Systematic, noninvasive endometriosis diagnosis in transvaginal sonography by the Swiss Society of Ultrasound in Medicine.

We present a new systematic, comprehensive, checklist-based sonographic assessment of endometriosis in the female true pelvis. Emphasis is placed on practical skills teaching. The newly introduced White Sliding Line (WSL) is the core structure. The WSL separates five compartments (anterior, central, posterior, and lateral right and left) containing dedicated endometriosis signs of mobility and morphology to be checked. This approach relies on the 2016 IDEA Consensus and further developments. It directly connects to the 2021 #ENZIAN Classification Standard. In practice, evaluation follows the proposed checklist in all compartments, judging first sliding mobility between organs and structures in a highly dynamic investigation. A rigorous search for deep endometriosis (DE) is then performed. We treat adhesions due to their great clinical importance and possible, reliable diagnosis by TVS as the fifth endometriosis unit, next to endometrioma, DE, adenomyosis, and superficial endometriosis. Including superficial (peritoneal) endometriosis is a future goal.

Judging Urgency in 343 Ectopic Pregnancies Prior to Surgery - The Importance of Transvaginal Sonographic Diagnosis of Intraabdominal Free Blood.

OBJECTIVES: Assessing urgency in ectopic pregnancies (ECP) remains controversial since the disorder covers a large clinical spectrum. Severe conditions such as acute abdomen or hemodynamic instability are mostly related to intra-abdominal blood loss diagnosed as free fluid (FF) on transvaginal sonography (TVS). The aims of the current study were to investigate the value of FF and to assess other potentially predictive parameters for judging urgency. METHODS: Retrospective cohort analysis on prospectively collected cases of proven ECP (n = 343). Demographics, clinical and laboratory parameters, and findings on TVS and laparoscopy (LSC) were extracted from the digital patient file. FF on TVS and free blood (FB) in LSC were evaluated. Low urgency was defined as FB (LSC) < 100 ml and high urgency as FB (LSC) ≥ 300 ml. The best subset of variables for the prediction of FB was selected and predictors of urgency were evaluated using receiver operator characteristic (ROC) curves. RESULTS: Clinical symptoms, age, ß-HCG, hemoglobin (HB) preoperative, and FF were examined in multivariate analysis for the cutoff values of 100 ml and 300 ml. FF was the only independent predictor for low and high urgency; HB preoperative was only significant for high urgency offering marginal improvement. ROC analysis revealed FF as an excellent discriminatory parameter for defining low (AUC 0.837, 95% CI 0.794-0.879) and high urgency (AUC 0.902, 95 % CI 0.860-0.945). CONCLUSION: Single assessment of FF on TVS is most valuable for judging urgency. However, the exact cutoff values for a low- and high-risk situation must still be defined.

The Predictive Value of Decisive and Soft Ultrasound Criteria for Ectopic Pregnancy Identification in 321 Preoperative Cases.

PURPOSE: To define the predictive value of morphological types (MTs) and further criteria in diagnosing ectopic pregnancy (ECP) by transvaginal sonography (TVS) prior to operative confirmation and treatment. MATERIALS AND METHODS: Retrospective cohort analysis of 321 consecutive patients with suspected ECP who were advised to undergo operation. RESULTS: ECP was investigated by TVS in all 321 patients. Application of the five selected MTs (blob sign, bagel sign, yolk sac, embryo, heart action) resulted in 85 % of cases receiving a conclusive diagnosis and 12 % receiving a presumed ECP diagnosis. 3 % remained nondiagnostic due to large or multiple ovarian cysts, large myoma, extended hemoperitoneum, or severe pain. ECP diagnosis was confirmed intraoperatively in 97 % of cases and was otherwise (3 %) immediately followed by curettage (CUR). The assessment of free fluid by TVS was achieved in most cases and correlated significantly with free blood. In the majority of cases, free blood was not bound to transmural ECP rupture. Histology confirmed the ECP diagnosis directly or by exclusion in 99 % of cases. Three cases of tubal ECP were diagnosed by TVS but not confirmed by LSC (1 %) and, finally, histology from CUR proved miscarriage (false-positive rate 1 %). CONCLUSION: We confirm the high accuracy of TVS diagnosis of ECP relying on five clearly different MTs, independent of its location. The blob and bagel sign emerged as important types (75 % of all ECPs). Histology from CUR was needed when ECP could not be visualized in LSC. Assessment of free fluid was essential and accurate in predicting free blood.

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.

The magnitude of clinical utility of preconception expanded carrier screening (ECS) concerning its potential to reduce the risk of affected offspring is unknown. Since neurodevelopmental disorders (NDDs) in their offspring is a major concern of parents-to-be, we addressed the question of residual risk by assessing the risk-reduction potential for NDDs in a retrospective study investigating ECS with different criteria for gene selection and definition of pathogenicity. We used exome sequencing data from 700 parents of children with NDDs and blindly screened for carrier-alleles in up to 3046 recessive/X-linked genes. Depending on variant pathogenicity thresholds and gene content, NDD-risk-reduction potential was up to 43.5% in consanguineous, and 5.1% in nonconsanguineous couples. The risk-reduction-potential was compromised by underestimation of pathogenicity of missense variants (false-negative-rate 4.6%), inherited copy-number variants and compound heterozygosity of one inherited and one de novo variant (0.9% each). Adherence to the ACMG recommendations of restricting ECS to high-frequency genes in nonconsanguineous couples would more than halve the detectable inherited NDD-risk. Thus, for optimized clinical utility of ECS, screening in recessive/X-linked genes regardless of their frequency (ACMG Tier-4) and sensible pathogenicity thresholds should be considered for all couples seeking ECS.

Audit of the first > 7500 noninvasive prenatal aneuploidy tests in a Swiss genetics center.

OBJECTIVES: Noninvasive prenatal testing (NIPT) is actually the most accurate method of screening for fetal chromosomal aberration (FCA). We used pregnancy outcome record to evaluate a complete data set of single nucleotide polymorphism-based test results performed by a Swiss genetics center. MATERIALS AND METHODS: The Panorama® test assesses the risk of fetal trisomies (21, 18 and 13), gonosomal aneuploidy (GAN), triploidy or vanishing twins (VTT) and five different microdeletions (MD). We evaluated all 7549 test results meeting legal and quality requirements taken in women with nondonor singleton pregnancies between April 2013 and September 2016 classifying them as high or low risk. Follow-up ended after 9 months, data collection 7 months later. RESULTS: The Panorama® test provided conclusive results in 96.1% of cases, detecting 153 FCA: T21 n = 76, T18 n = 19, T13 n = 15, GAN n = 19, VTT n = 13 and MD n = 11 (overall prevalence 2.0%). Pregnancy outcome record was available for 68.6% of conclusive laboratory results, including 2.0% high-risk cases. In this cohort the Panorama® test exhibited 99.90% sensitivity for each trisomy; specificity was 99.90% for T21, 99.98% for T18 and 99.94% for T13. False positive rate was 0.10% for T21, 0.02% for T18 and 0.06% for T13. CONCLUSION: SNP-based testing by a Swiss genetics center confirms the expected accuracy of NIPT in FCA detection.

Pregnancy outcomes in women with a hemoglobinopathy trait: a multicenter, retrospective study.

PURPOSE: To determine the risk of adverse maternal and neonatal outcomes in pregnant women with a hemoglobinopathy trait. MATERIALS AND METHODS: Retrospective cohort study was conducted to compare adverse maternal and neonatal outcomes between pregnant women with a hemoglobinopathy trait (study group; n = 172), and without a hemoglobinopathy trait (control group; n = 360). The medical data were extracted from clinical records of pregnant women attending antenatal care and delivering at the University Hospital Basel or University Hospital Zurich between 2015 and 2018. RESULTS: A total of 172 pregnant women with a hemoglobinopathy trait and 360 controls were recruited. Apart from fetal acidosis, the groups did not differ significantly in any variables of adverse neonatal outcomes. Whereas, among the maternal outcomes the rate of abortion, gestational diabetes mellitus, bacteriuria or urinary tract infection, intrahepatic cholestasis, abnormal placentation and anemia postpartum were significantly increased in women with a hemoglobinopathy trait. CONCLUSION: In our study, a hemoglobinopathy trait increased the risk of adverse maternal outcomes but did not increase adverse neonatal outcomes.

Retained placenta and postpartum hemorrhage: time is not everything.

PURPOSE: Postpartum hemorrhage is the major cause of maternal mortality worldwide. Retained placenta accounts for nearly 20% of severe cases. We investigated the influence of the time factor and retained placenta etiology on postpartum hemorrhage dynamics. METHODS: Our retrospective study analyzed a single-center cohort of 296 women with retained placenta. Blood loss was measured using a validated and accurate technique based on calibrated blood collection bags, backed by the post- vs pre-partum decrease in hemoglobin. We evaluated the relationship between these two blood loss parameters and the duration of the third stage of labor using Spearman rank correlation, followed by subgroup analysis stratified by third stage duration and retained placenta etiology. RESULTS: Correlation analysis revealed no association between third stage duration and measured blood loss or decrease in hemoglobin. A shorter third stage (< 60 min) was associated with significantly increased uterine atony (p = 0.001) and need for blood transfusion (p = 0.006). Uterine atony was significantly associated with greater decrease in hemoglobin (p < 0.001), higher measured blood loss (p < 0.001), postpartum hemorrhage (p = 0.048), and need for blood transfusion (p < 0.001). CONCLUSION: Postpartum blood loss does not correlate with third stage duration in women with retained placenta. Our results suggest that there is neither a safe time window preceding postpartum hemorrhage, nor justification for an early cut-off for manual removal of the placenta. The prompt detection of uterine atony and immediate prerequisites for manual removal of the placenta are key factors in the management of postpartum hemorrhage.

Improving Neonatal and Maternal Outcome by Inducing Mild Labor before Elective Cesarean Section: The Lacarus Randomized Controlled Trial.

BACKGROUND: Newborns delivered by elective cesarean section (CS) are at higher respiratory risk than those delivered vaginally or by CS proceeded by labor (secondary CS). The oxytocin challenge test (OCT) induces uterine contractions that trigger the release of fetal hormones regulating lung fluid clearance during transition from the uterine to an air-breathing environment. OBJECTIVES: The aim is to summarize current evidence and outline the Lacarus trial protocol. METHODS: Literature review informed the design of a randomized placebo-controlled multicenter trial of OCT preceding elective CS in 1,450 women with a singleton pregnancy due for CS at >35 weeks gestation, without preceding contractions, rupture of the membranes, or antenatal steroids. OCT comprises the infusion of oxytocin 5 IU/500 mL Ringer lactate at a rate of 12 mL/h, doubling every 10 min until inducing 5 uterine contractions per 15-min interval. The primary endpoint is the occurrence of neonatal respiratory morbidity within 24 h after birth. Secondary endpoints include biochemical and physiological parameters of fetal and maternal well-being, such as breastfeeding rate and fetal plasma copeptin concentrations. CONCLUSION: This is the first trial to test the hypothesis that oxytocin-induced contractions before elective CS is a promising application of physiologic principles gleaned from natural birth to improve neonatal and maternal outcomes.

Influence of newborn head circumference and birth weight on the delivery mode of primipara: what is more important?

Objectives Aim of the study was to analyze the impact of head circumference (HC) and birth weight (BW) on the delivery mode and delivery outcomes. Methods Study population consisted of pregnancy, delivery and newborn data from 1,762 women, who delivered between 2004 and 2016 at University Hospital of Zurich (UHZ). Odds ratio (OR) with 95% confidence intervals (CI) were calculated for mode of delivery. Newborns were sorted into four groups according HC or BW. To evaluate the association between HC and delivery outcome, a descriptive analysis was performed. In addition reference charts of newborn HC at term were constructed. Results OR for instrumental delivery (ID) was 2.37 (CI 95%, 1.63-3.46), for C-Section (CS) 3.74 (CI 95%, 1.49-9.37) when HC >36 cm. OR for ID was 1.59 (CI 95%, 1.02-2.50), for CS 3.18 (CI 95% 1.08-9.350) when BW was >4,000 g. OR for ID was 2.15 (95% CI, 1.69-2.73), for CS 1.93 (95% CI, 0.89-4.18) when HC ≥36 cm and BW <4000 g. OR for ID was 2.23 (95% CI, 1.35-3.67), for CS 4.39 (95% CI, 1.48-12.99) when HC ≥36 cm and BW ≥4,000 g. HC ≥36 cm was defined as large in our study. Mothers with higher age and body mass index delivered babies with larger HC (p<0.05). Blood loss and duration of expulsion period and BW was associated with larger HC (p<0.05). Conclusions The rate of ID and CS increased in case of a larger HC and greater BW. However, the main prognostic factor for ID was size of HC: ≥36 cm, but not macrosomia.

Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing.

OBJECTIVE: Non-invasive prenatal testing by targeted or genome-wide copy number profiling (cnNIPT) has the potential to outperform standard NIPT targeting the common trisomies 13, 18, and 21, only. Nevertheless, prospective results and outcome data on cnNIPT are still scarce and there is increasing evidence for maternal copy number variants (CNVs) interfering with results of both, standard and cnNIPT. STUDY DESIGN: We assessed the performance of cnNIPT in 3053 prospective and 116 retrospective cases with special consideration of maternal CNVs in singleton and multiple gestational pregnancies at any risk, as well as comprehensive follow-up. RESULTS: A result was achieved in 2998 (98.2%) of total prospective cases (89.2% analyzed genome-wide). Confirmed fetal chromosomal abnormalities were detected in 45 (1.5%) cases, of which five (11%) would have remained undetected in standard NIPTs. Additionally, we observed 4 likely fetal trisomies without follow-up and a likely phenotype associated placental partial trisomy 16. Moreover, we observed clinically relevant confirmed maternal CNVs in 9 (0.3%) cases and likely maternal clonal hematopoiesis in 3 (0.1%). For common fetal trisomies we prospectively observed a very high sensitivity (100% [95% CI: 91.96-100%]) and specificity (>99.9% [95% CI: 99.8-100%]), and positive predictive value (PPV) (97.8% [95% CI: 86.1-99.7%]), but our retrospective control cases demonstrated that due to cases of fetal restricted mosaicism the true sensitivity of NIPT is lower. After showing that 97.3% of small CNVs prospectively observed in 8.3% of genome-wide tests were mostly benign maternal variants, sensitivity (75.0% [95% CI: 19.4%-99.4%]), specificity (99.7% [99.5%-99.9%]) and PPV (30.0% [14.5%-52.1%]) for relevant fetal CNVs were relatively high, too. Maternal autoimmune disorders and medication, such as dalteparin, seem to impair assay quality. CONCLUSION: When maternal CNVs are recognized as such, cnNIPT showed a very high sensitivity, specificity and PPV for common trisomies in single and multiple pregnancies at any risk and very good values genome-wide. We found that the resolution for segmental aberrations is generally comparable to standard karyotyping, and exceeds the latter if the fetal fraction is above 10%, which allows detection of the 2.5 Mb 22q11.2 microdeletion associated with the velocardiofacial syndrome, even if the mother is not a carrier.

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures. / Empfehlungen der DEGUM, der ÖGUM, der SGUM und der FMF Deutschland zum Einsatz von Ersttrimester-Screening, früher Fehlbildungsdiagnostik, Screening an zellfreier DNA (NIPT) und diagnostischen Punktionen.

First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values.

[A Structured and Photographic Documentation of the Vacuum-Assisted Vaginal Delivery]. / Eine strukturierte und fotografische Dokumentation der Vakuumentbindung.

The correct placement of the vacuum cup is essential to reduce both maternal and neonatal morbidity after a vacuum-assisted vaginal delivery. Therefore, a checklist based report with all relevant clinical findings and a photo of the infant's head with the location of vacuum tag was introduced to make the exact application of the cup reproducible for. training/instruction purpose.

Detection of blood volumes and haemoglobin mass by means of CO re-breathing and indocyanine green and sodium fluorescein injections.

The main aim of the present study was to quantify the magnitude of differences introduced when estimating a given blood volume compartment (e.g. plasma volume) through the direct determination of another compartment (e.g. red cell volume) by multiplication of venous haematocrit and/or haemoglobin concentration. However, since whole body haematocrit is higher than venous haematocrit such an approach might comprise certain errors. To test this experimentally, four different methods for detecting blood volumes and haemoglobin mass (Hbmass) were compared, namely the carbon monoxide (CO) re-breathing (for Hbmass), the indocyanine green (ICG; for plasma volume [PV]) and the sodium fluorescein (SoF; for red blood cell volume [RBCV]) methods. No difference between ICG and CO re-breathing derived PV could be established when a whole body/venous haematocrit correction factor of 0.91 was applied (p = 0.11, r = 0.43, mean difference -340 ± 612 mL). In contrast, when comparing RBCV derived by the CO re-breathing and the SoF method, the SoF method revealed lower RBCV values as compared to the CO re-breathing method (p < 0.05, r = 0.95, mean difference -728 ± 184 mL). However, compared to the ICG and the SoF methods, the typical error (%TE) and hence reliability of the CO re-breathing method was lower for all measured parameters. Therefore, estimating blood volume compartments by the direct assessment of another compartment can be considered a suitable approach. The CO re-breathing method proved accurate in determining the induced phlebotomy and is at the same time judged easier to perform than any of the other methods.

Optimized Sonographic Weight Estimation of Fetuses over 3500 g Using Biometry-Guided Formula Selection.

Purpose The Hadlock et al. formula tends to underestimate fetal weight, in particular > 3500 g. At the high end of the range, the Merz et al. formula is more accurate, but becomes less so in smaller fetuses. This study was designed to improve fetal weight estimation in fetuses > 3500 g by identifying the fetal biometric parameter providing the most reliable guidance to optimal formula selection. Materials and Methods Regression analysis of 12 032 pregnancies showed that multiplication of abdominal circumference by femur length (AC × FL) gave the best choice of appropriate formula: Hadlock for AC × FL < 24 600, Merz for those ≥ 24 600. We then tested this rule, ('Zurich method'), prospectively in 4073 pregnancies, comparing it with the Hadlock, Merz and the Kehl formulas. Birth weights were merged into 7 categories (< 1500 to ≥ 4000 g, interval of 500 g). The percentage error (PE) and absolute percentage error (APE) were calculated. Results The PE using the Zurich method was lower in both > 3500 g groups than with the Hadlock formula alone (3500 - 3999 g: 0.9 % vs. - 5.3 %, > 4000 g: - 3.2 % vs. - 8.6 %), similar to that with the Merz formula alone, and lower than with the Kehl formulas (3500 - 3999 g: - 9.0 % vs. - 3.2 %, > 4000g: - 5.1 % vs. 0.9 %). The Zurich method and Hadlock formula also shared the lowest PE in the < 1500 g group: 0.2 % vs. 6.8 % (Kehl) vs. 9.6 % (Merz). In terms of APE the Zurich method performed almost as well as the Merz formula in the > 4000 g group, while sharing the lowest value with the Hadlock formula in the < 1500 g group (8.2 % vs. 10.5 % [Kehl], 23.6 % [Merz]). Conclusion The Zurich method uses a pivotal value of the biometry parameter AC × FL to switch between formulas and corrects for the errors of the Hadlock formula in fetuses ≥ 3500 g and those of the Merz formula in fetuses < 3500 g.

Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy.

OBJECTIVE: We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia. STUDY DESIGN: Fifty patients with moderate anemia (hemoglobin 8.0-9.9 g/dl) and iron deficiency (ferritin < 15 µg/l) were treated in the Anemia Clinic at the Department of Obstetrics. RESULTS: All patients showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte count at day eight of therapy and showed an increase in hemoglobin and hematocrit at the end of therapy (p < 0.001). The target hemoglobin (≥10.5 g/dl) was achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic disease and iron deficiency responded well to anemia treatment. 50% of women with anemia of chronic disease and iron deficiency (3/6) responded well to intravenous iron, and 67% (4/6) responded well to the combination of intravenous iron and recombinant human erythropoietin. CONCLUSION: Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia.

Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS: In a retrospective case-control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40-99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS: Estimated blood loss (median 400 [300-600] mL compared with 400 [300-600] mL, P=.22), ΔHb (14.0 [5.0-22.0] compared with 12.0 [4.0-21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or ΔHb and severity of intrahepatic cholestasis of pregnancy. CONCLUSIONS: In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen.

Fetal Release of Copeptin in Response to Maternal Oxytocin Administration: A Randomized Controlled Trial.

OBJECTIVE: To test whether an oxytocin challenge test raises neonatal levels of copeptin, the C-terminal portion of proarginine vasopressin, a sensitive stress marker elevated in neonates born by vaginal delivery as opposed to elective cesarean delivery. METHODS: In a randomized controlled trial in women with a singleton pregnancy undergoing elective cesarean delivery at greater than 36 weeks of gestation and no contractions or rupture of membranes, we compared arterial umbilical cord plasma concentrations of copeptin between neonates exposed to an oxytocin challenge test before elective cesarean delivery and those administered saline infusion (placebo group). Women randomized to an oxytocin challenge test received 5 international units/500 mL oxytocin Ringer lactate infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three uterine contractions per 10-minute interval, at which point it was discontinued. Neonatal copeptin levels were the primary endpoint. Secondary endpoints included biochemical and physiologic parameters of fetal and maternal well-being. RESULTS: From January 2012 to October 2012 and from September 2013 to January 2015, 78 women underwent an oxytocin challenge test and 78 placebo infusion, of whom 12 and 11, respectively, were excluded as a result of insufficient blood sample volume for analysis. Umbilical cord plasma copeptin levels [median (range)] were higher in neonates who underwent an oxytocin challenge test than those who underwent placebo infusion: 22.2 (3.22-2,319) compared with 7.39 (2.5-344.6) pmol/L (P<.001). There were no statistically significant differences between the two groups in secondary outcomes. CONCLUSION: Oxytocin challenge test-induced contractions before elective cesarean delivery trigger fetal copeptin release. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01962701.

Neurodevelopmental outcome in very low birthweight infants with pathological umbilical artery flow.

OBJECTIVE: To assess neurodevelopmental outcome during toddlerhood in very low birthweight (VLBW) infants with absent or reverse end-diastolic flow (AREDF) in the umbilical artery (UA) during pregnancy. DESIGN: Retrospective cohort study with matched control group. SETTING: Tertiary perinatal centre. PATIENTS AND OUTCOME MEASURES: We compared longitudinally collected data on neonatal and neurodevelopmental outcomes among 41 infants born in our institution from 1997 to 2010 with birth weight <1500 g and UA AREDF and 41 infants with prenatally normal UA Doppler parameters matched for gestational age, birth weight, sex and year of birth. We evaluated neurodevelopmental outcome at a median (range) corrected age of 23.3 (10.1-29.6) months using the Bayley scales of infant development, 2nd edition (BSID-II), and neurological examination. RESULTS: The mental development index in UA AREDF children (median (range) 84 (49-116)) was significantly lower than in controls (median (range) 91 (62-140)), including after adjustment for confounders. Intergroup differences in psychomotor development index (PDI; BSID-II) and the rate of cerebral palsy or minor neuromotor dysfunction were non-significant. CONCLUSIONS: VLBW infants with UA AREDF have a higher risk of poorer mental development during toddlerhood than controls matched for gestational age, birth weight, sex and year of birth. UA AREDF may be considered a prenatal predictor of poorer mental development in this population. Long-term follow-up studies with larger cohorts are needed to better evaluate the impact of this prenatal factor on later neurodevelopment.