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Objective: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5 th centile, and analyze their association with adverse perinatal outcome., Methods: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5 th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses., Results: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10 -3  mm 2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10 -3  mm 2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10 -3  mm 2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44))., Conclusion: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders., Methods: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods., Results: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9)., Conclusion: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR., Design: Population-based cohort study., Setting: All maternity units in 25 French regions in 2011., Population: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies., Methods: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth., Main Outcomes Measures: Live birth and survival to discharge from neonatal care., Results: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models., Conclusion: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed., Tweetable Abstract: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Objective: To test whether being small for gestational age, defined as having a birthweight less than the 10th centile of intrauterine growth references, is a risk factor for preterm delivery for singleton live births., Design: A case-control study., Setting: Maternity hospitals in 16 European countries., Sample: Four thousand and seven hundred preterm infants between 22 and 36 completed weeks of gestation and 6,460 control infants between 37 and 40 weeks of gestation., Methods: Newborn babies are identified as being small for gestational age using customized reference standards derived from models of fetal growth. The impact of being small for gestational age on preterm delivery is estimated using logistic regression., Main Outcome Measure: Spontaneous or induced preterm delivery., Results: Being small for gestational age is significantly associated with preterm birth, although the magnitude of this association differs greatly by type of delivery and gestational age. Over 40% of induced preterm births for reasons other than the premature rupture of membranes are small for gestational age compared with 10.7% of control infants (OR 6.41). For spontaneous or premature rupture of membranes related preterm births, the association is also significant, but weaker (OR 1.51). The relationship between growth restriction and preterm delivery is strongest for preterm births before 34 weeks of gestation., Conclusions: These findings highlight the phenomenon of abnormal fetal growth in all premature infants and, in particular, infants delivered by medical decision for reasons other than premature rupture of membranes. The observed association between being small for gestational age and preterm delivery among spontaneous preterm births merits further attention because the causal mechanisms are not well understood.

Objective: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR.Design: Population-based cohort study.Setting: All maternity units in 25 French regions in 2011.Population: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies.Methods: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth.Main Outcomes Measures: Live birth and survival to discharge from neonatal care.Results: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models.Conclusion: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed.Tweetable Abstract: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths. [ABSTRACT FROM AUTHOR]