The fetal behavioural states: an ultrasonic study

In order to accurately detect the fetal behavioural state, we simultaneously measured fetal heart rate and multiple fetal activities in 27 healthy pregnant women at 38 to 40 weeks of gestation. We ultrasonically identified gross body movements, breathing movements and micturition. Analysis of fetal heart rate allowed us to distinguish two different patterns of fetal behaviour: active and quiet phases. The frequency distribution of the analysed fetal events was significantly different in these two phases. These data suggest that a complete biophysical profile of the fetus is effective in differentiating behavioural states and may improve the predictive accuracy of fetal heart rate analysis alone.     

Growth charts of fetal biometry: a longitudinal study

Objective: The aim of this study was to construct reference charts for fetal biometry in Karachi, Pakistan. Methods: This was a prospective longitudinal study involving 1228 women with singleton pregnancies. Biparietal diameter, head circumference, abdominal circumference and femur length were measured repeatedly until delivery. Regression analysis and multilevel modeling was used to construct charts. Results: The mean age of the women in this study was 28.0 years with standard deviation of 4.6. For each gestational age percentiles were calculated and charts were then constructed. Conclusion: Our reference percentiles for fetal biometry measurements are the first of their kind in Karachi, Pakistan. They will not only help us in the diagnosis and management of fetal growth restriction but will provide the basis to develop charts at the national level.     

Classification of fetal and neonatal heart rate patterns in relation to behavioural states

For the assessment of behavioural states in the human fetus, the fetal heart rate (FHR) pattern is one of the state variables. A statistical method is described to classify FHR patterns. FHR recordings were made between 38 and 40 wk gestation. The tachogram was averaged over 3-s intervals. For FHR segments of 3 min duration the parameters of an autoregressive-moving average (ARMA) model were estimated. Simulated FHR patterns, generated by using these estimated ARMA parameters, resembled real recordings. The ARMA parameters were used as features for a retrospective classification of the FHR segments, using a linear discriminant function. The classification by the above method was compared with an independent visual classification of the FHR patterns. The computer/observer classification agreement was 85% (kappa = 0.70). These data were compared with classification results for neonatal heart rate segments. For prospective classification of FHR patterns a moving discriminant function was introduced.     

Effect of betamethasone administration on fetal heart rate tracing: a blinded longitudinal study

OBJECTIVE: Computerized fetal heart rate (FHR) analysis revealed that antenatal corticosteroids transiently suppress multiple parameters of fetal well-being, potentially leading to the erroneous diagnosis of fetal distress and to unnecessary iatrogenic delivery of premature infants. Our aim was to determine whether clinicians who visually analyze FHR tracings detect these suppressive effects, thereby potentially affecting their clinical management decisions. METHODS: Singleton pregnancies admitted for preterm labor between 26 and 34 weeks' gestation received two doses of betamethasone, 24 h apart, and were monitored daily between 16:00 and 19:00 h for 5 days. FHR tracings were randomly coded and presented in a non-consecutive order to four clinicians, who were unaware of the time of steroid administration. FHR baseline, FHR variability, number of accelerations and amplitude of maximal FHR acceleration were determined. Variability was scored semiquantitatively based on a modified Hon score. Analysis of variance (ANOVA) with repeated measures was used for primary analysis and followed up with the Wald test of significance. Corrections for multiple comparisons were made and only p < 0.005 considered significant. ANOVA was also used to assess the uniformity of trend in the interpretation by the four examiners for each given day. RESULTS: Baseline FHR was elevated, FHR variability was decreased, and the number of accelerations decreased on day 1 (p < 0.0001; p < 0.0001; p < 0.0001) and day 2 (p > 0.0001; p < 0.0001; p < 0.0001) in comparison to day 0. On day 3, the FHR baseline, variability and number of accelerations returned to pre-exposure values (p = NS). The maximal amplitude of FHR accelerations showed a trend towards reduction (p = 0.08). Subgroup analysis by gestational age (group I = 26-30 weeks and group II = 30-34 weeks) showed the same response patterns and significance levels for both groups. CONCLUSIONS: Betamethasone causes profound, but transient, suppression of FHR parameters, which can mimic fetal distress. This effect is clinically recognized by visual FHR analysis. Clinicians need to be aware of this phenomenon, in order to avoid unwarranted iatrogenic delivery.     

S100B protein cord blood levels and development of fetal behavioral states: a study in normal and small-for-dates fetuses

Objective: We aimed to determine whether S100B protein levels in cord blood and the development of fetal behavioral states were altered and interrelated in small-for-dates (SFD) fetuses. Methods:Umbilical cord blood samples were collected from 12 SFD fetuses with normal umbilical artery (UA) Doppler findings, from six SFD fetuses with abnormal Doppler waveform patterns and from 36 controls matched for gestational age. S100B protein levels were measured by means of a specific radioimmunoassay. Fetal behavioral state recordings were made before delivery by Cesarean section and data were expressed as percentage of quiet sleep coincidence (C1F), of activity state coincidence (C2-4F) and of no coincidence (NOC). Flow velocimetry waveforms were recorded from the uterine artery, UA and fetal middle cerebral artery (MCA). Results: Mean S100B protein levels in umbilical plasma were significantly higher in the six SFD infants with abnormal prenatal Doppler findings (3.31 ± 0.65 μg/l) than in SFD infants with normal Doppler findings (1.56 ± 0.35 μg/l) and in controls (1.23 ± 0.43 μg/l). Similarly in these fetuses NOC was higher and C2F significantly lower (p < 0.05), but there was no significant difference in C1F. S100B concentrations were correlated with the UA pulsatility index (PI) (r = 0.78, p < 0.01), with the MCA PI (r = -0.78, p< 0.01) and with the UA PI/MCA PI ratio (r = 0.80, p < 0.01). Also, NOC and C2F percentages were correlated with the UA PI (r = 0.61, p < 0.01 and r = -0.61, p < 0.01, respectively), with the MCA PI (r = -0.72, p < 0.001 and r = 0.66, p < 0.01, respectively), and with the UA PI/MCA PI ratio (r = 0.60, p < 0.01 and r = -0.54, p < 0.05, respectively). NOC was also correlated with S100B protein (r = 0.48, p < 0.05); the correlation of S100B protein and C2F almost reached significance (r = -0.47, p < 0.05). Conclusions: This study provides evidence of a relationship between a biochemical marker of brain development and/or integrity and the development of fetal behavioral states, offering additional information on brain maturation in normal and high-risk pregnancies.     

Estimated fetal weight in the evaluation of growth in twin gestations: a prospective longitudinal study

A prospective longitudinal study was conducted in order to determine by sonographically estimated fetal weight the patterns of fetal growth in twins. Thirty-five healthy women with normal twin pregnancies were examined every three weeks from the 15th week of gestation to delivery. Among the measurements obtained were the biparietal diameter (BPD), the abdominal circumference, and the calculated fetal weight. From 15-28 weeks, the growth velocity of the BPD and abdominal circumference remained fairly constant, with a steady increase in incremental growth. Beyond this age, we observed a slowing in growth of the BPD, while the abdominal circumference continued at a constant rate. The growth velocity of the weight steadily increased throughout pregnancy. Although greater biologic variability in weight between twin A and B was observed as gestational age progressed, the overall mean weights of twin A and B were not statistically different. We have generated a nomogram of fetal weight gain throughout pregnancy.     

The natural history of primary dysmenorrhoea: a longitudinal study

Objective   To describe the prevalence, severity, course and predictive factors of primary dysmenorrhoea in women of all reproductive ages.
Design   Prospective mailed surveys in 1985 and 1991.
Setting   University of Iowa, College of Nursing.
Population   We began with a stratified sample of 996 nurses who graduated between 1963 and 1984. We analysed data from 404 women who responded to both surveys, but denied endometriosis, pelvic inflammatory disease or uterine fibroids.
Methods   Participants were surveyed twice at an interval of six years (response rates 73% and 78%) regarding menstrual cycle characteristics. For analysis, dysmenorrhoea was dichotomised as none/mild or moderate/severe. We analysed predictive factors using χ² tests and stepwise logistic regression.
Main outcome measure   Severity of dysmenorrhoea. Menstrual cramps as experienced when not taking medication to prevent discomfort were rated on a four-point scale: 0 = no dysmenorrhoea, 1 = minimal (can work, somewhat uncomfortable), 2 = moderate (can work, but quite uncomfortable) or 3 = severe dysmenorrhoea (miss work, have to be in bed).
Results   In 1985, 80% of respondents were >25 years old and 60% were parous. There were few changes over six years in the prevalence of mild (51% to 53%), moderate (22% to 20%) or severe dysmenorrhoea (4% to 2%). After adjusting for dysmenorrhoea in 1985, each live birth during follow up (OR = 0.20, 95% CI = 0.08 to 0.53) and older age (OR = 0.92, 95% CI = 0.86 to 0.98) were associated with less dysmenorrhoea in 1991.
Conclusions   Primary dysmenorrhoea affects most women throughout the menstrual years. Dysmenorrhoea severe enough to cause absence from work occurs in less than 5% of women. Although improvement and worsening are equally likely for all women, improvement is more likely in women who bear children.     

Assessment of fetal lung development by quantitative ultrasonic tissue characterization: a methodical study

OBJECTIVES: This study was performed to evaluate the quantitative ultrasonic tissue characterization of the normal fetal lung development by using acoustic raw data captured after preprocessing. METHODS: One hundred and sixty-two patients with completed gestational ages between 22 and 37 weeks were enrolled in this study. Longitudinal and transverse sections of the fetal thorax and upper abdomen were imaged. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using an interactive software. RESULTS: A total of 162 patients met the inclusion criteria. The echogenicity of the fetal lung showed a particular changing pattern during pregnancy: the mean gray value of the fetal lung (MGV) is almost the same as the MGV of the fetal liver at 22 and 23 weeks, decreases between 22 and 31 weeks and increases between 31 and 37 weeks. The MGV of the fetal liver decreases significantly from 24 weeks to 31 weeks and increases significantly again toward 37 weeks. We stated that the MGV of the lung is smaller than the MGV of the liver during 31 weeks of gestation and the relation reverses in late gestation. At term, the MGV of the liver is greater than the MGV of the lung. The lung-to-liver ratio is <1 between 24 and 29 weeks and >1 between 30 and 35 weeks. CONCLUSION: The echogenicity of the fetal lung showed a particular changing pattern during pregnancy, which corresponds to morphologic changes of the fetal lung development.     

The fetal Doppler mechanical PR interval: a validation study

OBJECTIVE: To evaluate the accuracy of pulsed Doppler-derived fetal PR interval measurements obtained by physicians participating in a multicenter prospective fetal echocardiographic study. METHODS: Echocardiograms on healthy fetuses were performed and evaluated by 15 pediatric cardiologists/perinatologists across the United States who are participating in a larger clinical trial involving fetuses at risk for autoantibody-associated congenital heart block. Prior to enrolling women in the main trial, each physician was provided with a teaching tape to demonstrate how the pulsed Doppler-derived PR interval is measured. The procedure involves placing a gated pulsed Doppler sample volume in the left ventricle at the junction of the anterior leaflet of the mitral valve and the left ventricular outflow tract in an apical 5-chamber view, and simultaneously obtaining left ventricular filling and emptying. Time intervals are measured from the onset of the mitral A wave (atrial systole) to the onset of the aortic pulsed Doppler tracing (ventricular systole). This represents the mechanical PR interval. Each physician measured the pulsed Doppler-derived fetal PR interval on 5 different subjects recruited from the physician's specific site. To validate each physician's technique, the tapes were sent to a central facility and the same intervals were remeasured by an experienced central reader (D.M.F.). A physician was determined to have adequate ability to measure the fetal PR interval if all 5 measurements were within +/- 30 ms of the central reader's measurements, where 30 ms corresponds to 25% of the mean observed in normative PR interval data. This difference was deemed to be the minimum clinically important difference in Doppler PR interval. RESULTS: Fourteen of the 15 physicians were considered to have adequate ability to measure the fetal PR interval according to our established criterion. The overall mean difference between the physicians and the central reader's measurements was -0.26 +/- 11.04 ms (p = 0.84). In addition, 95% of the observed differences were included in the interval (-22.23 to 21.81), which is well within our clinically acceptable range of +/- 30 ms. CONCLUSIONS: The pulsed Doppler assessment of the mechanical PR interval in the fetus can be accurately performed after minimal training. This technique may be a valuable tool for identification of early and potentially reversible conduction abnormalities in fetuses at risk for more advanced and permanent forms of heart block associated with maternal antibodies to SSA/Ro-SSB/La.     

An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study

Objective.?Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF).

Methods.?This retrospective longitudinal nested case–control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n?=?124); and (2) patients who had a fetal death (n?=?19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis.

Results.?(1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p?<?0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p?<?0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p?=?0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p?<?0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p?<?0.05); (5) The ratio of PlGF/(sVEGFR-1?×?sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94–781%) and significantly lower (44–75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p?<?0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation.

Conclusions.?Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.     

The blood flow velocity waveform in the fetal internal carotid and umbilical artery; its relation to fetal behavioural states in normal pregnancy at 37-38 weeks

The relation between the blood flow velocity waveform in the fetal internal carotid artery (n = 12) and umbilical artery (n = 15) and fetal behavioural states at 37-38 weeks of gestation was studied. In the fetal internal carotid artery, under standardized fetal heart rate conditions, the pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during behavioural state 2F (active sleep) compared with state 1F (quiet sleep) according to the classification by Nijhuis et al. (1982), suggesting increased fetal cerebral blood flow during state 2F. In the umbilical artery, no significant difference in PI between the two behavioural states could be established. This suggests a fetal origin of the state dependency observed in fetal blood flow velocity waveforms.     

The physician-patient relationship before cancer treatment: a prospective longitudinal study

OBJECTIVES: To evaluate quality of life before surgery for genital cancer to determine risk factors that might influence the physician-patient relationship. METHODS: From 1993 until 2003, 129 women with cervical cancer entered this prospective study. Patients were contacted 1 to 5 days before surgery by a psychologist or psychotherapeutically trained physician on the surgical ward. The semistructured interview included questions on the patient's psychosocial well-being according to criteria of the biographic interview technique. The preoperative anxiety level was evaluated by the STAI and quality of life by the Cancer Rehabilitation Evaluation System (CARES) and EORTC questionnaires. Patients were assigned to groups undergoing pelvic exenteration (n = 62) or Wertheim procedure (n = 67). RESULTS: The preoperative anxiety level did not correlate with the treatment modality. Women with a high anxiety level complained of a lack of information which correlated with a dissatisfaction concerning the physician-patient relationship (r = 0.457, P = 0.001). Quality of life in terms of medical interaction and the need for information were indicated to be the most important aspects for cancer patients facing genital surgery. CONCLUSIONS: These data demonstrate the need for information strategies before surgery: first, to reduce anxiety by anticipating future quality of life outcome problems and, second, to improve medical interaction before stressful treatment options.     

Effects of ciprofloxacin and quercetin on fetal brain development: a biochemical and histopathological study

Purpose: Teratogens cause birth defects and malformations while human development is being completed. In pregnancy, urinary tract infection (UTI) is a common health problem caused by bacteria. The fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin can treat various types of bacterial infections successfully. The aim of this study is to determine whether the use of ciprofloxacin during pregnancy causes oxidative stress on brain tissues of the fetus, and whether quercetin contributes to prevent this damage if stress has already occurred.

Materials and methods: In our study, 22 young female Wistar albino rats weighing 250?g were used. Rats were mated overnight in separate plastic cages. Female rats were regarded as pregnant when a vaginal plug was observed, and these were divided into four groups of control, ciprofloxacin, quercetin, and cipro?+?quercetin. Two daily i.p. 20?mg/kg doses of ciprofloxacin were administered to ciprofloxacin group between 7 and 17 d of pregnancy. Throughout the study, daily (20 d) 20?mg/kg quercetin was dissolved in corn oil and administered to the quercetin group by oral gavage. Rats were fed ad libitum throughout the study. Fetuses were taken by C-section on the 20th day of pregnancy. Thereafter, the brain tissues were subjected to histological assessments and biochemical analyzes.

Results: The experimental groups were compared with the control group; ciprofloxacin affected fetal development, especially caused damage to neurons in brain tissue and cause hemorrhagic defects. And also, it was determined that many parameters were affected such as antioxidant parameters, enzyme levels and levels of malondialdehyde (MDA) (a marker of lipid peroxidation). Quercetin is a member of flavonoid with strong antioxidant properties, and our results indicate that the use of ciprofloxacin in pregnancy can result damage to fetal brain tissue.

Conclusions: Unlike these results when some parameters are evaluated it is understood that this harmful effects suppressed by quercetin.     

The effect of routine magnesium supplementation on fetal cardiac time intervals: a fetal magnetocardiographic study

Objectives

Magnesium deficiency in pregnancy is frequent, and in consequence magnesium supplementation is widely used. As magnesium crosses the placental barrier and since the fetal kidney does not excrete magnesium as efficiently as the mature kidney, effects on fetal cardiac time intervals are probable, but still unknown.

Study design

Sixty pregnant women were included in an observational study: 31 patients received oral routine magnesium supplementation. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate electrophysiological rhythm patterns with high temporal resolution. fMCG tracings were analyzed according to a predefined procedure for fetal cardiac time interval (CTI)-detection. fCTI findings (P-wave, PQ-segment, PR-interval, QRS complex, ST segment, T-wave and QTc interval) were registered.

Results

Significant widening of the QRS-complex (p = 0.004) was demonstrated in fetuses whose mothers received magnesium supplementation (240 mg/day) relative to the control group.

Conclusion

Magnesium exposed fetuses demonstrated a prolonged ventricular arousal, but healthy neonatal outcome was found in all exposed fetuses. Although fMCG is a preclinical method and limited in its availability, the procedure could help to monitor fetuses.     

The blood flow velocity waveform in the fetal internal carotid and umbilical artery; its relation to fetal behavioural states in normal pregnancy at 37–38 weeks

Summary. The relation between the blood flow velocity waveform in the fetal internal carotid artery ( n = 12) and umbilical artery ( n = 15) and fetal behavioural states at 37–38 weeks of gestation was studied. In the fetal internal carotid artery, under standardized fetal heart rate conditions, the pulsatility index (PI), as a measure of peripheral vascular resistance, was significantly lower during behavioural state 2F (active sleep) compared with state 1F (quiet sleep) according to the classification by Nijhuis et al . (1982), suggesting increased fetal cerebral blood flow during state 2F. In the umbilical artery, no significant difference in PI between the two behavioural states could be established. This suggests a fetal origin of the state dependency observed in fetal blood flow velocity waveforms.     

The biochemistry of fetal lung development

Surfactant therapy for RDS is likely to become widespread in the near future. Animal data indicate that this will not preclude a role for hormonal acceleration of lung maturation. In studies with prematurely delivered and ventilated fetal rabbits, Fiascone et al. have shown that the administration of betamethasone antenatally improves lung compliance, as does intratracheal administration of excess amounts of adult rabbit natural surfactant. If the two therapies are combined, however, an additive effect is observed. This suggests that some of the effects of glucocorticoids on lung compliance are not related to surfactant. Prior glucocorticoid therapy may provide a benefit that differs from that of surfactant therapy because steroids mature the lungs anatomically and enhance nonsurfactant-related tissue compliance. It is also possible that surfactant therapy itself may be more effective in the presence of larger and increased numbers of alveoli. It thus seems likely that in the future both hormonal enhancement of lung maturation and surfactant therapy may be used in combination to further reduce the morbidity and mortality from RDS.     

A longitudinal study comparing growth in diabetic pregnancies with growth in normal gestations: I. The fetal weight

Diabetes mellitus is associated with fetal growth acceleration and retardation. These aberrations in fetal growth seem to be influenced by a variety of factors including vascular disease, glycemic control, hypertension and smoking. In order to characterize fetal growth under the above conditions, longitudinal sonographic evaluations were performed in 52 pregnant, insulin-dependent diabetic women with the usual monitoring of the patients' metabolic control. Regression analyses revealed that vascular disease and glycemic conditions were the most important influences for growth, with manifestation beyond the second trimester. With stringent glucose control (mean whole blood less than or equal to 100 mg/dl) in the absence of vasculopathy (white classes A, B, C), fetal growth was similar to that in normal pregnancies. In the presence of vasculopathy (white classes D and FR), growth was reduced, especially when near-normal glycemic levels were achieved. Conversely, in poorly controlled diabetic women, enhanced fetal growth were observed in patients with and without vasculopathy. No aberrations in fetal growth were observed, however, before the third trimester. The findings of our study demonstrate that vasculopathy and glycemia are dominant and independent regulators of fetal growth. However, their influences are not manifested in growth changes before the third trimester.