Proposal for standardized prenatal assessment of fetal open dysraphisms by the European reference network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies (ITHACA) and eUROGEN.

Open dysraphisms, that is, myelomeningocele and myeloschisis, are rare diseases associated with a risk of severe disability, including lower limb motor and sensory deficiency, sphincter deficiency, and potential intellectual deficiency. Open dysraphism is diagnosed in Europe in 93.5% of cases. In case of suspicion of fetal open dysraphism, a detailed fetal morphologic assessment is required to confirm the diagnosis and exclude associated structural anomalies, as well as genetic assessment. In case of isolated fetal open dysraphism, assessment of prognosis is based on fetal imaging including the level of the lesion, the presence or not of a sac, the presence and nature of intra cranial anomalies, and the anatomical and functional evaluation of the lower extremities. Based on these biomarkers, a personalized prognosis as well as comprehensive information about prenatal management alternatives will allow parents to decide on further management options. Standardization of prenatal assessment is essential to compare outcomes with benchmark data and make assessment of surgical innovation possible. Herein, we propose a protocol for the standardized ultrasound assessment of fetuses with isolated open dysraphism.

The Arabin cervical pessary for the prevention of preterm birth in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation: a multicenter randomized controlled trial.

BACKGROUND: Miscarriage and preterm birth are leading causes of loss and disability in monochorionic twins after laser treatment of twin-twin transfusion syndrome. OBJECTIVE: This study aimed to investigate the use of cervical pessary to reduce preterm birth before 32 weeks of gestation in monochorionic diamniotic twin pregnancies after fetal surgery for twin-twin transfusion syndrome. STUDY DESIGN: In this open-label multicenter randomized trial, pregnant women carrying monochorionic diamniotic twins requiring fetoscopic laser coagulation for twin-twin transfusion syndrome were randomly assigned in a 1:1 ratio to pessary placement or conservative management. The primary outcome was birth before 32 weeks of gestation. The secondary outcomes were birth before 28, 30, 34, or 37 weeks of gestation; preterm premature rupture of membranes; fetal and neonatal survival; and a composite of maternal and neonatal complications. The estimated sample size was 364 patients, with 182 cases in each arm of the study. The analysis was performed according to the intention-to-treat principle. Moreover, 2 interim analyses were planned. RESULTS: The trial was stopped prematurely after the first planned interim analysis for futility. Overall, 137 women were included in the analysis, 67 in the pessary group and 70 in the conservative management group. Preterm birth before 32 weeks of gestation occurred in 27 of 67 women (40.3%) in the pessary group and in 25 of 70 women (35.7%) in the conservative management group (adjusted odds ratio, 1.19; 95% confidence interval, 0.58-2.47; P=.63). No differences between groups was observed in the rate of deliveries before 28, 30, 34, and 37 weeks of gestation. Overall survival to delivery was 91.2% (125/137) for at least 1 twin, and 70.8% (97/137) for both twins, with no difference between groups. Neonatal survival at 30 days was 76.5% (208/272). There was no difference between the groups in maternal or neonatal morbidity. CONCLUSION: In monochorionic diamniotic twin pregnancies requiring fetal therapy for twin-twin transfusion syndrome, routine use of cervical pessary did not reduce the rate of preterm birth before 32 weeks of gestation.

Pregnancy-related aortic complications in women with bicuspid aortic valve.

OBJECTIVES: To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy. METHODS: Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention. RESULTS: Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380). CONCLUSIONS: Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.

Fetal abdominal cysts: Predicting adverse outcomes.

INTRODUCTION: The primary aim of the study was to identify risk factors associated with fetal or neonatal loss, neonatal morbidity, and the need for surgery in fetuses diagnosed with an abdominal cyst. The secondary aim was to compare the characteristics of the cyst according to trimester at diagnosis. MATERIAL AND METHODS: This was an observational retrospective study performed at Vall d'Hebron University Hospital. The study included pregnant women aged 18 years or older with diagnosis of a fetal abdominal cyst from 2008 to 2021. RESULTS: A total of 82 women with a median gestational age of 31+1 weeks (12+0-39+4) were included in the analysis. Seven (8.5%) cases were diagnosed in the first trimester, 28 (34.1%) in the second trimester, and 47 (57.3%) in the third trimester. Fetal or neonatal loss occurred in 10 (12.2%) cases; significant predictors were diagnosis in the first trimester (OR 36.67, 95% CI: 4.89-274.79), male gender (OR 4.75, 95% CI: 1.13-19.9), and associated abnormalities (OR 15.2, 95% CI: 2.92-79.19). A total of 10 of 75 (13.3%) neonates showed at least one neonatal complication, and the only predictor was occurrence of associated abnormalities (OR 7.36, 95% CI: 1.78-30.51). A total of 16 of 75 (21.3%) neonates required postnatal surgery, and the predictors were second-trimester diagnosis (OR 3.92, 95% CI: 1.23-12.51), associated abnormalities (OR 3.81, 95% CI: 1.15-12.64), and bowel location (OR 10.0, 95% CI: 1.48-67.55). CONCLUSIONS: Factors associated with adverse outcomes in fetuses diagnosed with abdominal cysts are first-trimester diagnosis and associated abnormalities. Cysts detected in the second trimester and those of intestinal origin are more likely to require surgery.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial.

Importance: Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy. Objective: To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia. Design, Setting, and Participants: Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants. Interventions: Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group). Main Outcomes and Measures: Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%. Results: Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority. Conclusions and Relevance: Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio. Trial Registration: ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: a prospective observational study.

OBJECTIVES: To create a predictive model including biomarkers and evaluate its ability to predict adverse perinatal outcomes in late-onset small fetuses, ultimately helping to provide individualized counseling at the time of diagnosis. METHODS: This was a prospective observational study, including singleton pregnancies with an estimated fetal weight (EFW) below the 10th percentile, at a gestational age between 32 + 0 and 36 + 6 weeks of gestation (WG). Variables recorded at diagnosis to predict adverse pregnancy outcomes were: soluble fms-like tyrosine-kinase-1 to placental growth factor ratio (sFlt-1/PlGF), fetal Doppler (umbilical artery and middle cerebral artery), uterine artery pulsatility index (UtAPI), EFW percentile, gestational age, and the presence of maternal risk factors for placental insufficiency. Logistic regression models were developed for the prediction of three co-primary outcomes: composite adverse perinatal outcomes (APO), and the need for elective delivery before 35 or 37 WG. RESULTS: Sixty (52.2%) fetal growth restricted (FGR) and 55 (47.8%) small for gestational age (SGA) were enrolled. Thirteen (11.3%) women needed elective delivery before 35 WG and 27 (23.5%) women before 37 WG. At least one APO occurred in 43 (37.4%) pregnancies. The best marker in univariate analyses was the sFlt-1/PlGF ratio [AUC = 0.932 (95% CI, 0.864-0.999)]. The multivariate model including sFlt-1/PlGF showed a better predictive performance for APO than the multivariate model without sFlt-1/PlGF (P < 0.024). CONCLUSIONS: sFlt-1/PlGF is a good predictor of APO at the time of late-onset FGR/SGA diagnosis. Our predictive models may be useful to provide early individualized prenatal counseling in this group of women. Further studies are needed to validate these preliminary findings in a larger cohort.

Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE: This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN: This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1-to-placental growth factor ratio). RESULTS: A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION: More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1-to-placental growth factor ratio in future research and before making clinical decisions.

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study.

OBJECTIVES: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. METHODS: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. RESULTS: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. CONCLUSIONS: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.

Intrauterine cannabis exposure and fetal and maternal blood flow: a case-control study.

INTRODUCTION: Cannabis consumption during pregnancy increases the risk of pregnancy and neonatal complications. Since the underlying mechanism is unknown, the purpose of this study is to evaluate the changes in maternal and fetal blood flow in pregnancies exposed to cannabis, Δ9-tetrahydrocannabinol (THC). MATERIAL AND METHODS: A case-control study between 2013 and 2020, included women with continued cannabis exposure during the pregnancies, defined by qualitative detection of THC in urine (Cannabis Group), and low-risk pregnancy women divided into tobacco smokers (Tobacco Group), and non-tobacco smokers (Control Group). We evaluated the association between cannabis consumption and maternal and fetal blood flow parameters measured by Doppler ultrasound: uterine artery at 11-14, 20-22 and 33-35 weeks, umbilical artery and middle cerebral artery at 33-35 weeks. Cerebral-placental ratio was calculated. RESULTS: Overall, 275 participants were included, 60 in the Cannabis Group, 17 in the Tobacco Group and 198 in the Control Group. At 33-35 weeks, differences were found in the umbilical artery pulsatility index (PI) (1.05 ± 0.23, 1.06 ± 0.19, 0.93 ± 0.15, P < 0.01), middle cerebral artery PI (1.75 ± 0.35, 1.90 ± 0.45, 1.88 ± 0.34, P < 0.05), cerebral-placental ratio (1.69 ± 0.40, 1.85 ± 0.53, 2.07 ± 0.47, P < 0.05) and mean uterine artery PI (0.89 ± 0.26, 0.73 ± 0.19, 0.74 ± 0.20, P < 0.01), respectively. On logistic regression analysis, adjusted for maternal age, maternal body mass index, maternal weight and white ethnicity, both cannabis and tobacco were predictors for increased umbilical artery PI, but only cannabis was a predictor for a decreased cerebral-placental ratio and an increased uterine artery PI at 33-35 weeks. CONCLUSIONS: Data from a large cohort of continuous cannabis exposure pregnancies show that cannabis is associated with maternal and fetal blood flow changes. However, it is not possible to disentangle the association of the tobacco and cannabis.

The Overlooked Impact of Lower Uterine Segment Contractions on Second Trimester Cervical Assessment.

INTRODUCTION: Asymptomatic contractions in the lower uterine segment (LUS) may affect uterocervical angle and cervical length (CL); however, this has never been investigated. Therefore, the aim of this study was to evaluate the effect of LUS contractions on uterocervical angle, CL, and LUS thickness. MATERIALS AND METHODS: This was a prospective, observational, single-cohort study conducted on 102 asymptomatic singleton pregnancies between 19.0 and 22.6 weeks of gestation. Uterocervical angle and CL were measured by transvaginal ultrasound at two different time points with an interval of at least 20 min. LUS thickness was also measured as an indirect marker of myometrial contraction. A linear and curvilinear regression were performed to explore a potential association between LUS contractions, measured as increments in LUS thickness, and changes in CL and uterocervical angle. RESULTS: The linear regression between changes in LUS thickness and changes in CL showed that LUS contractions impact CL; for every 1-mm increase in LUS thickness, CL increased by 0.909 mm, when the isthmus was included in the CL measurement (R2 = 0.358; ß = 0.909; p < 0.001). By contrast, when the isthmus was not included in the measurement, a curvilinear relation between changes in LUS thickness and changes in CL was found (R2 = 0.077; ß1 = 0.575, ß2 = 0.038; p = 0.018). The relation between changes in uterocervical angle and changes in LUS thickness was not significant. DISCUSSION/CONCLUSION: LUS contractions can be observed in many asymptomatic women during the second trimester of pregnancy. LUS contractions lead to an increase in CL and LUS thickness, thus impacting ultrasound cervical assessments. These contractions do not affect the uterocervical angle.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.

BACKGROUND: Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE: The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN: A retrospective cohort study. SETTING: Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION: Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS: Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. CONCLUSION: Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.

A mixture model of ductus venosus pulsatility index in screening for aneuploidies at 11-13 weeks' gestation.

OBJECTIVE: To assess the value of ductus venosus pulsatility index for veins (DV PIV) in screening for aneuploidies at 11-13 weeks' gestation. METHODS: Fetal DV PIV was measured in singleton pregnancies undergoing first-trimester screening for aneuploidies. In euploid (n = 44,756) and aneuploid (202 cases of trisomy 21, 72 cases of trisomy 18 and 30 cases of trisomy 13) fetuses, DV PIV was best described by a mixture model of distributions. Performance of screening for aneuploidies by DV PIV alone and in combination with fetal nuchal translucency (NT) thickness and serum free ß-hCG and PAPP-A was estimated. RESULTS: In euploid pregnancies there was a bimodal distribution of DV PIV with a dominant crown-rump length (CRL)-dependent part, accounting for around 97% of cases in Caucasians and around 93% in Afro-Caribbeans, and a smaller CRL-independent distribution. In aneuploidies the dominant part was the CRL-independent distribution, which accounted for around 85% cases of trisomies 21 and 18 and 70% of cases of trisomy 13. In screening for trisomy 21 by maternal age, NT and biochemistry at a risk cutoff of 1 in 100, the detection rate was 89.7% and false positive rate was 2.74%; with addition of DV PIV, the values were 93.5 and 1.63%, respectively. CONCLUSIONS: Measurement of DV PIV improves the performance of first-trimester combined test for aneuploidies.

Ultrasonographic prediction of early miscarriage.

BACKGROUND: The aim of this retrospective study was to assess the value of maternal history and ultrasound scan findings at 6-10 weeks for predicting early miscarriage. METHODS: Embryonic crown-rump length (CRL), heart rate (HR), gestational sac diameter (GSD) and yolk sac diameter (YSD) were compared in two groups of women with singleton pregnancies attending an early pregnancy unit. In the first group the initial scan demonstrated a live embryo but in a subsequent visit the scan showed a dead embryo, complete or incomplete miscarriage. In the second group with a live embryo there was subsequent live birth of a normal neonate. RESULTS: There were 729 pregnancies with miscarriage and 4698 with normal outcome. Logistic regression analysis demonstrated that in the prediction of miscarriage the risk was higher in women of African racial origin [odds ratio (OR) 1.62], cigarette smokers (OR 1.91) and those with vaginal bleeding (OR 2.03) and increased with maternal age (OR 1.05) and YSD (OR 1.88) and was inversely related to CRL (OR 0.79), HR (OR 0.96) and GSD (OR 0.84). At false-positive rate of 30%, the detection rate of miscarriage in screening by vaginal bleeding was 45%, 53% by the addition of maternal history factors and 85.7% by the addition of ultrasound findings. CONCLUSIONS: In early pregnancy a prediction of miscarriage can be provided by a combination of maternal characteristics and ultrasound findings and the estimated risk can be used to rationalize follow-up. Our multivariate model requires prospective evaluation in a new sample population.

Maternal thyroid function at 11-13 weeks of gestation in fetal trisomies 21 and 18.

OBJECTIVE: To examine the association between maternal serum levels of thyroid stimulating hormone (TSH) and free ß-human chorionic gonadotrophin (free ß-hCG) in trisomy 21, trisomy 18 and euploid pregnancies at 11-13 weeks and investigate the potential value of TSH in first-trimester screening for aneuploidies. METHODS: Maternal serum TSH and free ß-hCG levels at 11-13 weeks in 25 trisomy 21 and 25 trisomy 18 pregnancies were compared with levels in 3592 unaffected pregnancies. Only women with no history of thyroid disease and negative for antithyroid antibodies were included. RESULTS: Serum TSH in the trisomy 21 pregnancies was lower [0.76 multiples of the normal median (MoM), interquartile range (IQR) 0.46-1.09 MoM] and in trisomy 18 it was higher (1.25 MoM, IQR 0.88-1.98 MoM) than in unaffected pregnancies (1.01 MoM, IQR 0.61-1.51 MoM). There were significant associations between TSH and free ß-hCG in the unaffected pregnancies (r = - 0.214, p < 0.0001), but not in those with trisomy 21 (r = - 0.157, p = 0.452) or trisomy 18 (r = - 0.176, p = 0.401). CONCLUSIONS: hCG, rather than TSH, may be the primary thyrotropic factor in early pregnancy. Measurement of TSH does not improve the performance of screening for trisomies 21 and 18 provided by nuchal translucency, free ß-hCG and pregnancy-associated plasma protein-A.

Contribution of ductus venosus Doppler in first-trimester screening for major cardiac defects.

OBJECTIVE: To determine whether assessment of ductus venosus flow at 11-13 weeks' gestation improves the detection rate of cardiac defects achieved by screening with nuchal translucency (NT) thickness. METHODS: Prospective first-trimester screening for aneuploidies, including measurement of fetal NT and assessment of ductus venosus flow. The performance of different combinations of increased fetal NT and abnormal blood flow in the ductus venosus in screening for major cardiac defects was examined. RESULTS: The study population of euploid fetuses included 85 cases with major cardiac defects and 40,905 with no cardiac defects. The fetal NT was above the 95th and above the 99th centile in 30 (35.3%) and 18 (21.2%) of the fetuses with cardiac defects, respectively, and in 1,956 (4.8%) and 290 (0.7%) of those without cardiac defects, respectively. Reversed a-wave was observed in 24 (28.2%) of the fetuses with cardiac defects and in 856 (2.1%) of those with no cardiac defects. Specialist fetal echocardiography for cases with NT above the 99th centile and those with reversed a-wave, irrespective of NT, would detect 38.8% of major cardiac defects at an overall false- positive rate of 2.7%. CONCLUSIONS: Assessment of ductus venosus flow improves the performance of NT screening for cardiac defects.

Outcome of pregnancies with trisomy 2 cells in chorionic villi.

OBJECTIVE: To describe the outcome of pregnancies with trisomy 2 in cultures of first-trimester chorionic villous samples (CVS) and determine whether amniocentesis is necessary in the management of such cases. METHODS: Cultures of chorionic villi were performed at 11-13 weeks in 37 474 pregnancies. In those with trisomy 2 cells, amniocentesis was performed at 16 weeks. Pregnancy outcome was obtained from maternity records. RESULTS: Trisomy 2 cells in CVS cultures were observed in 45 of 37 474 pregnancies (1.2 per 1000). In 43 cases ultrasound examination at 16-20 weeks showed no fetal abnormalities, amniocentesis demonstrated the presence of only normal cells, and all 43 pregnancies ended in normal healthy live births. The birth weight was below the 5th centile in six neonates (13.9%). There was a significant association between the birth weight centile and the percentage of trisomic cells in the CVS culture (r = 0.409, p = 0.010). In one case, there was fetal death at 15 weeks. In a second case, amniocentesis showed one cell with trisomy 2 in a total of 53 cells, and ultrasound examination at 18 weeks showed severe fetal growth restriction and coarctation of the aorta. CONCLUSION: In at least 95% of cases with trisomy 2 in CVS cultures there is confined placental mosaicism (CPM). The prognosis is good, but in about 15% of cases there is fetal growth restriction.

Decreased annexin A5 mRNA placental expression in pregnancies complicated by fetal growth restriction.

BACKGROUND: The placental anticoagulant protein Annexin A5 (ANXA5) is highly expressed on the apical surfaces of syncytiotrophoblasts and plays an important role in maintaining blood fluidity in the placental circulation. We investigated the mRNA and protein expression of ANXA5 in placentas from pregnancies complicated by fetal growth restriction (FGR) compared with uncomplicated pregnancies. MATERIALS AND METHODS: Placental tissue was collected from 18 pregnancies complicated by FGR and 16 pregnancies with a normal outcome. ANXA5 mRNA expression was quantified by Real-Time PCR (RT-PCR), and protein concentrations were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: A decreased ANXA5 mRNA expression was observed in placenta samples from FGR-affected pregnancies compared to those from uncomplicated pregnancies. However, similar ANXA5 protein levels were measured in both specimen groups. No correlation was observed between ANXA5 mRNA and protein levels. CONCLUSIONS: Transcriptional ANXA5 down-regulation was demonstrated in FGR-affected pregnancies, although protein levels were similar in FGR-related placentas and controls. We can speculate that either recruitment of the protein from the bloodstream or increased apoptosis or post-transcriptional modifications occur, which affect ANXA5 protein levels in FGR-related placentas. Further studies are required to reveal the role of ANXA5 in FGR pathology.

Maternal serum activin a at 11-13 weeks of gestation in hypertensive disorders of pregnancy.

OBJECTIVES: To investigate whether the maternal serum concentration of activin A at 11-13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-alpha receptor-1 (TNF-R1). MATERIAL AND METHODS: Serum activin A, TNF-R1, PAPP-A and uterine artery PI were determined in a case-control study of 126 cases that developed preeclampsia, 88 that developed gestational hypertension and 214 controls. RESULTS: In preeclampsia, compared to controls, uterine artery PI, serum activin A and serum TNF-R1 were higher and serum PAPP-A was lower. In gestational hypertension, compared to controls, serum activin A was higher but uterine artery PI, serum PAPP-A and serum TNF-R1 were not significantly different. There were no significant associations between serum activin A and either uterine artery PI or serum TNF-R1 in either the hypertensive groups or the controls. DISCUSSION: The data do not support the hypothesis linking activin A with impaired trophoblastic invasion of the maternal spiral arteries, placental hypoxia and the release of cytokines which in turn cause endothelial dysfunction and the development of the clinical symptoms of the disease.