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.

Pre-eclampsia- an additional risk factor for cognitive impairment at school age after intrauterine growth restriction and very preterm birth.

OBJECTIVE: To explore the possible influence of pre-eclampsia on cognitive outcome in children born very preterm after intrauterine growth restriction (IUGR) and abnormal umbilical artery blood flow. METHODS: Cognitive function was evaluated at 5-8 years of age with Wechsler scales in 34 children born before 30 gestational weeks after IUGR (PT-IUGR) (11 children were exposed to maternal pre-eclampsia, 23 non-exposed) and in 34 children with no maternal pre-eclampsia and birth weight appropriate-for-gestational age (PT-AGA) matched for gestational age at birth, gender and age at examination. RESULTS: The subjects in the PT-IUGR group exposed to maternal pre-eclampsia had lower mean verbal IQ (VIQ) (mean ± SD 74 ± 16) and lower full scale IQ (FSIQ) (70 ± 19) in comparison with both the non-exposed PT-IUGR (VIQ 89 ± 15; p=0.013; FSIQ 83 ± 14, p=0.029), and, the PT-AGA group (VIQ 96 ± 15, p<0.001; FSIQ 90 ± 14, p=0.001). The differences remained significant after adjustment for known confounders. VIQ and FSIQ did not differ between the non-exposed IUGR and PT-AGA children. CONCLUSION: Fetal exposure to maternal pre-eclampsia seems to have an additional negative impact to that of IUGR on cognitive function in children born very preterm.

Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow.

OBJECTIVES: To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. METHODS: We examined 19 young adults (aged 22-25 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. RESULTS: The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (P < 0.05). The aortic pressure augmentation index was higher in the IUGR group (P < 0.05). The common carotid artery diameter, intima-media thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. CONCLUSIONS: IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.

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.

Intrauterine infection may be a major cause of stillbirth in Sweden.

AIM OF THE STUDY: To investigate intrauterine infection as a cause for unexplained stillbirth. METHODS: Chorioamnionitis was studied in a material of stillbirths (117 subjects from the years 1985-1994) from a region in the south Sweden. Control material (126 alive and healthy newborns and with healthy mothers) was gathered from the same region. RESULTS: Chorioamnionitis was a common diagnosis both with stillbirths and 'healthy' deliveries (82 and 68%, respectively). Extension of the inflammation to decidua basalis was seven times more common among stillbirths than among controls (odds ratio 7.2, confidence interval 2.8-21.9). The most common bacteria found at cultures were Escherichia coli, Coagulase negative staphylococcus, Enterococcus faecalis and group B Streptococcus. The risk for stillbirth was doubled if both inflammation and bacteria were present (odds ratio 2.3, confidence interval 0.92-5.8). Meconium discharge was more common among stillbirths than controls (odds ratio=4.7, confidence interval 1.7-14). There were no differences in any respect regarding macerated and non-macerated stillbirths. Our findings are similar to the results from studies in developing countries except for the higher incidence of stillbirths in such countries. CONCLUSIONS: Thus, a large part of otherwise unexplained stillbirths might be due to ascending infections.