Volume 51, Issue 1 - 50 Years of JPM — Special Anniversary Issue

Objectives To apply scientometric methodology to characterize influential articles in the Journal of Perinatal Medicine (JPM). Methods We performed a cross-sectional study of all JPM articles indexed in Clarivate Web of Science (WOS), NIH Open Citation Collection, and Altmetric Explorer databases (1973–2022). We identified articles cited ≥100 times in WOS and articles with highest Relative Citation Ratios (RCR, a metric of influence based on citations) and highest Altmetric Attention Scores (AAS, a metric of engagement with social media and public platforms). We performed descriptive analysis to characterize influential articles based on citation rates vs. highest AAS, and quantile regression with bootstrapping to estimate the median differences (95% confidence intervals). Results We identified 4095 JPM articles that were indexed in the WOS, of which 3,959 (96.7%) had RCRs and 939 (22.9%) had AASs. The study cohort included 34 articles cited ≥100 times and the 34 top-RCR and 34 top-AAS articles, representing 83 unique articles. These influential articles had median 67 citations (IQR 17–114), median RCR 3.4 (IQR 1.7–5.0), and median AAS 14 (IQR 3–28). The majority were observational studies and reviews. Compared to top-AAS articles, top-cited articles had higher median citations (117 [IQR 111–147] vs. 13 [IQR 5–62]; median difference 104.0, 95% CI 86.6–121.4) and citations per year (7.3 [IQR 4.9–10.6] vs. 2.3 [0.7–4.6]; median difference 5.5 [95% CI 3.1–7.9]). Results were similar for top-RCR vs. top-AAS articles. Conclusions We identified influential articles during 50 years of JPM, providing insight into the impact of the journal and providing a template for future studies of academic journals.

Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary development and those with sickle cell disease. Our research group, therefore, has focused on the early origins of chronic respiratory disease. This has included assessing antenatal diagnostic techniques and potentially therapeutic interventions in infants with congenital diaphragmatic hernia. Undertaking physiological studies, we have increased the understanding of the premature baby’s response to resuscitation and evaluated interventions in the delivery suite. Mechanical ventilation modes have been optimised and randomised controlled trials (RCTs) with short- and long-term outcomes undertaken. Our studies highlighted respiratory syncytial virus lower respiratory tract infections (LRTIs) and other respiratory viral LRTIs had an adverse impact on respiratory outcomes of prematurely born infants, who we demonstrated have a functional and genetic predisposition to respiratory viral LRTIs. We have described the long-term respiratory outcomes for children with sickle cell disease and importantly identified influencing factors. In conclusion, it is essential to undertake long term follow up of infants at high risk of chronic respiratory morbidity if effective preventative strategies are to be developed.

Hypoxanthine is a purine metabolite which increases during hypoxia and therefore is an indicator of this condition. Further, when hypoxanthine is oxidized to uric acid in the presence of xanthine oxidase, oxygen radicals are generated. This was the theoretical basis for suggesting and studying, beginning in the 1990s, resuscitation of newborn infants with air instead of the traditional 100% O 2 . These studies demonstrated a 30% reduction in mortality when resuscitation of term and near term infants was carried out with air compared to pure oxygen. The mechanism for this is not fully understood, however the hypoxanthine –xanthine oxidase system increases oxidative stress and plays a role in regulation of the perinatal circulation. Further, hyperoxic resuscitation inhibits mitochondrial function, and one reason may be that genes involved in ATP production are down-regulated. Thus, the study of one single molecule, hypoxanthine, has contributed to the global prevention of an estimated 2–500,000 annual infant deaths.

Objectives Establishing immediate intravenous access to a newborn is challenging even for trained neonatologists in an emergency situation. Correct placement of umbilical catheter or an intraosseous needle needs consistent training. We evaluated the time required to correctly place an emergency umbilical button cannula (EUC) or an umbilical catheter (UC) using the standard intersection (S-EUC or S-UC, respectively) or lateral umbilical cord incision (L-EUC) by untrained medical personnel. Methods Single-center cross-over pilot-study using a model with fresh umbilical cords. Video-based teaching of medical students before probands performed all three techniques after assignment to one of three cycles with different sequence, using a single umbilical cord divided in three pieces for each proband. Results Mean time required to establish L-EUC was 89.3 s, for S-EUC 82.2 s and for S-UC 115.1 s. Both application routes using the EUC were significantly faster than the UC technique. There was no significant difference between both application routes using EUC (p=0.54). Conclusions Using an umbilical cannula is faster than an umbilical catheter, using a lateral incision of the umbilical vein is an appropriate alternative.

COVID-19 is caused by the 2019 novel coronavirus (2019-nCoV). The first cases of COVID-19 were identified in December 2019, and the first United States (US) case was identified on January 20th, 2020. Since then, COVID-19 has spread throughout the world and was declared a pandemic by the WHO on March 11, 2020. As of July 2022, about 90 million persons have been infected with COVID-19 in the US, and there have been over 1 million deaths There have been 224,587 pregnant patients infected with COVID-19, and 34,527 were hospitalized. Pregnancy increases the risk of severe disease associated with COVID-19 and vaccinated patients are significantly less likely to develop severe disease. Adverse pregnancy and neonatal outcomes are more common among women infected with SARS-CoV-2 during pregnancy, especially among those with severe disease, and vaccination also protects the newborn infant. The intrauterine transmission of SARS-CoV-2 appears to be rare. COVID-19 vaccinations and booster shots in pregnancy are safe. In addition, the available data suggest that vaccination during pregnancy is associated with the transmission of SARS-CoV-2 antibodies to the fetus. The vaccination of lactating women is associated with high levels of SARS-CoV-2 antibodies in the breast milk. It is important that with future pandemics the concept of vaccine recommendations in pregnancy should be made early on to prevent maternal, fetal, and neonatal morbidity and mortality. Physicians and other healthcare professionals should strongly recommend COVID-19 vaccination to patients who are pregnant, planning to become pregnant, and to those who are breastfeeding.

It is very complicated to give correct answer to the question “How to define human life?” Nowadays dilemmas consider the respect of human life from the birth to death involve not just biology but also other sciences like philosophy, theology, sociology, psychology, law and politics. These sciences evaluate the topic from different points of view. Integration of all of these perspectives could result with a proper definition. The principal purpose of this paper is to try to determine when a human individual begins. If this proves to be too difficult, we might have to settle for a specific stage in the reproductive process before which it would be impossible to say with any plausibility that a human individual exists. It is necessary to return the moral dimension of observation to the science of life. The point is to reconcile the universal ethical principles concerning the absolute value of life with the everyday challenges and dilemmas. It is our deepest conviction that life has an absolute value and that there always remains something indestructible and substantial in life, which may neither be evaluated by anything final, nor completely reduced to the material biological equivalent and the genetic substratum.

Objectives The heterogeneous nature of preeclampsia is a major obstacle to early screening and prevention, and a molecular taxonomy of disease is needed. We have previously identified four subclasses of preeclampsia based on first-trimester plasma proteomic profiles. Herein, we expanded this approach by using a more comprehensive panel of proteins profiled in longitudinal samples. Methods Proteomic data collected longitudinally from plasma samples of women who developed preeclampsia (n=109) and of controls (n=90) were available from our previous report on 1,125 proteins. Consensus clustering was performed to identify subgroups of patients with preeclampsia based on data from five gestational-age intervals by using select interval-specific features. Demographic, clinical, and proteomic differences among clusters were determined. Differentially abundant proteins were used to identify cluster-specific perturbed KEGG pathways. Results Four molecular clusters with different clinical phenotypes were discovered by longitudinal proteomic profiling. Cluster 1 involves metabolic and prothrombotic changes with high rates of early-onset preeclampsia and small-for-gestational-age neonates; Cluster 2 includes maternal anti-fetal rejection mechanisms and recurrent preeclampsia cases; Cluster 3 is associated with extracellular matrix regulation and comprises cases of mostly mild, late-onset preeclampsia; and Cluster 4 is characterized by angiogenic imbalance and a high prevalence of early-onset disease. Conclusions This study is an independent validation and further refining of molecular subclasses of preeclampsia identified by a different proteomic platform and study population. The results lay the groundwork for novel diagnostic and personalized tools of prevention.

Access to maternal-fetal medicine (MFM) subspecialty services is a critical part of a healthcare system that optimizes pregnancy outcomes for women with complex medical and obstetrical disorders. Healthcare services in the State of Hawaiʻi consist of a complicated patchwork of independently run community health clinics and hospital systems which are difficult for many pregnant patients to navigate. Maternal telehealth services have been identified as a solution to increase access to subspecialty prenatal services for women in rural communities or neighboring islands, especially during the COVID-19 pandemic. Telehealth innovations have been rapidly developing in the areas of remote ultrasound, hypertension management, diabetes management, and fetal monitoring. This report describes how telehealth innovations are being introduced by MFM specialists to optimize care for a unique population of high-risk patients in a remote area of the world such as Hawai‘i, as well as review currently available telemedicine technologies and future innovations.

Overweight and obesity in pregnancy and prepregnancy are perinatal risks. Studies showed prevention of these risks with counseling about the risks and treatment strategies like lifestyle interventions as exercise on a daily basis, nutritional health and diet.

Objectives Histological examination of uterine scars provides insight into uterine wound healing and helps to develop prevention methods of uterine wall rupture after previous uterine surgery. Therefore, exact intraoperative scar identification is needed for specimen collection from the actual scar tissue. The aim of this study was to correlate pre- and intraoperative ultrasound measurements of the lower uterine segment (LUS) with histological findings of scar tissue and to evaluate the relevance of intraoperative ultrasound. Methods In a prospective observational study, preoperative and intraoperative sonographic measurements of the LUS thickness were performed in 33 women with a history of at least one cesarean delivery. Intraoperative ultrasound with a linear transducer placed directly on the uterus identified the scar area and uterotomy was performed 2 cm cranially. Tissue samples were taken after extraction of the fetus, embedded in paraffin wax, and stained according to Gomori Trichrome to identify scar tissue. Collagen content was evaluated with imaging software Fiji (NIH, Bethesda, USA). Preoperative and intraoperative sonographic measurements were correlated with histologic evidence of scar tissue. Results Histological evidence of scar tissue was found in 11 out of 33 samples with significantly lower ultrasonographic thickness of the lower uterine segment compared to the other 22 samples, both antepartum (1.4 mm [1.3–1.9] vs. 2.0 mm [1.6–2.6], p=0.03) and intrapartum (1.6 mm [1.3–1.9] vs. 3.7 mm [2.0–4.7], p<0.01). Intraoperative ultrasound had a significantly higher predictive power (AUC difference 0.18 [0.03–0.33], p=0.01). Conclusions Intraoperative sonography identifies the uterine wall area with histologically confirmable scar tissue far better than preoperative sonography.

Objectives Abnormal placentation may affect the maternal serum fraction of cell-free fetal DNA (fetal fraction) determined as part of non-invasive prenatal screening (NIPS). This study aimed to assess whether the fetal fraction can predict placenta accreta spectrum (PAS) with or without placenta previa (PP). We also investigated the impact of trophoblastic invasion depth on the fetal fraction. Methods This is a retrospective case-control study of pregnant women with and without abnormal placentation carrying a singleton and having undergone NIPS prior to 20 weeks of gestation. The eligible subjects were selected from a cohort managed at our institution for PAS suspected antenatally. We compared women with normal placentation (controls) to PAS, PP, or PAS + PP cases. Data were abstracted from electronic medical records, and PAS was confirmed histologically. Results Of the 146 patients in our cohort, 8 controls, 10 PP, 6 PAS, and 7 PAS + PP cases were eligible for the study. Among the groups, there were no significant differences in baseline demographic and clinical characteristics except the median number of prior uterine surgeries. Also, the groups did not significantly differ in their median fetal fraction. The fetal fraction did not discriminate any group when stratified according to the depth of placental invasion, i.e., no PAS, abnormally adherent, and abnormally invasive placenta. Conclusions The maternal serum fraction of cell-free fetal DNA measured before 20 weeks of gestation is not predictive of PAS with or without concurrent PP or the depth of trophoblastic invasion.

Objectives To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection. Methods In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection. Results One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as ≥100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12. Conclusions Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load.

Ventriculomegaly (VM) is defined as an enlargement of the lateral ventricles of the developing fetal brain. The diagnosis is easily made by measuring the lateral ventricle width at the level of the atrium, which is normally <10 mm. VM is defined as mild when the atrial width is 10–12 mm, moderate 12–15 mm, severe >15 mm. VM is a non-specific sonographic sign which is common to different pathological entities and genetic conditions. When no associated anomaly can be found VM is defined as isolated. Since the prognosis of fetal VM mainly depends on the presence of associated anomalies, a careful diagnostic approach is necessary to rule out CNS and extra- CNS fetal anomalies. Magnetic Resonance Imaging can be a useful diagnostic tool complementary to ultrasound in order to recognize subtle brain anomalies, particularly cortical disorders. In this review the diagnostic approach to fetal VM will be discussed starting from ultrasound screening, moving to neurosonographic and MRI examination and genetic evaluation, in order to recognize the cause of VM and offer the appropriate counselling to the parents.

Objectives To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. Methods Amniotic fluid was collected by laparotomy – a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. Results Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. Conclusions The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe.

Vaginal progesterone (VP) has been recommended to prevent preterm birth (PTB) in women at high-risk. However, there is controversy as to whether VP is efficacious in some subsets of high-risk women. In this review, we examined the current best evidence on the efficacy of VP to prevent PTB in several subsets of high-risk women and provided recommendations for its clinical use. Compelling evidence indicates that VP reduces the risk of PTB and improves perinatal outcomes in singleton gestations with a short cervix (≤25 mm), both with and without a history of spontaneous PTB. VP appears promising to reduce the risk of PTB in twin gestations with a short cervix (≤25 mm) and in singleton gestations conceived by assisted reproductive technologies, but further research is needed. There is no convincing evidence that supports prescribing VP to prevent PTB in singleton gestations based solely on the history of spontaneous preterm birth. Persuasive evidence shows that VP does not prevent PTB nor does it improve perinatal outcomes in unselected twin gestations and in singleton gestations with a history of spontaneous PTB and a cervical length >25 mm. There is no evidence supporting the use of VP to prevent PTB in triplet or higher-order multifetal gestations, singleton gestations with a positive fetal fibronectin test and clinical risk factors for PTB, and gestations with congenital uterine anomalies or uterine leiomyoma. In conclusion, current evidence indicates that VP should only be recommended in singleton gestations with a short cervix, regardless of the history of spontaneous PTB.

Intrapartum fetal surveillance aims to predict significant fetal hypoxia and institute timely intervention to avoid fetal injury, and do so without unnecessary operative delivery of fetuses at no risk of intrapartum hypoxia. However, the configuration and application of current clinical guidelines inadvertently undermine these aims because of persistent failure to incorporate increased understanding of fetal cardiovascular physiology and adaptations to oxygen deprivation, advances in signal acquisition/processing, and related technologies. Consequently, the field on intrapartum fetal surveillance is stuck in rudimentary counts of the fetal R–R intervals and visual assessment of very common, but nonspecific fetal heart decelerations and fetal heart rate variability. The present authors argue that the time has come to move away from classifications of static morphological appearances of FHR decelerations, which do not assist the thinking clinician in understanding how the fetus defends itself and compensates for intrapartum hypoxic ischaemic insults or the patterns that suggest progressive loss of compensation. We also reappraise some of the controversial aspects of intrapartum fetal surveillance in modern obstetric practice, the current state of flux in training and certification, and contemplate the future of the field particularly in the context of the emerging role of artificial intelligence.

Objectives The objective of this study is to present the why, what and how about computerized analysis of cardiotocograms (cCTG) and the SisPorto system for cCTG. Content A narrative review about cCTG and the SisPorto system for cCTG is presented. The meta-analysis of randomized controlled trials (RCT) performed so far have evidenced that cCGT compared to traditional CTG analysis may save time spent in hospital for women, in the antepartum period, and is objective with at least equivalent results in maternal and perinatal outcomes, both in the ante and intrapartum periods. The SisPorto system for cCTG closely follows the FIGO guidelines for fetal monitoring. It may be used both in the ante and intrapartum periods, alone or connected to a central monitoring station, with simultaneous monitoring of fetal and maternal signals, not only in singletons but also in twins. It has been assessed in technical, physiopathological and clinical studies, namely in one large multicentric international RCT during labor and two meta-analysis. Summary and outlook There is evidence that cCTG may be useful in clinical practice with advantages compared to traditional CTG analysis, although without clear impact on the decrease of preventable maternal and perinatal mortality and morbidity. More studies are warranted, namely on technical improvements and assessment in larger studies in a wider range of clinical settings.