Small size, big problems: insights and difficulties in prenatal diagnosis of fetal microcephaly.

Microcephaly is a sign, not a diagnosis. Its incidence varies widely due to the differences in the definition and the population being studied. It is strongly related to neurodevelopmental disorders. Differences in definitions and measurement techniques between fetuses and newborns pose a great challenge for the diagnosis and prognostication of fetal microcephaly. A false positive diagnosis can result (in countries where it is legal) in erroneous termination of pregnancy, where a false negative diagnosis might lead to the birth of a microcephalic newborn. Microcephaly in growth restricted fetuses deserves special attention and separate evaluation as it is an important prognostic factor, and not necessarily part of the general growth retardation. Several genetic syndromes incorporating microcephaly and intrauterine growth retardation (IUGR) are discussed. Deceleration of the head circumference (HC) growth rate even when the HC is still within normal limits might be the only clue for developing microcephaly and should be considered during fetal head growth follow up. Combining additional parameters such as a positive family history, associated anomalies, and new measurement parameters can improve prediction in about 50% of cases, and thus should be part of the prenatal workup. Advances in imaging modalities and in prenatal genetic investigation along with the emergence of new growth charts can also improve diagnostic accuracy. In this article, we review the different definitions and etiologies of fetal microcephaly, discuss difficulties in diagnosis, investigate the reasons for the low yield of prenatal diagnosis, and provide improvement suggestions. Finally, we suggest an updated algorithm that will aid in the diagnosis and management of fetal microcephaly.

In-utero evaluation of the fetal umbilical-portal venous system among fetuses with persistent right umbilical vein: Two-and three-dimensional ultrasonographic study.

OBJECTIVE: The aim of this study was to describe the anatomy of the portal system in fetuses with persistent right umbilical vein (PRUV). METHODS: Prospective observational study of fetuses diagnosed with PRUV. All patients underwent a comprehensive portal system anatomy scan supplemented by two-dimensional (2D) and three-dimensional (3D) color doppler modalities. RESULTS: 29 fetuses with PRUV were studied. We perceived an identical anatomical pattern in 28 fetuses. The right umbilical vein drains to the portal sinus (future right portal vein, RPV), which has a configuration of a left portal vein (LPV) in the normal left portal system, with three emerging branches: inferior (RPVi), medial (RPVm) and superior (RPVs). The RPV then courses to the left, towards the stomach to the point of the bifurcation of the main portal vein (MPV) to become the left portal vein. The LPV has an RPV configuration in a normal portal system with anterior (LPVa) and posterior (RPVp) branches. This anatomical layout mimics a mirror image of the normal anatomy of left portal system. CONCLUSION: PRUV has unique umbilical portal venous anatomy, which is a mirror image of the normal left portal system. It can be demonstrated prenatally and serve as an additional tool for prenatal diagnosis of PRUV.

Effect of magnet strength on fetal brain biometry - a single-center retrospective MRI-based cohort study.

PURPOSE: Abnormal fetal brain measurements might affect clinical management and parental counseling. The effect of between-field-strength differences was not evaluated in quantitative fetal brain imaging until now. Our study aimed to compare fetal brain biometry measurements in 3.0 T with 1.5 T scanners. METHODS: A retrospective cohort of 1150 low-risk fetuses scanned between 2012 and 2021, with apparently normal brain anatomy, were retrospectively evaluated for biometric measurements. The cohort included 1.5 T (442 fetuses) and 3.0 T scans (708 fetuses) of populations with comparable characteristics in the same tertiary medical center. Manually measured biometry included bi-parietal, fronto-occipital and trans-cerebellar diameters, length of the corpus-callosum, vermis height, and width. Measurements were then converted to centiles based on previously reported biometric reference charts. The 1.5 T centiles were compared with the 3.0 T centiles. RESULTS: No significant differences between centiles of bi-parietal diameter, trans-cerebellar diameter, or length of the corpus callosum between 1.5 T and 3.0 T scanners were found. Small absolute differences were found in the vermis height, with higher centiles in the 3.0 T, compared to the 1.5 T scanner (54.6th-centile, vs. 39.0th-centile, p < 0.001); less significant differences were found in vermis width centiles (46.9th-centile vs. 37.5th-centile, p = 0.03). Fronto-occipital diameter was higher in 1.5 T than in the 3.0 T scanner (66.0th-centile vs. 61.8th-centile, p = 0.02). CONCLUSIONS: The increasing use of 3.0 T MRI for fetal imaging poses a potential bias when using 1.5 T-based charts. We elucidate those biometric measurements are comparable, with relatively small between-field-strength differences, when using manual biometric measurements. Small inter-magnet differences can be related to higher spatial resolution with 3 T scanners and may be substantial when evaluating small brain structures, such as the vermis.

Fetal Micro and Macroglossia: Defining Normal Fetal Tongue Size.

OBJECTIVES: Abnormal fetal tongue size is a phenotypic feature of various syndromes including Beckwith-Wiedemann, Pierre-Robin, oromandibular limb hypoplasia, chromosomal aberrations, etc. Current data regarding normal fetal tongue size are limited. Hence, micro/macroglossia are subjectively determined. The aim of the study was to construct a contemporary fetal tongue nomogram and to assess its clinical contribution. METHODS: A prospective cross-sectional study was performed in well dated, low risk, singleton pregnancies. Fetal tongues were measured by 5 trained sonographers. Highest quality images were selected. Intra- and interobserver variability was assessed. Tongue length, width, area, and circumference 1st to 99th centiles were calculated for each gestational week. Based on the normal tongue size charts, we created a Tongue Centile Calculator. RESULTS: Over 18 months, 664 tongue measurements were performed. A cubic polynomial regression model best described the correlation between tongue size and gestational age. The correlation coefficient (r2 ) was 0.934, 0.932, 0.925, and 0.953 for tongue length, width, area, and circumference, respectively (P < .001). Intra- and interobserver variability had high interclass correlation coefficients (>0.9). Using the new charts, we were able to identify 2 cases of macroglossia, subsequently diagnosed with Beckwith-Wiedemann, and 4 cases of microglossia, 3 associated with Pierre-Robin sequence, and 1 associated with persistent buccopharyngeal membrane. CONCLUSIONS: We present novel fetal tongue size charts from 13 to 40 weeks of gestation. Clinical application of these nomograms may be beneficial in the prenatal diagnosis of syndromes or malformations associated with abnormal fetal tongue size.

Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study.

RESEARCH QUESTION: What is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity? DESIGN: A retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases (exposed) were defined as women presenting with three or more unexplained confirmed pregnancy losses at 5-24 weeks, whose first visit to the RPL clinic was between 1990 and 2010. The unexposed group included women giving birth who were not RPL patients; these were matched by age and year of giving birth/admission (1:5 ratio). Data from the RPL and the live birth registries were cross-linked to the Israeli national cancer registry according to the unique ID number and merged into one database. RESULTS: The study group comprised 937 RPL patients who were matched by maternal age (P = 1.0) and admission date (P = 0.84) to 4685 women achieving a live birth. There was no difference in overall cancer incidence between groups (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.55-1.03; P = 0.08). The secondary RPL group showed a trend towards decreased cancer morbidity incidence compared with primary RPL (adjusted OR 0.65, 95% CI 0.41-1.03; P = 0.07). Analysis by cancer type showed a similar risk for breast cancer among women with RPL compared with live birth, but a significantly lower risk for gynaecological cancers among women with RPL (adjusted OR 0.25, 95% CI 0.08-0.79; P = 0.018). CONCLUSIONS: Unexplained RPL may be related to a lower risk of gynaecological cancers, possibly explained by hyper-responsive immunological mechanisms involving uterine natural killer cells.

Dynamic esophageal patency assessment: an effective method for prenatally diagnosing esophageal atresia.

BACKGROUND: Esophageal atresia is a major anomaly with a low prenatal detection rate. We propose a sonographic method termed dynamic esophageal patency assessment. OBJECTIVE: This study aimed to assess the feasibility and performance of the dynamic esophageal patency assessment in a high-risk population. STUDY DESIGN: A prospective study was conducted in a single tertiary fetal ultrasound unit for 12 months. The study group included pregnant women referred for a targeted scan because of one or more of the following: (1) polyhydramnios; (2) small or absent stomach; (3) vertebral, anal atresia, cardiac, tracheoesophageal fistula, renal, and limb abnormalities; (4) first-degree relative with esophageal atresia; and (5) genetic mutation associated with esophageal atresia. In addition to dynamic esophageal patency assessment, a comprehensive anomaly scan was carried out. The fetal esophagus was observed during swallowing. Cases that demonstrated uninterrupted fluid propagation through the esophagus were classified as normal. Cases that demonstrated interrupted fluid propagation, with the formation of a pouch, were classified as abnormal. Cases with unclear visualization of the esophagus or cases that failed to demonstrate either fluid propagation or a pouch were classified as undetermined. Dynamic esophageal patency assessment results were compared with postnatal findings, considered "gold standard." Test performance indices and intra- and interobserver agreements were calculated. RESULTS: For 12 months, 130 patients were recruited, and 132 fetuses were scanned. The median gestational age (interquartile range) at the time of scan was 31.4 weeks (29.0-35.3). Of 132 fetuses enrolled, 123 (93.2%) were normal, 8 (6%) were abnormal, and 1 (0.8%) was undetermined. Excluded from test performance analysis were 3 cases that were terminated without postmortem autopsy (1 was abnormal and 2 were normal), and a fourth case was excluded as it was classified as undetermined. The detection rate of esophageal atresia was 100%, with no false-positive or false-negative case. Sensitivity, specificity, and positive and negative predictive values of the dynamic esophageal patency assessment were 100%. The Kappa coefficient was 1 for both inter- and intraobserver agreements (P<.0001). The median time (interquartile range) required to complete the dynamic esophageal patency assessment was 6.00 minutes (3.00-13.25). CONCLUSION: The dynamic esophageal patency assessment is a feasible and highly effective method of ascertaining an intact esophagus and detecting esophageal atresia in suspected cases.

Physiological and psychological stress responses to labor and delivery as expressed by salivary cortisol: a prospective study.

BACKGROUND: Labor is considered a stressful event, yet no study has described the course of stress measured by cortisol during labor and postpartum. OBJECTIVE: The objective of the study was to describe the patterns of physiological and psychological stress during labor as measured by salivary cortisol concentrations and stress questionnaires and their correlation to obstetric and neonatal outcomes. STUDY DESIGN: This prospective, observational study included 167 women with low-risk, singleton, term deliveries at a tertiary academic center. Physiological stress was evaluated by salivary cortisol measurements and emotional stress by questionnaire (stress scale ranging from 0 to 10) during the latent phase, active phase, and full dilation stages of labor as well as 2 minutes, 2 hours, and 24 hours after delivery. Cord blood cortisol and pH were also obtained. Modes of delivery, complications during labor and delivery, and early neonatal outcomes were evaluated. RESULTS: Salivary cortisol concentrations increased gradually from latent phase to active phase. The maximum increase was observed within 2 minutes of the delivery (from an average of 1.06 µg/dL to 1.67 µg/dL; 57% increase). Within 2 hours after delivery, cortisol decreased and reached a nongravid concentration after 24 hours (0.16 µg/dL). Cortisol concentrations during labor and up to 2 hours postpartum were above the average concentration of nongravid women (0.5 µg/dL). Women with epidural anesthesia had lower cortisol concentrations at complete dilation (P = .026) and 2 hours postpartum (P = .016) compared with women without epidural. Psychological stress peaked during latent and full dilation phases (mean 4.56 and 4.29, respectively). Maximum decrease from 4.29 to 2.04 (52%) occurred immediately postpartum. Cord cortisol was higher among women delivered by vacuum extraction compared with spontaneous vaginal delivery (17 ± 2 vs 11 ± 3.8, P = .03). CONCLUSION: This study reveals the course of cortisol concentrations during labor for low-risk pregnancies, with maximum increase immediately postpartum. Subjective stress levels decreased over the course of labor. Salivary cortisol portrays stress during labor and may be used as a reference to evaluate complicated pregnancies and to evaluate the role of cortisol during these deliveries.

Neutrophils to lymphocytes ratio and platelets to lymphocytes ratio in pregnancy: A population study.

BACKGROUND: Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are both inflammatory ratios that can be easily calculated from a simple blood count. They are frequently reported and tested as prognostic factors in several medical disciplines. Pregnancy involves special reference values for laboratory assays. OBJECTIVE: The aim of this study was to define pregnancy-related reference values for NLR and PLR according to trimester, background morbidity and according to the patient's age. STUDY DESIGN: A retrospective analysis of a large cohort undergoing community-based pregnancy surveillance between the years 2011-2016. Data were analyzed according to high-risk patient versus normal-risk patient. RESULTS: A total of 11,415 patients were included. Mean PLR and NLR values were 136.3±44.3, 2.6±1, respectively during the first trimester, 144.6±47.1, 4.0±1.4 respectively during the second trimester and 118.1±42.0, 3.5±1.2 respectively during the third trimester. No difference was detected between the high-risk and the normal population (P-values 0.3, 0.5 and 0.4 for PLR in each trimester respectively and 0.3, 0.4, 0.6 for NLR in each trimester, respectively). No differences were detected among parity categories. The correlation between patient's age and either PLR and NLR was a weak positive correlation (though statistically significant). Both PLR and NLR reached a maximum value during the second trimester. The differences between mean NLR and PLR between trimesters were significant (P <0.01 for all differences tested). PLR rises in the presence of anemia, reaching statistical significance (P-value for PLR in each trimester was <0.01). NLR showed an opposite trend (P-values for NLR were 0.4, 0.005 and 0.06 in each trimester, respectively). CONCLUSIONS: In our cohort, there were generally no differences between the high-risk and the normal population, excluding patients with a fibroid uterus or inflammatory bowel disease who presented a significantly elevated PLR through all trimesters. Both PLR and NLR reached a maximum value during the second trimester and were positively correlated with age. We anticipate that the population-based data will assist in providing accurate reference values for future research testing NLR and PLR measures during pregnancy.

Sonographic appearance of uterine lymphoma: case report and review of the literature.

Uterine lymphoma is rare and tends to be misdiagnosed due to lack of specific radiologic features. Few reports have been published on the sonographic characteristics of uterine lymphoma. We present a case report of uterine lymphoma manifested by a fast growing uterus and describe the sonographic findings.

Telomere aggregates in trisomy 21 amniocytes.

Trisomy 21 is the most common chromosomal abnormality among persons with intellectual disability, with a live birth rate of 1 in 800-1,000. As such, this abnormality may serve as a model for human disorders that result from supernumerary copies of a genomic region. Down syndrome carries an increased risk of developing acute leukemia and other malignancies. Telomeres of tumor cells nuclei tend to form aggregates (TA). This study evaluated TA formation in amniocytes from trisomy 21 pregnancies, compared with amniocytes from normal euploid pregnancies. A commercially available peptide nucleic acid telomere kit was used to evaluate TA formation, using two-dimensional fluorescence microscopy. Significantly higher frequencies of TA were found in trisomy 21 amniocytes than in amniocytes from normal pregnancies. The TAs found in trisomy 21 amniocytes apparently represent an additional parameter that reflects the high genetic instability of this syndrome and its recognized predisposition to develop leukemia and other malignancies.

[Pregnancy, labor and delivery: the pelvic floor injury].

The association between pregnancy, labor and delivery, and pelvic floor injury is well known. Pregnancy itself may be associated with some injury, but the main damage occurs during vaginal delivery. It is well documented that vaginal delivery may cause denervation of the pelvic floor as well as direct injury to muscles and connective tissue. These injuries may lead to the development of stress urinary incontinence, anal incontinence, voiding difficulties, and/or urogenital prolapse. Previous studies showed correlation between various obstetric risk factors and the development of these symptoms, however, there is no consensus regarding the relative contribution of the different parameters. Moreover, the apparently protective effect of cesarean section is questionable. Further studies are required to define obstetric risk factors as well as patients at increased risk. These factors should be taken into consideration in modern obstetric practice.

Early postpartum voiding dysfunction: incidence and correlation with obstetric parameters.

OBJECTIVE: To investigate the incidence and obstetric risk factors in early postpartum voiding dysfunction. STUDY DESIGN: Two hundred seventy-seven consecutive women in the early postpartum period were prospectively enrolled. Evaluation included history, physical examination, urinary questionnaire and non-invasive uroflowmetry measurements. Patients were interviewed regarding the presence and severity of voiding symptoms and were categorized into symptomatic versus asymptomatic subgroups. Obstetric parameters were compared in symptomatic versus asymptomatic patients as well as in cases of decreased (< 15 mL/sec) versus normal maximum urinary flow rates. RESULTS: One hundred twenty-five women (45% of the study population) hadearly postpartum voiding difficulties. Symptoms were significantly more common after vacuum extraction (38%) than spontaneous vaginal delivery (27%) or cesarean section (15%). The second stage of labor was significantly prolonged in symptomatic versus asymptomatic patients (62+/-52 versus 47+/-48 minutes). Voided volume, maximum and average flow rates and continuous flow pattern were significantly decreased in symptomatic versus asymptomatic patients. Twenty-eight patients (10%) demonstrated decreased (<15 mL/sec) maximum flow rates. The first stage of labor was significantly prolonged in these patients (9.7+/-5.8 versus 6.4+/-3.9 hours). Twenty-five patients (13%) gave birth to a neonate weighing > or =3,800 g. Maximum flow rates among these women were significantly decreased as compared to women with smaller infants (25.6+/-11 versus 32.9+/-19.2 mL/sec, respectively). CONCLUSION: Approximately 50% of patients complained of voiding difficulties in the immediate postpartum period. Main risk factors were prolonged first and second stages of labor, vacuum extraction and birth weight > or = 3,800 g. Long-term follow-up is needed to determine the significance of this clinically common entity.