• Abnormal fetal cardiac axis
• Congenital heart defect
• Doppler
• Fetal cardiac axis
• Fetal echocardiography
• Four-chamber view

• Pregnancy
• Female
• Humans
• Arthrogryposis/diagnostic imaging
• Prospective Studies
• Ultrasonography, Prenatal
• Prenatal Care
• Parents

Beckwith-Wiedemann syndrome (BWS) is a clinically and genetically heterogeneous overgrowth disease. BWS is caused by (epi)genetic defects at the 11p15 chromosomal region, which harbors two clusters of imprinted genes, IGF2/H19 and CDKN1C/KCNQ1OT1, regulated by differential methylation of imprinting control regions, H19/IGF2:IG DMR and KCNQ1OT1:TSS DMR, respectively. A subset of BWS patients show multi-locus imprinting disturbances (MLID), with methylation defects extended to other imprinted genes in addition to the disease-specific locus. Specific (epi)genotype-phenotype correlations have been defined in order to help clinicians in the classification of patients and referring them to a timely diagnosis and a tailored follow-up. However, specific phenotypic correlations have not been identified among MLID patients, thus causing a debate on the usefulness of multi-locus testing in clinical diagnosis. Finally, the high incidence of BWS monozygotic twins with discordant phenotypes, the high frequency of BWS among babies conceived by assisted reproductive technologies, and the female prevalence among BWS-MLID cases provide new insights into the timing of imprint establishment during embryo development. In this review, we provide an overview on the clinical and molecular diagnosis of single- and multi-locus BWS in pre- and post-natal settings, and a comprehensive analysis of the literature in order to define possible (epi)genotype-phenotype correlations in MLID patients.

• Beckwith-Wiedemann syndrome
• X-chromosome inactivation
• clinical diagnosis
• discordant monozygotic twins
• molecular testing
• multilocus imprinting disturbance

• Cleft palate
• Diagnostic accuracy
• MRI
• Prenatal

• arthrogryposis multiplex congenita
• fetal movement
• multiple congenital contractures
• prenatal arthrogryposis

• Autopsy
• Fetus
• First trimester
• Micro-focus computed tomography
• Neuroimaging
• Postmortem imaging

• Autopsy
• Brain/diagnostic imaging
• Brain/embryology
• Cadaver
• Fetus/diagnostic imaging
• Gestational Age
• Humans
• Radiographic Image Interpretation, Computer-Assisted
• X-Ray Microtomography

Background: No universal  demarcation of gestational age  distinguishes miscarriage and stillbirth or extreme preterm birth (exPTB). This study provides a synopsis of outcome between 22 to <28 weeks gestation from a low resource setting.

Methods: A retrospective record review of a population on the Thailand-Myanmar border was conducted. Outcomes were classified as miscarriage, late expulsion of products between 22 to < 28 weeks gestation with evidence of non-viability (mostly ultrasound absent fetal heart beat) prior to 22 weeks; or  exPTB (stillbirth/live born) between 22 to < 28 weeks gestation when the fetus was viable at ≥22 weeks. Termination of pregnancy and gestational trophoblastic disease were excluded.

Results: From 1995-2015, 80.9% (50,046/ 61,829) of registered women had a known pregnancy outcome, of whom 99.8% (49,931) had a known gestational age. Delivery  between 22 to <28 weeks gestation included 0.9% (472/49,931) of pregnancies after removing 18 cases (3.8%) who met an exclusion criteria. Most  pregnancies had an ultrasound: 72.5% (n=329/454);  43.6% (n=197) were classified as  miscarriage and 56.4% (n=257) exPTB.  Individual record review of miscarriages estimated that fetal death had occurred at a median of 16 weeks, despite late expulsion between 22 to <28 weeks. With available data (n=252, 5 missing) the proportion of stillbirth was 47.6% (n=120), congenital abnormality 10.5% (24/228, 29 missing) and neonatal death was 98.5% (128/131, 1 missing). Introduction of ultrasound was associated with a 2-times higher odds of classification of outcome as exPTB rather than miscarriage.

Conclusion: In this low resource setting few (<1%) pregnancy outcomes occurred in the 22 to <28 weeks gestational window; four in ten  were miscarriage (late expulsion) and neonatal mortality approached 100%.  In the scale-up to preventable newborns deaths (at least initially) greater benefits will be obtained by focusing on the viable newborns of ≥ 28 weeks gestation.

• extreme preterm birth
• limited-resource
• low-income
• marginalized
• miscarriage
• neonatal death
• stillbirth
• ultrasound

• extreme preterm birth
• limited-resource
• low-income
• marginalized
• miscarriage
• neonatal death
• stillbirth
• ultrasound

• elective early-term delivery
• indicated preterm
• preterm birth
• provider-initiated preterm
• public health
• racial disparities
• spontaneous preterm

• Adult
• Congenital Abnormalities/diagnostic imaging
• Female
• Fetal Growth Retardation/diagnostic imaging
• Fetus
• Humans
• Imaging, Three-Dimensional
• Pregnancy
• Pregnancy Trimester, First
• Ultrasonography

• First trimester scan
• fetal brain anomalies
• prenatal care

• Korean Society of Ultrasound in Obstetrics and Gynecology
• Nuchal translucency measurement
• Pregnancy trimester, first
• Ultrasonography

Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a “genetic sonogram”, including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down’s syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.).

• Prenatal diagnosis
• Prenatal sonography
• Chromosome abnormalities
• Nuchal translucency
• Fetal echocardiography
• Skeletal dysplasia