Alcohol delays the emergence of the fetal elicited startle response, but only transiently.

Prenatal exposure to alcohol may exert a significant detrimental effect on the functioning of the individual's brain, however few studies have examined this before birth. This longitudinal study examined the effect of maternal alcohol consumption on the elicited startle response of the fetus. Two groups of fetuses were examined: one whose mothers drank alcohol (approximately 10 units per week); the other whose mothers did not drink alcohol. Fetuses were examined at 29, 32 and 35 weeks gestation and their startle response observed using ultrasound in response to 2 presentations of a pink noise (70-250Hz) at 90dB(A) separated by 30s. Fetuses exposed to alcohol exhibited a weaker startle response at 29 weeks gestation than did fetuses not exposed to alcohol. There was no difference in the response at 32 and 35 weeks gestation. To ensure that the effects were not due to a more general effect of alcohol on fetal movement, a second experiment compared the spontaneous movements (observed on ultrasound for 45 min) of fetuses whose mothers drank alcohol and fetuses of mothers who didn't drink alcohol. There were no differences in movements exhibited by the fetuses. The results suggest that exposure to alcohol delays the emergence of the elicited startle response at 29 weeks gestation but this delay has disappeared by 32 weeks gestation. The possible role of altered neural development, acute exposure to alcohol and disruptions to the fetus's behavioural repertoire, in mediating these effects are discussed.

The use of ultrasonography to study teratogenicity in ruminants: evaluation of Ipomoea carnea in goats.

BACKGROUND: Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and other tropical countries that often poison livestock. The plant contains the alkaloids calystegines and mainly swainsonine, which inhibit cellular enzymes and cause systematic cell death. The objective of this study was to evaluate the perinatal effects of I. carnea in goats. METHODS: Forty-seven pregnant goats were randomly allocated into 5 treatment groups and given the following doses (g/kg BW) of I. carnea: 0 (IC0), 1.0 (IC1), 3.0 (IC3), 5.0 (IC5) and 7.5 (IC7). The treatment animals were given fresh I. carnea from day 27 of gestation to parturition. Weight gains and serum biochemistry were evaluated. Fetuses were evaluated using ultrasonographic measurements. RESULTS: Goats from the IC7 group showed clinical signs of poisoning. Ultrasound examination revealed that I. carnea feeding in all treatment groups reduced fetal movement compared to the controls. There was an increase in the total number of birth defects (retrognathia and arthrogyposis) in the IC7 and IC5 groups compared to the controls. CONCLUSION: The results show that I. carnea has teratogenic potential in goats. In addition, ultrasounds were useful in evaluating fetotoxicity and teratogenicity.

Maternal coffee intake and associated risk factors: effects on fetal growth and activity.

Empirical studies have shown that fetal growth and activity can be affected by several risk factors, such as maternal anxiety, depression and tobacco or alcohol consumption. Caffeine intake has received less attention in the literature, as well as the analysis of the mutual interplay of the range of such risk factors. This study aimed to examine effects of mother's coffee intake and associated risk factors during early pregnancy on fetal growth and activity. The sample involved 47 fetuses (51.1% male and 48.9% female) with gestational ages between 20-22 weeks whose mothers were recruited in a Portuguese antenatal obstetric unit. Repeated measures of mother's anxiety (STAI-S) and depression (EPDS) and information about socio-demographics and substances consumption were collected during the first and second trimesters of pregnancy. Fetal activity and biometry were measured during the 2(nd) trimester ultrasound. Results showed that 1) 23.4% of the pregnant women (N = 11) had regular coffee intake; 2) no significant differences were found neither on fetal growth nor on fetal movements considering mother's coffee intake; 3) when mother's socio-demographics and substances consumption were considered, tobacco consumption and anxiety at the 2(nd) trimester appeared as significant predictors of fetal growth and mother's coffee intake and anxiety symptoms at the 2(nd) trimester emerged as significant predictors of fetal movements. An adverse impact of maternal coffee intake during pregnancy was found on fetal activity but not on fetal growth. A deeper understanding of the multiple pathways by which these risk factors affect fetal growth and activity is needed.

Mother's anxiety and depression and associated risk factors during early pregnancy: effects on fetal growth and activity at 20-22 weeks of gestation.

To examine effects of mother's anxiety and depression and associated risk factors during early pregnancy on fetal growth and activity. Repeated measures of mother's anxiety (State-Anxiety Inventory (STAI-S)) and depression (Edinburgh Postnatal Depression Scale (EPDS)) and related socio demographics and substance consumption were obtained at the 1st and 2nd pregnancy trimesters, and fetus' (N = 147) biometric data and behavior was recorded during ultrasound examination at 20-22 weeks of gestation. Higher anxiety symptoms were associated to both lower fetal growth and higher fetal activity. While lower education, primiparity, adolescent motherhood, and tobacco consumption predicted lower fetal growth, coffee intake predicted lower fetal activity. Vulnerability of fetal development to mother's psychological symptoms as well as to other sociodemographic and substance consumption risk factors during early and mid pregnancy is suggested.

Foetal response to maternal coffee intake: role of habitual versus non-habitual caffeine consumption.

Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 µg/mL) reflecting normal lifestyle conditions (day 0) and again following intake of two cups of regular coffee (~300 mg of caffeine) intermitted by 50 h of abstinence (day 2; acute effects). On either day, 2 h simultaneous recordings were made of foetal heart rate, general-, eye-, and breathing-movements. The recordings were analysed for the presence of each of four foetal behavioural states: quiet- and active-sleep, quiet- and active-wakefulness. There was a linear relationship between maternal caffeine content and the incidence of foetal general movements during active sleep on day 0 (R = 0.74; P < 0.02). After coffee loading on day 2, foetuses of non- or low-caffeine consumers showed increases in active wakefulness (P < 0.001), general movements (P < 0.05) and heart rate variation (P < 0.01) but lower basal heart rate (P < 0.01) compared with their day 0 values. The changes in foetal heart rate (variation) and behaviour occurred between 90 and 180 min post-consumption. In contrast, foetuses of habitual caffeine consumers remained unaffected suggestive of foetal tolerance to caffeine. The results indicate differential performance between foetuses regularly exposed to caffeine and those caffeine-naive, both under normal maternal lifestyle conditions and in response to maternal coffee ingestion.

The effects of the tocolytics atosiban and nifedipine on fetal movements, heart rate and blood flow.

BACKGROUND: The choice of first-line tocolytic agent is a topic of worldwide debate. The oxytocin receptor antagonist atosiban and the calcium antagonist nifedipine appear to be effective in postponing delivery. However, information is lacking on their possible effects on the fetal biophysical profile. OBJECTIVE: To study the direct fetal effects of tocolysis with atosiban or nifedipine combined with a course of betamethasone. METHOD: We performed a randomised controlled study including women with preterm labour requiring tocolytic treatment. Primary outcome measures were the effects on fetal heart rate (FHR) and its variation. Secondary endpoints were the effects on fetal movement and blood flow (pulsatility index - PI) of the umbilical (UA) and medial cerebral arteries (MCA). RESULTS: One-hour recordings of FHR and fetal movements were made on each of five successive days (days 0-4). Fetal blood flow velocity patterns were studied daily by Doppler ultrasound. Baseline characteristics of 31 women who had not delivered at day 0 and needed no escape tocolysis did not differ between the study groups. Multilevel analysis showed no significant effect of either tocolytic on FHR and movement parameters over the 5-day study period. The use of tocolytics also did not significantly alter the time courses of PI-values for UA (p = 0.37) and MCA (p = 0.62). CONCLUSION: This study demonstrates for the first time the direct effects of atosiban on fetal movement, heart rate and blood flow. Tocolysis with either atosiban or nifedipine combined with betamethasone administration appears to have no direct fetal adverse effects.

Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women.

OBJECTIVE: The present report evaluates the effect of acute L-arginine administration on fetal heart variables by a computerized non-stress test (NST) analysis. METHODS: Fifteen pregnant women at 30-34 weeks of gestational age affected by mild to moderate gestational hypertension were enrolled in the study. The study was performed in the second and third days of hospitalization. Each woman received both active (Arg) or placebo treatment (Placebo), in a double-blind, randomized, cross-over design. Women received saline infusion for 40 min, then they were infused with either placebo (saline infusion prepared by Damor Pharmaceutics and labeled as Arg-B) or Arg (L-Arg 20 g/500 ml labeled as Arg-A). RESULTS: Multiple analysis of variance (MANOVA) indicated that both placebo and Arg infusion were unable to affect cardiac variables and fetal movements. As far as maternal blood pressure changes were concerned, MANOVA indicated that active treatment showed an acute hypotensive effect on both systolic (F=8.98, p<0.001) and diastolic values (F=15.78, p>0.001). Conversely, placebo infusion does not seems to have induced any change. Considering each time of infusion we observed that Arg treatment was able to lower systolic and diastolic blood pressure after the 40 min of infusion, with this effect persisting for 20 min. CONCLUSIONS: These data indicate that the acute, intravenous administration of high-dose L-arginine does not induce significant changes in fetal heart rate (FHR), whereas it lowers maternal blood pressure. Such conclusions are reinforced by the observation that saline administration in the same pregnant women was neutral for both FHR and maternal blood pressure values. According to previous studies, it seems conceivable that maternal L-arginine treatment enters the fetal circulation by crossing the placenta. The lack of changes in FHR, however, suggests that no significant hemodynamic changes were induced by the treatment. Contrary to what happens in the mother, this may possibly be due to a low, if any, conversion of L-arginine to nitric oxide in the fetus.

Randomized controlled trial of prenatal zinc supplementation and the development of fetal heart rate.

OBJECTIVES: This study was undertaken to evaluate whether prenatal zinc supplementation affects maturation of fetal cardiac patterns. STUDY DESIGN: A randomized double-blind controlled trial among 242 low-income Peruvian women was performed. Beginning at 10 to 16 weeks' gestation, women received supplements containing 60 mg iron, 250 microg folic acid with or without 25 mg zinc. Fetal heart rate (mean FHR, variability [HRV], number of accelerations) and movements (number and amplitude of movement bouts, time spent moving) were electronically monitored monthly from 20 weeks' gestation. Developmental trends were evaluated by supplement type among 195 women who completed the trial and had no serious complications of pregnancy. RESULTS: Zinc supplementation was associated with lower FHR, greater number of accelerations, and greater HRV. Supplementation effects on HRV and accelerations were more pronounced after 28 weeks' gestation. No differences in motor activity were observed. CONCLUSION: Prenatal supplementation of zinc-deficient mothers may be beneficial to fetal neurobehavioral development.

Moxibustion in breech version--a descriptive review.

The management of breech presentation at term remains controversial. It appears logical that maternal and perinatal outcomes would be improved if breech presentation could be avoided. External cephalic version is considered a safe procedure if cases are selected appropriately and anaesthesia avoided. Moxibustion is a traditional Chinese method of treatment, which utilizes the heat generated by burning herbal preparations containing the plant Artemisia vulgaris to stimulate the acupuncture points. It is used for breech version with a reported success rate of 84.6% after 34 weeks gestation. Moxibustion technique is cheap, safe, simple, self-administered, non-invasive, painless and generally well tolerated. Although many studies give encouraging results regarding the use of moxibustion in inducing cephalic version of breech presentation, a definitive conclusion cannot be made as most involve small sample sizes and are not randomised. Moxibustion could be an extra option offered to women with breech presentation along with vaginal delivery, caesarean section and external cephalic version. This article discusses the possible role of moxibustion in correction of breech presentation in the hope that, some interest will be stimulated in what is a very interesting area for future research.

Moxibustion for breech presentation.

Breech presentation at term is considered a possible obstetric complication, and the management before and during labour remains controversial. A technique called 'moxibustion' is used in traditional Chinese medicine to encourage version of the fetus in breech presentation. It has been used in the maternity unit in Plymouth for 11 years. The results would seem to suggest it may have a positive effect and play a part in reducing the number of breech presentations at term and therefore also a reduction in the number of caesarean sections which are so often advocated in breech presentation. This article describes the technique in greater detail and discusses the potential for the future.

Intrapartum vibratory acoustic stimulation after maternal meperidine administration.

OBJECTIVE: To examine the effectiveness of the acoustic stimulation test in the interpretation of suspicious cardiotocograms obtained after meperidine administration to the mother during the first stage of labor. SUBJECTS AND METHODS: We studied 45 unselected parturients who received 50 mg meperidine i.m. when cervical dilatation was 5 cm. In all cases a decreased beat-to-beat variability of the fetal heart rate and fetal movements was noted after the injection of meperidine. A vibratory acoustic stimulation was performed in 25 patients (group A) while the remaining 20 (group B) had no stimulation. RESULTS: After the meperidine injection, the acoustic-induced reactivity returned immediately in group A, while the spontaneous reactivity returned 30 minutes later. The mean number of fetal movements in all parturients was 8.71 +/- 2.18 before meperidine administration. Sixty minutes after the meperidine injection the mean number was 8.52 +/- 2.48 in group A and 1.65 +/- 1.81 in group B (p < 0.0001). CONCLUSION: The acoustic stimulation test is an effective method of interpreting suspicions CTG's obtained after meperidine administration to the mother during the first stage of labour.

Reproductive toxicity studies of D-camphor in rats and rabbits.

The embryotoxicity of D-Camphor (CAS 76-22-2), orally employed for the treatment of hypotonic circulatory dysregulations, was investigated in rats and rabbits. D-Camphor elicited no evidence of teratogenicity when administered orally during the fetal period of organogenesis to pregnant rats at doses up to 1000 mg/kg b.w./day, and to pregnant rabbits at doses up to 681 mg/kg b.w./day. The no-observed-effect level for the fetal organism for the rat was above 1000 mg/kg b.w., and for the rabbit above 681 mg/kg b.w. In rat dams a dose-dependent reduction in food intake and salivation was noted from 464 mg/kg b.w./p.o. onwards. The high dose of 1000 mg/kg b.w./d p.o. resulted in fairly pronounced signs of toxicity such as clonic convulsion, pilo-erection, reduced motility and reduced body weight gain. In rabbit dams the high dose level of 681 mg/kg b.w./d p.o. resulted in reduced body weight gain and food consumption. No increased incidence in variations, retardations or malformations were observed at any of the treated dose levels not even at the highest tested dose level (rat: 1000 mg/kg b.w./d p.o.; rabbit: 681 mg/kg b.w./d p.o.). The daily maximum human therapeutic camphor dose is approximately 1.43 mg/kg b.w. Hence, under the present test conditions the therapeutic ratio is above 450 for the endpoint embryotoxicity reflecting a wide margin of safety.

Developmental toxicity of 1,2-dichloropropane (PDC) in rats and rabbits following oral gavage.

1,2-Dichloropropane (PDC) was evaluated for its potential to cause embryonal/fetal toxicity and teratogenicity in pregnant rats and rabbits. PDC was administered via oral gavage at dose levels of 0, 10, 30, or 125 mg/kg/day on Days 6 through 15 of gestation (rats) or 0, 15, 50, or 150 mg/kg/day on gestation Days 7 through 19 (rabbits). Fetuses were examined on Gestation Day 20 (rats) or Day 28 (rabbits). Maternal toxicity was observed in both rats and rabbits at the high dose levels. Rats given 125 mg/kg/day of PDC showed clinical signs of toxicity and decreased body weight and body weight gain. Rabbits given 150 mg/kg/day PDC showed changes in hematologic parameters and decreased body weight gain. Although maternal toxicity was apparent, no indication of teratogenicity was observed in rat or rabbit fetuses at any dose level. Significant increases in the incidence of delayed ossification of skull bones, considered secondary to decreased maternal body weight gain, were observed in rats given 125 mg/kg/day and in rabbits given 150 mg/kg/day. No maternal or developmental effects were observed in rats given 10 or 30 mg/kg/day or in rabbits given 15 or 50 mg/kg/day of PDC. Based on the results of these studies the maternal and developmental NOELs in rats and rabbits were 30 and 50 mg/kg/day, respectively.

Blunted fetal response to vibroacoustic stimulation associated with maternal intravenous magnesium sulfate therapy.

Maternal intravenous magnesium sulfate (MgSO4) therapy has been associated with decreased fetal heart rate (FHR) variability and reactivity, resulting in an increased incidence of nonreactive nonstress tests, frequently requiring further assessment of fetal well-being. This study was designed to assess fetal response to vibroacoustic stimulation in association with maternal intravenous MgSO4 therapy. Five gravidas with singleton gestations with normal fetal anatomy, intact membranes, and normal amniotic fluid volume at 31 weeks or more presenting with preterm labor were included. Vibroacoustic stimulation was performed prior to and during subsequent intravenous MgSO4 therapy so that each fetus served as its own control. Ultrasound was applied during vibroacoustic stimulation to assess fetal movement response. Response to vibroacoustic stimulation was considered normal if a FHR acceleration of at least 15 beats/min for at least 15 seconds occurred within 15 seconds after the stimulation with prolonged fetal movements. Maternal serum magnesium levels were obtained prior to each stimulation. All fetal responses prior to treatment were normal. All subsequent fetal responses in association with intravenous MgSO4 were abnormal, consisting of blunted FHR accelerations of 10 to 15 beats/min and ranging between 10 and 15 seconds in duration associated with brief limited fetal movements. Mean maternal serum magnesium levels (+/- standard error) during vibroacoustic stimulation, prior to and following intravenous MgSO4, were 1.4 +/- 0.1 and 5.2 +/- 0.4 mEq/L, respectively (P = 0.008). All 5-minute Apgar scores were 8 or higher. This occurrence may reflect an effect of magnesium on the fetus as either a central nervous system depressant or alternatively as a peripheral neuromuscular relaxant.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovine fetal breathing and swallowing activity in response to plasma glucose changes.

Fetal swallowing activity generally occurs simultaneously with fetal breathing movements (FBM) in sheep. The present study investigated the FBM and swallowing responses to altered fetal plasma glucose. Fetal lambs were chronically prepared with laryngeal, esophageal and diaphragm electromyogram (EMG) wires, an esophageal flow probe and vascular catheters. Beginning at 138 +/- 1 day, FBM and swallowing were monitored during control periods and in response to intravenous glucose infusions (14 mg/kg/min for 120 min) to fetuses of fed and fasted ewes. Glucose infusions to fetuses of fed ewes resulted in significant increases in fetal plasma glucose (21.2 +/- 0.7 to 40.5 +/- 1.9 mg/dl) and time breathing (46.2 +/- 6.3 to 60.0 +/- 9.5 min/2 h). In response to maternal fasting, fetal glucose levels (13.4 +/- 1.0 mg/dl) and time breathing (23.0 +/- 7.2 min/2 h) decreased significantly. Glucose infusion to fetuses of fasted ewes resulted in significant increases in time breathing (50.3 +/- 13.4 min/2 h) and diaphragmatic EMG activity (1,295 +/- 654 to 3,012 +/- 1,182 spikes/2 h). There was no change from basal levels of fetal EMG swallows (83.2 +/- 4.3 swallows/2 h) or esophageal flow (40.8 +/- 7.9 ml/2 h) in response to maternal fasting or fetal glucose infusions.

Intrauterine neuromuscular blockade in fetus.

Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/- 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method.

Intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization.

Intravenous pancuronium bromide was administered into the umbilical cord by funipuncture to effect temporary fetal paralysis. Neuromuscular blockade was achieved in 12 fetuses undergoing a total of 34 intrauterine procedures for the treatment of severe red-cell alloimmunization. The same initial dose of 0.2 mg/kg fetal weight estimated by ultrasound was used in all cases, but anemic fetuses did not resume movement for prolonged periods. A relationship among fetal hematocrit, adjusted dose, and duration of paralysis was described by the equation: Duration (hours) = 5.24 + 10.30 adjusted dose (mg/kg) - 0.16 hematocrit (%) (R2 = 0.49; P less than .001). Intravenous pancuronium was found to be a safe and effective method for cessation of fetal movement during intrauterine procedures.

Effects of regular and decaffeinated coffee on fetal breathing and heart rate.

The effects of maternal consumption of regular or decaffeinated coffee on the fetus were determined in eight pregnant women at 32 to 36 weeks of gestation. This was a single-blind crossover study in which two cups of caffeinated or decaffeinated coffee were consumed after an overnight fast. The total maternal caffeine ingested was 454 +/- 4 mg for regular coffee and 12 +/- 0.4 mg for decaffeinated coffee. Maternal consumption of regular coffee was associated with a twofold increase in the incidence of fetal breathing activity and a significant fall in baseline fetal heart rate. Decaffeinated coffee also increased the incidence of fetal breathing activity and produced a slight reduction in fetal heart rate. These results indicate that maternal consumption of regular and decaffeinated coffee can stimulate fetal breathing. Moreover, these results suggest that caffeinated coffee can produce baseline shifts in fetal heart rate.

Effect of hypoxia and catecholamines on the habituation rates of chronically catheterized ovine fetuses.

Integrated electromyographic, electrocortical (ECoG) and electro-ocular activity were recorded in 13 chronically prepared fetal sheep (130-145 days). Fetal movements and the rate of habituation to repeated suffusions of cold saline against the fetal skin were recorded. Experiments were repeated during an intravenous infusion of noradrenaline to the fetus (0.4 microgram/kg estimated fetal weight/min) and during hypoxia induced by altering the oxygen content of the inspired air to the ewe to 9%. Repeated stimulation with cold saline resulted in an increase in fetal movements (p = 0.009). The number of stimuli for habituation was similar in high-voltage and in low-voltage ECoG activity. The rate of fetal habituation was significantly faster during the infusion of noradrenaline compared with control measurements (p = 0.009). During hypoxia, the number of spontaneous fetal movements prior to stimulation decreased (p = 0.002). Habituation rates were also faster during hypoxemia compared with control measurements (p = 0.003). These findings may help to explain the rapid habituation rates seen in some human fetuses in at 'at risk' pregnancies.