Validation of Reference Charts for Mid-Trimester Fetal Biometry.

OBJECTIVE: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project. METHODS: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18-23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution. RESULTS: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight. CONCLUSIONS: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account.

Prevalence, diagnosis and outcome of cleft lip with or without cleft palate in The Netherlands.

OBJECTIVE: To examine the accuracy and timing of diagnosis of fetal cleft lip with or without cleft palate (CL ± P) in the years following the introduction of a national screening program, and to assess the completeness and accuracy of information in The Netherlands Perinatal Registry. METHODS: A list was obtained of cases with a prenatal or postnatal diagnosis of CL ± P from two fetal medicine units between 2008 and 2012. All cases of CL ± P were included irrespective of the presence or absence of additional anomalies. Cases were included if the estimated date of delivery was between 1 January 2008 and 31 December 2012. RESULTS: During the study period, 330 cases of CL ± P were identified, with a prevalence of 15 per 10 000 pregnancies. The number of cases that were detected before 24 weeks' gestation increased during the study period, while the rate of termination of pregnancy did not change significantly (P = 0.511). CL ± P was isolated in 217 (66%) cases and karyotype was abnormal in 69 (21%) cases. In 5% of the cases in which CL ± P seemed to be isolated during the 18-23-week anomaly scan, postnatal array comparative genomic hybridization (array-CGH) revealed an abnormal karyotype and 50% of these cases had major additional anomalies. Examination of data from The Netherlands Perinatal Registry demonstrated that in 37% of cases CL±P was not recorded in the pregnancy records. CONCLUSION: CL ± P is increasingly being diagnosed prenatally, without a significant effect on the rate of pregnancy termination. Further improvement in the diagnostic accuracy may be achieved by advocating prenatal array-CGH to reduce the frequency of unexpected anomalies being diagnosed after birth. It is important that healthcare providers register accurately the presence or absence of anomalies in the birth records to ensure that, in the future, data from The Netherlands Perinatal Registry can be relied upon to monitor prevalence. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Timing of detection of anencephaly in The Netherlands.

OBJECTIVE: The objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period. METHODS: A case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013. RESULTS: Overall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and gestational age at or beyond 11 weeks of gestation (p = 0.024). CONCLUSION: Improving detection of anencephaly in the first trimester requires ultrasound screening at or after 11 weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies.

Impact of introduction of mid-trimester scan on pregnancy outcome of open spina bifida in The Netherlands.

OBJECTIVE: To examine the impact of introduction of the mid-trimester scan on pregnancy outcome in cases of open spina bifida in two regions of The Netherlands. METHODS: This was a retrospective cohort study of 190 cases of open spina bifida diagnosed pre- or postnatally, with an estimated date of delivery between 2003 and 2011. RESULTS: With implementation of the mid-trimester scan the percentage of cases of open spina bifida detected before the 24(th) week of pregnancy increased from 43% to 88%. The rise in prenatal detection rate was associated with a significant increase in the number of terminated pregnancies and a decrease in the rate of perinatal loss; the percentage of children born alive did not change significantly. In the subgroup that underwent a scan between 18 and 24 weeks of pregnancy, cranial signs were present in 94.4% of cases. CONCLUSION: Introduction of the mid-trimester scan has led to an increase in early identification of pregnancies complicated by open spina bifida. Pregnancies previously destined to end in perinatal loss are now terminated whilst pregnancies with a relatively good prognosis are frequently continued; the number of children with open spina bifida who are born alive has not changed significantly. Our study confirms that prenatal diagnosis is usually triggered by visualization of a lemon-shaped skull or a banana-shaped cerebellum.

High macrosomia rate in healthy fetuses after enlarged nuchal translucency.

OBJECTIVE: The aim of this study was to investigate the association of the first trimester screening variables nuchal translucency (NT), pregnancy associated plasma protein (PAPP-A), and free beta-human chorionic gonadotrophin (ßhCG) and birth weight, with a focus on the prediction of macrosomia. METHODS: The database of our Fetal Medicine Unit was searched for all singleton pregnancies, who underwent first trimester Down syndrome screening. Live born infants born at term without chromosomal or structural defects from non-diabetic mothers constituted the study population. Birth weight percentiles were corrected for gestational age at delivery, parity, and gender. Macrosomia was defined as birth weight ≥95th centile. RESULTS: We included 6503 fetuses. Multivariate analysis demonstrated that birth weight centile was positively correlated with NT multiples of the median (MoM), PAPP-A MoM, and maternal body mass index, and it was negatively correlated with smoking. An NT ≥95th centile was present in 315 fetuses (4.8%). Although median birth weight centile was not significantly different between cases with NT ≥95th centile and those <95th (P54 vs P52), a birth weight >95th centile was more common (11% vs 7%) in the presence of NT ≥95th centile. Pregnancy associated plasma protein was elevated (≥95th centile) in 303 cases (7.9%). Median birth weight was higher (P56 vs P51, P = 0.03) in case of elevated PAPP-A compared with PAPP-A <95th centile. There was a trend toward higher macrosomia rate in case of PAPP-A ≥95th centile (7.4% vs 6.3%, P = 0.07). Area under the receiver operating characteristics (ROC) curve for the prediction of macrosomia (birth weight ≥95th centile) by NT MoM, PAPP-A MoM, maternal body mass index, and maternal smoking was 0.64 (P < 0.001). CONCLUSIONS: First trimester PAPP-A MoM and NT MoM are significantly related to birth weight centiles. Enlarged NT is associated with macrosomia.

Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta-analysis.

OBJECTIVE: To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan. METHODS: We searched MEDLINE (1948-2012), EMBASE (1980-2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI. RESULTS: We identified three cohort studies and four case-control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case-control studies. Compared to fetuses with a three-vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97-2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9-4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, -154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy. CONCLUSION: In view of the non-significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice.

New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study.

OBJECTIVES: Correct assessment of gestational age and fetal growth is essential for optimal obstetric management. The objectives of this study were, first, to develop charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter and, second, to derive reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from 10 weeks of gestational age onwards. METHODS: A total of 8313 pregnant women were included for analysis in this population-based prospective cohort study. All women had repeated ultrasound assessments to examine fetal growth. RESULTS: Charts for ultrasound dating of pregnancy, based on crown-rump length and biparietal diameter, were derived. Internal validation with the actual date of delivery showed that ultrasound imaging provided reliable gestational age estimates. Up to 92% of deliveries took place within 37-42 weeks of gestation if gestational age was derived from ultrasound data, compared with 87% based on a reliable last menstrual period. The earlier the ultrasound assessment the more accurate the prediction of date of delivery. After 24 weeks of gestation a reliable last menstrual period provided better estimates of gestational age. Reference curves for normal fetal growth from 10 weeks of gestational age onwards were derived. CONCLUSIONS: Charts for ultrasound dating of pregnancy and reference curves for fetal biometry are presented. The results indicate that, up to 24 weeks of pregnancy, dating by ultrasound examination provides a better prediction of the date of delivery than does last menstrual period. The earlier the ultrasound assessment in pregnancy, preferably between 10 and 12 weeks, the better the estimate of gestational age.

Ethnic differences in prenatal growth and the association with maternal and fetal characteristics.

OBJECTIVES: The objectives of this study were to determine ethnic differences in prenatal growth and to examine their association with differences in maternal and fetal characteristics such as maternal height, weight, age, parity and fetal gender. METHODS: A total of 1494 women from Rotterdam, The Netherlands, with a low-risk pregnancy who participated in a population-based cohort study, the Generation R Study, were offered three ultrasound examinations during pregnancy. Multilevel modeling was applied to determine ethnic differences in (estimated) fetal weight (including birth weight) and in the separate biometric variables that were used to calculate the estimated fetal weight (abdominal circumference, head circumference and femur length). Additionally the association of ethnic differences with maternal and fetal characteristics (i.e. maternal weight, height, age, parity and fetal gender) was studied. RESULTS: Turkish, Cape Verdian, Surinamese-Creole and Surinamese-Hindustani women had on average smaller fetuses than the native Dutch women. The differences became more pronounced towards term. In the Turkish group the differences were no longer statistically significant when adjusted for maternal weight, height, age, parity and fetal gender. In the Cape Verdian, Surinamese-Creole and Surinamese-Hindustani groups the differences decreased after adjustment (31%, 16% and 39%, respectively). CONCLUSIONS: This study shows that there are ethnic differences in fetal growth, which to a large extent may be attributed to differences in maternal weight, height, age and parity. For some ethnic groups, however, additional factors are involved, as differences remain significant after correction for fetal and maternal characteristics.

First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.

OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.