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 trialBMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5517 (Published 15 October 2019) Cite this as: BMJ 2019;367:l5517
- Jens Henrichs, assistant professor1,
- Viki Verfaille, researcher and policy adviser1 2,
- Petra Jellema, senior researcher1,
- Laura Viester, senior researcher1,
- Eva Pajkrt, professor3,
- Janneke Wilschut, statistician4,
- Henriëtte E van der Horst, professor5,
- Arie Franx, professor6,
- Ank de Jonge, associate professor1
- on behalf of the IRIS study group
- 1Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Department of Midwifery Science, AVAG/Amsterdam Public Health, Van der Boechhorststraat 7, 1081 BT Amsterdam, Netherlands
- 2Dutch Professional Organisation of Sonographers, Woerden, Netherlands
- 3Amsterdam University Medical Centre, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development, Amsterdam, Netherlands
- 4Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health, Amsterdam, Netherlands
- 5Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Department of General Practice and Elderly Care Medicine, Amsterdam Public Health, Amsterdam, Netherlands
- 6Department of Obstetrics and Gynaecology, Erasmus Medical University Centre, Rotterdam, Netherlands
- Correspondence to: A de Jonge @midwifescience on Twitter) (or
- Accepted 27 August 2019
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.
The IRIS study group: Anneloes L van Baar, Utrecht University, Utrecht, Netherlands; Joke M J Bais, Medical Centre Alkmaar, Alkmaar, Netherlands; Gouke J Bonsel, University Medical Centre Utrecht, Utrecht, Netherlands; Judith E Bosmans, VU University Amsterdam, Amsterdam, Netherlands; Jeroen van Dillen, Radboud University Medical Centre, Nijmegen, Netherlands; Noortje T L van Duijnhoven, Radboud University Medical Centre, Nijmegen, Netherlands; William A Grobman, Northwestern University, Chicago, IL, USA; Henk Groen, University of Groningen, Groningen, Netherlands; Chantal W P M Hukkelhoven, Wageningen University and Research, Wageningen, Netherlands; Trudy Klomp, Amsterdam University Medical Centre/AVAG, Amsterdam, Netherlands; Marjolein Kok, Amsterdam University Medical Centre, Amsterdam, Netherlands; Marlou L de Kroon, University of Groningen, Groningen, Netherlands; Maya Kruijt, Dutch Society of Obstetrics and Gynaecology NVOG, Utrecht, Netherlands; Anneke Kwee, University Medical Centre Utrecht, Utrecht, Netherlands; Sabina Ledda, Midwifery practice het Palet/BEN, Rotterdam, Netherlands; Harry N Lafeber, Amsterdam University Medical Centre, Netherlands; Jan M M van Lith, Leiden University Medical Centre, Leiden, Netherlands; Ben Willem Mol, University of Adelaide, Adelaide, Australia; Bert Molewijk, Amsterdam University Medical Centre, Amsterdam, Netherlands; Marianne Nieuwenhuijze, Academie Verloskunde Maastricht, Maastricht, Netherlands; Guid Oei, Maxima Medical Centre, Eindhoven, Netherlands; Cees Oudejans, Amsterdam University Medical Centre, Amsterdam, Netherlands; K Marieke Paarlberg, Gelre Hospitals, location Apeldoorn, Netherlands; Aris T Papageorghiou, University of Oxford, Oxford, UK; Uma M Reddy, Yale University, New Haven, CT, USA; Paul De Reu, Prenataal Screenigscentrum “de Meierij,” Eindhoven, Netherlands; Marlies Rijnders, TNO, Leiden, Netherlands; Alieke de Roon-Immerzeel, Royal Dutch Organisation of Midwives, Netherlands; Connie Scheele, University Medical Centre Utrecht/BEN, Utrecht, Netherlands; Sicco A Scherjon, University Medical Centre Groningen, Groningen, Netherlands; Rosalinde Snijders, Amsterdam University Medical Centre, Amsterdam, Netherlands; Marc E Spaanderman, University Medical Centre Maastricht, Maastricht, Netherlands; Pim W Teunissen, Amsterdam University Medical Centre, Amsterdam, Netherlands; Hanneke W Torij, Rotterdam University of Applied Sciences, Rotterdam, Netherlands; Tanja G Vrijkotte, Amsterdam University Medical Centre, Amsterdam, Netherlands; Myrte Westerneng, Amsterdam University Medical Centre, Amsterdam, Netherlands Kristel C Zeeman, University of Amsterdam, Amsterdam, Netherlands; and Jun Jim Zhang, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Contributors: JH and VV contributed equally to the manuscript and are first authors. AdJ, AF, HEvdH, PJ, VV, and EP conceived and designed the study. AdJ, PJ, LV, VV, and JH were involved in the development, implementation, or data collection of the study. JH, JW, and VV conducted data analyses. JH, VV, and AdJ drafted the manuscript and interpreted the results. All authors critically revised the manuscript for important intellectual content, approved its final version, and agree to be accountable for all aspects of the work presented in this manuscript. AdJ is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This study was supported by a grant from the Netherlands Organisation for Health Research and Development (ZonMw; grant No 209030001). This funding source had no role in study design, data collection, data analysis, data interpretation, writing of the scientific article, or the decision to submit the paper for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: for the current study (the IRIS study), AdJ and JW received funding from the Netherlands Organisation for Health Research and Development; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The IRIS study was approved by the Dutch Institutional Review Board of the VU Medical University Centre Amsterdam (reference No 2013.409).
Data sharing: No additional data available.
The manuscript’s guarantor (AdJ) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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