S. Ioffe

Effects of maternal alcohol intake and smoking on neonatal electroencephalogram and anthropometric measurements

Anthropometric data and computerized electroencaphalogram analysis during quiet, indeterminate, and active sleep were obtained from infants of mothers of four groups: (1) heavy drinking mothers (greater than 2 ounces of alcohol per day); (2) nondrinking mothers; (3) smoking, nondrinking mothers; (4) nonsmoking, nondrinking mothers. Infants in groups 1 and 2 were matched as closely as possible for postconceptional age, sex, race, and socioeconomic status. Infants in groups 3 and 4 were matched similarly. Infants of alcoholic mothers had a significantly lower birth weight, length, and head circumference than those from the matched control group. Infants of smoking mothers had lower birth weights and lengths than infants of nonsmoking mothers, but head circumference was identical. Hypersynchrony of the electroencephalogram was seen only in alcoholic infants, and power spectral density analysis revealed that the average integrated power was significantly increased in quiet, active, and indeterminate sleep. The greatest increase in electroencephalogram power (212%) was seen in active sleep, and this analysis clearly separated 15 of 17 alcohol-exposed infants from the control infants. These data suggest that alcohol has a specific toxic effect on the fetal brain that is not linked with smoking habits. The neonatal electroencephalogram is affected even in the absence of dysmorphology and thus may be the most sensitive indicator of fetal alcohol toxicity.

Sleep, wakefulness and the monosynaptic reflex in fetal and newborn lambs

Abstract1.Electrocorticogram (ECoG), electromyogram (EMG) of the lateral rectus and antigravity muscles (neck and masseter) and breathing activity (FB) were monitored in chronically prepared fetal sheep of 125–140 days gestation and in newborn lambs up to 11 days postnatal age.2.Awake state (AW), non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) were defined using standard criteria for ECoG, eye movements and postural muscle tone.3.The percentage of time the fetuses spent in each state was: NREM sleep 53%, REM sleep 41.4%, and AW 5.6%.4.Spontaneous intrauterine breathing activity occurred only during REM sleep, but 35% of REM sleep was not associated with FB.5.Gasps (isolated deep inspirations) appeared occasionally throughout the recording and were not related to any specific sleep state or wakefulness.6.In the fetus, the monosynaptic reflex (MSR) induced by direct electrical stimulation of the fibular nerve was enhanced by about 75% during REM sleep compared to NREM and AW. In the newborn lamb the adult pattern of suppression of MSR during REM sleep was not seen until several days after birth.

Influence of sleep state on the response to hypercapnia in fetal lambs

The effect of sleep state on the respiratory response to hypercapnia was studied in 14 chronic fetal sheep, 125-140 days gestation. Fetal PaCO2 was raised by 11 to 34 Torr by gradually increasing the maternal FICO2 to 0.09. Fetal sleep state was monitored. Fetal breathing (FB) was analysed in terms of frequency (f), tracheal pressure (TP) and ventilation equivalent (VEq) = sigma TP /min. In 16 out of 17 experiments on apneic fetuses in NREM sleep, the fetuses switched to REM sleep and in 14 instances began to breathe within 2 1/2 min thereafter. The PaCO2 at which apneic fetuses started breathing was 54.8 +/- 8.4 Torr (mean +/- SD). In 4 out of 10 trials on breathing fetuses in REM sleep the fetuses switched to NREM sleep and stopped breathing before removal of the CO2 stimulus. During REM sleep hypercapnia stimulated FB by an increase in TP and by a reduction in the number and duration of apneic pauses. It is concluded that in the fetal lamb CO2 stimulates breathing only during REM sleep and that this stimulus is superimposed on the basic mechanism that stimulated spontaneous FB during this sleep state.

Maternal alcohol ingestion and the incidence of respiratory distress syndrome

The risk of respiratory distress syndrome in infants born to mothers with varying quantities of alcohol intake during pregnancy was assessed. In infants less than 37 weeks gestation, there was a decreasing incidence of respiratory distress syndrome with increasing maternal alcohol consumption (p less than 0.02). In addition, in infants less than 37 weeks gestation, maternal alcohol ingestion was associated with a decreased risk of respiratory distress syndrome even when adjusted for other factors such as smoking, gestational age, birth weight, Apgar score, and sex of the infant. It is suggested that maternal alcohol ingestion enhances the maturation of the fetal lung.

Respiratory response to somatic stimulation in fetal lambs during sleep and wakefulness

Abstract1.The respiratory response to electrical stimulation of the nose, tail, gum and fibular nerve (nonspecific somatic stimulation) was tested in chronically instrumented fetal lambs during sleep and wakefulness.2.The respiratory response to somatic stimulation was greatest during REM sleep, lowest during NREM sleep, and intermediate during the awake state (AW).3.Respiratory responses could follow electrical somatic stimulation up to 2 Hz in any sleep state without changing sleep state.4.The fetal breathing (FB) response to repetitive stimulation depended on the initial sleep state and whether or not the sleep state was affected by the stimulation. Five patterns of response were seen:a)NREM→NREM (initial sleep state and sleep state at end of stimulation) — FB was initated and did not continue beyond the duration of the stimulation.b)NREM → REM sleep — FB was initiated and continued beyond the time of stimulation.c)REM → REM sleep — spontaneous FB was enhanced and continued beyond the time of stimulation.d)REM → NREM sleep — spontaneous FB was enhanced but did not continue beyond the time of stimulation.e)NREM, REM sleep, Awake → Awake — FB was initiated or enhanced and continued beyond the time of stimulation until the onset of NREM sleep.

Effect of medullary lesions, vagotomy and carotid sinus denervation on fetal breathing

Chronically prepared fetal sheep were subjected to bilateral surface lesions of the Area S on the ventrolateral medulla and/or to peripheral chemoreceptor denervation by section of the vagus, sinus or both nerves. Sino-aortic denervation or Area S lesions reduced the incidence of fetal breathing (FB) for several days. Area S lesions also disrupted the pattern of FB; diaphragmatic EMG activity initially was mostly tonic and then of very high frequency, up to 7 Hz. Incidence and pattern of FB generally recovered by 7 days, but mean Ti was reduced in Area S lesioned fetuses (0.14 +/- 0.01 sec) compared to nonlesioned fetuses (0.19 +/- 0.01 sec) (P < 0.0001). Respiratory sensitivity to CO2 was variable but not different between control, denervated, and Area S lesioned groups. Eight of eight fetuses with Area S lesions were unable to initiate breathing at birth, but three sham operated fetuses were born normally. These data suggest that the classical peripheral and central chemoreceptors have a negligible influence on the control of FB, and that breathing activity in the fetus is mediated by a different mechanism than during postnatal life.

Influence of naloxone on fetal breathing and the respiratory response to hypercapnia

The effect of naloxone on fetal breathing and the respiratory sensitivity to CO2 was tested on chronically prepared fetal lambs on days one and four post-surgery. After a control period the fetus was challenged with hypercapnia for 10 min and after another control period 9 mg naloxone was administered to the fetus followed by another CO2 test 15 min later. An index of fetal breathing (Veq), tidal volume (VT) and frequency of breathing (f) was determined from tracheal pressure deflections and from the integrated diaphragmatic EMG, expressed as power of diaphragmatic activity per min. Naloxone consistently caused fetal arousal but the duration was variable. The respiratory response to naloxone was also variable and not statistically different from control. The respiratory sensitivity to CO2 (% delta Veq/Torr delta PaCO2 or % delta Diaph. Power/min/Torr delta PaCO2) was not changed by naloxone on either day. We conclude that endorphins do not have a significant direct role in the fetal respiratory response to CO2 but may be involved in the control of state.