Fetal Anomalies Research Articles

Incidence of new, non-physiologic maternal findings on fetal magnetic resonance imaging.

Fetal magnetic resonance imaging (MRI) is increasingly used for evaluation of fetal anomalies, and rates of incidental maternal findings are not well characterized. Our objective was to evaluate the rate of incidental maternal findings at the time of antenatal MRI performed for fetal indications. This was a retrospective cohort study that included all fetal MRIs performed between 2018-2023 at a single tertiary care institution with a multidisciplinary fetal diagnosis and treatment center. The electronic medical record was reviewed to identify all documented maternal findings and any new, non-physiologic maternal findings. The latter was defined as previously unknown abnormalities of maternal structures unrelated to normal physiology. Our study included 834 imaging events, performed at an average gestational age of 23 weeks. The most common indication for imaging was fetal anomaly (81.1%). The most common imaging type was fetal brain MRI (81.4%). Overall, 16.2% reported a maternal finding and 7% reported a new, non-physiologic finding. The most common new, non-physiologic findings were renal cysts (n=11), liver cysts (n=6), and gallstones or gallbladder sludge (n=5). Compared to imaging events that included a fetal brain MRI, imaging events that included a fetal body MRI had a significantly higher rate of any maternal findings (53.0% vs 10.4%, p< 0.001) and new, non-physiologic maternal findings (26.9% vs 3.7%, p< 0.001). Our results suggest that the risk of identifying new, non-physiologic maternal findings on fetal MRI is low. The rate of any maternal and new, non-physiologic maternal findings may differ by fetal MRI type due to differences in imaging depth and extent of radiology subspecialist review. These data should be incorporated into pre-test counseling for patients planning to have fetal MRI.

Prenatal diagnosis of fetal skeletal anomalies via whole-exome sequencing in a tertiary referral center

The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Implementation of a national rapid prenatal exome sequencing service in England: evaluation of service outcomes and factors associated with regional variation

IntroductionPrenatal exome sequencing (pES) can enhance genetic diagnosis of fetuses with structural anomalies and has recently been introduced as a national service in England. We aimed to examine service outcomes such as diagnostic yield (definite final diagnosis), referral rate, and sources of referral, and explore variation in outcomes of pES by individual or service level factors between 01 October 2021 and 30 June 2022.MethodspES testing results from the National Health Service laboratories performing testing were linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set and descriptive statistics computed.ResultsThere were 475,089 women who gave birth in England during the study period. The referral rate for pES was 8.6 (95% CI 7.8, 9.4) per 10,000 maternities. About 59% of those referred proceeded with pES testing and 35% of women who proceeded received a definite final diagnosis with a median turnaround time of 15 days. Of those who had pES testing, 64.6% had a live birth, 25.3% underwent termination of pregnancy (median gestational age at termination: 26 weeks), and 9.3% had a stillbirth. Among the 85 women who had a definite final diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth, and 42% had a live birth. The corresponding figures among women without a definite final diagnosis were 18%, 5%, and 78%, respectively. Among women who had a termination of pregnancy, the median gestational age at final report was 24.9 weeks and 26.2 weeks at termination. Variation observed in some of the characteristics and outcomes between regional services were limited by small sample size.ConclusionThis study showed that of those referred, pES testing provided a diagnosis for one in three pregnancies with a fetal anomaly across England during the study period when other tests had been non-informative. Women who opted for a termination of pregnancy underwent the procedure at relatively late gestations. Earlier referral for pES, streamlining pathways, and faster turnaround times may help results to be available at an earlier gestation to allow families more time to make decisions around continuing or terminating their pregnancy. The variation in service outcomes between regional services needs to be investigated further to understand the reasons for these differences.

Perceived Social Support and Depression, Anxiety and Stress in Pregnant Women Diagnosed With Foetal Anomaly.

To examine the relationship between perceived social support level and depression, anxiety and stress in pregnant women diagnosed with foetal anomaly. This descriptive and correlational study was conducted in an advanced prenatal evaluation unit of a university hospital between December 2021 and May 2022. The study data collected from 131 pregnant women through a personal information form, depression, anxiety and stress scale (DASS-42) and multidimensional scale of perceived social support (MSPSS). Most of the pregnant women were in the second trimester of pregnancy, and more than half had been advised by a healthcare professional to terminate their pregnancy. Overall, the pregnant women reported moderate levels of social support, while their depression, anxiety and stress levels varied. There was a weak negative correlation between perceived social support from family, friends and multidimensional sources with stress, but the effect rate was low. Most pregnant women diagnosed with foetal anomaly have normal levels of depression, stress and anxiety. There is a weak negative correlation between perceived social support and stress, with family and friend support affecting stress levels at a low rate. Professional support should be provided, and both the woman's mental health and social support mechanisms must be evaluated. This study highlights the importance of social support in managing stress among pregnant women with foetal anomalies. While most women had normal levels of depression, anxiety and stress, increased social support from family and friends was shown to reduce stress. The findings underscore the need for healthcare professionals to assess and strengthen mental health and social support systems in this vulnerable population, informing interventions to improve psychosocial outcomes. This descriptive and correlational study adhered to the CONSORT guidelines for reporting non-randomised trials. No patient or public contribution.

Perinatal deaths in twin and singleton infants in Ireland: A comparison of characteristics and causes.

Twin pregnancies are associated with significantly higher perinatal mortality (PM) rates compared to singletons, primarily due to complications like fetal growth restriction, preterm birth, and congenital anomalies. This study aimed to compare the characteristics associated with PM in twin pregnancies and compare maternal and obstetric factors and cause of death among twins and singletons in the Republic of Ireland. Data spanning 2011 to 2022 from the National Perinatal Epidemiology Centre's annual perinatal mortality clinical audit included 4494 perinatal deaths. Maternal characteristics, antenatal care factors and cause of death were analysed with relative risk calculated using national Hospital In-Patient Enquiry data. Pearson's chi-squared tests studied the difference between mortality in twins and singletons. Twins accounted for 10.4% of all perinatal deaths, despite representing only 3.6% of total births. The PM rate for twins was 17.3 per 1000 births, 3.1 times higher than for singletons. Early neonatal deaths (ENNDs) were more frequent in twins (54.2%), while stillbirths predominated among singletons (68.6%). Younger maternal age and lower BMI were associated with higher PM risks in twins. A considerable proportion of twin deaths with major congenital anomalies or birth before 28weeks gestation occurred in non-tertiary hospitals, suggesting limitations in referral pathways to centres with appropriate neonatal expertise. Twin pregnancies pose a higher risk of perinatal mortality, particularly among younger mothers and preterm births. The findings highlight the need for updated guidelines that prioritise early risk assessment, targeted interventions, and improved referral systems.

Oropouche Virus Infection: Differential Clinical Outcomes and Emerging Global Concerns of Vertical Transmission and Fatal Cases

Oropouche virus (OROV), a member of the Peribunyaviridae family, has emerged as a significant arboviral threat, particularly in South and Central America. Traditionally causing mild febrile illness, recent outbreaks have revealed severe clinical outcomes, including aseptic meningitis, encephalitis, and, more recently, vertical transmission leading to congenital anomalies and fatalities. Environmental changes, including deforestation and climate shifts, have expanded the virus's geographic range, as seen in Brazil, where over 8,000 cases were reported by August 2024, compared to fewer than 831in 2023. For the first time, vertical transmission has been confirmed, with cases of fetal deaths and congenital anomalies such as microcephaly and agenesis of the corpus callosum, drawing parallels to the Zika virus outbreak in 2015–2016. Despite these alarming trends, key mechanisms of placental transmission, maternal immunity, and fetal susceptibility remain poorly understood. This perspective highlights the urgent need for a coordinated global response, focusing on enhanced surveillance in newly affected regions, vector control strategies, and research into the factors driving severe clinical outcomes. Strengthening global efforts will be crucial in mitigating the public health threat posed by OROV, particularly in light of its potential for further geographic expansion and severe clinical manifestations.

Effect of Indoor Residual Spraying on Malaria in Pregnancy and Pregnancy Outcomes: A Systematic Review.

Malaria in pregnancy increases maternal and perinatal morbidity and mortality. Indoor residual spraying (IRS) is a core vector control strategy used to reduce transmission in endemic areas; however, its efficacy in reducing the sequelae of malaria in pregnancy is not well described. PubMed, Embase, Cochrane, and Web of Science were searched for all studies assessing IRS exposure during pregnancy. Abstracts and full texts were reviewed independently by two researchers, with discrepancies adjudicated by a third. Of 3,319 studies that met the search criteria, 17 met the inclusion criteria. Thirteen studies reported on the effect of IRS on malaria endpoints during pregnancy, five on birth outcomes, and one on a fetal anomaly. Twelve of the 13 studies exploring maternal malaria and 3 of 3 studies reporting on placental malaria demonstrated a reduction among those exposed to IRS during pregnancy. Results were more mixed for obstetric outcomes. Two of the best-quality studies showed reductions in preterm birth, low birthweight, and fetal/neonatal mortality; a third high-quality study did not demonstrate a reduction in perinatal mortality but did not evaluate preterm birth. One study found a significantly increased risk of preterm birth in those exposed to IRS, although the study was of lower quality. A final study demonstrated a small, although statistically significant, association between IRS and male urogenital birth defects. In malaria-endemic areas, the published literature suggests that IRS during pregnancy reduces the incidence of malaria parasitemia. However, without high-quality prospective studies directly examining IRS in pregnancy, the impact on birth outcomes is less clear.

ACE inhibitor and angiotensin receptor blocker use during pregnancy: data from the ESC Registry of pregnancy and cardiac disease (ROPAC)

Abstract Background and Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester due to the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and to evaluate the impact on perinatal outcomes. Methods The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. In addition, the perinatal outcomes of patients who stopped ACE-Is and/or ARBs before pregnancy were assessed. Results ACE-I (n=35) and/or ARB (n=8) were used in 42 (0.7%) of the 5739 ROPAC pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p=0.021), had chronic hypertension (31% vs 6%, p&amp;lt;0.001), or a left ventricular ejection fraction &amp;lt;40% (33% vs 4%, p&amp;lt;0.001). No pregnancy terminations due to fetal anomaly were reported. ACE-I use during the first trimester was independently associated with an increased risk of congenital anomaly (OR 3.1; 95% CI 1.0-9.3). No adverse fetal or neonatal effects were seen when ACE-I and/or ARB were discontinued prior to pregnancy. Conclusions ACE-Is and ARBs are seldom used during pregnancy and based on our data, ACE-Is should also be avoided in the first trimester due to a higher risk of congenital anomalies. Preconception counseling is crucial to discuss the potential risks of these medications, and to evaluate the clinical condition and, if possible, the woman can be switched to an alternative medication.

The Analysis of the Fetal Abdominal Wall and Gastrointestinal Tract Abnormalities in a Single Tertiary Center

OBJECTIVE: We aimed to evaluate the fetuses with gastrointestinal anomalies and anterior abdominal wall defects detected in the prenatal period in our clinic and to analyze their perinatal outcomes. STUDY DESIGN: This retrospective study analyzed the data of 67 cases evaluated by the perinatology department of the Basaksehir Cam and Sakura City Hospital between January 2021 and May 2023 with a diagnosis of fetal anterior abdominal wall and gastrointestinal tract abnormalities. RESULTS: A total of 67 cases were included in our study with a mean maternal age of 26.4 ± 3.1 years and a median gestational week of first assessment at our center of 22 weeks (12-39 weeks). The most common anterior abdominal wall malformations were omphalocele (n=29, 43.3%) and gastroschisis (6 cases, 9.0%), and the most common fetal gastrointestinal tract anomalies were duodenal atresia (n=10, 14.9%), dilated bowel (n=5, 7.4%), and intestinal atresia (n=4, 5.9%). While genetic testing was carried out in 18 cases (27%), chromosomal abnormality was found in 6 (9.0%) cases. Termination of pregnancy was performed in 6 cases (9.0%). Postnatally, surgery was performed in 49 cases (73.1%) with a diagnosis of postpartum omphalocele, duodenal atresia, gastroschisis, intestinal and anal atresia. An uneventful surgical course was recorded for 47 cases that underwent surgery. CONCLUSION: The most common abdominal wall defects are omphalocele and gastroschisis, and the most frequent gastrointestinal anomalies are small bowel abnormalities (duodenal atresia, dilated bowel, intestinal atresia) in our study cohort. These abnormalities might be an isolated anomaly or part of a syndrome or associated with chromosomal abnormalities. The prognosis for infants with gastrointestinal malformation depends on the presence of associated anomalies or karyotype anomalies.

Chromosomal Anomalies in Fetuses With Increased Nuchal Translucency: A Vietnamese Retrospective Study

Chromosomal Anomalies in Fetuses With Increased Nuchal Translucency: A Vietnamese Retrospective Study

Perinatal outcomes of selective termination in dichorionic twin pregnancies: a retrospective study from a single center.

Selective termination (ST) is an appropriate procedure for managing discordant fetal anomalies in dichorionic diamniotic (DCDA) twin pregnancies. The aim of this study was to investigate the perinatal outcomes of ST at different gestational ages in DCDA twin pregnancies. This retrospective study was conducted on DCDA twin pregnancies with STs at West China Second University Hospital between January 2012 and December 2022. According to the gestational age at which ST was performed, the patients were assigned to four groups: Group 1 (13 to 17 + 6weeks), Group 2 (18 to 23 + 6weeks), Group 3 (24 to 27 + 6weeks), and Group 4 (≥ 28weeks). We identified 230 patients for this study. The overall rates of miscarriage, preterm delivery at < 32weeks, and term delivery were 1.3%, 10.5%, and 50%, respectively, while the rates of live birth and neonatal survival were 98.7% and 98.2%, respectively. The rate of term birth was highest (70.6%) and the birth weight was heaviest (2931 ± 535g) in Group 1 (p = 0.000). In the presence of a fetus subjected to feticide, the mean delivery age was earlier than that in the non-presenting group (p = 0.017); accordingly, the mean birth weight in the feticide group was lower (2366 ± 628g) than that in the non-presenting group (2590 ± 634g) (p = 0.011). When we examined the relative relationship between reduction weeks and delivery weeks of twins by correlation analysis, we observed that with regard to maternal prognosis, two pregnancies involved preterm premature rupture of membranes (PPROM) at 7days and 3days after the procedure. Intrauterine infection occurred in two patients in Group 4, but there were no maternal deaths or maternal coagulatory abnormalities. Optimal perinatal outcomes were obtained by ST of DCDA pregnancies before 18weeks, regardless of whether or not the reduced fetus was the presenting twin. However, if legally possible, late (i.e., after 28weeks) procedures can be a safe alternative for patients diagnosed after the 18th week of gestation. Overall, we herein noted a negative correlation between the procedure week and the delivery week in this study. Moreover, ST of the non-presenting twin was associated with a heavier birth weight and later gestational age at delivery.

Congenital Cytomegalovirus Infection: Update on Screening, Diagnosis and Treatment: Scientific Impact Paper No. 56.

Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby becoming infected. Where CMV infection of the fetus in the womb has been confirmed (by amniocentesis, for example), regular ultrasound scans should be offered every 2-3 weeks until birth. Detailed assessment of the fetal brain is an essential part of these scans. Where maternal CMV infection occurs, but fetal infection is not confirmed, repeated ultrasound scans of the fetus should be offered every 2-3 weeks until birth. In infected fetuses, as well as ultrasound scans, an MRI scan of the brain should be offered at 28-32 weeks of gestation (and sometimes repeated 3-4 weeks later) to assess for any signs of harm to the fetal brain. All babies born to women with confirmed or suspected CMV infection should be tested for CMV with a urine or saliva sample within the first 21 days of life. In newborns with symptomatic CMV infection at birth, treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some. There is no licensed vaccine for CMV.

Aberrant Number of Vessels in the Umbilical Cord: What Do We Know?

The umbilical cord, comprising three vital blood vessels, serves as the lifeline between mother and fetus. Prenatal care emphasizes detailed ultrasound examinations of the umbilical cord and postnatal inspections of the placenta and cord to preemptively address potential complications. Studies have consistently shown a significant link between a single umbilical artery and unfavorable perinatal consequences, such as mortality and congenital abnormalities. Conversely, the impact of additional vessels remains uncertain. This review is dedicated to enhancing our understanding and refining diagnostic and therapeutic approaches in prenatal healthcare. The objective is to identify knowledge gaps and propose evidence-based solutions to improve care for pregnant women and their unborn babies. The presence of a single umbilical artery in prenatal diagnosis may signify potential risks for fetal anomalies and adverse pregnancy outcomes such as hemodynamic instability, ischemia, and an increased likelihood of intrauterine growth restriction. Additionally, even the presence of supernumerary vessels may be associated with fetal malformations. Serial fetal evaluations are recommended for detecting anomalies and monitoring fetal growth throughout pregnancy. Despite the generally benign nature of isolated SUA and supernumerary vessels, close monitoring and comprehensive prenatal care are essential to ensuring optimal outcomes for both mother and baby.

Diagnosis, Management and Outcome of Truncus Arteriosus Communis Diagnosed during Fetal Life-Cohort Study and Systematic Literature Review.

Background/Objectives: Truncus arteriosus communis (TAC) is a rare congenital heart defect characterized by a single arterial trunk that supplies systemic, pulmonary, and coronary circulations. This defect, constituting approximately 1-4% of congenital heart diseases, poses significant challenges in prenatal diagnosis, management, and postnatal outcomes. Methods: A retrospective analysis was conducted at the local tertiary referral center on cases of TAC diagnosed prenatally between 2019 and 2024. Additionally, a systematic literature review was performed to evaluate the accuracy of prenatal diagnostics and the presence of associated anomalies in fetuses with TAC and compare already published data with the local results. The review included studies that especially described the use of fetal echocardiography, the course and outcome of affected pregnancies, and subsequent management strategies. Results: The analysis of local prenatal diagnoses revealed 14 cases. Of the 11 neonates who survived to birth, the TAC diagnosis was confirmed in 7 instances. With all seven neonates undergoing surgery, the intention-to-treat survival rate was 86%, and the overall survival rate was 55%. By reviewing published case series, a total of 823 TAC cases were included in the analysis, of which 576 were diagnosed prenatally and 247 postnatally. The presence of associated cardiac and extracardiac manifestations as well as genetic anomalies was common, with a 22q11 microdeletion identified in 27% of tested cases. Conclusions: Advances in prenatal imaging and early diagnosis have enhanced the management of TAC, allowing for the detailed planning of delivery and immediate postnatal care in specialized centers. The frequent association with genetic syndromes underscores the importance of genetic counseling in managing TAC. An early surgical intervention remains crucial for improving long-term outcomes, although the condition is still associated with significant risks. Long-term follow-up studies are essential to monitor potential complications and guide future management strategies. Overall, a coordinated multidisciplinary approach from prenatal diagnosis to postnatal care is essential for improving outcomes for individuals with TAC.

Two Concurrent Cases of NAIT in Pregnant Sisters

Abstract Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal antibodies directed against fetal platelet antigens inherited from the father. Approximately 80% of cases of NAIT are attributed to antibodies against human platelet antigen (HPA)-1a and less commonly to antibodies against HPA-5b. We present two cases of possible NAIT attributed to anti-HPA-5b that were identified in sisters requiring concurrent management. Patient #1 is a 32-year-old G9P4044 woman with one pregnancy complicated by intrauterine growth retardation and partial placental abruption, another pregnancy complicated by fetal anomaly (intracerebral hemorrhage) status post termination of pregnancy at 23 weeks’ gestation and three miscarriages (one with chromosomal abnormality). The patient is homozygous for HPA-1a and HPA-5a, and the partner is homozygous for HPA-5b. HPA-5b antibodies and HLA antibodies were identified in the patient’s serum. Deemed at high risk for subsequent NAIT, she was started on intravenous immunoglobulin twice weekly and steroids during her second trimester until delivery. The patient underwent weekly fetal sonograms during pregnancy which were normal. The patient’s platelet counts were stable. The patient refused caesarean delivery. At 38 weeks’ gestation, the patient gave birth to a healthy female via normal spontaneous vaginal delivery. HPA-5b negative platelets were procured from our blood supplier, but neither the mother nor neonate required transfusion. The neonate showed no signs of bleeding and had normal platelet counts. Ultrasound imaging of the head was unremarkable. The patient and neonate were discharged home. Patient #2 is a 33-year-old G13P6156 woman with a prior pregnancy complicated by stillbirth at 32 weeks’ gestation. Considering her personal and family history, HPA testing was performed and HPA-5b antibodies were identified in the patient’s serum. The patient’s partner is heterozygous for HPA-5b. Crossmatched platelets were procured from our blood supplier. The patient refused caesarean delivery. The patient gave birth at 37 weeks’ gestation to a healthy male via normal spontaneous vaginal delivery. The fetus had mild thrombocytopenia (107 x 103/uL), with no bleeding or bruising identified. Neither the mother nor neonate required transfusion. The patient and neonate were discharged home. Ultrasound imaging of the head was unremarkable, and his thrombocytopenia resolved. While some studies postulate that anti-HPA-5b identification may be coincidental rather contributory to the disease process, these cases re-emphasize the importance of obtaining pregnancy, neonatal and family history to best risk stratify patients and determine management from both the clinical and transfusion medicine perspectives. If transfusion is needed, transfusion options include HPA negative platelets, crossmatched platelets and random donor platelets depending on clinical urgency and platelet availability.

TARS2 c.470 C > G is a chinese-specific founder mutation in three unrelated families with mitochondrial encephalomyopathy

Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21.

Confined Placental Mosaicism Detected With Non-Invasive Prenatal Testing: Is There an Association Between Mosaic Ratio and Pregnancy Outcome?

Confined placental mosaicism (CPM) is associated with an increased risk for pregnancy complications, such as fetal growth restriction (FGR), preterm birth and hypertensive disorders. Pregnancies with possible CPM can be identified with non-invasive prenatal testing (NIPT). We performed a retrospective cohort study to investigate whether the mosaic ratio, as calculated with the Veriseq v2 used for NIPT, can predict adverse pregnancy outcomes in cases of CPM. A mosaic ratio for trisomies detected by NIPT and obstetric data such as fetal growth, structural fetal anomalies and birthweight were retrospectively studied in a cohort of patients with CPM diagnosed between February 2021 and October 2023. Structural and sex chromosomal aberrations were not included in this study. Of 122 CPM cases, 52 cases (42.6%) showed adverse perinatal outcomes, including FGR, low birthweight, hypertensive disorders, or preterm birth. A significantly higher mosaic ratio was found in the adverse outcome group compared to those with normal outcome, but a clear-cut threshold could not be set, except potentially for trisomy 16. There is an association between the mosaic ratio and adverse pregnancy outcomes in cases of CPM. However, without a clear-cut threshold, it cannot be used for the individual patient for differentiation between CPM with and without clinical consequences.

The relationship between early-onset preeclampsia and the prognostic nutritional index and inflammatory markers

Background Preeclampsia is still a disease whose cause and treatment have not been fully characterised. Early-onset preeclampsia occurs before the 34th week of pregnancy, and late-onset preeclampsia occurs at 34 weeks or older. In our study, we investigated whether the prognostic nutritional index (PNI) and pan immune inflammation value (PIV), which are used in the prognosis and prediction of diseases in new studies in the literature, are useful for predicting early-onset preeclampsia. Methods The first group consisted of healthy pregnant women who had a single foetus without any additional disease between 24 and 34 gestational weeks, and the second group consisted of pregnant women who were diagnosed with early-onset preeclampsia and did not have any additional disease or foetal anomalies during the same gestational week. Neutrophil, lymphocyte, monocyte, thrombocyte, ALB, pan immune inflammation value (PIV) and prognostic nutritional index (PNI) scores were recorded. Results In our case control study, 70 patients with early-onset preeclampsia and 140 pregnant women composed the normotensive (control) group. There was a significant difference between the groups according to PIV (p = 0.04). The prognostic nutritional index (PNI) was significantly lower in the early-onset preeclampsia group than in the normotensive group (p < 0,001). A PNI lower than 36, 30 could only predict early-onset preeclampsia with a low sensitivity of 31.1% and specificity of 45%; the area under the curve was 0,24 (95% confidence interval 0.18–0.31), p < 0,001. Conclusion Patients with PNI scores lower than 36,30 may have early-onset preeclampsia.

Whole-body non-forensic fetal virtopsy using postmortem magnetic resonance imaging at 7 Tesla vs classical autopsy.

To determine the diagnostic accuracy of virtual autopsy using whole-body postmortem ultra-high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2-weighted imaging (T2-WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second-trimester fetuses. Thirty consecutive fetuses at 13-19 weeks' gestation (weight, 17-364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two-dimensional turbo high-resolution T2-WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational-age intervals (13-14, 15-16 and 17-19 weeks). Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42-96.29%) and a specificity of 97.87% (95% CI, 94.64-99.42%), with a positive predictive value of 96.30% (95% CI, 90.78-98.56%) and a negative predictive value of 95.34% (95% CI, 91.61-97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73-97.68%) for detecting structural abnormalities in second-trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. Virtual fetal autopsy using 7-T MRI and a turbo high-resolution T2-WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Is lifestyle different in male partners experiencing recurrent pregnancy loss compared to men fathering a live birth?

Recurrent pregnancy loss is characterized by three or more consecutive pregnancy losses. Although the causes of recurrent pregnancy loss are often unknown, chromosomal defects and fetal anomalies account for a significant proportion of cases. Previous research has primarily focused on maternal factors, but recent attention has shifted to the role of male lifestyle factors. This study examined how male lifestyle factors and chronic illnesses affect recurrent pregnancy loss in a Danish cohort. Objectives included analyzing demographic and clinical features, as well as assessing lifestyle factors and pregnancy outcomes. We included 741 males referred to the Danish recurrent pregnancy loss unit between 2009 and 2021, alongside a control group of 1173 males from the PREGCO study. Data on demography, clinical features, lifestyle factors, and pregnancy outcomes were collected and analyzed. The recurrent pregnancy loss group had a higher mean age compared to the controls. Although there was a trend suggesting a higher prevalence of obesity in the recurrent pregnancy loss group, statistical significance was not reached. The prevalence of chronic illnesses was similar in both groups. In the recurrent pregnancy loss group, a higher body mass index and history of previous or current smoking were associated with a lower pregnancy rate, and men who never smoked had an increased likelihood of achieving pregnancy. However, these associations lost significance after adjusting for potential confounders. The study suggests an association between male obesity and smoking, and decreased pregnancy rates after referral for recurrent pregnancy loss. However, further research is needed to understand the underlying mechanisms and establish causality in this association. The study reveals potential associations between male smoking, male obesity, and reduced pregnancy rates in individuals referred for recurrent pregnancy loss. These findings emphasize the importance of considering male lifestyle factors in the evaluation and management of recurrent pregnancy loss.