Fetal Blood Sampling Research Articles

Development of a surgical technique for long-term catheterisation of bovine fetuses.

The aim of this study was to further develop and extensively describe a surgical technique in order to realise long-term fetal blood sampling in the bovine species. Eleven Holstein-Friesian 6- to 8-month pregnant cows (4-10 years old) were used for this study. Gestational age on the day of surgery varied from approximately 180 days (n = 1) to 240 days (minimum: 232 days, maximum 252 days; n = 10). The fetal medial tarsal artery was catheterised in pregnant cows with a polyvinyl catheter in dorsal recumbency under general anaesthesia. Although 5 out of 11 operations (45.5%) performed between 232 and 252 days of gestation were lost due to different causes mainly associated with peritonitis and septicaemia, the mean interval between operations and calvings was 42.5 days (between 27 and 95 days). It is important to emphasise that a well-trained surgical team is needed for bovine fetal cannulation in order to be able to decrease the risk factors during the operations. Due to the fact that after 5 unsuccessful cases none of the pregnancies were lost, this skill can be reached, and our technique can enable bovine fetal blood sampling for long-term endocrinological and physiological investigations before and during parturition.

Fetoscopic Balloon Dilation and Cricotracheal Resection for Laryngeal Atresia in CHAOS.

View Supplementary Video 1 Laryngoscope, 131:660–662, 2021

Effectiveness of fetal scalp stimulation test in assessing fetal wellbeing during labor, a retrospective cohort study

BackgroundIt is discussed whether fetal scalp stimulation (FSS) test is a reliable complimentary tool to cardiotocography (CTG) to assess fetal wellbeing during labor. The test is based on the assumption that a well-oxygenated fetus, in contrast to the depressed fetus, will respond to a certain stimulus. The aim of this study was to investigate the effectiveness of the FSS-test.MethodsA retrospective observational study carried out Copenhagen University Hospital, Herlev, Denmark. Laboring women with singleton pregnancies in cephalic presentation after gestation week 33 and indication for fetal blood sampling (FBS) were eligible for inclusion. The FSS-test was classified as positive when an acceleration was absent at the time of FBS and negative when an acceleration was present. Lactate in scalp blood was measured by the point-of-care device LactatePro™ and pH in artery umbilical cord blood by the stationary blood gas analyzer ABL800. Lactate level < 4.2 mmol/L in scalp blood and arterial cord pH > 7.1 were cut-offs for normality.ResultsThree hundred eighty-five women were included. The cohort was divided by the FBS-to-delivery time: Group 1 (n = 128) ≤ 20 min, Group 2 (n = 117) 21–59 min and Group 3 (n = 140) ≥ 60 min. The proportion of FSS-positive tests differed significantly between the groups (p < 0.000). In Group 1 the sensitivity, specificity and likelihoods for scalp lactate ≥4.2 mmol/L were 81.5 (95% CI 67–90.1), 13.3 18.5 (95% CI 5.9–24.6), LHR+ 0.94 (95% CI 0.8–1.1) and LHR – 1.4 (95% CI 0.6–3.2) and for umbilical artery pH ≤ 7.10 the values were 82.6% (95% CI 61.2–95.1), 16% (95% CI 9.4–24.7), 1.0 (95% CI 0.8–1.2) and 1.1 (95% CI 0.4–3) respectively. Regardless of the FBS-to-delivery time the LHR+ for lactate ≥4.2 mmol/L increased to 1.38 (95% CI 1.2–1.6).ConclusionThe effectiveness of scalp stimulation test was poor for both ruling in and out fetal hypoxia during labor. Absence of a provoked acceleration seems to be a normal phenomenon in the second stage of labor.

Non-invasive risk-assessment and bleeding prophylaxis with IVIG in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia: management to minimize adverse events

IntroductionIn pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT), prenatal intervention in subsequent pregnancies may be required to prevent fetal bleeding. Several invasive and non-invasive protocols have been published: amniocentesis for fetal genotyping, fetal blood sampling for the determination of fetal platelet count, intrauterine platelet transfusions, and weekly maternal i.v. immunoglobulin (IVIG) infusion with or without additional corticosteroid therapy. This is the first retrospective study that report the experience with a non-invasive protocol focused on side effects of maternal IVIG treatment and neonatal outcome.MethodsPregnant women with proven FNAIT in history and an antigen positive fetus were treated with IVIG (1 g/kg/bw) every week. To identify potential IVIG-related hemolytic reactions isoagglutinin titer of each IVIG lot and maternal blood count were controlled. IVIG-related side effects were prospectively documented and evaluated. Furthermore, ultrasound examination of the fetus was performed before starting IVIG administration and continued regularly during treatment. Outcome of the index and subsequent pregnancy was compared. Corresponding data of the newborns were analyzed simultaneously.ResultsIVIG was started at 20 weeks of gestation (median). Compared to the index pregnancy, platelet counts of the newborns were higher in all cases. No intracranial hemorrhage occurred (Index pregnancies: 1 case). Platelet counts were 187 × 109/l (median, range 22–239, 95% CI) and one newborn had mild bleeding. No severe hemolytic reaction was observed and side effects were moderate.ConclusionAmong pregnant women with FNAIT history, the use of non-invasive fetal risk determination and maternal IVIG resulted in favorite outcome of all newborns. Invasive diagnostic or therapeutic procedures in women with a history of FNAIT should be abandoned.

Perinatal outcomes of intrauterine transfusion for the surviving twin in monochorionic twin gestation involving a single fetal demise.

This study aimed to evaluate the feasibility and outcome of intrauterine transfusion (IUT) for the surviving co-twin in monochorionic diamniotic (MCDA) twin gestations involving single intrauterine fetal death (sIUFD). Cases of MCDA twin gestations involving emergent IUT for co-twins experiencing acute feto-fetal hemorrhage (AFFH) subsequent to sIUFD during the second trimester were reviewed. Fetal anemia was confirmed via fetal blood sampling, and perinatal data were retrieved from medical charts to determine the outcomes of surviving co-twins. A poor outcome at 28 days of age was defined as fetal death, neonatal death or neurological impairment such as severe intraventricular hemorrhage or cystic periventricular leukomalacia (PVL). This study included 16 cases of sIUFD diagnosed at a median of 22.5 weeks of gestation (range: 18-25 weeks). The median interval in hours between diagnosis of fetal demise and IUT was approximately 4.2 (0-22) hours. All cases achieved IUT without significant intraoperative complications. Four cases experienced a fetal loss of the co-twin, whereas 12 co-twins were born alive (including 9 preterm births), with only 1 poor outcome in a preterm infant with PVL. IUT may be a feasible prenatal intervention for surviving co-twins with AFFH. However, more extensive or pooled studies are needed to determine the efficacy of this intervention.

Fetal scalp blood sampling during second stage of labor – analyzing lactate or pH? A secondary analysis of a randomized controlled trial

Background Cardiotocography (CTG) is a widely used method for assessing fetal wellbeing during labor. It is well-known that CTG has high sensitivity but low specificity. To avoid unnecessary operative interventions, adjunctive methods such as fetal blood sampling (FBS) are used. Few studies have looked into whether FBS can be used during second stage of labor, and in that case, which of the methods (lactate or pH) are preferred. Objective To evaluate clinical effectiveness of measuring lactate versus pH in preventing birth acidemia when FBS was performed during second stage of labor. Methods Secondary analysis of a randomized controlled trial . Thousand three hundred and thirty-eight women with a singleton pregnancy, cephalic presentation, gestational age ≥34 weeks, and indication for FBS during second stage of labor were included. Main outcome measures Metabolic acidemia (pH <7.05 and base deficit >12 mmol/l) or pH < 7.00 in cord arterial blood at birth. Secondary outcomes A composite outcome (metabolic acidemia, pH <7 or Apgar score <4), and rates of operative deliveries. Results Metabolic acidemia occurred in 4.1% in the lactate versus 5.1% in the pH group (relative risk (RR): 0.80; 95% confidence interval (CI): 0.48–1.35) and pH <7 in 1.4% versus 2.8% (RR: 0.51, 95% CI: 0.23–1.13). Composite outcome was found in 3.8 versus 4.9%, respectively (RR: 0.76; 95% CI: 0.46–1.26). No difference in total operative interventions was found. More cesarean deliveries were performed in the lactate group (16.5 vs. 12.4%; RR: 1.33; 95% CI: 1.02–1.74). Conclusion When analyzing lactate or pH in fetal scalp blood during second stage of labor neonatal outcomes were comparable. The frequency of total operative interventions was similar but more cesarean deliveries were performed in the lactate group.

Clinician Identification of Birth Asphyxia Using Intrapartum Cardiotocography Among Neonates With and Without Encephalopathy in New Zealand

Despite improvements in antenatal care and increasing cesarean delivery rates, birth asphyxia leading to neonatal encephalopathy (NE) continues to contribute to neonatal death and long-term neurodevelopmental disability. Cardiotocography (CTG) has been used in labor for several decades to detect a stressed fetus so that delivery can be expedited and NE avoided. To investigate whether experienced clinicians can detect and respond to abnormal readings from CTGs during the penultimate hour before birth in infants with moderate to severe NE but no acute peripartum event. This case-control study included 10 practicing obstetricians and midwives at maternity hospitals in New Zealand. Participants, who were masked to the perinatal outcome, were asked to assess CTG tracings from 35 neonates with NE and evidence of birth hypoxia (ie, cases) and 105 neonates without NE or birth hypoxia (ie, controls), all of whom were born in 2010 to 2011. Data analysis was conducted from May to December 2017. Brief clinical details and 1 hour of CTG tracings from the penultimate hour before birth were provided for each baby. Clinicians assessed the CTG tracings and recommended a plan. Intra-assessor and interassessor agreement on CTG findings and action plans as well as sensitivity (ie, detection of NE) and specificity (ie, ruling out those without NE) for the assessment of abnormal CTG readings leading to immediate action (ie, fetal blood sample or immediate delivery) were reported. A total of 35 infants (mean [SD] gestational age, 40 [1.4] weeks; 16 [45.7%] cesarean deliveries) were designated cases, and 105 infants (mean [SD] gestational age, 39.4 [1.2] weeks; 22 [21.0%] cesarean deliveries) were designated controls. No infants had congenital anomalies. The mean (range) sensitivity for detection of abnormal CTG results and for recommending immediate action for all assessors was 75% (63%-91%) and 41% (23%-57%), respectively, with a mean (range) specificity of 67% (53%-77%) and 87% (65%-99%), respectively. A sensitivity analysis including only assessors with 80% or more interassessor agreement only differed from the main analysis by 6% or less (mean [range] sensitivity for detection, 76% [63%-91%]; sensitivity for action plan, 36% [25%-49%]; specificity for detection, 71% [53%-77%]; and specificity for action plan, 93% [88%-99%]). Experienced clinicians detected 3 of 4 infants who were subsequently diagnosed with NE. Action to expedite delivery was recommended for more than 40% of infants with NE. These results indicate that CTG does not identify all infants at risk of NE, and that there is a need for further investment in new approaches to fetal surveillance in labor.

First-trimester screening for trisomies in pregnancies with vanishing twin.

To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy. This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling. First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparing second-line tests to assess fetal wellbeing in Labor: a feasibility study and pilot randomized controlled trial

Objective To explore the feasibility of conducting a randomized controlled trial (RCT) designed to compare the performance of digital fetal scalp stimulation (dFSS) and fetal blood sampling (FBS) as second-line tests of fetal wellbeing in Labor. Design A feasibility study included 66 women who consented to both dFSS and FBS performed contemporaneously. A pilot randomized controlled trial included 50 women who were randomized to either dFSS or FBS. Setting University-affiliated maternity hospital. Population Women in Labor who required second-line testing of fetal well-being following abnormal fetal heart rate monitoring. Outcome measures The primary outcome of interest was delivery by emergency cesarean section. Secondary outcomes included maternal and perinatal morbidity outcomes and procedural factors. Results Of the 66 women recruited to the feasibility study 50 (76%) received the two interventions as per protocol. The demographic data indicated that future RCT should be limited to nulliparous women. After initial training and reminders, the dFSS procedure appeared to be acceptable to patients and clinicians and was interpreted appropriately. Recruitment of eligible women to the pilot RCT was successful (88%) with 50 of 63 eligible women randomized (79%) and no drop-outs. The cesarean section rate was high in both arms as expected with a cohort of women requiring second-line tests for abnormal fetal heart rate monitoring in Labor (5/25; 20% dFSS versus 13/25; 52% FBS, p = .018). Conservative estimates suggest that a sample size of 2500 randomized women would be required for a definitive RCT. Conclusions This study suggests that dFSS, which has the potential to be a reliable alternative to FBS, could be evaluated in a well-designed randomized controlled trial. Trial registration The definitive trial has been registered ISRCTN 13295826.

An investigation of the relationship between base deficit and crp in asphytic infants

Aim: To investigate the relationship between base deficit (BD) and C-reactive protein (CRP) findings evaluated during diagnosis of infants followed up for a diagnosis of perinatal asphyxia (PA).Material and Methods: This prospective observational study included 66 cases as 33 cases treated and followed up for a diagnosis of PA in the Neonatal Intensive Care Unit of Harran University Medical Faculty Hospital, and a control group of 33 healthy infants. Using a syringe washed with heparin, a fetal blood sample of 2ml was taken from the umbilical artery of the neonates thought to have PA, and blood gases were examined in an anaerobic environment. CRP values were obtained from spectrophotometric biochemical analysis of the 2ml blood sample using an Architect C16000 device (Abbott Diagnostics, Abbott Park, IL, USA). Results: Evaluation was made of 33 infants with a diagnosis of PA hospitalised in NICU and a control group of 33 healthy infants. All the cases were statistically similar in respect of gestational week at birth (GW), birthweight (BW), and gender. In the blood gas examinations of the cord blood, pH value was determined as mean 6.9 (range, 6.50-7.06), mean BD as 17mmol/L (range, 12-28 mmol/L), and CRP values as 0.2-57 mg/dl. The CRP values of the PA cases on days 2 and 3 were determined to be significantly higher than those of the control group (p0.001). As the BD value at the time of diagnosis increased, so there was determined to be a significant increase in CRP value, and this was confirmed by the Spearman correlation test (r1:0.423, p1:0.014) (r2:0.342, p2:0.05) (r3:0.451, p3:0.009). No statistically significant relationship was determined between the pH value in blood gas and the CRP level (p:0.18). Conclusion: The results of this study demonstrated that the CRP level was statistically significantly higher in cases that developed asphyxia than in the control group. A positive correlation was determined between BD at diagnosis and CRP level. A high CRP level during treatment and follow-up can be considered for use as a supportive finding showing the severity of hypoxia.

185: Recurrent Hemoglobin H hydrops Caused by a Compound Heterozygosity of HBA2: c.* 93_* 94delAA and ɑ0- thalassemia (-- SEA)

We report Hb H hydrops fetalis resulting from non-deletional ɑ-thalassemia mutations, a polyadenylation (polyA) mutation (AATAAA → AATA--) of the ɑ2 globin gene (HBA2: c.*93_*94delAA), and ɑ0-thalassemia (--SEA) in 2 subsequent pregnancies from a Thai family living in Nakhon Pathom. Case Report In the first pregnancy, a 20 years old woman, GA 28+4 weeks, was referred to our hospital due to fetal cardiomegaly, marked anemia and pericardial effusion. She was ɑ0-thalassemia carrier (--SEA/ɑɑ), but her husband who had low mean cell volume (MCV) of 74 fL was negative for common ɑ-thalassemia mutation test. Therefore, they were not identified as a couple at risk for Hb Bart’s hydrops fetalis (--/--). Intrauterine transfusion (IUT), Hb typing, and complete ɑ-globin gene analysis were performed. The results showed that this fetus carried this rare ɑ globin genotype (--SEA/ɑPAɑ). The baby boy was born at 34+6 weeks, and subsequently died at 2 days of life owing to severe hydropic features and multiple organ failure. In the second pregnancy, the mother was detected with fetal cardiomegaly, pericardial effusion and marked fetal anemia at 30+1 weeks. We performed a fetal blood sampling and demonstrated a high level of Hb Bart (70.6%) and confirmed the same ɑ globin genotype again. Due to the grave prognosis of this genetic interaction, the couple decided for a termination of pregnancy rather than IUT, and our postmortem study revealed a full-blown hydrops fetalis in this female stillborn baby. Although recent publications have revealed a variety of clinical severity associated with this polyA mutation, varying from mild non-transfusion dependent to transfusion dependent, to the best of our knowledge, this is for the first time that this polyA mutation is associated with Hb H hydrops. Our probands were far more severe than those reported earlier even though they all had identical genotype, suggesting that there would be additional genetic and/or epigenetic determinants that might supersede or further deteriorating the clinical severity leading to hydropic development.

Clinical reflective practice

Clinical reflective practice

345 The effects of maternal nutrient restriction followed by re-alimentation on offspring growth and metabolism in sheep

Abstract The duration and timing of inadequate maternal nutrition can have detrimental effects on metabolism and organogenesis in the offspring. Re-alimentation, a common management practice that involves feeding full nutrient requirements following a period of nutrient restriction, may reduce the negative impacts of maternal nutrient restriction. To determine the effects of maternal nutrient restriction and re-alimentation on offspring growth,48 primiparous ewes, confirmed pregnant with singletons, were fed a control diet consisting of100% NRC requirements (CON) starting on day25 of gestation. On day50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or60% NRC requirements (RES). On day90 of gestation, a portion of ewes were euthanized (n = 7 per treatment) and fetal samples and weights were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternative diet (CON-RES, RES-CON; n = 7/treatment). On day130 of gestation, all remaining ewes were euthanized. All fetal BW, liver, longissimus muscle, semitendinosus, and triceps brachii weights were determined for each day of gestation. Fetal BW’s were not different between treatment groups (P = 0.29; P = 0.83). Fetal liver weights decreased12.89% in RES-RES compared with CON-CON at day130 (P = 0.049), but were not different at day90 (P = 0.69). There was a tendency for decreased semitendinosus weight in RES group compared with CON at day90 (P = 0.055). Liver lipid droplet accumulation was analyzed for day90 and130 using histochemistry and an effect of maternal nutrition was not observed (P = 0.562). In summary, maternal nutrient restriction reduces offspring muscle and liver growth. To gain insight into the effects of maternal nutrient restriction and re-alimentation on liver development and metabolism, analysis of liver morphology, gene expression, and global metabolomics are needed. Supported by USDA-AFRI grant2016-67016-24884

Elemental metabolomics in human cord blood: Method validation and trace element quantification

BackgroundTrace elements are an essential requirement for human health and development and changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth. Elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide important insights into these gestational disorders. MethodsThis study used an Agilent 7900 inductively coupled plasma mass spectrometer (ICP-MS) to simultaneously measure 68 elements, in 166 placental cord blood samples collected from women with various pregnancy complications (control, hypertensive, PE, GDM, FGR, pre-term, and post-term birth). ResultsThere were single element differences across gestational outcomes for elements Mg, P, Cr, Ni, Sr, Mo, I, Au, Pb, and U. Hypertensive and post-term pregnancies were significantly higher in Ni concentrations when compared to controls (control = 2.74 μg/L, hypertensive = 6.72 μg/L, post-term = 7.93 μg/L, p < 0.05), iodine concentration was significantly higher in post-term pregnancies (p < 0.05), and Pb concentrations were the lowest in pre-term pregnancies (pre-term = 2.79 μg/L, control = 4.68 μg/L, PE = 5.32 μg/L, GDM = 8.27 μg/L, p < 0.01). Further analysis was conducted using receiver operating characteristic (ROC) curves for differentiating pregnancy groups. The ratio of Sn/Pb showed the best diagnostic power in discriminating between control and pre-term birth with area under the curve (AUC) 0.86. When comparing control and post-term birth, Mg/Cr (AUC = 0.84), and Cr (AUC = 0.83) had the best diagnostic powers. In pre-term and post-term comparisons Ba was the best single element (81.5%), and P/Cu provided the best ratio (91.7%). ConclusionsThis study has shown that analysis of multiple elements can enable differentiation between fetal cord blood samples from control, hypertensive, PE, GDM, FGR, pre and post-term pregnancies. This data highlights the power of elemental metabolomics and provides a basis for future gestational studies.

Maternal Serum and Fetal Cord Blood C-Reactive Protein Levels but not Procalcitonin Levels Are Increased in Idiopathic Intrauterine Growth Restriction.

BackgroundThe aim of the present study was to compare procalcitonin and CRP levels in maternal serum and fetal cord blood samples of patients with idiopathic intrauterine growth restriction (IUGR) vs. a control group of appropriate for gestational age (AGA) infants.Material/MethodsThe present prospective study included 43 patients: 27 patients with idiopathic IUGR (IUGR group) and 26 AGA infants at similar gestational ages (control group). Maternal serum and fetal cord blood samples were collected from the control group and IUGR group at time of delivery. Procalcitonin and CRP levels were analyzed in maternal blood. Procalcitonin and CRP levels were analyzed in fetal cord blood.ResultsThe median value of CRP levels in maternal blood was 47.5 mg/dl in the IUGR group and 15.255 mg/dl in the AGA group (p=0.001). The mdian CRP level in cord blood was 36.4 mg/dl (range, 17.3–47.2) in the IUGR group and 10.1 mg/dl (range, 4.07–16.5) in the control group, and the difference was statistically significant (p=0.001). The median maternal serum procalcitonin level was 0.05 μg/l in the IUGR group and 0.04 μg/l in the AGA group, and the difference was not statistically significant (p=0.435). The median procalcitonin value in fetal cord blood was 0.06 μg/l in the IUGR group and 0.04 μg/l in the AGA group, and the difference was not statistically significant (p=0.741).ConclusionsMaternal serum and fetal cord CRP levels were higher in the IUGR group; however, there was no difference in procalcitonin, which is another inflammatory indicator, between the groups.

Time advantage of HemoCue versus traditional complete blood count during cordocentesis

Objectives During cordocentesis, a significant risk factor for adverse outcome is procedure length. One of the greatest contributors to total procedure length is the time that elapses between obtaining a fetal sample and receiving the results of the complete blood count (CBC) from the hospital laboratory. We aimed to evaluate whether there is an advantage to using a point of care hemoglobinometer (HemoCue) compared with traditional CBC during cordocentesis, measured in time elapsing between obtaining fetal sample, and available result. Secondarily we aimed to compare accuracy of HemoCue in relation to traditional CBC. Methods A prospective cohort study was conducted on women undergoing cordocentesis and fetal transfusion for suspected fetal anemia from July 2016 to July 2018 at an urban academic medical center. Fetal blood samples were obtained during cordocentesis, and concurrently sent for traditional CBC, as well as immediately analyzed at bedside using a HemoCue machine. The time elapsing between the obtained fetal sample and availability of results with HemoCue versus traditional CBC were recorded. Primary outcome was time elapsed between obtaining fetal sample and result available for HemoCue versus traditional CBC. Secondary outcome was comparison of HemoCue and CBC hemoglobin values for accuracy. Results Forty-five fetal samples were compared using CBC and HemoCue. Sixteen cordocentesis procedures were performed on 10 patients during the study period. Use of HemoCue was associated with a significantly shorter time to yield a fetal hemoglobin result, compared to traditional CBC (1.5 versus 5.5 min, p = .0001). Results yielded by the HemoCue highly correlated to those yielded by traditional CBC (R = 0.96). Conclusions Use of HemoCue during cordocentesis is associated with a 4-min time advantage over traditional CBC. Hemoglobin results yielded by HemoCue and traditional CBC are highly correlated. KEY MESSAGE Use of a point-of-care hemoglobinometer is associated with a time advantage of 4 min over traditional complete blood count during cordocentesis. This represents a potentially modifiable risk factor for procedure length, and thus procedure complications.

Maternal and fetal thiol/disulfide homeostasis in fetal growth restriction

Purpose To evaluate thiol/disulfide homeostasis in both maternal and fetal compartment in the presence of fetal growth restriction (FGR). Materials and methods A prospective case-control study was carried out in women with FGR (n: 40) or normally growing fetus (n: 40). FGR was defined as estimated fetal weight below the 10th percentile for the gestational age. Maternal serum and fetal cord blood samples were collected from all participants and native thiol-disulfide exchanges were examined with automated method enabling the measurement of both sides of thiol-disulfide balance. Results Native thiol, total thiol and disulfide amounts were decreased in the maternal serum and fetal cord blood of babies born to women with FGR (p < .05). The most sensitive marker was maternal native thiol (82.5, 95% confidence interval, 67.22–92.66%), while the maternal total thiol had highest specificity value (77.5, 95% confidence interval, 61.55–89.16%). Conclusions Maternal and fetal serum thiol/disulfide profiles may use prediction of FGR severity and its neonatal outcome.

Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure.

Background: SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect un-treated depression. SSRIs undergo extensive hepatic first-pass metabolism with the involvement of several cytochrome P450 (CYPs) enzymes. Genetic polymorphisms may influence the expression and activity of CYPs genes. The first aim of this study was to evaluate neonatal outcomes in depressed mothers exposed to SSRIs during pregnancy. SSRIs pharmacogenetics was also evaluated in a subset of mothers and fetuses.Methods: In this case-control study, cases (n = 42) were Caucasian women with a diagnosis of depression and/or anxiety, treated with SSRIs for the whole pregnancy. Controls (n = 85) were Caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptics, drug of abuse, alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples were obtained at delivery to analyze genotype in 33 cases.Results: The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean hemoglobin values before delivery. Obstetric features were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be Low Birth Weight (LBW) (birth weight <2,500 g) (p = 0.01), had significantly lower mean Apgar scores at 1' (p = 0.006) and at 5' (p = 0.023) and worse Apgar distribution at 1' (p = 0.017) and at 5' (p = 0.013). Fifty-six percent of newborns presented one or more symptoms consistent with poor neonatal adaptation syndrome (PNAS). Pharmacogenetic analysis at delivery did not show significant differences in the frequencies of obstetric or neonatal complications in relation to polymorphisms.Conclusions: We found that newborns exposed to SSRIs are at increased risk of poor neonatal outcomes in terms of low birth weight, low Apgar scores and, clinically, poor neonatal adaptation syndrome. Preliminary pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence neonatal outcomes.

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases

BackgroundThis study aims to provide genetic diagnoses for 30 cases of fetal skeletal dysplasia, and a molecular basis for the future prenatal diagnosis of fetal skeletal dysplasia.MethodsA total of 30 cases of fetal skeletal dysplasia detected with ultrasound between January 2014 and June 2017 were analyzed. Among these fetuses, 15 fetuses had local skeletal malformations, while 15 fetuses had short limb malformations. Samples of fetal umbilical cord blood, amniotic fluid, and/or aborted tissue were collected from all cases. Karyotyping, whole genome sequencing, and targeted next-generation sequencing of skeletal disease-related pathogenic genes were performed, as needed. Blood samples were taken from the parents for verification using Sanger sequencing.ResultsAmong the 30 cases of fetal skeletal dysplasia, two cases were diagnosed with trisomy 18. However, none of these cases were identified with any microdeletions or microreplications associated with skeletal dysplasia. Among the 28 chromosomally normal cases with fetal skeletal dysplasia, 21 cases were detected with mutations in genes related to skeletal diseases. Furthermore, collagen gene mutations were detected in six fetuses with short limb malformations, while heterozygous disease-causing mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were detected in seven fetuses. The remaining fetuses carried mutations in other various genes, including tumor protein p63 (TP63), cholestenol delta-isomerase (EBP), cholinergic receptor nicotinic gamma subunit (CHRNG), filamin B (FLNB), and SRY-box 9 (SOX9). Three compound heterozygous mutations in CHRNG, COL11A2 and SOX9 were carried by phenotypically healthy parents.ConclusionTargeted next-generation sequencing can significantly improve the prenatal diagnoses of fetal skeletal dysplasia, providing parents with more precision medicine, and improved genetic counseling.

The utility of MRI for measuring hematocrit in fetal anemia

Doppler ultrasound measurements of the peak systolic velocity of the middle cerebral artery can be used to noninvasively diagnose fetal anemia but are less precise following fetal blood transfusion and in late gestation. We have previously demonstrated the feasibility of estimating fetal hematocrit invitro using magnetic resonance imaging relaxation times. Here we report the use of magnetic resonance imaging as a noninvasive tool to accurately detect fetal anemia invivo. This study has 2 objectives: (1) to determine the feasibility and accuracy of magnetic resonance imaging in estimating hematocrit in anemic fetuses and (2) to compare magnetic resonance imaging and middle cerebral artery Doppler in detecting moderate to severe fetal anemia. Fetuses undergoing fetal blood sampling or transfusion underwent magnetic resonance imaging examinations prior to and following their procedures at 1.5 Tesla (Siemens Avanto). A modified Look-Locker inversion pulse sequence and T2 preparation sequence were applied for T1 and T2 mapping of the intrahepatic umbilical vein. Estimated fetal hematocrit was calculated using a combination of T1 and T2 values and compared with conventional hematocrit obtained from fetal blood samples and middle cerebral artery Doppler measurements. Twenty-three fetuses were assessed during 33 magnetic resonance imaging scans. The mean absolute difference between the laboratory and magnetic resonance imaging-estimated hematocrit was 0.06± 0.05 with a correlation of 0.77 (P < .001) determined by a multilevel, mixed-effects model adjusting for the repeated measurements from the same participants, multiple gestation pregnancies, and the scan type (ie, before or after transfusion scan). Bland-Altman analysis revealed a systematic bias of -0.03 between the magnetic resonance imaging and fetal blood sampling measurements. Magnetic resonance imaging and middle cerebral artery Doppler had similar sensitivities of approximately 90% to detect moderate to severe anemia. However, magnetic resonance imaging had a higher specificity (93% [13/14], 95% confidence interval, 66-100%) than Doppler (71% [10/14], 95% confidence interval, 42-92%). Moderate to severe fetal anemia can be detected noninvasively by magnetic resonance imaging with high sensitivity and specificity. Our results suggest an adjunct role for magnetic resonance imaging in fetuses with suspected anemia, particularly following previous transfusion and in late gestation.