William P. Fifer

Two-day-olds prefer their native language

Newborn infants whose mothers were monolingual speakers of Spanish or English were tested with audio recordings of female strangers speaking either Spanish or English. Infant sucking controlled the presentation of auditory stimuli. Infants activated recordings of their native language for longer periods than the foreign language.

Maternal stress responses and anxiety during pregnancy: effects on fetal heart rate.

This study examined the effect of an acute maternal stress response and anxiety on fetal heart rate. Seventeen healthy, 3rd-trimester pregnant women (mean age = 26 +/- 6 years) were instrumented for continuous electrocardiography, blood pressure (BP), respiration, and fetal heart rate (HR). Subjects completed the state anxiety subscale of the State Trait Personality Inventory (STPI), then rested quietly in a semirecumbent position for a 5-min baseline period, followed by either a 5-min arithmetic or Stroop color-word task. Over the entire 5-min stress period and when averaged across all subjects, the stressors led to significant increases in maternal systolic BP and respiratory rate but changes in maternal HR, diastolic BP, and fetal HR were not significant. However, when subjects were dichotomized into groups that had above or below average anxiety scores [ANX(+) and ANX(-)], both groups had similar respiration rate increases to the stressors, but the BP and fetal heart rate (FHR) responses were significantly different. Women in the ANX(-) group had significantly greater BP responses compared to women in the ANX(+) group whereas the fetuses of ANX(+) women showed significant HR increases and the fetuses of ANX(-) women exhibited nonsignificant decreases. These findings suggest that womens acute emotional reactivity during pregnancy can influence fetal HR patterns and that a stress-induced increase in maternal BP is not the primary signal by which a womens stress response is transduced to her fetus. The results are consistent with the hypothesis that maternal psychological variables may shape the neurobehavioral development of the fetus.

Fetal heart rate reactivity differs by women's psychiatric status: An early marker for developmental risk?

OBJECTIVE To determine whether there are differences in fetal heart rate (FHR) reactivity associated with womens psychiatric status. METHOD In 57 women in their 36th to 38th week of pregnancy (mean age 27 +/- 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological challenge (a Stroop color-word matching task). Subjects underwent the Structured Clinical Interview for DSM-IV (SCID) and completed the Spielberger State-Trait Anxiety Inventory prior to testing. RESULTS There was a significant main effect of maternal diagnostic group on FHR reactivity during the Stroop task even after controlling for birth weight and womens BP reactivity (F4,44 = 2.68, p =.04). Fetuses of depressed women had greater heart rate increases compared to fetuses of women with anxiety disorders and those of healthy, low-anxiety women (post hoc comparisons using the Fisher protected least significant difference test; t = 4.12, p <.05; t = 4.72, p <.01, respectively). There was a similar pattern comparing fetuses of healthy, high-anxiety women to the same two groups (t = 3.29, p <.05; t = 3.99, p <.05, respectively). There were no group differences in FHR during a resting baseline period (F4,52 = 1.2, p =.35). CONCLUSIONS Maternal mood disturbance is associated with alterations in childrens physiological reactivity prior to birth.

Evidence of transnatal auditory learning.

There is converging evidence for fetal retention of auditory experience into early postnatal life, but critical tests with appropriate controls are rare due to methodological hurdles. Research has been conducted on newborn response to naturally occurring stimuli such as heartbeats, intrauterine recordings, pre- and postnatal versions of the maternal voice, fathers voice, and unfamiliar voices. Postnatal experience cannot be ruled out as a possible explanation for many results. Only one critical prenatal exposure experiment with postnatal testing has been carried out and published in a peer-reviewed scientific journal. Interpretation of acoustic and linguistic information on intrauterine recordings suggests that the prosodic features of speech (pitch contours, rhythm, and stress) are available to the fetus. This is compatible with newborn responses and may contribute to language acquisition during the first year. There is no sound evidence that providing extra prenatal auditory stimulation benefits the developing child, and there are potential risks.

Effects of women's stress-elicited physiological activity and chronic anxiety on fetal heart rate.

ABSTRACT. This study examined the effects of pregnant women’s acute stress reactivity and chronic anxiety on fetal heart rate (HR). Thirty-two healthy third trimester pregnant women were instrumented to monitor continuous electrocardiography, blood pressure, respiration, and fetal HR. Subjects completed the trait anxiety subscale of the State Trait Anxiety Index, then rested quietly for a 5-minute baseline period, followed by a 5-minute Stroop color-word matching task and a 5-minute recovery period. Fetal HR changes during women’s recovery from a stressful task were associated with the women’s concurrently collected HR and blood pressure changes (r = .63, p < .05). Fetal HR changes during recovery, as well as during women’s exposure to the Stroop task, were correlated with their mothers’ trait anxiety scores (r = .39, p < .05 and r = −.52, p < .01, respectively). Finally, a combination of measures of women’s cardiovascular activity during recovery and trait anxiety scores accounted for two thirds of the variance in fetal HR changes during the same recovery period (R2 = .69, p < .001). The results from this study link changes in fetal behavior with acute changes in women’s cardiovascular activity after psychological stress and women’s anxiety status. This indicates that variations in women’s emotion-based physiological activity can affect the fetus and may be centrally important to fetal development.

Academic Achievement Varies With Gestational Age Among Children Born at Term

OBJECTIVE: The goal of this study was to examine the degree to which children born within the “normal term” range of 37 to 41 weeks’ gestation vary in terms of school achievement. METHODS: This study analyzed data from 128 050 singleton births born between 37 and 41 weeks’ gestation in a large US city. Data were extracted from city birth records to assess a number of obstetric, social, and economic variables, at both the individual and community levels. Birth data were then matched with public school records of standardized city-wide third-grade reading and math tests. Specifically, we assessed (1) whether children born within the normal term range of 37 to 41 weeks’ gestation show differences in reading and/or math ability 8 years later as a function of gestational age, and (2) the degree to which a wide range of individual- and community-level social and biological factors mediate this effect. RESULTS: Analyses revealed that gestational age within the normal term range was significantly and positively related to reading and math scores in third grade, with achievement scores for children born at 37 and 38 weeks significantly lower than those for children born at 39, 40, or 41 weeks. This effect was independent of birth weight, as well as a number of other obstetric, social, and economic factors. CONCLUSIONS: Earlier normal term birth may be a characteristic considered by researchers, clinicians, and parents to help identify children who may be at risk for poorer school performance.

Subtle autonomic and respiratory dysfunction in sudden infant death syndrome associated with serotonergic brainstem abnormalities: a case report.

Sudden infant death syndrome (SIDS) is characterized by a sleep-related death in a seemingly healthy infant. Previously, we reported abnormalities in the serotonergic (5-HT) system of the medulla in SIDS cases in 2 independent datasets, including in the Northern Plains American Indians. The medullary 5-HT system is composed of 5-HT neurons in the raphé, extra-raphé, and arcuate nucleus at the ventral surface. This system is thought to modulate respiratory and autonomic function, and thus abnormalities within it could potentially lead to imbalances in sympathetic and parasympathetic tone. We report the case of a full-term American Indian boy who died of SIDS at 2 postnatal weeks, and who had subtle respiratory and autonomic dysfunction measured prospectively on the second postnatal day. Cardiorespiratory assessment of heart rate variability suggested that the ratio of parasympathetic to sympathetic tone was higher than normal in active sleep and lower than normal in quiet sleep in this case. At autopsy, arcuate nucleus hypoplasia and 5-HT receptor-binding abnormalities in the arcuate nucleus and other components of the medullary 5-HT system were found. This case suggests that medullary 5-HT system abnormalities may be able to be identified by such physiological tests before death. Replication of these findings in a large population may lead to the development of predictive cardiorespiratory assessment tools for future screening to identify infants with medullary 5-HT abnormalities and SIDS risk.

Prenatal nicotine-exposure alters fetal autonomic activity and medullary neurotransmitter receptors: implications for sudden infant death syndrome

During pregnancy, exposure to nicotine and other compounds in cigarette smoke increases the risk of the sudden infant death syndrome (SIDS) two- to fivefold. Serotonergic (5-HT) abnormalities are found, in infants who die of SIDS, in regions of the medulla oblongata known to modulate cardiorespiratory function. Using a baboon model, we tested the hypothesis that prenatal exposure to nicotine alters 5-HT receptor and/or transporter binding in the fetal medullary 5-HT system in association with cardiorespiratory dysfunction. At 87 (mean) days gestation (dg), mothers were continuously infused with saline (n = 5) or nicotine (n = 5) at 0.5 mg/h. Fetuses were surgically instrumented at 129 dg for cardiorespiratory monitoring. Cesarean section delivery and retrieval of fetal medulla were performed at 161 (mean) dg for autoradiographic analyses of nicotinic and 5-HT receptor and transporter binding. In nicotine-exposed fetuses, high-frequency heart rate variability was increased 55%, possibly reflecting increases in the parasympathetic control of heart rate. This effect was more pronounced with greater levels of fetal breathing and age. These changes in heart rate variability were associated with increased 5-HT(1A) receptor binding in the raphé obscurus (P = 0.04) and increased nicotinic receptor binding in the raphé obscurus and vagal complex (P < 0.05) in the nicotine-exposed animals compared with controls (n = 6). The shift in autonomic balance in the fetal primate toward parasympathetic predominance with chronic exposure to nicotine may be related, in part, to abnormal 5-HT-nicotine alterations in the raphé obscurus. Thus increased risk for SIDS due to maternal smoking may be partly related to the effects of nicotine on 5-HT and/or nicotinic receptors.

Newborn infants learn during sleep

Newborn infants must rapidly adjust their physiology and behavior to the specific demands of the novel postnatal environment. This adaptation depends, at least in part, on the infants ability to learn from experiences. We report here that infants exhibit learning even while asleep. Bioelectrical activity from face and scalp electrodes was recorded from neonates during an eye movement conditioning procedure in which a tone was followed by a puff of air to the eye. Sleeping newborns rapidly learned the predictive relationship between the tone and the puff. Additionally, in the latter part of training, these infants exhibited a frontally maximum positive EEG slow wave possibly reflecting memory updating. As newborns spend most of their time sleeping, the ability to learn about external stimuli in the postnatal environment during nonawake states may be crucial for rapid adaptation and infant survival. Furthermore, because eyelid conditioning reflects functional cerebellar circuitry, this method potentially offers a unique approach for early identification of infants at risk for a range of developmental disorders including autism and dyslexia.

Spatial correlation of the infant and adult electroencephalogram

OBJECTIVE To examine the effects of volume conduction of current on measurements of spatial correlation in the high-density electroencephalogram (EEG) at extremes of human development: infancy and adulthood. METHODS To calculate theoretical spatial correlation of EEG from volume conduction of uncorrelated cortical sources and compare theory with observations of intra/interhemispheric coherence. RESULTS Result verified prediction of reduced spatial correlation in infants due to volume conduction. Theoretical magnitude of spatial correlation from volume conduction demonstrated as lower bound on observed magnitude of coherence (MC). MC of adults is greater than MC of infants. Adult intrahemispheric MC is greater than interhemispheric MC. Scalp muscle electromyogram (EMG) produces artifactually low values of MC. CONCLUSIONS Volume conduction of current from uncorrelated cortical sources produces an erroneous component of spatial correlation that is smaller in infants than adults. The increased MC in adults is indicative of increased adult neuronal myelination. EMG artifact causes erroneous observations of coherence. SIGNIFICANCE Measured EEG spatial correlation contains contributions from both neural activity and volume conduction of current. This is an important issue when measurements are used to deduce physiological correlates of neuropsychological phenomena. Measurements of the neural component of spatial correlation are more accurate early in life because of reduced volume conduction.