BACKGROUND AND PURPOSE: A malformed corpus callosum carries a risk for abnormal neurodevelopment. The advent of high-frequency transducers offers the opportunity to assess corpus callosum development in early pregnancy. The aim of the study was to construct a reference chart of the fetal corpus callosum length on ultrasound between 13 and 19 weeks of gestation and to prospectively examine growth patterns in pathologic cases. MATERIALS AND METHODS: We performed a prospective cross-sectional study between 2020 and 2022 in well-dated, low-risk, singleton pregnancies between 13 and 19 weeks of gestation. A standardized image was obtained in the midsagittal plane. Imaging criteria were used as a confirmation of the early corpus callosum. Measurements were taken by 4 trained sonographers. Intra- and interobserver variability was assessed. Corpus callosum length in centiles were calculated for each gestational week. RESULTS: One hundred eighty-seven fetuses were included in the study. All cases met inclusion criteria. At 13 weeks of gestation, the margins of the early corpus callosum were sufficiently clear to be measured in 80% (20/25) of fetuses. A cubic polynomial regression model best described the correlation between corpus length and gestational age. The correlation coefficient (r2) was 0.929 (P < .001). Intra- and interobserver variability had high interclass correlation coefficients (>0.99). Presented is the earliest published case of agenesis of corpus callosum and a case of dysgenetic corpus callosum in Rubinstein-Taybi syndrome. CONCLUSIONS: Provided is a nomogram of the early fetal corpus callosum. Applying imaging criteria helped to identify a case of complete agenesis of the corpus callosum as early as 14 weeks.

Conclusions: There has been a steady improvement in detection of fetal defects in the first trimester over the last two decades.Subsequent to regular audits, introduction of newer markers has shown to significantly improve detection of specific fetal defects, especially, that of the spine, cardia and clefts of the palate.

Postnatal imaging studies have shown structural brain anomalies in patients suffering from fetal alcohol spectrum disorders, including enlarged and malformed hippocampi.1,2 This atlas-based fetal MRI study aimed to identify early regional effects of prenatal alcohol exposure (PAE) on human fetal brain development. This IRB-approved prospective single-centre study identified pregnant women referred for fetal MRI with variable amounts of alcohol intake during pregnancy using two standardised questionnaires (PRAMS and TACE).3,4 Postprocessing was conducted based on semiautomated segmentations of super resolution fetal brain 1.5T and 3T MR datasets. After assessment of data quality, an atlas-based analysis of various fetal brain structures was performed. After excluding subjects with structural brain anomalies and/or poor super resolution image quality, a total of 27 patients with PAE and 36 controls (gestational age 20-37 GW, mean 27.2 GW) were included and analysed. In fetuses exposed to alcohol both hippocampi (left p = 0.035, right p = 0.024) and the corpus callosum (p = 0.035) showed significantly larger volumes (mean volumes ± SD), whereas the periventricular/germinal zone (p = 0.003) showed smaller volumes compared to controls. While it is well known that PAE may cause neurodevelopmental deficits, this study systematically documented selective effects on regional brain volumes at prenatal stages. Besides reduction in the size of the germinal matrix, an increased regional growth of the hippocampus and the corpus callosum was found. Norman AL et al. 2009 Dev Disabil Res Rev.15(3):209–217. Roediger DJ et al. Jan–Feb 2021 Neurotoxicol Teratol. 83:106944. Shulman HB et al. Oct 2018 Am J Public Health.108(10):1305–1313. Sokol RJ et al. Apr 1989 Am J Obstet Gynecol.160(4):863–870.

Figure 1. Axial view (1) midline, (a+b) reference lines, (*)angle Results During fetal development in week 18-24, the hippocampus underwent a mean rotational movement from 97,53° to 169,40° with a mean increase of 40,55° between week 18-21 and 31,32° between week 2124. The angle on the right side tended to be bigger than on the left side. In week 20 the side difference was statistically significant (p=0,039).

Das Durchschnittsalter der Schwangeren steigt weiterhin an, und damit auch die Bedeutung der Aneuploidien. Der größte Meilenstein der vergangenen Jahre, der Screeningtest der Zukunft, ist die Untersuchung der zellfreien DNA im Blut der Mutter im Hinblick auf fetale Aneuploidien. Besonders hoch ist die Genauigkeit bei der Trisomie 21. Die Möglichkeiten der Fehlbildungsdiagnostik, besonders im Bereich des Zentralnervensystems, werden im 2. Trimenon durch fetale Magnetresonanzuntersuchungen erweitert. Pränatale Eingriffe verbessern beim fetofetalen Transfusionssyndrom sowie bei manchen Formen der Zwerchfellhernie und der Spina bifida die Prognose. Erstmals konnte in den vergangenen Monaten und Jahren die Wirksamkeit von prophylaktischen Maßnahmen bei hohem Risiko für Plazentainsuffizienz und Frühgeburt gezeigt werden.

Die pränatale Ultraschalluntersuchung dient neben der Diagnose von angeborenen Fehlbildungen auch der Erkennung von fetalen Chromosomenstörungen. Als Screening-Methoden zur Vorhersage der Wahrscheinlichkeit einer fetalen Aneuploidie wurden die Altersindikation, biochemische und sonographische Marker im zweiten Trimenon, das Ersttrimester-Screening, der Combined Test und seit 2012 der nichtinvasive pränatale Test (NIPT) verwendet. Die Vorhersagesicherheit dieser Wahrscheinlichkeitsrechnungen ließ sich immer weiter steigern, die Falsch-positiv-Rate immer mehr senken. Kam es durch das Ersttrimester-Screening zu einer Reduktion der invasiven Eingriffe um etwa 90 %, führt der NIPT seinerseits zu einer neuerlichen Reduktion der invasiven Eingriffe um 50 %. Somit wird zurzeit nur etwa 1 % aller Schwangeren punktiert, die einen möglichst sicheren Ausschluss der fetalen Trisomie 21 wünschen. Aus dieser Reduktion lässt sich ableiten, dass die Zahl der unerwünschten Schwangerschaftsverluste als Komplikation der invasiven Pränataldiagnostik gegen Null streben wird.

Fragestellung: Verändert die Einführung der zellfreien DNA Untersuchung im Blut der Mutter die Anzahl pränataldiagnostischer Eingriffe nach Combined Test. Methodik: Retrospektiver Vergleich von 2967 konsekutiven Patientinnen nach Einführung der cfDNA Untersuchung mit 2967 Patientinnen vor Einführung der cfDNA Untersuchung in einem privaten Zentrum für pränatale Diagnostik. Die Anzahl von Punktionen nach Combined Test und der Prozentsatz auffälliger Karyogramme wurden zwischen den beiden Gruppen verglichen. Ergebnisse: 4,3% (127/2967) aller Patientinnen nach Combined Test und 26,3% (57/217) der Patientinnen, deren Combined Test eine Wahrscheinlichkeit > 1 : 1000 für Trisomie 21 ergab, entschieden sich für die cfDNA Untersuchung. Die Rate pränataldiagnostischer Eingriffe nach Einführung der cfDNA Untersuchung sank signifikant von 2,5% (75/2967) auf 1,1% (32/2967, p < 0,001). Darüber hinaus stieg der Anteil auffälliger Karyogramme nach Punktionen von 25,3% (19/75) auf 46,9% (15/32, p = 0,03). Bei 1,6% (2/127) der cfDNA Untersuchungen ergab diese ein erhöhtes Risiko für Trisomie 21. Beide Trisomie 21 Fälle wurden mittels invasiver Diagnostik bestätigt. Schlussfolgerung: Die Einführung der cfDNA Untersuchung führte zu einer Halbierung invasiver Eingriffe nach Combined Test. Die Rate an auffälligen Karyogrammen nach invasiver Diagnostik stieg auf das Doppelte an.

Progesterone treatment in second and third trimester of pregnancy has been shown to reduce the risk of preterm delivery in high-risk singleton gestations. This study was conducted to investigate the preventive effect of vaginal progesterone in a large population of twin gestations. A double-blind, placebo-controlled randomised trial was performed in 17 centres in Denmark and Austria. Women with twin gestations were randomised at 20–24 weeks' gestation to daily treatment with progesterone pessaries or identically looking placebo pessaries until 34 weeks' gestation. Primary outcome was spontaneous delivery or intrauterine death before 34 weeks' gestation. Secondary outcomes were neonatal complications and long-term infant follow-up by Ages and Stages Questionnaire (ASQ) at 6 and 18 months of age. All analyses were performed according to the intention-to-treat principle. A total of 677 women were randomised (334 to the progesterone group and 343 to the placebo group). Two women in the placebo group were lost to follow-up. Baseline characteristics for the progesterone and placebo group were similar. The rate of spontaneous delivery or intrauterine death before 34 weeks was 12.6% in the progesterone group versus 15.5% in the placebo group, odds ratio 0.8 (95% confidence interval 0.5–1.2). Risks of selected maternal and neonatal complications were comparable for the groups. Mean ASQ-score at 6 months was 215 for infants in the progesterone group and 218 for infants in the placebo group (P = 0.45), and 193 and 194, respectively, at 18 months of age (P = 0.89). Progesterone treatment did not prevent preterm delivery in twin gestations. No beneficial or harmful effects were observed in women or infants.

OBJECTIVES:Levels of SRY-specific cell free fetal DNA (SRY-cffDNA) in maternal plasma were investigated in twin pregnancies with two male fetuses versus one male and one female fetus and singleton male pregnancies during second and third trimester. The aim was to evaluate at which gestational age the amount of SRY-cffDNA reflects the number of fetuses and placentas respectively.METHODS:251 venous blood samples were analyzed from a total of 178 women with male or mixed-gender twin pregnancies and male singleton pregnancies in the second and the third trimester. The concentration of SRY-cffDNA was determined by quantitative real time PCR using the Y-chromosome specific SRY assay. For statistical analysis these three groups were divided into four subgroups according to their gestational age.RESULTS:During second trimester levels of SRY-cffDNA showed no differences between twin and singleton pregnancies. After 28 weeks SRY-cffDNA of male twin pregnancies was significantly increased compared to singleton male pregnancies and mixed-gender twin pregnancies with no differences between the latter two.CONCLUSION:The level of SRY-cffDNA in maternal serum of twin pregnancies reflects the number of fetuses only during the third trimester. Hence its use as a diagnostic tool for complications related to altered SRY-cffDNA levels in twin pregnancies should be evaluated at different weeks of gestation, especially during the second trimester.

Die Schwangerschaft bringt beträchtliche körperliche Veränderungen mit sich und ist eine Zeit der Umstellung auf eine vollkommen neue psychosoziale Situation. Mortalität und Morbidität von Mutter und Kind sind auf einem historischen Tiefpunkt, daher richtet sich das Augenmerk zunehmend auf die Optimierung der „Brutzeit“.

Fragestellung: Opioide beeinflussen die basale Herzfrequenz, die Herzfrequenz-Variabilität und die Anzahl an Herzfrequenz-Akzelerationen bei reifen Feten. Bei opiodabhängigen Müttern ist bereits im ersten Trimenon ein signifikanter Unterschied in der fetalen Herzfrequenz zu nicht-opiodabhängigen Müttern nachweisbar. Inwieweit hierbei Unterschiede zwischen den zur Substitution eingesetzten Opioidpräperaten in ihrem Einfluss auf die fetale Herzfrequenz bestehen, wollten wir durch diese Untersuchung klären.

Objectives Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins.Methods This was a subanalysis of a Danish-Austrian, double-blind, placebo-controlled, randomized trial (PREDICT study), in which women with twin pregnancies were randomized to daily treatment with progesterone or placebo pessaries from 20-24 weeks until 34 weeks' gestation. This subpopulation consisted of high-risk pregnancies, defined by the finding of cervical length <= 10(th) centile at 20-24 weeks' gestation or history of either spontaneous delivery before 34 weeks or miscarriage after 12 weeks. Primary outcome was delivery before 34 weeks. Secondary outcomes were complications for infants including long-term follow-up by Ages and Stages Questionnaire (ASQ) at 6 and 18 months of age.Results In 72 (10.6%) of the 677 women participating in the PREDICT study, the pregnancy was considered to be high-risk, including 47 with cervical length <= 10(th) centile, 28 with a history of preterm delivery or late miscarriage and three fulfilling both criteria. Baseline characteristics for progesterone and placebo groups were similar. Mean gestational age at delivery did not differ significantly between the two groups either in patients with a short cervix (34.3 +/- 4.1 vs 34.5 +/- 3.0 weeks, P = 0.87) or in those with a history of preterm delivery or late miscarriage (34.6 +/- 4.2 vs 35.2 +/- 2.7 weeks, P = 0.62). Similarly, there were no significant differences between the treatment groups in maternal or neonatal complications and mean ASQ score at 6 and 18 months of age.Conclusion In high-risk twin pregnancies, progesterone treatment does not significantly improve outcome. Copyright. (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

The risk of preterm delivery and admission to neonatal intensive care units is much higher in twin compared with singleton gestations. Procedures and drugs studied to prevent preterm delivery include bed rest, cerclage, antibiotics, and tocolytics; none have been found to be effective. Two large trials have shown that progesterone treatment in singleton women is effective in preventing preterm birth.The PREDICT study was a double-blind, placebo-controlled randomized trial that tested the hypothesis that treatment of women carrying twin gestations with vaginal micronized progesterone would reduce the rate of preterm delivery. The trial was conducted in 17 hospitals in Denmark and Austria between 2006 and 2008. Study subjects were randomized to receive daily treatment with either progesterone (n = 334) or placebo (n = 343) pessaries. Treatment started between 18 and 24 weeks' gestation and continued until 34 weeks. The primary study outcome was incidence of delivery before 34 weeks' gestation. Prespecified secondary outcomes included maternal and neonatal complications and long-term follow-up of neurophysiological development at 6 and 18 months after the estimated date of delivery using the Ages and Stages Questionnaire. A published meta-analysis was updated to include the present data and those of a recently published twin trial.Baseline characteristics were comparable in the 2 groups. There was no significant difference between the groups in the incidence of delivery before 34 weeks' gestation (progesterone: 15.3% vs. placebo: 18.5%); the odds ratio was 0.8, with a 95% confidence interval of 0.5-1.2. Moreover, no difference was found among the groups in the mean Ages and Stages Questionnaire scores at 6 months (progesterone: 215 vs. placebo: 218; P = 0.45) or at 18 months (progesterone: 193 vs. placebo: 194; P = 0.89). Risks of maternal and neonatal complications were also similar. Inclusion of all new data in the meta-analysis gave a pooled odds ratio of 1.06 (95% confidence interval: 0.86-1.31).The findings suggest that vaginal progesterone is not effective for preventing preterm delivery in twin gestations.

Progesterone treatment reduces the risk of preterm delivery (PTD) in high-risk singleton gestations. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twin gestations. This is a sub study of a Danish-Austrian double-blind, placebo-controlled randomized trial (PREDICT study), where women with twin gestations were randomized to daily treatment with progesterone or placebo pessaries from 20–24 weeks until 34 weeks' gestation. This sub population consists of high-risk pregnancies defined as cervical length ⩽ 10th centile at 20–24 weeks in current pregnancy or history of either spontaneous delivery before 34 weeks or miscarriage after 12 weeks. Primary outcome was delivery before 34 weeks. Secondary outcomes were complications for infants including long-term follow-up by Ages and Stages Questionnaire (ASQ) at 6 and 18 months of age. Of 677 women in the PREDICT study, 72 women were defined as high-risk and were included in this study. A total of 47 women (17 treated with progesterone and 30 with placebo) had a short cervix and 28 women (10 treated with progesterone and 18 with placebo) had a history of spontaneous PTD or late miscarriage. Three women had history of PTD or miscarriage and also a short cervix. Baseline characteristics for progesterone and placebo groups were similar. In women with a short cervix rate of spontaneous delivery before 34 weeks was 29% in the progesterone group versus 40% in the placebo group, odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2–2.2). The corresponding proportions were 30% and 22%, respectively, OR 1.5 (95% CI 0.3–8.6) for women with history of PTD or late miscarriage. Risks of maternal and neonatal complications were comparable for the two treatments. Mean ASQ score at 6 and 18 months did not differ significantly between the progesterone and the placebo group in any of the two high-risk groups. Progesterone treatment did not affect the rate of preterm delivery in high-risk twin gestations.