Catestatin is a chromogranin A-derived peptide involved in sympathetic, cardiovascular, inflammatory, and metabolic regulation, but its longitudinal profile during pregnancy remains insufficiently defined. This prospective cohort study aimed to evaluate changes in serum catestatin concentrations from the first to the third trimester and to explore their associations with blood pressure and metabolic parameters in initially low-risk singleton pregnancies. Fifty pregnant women were followed longitudinally from 11-13 + 6/7 to 30-41 + 5/7weeks of gestation. Clinical and biochemical parameters were assessed at both visits, and serum catestatin concentrations were measured using a commercial enzyme immunoassay. Serum catestatin concentrations were significantly lower in the third trimester than in the first trimester (median [IQR]: 9.4 [4.9-15.5] vs. 13.4 [9.9-24.6] ng/mL; p < 0.001). Longitudinal changes in catestatin were positively associated with third-trimester insulin concentrations after adjustment for selected covariates. Third-trimester catestatin concentrations were positively correlated with systolic blood pressure (r = 0.356, p = 0.011) and remained associated with systolic blood pressure in a limited multivariable model. These findings suggest that catestatin concentrations decline from early to late pregnancy and may reflect selected metabolic and hemodynamic changes. Larger longitudinal studies including pathological pregnancy cohorts are needed to clarify its clinical relevance.

BACKGROUND:Animal experimental studies and human observational data suggest that fetal inflammatory response to chorioamnionitis is associated with increased risk of neonatal encephalopathy and attenuation of fetal responses to intrapartum hypoxia-ischemia, but the effects of clinical and/or histological chorioamnionitis and fetal inflammatory response on fetal heart rate patterns during labor in the term human fetus remain undefined. OBJECTIVE:To compare intrapartum fetal heart rate responses to hypoxia, assessed by fetal heart rate deceleration frequency and cumulative deceleration area, in acidemic fetuses in term labor to their peers with and without hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis. STUDY DESIGN:This retrospective cohort study included 317,126 term singleton deliveries from 7 hospitals in the Helsinki University Hospital district, Finland, between 2005 and 2024. Among these, 3487 newborns with umbilical artery acidemia, defined as pH<7.10, and continuous intrapartum cardiotocographic recordings were identified. Fetal heart rate data from the final 9 hours before birth were analyzed, with hourly median values calculated for deep deceleration (decreases of ≥60 beats per minute below baseline lasting >15 seconds) and shallow deceleration (decreases of 10-15 beats per minute lasting >15 seconds) frequencies, cumulative deceleration area (all decelerations of ≥10 beats per minute lasting >15 seconds), and uterine contraction frequency. Neonatal hypoxic-ischemic encephalopathy was diagnosed according to Sarnat staging, and chorioamnionitis based on clinical criteria and/or placental histology. Acidemic cases were categorized into 4 groups: acidemia with hypoxic-ischemic encephalopathy and clinical and/or histological chorioamnionitis (N=133), acidemia with hypoxic-ischemic encephalopathy without chorioamnionitis (N=181), acidemia with clinical and/or histological chorioamnionitis without hypoxic-ischemic encephalopathy (N=436), and acidemia without hypoxic-ischemic encephalopathy or chorioamnionitis (N=2737). RESULTS:Among 3487 term fetuses with umbilical artery acidemia, clinical and/or histological chorioamnionitis was associated with an increased risk of hypoxic-ischemic encephalopathy (adjusted odds ratio, 4.61; 95% confidence interval, 3.60-5.87; P<.001), despite a shift toward less severe umbilical artery acidemia, with a greater proportion of moderate (pH 7.09-7.00) and a lower proportion of severe (pH<7.00) acidemia (P=.026). Among histological chorioamnionitis cases, funisitis, a histopathologic manifestation of the fetal inflammatory response, remained independently associated with hypoxic-ischemic encephalopathy after adjustment for acidemia severity (adjusted odds ratio, 2.21; 95% confidence interval, 1.32-4.13; P<.001). Consistent with these findings, clinical and/or histological chorioamnionitis was associated with attenuated fetal heart rate responses to intrapartum hypoxic stress. Among fetuses who developed hypoxic-ischemic encephalopathy, those with clinical and/or histological chorioamnionitis exhibited fewer deep decelerations (adjusted ratio of medians, 0.62; 95% confidence interval, 0.49-0.76), a smaller cumulative deceleration area (adjusted ratio of medians, 0.70; 95% confidence interval, 0.59-0.82), and more shallow decelerations (adjusted ratio of medians, 2.45; 95% confidence interval, 2.33-2.63; all P<.001), despite similar uterine contraction frequency, with attenuation most pronounced among fetuses with funisitis. Clinical chorioamnionitis alone remained independently associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.44; 95% confidence interval, 1.02-2.05; P<.001), whereas histological chorioamnionitis was associated with a 2.5-fold higher risk than clinical chorioamnionitis alone (adjusted odds ratio, 2.54; 95% confidence interval, 1.68-3.86; P<.001). CONCLUSIONS:Clinical and histological chorioamnionitis, particularly when accompanied by funisitis, are associated with attenuated fetal heart rate responses to intrapartum hypoxic stress and reduced fetal tolerance to hypoxia, thereby increasing the risk of hypoxic-ischemic encephalopathy at milder degrees of acidemia.

Background:Maternal autoimmune diseases, including Sjögren's disease (SjD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), and mixed connective tissue disease (MCTD), are associated with adverse pregnancy outcomes. However, comprehensive population-based studies evaluating the impact of these diseases across multiple countries are limited. Objective:To characterize outcomes in pregnancies complicated by SjD, SLE, RA, IIM, and/or MCTD in Denmark, Finland, and Sweden. Study Design:A population-based cohort study was conducted using data from national health registers from Denmark (1995-2017), Finland (2000-2022), and Sweden (2000-2021). The study included singleton pregnancies in women aged ≥15 years at delivery and with any of the five specified autoimmune diseases diagnosed before or during pregnancy, or within one year postpartum. Maternal demographics and complications, birth outcomes, neonatal characteristics, and long-term outcomes in children were described. Results:The present study included 20,425 singleton pregnancies complicated by maternal SjD (n=1913), SLE (n=3570), RA (n=13,328), IIM (n=1078), or MCTD (n=536). Across the three countries, common pregnancy complications included preeclampsia and preterm premature rupture of membranes, which occurred in 2% to 12%, and 1% to 16% of pregnancies, respectively; fetal growth restriction was reported in 3% to 11% of pregnancies complicated by SjD, SLE, RA, or MCTD. Emergency caesarean section was performed in 10% to 21% of all pregnancies. A total of 20,304 liveborn children were identified, of which 6% to 18% were preterm and 5% to 24% were small for gestational age. Neonatal unit admission rate varied between 9% and 24%. Second/third-degree atrioventricular block was reported in 1.5% and 0.9% of SjD pregnancies in Sweden and Finland, respectively. Conclusion:The study provides a comprehensive overview of outcomes in pregnancies complicated by autoimmune diseases in three Nordic countries. These pregnancies show notable proportions of adverse maternal and neonatal outcomes, underscoring the importance of tailored clinical management and specialized perinatal care to address the unique challenges faced by the mothers and their children.

Introduction: The Nordic Fetal Therapy Alliance centralizes treatment of twin-to-twin transfusion (TTTS) to ensure high-quality fetal therapy. This study reports the outcomes of treated TTTS cases and highlights the importance of international collaboration. METHODS:We conducted a prospective observational study on all pregnancies undergoing TTTS surgery between May 2019 and April 2022 in the Nordic countries. The primary outcome was perinatal survival at 28 days. Secondary outcomes were gestational age (GA) at delivery, procedure-related complications, and mode of delivery. RESULTS:A total of 200 cases underwent fetal surgery; 185 were treated with fetoscopic laser photocoagulation (FLP), and 15 with primary selective reduction by cord occlusion (CO). FLP resulted in at least one surviving neonate in 86% and in at least two survivors in 64%. Median GA at surgery was 20+1 weeks (range 15+1; 29+0), and median GA at delivery was 32+2 weeks (range 24+3; 41+0). In the CO group, 80% had at least one surviving neonate. Preterm premature rupture of membranes occurred in 13.6% within the FLP group and none in the CO group. Post-laser twin-anemia polycythemia sequence occurred in 5.4%. CONCLUSION:Collaboration across borders on TTTS treatment in the Nordic region is possible, and outcome results are comparable to other International Centers. .

To compare pregnancy prolongation and neonatal outcomes in women with signs of threatened preterm birth (PTB) and intact membranes by administration of low-doses of prednisone for 3 weeks compared to women who received standard protocols of tocolysis and respiratory distress syndrome (RDS) prophylaxis in a pilot randomized controlled trial. We randomized 26 women with signs of threatened PTB and intact membranes between 24 and 34 weeks of gestation to either continued prednisone administration for 3 weeks following the initiation of the standard protocol (intervention group) or standard therapy for threatened PTB (control group). The primary outcome was the gestational length in women with and without using low-doses of prednisone. The secondary outcome included incidence of RDS, intraventricular hemorrhage, necrotizing enterocolitis, the need for mechanical ventilation, and perinatal mortality in newborns from both study groups. Participants in the intervention group had significantly longer pregnancy prolongation than the control group (65.38 vs. 40.54 days, p=0.001). Although the difference was not statistically significant (p=0.153), the gestational age at delivery in the intervention group (38.35 weeks) was 10 days longer than in the control group (36.89 weeks). There were no significant differences between the groups in neonatal outcomes. The first pilot randomized controlled study on low-dose prednisone in threatened PTB and intact membranes suggests it may prolong pregnancy without adverse neonatal outcomes. Due to the small sample size and single-centre design, these preliminary findings should be interpreted with caution and confirmed in larger, adequately powered trials.

BACKGROUND:Neonatal hypoxic-ischemic encephalopathy remains a leading cause of neonatal death and lifelong neurological impairment, imposing substantial economic burdens on affected families and healthcare system. While prior research has examined the cost-effectiveness of therapeutic hypothermia and hospital resource utilization, the economic impact of preventive strategies reflecting real-world variations in obstetric care has not been studied. OBJECTIVE:To compare the true cost of optimal vs substandard obstetric care in cases with and without neonatal hypoxic-ischemic encephalopathy. STUDY DESIGN:This retrospective economic analysis included a 20-year (2005-2024) cohort of 317,126 term singleton deliveries with 314 cases of hypoxic-ischemic encephalopathy across 7 hospitals within the Helsinki University Hospital district, Finland. Optimal care was defined as timely delivery in response to nonreassuring fetal status, while substandard care referred delayed or missed responses. The primary outcome was the direct neonatal healthcare cost from birth to hospital discharge. Secondary outcomes included the relative risk of hypoxic-ischemic encephalopathy and the incremental cost per disability-free life year gained by age 4. Costs across 4 groups (optimal or substandard care, with or without hypoxic-ischemic encephalopathy) were compared using generalized linear models. The study was powered at 90% to detect a ≥$1448 mean cost difference. RESULTS:The mean cost per newborn was lower in the optimal care group compared with the substandard care group, irrespective of hypoxic-ischemic encephalopathy occurrence ($1269 vs $2807; mean difference $1537 [+121%]; 95% confidence interval, $662-$2413; P<.001). The largest disparity was between neonatal hypoxic-ischemic encephalopathy cases after substandard care and cases without hypoxic-ischemic encephalopathy under optimal care ($28,315 vs $988; mean difference $27,327 [+2766%]; 95% confidence interval, $19,721-$34,779; P<.001). Optimal care yielded a 4-year disability-free life year gain of 0.06 per newborn (95% confidence interval, 0.05-0.07), with an incremental cost of $25,617 (95% confidence interval, $40,221 to $11,013; P<.001) per disability-free life year gained. The incidence of hypoxic-ischemic encephalopathy was 1.53% (95% confidence interval, 1.21-1.93) in the substandard care group, representing a 20-fold increase in risk (relative risk, 19.60; 95% confidence interval, 15.00-25.50) compared with the optimal care group (0.08%; 95% confidence interval, 0.07-0.09; P<.001). CONCLUSION:Optimal obstetric care was more cost-effective, less costly, and clinically more effective, lowering average healthcare costs per newborn while reducing the incidence of hypoxic-ischemic encephalopathy compared with substandard care.

OBJECTIVE:This study aims to assess the diagnostic value of post-mortem radiographic imaging compared with prenatal ultrasound in suspected fetal skeletal dysplasias in a large Finnish cohort. METHOD:Prenatal ultrasound findings and their association with post-mortem radiographic imaging were evaluated in a cohort of 36 fetuses with prenatally suspected skeletal dysplasia. RESULTS:Prenatal ultrasound performed well in detecting skeletal dysplasias and severe forms of the disease. Additional radiographic imaging was performed post-mortem in 16/27 terminated pregnancies. Post-mortem X-ray and 3D-CT detected several features not seen with US. They were superior to US in identifying spinal and thoracic anomalies and performed better in discovering fractures and deformities of long bones. In addition, disease-specific findings became more accurate with X-ray/CT, especially in the group of true skeletal dysplasias (14/18, 77.8%). Post-mortem X-ray and CT increased phenotypic data and facilitated interpretation of genetic findings. CONCLUSION:Post-mortem X-ray and CT offer additional information supporting the diagnostic process. Detailed phenotypic data are important in interpreting the results of genetic analyses and in assessing the recurrence risk in future pregnancies. Complementary imaging methods including post-mortem radiography are therefore recommended.

Background:Red blood cell (RBC) alloimmunization is an immune response where the maternal immune system produces antibodies against fetal RBCs, which can lead to hemolytic disease of the fetus and newborn (HDFN). Despite the significant clinical burden of HDFN, there are few large international cohorts that focus on perinatal care and outcomes of at-risk pregnancies. Objective:To describe the maternal characteristics and outcomes of pregnancies affected by RBC alloimmunization, as well as the characteristics and outcomes of neonates from such pregnancies. Study Design:Utilizing data from nationwide health registers, this population-based cohort study identified all singleton pregnancies in individuals who had ≥1 pregnancy monitored or treated for potential alloimmunization, or ≥1 child with a postnatal diagnosis of HDFN-related conditions, between January 1, 2000, and December 31, 2021, in Sweden and Finland, and between January 1, 1997, and December 31, 2018, in Denmark. Among the identified pregnancies, those with a diagnosis of maternal care for alloimmunization or fetal hydrops, or neonates with a postnatal diagnosis of HDFN-related conditions, were categorized as HDFN pregnancies. The remaining pregnancies-sibling pregnancies that may have been at risk of alloimmunization but did not receive any alloimmunization- or HDFN-related diagnosis-were categorized as non-HDFN pregnancies. Results:This study included 14,732 singleton pregnancies in Sweden, 5863 in Finland, and 11,964 in Denmark. Among these pregnancies, 7391 (50%) in Sweden, 2885 (49%) in Finland, and 6150 (51%) in Denmark were categorized as HDFN pregnancies. Maternal complications and stillbirth rates were comparable between HDFN and non-HDFN pregnancies. Caesarean deliveries were more frequent in HDFN pregnancies. A total of 14,519 neonates in Sweden, 5827 in Finland, and 11,803 in Denmark were born to all pregnancies identified. Of these, 7289 (50%), 2849 (49%), and 6076 (51%) had HDFN. Among the neonates with HDFN, 27% in Sweden, 38% in Finland, and 12% in Denmark received HDFN-related treatment, including intrauterine transfusion (IUT; data unavailable for Finland), neonatal transfusion, and phototherapy. Compared to non-HDFN neonates, those in the IUT and neonatal transfusion groups had lower gestational age, birth weight and length, and higher rates of neonatal unit admission, and were more frequently diagnosed postnatally with growth disturbances and disorders of the nervous system. Conclusion:This is a comprehensive overview of perinatal characteristics and outcomes of pregnancies at risk of HDFN in Sweden, Finland, and Denmark. Our findings highlight the significant unmet need in perinatal care among neonates with HDFN, particularly those treated with IUT or neonatal transfusion. Further research is warranted to improve the management of severe HDFN pregnancies.

OBJECTIVE:The optimal management of placenta accreta spectrum (PAS) requires the participation of multidisciplinary teams that are often not locally available in low-resource settings. Telehealth has been increasingly used to manage complex obstetric conditions. Few studies have explored the use of telehealth for PAS management, and we aimed evaluate the usage of telehealth in the management of PAS patients in low-resource settings. METHODS:Between March and April 2023, an observational, survey-based study was conducted, and obstetricians-gynecologists with expertise in PAS management in low- and middle-income countries were contacted to share their opinion on the potential use of telehealth for the diagnosis and management of patients at high-risk of PAS at birth. Participants were identified based on their authorship of at least one published clinical study on PAS in the last 5 years and contacted by email. This is a secondary analysis of the results of that survey. RESULTS:From 158 authors contacted we obtained 65 responses from participants in 27 middle-income countries. A third of the participants reported the use of telehealth during the management obstetric emergencies (38.5%, n = 25) and PAS (36.9%, n = 24). Over 70% of those surveyed indicated that they had used "informal" telemedicine (phone call, email, or text message) during PAS management. Fifty-nine participants (90.8%) reported that recommendations given remotely by expert colleagues were useful for management of patients with PAS in their setting. CONCLUSION:Telehealth has been successfully used for the management of PAS in middle-income countries, and our survey indicates that it could support the development of specialist care in other low resource settings.

Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

This study aimed to validate the Sargent risk stratification algorithm for the prediction of placenta accreta spectrum (PAS) severity using data collected from multiple centers and using the multicenter data to improve the model. We conducted a multicenter analysis using data collected for the IS-PAS database. The Sargent model's effectiveness in distinguishing between abnormally adherent placenta (FIGO grade 1) and abnormally invasive placenta (FIGO grades 2 and 3) was evaluated. A new model was developed using multicenter data from the IS-PAS database. The database included 315 cases of suspected PAS, of which 226 had fully documented standardized ultrasound signs. The final diagnosis was normal placentation in 5, abnormally adherent placenta/FIGO grade 1 in 43, and abnormally invasive placenta/FIGO grades 2 and 3 in 178. The external validation of the Sargent model revealed moderate predictive accuracy in a multicenter setting ( C -index 0.68), compared to its higher accuracy in a single-center context ( C -index 0.90). The newly developed model achieved a C -index of 0.74. The study underscores the difficulty in developing universally applicable PAS prediction models. While models like that of Sargent et al. show promise, their reproducibility varies across settings, likely due to the interpretation of the ultrasound signs. The findings support the need for updating the current ultrasound descriptors and for the development of any new predictive models to use data collected by different operators in multiple clinical settings.