Alterations of the Short-Term Variation of the Fetal Heart Rate after Antenatal Maternal Betamethasone Administration: Validation with Two Different Computational Algorithms.

INTRODUCTION: Antenatal betamethasone administration in the context of foetal lung maturity enhancement has a transient impact on the short-term variation (STV) of the foetal heart rate. There are currently various algorithms for computing the STV, each one resulting in different STV values. We studied the results of betamethasone administration on the STV using 2 different algorithms in order to investigate whether the effects of steroids on the STV depend on the algorithm used or not. MATERIALS AND METHODS: In the context of a larger, single-centre, prospective, observational study, we gathered CTG traces under and without the influence of steroids in order to study their effect on the STV using 2 different computational algorithms (STV240 and STV16). RESULTS: A total of 285 CTGs were registered and subsequently analysed with both algorithms. When compared to the STV240 and STV16 without or at least 72 h after the first intramuscular corticosteroid administration, a transient increase of both the STV240 and STV16 was documented in the first 24 h, followed by a transient decrease of both the STV240 and STV16 between 24 h and 72 h after the first intramuscular corticosteroid injection. CONCLUSION: Our results confirmed that betamethasone administration has a transient but significant effect on the STV independently of the algorithm used. These observations stress once again the fact that a decreased STV within the first 72 h after maternal bethametasone administration should not be an indication for early delivery.

Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy.

AIM: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. METHODS: Fetal behavior was assessed using Kurjak's antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. RESULTS: The total KANET score was normal (except for one fetus in the case group: total score of 9) in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in any of the eight parameters. CONCLUSION: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Magnesium sulfate and sex differences in cardiovascular and neural adaptations during normoxia and asphyxia in preterm fetal sheep.

Magnesium sulfate (MgSO4) is recommended for preterm neuroprotection, preeclampsia, and preterm labor prophylaxis. There is an important, unmet need to carefully test clinical interventions in both sexes. Therefore, we aimed to investigate cardiovascular and neurophysiological adaptations to MgSO4 during normoxia and asphyxia in preterm male and female fetal sheep. Fetuses were instrumented at 98 ± 1 days of gestation (term = 147 days). At 104 days, unanesthetized fetuses were randomly assigned to intravenous MgSO4 ( n = 12 female, 10 male) or saline ( n = 13 female, 10 male). At 105 days fetuses underwent umbilical cord occlusion for up to 25 min. Occlusions were stopped early if mean arterial blood pressure (MAP) fell below 8 mmHg or asystole occurred for >20 s. During normoxia, MgSO4 was associated with similar reductions in fetal heart rate (FHR), EEG power, and movement in both sexes ( P < 0.05 vs. saline controls) and suppression of α- and ß-spectral band power in males ( P < 0.05 vs. saline controls). During occlusion, similar FHR and MAP responses occurred in MgSO4-treated males and females compared with saline controls. Recovery of FHR and MAP after release of occlusion was more prolonged in MgSO4-treated males ( P < 0.05 vs. saline controls). During and after occlusion, EEG power was lower in MgSO4-treated females ( P < 0.05 vs. saline controls). In conclusion, MgSO4 infusion was associated with subtle sex-specific effects on EEG spectral power and cardiac responses to asphyxia in utero, possibly reflecting sex-specific differences in interneuronal connectivity and regulation of cardiac output.

Complete inhibition of fetal movement in the day 40 pregnant goat model by the piperidine alkaloid anabasine but not related alkaloids.

Four chemically similar alkaloids, anabasine, anabaseine, epibatidine and dimethylphenylpiperazinium (DMPP), are potent nicotinic acetylcholine receptor agonists of fetal muscle nicotinic acetylcholine receptors in human TE-671 cells. Based on results with these cells, we hypothesized that the alkaloids would completely inhibit ultrasound-monitored fetal movement in a goat model. Different, single doses of anabasine, anabaseine, epibatidine, DMPP, or saline control were administered I.V. to pregnant goats on day 40 of gestation and the number of fetal movements per 5 min sample was measured by ultrasound at times 0, 0.5, 1, 2, 4 and 8 h. The differences among does in fetal movements were more consistent at dosing and following recovery for doses of anabasine above 0.125 mg/kg compared to the other compounds and dosages. Anabasine actions were dose-dependent with an IC50 value of ∼0.1 mg/kg, and, at a dose of 0.8 mg/kg, completely inhibited fetal movement for 1.5 h after dosing. Anabaseine, epibatidine, and DMPP failed to completely inhibit fetal movement in day 40 pregnant goats at doses predicted to be effective. These results suggest that while experiments with TE-671 cells provide valuable information and predictions of the actions of plant alkaloids on fetal movement, in vivo experiments are still required in order to determine the ability of an alkaloid to inhibit fetal movement in livestock species. Moreover, other pharmacological properties such as receptor differences between mammalian species and differences in the pharmacokinetic properties of the alkaloids also are likely to weaken teratologic predictions based solely on the in vitro data.

Maternal buprenorphine treatment and fetal neurobehavioral development.

BACKGROUND: Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. RESULTS: Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSION: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

Effects of Maternal Valium Administration on Fetal MRI Motion Artifact: A Comparison Study at High Altitude.

PURPOSE: Fetal MRI is performed without sedation. In cases of maternal claustrophobia or when reduction of fetal motion is critical, benzodiazepines may help. The purpose of this study was to evaluate the effects of low-dose benzodiazepine on fetal motion MRI and its effect on maternal oxygen levels at higher elevation. METHODS: A total of 131 fetal MRI scans performed from March 2012 through December 2013 were studied. Nineteen of the cases were performed following Valium administration. Images were graded with a 5-point Likert scale. Using pulse oximetry, maternal oxygen levels were recorded. RESULTS: Results were analyzed for each category combining 3 readers' interpretations. Using a 2-sample t test model, the average imaging scores were better for the control than the Valium group (p = 0.0139). Maternal oxygen levels at different times and positions were compared using independent 2-sample t test between the Valium and control groups showing no change in O2 saturation, except when controlling for altitude and gestational age (p = 0.0326). CONCLUSION: Administration of low-dose Valium did not decrease fetal motion on MRI. Valium did not pose any risk of maternal hypoxemia, except when controlling for altitude and gestational age on supine position. Thus, caution should be exercised to prevent the risk of fetal hypoxemia.

Maternal Nutrition During Pregnancy: Intake of Nutrients Important for Bone Health.

Objectives Maternal nutrition during pregnancy plays an important role in predisposing offspring to the development of chronic disease in adulthood, including osteoporosis. Our aim was to investigate maternal dietary intakes during pregnancy, with a focus on nutrients important for skeletal development in the offspring. Methods In this case-control study, cases were pregnant women recruited for the Vitamin D in Pregnancy Study (n = 350, age 20-40 years) and controls were non-pregnant peers participating in the Geelong Osteoporosis Study (n = 305, age 20-40 years). Dietary intakes of nutrients were quantified using a validated food frequency questionnaire. Results Compared to controls, cases consumed more energy [median (interquartile range): 7831 (6506-9461) vs. 7136 (6112-8785) kJ/day]; median intakes for cases were greater for carbohydrates [206.2 (172.5-249.9) vs. 188.2 (147.7-217.5) g/day], fat [77.9 (60.3-96.6) vs. 72.1 (53.3-87.4) g/day], potassium [2860 (2363-3442) vs. 2606 (2166-3442) mg/day] and calcium [1022 (819-1264) vs. 918 (782-1264) mg/day] (all p ≤ 0.05). However, pregnant women were not consuming greater amounts of those nutrients which had an increased demand (protein, magnesium, phosphorus and zinc). Similarly, this translated to the likelihood of achieving national recommendations for corresponding nutrients. Conclusions for Practice Compared to their non-pregnant peers, pregnant women were more likely to meet dietary recommendations for calcium and potassium; however, this was not the pattern observed for protein, magnesium and zinc. Future public health messages should perhaps focus on increasing awareness of the importance of all these nutrients during pregnancy.

Does antenatal betamethasone have negative effects on fetal activities and hemodynamics in cases of preeclampsia without severe features? A prospective, placebo-controlled, randomized study.

AIM: To evaluate whether antenatal betamethasone affects the fetal biophysical profile (BPP) and Doppler indices of umbilical and middle cerebral arteries (MCAs) in cases of preeclampsia without severe features. MATERIALS AND METHODS: Forty singleton preeclamptic pregnancies without severe features at gestational ages of 28-34 weeks were randomly divided into two groups of 20 patients: betamethasone and control groups. Patients in the betamethasone group were administered two consecutive doses of 12 mg betamethasone intramuscularly, 24 h apart, and patients in the control group were administered the same volume of saline as a placebo. All participants were evaluated before (0 h) and at hours 24, 48, and 72 of betamethasone/placebo administration using BPP scoring and umbilical and MCA Doppler examinations. RESULTS: Total BPP scores were significantly lower in the betamethasone group across the three time points during the follow-up period (p < 0.001). None of the Doppler indices differed significantly between the groups (p > 0.05). CONCLUSION: Antenatal betamethasone negatively affects fetal BPP score parameters, including the non-stress test, fetal body and breathing movements, without affecting vascular indices of umbilical arteries and MCAs. Clinician awareness of this transient drug-induced effect might be valuable for preventing iatrogenic preterm delivery for fetuses in preeclamptic pregnancies without severe features.

Maternal Use of Selective Serotonin Reuptake Inhibitors and Lengthening of the Umbilical Cord: Indirect Evidence of Increased Foetal Activity-A Retrospective Cohort Study.

BACKGROUND: Antenatal depression affects up to 19% of pregnant women. Some of these women are also in need of antidepressant treatment. Nevertheless, the impact of maternal antidepressant treatment and prenatal depression on the course of pregnancy, foetal development and delivery outcomes is not fully understood. METHODS: We analysed data from 24 818 women who gave birth at Kuopio University Hospital between 2002-2012. Logistic regression analysis was used to estimate associations between the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and the progression of pregnancy, development of the foetus and delivery outcomes. RESULTS: Altogether, 369 (1.5%) women used SSRIs. A regression model adjusted for age, overweight, nulliparity, prior termination, miscarriages, smoking, maternal alcohol consumption, chronic illness and polyhydramnion showed that pregnant women exposed to SSRI medication had significantly lower Apgar scores at 1 minute (p < 0.0001) and 5 minutes (p < 0.0001) and more admissions to the neonatal intensive care unit (p < 0.0001) than unexposed pregnant women. In addition, exposed newborns had longer umbilical cords (p < 0.0001) than non-exposed newborns. CONCLUSION: In addition to the previously known associates with maternal SSRI exposure, such as lowered Apgar scores, SSRI exposure appeared to be associated with increased umbilical cord length. The observation related to increased umbilical cord length may be explained by an SSRI-induced increase in the movements of the developing foetus.

Direct intramuscular fetal or maternal antenatal corticosteroid therapy: short-time effects on fetal behavior and oxygenation: a comparative study.

OBJECTIVE: To compare the effects of antenatal administration of corticosteroids used in two different regimens, on fetal biophysical profile (BPP), baseline fetal heart rate (BFHR), nonstress test (NST) and perinatal outcomes. STUDY DESIGN: We evaluated the effects of single direct intramuscular (i.m.) fetal dose of dexamethasone (4 mg/kg), or four doses of 6 mg dexamethasone given to the mother 12 hours apart on the parameters of fetal BPP 0-4 hours before and after antenatal contraction stress (ACST). We evaluated two groups of 41 fetuses in the 31st gestation week at risk of fetal hypoxia at the Department of Gynecology/Obstetrics, Clinical Center of Serbia in 2013. RESULTS: In fetal ACST group, we found significantly different changes in fetal breathing movement before (D0-f) and after therapy (D1-f), p = 0.019 (-11.75; -1.12), 95% confidence interval (CI), as well as in the maternal ACST group, p = 0.001; (-11.75; -1.12), 95% CI. We found significant difference between BPP 0-m and BPP1-m in the maternal group, p = 0.000. Neonatal asphyxia occurred more often with the increased frequency of fetal breath movements after both ACST (p = 0.04 versus p = 0.07). CONCLUSION: Fetal ACST results in increased fetal breathing movements. Maternal ACST can result in changes to BPP. The increase in fetal breathing movements determinates neonatal asphyxia regardless of the ACST.

Differences between Angus and Holstein cattle in the Lupinus leucophyllus induced inhibition of fetal activity.

Calves with congenital defects born to cows that have grazed teratogenic Lupinus spp. during pregnancy can suffer from what is termed crooked calf syndrome. Crooked calf syndrome defects include cleft palate, spinal column defects and limb malformations formed by alkaloid-induced inhibition of fetal movement. In this study, we tested the hypothesis that there are differences in fetal activity of fetuses carried by Holstein verses Angus heifers orally dosed with 1.1 g/kg dried ground Lupinus leucophyllus. Fetal activity was monitored via transrectal ultrasonography and maternal serum was analyzed for specific lupine alkaloids. There were more (P < 0.05) movements in fetuses of Holstein heifers than those in Angus heifers at eight and 12 h after oral dosing. In addition to serum alkaloid toxicokinetic differences, the Holstein heifers had significantly lower serum concentrations of anagyrine at 2, 4, and 8 h after oral dosing than Angus heifers. Holstein heifers also had significantly greater serum concentrations of lupanine at 12, 18 and 24 h after dosing than the Angus heifers. These results suggest that there are breed differences in susceptibility to lupine-induced crooked calf syndrome. These differences may also be used to discover genetic markers that identify resistant animals, thus facilitating selective breeding of resistant herds.

Effect of Acetaminophen on Fetal Activity.

OBJECTIVES: The aim of this study is to determine if maternal administration of acetaminophen affects fetal activity and thereby the interpretation of clinical assessments of fetal well being. STUDY DESIGN: A longitudinal study was performed in 20 women between 30 and 34 weeks' gestation with uncomplicated pregnancies. A 1-hour ultrasound was performed and recorded to document baseline fetal breathing and body movements. All the subjects were then given a 1,000 mg dose of oral acetaminophen. One hour later, a second 1 hour ultrasound was performed to document postacetaminophen fetal breathing and body movements. The number of episodes and total duration of gross body and fetal breathing movements were then assessed by a blinded observer. The pre- and post-acetaminophen values were compared using a repeated measures t-test. RESULTS: There was no significant effect of acetaminophen on the number of episodes or time spent in fetal breathing or body movements when each activity parameter was analyzed separately. In addition, there was no effect when fetal breathing and body movements were combined into a single composite activity score. CONCLUSION: Although acetaminophen has been shown to affect fetal activity in animal models, it has little effect on humans. Thus, maternal administration of acetaminophen should not affect assessment of fetal well being.

The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats.

Sustained inhibition of fetal movement in livestock species, induced by several poisonous plants, can result in numerous skeletal-contracture malformations. Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" that occurs when pregnant cattle graze teratogenic lupines. Similar malformations are also seen in animals poisoned by Conium maculatum (coniine) and Nicotiana glauca (anabasine). A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to use a goat model to determine if an intermittent schedule of five continuous days on treatment followed by two days off treatment would be sufficient to decrease, or prevent, the incidence of anabasine-induced malformations. The data from this study suggest that, for N. glauca in goats, the intermittent grazing program of five days exposure with two days of non-exposure is insufficient to prevent significant skeletal malformations from occurring. However, this study did demonstrate an inverse relationship between the amount of serum anabasine in the dam and the extent of fetal movement.

Piperidine, pyridine alkaloid inhibition of fetal movement in a day 40 pregnant goat model.

Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals. We tested the alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells. We also determined if the alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model. In TE-671 cells, all three alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence. 1.0 µM alpha conotoxin GI shifted the concentration-effect curves of anabasine and myosmine to the right, and decreased maximal responses. Neither of the conotoxins blocked the actions of lobeline in TE-671 cells. In the day 40 pregnant goats, 0.8 mg/kg anabasine abolished fetal movement at 30 and 60 min after dosing and fetal movement was reduced by lobeline and myosmine. The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR. All three alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these alkaloids to cause multiple congenital contracture-type defects in developing fetuses.

The effects of different concentrations of cocoa in the chocolate intaken by the mother on fetal heart rate.

OBJECTIVE: To analyze the effects of different concentrations (30% and 80%) of cocoa on fetal heart rate (FHR). STUDY DESIGN: One hundred pregnant women with uncomplicated gestation, matched for age and parity, underwent computerized FHR recording before and after the consumption of 30 g of 30% and 80% cocoa chocolate. After 1 week, those who had received 30% were shifted to 80% and vice versa to have a crossover. Computerized cardiotocography parameters (contractions, fetal movements, baseline FHR, accelerations greater than 15 bpm for 15 s, number of decelerations, minutes of high variability, short term variability in ms) were recorded and expressed as mean and SD. The differences were tested for statistical significance using the paired t test, with the significance at p < 0.05. The percent change after chocolate intake for accelerations and short-term FHR variation was calculated. RESULTS: The number of fetal movements, accelerations, the duration of episodes of high variation and the short-term FHR variation were significantly higher (p < 0.0001) after 80% cocoa intake. After 30% cocoa chocolate intake, only the number of accelerations was significantly increased. The percent change of the number of accelerations and the short-term FHR variation were significantly higher after 80% cocoa chocolate maternal intake. CONCLUSIONS: Maternal intake of dark chocolate has a stimulating action on fetal reactivity. The effect is more marked with high concentrations (80%) of cocoa. This finding is likely due to the pharmacological action of theobromine, a methilxanthine present in cocoa.

The effect of abused substances on antenatal and intrapartum fetal testing and well-being.

Recognition that use and abuse of substances by pregnant patients perpetuates, despite ongoing efforts to educate the public, necessitates clinicians to integrate understanding of potential effects on antepartum and intrapartum fetal testing into their interpretation and implementation of clinical findings. This includes acknowledging some anticipated alterations in results and selecting the appropriate type and frequency of testing methods and interventions. Certain substances are well documented in terms of expected variations in test results; others are not as clearly defined. An overview of information that may be helpful to the clinician is presented to promote understanding of fetal evaluation performed through common tests such as contraction stress test, the nonstress test, the biophysical profile, the modified biophysical profile, fetal movement counting, and Doppler velocimetry. What evidence is available should be used to assist in defining the actual status of the fetus as best as possible, even when the effects of substances may be unknown or have obscure results.

Efficacy of betamethasone on the fetal motion and biophysical profile and amniotic fluid index in preterm fetuses.

The term ofpreterm birth is used to define the premature neonates considering pregnancy age. In less than 34 week pregnancies, corticosteroids are prescribed to promote embryos' lung maturity. The presents study aimed at evaluating effects of betamethasone injection on feeling embryo motion by mother and index and biophysical profile in preterm pregnancies. In a descriptive-analytical study, 40 pregnant women with the pregnancy age of 30-34 weeks were evaluated. Embryo motion and index and biophysical profile of the amniotic fluid were checked before prescription of double dosage of muscular betamethasone (12 mg) at a 24 h time interval. The injection was repeated for 24 and 48 h after the first injection. The resulted outcomes were compared with those results related to before betamethasone injection. In this study, there was statistically meaningful relationship between embryo motions before injection of betamethasone and 12 h after its injection (p = 0.03). Also, there was a significant relationship between embryo motions 24 and 48 h after injection of betamethasone (p = 0.001). In other words, the embryo motions decreased 12 h after injection of betamethasone. They were improved 48 h after betamethasone injection. But, index and biophysical profile results of amniotic fluid were left unchanged. Application of betamethasone leads to evident but transient decrease in embryo motions. Although motion element of index and biophysical profile of amniotic fluid which is one of the tests used in evaluating the embryo health is fixed and normal, it can be concluded that injection of betamethasone may not affect embryo health.

Fetal muscle-type nicotinic acetylcholine receptor activation in TE-671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid coniine.

Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (-)-coniine, (+)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (-)-coniine in TE-671 cells. (-)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner.

Fetal assessment before and after dosing with buprenorphine or methadone.

AIM: To determine pre- and post-dosing effects of prenatal methadone compared to buprenorphine on fetal wellbeing. DESIGN: A secondary analysis of data derived from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial. SETTING: Six United States sites and one European site that provided comprehensive opioid-dependence treatment to pregnant women. PARTICIPANTS: Eighty-one of the 131 opioid-dependent pregnant women completing the MOTHER clinical trial, assessed between 31 and 33 weeks of gestation. MEASUREMENTS: Two fetal assessments were conducted, once before and once after study medication dosing. Measures included mean fetal heart rate (FHR), number of FHR accelerations, FHR reactivity in the fetal non-stress test (NST) and biophysical profile (BPP) score. FINDINGS: Significant group differences were found for number of FHR accelerations, non-reactive NST and BPP scores (all Ps < 0.05). There were no significant group differences before time of dosing. Significant decreases (all Ps < 0.05) occurred from pre- to post-dose assessment for mean FHR, FHR accelerations, reactive NST and fetal movement. The decrease in accelerations and reactive NST were significant only for fetuses in the methadone group, and this resulted in a significantly lower likelihood of a reactive NST compared to fetuses in the buprenorphine group. CONCLUSION: Buprenorphine compared with methadone appears to result in less suppression of mean fetal heart rate, fetal heart rate reactivity and the biophysical profile score after medication dosing and these findings provide support for the relative safety of buprenorphine when fetal indices are considered as part of the complete risk-benefit ratio.

[Fetal heart rate variability and clozapine treatment]. / Absence de variabilité du rythme cardiaque fœtal chez les fœtus exposés in utero à la clozapine.

We report the 2 cases of schizophrenic patients with clozapine treatment and particularly, we underlined a reduced variability and low short-term variability, whereas biophysical ultrasound score, Dopplers and perception of fetal movements were acceptable and comfortable concerning the fetal vitality. Our aim is to show the limits of the analyzed fetal heart rate under clozapine. So, we may change our observation of fetus in chronic suffering that is usually mainly made with an informatics analysis of pregnants under clozapine.