Chromosomal Microarray Analysis in Fetuses With Ultrasonographic Soft Markers: A Meta-Analysis of the Current Evidence.

BACKGROUND: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype. METHODS: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study. RESULTS: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%). CONCLUSION: CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

Fetal insular measurements in pregnancy with estimated fetal weight <10th centile and childhood neurodevelopmental outcomes.

BACKGROUND: A growing body of evidence suggests that fetal growth restriction is associated with changes in brain structures as a result of chronic hypoxia. However, less is known about the effects of growth restriction on the fetal insula, particularly in less severely affected late-onset growth-restricted fetuses. OBJECTIVE: This study aimed to (1) compare sonographic insular measurements between fetal-growth restricted, small-for-gestational-age, and appropriate-for-gestational-age control fetuses; and (2) evaluate the association of sonographic insular measurements with perinatal and neurodevelopmental outcomes in fetuses categorized as fetal-growth restricted or small-for-gestational-age. STUDY DESIGN: This was a cohort study of singleton nonanomalous pregnancies with an estimated fetal weight <10th centile. Using data from the last examination before delivery, fetal insular depth, Sylvian fissure depth, hypoechoic insular zone thickness, circumference, and area were measured. All measurements were adjusted for by head circumference. Neurodevelopmental outcomes were evaluated at 2 to 3 years of age using the Bayley-III scales. Kruskal-Wallis H tests were performed to compare insular measurements between groups. Paired t tests were used to compare insular measurements between appropriate-for-gestational-age fetuses and gestational age-matched growth-restricted fetuses. Insular measurements for patients with and without an adverse perinatal outcome were compared using independent-samples t-tests. Spearman correlations were performed to evaluate the relationship of insular measurements to the percentile scores for each of the 5 Bayley-III subscales and to a summative percentile of these subscales. RESULTS: A total of 89 pregnancies were included in the study; 68 of these pregnancies had an estimated fetal weight <10th percentile (fetal-growth restricted: n=39; small-for-gestational-age: n=29). The appropriate-for-gestational-age cohort consisted of 21 pregnancies. The gestational age at measurement was similar between fetal-growth restricted and small-for-gestational-age groups, but lower in the appropriate-for-gestational-age group. Differences between groups were noted in normalized insular depth, Sylvian fissure depth, and hypoechoic insular zone (P<.01). Normalized insular depth and hypoechoic insular zone circumference were larger in the growth-restricted cohort (P<.01). Normalized Sylvian fissure depth was smaller in the growth-restricted cohort (P<.01). There were no significant differences in insular measurements between pregnancies with and without an adverse perinatal outcome. Bayley-III results were available in 32 of the growth-restricted cases. Of all insular measurements, hypoechoic insular zone circumference was inversely correlated with the adaptive behavior Bayley-III score. CONCLUSION: In our cohort, fetuses with estimated fetal weight <10th percentile had smaller Sylvian fissure depths and larger insular depths and hypoechoic insular zone circumferences than normally grown controls. A larger hypoechoic insular zone circumference was substantially correlated with worse neurodevelopmental outcomes in early childhood. We speculate that enlargement of this region may be an indication of accelerated neuronal maturation in growth-restricted fetuses with mild hypoxia.

Clinical and genetic aspects of termination of pregnancy; tertiary center experience.

Objective: The aim of the study was to retrospectively analyze the indications Techniques and complications of pregnancy termination performed in a tertiary center. Materials and Methods: All cases between 10 and 33 weeks of gestation between January 2021 and June 2023 were retrospectively analyzed. The patients were divided into two groups as group 1 with 11+0 to 21+6 gestational weeks and group 2 for those at 22+0 and 33+0 gestational weeks. Results: A total of 568 pregnancy terminations were included in the study. Among all terminations the most common fetal indications were central nervous system anomalies (148 cases, 26%) and trisomy 21 (53 cases, 9%) and the most common maternal/obstetrical Indication was previable premature rupture of the membranes (179 cases, 31.5%). Abnormal genetic results were found in 50 of 173 cases (28.9%) with a termination indication of Structural malformation who accepted invaziv genetic testing. The number of terminations with fetal indications performed after 22 weeks were 148 (41%) and 11 (7.4%) cases of these late terminations of pregnancy were anomalies expected to be diagnosed in the first trimester. Complication rates (12.4%) and abdominal termination rates (3.5%) were significantly higher in group 2 than in group 1 (p<0.05). Conclusion: Improvements in prenatal genetic screening and diagnostic techniques will undoubtedly decrease the gestational ages in terminations of pregnancies. However, there will always be cases that can neither be diagnosed earlier nor can be treated due to the nature of the anomaly. In the management of such cases, terminations will always occupy an important place in prenatal care.

Fetal Cardiac Hemodynamic and Sonographic Anomalies in Maternal COVID-19 Infection Depending on Vaccination Status-Polish Multicenter Cohort Study.

Most obstetrical studies have focused on maternal response to the SARS-CoV-2 virus but much less is known about the effect of COVID-19 on fetal physiology. We aimed to evaluate the effect of the maternal SARS-CoV-2 infection on the fetal homeostasis with the use of detailed ultrasonography and echocardiography and consideration of the effect of vaccination. This was a multi-center study of fetuses who had prenatal detailed ultrasound and echocardiographic examinations performed by fetal cardiology specialists. The subjects were divided based on the COVID vaccination status (vaccinated women who did not have COVID-group V, unvaccinated women who had COVID-group UV, and unvaccinated women who did not have COVID-control group). We evaluated the ultrasound and echocardiography results obtained. The study group included 237 gravidas from four prenatal cardiology centers. In the group of fetuses with normal heart anatomy, normal cardiovascular function had 147 (81%) fetuses and functional cardiovascular anomalies were present in 35 (19%) cases. Functional cardiovascular anomalies were present in 11 (16%) fetuses in the V group, 19 (47%) fetuses in the UV group and 5 (8%) fetuses in the control group (p < 0.01). There were 56 (24%) fetuses with extracardiac anomalies. Extracardiac anomalies were present in 20 (22%) fetuses in the V group, 22 (45%) fetuses of the UV group and in 14 (14%) fetuses in the control group (p < 0.01). Our study has proved that maternal COVID-19 infection can affect the fetal physiology and mild cardiac and extracardiac markers detected by fetal ultrasonography and echocardiography. Moreover, maternal vaccination results in lower occurrence of these findings in fetuses.

A Comparison of Changes in the Mean Arterial Blood Pressure and Mean Uterine Artery Pulsatility Index from 11-14 to 19-24 + 6 Gestation Weeks in Low-Risk and High-Risk Asian Indian Pregnant Women.

Aim The aim of this study was to determine the changes in the mean arterial blood pressure (MAP) and mean uterine artery (UtA) pulsatility index (PI) from 11-14 to 19-24 + 6 gestation weeks in Asian Indian pregnant women. Methods Clinical and demographic details, MAP, and mean UtA PI measures were ascertained for pregnant women at 11 to 14 gestation weeks and 19-24 + 6 gestation weeks. Women were categorized as a high-or-low risk for preterm preeclampsia using the Fetal Medicine Foundation algorithm and 1 in 150 cutoff. High-risk pregnant women were recommended low-dose aspirin 150 mg daily at bedtime. Changes in MAP and mean UtA PI were compared for gestational age intervals and high-and-low risk women using nonparametric tests. Results The study analyzed the results of 1,163 pregnant women. Both MAP (mean difference: 5.14, p < 0.001) and mean UtA PI (mean difference: 0.14, p < 0.001) remained significantly higher at the second-trimester assessment in high-risk pregnant women compared to low-risk pregnant women. Seventy-seven (35.16%) of the 219 pregnant women with abnormal mean UtA PI in the first trimester had an abnormal mean UtA PI in the second-trimester assessment. One hundred (10.59%) of the 944 pregnant women with normal mean UtA PI in the first trimester had an abnormal mean UtA PI in the 19-24 + 6 weeks assessment. Seventy-seven pregnant women (6.62% of 1,163 women, 95% confidence interval: 5.33, 8.20) had an abnormal mean UtA PI at both gestation age intervals. High-risk pregnant women taking low-dose aspirin daily showed a larger reduction in mean UtA PI compared to high-risk pregnant women that did not report the use of low-dose aspirin (0.89 vs. 0.62, p <0.001) Conclusion MAP and mean UtA PI decreased significantly from the first to the second trimester of pregnancy. Sequential assessment of the MAP and mean UtA PI in the first and second trimesters of pregnancy will be useful for fetal radiologists in India to identify a subgroup of women with abnormal mean UtA PI at both trimesters that may need more intense surveillance and follow-up till childbirth.

Minute Stroke Distance Is a More Reproducible Measurement Than Cardiac Output in the Assessment of Fetal Ventricular Systolic Function.

BACKGROUND: Echocardiographic quantification of fetal cardiac output (CO) aids clinical decision-making in the management of various cardiac and extracardiac diseases. Small variability in measuring semilunar valve dimension significantly reduces the reproducibility of the calculated CO. The authors propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. The aim of this study was to test the hypothesis that right and left ventricular minute VTI increase predictably with estimated fetal weight and are more reproducible than CO. METHODS: Five hundred seventy-one singleton fetuses without cardiovascular pathology between 16 and 36 weeks' gestation were reviewed retrospectively. Twenty-two fetuses with pathology resulting in low- or high-CO states were also assessed for comparison. VTI was measured in both ventricular outflow tracts at the level of the semilunar valve, excluding a Doppler insonation angle of >30°. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter- and intrarater variability were evaluated in a random 10% subset. RESULTS: Minute VTI and CO measurements were feasible in 67% to 89% of fetuses in this retrospective study. Minute VTI and CO increased with estimated fetal weight nonlinearly (R = 0.61-0.94). The mean inter- and intrarater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (P < .001 for all). CONCLUSIONS: Minute VTI is an easily measured, highly reproducible method of quantifying fetal ventricular systolic function. Variability in calculated CO from valve measurement differences is minimized by solely using VTI. Nomograms of minute VTI provide an efficient and precise assessment of fetal systolic function and may be used to track fetuses in disease states with low or high CO.

Prenatal diagnosis of fetal intracranial medulloepithelioma: a case report.

Intracranial medulloepithelioma is a very rare and highly malignant tumor that is typically diagnosed in childhood and has an inferior prognosis. In the current report, we described a case of fetal intracranial medulloepithelioma that was detected during the third trimester by prenatal ultrasonography, which displayed homogenous echogenicity with well-circumscribed margins and abundant blood flow. On magnetic resonance imaging, it was hyperintense on both T1- and T2-weighted magnetic resonance imaging. The fetal intracranial tumor was progressive, with rapid expansion within 3 weeks. The report aimed to provide knowledge on the clinical characteristics of fetal intracranial medulloepithelioma in prenatal diagnosis, particularly the radiological features.

Severe Congenital Diaphragmatic Hernia With Trisomy 9: A Case Report and Review of the Literature.

Congenital diaphragmatic hernia (CDH) is known to be complicated with various chromosomal abnormalities. However, the grade of pulmonary hypoplasia of CDH complicated by trisomy 9 is not known. This information is essential to the mother who has had a fetus with the same complication. We report a case of severe CDH with trisomy 9. The fetus had fetal growth restriction and multiple anomalies, including severe left CDH (observed/expected lung-to-head ratio 13.7%, liver-up, stomach grade 3 in Kitano classification), mild ventriculomegaly, low-set ear, rocker bottom, and single umbilical artery. Chromosomal test by amniocentesis showed a karyotype of 47,XX,+9. The neonate was born alive at 34 weeks but died 49 minutes after birth. In the literature review, this case and seven cases of complete trisomy 9 had CDH, and four of them were explained as "large" or "severe" CDH. In conclusion, trisomy 9 might be occasionally complicated by severe CDH.

Insulin Resistance in Gestational Diabetes Mellitus and Its Association With Anthropometric Fetal Indices.

Background: In pregnant women with gestational diabetes mellitus (GDM), insulin resistance (IR) increases the risk of developing manifest type 2 diabetes mellitus and is associated with complications in both mother and fetus. Objectives: This research aimed to evaluate the associations between IR evaluated by 3 indices (namely updated homeostasis model assessment model (HOMA2), QUICKI, and McAuley's index) and the diabetes risk factors and the fetal growth indices in Vietnamese women with GDM. Methods: A cross-sectional descriptive study was conducted on 370 women with GDM and 40 healthy pregnant women from January 2015 to May 2019. IR was calculated by HOMA2 (HOMA2-IR), QUICKI, and McAuley's index. Fetal anthropometric measurements were assessed via ultrasound which was performed and interpreted by ultrasound experts. Results: In the simple regression analysis, McAuley's index illustrated had statistically significant correlations to the highest number of risk factors of diabetes mellitus compared with HOMA2-IR and QUICKI indices. Moreover, McAuley's index correlated statistically significantly to the highest number of fetal ultrasound measurements factors such as including biparietal diameter (BPD) (r = -0.271, P < .001), head circumference (HC) (r = -0.225, P < .001), abdominal circumference (AC) (r = -0.214, P < .001), femur length (FL) (r = -0.231, P < .001), estimated fetal weight (EFW) (r = -0.239, P < .001) and fetal estimated age (r = -0.299, P < .001). In the multivariable analysis, the McAuley's index contributed the greatest to AC (Standardized B of -0.656, P < .001). Conclusion: The McAuley's index was significantly associated with a higher number of more risk factors for diabetes mellitus as well as fetal ultrasound sonography findings measurements than compared with HOMA2-IR and QUICKI indices.

Can sonographic imaging of the fetal pancreas predict perinatal outcomes in gestational diabetes mellitus?

OBJECTIVES: To evaluate whether fetal pancreatic echogenicity and its measurements are associated with gestational diabetes mellitus (GDM) and perinatal outcomes. METHODS: A prospective cohort study was conducted with 150 pregnant women with a singleton pregnancy. The study included pregnant women between 30 and 41 weeks with or without GDM. Fetal pancreatic circumference was measured using the free-hand tracking function. The echogenicity of the fetal pancreas was compared with the echogenicity of the liver and bone (ribs, spine) and classified as Grades 1, 2 and 3. The relationship between maternal characteristics and perinatal outcomes with fetal pancreas measurements and echogenicity was evaluated. RESULTS: Pregnant women with 75 GDM and 75 without GDM were included in the study. Mean fetal pancreas circumference measurements were significantly higher in pregnant women with GDM than in those without GDM (p=0.001). Hyperechogenic (Grade 3) fetal pancreas was significantly higher in pregnant women with GDM than in pregnant women without GDM, and there was a positive correlation between pancreatic echogenicity and HbA1c levels in pregnant women with GDM (r=0.631, p<0.01). There was a significant relationship between pancreatic echogenicity, measurements and adverse neonatal outcomes in pregnant women with GDM, and pancreas measurements were significantly higher in pregnant women with cesarean delivery. CONCLUSIONS: Fetal pancreatic echogenicity and measurements in pregnant women with GDM can give an idea about glucose regulation and adverse perinatal outcomes.

Decreased fetal thymus size at 24 weeks gestation by ultrasound measurement in gestational diabetes mellitus fetal thymus examination for diabetes.

AIM: This study aimed to evaluate the difference in fetal thymus diameter, which we measured ultrasonographically, between the healthy pregnant group and the pregnant group with gestational diabetes. METHOD: Fetal thymus and thymus/thorax ratio parameters were assessed in this case-control study. Patients were examined in two groups. They included 49 diabetics (study group) women and 71 nondiabetic (control group). We performed a binary logistic regression analysis to determine the predictive value of ultrasonographic measurements. We completed the receiver curve characteristic analysis to evaluate the cut-off thymus diameter. RESULTS: The median age of pregnant women was 27. Thymus diameter and thymus-thorax ratio were smaller in fetuses of diabetic mothers than in the nondiabetic group (p <0.05). Thymus diameter was found to be more predictive of gestational diabetes prediction (p: 0.019). There was no correlation between fasting blood glucose and thymus diameter. CONCLUSION: Decreased fetal thymus anterior-posterior diameter seems to be associated with diabetic pregnancy.

Risk factor analysis of irreversible renal dysfunction based on fetal ultrasonographic findings in patients with persistent cloaca: Results from a nationwide survey in Japan.

AIM OF THE STUDY: We conducted a nationwide survey of persistent cloaca (PC) to determine its current status in Japan. We focused on the relationship between fetal ultrasonographic findings and irreversible renal dysfunction in PC. METHOD: Patient information was obtained via questionnaire, and 466 PC patients were ultimately enrolled in this study. Fifteen patients (3.2%) who required dialysis or kidney transplantation were compared to those who were able to survive with their native kidney. Univariable and multivariable analyses were performed using a logistic regression analysis to clarify the relationship between irreversible renal dysfunction and fetal ultrasonographic findings. RESULTS: A multivariable logistic analysis showed that fetal ultrasonic findings of oligohydramnios independently increased the risk of irreversible renal dysfunction (adjusted odds ratio [OR] 5.8, 95% confidence interval [CI] 1.7-20, p = 0.005). A regression analysis showed that fetal ultrasonographic findings of hydroureteronephrosis (crude OR 5.6, 95% CI 0.9-24, p = 0.03) tended to be associated with irreversible renal dysfunction. In the PC patients with oligohydramnios, however, the ultrasonographic findings and associated anomalies did not affect the renal prognosis. The 15 renal dysfunction patients were treated as follows: hemodialysis (n = 4), peritoneal dialysis (n = 3), living donor renal transplantation (n = 8), and cadaveric renal transplantation (n = 1). CONCLUSION: Fetal ultrasonographic findings of oligohydramnios increase the risk of irreversible renal dysfunction. Such findings suggest we consider the need for earlier therapeutic intervention, such as fetal and postnatal treatment, to prevent the progression of renal dysfunction. LEVEL OF EVIDENCE: III (Study of diagnostic test, study of nonconsecutive patients and/or without a universally applied "gold" standard).

Prenatal ultrasound diagnostic approach to Omenn syndrome: case report / Aproximación diagnóstica ultrasonográfica prenatal al síndrome de Omenn: reporte de caso

Objective: To report the case of a pregnant woman with ultrasound diagnosis of altered fetal tegumental system and postnatal diagnosis of Omenn syndrome. Case presentation: A 27-year-old patient who presented at 31 weeks of gestation with prenatal ultrasound evidence of a fetus with significant scalp edema, echogenic amniotic fluid and scaly abdominal skin, with ichtyosis variant impression on diagnostic ultrasound. The baby was born with congenital erythroderma complicated with skin infection, and later developed septic shock and died. The genetic and pathologic workup led to the conclusion of Omenn syndrome. Conclusion: Omenn syndrome must be considered as part of the differential diagnoses when prenatal ultrasound shows findings of altered tegument system. Studies are required to assess the accuracy of ultrasound for prenatal diagnosis of erythroderma.

Objetivo: reportar el caso de una gestante con diagnóstico ultrasonográfico de alteración del sistema tegumentario fetal y diagnóstico posnatal de síndrome de Omenn. Presentación de caso: se presenta el caso de paciente de 27 años con embarazo de 31 semanas, con exploración ultrasonográfica prenatal que evidencia feto con edema significativo del cuero cabelludo, líquido amniótico ecogénico y descamación de la piel abdominal, con aproximación diagnóstica ultrasonográfica de variante de ictiosis. El recién nacido presentó eritrodermia congénita complicada con infección de piel, con posterior choque séptico y muerte. El estudio genético y patológico concluye síndrome de Omenn. Conclusión: el síndrome de Omenn debe ser tomado en cuenta en los diagnósticos diferenciales cuando en la ultrasonografía prenatal existan hallazgos ultrasongráficos de una alteración del sistema tegumentario. Se requieren estudios que evalúen la exactitud del ultrasonido en el diagnóstico antenatal de las eritrodermias.

Prenatal diagnosis of congenital heart defects: echocardiography.

Congenital heart defects (CHD) are the most common congenital anomaly, and the majority can be diagnosed during prenatal life. Prenatal detection rates remain highly variable, as most CHD occur in low risk pregnancies and therefore depend on the maternal obstetric provider to recognize fetal cardiac abnormality on obstetric screening anatomic ultrasound. Fetuses with abnormal findings on obstetric screening anatomic ultrasound and/or risk factors for cardiac disease should be referred for evaluation with fetal echocardiography. Fetal echocardiography should be performed by specialized sonographers and interpreted by physicians with knowledge of evolving fetal cardiac anatomy and physiology throughout gestation. A fetal echocardiography examination, which can be done from the late first trimester onward, utilizes a standardized and systemic approach to diagnose fetuses with CHD or other forms of primary or secondary cardiac disease. The field of fetal cardiology has advanced past the accurate prenatal diagnosis of simple and complex CHD, as fetal echocardiography enables understanding of dynamic fetal cardiac physiology and consideration of potential fetal/neonatal treatment. The greatest impact of fetal echocardiography remains identification of critical CHD before birth to allow immediate cardiac management after delivery to decrease neonatal morbidity and mortality. Analyzing the severity of abnormal cardiac physiology in various forms of CHD before birth allows the fetal cardiologist to prognosticate effects on the developing fetus, predict risk of postnatal hemodynamic instability, guide delivery planning through multidisciplinary collaboration, and anticipate how the disease will impact the neonate after delivery.

Aproximación diagnóstica ultrasonográfica prenatal al síndrome de Omenn: reporte de caso / Prenatal ultrasound diagnostic approach to Omenn syndrome: case report

Objetivo: reportar el caso de una gestante con diagnóstico ultrasonográfico de alteración del sistema tegumentario fetal y diagnóstico posnatal de síndrome de Omenn. Presentación de caso: se presenta el caso de paciente de 27 años con embarazo de 31 semanas, con exploración ultrasonográfica prenatal que evidencia feto con edema significativo del cuero cabelludo, líquido amniótico ecogénico y descamación de la piel abdominal, con aproximación diagnóstica ultrasonográfica de variante de ictiosis. El recién nacido presentó eritrodermia congénita complicada con infección de piel, con posterior choque séptico y muerte. El estudio genético y patológico concluye síndrome de Omenn. Conclusión: el síndrome de Omenn debe ser tomado en cuenta en los diagnósticos diferenciales cuando en la ultrasonografía prenatal existan hallazgos ultrasongráficos de una alteración del sistema tegumentario. Se requieren estudios que evalúen la exactitud del ultrasonido en el diagnóstico antenatal de las eritrodermias.

Objective: To report the case of a pregnant woman with ultrasound diagnosis of altered fetal tegumental system and postnatal diagnosis of Omenn syndrome. Case presentation: A 27-year-old patient who presented at 31 weeks of gestation with prenatal ultrasound evidence of a fetus with significant scalp edema, echogenic amniotic fluid and scaly abdominal skin, with ichtyosis variant impression on diagnostic ultrasound. The baby was born with congenital erythroderma complicated with skin infection, and later developed septic shock and died. The genetic and pathologic workup led to the conclusion of Omenn syndrome. Conclusion: Omenn syndrome must be considered as part of the differential diagnoses when prenatal ultrasound shows findings of altered tegument system. Studies are required to assess the accuracy of ultrasound for prenatal diagnosis of erythroderma.

Normal Mid-Gestation Fetal Ultrasonography Cannot Reliably Exclude Severe Perinatal Hypophosphatasia.

INTRODUCTION: Hypophosphatasia is a systemic bone disease characterized by inhibition of bone mineralization due to mutations in the ALPL gene that results in a deficiency of tissue nonspecific alkaline phosphatase. The perinatal form is the most severe. In the past, this form was lethal, although human recombinant enzyme replacement therapy has now been developed and licensed, which improves survival. Perinatal hypophosphatasia is usually suggested on antenatal ultrasonography with undermineralization of the long bones, skull, and thoracic cavity. In the UK, antenatal ultrasonography for fetal anomalies is conducted at mid-gestation (i.e., 18-21 weeks gestational age), and if normal, no further routine scans are performed. Usually, this would identify abnormalities in bone mineralization suggestive of perinatal hypophosphatasia. CASES: We describe 2 cases of perinatal hypophosphatasia where mid-gestation ultrasonography was normal. In the first case, where a previous pregnancy had been terminated for perinatal hypophosphatasia, third trimester ultrasonography revealed skeletal features of hypophosphatasia. In the second case, the diagnosis of perinatal hypophosphatasia was made only immediately after birth. CONCLUSION: We conclude that serial antenatal ultrasonography or antenatal genetic testing should be considered in all pregnancies with a positive family history of hypophosphatasia, as mid-gestation ultrasonography cannot reliably exclude perinatal hypophosphatasia. This is especially important given that effective enzyme replacement therapy is now available.

Modern fetal surgery-a historical review of the happenings that shaped modern fetal surgery and its practices.

The history of fetal surgery is one of constant evolution. Over the last 50 years, fetal surgery has progressed from a mere idea to an internationally respected innovative field of surgery. This article aims to provide a historical review of how the enterprise of maternal-fetal surgery came to be its modern version. This review is less focused on the history of specific therapies for a relatively small number of conditions, and more on how the whole field of maternal-fetal surgery evolved. The various internal and external influences that steered the field's evolution are discussed in chronologic order. Since the start of modern fetal surgery in the 1980s, large paradigm shifts have characterized the growth of the field as a whole. Innovative interventions are now based on physiologic manipulation as opposed to simple anatomic repair, fetoscopy has become the more frequently preferred surgical approach, and rigorous scientific evaluation with randomized controlled trials is now the standard expected by the community. In a very similar fashion to when the field first began in the early 1980s, recently community's leaders have risen to protect the integrity of maternal-fetal surgery by publishing ethical guidelines for innovation and clinical practice. This incredible history of innovation, rigorous science and ethical contemplation is the foundation on which modern maternal-fetal surgery rests.