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 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.

Early lexical development and risk of verbal and nonverbal cognitive delay at school age.

AIM: To characterise the relationship between preschool lexical delay and language comprehension and nonverbal intelligence at school age. METHODS: The mothers of 2724 children completed the MacArthur Communicative Development Inventory when their child reached 1.5 years and the Language Development Survey and the Parent Report of Children's Ability at 2.5 years. When the children were 6 years old, we assessed vocabulary comprehension and nonverbal intelligence using Dutch batteries for language and nonverbal intelligence. RESULTS: Demographic factors explained 9.9% of the variance in vocabulary comprehension and 8.7% of the variance in nonverbal intelligence at 6 years. Male gender, low maternal education and non-Western ethnic background predicted vocabulary comprehension delay at 6 years. Lexical development at 1.5 and 2.5 years explained only 3.8% of the variance in language comprehension at the age of six. Late onset expressive vocabulary delay increased the risk of language comprehension and nonverbal intelligence delay at 6 years (OR=2.31, 95% CI: 1.62-3.29 and OR=1.74, 95% CI: 1.17-2.58, respectively). CONCLUSION: Sociodemographic factors are important predictors of delays in language and nonverbal abilities as children enter school. In contrast, early expressive lexical delays, in particular before the age of two, have limited predictive power for language delays at the age of six.

Early infant neuromotor assessment is associated with language and nonverbal cognitive function in toddlers: the Generation R Study.

OBJECTIVE: Numerous studies in high-risk populations established that variations in infant neuromotor development predict poor cognitive function. It is unclear whether this association is found in the general population. Moreover, previous population-based studies mostly focused on motor milestone achievement. METHODS: This study was embedded in the Generation R Study, a population-based cohort in Rotterdam, the Netherlands. Neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination when infants (1205 males, 1278 females) were on average 12 weeks old (standard deviation 1, range, 9-15 weeks). To measure language function at age 1.5 years, the MacArthur Short Form Vocabulary Checklist was used. At 2.5 years, mothers completed the Language Development Survey and the Parent Report of Children's Abilities measuring language and nonverbal cognitive functioning, respectively. RESULTS: After adjustment for confounders, less optimal neuromotor development, that is, more low tone symptoms, was associated with a delay in receptive language at 1.5 years (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.05-1.34) and in expressive language at multiple time points (OR, 1.11; 95% CI, 1.02-1.21). Higher scores on overall neuromotor development, indicating a less optimal neuromotor development, was associated with an increased risk of a delay in nonverbal cognitive function at 2.5 years (OR, 1.19; 95% CI, 1.05-1.35). CONCLUSIONS: The results of this study suggest that infants with more low tone symptoms, indicating minor deviances from normal neuromotor development, are somewhat more vulnerable to language delays than those infants who do not have these symptoms.

Correlates of physical activity in 2-year-old toddlers: the generation R study.

OBJECTIVE: To describe and identify correlates of objectively measured physical activity and sedentary behavior in 2-year-old toddlers. STUDY DESIGN: A total of 347 children participating in a birth cohort study wore a unaxial ActiGraph accelerometer during 1 weekday and 1 weekend day. Information on potential correlates was assessed by parent-reported questionnaires, delivery reports, and regular visits to child health centers. Univariate and multivariable linear regression analyses were conducted to examine the associations between potential correlates and the following physical activity outcomes: percentage of time spent in sedentary behavior, percentage of time spent in moderate-to-vigorous physical activity, and mean counts per minute. RESULTS: A high percentage of monitored time was spent in sedentary behavior; 85.6% on weekdays and 84.5% on weekend days. Four correlates were significantly associated with at least 1 physical activity outcome in the multivariable regression models: child's sex, child's age, number of siblings, and season of measurement. The associations of gross motor development with moderate-to-vigorous physical activity and mean counts per minute approached significance. Associations of socioeconomic variables and child's body mass index z-score with physical activity outcomes were not significant. CONCLUSION: Two-year-old toddlers spend most of their time in sedentary behavior. No modifiable correlates were identified. Further research on physical activity and associated health benefits among very young children is warranted.