Objectives To evaluate pregnancy and postnatal outcomes of fetuses with NT between 95th and 99th percentile and whether they could benefit from further investigations rather that routine scans. Design Retrospective multicenter observational study. Setting Two Italian Fetal Medicine centre Population All cases with NT between 95th and 99th percentile (667) among women undergoing NT measurement between January 2015 and December 2020. Methods Unfavourable outcome was considered as: miscarriage or intrauterine fetal death (IUFD), chromosomal abnormality/genetic syndrome, major malformation or neurodevelopmental delay. Study population outcomes were compared with general population. Main Outcome Measures Unfavourable pregnancy and postnatal outcomes. Results The rate of unfavourable outcome was 25.44%. We reported: 6 (0.90%) second trimester miscarriage or IUFD, 90 (13.49%) chromosomal abnormalities/genetic syndromes, 57 (8.55%) major malformations, 13 (1.95%) cases of neurodevelopmental delay. The incidence of chromosomal abnormalities/genetic syndromes and major malformations were significantly higher (OR 6.99 (IC 95% 4.33 - 11.28), p<0.001 and OR 17.77 (IC 95%7.22 - 43.75), p<0.001 respectively) compared to the general population. The incidence of neurodevelopmental delay was not increased (OR of 0.64 CI 95% 0.33 - 1.24 p=0.185). Conclusions Fetuses with NT between 95th and 99th percentile have an increased risk of pregnancy and postnatal adverse outcomes. According to our data it is reasonable to consider a lower NT cut off (NT>95th percentile) for offering further investigations such as detailed ultrasound scan, fetal echocardiography and counselling where the option of performing fetal karyotype and CGH array should be discussed. Funding The authors have no funding to declare.

Objective To establish pregnancy-specific reference ranges for fasting and postprandial total serum bile acids (TSBA) levels. Design Cross-sectional study. Setting Tertiary care university hospital. Population Healthy pregnant women at term admitted to the Obstetrics Department over one year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any co-existing condition of increased risk for ICP. Methods and Main Outcome Measures Both fasting and postprandial TSBA levels were measured in 612 women (528 fasting and 377 postprandial samples). Results Reference intervals of 4.4-14.1 µmol/L for fasting TSBA, and 4.7-20.2 µmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting measurements, with a mean increase of 1.77 µmol/L (22%). A correlation between fasting TSBA levels and postprandial levels was found, as well as with fetal gender, parity, and the use of assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values in the winter season (p < 0.01 and 0.02, respectively). Conclusions Normal pregnancy is a sub-cholestatic state and is associated with a physiological elevation of TSBA levels, therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limit observed in our healthy pregnant population (fasting ≥14 µmol/L and postprandial ≥20 µmol/L). As the fasting measurement is more specific for the diagnosis, and the postprandial is essential for severity assessment, it is recommended to measure both values, rather than use random samplings. Funding No funding to declare.