Routine clinical policy and application of Doppler measurements in suspected intrauterine growth retardation in university hospitals in The Netherlands.

Suspected intrauterine growth retardation is a clinical problem with financial consequences, as it can lead to costly, in-hospital fetal monitoring. At present, no prospective 'gold standard' for growth retardation exists. Hence, a proportion of the fetuses suspected are likely to be genetically small, in which case hospitalization is superfluous. Doppler ultrasound measurements might be applied to differentiate between growth retardation and genetically based smallness. Before the diagnostic effectiveness of Doppler ultrasound can be evaluated, however, the magnitude of the problem of suspected intrauterine growth retardation, or what it is experienced to be, must be known. The occurrence of suspected intrauterine growth retardation, routine clinical policy, and use of Doppler ultrasound techniques were assessed by a questionnaire among obstetricians in the university hospitals in The Netherlands. Of the obstetricians approached, 81% responded (59/73). Intrauterine growth retardation was defined mainly by a lag in fundal height of at least 3 weeks. It is suspected in about 11% of singleton pregnancies. An estimated 70% of those suspected of growth retardation are hospitalised. Fewer than half of the respondents thought Doppler ultrasound measurements an asset to antenatal diagnosis. Five of the eight university hospital clinics used Doppler measurements in clinical decision making. Sixty percent of responding obstetricians were of the opinion that there was a 'routine clinical policy' in suspected intrauterine growth retardation.

Fetal Candida sepsis at midgestation: a case report.

A patient presented with intrauterine fetal death at 21 weeks. A Candida vaginitis was treated at 18 weeks of gestation. Fatal fetal Candida sepsis caused by Candida albicans can occur in the absence of known risk factors such as prolonged rupture of membranes, the presence of an intrauterine contraceptive device or cervical cerclage.

Activated protein C resistance during in vitro fertilization treatment.

Acquired resistance to the anticoagulant action of activated protein C (APC) has been proposed to explain the increased risk of venous thrombosis associated with pregnancy, hormone replacement therapy and the use of oral contraceptives. In this study, we have investigated whether the hormonal changes induced during in vitro fertilization (IVF) treatment are also associated with acquired APC resistance. Twenty-nine women, who were planned for an IVF cycle, donated blood at four time points during treatment, i.e. at baseline, down-regulation, hyperstimulation and luteal support. In the plasma samples, APC sensitivity ratios (APCsr) and the levels of progesterone and estradiol were measured. The changes in plasma concentrations of hormones were in accordance with literature. The APCsr increased significantly during hyperstimulation and remained high during luteal support. The extent of APC resistance occurring during IVF treatment was comparable to that observed during the use of second generation OC and was less pronounced than that occurring during pregnancy. The change in estradiol between baseline and hyperstimulation correlated with the change in APCsr. Although this suggests that plasma estrogen levels are an important determinant for acquired APC resistance, it remains to be established which plasma proteins are responsible for estrogen-induced APC resistance.

Variation in early fetal growth.

OBJECTIVE: To obtain more information on interindividual variation in early fetal growth by using early fetal ultrasound parameters. DESIGN AND SUBJECTS: Individual fetal growth was assessed prospectively in 109 pregnancies by serial ultrasound measurements of CRL and BPD. From the resulting biometry data, individual CRL and BPD growth curves for each fetus were constructed and compared. RESULTS: A high correlation was found between growth rate and the start of growth of CRL and BPD, r = 0.79 and r = 0.84, respectively. CONCLUSION: The high correlation between growth rate and the start of growth of CRL and BPD might imply that a fetus with an impeded start of growth generally has a higher growth rate. This could be called an early pregnancy 'catch-up growth'. This interindividual variation of starting time and fetal growth rate may influence the assessment of gestational age in early pregnancy, if a CRL-curve obtained from cross-sectional measurements is used as a reference. BPD seems to be a more constant parameter with less variation in growth rate.

Doppler ultrasonography in suspected intrauterine growth retardation: a randomized clinical trial.

A randomized clinical trial was performed to test the hypothesis that if suspected intrauterine growth retardation (IUGR) is associated with normal umbilical artery Doppler ultrasound findings, hospitalization can safely be avoided. One hundred and fifty women with singleton pregnancies and suspected IUGR were randomized between an intervention (n = 74) and a control group (n = 76). In the intervention group, clinicians were strongly requested not to hospitalize for suspected IUGR if the Doppler findings were normal. In the control group, the Doppler results were not revealed and the participants received the standard management for suspected IUGR. Endpoints of the trial were: costs in terms of hospitalization, perinatal outcome, neurological development, and postnatal growth. Duration of hospitalization was significantly shorter in the intervention group than in the control group. Contrary to expectations, the hospitalization rate during pregnancy in the intervention group was not below that of the control group. This negative finding was partly due to the admission of patients in the intervention group despite their normal Doppler results. Moreover, the trial might have induced a more critical attitude towards hospitalization in suspected IUGR, decreasing admission in the control group. No clear differences were found in perinatal outcome, neurological development, or postnatal growth. The results suggest that normal umbilical artery Doppler findings in suspected cases of IUGR justify outpatient management.

Comparison of blood velocity waveform indices recorded by pulsed Doppler and continuous wave Doppler in the umbilical artery.

A comparison was made between the AB ratio, resistance index (RI), and pulsatility index (PI), calculated from tracings obtained by pulsed Doppler (PD) and continuous wave (CW) Doppler devices in 14 uncomplicated singleton pregnancies. The AB ratio, RI, and PI were a slightly higher for the CW Doppler compared to the PD system, although not significantly (p = 0.18, p = 0.21, and p = 0.44, respectively). The difference in signal to noise ratio (S/N ratio) between the PD and CW Doppler systems was felt to be the reason for the discrepancy in the calculated velocity waveform indices.

Interexaminer variability of fetal Doppler velocity waveforms.

A study was made of the interexaminer variability of Doppler velocity waveform determinations of the fetal circulation. Three investigators recorded Doppler ultrasound tracings of the blood velocity in the fetal thoracic and abdominal aorta and umbilical artery in 23 uncomplicated pregnancies. Of these recordings, a hard copy was made, and the pulsatility indices were computed. An analysis of variance was performed and the reliability calculated. The interexaminer variability was nonsignificant in measurements of the three blood vessels under examination. Both thoracic and abdominal aorta measurements showed poor reliability (intraclass correlation coefficient of reliability 0.30 and 0.19, respectively) due to high random errors. Umbilical artery measurements showed a better reliability (intraclass correlation coefficient of reliability 0.61), and, therefore, these hold the greatest clinical applicability.

Effect of in vitro fertilization treatment and subsequent pregnancy on the protein C pathway.

Thirty-three women who were planned for an in vitro fertilization (IVF) cycle donated blood at four time points during treatment: at baseline, after downregulation, hyperstimulation and luteal support. Levels of progesterone, 17beta-oestradiol and indicators of the protein C pathway, i.e. activated protein C sensitivity ratios (APCsr), protein C, protein C inhibitor and protein S were measured. Compared with baseline, oestradiol decreased twofold at downregulation and increased 40-fold at hyperstimulation. Progesterone was elevated 2.5-fold at hyperstimulation and 40-fold at luteal support. The APCsr increased slightly at downregulation, significantly increased during hyperstimulation and remained high during luteal support. The plasma levels of the anticoagulant proteins did not change or changed moderately during treatment. During downregulation, progesterone correlated negatively with APCsr (r = -0.398, P = 0.024). At hyperstimulation oestradiol correlated with the APCsr (r =0.615, P < 0.0005). Moreover, there was a significant correlation (r = 0.599, P < 0.0005) between the difference in baseline and hyperstimulation values of oestradiol (Delta E2 = 6.6 nmol/l) and the APCsr (Delta APCsr = 0.30). Six women who participated in this study became pregnant. Compared with baseline, the APCsr was increased 1.9-fold (Delta APCsr = 1.48) and free protein S free level decreased 30% at 7 weeks of pregnancy. This study demonstrates that despite the considerable changes in endogenous oestradiol and progesterone during an IVF cycle, changes in plasma levels of anticoagulant proteins are moderate. The significant increase in the APCsr during hyperstimulation indicates that acquired APC resistance observed during sex steroid hormone changes in women is at least partially caused by high oestrogen levels. Our findings demonstrate that IVF treatment is accompanied by the development of a mild prothrombotic condition.