Predicting perinatal outcome through changes in umbilical artery Doppler studies after antenatal corticosteroids in the growth-restricted fetus.

OBJECTIVE: To investigate whether persistently absent umbilical artery end-diastolic flow in the intrauterine growth-restricted fetus after betamethasone administration is associated with altered perinatal outcomes. METHODS: This is a retrospective cohort study of 92 pregnancies complicated by intrauterine growth restriction (IUGR) and absent end-diastolic flow in which antenatal betamethasone was given. Predefined maternal outcomes (maternal age, gestational age at diagnosis of absent end-diastolic flow, gestational age at delivery, preexisting medical conditions) and neonatal outcomes (including birth weight; perinatal mortality; duration of neonatal intensive care unit admission; requirement for intubation, assisted ventilation, inotropic support; duration of supplemental oxygen, assisted ventilation; respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage) were analyzed. RESULTS: Betamethasone administration was associated with a transient return of end-diastolic umbilical artery flow in 58 pregnancies (63%) and persistent absent end-diastolic flow in 34 (37%). Persistent absent end-diastolic flow was seen more frequently in women with prepregnancy medical disorders (59% compared with 24%, P<.001). Neonates from the persistent absent end-diastolic flow subgroup were more likely to require assisted ventilation (93.1% compared with 73.5%, P=.03) and to have longer durations of assisted ventilation (median time 30 days compared with 4 days, P=.03) and supplemental oxygen (median time 45 days compared with 4 days, P=.04). CONCLUSION: Betamethasone administration is associated with a transient return of end-diastolic flow in two thirds of pregnancies complicated by IUGR and umbilical artery absent end-diastolic flow. Persistent absent end-diastolic flow in the umbilical artery after betamethasone administration may identify a subgroup of fetuses with IUGR at further heightened perinatal risk that, as neonates, are more likely to require assisted ventilation and a longer duration of ventilation and supplemental oxygen.

Maternal serum activin A and the prediction of intrauterine growth restriction.

BACKGROUND: Differentiating between the small healthy fetus and the high risk growth restricted fetus remains a significant obstetric challenge. It has been previously shown that maternal activin A levels are increased in association with fetal growth restriction. AIM: To evaluate maternal serum activin A as a marker of fetal growth restriction. METHODS: Prospective cohort study of 62 women referred for fetal assessment because of a clinical suspicion of a small for gestation fetus. Maternal serum levels of activin A were measured with an ELISA. RESULTS: Activin A levels, expressed as median (95% CI) MoMs, were similar in the women with a normal-sized fetus and in those with a healthy small for gestational age fetus, 1.14 (95% CI 1.0-1.5) and 1.31 (95% CI 0.8-2.1), respectively (P = 0.97). Compared to the women with a normal-sized fetus or a healthy small fetus, activin A levels were significantly elevated in the women who had an intrauterine fetal growth restriction fetus 2.37 (95% CI 1.6-3.7; P = 0.01 compared to normal and P = 0.04 compared to healthy small). CONCLUSIONS: These data confirm that circulating activin A is increased in association with fetal growth restriction. However, a single blood sample for activin A will not efficiently discern between healthy and compromised small fetuses.

Uterine artery Doppler velocimetry for the detection of adverse obstetric outcomes in patients with elevated mid-trimester beta-human chorionic gonadotrophin.

AIM: The aim of this study is to review the clinical usefulness of Doppler velocimetry of the uterine artery for the detection of adverse obstetric outcome in a population of women with elevated mid-trimester serum beta-human chorionic gonadotrophin (betahCG). METHODS: Women with an unexplained elevated mid-trimester betahCG level (> or = 4.0 multiples of the median) are offered uterine artery Doppler assessment at 22-24 weeks of gestation. We have audited the clinical usefulness of this practice by reviewing the prevalence of the adverse outcomes of gestational hypertension, intrauterine growth restriction (IUGR) and preterm birth and the predictive capacity of the test when applied to this subgroup of high-risk patients. RESULTS: Sixty-two women had an elevated serum betahCG and underwent Doppler study of uterine artery flow velocity waveform. Notching afforded better predictive utility for any outcome than the resistance index alone or in combination with notching. For a composite adverse outcome of any or all of gestational hypertension, birthweight < or = 10th centile, and preterm delivery, the presence of a uterine notch alone had sensitivity of 30.7% and specificity of 93.8%. For the identification of severe fetal growth restriction (< 5th centile) and/or preeclampsia, the presence of a notch offered a sensitivity of 50%, specificity of 96.3%, a positive likelihood ratio of 13.5, and a negative likelihood ratio of 0.5. CONCLUSIONS: The identification of uterine artery notching by means of Doppler ultrasound as a component of the surveillance of women with unexplained elevated betahCG levels significantly improves the prediction of preeclampsia and/or severe IUGR, although the low prevalence of 13% of these adverse outcomes limits the usefulness of the test in routine clinical practice.

Maternal serum activin A levels in association with intrauterine fetal growth restriction.

OBJECTIVE: To assess maternal serum activin A as a potential marker of fetal growth restriction. DESIGN: A cohort study. SETTING: A maternal-fetal medicine unit, university teaching hospital. POPULATION: Fifty-seven women with a small fetus (less than 10th centile for gestation) referred for assessment of fetal size by ultrasound biometry. METHODS: At the time of presentation for fetal biometry, maternal blood was collected for activin A measurement. The case records of each woman were independently reviewed after delivery and the pregnancy grouped into one of three groups: constitutionally small fetus, intrauterine growth restricted (IUGR) fetus or IUGR fetus and maternal pre-eclampsia (IUGR-pre-eclampsia). Activin A levels in the three groups were compared. MAIN OUTCOME MEASURES: Maternal serum activin A levels. RESULTS: Sixteen of the 57 pregnancies were classified as constitutionally small, 17 as IUGR and 24 as IUGR-pre-eclampsia. Expressed as multiples of a normal median (MoMs), the median (95% CI) activin A level in the constitutionally small pregnancies was 1.12 (0.72-1.39) MoMs significantly lower than the level in both the IUGR pregnancies, 3.00 (1.84-4.11) MoMs, and the IUGR-pre-eclampsia pregnancies, 7.96 (5.73-10.62) MoMs (P = 0.002 and 0.0001 for IUGR vs constitutionally small and IUGR-pre-eclampsia vs constitutionally small, respectively). CONCLUSIONS: Maternal serum activin A may be useful in the assessment of the small for gestational age fetus.

Changes in umbilical artery flow velocity waveforms following maternal administration of betamethasone.

In a retrospective cohort study we have previously shown that administration of betamethasone to women with a pregnancy complicated by absent end-diastolic flow in the umbilical artery (UA) is associated with altered UA flow velocity waveforms. To examine this phenomenon further we undertook a prospective study of 30 similar singleton pregnancies. Umbilical artery FVWs were recorded before and after betamethasone administration using real-time pulsed wave colour flow Doppler. The results of this prospective cohort were similar to those of the retrospective study allowing pooling of the data. Of the 55 total pregnancies with umbilical artery AEDF studied betamethasone administration was associated with the return of end-diastolic flow in 39 (71 per cent; 95 per centCI: 59-83 per cent). The median (range) duration of this change was 3 (1-10) days. There is no evidence that this change has either a beneficial or detrimental effect on foetal health. Administration of betamethasone to women with a pregnancy complicated by umbilical artery AEDF is associated with the transient return of end-diastolic flow in most cases. While the mechanisms underlying this effect are yet to be fully elucidated it has implications for foetal surveillance in these high-risk pregnancies.

Betamethasone associated changes in umbilical artery flow velocity waveforms in multiple pregnancies with umbilical artery absent end diastolic flow.

OBJECTIVES: It has been previously shown that glucocorticoids alter umbilical artery flow velocity waveforms in singleton pregnancies complicated by umbilical artery absent end diastolic flow. Whether similar effects are evident in multiple pregnancies where one fetus has umbilical artery absent end diastolic flow is not known. METHODS: Women with a twin or triplet pregnancy complicated by umbilical artery absent end diastolic flow in one fetus were admitted to hospital for intensive fetal surveillance including daily umbilical artery flow velocity waveform studies, as per hospital protocol. All women received prophylactic betamethasone (11.4 mg x 2, 24 h apart) in anticipation of preterm delivery. RESULTS: Between October 1996 and February 2002, 24 women with a multiple pregnancy complicated by umbilical artery absent end diastolic flow were cared for. Of these, six had a pregnancy with feto-fetal transfusion and excluded from further analysis. Of the remaining 18 women, eight had monochorionic diamniotic twins, eight had dichorionic twins, and two had trichorionic, triamniotic triplets. The median (range) gestation at diagnosis of umbilical artery absent end diastolic flow was 210.5 days (173-241). In nine (50%) of the 18 pregnancies the administration of betamethasone was associated with return of umbilical artery end diastolic flow for a median of 5 days. There was no association between this effect and chorionicity. The median (range) interval from diagnosis of umbilical artery absent end diastolic flow to delivery was 11 days (1-46). CONCLUSIONS: As previously reported in singleton pregnancies, the maternal administration of betamethasone in multiple pregnancies with umbilical artery absent end diastolic flow is associated with a transient return of end diastolic flow.

Optimising the timing for nuchal translucency measurement.

It appears from current evidence that the most effective screening strategy for Down syndrome will involve a combination of first trimester nuchal translucency and serum biochemistry, whether performed in the first or second trimester. The aim of this study was to determine the optimum gestation based upon menstrual dates at which to schedule nuchal translucency (NT) measurement for the evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty-five pregnancies had an ultrasound scan scheduled between 11 and 14 completed weeks of gestation based upon either the last menstrual period (n = 3199) or a prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound scans, with advancing gestation the frequency of missed miscarriage significantly decreased (p = 0.009, chi squared test), as did the need to reschedule a further scan because the gestation of the scheduled scan was too early to measure NT (p < 0.0001, Chi-squared test). In contrast, with advancing gestation the rate of unsuccessful NT measurement because the crown-rump length (CRL) was greater than 84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%) were over gestation at the time of the NT scan. These data suggest that when only the last menstrual period is known the optimum time to schedule a nuchal translucency measurement is at 12 to 13 weeks' gestation.