PHACEing a challenging diagnosis: Should we expand the phenotype?

PHACE syndrome is a challenging but important prenatal diagnosis due to its protean clinical consequences. The 'tilted telephone receiver' sign (TTRS), consisting of asymmetric cerebellar volume reduction and marked counterclockwise, Dandy-Walker-like upward vermis rotation on prenatal MRI and ultrasound has high specificity for PHACE. Recently, a case report of the prenatal imaging findings in an infant with PHACE described more mild upward vermis rotation and cerebellar clefting. It recommended consideration of expansion of the currently accepted phenotype to improve prenatal detection of the condition. We describe a case with imaging features essentially indistinguishable from the recently published case of PHACE with mild upward vermis rotation, asymmetric cerebellar hemispheric volume loss and a cerebellar hemispheric cleft. Our patient did not have PHACE postnatally at 1 year of follow up. Neurodevelopmental testing in infancy demonstrated mildly atypical development. Fetuses with asymmetric cerebellar hemispheric volume loss, a cleft in the smaller hemisphere and only mild upward vermis rotation, consistent with the proposed 'expanded PHACE phenotype' do not always have PHACE. Erroneously adverse prenatal prognostic counselling may result from such prenatal phenotypic expansion.

Factors affecting the accuracy of fetal cardiac ultrasound screening in the first trimester of pregnancy.

PURPOSE: Most studies on the performance of first-trimester cardiac screening have concentrated on comparing the detection rate between different protocols and not on the actual reason for false-negative results. Herein, we report the performance of first-trimester congenital heart disease (CHD) screening and factors that may affect the detection rate of CHDs. METHODS: This retrospective observational study included patients who underwent first-trimester screening and subsequently gave birth at our facility. We analyzed the performance of first-trimester screening for CHD and major CHD (CHD requiring cardiac surgery or interventional catheterization within 12 months of birth). RESULTS: Of the 6614 fetuses included, 53 had CHD and 35 had major CHD. For the prenatal diagnosis of CHD, the detection rate, specificity, positive predictive value, negative predictive value, and first-trimester detection rate for CHD were 64.1%, 99.9%, 94.4%, 99.7%, and 82.9%, respectively; the respective values for major CHD were 85.7%, 99.96%, 93.75%, 99.92%, and 85.7%. The detection rate was not significantly different when classified by crown-rump length or number of fetuses. A weak correlation was observed between low detection rate of major CHD and lower maternal body mass index (BMI) (correlation ratio: 0.17). The detection rate was significantly higher when the fetus was scanned with its spine at the 5-7 o'clock position (posterior spine) than at other positions (odds ratio: 3.82, 95% confidence interval: 1.16-12.5, p = 0.02). CONCLUSION: Posterior spine contributes to an improved diagnostic rate in first-trimester CHD screening. In addition, sonographers must recognize that low maternal BMI is a risk factor of false-negative results.

The role of first-trimester systemic immune-inflammation index for the prediction of gestational diabetes mellitus

SUMMARY OBJECTIVE: The aim of this study was to investigate the role of systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios calculated in the first trimester as inflammatory markers in predicting gestational diabetes mellitus diagnosis. METHODS: This study was conducted retrospectively at a tertiary center between January 2020 and June 2023. A total of 111 pregnant women with gestational diabetes and 378 pregnant women in the control group were included in the study. Systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios values were compared between the gestational diabetes mellitus group patients and the healthy group. Receiver operating characteristic analysis curve was used for predicting gestational diabetes mellitus using systemic immune-inflammation index and lymphocyte-monocyte ratio. RESULTS: In pregnant women in the first trimester, systemic immune-inflammation index and lymphocyte-monocyte ratio values based on routine complete blood count parameters were found to be statistically significantly higher in gestational diabetes mellitus patients compared to healthy patients, while neutrophil-lymphocyte ratio and platelet-lymphocyte ratios values were found to be similar (p=0.033, p=0.005, p=0.211, and p=0.989). For predicting gestational diabetes mellitus, a cut-off value of 655.75 for systemic immune-inflammation index resulted in 80.2% sensitivity and 34.4% specificity, and a cut-off value of 3.62 for lymphocyte-monocyte ratio resulted in 56.8% sensitivity and 63.2% specificity, indicating good discriminatory ability. CONCLUSION: We believe that systemic immune-inflammation index and lymphocyte-monocyte ratio values measured in the first-trimester complete blood count parameters are effective in predicting gestational diabetes mellitus but are not effective in determining insulin requirement.

Biparietal diameter vs crown-rump length as standard parameter for late first-trimester pregnancy dating.

OBJECTIVE: To compare the precision of biparietal diameter (BPD) and crown-rump length (CRL) as predictors of gestational age in the human fetus in the late first and early second trimesters, using a population-based approach. METHODS: We constructed term and gestational-age prediction curves for first-trimester dating, based on 11 041 pregnancies with 12 260 measurements of CRL and/or BPD from a population-based Norwegian clinical database. We used a population-based approach with local linear quantile regression, combined with a time-to-event strategy that compensates for induced births. Term prediction precision was assessed by estimating and comparing the prediction residual curves using a time-to-event analysis. Individual differences in gestational-age predictions from CRL and BPD were assessed using measurements performed on the same fetus on the same day. A sensitivity analysis was performed to evaluate the effect of not distinguishing between non-spontaneous and spontaneous births. RESULTS: CRL and BPD provided almost identical term prediction precision judged from the residual distribution. In about 51% of examinations, the difference in predicted gestational age was 1 day or less; 24% of examinations had a difference of 2 days, 14% had a difference of 3 days, 7% had a difference of 4 days and only 5% of all examinations had a difference of 5 days or more. Incorrectly removing induced births from the analysis, or treating them as spontaneous, would cause a substantial systematic prediction bias of about 2 days. CONCLUSIONS: Based on population data, using comparisons at an individual level, our study found that BPD is as precise as CRL when used for first-trimester dating. BPD has advantages from a clinical point of view, since it is technically less challenging and less time-consuming to measure compared with CRL, and can be measured and assessed throughout the entire pregnancy. © 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.

First-Trimester Prediction Models Based on Maternal Characteristics for Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Early risk stratification can facilitate timely interventions for adverse pregnancy outcomes, including preeclampsia (PE), small-for-gestational-age neonates (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). OBJECTIVES: To perform a systematic review and meta-analysis of first-trimester prediction models for adverse pregnancy outcomes. SEARCH STRATEGY: The PubMed database was searched until 6 June 2024. SELECTION CRITERIA: First-trimester prediction models based on maternal characteristics were included. Articles reporting on prediction models that comprised biochemical or ultrasound markers were excluded. DATA COLLECTION AND ANALYSIS: Two authors identified articles, extracted data and assessed risk of bias and applicability using PROBAST. MAIN RESULTS: A total of 77 articles were included, comprising 30 developed models for PE, 15 for SGA, 11 for sPTB and 35 for GDM. Discriminatory performance in terms of median area under the curve (AUC) of these models was 0.75 [IQR 0.69-0.78] for PE models, 0.62 [0.60-0.71] for SGA models of nulliparous women, 0.74 [0.72-0.74] for SGA models of multiparous women, 0.65 [0.61-0.67] for sPTB models of nulliparous women, 0.71 [0.68-0.74] for sPTB models of multiparous women and 0.71 [0.67-0.76] for GDM models. Internal validation was performed in 40/91 (43.9%) of the models. Model calibration was reported in 21/91 (23.1%) models. External validation was performed a total of 96 times in 45/91 (49.5%) of the models. High risk of bias was observed in 94.5% of the developed models and in 58.3% of the external validations. CONCLUSIONS: Multiple first-trimester prediction models are available, but almost all suffer from high risk of bias, and internal and external validations were often not performed. Hence, methodological quality improvement and assessment of the clinical utility are needed.

Embryonic and Fetal Heart Development Before 12 Weeks of Gestation.

OBJECTIVE: To assess embryonic and fetal cardiac growth and development using transvaginal 2-dimensional sonography before 12 weeks of gestation. METHODS: Transvaginal scans for first-trimester dating were performed for 131 normal fetuses at 8-11 + 6 weeks of gestation. The basal-apical length (BAL), transverse length (TL), cardiac circumference (ECC), embryonic cardiac area (ECA), global sphericity index (GSI), and cardio-thoracic area ratio (CTAR) were able to be obtained in 105 normal embryos and fetuses. RESULTS: Nomograms for several cardiac parameters including BAL, TL, ECC, ECA, GSI, and CTAR were constructed. BAL, TL, ECC, and ECA increased curvilinearly with advancing gestation (R2 = 0.97406, 0.980396, 0.978359, and 0.920705, respectively, P < .001). GSI (mean, 1.14; SD, 0.10) and CTAR (mean, 15.7%; SD, 3.3%) values were constant at 8-11 + 6 weeks of gestation. There were significant curvilinear correlations between BAL, TL, ECC, and ECA, and crown-rump length (CRL) (R2 = 0.975976, 0.983482, 0.980673, and 0.929936, respectively, P < .001). GSI and CTAR values were not changed with the increase of CRL during this period. CONCLUSION: Our results provide nomograms for several cardiac parameters which may improve the understanding of embryonic and fetal cardiac growth and development prior to 12 weeks of gestation.

Firsttrimester Diagnosis and Therapy @ 11 - 13 +6 Weeks of Gestation - Part 2 : Guideline of the DEGUM, ÖGUM, SGUMGG, DGGG, ÖGG, Gynecologie Suisse, DGPM, DGPGM, BVF, ACHSE (AWMF S2e LL 085-002 1.1.2024) (https://register.awmf.org/de/leitlinien/detail/085-002).

This extensive AWMF 085-002 S2e-guideline "First Trimester Diagnosis and Therapy @ 11 - 13 +6 Weeks of Gestation" has systematically analyzed high-quality studies and publications and the existing evidence (evidence tables) and produced recommendations (level of recommendation, level of evidence, strength of consensus). This guideline deals with the following topics in the context of the 11 - 13 +6 weeks scan: the legal basis, screening for anatomical malformations, screening for chromosomal defects, quality assessment and audit, screening for preeclampsia and FGR, screening for preterm birth, screening for abnormally invasive placenta (AIP) and placenta accreta spectrum (PAS), screening for velamentous cord insertion and vasa praevia, screening for diabetes mellitus and LGA. Screening for complications of pregnancy can best be carried out @ 11 - 13 +6 weeks of gestation. The issues of how to identify malformations, chromosomal abnormalities and certain disorders of placentation (high blood pressure and proteinuria, intrauterine growth retardation) have been solved. The problem of how to identify placenta percreta and vasa previa has been partially solved. What is still unsolved is how to identify disorders of glucose metabolism and preterm birth. In the first trimester, solutions to some of these problems are available: parents can be given extensive counselling and the risk that a pregnancy complication will manifest at a later stage can be delayed and reduced. This means that screening is critically important as it helps in decision-making about the best way to manage pregnancy complications (prevention and intervals between follow-up examinations). If no treatment is available and if a termination of pregnancy is considered, the intervention can be carried out with far lower complications compared to the second trimester of pregnancy. In most cases, further examinations are not required and the parents can be reassured. A repeat examination at around week 20 of gestation to complete the screening for malformations is recommended. Note: The guideline will be published simultaneously in the official journals of both professional societies (i.e. Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM and Geburtshilfe und Frauenheilkunde for the DGGG).

Firsttrimester Diagnosis and Therapy @ 11 - 13 +6 Weeks of Gestation - Part 1 : Guideline of the DEGUM, ÖGUM, SGUMGG, DGGG, ÖGG, Gynecologie Suisse, DGPM, DGPGM, BVF, ACHSE (AWMF S2e LL 085-002 1.1.2024) (https://register.awmf.org/de/leitlinien/detail/085-002).

This extensive AWMF 085-002 S2e-guideline "First Trimester Diagnosis and Therapy @ 11 - 13 +6 of Gestation" has systematically analyzed high-quality studies and publications and the existing evidence (evidence tables) and produced recommendations (level of recommendation, level of evidence, strength of consensus). This guideline deals with the following topics in the context of the 11 - 13 +6 weeks scan: the legal basis, screening for anatomical malformations, screening for chromosomal defects, quality assessment and audit, screening for preeclampsia and FGR, screening for preterm birth, screening for abnormally invasive placenta (AIP) and placenta accreta spectrum (PAS), screening for velamentous cord insertion and vasa praevia, screening for diabetes mellitus and LGA. Screening for complications of pregnancy can best be carried out @ 11 - 13 +6 weeks of gestation. The issues of how to identify malformations, chromosomal abnormalities and certain disorders of placentation (high blood pressure and proteinuria, intrauterine growth retardation) have been solved. The problem of how to identify placenta percreta and vasa previa has been partially solved. What is still unsolved is how to identify disorders of glucose metabolism and preterm birth. In the first trimester, solutions to some of these problems are available: parents can be given extensive counselling and the risk that a pregnancy complication will manifest at a later stage can be delayed and reduced. This means that screening is critically important as it helps in decision-making about the best way to manage pregnancy complications (prevention and intervals between follow-up examinations). If no treatment is available and if a termination of pregnancy is considered, the intervention can be carried out with far lower complications compared to the second trimester of pregnancy. In most cases, further examinations are not required and the parents can be reassured. A repeat examination at around week 20 of gestation to complete the screening for malformations is recommended. Note: The guideline will be published simultaneously in the official journals of both professional societies (i.e. Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM and Geburtshilfe und Frauenheilkunde for the DGGG).

Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy.

Objectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility. Design: and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4-14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses. Results: During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p < 0.001), maternal weight (p < 0.001), and smoking (p = 0.02). For miscarriage prediction fPAPP-A was equal to PAPP-A (area under the receiver operating characteristics curve 0.79 vs. 0.81, p = 0.44). Conclusions: Investigating fPAPP-A presence and concentration directly in first trimester serum has not been done previously. This study report lower fPAPP-A values than anticipated from prior enzymatic studies of fPAPP-A. fPAPP-A was not superior to PAPP-A as a first trimester biomarker in this dataset.

Pentalogy of Cantrell Marked With Ectopia Cordis, Gastroschisis, and Cystic Hygroma in the First Trimester: A Rare Case.

Pentalogy of Cantrell is a rare congenital syndrome characterized by defects in the abdominal wall, sternum, diaphragm, and heart. A severe manifestation of this syndrome is ectopia cordis, where the heart is located partially or entirely outside the chest cavity. Gastroschisis involves a defect in the abdominal wall, where the intestines protrude outside the abdomen without a protective membrane. Cystic hygroma is a malformation of the lymphatic system leading to fluid-filled cysts. We present the case of a 29-year-old G3P0020 female initially seen for obstetric follow-up due to a threatened abortion at 11 weeks of gestation with vaginal bleeding. During a routine limited outpatient ultrasound at 11 weeks and four days of gestation, the heart was found to be entirely extrathoracic. Further ultrasound imaging confirmed the presence of ectopia cordis, gastroschisis, and cystic hygroma. Despite the poor prognosis and high risk of intrauterine fetal demise, the patient was referred to a higher-level care facility. This case highlights the critical role of first-trimester ultrasound in diagnosing severe fetal anomalies and the importance of early recognition and prompt referral for the best possible outcomes.

The association between first trimester blood pressure, blood pressure trajectory, mid-pregnancy blood pressure drop and maternal and fetal outcomes: A systematic review and meta-analysis.

BACKGROUND: Hypertensive disorders of pregnancy occur in 5-10 % of pregnancies and are associated with an increased risk of adverse perinatal outcomes. OBJECTIVES: This review investigates the association between first trimester blood pressure (BP), mid-pregnancy BP drop, and BP-trajectories during pregnancy and adverse perinatal outcomes, exploring the fit of prediction and prevention. SEARCH STRATEGY: Observational studies published before September 2023, reporting on desired determinants of BP and outcomes (preeclampsia (PE), severe hypertension, small for gestational age (SGA), fetal growth restriction (FGR)) were identified in MEDLINE, Embase and Cochrane. DATA COLLECTION AND ANALYSIS: Data were collected in Excel. Results were analysed per BP-determinant. Meta analysis was performed for first trimester BP. MAIN RESULTS: Ten studies met selection criteria. A great variety of cut-off values were used for BP categorization. Pooled analysis of 6 studies showed that women with borderline or hypertensive first trimester BP had a higher risk of PE compared to normotensive BP, OR 3.23 (95 % CI 1.99-5.26) and 7.86 (95 % CI 1.28-48.31), respectively. Additionally, first trimester hypertension correlated with a higher risk of SGA neonate (pooled OR of 1.87 (95 % CI 1.17-2.99)) compared to normotension or borderline hypertension. Throughout pregnancy, prehypertension, hypertension, elevated and high stable trajectories increased PE risk. High-stable trajectory increased SGA neonate risk. CONCLUSIONS: The findings suggest that women with borderline and hypertensive BP in the first trimester are at increased risk for PE and SGA. However, standardization of cut-off values and BP measurement is necessary to estimate outcome risks more accurately.

First-trimester uterine artery pulsatility index and preeclampsia risk pregnancies after artificial frozen embryo transfer: analysis of over 27,000 pregnancies.

BACKGROUND: Accumulating evidence indicates that pregnancies after Artificial Cycle Frozen Embryo Transfer are associated with an increased risk of preeclampsia. Uterine Artery Doppler, along with maternal factors and serum biomarkers, is a crucial biomarker for first-trimester preeclampsia screening, aiding in identifying "high-risk" patients. Guidelines strongly recommend administering aspirin (150mg/day) in these women, owing to robust evidence demonstrating a 62% reduction in the incidence of preeclampsia. Although previous studies suggested lower Uterine Artery Pulsatility Index after Frozen Embryo Transfer, no previous studies explored the impact of the type of endometrial preparation in Uterine Artery Doppler or its influence on estimating 1st-trimester preeclampsia risk. OBJECTIVE: The study aims to evaluate the possible impact of endometrial preparation for frozen embryo transfer on the Uterine Artery Pulsatility Index during the first-trimester preeclampsia screening. STUDY DESIGN: This is a retrospective single-center study including 27289 singleton pregnancies (naturally conceived or after assisted reproductive treatment) who underwent the 1st-trimester ultrasound screening at our University Hospital between January 2010 and May 2023. Overall, 27289 pregnancies were included: 23410 naturally conceived and 3879 following assisted reproductive technologies including 391 after ovulation induction and intrauterine insemination, 888 in-vitro fertilization and fresh embryo transfer, and 2600 natural or artificial frozen embryo transfer cycles. An Analysis of covariance (ANCOVA) was conducted to assess if there is an association between the UtAPI value and the mood of conception, adjusting for confounding factors (age, weight, smoking, and oocyte donation). RESULTS: Overall, pregnancies after artificial frozen embryo transfer demonstrated significantly lower 1st-trimester Uterine Artery Pulsatility Index as compared with all other modes of conception in a multivariable regression analysis adjusted for age, weight, smoking, and oocyte donation. The percent difference was 22.6 [CI95%: 20,6; 24,5] compared to naturally conceived pregnancy, 24.5 [CI95%:20,7; 28,1] to Ovulation Induction or intrauterine insemination, 24.8 [CI95%: [22,9; 27,6] to fresh Embryo Transfer and 21.7 [CI95%: [17,6; 25,5] compared to Natural Cycle Frozen Embryo Transfer. When calculating the risk for initiating preventive aspirin administration, the number of patients with increased risk (>1/100) who initiated prophylactic aspirin was significantly lower in the artificial cycle frozen embryo transfer group (7.8% vs 16.0% in natural cycle p<0.001 vs. 11.0% in Fresh embryo transfer p=0.01 vs. 10.5% in ovulation induction or intrauterine insemination p=0.14 vs. 9,3% in naturally conceived pregnancy p=0.03). Surprisingly although significantly fewer patients were considered at high risk for preeclampsia in the Artificial Cycle Frozen Embryo Transfer group, analysis of the actual incidence of preeclampsia demonstrated three times higher preeclampsia incidence in Artificial Cycle group 5.3% (122/2284) as compared with naturally conceived 1.4 % (321/23410), Ovulation Induction and intrauterine insemination 1.3 % (5/391) or Natural Cycle pregnancies 1.6 % (5/316) and more than two times higher when compared to fresh Embryo Transfer pregnancies 2.3 % (20/888), p<0.001. CONCLUSION: Pregnancies following frozen embryo transfer in artificial cycle are associated with significantly lower Uterine Artery Pulsatility Index during 1st-trimester preeclampsia screening. This results in a significantly lower number of patients being classified as high-risk for developing preeclampsia, despite accumulating evidence that artificial cycles are linked to an increased risk of preeclampsia. Therefore, the first-trimester preeclampsia risk algorithm should be adjusted to accurately assess risk for those undergoing Artificial Cycle Frozen Embryo Transfer, to prevent the under-treatment of patients who are at very high risk of developing preeclampsia and may benefit from prophylactic aspirin.

First-trimester predictive models for adverse pregnancy outcomes-a base for implementation of strategies to prevent cardiovascular disease development.

Introduction: This study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics. Methods: This retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Most pregnancies with adverse outcomes were identified using the proposed approach (the combinations of selected miRNAs and appropriate maternal clinical characteristics) (GH, 69.88%; PE, 83.33%; HELLP, 92.86%; FGR, 73.17%; SGA, 81.08%; GDM on therapy, 89.47%; and late miscarriage, 84.85%). In the case of stillbirth, no addition of maternal clinical characteristics to the predictive model was necessary because a high detection rate was achieved by a combination of miRNA biomarkers only [91.67% cases at 10.0% false positive rate (FPR)]. Conclusion: The proposed models based on the combinations of selected cardiovascular disease-associated miRNAs and maternal clinical variables have a high predictive potential for identifying women at increased risk of adverse pregnancy outcomes; this can be incorporated into routine first-trimester screening programs. Preventive programs can be initiated based on these models to lower cardiovascular risk and prevent the development of metabolic/cardiovascular/cerebrovascular diseases because timely implementation of beneficial lifestyle strategies may reverse the dysregulation of miRNAs maintaining and controlling the cardiovascular system.

First Trimester Fetal Clubfoot: A Novel Presentation of Severe Osteogenesis Imperfecta.

Talipes equinovarus, also called clubfoot, is a relatively common congenital defect affecting approximately one in every 1000 live births. Most cases of clubfoot are expected to be idiopathic and unrelated to an underlying genetic syndrome. In approximately 20% of cases, a clear genetic etiology is identified. Here we present two cases of bilateral clubfoot identified via fetal ultrasound in the first trimester associated with osteogenesis imperfecta diagnosed in the second trimester. Both fetuses presented with multiple fractures and were identified to have loss-of-function variants in COL1A1. An association between clubfeet in the first trimester and osteogenesis imperfecta has not been previously reported to the best of our knowledge, which leads to unique opportunities for prompt diagnosis, genetic counseling and testing, and appropriate management.

First trimester maternal serum PAPP-A and free ß-hCG levels and risk of SGA or LGA in women with and without GDM.

BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.

Study on ultrasound diagnosis and pathological anatomy of fetal complex congenital heart disease in the first trimester.

PURPOSE: To assess the feasibility of using the stereo-microscope to identify the pathological anatomy of the congenital heart diseases in the first trimester. METHODS: Fifteen fetuses of 8-12 weeks aborted due to prevent miscarriage failure and 42 fetuses of 11-14 weeks with congenital heart diseases were included in the study, we dissected their hearts through a stereo-microscope, then compared with the prenatal ultrasonographic diagnosis. RESULTS: Using stereomicroscopy, the positive view of the heart and the great arteries, the long axis view of the aortic arch, the inflow tract view of the bottom heart, the semilunar valve view of the bottom heart, and the transverse section of the ventricle were showed contented and obtained satisfactory images, but the structure of atrioventricular valve and venous system had a lower rate of display. CONCLUSION: The characteristic pathological changes of cardiac inflow and outflow tract can be obtained by dissecting the heart sequential under the stereo-microscopy. However it is often difficult to obtain satisfactory pathological sections for pulmonary venous abnormalities and Ebstein anomaly.

Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Fetal Echocardiography From 10 to 15 Weeks of Gestation-Reliability, Genetic Associations, and Outcomes.

INTRODUCTION: There is increasing demand for accurate early fetal cardiac disease (FCD). We assessed the accuracy of early fetal echo (EFE) conducted in our high-volume fetal cardiac program and reviewed the spectrum of FCD, associated genetic anomalies, and outcomes encountered. METHODS: We identified all EFEs performed from 10+0 to 15+6 weeks of gestation from 2009 to 2021. We compared findings at EFE to fetal echo at ≥18+0 weeks or autopsy and documented genetic testing results for all FCD cases. For those with discrepancy between EFE and later exam, the discrepancy impact was reviewed. A score was used to quantify the anatomy assessed. RESULTS: A total of 1,662 EFEs were performed in 1,387 pregnancies; all but 41 were considered diagnostic. Fetal cardiac disease was diagnosed at EFE in 130, including 101 major, 12 minor, 13 other FCD, and 4 arrhythmias. In 14/130 with FCD, endovaginal imaging was undertaken, which increased the score (1.6/9 vs 3.5/9; P = .049). Thirty-five of 130 had repeat EFE, which increased the score (5.2/9 vs 7.4/9, P < .0001). Fetal loss occurred before confirmation of FCD in 16 and termination in 64, and 11 were lost to follow-up. Thirty-nine had autopsy and/or fetal echo ≥18+0: 35 had FCD confirmed, and 4 had resolution. Of the 35 confirmed FCD, 27 had no, 7 minor, and 1 major change. Of 1,489 with normal EFE, later echo demonstrated FCD in 14: 3 major and 11 minor. In 16, FCD evolved, including 4 arrhythmias and 12 with progressive FCD. Sensitivity, specificity, and positive and negative predictive values of EFE in identifying major FCD were 92.9%, 100%, 100%, and 99.7%, respectively. In cases with FCD, 85.4% had genetic testing, of whom 71% (60.8% of the total) had abnormal results. CONCLUSIONS: In our experience, EFE permits accurate diagnosis and exclusion of most FCD. Endovaginal imaging and repeat EFE studies improved the ability to visualize structures adequately.

Point-Of-Care Ultrasound to Diagnose Molar Pregnancy in the Emergency Department: A Case Report and Topic Review.

Molar pregnancy is a topic in emergency medicine frequently tested and regularly discussed but is perhaps overshadowed by other conditions such as ectopic pregnancy. It is a rare diagnosis encountered in the emergency department (ED) and is part of a broad spectrum of pathological conditions that fall into the category of gestational trophoblastic disease (GTD). Diagnosis of this potentially malignant condition requires the emergency physician to bear this condition in mind when treating any woman while considering obstetric-related conditions in the first trimester, vaginal bleeding, pelvic pain or pressure, and excessive nausea and vomiting. We present the case of a 20-year-old primigravida 12-week pregnant female who presented to the ED sent in by the midwifery clinic for evaluation with concerns for absent fetal heart tones and abnormal uterine appearance. Point-of-care ultrasound (POCUS) performed upon arrival demonstrated an irregular complex echogenic uterine mass with anechoic areas and cystic structures suspicious for a molar pregnancy. Obstetrics-gynecology (OB-GYN) admitted the patient promptly for definitive surgical care, and tissue analysis confirmed a complete molar gestation. This case highlights the effectiveness of POCUS for prompt diagnosis and treatment of molar pregnancy in the ED.