and second-trimester maternal serum measurements as alternative methods of antenatal screening for Down syndrome in a low-risk population and to evaluate the consequence of combining the results in the estimation of risk. DESIGN: In a consecutive series of 4130 women aged less than 38 years with a singleton pregnancy, we examined both the detection rate of Down syndrome by nuchal translucency measurement at 10-14 weeks and maternal serum screening by human chorionic gonadotrophin and alpha-fetoprotein at 14-18 weeks. Women with a nuchal translucency measurement of > or = 3 mm and women with a maternal serum screening-derived risk > or = 1/250 were recommended to have amniocentesis. A second-trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was recorded prospectively and the detection rate and false-positive rate of different screening strategies were retrospectively analyzed. RESULTS: Out of the 4130 pregnancies that were followed (mean maternal age, 30.1 years), 12 cases of Down syndrome were observed (0.28%), all detected prenatally. Seven of 12 cases had a nuchal translucency measurement of > or = 3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of > or = 1/250 (60%). Four of the five Down syndrome cases with a nuchal translucency measurement of < 3 mm were detected by subsequent maternal serum screening. At a threshold giving 5% of positive tests, the sensitivity of nuchal translucency, maternal serum screening and combined risk screening were 75%, 60% and 90%, respectively. CONCLUSIONS: In screening for Down syndrome, an approach which combines the results from first-trimester nuchal translucency and second-trimester biochemistry is effective and increases the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of maternal serum screening-derived risk should be combined with the first-trimester nuchal translucency measurement.

[Cervical cerclage with buried prosthetic band: technique, indications and results in a series of 28 pregnancies]. / Cerclage cervical par enfouissement d'une bandelette prothétique. Technique, indications et résultats à partir d'une série de 28 grossesses.

OBJECTIVES: We performed a retrospective study to evaluate the results of a new approach to cervical cerclage using a prosthetic band. MATERIALS AND METHODS: Twenty-four patients were recruited over an 8-year period between 1991 and 1999. All had a history of at least two late abortions and/or preterm delivery and a failed attempt with McDonald or Hervet cerclage. We used a cervical cerclage technique with prosthetic band inspired from the Shirodkar technique but which has been simplified and quite easy to reproduce. The technique consists in placing a prosthetic band around the internal os under the vaginal mucosa at the vesicovaginal reflection level. Outcome of pregnancy before and after inserting the prosthetic band was compared. RESULTS: Outcome of 28 pregnancies after cerclage were assessed (4 patients had two successive pregnancies with the same cerclage left in place). 82% of the children were liveborn after cerclage versus 21.7% before cerclage. 53.3% of the patients delivered at term after cerclage versus 2.8% before cerclage. We had 7.1% late miscarriages after cerclasge versus 65.2% before. There were no surgical complications. 22 of the 23 liveborn children were delivered by cesarean section. Conclusion. These results show that the cervical prosthesis is a solution of these patients with an obstetric history of cervical incompetence with failure of classical techniques.

The relationships between antenatal management, the cause of delivery and neonatal outcome in a large cohort of very preterm singleton infants.

OBJECTIVE: To determine whether the cause of very preterm delivery influences neonatal outcome. DESIGN: A cohort study of 685 consecutive singletons born before 33 weeks of gestation. METHODS: Causes of birth and perinatal outcome variables were correlated for statistical significance by uni- and multi-variate analyses. RESULTS: Intrauterine growth retardation or pre-eclampsia were associated with a higher rate of respiratory distress syndrome compared with prolonged rupture of membranes, after controlling for gestational age, antenatal corticosteroid therapy, antenatal antibiotic administration, mode of delivery and origin (inborn or outborn) (adjusted OR 3.12; 95% CI 1.55-6.28). The prevalence of grade 3-4 intraventricular haemorrhage or cystic periventricular leukomalacia was 25% in newborn babies born after intrauterine infection or prolonged rupture of membranes. Among infants born after intrauterine growth retardation/pre-eclampsia, the rate of severe intraventricular haemorrhage was 3.2% and the rate of periventricular leukomalacia was 0.9%. Compared with intrauterine infection and after controlling for potential confounding covariates, intrauterine growth retardation/pre-eclampsia was associated with a lower rate of periventricular leukomalacia (adjusted OR 0.08; 95% CI 0.02-0.41). In the same multiple logistic regression model, antenatal corticosteroid administration was associated with a lower incidence of periventricular leukomalacia (adjusted OR 0.36; 95% CI 0.16-0.79). CONCLUSIONS: The cause of very preterm delivery has an important influence on neonatal outcome.

Outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks of gestation.

OBJECTIVE: To identify factors influencing the outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks' gestation. DESIGN AND POPULATION: All premature infants with gestational age <34 weeks, either inborn or outborn, with history of rupture of membranes before 25 weeks' gestation, admitted to our NICU between January 1992 and July 1997, were eligible for this retrospective study. Collected information included birth weight, gestational age at rupture of membranes and at delivery, duration between rupture of membranes and delivery (latency period), severity of oligohydramnios, pre- and post-natal managements, and follow-up of survivors. RESULTS: A total of 28 neonates fulfilled the inclusion criteria. Despite new strategies of ventilation and optimal management, the overall mortality rate was 43% (12/28). Nonsurvivors were significantly less mature at rupture of membranes, and had severe oligohydramnios (anamnios). We also noted less antenatal corticosteroids and antibiotic therapy in this group. Nine of eleven infants (82%) following rupture of membranes before 22 weeks' gestation died shortly after birth. The two remaining infants developed severe bronchopulmonary dysplasia. Nine deaths occurred in thirteen cases (69%) of anamnios. The major death causes were refractory respiratory failure and neurologic complications. Half of all survivors (8/16) developed bronchopulmonary dysplasia. CONCLUSION: The outcome of premature infants following prolonged premature rupture of membranes before 25 weeks' gestation is influenced by gestational age at rupture, severity of oligohydramnios, and antenatal antibiotics and corticosteroids. Neonates with rupture of membranes before 22 weeks have a very low chance of survival at the present time.

Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.

BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants.

Efficiency of ultrasound and biochemical markers for Down's syndrome risk screening. A prospective study.

OBJECTIVE: To evaluate the sequential combination of ultrasound screening for fetal aneuploidy at 11-14 weeks with maternal biochemistry at 12-14 and 15-18 weeks of gestation. METHODS: A prospective study including 1,656 women, with a singleton pregnancy booked before 13 weeks of gestation. Nuchal translucency (NT) thickness was measured by transabdominal ultrasound examination. alpha-Fetoprotein, free betahCG and hCG were measured by immunoradiometric (12-14 weeks) or immunometric (15-18 weeks) assays. Derived risks were then calculated. Cutoff risks were chosen first arbitrarily at 1/250 and then adjusted for a 5% false-positive rate. RESULTS: Seven fetal aneuploidies were diagnosed, including 5 Down's syndromes, 1 trisomy 18 and 1 triploidy. Three Down's syndromes had concordant high risk with the 3 screenings. One was at low risk with NT, and another was at low risk by maternal serum screening, but sequential combination of screenings led to a 100% detection rate with cutoffs of 1/240, 1/160 and 1/250 for NT, first- and second-trimester biochemistry, respectively (i.e. for a cutoff adjusted for a 5% false-positive rate). CONCLUSION: This preliminary study suggests a benefit in combining maternal age-related risk together with NT and biochemical markers in the first or the second trimester. The algorithm combining these risks needs to be established in a wide population.