Coordination between glottic adductor muscle and diaphragm EMG activity in fetal lambs in utero

It has previously been reported that active glottic adduction is present during prolonged apneas but absent during periods of breathing movements in fetal lambs in utero. The present study was aimed at examining the precise coordination between fetal breathing movements [diaphragm electromyographic (EMG) activity (Di EMG)] and glottic adduction [thyroarytenoid muscle EMG activity (TA EMG)]. Electrodes for electroencephalogram, eye movements, TA EMG, and Di EMG and an arterial catheter were surgically implanted in fetal lambs 123-142 days postconception. Polygraphic recordings were performed without sedation while the ewe breathed room air (n = 11) or various gas mixtures (hypoxia, n = 5; hyperoxia, n = 4; hypercapnia, n = 5; hypercapnia+hyperoxia, n = 5). Tonic TA EMG was observed throughout >90% of apneas (>6 s) in both non-rapid-eye-movement and rapid-eye-movement sleep, and when Di EMG frequency decreased in rapid-eye-movement sleep. In all but two fetuses, TA EMG was immediately inhibited when Di EMG appeared. Altering blood gases did not modify these results. In conclusion, Di EMG and TA EMG are well coordinated in late gestation in fetal lambs, except in a few cases. These findings may have consequences for understanding the pathogenesis of mixed/obstructive apneas of prematurity.     

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1-79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average interscorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89-96% for NREM sleep and 54-67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.     

Causality and control: key to the experiment

Maternal betamethasone administration causes a transient but considerable reduction in fetal body and breathing movements and in fetal heart rate variation. The aim of the present prospective study was to investigate whether there is evidence of circulatory changes in fetal, placental or uterine arteries, consistent with hypoxemia. Eighteen women at risk for preterm delivery received betamethasone to enhance fetal lung maturation. Doppler studies were performed before treatment, and 24 and 72 h after the second dose of betamethasone. Blood flow velocity waveforms were obtained from both uterine arteries, umbilical arteries, fetal descending aorta, fetal renal artery, and fetal cerebral arteries. No significant changes occurred in the pulsatility index of any of these blood vessels, suggesting that the transient reduction in fetal heart rate variation and fetal body and breathing movements following maternal betamethasone administration is not mediated through fetal hypoxemia.     

Dependence of aortic pulse wave assessments on behavioural state in normal term fetus

To investigate any influence of behavioural states on the pulse waves in the descending aorta, 21 human fetuses were studied in utero in uncomplicated gestation at the age of 36-41 weeks. The fetal behavioural states were identified using two real-time scanners and one cardiotocograph. The aortic waveform data and pulse wave velocity (PWV) were recorded by means of two double phase-locking echo-trackers. The PWV of the fetal aorta was significantly lower in fetal behavioural state (FBS) 2F than in FBS 1F, when the fetus was apnoeic, and was also reduced in both states during fetal breathing. The calculated pulse pressure showed the same trend as the PWV. The fetal aortic end diastolic diameter and the pulse amplitude did not alter, when the two states changed. Our data suggest that the central haemodynamics in term fetuses are independently influenced by their behavioural state as well as by fetal breathing. The study of pulse waves in the fetal aorta should preferably be performed during apnoea in state 1F, when neither gross body movements nor breathing movements disturb the recording.     

Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep

Rapid eye movements during rapid-eye-movement (REM) sleep are associated with rapid, shallow breathing. We wanted to know whether this effect persisted during increased respiratory drive by CO2. In eight healthy subjects, we recorded electroencephalographic, electrooculographic, and electromyographic signals, ventilation, and end-tidal PCO2 during the night. Inspiratory PCO2 was changed to increase end-tidal PCO2 by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decrease in total breath time by -0.71 +/- 0.19 (SE) s (P < 0.05) because of shortened expiratory time (-0.52 +/- 0.08 s, P < 0.001) and with a reduced tidal volume (-89 +/- 27 ml, P < 0.05) because of decreased rib cage contribution (-75 +/- 18 ml, P < 0.05). Abdominal (-11 +/- 16 ml, P = 0.52) and minute ventilation (-0.09 +/- 0.21 ml/min, P = 0.66) did not change. In hypercapnia, however, rapid eye movements were associated with a further shortening of total breath time. Abdominal breathing was also inhibited (-79 +/- 23 ml, P < 0.05), leading to a stronger inhibition of tidal volume and minute ventilation (-1.84 +/- 0.54 l/min, P < 0.05). We conclude that REM-associated respiratory changes are even more pronounced during hypercapnia because of additional inhibition of abdominal breathing. This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.     

Behavioral states in the fetal baboon

This study was designed to characterize behavioral states in the fetal baboon. Automated methods were developed and validated to recognize behavioral states based on relationships among three physiologic variables (EEG patterns, eye movements, heart period variability). Data included twelve 16-h records from 3 chronically instrumented fetal baboons at 0.8-0.9 of term. Randomly generated control records were used to differentiate occurrences of state from chance association of the variables. For 41.2 +/- 4.6% (mean +/- S.E.) of the time, the physiologic variables were synchronous and formed cycles of state with a mean duration of 34.4 min. Components of these cycles had mean +/- S.E. durations of 7.2 +/- 0.3 min for state 1FB (the analogue of quiet sleep in the human infant and state 1F in the human fetus), 20.7 +/- 1.2 min for the state 2FB (the analogue of active sleep in the human infant and state 2F in the human fetus), and 3.6 +/- 0.2 min for state transitions. For 24.6 +/- 2.4% of the time, the state variables exhibited coincidental, state-like agreements, that were not part of state cycles. Finally, for 34.3 +/- 2.7% of the time, there was no systematic agreement among the three variables. These data provide convincing evidence that organized behavioral states are present in the fetal baboon as early as 0.8 of term gestation.     

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.     

Short-term effects of maternal alcohol consumption on lactational performance

Previous research demonstrated that breast-feeding infants consumed significantly less milk during the immediate hours after their mothers consumed an acute dose of alcohol when compared with a nonalcoholic beverage. The present study tested the hypothesis that maternal alcohol consumption decreases the amount of milk available to the infant and alters milk composition in the short term. To this aim, 22 lactating women were tested on 2 days separated by 1 week; the women reported that they drank very little during pregnancy, but significantly increased alcohol intake during lactation. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other; the order was counterbalanced. Immediately before drinking the beverage (baseline) and 2 hr after (postconsumption), women expressed their milk by using an electric breast pump until no milk had been secreted from either breast for 5 min. Although there was no difference in the energy content of the milk, maternal alcohol consumption slightly, but significantly, reduced the amount of milk produced by the lactating mother. These findings underscore the importance of determining whether and when infants compensate for the reductions in intake experienced at the breast following maternal alcohol consumption and how such changes impact on mother-infant interaction.     

The development of falling asleep during the first months of life in man (author's transl)

Ten normal infants were studied at 2, 6, 12 and 20 weeks of age. EEG, respiratory rhythm, eye movements and chin EMG were recorded after the evening meal. Recording was continued during the stages of sleep. During the period of falling asleep the periods of REM sleep have been analyzed and compared with the periods of REM sleep occurring after non-REM sleep. REM sleep occurring on falling asleep and that occurring after non-REM sleep differed. Some of the following criteria were different at the earliest time of examination; absence of chin EMG activity, number of apnoeic episodes; other criteria (eye movements, respiration) differed during the first 5 months. The large number of eye movements at 2 and 6 weeks and the high respiratory rate, corresponding to that occurring during waking, could indicate that during REM sleep occurring on falling asleep, one is observing manifestations connected with the waking state.     

Polysomnographic sleep measures in patients with uremic and idiopathic restless legs syndrome

In the present study, the nocturnal electroencephalographic sleep pattern, the number of periodic leg movements (PLM) during sleep and wakefulness, and the subjective sleep parameters of patients with uremic (n = 10) and idiopathic (n = 17) restless legs syndrome (RLS) were compared. The main finding was that the total number of PLM (p = 0.019), the PLM index (p = 0.018), and the PLM index while awake (p = 0.003) were significantly higher in patients with uremic RLS compared with patients who had idiopathic RLS. Additionally, both groups showed a distinct time-of-night pattern of PLM activity. Polysomnographic measures of sleep continuity (total sleep time, sleep efficiency, sleep onset latency, time awake) and sleep architecture (amount of nonrapid eye movement sleep stages 1, 2, 3, and 4 and the amount of rapid eye movement sleep) did not differ between uremic and idiopathic RLS patients. With regard to subjective parameters, sleep quality was estimated to be worse in uremic RLS (p = 0.033), whereas other parameters (for example, severity of RLS, quality of life) did not differ between the two groups. It is suggested that uremia itself worsens the motor symptoms of RLS, probably as a result of increased excitability.     

Effects of maternal alcohol intake on fractal properties in human fetal breathing dynamics

Fractal methods have been found to be useful in characterizing biomedical signals. The use of fractal estimation requires the estimation of parameter H, which is directly related to the fractal dimension D. Here, we propose a new approach which is a combination of the wavelet transform and fractal estimators to characterize the human fetal breathing signals before and after the intake of two glasses of wine by a mother. This study was performed on 26 fetuses. The variances of the wavelet coefficients were estimated at each scale. The slope of the representation on a logarithmic plot from the scales 5 to 1 was found to be increased after alcohol intake. Our results suggested that fetal breathing rates have a rough structure before the alcohol intake and a smooth structure after alcohol intake.     

Cheating in medical school: a survey of second-year students at 31 schools

This study examined mechanisms by which fluoxetine may reduce energy consumption and body weight. Women with binge-eating disorder (BED; n = 38) and age- and weight-matched women without BED (n = 32) monitored their dietary intake and concurrently recorded mood variables on a hand-held computer for 6 d of baseline and for 6 d after being randomly assigned to receive placebo or fluoxetine (60 mg). Fluoxetine reduced eating more than did the placebo on days 4-6 of treatment. The frequency of episodes was not affected, suggesting that fluoxetine affects satiety, not hunger. Fluoxetine did not preferentially reduce carbohydrate intake, did not affect snack consumption as compared with meal consumption, and did not affect negative-mood eating more than positive-mood eating, nor did fluoxetine affect subjects' mood ratings. Benefits of fluoxetine were of approximately equal magnitude for women with and without BED. However, women who reported higher energy consumption at baseline were more responsive to fluoxetine than were women who reported lower energy consumption at baseline, and binge-eating status was associated with greater energy consumption at all time points, including baseline. Fluoxetine affects dietary intake within 4 d of its consumption, and if future research shows that this remains true on repeated applications, this drug may be useful for short periods when difficulty with overeating is anticipated, such as during vacations.     

Pre-mRNA processing enhancer (PPE) element increases the expression of an intronless thymidylate synthase gene but does not affect intron-dependent S phase regulation

Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A2-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60-80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using 14C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.     

Surveyed use of fetal and uterine monitoring during maternal surgery

The goal of this study was to determine the frequency and methods of intraoperative fetal and uterine monitoring during maternal surgery in the United States. Maternal surgery was defined as nonobstetric surgery during pregnancy that required general or regional anesthesia. We mailed a 21-item questionnaire to the perioperative nurse managers of US hospitals at which more than 2,000 babies are delivered annually (n = 579). Nearly 60% of responding hospitals routinely used some form of fetal monitoring during maternal surgery; more than 40% of responding hospitals did not use intraoperative fetal and uterine monitoring routinely during maternal surgery.     

Effects of ethanol intake on retinol concentration in the milk of lactating rats

The effect of the consumption of ethanol (5%) on retinol concentration in milk was studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5%) in drinking water during lactation (N = 7) were compared to normal controls fed ad libitum (N = 6). The mean maternal alcohol intake was 3.96 +/- 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores ((1978) Clinical Chemistry, 24:386-392). The pups were separated from dams for a 2-4-h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 +/- 10.60 micrograms/dl in the control group and 60.02 +/- 8.22 micrograms/dl in the ethanol group (P < 0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 +/- 0.43, 16.12 +/- 0.48 and 18.60 +/- 0.91 g, respectively) were significantly lower (P < 0.05) than the weight of pups from controls (15.2 +/- 0.44, 18.36 +/- 0.54, 20.77 +/- 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.     

The PY-motif of Bul1 protein is essential for growth of Saccharomyces cerevisiae under various stress conditions

The effects of chronic maternal administration of ethanol on nitric oxide synthase (NOS) activity and the numbers of NOS containing neurons, and CA1 and CA3 pyramidal neurons in the hippocampus of the near term fetal guinea pig at gestational day (GD) 62 were investigated. Pregnant guinea pigs received oral administration of 4 g ethanol/kg maternal body weight (n = 5), isocaloric sucrose/pair feeding (n = 5) or water (n = 5), or no treatment (NT; n = 5) from GD 2 to GD 61. NOS activity in the 25,000 x g supernatant of hippocampal homogenate was determined using a radiometric assay. The numbers of NOS containing neurons, and CA1 and CA3 pyramidal neurons were determined using NADPH diaphorase histochemistry and cresyl violet staining, respectively. The chronic ethanol regimen produced a maternal blood ethanol concentration of 193 +/- 13 mg/dl at 1 h after the second divided dose on GD 57. Chronic ethanol exposure produced fetal body, brain, and hippocampal growth restriction and decreased fetal hippocampal NOS activity compared with the isocaloric sucrose/pair feeding, water, and NT experimental groups, but did not affect the number of NOS containing and CA1 or CA3 pyramidal neurons. These data demonstrate that, in the near term fetus, chronic maternal administration of ethanol suppresses hippocampal NOS activity and consequent formation of NO, without loss of NOS containing neurons and prior to loss of CA1 pyramidal neurons that occurs in the adult.     

Maternal folate status during extended lactation and the effect of supplemental folic acid

BACKGROUND: Folate requirements during lactation are not well established. OBJECTIVE: We assessed the effects of dietary and supplemental folate intakes during extended lactation. DESIGN: Lactating women (n = 42) were enrolled in a double-blind, randomized, longitudinal supplementation trial and received either 0 or 1 mg folic acid/d. At 3 and 6 mo postpartum, maternal folate status was assessed by measuring erythrocyte, plasma, milk, and dietary folate concentrations; plasma homocysteine; and hematologic indexes. Infant anthropometric measures of growth, milk intake, and folate intake were also assessed. RESULTS: In supplemented women, values at 6 mo for erythrocyte and milk folate concentrations and for plasma homocysteine were not significantly different from those at 3 mo. In supplemented women compared with unsupplemented women at 6 mo, values for erythrocyte folate (840 compared with 667 nmol/L; P < 0.05), hemoglobin (140 compared with 134 g/L; P < 0.02), and hematocrit (0.41 compared with 0.39; P < 0.02) were higher and values for reticulocytes were lower. In unsupplemented women, milk folate declined from 224 to 187 nmol/L (99 to 82 ng/mL), whereas plasma homocysteine increased from 6.7 to 7.4 micromol/L. Dietary folate intake was not significantly different between groups (380+/-19 microg/d) and at 6 mo was correlated with plasma homocysteine in unsupplemented women (r = -0.53, P < 0.01) and with plasma folate in supplemented women (r = 0.49, P < 0.02). CONCLUSIONS: A dietary folate intake of approximately 380 microg/d may not be sufficient to prevent mobilization of maternal folate stores during lactation.     

Prenatal cocaine, alcohol, and undernutrition differentially alter mineral and protein content in fetal rats

Alcohol exposure and undernutrition during pregnancy have been associated with altered fetal body composition. Recent observations suggest that cocaine exposure during pregnancy may impair delivery of nutrients to the fetus and could thereby alter body growth and composition. Such effects are important because they can adversely influence physical and neural development. Consequently, we investigated the dose-dependent effects of cocaine on fetal body composition in an animal (rat) model and compared such effects with those caused by prenatal alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed (undernutrition) and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11 to 14/group). Females were sacrificed on gestation day 20. One male and one female fetus was removed from each dam. The fetuses were minced, dehydrated, defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K, and Na. In terms of concentration per unit of fat-free dry solids, male fetuses in the cocaine groups showed significant decreases in protein compared to untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male fetuses in the alcohol group had significantly elevated Mg levels compared to male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p < 0.05). There were some sex differences, with female fetuses having significantly lower concentrations of Mg, Fe, K, and higher protein concentrations than male fetuses. Although the effects were few and modest, these results suggest that prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body weight and composition and, therefore, adversely influence fetal development.     

Eye movements, prematurity and developmental co-ordination disorder

Horizontal pursuit eye movements were investigated in two separate groups of children: One group exhibited developmental co-ordination disorder (n = 8) whilst another group of children were born prematurely (n = 8). Both studies found a reduced gain in pursuit eye movements when the respective populations were compared with control groups (n = 32). A difference was also found in the ability of some children to temporally synchronize their tracking response to the stimulus, which was indicative of poor predictive control rather than lags in the control system. We suggest that horizontal eye movements may be a sensitive indicator of more general motor deficits during childhood development.