Adverse pregnancy outcome in fetuses with early increased nuchal translucency: prospective cohort study.

OBJECTIVES: An increased nuchal translucency (NT) thickness of ≥ 3.5 mm is a well-established marker for congenital anomalies and adverse pregnancy outcome between 11 and 14 weeks' gestation, but little is known about its performance as a screening tool before 11 weeks. We aimed to investigate, in a prospective setting, whether fetuses with increased NT before 11 weeks are at risk for adverse pregnancy outcome. METHODS: This was a prospective cohort study including pregnant women with a viable fetus with NT ≥ 2.5 mm and a crown-rump length (CRL) < 45 mm. All included women were referred to our fetal medicine unit (FMU) and scheduled for a follow-up scan where the NT was remeasured after 1 week when the CRL was > 45 mm. Two groups were evaluated: cases with a normalized NT (< 3.5 mm) and cases with persistently increased NT (≥ 3.5 mm). The cases were monitored until 4 weeks after delivery. The main outcome was a composite adverse outcome of aneuploidy, other genetic disorders, structural anomalies and pregnancy loss. We performed subgroup analyses of NT thickness at inclusion and normalized or persistently increased NT at follow-up. RESULTS: The study included 109 cases, of which 39 (35.8%) had an adverse pregnancy outcome. Of these, 64.1% (25/39) were aneuploid, corresponding to 22.9% (25/109) of the total study population. In the subgroups of NT thickness at inclusion of 2.5-3.4 mm, 3.5-4.4 mm and ≥ 4.5 mm, an adverse outcome was reported in 22.0% (9/41), 40.0% (18/45) and 52.2% (12/23), respectively. In fetuses with a normalized NT and without ultrasound abnormalities at the follow-up scan, the incidence of adverse outcome was 8.5% (5/59), of which 5.1% (3/59) cases were aneuploid. CONCLUSIONS: Fetuses with an early increased NT thickness are at considerable risk of an adverse pregnancy outcome, even if the NT normalizes after 11 weeks. Not all congenital anomalies can be diagnosed with routine first-trimester screening, such as non-invasive prenatal testing and/or a first-trimester anomaly scan. Therefore, expectant parents should always be referred to a FMU for detailed ultrasonography. Invasive prenatal testing should be offered if an increased NT of ≥ 2.5 mm is observed before 11 weeks' gestation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Resultado adverso del embarazo en fetos con aumento precoz de la translucencia nucal: estudio prospectivo de cohortes OBJETIVOS: El aumento del grosor de la translucencia nucal (TN) de ≥3,5 mm es un marcador bien establecido de anomalías congénitas y resultados adversos del embarazo entre las semanas 11 y 14 de gestación, pero se sabe poco sobre su rendimiento como herramienta de cribado antes de las 11 semanas. El objetivo fue investigar, en un contexto prospectivo, si los fetos con aumento de la TN antes de las 11 semanas corren riesgo de presentar resultados adversos del embarazo. MÉTODOS: Se trató de un estudio prospectivo de cohortes que incluyó a embarazadas con un feto viable con una TN ≥2,5 mm y una longitud céfalo­caudal (LCC) <45 mm. Todas las mujeres incluidas fueron remitidas a una unidad de medicina fetal (UMF) y con cita para una prueba de seguimiento en la que se volvió a medir la TN al cabo de 1 semana cuando la LCC era >45 mm. Se evaluaron dos grupos: casos con una TN normalizada (<3.5 mm) y casos con una TN persistentemente aumentada (≥3,5 mm). A los casos se les dio seguimiento hasta 4 semanas después del parto. El resultado principal fue un resultado adverso compuesto de aneuploidía, otros trastornos genéticos, anomalías estructurales y pérdida del embarazo. Se realizaron análisis de subgrupos del grosor de la TN en el momento de la inclusión y de la TN normalizada o persistentemente aumentada en el seguimiento. RESULTADOS: El estudio incluyó 109 casos, de los cuales 39 (35,8%) tuvieron un resultado adverso del embarazo. De ellos, el 64,1% (25/39) eran aneuploides, lo que supone el 22,9% (25/109) de la población total del estudio. En los subgrupos de grosor de la TN en el momento de la inclusión de 2,5­3,4 mm, 3,5­4,4 mm y ≥4,5 mm, se notificó un resultado adverso en el 22,0% (9/41), el 40,0% (18/45) y el 52,2% (12/23), respectivamente. En los fetos con una TN normalizada y sin anomalías ecográficas en la ecografía de seguimiento, la incidencia de resultados adversos fue del 8,5% (5/59), de los cuales el 5,1% (3/59) de los casos eran aneuploides. CONCLUSIONES: Los fetos con un aumento precoz del grosor de la TN corren un riesgo considerable de sufrir un resultado adverso del embarazo, incluso si la TN se normaliza después de 11 semanas. No todas las anomalías congénitas pueden diagnosticarse con un cribado rutinario en el primer trimestre, como las pruebas prenatales no invasivas y/o una ecografía de anomalías en el primer trimestre. Por lo tanto, los futuros padres siempre deben ser remitidos a una UMF para una ecografía detallada. Se debería ofrecer una prueba prenatal invasiva si se observa un aumento de la TN de ≥2,5 mm antes de las 11 semanas de gestación.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

United States' experience in nuchal translucency measurement: variation according to provider characteristics in over five million ultrasound examinations.

OBJECTIVE: The Nuchal Translucency Quality Review (NTQR) program has provided standardized education, credentialing and epidemiological monitoring of nuchal translucency (NT) measurements since 2005. Our aim was to review the effect on NT measurement of provider characteristics since the program's inception. METHODS: We evaluated the distribution of NT measurements performed between January 2005 and December 2019, for each of the three primary performance indicators of NT measurement (NT median multiples of the median (MoM), SD of log10 NT MoM and slope of NT with respect to crown-rump length (CRL)) for all providers within the NTQR program with more than 30 paired NT/CRL results. Provider characteristics explored as potential sources of variability included: number of NT ultrasound examinations performed annually (annual scan volume of the provider), duration of participation in the NTQR program, initial credentialing by an alternative pathway, provider type (physician vs sonographer) and number of NT-credentialed providers within the practice (size of practice). Each of these provider characteristics was evaluated for its effect on NT median MoM and geometric mean of the NT median MoM weighted for the number of ultrasound scans, and multiple regression was performed across all variables to control for potential confounders. RESULTS: Of 5 216 663 NT measurements from 9340 providers at 3319 sites, the majority (75%) of providers had an NT median MoM within the acceptable range of 0.9-1.1 and 85.5% had NT median MoM not statistically significantly outside this range. Provider characteristics associated with measurement within the expected range of performance included higher volume of NT scans performed annually, practice at a site with larger numbers of other NT-credentialed providers, longer duration of participation in the NTQR program and alternative initial credentialing pathway. CONCLUSIONS: Annual scan volume, duration of participation in the NTQR program, alternative initial credentialing pathway and number of other NT-credentialed providers within the practice are all associated with outcome metrics indicating quality of performance. It is critical that providers participate in ongoing quality assessment of NT measurement to maintain consistency and precision. Ongoing assessment programs with continuous feedback and education are necessary to maintain quality care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Neurodevelopmental outcome at 2 years of corrected age in fetuses with increased nuchal translucency thickness and normal karyotype compared with matched controls.

OBJECTIVES: Increased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long-term neurodevelopmental prognosis of infants who had isolated increased NT in utero. METHODS: This was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet-Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability. RESULTS: A total of 203 chromosomally normal infants were included in the increased-NT group and 208 in the control group. The mean global DQ was significantly lower in the increased-NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P < 0.0001), but it was within the normal range expected for that age in both groups. Similarly, the mean DQs for coordination, sociability and language, but not for posture, were significantly lower in infants with increased NT than in controls. Only one case with increased NT had a DQ < 70 (defined as severe neurodevelopmental impairment), compared with none in the control group. The difference between the two groups remained significant for a NT threshold ≥ 99th percentile and when the data were adjusted for NT thickness, the infant's sex and the mother's educational level. In the increased-NT group, NT thickness was < 3.5 mm in over half (56%) of the infants, between 3.5 mm and 5 mm in 33% and > 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively. CONCLUSIONS: Infants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Machine learning improves early prediction of small-for-gestational-age births and reveals nuchal fold thickness as unexpected predictor.

OBJECTIVE: To investigate the performance of the machine learning (ML) model in predicting small-for-gestational-age (SGA) at birth, using second-trimester data. METHODS: Retrospective data of 347 patients, consisting of maternal demographics and ultrasound parameters collected between the 20th and 25th gestational weeks, were studied. ML models were applied to different combinations of the parameters to predict SGA and severe SGA at birth (defined as 10th and third centile birth weight). RESULTS: Using second-trimester measurements, ML models achieved an accuracy of 70% and 73% in predicting SGA and severe SGA whereas clinical guidelines had accuracies of 64% and 48%. Uterine PI (Ut PI) was found to be an important predictor, corroborating with existing literature, but surprisingly, so was nuchal fold thickness (NF). Logistic regression showed that Ut PI and NF were significant predictors and statistical comparisons showed that these parameters were significantly different in disease. Further, including NF was found to improve ML model performance, and vice versa. CONCLUSION: ML could potentially improve the prediction of SGA at birth from second-trimester measurements, and demonstrated reduced NF to be an important predictor. Early prediction of SGA allows closer clinical monitoring, which provides an opportunity to discover any underlying diseases associated with SGA.

Increased nuchal translucency before 11 weeks of gestation: Reason for referral?

OBJECTIVES: In this era of non-invasive-prenatal testing (NIPT), when dating scans are usually performed around 10 weeks of gestation, an increased NT before the official established timeframe (CRL between 45 and 84 mm) may be encountered. Information on management of these pregnancies is limited. Therefore, we evaluated the relationship between an early increased NT and adverse pregnancy outcome. Secondary, we evaluated the rate of chromosomal anomalies that might have been missed in first trimester should solely NIPT be performed as first-tier test, and the rate of adverse pregnancy outcome if NT normalizes before 14 weeks. METHODS: We performed a retrospective cohort study that included all pregnancies between January 1, 2007 and June 1, 2020 in Amsterdam UMC locations AMC and VUmc. We included fetuses with a crown-rump length (CRL) < 45 mm (∼11 weeks) and a nuchal translucency (NT) measurement ≥2.5 mm. Fetuses referred with an early increased NT and a major fetal anomaly at the dating scan were excluded, as were cases of parents with a family history of monogenetic disease(s) or recognized carriers of a balanced translocation. RESULTS: We included 120 fetuses of which 66.7% (80/120) had an adverse pregnancy outcome. Congenital anomalies were present in 56.7% (68/120), 45.8% (55/120) had a chromosomal anomaly. The prevalence of congenital anomalies was 30.3% in fetuses with NT 2.5-3.4 mm compared to 66.7% with NT ≥ 3.5 mm (p < 0.001). 16.7% (20/120) had a chromosomal anomaly that might have been missed by conventional NIPT in first trimester. We found an adverse pregnancy outcome of 24% in the group with a normalized NT compared to 78.1% in the group with a persistently increased NT (p < 0.001). CONCLUSION: An early increased NT should make the sonographer alert. In this selected cohort, an early increased NT was associated with a high probability of having an adverse pregnancy outcome. Regardless of CRL, we deem that an early increased NT ≥ 3.5 mm warrants referral to a Fetal Medicine Unit for an extensive work-up. NT normalization seems favorable, but a prospective study should define the appropriate work-up for NT in the lower range (2.5-3.4 mm).

Abnormal nuchal translucency followed by normal microarray analysis is associated with placental pathology-related complications.

OBJECTIVE: Identify placental pathology-related complications, labor and neonatal outcomes in pregnancies complicated by pathological nuchal translucency (NT) with normal microarray analysis. METHODS: A retrospective study in which all women with singleton pregnancy who demonstrated NT above 3 mm and a normal microarray analysis were matched to women with normal NT and a normal microarray analysis (2013-2019) in a single tertiary academic center. The following placental pathology-related parameters were measured: preeclampsia, oligohydramnios, suspected intrauterine growth restriction, abnormal Doppler studies or small for gestational age (SGA) neonates. The primary outcome was defined as a composite of complications related to placental pathology including preeclampsia and SGA neonate. Secondary outcomes were labor complications and neonatal morbidity. RESULTS: A total of 185 women were included in the study: of them, 47 presented an abnormal NT (study group) and 138 presented normal NT (controls). Groups did not significantly differ in baseline characteristics. Regarding primary outcome, all placental-related complications frequencies were higher in the study group, with a composite rate of 17.02% versus 6.52% in controls (p = 0.042%). Secondary outcomes did not differ between groups. CONCLUSIONS: Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications.

Increased nuchal translucency after low-risk noninvasive prenatal testing: What should we tell prospective parents?

Three decades ago, the observation that first trimester fetuses with excess fluid accumulation at the back of the neck were more likely to be aneuploid, gave rise to a new era of prenatal screening. The nuchal translucency (NT) measurement in combination with serum biomarkers and maternal age, resulted in the first trimester combined screening (FTCS) program. The introduction of noninvasive prenatal testing (NIPT) over the past decade has introduced the option for parents to receive highly sensitive and specific screening information for common trisomy from as early as 10 weeks gestation, altering the traditional pathway FTCS pathway. The retention of the 11-13-week NT ultrasound remains important in the detection of structural anomalies; however, the optimal management of pregnancies with a low-risk NIPT result and an isolated increased NT measurement in an era of advanced genomic testing options is a new dilemma for clinicians. For parents, the prolonged period between the initial diagnosis in first trimester, and prognostic information at each successive stage of investigations up to 22-24 weeks, can be emotionally challenging. This article addresses the common questions from parents and clinicians as they navigate the uncertainty of having a fetus diagnosed with an increased NT after a low-risk NIPT result and presents suggested approaches to management.

Diagnosis of fetal defects in twin pregnancies at routine 11-13-week ultrasound examination.

OBJECTIVES: To examine the performance of the routine 11-13-week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95th and ≥ 99th percentiles or intertwin discordance in crown-rump length (CRL) ≥ 10% and ≥ 15%. METHODS: This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11-13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal defects was determined. RESULTS: The study population of 6366 twin pregnancies with two live fetuses at 11-13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11-13-week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always-detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body-stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95th percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99th percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins). CONCLUSIONS: First, fetal defects are more common in MC than in DC twin pregnancies. Second, first-trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first-trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Diagnóstico de defectos del feto en embarazos de gemelos en el examen ecográfico de rutina de las 11-13 semanas OBJETIVOS: Examinar la eficacia del examen rutinario de 11-13 semanas para detectar defectos fetales en embarazos de gemelos y examinar si, en los embarazos con un defecto fetal, en comparación con los de fetos normales, hay una mayor incidencia del grosor de la translucencia nucal (TN) ≥ percentil 95o y ≥ percentil 99o o una discordancia entre gemelos en la longitud céfalo-caudal (LCC) ≥10% y ≥15%. MÉTODOS: Este estudio fue un análisis retrospectivo de datos recogidos prospectivamente de embarazos de gemelos sometidos a exámenes ecográficos de rutina entre 2002 y 2019 para determinar la anatomía del feto, según protocolos estándar a las 11-13 semanas de gestación. Se excluyeron los embarazos con anomalías cromosómicas conocidas. El diagnóstico final de la anomalía fetal se basó en los resultados del examen posnatal en los casos de nacimientos vivos y en los hallazgos del último examen ecográfico en los casos de interrupción del embarazo, aborto o éxitus fetal. Se determinó la eficacia de la exploración de las 11-13 semanas en la detección de anomalías fetales. RESULTADOS: La población de estudio fue de 6366 embarazos de gemelos con dos fetos vivos a las 11-13 semanas de gestación e incluyó 4979 (78,2%) embarazos bicoriales (BC) y 1387 (21,8%) monocoriales (MC). Los principales hallazgos fueron: primero, la prevalencia total de defectos fetales fue mayor en los gemelos MC que en los gemelos BC (2,8% vs. 1,3%); segundo, la proporción de defectos diagnosticados en el primer trimestre fue mayor en los gemelos MC que en los gemelos BC (52,6% vs. 27,1%); tercero, la pauta de defectos en relación con la detectabilidad en la exploración de 11-13 semanas (siempre detectable, a veces detectable y nunca detectable) fue similar a la reportada previamente para los embarazos con feto único; cuarto, entre los defectos siempre detectables estaban la acrania, la holoprosencefalia alobar, el encefalocele, la pentalogía de Cantrell, el onfalocele, la anomalía del pedículo embrionario, la secuencia de perfusión arterial inversa de los gemelos y los gemelos unidos; quinto, la frecuencia del percentil de la TN fetal ≥95o fue mayor en los que tenían un defecto que en los que no lo tenían (16,5% vs 4,5% en los gemelos BC y 19,2% vs 5,9% en los gemelos MC) y esto también fue cierto para el percentil de la TN ≥99o (8,3% vs 1,0% en gemelos BC y 15,4% vs 2,0% en gemelos MC); y sexto, la frecuencia de una discordancia de la LCC ≥10% fue mayor en los que tenían un defecto que en los que no lo tenían (20,2% vs 7,9% en los gemelos BC y 33,8% vs 9,3% en los gemelos MC) y esto también fue cierto para la discordancia de la LCC ≥15% (10,1% vs 1,9% en los gemelos BC y 28,2% vs 2,8% en los gemelos MC). CONCLUSIONES: Primero, los defectos fetales son más comunes en embarazos de gemelos MC que en los de gemelos BC. Segundo, la detección en el primer trimestre de defectos fetales en los embarazos de gemelos BC es similar a la de los embarazos con feto único. Tercero, la detectabilidad en el primer trimestre de los defectos en los gemelos MC es mayor que en los gemelos BC. Cuarto, en los embarazos de gemelos con un defecto fetal, hay mayor discordancia entre los gemelos en la LCC y prevalencia de una mayor TN, pero la eficacia predictiva del cribado mediante estos marcadores es escasa.

Increased nuchal translucency at 11-13 weeks' gestation and outcome in twin pregnancy.

OBJECTIVE: To investigate the value of increased fetal nuchal translucency thickness (NT) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major defects or chromosomal abnormalities, we examined the value of increased NT ≥ 95th percentile in one or both fetuses in the prediction of, first, miscarriage or death of one or both fetuses at < 20 and < 24 weeks' gestation in DC, MCDA and MCMA twin pregnancies, second, death of one or both fetuses or neonates at ≥ 24 weeks in DC, MCDA and MCMA twin pregnancies, third, development of twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) treated by endoscopic laser surgery at < 20 and ≥ 20 weeks' gestation in MCDA pregnancies, and, fourth, either fetal loss or laser surgery at < 20 weeks' gestation in MCDA pregnancies. RESULTS: The study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA pregnancies. The incidence of NT ≥ 95th percentile in one or both fetuses in DC twin pregnancies was 8.3%; in MCDA twins the incidence was significantly higher (10.4%; P = 0.016), but in MCMA twins it was not significantly different (9.1%; P = 0.804) from that in DC twins. In DC twin pregnancies, the incidence of high NT was not significantly different between those with two survivors and those with adverse outcome. In MCMA twin pregnancies, the number of cases was too small for meaningful assessment of the relationship between high NT and adverse outcome. In MCDA twin pregnancies with at least one fetal death or need for endoscopic laser surgery at < 20 weeks' gestation, the incidence of NT ≥ 95th percentile was significantly higher than in those with two survivors (23.5% vs 9.8%; P < 0.0001). Kaplan-Meier analysis in MCDA twin pregnancies showed that, in those with NT ≥ 95th percentile, there was significantly lower survival at < 20 weeks' gestation than in those with NT < 95th percentile (P = 0.001); this was not the case for survival at ≥ 20 weeks (P = 0.960). The performance of screening by fetal NT ≥ 95th percentile for prediction of either fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation was poor, with a detection rate of 23.5% at a false-positive rate of 8.9%, and the relative risk, in comparison to fetal NT < 95th percentile, was 2.640 (95% CI, 1.854-3.758; P < 0.0001). In MCDA twin pregnancies, the overall rate of fetal loss or need for laser surgery at < 20 weeks' gestation was 10.7% but, in the subgroups with NT ≥ 95th and NT ≥ 99th percentiles, which constituted 10.4% and 3.3% of the total, the rates increased to 24.1% and 40.5%, respectively. CONCLUSIONS: In MCDA twin pregnancies with no major fetal abnormalities, measurement of NT at the 11-13-week scan is a poor screening test for adverse pregnancy outcome. However, the finding in one or both fetuses of NT ≥ 95th percentile, and more so ≥ 99th percentile, is associated with a substantially increased risk of fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation. The extent to which closer monitoring and earlier intervention in the high-risk group can reduce these complications remains to be determined. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Should cell-free DNA testing be used in pregnancy with increased fetal nuchal translucency?

OBJECTIVE: To assess the frequency of atypical chromosomal and submicroscopic anomalies, as well as fetal structural abnormalities, observed on first-trimester ultrasound scan in fetuses with nuchal translucency (NT) thickness > 99th centile, in order to evaluate the suitability of using standard cell-free DNA (cfDNA) testing as the sole screening test in these pregnancies. METHODS: This was a retrospective cohort study of 226 fetuses with NT > 99th centile at 11-14 weeks' gestation, between January 2013 and December 2017, in a clinical setting in which greater than 95% of pregnant women receive first-trimester combined screening. All patients underwent genetic testing by means of quantitative fluorescence polymerase chain reaction and chromosomal microarray analysis, mainly in chorionic villus samples. We assessed the theoretical yield of two cfDNA testing models, targeted cfDNA (chromosomes 21, 18 and 13) and extended cfDNA (chromosomes 21, 18, 13 and sex chromosomes), and compared it with that of cytogenetic testing and ultrasound assessment in the first and second or third trimesters. RESULTS: In the 226 fetuses analyzed, cytogenetic testing revealed 84 (37%) anomalies, including 68 typical aneuploidies (involving chromosomes 13, 18 or 21), six sex chromosome aneuploidies (four cases of monosomy X and two of trisomy X), three clinically relevant atypical chromosomal anomalies (one trisomy 22, one trisomy 21 mosaicism and one unbalanced translocation), five submicroscopic pathogenic variants and two cases with Noonan syndrome. Targeted and extended cfDNA testing would miss at least 12% (10/84) and 19% (16/84), respectively, of genetic anomalies, accounting for 4.4% and 7.1% of the fetuses with an increased NT, respectively. Finally, of the 142 fetuses with no identified genetic anomaly, a major fetal malformation was observed in 15 (10.6%) fetuses at the early anomaly scan, and in 19 (13.4%) in the second or third trimester. CONCLUSIONS: cfDNA does not appear to be the appropriate genetic test in fetuses with NT > 99th centile, given that it would miss 12-19% of genetic anomalies in this group. Additionally, first-trimester ultrasound will identify a major structural abnormality in 11% of the fetuses with NT > 99th centile and no genetic anomaly. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with increased nuchal translucency, tricuspid regurgitation and abnormal flow in ductus venosus.

OBJECTIVE: To examine the association between fetal major heart defects and increased nuchal translucency thickness (NT), tricuspid regurgitation and abnormal flow in the ductus venosus in a large population of singleton pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation. METHODS: This was a retrospective study of prospectively collected data from singleton pregnancies attending for a routine ultrasound scan at 11-13 weeks' gestation, which included examination of fetal anatomy, measurement of NT and assessment of blood flow across the tricuspid valve and in the ductus venosus, according to a standardized protocol. The incidence of fetal NT ≥ 95th and ≥ 99th percentiles, tricuspid regurgitation and reversed a-wave in the ductus venosus in fetuses with and those without a major heart defect was determined and the performance of each marker and their combination in the detection of major heart defects was calculated. RESULTS: The study population of 93 209 pregnancies with no apparent chromosomal abnormality included 211 (0.23%) with a fetal major heart defect and 92 998 morphologically normal neonates. In 113 (53.6%) cases with a major heart defect, the diagnosis was made at the 11-13-week scan, in 82 (38.9%) at the 18-24-week scan, in 10 (4.7%) at the third-trimester scan and in six (2.8%) postnatally. At the 11-13-week scan, we diagnosed all cases of tricuspid or pulmonary atresia and polyvalvular dysplasia, > 90% of cases of hypoplastic left heart syndrome or atrioventricular septal defect, about 60% of complex heart defects and cases of left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), 30-40% of cases of tetralogy of Fallot and arch abnormalities, 25% of tricuspid valve abnormalities and about 15% of cases of transposition of the great arteries, but none of aortic or pulmonary stenosis or common arterial trunk. Fetal NT ≥ 95th or ≥ 99th percentile, tricuspid regurgitation or abnormal ductus venosus flow was observed in 77 (36.5%), 45 (21.3%), 61 (28.9%) and 58 (27.5%) fetuses with a major heart defect, respectively, and in 5678 (6.1%), 857 (0.9%), 1136 (1.2%) and 1644 (1.8%) of those without a heart defect. Any one of NT ≥ 95th percentile, tricuspid regurgitation or abnormal flow in the ductus venosus was found in 117 (55.5%; 95% CI, 48.5-62.3%) fetuses with a heart defect and in 8166 (8.8%; 95% CI, 8.6-9.0%) of those without a heart defect. Any one of NT ≥ 99th percentile or the other two markers was found in 99 (46.9%; 95% CI, 40.0-53.9%) fetuses with a heart defect and in 3517 (3.8%; 95% CI, 3.7-3.9%) of those without a heart defect. CONCLUSION: At 11-13 weeks' gestation, measurement of fetal NT and assessment of flow across the tricuspid valve and in the ductus venosus can lead to early diagnosis of major heart defect. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Pregnancy outcome in foetuses with increased nuchal translucency - 10-years' experience in a prenatal medical practice.

This retrospective study describes pregnancy outcome for foetuses with increased nuchal translucency (NT) in relation to the degree of increase in a local specialised medical practice. Data from 7352 first trimester pregnancies examined by a single observer between 10/07 and 07/17 were screened. Three hundred and ninety-three foetuses (5.3%) that had an increased NT ≥ 95th percentile and available pregnancy outcome were identified. For this population, the frequencies of chromosomal abnormality, foetal malformation, intrauterine death (IUD) and termination of pregnancy (TOP) were determined in relation to the degree of NT thickness. Favourable pregnancy outcome decreased from 77.8% (lowest NT group, 95th percentile-3.5 mm) to 5% (highest NT ≥ 6.5 mm), whereas chromosomal abnormalities rose from 18.1% to 70%. An abnormal karyotype occurred in 39.2% of foetuses with increased NT. In euploid foetuses, cardiac defects were the most common structural abnormalities. The data largely matches with earlier studies conducted in large hospital-based settings. However, a rather high proportion of foetuses with abnormal karyotype was observed.IMPACT STATEMENTWhat is already known on this subject? Increased NT is associated with chromosomal abnormalities as well as an adverse perinatal outcome also in foetuses with a normal karyotype. The prevalence of an adverse outcome increases with NT thickness. These studies were conducted more than 10 years ago mainly in academic settings.What do the results of this study add? This study describes pregnancy outcome of a population of foetuses with increased NT that were examined in a medical practice by a single observer over a period of 10 years with state of the art ultrasound equipment. We observed a relatively large proportion of foetuses with abnormal karyotype. In euploid foetuses, increased NT was associated with a wide range of foetal malformations and genetic syndromes.What are the implications of these findings for clinical practice and/or further research? Even mildly increased NT thickness is associated with an adverse pregnancy outcome, underlining the importance of thorough ultrasound examinations. Specialised prenatal medical practices can provide state-of the art technology and provide improve parental counselling.

Prevalence and outcome of increased nuchal translucency in usmanu danfodiyo university teaching hospital, Sokoto, Nigeria: A cohort study.

BACKGROUND: An important component of the first-trimester scan is nuchal translucency thickness at 11 weeks to 13 weeks 6 days of gestation. A nuchal translucency ≥3.3 mm is a significant early pregnancy scan finding associated with Trisomies 13, 18, and 21 and congenital heart diseases. AIMS: To determine the prevalence and outcome of increased fetal nuchal translucency among pregnant women. SUBJECTS AND METHODS: A prospective cohort study at the Obstetrics and Gynaecology Department of Usmanu Danfodiyo University Teaching Hospital Sokoto. This was a prospective study of 265 consecutively recruited women in the first trimester of pregnancy who presented to antenatal clinics over a 20-week period. An NT scan was conducted at 11 weeks to 13 weeks 6 days followed by an anomaly scan at 18-22 weeks. Patients were followed up to delivery and 6-week post-partum. The neonates were examined at delivery and at 6-week postnatal life. Data entry and analysis was done with IBM SPSS version 20. The level of significance was set at less than 0.05. Frequency distribution; student t-test and Chi-squared test. RESULTS: The 95th percentile NT was 3.3 mm and the prevalence of increased NT above 3.3 mm was 3%. The mean maternal age of the participants was 28.1 ± 5.1 years and the modal parity was Para 0. The most common anomalies associated with increased NT were ventricular septal defect and spina bifida. A congenital anomaly was significantly associated with increased NT (P < 0.001). CONCLUSIONS: The prevalence of increased fetal nuchal translucency is relatively high in our environment and is associated with congenital fetal defects. Routine screening with first-trimester ultrasound will help detect congenital anomalies early.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Chromosomal microarray as primary diagnostic genomic tool for pregnancies at increased risk within a population-based combined first-trimester screening program.

OBJECTIVE: To evaluate the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first-trimester screening (cFTS). METHODS: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population-based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non-invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180-K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings. RESULTS: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5-5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4-4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5-4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8-11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0-9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed. CONCLUSIONS: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first-trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effectiveness of 12-13-week scan for early diagnosis of fetal congenital anomalies in the cell-free DNA era.

OBJECTIVES: The main aim of this study was to assess the proportion and type of congenital anomalies, both structural and chromosomal, that can be detected at an early scan performed at 12-13 weeks' gestation, compared with at the 20-week structural anomaly scan offered under the present screening policy. Secondary aims were to evaluate the incidence of false-positive findings and ultrasound markers at both scans, and parental choice regarding termination of pregnancy (TOP). METHODS: Sonographers accredited for nuchal translucency (NT) measurement were asked to participate in the study after undergoing additional training to improve their skills in late first-trimester fetal anatomy examination. The early scans were performed according to a structured protocol, in six ultrasound practices and two referral centers in the north-east of The Netherlands. All women opting for the combined test (CT) or with an increased a-priori risk of fetal anomalies were offered a scan at 12-13 weeks' gestation (study group). All women with a continuing pregnancy were offered, as part of the 'usual care', a 20-week anomaly scan. RESULTS: The study group consisted of 5237 women opting for the CT and 297 women with an increased a-priori risk of anomalies (total, 5534). In total, 51 structural and 34 chromosomal anomalies were detected prenatally in the study population, and 18 additional structural anomalies were detected after birth. Overall, 54/85 (63.5%) anomalies were detected at the early scan (23/51 (45.1%) structural and all chromosomal anomalies presenting with either an increased risk at first-trimester screening or structural anomalies (31/34)). All particularly severe anomalies were detected at the early scan (all cases of neural tube defect, omphalocele, megacystis, and multiple severe congenital and severe skeletal anomalies). NT was increased in 12/23 (52.2%) cases of structural anomaly detected at the early scan. Of the 12 cases of heart defects, four (33.3%) were detected at the early scan, five (41.7%) at the 20-week scan and three (25.0%) after birth. False-positive diagnoses at the early scan and at the 20-week scan occurred in 0.1% and 0.6% of cases, respectively, whereas ultrasound markers were detected in 1.4% and 3.0% of cases, respectively. After first- or second-trimester diagnosis of an anomaly, parents elected TOP in 83.3% and 25.8% of cases, respectively. CONCLUSIONS: An early scan performed at 12-13 weeks' gestation by a competent sonographer can detect about half of the prenatally detectable structural anomalies and 100% of those expected to be detected at this stage. Particularly severe anomalies, often causing parents to choose TOP, are amenable to early diagnosis. The early scan is an essential part of modern pregnancy care. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting.

OBJECTIVES: The primary aim of this study was to compare the screening performance for trisomy 21 (T21) between combined first-trimester screening (cFTS) with referral for invasive testing at a T21 risk ≥ 1 in 300, and contingent screening consisting of referral for invasive testing at a cFTS-T21 risk ≥ 1 in 100 and referral for cell-free DNA (cfDNA) testing at a cFTS-T21 risk between 1 in 100 and 1 in 1000. Secondary aims were to compare the incidence of fetuses diagnosed with trisomy 18 (T18), trisomy 13 (T13) or sex chromosome aneuploidy, and examine the association between fetal fraction of cfDNA in maternal blood and maternal/fetal characteristics. METHODS: Women with a singleton pregnancy and a cFTS-T21 risk of ≥ 1 in 1000 were recruited consecutively from two Danish hospitals between August 2014 and May 2015. First-trimester combined screening was based on maternal age, nuchal translucency thickness and levels of pregnancy-associated plasma protein A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Blood samples for cfDNA testing were analyzed for risks of T21, T18, T13 and sex chromosomal aneuploidies. cfDNA analysis was conducted blinded to the cFTS assessment and karyotype results. Pregnancy outcomes and pre- and postnatal karyotypes were obtained from the Danish Fetal Medicine Database. RESULTS: Among 6449 women who underwent cFTS risk assessment, 869 (13.5%) had a T21 risk of ≥ 1 in 1000 and 597 were included for cfDNA testing. Among these, there were 15 cases of T21, one case of T18 and two cases of T13. The sensitivity for detection of T21 was 100% using both screening strategies, while specificity increased significantly (P < 0.0001) from 97.0% using the cFTS strategy to 98.8% using the contingent approach. The sensitivity for detection of T21, T18 and T13 increased from 94.4% using the cFTS strategy to 100% using the contingent approach, with overlapping CIs, while specificity increased significantly (P < 0.0001) from 97.1% for cFTS to 98.9% for the contingent strategy. Seven pregnancies were categorized as being at increased risk of a sex chromosomal aneuploidy by cfDNA testing but chromosome analysis was discordant, corresponding to a false-positive rate of 1.2%. The fetal fraction decreased significantly with increasing maternal weight and increased significantly with the level of ß-hCG and PAPP-A and among female fetuses, in both univariate and multivariate analyses. CONCLUSIONS: In a clinical setting with efficient cFTS, contingent screening offering women with a cFTS risk of ≥ 1 in 100 an invasive test and women with a risk from 1 in 100 to 1 in 1000 a cfDNA test had the same sensitivity for T21, T18 and T13, but significantly increased specificity, when compared with offering an invasive test to all women with a risk of ≥ 1 in 300. Implementing contingent screening would therefore reduce significantly the number of invasive tests performed at no loss of sensitivity. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Impact of a shift in nuchal translucency measurements on the detection rate of first-trimester Down syndrome screening: A population-based study.

OBJECTIVE: To assess the distribution of nuchal translucency (NT) measurements following a national policy without credentialing and its impact on first-trimester Down syndrome screening (DSS) detection rate. METHOD: All first-trimester DSS data recorded in France (2010-2014) were collected by the laboratories in charge via an Internet database (https://www.bionuqual.org/echo.php). There was no minimal requirement for image quality to allow sonographers to enter the screening process. A subgroup of DSS with complete DS follow-up corresponded to 1614 sonographers. Based on the distribution of maternal age, DS detection rate was calculated and split as a function of the distribution of NT multiple of the median (MoM). RESULTS: Four thousand nine hundred forty-three sonographers performed 2,337,372 NT measurements. Median NT expressed in MoM was 0.83. Screenings with complete follow-up consisted of 197,417 screenings, in which DSS detection rates were respectively 70.4%, 70.9%, 79.4%, 87.7%, and 79.5% for the following median NT MoM ranges: <0.7, 0.70 to 0.79, 0.80 to 0.89, 0.90 to 0.99, and >0.99 (trend χ = 12.21; P = .0158). CONCLUSION: In France, following a policy of quality assessment without standardized credentialing, the distribution of NT measurements did not fit the expected distribution. Down syndrome detection rate was 10% lower in screenings by sonographers with a median NT < 0.80 MoM.

Inequity in timing of prenatal screening in New Zealand: Who are our most vulnerable?

BACKGROUND: In New Zealand (NZ), Maori and Pacific women are less likely to complete prenatal screening for Down syndrome and other aneuploidies than other ethnic groups. Young women <20 have low rates of completed screening compared with women >20 years. Women living in deprived areas have lower completed screen rates than women living in more affluent areas. Combined first trimester screening has a superior sensitivity (85%) compared with second trimester screening (75%) for trisomy 21. The relative contribution of demographic factors to timing of screening uptake (first vs second trimester) has not previously been examined. AIM: To evaluate the association of ethnicity, deprivation, District Health Board (DHB) of domicile and maternal age with timing of prenatal screening (first vs second trimester) in pregnant women screened in NZ from 2010 to 2013. METHODS AND MATERIALS: Univariate logistic regression analyses were used to explore the association between timing of completed screening and each of ethnicity, deprivation index, DHB of domicile and maternal age. Multivariate logistic regression models were developed to calculate odds ratios (OR) and 95% confidence intervals (CI). Statistical analyses were performed using SAS v9.3 RESULTS: Of completed prenatal screens, 88% were completed in the first trimester. Ethnicity, age, deprivation and DHB were all significant predictors of completed first versus second trimester screening. Maori women were almost 60% less likely (adjusted OR 0.37, CI 0.35-0.39) and Pacific women almost 80% less likely (adjusted OR 0.23, CI 0.21-0.24) than NZ European women to have completed first versus second trimester screening. Women <30 years were less likely to have completed first trimester screening, as were more deprived women. Variation was also seen by DHB with women living in Whanganui DHB less likely to have completed first versus second trimester screening than women living in Auckland (adjusted OR 0.76, CI 0.71-0.81). Women living in Bay of Plenty DHB were more likely to be screened in the first versus second trimester compared with women living in Auckland (adjusted OR 1.55, CI 1.38-1.74). Within Auckland itself, women living in Counties Manukau DHB were less likely to be screened in the first versus second trimester than women living in Auckland DHB even after adjusting for ethnicity, deprivation and maternal age. CONCLUSION: Maori and Pacific women have the lowest uptake of completed first versus second trimester screening after adjusting for age, deprivation and DHB. Research is required to understand if this relates to characteristics of the carer making the offer of screening, language and/or cultural barriers to care or specific collective cultural or religious views held by women from these ethnicities. The lower completed first trimester versus second trimester prenatal screening in deprived areas, as well as variation by DHB, may relate to the availability of ultrasound and/or laboratory services in specific regions. Cost may be a contributing factor to inequity in timing of completed prenatal screening uptake, as first trimester screening incurs a part-charge to the individual, while second trimester screening is fully funded. Systemic factors within the NZ maternity model of care may also be contributory with a potential disconnect occurring for the woman between primary medical care and later registration with a Lead Maternity Carer in the first trimester.