Introduction and Importance: Bronchogenic cysts are rare congenital foregut malformations, usually asymptomatic in early life. Gastric bronchogenic cysts (GBCs) are exceedingly uncommon and often pose diagnostic challenges due to nonspecific symptoms and inconclusive imaging. Misdiagnosis is common, as GBCs can mimic solid tumors or other cystic lesions. Case presentation: A 53-year-old asymptomatic man was found to have an incidental gastric mass on abdominal CT, revealing a 4.0 × 2.1 cm non-enhancing lesion along the lesser curvature. Gastroscopy was unremarkable. He reported no symptoms such as nausea, vomiting, acid reflux, belching, chest tightness, or dyspnea. Physical examination revealed no significant abnormalities. Clinical discussion: Laparoscopic resection identified a cystic lesion within the gastric wall. Histopathology showed pseudociliated columnar epithelium, smooth muscle hyperplasia, and bronchial glands, confirming a bronchogenic cyst. The postoperative course was uneventful, and the patient remained symptom-free at 3-month follow-up. Conclusion: Although benign, GBCs warrant early surgical removal due to potential complications, including infection and malignant transformation. While abdominal CT is useful for initial detection, definitive diagnosis rests on histopathological examination. Laparoscopic resection proves to be a safe and effective treatment, underscoring the paramount importance of clinical vigilance to prevent misdiagnosis and ensure timely intervention.

Bone and cartilage defects resulting from trauma, degenerative diseases, or congenital malformations remain a major clinical challenge due to the limited intrinsic healing capacity of these tissues often leads to unsatisfactory outcomes. Piezoelectric biomaterials, which are capable of generating localized electrical signals under mechanical stimulation, have attracted considerable attention as they could mimic the electromechanical microenvironment of native tissues and modulate key cellular processes. However, conventional fabrication strategies were usually failed to meet the personalized requirements of bone and cartilage regeneration. Three-dimensional (3D) printing offers powerful tools for producing patient-specific scaffolds with complex architectures and controlled functionality. In this review, we firstly introduced the piezoelectric properties of the natural bone and cartilage tissue, and then discussed the characteristics of piezoelectric materials in regenerative medicine, with particular emphasis on the advantages and limitations of usage of 3D printing techniques in the fabrication of the piezoelectric biomaterials. Finally, we summarized the recent advances in 3D-printed piezoelectric scaffolds for bone and cartilage regeneration. Consequently, this review highlights the significant potential and practical value of 3D-printed piezoelectric scaffolds as the next generation of osteochondral implants.

Port-wine stain (PWS) is a congenital capillary malformation in which ecstatic venules reside several millimeters beneath the epidermis, limiting the effectiveness of visible-light therapies that suffer from shallow penetration and significant photothermal deposition. To address these challenges, we engineered a UCNP@HMME nanoplatform that transduces near-infrared (NIR) light into visible emission to activate the photosensitizer hematoporphyrin monomethyl ether (HMME) at depth. In a vascular-rich chicken wattle model of PWS, we compared the therapeutic effect of UCNP@HMME-mediated NIR-PDT with visible-light-activated HMME-PDT. UCNP@HMME with 980 nm irradiation produced immediate purpura, progressive bleaching, and significant reductions in dermal capillaries with sustained antivascular effects. In contrast, 532 nm HMME-PDT achieved strong superficial bleaching but induced blistering and ulceration. Thermal profiling showed that 532 nm irradiation elevated blood temperature, whereas 980 nm irradiation did not measurably increase temperature, mitigating nonspecific thermal injury. These findings demonstrate that UCNP-mediated NIR activation decouples photochemical efficacy from epidermal heating, enabling deeper, safer, and more durable vascular photoablation in a PWS model.

IntroductionAlthough the reported incidence of congenital vascular malformations is ~1.5% of the general population, the true incidence of these lesions is difficult to assess due to the heterogeneity of vascular anomalies and the variability in terminology used in reporting. These vascular anomalies can involve capillaries, lymphatics, venous, and/or arterial structures and can occur anywhere in the body. Rarely does a vascular malformation originate from the gastrointestinal (GI) mesentery and present as a bowel obstruction.Case ReportThis report describes an adolescent patient with an unusual presentation of a vascular malformation involving the GI mesentery, manifesting as midgut volvulus. Emergent laparotomy revealed a large intra‐abdominal cystic structure that volvulized resulting in a small bowel obstruction. The lesion and involved segment of small bowel were resected and found to be a mesenteric venous malformation on pathology.ConclusionVascular anomalies of the GI tract are uncommon but should be included in the broad differential for patients presenting with abdominal pain, symptoms consistent with a small bowel obstruction, and/or a cystic intra‐abdominal mass. In addition, utilization of accurate and standardized terminology when reporting these lesions is important to facilitate prompt and accurate diagnosis and treatment of patients and to establish a reliable foundation of continued research on vascular anomalies.

Bronchogenic cysts, a subgroup of foregut duplication cysts, are rare congenital malformations of ventral foregut development. These cysts can be found ectopically along the entire developmental pathway of the foregut. Less than 1% of bronchogenic cysts are found in the oral cavity, with fewer than 10 cases previously reported in the literature. These lesions typically present asymptomatically shortly after birth but have the potential to cause respiratory and/or feeding difficulties. Treatment is surgical excision, and histopathology is ultimately required to reach a definitive diagnosis and rule out other similar congenital tongue masses. This paper presents the case of a 5-month-old child who was found to have a cystic mass involving the anterior tongue, along with its treatment.

Congenital Pulmonary Airway malformations (CPAM) may lead to malignant degeneration, and therefore many surgeons opt to resect CPAM even in asymptomatic patients. Previously, we identified Kirsten rat sarcoma virus (KRAS) mutations in a subset of CPAM patients, possibly indicating a pre-malignant state. In order to unify treatment strategy in (asymptomatic) patients we focused on KRAS mutations as a potential risk factor for developing malignancy in CPAM. Resected lung tissue of CPAM patients was separated in affected region ("cyst") and non-affected region ("control") to subsequently initiate airway organoids. Cyst and control organoids from the same patients with and without KRAS mutations (KRASPOS vs. KRASNEG) (n = 3) where processed for single cell RNA sequencing (scRNA-Seq), and the cellular composition of the organoids was validated by immunofluorescent staining. The role of KRAS was identified by manipulating the expression in the organoids. ScRNA-Seq data revealed differences in cell proportions between KRASPOS and KRASNEG cyst, and control organoids. The significant differentially expressed genes in the KRASPOS cyst are comparable to those identified in lung cancer patients with KRAS mutations. Manipulation of KRAS expression showed that KRASPOS cyst organoids grew larger due to more proliferative cells and that KRAS directly affected the cell cycle. KRASPOS cyst organoids show transcriptomic similarities with KRAS mutated lung cancers, show changes in cellular composition and have increased growth and proliferation. These findings support the hypothesis that KRAS mutated CPAM cysts belong to a group of CPAM patients at higher risk of developing a malignancy.

Development and Preliminary Validation of a Rapid On-Site Detection Method for Schmallenberg Virus Using RT-RAA-LFD.

Hypospadias is a common congenital external genital structural malformation in the males, where significant deviations in appearance primarily affect the psychosocial health of the entire family during childhood, ultimately harming the patient's social integration, leading to high expectations for normal appearance from the patients and their families. The anatomical abnormalities of hypospadias exhibit considerable individual differences, and the difficulty of surgical repair largely depends on the experience of the surgeon, with high rates of complications and reoperations. Therefore, surgeons' expectations for surgical outcomes are more focused on functional reconstruction and reducing complication rates, creating a gap between the expectations of both doctors and patients. By measuring anatomical abnormalities, it may be a feasible approach to set normal appearance goals to achieve normal appearance outcomes. This article introduces the use of anthropometric assessment methods to accurately describe the anatomical abnormalities of hypospadias and proposes specific morphological goals for the reconstruction of various parts, implementing surgical operations in a goal-oriented manner. The aim is to establish a unified baseline decision-making system for hypospadias surgery, shorten the learning curve, improve the quality of clinical research, and achieve integrated reconstruction of structure, function, and aesthetics for patients.

Pulmonary sequestration is a congenital lung malformation involving the systemic arterial blood. Infection is a common complication; however, Nocardia infection is rare. We report the case of a 55-year-old immunocompetent male with recurrent infection of a pulmonary cyst in the left lower lobe. Despite the use of empirical antibiotics, the inflammation recurred. Contrast-enhanced computed tomography confirmed pulmonary sequestration, and bronchoscopy revealed Nocardia cyriacigeorgica. Although trimethoprim-sulfamethoxazole was effective, it was discontinued because of severe drug-induced rash. Surgical resection resolved the infection without the use of long-term antibiotics. Timely consideration of surgical intervention may be important for infection control in pulmonary sequestration complicated by Nocardia, especially when antibiotic management is difficult.

ABSTRACT We will see that providing care with empathy and centered on the patient and the patient’s family in the neonatal intensive care unit (NICU) is very difficult for professionals. The healthcare team needs to balance the clinical needs of the newborn with the demands of parents and family. We know that parents are deeply influenced by the compassion and treatment they receive from health professionals during the terminal process of their beloved children’s lives. Although the death of a newborn is a devastating event, the knowledge and skills of the multidisciplinary team can substantially influence the parents’ ability to effectively cope with the loss. Despite advances in neonatal care in recent years, more children die in the perinatal and neonatal periods than in any other period of childhood. In the USA, the majority of newborn deaths are due to congenital malformations and disorders related to shortened gestation and low birth weight. Keywords: Terminality of neonatal life, monitoring of neonatal grief, end of neonatal life.

Pericardial cysts are rare, benign congenital cardiovascular malformations that account for approximately 7% of mediastinal masses. Epicardial cysts attached to the cardiac surface with intimate coronary artery involvement are even rarer and pose significant diagnostic and surgical challenges. This case highlights a giant pericardial cyst with intimate right coronary artery involvement in a 10-month-old infant, where subtotal resection was necessary to preserve coronary integrity. A 10-month-old male infant with a pericardial cyst initially detected at 27 weeks of gestation presented with progressive compression of right heart chambers. Imaging revealed a large multiloculated cystic mass (5.3 × 3.5 × 3.9 cm) compressing the right atrium and right ventricle, with associated pulmonary valve stenosis. Intraoperatively, the cyst was found on the epicardial surface with intimate involvement of the right coronary artery. Complete excision was not feasible due to the risk of coronary injury. The main cystic mass was excised with cavity obliteration, while the portion adjacent to the right coronary artery was intentionally preserved. Concurrent pulmonary valve commissurotomy and pulmonary artery augmentation were performed. Histopathology confirmed a mesothelial-lined pericardial cyst. The patient recovered uneventfully and was discharged. This case underscores the importance of comprehensive preoperative coronary artery assessment in pericardial cysts with atypical locations. When complete excision risks vital structure injury, subtotal resection with cavity obliteration represents a safe alternative strategy.

We aimed to investigate prevalence, associated anomalies and survival of congenital intestinal atresia and to examine maternal risk factors for jejunoileal atresia (JIA). All children born with, or pregnancies terminated because of, JIA or colonic atresia (CA) in Finland during 1987-2019 were identified from the Finnish Register of Congenital Malformations. Clinical information was obtained from national health registers. Maternal risk factors were assessed using all JIA cases from 2004 to 2017 (n = 101). For each case, five appropriately matched live-born controls were selected. We identified 175 JIA and 48 CA cases. About half were isolated anomalies. Gastrointestinal anomalies were the most common associated defects (26% in JIA, 35% in CA), followed by cardiac anomalies in JIA (13%) and urinary tract anomalies in CA (19%). Survival was 88% in JIA and 94% in CA. Only two of 224 patients died directly due to intestinal atresia. Maternal insulin use (adjusted odds ratio [aOR] 8.4, 95% CI 1.4-51.0) and propionic acid derivatives (aOR 4.6, 95% CI 1.5-14.8) were associated with increased JIA risk. Although associated anomalies were frequent, mortality in intestinal atresia remained low. Maternal insulin and propionic acid derivative use may meaningfully contribute to JIA risk. IV.

Delayed villous maturation (DVM) is a placental maturation disorder that mainly affects maternal-to-foetal oxygen transfer. We conducted a systematic review, meta-analysis, and sensitivity analysis exploring study heterogeneities (I2) of risk factors and outcomes associated with histopathological findings of DVM. Medline, EMBASE, Web of Science, and MIDIRS databases were searched from inception to December 2023. Peer-reviewed, observational studies including cohort, case-control, and cross-sectional studies reported the histopathological findings of DVM after placenta delivery. All eligible studies were included and assessed for their risk of bias using the Newcastle-Ottawa scale (NOS) for cohort and case-control studies. Two reviewers independently performed the systematic article screening, bias assessment, and data extraction. Senior authors resolved the disagreement between reviewers. The risk of bias was assessed by two reviewers using NOS criteria. The random-effects model was used for meta-analysis due to heterogeneity across studies. Sensitivity analyses were performed according to the NOS risk of bias assessment and the DVM definition per the Amsterdam criteria. Fifty-two eligible studies reporting DVM and linked risk factors and outcomes were included. The risk factors associated with DVM were gestational diabetes (GDM) (OR = 4.90; 95% CI = 2.98, 8.06; I2 = 39%), pregestational diabetes (PGDM) (OR = 2.77; 95% CI = 1.56, 4.92; I2 = 0%), and maternal obesity (OR = 1.88; 95% CI = 1.20, 2.96; I2 = 0%). DVM was also associated with congenital foetal malformations (OR = 5.22; 95% CI =2.39, 11.39; I2 = 40), stillbirth (OR = 4.89; 95% CI = 3.55, 6.72; I2 = 0) and preterm birth (OR = 17.41; 95% CI = 10.14, 29.90; I2 = 0). The association between DVM and stillbirth (OR = 12.06; 95% CI =3.40, 42.78; I2 = 50; 2/5 studies) persisted in analyses limited to studies that used Amsterdam criteria exclusively for DVM. DVM is a placental abnormality associated with congenital foetal malformations and maternal dysmetabolism, including GDM, PGDM, and maternal obesity; and with adverse outcomes including stillbirth and preterm birth. In studies using Amsterdam criteria, placenta with DVM was associated with stillbirth and congenital malformations. Optimising metabolism could prevent harm to the baby.

BackgroundNirsevimab, a highly effective monoclonal antibody, is recommended for all infants < 8 months of age and high-risk patients 8 to < 20 months of age with chronic lung disease (CLD) of prematurity, cystic fibrosis (CF), severe immunocompromise or who are American Indian/Alaska Native (AI/AN) to prevent RSV.1,2 Other children with underlying medical conditions (UMCs) may also benefit from nirsevimab. We characterized the clinical course of RSV-associated hospitalization in children with UMCs by nirsevimab eligibility.Figure 1.Underlying medical conditions1 for hospitalized children with at least one underlying medical condition aged 8 to <20 months ineligible for nirsevimab (n=523, 12/01/2016 to 07/16/2023).1Prematurity defined as <37 weeks gestation. Atopic conditions include atopic/allergic conditions not including asthma/RAD. Genetic/metabolic conditions include development disorders (autism spectrum disorder, global developmental delay, pervasive development disorder, intellectual disability, gross motor delay, other developmental disorder) and genetic conditions (down syndrome, congenital syndromes, inborn errors of metabolism, disorders of fatty acid metabolism, chromosomal deletion/duplication/translocation, other genetic syndrome). Cardiovascular conditions include congenital heart malformations and heart conditions. Neurologic/neuromuscular conditions include cerebral palsy, seizure disorder, and other neurologic/neuromuscular conditions (e.g., autonomic dysfunction, agenesis, blindness, muscular dystrophy, severe scoliosis). Gastrointestinal/hepatic conditions include chronic liver disease, surgical/congenital GI disease, inflammatory bowel disease, eosinophilic esophagitis, pancreatic insufficiency, and other gastrointestinal conditions. Airway disorders include, e.g., tracheostomy dependence, tracheomalacia, cleft lip/palate, vocal cord paralysis, etc. Other conditions include other significant medical conditions requiring chronic treatment. Hematologic conditions include sickle cell disease, other anemias, coagulopathy, arterial or venous thromboses, thrombocytopenia, and other blood disorders. Renal conditions include chronic renal failure, end stage renal disease, chronic nephritis, nephrotic syndrome, and other kidney conditions. Endocrine conditions include diabetes mellitus, adrenal insufficiency, hypothyroidism or hyperthyroidism, and other endocrine conditions. Oncologic/immune conditions include cancer and undergoing treatment, transplant recipient, asplenia, rheumatologic disease, primary immunodeficiency, and other immune conditions.Table 1.Children with an underlying medical condition 8 to <20 months hospitalized with RSV (N=581), stratified by eligibility for nirsevimab1 (12/01/2016 to 07/16/2023).Abbreviations: IQR, interquartile range; ICU, intensive care unit.1Eligibility defined as children 8 to<20 months old with CF, CLD of prematurity, or immunocompromising condition, or AI/AN children.2p-values calculated by Pearson’s χ² test for categorical variables and the two-sample t-test with unequal variances for continuous variables.MethodsData were obtained by the New Vaccine Surveillance Network (NVSN; a 7-site, prospective surveillance platform of acute respiratory illness) from December 1, 2016 through July 16, 2023. Analysis was restricted to hospitalized children 8 to < 20 months with a positive RT-PCR for RSV, and p-values were calculated by Pearson’s χ² test for categorical variables and the two-sample t-test with unequal variances for continuous variables. Clinical history and UMCs were obtained by parent/guardian interview and/or chart review. We stratified by eligibility for nirsevimab, which was broadly defined as AI/AN, those with CLD of prematurity, CF, and/or immunocompromise.ResultsA total of 581 children 8 to < 20 months with UMCs were hospitalized with RSV. Of these, 58 (10%) were nirsevimab-eligible (Table 1), including 55.2% with CLD of prematurity, 12.1% with immunocompromise, and 6.9% with CF; 22.4% were AI/AN and 3.4% were AI/AN with CLD of prematurity. Compared with nirsevimab-ineligible children, nirsevimab-eligible children had longer duration of hospitalization and higher frequency of ICU admission (Table 1, p=0.015 and p< 0.001, respectively); notably, 80% of ICU admissions were nirsevimab-ineligible children. Of 523 (90%) nirsevimab-ineligible children, the majority (51.6%) were premature (median gestational age 34 weeks (IQR: 32, 36) (Figure 1) vs. 26 weeks (IQR: 25, 28.8) in nirsevimab-eligible children). Other UMCs were not as commonly present as prematurity.ConclusionMost hospitalized RSV-positive children 8 to < 20 months of age with UMCs were not eligible for nirsevimab and most ineligible children were premature. Additional analyses are needed to further characterize children in their second RSV season who are at highest risk for severe RSV disease.DisclosuresPedro A. Piedra, MD, Gilead: Honoraria|GSK: Grant/Research Support|Icosavax: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Novavax: Grant/Research Support|Pfizer: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support Marian G. Michaels, MD, MPH, Merck: Grant/Research Support Rangaraj Selvarangan, PhD, Altona: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Biomerieux: Honoraria|Cepheid: Grant/Research Support|Hologic: Grant/Research Support|Hologic: Honoraria|Meridian: Grant/Research Support|Qiagen: Grant/Research Support Daniel C. Payne, PhD, MSPH, Merck: Advisor/Consultant|Moderna: Advisor/Consultant Mary A. Staat, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|National Institutes of Health: Grant/Research Support|Up-To-Date: Royalties Janet A. Englund, MD, AstraZeneca: Board Member|AstraZeneca: Grant/Research Support|Cidarra: Member Data Safety Monitoring Board|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Geoffrey A. Weinberg, MD, Inhalon Biopharma: Advisor/Consultant|Merck & Co: Honoraria Natasha B. Halasa, MD, CSL-Seqirus: Advisor/Consultant|Merck: Grant/Research Support

Androgen signaling is critical for male sex differentiation and proper penile development. Disruption of this pathway results in congenital malformations of the male external genitalia, such as hypospadias. Hypospadias is a malformation of the penis, where the urethral opening is located along the ventral shaft rather than the tip. Although the molecular link between androgen signaling, penile differentiation, and proper urethra closure has been established for over 70 years, most hypospadias cases do not have a defined etiology. To clarify how the androgen receptor contributes to human hypospadias, we conducted a quantitative meta-analysis comparing androgen receptor expression in hypospadias patients and healthy boys. Due to substantial heterogeneity and imprecision in both mRNA and protein assays, no consistent direction of androgen receptor expression could be demonstrated, suggesting that hypospadias etiology may be more complicated than just the sole expression of the androgen receptor. To contextualize these results, we complemented the meta-analysis with a mini-review summarizing the various mechanisms through which androgen receptors can be regulated in the developing penis. This review aims to provide a framework for future investigations of androgen signaling and urethral closure mechanisms during penile development.

Prediabetes, Diabetes and Folate Status among U.S. Women of Reproductive Age: National Health and Nutrition Examination Survey (NHANES) 2011-March 2020.

It is becoming increasingly evident that congenital abnormalities of the kidneys and urinary tract (CAKUT) represent significant public health concerns. The purpose of this study was to investigate the relationship between maternal diseases and the occurrence of CAKUT in offspring. This retrospective study covered pregnant women in Hainan between 2021 and 2023. In newborns with and without CAKUT, medical data on maternal chronic diseases, such as hypertension, diabetes mellitus, hyperthyroidism, and hypothyroidism, were gathered. Psychiatric illnesses, syphilis, cholestasis, and uterine fibroids were examined. Among the 11,572 pregnant women in the study group, 123 cases of CAKUT were discovered in their children. A strong association between maternal chronic illnesses, particularly gestational diabetes and chronic hypertension, and CAKUT in children was found by the data. Compared to the fetuses of young women, the fetuses of older mothers were more prone to prenatal CAKUT. Advanced maternal age and maternal chronic illnesses are associated with CAKUT in offspring and should be treated to improve outcomes.

To evaluate the diagnostic performance of an artificial intelligence (AI) system for detecting eight abnormal fetal ultrasound findings across cephalic, thoracic, and abdominal regions in routine, unfiltered, multicenter images. We performed a multicenter, retrospective evaluation of an AI software that detects eight abnormal ultrasound findings on still images. Ground truth was established by a multidisciplinary panel (board-certified reviewers with 5 or more years of experience) using a three-step process (view identification, structure visibility, sign presence or absence) with majority consensus. The software evaluated eight findings on six standard views: absence of the cavum septum pellucidum, absence of the corpus callosum, malposition of the great vessels, absence or unusual size of one of the three vessels, disequilibrium or absence of at least one of the two ventricles, thoracic situs inversus, abdominal situs inversus, and nonvisibility of a single stomach bubble or abnormally big stomach. For thoracic and abdominal situs, an evaluability step preceded classification. Primary end points were sensitivity and specificity per finding on evaluable images, with subgroup analyses by geography, device manufacturer, trimester, body mass index (BMI), demographics, anatomy, indication, and finding status. Cluster bootstrap accounted for within-patient clustering; multiplicity was controlled with Bonferroni or Hochberg correction. We analyzed 6,452 images from 1,115 examinations (11-41 weeks of gestation) from approximately 1,000 pregnancies in 942 patients across 75 international sites over five countries; 6,094 images contributed to performance estimates. Mean sensitivity for AI detection was 93.2% (95% CI, 91.6-94.6%) and mean specificity was 90.8% (95% CI, 89.5-92.0%) across the eight findings. Sensitivity was superior to 87% and specificity was superior to 81% for all findings. Abdominal situs inversus had the highest performance (sensitivity 99.3%, 95% CI, 97.6-100%; specificity 99.3%, 95% CI, 98.4-100%). Among thoracic findings, sensitivity was lowest for malposition of the great vessels (87.7%), and specificity was lowest for absence or unusual size of at least one of the three vessels (81.5%). Subgroup performance was generally consistent across manufacturers, regions, BMI categories, and trimesters. In a heterogeneous, multicenter dataset, the software reliably identified predefined ultrasound findings suggestive of congenital malformations. These results support its potential as a real-time assistant to standardize interpretation and to flag suspicious findings.

Pregabalin is a gabapentinoid. It does not act on GABA receptors; rather, it inhibits calcium influx into neurons by acting on the α2δ-1 subunit of voltage-gated calcium channels. This reduces release of excitatory neurotransmitters, thereby, perhaps, explaining the sedative, anxiolytic, anticonvulsant, and other properties of the drug. Pregabalin has been approved for neuropathic pain, fibromyalgia, partial-onset seizures, and generalized anxiety disorder, and is used, off-label, for pain in many other contexts and for alcohol use disorder, pruritus, restless legs syndrome, and sleep disorders. It may also be abused. About 0.04%-0.14% of women may use pregabalin during pregnancy. This article examines outcomes of pregnancies that were exposed to pregabalin. A meta-analysis of 7 cohort studies found that, even in unadjusted analysis, pregabalin was not associated with an increased risk of major congenital malformations. This finding was confirmed in later studies; or, if the unadjusted risk was significantly elevated, it was no longer so in adjusted analysis. Many studies found that anytime gestational exposure to pregabalin was not associated with a significantly elevated risk of other important birth outcomes such as stillbirth, low birth weight, preterm birth, small for gestational age, low Apgar score, and microcephaly; or the risks were elevated before but not after adjustment for covariates and confounds; or the risks were not significant relative to disease controls. Similarly, studies found that anytime gestational exposure to pregabalin was associated with no increase in risk, or with a significantly increased risk of attention-deficit/ hyperactivity disorder and related disorders, autism spectrum disorder and related disorders, and intellectual disability before but not after adjustment for covariates and confounds. As a limitation, pregabalin-exposed pregnancy sample sizes were small in all studies. On the positive side, safety impressions were obtained despite negligible adjustment for genetic, illness behavior, and environmental confounds.

Using valproate during pregnancy carries risks of major congenital malformations and neurodevelopment disorders. Women with epilepsy and pregnancy plans should switch to an alternative and safe epilepsy management strategy. The present healthcare database study aimed at identifying treatment patterns that lead to successful epilepsy management and their associated factors, in females of childbearing potential (FCBP) after valproate discontinuation. FCBP who had been using valproate for epilepsy and discontinued its use (index date) between 2014 and 2017 were identified in the French and UK databases, Système National des Données de Santé/ Clinical Practice Research Datalink (SNDS/CPRD) and followed-up for 1 year. Clusters that most likely reflected a 'success' in epilepsy management were identified using a partition-around-medoids clustering algorithm. Success was defined on the basis of a combined approach including no valproate reintroduction and no negative medical parameters during follow-up. Baseline factors associated with successful/unsuccessful clusters were assessed in SNDS. A total of 7345/358 (SNDS/CPRD)FCBP diagnosed with epilepsy were included, of whom 67.3%/49.4% identified in successful clusters. The three most frequent clusters were 'predominantly no antiseizure medication (ASM)' (27.7%/20.9%), "predominantly monotherapy with another ASM' typically lamotrigine or levetiracetam (25.5%/20.7%), and 'predominantly return to valproate monotherapy' (17.5%/24.0%). Factors most strongly associated with no reintroduction of valproate were closer medical supervision (OR = 2.30), valproate dose-tapering prior discontinuation (OR = 2.40), pregnancy at index date (OR = 1.96), levetiracetam or lamotrigine delivery in the 90-days pre-index date (OR = 1.81, OR = 1.54). Factors most strongly associated with reintroduction of valproate included: older age (OR = 0.49 for [40-49] versus [13-29] year old), longer duration of epilepsy (OR = 0.63 for ≥ 5 versus < 1 year of history). Around half of women discontinued valproate successfully, especially if young, with a stabilised disease, with one quarter switching to monotherapy with another ASM, mainly lamotrigine or levetiracetam. Risk factors for unsuccessful discontinuation were identified, which may be useful as 'warning signs' to identify patients who need close follow-up during valproate discontinuation.