Infant outcome after active management of early-onset fetal growth restriction with absent or reversed umbilical artery blood flow.

OBJECTIVE: To describe the short- and long-term outcomes of infants with early-onset fetal growth restriction (FGR) and umbilical artery absent or reversed end-diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively. METHODS: This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early-onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level-3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small-for-gestational-age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non-FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery. RESULTS: There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non-FGR group. The FGR infants had a median birth weight of 630 g (range, 340-1165 g) and gestational age at birth of 187 days (range, 164-209 days), as compared with 950 g (range, 470-2194 g) and 185 days (range, 154-209 days), respectively, in the non-FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non-FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non-FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent (P = 0.008, P < 0.001 and P = 0.017, respectively). In the FGR group, the survival rate at 2 years (83% of liveborn infants) and the rate of cerebral palsy (7%) did not differ significantly from those in the non-FGR group (82% and 8%, respectively). The rate of survival without neurodevelopmental impairment was higher in the non-FGR group (83%) than in the FGR group (62%) (P < 0.001), as well as in infants in the FGR group delivered at or after 26 weeks (72%) compared with those delivered before 26 weeks (40%) (P = 0.003). Within the FGR group, outcomes were similar between twins and singletons and, in those who survived beyond 2 years, outcomes were similar between fetuses with absent and those with reversed end-diastolic flow in the umbilical artery. CONCLUSIONS: Infants delivered very preterm after severe FGR with AREDF in the umbilical artery had a similar rate of survival as did non-FGR infants of corresponding gestational age; however, they were at higher risk of neurodevelopmental impairment, the risk being most pronounced following birth before 26 weeks. Gestational age remains an important factor associated with the prognosis of early-onset FGR; nevertheless, the present results support the hypothesis, which should be tested prospectively, that fetuses with early-onset FGR and umbilical artery AREDF may benefit from early intervention rather than expectant management, and that umbilical artery Doppler findings could be incorporated into clinical protocols for cases very early in gestation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Extent of absent end-diastolic flow in umbilical artery and outcome of pregnancy.

OBJECTIVE: To investigate if the extent of absent end-diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome. METHODS: This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (Ta /Ttot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the Ta /Ttot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed. RESULTS: A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163-279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320-3326 g) and deviation from expected birth weight (standard deviation score) was -2.975 (range, -6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the Ta /Ttot ratio in the total study group. Mean Ta /Ttot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively (P = 0.002). For fetuses examined before 30 weeks' gestation, a Ta /Ttot ratio cut-off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver-operating-characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66). CONCLUSIONS: In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth-restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision-making in very preterm growth-restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Effect of maternal betamethasone on fetal and uteroplacental blood flow velocity waveforms.

OBJECTIVES: To investigate the effects of antenatal betamethasone on fetal and uteroplacental hemodynamics. METHODS: The study comprised 33 women with singleton high-risk pregnancies (23-33 weeks; 27 pregnancies < 30 weeks) not in labor, but at risk for preterm delivery based on fetal or maternal indications. They were treated with two doses of 12 mg betamethasone intramuscularly 24 h apart to enhance fetal lung maturity. Flow velocity waveforms were recorded with Doppler ultrasound from the umbilical artery, the fetal middle cerebral artery, the ductus venosus and both maternal uterine arteries, once before and twice after betamethasone administration. RESULTS: Twenty-one (64%) women delivered within 4 days, nine (27%) women within 5-7 days and three (9%) within 8-15 days after the first dose of betamethasone. Two days after betamethasone, a decrease in pulsatility index was found in the umbilical artery (P = 0.0002) and ductus venosus (P = 0.003). Changes in the umbilical artery waveform from reversed to absent, and from absent to positive diastolic flow, were noted in 12 of 15 cases (P < 0.01). After 4 days, umbilical artery and ductus venosus velocity waveforms in the undelivered fetuses either returned to the type of waveform observed before treatment or showed further deterioration. No significant effects of betamethasone were observed in the fetal middle cerebral artery and uteroplacental circulation. CONCLUSIONS: Maternal antenatal betamethasone resulted in a significant transient change in the velocity waveform and a decrease in the pulsatility index in the umbilical artery and ductus venosus, but did not influence uteroplacental circulation. These findings indicate a direct effect of betamethasone on fetal circulation.

Ductus venosus blood flow velocity waveform in diabetic pregnancies.

OBJECTIVE: Maternal diabetes during pregnancy is associated with congenital cardiac malformations and hypertrophic cardiomyopathy. Blood flow in the ductus venosus (DV) has been postulated to reflect cardiac function. The aim of our study was to investigate if diabetic pregnancies exhibit abnormal DV hemodynamics, hence indicating changes in fetal cardiac function. METHODS: The pulsatility index of the DV (DV-PI) was analyzed retrospectively in 142 diabetic patients and compared to previously published DV-PI reference values from a non-diabetic low-risk population. DV values were then correlated with maternal glycosylated hemoglobin (HbA1c). RESULTS: DV-PI was significantly higher in pregnancies complicated by either pre-existing insulin-dependent (DM) or gestational diabetes when compared with normal reference values. Increased DV-PI values were still evident in both diabetic groups when neonates that were small-for-gestational age and neonates with pathological umbilical blood flow pattern were excluded from the analysis. In DM pregnancies a statistically significant correlation was found between DV-PI and maternal HbA1c. CONCLUSION: Diabetic pregnancies exhibit increased DV-PI values when compared to a normal low-risk pregnant population, possibly indicating a fetal cardiac effect.

Uterine venous blood flow in normal and complicated pregnancies: a methodological study.

OBJECTIVE: To investigate the possibility of recording Doppler flow signals from the maternal uterine veins (UtVs) during pregnancy and to assess the relationship between UtV signals and other Doppler parameters as well as pregnancy outcomes. METHODS: Transabdominal Doppler ultrasound examination of the UtVs on both sides of the uterus was performed in 40 normal and 44 high-risk singleton pregnancies at 23-39 weeks' gestation. The UtV was identified using color Doppler imaging and the flow velocity signals of the UtV and uterine artery (UtA) were recorded. Morphological examination of the placenta was carried out in 45 of the pregnancies (14 uncomplicated and 31 high-risk pregnancies). RESULTS: Flow-velocity signals of the UtVs were recorded from at least one side of the uterus in all patients (success rate of 81 and 89% for the right and left UtV, respectively). Three types of flow-velocity pattern were identified: continuous non-pulsatile flow (Type I, n = 70), pulsatile flow with a notch touching the zero line (Type II, n = 6) and pulsatile flow with absent flow signals for part of the heart cycle (Type III, n = 8). The UtA pulsatility index was significantly higher in women with UtV Types II and III than in those with UtV Type I (P = 0.039). Similarly, UtV Types II and III were more often found in pregnancies with bilateral UtA notching (P = 0.013) and with UtA score 3-4 (P = 0.024) than in those with normal UtA. No statistically significant association was found between the UtV flow pattern and abnormal histopathological findings in the placenta, or between the UtV and umbilical artery findings. CONCLUSION: It is possible to record Doppler signals from the UtVs in the late second and third trimesters of pregnancy. Pulsatile flow-velocity patterns of the UtVs are associated with abnormal UtA Doppler findings.

Early intervention in management of very preterm growth-restricted fetuses: 2-year outcome of infants delivered on fetal indication before 30 gestational weeks.

OBJECTIVES: To describe the outcome of growth-restricted fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks. METHODS: Between 1998 and 2004, 42 fetuses with intrauterine growth restriction (IUGR) and ARED in the umbilical artery were delivered liveborn by Cesarean section on fetal indication before 30 gestational weeks. The median gestational age at delivery was 27 + 1 (range, 24 + 4 to 29 + 5) weeks. An additional four fetuses died in utero at a median gestational age of 24 + 2 (range, 23 + 5 to 25 + 4) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared with those in two control groups: all 371 liveborn infants delivered at < 30 weeks during the corresponding time period (Group A) and a subset of these, 42 matched infants without IUGR (Group B). RESULTS: Thirty-two fetuses (76%) [corrected] were delivered within 48 h of the occurrence of ARED (25 absent, seven reversed end-diastolic flow). The remaining 10 fetuses (five absent, five reversed end-diastolic flow) were monitored for a median of 6.5 (range, 3-18) days before delivery. One infant died in the neonatal period and three during the first year of postnatal life (2-year survival 90%). The incidence of chronic lung disease was higher in the ARED Group than in Control Groups A and B (P = 0.001 and P = 0.03, respectively). There were no differences between the groups in the occurrence of necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of the index group compared with 11% and 17% of Control Groups A and B (P > 0.05). CONCLUSIONS: Very preterm growth-restricted fetuses with umbilical artery ARED delivered on fetal indication, in most cases before the occurrence of severe changes in the ductus venosus velocity waveforms and/or fetal heart rate tracings, showed high 2-year survival and low morbidity.