There is significant current interest in the degree to which prenatal exposures, including maternal psychological factors, influence child outcomes. Studies that detect an association between prenatal maternal psychological distress and child developmental outcomes are subject to a number of interpretative challenges in the inference of causality. Some of these are common to many types of prenatal exposures that must necessarily rely on observational designs. Such challenges include the correlation between prenatal and postnatal exposures and the potential role of other sources of shared influence, such as genetic factors. Others are more specific to this area of research. These include: confounding between maternal report of child outcomes and the maternal psychological attributes under study; difficulties in distinguishing maternal stress from more ubiquitous aspects of maternal personality; and the lack of association between cortisol and measures of maternal psychological stress. This article considers these methodological issues and offers an additional methodology focused on fetal neurobehavior for discerning potential mechanisms that may mediate associations between maternal psychological functioning and the developing fetal nervous system.
Pregnancy; fetus; prenatal stress; fetal development; fetal behavior; programming
Alteration to blood flow in the maternal-fetal compartment has been proposed as a mechanism underlying maternal psychological effects on pregnancy outcomes. This study characterized the progression of umbilical and uterine blood flow resistance in healthy pregnancies and evaluated concurrent and longitudinal associations with maternal anxiety and other psychological factors.
The study assessed participants (n = 107) at five visits spanning 24 to 38 weeks gestation. The resistance index (RI) in the uterine and umbilical arteries was measured with Doppler ultrasound. Maternal psychological function was assessed using validated, self-report instruments.
Hierarchical linear modeling revealed that uterine and umbilical RI decreased during the second half of gestation, and that uterine RI was lower in nulliparous women. Few concurrent associations emerged between psychological factors and RI. Longitudinal analyses determined that psychological well-being was associated with decreased left uterine artery RI, and psychological distress was associated with lower right artery RI.
While uterine artery resistance was modestly associated with the maternal psychological milieu during gestation, our findings do not indicate an association between increased maternal distress and decreased RI. Thus, this study fails to affirm a key component of the hypothesized relation of maternal stress to fetal outcomes via vasoconstriction.
Doppler; maternal anxiety; resistance index; umbilical artery; uterine artery
There is accumulating evidence that pregnancy is accompanied by hyporesponsivity to physical, cognitive, and psychological challenges. This study evaluates whether observed autonomic blunting extends to conditions designed to decrease arousal. Physiological and psychological responsivity to an 18-minute guided imagery relaxation protocol in healthy pregnant women during the 32nd week of gestation (n = 54) and non-pregnant women (n = 28) was measured. Data collection included heart period (HP), respiratory sinus arrhythmia (RSA), tonic and phasic measures of skin conductance (SCL and NS-SCR), respiratory period (RP), and self-reported psychological relaxation. As expected, responses to the manipulation included increased HP, RSA, and RP and decreased SCL and NS-SCR, followed by post-manipulation recovery. However, responsivity was attenuated for all physiological measures except RP in pregnant women, despite no difference in self-reported psychological relaxation. Findings support non-specific blunting of physiological responsivity during pregnancy.
Pregnancy; Relaxation; Autonomic Nervous System; Heart Rate; Respiratory sinus arrhythmia
Sleep-wake behaviors and temperament were examined longitudinally for trait stability and relationship to behavioral state regulation from infancy to early childhood. Subjects were 120 low-risk, full-term infants from a middle class sample. At 6 weeks, parents completed 3 consecutive days of the Baby’s Day Diary which measures sleep, wake, fuss, feed and cry states and the Infant Characteristics Questionnaire. At 16 months, parents assessed sleep behaviors with the Sleep Habits Inventory and temperament with the Toddler Symptom Checklist. At 24 months, parents repeated 3 days of the Baby’s Day Diary. Structural Equation Modeling was used to examine cross-age hypotheses for sleep-wake and temperament associations. From early infancy to toddlerhood, sleep-wake behaviors and irritable temperament were notably stable but independent in this cohort.
Sleep; wake; infant; toddler; temperament; continuity; fuss; diary method; longitudinal
Maternal salivary cortisol was measured at weekly intervals from 24 to 38 weeks gestation. The total sample consisted of 120 women enrolled in staggered intervals in such a way as to generate weekly measures of salivary cortisol during the latter half of pregnancy. Hierarchical linear modeling revealed the expected increase in unbound maternal cortisol during this period, with a slight deceleration in rate of increase at 33 weeks gestation. Women carrying male fetuses had higher levels of salivary cortisol initially as compared to women carrying female fetuses; at 30 weeks gestation there was cross-over such that higher maternal cortisol was observed in women carrying female fetuses beyond this time and through term. Results highlight the importance of considering fetal sex as a moderator of contemporaneous and predictive associations between maternal cortisol and prenatal or postnatal development.
cortisol; pregnancy; sex differences; male vulnerability; HPA axis
As part of a double-blind study of medication treatment for opioid dependence during pregnancy, 17 opioid-dependent pregnant women maintained on either buprenorphine or methadone underwent fetal monitoring at 24, 28, 32, and 36 weeks gestation. Maternal demographic information and infant outcomes did not significantly differ by medication group. Earlier in gestation (24 and 28 weeks), buprenorphine-exposed fetuses had higher levels of fetal heart rate variability, more accelerations in fetal heart rate and greater coupling between fetal heart rate and fetal movement than the methadone-exposed group (all p’s <.05). Later in gestation (32 and 36 weeks), buprenorphine-exposed fetuses displayed less suppression of motor activity and longer duration of movements than the methadone-exposed group (all p’s <.05). These results may have implications for the optimal treatment of the opioid-dependent pregnant woman.
buprenorphine; drug dependency; fetal heart rate; fetus; methadone; opioids; pregnancy
Neonatal abstinence syndrome (NAS) expression is widely variable among affected infants and the reasons for this variability are largely unknown; mechanisms that predispose infants to NAS expression are not understood. It has been postulated that the regulatory problems of prenatally drug exposed infants are manifested in dysfunctional vagal regulation of autonomic processes. The current study examines whether cardiac vagal tone, an indicator of parasympathetic neuroregulation, provides a marker for autonomic dysregulation subsequently expressed as NAS in prenatally opioid-exposed newborns.
Heart period (HP) and cardiac vagal tone (V) were derived from electrocardiogram data collected from 64 methadone-exposed infants on postnatal days 1 and 3. The postpartum NAS course was assessed serially.
Infants with lower V on day 1 had significantly higher NAS symptomatology on day 3. Boys had more severe NAS symptoms than girls through the first 4 days of life and, among infants receiving pharmacologic treatment for NAS, boys required longer treatment course and hospitalizations. Greater poly-drug exposure, detected through toxicology screening throughout pregnancy, and cocaine use in particular, were associated with lower V and shorter HP (faster heart rate) in newborns. Multiple regression models accounted for 25 to 35% of the variance in NAS symptoms and duration of hospitalization in methadone-exposed infants. Significant predictors included infant sex, SSRI/SNRI use, and cigarette smoking.
Results support the hypothesis of a biologic vulnerability of autonomic regulatory functioning in methadone-exposed infants and greater male infant vulnerability to maternal methadone use.
vagal tone; infant; methadone; neonatal drug exposure; neonatal abstinence syndrome
The earliest relationship does not begin with birth. Pregnant women construct mental representations of the fetus, and feelings of affiliation or “maternal-fetal attachment” generally increase over the course of gestation. While there is a fairly substantial literature on the development and moderation of psychological features of the maternal-fetal relationship, including the role of ultrasound imaging, relatively little is known about the manner in which maternal psychological functioning influences the fetus. Dispositional levels of maternal stress and anxiety are modestly associated with aspects of fetal heart rate and motor activity. Both induced maternal arousal and relaxation generate fairly immediate alterations to fetal neurobehaviors; the most consistently observed fetal response to changes in maternal psychological state involves suppression of motor activity. These effects may be mediated, in part, by an orienting response of the fetus to changes in the intrauterine environment. Conversely, there is evidence that fetal behaviors elicit maternal physiological responses. Integration of this finding into a more dynamic model of the maternal-fetal dyad, and implications for the postnatal relationship are discussed. Research on the period before birth affords tremendous opportunity for developmental scientists to advance understanding of the origins of human attachment.
Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24- to -38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the 1st weeks after birth were examined. Prenatal measures included fetal heart rate variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity; fetal heart rate variability and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation.
The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77)=.27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 minute observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann-Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses.
Fetus; Pregnancy; Cortisol; Fetalmotor activity; Temperament; Maternal stress/anxiety
Maternal psychological functioning during pregnancy affects both maternal and fetal well-being. The hypothalamic-pituitary-adrenal (HPA) axis provides one mechanism through which maternal psychosocial factors may be transduced to the fetus. However, few studies have examined maternal psychological factors or birth outcomes in relation to the diurnal pattern of cortisol across the day. The current study examined maternal psychological well-being, parity status, and birth weight in relation to the maternal cortisol diurnal rhythm in a group of 98 low-risk pregnant women (51 primiparae). At 36 weeks gestation, participants completed both pregnancy-specific and general self-report measures of psychological functioning and provided saliva samples at 800, 1200, and 1600h on 2 consecutive working days for the assay of cortisol. The expected diurnal decline in salivary cortisol was observed. Higher trait anxiety was associated with a flatter afternoon decline for all mothers. For primiparae, steeper morning cortisol declines were associated with lower infant birth weight. The findings suggest that regulation of the HPA axis may differ by parity status with downstream implications for fetal growth and development.
cortisol diurnal rhythm; pregnancy; parity; fetus; anxiety; birth weight
The role of maternal stress during pregnancy remains a focus of academic and clinical inquiry, yet there are few instruments available that measure pregnancy-specific contributors to maternal psychological state. This report examines the psychometric properties of an abbreviated version of the Pregnancy Experience Scale (PES) designed to evaluate maternal appraisal of positive and negative stressors during pregnancy. The PES-Brief consists of the top 10 items endorsed as pregnancy hassles and 10 pregnancy uplifts from the original scale. The PES-Brief was administered to 112 women with low risk, singleton pregnancies five times between 24 and 38 weeks gestation. Scoring includes frequency and intensity measures for hassles and uplifts, as well as composite measures for the relation between the two. Internal reliability, test-retest reliability, and convergent validity were comparable to the original version. The PES-Brief provides an economical source of information on stress appraisal and emotional valence towards pregnancy.
Pregnancy stress; anxiety; Uplifts; Hassles; Questionnaire
Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration.
Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens.
All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition.
Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women.
methadone; methadone dosing; pregnancy; fetus; fetal neurobehavior
Temperament theory has long considered individual differences in reactivity and regulation to be present at birth. Recent evidence suggests that such differences may be present prenatally and moderated by maternal emotionality.
To determine whether induced maternal emotional activation generates a fetal response and whether observed fetal responsivity is associated with early infant temperament.
Women viewed an emotionally evocative labor and delivery documentary at 32 weeks gestation while physiological indices were evaluated and their infant’s temperament was assessed at 6 weeks postnatal age.
Participants were 137 pregnant women and their infants.
Maternal physiological (heart rate and skin conductance) and fetal neurobehavioral (heart rate and motor activity) data were collected during gestation in response to the stimulus. Infant temperament (irritability and consolability) data were based on observational methods after birth.
Fetuses reacted to maternal viewing of the video with decreased heart rate variability, fewer motor bouts, and decreased motor activity. There was correspondence between the nature of individual maternal physiological responses to the full video, as well as phasic responses to a graphic birth scene, and fetal responsivity. Fetuses that reacted more intensively to maternal stimulation were significantly more likely to become infants that demonstrated greater irritability during a developmental examination at 6 weeks of age.
These results support the presumption that early postnatal temperamental characteristics emerge during the prenatal period.
Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-minute guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed.
Stability in cardiac indicators before birth and their utility in predicting variation in postnatal development were examined. Fetal heart rate and variability were measured longitudinally from 20 through 38 weeks gestation (n = 137) and again at age 2 (n = 79). Significant within-individual stability during the prenatal period and into childhood was demonstrated. Fetal heart rate variability at or after 28 weeks gestation and steeper developmental trajectories were significantly associated with mental and psychomotor development at 2 years (n = 82) and language ability at 2.5 years (n = 61). These data suggest that the foundations of individual differences in autonomic control originate during gestation and the developmental momentum of the fetal period continues after birth.