Generation of an iPSC line from skin fibroblasts of a patient with Joubert syndrome carrying the homozygous loss of function variant c.787dupC in the AHI1 gene.

We produced an iPSC line from a patient with Joubert syndrome carrying the homozygous c.787dupC variant in the AHI1 gene. The iPSC line was obtained by reprogramming skin fibroblasts, mycoplasma-free, using Sendai-virus-based technique. Characterization of iPSCs showed the same Short Tandem Repeats profile than fibroblasts, normal karyotype, expression of staminal markers (OCT4, SOX2, SSEA4 and NANOG) and ability to differentiate into three germ layers in vitro.

Long-term outcome of consecutive case series of congenital isolated agenesis of corpus callosum.

OBJECTIVE: To describe the long-term outcome of children with prenatally diagnosed isolated complete agenesis of the corpus callosum (cACC). METHODS: In this single-center case series, we reviewed retrospectively the charts of fetuses referred to our fetal therapy unit from January 2004 to July 2020 for a suspected anomaly of the corpus callosum (CC). Cases with prenatally diagnosed isolated cACC were included. Fetal karyotype and comparative genomic hybridization microarray of amniotic fluid, in addition to fetal magnetic resonance imaging, were offered to all pregnant women with a diagnosis of fetal CC malformation. The surviving children were enrolled in the neurodevelopmental follow-up program at our institution, which included postnatal magnetic resonance imaging, serial neurological examinations and neurodevelopmental evaluations with standardized tests according to age. Families living in remote areas or far from our institution were offered a structured ad-hoc phone interview. RESULTS: A total of 128 pregnancies with fetal CC malformation were identified (mean gestational age at diagnosis, 24.5 (range, 21-34) weeks), of which 53 cases were diagnosed prenatally with apparently isolated cACC. Of these, 12 cases underwent termination of pregnancy, one resulted in intrauterine demise at 24 weeks of gestation and 13 cases were lost to follow-up. Of the remaining 27 children, one was excluded due to an associated chromosomal anomaly (8p21.3q11.21 mosaic duplication) diagnosed after birth, which could have been detected prenatally if the parents had consented to amniocentesis. In the 26 children included in the analysis, neurodevelopmental follow-up was available for a median of 3 (range, 1-16) years. Three (11.5%) infants had severe neurodevelopmental impairment, two of which were diagnosed postnatally with a genetic syndrome (Mowat-Wilson syndrome and Vici syndrome) that would not have been diagnosed prenatally. Seven (26.9%) children had mild neurodevelopmental impairment and 16 (61.5%) had normal neurodevelopmental outcome. The Full-Scale Intelligence Quotients of the three children with severe neurodevelopmental impairment were 50, 64 and 63, respectively, while that of the remaining children was in the normal range (median, 101; range, 89-119). CONCLUSIONS: In 88% of the children with cACC included in this study, neurodevelopment was not severely impaired. However, long-term follow-up is recommended in all cases of congenital isolated cACC to recognize subtle neurodevelopmental disorders as early as possible. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Selective intrauterine growth restriction in monochorionic twins: changing patterns in umbilical artery Doppler flow and outcomes.

OBJECTIVES: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. METHODS: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. RESULTS: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). CONCLUSIONS: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome: a single-center experience.

OBJECTIVE: To report the incidence of fetal and maternal complications after selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS). METHODS: A total of 150 cases of TTTS were treated from January 2004 to June 2009 (period 1, 2004-2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal complications (double and single intrauterine fetal death, recurrence of TTTS, twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in one twin) and maternal complications were recorded, and retrospectively analyzed. RESULTS: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were classified preoperatively as Quintero stage I, II, III and IV, respectively. The anterior placenta was described in 73 cases (48.6%). Double and single fetal death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8 bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at a median gestational age of 30.2 weeks compared to 32.1 weeks for those not repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1 to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries performed, there was an average improvement of 1.5% in the predicted percentage of survival of at least one twin (OR 1.09, 95% CI 1.00-1.19). Major maternal complications occurred in 9 cases (6.0%), 3 of which required admission to intensive care unit. CONCLUSIONS: Fetal complications are common after fetoscopic laser surgery. In this experience, an increasing number of procedures improved the performance of a new fetoscopic laser center.

Bipolar cord coagulation for selective feticide in complicated monochorionic twin pregnancies: 118 consecutive cases at a single center.

OBJECTIVE: To review the experience of performing selective feticide with bipolar cord coagulation (BCC) in complicated monochorionic (MC) twin pregnancies at a single center. METHODS: This was a retrospective analysis of BCC performed using 3-mm bipolar forceps under ultrasound control in cases complicated by twin-to-twin transfusion syndrome, selective growth restriction, discordant anomaly or twin reversed arterial perfusion sequence. RESULTS: The series comprised 118 cases with a median gestational age at the time of the procedure of 22 (range, 16-30) weeks. There were 14 (12%) intrauterine deaths of the cotwin, eight (7%) miscarriages and one (1%) termination of pregnancy. When BCC was performed before 19 weeks of gestation, the rate of miscarriage was 45%, whereas it was 3% (P < 0.001) when BCC was performed after 19 weeks. Preterm prelabor rupture of membranes (PPROM) occurred in 45 (38%) cases. The median interval between BCC and PPROM was 4 (interquartile range, 2-9) weeks. In 15 (13%) cases, PPROM occurred within 2 weeks after the procedure. Median gestational age at delivery was 34 (range, 24-41) weeks. The median birth weight was 2103 (range, 480-3875) g. Neonatal death occurred in 11 (9%) cases, and two (2%) children had severe neurologic morbidity. The overall survival rate was 71% (84/118). CONCLUSION: BCC is an effective procedure in complicated MC twin pregnancies for selective feticide or when one fetus is severely jeopardized and delivery is not yet an option. Better outcomes can be achieved when this procedure is performed after 19 weeks.

[Eating behavior disorders. Epidemiologic study of 434 adolescents]. / Disturbi del comportamento alimentare. Studio epidemiologico di 434 adolescenti.

METHODS: An epidemiological investigation of behavior disorders in a population of 434 students (52.3% males, 47.7% females) ranging from 16 to 19 years of age has been carried out. Possible correlations between eating disturbances, drug addiction related behaviors, suicide attempts and former sexual abuses have been discussed. An anonymous self administered questionnaire, prepared by the authors, had been used. The statistical analysis was carried out with the SPSS/PC Factor software. RESULTS: This study revealed the presence of adolescents with unstable or quantitatively not adequate eating behaviors, which are expressed by borderline symptoms and not by clear syndromes. Distorted attitudes towards weight, body and food, related to disturbances of body image, were pointed out. In particular, girl seemed to be unhappy with their own body. There was a correlation between abnormal eating behaviors (borderline bulimia) and low level of selfesteem. "Anorexic behavior" and "bulimic behavior" had a significant correlation to suicide attempts. A relationship between "bulimic behavior" and use/abuse of drugs and/or alcohol was found. In our population several kinds of violence were found (2.6% sexual abuse with physical contact; 13.5% sexual abuse without physical contact; 9.4% physical abuse) experienced inside or outside families. The adolescent victims of sexual abuse showed abnormal eating behavior, mostly a tendency to a "bulimic behavior". CONCLUSIONS: This study seems to confirm that there are significant correlations and several conduct disorders. Moreover the presence of a correlation between eating disturbances, even if borderline and traumatic events of sexual nature is confirmed.

Response to pain in a group of healthy term newborns: behavioral and physiological aspects.

Various reports have documented the difficulty in assessing neonatal response to painful stimuli. The aim of our study was to evaluate previously described scales for assessing pain in a group of 18 healthy term newborns selected according to Prechtl's optimality criteria and subjected to a routine metabolic screening blood test performed on the 5th day of life. Both a modified CHEOPS scale and Grunau-Craig Scale, to assess pain behavior response before, during and after a painful stimulus, revealed definite modifications in scores. Response to pain was also evaluated by measuring variations in decreases in transcutaneous oxygen pressure in all newborns during application of the stimulus and in returns to baseline or higher values upon removal of the stimulus. Our study confirms that healthy term newborns feel pain when subjected to limited painful stimuli such as the routine blood test and suggests useful and easy methodological tools to evaluate pain in the newborn.