Effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes in low risk pregnancy (the IRIS study): nationwide, pragmatic, multicentre, stepped wedge cluster randomised trial

Objectives To investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions. Design Pragmatic, multicentre, stepped wedge cluster randomised trial. Setting 60 midwifery practices in the Netherlands. Participants 13 046 women aged 16 years or older with a low risk singleton pregnancy. Interventions 60 midwifery practices offered usual care (serial fundal height measurements with clinically indicated ultrasonography). After 3, 7, and 10 months, a third of the practices were randomised to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered two routine biometry scans at 28-30 and 34-36 weeks’ gestation. The same multidisciplinary protocol for detecting and managing fetal growth restriction was used in both strategies. Main outcome measures The primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score <4, impaired consciousness, asphyxia, seizures, assisted ventilation, septicaemia, meningitis, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leucomalacia, or necrotising enterocolitis. Secondary outcomes were two composite measures of severe maternal morbidity, and spontaneous labour and birth. Results Between 1 February 2015 and 29 February 2016, 60 midwifery practices enrolled 13 520 women in mid-pregnancy (mean 22.8 (SD 2.4) weeks’ gestation). 13 046 women (intervention n=7067, usual care n=5979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) v 78 of 407 (19%), P<0.001). The incidence of severe adverse perinatal outcomes was 1.7% (n=118) for the intervention strategy and 1.8% (n=106) for usual care. After adjustment for confounders, the difference between the groups was not significant (odds ratio 0.88, 95% confidence interval 0.70 to 1.20). The intervention strategy showed a higher incidence of induction of labour (1.16, 1.04 to 1.30) and a lower incidence of augmentation of labour (0.78, 0.71 to 0.85). Maternal outcomes and other obstetric interventions did not differ between the strategies. Conclusion In low risk pregnancies, routine ultrasonography in the third trimester along with clinically indicated ultrasonography was associated with higher antenatal detection of small for gestational age fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. The findings do not support routine ultrasonography in the third trimester for low risk pregnancies. Trial registration Netherlands Trial Register NTR4367

Evolutionary Substitution and Replacement in N-Species Lotka-Volterra Systems

The successful invasion of a multi-species resident system by mutants has received a great deal of attention in theoretical ecology but less is known about what happens after the successful invasion. Here, in the framework of Lotka-Volterra (LV) systems, we consider the general question where there is one resident phenotype in each species and the evolutionary outcome after invasion remains one phenotype in each species but these include all the mutant phenotypes. In the first case, called evolutionary substitution, a mutant appears in only one species, the resident phenotype in this species dies out and the mutant coexists with the original phenotypes of the other species. In the second case, called evolutionary replacement, a mutant appears in each species, all resident phenotypes die out and the evolutionary outcome is coexistence among all the mutant phenotypes. For general LV systems, we show that dominance of the resident phenotype by the mutant (i.e. the mutant is always more fit) in each species where the mutant appears leads to evolutionary substitution/replacement. However, it is shown by example that, when dominance is weakened to only assuming the average fitness of the mutants is greater than the average for the resident phenotype, the residents may not die out. We also show evolutionary substitution occurs in two-species competitive LV systems when the initial invasion of the resident system (respectively, of the new coexistence system) is successful (respectively, unsuccessful). Moreover, if sequential evolutionary substitution occurs for either order that the two mutant phenotypes appear (called historically independent replacement), then it is shown evolutionar