The role of self-rated health in the association between chronic somatic diseases and climacteric-related symptoms.

OBJECTIVES: We have previously shown an association between several chronic somatic diseases and climacteric-related symptoms. This time, we investigated whether self-rated health (SRH) contributes to this association. METHODS: The Women's Health Questionnaire was used to evaluate the climacteric-related symptoms, and existence of the diseases was investigated in 3421 women (41-54 years). In our previous study, the associations were defined with multivariable analyses. In the present study, SRH (good, moderate or bad) was included as a covariate. RESULTS: Most of the previously found associations between the diseases and the symptoms lost their significance. Accordingly, SRH played an important role in the association between the diseases and the symptoms related to the climacteric. CONCLUSIONS: SRH seems to be of significant importance regarding the relationship between the chronic somatic diseases and the symptoms related to climacteric. Most of the diseases are not associated with the climacteric-related symptoms if the disease does not deteriorate the SRH. Thus, women's own perception of their health is crucial for their symptomatology.

The need for adjustment of dosage regimen of penicillin V during pregnancy.

OBJECTIVE: To determine whether the normal regimen of dosage of oral penicillin V is relevant during pregnancy. METHODS: Twelve pregnant and six nonpregnant women volunteered for the study. Six women were in the second trimester of pregnancy (mean +/- standard deviation 19 +/- 7 weeks' gestation) and six women were in the third trimester (35 +/- 2 weeks). All of the women took 1 x 10(6) IU phenoxymethylpenicillin orally, and multiple blood and urine samples were obtained. Assays were performed by means of a disk agar diffusion method. The results were compared by Mann-Whitney U test. RESULTS: Compared with nonpregnant women, pregnant women had smaller area under the curve values (433 +/- 93 minutes.IU/mL, P < .05 in the second trimester; 550 +/- 220 minutes.IU/mL in the third trimester) and a shorter half-life (57 +/- 56 minutes in the second trimester; 34 +/- 21 minutes, P < .05 in the third trimester). Plasma and renal clearances were faster in the pregnant women. CONCLUSION: Elimination of penicillin V is enhanced during pregnancy, necessitating either a shorter dosing interval (6-8 hours) or an increased dose with the standard dosing interval.

Uterine and umbilical flow velocity waveforms in the supine hypotensive syndrome.

Changes in central hemodynamics and uterine and umbilical artery flow velocity waveforms were studied in ten healthy women 33-41 weeks pregnant who had signs of the supine hypotensive syndrome. When changing the position from left lateral recumbency to supine, there was an initial increase in mean arterial pressure (MAP) of 13% and in maternal heart rate of 30%. After this, the MAP decreased by 19% and, simultaneously, a 26% increase (P = .002) in uterine artery systolic/diastolic (S/D) ratio was recorded. When the changes in MAP and in the uterine artery S/D ratio were compared, the response was slower and recovery faster in the uterine circulation. Two patients evidenced a transient deceleration in the fetal heart rate and a simultaneous increase in the umbilical artery S/D ratio.

Flow velocity waveforms in uterine and umbilical arteries during submaximal bicycle exercise in normal pregnancy.

Eight healthy women who were not conditioned athletes, at 35-38 weeks' gestation, performed a submaximal bicycle exercise test three times for 4 minutes each with stepwise increases (73 +/- 27, 114 +/- 29, and 161 +/- 16 W) of the work load. The target heart rate at the end of the last load was 170 beats per minute. The systolic-diastolic ratios (S/Ds) of flow velocity waveforms were measured with pulsed color Doppler ultrasound in the uterine and umbilical arteries immediately after each work load and during recovery. The heart rates at the end of each load (133 +/- 3, 156 +/- 3, and 173 +/- 7 beats per minute) corresponded to an average of 70, 83, and 92% of the calculated maximum heart rate. With the subject in the sitting position on the ergometer before exercise, the S/D in the uterine artery was 1.49 +/- 0.09, increasing gradually and significantly during the exercise to the maximum of 2.04 +/- 0.06 at 1 minute of recovery. Heart rate and S/D in the uterine artery correlated significantly (r = 0.58, P less than .01). Although the mean arterial pressure increased significantly during exercise from 92 +/- 6 to 109 +/- 10 mmHg, the significant decrease of the ratio of the mean arterial blood pressure and S/D suggests that the flow in the main uterine artery may decrease during intense exercise. No changes occurred in the S/D of the umbilical artery flow velocity, but the fetal heart rate increased significantly.

The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term pregnancies.

OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35-41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes and, after a 5-minute recovery period, to a stepwise increase in oxygenation with 50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and oxygenation were assessed noninvasively, and maternal and fetal vascular responses were assessed with pulsed-wave color Doppler velocimetry. Computerized cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS: Substantial maternal hypoxia was achieved and accompanied by a statistically significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg). Doppler measurements demonstrated a statistically significant decline in the pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3 to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to 0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in the umbilical artery and the middle cerebral artery showed no statistically significant changes. Hyperoxia did not cause changes in the maternal circulation, but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation, suggesting redistribution of maternal blood flow, but exerts no detectable effects on the healthy fetus. Maternal hyperoxygenation induces no apparent adverse effects.

Nitrous oxide inhalation: effects on maternal and fetal circulations at term.

OBJECTIVE: To evaluate the hemodynamic effects of nitrous oxide inhalation in normal term pregnancy. METHODS: Twenty healthy term pregnant women were given 30% nitrous oxide in pure oxygen for 2 minutes, and the hemodynamics were assessed by pulsed-wave color Doppler velocimetry of the uterine and internal carotid artery of the mother and the umbilical and middle cerebral artery of the fetus. Each vessel was assessed separately, allowing a 5-minute wash-out period between the inhalations. The measurements were continued for 2 minutes after the inhalation, and the pulsatility index (PI) was determined at 1-minute intervals. The maternal heart rate and blood pressure (BP) were recorded before and after inhalation; fetal well-being was confirmed with cardiotocography. Analysis of variance for repeated measurements and paired-sample t test were used for statistical analysis. RESULTS: A significant decrease in the PI of the maternal internal carotid artery was observed after 2-minutes of inhalation (from 0.83 +/- 0.22 to 0.71 +/- 0.20; P < .001). The uterine artery PI and maternal BP and heart rate were not affected by nitrous oxide. A significant decrease was evident even in the fetal middle cerebral artery PI (from 1.37 +/- 0.27 to 1.22 +/- 0.17; P = .02). The umbilical artery PI remained unchanged. CONCLUSION: Both maternal and fetal central vascular resistance were decreased by 30% nitrous oxide inhalation. So far, no adverse effects to mother or fetus have been demonstrated in clinical practice. However, preterm fetuses are susceptible to intracranial hemorrhage, and the cerebral hyperemia by nitrous oxide might increase the risk of hemorrhage in these fetuses. This hypothesis requires further investigation.

Single dose of nifedipine in normotensive pregnancy: nifedipine concentrations, hemodynamic responses, and uterine and fetal flow velocity waveforms.

The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in ten healthy, normotensive women at 38 weeks' gestation admitted to the hospital for elective cesarean delivery. Within 1 hour after nifedipine administration, mean arterial pressure had decreased by 10% and a slight increase was observed in maternal heart rate. A statistically significant (P less than .01) decrease in the systolic-diastolic ratio was found in the flow velocity waveform from the uterine artery, but no change was seen in that from the arcuate artery. No changes were observed in the fetal heart rate pattern or in umbilical or thoracic aortic flow velocity waveforms. Nifedipine concentrations in the mother had no correlation with maternal or fetal hemodynamic responses. At delivery 2.5 hours after nifedipine ingestion, the umbilical venous-maternal ratio of nifedipine concentrations was 0.76.

Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine.

The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in 12 women with pregnancy-induced hypertension. Within an hour after nifedipine, the mean arterial blood pressure fell by 17% and there was a slight increase in maternal heart rate. There was also a decrease in the systolic/diastolic (S/D) ratio in the flow velocity waveform in the uterine artery in seven subjects, whereas the S/D ratio was unaffected in five subjects. Lack of change in the S/D ratio was associated with a less optimal pregnancy outcome: The neonates were delivered earlier, the rate of cesarean delivery was higher, and the newborns were smaller. No changes were observed in the fetal heart rate pattern or in the umbilical or middle cerebral artery flow velocity waveforms after nifedipine in hypertensive pregnancies.

Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women.

OBJECTIVE: Selective estrogen receptor modulators (SERMs) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific. Ospemifene (FC-1271a) is a novel SERM compound, which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system, while having antiestrogen-like effects in uterus and breast. In this study, we investigated the effects of ospemifene on the uterine endometrium, vaginal maturation index and hormonal status in healthy postmenopausal women. METHODS: The study was conducted as a double-blind, placebo-controlled phase I study, where 40 healthy postmenopausal women volunteers were randomized to receive daily oral doses of ospemifene either 25, 50, 100 or 200 mg or placebo for 12 weeks. Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks' visit. Serum concentrations of estradiol, luteinizing hormone, follicle stimulating hormone (FSH), sex-hormone binding globulin (SHBG), parathyroid hormone and prolactin were determined from samples taken at baseline, at 4 days and at 4, 12, and 16 weeks' visits. Climacteric symptoms were assessed using 12 visual analogue scales (VAS) at baseline and at the end of the study. RESULTS: No clinically significant changes were seen in endometrial thickness at any dose level. Ospemifene exerted a very weak estrogenic effect on endometrial histology. On the other hand, it induced a clear estrogenic effect on vaginal epithelium. Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes; FSH decreased and SHBG increased during the treatment. In general, ospemifene was well tolerated. The 25 and 50 mg doses tended to reduce climacteric symptoms, but no statistically significant differences were observed between different doses of ospemifene and placebo. The highest dose level (200 mg) induced more subjective adverse reactions, especially hot flushes, than lower doses. CONCLUSION: Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg. Further studies are needed to substantiate the results of this Phase I pilot study.

Association of abnormal flow velocity waveforms in the uterine artery with frequency-specific fetal heart rate variability.

The aim of the study was to determine if abnormal flow velocity waveforms in the uterine artery are associated with altered frequency-specific fetal heart rate variability (HRV). Fetuses in the last third of gestation were studied. In seven fetuses the pulsatility index (PI) of the blood flow velocity waveform in the uterine artery was increased (Group II), and in ten fetuses the PI was normal (Group I). Frequency-specific HRV (0.025-0.07 Hz, 0.07-0.13 Hz, 0.13-1.0 Hz) was quantified by power spectral analysis and correlated with the PI in the uterine artery, umbilical artery and the middle cerebral artery. The slow variability dominated the fetal HRV. There was no difference between the groups in the mean frequency-specific variability. In Group II, an increase of the PI in the umbilical artery and a decrease in the middle cerebral artery correlated with an increase of HRV, the increase being greatest at the lowest frequency band.

Autonomic cardiovascular control in pregnancy.

Pregnancy is associated with profound adaptive changes in the maternal hemodynamics. Although the autonomic nervous system plays a central role in the adaptation of the cardiovascular system to various needs, its role in the adaptation of the circulation to the demands of pregnancy is poorly understood. This paper reviews the literature of autonomic cardiovascular control in pregnancy as studied with the cardiovascular reflex tests. A Medline search and manual cross-referencing for prior publications were used. All papers found on the hemodynamic effects of the Valsalva maneuver, the orthostatic test, the deep breathing test, the isometric handgrip test and maternal heart rate variability in pregnancy were reviewed and all publications that studied short-term changes in maternal heart rate and blood pressure were included. The beginning of pregnancy is associated with sympathetic reactivity, whereas the latter half of pregnancy is characterized by increased hemodynamic stability during orthostatic stress. The heart rate response to the Valsalva maneuver is blunted in mid-pregnancy, possibly due to changes in the baroreflex and increased maternal blood volume. Heart rate variability is significantly reduced in the second trimester. Cardiovascular reflex tests can be used to study drug effects on maternal circulation non-invasively.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

Impact of prematurity on perinatal mortality and morbidity.

Severe prematurity is a prime factor causing perinatal mortality or morbidity. In Finland 1% of babies are born before 32 completed weeks of pregnancy and 0.9% are delivered with a birth weight of 1500 g or less. Since transport of a baby in utero is preferable to transporting a neonate, approximately 85% of infants below 1000 g and 90% of infants between 1000 to 1499 g are delivered in departments with facilities for neonatal intensive care. The rate of caesarean delivery is approximately 50% in pregnancies between 26 and 28 weeks, while the overall caesarean section rate is 15%. Deaths of low birth weight babies account for 66% of the total perinatal mortality and those of very low birth weight babies 46%. Intrauterine deaths constitute two thirds and neonatal deaths one third of perinatal mortality among very low birth weight babies. In Turku, neonatal survival rate for infants of 500 to 749 g was 61.5% and for infants of 750 to 999 g, 77.3%. In Turku respiratory distress syndrome is one of main complications of prematurity that has led to death in 11.2% of infants in recent years. Of the survivors, 85% have been healthy at the age of two years. The incidence of the bronchopulmonary dysplasia among very low birth weight infants has been 19.7%. In recent years, the incidence of severe brain haemorrhage has been 32% among infants with a birth weight below 1000 g.

Uterine and umbilical flow velocity waveforms in normotensive and hypertensive subjects during the angiotensin II sensitivity test.

The systemic and uterine circulatory effects of angiotensin II infusion in five normotensive and 10 hypertensive subjects at the end of the third trimester of gestation were studied. Color Doppler ultrasonography was used for investigating the systolic/diastolic ratios on flow velocity waveforms in the uterine and umbilical arteries. A significant increase was observed in the systolic/diastolic ratio in the uterine artery in both groups. In normotensive subjects a differential effect of angiotensin II on the systemic diastolic blood pressure and on the systolic/diastolic ratio was observed; the uterine circulation had a slower response and a faster recovery than the maternal diastolic blood pressure. In hypertensive subjects this relative refractoriness to angiotensin II was less marked; the increase in uterine vascular resistance was faster and the recovery slower than in the normotensive group. No changes in the systolic/diastolic ratio in the umbilical artery were observed in either group. These results indicate that the uterine circulation of normotensive subjects is remarkably more refractory to angiotensin II than the circulation of hypertensive subjects.

Flow velocity waveforms in uterine and umbilical arteries during the angiotensin II sensitivity test.

The angiotensin II sensitivity test has been used to predict the development of hypertension during pregnancy. We investigated the systolic/diastolic ratios of flow velocity waveforms in the uterine and umbilical arteries by means of a color Doppler system in 15 healthy women at 24 to 26 weeks' gestation. A significant increase (p less than 0.001) was observed in the systolic/diastolic ratio in the uterine artery, which was unaffected by the location of the placenta. In five women a differential effect of angiotensin II on the systemic diastolic blood pressure and on the systolic/diastolic was observed: the uterine circulation appeared to have a slower response and a faster recovery than the diastolic blood pressure. No changes in the systolic/diastolic ratio in the umbilical artery were observed.

Vaginal and intracervical prostaglandin E2 for cervical ripening: a Doppler study of hemodynamic effects.

The hemodynamic effects of vaginally and intracervically administered prostaglandin E2 gel were evaluated by pulsed wave color Doppler ultrasound. Twenty term pregnant mothers were recruited. Mothers were randomized to receive either vaginal or intracervical prostaglandin E2 gel. The hemodynamics was assessed by repeated color Doppler velocimetry of the uterine artery and fetal umbilical and middle cerebral arteries; analysis of variance was used to test statistical significance. In the uterine artery a statistically significant rise (P < or = 0.001) of the pulsatility index (PI) was observed. A slightly higher rise of the PI was observed after intracervical administration, but the difference between the groups was not statistically significant (P = 0.4). The fetal PI remained unchanged both in the umbilical and cerebral vessels throughout the study. The rise in the uterine artery PI is probably caused by an increase in the uterine tone as prostaglandins of the E series usually cause vasodilation. No detectable fetal effects were evident.

Use of medication during pregnancy--a prospective cohort study on use and policy of prescribing.

Pregnancy is associated with special problems with respect in selection of medication and dosage, primarily due to potential teratogenic or toxic effects on the fetus by the drug itself, and secondly due to the physiologic adjustments in the mother in response to pregnancy. This prospective survey was designed to record the use of medications and the policy of prescribing during the course of pregnancy. In total, 5851 pregnant women residing in a county in southwestern Finland during the period June 15, 1987 and June 14, 1988 were studied, which is 69% of the total amount of births in the same area. Iron and vitamin supplementation was used by all the pregnant women during the third trimester, and by 35% and 88% during the first and second trimesters, respectively. Analgetics were used on an irregular basis by 12% of the pregnant women, and no correlation to the length of pregnancy could be observed. 9% of the women used medication on a regular basis for reasons such as bronchial asthma, arterial hypertension and hyperthyreosis. Some kind of a symptomatic medication was taken by 43% of the women with no correlation of the length of pregnancy, the most common symptoms needing medication being candidiasis, cough, reflux esophagitis and pregnancy-associated hyperemesis. Tocolytic agents had been given to 8% of the pregnant women. Most tocolytics were used during the end of the second trimester and beginning of the third one. It is concluded that the general use of medicines is quite reasonable in the normal pregnant population in Finland. Iron supplementation should probably be more individualized instead of regular use.

Causes of the increase in the incidence of ectopic pregnancy. A study on 1017 patients from 1966 to 1985 in Turku, Finland.

The relationship between the increased incidence of ectopic pregnancy and the known risk factors of this disorder was examined by 5-year age groups and equivalent calendar periods to determine the causes of the recent "epidemic" of ectopic pregnancy. None of the known risk factors would alone explain the observed increase. Consequently, multivariate analysis by log-linear models was applied: age, past pelvic operation, previous pelvic inflammatory disease, antecedent legal abortion, and current use of an intrauterine contraceptive device were responsible for the increase in the occurrence of the disease. The strongest association with the observed temporal trend in the increase of ectopic pregnancy was found for pelvic operation (including previous ectopic pregnancy), pelvic inflammatory disease, and current use of an intrauterine contraceptive device. Improved diagnosis and changing demographic patterns also contributed to the increase in the annual number of ectopic pregnancies.

Autonomic cardiovascular reflexes in pregnancy. A longitudinal study.

Cardiovascular reflexes were studied in 22 healthy women before they were pregnant, once during each pregnancy trimester and after delivery to evaluate the effect of pregnancy on autonomic control of haemodynamics. The Valsalva manoeuvre, the deep breathing test, the orthostatic test and the isometric handgrip test were used to assess changes in autonomic nervous function. We found that pregnancy altered the heart rate response in the Valsalva manoeuvre, the deep breathing test and the orthostatic tests. The deep breathing difference (p = 0.03) and max/min ratio (p = 0.03) decreased in pregnancy, whereas standing heart rate increased (p < 0.0001). Both the systolic and diastolic blood pressure increased after standing up during pregnancy. The circulatory responses to isometric exercise were not affected by pregnancy. The results show that parasympathetic responsiveness is decreased in pregnancy and that it returns to normal after delivery.