Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Non-obstetric surgery during pregnancy - an eleven-year retrospective analysis.

BACKGROUND: Diagnosis and management of non-obstetric abdominal pathologies during pregnancy are clinically challenging for both obstetricians and general surgeons. Our aim was to evaluate the outcome of pregnant patients who had undergone non-obstetric abdominal surgery. METHODS: We retrospectively reviewed 76 pregnant patients who had required surgery for non-obstetric abdominal pathologies during pregnancy at our department from January 2005 to December 2015. Data were collected retrospectively from medical records as well as from our institutional perinatal database. We evaluated data for clinical presentation, perioperative management, preterm labor, and maternal and fetal outcomes. RESULTS: The patients' mean age was 29 (interquartile range IQR 25-33) years. Indications for surgery were acute appendicitis in 63%, adnexal pathology in 11%, cholecystolithiasis in 5% and other indications in 21%; surgery was performed in an elective setting in 18% and in an emergent/urgent setting in 82%. In five cases, complications, three of them oncological, called for further surgery. Ninety-seven percent of operations were conducted under general anesthesia. Median skin-to-skin time was 50 (37-80) minutes, median in-hospital stay was 4 (3.5-6) days, and 5 % required postoperative intensive care. Preterm labor occurred in 15%, miscarriage in 7% (none of them directly related to abdominal surgery). CONCLUSION: Abdominal surgery for non-obstetric pathology during pregnancy can be performed safely, if mandatory, without increases in maternal and fetal pathology, miscarriage, and preterm birth rates.

Labour and Childbirth After Previous Caesarean Section: Recommendations of the Austrian Society of Obstetrics and Gynaecology (OEGGG).

The new expert recommendation from the Austrian Society of Obstetrics and Gynaecology (OEGGG) comprises an interpretation and summary of guidelines from the leading specialist organisations worldwide (RCOG, ACOG, SOGC, CNGOF, WHO, NIH, NICE, UpToDate). In essence it outlines alternatives to the direct pathway to elective repeat caesarean section (ERCS). In so doing it aligns with international trends, according to which a differentiated, individualised clinical approach is recommended that considers benefits and risks to both mother and child, provides detailed counselling and takes the patient's wishes into account. In view of good success rates (60-85 %) for vaginal birth after caesarean section (VBAC) the consideration of predictive factors during antenatal birth planning has become increasingly important. This publication provides a compact management recommendation for the majority of standard clinical situations. However it cannot and does not claim to cover all possible scenarios. The consideration of all relevant factors in each individual case, and thus the ultimate decision on mode of delivery, remains the discretion and responsibility of the treating obstetrician.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.

STUDY QUESTION: Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? SUMMARY ANSWER: A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. WHAT IS KNOWN ALREADY: Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. STUDY DESIGN, SIZE, DURATION: Retrospective matched cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS: Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care. STUDY FUNDING/COMPETING INTERESTS: Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).

Etiology and perinatal outcome of polyhydramnios.

PURPOSE: To determine causes of polyhydramnios and the respective perinatal outcome. MATERIALS AND METHODS: We retrospectively analyzed cases with polyhydramnios at the Medical University Graz, Austria from 2003 - 2011. Inclusion criteria were single deepest pocket ≥ 8  cm, amniotic fluid index ≥ 25  cm, each of the latter parameters > 95th percentile or subjective impression. Etiologies, including TORCH infection, diabetes and congenital malformations, as well as perinatal outcome were evaluated. RESULTS: Out of 860 singleton pregnancies with polyhydramnios, 2.9 % had positive TORCH serology, 8.5 % had congenital anomalies, 19.8 % had maternal diabetes, and 68.8 % were idiopathic. The most common fetal anomalies were cardiac defects (32.9 %). Elective caesarean sections were more common in the groups with malformations and maternal diabetes. Low birth weight combined with severe polyhydramnios or maternal diabetes was associated with malformations. CONCLUSION: Diagnosis of polyhydramnios should prompt glucose-tolerance testing, detailed sonography including fetal echocardiography, and TORCH serology. Especially pregnancies with polyhydramnios and small fetuses as well as those with maternal diabetes should be carefully evaluated for malformations.

Procedure-related complications after genetic amniocentesis and chorionic villus sampling.

PURPOSE: Amniocentesis (AC) and chorionic villus sampling (CVS) play an important role in the diagnosis of genetic anomalies. The aim of this study was to evaluate presentable numbers of procedure-related complications of genetic interventions in a tertiary referral hospital. MATERIALS AND METHODS: The pregnancy outcome of women who underwent genetic AC or CVS during 2003-2010 at the Department of Obstetrics and Gynecology, Medical University of Graz, Austria, was analyzed retrospectively. The primary outcome was miscarriage or membrane rupture after an invasive procedure. Only singleton gestations were included. RESULTS: 1,569 AC procedures and 334 CVS procedures (234 transabdominal, 99 transcervical, 1 with undocumented route) were performed. Of these, 57 cases were excluded from further analysis because of severe anomalies. Complete outcome data were available for 93.17% of cases. In 164 (8.89%) cases the pregnancy was terminated due to genetic anomalies or severe malformations. In the remaining collective 10 of 1,342 (0.75%) AC procedures, 3 of 150 (2.00%) transabdominal CVS procedures and 2 of 64 (3.13%) transcervical CVS procedures lead to complications resulting in miscarriage < 24 weeks (n = 13) or rupture of membranes (n = 2) within 2 weeks after procedure. Complication rates were significantly higher after CVS than after AC (OR 3.19). CONCLUSION: Over an observation period of seven years, the complication rates after AC, transabdominal CVS and transcervical CVS were 0.75%, 2.00% and 3.13%, respectively. These results are comparable to recent international investigations.

Reference ranges for middle cerebral artery peak systolic velocity in monochorionic diamniotic twins: a longitudinal study.

OBJECTIVES: The role of middle cerebral artery (MCA) peak systolic velocity (PSV) has become established in the management of fetal anemia. To date, singleton reference ranges have also been used in twin pregnancies. However, in monochorionic twin pregnancies, normal ranges for cerebral blood flow may differ from those in singletons owing to intertwin blood exchange. We aimed to establish gestational age-specific reference ranges for MCA-PSV in monochorionic diamniotic (MCDA) twin pregnancies, to compare them with previously reported singleton reference ranges, and to establish terms for calculating conditional reference intervals appropriate for individual serial measurements. METHODS: In a prospective longitudinal study we examined 50 uncomplicated MCDA pregnancies that were recruited between 11 and 14 weeks of gestation. Fetal MCA Doppler waveforms were assessed biweekly from 15 weeks of gestation onwards. Multilevel modeling was used to estimate gestational age-specific reference ranges for MCA-PSV and terms for conditional reference intervals were established. RESULTS: Based on 824 observations in 100 fetuses, normative ranges from 15 to 37 weeks of gestation were constructed. Median MCA-PSV increased with advancing gestational age. Measurements between 18 and 37 weeks were comparable to those in singletons. However, before 18 weeks MCA-PSV values were higher in MCDA twin pregnancies compared with singleton references. CONCLUSIONS: Between 18 and 37 weeks of gestation, reference ranges of singletons can be used to assess fetal anemia in MCDA twin pregnancies. Prior to 18 weeks the application of singleton references may lead to an increased number of false-positive diagnoses of presumed fetal anemia in MCDA twin pregnancies.

Instrumental requirements for minimal invasive fetal surgery.

Minimal invasive intrauterine interventions have gained their place in fetal medicine. Interventions on the placenta, umbilical cord, fetal membranes or on the fetus require special endoscopes with their respective sheaths, cannulas and additional instruments. Instruments for fetal therapy are purpose designed for the procedure of interest and most gynaecologists are therefore not familiar with them. We review the currently available instrumentation used during operations for complicated monochorionic multiple pregnancies, congenital diaphragmatic hernia, amniotic band syndrome, urinary tract obstruction and hydrothorax.

Spontaneous intrauterine umbilical artery thrombosis leading to severe fetal growth restriction.

Intrauterine thrombosis of umbilical cord vessels is a rare event (2.5-4.5/10,000) and usually followed by poor fetal outcome. We present the rare case of spontaneous intrauterine thrombosis of an umbilical artery leading to severe intrauterine growth restriction (IUGR) and provide clinical and pathological findings. A 28-year-old nulliparous third gravida was referred to our institution because of IUGR at 32+4 weeks of gestation. Fetal growth had been appropriate until the 31st week of gestation and had stopped thereafter. There were no signs of abruption of the placenta and no structural abnormalities except an absent paravesical colour Doppler flow in the region of the right umbilical artery. Other Doppler measurements, karyotype and TORCH serology were normal. Intermittent non-reassuring fetal heart rate led to cesarean section at 34+3 weeks of gestation. A healthy girl with measurements on the 3rd centile was born (weight of 1,590 g, length of 41 cm and head circumference of 29 cm). Gross examination displayed an elongated, highly twisted umbilical cord with a length of 70 cm, central insertion and three umbilical vessels. Microscopic examination confirmed the diagnosis of umbilical artery thrombosis along the entire length of the umbilical cord. Calcification within the thrombus and microcalcification in occluded chorionic vessels were observed as well as hemorrhagic endovasculitis and endangiopathia obliterans in the stem villi arteries. This fetal thrombotic vasculopathy (FTV) comprised about 40% of the parenchyma. The coagulation parameters and blood counts of the mother and the infant were normal apart from transient neonatal thrombocytopenia. The reason for thrombosis remained unclear but could be attributed to the elongated and highly twisted umbilical cord. Intrauterine arterial thrombosis may cause severe IUGR. This condition might be detectable by ultrasound in the course of an IUGR workup, especially when no other reasons can be found.

Peripheral oxygenation in term neonates.

The aim of this study was to analyse changes in peripheral oxygenation in healthy term neonates within the first week of life with near-infrared spectroscopy and venous occlusion. Oxygen delivery did not change with increasing age. Oxygen consumption and fractional oxygen extraction increased, whereas tissue oxygenation index decreased with increasing age.

Recurrent endometrial stromal sarcoma after treatment with high-dose chemotherapy and autologous stem-cell support: A case report.

INTRODUCTION: The efficacy of high-dose chemotherapy plus transplantation of autologous hematopoetic stem cells in patients with endometrial stromal sarcomas is unknown. CASE REPORT: A 39-year-old woman with Stage III endometrial stromal sarcoma (ESS) underwent radical surgery, followed by five courses of ifosfamide, adriamycin and dacarbazine postoperatively. Six months after primary surgery stem cell priming was performed. Five months later bone marrow was aspirated and high-dose chemotherapy with carboplatin, vepeside and holoxan were administered after which bone marrow was retransfused. Seven years after primary surgery the patient developed an abdominal recurrence which was removed surgically and adjuvant radiotherapy was administered. One year later the patient underwent hemicolectomy because of a new recurrence infiltrating the ascending colon. Treatment with 25 mg exemestane was begun. The patient is currently alive and free of disease nine years after the initial diagnosis. CONCLUSION: Aggressive chemotherapy with autologous stem-cell support seems to be ineffective in patients with ESS.

Prognostic significance of preoperative DNA flow cytometry in surgically-treated cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of preoperative DNA flow cytometry compared with other clinical and histologic variables in cervical carcinoma. STUDY DESIGN: Sixty-four patients with FIGO Stage Ib-II cervical cancer treated with radical abdominal hysterectomy and systematic pelvic lymphadenectomy were analyzed. The mean follow-up was 3.4 (range 0.3-9.8) years. DNA flow cytometry was performed with fresh tumor tissue. Four biopsies were recut from the surgical specimen within 30 minutes of the operation. The ectocervix was divided into four quadrants and a specimen obtained from each. DNA-low-grade tumors (diploid, near-diploid, tetraploid and near-tetraploid) were distinguished from DNA-high-grade tumors (aneuploid and hypoploid). Carcinomas with more than one non-diploid stem line were considered heterogeneous. An S phase fraction >7% was classified as low, 7% - < 14% as moderate, and > or = 14 as high. DNA ploidy, DNA heterogeneity, S phase fraction and various clinical and histological variables were related to disease-free survival. RESULTS: In the univariate analysis patients with DNA-low-grade carcinomas had significantly better disease-free survival than patients with DNA-high-grade tumors (82% vs 45%, p = 0.021). Carcinomas with an S-phase fraction < 7% were associated with better disease-free survival (0.8) than those with an S-phase fraction 7% - > 14% (0.62) and those with > or = 14% (0.64), but this was not statistically significant. Cox stepwise regression analysis showed DNA-heterogeneity, age, grade, parametrial involvement and extrapelvic metastasis to be independent prognostic factors. CONCLUSION: DNA ploidy and DNA heterogeneity are of prognostic importance in cervical cancer. DNA flow cytometry may be used preoperatively to identify low-risk and high-risk patients within a given stage.