Fetal Blood Sampling Research Articles

Dietary Route of Exposure for Rabbit Developmental Toxicity Studies.

Dietary administration is a relevant route of oral exposure for regulatory toxicity studies of agrochemicals as it mimics potential human intake of the chemical via treated crops and commodities. Moreover, dietary administration of test compounds during a developmental toxicity study can deliver a prolonged and stable systemic exposure to the embryo or fetus at all stages of development. In this study, strategies were employed to optimize rabbit test material consumption via diet. Comparative toxicokinetic profiles of gavage versus dietary administration were evaluated in pregnant or non-pregnant New Zealand White rabbits for 2 novel agrochemicals with different plasma half-lives of elimination (sulfoxaflor, t½ = 13.5 h and halauxifen, t½ = 1 h). Dietary administration of sulfoxaflor resulted in stable 24-h plasma concentrations, whereas gavage administration resulted in a 3-fold fluctuation in plasma levels between Cmax and Cmin Dietary administration of sulfoxaflor resulted in a 2-fold higher nominal and diurnal systemic dose when compared with gavage dosing due to Cmax-related maternal toxicity following gavage. Results with the shorter half-life molecule, halauxifen, were more striking with a 6-fold diurnal fluctuation by the dietary route compared with a 368-fold fluctuation between Cmax and Cmin by gavage. Furthermore, plasma halauxifen was detectable only up to 12 h following gavage but up to 24 h following dietary administration. Finally, the presence of these compounds in fetal blood samples was demonstrated, confirming that dietary exposure is appropriate for achieving fetal exposure. Collectively, the results of these studies support the use of dietary exposure in rabbit developmental toxicity studies.

Absence of accelerations during labor is of little value in interpreting fetal heart rate patterns.

The aim of this study was to investigate the correlation between increasing time since fetal heart rate (FHR) accelerations, positive (no acceleration) stimulation tests and fetal acidemia. Observational study of FHR recordings from 1070 laboring women with indication for fetal scalp blood sampling (FBS). FHR traces were scrutinized regarding acceleration at FBS and duration since most recent acceleration. The appraiser was blinded to the FBS result. At the first sampling, 8.8% of fetuses had lactate concentration >4.8 mmol/L. There were no differences between those with recent accelerations (≤60 min), and absent accelerations (>60 min or never) prior to FBS (8.3% vs. 8.9%, p = 0.71). Corresponding analyses for subgroups were: fetuses with isolated absence of accelerations, 3.7% vs. 1.5% (p = 0.41), fetuses without decelerations (i.e. reduced variability and/or tachycardia), 6.1% vs. 5.1% (p = 0.81) and fetuses with serious decelerations (i.e. late or complicated variable), 15.0% vs. 16.1% (p = 0.87). Among fetuses with serious decelerations, increasing duration from most recent acceleration had a weak but statistically significant correlation to increased lactate concentration (rs = 0.12, p = 0.03). The positive likelihood ratio for acidemia with no response at FBS was 1.15. In a population with FBS performed upon indication, there was no correlation between duration since last FHR acceleration and increased lactate concentration. The majority of fetuses are not acidemic even when the FHR trace is pathological and stimulation tests are only helpful when accelerations are provoked.

Development of the independent function of fetal thyroid glands in the dog in connection with iodothyronine concentrations in pregnant bitches, fetal fluids, and fetal serum

Thyroxine (T4) and triiodothyronine (T3) concentrations in pregnant and nonpregnant bitches were measured. The allantoic and amniotic fluid samples were collected separately in the third week of pregnancy, and fetal blood samples were collected in the fourth week of pregnancy. There was no difference between T4 results in the pregnant and nonpregnant animals, but the measured serum concentrations exceeded the healthy range for normal adults. Serum T4 concentrations were lower in the fetus than those in adults (P < 0.01). Fetal T4 concentrations continuously increased and reached 13.38 ± 6.19 nmol/L before birth. The fetal serum T4 concentrations were lower than the T4 concentrations in allantoic and amniotic fluid until the seventh week, and the fetal serum T3 concentrations were lower than those in fetal fluids throughout the pregnancy (P < 0.01). Maximum T3 concentrations in allantoic and amniotic fluid exceeded the concentrations in the fetal and maternal serum. It is conceivable that the considerable differences between maternal and fetal serum T4 concentrations in healthy animals are explained by the T4 impermeability of the placenta. Extremely high maternal T4 (193.5 nmol/L) in 1 bitch was associated with T4 concentrations under the detection limit in the fetal fluids and serum suggesting an inhibitory effect. The T4 concentrations in all the fetal fluids and serum were under the detectable concentration that can be defined by 3.0 nmol/L in that bitch. We have demonstrated that fetal thyroid glands start functioning independently at the same time as thyroid cell formation in the dog, but the overproduction of maternal T4 may have a suppressive effect on fetal iodothyronine production.

Relationship between paired cord blood and milk POPs levels as a tool for assessing perinatal exposure, a pilot study

ABSTRACTThe long-term health threats posed to humans exposed to pollutants acting as endocrine disruptors (EDs) is yet to be quantified. There is insufficient knowledge about the sources and magnitude of exposure to selected polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) during the most sensitive period of fetal development, suggesting the need for a study. Organochlorine pesticides, classified as being persistent organic pollutants (POPs) and potential EDs, were also included in this analysis. Xenobiotics were measured in paired fetal cord blood and maternal breast milk samples. There were no significant differences in the concentrations of PCB-101, PBDE-47, and PBDE-99 between maternal milk and cord blood according to the Wilcoxon test, and the Spearman tests demonstrated significant correlations in β-HCH, γ-HCH, p,p'-DDE, and PCB-118 between maternal milk and cord blood from the same subjects. All others tested (HCB, β-HCH, γ-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT, PCB-101, PCB-138, PCB-153, PCB-170, PCB-180, PBDE-153) demonstrated significant differences in the same subject women with concentrations significantly higher in maternal milk than in cord blood. The presence of these compounds found in cord blood and maternal milk indicates that both are a source of perinatal exposure to these pollutants. This study opens up the opportunity for new research in estimating a prenatal exposure based on breast milk concentrations of organohalogen compounds.

Exogenous melatonin reduced blood pressure in late-term ovine fetus via MT1/MT2 receptor pathways

Melatonin is involved in the regulation of blood pressure through the receptor dependent or independent route. However, the effect of melatonin on fetal blood pressure is unknown. This study investigated the effect of melatonin on blood pressure of the late-term ovine fetus in utero. Melatonin and/or antagonists were intravenously administered into the fetuses. Mean arterial pressure and heart rate were recorded. Fetal blood samples were analyzed for biochemical parameters and hormones, including cortisol, angiotensin I, angiotensin II, aldosterone, atrial natriuretic peptide, corticotrophin-releasing hormone, adrenocorticotropic hormone, and endothelin. Fetal blood pressure was decreased following administration of melatonin, whereas it was increased following administration of luzindole, but not prazosin. Plasma level of endothelin was decreased by melatonin, which was blocked by luzindole. Our study suggested that melatonin reduced fetal blood pressure via MT1/MT2 receptors and possibly involving release of endothelin.

Involving the consultant before fetal blood sampling.

Fetal scalp lactate (FSL) is used when the cardiotocography (CTG) is not normal in an attempt to reduce the false-positive rate and the likelihood of unnecessary intervention. Whilst the test has almost a 100% negative predictive value, the positive predictive value of this test is very low. To measure the effect of introducing consultant obstetrician review of every abnormal CTG prior to the decision toperform FSL. A retrospective cohort study was performed using routinely collected de-identified data. Mode of birth outcomes for women who had a continuous CTG in labour were compared in two equal time periods, 12months before and after a change in hospital policy. Change in hospital policy dictated that FSL was only performed on a pathological CTG after consultant obstetrician review of the CTG. Consultant obstetrician review of CTG prior to FSL was associated with fewer FSL performed (1.7% vs 3.5%; P≤0.01), fewer babies acidaemic at birth pH<7.1 (0.8% vs 2.2%; P<0.01), fewer caesarean sections for presumed fetal distress (CS for FD) (6.6% vs 8.1%; P=0.05) and fewer instrumental births (17.6% vs 20%; P=0.04). When adjusted for confounders, the change in policy was independently associated with a reduced likelihood of CS for FD (adjusted odds ratios=0.78 (0.63-0.97); P=0.03). A hospital policy whereby a consultant obstetrician reviews abnormal CTGs prior to performing FSL mayhelp to increase the pretest probability and reduce the rate of CS for FD, as well as instrumental birth and unnecessary FSL.

Omission of fetal sampling in treatment of subsequent pregnancies in fetal-neonatal alloimmune thrombocytopenia

Fetal-neonatal alloimmune thrombocytopenia affects approximately 1 of 1000 live births, most of which are not severely thrombocytopenic. Despite effective treatment with intravenous gammaglobulin and/or prednisone, antenatal management of a subsequent affected pregnancy is complicated by the risks associated with fetal bloodsampling. Furthermore, there are no biomarker(s) of high risk other thanthe occurrence of intracranial hemorrhage in a previous sibling. Management of these high-risk pregnancies requires intensive treatment initiated at 12 weeks of gestation. The objective of the study was to evaluate whether empiric escalation of therapy at 32 weeks allows the omission of fetal blood sampling in all fetal-neonatal alloimmune thrombocytopenia-affected patients. Specifically, we sought to determine whether intensive intravenous gammaglobulin-based regimens for the treatment of a subsequent fetal-neonatal alloimmune thrombocytopenia-affected pregnancy followed by empirically escalated intravenous gammaglobulin and prednisone treatment would increase the fetal platelet count and thus safely allow omission of fetal blood sampling in the antepartum management of these patients. In this prospective, multicenter, randomized controlled study, 99 women with fetal-neonatal alloimmune thrombocytopenia whose prior affected child did not have an intracranial hemorrhage were randomized to receive an intensive intravenous gammaglobulin-based regimen: 2 g/kg per week or intravenous gammaglobulin 1 g/kg per week plus prednisone 0.5 mg/kg per day, starting at 20-30 weeks of gestation. Escalated therapy (intravenous gammaglobulin 2 g/kg per week plus prednisone 0.5 mg/kg per day) was recommended and usually initiated at 32 weeks when fetal counts were <50,000/mL(3) or when fetalblood sampling was not performed. The preliminary report of this study from 2007 demonstrated the efficacy of both intravenous gammaglobulin-based regimens in most patients. Most patients who underwent fetal sampling had adequate fetal counts and therefore did nothave their treatment escalated. This post hoc analysis describes the 29fetuses who had their treatment escalated either because they had lowcounts at 32 weeks or when sampling was not performed. This studyexplored whether the empiric escalation of treatment at 32 weeks was sufficiently effective in increasing fetal platelet counts in these patients. Mean fetal and birth counts of fetuses randomized to each of the 2 initial treatment groups were all >100,000/mL(3). Three neonates had an intracranial hemorrhage; all 3 were grade 1 and all had birth platelet counts >130,000/mL(3). In a post hoc analysis, 19 fetuses undergoing fetal blood sampling at 32 weeks had fetal platelet counts <50,000/mL(3) despite their initial treatment. Of these 19, birth platelet counts were >50,000/mL(3) in 11 of 13 fetuses who received escalated treatment compared with only 1 of 6 of those who did not (P= .01); only 3 fetuses that received initial therapy followed by escalated treatment hadbirth platelet counts <50,000/mL(3) and none had an intracranial hemorrhage. The platelet counts of 14 of 15 fetuses that received empirically escalated treatment without sampling were >50,000/mL(3) at birth. In addition, none of these had an intracranial hemorrhage. The 2 recommended protocols of intensive initial treatment followed by empiric escalation of therapy at 32 weeks of gestation are reasonably safe, effective in increasing fetal platelet counts, and allow omission of fetal blood sampling by increasing the fetal platelet count in almost all cases.

Craniofacial tissue oxygen saturation is associated with blood pH using an examiner's finger-mounted tissue oximetry in mice.

Although fetal scalp blood sampling is an examination to assess fetal acidosis during the intrapartum period, it has not been widely used by obstetricians because of its invasiveness. We have developed a small, portable oximetry with a sensor attached to the examiner's finger. Our previous report using this oximetry concluded that fetal head tissue oxygen saturation (StO 2 StO2 ) correlated with umbilical cord artery blood pH. We investigated whether the association between StO 2 StO2 and blood pH in mice could be validated using this oximetry. Eleven the Institute for Cancer Research (ICR) mice were measured using a near-infrared spectroscopy probe at the craniofacial site in a closed polyethylene bag while changing the oxygen concentration. A total of nine blood samples were collected and analyzed for pH. The StO 2 StO2 and tissue blood pH showed a strong positive correlation (r=0.90 r=0.90 and P=0.0009 P=0.0009 ). The StO 2 StO2 and total hemoglobin index also showed a positive correlation (r=0.84 r=0.84 and P=0.0049 P=0.0049 ). Thus, the results of the present study support those of our previous report on clinical cases and allow examiners to easily check the status of fetal acidosis. Fetal management using this oximetry might gain popularity with obstetricians in the near future.

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis

Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P= .001, and P= .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive valuefor symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively. Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.

Prenatal genetic diagnosis for a fetus with atypical neurofibromatosis type 1 microdeletion

To analyze the correlation between atypical neurofibromatosis type 1(NF1) microdeletion and fetal phenotype. Fetal blood sampling was carried out for a woman bearing a fetus with talipes equinovarus. G-banded karyotyping and single nucleotide polymorphism array (SNP-array) were performed on the fetal blood sample. Fluorescence in situ hybridization (FISH) was used to confirm the result of SNP array analysis. FISH assay was also carried out on peripheral blood specimens from the parents to ascertain the origin of mutation. The karyotype of fetus was found to be 46, XY by G-banding analysis. However, a 3.132 Mb microdeletion was detected in chromosome region 17q11.2 by SNP array, which overlaped with the region of NF1 microdeletion syndrome. Analyzing of the specimens from the fetus and its parents with FISH has confirmed it to be a de novo deletion. Talipes equinovarus may be an abnormal sonographic feature of fetus with atypical NF1 microdeletion which can be accurately diagnosed with SNP array.

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals, correlated uniquely to M1 ileum macrophages increasing due to lipopolysaccharide. We identified a unique subset of fetal heart rate variability measures reflecting 1.5 days ahead of time the levels of macrophage activation and increased leakiness in terminal ileum. We propose that such subset of fetal heart rate variability measures reflects brain-gut communication via the vagus nerve. Detecting such noninvasively obtainable organ-specific fetal heart rate variability signature of inflammation would alarm neonatologists about neonates at risk of developing necrotizing enterocolitis and sepsis. Clinical validation studies are required.

Correlation of fetal scalp blood sampling pH with neonatal outcome umbilical artery pH value

Fetal scalp blood sampling is considered as a complimentary tool in addition to cardiotocography to assess fetal well-being. This blood sampling is important as the obstetrician has to judge and make decisions regarding the further management of the delivery based on this pH result. The aim of this study was to analyze the correlation between fetal scalp blood pH and the umbilical artery pH after birth. Furthermore, it was investigated whether tocolysis, a performed episiotomy or cord encirclement have an influence on the umbilical artery pH. This retrospective study over a period of 11years included all singleton pregnancies without fetal anomalies, which were monitored by fetal scalp blood sampling during labor. 844 out of 1502 deliveries were included for analysis. The analysis demonstrates a good correlation between fetal scalp pH value and outcome pH value. Subgroup analysis with fetal scalp blood pH<7.20 showed a difference in 40 of 82 cases, with an outcome pH value ≥7.20, but this difference was statistically insignificant. Neither did tocolysis, episiotomy or the presence of cord encirclement show an overall effect, nor did they have an impact on the subgroup. Obstetricians must consider that the values of fetal scalp blood are not always reliable and can be false. However, on the basis of CTG and fetal scalp blood pH, decisions are made regarding delivery interventions. Therefore, we would encourage the consideration of taking two samples routinely at every attempt of fetal blood sampling.

Should fetal scalp blood sampling be performed in the case of meconium-stained amniotic fluid?

Objective: To investigate the effect of using fetal scalp blood sampling on the risk of neonatal respiratory distress syndrome (NRDS) with meconium-stained amniotic fluid (MSAF).Methods: Prospective data collection with regard to MSAF during labor for low-risk term cephalic singleton live birth from 2012 to 2014. Maternal, obstetric and neonatal data were compared according to the occurrence of respiratory distress syndrome (RDS group) or not (no RDS group).Results: Of 515 newborns born through MSAF, 46 experienced RDS and from them 10 experienced meconium aspiration syndrome. No difference was observed according to maternal characteristic, abnormal fetal heart rate tracing pattern irrespective of its category and cesarean rate. Apgar at one minute was lower in the group RDS (7.6 versus 8.5, p < 0.05). The mean umbilical artery pH values did not differ between the two groups. Significant difference between newborns with and without RDS in terms of fetal scalp lactate sampling during the labor (71.1% versus 55.1%, p < 0.05), and neonatal care unit (NCU) admissions (22.8% versus 10.8%, p < 0.05). Secondary rather than primary meconium was associated with RDS when performing fetal scalp blood assessment (p < 0.05). A significant correlation between RDS, fetal scalp blood assessment and MSAF diagnosed during the first stage of labor (after spontaneous rupture of membranes or at amniotomy) was found.Conclusion: In case of MSAF, fetal scalp blood sampling did not reduce the risk of RDS.

The Effect of Maternal Hypothyroidism on Fetal Umbilical Cord Brain-Derived Neurotrophic Factor Levels

Objective: Brain derived neurotrophic factor (BDNF) is the most important neurotrophin, which helps the differentiation and growth of central and peripheral neurons, and facilitates synaptic transmission. In this study we aimed to investigate fetal cord BDNF levels of infants born from subclinical and clinical maternal hypothyroidism. Methods: This study was conducted on a total of 67 pregnant women who were followed up in Obstetrics and Gynecology outpatient clinics, 27 with maternal hypothyroidism and 40 age-parity matched healthy pregnants without hypothyroidism. Immediately after vaginal or cesarean delivery fetal cord blood samples were taken from these patients and BDNF levels were measured. Results: BDNF levels of infants born from pregnants with maternal hypothyroidism were significantly lower than the control group (23.3 ± 17.4 ng/dl and 50.7 ± 28.3 ng/dl respectively; p<0.001). In multiple linear regression analysis, while BDNF level was related with maternal hypothyroidism and infant sex, it was not associated with mode of delivery, maternal age, total weight gain during pregnancy, gestational age at birth, thyroid stimulating hormone (TSH) levels and other neonatal data. Conclusion: This study showed that fetal cord BDNF levels significantly decreased in infants of the pregnants with hypothyroidism. Key words: Pregnancy, maternal hypothyroidism, brain derived neurotrophic factor, levothyroxine

Birth Outcomes, Intervention Frequency, and the Disappearing Midwife-Potential Hazards of Central Fetal Monitoring: A Single Center Review.

Many birth units use central fetal monitoring (CFM) under the assumption that greater surveillance improves perinatal outcomes. The unexpected loss of the CFM system at a tertiary unit provided a unique opportunity to evaluate outcomes and staff attitudes toward CFM. This retrospective cohort study compared patient data from 2,855 electronically monitored women delivering over a 12-month period, where CFM was available for the first 6 months but unavailable for the following 6 months. Primary outcomes relating to neonatal morbidity and secondary outcomes relating to intrapartum interventions were examined. Additionally, birth unit staff members were surveyed about aspects of care related to CFM. There were no significant differences in perinatal outcomes between the cohorts. While unadjusted analysis suggested a lower spontaneous vaginal birth rate (55.4% vs 60.3%) and a higher cesarean delivery rate (25.1% vs 22.0%, p = 0.026), together with higher epidural (53.0% vs 49.2%, p = 0.04) and fetal blood sampling (11.8% vs 9.4%, p = 0.03) rates in the presence of CFM, these differences were lost when adjusted for prostaglandin ripening. Over half of the staff (56.0% of midwives, 54.0% of obstetricians) reported spending more time with the laboring woman in the period without CFM. This single institution's experience indicates that in birth units staffed for one-to-one care in labor, central fetal monitoring does not appear to be associated with either a benefit on perinatal outcomes or an increase in cesarean delivery and other interventions. However, it is associated with a reduction in the time a midwife spends with the laboring woman.

Cardiovascular biomarkers in paired maternal and umbilical cord blood samples at term and near term delivery

BackgroundCardiovascular biomarkers might help to identify fetuses or pregnancies at risk. AimTo examine the umbilical cord neonatal and maternal levels of cardiovascular biomarkers at the time of delivery, and to correlate maternal and fetal biomarker levels to each other, to gestational age and to delivery mode. Study designIn a prospective, observational, cross-sectional, single-center study biomarkers were measured in paired maternal and umbilical venous cord blood samples. SubjectsThe sample cohort included 66 sets of fetal and maternal blood samples (11 after multiple gestation, 53 after cesarean section, 17 after exposure to labor). Outcome measuresMidregional pro-adrenomedullin (MRproADM), midregional-pro atrial natriuretic peptide (MRproANP), brain natriuretic peptide (BNP), n-terminal-pro brain natriuretic peptide (NTproBNP), copeptin, and high sensitive troponin I (hsTnI) levels were measured. ResultsMean±SEM for biomarker levels in umbilical venous/maternal blood were: MRproADM [nmol/L] 1.02±0.04/1.24±0.08, MRproANP [pmol/L] 215.53±12.96/54.65±3.41, BNP [pg/mL] 32.02±3.37/19.76±3.29, NTproBNP [pg/mL] 1228.94±91.73/71.48±8.65, copeptin [pmol/L] 103.42±22.89/10.41±1.71, and hsTnI [pg/mL] 13.54±5.17/4.91±2.37. Fetal MRproANP, NTproBNP, and BNP were inversely correlated with gestational age. Maternal and fetal MRproANP (r=0.472, p=0.002) and copeptin (r=0.572, p<0.001) levels were correlated, whereas there was no feto-maternal correlation for the other biomarkers. Fetal copeptin was elevated after exposure to labor. ConclusionsBiomarker levels appear to be regulated independently in mother and fetus. Fetal biomarkers are influenced by gestational age and delivery mode. In this study on term and near term pregnancies without specific fetal pathology, correlation between paired maternal and fetal biomarker levels was weak or not demonstrable.

Maternal Nutrient Restriction in Guinea Pigs as an Animal Model for Inducing Fetal Growth Restriction.

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs on pregnancy outcomes, maternal/fetal growth parameters, and blood analytes to further characterize the utility of this model for inducing fetal growth restriction (FGR). Thirty guinea pig sows were fed ad libitum (Control) or 70% of the control diet prepregnant switching to 90% at midpregnancy (MNR). Animals were necropsied near term with weights obtained on all sows, fetuses, and placenta. Fetal blood sampling and organ dissection were undertaken in appropriate for gestational age (AGA) fetuses from Control litters and FGR fetuses from MNR litters using > or < 80 g which approximated the 10th percentile for the population weight distribution of the Control fetuses. MNR fetal demise rates (1/43) were extremely low in contrast to that seen with uterine artery ligation/ablation models, albeit with increased preterm delivery in MNR sows (3 of 15). We confirm that MNR fetuses are smaller and have increased placental/fetal weight ratios as often seen in human FGR infants. We provide justification for using a fetal weight threshold for categorizing AGA Control and FGR-MNR cohorts reducing population variance, and show that FGR-MNR fetuses have asymmetrical organ growth, and are polycythemic and hypoglycemic which are also well associated with moderate FGR in humans. These findings further support the utility of moderate MNR in guinea pigs for inducing FGR with many similarities to that in humans with moderate growth restriction whether resulting from maternal undernourishment or placental insufficiency.

MR Imaging–derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities

Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging-based oxygen-hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging-based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood. Online supplemental material is available for this article.

Fetal Anemia and Hydrops Fetalis Associated with Homozygous Hb Constant Spring (HBA2: c.427T > C)

Hb Constant Spring (Hb CS, HBA2: c.427T > C) is a common nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at the termination codon of the α2-globin gene. Homozygosity for Hb CS (αCSα/αCSα) is relatively rare, and generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. In this report we present a fetus with cardiomegaly, pericardial effusion, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 24 weeks’ gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 4.8 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart’s (γ4) level of 17.9%. DNA sequencing of the α-globin genes found that both partners were Hb CS carriers and the fetus was an Hb CS homozygote. Therefore, this was a rare case of homozygous Hb CS which demonstrated an unusual and serious anemia and hydrops fetalis in utero.

Evaluation of Clinical Diagnosis of Fetal Distress and Perinatal Outcome in a Low Resource Nigerian Setting.

Fetal distress has been shown to contribute to the increasing caesarean section rate. There has been controversy on the usefulness of clinical diagnosis of fetal distress using only the intermittent counting of the fetal heart rate and/or passage of meconium-stained liquor. To evaluate the clinical diagnosis of fetal distress and the perinatal outcome. This was a retrospective study in which the case records of the patients, who were diagnosed of fetal distress at Federal Teaching Hospital, Abakaliki, Nigeria, from January 1, 2008 to December 31, 2014, were collated. The statistical analysis was done using the Statistical Package for Social Sciences version 17 software (SPSS Inc., Chicago IL, USA). Out of the 15,640 deliveries carried out within the study period, 3,761 (24.05%) deliveries were through caesarean section. A total of 326 (8.9%) of the 3,761 caesarean sections were due to fetal distress within the study period. More so, a total of 227 (70.9%) babies were born with ≥ 7 Apgar score at the 1(st) minute of delivery. The perinatal mortality rate was 31.25 per 1000 deliveries. Though birth asphyxia was recorded more on babies of mothers that had fresh meconium-stained liquor and whose decision-intervention interval was more than 30 minutes when compared with those without any of the two conditions, there was no statistical significant difference between them. The clinical diagnosis of fetal distress is accurate in 29.1% of the cases. However, it has led to an unnecessary caesarean section in the remaining 70.9% of the parturients. In order to reduce this high trend of unnecessary caesarean sections due to clinical diagnosis of fetal distress in this environment, antepartum fetal assessment with non-stress test or biophysical profile and intrapartum use of continuous electronic fetal monitoring should be used to confirm or refute the fetal distress before any surgical intervention. Fetal blood sampling and fetal pulse oximetry should be performed in event of non- re-assuring or abnormal cardiotocography.