Jens Henrichs, Viki Verfaille, Arie Franx, and Ank de Jonge

Fetal growth restriction is a risk factor for perinatal mortality and morbidity, and adult disease. [1] Small-for-gestational age (SGA) is often used as proxy for fetal growth restriction. Routine third trimester biometry ultrasound scans predict SGA at birth substantially better than care as usual, i.e. ultrasonography, if clinically indicated. [2]

In 2010, the Dutch Ministry of Health considered introducing routine third trimester biometry as a means to reduce perinatal mortality. However, the Ministry postponed its decision because evidence of the effectiveness of routine biometry in reducing severe adverse perinatal outcome was lacking. In maternity care in the Netherlands, healthcare professionals also wanted evidence on this as pregnant women were increasingly asking for and receiving biometry scans. [3] Professionals disagreed about the usefulness of routine biometry for improving perinatal outcomes. [4] So, we performed a large pragmatic cluster-randomised stepped wedge trial, the IRIS study, published in The BMJ. We compared the clinical effectiveness of offering routine third trimester biometry to low-risk pregnant women in reducing severe adverse perinatal outcome compared to clinically indicated ultrasonography. Instead of conducting an efficacy trial into the usefulness of biometry in ideal circumstances, we chose a pragmatic design to evaluate the impact of routine third trimester biometry on management and outcome in daily practice. We developed a multidisciplinary protocol for the detection and management of fetal growth restriction, as in many previous trials the clinical management of fetal growth restriction was unclear. [5,6] This protocol was used in both screening strategies applied in the trial, because screening for fetal growth restriction alone cannot reduce adverse perinatal outcomes. [2]

Because of the relevance of the trial for maternity care and for maternal and child health, 60 Dutch midwifery practices participated in the trial. They enrolled 13 520 women within a 13-month period. We could only extend the inclusion period by one month halfway through the study due to its stepped wedge design.

A challenge we faced concerned the data collection of perinatal outcomes. We chose to use data from the Netherlands Perinatal Registry. [8] Neonates in the IRIS study were born between March 2015 and August 2016. However, it took almost a year to receive the respective annual perinatal registration data. These data enabled us to identify 2339 neonates with potential severe adverse perinatal outcomes. During a 14-month period five trained research assistants retrieved additional in-depth clinical data from hospital files of these neonates born in 58 Dutch hospitals, to ensure our main outcome was as reliable as possible.    

In line with previous trials, our findings do not support the introduction of routine third trimester biometry for low-risk pregnancies. [6] We acknowledge that ultrasonography itself is highly relevant in antenatal care. Nonetheless, our findings simply indicate that two routine third trimester biometry scans do not confer any additional benefit to neonatal outcome and health in addition to clinically indicated ultrasonography. As one midwife said to the research team: “We only refer women for an ultrasound scan if we have a good question because only then, can a scan provide a good answer.” Many women seek reassurance from additional tests, including ultrasound scans, tempting busy healthcare professionals to grant their wish instead of explaining why these scans may not be useful. However, there is currently an increasing awareness of the overuse of healthcare interventions without proven benefit. [9] This overuse leads to pressure on healthcare resources and sometimes induces harm. [9] Therefore, there is a need to avoid not only “too little too late” but also “too much too soon” when considering diagnostic and therapeutic interventions. [10] 

Our study also suggests that fetal growth restriction screening strategies need improvement. Antenatal estimations of SGA alone, are poor proxies of fetal growth restriction and insufficiently predict severe adverse perinatal outcome. [2] Promising screening and diagnostic tools to identify fetal growth restriction include combined ultrasound assessments of fetal size and fetal growth velocity, placental biomarkers, Doppler indices and maternal awareness of fetal compromise. [2, 11, 12, 13] These approaches should be further developed and evaluated in future cohort studies and clinical trials to balance the detection of fetal growth restriction and timely intervention against prevention of overdiagnosis and unnecessary interventions. 

Our study did not show a reduction in severe perinatal outcomes in low-risk pregnancies by routine third trimester biometry. These findings are disappointing and counterintuitive. Many women and professionals like ultrasound and seem to believe that a universal screening strategy must be superior to a selective strategy to achieve good neonatal and long-term health outcomes. Perhaps most importantly the IRIS study reconfirms a lesson we learn time and again, but do not seem to accept, that the use of technology, how attractive it may be, must be evaluated in the specific setting before its implementation.

Jens Henrichs is an epidemiologist and psychologist and Assistant Professor at the Department of Midwifery Science, Amsterdam University Medical Center, AVAG, Amsterdam Public Health. 

Viki Verfaille is a midwife, a sonographer and a policy advisor at the Dutch Professional Association of Sonographers.

Arie Franx is a gynaecologist and Professor of obstetrics focusing on the life course approach of fetal development and maternal health at Erasmus Medical Center in Rotterdam.

Ank de Jonge is a midwife and Associate Professor and ad interim chair of the Department of Midwifery Science, Amsterdam University Medical Center, AVAG, Amsterdam Public Health.

Twitter: @MidwifeScience

Competing interests: The authors have no competing interests. 

References: 

1. Kesavan K, Devaskar SU. Intrauterine Growth Restriction: Postnatal Monitoring and Outcomes. Pediatr Clin North Am 2019;66(2):403-23. doi: 10.1016/j.pcl.2018.12.009 [published Online First: 2019/03/02]
2. Sovio U, White IR, Dacey A, et al. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet 2015;386(10008):2089-97. doi: 10.1016/S0140-6736(15)00131-2
3. NRC. De verloskundige: geen echo meer zonder medische noodzaak [The midwife: No more ultrasound scan without medical indication]. 2013 22 june 2013.
4. de Reu P. De stelling in de afgelopen periode luidde ‘Het derde-trimester echo moet ingevoerd worden om groeivertragingen tijdig op te sporen’ [Third-trimester ultrasound should be introduced to detect fetal growth restriction] Kennisport Verloskunde; 2012] Available from: https://www.kennispoort-verloskunde.nl/reactie-op-stelling-derde-trimester-echo-de-nieuwe-stelling/.
5. Verfaille V, de Jonge A, Mokkink L, et al. Multidisciplinary consensus on screening for, diagnosis and management of fetal growth restriction in the Netherlands. BMC Pregnancy Childbirth 2017;17(1):353. doi: 10.1186/s12884-017-1513-3
6. Bricker L, Medley N, Pratt JJ. Routine ultrasound in late pregnancy (after 24 weeks’ gestation). Cochrane Database Syst Rev 2015(6):CD001451. doi: 10.1002/14651858.CD001451.pub4
7. Henrichs J, Verfaille V, Viester L, et al. Effectiveness and cost-effectiveness of routine third trimester ultrasound screening for intrauterine growth restriction: study protocol of a nationwide stepped wedge cluster-randomized trial in The Netherlands (The IRIS Study). BMC Pregnancy Childbirth 2016;16(1):310. doi: 10.1186/s12884-016-1104-8
8. Dijs-Elsinga J, Groenendaal F, van Huis AM, et al. Perined. Perinatale Zorg in Nederland 2014 [Perined. Perinatal Care in the Netherlands 2014]. Utrecht, NL: Perined, 2015.
9. WHO. WHO recommendations: Intrapartum care for a positive childbirth experience. Geneva: WHO 2018.
10. Miller S, Abalos E, Chamillard M, et al. Beyond too little, too late and too much, too soon: a pathway towards evidence-based, respectful maternity care worldwide. Lancet 2016;388(10056):2176-92. doi: 10.1016/S0140-6736(16)31472-6 [published Online First: 2016/09/20]
11. Gaccioli F, Sovio U, Cook E, et al. Screening for fetal growth restriction using ultrasound and the sFLT1/PlGF ratio in nulliparous women: a prospective cohort study. Lancet Child Adolesc Health 2018;2(8):569-81. doi: 10.1016/S2352-4642(18)30129-9
12. McCowan LM, Figueras F, Anderson NH. Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. Am J Obstet Gynecol 2018;218(2S):S855-S68. doi: 10.1016/j.ajog.2017.12.004
13. Mangesi L, Hofmeyr GJ, Smith V, et al. Fetal movement counting for assessment of fetal wellbeing. Cochrane Database Syst Rev 2015(10):CD004909. doi: 10.1002/14651858.CD004909.pub3