Longitudinal study of computerised cardiotocography in early fetal growth restriction.

OBJECTIVES: To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term fetal heart rate (FHR) variation (STV) can be used for identifying imminent fetal distress and if abnormalities of FHR registration associate with two-year infant outcome. METHODS: The original TRUFFLE study assessed if in early FGR the use of ductus venosus Doppler pulsatility index (DVPI), in combination with a safety-net of very low STV and / or recurrent decelerations, could improve two-year infant survival without neurological impairment in comparison to computerised cardiotocography (cCTG) with STV calculation only. For this secondary analysis we selected women, who delivered before 32 weeks, and who had consecutive STV data for more than 3 days before delivery, and known infant two-year outcome data. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values except the last one were calculated. Life table analysis and Cox regression analysis were used to calculate the day by day risk for a low STV or very low STV and / or FHR decelerations (DVPI group safety-net) and to assess which parameters were associated to this risk. Furthermore, it was assessed if STV pattern, lowest STV value or recurrent FHR decelerations were associated with two-year infant outcome. RESULTS: One hundred and fourty-nine women matched the inclusion criteria. Using the individual STV regression lines prediction of a last STV below the cCTG-group cut-off had a sensitivity of 0.42 and specificity of 0.91. For each day after inclusion the median risk for a low STV(cCTG criteria) was 4% (Interquartile range (IQR) 2% to 7%) and for a very low STV and / or recurrent decelerations (DVPI safety-net criteria) 5% (IQR 4 to 7%). Measures of STV pattern, fetal Doppler (arterial or venous), birthweight MoM or gestational age did not improve daily risk prediction usefully. There was no association of STV regression coefficients, a last low STV or /and recurrent decelerations with short or long term infant outcomes. CONCLUSION: The TRUFFLE study showed that a strategy of DVPI monitoring with a safety-net delivery indication of very low STV and / or recurrent decelerations could increase infant survival without neurological impairment at two years. This post-hoc analysis demonstrates that in early FGR the day by day risk of an abnormal cCTG as defined by the DVPI protocol safety-net criteria is 5%, and that prediction of this is not possible. This supports the rationale for cCTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DVPI is in the normal range

Neurodevelopmental outcome of preterm infants with severe intraventricular hemorrhage and therapy for post-hemorrhagic ventricular dilatation

Objective To evaluate the neurodevelopmental outcome of preterm infants 8,with a grade III or IV hemorrhage and to assess the effect of routine low-threshold therapy of post-hemorrhagic ventricular dilatation (PRVD) on neurodevelopmental outcome. Study design Of the 214 preterm infants ( Results PHVD developed significantly more often in the surviving infants with a grade III hemorrhage (53/68, 78%) than in infants with a grade IV hemorrhage (40/76, 53%; P = .002). Intervention for PHVD was required significantly more often in the grade III group, than in the grade IV group (P <.001). In the grade III group, cerebral palsy developed in 5 of the 68 surviving infants (7.4%), compared with 37 of the 76 infants (48.7%) with a grade IV hemorrhage (P <.001). The mean developmental quotient (DQ) in the grade III group was 99, and in the grade IV-group it was 95 at 24 months corrected age. Conclusions Short-term neurodevelopmental outcome of preterm infants with grade III or IV hemorrhage was better than reported earlier. Requiring intervention for PHVD only had a negative effect on DQ in infants with a grade W hemorrhage. Infants with cerebral palsy had significantly lower DQs, irrespective of the severity of IVH

Non-right-handedness in children born extremely preterm: Relation to early neuroimaging and long-term neurodevelopment.

OBJECTIVE:This study aimed to define the prevalence and predictors of non-right-handedness and its link to long-term neurodevelopmental outcome and early neuroimaging in a cohort of children born extremely preterm (<28 weeks gestation). METHODS:179 children born extremely preterm admitted to the Neonatal Intensive Care Unit of our tertiary centre from 2006-2013 were included in a prospective longitudinal cohort study. Collected data included perinatal data, demographic characteristics, neurodevelopmental outcome measured by the Bayley Scales of Infant and Toddler Development at 2 years and the Movement Assessment Battery for Children at 5 years, and handedness measured at school age (4-8 years). Magnetic resonance imaging performed at term-equivalent age was used to study overt brain injury. Diffusion tensor imaging scans were analysed using tract-based spatial statistics to assess white matter microstructure in relation to handedness and neurodevelopmental outcome. RESULTS:The prevalence of non-right-handedness in our cohort was 22.9%, compared to 12% in the general population. Weaker fine motor skills at 2 years and paternal non-right-handedness were significantly associated with non-right-handedness. Both overt brain injury and fractional anisotropy of white matter structures on diffusion tensor images were not related to handedness. Fractional anisotropy measurements showed significant associations with neurodevelopmental outcome. CONCLUSIONS:Our data show that non-right-handedness in children born extremely preterm occurs almost twice as frequently as in the general population. In the studied population, non-right-handedness is associated with weaker fine motor skills and paternal non-right-handedness, but not with overt brain injury or microstructural brain development on early magnetic resonance imaging

2 Year Neurodevelopmental and Intermediate Perinatal Outcomes in Infants With Very Preterm Fetal Growth Restriction (TRUFFLE):A Randomised Trial

There is no consensus on the best methods to monitor fetal growth restriction or to trigger delivery. Previous studies have suggested that the abnormal ductus venosus (DV) pulsatility index is the best discriminating variable for neonatal outcome. This study hypothesized that changes in the fetal DV Doppler waveform, rather than cardiotocograph short-term variation, should be used as indications for delivery. The study (TRUFFLE [TRrial of Umbilical and Fetal Flow in Europe]) was conducted in 20 tertiary-care centers in 5 European countries from January 1, 2005, to October 1, 2010. Women were assigned randomly to 3 different groups. One group decided on the timing of delivery with criteria for reduced short-term variation (CTG STV). The others assessed timing of delivery based on abnormalities of the DV waveform. In the second group, delivery timing was based on early DV changes, and in the third group, delivery timing was based on late DV changes. Early DV changes were defined as pulsatility index greater than the 95th percentile (DV p95), and late DV changes were defined as no or reversed flow in the DV A wave (DV no A). Survival without neurodevelopmental impairment at 2 years of age, corrected for prematurity, was the primary outcome. Data were obtained for 503 women included in the study. Of those, 461 infants survived until 2 years of age, and 402 completed follow up at 2 years. Of the 503 infants, 354 (69%) survived without severe neonatal morbidity. One hundred forty-four infants were assigned to the CTG STV group, of whom 111 survived without impairment (77%). Of the 142 assigned to the DV-p95 group, 118 (84%) survived without impairment, and 133 (85%) of 157 survived without impairment in the DV-no-A group (P-trend = 0.09). In the CTG STV group, there were 13 deaths in 166 infants (8%); in the DV p85 group, 11 (7%) deaths of 167, and in the DV-no-A group, 17 (10%) of 170 (P-trend = 0.35). Impairment in survivors was found in 15% of the CTG STV group (20 of 131), 9% in the DV-p95 group (12 or 131), and 5% of the DV-no-A group (7 of 140) (P-trend = 0.004). No differences in short-term outcomes or baseline variables were seen between the 3 study groups. Improved outcome in survivors was shown in the DV-no-A group compared with the CTG STV group (P-trend = 0.005). At 2 years, neuroimpairment was less frequent in the DV-no-A group than in the CTG STV group, and these findings support waiting for late DV changes, contrasting with previous study suggesting a worse outcome is associated with this method

Longitudinal study of computerized cardiotocography in early fetal growth restriction

Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. Methods: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome. Results: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2–7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4–7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes. Conclusion: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range

Ward & Branstetter ESM figures from The acacia ants revisited: convergent evolution and biogeographic context in an iconic ant/plant mutualism

Electronic supplementary material, figures S1-S