Associations of severe adverse perinatal outcomes among continuous birth weight percentiles on different birth weight charts: a secondary analysis of a cluster randomized trial.

OBJECTIVE: To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart. BACKGROUND: Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management. METHODS: This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included. We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes. Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis. RESULTS: We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low. CONCLUSIONS: The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk. TRIAL REGISTRATION: Netherlands Trial Register NTR4367 . Registration date March 20th, 2014.

Cost-Effectiveness of Routine Third Trimester Ultrasound Screening for Fetal Growth Restriction Compared to Care as Usual in Low-Risk Pregnancies: A Pragmatic Nationwide Stepped-Wedge Cluster-Randomized Trial in The Netherlands (the IRIS Study).

Routine third trimester ultrasonography is increasingly used to screen for fetal growth restriction. However, evidence regarding its cost-effectiveness is lacking. We aimed to evaluate the cost-effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes compared to usual care (selective ultrasonography). An economic evaluation alongside a stepped-wedge cluster-randomized trial was conducted. Via 60 midwifery practices 12,974 Dutch women aged ≥16 years with low-risk pregnancies were enrolled at 22.8 (SD = 2.4) weeks' gestation. All practices provided usual care. At 3, 7, and 10 months a third of the practices were randomized to the intervention strategy providing routine ultrasonography at 28-30 and 34-36 weeks' gestation and usual care. The primary clinical outcome was a dichotomous composite measure of 12 severe adverse perinatal outcomes (SAPO) up to one week postpartum. Information on perinatal care and societal costs was derived from Netherlands Perinatal Registry, hospital records and a survey. Cost-effectiveness analyses revealed no significant differences in SAPO and healthcare and societal costs between the intervention strategy (n = 7026) and usual care (n = 5948). Cost-effectiveness acceptability curves showed that the probability of cost-effectiveness was never higher than 0.6 for all possible ceiling ratios. Adding routine third trimester ultrasonography to usual care is not cost-effective in reducing SAPO.

Quality assessment of ultrasonic foetal biometry during the IUGR Risk Selection (IRIS) trial: A cross sectional study.

OBJECTIVE: Intrauterine growth restriction is a major risk factor for perinatal morbidity and mortality. Ultrasonic foetal biometry is an important tool to monitor foetal growth. Therefore, the quality of these biometry scans is vital to achieve good diagnostic accuracy. We assessed the quality of foetal biometry during a nationwide trial and explored its association with sonographer's characteristics. METHODS: Four scans from every sonographer (n = 154), performed at 29 and 35 weeks gestational age were collected. Two assessors scored these scans according to a national audit system. A quality score ≥ 65% was considered 'adequate'. We compared the quality scores per scoring criterion (i.e. foetal head measurements, abdominal circumference and femur length with regard to magnification, correctness of the plane and calliper placement) and gestational age. We analysed the associations between characteristics of the sonographers and their scores. In a subsample of scans of 30 sonographers we determined the interrater agreement on the quality scores given by the two assessors independently. FINDINGS: The mean score was 81.3%. Thirteen sonographers (8.4%) failed to achieve 'adequate quality'. Scores for femur length (83.8%) were significantly higher than those for head (77.9%) and abdominal circumference (78.6%) (both P < 0.05). Scores for correctness of the plane (73.4%) were lower than those for magnification (81.2%) and calliper placement (85.7%) (both P < 0.05). Gestational age did not affect the quality scores. Only the number of scans performed in the previous year was positively associated with the scores (ß = 0.01; P < 0.05). The mean interrater difference in quality scoring was 11.1%, with 77.6% agreement on scans of 'adequate quality', but with no agreement on scans with 'insufficient quality'. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Most sonographers achieved an 'adequate quality' score. Highest quality scores were attained for femur length, lowest quality scores for the correct plane. The number of scans one performs is associated with the quality scores, yet the minimum number of scans to perform for guaranteed quality still needs to be determined. Further research is needed to develop a standardized method to assess and maintain good ultrasonic foetal biometry quality.

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.

Multidisciplinary consensus on screening for, diagnosis and management of fetal growth restriction in the Netherlands.

BACKGROUND: Screening for, diagnosis and management of intrauterine growth restriction (IUGR) is often performed in multidisciplinary collaboration. However, variation in screening methods, diagnosis and management of IUGR may lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do not fully align. To facilitate effective collaboration between different professionals in perinatal care, we undertook a Delphi study with uniform recommendations as our primary result, focusing on issues that are not aligned or for which specifications are lacking in the current guidelines. METHODS: We conducted a Delphi study in three rounds. A purposively sampled selection of 56 panellists participated: 27 representing midwife-led care and 29 obstetrician-led care. Consensus was defined as agreement between the professional groups on the same answer and among at least 70% of the panellists within groups. RESULTS: Per round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27 issues, leading to four consensus based recommendations on screening for IUGR in midwife-led care and eight consensus based recommendations on diagnosis and eight on management in obstetrician-led care. The multidisciplinary project group decided on four additional recommendations as no consensus was reached by the panel. No recommendations could be made about induction of labour versus expectant monitoring, nor about the choice for a primary caesarean section. CONCLUSIONS: We reached consensus on recommendations for care for IUGR within a multidisciplinary panel. These will be implemented in a study on the effectiveness and cost-effectiveness of routine third trimester ultrasound for monitoring fetal growth. Research is needed to evaluate the effects of implementation of these recommendations on perinatal outcomes. TRIAL REGISTRATION: NTR4367 .

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).

BACKGROUND: Intrauterine growth retardation (IUGR) is a major risk factor for perinatal mortality and morbidity. Thus, there is a compelling need to introduce sensitive measures to detect IUGR fetuses. Routine third trimester ultrasonography is increasingly used to detect IUGR. However, we lack evidence for its clinical effectiveness and cost-effectiveness and information on ethical considerations of additional third trimester ultrasonography. This nationwide stepped wedge cluster-randomized trial examines the (cost-)effectiveness of routine third trimester ultrasonography in reducing severe adverse perinatal outcome through subsequent protocolized management. METHODS: For this trial, 15,000 women with a singleton pregnancy receiving care in 60 participating primary care midwifery practices will be included at 22 weeks of gestation. In the intervention (n = 7,500) and control group (n = 7,500) fetal growth will be monitored by serial fundal height assessments. All practices will start offering the control condition (ultrasonography based on medical indication). Every three months, 20 practices will be randomized to the intervention condition, i.e. apart from ultrasonography if indicated, two routine ultrasound examinations will be performed (at 28-30 weeks and 34-36 weeks). If IUGR is suspected, both groups will receive subsequent clinical management as described in the IRIS study protocol that will be developed before the start of the trial. The primary dichotomous clinical composite outcome is 'severe adverse perinatal outcome' up to 7 days after birth, including: perinatal death; Apgar score <4 at 5 minutes after birth; impaired consciousness; need for assisted ventilation for more than 24 h; asphyxia; septicemia; meningitis; bronchopulmonary dysplasia; intraventricular hemorrhage; cystic periventricular leukomalacia; neonatal seizures or necrotizing enterocolitis. For the economic evaluation, costs will be measured from a societal perspective. Quality of life will be measured using the EQ-5D-5 L to enable calculation of QALYs. Cost-effectiveness and cost-utility analyses will be performed. In a qualitative sub-study (using diary notes from 32 women for 9 months, at least 10 individual interviews and 2 focus group studies) we will explore ethical considerations of additional ultrasonography and how to deal with them. DISCUSSION: The results of this trial will assist healthcare providers and policymakers in making an evidence-based decision about whether or not introducing routine third trimester ultrasonography. TRIAL REGISTRATION: NTR4367 , 21 March 2014.