Median Gestational Age Research Articles

Transcatheter closure of tubular PDA with amplatzer plug 4 in preterm infants weighing between 900 and 3,400 g: the pros and cons.

To our knowledge, no prior study has focused on the outcome of PDA occlusion using an Amplatzer™ Vascular Plug 4 (AP4) in ill preterm infants. This study aims to highlight the pros and cons of AP4 in this cohort. Between 2020 and 2022, 26 ill preterm infants underwent PDA closure in our centre. The median age, weight, and gestational age were 60 days (11-180 days), 1,900g (900-3,400 g), and 25 weeks (22-33 weeks), respectively. The indication of the intervention was hemodynamically significant PDA. A medical trial with non-steroid medication failed to close the ducts in all patients. Follow-up using echocardiography was done 24, 48, and 72 h after the intervention. Of 26 ducts, 21 were successfully closed with AP4. Five ducts shorter than 7 mm were unsuitable for AP4 and were closed with the Amplatzer Piccolo device. The median radiation time was 4 min (3-9 min). No early plug-related complications or deaths were documented. Plug-related jailing of the left pulmonary artery as a late complication was 9.5%, and LPA reintervention was required. All ducts were closed after 48 h. Implantation of the AP4 using a 4 F 0.38 guide wire-compatible catheter without inserting a long sheath makes the closure of tubular ducts with this device feasible and uncomplicated with a short intervention time. However, the limited sizes with fixed lengths of the AP4 make it unsuitable for ducts wider than 4.5 mm and shorter than the chosen device length, which can increase the risk of significant left pulmonary stenosis. A wide range of plug diameters and lengths is required to accommodate the large and short ducts.

Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders.

Haplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a prospective study, recruiting 219 proband families with singleton pregnancies at risk for eight recessive single-gene disorders (Duchenne muscular dystrophy, spinal muscular atrophy, phenylketonuria, methylmalonic acidemia, hemophilia A, hemophilia B, non-syndromic hearing loss, and congenital adrenal hyperplasia) at 7-14 weeks of gestation. Haplotype-based NIPD was performed by evaluating the relative haplotype dosage (RHDO) in maternal circulation, and the results were validated via invasive prenatal diagnosis or newborn follow-ups. Among the 219 families, the median gestational age at first blood draw was 8+5 weeks. Initial testing succeeded for 190 families and failed for 29 due to low fetal fraction (16), insufficient informative SNPs (9), and homologous recombination near pathogenic variation (4). Among low fetal fraction families, successful testing was achieved for 11 cases after a redraw, while 5 remained inconclusive. Test failures linked to insufficient informative SNPs correlated with linkage disequilibrium near the genes, with F8 and MMUT exhibiting the highest associated failure rates (14.3% and 25%, respectively). Homologous recombination was relatively frequent around the DMD and SMN1 genes (8.8% and 4.8%, respectively) but led to detection failure in only 44.4% (4/9) of such cases. All NIPD results from the 201 successful families were consistent with invasive diagnostic findings or newborn follow-up. Fetal fraction, informative SNPs count, and homologous recombination are pivotal to NIPD performance. Redrawing blood effectively improves the success rate for low fetal fraction samples. However, informative SNPs count and homologous recombination rates vary significantly across genes, necessitating careful consideration in clinical practice. We have designed an in silico method based on linkage disequilibrium data to predict the number of informative SNPs. This can identify genomic regions where there might be an insufficient number of SNPs, thereby guiding panel design. With these factors properly accounted for, NIPD is highly accurate and reliable.

Reducing macrosomia-related birth complications in primigravid women: ultrasound- and magnetic resonance imaging–based models

Many complications increase with macrosomia, which is defined as birthweight of ≥4000 g. The ability to estimate when the fetus would exceed 4000 g could help to guide decisions surrounding the optimal timing of delivery. To the best of our knowledge, there is no available tool to perform this estimation independent of the currently available growth charts. This study aimed to develop ultrasound- and magnetic resonance imaging-based models to estimate at which gestational age the birthweight would exceed 4000 g, evaluate their predictive performance, and assess the effect of each model in reducing adverse outcomes in a prospectively collected cohort. This study was a subgroup analysis of women who were recruited for the estimation of fetal weight by ultrasound and magnetic resonance imaging at 36 0/7 to 36 6/7 weeks of gestation. Primigravid women who were eligible for normal vaginal delivery were selected. Multiparous patients, patients with preeclampsia spectrum, patients with elective cesarean delivery, and patients with contraindications for normal vaginal delivery were excluded. Of note, 2 linear models were built for the magnetic resonance imaging- and ultrasound-based models to predict a birthweight of ≥4000 g. Moreover, 2 formulas were created to predict the gestational age at which birthweight will reach 4000 g (predicted gestational age); one was based on the magnetic resonance imaging model, and the second one was based on the ultrasound model. This study compared the adverse birth outcomes, such as intrapartum cesarean delivery, operative vaginal delivery, anal sphincter injury, postpartum hemorrhage, shoulder dystocia, brachial plexus injury, Apgar score of <7 at 5 minutes of life, neonatal intensive care unit admission, and intracranial hemorrhage in the group of patients who delivered after the predicted gestational age according to the magnetic resonance imaging-based or the ultrasound-based models with those who delivered before the predicted gestational age by each model, respectively. Of 2378 patients, 732 (30.8%) were eligible for inclusion in the current study. The median gestational age at birth was 39.86 weeks of gestation (interquartile range, 39.00-40.57), the median birthweight was 3340 g (interquartile range, 3080-3650), and 63 patients (8.6%) had a birthweight of ≥4000 g. Prepregnancy body mass index, geographic origin, gestational age at birth, and fetal body volume were retained for the optimal magnetic resonance imaging-based model, whereas maternal age, gestational diabetes mellitus, diabetes mellitus type 1 or 2, geographic origin, fetal gender, gestational age at birth, and estimated fetal weight were retained for the optimal ultrasound-based model. The performance of the first model was significantly better than the second model (area under the curve: 0.98 vs 0.89, respectively; P<.001). The group of patients who delivered after the predicted gestational age by the first model (n=40) had a higher risk of cesarean delivery, postpartum hemorrhage, and shoulder dystocia (adjusted odds ratio: 3.15, 4.50, and 9.67, respectively) than the group who delivered before this limit. Similarly, the group who delivered after the predicted gestational age by the second model (n=25) had a higher risk of cesarean delivery and postpartum hemorrhage (adjusted odds ratio: 5.27 and 6.74, respectively) than the group who delivered before this limit. The clinical use of magnetic resonance imaging- and ultrasound-based models, which predict a gestational age at which birthweight will exceed 4000 g, may reduce macrosomia-related adverse outcomes in a primigravid population. The magnetic resonance imaging-based model is better for the identification of the highest-risk patients.

Validating the early phototherapy prediction tool across cohorts.

Hyperbilirubinemia of the newborn infant is a common disease worldwide. However, recognized early and treated appropriately, it typically remains innocuous. We recently developed an early phototherapy prediction tool (EPPT) by means of machine learning (ML) utilizing just one bilirubin measurement and few clinical variables. The aim of this study is to test applicability and performance of the EPPT on a new patient cohort from a different population. This work is a retrospective study of prospectively recorded neonatal data from infants born in 2018 in an academic hospital, Regensburg, Germany, meeting the following inclusion criteria: born with 34 completed weeks of gestation or more, at least two total serum bilirubin (TSB) measurement prior to phototherapy. First, the original EPPT-an ensemble of a logistic regression and a random forest-was used in its freely accessible version and evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Second, a new version of the EPPT model was re-trained on the data from the new cohort. Third, the predictive performance, variable importance, sensitivity and specificity were analyzed and compared across the original and re-trained models. In total, 1,109 neonates were included with a median (IQR) gestational age of 38.4 (36.6-39.9) and a total of 3,940 bilirubin measurements prior to any phototherapy treatment, which was required in 154 neonates (13.9%). For the phototherapy treatment prediction, the original EPPT achieved a predictive performance of 84.6% AUROC on the new cohort. After re-training the model on a subset of the new dataset, 88.8% AUROC was achieved as evaluated by cross validation. The same five variables as for the original model were found to be most important for the prediction on the new cohort, namely gestational age at birth, birth weight, bilirubin to weight ratio, hours since birth, bilirubin value. The individual risk for treatment requirement in neonatal hyperbilirubinemia is robustly predictable in different patient cohorts with a previously developed ML tool (EPPT) demanding just one TSB value and only four clinical parameters. Further prospective validation studies are needed to develop an effective and safe clinical decision support system.

Pregnancy Outcomes of Conservative Management in Preeclampsia with Severe Features.

Objective: To study the pregnancy outcomes of conservative treatment for preeclampsia with severe features. Methods: A retrospective study was conducted on pregnancies with preeclampsia with severe features at gestational age 23-34 weeks and that received conservative management at Chiang Mai University Hospital between January 2014 and August 2020. The women were divided into two groups: (1) pregnancy prolongation of at least 48 h and (2) pregnancy prolongation of less than 48 h. Results: Of the 100 recruited pregnancies, the median gestational age was 29 weeks (range 23-34). Of these, 65 cases (65%) had pregnancy prolongation of at least 48 h, and 35 cases (35%) had prolongation of less than 48 h. The median pregnancy prolongation was 2.9 days (range 4 h-27.7 days). Eighty-seven (88%) pregnant women experienced no complications. Multivariate analysis shows that high urine protein/creatinine ratio (UPCI) at admission was significantly associated with pregnancy prolongation of less than 48 h with an odds ratio for prolongation for at least 48 h of 0.86 (95% CI 0.75-0.99: p-value 0.04). Kaplan-Meier analysis shows that the mean time of prolongation was 3.6 days vs. 6.7 days, and median time of prolongation was 2.1 days vs. 4.4 days in the group of high and low UPCI (using cut-off 1.0), respectively. The number of prolonged days was significantly lower in the high UPCI group than in the low UPCI group (log-rank test, p = 0.01). The maternal and fetal outcomes between the two groups were not significantly different. The cesarean section rate was also comparable. The mean birth weight and gestational age at delivery were not significantly different, though they had a higher trend in the group of successful conservative management. Conclusion: The rate of pregnancy prolongation of at least 48 h with conservative management was 65%, with a median prolongation time of 2.9 days. A new insight gained from this study is that high UPCI at admission is an independent factor for prolongation of less than 48 h with conservative treatment. Nevertheless, the maternal and fetal outcomes between the two groups were not significantly different. Therefore, the benefit and risk of expectant management in actual practice of service settings in terms of maternal and fetal morbidity is still unclear.

Fetal surgery using fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: a single-center experience.

To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers.

Screen-positive rate in cell free DNA screening for trisomy 21.

To assess whether the fetal fraction (FF) has an impact on the screen-positive rate (SPR) in cell-free DNA (cfDNA) screening for trisomy 21. Retrospective analysis based on samples analyzed using the Harmony® Prenatal Test (Roche Inc). Due to the size of the data set, we focused on the SPR, which was stratified according to the maternal age, weight, gestational age, and FF distribution. The study cohort consisted of 364,881 patients, including 2614 with a high-risk-result. Median maternal and gestational ages were 34.6years and 12.4weeks. FF was dependent on maternal age, weight, and gestational age. SPR was 0.72% and it was independent of maternal weight but was dependent on maternal age. There was a positive but weak association between the FF and the SPR until the FF reached 20.0% (OR p=1.021, p<0.001, Nagelkerkes r2=0.001). This group included 357,800 pregnancies or 98.1% of the study population. In the group of pregnancies with a FF > 20%, the association was stronger (OR 1.099, p<0.001, Nagelkerkes r2=0.042). The SPR in cfDNA screening for trisomy 21 was relatively constant up to a FF of about 20%.

Infants Eligible for Neonatal Hypoglycemia Screening

Neonatal hypoglycemia is common, occurring in up to 50% of infants at risk for hypoglycemia (infant of diabetic mother [IDM], small for gestational age [SGA], large for gestational age [LGA], and preterm) and is associated with long-term neurodevelopmental impairment. Guidelines recommend screening infants at risk of hypoglycemia. The proportion of infants who require screening for neonatal hypoglycemia is unknown. To determine the proportion of infants eligible for neonatal hypoglycemia screening using criteria from the highest-scoring critically appraised clinical guideline. This systematic review of the literature was conducted to identify clinical practice guidelines for neonatal hypoglycemia and took place at a tertiary maternity hospital in Auckland, New Zealand. Eligible guidelines were critically appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Using screening criteria extracted from the highest-scoring guideline, the proportion of infants eligible for neonatal hypoglycemia screening was determined in a retrospective observational cohort study of infants born January 1, 2004, to December 31, 2018. Data were analyzed by logistic regression. Infant participants were included if gestational age was 35 weeks or more, birth weight was 2000 g or more, and they were not admitted to a neonatal intensive care unit less than 1 hour after birth. The data were analyzed from November 2022 through February 2023. A total of 101 372 infants met the inclusion criteria. Risk factors for neonatal hypoglycemia. Proportion of infants eligible for neonatal hypoglycemia screening. The study team screened 2366 abstracts and 18 guidelines met inclusion criteria for appraisal. There was variability in the assessed quality of guidelines and a lack of consensus between screening criteria. The highest-scoring guideline defined screening criteria as: IDM, preterm (less than 37 weeks' gestation), SGA (less than 10th percentile), birth weight of less than 2500 g or more than 4500 g, LGA (more than 90th percentile), or gestational age more than 42 weeks. A total of 101 372 infants met criteria for inclusion in the cohort study; median (IQR) gestational age was 39 (38-40) weeks and 51% were male. The overall proportion of infants eligible for screening was 26.3%. There was an increase in the proportion of eligible infants from 25.6% to 28.5% over 15 years, which was not statistically significant after adjustment for maternal age, body mass index, ethnicity, and multiple pregnancy (odds ratio, 0.99; 95% CI, 0.93-1.03; change in proportion per year). A systematic review found that practice guidelines providing recommendations for clinical care of neonatal hypoglycemia were of variable quality with is a lack of consensus regarding definitions for infants at risk for hypoglycemia. In the cohort study, one-quarter of infants were eligible for hypoglycemia screening. Further research is required to identify which infants may benefit from neonatal hypoglycemia screening.

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.

Predicting body fat percentage at 36 weeks of postmenstrual age in infants born preterm: A diagnostic accuracy study.

Current standards for assessing body composition can be costly and technically challenging. There is a need for a predictive equation that combines multiple clinical and anthropometric factors to predictbody composition outcomes at 36 weeks of postmenstrual age (PMA) or discharge. To develop a widely applicable equation that predicts body fat percentage in preterm infants, we analyzed anthropometric data collected prospectively from a cohort of infants born very preterm between 2017 and 2018. We integrated clinical variables significantly associated with adiposity into a predictive equation using Bayesian linear regression models and leave-one-out cross-validation. We analyzed data from 86 infants born at 32 weeks of gestation or less (median gestational age, 30 weeks; mean birthweight, 1471 ± 270 g). Weight gain and increase in length per week from birth to 36 weeks of PMA, midarm circumference at 36 weeks of PMA, male sex, and higher enteral fluid intake (>180 ml/kg/day) were the strongest predictors of body fat percentage in the model with the highest predictive value (R2 = 0.65). The correlation between actual and predicted body fat percentage using this Bayesian model was high (r = 0.82). Weight gain and increase in length per week from birth to 36 weeks of PMA, midarm circumference at 36 weeks of PMA, male sex, and enteral fluid intake are significant predictors of body fat percentage at 36 weeks of PMA in very preterm infants.

Prenatal diagnosis of 15q11.2 microdeletion fetuses in Eastern China: 21 case series and literature review

Objective 15q11.2 microdeletion can lead to syndromes affecting the nervous system. However, 15q11.2 microdeletion has large phenotypic differences and incomplete penetrance, which brings challenges to prenatal diagnosis. We reported 21 cases of 15q11.2 microdeletion fetuses in Eastern China and reviewed literature on the prenatal clinical characteristics related to the deletion variants to provide a basis for prenatal genetic counseling. Methods The clinical data of 21 cases of 15q11.2 microdeletion fetuses collected from June 2018 to September 2021 were retrospectively analyzed, and chromosomal microarray analysis was performed. The reported prenatal clinical features of 15q11.2 microdeletion fetuses were reviewed and summarized. A meta-analysis of 20 studies was performed to test heterogeneity, data integration, and sensitivity on the correlation between 15q11.2 microdeletion and neuropsychiatric diseases. Results The median age of the women was 29.5 years. The median gestational age at interventional examination was 24 weeks. All fetuses showed deletion variants of the 15q11.2 fragment, and the median deletion range was approximately 0.48 MB. Ultrasound of five cases showed no abnormalities; however, four of them showed a high risk of Down’s syndrome (risk values were 1/184, 1/128, 1/47, and 1/54, respectively). The remaining 16 fetuses showed congenital heart disease (7/16), elevated nuchal translucency (5/16), abnormal brain structure (2/16) and renal disease (2/16). In a literature review of 82 prenatal cases, 44% (36/82) had abnormal ultrasound features, 31% (11/36) showed abnormal nuchal translucency, approximately 28% (10/36) showed abnormal cardiac structure, and 14% (5/36) had brain structural abnormalities. The meta-analysis revealed that the frequency of the 15q11.2 microdeletion mutation in patients with schizophrenia and epilepsy was significantly higher (odds ratio 2.04, 95% confidence interval: 1.78–2.33, p < 0.00001; odds ratio 5.23, 95% confidence interval: 2.83–9.67, p < 0.00001) than that in normal individuals. Conclusion More than half of the 15q11.2 microdeletion cases presented no abnormalities in prenatal ultrasound examination. The cases with ultrasound features mainly showed isolated malformations such as elevated nuchal translucency, congenital heart disease, and brain structural abnormalities. Postpartum 15q11.2 microdeletion patients are at an increased risk of suffering from schizophrenia, epilepsy, and other neurological and mental diseases from 15q11.2 microdeletion. Therefore, prenatal diagnosis of 15q11.2 microdeletion not only depends on molecular diagnostic techniques but also requires cautious genetic counseling.

Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates: A Pooled Population Pharmacokinetic Study.

There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI. In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used. The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration. This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.

Analysis of clinical effect and influencing factors of history-indicated cerclage or ultrasound-indicated cerclage in singleton pregnancy

Objective: To investigate the clinical effect and the influencing factors of ultrasound-indicated cerclage and history-indicated cerclage in singleton gestation. Methods: The clinical data of 272 singleton pregnant women with cervical incompetence who underwent McDonald cervical cerclage due to medical history indication (history-indicated group) or ultrasound indication (ultrasound-indicated group) in Peking University First Hospital from January 2010 to February 2021 were retrospectively analyzed. The general clinical data and maternal and fetal outcomes were compared between the history-indicated group (141 cases) and ultrasound-indicated group (131 cases). According to the gestational age at delivery, 272 pregnant women who underwent cervical cerclage were further divided into ≥34 weeks group (225 cases) and <34 weeks group (47 cases), and the influencing factors of preterm birth before 34 weeks of gestation were analyzed. Results: (1) The median gestational age at cerclage was 16.6 weeks in the history-indicated group and 23.4 weeks in the ultrasound-indicated group, and the median gestational age extension at delivery was 21.4 weeks and 14.7 weeks, respectively, with statistically significant differences between the two groups (all P<0.05). (2) The full-term birth rate was 76.6% (108/141) in the history-indicated group and 71.0% (93/131) in the ultrasound-indicated group, the live birth rate was 97.2% (137/141) and 97.7% (128/131), and the median birth weight of live birth was 3 155 g and 3 055 g, respectively. The differences were not statistically significant (all P>0.05). Among 272 pregnant women with cervical cerclage, 265 neonates survived (97.4%, 265/272). The gestational age of 7 pregnant women who did not have live birth was ≤25 weeks of gestation (range: 19+1-25 weeks), and they were all clinically infected or confirmed chorioamnionitis or pathogenic microorganisms carrying during pregnancy, and their families gave up. The minimum birth weight of the surviving neonate was 850 g (gestational week of delivery was 26+6 weeks). (3) Univariate analysis showed that compared with ≥34 weeks group, the body mass index (BMI) of pregnant women in <34 weeks group was higher at 6-7 weeks of gestation (median: 24.5 vs 25.4 kg/m2), shorter cervical length (CL) at 1-2 weeks after surgery [(31.1±8.4) vs (26.1±11.0) mm], shorter CL at 26-28 weeks of gestation after surgery (median: 26.3 vs 16.0 mm), and higher incidence of elevated C-reactive protein (CRP) before and after surgery and before delivery. The differences were all statistically significant (all P<0.05). Multivariate logistic regression analysis showed that preterm birth before 34 weeks was negatively associated with CL at 26-28 weeks of gestation after cerclage (OR=0.902, 95%CI: 0.858-0.947; P<0.001), and was positively correlated with elevated CRP before delivery (OR=3.492, 95%CI: 1.652-7.381; P=0.001). There were no significant correlations between preterm birth and preoperative or postoperative CRP elevation, CL at 1-2 weeks after surgery, and BMI at 6-7 weeks of gestation (all P>0.05). Conclusions: Cervical cerclage for singleton pregnant women with cervical incompetence indicated by history or ultrasound both have good clinical efficacy, and there is no significant difference in maternal and fetal outcomes between the two groups. CL at 26-28 weeks of gestation and CRP before delivery are risk factors for preterm birth before 34 weeks of gestation after cervical cerclage.

Severity of haemolytic disease of the fetus and newborn in patients with a history of intrauterine transfusions in a previous pregnancy: A nationwide retrospective cohort study.

Pregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort. Retrospective cohort study of a nationwide Dutch database. The Netherlands. All women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded. Electronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression. Percentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies. Of the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy. Our study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling.

Management and outcomes of pregnant ICU patients with severe COVID-19 pneumonia in Qatar: A retrospective cohort study.

Pregnant women are considered a high-risk group for COVID-19 due to their increased vulnerability to viral infections. The impact of COVID-19 on pregnant women is not well understood, and there is a need for data on managing severe COVID-19 in pregnant patients. This retrospective descriptive cohort study described the characteristics, hospital stay, interventions, and outcomes of pregnant patients admitted to the intensive care units (ICUs) with severe COVID-19 pneumonia in Qatar. Data were collected from medical records and chart reviews of pregnant women admitted to Hamad Medical Corporation (HMC) with COVID-19 pneumonia from March 01, 2020, to July 31, 2021. The inclusion criteria encompassed pregnant women with a positive polymerase chain reaction (PCR) antigen test or radiological changes at admission, requiring respiratory support, and hospitalized for more than 24 hours. A total of 43 pregnant women were included in this study. Most patients were admitted during the first wave of the pandemic, with a median gestational age of 212 days [interquartile range 178-242 days] at presentation. The most common respiratory support methods were high-flow nasal cannula, non-invasive positive pressure ventilation, and invasive positive pressure ventilation. Convalescent plasma therapy was administered to 58% of patients, and tocilizumab was used in 28%. Renal replacement therapy was required by 4.6% of patients and 7% required extracorporeal membrane oxygenation. This study provides valuable insights into the impact of COVID-19 on pregnant patients admitted to the ICUs in Qatar. The results suggest that pregnant patients with COVID-19 pneumonia require close monitoring and appropriate interventions to minimize adverse outcomes for both mother and fetus. The data may contribute to future guidelines and management strategies for severe COVID-19 in pregnant patients.

Hypertensive disorders of pregnancy in moyamoya disease: A single institution experience

ObjectiveThe characteristics of pregnancy and delivery in patients with moyamoya disease (MMD) remain unclear. We retrospectively investigated perinatal outcomes in patients with MMD to evaluate the risks associated to this condition. Materials and methodsClinical data of women with MMD who delivered at the University of Tokyo Hospital between 2000 and 2021 were collected. Maternal characteristics including genetic data, obstetric complications, method of delivery and anesthesia, neonatal outcomes, neurological events during pregnancy, delivery, and postpartum course, were reviewed. ResultsThirteen pregnancies with MMD were identified. The median maternal age was 30 years. The initial clinical symptoms were identified as transient ischemic attack, infarction, and headache. Eight patients had a history of bypass surgery. The median gestational age at delivery was 37 weeks. DNA samples were collected from five patients, responsible for six pregnancies. Of these six cases, five had the RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variant. Of the 13 pregnancies, seven had hypertensive disorder of pregnancy (HDP). Additionally, three of five pregnancy cases with RNF213 p.Arg4810Lys heterozygous variant presented with HDP. Nine patients underwent cesarean section, and four delivered vaginally with epidural anesthesia. One case of ischemic stroke was confirmed during the postpartum period. Regarding newborns, neither Apgar scores lower than 7 nor neonatal intensive care unit admissions were reported. ConclusionsThis study suggests that the frequency of HDP is higher in patients with MMD compared to those with normal pregnancies. Strict blood pressure control should be performed in patients with MMD during pregnancy and postpartum period.

Analysis of Pregnancy Outcomes Following Exposure to Intramuscular Interferon Beta-1a: The AVONEX® Pregnancy Exposure Registry.

There is a lack of well-controlled US studies of intramuscular (IM) interferon beta (IFNβ)-1a use in pregnant women with multiple sclerosis; however, in the European Medicines Agency region, IFNβ formulations may be considered during pregnancy if clinically needed based on data from European Union cohort registries. The AVONEX Pregnancy Exposure Registry was established to prospectively study the effects of IM IFNβ-1a on the risk of birth defects and spontaneous pregnancy loss in a US population. Pregnant women with multiple sclerosis exposed to IM IFNβ-1a within ~ 1 week of conception or during the first trimester were included. Participants were followed until there was a pregnancy outcome, live-born infants were followed until age 8-12 weeks. Data were collected on IM IFNβ-1a exposure, demographics, patient characteristics, medical history, and pregnancy outcomes, including live births (with or without birth defect), spontaneous abortions/miscarriages and fetal death/stillbirth, elective abortions (with and without birth defect), and ectopic pregnancies. A population-based birth defect surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), served as the primary external control group for evaluating the risk of birth defects. Three-hundred and two patients with a median (range) age of 31.0 (16-48) years and a median (range) gestational age at the time of enrollment of 10.1 (4-39) weeks were evaluable. Most patients (n = 278/302; 92%) reported IM IFNβ-1a exposure in the week before conception and most (n = 293/302; 97%) discontinued treatment before the end of the first trimester. Of 306 pregnancy outcomes, there were 272 live births, 28 spontaneous abortions of 266 pregnancies enrolled before 22 weeks' gestation (rate 10.5%; 95% confidence interval 7.2-15.0), five elective abortions, and one stillbirth. There were 17 adjudicator-confirmed major birth defects of 272 live births (rate 6.3%; 95% confidence interval 3.8-10.0); the pattern of birth defects observed was not suggestive of a relationship to prenatal IM IFNβ-1a exposure. This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy. ClinicalTrials.gov: NCT00168714, 15 September, 2005.

Critical care, maternal and neonatal outcomes of pregnant women with COVID-19 admitted to eight intensive care units during the wildtype, alpha and delta waves of the pandemic across the North West of England-a retrospective review.

Few studies have described obstetric and critical care outcomes in pregnant women with COVID-19 needing intensive care unit (ICU) admission. Obstetric and critical care outcomes of COVID-19 women admitted to eight ICUs from April 1, 2020 to September 15, 2021, in the North West of England were retrospectively analyzed. Women admitted to ICU were assigned to three groups: antepartum women discharged from ICU prior to delivery (antepartum ICU-discharged group), antepartum women who had expedited delivery (antepartum ICU-delivered group) and a postpartum group. Our aims were to describe maternal characteristics and assess how delivery influenced the obstetric and critical care outcomes in these women. During the study period, 615 women tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of whom 62 (10.1%) needed ICU admission due to symptomatic COVID-19. Pregnancy loss (3.2%) was recorded in two women. Detailed obstetric and critical outcomes from 60 women are reported. Nine antepartum women (15%) admitted to ICU were discharged and continued their pregnancy, 13 antepartum women (21.7%) had expedited delivery by cesarean birth after ICU admission and 38 (63.3%) women were admitted to ICU during the postpartum period. Antepartum ICU-discharged women contracted the SARS-CoV-2 at an earlier median gestational age (23 weeks; p = 0.0003) and needed ICU admission at an earlier median gestational age (28 weeks, p = 0.03) compared with antepartum ICU-delivered (28 and 32 weeks) and postpartum women (35.5 and 36 weeks). Antepartum ICU-discharged women had the lowest rate of mechanical ventilation receipt (11.1%) compared with antepartum ICU-delivered women (52.3%) and postpartum women (44.3%) but the difference was not statistically significant (p = 0.13). No significant differences were observed in the frequency and severity of critical care complications in the antepartum ICU-discharged, antepartum-ICU delivered and postpartum women. Of the women admitted to ICU antepartum, 40% were discharged while remaining pregnant and 60% had expedited delivery. Antepartum women who were discharged from ICU without giving birth may receive lower rates of mechanical ventilation than those who delivered in ICU or admitted postpartum; however, further studies are needed to confirm or refute this association.

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients

Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January2022. Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day8. Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

The effect of oscillometric blood pressure measurement on pain response in preterm infants.

Preterm neonates are exposed to many painful procedures in neonatal intensive care units. This study aims to evaluate the effect of oscillometric blood pressure (BP) measurement on pain response in preterm infants. This prospective study was performed over 4 months in a level III neonatal intensive care unit. Premature neonates whose gestational age was <34 weeks and postmenstrual age <36 weeks were included if they had no systemic diseases. BP measurement was performed on the right arm. The Premature Infant Pain Profile-Revised (PIPP-R) scores were evaluated three times before, during, and 10 min after BP measurement. During the 5-month period, 100 preterm neonates (53 male infants) were included in the study. Median birth weight and gestational age of the infants were 1148 (IQR: 1015-1300) g and 28 (IQR: 27-30) weeks, respectively. PIPP-R scores were found to be ≥7 in 34% of neonates. PIPP-R scores increased during BP measurement and decreased after. Our results demonstrated that oscillometric BP measurement which is generally accepted as a non-invasive tool for monitoring can produce mild pain in premature neonates of postmenstrual age <36 weeks.