The TRUFFLE study; fetal monitoring indications for delivery in 310 IUGR infants with 2 year's outcome delivered before 32 weeks of gestation.

OBJECTIVE: In the TRUFFLE study on outcome of early fetal growth restriction women were allocated to three timing of delivery plans according to antenatal monitoring strategies based on reduced computerized cardiotocographic heart rate short term variation (c-CTG STV) , early Ductus Venosus (DV p95) or late DV (DV noA) changes. However, many infants were per protocol delivered because of 'safety net' criteria, or for maternal indications, or 'other fetal indications' or after 32 weeks of gestation when the protocol was not applied anymore. It was the objective of the present post-hoc sub-analysis to investigate the indications for delivery in relation to outcome at 2 years in infants delivered before 32 weeks, to come to a further refinement of management proposals. METHODS: we included all 310 cases of the TRUFFLE study with known outcome at 2 years corrected age and 7 perinatal and infant deaths, apart from 7 cases with an inevitable death. Data were analyzed according to the randomization allocation and specified for the intervention indication. RESULTS: overall only 32% of fetuses born alive were delivered according to the specified monitoring parameter for indication for delivery. 38% were delivered because of safety net criteria, 15% because of other fetal reasons and 15% because of maternal reasons. In the c-CTG arm 51% of infants were delivered because of reduced STV. In the DV p95 arm 34% were delivered because of an abnormal DV and in the DV no A wave arm only 10% of cases were delivered accordingly. The majority of fetuses in the DV arms delivered for safety net criteria were delivered because of spontaneous decelerations. Two year's intact survival was highest in the combined DV arms as compared to the c-CTG arm (p = 0.05 when life born, p = 0.21 including fetal death), with no difference between the DV arms. Poorer outcome in the c-CTG arm was restricted to fetuses delivered because of decelerations in the safety net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significant higher intact survival. CONCLUSIONS: In this sub-analysis of fetuses delivered before 32 weeks the majority of infants were delivered for other reasons than according to the allocated CTG or DV monitoring strategy. Since in the DV arms CTG criteria were used as safety net criteria, but in the c-CTG arms no DV safety net criteria were applied, we speculate that the slightly poorer outcome in the CTG arm might be explained by absence of DV data. Optimal timing of delivery of the early IUGR fetus may therefore best be achieved by monitoring them longitudinally with DV and CTG monitoring

How to monitor pregnancies complicated by fetal growth restriction and delivery below 32 weeks: a post-hoc sensitivity analysis of the TRUFFLE-study.

OBJECTIVES: In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. METHODS: We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: The primary outcome (two year survival without neurological impairment) occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however the difference was not statistically significant (p = 0.21). Nevertheless, in surviving infants 93% was free of neurological impairment in the DV groups versus 85% in the CTG-STV group (p = 0.049). All fetal deaths (n = 7) occurred in women allocated to DV monitoring, which explains this difference. Assessment of the monitoring parameters that were obtained shortly before fetal death in these 7 cases showed an abnormal CTG in only one. Multivariable regression analysis of factors at study entry demonstrated that higher gestational age, larger estimated fetal weight 50th percentile ratio and lower U/C ratio were significantly associated with the (normal) primary outcome. Allocation to the DV groups had a smaller effect, but remained in the model (p < 0.1). Assessment of the last monitoring data before delivery showed that in the CTG-STV group abnormal fetal arterial Doppler was significantly associated with adverse outcome. In contrast, in the DV groups an abnormal DV was the only fetal monitoring parameter that was associated with adverse infant outcome, while fetal arterial Doppler, STV below CTG-group cut-off or recurrent fetal heart rate decelerations were not. CONCLUSIONS: In accordance with the results of the overall TRUFFLE study of the monitoring-intervention management of very early severe FGR we found that the difference in the proportion of infants surviving without neuroimpairment (the primary endpoint) was non-significant when comparing timing of delivery with or without changes in the DV waveform. However, the uneven distribution of fetal deaths towards the DV groups was likely by chance, and among surviving children neurological outcomes were better. Before 32 weeks, delaying delivery until abnormalities in DVPI or STV and/or recurrent decelerations occur, as defined by the study protocol, is therefore probably safe and possibly benefits long-term outcome

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

Effects of antenatal betamethasone on fetal Doppler indices and short term fetal heart rate variation in early growth restricted fetuses

Purpose To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses.Materials and Methods Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (base-line value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV.Results We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001).Conclusion Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.Developmen

Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks.

OBJECTIVE: To provide individualized risk prediction of severe adverse pregnancy outcome based on uterine artery Doppler screening at 23 weeks. METHODS: Color Doppler assessment of the uterine arteries was carried out in 5121 women attending for routine care at 23 weeks in two inner-city obstetric units. The mean uterine artery pulsatility index (PI) was calculated, and the likelihood ratios in relation to PI were generated for severe adverse outcome. This was defined as fetal death, placental abruption, and delivery before 34 weeks associated with preeclampsia and birth weight less than the 10th centile. RESULTS: The likelihood of severe adverse pregnancy outcome increased quadratically with mean uterine artery PI. This relationship was not affected by maternal age, ethnicity, or parity. At a mean PI of 1.45, the 95th centile for our population, the likelihood ratio for severe adverse pregnancy outcome was 5. Cigarette smoking had an additional contribution to PI in predicting severe adverse outcome, roughly doubling the risk for a given PI. CONCLUSION: The individualized risk of severe adverse pregnancy outcome can be determined by uterine artery Doppler screening at 23 weeks and knowledge of cigarette smoking history. Such individualized risk would allow ultrasound resources and clinical follow-up to be tailored to the pregnant woman for the most appropriate use of antenatal care

Palliative care for prenatally diagnosed lethal fetal abnormality

Diagnosis of lethal fetal abnormality raises challenging decisions for parents and clinicians. Most parents opt for termination, which may include feticide. Advances in imaging seem unlikely to lead to earlier diagnoses. Perinatal palliative care offers an alternative. Parental decision making and the clinical aspects of perinatal palliative care were studied after a prenatal diagnosis of lethal fetal abnormality in 20 pregnancies. 40% of parents chose to continue the pregnancy and pursue perinatal palliative care. Six of these eight babies were liveborn and lived for between 1½ h and 3 weeks