This study shows an association between anxiety and a high resistance index whether analysed as continuous data (fig ) or dichotomised (table). Women with increased anxiety are more likely to have abnormal variables for uterine artery blood flow than those with less anxiety, whether considered as mean resistance index, maximum resistance index, or notching. This association was more pronounced for state anxiety than for trait anxiety. There were, however, more women in the high trait anxiety group than in the high state anxiety group.
Furthermore those women with abnormal Doppler ultrasonograms were more likely to be anxious. All eight women with a notch had an abnormal score on the Spielberger questionnaire (0 scores often signify denial and an underlying psychopathology20
). In addition, 6/7 women with resistance indexes
0.68—that is, the 95th centile—had high anxiety scores, four had high state anxiety scores, and six had high trait anxiety scores.
Women with high state anxiety scores had slightly, although insignificantly, faster heart rates. However, we used multiple regression to show that the association between mean resistance index and state anxiety score was not a confounding effect of maternal heart rate.
The 100 women we studied seem reasonably representative of a non-selected population. Seven had mean resistance indexes on or above the 95th centile, eight had notches (a similar freqency to that found in a large population study16
), six had babies with birth weights at or below the 5th centile. In the general population about 30% of women score >40 for both state anxiety and trait anxiety.21
We observed the same proportion for trait anxiety scores, but not for state anxiety scores. State anxiety scores were lower. It may be that pregnancy in itself was relaxing, at least in the middle of the third trimester in this cohort of women with no obstetric complications.
The Doppler ultrasound waveforms studied here predominantly represent downstream resistance, and not strictly blood flow. However, assuming a relatively stable cardiac output, they are a reasonable index of uterine blood flow. Studies on Doppler ultrasound of uterine arteries to predict impaired trophoblastic invasion have attempted to concentrate on the side supplying the placenta. In this study we have chosen to determine the mean of the resistance indexes on both sides of the uterus (mean resistance index), because ascribing placentation entirely to one side is necessarily artificial. As the highest resistance index (maximum resistance index) is the more abnormal, and possibly thus more clinically relevant, we also analysed this. Whether mean or maximum resistance index was used, the results were generally similar. Impaired uterine blood flow is generally considered a chronic phenomenon, predominantly due to failure of invasion of the placenta by the trophoblast in early pregnancy,22
and abnormal patterns, either high resistance indexes or notching, are predictive of pre-eclampsia and intrauterine growth retardation.16
This does not, however, exclude later changes in uterine blood flow, such as might be associated with transient changes in maternal hormone concentrations, as shown in animal models.23
Indeed, exercise transiently increases uterine resistance indexes in pregnant women at around 34 weeks of gestation,24
and treatment interventions can acutely improve blood flow.25,26
The hypothalamic-pituitary-adrenal axis may be involved in the altered blood flow pattern described here,27
but an obvious candidate for mediator is noradrenaline. High scores for state anxiety are associated with increased plasma noradrenaline concentrations.28
Also, infusion of noradrenaline decreases uterine blood flow, both in pregnant sheep and pregnant guinea pigs.23,29
In fact, in sheep, reproductive tissues (including the uterus) were more sensitive to the vasoconstrictive effects of noradrenaline than were other body tissues.29
It may be that in times of stress the mother has evolved to protect herself at the expense of her fetus.30
We do not know whether the associations between anxiety and Doppler ultrasonograms are acute or chronic. Although we found stronger associations for state anxiety than for trait anxiety, the top 15% of women with either score were largely the same patients, and had similarly abnormal waveforms. Further work is needed to determine whether overall anxiety during pregnancy or even before or at conception might affect uterine artery blood flow, or instead whether the association is only with the current emotional state. It is also possible that there is some underlying factor that causes both increased anxiety and diminished trophoblastic invasion. It is unlikely that the women in our study had reason to be concerned about the progress of their pregnancy, as we excluded those with pre-eclampsia or fetal growth retardation known before Doppler ultrasound.
Although there are many contributors to fetal growth and birth weight, reduced blood flow through the uterine arteries could partially explain why women who are anxious during pregnancy tend to have smaller babies. It is also possible that this mechanism is related to some of the findings by Barker,7,31
which have linked low birth weight to a later predisposition to coronary heart disease.