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This article describes an inexpensive simulator developed for teaching intrauterine blood transfusion. The model is constructed from a boneless chicken thigh folded over a Penrose drain placed in a water-filled snap-lock lid container and covered by melted ballistic gel to simulate the fetal intrahepatic vessel. Participants valued this educational tool and reported feeling the model was practical and realistic. This low-cost, high-fidelity model provides realistic tissue resistance and represents a sonographically accurate intrahepatic fetal blood transfusion training tool.

OBJECTIVES To assess short- and long-term outcome in a cohort of fetuses diagnosed with hydrothorax (FHT) which underwent thoracoamniotic shunting in utero, and to examine the antenatal predictors of survival and of survival with normal neurodevelopmental outcome. METHODS This was a retrospective analysis of 132 fetuses that underwent thoracoamniotic shunting at our center between 1991 and 2014. Data were extracted from hospital obstetric and relevant neonatal intensive care and neonatal developmental follow-up databases. Outcomes included survival to discharge and survival with normal neurodevelopmental outcome beyond 18 months. Information on malformations, syndromes and genetic abnormalities were obtained from antenatal, postnatal and pediatric hospital records or by parent report. We compared pregnancy characteristics among those who survived vs non-survivors and among those with normal neurodevelopmental outcome vs those who were abnormal or died. We explored whether there was a trend in survival over the study period. RESULTS The mean gestational age at diagnosis of FHT was 25.6 weeks. The fetus was hydropic at diagnosis in 61% of cases, 69% had bilateral effusions and 55% had bilateral shunts inserted. Other diagnoses were present in 24% of cases, two-thirds of which were discovered only postnatally. There were 16 intrauterine and 30 neonatal deaths, with a 65% survival rate overall. The mean gestational age at delivery of liveborns was 35.4 (range, 26.9-41.6) weeks, and 88/116 (76%) were preterm (

Objective To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest. Methods In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test. Results From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group. Conclusion Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest. Clinical trial registration ClinicalTrials.gov, NCT01869556.

ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart’s hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive.DesignTo evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent β-thalassaemia (TDT-β).ResultsOf the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-β patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with ‘silent’ ischaemic infarcts.ConclusionsIn patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-β counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Background Pregnancy-related critical illness results in approximately 300,000 deaths globally each year. The objective was to describe the variation in ICU admission and the contribution of patient- and hospital-based factors in ICU admission among acute care hospitals for pregnant and postpartum women in Canada. Methods A nationwide cohort study between 2004 and 2015, comprising all pregnant or postpartum women admitted to Canadian hospitals. The primary outcome was ICU admission. Secondary outcomes were severe maternal morbidity (a potentially life-threatening condition) and maternal death (during and within 6 weeks after pregnancy). The proportion of total variability in ICU admission rates due to the differences among hospitals was described using the median odds ratio from multi-level logistic regression models, adjusting for individual hospital clusters. Results There were 3,157,248 identifiable pregnancies among women admitted to 342 Canadian hospitals. The overall ICU admission rate was 3.2 per 1000 pregnancies. The rate of severe maternal morbidity was 15.8 per 1000 pregnancies, of which 10% of women were admitted to an ICU. The most common severe maternal morbidity events included postpartum hemorrhage (n = 16,364, 0.52%) and sepsis (n = 11,557, 0.37%). Of the 195 maternal deaths (6.2 per 100,000 pregnancies), only 130 (67%) were admitted to ICUs. Patients dying in hospital, without admission to ICU, included those with cardiovascular compromise, hemorrhage, and sepsis. For 2 pregnant women with similar characteristics at different hospitals, the average (median) odds of being admitted to ICU was 1.92 in 1 hospital compared to another. Hospitals admitting the fewest number of pregnant patients had the highest incidence of severe maternal morbidity and mortality. Patient-level factors associated with ICU admission were maternal comorbidity index (OR 1.88 per 1 unit increase, 95%CI 1.86–1.99), urban residence (OR 1.09, 95%CI 1.02–1.16), and residing at the lowest income quintile (OR 1.44, 95%CI 1.34–1.55). Conclusions Most women who experience severe maternal morbidity are not admitted to an ICU. There exists a wide hospital-level variability in ICU admission, with patients living in urban locations and patients of lowest income levels most likely to be admitted to ICU. Cardiovascular compromise, hemorrhage, and sepsis represent an opportunity for improved patient care and outcomes.

Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.

OBJECTIVES To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. METHODS Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. RESULTS In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate-ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi-organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants. We report a case of GS deficiency caused by homozygous GLUL gene deletion, diagnosed prenatally and likely representing the most severe end of the spectrum. We expand the known phenotype of this rare condition with novel dysmorphic, radiographic and neuropathologic features identified on post-mortem examination. The biallelic deletion identified in this case also included the RNASEL gene and was associated with immune dysfunction in the fetus. This case demonstrates that total absence of the GLUL gene in humans is viable beyond the embryonic period, despite the early embryonic lethality found in GLUL animal models.

Monoamniotic twin pregnancies are rare, but early diagnosis of such pregnancies is critical, as the incidence of complications in these pregnancies is much higher than in diamniotic or dichorionic twin pregnancies. Overall, only 70% of all monoamniotic twins will survive. Furthermore, approximately half of fetal deaths in these pregnancies are because of the high incidence of fetal anomalies (15%-25%), such as twin reversed arterial perfusion sequence and conjoined twinning. Therefore, early anatomy screening in the first trimester of pregnancy is recommended. Other causes of fetal death in these pregnancies include twin-twin transfusion syndrome, tight cord entanglement, or acute hemodynamic imbalances through the large placental vascular anastomoses. After viability, fetal surveillance can be intensified, as this decreases the risk of in utero death. Both inpatient and outpatient surveillance are reasonable. If otherwise uncomplicated, monoamniotic twins should be delivered at 33 to 34 weeks' gestation. Most centers will deliver by cesarean delivery, but some continue to advocate for vaginal delivery. Lastly, neonatal morbidity is high in monoamniotic twin pregnancies and is mainly related to prematurity.

To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest.In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test.From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group.Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest.ClinicalTrials.gov, NCT01869556.

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed < 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on 'Statistical Package for Social Science Version 16.0' (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different antigens capable of causing maternal red blood cell (RBC) alloimmunization and severe fetal hemolytic disease. Anti-K and anti-D are responsible for a significant proportion of fetal anemia requiring intrauterine transfusion (IUT). Whilst IUT of packed RBCs improves neonatal survival and morbidity, clinical prognostic indicators are lacking. Our primary objective was to identify predictors of adverse outcome. Methods: We conducted a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada. All pregnant patients alloimmunized with anti-K and anti-D as a single antibody, between 1991 and 2018 were included. Data were obtained from patient medical records, ultrasound reports and information from the transfusion medicine laboratory. Data included maternal demographics, antibody titers, pregnancy history, number of IUTs, hemoglobin (HB) concentration at the beginning and end of all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age at delivery, birth weight, HB at birth and need for neonatal transfusion, phototherapy or intravenous immunoglobulins (IVIG). Our primary outcome was the composite outcome of stillbirth or neonatal death (SB/NND). We also constructed a secondary outcome consisting of top-up neonatal transfusion, exchange transfusion, phototherapy, or use of IVIG. Medians and interquartile ranges (IQR) or mean±SD were used as summary statistics and compared by Mann-Whitney or t-test; p Results: 116 women with 128 pregnancies and 425 IUTs with anti-K or anti-D as a single antibody were identified. Median maternal age was 31 years (27.0-35.0) for anti-K and 32 years (23.6-40.6) for anti-D. The gestational age at 1st IUT differed significantly between anti-K and anti-D (24.3 vs 28.7 weeks respectively, p=0.004). Women with anti-K antibodies required more IUTs than women with anti-D (3.84 vs 3.12 IUTs, p=0.036) and HB at 1st IUT was significantly lower in the anti-K group (5.10 vs 7.05 g/dL, p=0.001) (Table 1). Following initiation of IUT, the time from 1st IUT to delivery was 69.6 days in the anti-K group and 54.6 in the anti-D group (p=0.06). The daily decrease of HB between 1st and 2nd IUT (as a marker of disease severity), development of fetal hydrops and severe preterm birth did not differ significantly between the two groups. Mean gestation age at delivery was 35.0 weeks in the anti-K and 36.0 weeks in the anti-D group (p=0.28), with 87.1% and 93.9% survival (p=0.37), respectively. The proportion of neonates requiring phototherapy, IVIG and exchange/top-up transfusion was comparable across the two antibody groups (Table 1). Regression analysis showed that delivery occurred sooner if HB dropped more rapidly between the first two IUTs (p=0.01). Each additional transfusion gained on average 22.5 days in utero (Table 2). In multivariable analysis, gestational age at 1st IUT was the only predictor of a SB/NND outcome (adjusted OR 0.79 [95%CI 0.67-0.93]; p=0.006). With 1st IUT at 23 weeks, the risk of SB/NND was 8%, but only 2.5% at 28 weeks and Conclusion: The earlier in gestation that IUTs are implemented, the higher the odds of a SB/NND; however the later the gestation at delivery, the greater the odds of the neonate requiring blood products post-partum. The greater the HB drop between the 1st and 2nd IUT, the shorter the 'time between the first IUT and delivery', which increases the odds of a SB/NND outcome. Disclosures Garbowski: Vifor Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Consultancy. Shehata:Ferring: Honoraria.

Key Points Question Is maternal age associated with severe maternal morbidity and with maternal death in Canada? Findings In this nationwide population-based cohort study of 3.1 million pregnancies in Canada, severe maternal morbidity has increased over the past decade, and this trend coincided with an increase over time in maternal age and in the proportion of pregnancies to older mothers. Extremes of maternal age, especially those 45 years or older compared with those aged 20 to 24 years, were associated with severe maternal morbidity and with maternal mortality. Meaning Increasing maternal age was an independent characteristic associated with severe maternal morbidity and mortality., This nationwide population-based cohort study investigates the association of maternal age, adjusting for patient-level and hospital-level factors, with severe maternal morbidity and maternal death in Canada., Importance Over the past 2 decades, there has been a trend toward increasing maternal age in many high-income countries. Maternal age may lead to greater attendant morbidity and mortality for Canadian mothers. Objective To investigate the association of maternal age, adjusting for patient-level and hospital-level factors, with severe maternal morbidity (SMM) and maternal death in Canada. Design, Setting, and Participants A nationwide population-based cohort study of all antepartum, peripartum, and postpartum women and adolescents seen at Canadian acute care hospitals from April 1, 2004, to March 31, 2015. All analyses were completed on September 13, 2018. Exposures Maternal age at the index delivery. Main Outcomes and Measures Severe maternal morbidity and maternal death during pregnancy and within 6 weeks after termination of pregnancy. Results During the study period, there were 3 162 303 new pregnancies (mean [SD] maternal age, 29.5 [5.6] years) and 3 533 259 related hospital admissions. There were 54 219 episodes of SMM (17.7 cases per 1000 deliveries) in the entire study period, with a 9.8% relative increase from 2004-2005 to 2014-2015, in addition to an increasing proportion of pregnancies to older mothers. Independent patient-level factors associated with SMM included increasing Maternal Comorbidity Index; maternal age 19 years or younger and 30 years or older, with the greatest risk experienced by women 45 years or older (odds ratio [OR], 2.69; 95% CI, 2.34-3.06 compared with maternal age 20-24 years); and lowest income quintile (OR, 1.19; 95% CI, 1.14-1.22 compared with highest income quintile). Hospital-level factors associated with SMM included specific provinces. Independent patient-level factors associated with maternal mortality included increasing Maternal Comorbidity Index, age 40 to 44 years (OR, 3.39; 95% CI, 1.68-6.82 compared with age 20-24 years), age 45 years or older (OR, 4.39; 95% CI, 1.01-19.10 compared with age 20-24 years), and lowest income quintile (OR, 4.14; 95% CI, 2.03-8.50 compared with highest income quintile). Hospital-level factors associated with maternal mortality included lowest hospital pregnancy volume. Conclusions and Relevance In Canada, maternal age and SMM have increased over the past decade. Results of this study suggest that province of residence, maternal comorbidity, residence income quintile, and extremes of maternal age, especially those 45 years or older, were associated with SMM and mortality. These findings are relevant to prospective parents, their health care team, and public health planning.

OBJECTIVE To evaluate the impact of introduction of noninvasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies. METHODS Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Cases were segregated according to whether they were seen prior to introduction of NIPT (group A, 2010-2013) or thereafter (group B, 2014-2017). We examined the rate of invasive and noninvasive genetic testing in each group. RESULTS We retrieved 500 cases: 308 (62%) were isolated CNS anomalies, and 192 (38%) had additional structural anomalies. In the total cohort, 165 women (33%) underwent expectant management with no further prenatal genetic testing, 166 (33%) had invasive testing, 52 (10%) had NIPT, and 117 pregnancies (23%) were terminated without further prenatal investigations. The introduction of NIPT significantly decreased the number of pregnancies having no testing (44% group A vs 22% in group B, p

Microcystic congenital cystic adenomatoid malformations (CCAM), when associated with hydrops, carry a dismal prognosis. Options for treatment are limited and experimental, including antenatal corticosteroids, open fetal surgery, laser ablation and, more recently, sclerotherapy. We describe a case of a large, predominantly microcystic CCAM in a hydropic fetus treated successfully with direct interstitial injection of a sclerosant agent (3% sodium tetradecyl sulfate) at 23+3 weeks gestation, after multiple failed courses of steroids. Elective thoracoscopic right lower lobectomy was performed at 1 year of life and there have been no respiratory or other medical morbidities since. A literature review of fetal lung masses treated with sclerosants antenatally reveals that sclerotherapy may represent a novel treatment option for large hydropic microcystic CCAMs, which are unresponsive to corticosteroids. Further studies are required to evaluate the utility and safety of fetal sclerotherapy, as this may represent an alternative minimally invasive treatment option to fetal lobectomy.

Background: Kell and Rhesus (Rh) maternal red blood cell (RBC) alloimmunization are the most common causes of severe fetal haemolytic disease. Widespread use of anti-D immune globulin has dramatically reduced the incidence of Rh(D) alloimmunization, leaving K alloimmunization responsible for a significant proportion of cases of fetal anemia requiring intrauterine transfusion ( ). K antigens are expressed on fetal erythrocytes at 10-11 weeks and k antigens at 6-7 weeks gestation (Tovey et al, 1986). In alloimmunized women, erythroid specific antibodies traverse the placenta, causing immune destruction of fetal erythroid cells leading to progressive haemolytic anaemia. The mechanism of fetal anaemia in K alloimmunization differs somewhat from that in Rh-D, in that anti-K antibodies cause suppression of fetal erythropoiesis (Gariod et al, 2004; Weiner et al, 1996). Whilst IUT of RBCs has improved fetal and neonatal survival, important information such as the critical anti-K titres to guide appropriate timing and frequency of IUT, is somewhat conflicting. Currently anti-K alloimmunized pregnancies do not have a standardized protocol for titer monitoring throughout pregnancy and, once alloimmunized, patients are usually referred to a regional fetal center for close ultrasound (US) surveillance. Our primary objective is to determine from a retrospective analysis of our population whether there is a critical anti-K titer that should trigger intensive US monitoring or intervention and to investigate the rate of progression of fetal anemia following IUTs. Methods: This is a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada, of all pregnant patients with anti-K as the primary alloimmunizing antibody, between 1991 and 2018. MSH is the largest fetal medicine center in Canada and the largest referral center for IUTs. Ethical approval was granted by the Research Ethics Board (REB # 12-0113-C). Data were obtained from a database of patient medical records, US reports and the transfusion medicine laboratory, including maternal demographics, pregnancy history, presence of other alloantibodies and hemoglobin concentration before and after all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age (GA) at delivery, birth weight and need for neonatal exchange transfusion, phototherapy or IVIG. Data were analyzed using GraphPad Prism 6 and linear correlations are expressed as a p-value. Results: Thirty-eight women underwent 163 IUTs in 44 pregnancies where K was the predominant antibody. Two patients in whom anti-K was a secondary antibody were excluded. In 5 of these pregnancies, 2 had a total of three alloantibodies and 5 had 2 alloantibodies each. The median maternal age was 31 (29 - 35) years. Four women had a history of intrauterine fetal death (IUFD) and 9 of neonatal haemolytic disease. The median GA at 1st IUT was 24.2 weeks (14.9-34.7), and there was a median of 4 IUTs per patient. There were seven cases of hydrops fetalis. The number of IUTs a patient received throughout pregnancy was correlated directly with the anti-K titer (Figure 1). Every 4-fold dilution resulted in a further increase in the IUT number by 2.2 above the mean of 2.5 at a titer of 1:32 (p=0.0137). Figure 2 illustrates the correlation between the GA at 1st IUT and antibody titer. IUTs were required at earlier GAs if the titers were higher. Following a 1:32 titer, every 2-fold titer increase reduced the mean gestational age at 1st IUT by 2 weeks (p Conclusion: Our data support a critical anti-K titer of 1:32 and support a role for anti-K titer monitoring as a predictor of disease severity, counselling women appropriately and establishing a balance between paternal K antigen typing, US middle cerebral artery peak systolic velocity monitoring of the fetus and IUTs. Disclosures Garbowski: Vifor Pharma: Consultancy; Imara: Consultancy.

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN71416914.

Purpose Pregnancy-related critical illness leads to death for 3–14% of affected women. Although identifying patients at risk could facilitate preventive strategies, guide therapy, and help in clinical research, no prior systematic review of this literature exploring the validity of risk prediction models for maternal mortality exists. Therefore, we have systematically reviewed and meta-analyzed risk prediction models for maternal mortality. Methods Search strategy: MEDLINE, EMBASE and Scopus, from inception to May 2017. Selection criteria: Trials or observational studies evaluating risk prediction models for maternal mortality. Data collection and analysis: Two reviewers independently assessed studies for eligibility and methodological quality, and extracted data on prediction performance. Results Thirty-eight studies that evaluated 12 different mortality prediction models were included. Mortality varied across the studies, with an average rate 10.4%, ranging from 0 to 41.7%. The Collaborative Integrated Pregnancy High-dependency Estimate of Risk (CIPHER) model and the Maternal Severity Index had the best performance, were developed and validated from studies of obstetric population with a low risk of bias. The CIPHER applies to critically ill obstetric patients (discrimination: area under the receiver operating characteristic curve (AUC) 0.823 (0.811–0.835), calibration: graphic plot [intercept—0.09, slope 0.92]). The Maternal Severity Index applies to hospitalized obstetric patients (discrimination: AUC 0.826 [0.802–0.851], calibration: standardized mortality ratio 1.02 [0.86–1.20]). Conclusions Despite the high heterogeneity of the study populations and the limited number of studies validating the finally eligible prediction models, the CIPHER and the Maternal Severity Index are recommended for use among critically ill and hospitalized pregnant and postpartum women for risk adjustment in clinical research and quality improvement studies. Neither index has sufficient discrimination to be applicable for clinical decision making at the individual patient level.

Objective To evaluate the incidence and consequences of ‘misdiagnosed’ cases of twin–twin transfusion syndrome (TTTS). Methods Chorionicity and referral diagnoses were reviewed in pregnant women with monochorionic twin pregnancies complicated by TTTS treated with fetoscopic laser ablation. ‘Misdiagnosed’ cases, defined as failure to correctly identify chorionicity and/or to diagnose TTTS prior to referral, were compared with cases in whom chorionicity and TTTS were diagnosed correctly. TTTS stage, gestational age at referral, overall survival, fetal and perinatal mortality, gestational age at delivery, operating time and maternal complications were compared. Results Failure to identify monochorionicity and/or TTTS was observed in 33% (107/323) of referrals to our center. Compared with cases in whom chorionicity and TTTS were correctly diagnosed, misdiagnosed patients were referred at a more advanced stage of disease (Stage IV TTTS: 16.8% vs 7.9%, P = 0.014) and later in pregnancy (gestational age at laser: 20.9 weeks vs 20.1 weeks, P = 0.018). They also delivered more prematurely (30.3 weeks' gestation vs 31.5 weeks' gestation, P = 0.04) and fetal and neonatal mortality were higher (neonatal death within 7 days: 19.6% vs 6.0%, P

Objective The aims of this study were to review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support or ex utero intrapartum treatment and to discuss implications for future management of these complex and rare cases. Methods We have presented a retrospective case series of 12 neonates requiring airway management on placental support at a single tertiary care, academic center. Results One mother experienced significant blood loss. Operative recovery times were unremarkable. Eight neonates required airway management due to mass obstruction, two for removal of an endotracheal balloon for fetoscopic treatment of congenital diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia. One of our series is an unusual case of management on placental support after vaginal delivery. Another child would have ideally been managed on placental support, but an extremely short umbilical cord prevented this. Even though the airway was secured in all 12 cases, five neonates died in the perinatal period. Conclusions These procedures have a risk for substantial maternal blood loss. Despite excellent rates of success securing the neonatal airway, children who require management on placental support still have high mortality. A formalized multidisciplinary approach at our institution has enhanced preparedness for these cases. © 2013 John Wiley & Sons, Ltd.

Objective Morbidity from postpartum hemorrhage (PPH) affects 20% of pregnancies worldwide and remains a significant cause of maternal mortality. This study compared the impressions of experienced clinicians on the effect of two methods of educational interventions in a More OB training program designed to improve recognition and management of PPH. Methods Participants were exposed to a traditional didactic lecture and an interactive clinical intervention exercise incorporating video simulation of a PPH event with opportunities for feedback and discussion of how to proceed. They were then invited to respond to a questionnaire regarding their impressions of both methods. Results Of 150 participants, 110 completed the questionnaire. Respondents considered the interactive format to be more effective (55%) and enjoyable (72%) than the traditional didactic format. The majority (81%), however, still recommended a mixture of both interactive and didactic formats in future events, supported by a multidisciplinary drill. Conclusion Clinical learners value interactivity and mutual reinforcement among varied learning exercises in their educational experiences. Future educational programs may consider incorporating similar methods in order to maximize participants' receptiveness.

Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

Objective To describe the common characteristics, clinical management, and outcome of patients requiring blood transfusion within 24 hours of delivery. Methods We conducted a retrospective cohort study of patients who received blood transfusion for postpartum hemorrhage (PPH) in the first 24 hours post-delivery, over a five-year period (2000–2005). The medical records of patients were reviewed to obtain information about demographics, pregnancy and delivery characteristics, transfusion data, and complications. Results The overall blood transfusion rate for PPH was 0.31% (104/33 631 deliveries). The rate of blood transfusion in women who had a Caesarean section during labour was 0.49%, whereas in women who had a vaginal delivery or elective Caesarean section it was 0.28% and 0.23%, respectively. Antenatal risk factors for PPH were identified in 61% of patients, and 39% of patients developed intrapartum risk factors. The most important etiological factors were uterine atony (38.5%) and retained products of conception (33.7%). Twenty-one percent of the patients developed coagulopathy, and 24% required admission to the intensive care unit. Conclusion Severe primary PPH requiring blood transfusion can be predicted in the majority of patients on the basis of antenatal risk factors, while the remaining patients require vigilant monitoring for risk factors during labour and delivery. In the multidisciplinary effort to prevent and control major PPH, we should re-evaluate the pharmacotherapy for PPH and ensure careful removal of retained placental tissue after delivery.

Objective: To determine the effect of extreme macrosomia on perinatal outcome. Methods: We conducted a retrospective review of all deliveries with birth weight ≥ 5000 g in a tertiary centre from 1986 to 2000 and analyzed the method of delivery and perinatal outcome. Results: Extreme macrosomia (birth weight ≥ 5000 g) was coded in 111 deliveries. There were 62 deliveries by Caesarean section (CS) (25 in labour and 37 elective). The 49 vaginal deliveries were complicated by 10 (20%) cases of shoulder dystocia and 3 (6%) of Erb's palsy. Permanent Erb's palsy was noted in only 1 of these 3 cases. Shoulder dystocia was associated with use of oxytocin and instrumental deliveries. Conclusion: Implementing the 2002 guidelines from the American College of Obstetricians and Gynecologists (that is, recommending Caesarean delivery of fetuses with an estimated weight of at least 5000 g) would have a negligible effect on the CS rate while eliminating 10 cases of shoulder dystocia in 49 births. A policy eliminating the use of oxytocin and instrumental deliveries would have prevented most birth traumas in this group. Unfortunately, this high-risk group is difficult to identify in the antepartum period, complicating the implementation of these guidelines and probably leading to higher rates of CS. In addition, the effect of endorsing such a policy on overall neonatal and maternal morbidity is minimal, because most morbidity occurs in newborns weighing less than 4000 g.

We report on trisomy of the short arm of the X chromosome (Xp11.2 --> pter) due to a de novo unbalanced X;13 translocation diagnosed prenatally in a female fetus. Amniocentesis was performed at 20-weeks' gestation following ultrasound finding of a Dandy-Walker malformation. The trisomy of Xp11.2 --> pter was confirmed with fluorescence in situ hybridization (FISH), using an X chromosome painting probe and telomeric FISH probes specific for the short arm of chromosome X. The karyotype was defined as 46,XX,der(13)t(X;13)(p11.2;p11.2). Molecular analysis suggested that the extra Xp material was of paternal origin. FISH analysis with an XIST probe showed that the derivative chromosome 13 did not include the XIST locus at the X-inactivation center (XIC). A complex phenotype was seen at birth including macrosomia, facial dysmorphism with preauricular tag, congenital heart defects, and structural brain malformations. Because the derivative chromosome was not subject to X inactivation, functional disomy of Xp11.2 --> pter most likely accounts for the abnormal phenotype in this patient.

The aim of this study was to estimate the effective dose 90% (ED90) of carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. We conducted a double-blind dose-finding study of carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 µg (maximum 140 µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. The ED90 of carbetocin to produce adequate uterine tone was estimated at 121 µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 µg; however, the observed response rate across all doses was

Objective: This study was undertaken to compare test characteristics of ultrasound and Doppler parameters in the prediction of fetal anemia in alloimmunized pregnancies. Study Design: In a prospective cohort study, 16 nonhydropic fetuses with red blood cell alloimmunization were evaluated with ultrasound and Doppler imaging. Middle cerebral artery (MCA) peak systolic velocity, intrahepatic umbilical venous (IHUV) maximum velocity, liver length, and spleen perimeter were measured. Results before first fetal blood sampling (FBS) or delivery were analyzed. Fetal anemia was defined as hemoglobin deficit 5 SD or greater. Sensitivity and specificity were calculated. Results: Six fetuses were anemic and required intrauterine transfusion, and 10 were not severely anemic at birth. MCA Doppler imaging was the best predictor of fetal anemia (100%), followed by IHUV (83%). Sensitivity was low for spleen perimeter (66%) and liver length (33%). Conclusion: Doppler evaluation of MCA peak systolic velocity is better than IHUV maximum velocity, liver, or spleen size in the prediction of fetal anemia in red blood cell alloimmunization. (Am J Obstet Gynecol 2003;188:1310-4.)

Objectives To evaluate the potential usefulness of noninvasive ultrasound assessment of fetal anemia in the diagnosis and management of fetuses with homozygous alpha-thalassemia-1. Methods We describe four pregnancies complicated by fetal homozygous alpha-thalassemia-1. They presented with ultrasound abnormalities before the development of hydrops. As part of evaluating the fetal condition, we performed ultrasound and Doppler studies aimed at identifying fetal anemia. These studies included evaluation of intrahepatic umbilical venous maximum flow velocity, middle cerebral artery peak flow velocity, fetal liver length and spleen perimeter. Results In all four fetuses, ultrasound and Doppler studies suggested the presence of fetal anemia. Homozygous alpha-thalassemia-1 was diagnosed in all cases, with fetal blood sampling confirming anemia in three fetuses. The majority of the intrahepatic umbilical venous maximum flow velocity and middle cerebral artery peak flow velocity measurements were above the 95th centile. Two fetuses underwent intrauterine transfusion and fetal blood flow velocities returned to normal after correction of the fetal anemia. The fetal liver length and spleen perimeter measurements showed a similar trend, although they were less consistent before 28 weeks. Conclusion Non-invasive ultrasound parameters, in particular quantification of intrahepatic umbilical venous maximum flow velocity and middle cerebral artery peak flow velocity, were found to be useful in the diagnosis and management of fetal anemia in pregnancies with fetal homozygous alpha-thalassemia-1. Copyright © 2002 ISUOG

Contains fulltext : 154930.pdf (Publisher’s version ) (Open Access) Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway.

We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ hybridization (FISH) analyses performed from October 1995 to June 1999 to assess the role of interphase FISH in the management of patients at increased risk for fetal aneuploidies. Gestational age and indications for amniocentesis, clinical interventions after FISH results, as well as interventions after final culture reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%) inconclusive FISH results. There were no false-positive or false-negative results, but there were nine (3%) clinically significant chromosomal abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results, 26 (52%) elected to terminate the pregnancy prior to the availability of the standard chromosome analysis. In two of the fetuses with trisomy 21 no abnormalities were reported by ultrasound examination. Our experience indicates that interphase FISH results played an important role in decision making, especially for pregnancies close to 24 weeks' gestation. Standard karyotype analysis is still required for detection of chromosome abnormalities not detectable by interphase FISH techniques and for clarification of unusual or inconclusive FISH results. Copyright © 2001 John Wiley & Sons, Ltd.

The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED90) undergoing elective Cesarean delivery (CD) under spinal anesthesia.We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED90. The initial dose was 10 μg, with increments/decrements of 5 μg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects.The ED90 of carbetocin was 14.8 μg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%.Based on our study, the ED90 of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 μg. This study was registered at clinicaltrials.gov (NCT-01651130).

To review a series of critically ill obstetric patients admitted to a general intensive care unit in a Canadian centre, to assess the spectrum of diseases, interventions required and outcome.A retrospective chart review was performed of obstetric patients admitted to the intensive care unit of an academic hospital with a high-risk obstetric service, during a five-year period. Data obtained included the admission diagnosis, ICU course and outcome. Daily APACHE II and TISS scores were recorded.Sixty-five obstetric patients, representing 0.26% of deliveries in this hospital, were admitted to the ICU during the study period. All had received prenatal care. Admission diagnoses included obstetric (71%) and non-obstetric (29%) complications. The mean APACHE II score was 6.8 +/- 4.2 and mean TISS score was 24 +/- 8.1. Twenty-seven patients (42%) required mechanical ventilation. No maternal mortality occurred and the perinatal mortality rate was 11%.A small proportion of obstetric patients develop complications requiring ICU admission. The outcome in this study was excellent, in contrast to that reported in other published studies with similar ICU admission rates. The universal availability of prenatal care may be an important factor in the outcome of this group of patients. The lack of a specific severity of illness scoring system for the pregnant patient makes comparison of case series difficult.

To estimate obstetric and neonatal outcomes after induction of labor at 37 weeks of gestation compared with expectant management in pregnancies complicated by fetal gastroschisis.The management of 296 pregnancies involving fetal gastroschisis (1980-2011) was reviewed from a single perinatal center. Ultrasound surveillance and nonstress testing were performed every 2 weeks from 30 weeks of gestation, weekly from 34 weeks of gestation, and twice weekly after 35 weeks of gestation until delivery. Labor was induced if fetal well-being testing was abnormal and, since 1994, labor was routinely induced at 37 weeks of gestation.Of 153 pregnancies reaching 37 weeks of gestation, labor was induced in 77 (26%) and 76 (25.7%) were allowed to labor spontaneously. There were no significant differences in mean maternal age (22 years in both), parity (56% compared with 66% nulliparous), presence of other fetal anomalies (12% compared with 9%), cesarean delivery rate (20% in both), 5-minute Apgar score less than 7 (10% compared with 12%), meconium at birth (36% compared with 49%), or respiratory distress syndrome (16% compared with 7%) between the induced and expectantly managed groups. However, neonatal sepsis (25% compared with 42%; P=.02) and a composite outcome of neonatal death and bowel damage (necrosis, atresia, perforation, adhesion; 8% compared with 21%; P=.02) were more common in expectantly managed pregnancies. Moreover, time to oral feeds (-3.4 days), time on total parenteral nutrition (-6.2 days), and hospital stay (-6.7 days) were reduced when labor was induced.In fetuses with gastroschisis, induction of labor at 37 weeks of gestation was associated with reduced risks of sepsis, bowel damage, and neonatal death compared with pregnancies managed expectantly beyond 37 weeks of gestation.II.

The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED95) undergoing elective Cesarean delivery under spinal anesthesia.One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 μg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects.Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin.In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 μg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 μg. This trial was registered at www.clinicaltrials.gov (NCT01428817).

The aims of this study were to review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support or ex utero intrapartum treatment and to discuss implications for future management of these complex and rare cases.We have presented a retrospective case series of 12 neonates requiring airway management on placental support at a single tertiary care, academic center.One mother experienced significant blood loss. Operative recovery times were unremarkable. Eight neonates required airway management due to mass obstruction, two for removal of an endotracheal balloon for fetoscopic treatment of congenital diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia. One of our series is an unusual case of management on placental support after vaginal delivery. Another child would have ideally been managed on placental support, but an extremely short umbilical cord prevented this. Even though the airway was secured in all 12 cases, five neonates died in the perinatal period.These procedures have a risk for substantial maternal blood loss. Despite excellent rates of success securing the neonatal airway, children who require management on placental support still have high mortality. A formalized multidisciplinary approach at our institution has enhanced preparedness for these cases.

Objective We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. Study Design In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. Results Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78–1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. Conclusion Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

Background: Significant fetomaternal hemorrhage (FMH) is an uncommon event that places the fetus at risk of severe morbidity and mortality. Symptoms and signs at presentation are subtle and, if promptly recognized, appropriate management may permit the fetus to escape serious injury. Cases: Four cases of significant FMH were diagnosed in the high-risk obstetrical unit at Mount Sinai Hospital, Toronto, during 2003. Three of the women complained of reduced fetal movements and were investigated initially with a non-stress test, a Kleihauer-Betke test, and ultrasound, including Doppler of the middle cerebral artery. These women all required emergency Caesarean section for non-reassuring fetal status. One fetus was treated by intravascular transfusion. Another identified case was transfused postnatally. One asymptomatic case was identified after spontaneous vaginal birth and also treated by neonatal transfusion. Neurological outcomes were good in all four cases. Conclusions: Reduced fetal movements may be the only complaint of FMH. Increased awareness is required to ensure a diagnosis is made. When a non-stress test for reduced fetal movement is non-reactive, a Kleihauer-Betke test should be ordered, as well as detailed ultrasonography, including fetal Doppler studies. The perinatal prognosis for FMH may improve by facilitating the appropriate use of fetal blood transfusion or delivery by Caesarean section.

Objective: To determine the effect of different methods of pregnancy termination on the culture success rate of postmortem fetal tissue. Methods: In a randomized trial, umbilical cord specimens were collected in a standardized manner and culture success rates were compared according to the method of pregnancy termination. Results: There was a significantly higher culture success rate in the vaginal (90.0%) and oral misoprostol (83.0%) groups compared to the intra-amniotic injection of prostaglandin group (52.8%). Conclusion: The results of our study and the very high success rate reported by others from specimens following dilatation and evacuation lead us to suggest that exposure to drugs used to induce abortion may be a more important factor in culture failure than either tissue type or time in transit.

Objective This study was undertaken to determine the maternal and fetal steady-state concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites during transdermal administration, at the time of fetal blood sampling for obstetric indications. Study design Transdermal GTN (0.4 mg/h) was applied approximately 2 hours before investigative fetal blood sampling to maintain uterine quiescence. Serial maternal venous (MV) and a single fetal venous (FV) plasma samples were collected and assayed for GTN and its metabolites, 1,2- and 1,3-glyceryl dinitrate. Results The steady-state MV plasma concentration was 4.3±0.84 nmol/L (mean±SEM, n = 7), and the dinitrate metabolites were detectable in the MV but not quantifiable. GTN was detectable in the FV (n = 7) but was not quantifiable as the levels were less than the lower limit of sensitivity of the assay ( Conclusion During transdermal GTN administration, the steady-state FV/MV concentration ratio is less than 0.23 at the time of fetal blood sampling.

Objectives This study was undertaken to review and analyze the fertility and pregnancy outcomes in patients who have undergone radical trachelectomy as the method of management of invasive carcinoma of the cervix. Study design All preoperative, operative, and follow-up data were collected prospectively. Perinatal information was completed by chart reviews and patient questionnaires. Results Of 80 patients having undergone the above procedure, 39 have attempted to conceive for a median of 11 months (range 1-85). There have been a total of 22 pregnancies in 18 patients (4 patients pregnant twice). Of the 22 pregnancies, 18 were viable, with 12 progressing to term and delivering by caesarean section. Preterm premature rupture of membranes was the primary cause of preterm delivery. Conclusion This series confirms that pregnancy is a safe and realistic outcome for women undergoing radical trachelectomy for invasive carcinoma of the cervix. Given the apparently high incidence of preterm premature rupture of membranes, these pregnancies should be managed as high risk.