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.

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.

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.

Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood.

OBJECTIVE: To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV). DESIGN: Retrospective observational study. SETTING: Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy. POPULATION: HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995-2009. METHODS: Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection. MAIN OUTCOME MEASURES: A statistical analysis was performed to determine the value of each parameter in predicting outcome. RESULTS: Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were ß(2) -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. ß(2) -Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy. CONCLUSIONS: The determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.

Prenatal Brain MR Imaging: Reference Linear Biometric Centiles between 20 and 24 Gestational Weeks.

BACKGROUND AND PURPOSE: Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. MATERIALS AND METHODS: From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. RESULTS: Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. CONCLUSIONS: Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development.

Increased risk of placental abruption after solomon laser treatment of twin-twin transfusion syndrome.

To evaluate the relative risk of placental abruption in monochorionic (MC) twin pregnancies complicated with twin-to-twin transfusion syndrome (TTTS) and treated with endoscopic laser coagulation of placental vessels (ELCPV). A retrospective analysis from January 2004 and December 2015 of 373 TTTS pregnancies, treated with selective ELCPV until January 2012 (287 cases), after which the Solomon technique was introduced (86 cases), compared with 243 normal MC pregnancies. A significant improvement in perinatal survival was observed after the introduction of the Solomon technique when compared to the selective procedure (77% vs 54%, p < 0.001). The rate of placental abruption was 1% (3/243) in normal MC pregnancies, 6% (21/373) in TTTS group, increased with Solomon technique (12/86, 14%, vs 9/287, 3%, p < 0.001). MC twin pregnancies treated with laser coagulation of placental vascular anastomoses could be at increased risk of placental abruption, especially when the Solomon technique is used.

Diagnostic Value of Prenatal MR Imaging in the Detection of Brain Malformations in Fetuses before the 26th Week of Gestational Age.

BACKGROUND AND PURPOSE: In several countries, laws and regulations allow abortion for medical reasons within 24-25 weeks of gestational age. We investigated the diagnostic value of prenatal MR imaging for brain malformations within 25 weeks of gestational age. MATERIALS AND METHODS: We retrospectively included fetuses within 25 weeks of gestational age who had undergone both prenatal and postnatal MR imaging of the brain between 2002 and 2014. Two senior pediatric neuroradiologists evaluated prenatal MR imaging examinations blinded to postnatal MR imaging findings. With postnatal MR imaging used as the reference standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the prenatal MR imaging in detecting brain malformations. RESULTS: One-hundred nine fetuses (median gestational age at prenatal MR imaging: 22 weeks; range, 21-25 weeks) were included in this study. According to the reference standard, 111 malformations were detected. Prenatal MR imaging failed to detect correctly 11 of the 111 malformations: 3 midline malformations, 5 disorders of cortical development, 2 posterior fossa anomalies, and 1 vascular malformation. Prenatal MR imaging misdiagnosed 3 findings as pathologic in the posterior fossa. CONCLUSIONS: The diagnostic value of prenatal MR imaging between 21 and 25 weeks' gestational age is very high, with limitations of sensitivity regarding the detection of disorders of cortical development.

A prenatally detected inv dup(15).

An extra G group-like chromosome was found in an amniotic fluid cell culture. With multiple banding techniques it was identified as inv dup(15). BUdR incorporation was used to determine the lateral asymmetry of the marker, which consisted of 2 distal spots arranged contralaterally, consistent with DNA polarity conservation in chromosome rearrangements.

Comparisons of first and second trimester screening for fetal anomalies.

Four thousand fifty unselected pregnant women bearing a total of 4,078 fetuses were examined by transvaginal sonography (TVS) at 14 weeks of gestational age and rescreened via transabdominal sonography (TAS) at 21 weeks. Fifty-four of 88 anomalies were correctly identified at first scan whereas 34 were not; of these, 24 were discovered at second trimester rescreening, and the remaining 10 were observed later in pregnancy or after birth. The sensitivity of TVS screening with respect to final outcome was 61.4% (54 of 88 malformations in total) and 69.2% in comparison to TAS screening results (54 malformations detected among 78 recognized within 21 weeks). The association between fetal malformation and chromosomal aberrations was also investigated: in our study population there were 21 aneuploidies, 14 of which were recognized because of abnormal findings at the 14 weeks' TVS, 5 at the TAS rescreening, and 2 after birth in neonates free of structural abnormalities.

Anatomic correlates of ultrasound prenatal diagnosis of urinary tract abnormalities.

In 52 fetuses, in utero sonographic diagnosis of urinary tract malformations was correlated with their autoptic or surgical findings. 39 malformations were correctly diagnosed prenatally, although 5 other extrarenal-associated anomalies were not detected; 10 diagnoses were incomplete; in 3 cases the characteristics of malformations found at sonography turned out to be different at the post-mortem examination. The following factors impaired sonographic diagnoses: limited number of examinations, gestational age at the time of examination, nature of malformation and, above all, oligohydramnios (which is common in most urinary tract malformations). The correlations between renal malformations and karyotype anomalies are also discussed in relation to the higher incidence present in polymalformative syndromes.

Fetal echocardiography: the role of the screening procedure.

1841 pregnant women without any risk factor for heart malformation of the fetus underwent an echocardiographic screening at an average gestational age of 23 weeks. Seven cases of heart diseases were diagnosed (0.38%), of which one died in utero at 28 weeks and another one was interrupted. In four cases the karyotype was carried out prenatally, while in the remaining three it was performed only after birth. There were 11 false-negative (0.59%), mainly concerning anomalies of minor clinical significance. Within this group, two newborns with interatrial defect of the ostium secundum type appeared to be affected by trisomy 21. Therefore, the rate of congenital heart diseases in live births not at risk (0.86%) was in line with the data reported in paediatric literature. On the other hand, the association with chromosomal anomalies was surprisingly frequent (4 out of the 9 karyotypes performed were anomalous). Such finding should be verified by studying a larger non-selected population. However, a fetal karyotype should be offered, for its practical consequences, also in those cases of cardiac anomalies of lesser clinical significance.

[Seasonal incidence of extrauterine pregnancy]. / Incidenza stagionale delle gravidanze extrauterine.

Ectopic pregnancy (EP) is becoming a more and more frequent problem in many developed countries, but the cause of such increase is not fully understood. Improved diagnosis certainly explains part of it, but also the changing lifestyle and sexual habits might play an important role. During the years 1990-1993, 56 women were admitted into the Divisione di Ostetricia e Ginecologia of the Istituto per l'Infanzia of Trieste because of EP diagnosed on the basis of clinical history and signs, transvaginal echography and serum HCG levels. 33 of them underwent surgical operation for the presence of severe abdominal pain, hemoperitoneum greater than 50 cc, and increases HCG level. The other 23 women were treated conservatively. Taking into account the approximate date of conception both for ectopic and other pregnancies, the monthly incidence of EP was computed and showed a statistically significant peak during the summer period (14.4%) compared to the other periods (6%). The increased frequency of EP among pregnancies started during the warmer months is interesting not only as a descriptive result, but also because it may contribute to a better understanding of the conditions under which the ectopic development of the fertilized ovum may take place.

[Conservative management of ectopic pregnancy]. / Il management conservativo della gravidanza ectopica.

BACKGROUND: The aim of this retrospective study was to analyze the safety and efficacy of the conservative approach in the management of ectopic pregnancy. METHODS: Thirty-five women with a tubal ectopic pregnancy, from 1990 to 1995, were subdivided into 2 treatment groups. Inclusion criteria were the following: tubal diameter < 3 cm, free fluid < 100 ml, no embryo heart activity, haemodynamic stability. Desire of future fertility and informed consent were requested. Eighteen women were treated with a single intramuscular injection of methotrexate, whereas in 17 cases expectant management was adopted. RESULTS: In the first group 2 cases required surgical treatment (resolution rate = 89%). In the second group no surgery was needed and spontaneous resolution was achieved in all cases (100%). In both groups the average resolution time was about 17 days. Serum hCG-beta levels were monitored daily until resolution. The initial hCG-beta value and its following trend seem to be the most important prognostic factors. CONCLUSIONS: More studies are indeed needed to establish the effect of conservative management on fertility after ectopic pregnancy.

[The indications for the management of fetuses with choroid plexus cysts]. / Indicazioni per il management dei feti portatori di cisti dei plessi corioidei.

Choroid plexus cysts (CPC) in the fetus are still the subject of considerable debate in the literature. Because of their association with aneuploidy, and especially with trisomy 18, of which they are an ultrasonographic marker, the detection of fetal CPC now poses the problem of how these cases should be managed, since most occur in young women (there being no correlation between CPC and age), and since the incidence among the general population is fairly high (around 1%). With the aim of contributing further to the debate, a retrospective study was performed of all cases of fetal CPC diagnosed in our Centre between January 1984 and August 1994, together with a review of the relevant literature. There were 95 cases of fetal CPC with complete neonatal and necroptic data available. These cases included women recruited in the course of routine screening for congenital malformations carried out in our Centre at 14 and 21 weeks gestation, women referred to us from other Centres, and women recruited in the course of amniocentesis indicated for those aged over 35. In all cases in which fetal CPC was detected, a careful ultrasonographic examination was performed to exclude the presence of even the smallest morphologic anomaly. Whenever the fetus was found to have an anomaly karyotyping was done. If the CPC was not associated with any morphologic anomaly, karyotyping was proposed only to those women at risk of aneuploidy because of their age. There were 11 cases of trisomy 18, all of which presented morphologic anomalies associated with CPC. Some of these anomalies where "minor", however, and therefore difficult to assess even when a careful ultrasonographic examination was performed by an experienced operator (Intra ventricular septal defect, single umbilical artery). In 2 cases, CPC was associated with trisomy 21. Both women were aged over 35. All the other cases of CPC not associated with morphologic anomaly were normal on postnatal examination. From a meta-analysis of the literature, two distinct management protocols emerge for the problem of "isolated CPC detected at ultrasonographic examination". One group of authors recommends karyotyping for all women with fetal CPC, considering the presence of CPC in itself a risk factor for aneuploidy. The second group, to which we ourselves belong, believes it is sufficient to perform a careful ultrasonographic examination so as to exclude the presence of other morphologic anomalies associated with the CPC. Karyotyping should be proposed only to women at risk of aneuploidy because of their age (> 35). A review of the biggest series reported in the literature shows that, of a total of 1670 fetuses with CPC, 94 were trisomy 18. None of the cases of CPC "in isolation" emerged as being associated with this aneuploidy. However, numerous cases of trisomy 18 have been described in which CPC is associated with "minor" morphologic anomalies in the fetus which may be difficult to detect. It is therefore essential to perform a careful ultrasonographic examination in all cases of CPC, preferably in a Centre with specialist knowledge of ultrasonography. If this option is not available, then karyotyping of all women with fetal CPC is clearly advisable.

[The diagnostic capacities of transvaginal echography and hysteroscopy in the characterization of endometrial pathology]. / Capacità diagnostica dell'ecografia transvaginale e dell'isteroscopia nella caratterizzazione della patologia endometriale.

The diagnostic accuracy of transvaginal sonography (TVS) and hysteroscopy in the assessment of endometrial pathology was studied comparing retrospectively both methods with the results of histologic findings after dilatation and curettage (D&C) performed in the last four years on 467 patients, 155 of whom were in postmenopause. Endometrial thickness, tissue texture, myometrial invasion and haemodynamic characteristics were studied with TVS. Uterine cavity, endometrial patterns and superficial vascularization were evaluated by hysteroscopy. For the purpose of this study all histologic findings were subdivided to a) normal (206 cases); b) benign lesions (240 cases); c) atypical hyperplasia or adenocarcinoma (21 cases). In our experience hysteroscopy was superior to TVS in detecting endometrial pathology. Both techniques were more sensitive in detecting premalignant and malignant lesions. Considering endometrial thickness evaluated with TVS as a single parameter in patients in postmenopause, we found that the most sensitive cut-off for defining normality was 3 mm; nevertheless, in the group of patients that had an endometrial thickness equal to or less than 3 mm there were 2 cases of malignancy. Therefore, neither TVS nor hysteroscopy are sufficiently reliable to replace curettage in the diagnosis of endometrial pathology.

A case of prune-belly syndrome: prenatal diagnostic problems.

The authors discuss a case of "Prune-belly syndrome" which could be diagnosed prenatally thanks to echography; they stress the importance of echographic controls since the first gestational weeks to better recognize pathological findings, and describe their attempts to drain the megavesica. However these attempts could not reverse the ominous prognosis.

Cesarean section plus delayed cord clamping approach in the perinatal management of congenital high airway obstruction syndrome (CHAOS): a case report.

In this case, we describe a newborn with prenatal diagnosis of congenital high airway obstruction syndrome (CHAOS), successfully managed with a cesarean section with delayed cord clamping 180 seconds. In case of prenatal diagnosis of CHAOS, prompt airway intervention at delivery allows survival of this otherwise fatal condition. Ex utero intrapartum treatment (EXIT) is considered the elective procedure to secure the fetal airway before the baby is completely separated from the maternal circulation. In cases where the EXIT procedure is not possible for maternal reasons (Ballantyne's syndrome), delayed cord clamping may serve as an alternative method to manage CHAOS.

Outcome of congenital diaphragmatic hernia: analysis of implicated factors.

AIM: Congenital diaphragmatic hernia remains a significant challenge for neonatologists and pediatric surgeons. Over the last years, new therapeutic approaches, as high-frequency oscillatory ventilation, inhaled nitric oxide, permissive hypercapnia, extracorporeal membrane oxygenation, have been used for the management of these newborns. We conducted a retrospective study of all infants who were managed for congenital diaphragmatic hernia in our NICU in order to identify possible clinical characteristics which were predictive for survival. METHODS: We reviewed a single institution's experience with 42 consecutive neonates with congenital diaphragmatic hernia admitted to our NICU from 1993 to 2009. RESULTS: Prenatal data and side of congenital diaphragmatic hernia were similar in survivors and no-survivors infants except for the lung-to-head ratio (LHR), which was higher and measured later in survivors than non-survivors. Multiple regression analysis showed that a gestational age ≥39 weeks, Apgar score at 5 min ≥7, FiO2<0.35, MAP<13 cmH2O, OI<10 and AaDO2 >282 before surgical repair, and the absence of persistent pulmonary hypoplasia were independent predictive factors of survival. CONCLUSION: Our study suggests that the outcome of newborns with congenital diaphragmatic hernia still depends on the severity of lung hypoplasia, despite the different respiratory and therapeutical approaches.