Are we ready for widespread implementation of lactate POCT in fetal blood sampling? An analytical and clinical verification of the novel statstrip POCT analyzer.

Objectives: Currently, pH values are used in fetal scalp blood sampling as a parameter to rule out fetal distress during the delivery. Due to a high number of pre-analytical errors in pH measurements, lactate measurement is already extensively examined as an alternative. Our objectives were to confirm the analytical performance of the StatStrip lactate POCT analyzer and to compare pH and lactate as a marker of fetal distress. Design: and methods: Fetal blood scalp, umbilical and arterial blood test results (n = 100) were analyzed to compare the current POC blood gas analyzer including lactate (iSTAT-1) with the new POCT analyzer (StatStrip) to test the analytical performance. Furthermore, in all fetal scalp blood tests with a lactate en pH measurement from 2021 to 2023, clinical delivery data was collected to perform a clinical verification. Results: The lactate concentration on the StatStrip analyzer correlated well with the iSTAT-1 (Pearson's r ≥ 0.95). 73 Fetal scalp blood tests showed 18% discrepant results when comparing pH and lactate with regard to fetal distress and consequent delivery intervention. Lactate showed more false positive results than pH (4 versus 1), but no false negatives as opposed to pH (0 versus 1). Conclusions: The lactate Statstrip and iSTAT-1 POCT analyzers were analytically equivalent. The clinical verification study showed that lactate is a good predictor of fetal distress, although more false positive results were found in our limited dataset. However, unnecessary interventions due to failed pH measurements might be prevented when a lactate measurement is introduced.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

The role of fetal hemoglobin in the artificial placenta: A premature ovine model.

INTRODUCTION: A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model. METHODS: Extremely premature lambs (n = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.5 ± 0.35 kg. Lambs were cannulated using 10-14Fr cannulae for drainage via the right jugular vein and reinfusion via the umbilical vein. Lambs were intubated and lungs were filled with perfluorodecalin to a meniscus with a pressure of 5-8 cm H2O. The first option for transfusion was fetal whole blood from twins followed by maternal red blood cells. Arterial blood gases were used to titrate AP support to maintain fetal blood gas values. RESULTS: The mean survival time on circuit was 119.6 ± 39.5 h. Hemodynamic parameters and lactate were stable throughout. As more adult blood transfusions were given to maintain hemoglobin at 10 mg/dL, the HbF% declined, reaching 40% by post operative day 7. The HbF% was inversely proportional to flow rates as higher flows were required to maintain adequate oxygen saturation and perfusion. CONCLUSIONS: Transfusion of adult blood led to decreased fetal hemoglobin concentration during AP support. The HbF% was inversely proportional to flow rates. Future directions include strategies to decrease the priming volume and establishing a fetal blood bank to have blood rich in HbF.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

OBJECTIVES: NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. METHODS: We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. RESULTS: In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CONCLUSION: CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

Are Maternal Vitamin D (25(OH)D) Levels a Predisposing Risk Factor for Neonatal Growth? A Cross-Sectional Study.

BACKGROUND: Neonatal bone mass may potentially be influenced by existing maternal vitamin D (25(OH)D) levels. Few studies evaluated maternal vitamin D deficiency (VDD) with neonatal anthropometrics such as weight, height and head circumference (HC), especially in Greece, which is a Mediterranean country with plenty of sunshine and consequently benefits the synthesis of 25(OH)D. We investigated this potential association in Greece, taking into account the administration or not of prenatal vitamin D supplements. The purpose of our study is to ascertain if there is a possible association between maternal VDD and neonatal specific anthropometric characteristics (weight, height and HC) at birth. If this is confirmed by future clinical studies, it would be of interest to develop a prenatal pregnancy selection program that would detect VDD early or during pregnancy in order to improve fetal-neonatal development in a Mediterranean country like ours. METHODS: We performed a cross-sectional study on 248 early early term infants (after 37 + 0 to 38 + 6 weeks of gestation) but also on full-term infants (after 39 to 40 weeks of gestation) and their Greek mothers from September 2019 to January 2022. Blood samples of 25(OH)D were taken from the mother at the beginning of labor and cord blood was taken from the newborn. Pregnant women were divided into two groups: those who received or did not receive a normal dose of calcium (500 mg/day) and vitamin D supplements (400-800 IU/day) as instructed by their treating physicians. RESULTS: Our findings revealed a positive association between maternal VDD and low neonate birth weight (LBW) in women receiving vitamin D during pregnancy and no association between maternal VDD and neonatal height or head circumference (HC) at birth. CONCLUSIONS: Overall, this study highlighted the association between maternal VDD at the end of gestation and LBW neonates born to mothers who received vitamin D supplementation. We did not find any correlation in two of the three somatometric characteristics studied, height and HC. In any case, more clinical studies are needed to further corroborate any potential association of maternal VDD with other neonatal somatometric characteristics.

Maternal Risk Factors and Their Effect on Outcome and Procedure-Related Complications in Cordocentesis: A Multicenter Retrospective Study.

BACKGROUND: Cordocentesis is used in clinical situations in which lower-risk diagnostic procedures do not deliver the desired results. The aim of this study was to evaluate the risk for procedure-related complications and fetal loss in correlation to maternal risk factors. METHODS: This is a multicenter retrospective study investigating the complications, risk factors and perinatal outcome of diagnostic cordocentesis between 1998 and 2019 in three different centers. RESULTS: A total of 1806 cordocenteses were performed and procedure-related complications (IUFD within 48 h, contractions, bradycardia, unsuccessful puncture, chorioamniotic separation) were noted in 1.6% of cases. Fetuses with chromosomal aberrations, intrauterine growth restriction and hydropic fetuses had a significantly higher rate of fetal loss compared to other indications. Fetal blood sampling (FBS) performed before 17+0 weeks of gestation was associated with a higher risk of procedure-related complications. Maternal BMI ≥ 40 increased the risk for fetal loss, whereas maternal age, number of previous miscarriages, number of previous abortions, history of vaginal bleeding or nicotine abuse did not affect the risk for complications or overall fetal loss rate. CONCLUSIONS: In the hands of experienced operators, FBS is a safe way to further fetal diagnostics, and the risk of complications is low.

Effects of iron supplementation to iron depleted and iron replete pregnant Danish women: Defining criteria for identification of women who can manage without supplements: A randomized, placebo-controlled study.

OBJECTIVE: To define criteria based on iron status parameters for the identification of healthy women who do need/do not need iron supplementation during normal pregnancy. METHODS: Randomized, double-blind, placebo-controlled study of 113 women (62 iron-, 51 placebo treated) and their newborns. Iron dose was 66 mg elemental iron as ferrous fumarate daily from 14-18 weeks gestation to delivery. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage, and S-erythropoietin were measured during gestation, prepartum, one week and 8 weeks postpartum. The women were divided in groups according to S-ferritin levels at inclusion:<30,≥30,≥40,≥50 and≥60µg/L. Iron deficiency (ID) was defined as S-ferritin < 15µg/L; iron deficiency anemia (IDA) as S-ferritin < 15µg/L and Hb < 110 g/L. RESULTS: Placebo treated women with S-ferritin levels < 30µg/L at inclusion had a much higher incidence of ID/IDA than placebo treated women with S-ferritin levels≥30,≥40,≥50, and≥60µg/L. S-ferritin levels≥40µg/L were associated with a very low risk of ID/IDA and none of the women with levels≥50 and≥60µg/L displayed ID/IDA. CONCLUSIONS: Women having S-ferritin < 30µg/L in early pregnancy, have a high risk of ID/IDA and should be recommended ferrous iron supplements in appropriate doses. With increasing iron reserves, i.e., increasing S-ferritin, the need for iron supplements diminishes, and placebo treated women having S-ferritin ≥40µg/L seldom develop IDA. Women with S-ferritin levels≥50 and≥60µg/L or higher, have adequate iron reserves and do not need routine iron prophylaxis in pregnancy. The results support the arguments for an individual iron supplementation guided by iron status, to avoid unwanted side effects of unnecessary iron intake.

Non-invasive prenatal testing for fetal Ss, Kidd, and CTL2 blood group prediction by multiplex digital droplet PCR.

Background: Some blood groups, such as S and s blood groups in the MNS blood group system, and Kidd and CTL2 blood group systems, can cause severe fetal and newborn alloimmune disorders. Non-invasive prenatal testing (NIPT) to predict fetal blood groups and knowledge of local blood group gene frequency are both important for pregnancy management decisions. Droplet digital PCR (ddPCR) has high specificity and sensitivity in detecting fetal single nucleotide variation. Objectives: The objective is to predict fetal Ss, Kidd, and CTL2 blood groups using multiplex ddPCR. The gene frequencies of three blood groups were detected by ddPCR in northwest China. Design: This is a prospective study. Methods: Cell-free fetal DNA isolated from 26 healthy single pregnant women at different gestational stages was tested with QX200 Droplet Digital PCR. Results were compared with fetal genotypes. DNA samples purified from 20 blood pools containing a total of 1000 donors in northwest China were subjected to ddPCR to detect the gene frequency of three blood groups. Results: Ss, Kidd, and CTL2 blood groups of 26 pregnant fetuses were accurately detected by multiplex ddPCR. The multiplex ddPCR results were consistent with the Sanger sequencing results of 26 fetal blood samples after birth. The gene frequencies of the three blood groups detected by ddPCR were 9.30% for S, 90.70% for s, 48.43% for Jka, 51.57% for Jkb, 66.57% for HNA-3A, and 33.43% for HNA-3B. Conclusions: It is reliable to predict fetal Ss, Kidd, and CTL2 blood groups by multiplex ddPCR. Meanwhile, we designed a simple and efficient method for inferring the gene frequency of three blood groups based on ddPCR.

Neonatal outcomes associated with time from a high fetal blood lactate concentration to operative delivery.

INTRODUCTION: Adjunctive technologies to cardiotocography intend to increase the specificity of the diagnosis of fetal hypoxia. If correctly diagnosed, time to delivery could affect neonatal outcome. In the present study, we aimed to investigate the effect of time from when fetal distress is indicated by a high fetal blood sample (FBS) lactate concentration to operative delivery on the risk of adverse neonatal outcomes. MATERIAL AND METHODS: We conducted a prospective observational study. Deliveries with a singleton fetus in cephalic presentation at 36+0 weeks of gestation or later were included. Adverse neonatal outcomes, related to decision-to-delivery interval (DDI), were investigated in operative deliveries indicated by an FBS lactate concentration of at least 4.8 mmol/L. We applied logistic regression to estimate crude and adjusted odds ratios (aOR) of various adverse neonatal outcomes, with associated 95% confidence intervals (CI), for a DDI exceeding 20 minutes, compared with a DDI of 20 minutes or less. CLINICALTRIALS: gov Identifier: NCT04779294. RESULTS: The main analysis included 228 women with an operative delivery indicated by an FBS lactate concentration of 4.8 mmol/L or greater. The risk of all adverse neonatal outcomes was significantly increased for both DDI groups compared with the reference group (deliveries with an FBS lactate below 4.2 mmol/L within 60 minutes before delivery). In operative deliveries indicated by an FBS lactate concentration of 4.8 mmol/L or more, there was a significantly increased risk of a 5-minute Apgar score less than 7 if the DDI exceeded 20 minutes, compared with a DDI of 20 minutes or less (aOR 8.1, 95% CI 1.1-60.9). We found no statistically significant effect on other short-term outcomes for deliveries with DDI longer than 20 minutes, compared with those with DDI of 20 minutes or less (pH ≤7.10: aOR 2.0, 95% CI 0.5-8.4; transfer to the neonatal intensive care unit: aOR 1.1, 95% CI 0.4-3.5). CONCLUSIONS: After a high FBS lactate measurement, the increased risk of adverse neonatal outcome is further augmented if the DDI exceeds 20 minutes. These findings give support to current Norwegian guidelines for intervention in cases of fetal distress.

Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies.

Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence.

Factors Influencing the Efficacy of Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury.

INTRODUCTION: We have previously described preclinical literature which supports umbilical cord blood-derived cell (UCBC) therapy as an efficacious treatment for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient population and intervention characteristics. OBJECTIVES: To systematically review the effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand the contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage, and number of doses. METHODS: A systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible. RESULTS: Differential benefits of UCBCs were seen across a number of subgroup analyses including intraventricular hemorrhage (IVH) vs. hypoxia ischemia (HI) model (apoptosis white matter (WM): chi2 = 4.07; P = .04, neuroinflammation-TNF-α: chi2 = 5.99; P = .01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2 = 5.01; P = .03, neuroinflammation-TNF-α: chi2 = 3.93; P = .05, apoptosis grey matter (GM), astrogliosis WM), and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2 = 7.51; P = .02, astrogliosis WM: chi2 = 12.44; P = .002). We identified a serious risk of bias and overall low certainty of evidence. CONCLUSIONS: Preclinical evidence suggests UCBCs to show greater efficacy in the injury model of IVH compared to HI, the use of UCB-MSCs compared to UCB-MNCs and the use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence and address knowledge gaps.

Suspected twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy: a case report.

BACKGROUND: Twin anemia polycythemia sequence is a rare complication in monochorionic twin pregnancy. CASE PRESENTATION: We describe a case of dichorionic twin pregnancy presenting with suspected twin anemia polycythemia sequence. A 31-year-old White female, on her third pregnancy, had a routine ultrasound scan at 12 weeks gestation, which demonstrated a dichorionic twin pregnancy with one placenta located in the anterior wall and the other in the posterior wall of the uterus. At 21 weeks, a scan demonstrated a 24% growth discordance between the two fetuses with normal Doppler studies and amniotic fluid. At 27 weeks, one twin showed signs of anemia and the other polycythemia; the fetal middle cerebral artery peak systolic velocity was high in the anemic fetus and low in the polycythemic twin (1.8 and 0.5 multiples of the median). An intrauterine blood transfusion was carried out and this increased the fetal hemoglobin concentration in the anemic twin from 3.5 to 12.5 g/dL. At 29 weeks, delivery by cesarean section was carried out because of evidence from middle cerebral artery peak systolic velocity of recurrence of anemia in one twin and worsening polycythemia in the co-twin; at birth the hemoglobin concentrations were 5.6 and 24.9 g/dL, respectively. Histopathological examination confirmed dichorionicity with no communicating vessels between the two placentas. CONCLUSIONS: This is the first case of twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy where intrauterine blood transfusion was used to prolong the pregnancy by almost 2 weeks in a "twin anemia polycythemia sequence-like" setting.

Patterns of placental injury in various types of fetal congenital heart disease.

OBJECTIVES: Fetal blood circulation may be modified in congenital heart disease (CHD). This retrospective analysis was performed to study whether the type of CHD is associated with specific placental pathology. METHODS: Three types of CHD based on presumed proportion of placental and systemic blood distribution in fetal circulation were analyzed: Group 1: 89 cases with low placental blood content (hypoplastic left heart syndrome, transposition of great arteries, coarctation of aorta), Group 2: 71 placentas with intermediate placental and systemic blood content due to increased intracardiac blood mixing (tetralogy of Fallot, truncus arteriosus, double inlet/outlet ventricle), and Group 3: 24 placentas with high placental blood content (tricuspid or pulmonary atresia, Ebstein anomaly). Frequencies of 27 independent clinical and 47 placental phenotypes of 184 placentas in those three groups were statistically compared. RESULTS: The most advanced gestational age at delivery, and large vessel (global) fetal vascular malperfusion (FVM) were most common in Group 1, while macerated stillbirths, neonatal mortality, abnormal amniotic fluid volume (oligohydramnios or polyhydramnios), other congenital anomalies, distal villous lesions of FVM, placental edema and amnion nodosum were most common in Groups 2 and 3, although the frequencies of placental lesions were statistically not significant. CONCLUSIONS: Left heart obstructive lesions potentially associated with brain maldevelopment show increase in lesions of global FVM (in aggregate and individually fetal vascular ectasia, stem vessel obliteration and intramural fibrin deposition) as may be seen in umbilical cord compromise. CHD with increased intracardiac blood mixing or with right heart defects is associated with average preterm gestational age at delivery and placental lesions of distal villous FVM, villous edema and amnion nodosum.

Accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies

SUMMARY OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying acidemia at birth by umbilical cord blood gasometry in high-risk pregnancies. METHODS: This was a retrospective cohort study of singleton high-risk parturients using intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by the analysis of umbilical cord arterial blood pH (<7.1). Associations between variables were determined using the chi-square test and Kruskal-Wallis tests. RESULTS: We included 105 cases of cardiotocography category I, 20 cases of cardiotocography category II, and 10 cases of cardiotocography category III. cardiotocography category III had a higher prevalence of cesarean sections compared to cardiotocography category I (90.0 vs. 42.9%, p<0.006). Venous pH was higher in patients with cardiotocography category I compared to cardiotocography category III (7.32 vs. 7.23, p=0.036). Prevalence of neonatal intensive care unit (NICU) admission was lower in neonates of patients with cardiotocography category I compared to cardiotocography category III (3.8 vs. 30.0%, p=0.014). Prevalence of composite adverse outcomes was lower in neonates of patients with cardiotocography category I compared to cardiotocography category II (9.5 vs. 30.0%, p=0.022) and cardiotocography category III (9.5 vs. 60.0%, p=0.0004). cardiotocography categories II and III had low sensitivity (0.05 and 0.00, respectively) and high negative predictive value (NPV) (0.84 and 0.91, respectively) for identifying fetal acidemia at birth. The three categories of intrapartum cardiotocography showed high specificities (96.0, 99.0, and 99.0%, respectively). CONCLUSION: All three categories of intrapartum cardiotocography showed low sensitivity and high specificity for identifying acidemia at birth.

Accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies

SUMMARY OBJECTIVE: The aim of this study was to evaluate the accuracy of intrapartum cardiotocography in identifying fetal acidemia by umbilical cord blood analysis in low-risk pregnancies. METHODS: This is a retrospective cohort study of low-risk singleton pregnancies in labor after performing intrapartum cardiotocography categories I, II, and III. The presence of fetal acidemia at birth was identified by analyzing the pH of umbilical cord arterial blood (pH<7.1). RESULTS: No significant effect of the cardiotocography category on the arterial (p=0.543) and venous (p=0.770) pH of umbilical cord blood was observed. No significant association was observed between the cardiotocography category and the presence of fetal acidemia (p=0.706), 1-min Apgar score <7 (p=0.260), hospitalization in the neonatal intensive care unit (p=0.605), newborn death within the first 48 h, need for neonatal resuscitation (p=0.637), and adverse perinatal outcomes (p=0.373). Sensitivities of 62, 31, and 6.0%; positive predictive values of 11.0, 16.0, and 10.0%; and negative predictive values of 85, 89.0, and 87.0% were observed for cardiotocography categories I, II, and III, respectively. CONCLUSION: The three categories of intrapartum cardiotocography presented low sensitivities and high negative predictive values to identify fetal acidemia at birth in low-risk pregnancies.

The cerebroplacental ratio and prediction of fetal growth restriction in twin pregnancies.

OBJECTIVES: The cerebroplacental ratio (CPR) represents the relationship between blood flow in the placenta and blood flow in the fetal brain. A low CPR in the third trimester has been associated with poor perinatal outcomes in both singleton and twin gestations. This study aimed to evaluate whether low CPR defined or high CPR discordance at 20-24 weeks in twin pregnancies is associated with an increased risk of fetal growth restriction (FGR) in the third trimester. METHODS: A total of 247 twin pregnancies were included in this retrospective cohort study. Monoamniotic monochorionic twins were excluded. An abnormal CPR was defined as one or both CPR <5%-ile or CPR discordance between fetuses >20%. FGR was evaluated using the last growth measurement performed between 28 and 36 weeks. RESULTS: Of the candidates for study, 177 twin pregnancies had normal CPRs and 70 twin pregnancies had abnormal CPRs. Maternal demographics were similar between groups. There was no difference in the risk of selective FGR, FGR of both twins, or growth discordance >20% in the third trimester between twin pregnancies with normal vs. abnormal CPRs at 20-24 weeks. The adjusted odds ratio for any growth disturbance was 1.00 (95% CI 0.56-1.79). CONCLUSIONS: This study suggests that FGR in twins may be the consequence of numerous maternal, fetal, and placental factors, and not fully explained by redistribution of blood flow or adaptive hypoxia in the mid-trimester.

Digital fetal scalp stimulation (dFSS) versus fetal blood sampling (FBS) to assess fetal wellbeing in labour-a multi-centre randomised controlled trial: Fetal Intrapartum Randomised Scalp Stimulation Trial (FIRSST NCT05306756).

BACKGROUND: Cardiotocography (CTG) is a screening test used to detect fetal hypoxia in labour. It has a high false positive rate resulting in many potentially unnecessary caesarean sections. Fetal blood sampling (FBS) is a second-line test of the acid-base status of the fetus. It is used to provide either reassurance that it is safe for labour to continue or objective evidence of compromise so that delivery can be expedited. Digital fetal scalp stimulation (dFSS) to elicit a fetal heart rate acceleration is an alternative less invasive second-line test of fetal wellbeing. This study aims to provide robust evidence on the role of these two second-line tests in assessing fetal wellbeing and potentially preventing operative delivery. METHODS: A multi-centre parallel group randomised controlled trial (RCT) is planned in four maternity centres in Ireland. The study aims to recruit 2500 nulliparous women with a term (≥37+0 weeks) singleton pregnancy who require a second-line test of fetal wellbeing in labour due to an abnormal CTG. Women will be allocated randomly to dFSS or FBS on a 1:1 ratio. The primary outcome is caesarean section. With 1250 women in each arm, the study will have 90% power to detect a difference of 5-6%, at a two-sided alpha significance level of 5%, assuming a caesarean section rate of at least 20% in the dFSS group. DISCUSSION: If the proposed study shows evidence that dFSS is a safe, reliable and effective alternative to FBS, this would have ground-breaking implications for labour management worldwide. It could potentially lead to a reduction in invasive procedures and emergency caesarean sections. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306756. Registered on 31 March 2022. The trial commenced enrolment on 10 May 2022. Ethical committee approval has been granted by the Research Ethics Committee (REC) of each hospital: Dublin/CWIUH REC: 12.06.2019; Cork/UCC REC: 29.11.2019; Galway/NUIG REC: 06.09.2019; Limerick/UL REC: 30.09.2019.

Experiences with intrapartum fetal monitoring in the Netherlands: A survey study.

INTRODUCTION: Worldwide, cardiotocography is used for continuous monitoring of fetal heart rate (FHR) and uterine contractions during labour. Different methods for FHR registration and registration of contractions are available. Literature about the frequency of use of different fetal monitoring methods is lacking. OBJECTIVE: To evaluate the use of and preferences for fetal monitoring methods for intrapartum fetal monitoring among Dutch obstetric care providers. STUDY DESIGN: Between October and November 2020 the Dutch Society of Obstetrics and Gynaecology sent an email invitation to all secondary care midwives and gynaecologists (in training) in the Netherlands to complete an online survey regarding the use and personal experience with fetal monitoring methods. The survey mainly consisted of multiple choice questions. Descriptive statistics are reported. Continuous variables were presented as median with interquartile ranges (IQR). Categorical variables were expressed as numbers with percentages. RESULTS: The response rate was 29 % (n/N = 510/1748). All Dutch hospitals were represented. The respondents estimated the use of fetal scalp electrode (FSE) at 71 % (IQR 58-85 %) of deliveries. The most common indication for use of the FSE was inadequate external FHR registration (94 %). More than half (54 %) of the respondents reported to use intrauterine pressure catheter with an estimated use of 5 % (IQR 2-8 %) of deliveries. The most common indication for use of intrauterine pressure catheter was inadequate external contraction registration (75 %). The use of ST-analysis was reported in 25 % of the respondents with an estimated use of 60 % (IQR 30-72 %) of deliveries. Almost all respondents (99 %) reported to use fetal blood sampling with an estimated use of 15 % (IQR 10-23 %) of deliveries. Ninety percent of respondents would prefer a valid and reliable external monitoring technique during labour. Thirty-one percent of respondents assume that external fetal monitoring with non-invasive fetal electrocardiography and electrohysterography will become standard care within the next 5 years. CONCLUSIONS: Currently, the FSE is the most used technique for FHR monitoring during labour in the Netherlands. The most common indication for use of FSE is inadequate external FHR registration. Obstetric care providers would prefer a non-invasive external registration method that provides reliable data.

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.

Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled study.

OBJECTIVE: To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies. METHODS: Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum. RESULT: From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight. CONCLUSION: Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.