Extreme Prematurity Research Articles

Association Between Laboratory Coagulation Parameters and Postpartum Hemorrhage in Preterm and Term Caesarean Section: A Retrospective Analysis

Background: Deranged antepartum laboratory parameters may be risk factors for postpartum hemorrhage (PPH). However, whether this is also valid in women who give birth prematurely is currently unknown. Methods: We performed a retrospective single-center study to assess the role of antepartum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time, and prothrombin time as risk factors for PPH following caesarean section. We defined PPH as documented blood loss of at least 1 L and/or transfusion of red blood cell concentrates. We stratified the included patients according to gestational age: extremely preterm (gestational age < 28 weeks), very preterm (gestational age between 28 and 32 weeks), late and moderate preterm (gestational age between 32 and 37 weeks), and term (gestational age ≥ 37 weeks). Results: We included 1734 patients, 112 (6%) of whom had PPH. In total, 19 patients (10%) were in the extremely preterm group, 13 patients (10%) were in the very preterm group, 44 patients (9%) were in the late and moderate preterm group, and 36 patients (4%) were in the term group. Hemoglobin predicted PPH in all gestational age groups. Platelet count was associated with PPH in term, but not in preterm patients. Fibrinogen was associated with PPH in late prematurity but not in term patients and not in patients with early or extreme prematurity. Conclusions: Antepartum hemoglobin was the only factor predicting PPH in preterm and term caesarean sections. Platelet count and fibrinogen concentration were associated with PPH in term and late prematurity, respectively, but not in earlier stages of prematurity.

Antenatal counselling at the cusp of viability and parental decision-making in the zone of parental discretion: A cohort study.

Safer Care Victoria updated a clinical guideline on extreme prematurity in 2020, reducing the threshold for offering resuscitation from 23 to 22 weeks gestation. The zone of parental discretion is the interval of shared decision-making between parents and doctors regarding resuscitation decisions. It is especially relevant at this periviable gestation. Our study aimed to establish current practices in antenatal counselling and steroid administration at this cusp of viability, and examine the decisions made during the zone of parental discretion. Single centre retrospective cohort study. Sixteen thousand three hundred fifty-four admissions and emergency department presentations between January 2021 and July 2023 were retrieved from Birthing Outcomes System (BOS) and patient details were imported and manually reviewed on Microsoft Excel, with particular note to the gestation at admission/emergency department presentation and duration of admission. Eighty-seven patients were identified as present in the hospital between 21 + 0 and 22 + 6 weeks gestation. These 87 scanned records on Clinical Patient Folder (CPF) were then manually reviewed to identify if antenatal counselling occurred during this window. Thirty-six patients were included who received antenatal counselling between 21 + 0 and 22 + 6 weeks gestation (the remaining patients did not receive antenatal counselling during this window), and relevant data was subsequently extracted from the scanned medical record and analysed using SPSS software (IBM SPSS Statistics 29). Thirty-six women received antenatal counselling between 21 + 0 and 22 + 6 weeks. 58% decided on full resuscitation and 39% opted for comfort care if their infant was to be born between 22 + 0 and 22 + 6 weeks. All but one baby born premature were exposed to steroids, with 83.3% receiving a full course. Twenty-eight infants (62.2%) were fully steroid loaded at the time of delivery. In those fully steroid loaded, 31.1% of the time steroids were initiated prior to transfer, 50% of the time deferred until neonatal review and a decision regarding the resuscitation status of the baby, and on one occasion requested by the neonatologist before counselling. Patients at risk for premature birth who attended our hospital at the cusp of viability were generally counselled about the opportunity for resuscitation between 22 + 0 and 22 + 6 weeks gestational age, and offered steroids. Further studies are required to establish whether the content of antenatal counselling, and the timing of steroids, are consistent in this population.

Neonatal care and developmental outcomes following preterm birth: A systematic review and meta-analysis.

Major amendments in neonatal care have been introduced in recent decades. It is important to understand whether these amendments improved the cognitive sequelae of preterm children. Through a large-scale meta-analysis, we explored the association between prematurity-related complications, neonatal care quality, and cognitive development from birth until 7 years. MEDLINE, APA PsycInfo, and EBSCO were searched. Peer-reviewed studies published between 1970 and 2022 using standardized tests were included. We evaluated differences between preterm and full-term children in focal developmental domains using random-effects meta-analyses. We analyzed data from 161 studies involving 39,799 children. Preterm birth was associated with inferior outcomes in global cognitive development (standardized mean difference = -0.57, 95% CI [-0.63, -0.52]), as well as in language/communication, visuospatial, and motor performance, reflecting mean decreases of approximately 7.3 to 9.3 developmental/intelligence quotients. Extreme prematurity, neonatal pulmonary morbidities, and older assessment age in very-to-extreme preterm cohorts were associated with worse outcomes. Contemporary neonatal medical and developmental care were associated with transient improvements in global cognitive development, evident until 2 to 3 years of age but not after. Blinding of examiners to participants' gestational background was associated with poorer outcomes in preterm cohorts, suggesting the possibility of a "compassion bias." The results suggest that preterm birth remains associated with poorer cognitive development in early childhood, especially following pulmonary diseases and very-to-extreme preterm delivery. Importantly, deficits become more pervasive with age, but only after births before 32 gestational weeks and not in moderate-to-late preterm cohorts. Care advancements show promising signs of promoting resiliency in the early years but need further refinements throughout childhood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Influence of severe pre-eclampsia in combination with premature rupture of members on the course of the early neonatal period

Aim. To assess the effect of preeclampsia in combination with premature rupture of membranes (PROM) on the condition of newborns in the early neonatal period.Materials and Methods. The study included 984 mothers and their newborns, divided into four groups. The main group comprised 94 women whose pregnancies were complicated by severe preeclampsia and PROM. The comparison group consisted of 840 patients, further divided into two subgroups: subgroup A included 70 patients with severe preeclampsia, and subgroup B included 770 patients with PROM. The control group comprised 50 healthy pregnant women.Results and Discussion. In the main group, 31 (33%) newborns were premature; in subgroup A, 21 (30%); and in subgroup B, 69 (9%). Newborns with extreme prematurity were born in the main group 3.1 and 5.4 times more often than in subgroups A and B, respectively (p = 0.013). It was found that the main group had a higher incidence of respiratory distress syndrome, apnea, and neonatal encephalopathy. Hypoglycemia was diagnosed in the main group 5.6 times more frequently than in cases of isolated PROM (p < 0.001) and 1.3 times more frequently than with preeclampsia alone (p > 0.05). In the Republic of Tajikistan, neonatal mortality reaches 56.3%.Conclusion. Reducing early neonatal morbidity and mortality in women with preeclampsia and PROM is possible through referral and delivery in tertiary care facilities.

A rare cause of respiratory distress in preterm infants: a case report of acquired subglottic cysts

BackgroundThe Subglottic Cysts (SGCs) are a rare cause of respiratory distress in infants. Typical risk factors include male gender, extreme prematurity, gastro-oesophageal reflux and invasive ventilation, the latter being associated with mucosal damage and blockage of the subglottic cysts’ ducts. We describe a case of acquired subglottic cysts in a premature infants presented with respiratory distress.Case presentationA premature male infant was born at 25 weeks + 2 days with a history of monochorionic diamniotic twin pregnancy with twin-to-twin transfusion syndrome. During hospitalization, invasive mechanical ventilation was necessary for a total of 18 days; the patient was discharged at postmenstrual age of 40 weeks + 1 day in good condition. At 43 weeks post-menstrual age, he presented to our department with mixed stridor and worsening of respiratory dynamics. A laryngotracheoscopy evaluation was performed. The exam showed the presence of multiple SGCs causing an almost complete obstruction of the airway. Because of the significant reduction of the airway’s patency, the child underwent a tracheotomy and thereafter cysts’ removal using cold steel microinstruments. A better airway patency was restored although a slight glottic edema persisted. The histopathology confirmed the benign nature of the lesions. Successive controls showed a completely patent airway and absence of SGCs.ConclusionIn conclusion, SGCs should be considered in preterm infants with respiratory distress previously intubated, which cannot be explained by the most common causes. Early diagnosis and treatment are fundamental to reducing the morbidity and mortality associated with this disease.

7828 First Trimester Serum 11-Deoxycorticosterone Predicts Extreme Premature Childbirth

Abstract Disclosure: E.K. Ronde Salminen: None. S. Schoenmakers: None. B.D. van Zelst: None. S.A. van den Berg: None. First Trimester Serum 11-Deoxycorticosterone Predicts Extreme Premature Childbirth Background: Preterm birth is the leading cause of perinatal mortality and morbidity worldwide. Unfortunately, the prediction of preterm birth remains challenging, causing unnecessary hospital admittance and overexposure to medication. Studies have shown that metabolites of progesterone can influence uterine contractility[1] and serum levels of 11-deoxycorticosterone have been shown to correlate with an increased risk of preterm birth before 32 weeks of gestation2. The aim of this prospective study was to determine whether first trimester measurement of the progesterone metabolites 11-deoxycorticosterone (11-DOC) and 16-alpha hydroxyprogesterone (16-OHP) could be used as a predictive marker for preterm birth. Methods and results: A cohort of 386 pregnant women were included at 12 weeks of gestation between 2014-2016. Their obstetric histories and comorbidities were noted and their plasma was frozen. Of these women, n=26 delivered prior to 32 weeks of gestation and n=286 delivered at term. 11-DOC and 16-OHP were determined using LC-MS/MS. Mann-Whitney U test was used to statistically analyze differences between the groups. There was a highly significant difference in the level of 11-DOC between women delivering prior to 32 weeks of gestation in comparison to women delivering after 37 weeks of gestation (p=0.007). 16-OHP levels tended to be different between the two groups, but this did not reach statistical significance (p=0.062). No difference was found in the ratio 16-alpha hydroxyprogesterone/11-deoxycorticosterone between the two groups (p=0.916). Conclusion: Plasma levels of progesterone metabolites collected late in the first trimester of pregnancy predicts preterm birth prior to 32 weeks of pregnancy.

Newborn screening for SCID: the very first prospective pilot study from Türkiye.

The measurement of T-cell receptor excision circle (TREC) is used for newborn screening (NBS) in dried blood spot (DBS) samples from Guthrie card for severe combined immunodeficiency (SCID). Here, we report the results of first newborn screening pilot program for SCID conducted in Türkiye. The study was carried out together with Ankara University School of Medicine and The Ministry of Health, Public Health General Directorate, Pediatric and Adolescent Health Department. TREC measurements were performed in randomly selected Guthrie card samples obtained from 20253 babies born between October 2018 and October 2020. The TREC analyses were performed together with beta Actin (β-Actin) via RT-PCR (Real Time Polymerase Chain Reaction). TRECs found to be normal (≥15 copies/µl) in 98,6% of the newborns (n: 19975) but low (<15 copies/µl) in 1.4% (n:278) at the initial analyses. TRECs were retested in 278 suspected infants and found to be normal in 160 (0.8%) while low in 118 (0.58%). New DBS were obtained from the babies with low TRECs (new sample test). TRECs were normal in 108 (0.53%) of the new sample tests and low in 10 (0.049%). Two among 10 babies who had abnormal (undetectable) TRECs were diagnosed as SCID; ADA (P1) and RAG1 (P2) defects were confirmed respectively. They both received curative treatments [gene therapy (P1) and HSCT (P2)]. The remaining 6 of 8 newborns with abnormal TRECs were found normal after clinical and laboratory immune work-up, while medical records of other two revealed early postnatal death due to extreme prematurity. In the light of this study the incidence of SCID was detected at least 1/10000 live births in Türkiye. This study shows the feasibility and usefulness of initiating SCID screening in Türkiye.

In-utero transfer, survival-focused care and survival to 28-days at 22-24 weeks’ gestation pre- and post- implementation of an extreme prematurity management guideline in Victoria, Australia

BackgroundCare for infants born at 22–24 weeks’ gestation varies globally, with an increasing willingness to provide survival-focused (‘active’) care for infants born at 22 weeks’ gestation in recent years. This...

Tidal Breathing Analysis as a Prognostic Index for Airway Obstruction Trajectory and Asthma in Preterm Infants.

An easy-to-implement and accurate lung function assessment tool for preterm infants is crucial to manage lifelong respiratory morbidities. We aimed to determine which pulmonary function parameters in preterm infants can predict the trajectory of airway obstruction and asthma development after 4years of age. We evaluated 52 preterm infants who had undergone both tidal breathing flow-volume loop (TBFVL) and multiple-breath washout (MBW) analyses in infancy and spirometry after the age of 4years. We evaluated the association between pulmonary function parameters in infancy and childhood and the pulmonary function trajectory until 13years of age and compared the changes in this trajectory according to pulmonary function parameters in infancy. Time to peak expiratory flow/expiratory time (TPEF/TE) in infancy was associated with FEV1, FEF25-75, and dysanapsis ratio in childhood and differed according to level of airway obstruction assessed by FEV1, FEV1/FVC, and FEF25-75, an asthma development. TPEF/TE was a significant predictive factor for airway obstruction and asthma after 4years of age, after adjusting for sex, extreme prematurity, duration of supplementary oxygen and mechanical ventilation, and recurrent wheezing during infancy. In premature infants with lower TPEF/TE, subsequent pulmonary function parameters remained low until 13years of age. In preterm infants, TPEF/TE could be useful to predict airway obstruction and asthma after 4years of age and even a lower pulmonary function trajectory until 13years of age. This information may help clinicians to provide lifelong care for pulmonary morbidity in children and adolescents born preterm.

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions

Introduction: The innate branch of the immune system is important in early life, in particular for infants born preterm. Methods: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively. Results: The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness. Conclusion: Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.

Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives.

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

The relationship between inflammatory markers and retinopathy of prematurity in extremely premature infants.

This study aimed to evaluate the relationships among blood parameters, clinical factors, and retinopathy of prematurity (ROP) in extremely premature (EP) infants. This retrospective study included 153 EP infants who were categorized into two groups based on the presence of inflammatory diseases such as necrotizing enterocolitis, neonatal sepsis, bronchopulmonary dysplasia, severe intraventricular hemorrhage, preeclampsia, and premature rupture of membranes. Complete blood count parameters, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio, platelet-lymphocyte ratio (PLR), systemic inflammatory index, and platelet mass index were recorded during the first week and first month after birth. The study analyzed the impact of parameters obtained through blood tests during the first week and first month on the development of ROP and the requirement for treatment. In this study, 96 infants were diagnosed with inflammatory diseases. After multivariate regression analyses, the duration of mechanical ventilation (p = 0.010) was found to be the only factor that led to ROP development. Moreover, lower gestational age (GA) (p = 0.006), higher NLR (p = 0.026), and lower PLR (p = 0.019) were observed in infants requiring treatment compared to infants with spontaneous resolution of ROP in this group. 57 infants did not have inflammatory diseases. Although the duration of mechanical ventilation (p = 0.041) and low levels of platelets (PLT) (p = 0.046) measured in the first month postnatally were significantly found to be associated with ROP developement, no parameter affecting the required treatment could be determined. EP infants with longer mechanical ventilation durations and lower PLT counts are vulnerable to ROP development. GA, PLR, and NLR are predictive factors for treatment.

Reducing Capillary Leak Syndrome Mortality in Extremely Premature Infants: A Pilot Investigation.

Neonatal capillary leak syndrome (CLS) is a rare, but life-threatening condition following neonatal sepsis or inflammatory injury. The objective of this study was to describe a standardized treatment approach for CLS that improves mortality and neonatal outcomes. A retrospective cohort study of 10 infants born at 22 to 26 weeks of gestation who developed CLS following a significant inflammatory insult was performed. Time to diagnosis and treatment approaches over 2 epochs were recorded and described. In epoch 2, with increased clinical awareness of CLS and implementation of a standardized treatment approach, there was a non-statistically significant decrease in the time to treatment with a significant decrease in mortality. An early targeted treatment approach for neonatal CLS can decrease mortality rates in this highly morbid condition.

Preterm birth and risk of hospitalisation for complex chronic conditions during childhood and adolescence.

To examine the relationship between preterm birth and hospitalisation for paediatric complex chronic conditions. We conducted a cohort study of 1 269 745 children born between 2006 and 2022 in Quebec, Canada. We classified preterm birth as extreme (<28 weeks), very (28-31 weeks), and moderate (32-36 weeks). The outcome was hospitalisation for complex chronic conditions, including neurologic, neuromuscular, cardiovascular, respiratory, renal, gastrointestinal, haematologic, immunologic, endocrine, and neoplastic disorders up to 16 years of age. We computed adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and complex chronic conditions during 9 948 734 person-years of follow-up. Hospitalisation rates for complex chronic conditions were higher for children born preterm than at term (6.88 vs. 2.24 per 1000 person-years). Preterm birth was associated with all complex chronic conditions, especially respiratory (HR 4.64, 95% CI 4.01-5.37), cardiovascular (HR 3.68, 95% CI 3.47-3.90), and neurologic disorders (HR 3.48, 95% CI 3.21-3.77). Associations were present at all ages and for all degrees of prematurity, but were strongest with extreme prematurity. Preterm birth increases the risk of hospitalisation for complex chronic conditions up to age 16 years. Preterm children may benefit from enhanced care throughout childhood and adolescence.

Obstructive Bilateral Renal Fungal Bezoars in an Extremely Premature Neonate Treated With Antifungals and Urokinase Irrigation: A Case Report and Review of the Literature.

An ex-27-week gestation female infant developed bilateral forearm nodules at 4 weeks of life during treatment for methicillin-sensitive Staphylococcus aureus bacteremia. A pure growth of Candida albicans was isolated on culture of both sterile aspiration of the forearm abscess and urine without evidence of methicillin-sensitive Staphylococcus aureus. The patient went on to develop bilateral obstructive renal fungal bezoars at 11 weeks of life. Bilateral nephrostomies were required to alleviate obstruction with the addition of local irrigation with amphotericin B deoxycholate. Two weeks later, urokinase via the nephrostomy tubes was added due to an unchanged appearance on ultrasound (US) and ongoing candiduria. A significant reduction in the size of bezoars was seen on US after 3 days. Sterilization of urine culture was achieved 7 weeks into treatment, and resolution of bezoars on US was seen 9 weeks after treatment began. No adverse events occurred from the use of local urokinase. Urokinase irrigation via nephrostomy is an effective and safe adjunctive treatment in refractory obstructive renal candidiasis in neonates.

Lamivudine dosing for preterm infants exposed to HIV: a population pharmacokinetic modelling and simulation study.

To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression. Different lamivudine dosing strategies, stratified by gestational age at birth (GA) bands, were simulated in a virtual population of preterm infants, aimed at maintaining lamivudine drug exposures (AUC0-12) within a reference target range of 2.95 to 13.25 µg·h/mL, prior to switching to WHO-weight band doses when ≥4 weeks of age and weighing ≥3 kg. A total of 154 infants (59% female) contributed 858 lamivudine plasma concentrations. Median (range) GA at birth was 38 (27-41) weeks. At the time of first pharmacokinetic sampling infants were older with median postnatal age (PNA) of 6.3 (0.52-26.6) weeks. Lamivudine concentrations were described by a one-compartment model, with CL/F and V/F allometrically scaled to weight. Maturation of CL/F was described using an Emax model based on PNA. CL/F was also adjusted on GA to allow extrapolation for extreme prematurity. Simulations predicted an optimal lamivudine dosing for infants GA ≥24 to <30 weeks of 2 mg/kg twice daily from birth until weighing 3 kg; and for GA ≥30 to <37 weeks, 2 mg/kg twice daily for the first 4 weeks of life, followed by 4 mg/kg twice daily until weighing 3 kg. Model-based predictions support twice daily pragmatic GA band dosing of lamivudine for preterm infants, but clinical validation is warranted.

Thirty-day outcomes of surgery for hydrocephalus: metrics in a large cohort from the National Surgical Quality Improvement Program-Pediatric.

Hydrocephalus is a lifelong condition punctuated in most cases by unpredictable hospital admissions for surgical maintenance. It occupies more of the attention of the pediatric neurosurgeon than any other condition. Benchmarks for the measurement of outcomes are of interest to patients, their families, and the healthcare system. Compared to other metrics, 30-day outcomes require modest resources to collect, are conceptually transparent, and are responsive to process improvement. The National Surgical Quality Improvement Program-Pediatric of the American College of Surgeons was queried for operations for hydrocephalus in the years 2013 through 2020. Demographic data and data regarding comorbidities were collected. Thirty-day rates of return to the operating room, of shunt infection, and of readmission to hospital were analyzed on a univariate basis and in multivariate models. There were 29,098 surgical procedures in the sample, including 10,135 shunt insertions, 16,420 shunt revisions, and 2543 endoscopic third ventriculostomies. The overall 30-day reoperation rate was 10.3%. The most powerful associations were with the nature of the index procedure and with a history of extreme prematurity. The 30-day shunt infection rate was 1.80%. The major associations were with young age, major cardiac risk factors, nutritional support, and ventilator dependence. The 30-day readmission rate was 17.2%. The nature of the index procedure, current malignancy, nutritional support, and recent steroid administration were major associations. Comorbidities negatively associated with these outcomes were highly prevalent. Precise benchmarks for important 30-day outcomes have been calculated from a very large sample of operations for hydrocephalus in childhood.

Use of interleukin-6 receptor antibodies in the second and third trimester of pregnancy: a retrospective cohort study

A paucity of data exists to inform the use of interleukin (IL)-6 receptor antibodies (anti-IL-6) in pregnancy, particularly in the third trimester. This study aimed to describe outcomes of pregnant women and their neonates exposed to these medications given after the first trimester to treat COVID-19. In this retrospective cohort study, we included all women with COVID-19 who were treated with an anti-IL-6 during pregnancy at two tertiary hospitals in London, UK-Guy's and St Thomas' NHS Foundation Trust and Imperial College Healthcare NHS Trust-between March 1, 2020, and Sept 30, 2022. Maternal demographics, clinical data, administered medications, and maternal and neonatal outcomes were assessed for all included women via a review of medical records and through maternal medicine networks. 25 women received an anti-IL-6 for COVID-19 in pregnancy during the study period and were followed up for 12 months. The group described were a population at high risk, with 24 requiring level two or three critical care. 24 women received tocilizumab and one received sarilumab. All women were prescribed at least three concomitant medications. 16 received the anti-IL-6 in the third trimester of pregnancy and nine during the seocnd trimester. There were no women with maternal neutropenia or pancytopenia; increases in liver enzymes in 16 of 20 women with available alanine aminotransferase data were in keeping with the severity of COVID-19 reported and all three women who developed a secondary bacterial infection mounted a C-reactive protein response. There was one maternal death due to COVID-19. All pregnancies resulted in livebirths and there was one twin pregnancy. 16 of 26 babies were born preterm. One baby died at age 6 months due to complications of extreme prematurity. A transient neonatal cytopenia was described in six of 19 babies in whom a full blood count was performed. Although these findings are likely to be in keeping with prematurity alone, we cannot exclude the possibility that transplacental transfer of anti-IL-6 was contributory. We report further data on the use of anti-IL-6 in the second and third trimesters of pregnancy for the management of COVID-19. When extrapolated, our data can inform shared decision making for individuals who would benefit from the use of anti-IL-6 into the third trimester of pregnancy for management of rheumatological disease. None.

A Necrotic Ulcer in an Extremely Premature Infant.

A Necrotic Ulcer in an Extremely Premature Infant.

Hypophosphataemia and late-onset sepsis in extremely preterm neonates: A case-control study.

Late-onset sepsis (LOS) is common in extreme prematurity. These infants are at risk of refeeding syndrome-associated hypophosphataemia. Our objective was to investigate whether hypophosphataemia predisposes to LOS in extremely premature neonates. A retrospective case-control study of neonates born before 29 weeks' gestation in an Australian NICU from 2016 to 2020. Cases developed LOS or localised infection. Two controls, matched within 2 gestational weeks and 90 calendar days, were selected per case. Amongst 48 cases and 93 controls, cases were smaller at birth (767 g vs. 901 g, P = 0.01), but were otherwise comparable. Hypophosphataemia was more common in cases (26% vs. 15%, P = 0.18). Increased intravenous protein intake in the first week was protective against LOS (OR = 0.9, 95% CI 0.76-1.00, P = 0.04); median 2.1 g/kg/day in cases, 2.3 g/kg/day in controls. Hypophosphataemia as part of refeeding syndrome is prevalent and under-recognised in extremely premature neonates. We did not find an association between hypophosphataemia and LOS. Low intravenous protein may be an independent risk factor for infection.