Congenital hypotonia: systematic approach for prenatal detection.

OBJECTIVES: Congenital hypotonic conditions are rare and heterogeneous, and some are severely debilitating or lethal. Contrary to its prominent postnatal manifestation, the prenatal presentation of hypotonia is frequently subtle, inhibiting prenatal detection. We aimed to characterize the prenatal sonographic manifestation of congenital hypotonia throughout pregnancy, evaluate the yield of diagnostic tests and propose diagnostic models to increase its prenatal detection. METHODS: This was a retrospective observational study of singleton pregnancies with congenital hypotonia, diagnosed either prenatally or immediately after birth, at a single tertiary center between the years 2012 and 2020. Prenatally, hypotonia was diagnosed if a fetus showed sonographic or clinical signs suggestive of hypotonia and had a confirmed underlying genetic condition, or in the absence of a known genetic abnormality if the fetus exhibited multiple prominent signs suggestive of hypotonia. Postnatally, it was diagnosed in neonates displaying reduced muscle tone leading to reduced spontaneous movement, reduced swallowing or feeding difficulty. We reviewed the medical records of pregnant patients carrying fetuses subsequently diagnosed with congenital hypotonia and assessed the yield of ultrasound scans, fetal magnetic resonance imaging, computed tomography and genetic tests. The detection rate of sonographic signs suggesting fetal hypotonia was calculated. The prevalence of non-specific signs, including polyhydramnios, persistent breech presentation, intrauterine growth restriction and maternal perception of reduced fetal movement, were compared between the study group and the local liveborn singleton population. Potential detection rates of different theoretical semiotic diagnostic models, differing in the threshold for referral for a targeted scan, were assessed based on the cohort's data. RESULTS: The study group comprised 26 cases of congenital hypotonia, of which 10 (38.5%) were diagnosed prenatally, and the controls included 95 105 singleton live births, giving a prevalence of congenital hypotonia of 1:3658. Nuchal translucency thickness and the early anomaly scan at 13-17 weeks were normal in all 22 and 23 cases, respectively, in which this was performed. The mid-trimester scan performed at 19-25 weeks was abnormal in four of 24 (16.7%) cases. The overall prenatal detection rate of congenital hypotonic conditions in our cohort was 38.5%. Only cases which underwent a targeted scan were detected and, among the 16 cases which underwent this scan, the prenatal detection rate was 62.5% compared with 0% in pregnancies that did not undergo this scan (P = 0.003). An abnormal genetic diagnosis was obtained in 21 (80.8%) cases using the following modalities: chromosomal microarray analysis (CMA) in two (9.5%), whole-exome sequencing (WES) in 14 (66.7%) and methylation analysis in five (23.8%). CMA was abnormal in 8% (2/25) of the cases and WES detected a causative genetic mutation in 87.5% (14/16) of the cases in which these were performed. Comparison of non-specific signs in the study group with those in the local singleton population showed that hypotonic fetuses had significantly more polyhydramnios (64.0% vs 3.0%, P < 0.0001), persistent breech presentation (58.3% vs 4.2%, P < 0.0001), intrauterine growth restriction (30.8% vs 3.0%, P < 0.0001) and maternal perception of reduced fetal movement (32.0% vs 4.7%, P < 0.0001). Prenatally, the most commonly detected signs supporting a diagnosis of hypotonia were structural anomaly (62.5%, 10/16), reduced fetal movement (46.7%, 7/15), joint contractures (46.7%, 7/15) and undescended testes ≥ 30 weeks (42.9%, 3/7 males). Proposed diagnostic strategies that involved performing a targeted scan for a single non-specific ultrasound sign or two such signs, and then carrying out a comprehensive genetic evaluation for any additional sign, offered theoretical detection rates in our cohort of 88.5% and 57.7%, respectively. CONCLUSIONS: Congenital hypotonic conditions are rare and infrequently detected prenatally. Sonographic signs are visible from the late second trimester. A targeted scan increases prenatal detection significantly. Comprehensive genetic testing, especially WES, is the cornerstone of diagnosis in congenital hypotonia. Theoretical diagnostic models which may increase prenatal detection are provided. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of preterm infants born to overweight and obese mothers†.

OBJECTIVES: To evaluate perinatal morbidity and mortality among preterm neonates who were born to overweight and obese mothers compared to preterm neonates who were born to mothers with normal pre-pregnancy body mass index (BMI). METHODS: Retrospective recordings of medical charts of 110 preterm infants born to overweight (n = 68) and obese (n = 42) mothers at gestational age (GA) 28-34 weeks, as well as 110 controls matched for GA and birth weight. All infants were born at the Sheba Medical Center between 2007 and 2014. Data regarding maternal pre-pregnancy weight and height were recorded, as well as maternal and neonatal complications and feeding methods. RESULTS: Obese mothers had more pregnancy-induced hypertension (52.4% versus 21.4%, p = 0.006) and caesarean section deliveries (81% versus 52.4%, p = 0.018). Overweight mothers had more gestational diabetes (20.6% versus 2.9%, p = 0.001). The study and control groups were similar on all neonatal outcome parameters. No differences between the groups were recorded throughout hospitalization with respect to Apgar score, respiratory distress and support, hypotension, cardiac manifestations, brain pathologies, infection, feeding type and total hospitalization days. CONCLUSIONS: Although the maternal complications are greater among obese and overweight women, it seems that preterm infants born to these women are not at increased risk for neonatal complications.

The use of short message services (SMS) to provide medical updating to parents in the NICU.

OBJECTIVE: Premature delivery and prolonged hospitalization of infants in the neonatal intensive care unit (NICU) are very stressful for parents. As technology has advanced, short message services (SMS) have been used increasingly in the medical disciplines. To date, the use of SMS for updating patients and families regarding medical information has not been reported. We implemented the SMS technique to daily update the parents regarding the health status of their preterm infant. The objective of this study was to evaluate the use of SMS technology and to assess its impact on the parents and the nursing staff. STUDY DESIGN: Parents and nurses completed questionnaires at two time periods: pre-SMS implementation (pre-SMSi) and post-SMS implementation (post-SMSi). The parent questionnaires included statements about medical information delivery, communication and trust between parents and medical staff, parental anxiety and overall satisfaction. The nurse questionnaires included statements about the expected and actual impact on their workload. RESULTS: Comparison of the parents' responses at the two time periods indicated that in the post-SMSi time period, they felt that the physician was more available when needed (P=0.002), they were more comfortable about approaching the physician (P=0.001) and more satisfied with the medical information provided by the staff (P=0.03). In the post-SMSi period, 78.1% of the nurses noted that the SMS communication is a convenient and user-friendly method. CONCLUSIONS: SMS updating is an easy and user-friendly technology that enriches the modalities of information delivery to parents of hospitalized preterm infants. It is a complementary and useful tool for encouraging and improving personal communication between parents and medical staff and should be considered part of quality improvement in health care.

Risk factors and associated diseases among preterm infants with isolated lenticulostriate vasculopathy.

OBJECTIVE: To determine the prevalence, risk factors and diseases associated with isolated lenticulostriate vasculopathy (LSV) among preterm infants. STUDY DESIGN: Medical records of 84 preterm infants (gestational age (GA) 25 to 34 weeks) with isolated LSV in a case-control retrospective study over a period of 6.5 years were reviewed and compared with matched control infants. LSV was defined as 'early' if it was documented in head ultrasound (HUS) before or on the fifth day of life and 'late' if it was not present in the first HUS and recorded later during neonatal hospitalization. RESULTS: A 3.9% prevalence of LSV was recorded among preterm infants (GA⩽34 weeks). Study and control groups were similar for all maternal parameters, neonatal outcomes and length of hospitalization. Infants with late LSV had more neonatal complications than control infants and were born with younger GA and lower birth weight in comparison to infants with early LSV. More infants with late LSV needed mechanical ventilation, were diagnosed with bronchopulmonary dysplasia and were hospitalized longer in comparison to infants with early LSV. Urine cytomegalovirus was negative in the entire study group. CONCLUSIONS: No risk factors or specific associated morbidities were identified among preterm infants with early isolated LSV. Infants with late isolated LSV were younger and had overall increased associated morbidities. Long-term outcome studies are needed to determine LSV impact.

Maternal anti-D prophylaxis during pregnancy and risk of hemolysis among preterm infants.

OBJECTIVE: To evaluate whether Rh-positive preterm newborn infants born to Rh-negative mothers treated with prophylactic anti-D immunoglobulins exhibited signs of hemolytic reaction, including anemia and hyperbilirubinemia. STUDY DESIGN: Retrospective data were collected for 94 Rh-positive preterm newborns born at gestational age (GA) 28 to 34 weeks to 76 Rh-negative mothers and for matched controls. RESULT: We found 11.7% positive Coombs' tests among infants in the study group and slightly higher bilirubin levels at birth and on the following 3 days. No differences were recorded between the study and the control groups for hematocrit levels throughout hospitalization, maximal bilirubin level, phototherapy treatment or the need for blood transfusion. CONCLUSION: Among preterm Rh-positive newborn infants born to Rh-negative mothers, there appears to be no evidence of significant hemolytic reaction derived from placental anti-D transfer. Further prospective studies are needed to confirm these findings in order to support anti-D administration close to preterm birth.

Split notochord syndrome - prenatal ultrasonographic diagnosis.

Split notochord syndrome is a rare condition that is characterized by a persistent connection of the gut and dorsal skin of the back, an enteric cyst and vertebral anomalies. We present two cases in which prenatal ultrasound showed polyhydramnios. In one case it was associated with vertebral abnormalities and a right-sided mediastinal cyst found to be the stomach. Postnatal evaluation confirmed the diagnosis of split notochord syndrome. The association of sonographic findings of hydramnios, thoracic cysts and vertebral anomalies suggests prenatal diagnosis of split notochord syndrome.

Coronary artery calcification in women with syndrome X: usefulness of double-helical CT for detection.

PURPOSE: To determine the usefulness of double-helical computed tomography (CT) for detection of diseased coronary arteries in women with anginal pain, positive exercise stress test results, and angiographically normal coronary arteries (syndrome X). MATERIALS AND METHODS: Double-helical CT of the coronary arteries was performed in 81 consecutive women who were referred for coronary angiography for evaluation of chest pain. Patients were classified into three groups according to stress test and angiographic results: normal (normal exercise test results and angiographically normal coronary arteries), syndrome X (abnormal exercise test results and angiographically normal coronary arteries), and coronary artery disease (at least one diseased vessel seen at angiography). RESULTS: The prevalence of coronary calcification in the syndrome X group was 63% (10 of 16 patients) compared with 96% (45 of 47 patients) in the coronary artery disease group (P = .002) and 22% (four of 18 patients) in the normal group (P = .02). The lowest total coronary calcification score and logarithmic transformed data were found in the normal group (2.9 +/- 0.7), statistically significantly higher values were found in the syndrome X group (4.3 +/- 1.5), and the highest values were found in the coronary artery disease group (5.1 +/- 2.0; for trend, P = .03). CONCLUSION: Double-helical CT may be useful in detection of atherosclerosis in women with syndrome X who demonstrate normal coronary arteries at angiography.

Does hormone replacement therapy inhibit coronary artery calcification?

OBJECTIVE: To determine the association between the use of hormone replacement therapy (HRT) and coronary calcium, in postmenopausal women who had no history of coronary artery disease by double helical computed tomography (CT). METHODS: We used CT to compare the prevalence and extent of coronary calcium in 41 postmenopausal women who were on HRT from the first year of menopause and 37 age-matched controls who had never used HRT. RESULTS: Both groups had a similar rate of smoking, hypertension, a positive family history, and hypercholesterolemia. Coronary calcification was observed in 28.2% of the 78 women studied. The prevalence of coronary calcium was significantly lower among HRT users: six of the 47 (14.6%), compared with 16 of the 37 nonusers (43.2%) (P < .01). The recorded risk factors had no effect on the prevalence of coronary calcium. Stepwise logistic regression analysis, including age, coronary risk factors, and HRT use as independent variables, yielded HRT as the only variable determining the presence of coronary calcium (odds ratio = 0.2; 95% confidence interval 0.06, 0.63; P = .006). CONCLUSION: The lower incidence of coronary calcium in the HRT users suggests that HRT is associated with decreased prevalence of the coronary calcification.

Anti-actin antibodies in sera from patients with autoimmune liver diseases and patients with carcinomas by ELISA.

UNLABELLED: Smooth muscle antibodies (SMA) were initially detected in sera of patients with chronic active hepatitis (CAH). Subsequently, their presence was demonstrated in a wide variety of other diseases. SMA are a mixture of antibodies directed towards different cytoskeletal antigens. Sera with high titers of anti-actin antibodies (AAA), a subgroup of SMA, are most frequently found among patients with autoimmune chronic active hepatitis (CAH) and, to a lesser extent, among patients with primary biliary cirrhosis (PBC) and other diseases. It is therefore established that AAA are a reliable marker to autoimmune CAH. The purpose of this study was to determine the titer of AAA in sera of patients with liver, autoimmune diseases and carcinomas, using the enzyme-linked immunoabsorbent assay (ELISA) method. The results were expressed as the optical density (OD) of the examined sera divided by the OD of a sera from a healthy control (presented as percentages +/- standard deviation). Sera of 33 patients with cirrhosis, nine patients with autoimmune CAH, fifteen patients with non-autoimmune CAH, eight patients with PBC, 30 patients with Sjogren's syndrome, 60 patients with SLE, 142 patients with carcinomas of different kinds, and 34 healthy donors were examined for the presence of AAA by ELISA. Statistically significant (P < 0.003) higher titers of AAA were detected in patients with autoimmune CAH (57 +/- 23%) compared with the control group and to other groups of diseases. AAA titers in non-autoimmune CAH were not significantly higher compared to the control group. High titers of AAA were detected in 67% of the patients with autoimmune CAH, as compared with other diseases in which only up to 13% of the patients exhibited AAA positivity. CONCLUSION: existence of higher levels of AAA noted in 67% of the patients with autoimmune CAH with regard to other groups of diseases, emphasizes the value of AAA as sensitive and specific markers, capable of characterizing the patients with autoimmune chronic active hepatitis.

Improved accuracy of computerized tomography based clinical staging in low stage nonseminomatous germ cell cancer using size criteria of retroperitoneal lymph nodes.

PURPOSE: We evaluated the significance of retroperitoneal lymph nodes detected by computerized tomography (CT) of low stage nonseminomatous germ cell tumor patients. MATERIALS AND METHODS: A blind retrospective review of 143 CTs of low stage nonseminomatous germ cell tumor revealed pathological stage A disease on 89 (62.2%) and pathological stage B disease on 54 (37.8%). A multivariate logistic regression model was used to evaluate the relationships between diameter of the retroperitoneal nodes detected in these CTs and pathological stage. RESULTS: Based on this model, as the diameter of the nodes increased within a 0 to 25 mm. range, the likelihood of pathological stage B disease increased in a continuous fashion. Using a 3 mm. threshold to define nonmetastatic nodes the sensitivity and negative predictive value of CT based staging was 90%. CONCLUSIONS: This measurement scheme improves the accuracy of staging compared to conventional methods.