Extreme Preterm Birth Research Articles

The molecular mechanisms of oxygen-sensing in human ductus arteriosus smooth muscle cells: A comprehensive transcriptome profile reveals a central role for mitochondria

The ductus arteriosus (DA) connects the fetal pulmonary artery and aorta, diverting placentally oxygenated blood from the developing lungs to the systemic circulation. The DA constricts in response to increases in oxygen (O2) with the first breaths, resulting in functional DA closure, with anatomic closure occurring within the first days of life. Failure of DA closure results in persistent patent ductus arteriosus (PDA), a common complication of extreme preterm birth. The DA's response to O2, though modulated by the endothelium, is intrinsic to the DA smooth muscle cells (DASMC). DA constriction is mediated by mitochondrial-derived reactive oxygen species, which increase in proportion to arterial partial pressure of oxygen (PaO2). The resulting redox changes inhibit voltage-gated potassium channels (Kv) leading to cell depolarization, calcium influx and DASMC constriction. To date, there has not been an unbiased assessment of the human DA O2-sensors using transcriptomics, nor are there known molecular mechanisms which characterize DA closure. DASMCs were isolated from DAs obtained from 10 term infants at the time of congenital heart surgery. Cells were purified by flow cytometry, negatively sorting using CD90 and CD31 to eliminate fibroblasts or endothelial cells, respectively. The purity of the DASMC population was confirmed by positive staining for α-smooth muscle actin, smoothelin B and caldesmon. Cells were grown for 96 h in hypoxia (2.5% O2) or normoxia (19% O2) and confocal imaging with Cal-520 was used to determine oxygen responsiveness. An oxygen-induced increase in intracellular calcium of 18.1% ± 4.4% and SMC constriction (−27% ± 1.5% shortening) occurred in all cell lines within five minutes. RNA sequencing of the cells grown in hypoxia and normoxia revealed significant regulation of 1344 genes (corrected p < 0.05). We examined these genes using Gene Ontology (GO). This unbiased assessment of altered gene expression indicated significant enrichment of the following GOterms: mitochondria, cellular respiration and transcription. The top regulated biologic process was generation of precursor metabolites and energy. The top regulated cellular component was mitochondrial matrix. The top regulated molecular function was transcription coactivator activity. Multiple members of the NADH-ubiquinone oxidoreductase (NDUF) family are upregulated in human DASMC (hDASMC) following normoxia. Several of our differentially regulated transcripts are encoded by genes that have been associated with genetic syndromes that have an increased incidence of PDA (Crebb binding protein and Histone Acetyltransferase P300). This first examination of the effects of O2 on human DA transcriptomics supports a putative role for mitochondria as oxygen sensors.

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth

To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. EPT infants (240/7-276/7weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36weeks of PMA and follow-up outcomes at 18-22months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26weeks, and the mean birth weight was 839g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32weeks PMA, and 32-36weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22months corrected age (P = .002). EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.

Lactobacillus species signature in association with term and preterm births from low-income group of Pakistan

Aim/Purpose of study It is estimated that around 15 million babies are born prematurely every year and approximately one million children die each year due to complications of preterm birth (PTB). Many survivors face a lifetime of disability, including learning disabilities and visual and hearing problems. The current study aimed to characterize Lactobacillus species isolated from vaginal swabs and determine their antibiotic susceptibility. Material and methods 40 term and 20 preterm samples were processed by culturing on MRS agar and initial identification was carried out using sugar fermentation reactions and 16S rRNA PCR. Moreover, Lactobacillus species from preterm and term cases using paired samples, i.e. vaginal swabs and placenta tissues from 8 preterm delivering mothers were further recruited for metagenomics study to possibly detect uncultured Lactobacillus species known to cause PTB. Results 40% samples from preterm delivering mothers lack any Lactobacillus species whereas in contrast vaginal microflora of all term delivering mothers carry one or more species of Lactobacillus. L. crispatus (46% in term group and 25% preterm group) was found to be the most abundant group followed by L. jensenii (25% in both groups) and L. gasseri (19% in term group and 10% in preterm group). The antimicrobial susceptibility profile suggests that preterm isolates were least resistant to linezolid (20% resistance rate) and trimethoprim/sulfamethoxazole (22% resistant rate) compared to term isolates (>60% for each drug group). Furthermore, the metagenomics data for paired samples (8 VS and 8 PT) from extreme PTB suggested that Lactobacillus Iners was the main difference between term and preterm deliveries. Moreover, overall lack of lactobacillus species or presence of rogue Lactobacillus species such as L. iners and L. vaginilis is associated with PTB. ERIC-PCR analysis using Lactobacillus crispatus revealed that all the pre-term samples are closely related and fall in same cluster while all the term samples fall in different cluster. Conclusion The study not only provides a baseline data of distinct signatures of associated lactobacillus species with the PTB which may be further transmitted to new born infants but also developing further therapeutic interventions to better manage the PTB.

Genetic testing in individuals with cerebral palsy.

AIM To determine which patients with cerebral palsy (CP) should undergo genetic testing, we compared the rate of likely causative genetic variants from whole-exome sequencing in individuals with and without environmental risk factors. METHOD Patients were part of a convenience and physician-referred cohort recruited from a single medical center, and research whole-exome sequencing was completed. Participants were evaluated for the following risk factors: extreme preterm birth, brain bleed or stroke, birth asphyxia, brain malformations, and intrauterine infection. RESULTS A total of 151 unrelated individuals with CP (81 females, 70 males; mean age 25y 7mo [SD 17y 5mo], range 3wks-72y) participated. Causative genetic variants were identified in 14 participants (9.3%). There was no significant difference in diagnostic rate between individuals with risk factors (10 out of 123; 8.1%) and those without (4 out of 28; 14.3%) (Fisher's exact p=0.3). INTERPRETATION While the rate of genetic diagnoses among individuals without risk factors was higher than those with risk factors, the difference was not statistically significant at this sample size. The identification of genetic diagnoses in over 8% of cases with risk factors suggests that these might confer susceptibility to environmental factors, and that further research should include individuals with risk factors. What this paper adds There is no significant difference in diagnostic rate between individuals with and without risk factors. Genetic variants may confer susceptibility to environmental risk factors. Six causative variants were identified in genes not previously associated with cerebral palsy. Global developmental delay/intellectual disability is positively associated with a genetic etiology. Extreme preterm birth, stroke/brain hemorrhage, and older age are negatively associated with a genetic etiology.

A new individualized prognostic approach to the management of women at risk of extreme preterm birth in France: Effect on neonatal outcome

IntroductionAfter discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. MethodsA before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks+6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. ResultsThe study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22–23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. ConclusionImplementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage.

Preterm Delivery; Who Is at Risk?

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Adverse effects of preterm birth have a direct correlation with the degree of prematurity, in which infants who are born extremely preterm (24–28 weeks gestation) have the worst outcomes. We sought to determine prominent risk factors for extreme PTB and whether these factors varied between various sub-populations with known risk factors such as previous PTB and multiple gestations. A population-based retrospective cohort study was conducted. Risk factors were examined in cases of extreme PTB in the general population, as well as various sub-groups: singleton and multiple gestations, women with a previous PTB, and women with indicated or induced PTB. A total of 334,415 deliveries were included, of which 1155 (0.35%) were in the extreme PTB group. Placenta previa (OR = 5.8, 95%CI 4.14–8.34, p < 0.001), multiple gestations (OR = 7.7, 95% CI 6.58–9.04, p < 0.001), and placental abruption (OR = 20.6, 95%CI 17.00–24.96, p < 0.001) were the strongest risk factors for extreme PTB. In sub-populations (multiple gestations, women with previous PTB and indicated PTBs), risk factors included placental abruption and previa, lack of prenatal care, and recurrent pregnancy loss. Singleton extreme PTB risk factors included nulliparity, lack of prenatal care, and placental abruption. Placental abruption was the strongest risk factor for extreme preterm birth in all groups, and risk factors did not differ significantly between sub-populations.

The Antenatal and Postnatal Consequences of Antenatal Exposure to Prolonged Low Dose Indomethacin.

Despite its many clinical applications, indomethacin is seldom used in pregnancy, principally because of concerns regarding the potential for constriction of the arterial duct. The aim of this study was to document adverse antenatal effects and postnatal outcomes after in utero exposure to low-dose indomethacin. We studied a retrospective cohort of pregnancies between 2005 and 2016 at the John Radcliffe Hospital, Oxford, UK, in which mothers at extremely high risk of preterm birth were treated as prophylaxis with indomethacin 25 mg, 12 hourly, before 29 weeks. Antenatal effects on the arterial duct and postnatal outcomes were analysed. Overall, 198 fetuses had in utero follow-up, and 13 (6.6%) had ductal constriction, all within 9 days of starting treatment. No ductal constriction was seen in pregnancies when therapy was started before 20 weeks, and all effects were reversed after cessation of therapy. An analysis of postnatal complications was possible in 181 neonates. There were eight (4.4%) neonatal deaths, all but one associated with extreme preterm birth. Seven (5%) patent ductus arteriosus cases occurred in the 140 neonates delivered after 28 weeks who were alive at discharge. Postnatal complications were not more common in neonates in whom antenatal ductal constriction had been demonstrated. In conclusion, fetuses exposed to prolonged low dose indomethacin have a low incidence of in utero complications; these complications can be diagnosed with ultrasound and are reversible. Adverse postnatal events are related to gestation at birth and do not appear more common.

Sildenafil administration improves right ventricular function on 4D flow MRI in young adults born premature.

Extreme preterm birth conveys an elevated risk of heart failure by young adulthood. Smaller biventricular chamber size, diastolic dysfunction, and pulmonary hypertension may contribute to reduced ventricular-vascular coupling. However, how hemodynamic manipulations may affect right ventricular (RV) function and coupling remains unknown. As a pilot study, 4D flow MRI was used to assess the effect of afterload reduction and heart rate reduction on cardiac hemodynamics and function. Young adults born premature were administered sildenafil (a pulmonary vasodilator) and metoprolol (a β blocker) on separate days, and MRI with 4D flow completed before and after each drug administration. Endpoints include cardiac index (CI), direct flow fractions, and ventricular kinetic energy including E/A wave kinetic energy ratio. Sildenafil resulted in a median CI increase of 0.24 L/min/m2 (P = 0.02), mediated through both an increase in heart rate (HR) and stroke volume. Although RV ejection fraction improved only modestly, there was a significant increase (4% of end diastolic volume) in RV direct flow fraction (P = 0.04), consistent with hemodynamic improvement. Metoprolol administration resulted in a 5-beats/min median decrease in HR (P = 0.01), a 0.37 L/min/m2 median decrease in CI (P = 0.04), and a reduction in time-averaged kinetic energy (KE) in both ventricles (P < 0.01), despite increased RV diastolic E/A KE ratio (P = 0.04). Despite reduced right atrial workload, metoprolol significantly depressed overall cardiac systolic function. Sildenafil, however, increased CI and improved RV function, as quantified by the direct flow fraction. The preterm heart appears dependent on HR but sensitive to RV afterload manipulations.NEW & NOTEWORTHY We assessed the effect of right ventricular afterload reduction with sildenafil and heart rate reduction with metoprolol on cardiac hemodynamics and function in young adults born premature using 4D flow MRI. Metoprolol depressed cardiac function, whereas sildenafil improved cardiac function including right ventricular direct flow fraction by 4D flow, consistent with hemodynamic improvement. This suggests that the preterm heart is dependent on heart rate and sensitive to right ventricular afterload changes.

Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.

Benefits and obstacles to cell therapy in neonates: The INCuBAToR (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research).

Cell‐based therapies hold promise to substantially curb complications from extreme preterm birth, the main cause of death in children below the age of 5 years. Exciting preclinical studies in experimental neonatal lung injury have provided the impetus for the initiation of early phase clinical trials in extreme preterm infants at risk of developing bronchopulmonary dysplasia. Clinical translation of promising therapies, however, is slow and often fails. In the adult population, results of clinical trials so far have not matched the enticing preclinical data. The neonatal field has experienced many hard‐earned lessons with the implementation of oxygen therapy or postnatal steroids. Here we briefly summarize the preclinical data that have permitted the initiation of early phase clinical trials of cell‐based therapies in extreme preterm infants and describe the INCuBAToR concept (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research), an evidence‐based approach to mitigate the risk of translating advanced therapies into this vulnerable patient population. The INCuBAToR addresses several of the shortcomings at the preclinical and the clinical stage that usually contribute to the failure of clinical translation through (a) systematic reviews of preclinical and clinical studies, (b) integrated knowledge transfer through engaging important stakeholders early on, (c) early economic evaluation to determine if a novel therapy is viable, and (d) retrospective and prospective studies to define and test ideal eligibility criteria to optimize clinical trial design. The INCuBAToR concept can be applied to any novel therapy in order to enhance the likelihood of success of clinical translation in a timely, transparent, rigorous, and evidence‐based fashion.

Reproductive and obstetric outcomes in women of racial minorities aged 40 years and older undergoing IVF

Research questionDo women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF? DesignA retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (<37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P < 0.05 was considered to be statistically significant. ResultsA total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24–28 weeks (5.5 versus 1.0%, P = 0.021). ConclusionMinority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Maternal and infant morbidity following birth before 27 weeks of gestation: a single centre study

Delivery at extreme preterm gestational ages (GA) <;27 weeks is challenging with limited evidence often focused only on neonatal outcomes. We reviewed management and short term maternal, fetal and neonatal outcomes of births for 132 women (22 + 0 to 26 + 6 weeks’ GA) with a live fetus at admission to hospital and in labour or at planned emergency Caesarean section: 103 singleton and 29 (53 live fetuses) twin gestations. Thirty women (23%) had pre-existing medical problems, 110 (83%) had antenatal complications; only 17 (13%) women experienced neither. Major maternal labour and delivery complications affected 35 women (27%). 151 fetuses (97%) were exposed to antenatal steroids, 24 (15%) to tocolysis and 70 (45%) to magnesium sulphate. Delivery complications affected 11 fetuses, with 12 labour or delivery room deaths; survival to discharge was 75% (117/156), increasing with GA: 25% (1/4), 75% (18/24), 69% (29/42), 73% (33/45) and 88% (36/41) at 22, 23, 24, 25 and 26 weeks GA respectively (p = 0.024). No statistically important impact was seen from twin status, maternal illness or obstetric management. Even in a specialist perinatal unit antenatal and postnatal maternal complications are common in extreme preterm births, emphasising the need to include maternal as well as neonatal outcomes.

Delivery room cuddles for extremely preterm babies and parents: concept, practice, safety, parental feedback.

AimFollowing extreme preterm birth, there has traditionally been felt an imperative to rush baby to the neonatal unit for ongoing intensive care. Immediate needs of parents to bond with their babies through direct early physical contact have often been overlooked; many weeks can pass before parents get to hold their babies for the first time. Recognition of the importance of early contact is growing. We aimed to review the safety and value of routinely practising delivery room cuddles for extremely preterm babies.MethodsWe reviewed delivery room cuddles in babies born <27 weeks’ gestation in our centre between 2006 and 2017 via case‐control. We also conducted a questionnaire survey of mothers who experienced a delivery room cuddle to gain their feedback and perspectives.ResultsWe found no difference in age or temperatures on neonatal unit admission. There was no case of inadvertent extubation associated with cuddles. Parental feedback was very positive.ConclusionWith appropriate safeguards, delivery room cuddles are feasible and achievable for extremely preterm babies irrespective of birth gestation. Facilitation of the cuddle is an early and very important family‐centred care practice which seems much appreciated by parents and which may improve bonding, lactation, and maternal mental health.

Research on the Incidence Rate of Extremely Preterm Birth in China and Relationship between Extremely Preterm Birth and Chorioamnionitis

To investigate the relationship between the extremely preterm birth and chorioamnionitis based on Chinese population. Retrospective analysis was performed to evaluate 164 cases hospitalized in Fujian Provincial Maternity and Children’s Hospital during 1st January 2017 and 31th June 2018. The clinical symptoms of the participators were recorded and the laboratory tests were performed. The incidence of the extremely preterm birth was 0.7 % accounting for 7.2 % in the total premature birth. The positive rate of the extremely preterm birth related with chorioamnionitis was 72 % and the positive rates in clinic and histological chorioamnionitis were 5.5 % and 66.5 %, which were significantly higher than those in early preterm birth, moderate preterm birth and late preterm birth. Histologic chorioamnionitis cases have no clinical symptoms. The positive rates of increased white blood cells count, neutrophils count and increased level of C-reactive protein in histological chorioamnionitis are 37.6 %, 39.4 %, 64.2 % and 0 % respectively, which are significantly lower than those in clinic chorioamnionitis (88.9 %, 100 %, 100 %, 11.1 %, respectively, p<0.05). The top three pathogens are ureaplasma urealytium, escherichia coli and group B streptococcus. 90.9 % of the extremely preterm born have severe neonatal complications; 63.6 % have septicemia and shared chorioamnionitis with the mother. Chorioamnionitis is an important risk factor of extremely preterm birth. The positive rate of the extremely preterm birth with chorioamnionitis is significantly higher than that early, modulate and late preterm birth. Histologic chorioamnionitis is the main type of chorioamnionitis, which may induce poor prognosis of the extremely preterm birth newborns.

Respiratory morbidity, healthcare resource use, and cost burden associated with extremely preterm birth in The Netherlands

Background Extremely preterm (EP) infants have high rates of respiratory morbidity and correspondingly high healthcare resource utilization. Objectives Data from the PHARMO Perinatal Research Network were analyzed to quantify the burden of EP birth in the Netherlands. Methods A retrospective analysis included infants <28 weeks gestational age with a birth record in the Perinatal Registry (1999–2015) and data in the PHARMO Database Network. Outcomes of interest included select comorbidities, hospital readmissions, and costs of hospitalization and medication up to 1- and 2-years corrected age. Outcomes were stratified by birth period (1999–2005, 2000–2009, 2010–2015) and by diagnosis of bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD). Results The cohort included 168 EP infants (37 born 1999–2005, 51 born 2006–2009, 80 born 2010–2015). Median (Q1–Q3) birth weights decreased by birth period from 970 (840–1,035) g in 1999–2005 to 853 (695–983) g in 2010–2015. Overall, BPD and CLD were reported during the birth hospitalization in 40% and 29% of infants, respectively; rates of BPD increased and rates of CLD decreased by birth period. Eighty-four percent of EP infants had an additional comorbidity. Mean (standard deviation) costs of birth hospitalization were €110,600 (€73,000) for 1999–2005, €119,350 (€60,650) for 2006–2009, and €138,800 (€130,100) for 2010–2015. Birth hospitalization and total costs for up to 1- and 2-years corrected age were higher for infants with BPD and/or CLD than for those without either complication. Conclusion Healthcare resource utilization and costs for EP infants, especially for those with respiratory morbidities, increased between 1999 and 2015. Future cost-effectiveness analyses are essential to determine the economic impact of this change and underscore the need for new therapeutic interventions to decrease clinical sequelae in this vulnerable population.

Study of mortality trends &amp; pattern in a tertiary care hospital in Kerala, South India

Mortality statistics are essential for the meaningful planning and allocation of resources for healthcare. It has been observed that in India, up-to-date, precise and reliable data regarding mortality patterns especially in the rural areas is inadequate or not properly documented. Data regarding mortality is often not analyzed and converted into a suitable information to be useful in knowing the common causes for death in specific and general populations. The mortality pattern at a Tertiary Care Hospital in Kerala from 2014–2018 and the sociodemographic characters associated with it were studied. The details from the case sheets were obtained and analyzed using descriptive methods. The total number of deaths recorded were 934, out of which, the maximum number of deaths has occurred in the elderly population (Above 60 Years). 11 cases are of infant deaths. The major cause for infant mortality was found to be preterm and extreme preterm birth. 576 deaths (61.6%) were males. Most number of deaths were due to Cardiovascular Causes (39.6%) followed by Malignancy (12.7%) and respiratory diseases (12.4%). Out of the 934 cases of deaths, 310 patients belonged to rural areas (33.1%). During the study it was noticed that the cause of death has been entered incompletely in many cases. Training of doctors & MRD faculty with respect to cause of death writing and ICD classification according to system wise has to be done periodically for better documentation which will help in future for data collection and easy analysis of the trends in disease and mortality.

The Outcomes Using a Questionnaire of School Age Children for Extremely Preterm Birth

The Outcomes Using a Questionnaire of School Age Children for Extremely Preterm Birth

A Mini-Review of the BAPM Framework for Practice – Perinatal Management of Extreme Preterm Birth before 27 Weeks of Gestation

The recent publication of a new framework for practice from the British Association of Perinatal Medicine has altered the management of babies born in the UK at the threshold of viability. A risk stratification is used to determine which infants will receive active management, and which receive palliative management. This is achieved through a combination of assessment of risk factors and discussion with parents. The most notable feature of the new framework is the recommendation to consider babies of 22 weeks gestation for active care. This has been the subject of much discussion amongst neonatal and obstetric teams. The framework also emphasises the importance of early transfer to a maternity unit with a co-located neonatal intensive care unit if active management is pursued. This new guidance has led to a change in the way the management of extreme prematurity is approached, and will continue to impact on neonatal, obstetric, and anaesthetic care.

Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum.

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

Aortic coarctation in pregnancy: outcomes and predictors for cardiovascular and hypertensive complications. Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC)

Abstract Background Pregnancy in women with repaired aortic coarctation (CoA) has a moderately increased risk (mWHO II-III) of an adverse cardiovascular, obstetric or fetal event, but prospective data to validate this estimated risk is scarce. Purpose We examined maternal and fetal outcomes in pregnant women with unrepaired and repaired CoA to identify predictors of adverse outcomes. Methods Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=5739). The frequency and predictors of major adverse cardiac events (MACE, defined as maternal cardiac death, heart failure, atrial fibrillation/flutter, ventricular tachyarrhythmia, endocarditis, thromboembolic events, aortic dissection and acute coronary syndrome), and hypertensive complications (defined as pregnancy-induced hypertension, (pre)eclampsia or HELLP syndrome) were analyzed. Results Of 303 pregnancies in women with CoA (median age 30 years, median pregnancy duration 39 weeks), 10% were in women with unrepaired CoA and 27% in women with pre-existing hypertension. There were no maternal deaths. There were 4 neonatal deaths of which 3 occurred after a spontaneous extreme preterm birth. MACE occurred in 4.3% of pregnancies, predominantly involving heart failure (3.3%). MACE rate was similar in unrepaired vs repaired CoA (3.4% vs 4.4%, p=0.814). Predictors of MACE included pre-pregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8–147.7), LVEF &amp;lt;40% (OR 10.4, 95% CI 1.8–59.5), NYHA class &amp;gt;1 (OR 11.4, 95% CI 3.6–36.3), cardiac medication use (OR 4.9, 95% CI 1.3–18.3) and living in an emerging country (OR 4.88, 95% CI 1.58–15.07). Hypertensive complications occurred in 6.3%, more often in the subgroup with pre-existing hypertension (11% vs 5%, p=0.040). Pre-existing hypertension was the only predictor (OR 2.6, 95% CI 1.01–6.6). Caesarean section was performed in 50% of the total cohort. Conclusions Pregnancies in women with CoA are safe, well tolerated and MACE and hypertensive complication rates are low. These findings support mWHO risk score reevaluation to mWHO II for women with CoA without cardiac impairment. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): ESC EURObservational Research Programme (EORP)