Array study in fetuses with nuchal translucency above the 95th percentile: a 4-year observational single-centre study.

PURPOSE: To evaluate the performance of chromosomal microarray analysis (CMA) in fetuses with nuchal translucency (NT) > 95th percentile. Secondary objectives were to analyze these results according to NT thickness, below or above 3.5 mm, and those without associated anomalies. METHODS: This observational single-cohort study was conducted between 2015 and 2018 in fetuses with NT > 95th percentile. Following an invasive test, quantitative fluorescence-polymerase chain reaction (QF-PCR) was performed, and if normal, CMA was performed. Pathogenic copy number variants (CNVs), non-reported pathogenic CNV, pathogenic autosomal recessive variants and variants of unknown significance (VUS) were analysed. RESULTS: One-hundred and sixty-two fetuses with NT > 95th percentile, normal QF-PCR and CMA were included. Amongst 128 fetuses with NT between the 95th percentile and 3.5 mm, one (0.8%) had a pathogenic CNV, four (3.1%) had non-reported pathogenic CNV, one (0.8%) had pathogenic autosomal recessive variant and 13 (10.2%) had VUS. Amongst 34 fetuses with NT ≥ 3.5 mm, four (11.8%) had pathogenic CNV, one (2.9%) had non-reported pathogenic CNV, one (2.9%) had pathogenic autosomal recessive variant and four (11.8%) had VUS. Four in 162 (2.5%) fetuses had CNVs at the chromosome 16p13.11 region. Amongst 154 fetuses without structural abnormalities and normal QF-PCR, three (1.9%) had a pathogenic CNV, 5 (3.2%) had non-reported pathogenic CNV, one (0.6%) autosomal recessive pathogenic CNV and 16 (10.4%) had VUS. CONCLUSION: Pathogenic CNVs were found in 1% of fetuses with an NT thickness between the 95th percentile and 3.5 mm and in 12% of fetuses with NT ≥ 3.5 mm. CNVs were found at the 16p13.11 region in 2.5% of cases.

Perinatal outcomes and central nervous system abnormalities following intrauterine fetal transfusion: 17 years' experience in a tertiary center.

BACKGROUND: This study aimed to describe the perinatal outcome and central nervous system (CNS) anomalies in fetuses undergoing red blood cell (RBC) intrauterine transfusion (IUT). METHODS AND MATERIALS: This was an observational single-cohort study carried out at Vall d'Hebron University Hospital in Barcelona, Spain, between 2002 and 2018 in women undergoing RBC IUT for suspected fetal anemia. Primary outcomes were adverse perinatal outcome (intrauterine or neonatal death and termination of pregnancy [TOP]), prenatal or postnatal CNS anomalies, and significant neurological impairment. RESULTS: A total of 145 RBC transfusions were performed in 68 pregnancies of 60 women. The median gestational age for the first transfusion was 26 weeks (range, 18-32). Twenty-two (32%) fetuses were hydropic at the first transfusion. Fifty-eight pregnancies (85.3%) resulted in live births and 10 (14.7%) in adverse perinatal outcomes. Adverse perinatal outcomes were associated with hydrops (odds ratio [OR], 6.69; 95% confidence interval [CI], 1.53-29.23; P = .012) and gestational age at first transfusion (OR, 0.69; 95% CI, 0.54-0.89; P = .04). Four (5.9%) cases of cerebellar hemorrhage were diagnosed prenatally. In 14 (35%) of the 41 neonates undergoing brain ultrasound and/or magnetic resonance imaging (MRI) abnormalities were reported. The median follow-up was 6.5 years (range, 3 months to 19 years). Significant neurological impairment was reported in two cases (4.2%). CONCLUSION: In fetuses undergoing intrauterine RBC transfusion, the survival rate is high, particularly in the absence of hydrops and if the gestational age at first transfusion is above 22 weeks. Significant neurological impairment is uncommon, despite the fact that postnatal CNS anomalies at ultrasound or MRI are frequent.

Management and outcome of pregnancies in women with red cell isoimmunization: a 15-year observational study from a tertiary care university hospital.

BACKGROUND: The aims of this study were to determine the prevalence of the different anti-erythrocytic alloantibodies, to describe pregnancy outcomes according to a low-risk and high-risk classification for fetal anemia and to determine the factors that influence adverse perinatal outcomes. METHODS: This retrospective observational study included women referred to our center following the identification of maternal anti-erythrocytic alloantibodies between 2002 and 2017. Pregnancies were classified as high risk for fetal anemia in cases with clinically significant antibodies, no fetal-maternal compatibility and titers ≥1:16 or any titration in cases of Kell system incompatibility. In high-risk pregnancies, maternal antibody titration and the fetal middle cerebral artery peak systolic velocity (MCA-PSV) were monitored. Low-risk pregnancies underwent routine pregnancy follow-up. RESULTS: Maternal antibodies were found in 337 pregnancies, and 259 (76.9%) of these antibodies were clinically significant. The most frequent antibodies were anti-D (53%) and anti-K (19%). One hundred forty-three pregnancies were classified as low risk for fetal anemia, 65 (25%) cases were classified as no fetal-maternal incompatibility, 78 had clinically nonsignificant antibodies, 4 (2.8%) resulted in first-trimester pregnancy loss, and 139 (97.2%) resulted in livebirths. Of the 194 high-risk pregnancies, 38 had titers < 1:16 (resulting in 38 livebirths), and 156 had titers ≥1:16 or anti-K antibodies. In the last group, 6 cases miscarried before 18 weeks, 93 had a MCA-PSV < 1.5 multiples of the median (MoM), resulting in 3 perinatal deaths that were unrelated to fetal anemia, one termination and 89 livebirths; and 57 had a MCA-PSV > 1.5 MoM, resulting in 3 intrauterine deaths, 6 terminations and 48 livebirths. Ninety-two intrauterine transfusions were performed in 45 fetuses (87% anti-D). Adverse outcomes were related to a MCA-PSV > 1.5 MoM (p < 0.001), hydrops (p < 0.001) and early gestational age at first transfusion (p = 0.029) CONCLUSION: Anti-D remains the most common antibody in fetuses requiring intrauterine transfusion. A low or high-risk classification for fetal anemia based on the type of antibody, paternal phenotype and fetal antigen allows follow-up of the pregnancy accordingly, with good perinatal outcomes in the low-risk group. In the high-risk group, adverse perinatal outcomes are related to high MCA-PSV, hydrops and early gestational age at first transfusion.

Niveles de PAPP-A y fßhCG en gestantes gemelares monocoriónicas y bicoriónicas espontáneas y sus implicaciones en el cálculo del riesgo del cribado prenatal del primer trimestre / Papp-a and ß - hCG levels in spontaneous monochorionic and dichorionic twin pregnancies and their implications in calculating the prenatal risk in first trimester screening

Objetivo: Evaluar los niveles de distribución de los valores bioquímicos de PAPP-A y fßhCG según su edad gestacional, en gestaciones gemelares monocoriónicas y bicoriónicas concebidas espontáneamente en nuestra población. Material y métodos: Se ha estudiado un grupo de 123 gestantes gemelares. Un subgrupo de 72 gestantes gemelares bicoriónicas, con una edad media de 32,1 años, y otro de 41 gestantes gemelares monocoriónicas, con una edad media de 31,1 años. Resultados: Las gestantes gemelares bicoriónicas presentan valores estadísticamente superiores a las monocoriónicas para los valores de las medias de PAPP-A (MoM) (2,55 versus 1,79; p < 0,001) y de fßhCG (MoM) (2,18 versus 1,70; p < 0,001), y no estadísticamente significativos en las medias de la translucencia nucal (Tn) (MoM) (0,96 versus 0,93; p = 0,3). Se analizan las diferentes distribuciones de las concentraciones de las curvas de normalidad de estos parámetros según edad gestacional y corionicidad. Conclusiones: Es necesario determinar ecográficamente si los gemelos son mono- o bicoriónicos ya que hemos comprobado que en nuestra población presentan curvas de normalidad diferenciadas para PAPP-A y fßhCG, utilizadas para el cálculo del riesgo de aneuploidías en el cribado prenatal de primer trimestre (AU)

Objective: To analyse the distribution of PAPP-A and fß-hCG levels in monochorionic and dichorionic twin pregnancies conceived spontaneously in our population. Materials and methods: One hundred twenty-three twin pregnancies were studied. A group of 72 dichorionic twin pregnancies, with an average age of 32.1 years, and another 32 monochorionic twin pregnancies, with an average age of 31.1 years. Results: Dichorionic twin pregnancies conceived spontaneously show values statistically higher than monochorionic of PAPP-A (MoM) (2.55 versus 1.79, P>.001) and fβHCG (MoM) (2.18 versus 1.70, P>.001). There were no significant differences in nuchal traslucency (NT) between both groups (MoM) (0.96 versus 0.93, P=.3). The distributions of PAPP-A and fßhCG levels according the gestation age and chorionic state have been studied. Conclusions: Ultrasound needs to be performed to determine whether twins are mono- or bichorionics as our population has different distribution curves for PAPP-A and fßhCG, which are used to calculate the first trimester prenatal risk (AU)