Eduard J. H. Mulder

Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review.

A direct link between antenatal maternal mood and fetal behaviour, as observed by ultrasound from 27 to 28 weeks of gestation onwards, is well established. Moreover, 14 independent prospective studies have shown a link between antenatal maternal anxiety/stress and cognitive, behavioural, and emotional problems in the child. This link generally persisted after controlling for post-natal maternal mood and other relevant confounders in the pre- and post-natal periods. Although some inconsistencies remain, the results in general support a fetal programming hypothesis. Several gestational ages have been reported to be vulnerable to the long-term effects of antenatal anxiety/stress and different mechanisms are likely to operate at different stages. Possible underlying mechanisms are just starting to be explored. Cortisol appears to cross the placenta and thus may affect the fetus and disturb ongoing developmental processes. The development of the HPA-axis, limbic system, and the prefrontal cortex are likely to be affected by antenatal maternal stress and anxiety. The magnitude of the long-term effects of antenatal maternal anxiety/stress on the child is substantial. Programs to reduce maternal stress in pregnancy are therefore warranted.

Stress during pregnancy is associated with developmental outcome in infancy

BACKGROUND Animal studies show that prenatal maternal stress may be related to cognitive impairments in offspring. Therefore, we examined whether psychological and endocrinologic measures of stress during human pregnancy predicted developmental outcome of the infant at 3 and 8 months. METHOD Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in 170 nulliparous women in early, mid- and late pregnancy in a prospective design, in which healthy infants born at term were followed up after birth. RESULTS High levels of pregnancy-specific anxiety in mid-pregnancy predicted lower mental and motor developmental scores at 8 months (p < .05). High amounts of daily hassles in early pregnancy were associated with lower mental developmental scores at 8 months (p < .05). Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months (p < .05 and p < .005, respectively) and motor development at 8 months (p < .01). On average a decline of 8 points on the mental and motor development scale was found. All results were adjusted for a large number of covariates. CONCLUSION Stress during pregnancy appears to be one of the determinants of delay in motor and mental development in infants of 8 months of age and may be a risk factor for later developmental problems. Further systematic follow-up of the present sample is needed to determine whether these delays are transient, persistent or even progressive.

Psychological measures of prenatal stress as predictors of infant temperament

OBJECTIVE To examine, in a prospective study, whether maternal stress during pregnancy is related to infant temperament. METHOD Self-report data on various aspects of prenatal stress were collected from nulliparous women in early pregnancy. Infant temperament was measured at 3 and 8 months by direct observation and by parent report. RESULTS Complete data were available for 170 term-born infants. Pregnancy-specific anxiety explained 3.3% of the variance of attention regulation at 3 months. Perceived stress and pregnancy anxiety taken together explained 5% of the variance of attention regulation at 8 months. Perceived stress accounted for 8.2% of the variance of difficult behavior of the 3-month-old infant. All results were adjusted for covariates. CONCLUSIONS Increased maternal prenatal stress seems to be associated with temperamental variation of young infants and may be a risk factor for psychopathology later in life.

The effects of prenatal stress on temperament and problem behavior of 27-month-old toddlers

AimTo examine, in a prospective study, the influence of prenatal stress on infant temperament and problem behavior.MethodSelf-report data on stress and anxiety, and levels of cortisol in saliva were collected from nulli-parous women during pregnancy. Temperament of the child was measured at 27 months by parent report on the Infant Characteristics Questionnaire. Behavior of the child was assessed by direct observation during the administration of the Bayley Scales of Development 2–30, and by parent report on the Child Behavior Checklist 2–3.ResultsComplete data were available for 103 healthy toddlers. Logistic regression analyses were performed and results were adjusted for possible prenatal, perinatal and postnatal confounders. Perceived stress during pregnancy was a predictor of lower levels of restless/disruptive temperament (OR=0.77), more total behavioral problems (OR=1.17), and more externalizing behavioral problems (OR=1.12) in 2-year-olds. Fear of bearing a handicapped child was a predictor of higher levels of restless/disruptive temperament (OR=1.39) and more attention regulation problems in toddlers (OR=1.46).ConclusionsIncreased levels of maternal prenatal stress appear to be associated with temperamental and behavioral problems in toddlers.

Antenatal corticosteroid therapy and fetal behaviour: a randomised study of the effects of betamethasone and dexamethasone

Objectives To compare the effects of maternal betamethasone and dexamethasone administration on fetal behaviour and fetal heart rate variation.

The effects of maternal betamethasone administration on the fetus

Objective To examine prospectively the effects of maternal betamethasone administration on fetal heart rate variation, body, breathing and eye movements and the rest‐activity cycle.

HEART-RATE VARIATION AND MOVEMENT INCIDENCE IN GROWTH-RETARDED FETUSES - THE SIGNIFICANCE OF ANTENATAL LATE HEART-RATE DECELERATIONS

In 37 intrauterine growth-retarded fetuses, combined 1-hour recordings of fetal heart rate and body movements were made within 24 hours of elective cesarean section. Fetal body movements were recorded simultaneously by use of real-time ultrasound. The study group was divided into two subgroups, according to the presence (n = 29) or absence (n = 8) of antepartum late heart rate decelerations. Correlations were made with umbilical blood gas values obtained immediately after cesarean section. Baseline heart rate variation was reduced below the normal range in 88% of the intrauterine growth-retarded fetuses with decelerations but in only 37% of the group without decelerations. A reduction in fetal heart rate accelerations and body movements and an increase in mean heart rate also were observed only in the group with decelerations. Late heart rate decelerations were associated with low PO2 values in both umbilical artery and vein. It is concluded that in intrauterine growth-retarded fetuses reduced heart rate variation and movement incidence correlate with the presence of late heart rate decelerations before birth and with hypoxemia at birth.

Fetal heart rate in relation to its variation in normal and growth retarded fetuses

OBJECTIVES (1) to assess the relationship of basal fetal heart rate (FHR) with both long term (LTV) and short term (STV) FHR variation in low-risk pregnancies, longitudinally from 24 weeks gestation onwards and (2) to investigate the relationship of FHR with LTV and STV in intrauterine growth retarded (IUGR) fetuses. STUDY DESIGN Computerised FHR recordings were made in twenty-nine uncomplicated pregnancies (n=224) and in twenty-seven IUGR fetuses who were selected retrospectively from three databases (n=135). Nomograms of FHR variation with FHR and GA were constructed using multilevel analysis. RESULTS AND CONCLUSIONS There was a strong negative relationship of FHR with both LTV and STV in the control group (R2=53% and 52%, respectively). In the IUGR fetuses, FHR was generally higher than in normal fetuses whereas LTV and STV were lower. The relationship of FHR with LTV and STV in the IUGR group was less strong (for both: R2=18%). Correction of FHR variation for basal FHR in the IUGR fetuses only resulted in a slight reduction in the number of recordings with a variation below the normal range. As it does not improve the recognition of fetuses being considered at the highest risk, such a correction of FHR variation for basal FHR is therefore not necessary. Intrafetal consistency, known to be present in healthy fetuses, was also present in the IUGR fetuses with a low FHR variation.

Adjustment to termination of pregnancy for fetal anomaly: a longitudinal study in women at 4, 8, and 16 months.

OBJECTIVE We studied psychological outcomes and predictors for adverse outcome in 147 women 4, 8, and 16 months after termination of pregnancy for fetal anomaly. STUDY DESIGN We conducted a longitudinal study with validated self-completed questionnaires. RESULTS Four months after termination 46% of women showed pathological levels of posttraumatic stress symptoms, decreasing to 20.5% after 16 months. As to depression, these figures were 28% and 13%, respectively. Late onset of problematic adaptation did not occur frequently. Outcome at 4 months was the most important predictor of persistent impaired psychological outcome. Other predictors were low self-efficacy, high level of doubt during decision making, lack of partner support, being religious, and advanced gestational age. Strong feelings of regret for the decision were mentioned by 2.7% of women. CONCLUSION Termination of pregnancy for fetal anomaly has significant psychological consequences for 20% of women up to > 1 year. Only few women mention feelings of regret.

NUMERIC ANALYSIS OF HEART-RATE VARIATION IN INTRAUTERINE GROWTH RETARDED FETUSES - A LONGITUDINAL-STUDY

OBJECTIVE We attempted to determine changes occurring with time in fetal heart rate and its variation in fetuses with intrauterine growth retardation in whom late antepartum fetal heart rate decelerations eventually develop. STUDY DESIGN Thirteen fetuses with intrauterine growth retardation were studied over a median period of 25 days. One-hour fetal heart rate records were made two to five times per week and were analyzed numerically. Fetal movements were recorded by the women. RESULTS On average long-term fetal heart rate variation decreased gradually with time and fell below the norm (30 milliseconds) at about the same time decelerations appeared. Mean heart rate showed a slight but statistically significant increase after the occurrence of decelerations. There were large interfetal differences in all parameters studied. CONCLUSION In fetuses with intrauterine growth retardation a decrease in long-term fetal heart rate variation is a rather late sign of impairment that coincides with the occurrence of late decelerations. In the surveillance of the fetus with intrauterine growth retardation it might be most appropriate to use each fetus as its own control.