A single course of antenatal steroid (ANS) therapy is standard of care for women at risk of preterm birth, reducing the risk of neonatal respiratory distress syndrome, neonatal morbidity, and mortality. An unresolved challenge relates to the potential risk of adverse long-term effects, and how these risks might be balanced with therapeutic benefit.

We outline key concepts in glucocorticoid signaling, pharmacokinetics/pharmacodynamics, and clinical use before presenting data on the potential long-term harms of ANS therapy.

Our assessment is that: i) Currently used, high dose ANS regimens can induce multi-system changes in the fetus that alter growth and development, potentially increasing long-term disease risk; and ii) relative risks likely increase proportionally to the magnitude and duration of steroid exposure, in late preterm and term ANS use, and in off-target treatments. A single course of ANS therapy to at risk women between 24- and 34-weeks' gestation is well justified. Efforts should be made to improve dosing and patient selection. At periviable gestations, the high immediate risk of serious disease or death justifies modest long-term risks. At late preterm and term gestations, where steroids do not provide notable survival or health benefits, supporting routine ANS use is more difficult.

Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhage (grades 3, 4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Previous randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born at <28 weeks' gestation, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks' gestation.

This study aimed to determine if the risk for severe intraventricular hemorrhage in infants delivered at <28 weeks' gestation increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment before delivery decreases the rate of hemorrhage.

This was an observational study that examined the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk for delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equation techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who were either delivered between 1 to 9 days (n=290) after the first 2-dose betamethasone course or ≥10 days (and eligible for retreatment) after the first course (n=120).

After adjusting for potential confounding variables, infants who were delivered ≥10 days after a single betamethasone course had an increased risk for either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (odds ratio, 2.8; 95% confidence interval, 1.2-6.6) when compared with infants who were delivered between 1 and 9 days after betamethasone. Among the 120 infants who were delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second or retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second or retreatment course of betamethasone was similar to the rate among infants who delivered within 1 to 9 days and significantly lower than among those who delivered ≥10 days without retreatment (odds ratio, 0.10; 95% confidence interval, 0.02-0.65). Following the change in guidelines, the rate of retreatment in infants who were delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%; P<.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (P<.001). In contrast, the rate of severe intraventricular hemorrhage among infants who were delivered 1 to 9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively).

Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course seems to restore its beneficial effects. Encouraging earlier retreatment of women at high risk for delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivered at <28 weeks' gestation.

When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks' gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive care, and infants with congenital anomalies were excluded. Data were analyzed from October 2021 to December 2024.

Time in hours from anenatal betamethasone administration to birth.

The primary outcome was survival to discharge. Secondary outcomes included survival without major morbidity and composites of individual morbidities and death. The association of time from antenatal betamethasone administration to birth with neonatal survival and morbidity was assessed using generalized linear models, adjusting for gestational age, infant sex, maternal race, education, small for gestational age, mode of delivery, multiple birth, prolonged rupture of membranes, and center of birth.

Of 7464 infants born during the study period, 1806 infants (928 [51.3%] boys) were included in the cohort: 475 with no betamethasone and 1331 with exposure to a single dose of betamethasone within 24 hours before birth. The median (IQR) administration-to-birth interval for infants born after a single dose of betamethasone was 3.8 (1.4-9.5) hours. The administration-to-birth interval was independently associated with survival (adjusted relative risk [aRR] per 1-hour increase, 1.01 [95% CI, 1.00-1.01]; aRR per 6-hour increase, 1.04 [95% CI, 1.01-1.07]) and survival without severe neonatal morbidity (aRR per 1-hour increase, 1.01 [95% CI, 1.01-1.02]; aRR per 6-hour increase, 1.09 [95% CI, 1.04-1.14].

In this cohort study, for women at risk of imminent preterm birth, even short duration of exposure to antenatal betamethasone was associated with improved neonatal survival and survival without severe neonatal morbidity.

To evaluate positive health outcomes among children born at < 32 weeks of gestation and to determine whether children with three common neonatal morbidities and 2 neurodevelopmental impairments would have similar positive health outcomes to children and adolescents without these exposures and impairments.

In this secondary analysis of prospectively acquired data derived from 3 multicenter cohorts of children born very preterm (the Extremely Low Gestational Age Newborn cohort [birth years 2001 to 2004], the Neurobehavior And Outcomes in Very Preterm Infants cohort [birth years 2014 to 2016], and the Developmental Impact of Neurobehavior And Outcomes in Very Preterm Infants Exposures cohort [birth years 2010 to 2020]), we examined associations between the 3 common neonatal morbidities (bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage, diagnosed before hospital discharge), 2 neurodevelopmental impairments (developmental delays and cerebral palsy, diagnosed at preschool age follow-up), and perceptions of physical, mental, and social well-being (in either early childhood or adolescence), using the Patient-Reported Outcomes Measurement Information System scales for positive health.

After adjusting for confounders, bronchopulmonary dysplasia, intraventricular hemorrhage, and cerebral palsy were associated with lower positive health scores, reported by parent-proxy during early childhood. None of the exposures or impairments were associated with lower positive health scores at adolescence, reported by the children themselves.

Parents of children born very preterm with bronchopulmonary dysplasia, intraventricular hemorrhage, or cerebral palsy rated their children's positive health lower than did parents of children without these morbidities. However, adolescents' own reports of positive health outcomes were not associated with either neonatal pre-discharge morbidities or preschool neurodevelopmental impairments.

Advancements in perinatal care have improved survival rates of extremely preterm infants born at 22 to 23 weeks of gestation, thus introducing new ethical challenges associated with their treatment. Therefore, we reviewed the epidemiological prognosis, treatment evolution, and ethical considerations associated with the care of preterm infants at the limit of viability. We comprehensively searched PubMed to find relevant English-language articles published between January 2014 and July 2024. Survival rates of infants born at 22 to 23 weeks of gestation have improved but remain low. Proactive treatment can result in survival rates exceeding 50% for infants born at 22 weeks; however, these infants are at high risk for complications and neurodevelopmental impairment. Advancements in obstetric and neonatal care have contributed to improved outcomes. Ethical challenges include balancing survival with the disability risk, managing patients with uncertain prognoses, and considering parental wishes.Conclusion: The care of preterm infants at the limit of viability presents complex ethical dilemmas. Shared decision-making between healthcare providers and families as well as engaging in societal discourse are crucial to addressing these challenges.

To pilot test and assess the feasibility and acceptability of chaplain-led decision coaching alongside the GOALS (Getting Optimal Alignment around Life Support) decision support tool to enhance decision-making in threatened periviable delivery.

Pregnant people admitted for threatened periviable delivery and their 'important other' (IO) were enrolled. Decisional conflict, acceptability, and knowledge were measured before and after the intervention. Chaplains journaled their impressions of training and coaching encounters. Descriptive analysis and conventional content analysis were completed.

Eight pregnant people and two IOs participated. Decisional conflict decreased by a mean of 6.7 (SD = 9.4) and knowledge increased by a mean of 1.4 (SD = 1.8). All rated their experience as "good" or "excellent," and the amount of information was "just right." Participants found it "helpful to have someone to talk to" and noted chaplains helped them reach a decision. Chaplains found the intervention a valuable use of their time and skillset.

This is the first small-scale pilot study to utilize chaplains as decision coaches. Our results suggest that chaplain coaching with a decision support tool is feasible and well-accepted by parents and chaplains.

Our findings recognize chaplains as an underutilized, yet practical resource in value-laden clinical decision-making.

The limit of periviability is constantly changing as infants born at 22-25 weeks of gestation increasingly survive. The data from our region are limited due to the small numbers of these infants among the NICU population. In this study, we evaluated the survival rates and short-term outcomes among preterm neonates between 22 and 24 weeks of gestation admitted to Tawam Hospital, United Arab Emirates. Our retrospective analysis included 100 cohorts of newborns from 22 to 25 weeks of gestation throughout the eight-year period in our level 3 NICU. We evaluated the use and effects of prenatal steroids and intrapartum antibiotics, in addition to perinatal complications, and examined their outcomes (survival, length of stay, and major morbidities). The survival rate of our periviable neonates was 18% (N = 18/100). Only one 22-week infant out of 32 cases (3%) survived during the study period in 2023. In contrast, the survival rate of infants of 23- and 24-week gestational age was 10% (N = 4/40) and 46% (N = 13/28), respectively. Although our focus in this study was to evaluate the survival of neonates who were born at around the limits of viability, we also reported the short-term outcomes at our single center, including intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). Our data demonstrate that the trend of increasing survival with higher gestational age continues to improve over time. However, there was a significant risk of short-term co-morbidities for those who survived. Further studies are required to have robust data on short and long-term outcomes for this population. The information provided by this study could be essential for counseling parents, enabling them to participate actively in formulating their infants' care plans. It may also help parents and healthcare professionals reach a more informed and collaborative decision regarding active resuscitation and subsequent care plans for these periviable neonates.

Preterm birth disrupts the natural progression of events in the parent-infant relationship and bestows many of the typical parent responsibilities to the clinical care team. In turn, the neonatal intensive care environment (NICU) introduces obstacles to parents that would not otherwise be encountered and forces parents to adapt to this artificial environment as they seek to bond with and care for their newborn. Facilitating parent presence at the bedside and incorporating them into the care of their preterm infant is critical for lessening the immediate burden to both the parent and offspring while also ensuring the best possible outcome for preterm infants. In this review, we explore the impact that parents exert on the neurodevelopmental outcome of preterm infants and identify several barriers and facilitators to parent presence.

Care 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 study aims to report changes in care for infants born at 22-24 weeks before and after the introduction of a statewide guideline for extreme prematurity (EP).

A retrospective cohort study was conducted, including all live births at 22-24 weeks in tertiary perinatal centres from 1 January 2015 to 31 December 2022 in Victoria, Australia. Medical records were reviewed to obtain antenatal history and perinatal outcomes. Data on in utero referral and transfer to tertiary perinatal centres were sourced from the statewide perinatal emergency retrieval service (Paediatric Infant Perinatal Emergency Retrieval, PIPER) database. Changes in PIPER referrals and transfers, survival-focused care and survival at 28 days preguideline and postguideline were assessed using logistic regression.

Following the guideline, at 22 weeks' gestation, there was an increase in referrals to PIPER and a 3.31 (95% CI 1.84 to 5.95) higher likelihood of in utero transfer to tertiary centres.Following the guideline, infants had a 6.67 (95% CI 1.40 to 31.72) higher likelihood of receiving survival-focused care at 22 weeks, and a 5.57 (95% CI 1.22 to 25.44) higher likelihood at 23 weeks. All 24-week live births received survival-focused care at birth. The 28-day survival for infants who received survival-focused care was unchanged preguideline and postguideline.

Following the publication of the EP guideline in Victoria, in utero referrals and transfers at 22 weeks' gestation have increased, as has survival-focused management of inborn live births at 22-24 weeks.

The incidence of necrotizing enterocolitis (NEC) is significantly associated with gestational age (GA). This study aimed to investigate risk factors for surgically treated NEC (sNEC) in extremely preterm infants (EPIs) using nationwide cohort registry.

Data were collected from 16,338 very-low-birth-weight infants registered in the Korean neonatal network. Clinical data of 5310 EPIs were retrospectively analyzed. sNEC was defined as infants with diagnosis of NEC requiring surgical treatment, who underwent surgical intervention for NEC or died before surgery. Infants were categorized into three groups based on their NEC status: infants without NEC (control), medically treated NEC (mNEC), and sNEC. These groups were matched based on GA to investigate risk factors for NEC.

In EPIs, small for gestational age (SGA; odds ratio 1.68, 95% confidence interval [CI], 1.17-2.36, p = 0.004), hypotension (1.49, 1.18-1.89, p = 0.001), and IVH (1.63, 1.30-2.05, p < 0.001) were identified as risk factors for sNEC. Complete administration of antenatal steroid reduced the risk of sNEC (0.80, 0.64-0.99, p = 0.044).

Our study demonstrated that EPIs who are SGA, and experience hypotension and IVH may be at an increased risk of developing NEC requiring surgery. These groups require close attention and monitoring for any signs of surgical indications of NEC.

This nationwide cohort study aimed to identify characteristics of infants with necrotizing enterocolitis (NEC) among extremely preterm infants (EPIs) and analyze the risk factors associated with NEC requiring surgical intervention. Small for gestational age (SGA), hypotension, and intraventricular hemorrhage (IVH) were identified as significant risk factors for surgically treated NEC (sNEC) in EPIs. The administration of antenatal steroids decreases the risk of sNEC. Close attention and monitoring for EPIs with early identifiable risk factors such as SGA, hypotension, and IVH should be considered to prevent and detect sNEC early, ultimately leading to improved long-term outcomes.

Many clinicians overestimate mortality and disability rates in infants born extremely preterm. We developed a digital tool ('NIC-PREDICT') that predicts infant mortality and survival with and without major disability in infants born 23-27 weeks' gestation.

To determine if clinicians could use NIC-PREDICT accurately, and if their perceptions of infant outcomes improved after its release in 2021.

Midwives, nurses, obstetricians, neonatologists and paediatricians working in tertiary and non-tertiary hospitals in Victoria were asked to use NIC-PREDICT to estimate three mutually exclusive outcomes: (i) mortality; (ii) survival free of major disability; and (iii) survival with major disability for six different scenarios where a liveborn infant was offered survival-focused care after birth. The proportions who completed the survey (responded to all six scenarios) and the proportions able to provide 100% accurate results for all scenarios were determined. Estimates of the three outcomes were compared with true rates.

A total of 85 clinicians responded: 70 (82%) completed the survey, with an overall accuracy of 76%. Overall, predictions of mortality were accurate (mean difference from true value 0.7% (95% confidence interval (CI) -0.7, 2.1) P = 0.33), as were predictions of survival without major disability (mean difference - 0.7 (95% CI -3.0, 1.7) P = 0.58). However, survival with major disability was overestimated by 4.9% ((95% CI 1.7, 8.0) P = 0.003).

Most perinatal clinicians who responded used NIC-PREDICT correctly to estimate expected outcomes in infants born extremely preterm who are offered intensive care. Undue pessimism about survival with major disability remains an ongoing concern.

In neonates, pulmonary diseases such as bronchopulmonary dysplasia and other chronic lung diseases (CLDs) pose significant challenges due to their complexity and high degree of morbidity and mortality. This review discusses the etiology, pathophysiology, clinical presentation, and diagnostic criteria for these conditions, as well as current management strategies. The review also highlights recent advancements in understanding the pathophysiology of these diseases and evolving strategies for their management, including gene therapy and stem cell treatments. We emphasize how supportive care is useful in managing these diseases and underscore the importance of a multidisciplinary approach. Notably, we discuss the emerging role of personalized medicine, enabled by advances in genomics and precision therapeutics, in tailoring therapy according to an individual's genetic, biochemical, and lifestyle factors. We conclude with a discussion on future directions in research and treatment, emphasizing the importance of furthering our understanding of these conditions, improving diagnostic criteria, and exploring targeted treatment modalities. The review underscores the need for multicentric and longitudinal studies to improve preventative strategies and better understand long-term outcomes. Ultimately, a comprehensive, innovative, and patient-centered approach can enhance the quality of care and outcomes for neonates with CLDs.

To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI).

A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed.

There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05).

Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth.

NCT06082414.

In light of increased cesarean section rates, the incidence of placenta accreta spectrum (PAS) disorder is increasing. Despite the establishment of clinical practice guidelines offering recommendations for early and effective PAS diagnosis and treatment, antepartum diagnosis of PAS remains a challenge. This ultimately risks poor mental health and poor physical maternal and neonatal health outcomes.

This case series details the experience of two high-risk patients who remained undiagnosed for PAS until they presented with antenatal hemorrhage, leading ultimately to necessary, complex surgical interventions, which can only be optimally provide in a tertiary care center. Patient 1 is a 37-year-old woman with a history of three cesarean sections, which elevates her risk for PAS. She had placenta previa detected at 19 weeks, and placenta percreta diagnosed upon hemorrhage. During a hysterectomy, invasive placenta was found in the patient's bladder, leading to a cystotomy and right ureteric reimplantation. After discharge, she was diagnosed with a vesicovaginal fistula, and is currently awaiting surgical repair. Patient 2 is a 34-year-old woman with two previous cesarean sections. The patient had complete placenta previa detected at 19- and 32-week gestation scans. She presented with antepartum hemorrhage at 35 weeks and 2 days. An ultrasound showed thin myometrium at the scar site with significant vascularity. A hysterectomy was performed due to placental attachment issues, with significant blood loss. Both patients were at high risk for PAS based on past medical history, risk factors, and pathognomonic imaging findings.

We highlight the importance of the implementation of clinical guidelines at non-tertiary healthcare centers. We offer clinical-guideline-informed recommendations for radiologists and antenatal care providers to promote early PAS diagnosis and, ultimately, better patient and neonatal outcomes through increased access to adequate care.

 The threshold of viability, as well as cutoffs for delivery interventions and neonatal resuscitation, vary by hospital and involve complex counseling. With improvements in neonatal resuscitation and intensive care, the threshold of viability has been decreasing. Decisions regarding delivery planning and neonatal resuscitation efforts should be based on the best available evidence. Our objective was to characterize survival rates and neonatal outcomes following periviable birth at different milestones beginning with prenatal admission through 1 year of life in a contemporary cohort.

 We performed a retrospective cohort study of all inborn infants without major congenital anomalies who delivered at the University of Alabama at Birmingham from 2013 to 2019 at gestational ages 22+0/7 to 25+6/7. Our primary outcome was to compared survival milestones throughout the pre- and postdelivery periods and neonatal complications in surviving newborns through 1 year of life at each gestational age.

 The survival rate to 1 year of life was 49% (48-56%, 95% confidence interval [CI]) for the entire cohort and varied according to gestational age at delivery (22 weeks 15% [10-23%, 95% CI], 23 weeks 48% [43-58%, 95% CI], 24 weeks 57% [52-67%, 95% CI], 25 weeks 71% [67-82%, 95% CI]). Overall for the entire cohort, the rate of lung disease requiring respiratory support at discharge was 51%, intraventricular hemorrhage was 42%, retinopathy of prematurity was 74%, pulmonary hypertension was 30%, and concerns for cerebral palsy at 1 year of life was 25%. All outcomes improved with advancing gestational age at delivery. Of infants who delivered during the 22nd week of gestation, 50% received antenatal corticosteroids. Infants exposed to antenatal corticosteroids had more interventions, less pulmonary hypertension, and improved survival to 1 year of life.

 Knowledge of maternal complications, longitudinal survival rates, and neonatal outcomes of periviable deliveries according to gestational age throughout the admission enhances obstetric and perinatal counseling after hospital admission.

· Periviable birth outcomes at different delivery milestones is important for counseling.. · Providing contemporary outcomes for periviable deliveries is critical for accurate counseling.. · Administration of antenatal corticosteroids at 22 weeks' gestation appears beneficial overall..

To investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus, METHODS: All patients with gestational diabetes mellitus who had a late preterm delivery at Etlik Lady Zübeyde Hospital between 2017 and 2021 were included. Women who met the inclusion criteria and were not given antenatal corticosteroid treatment during current pregnancy before 34 0/7 weeks of gestation were divided into two groups according to whether or not they received late preterm antenatal corticosteroid treatment. The two groups were compared in terms of adverse neonatal complications. The main outcomes were composite respiratory outcome and composite neonatal outcome. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome.

This retrospective cohort study included a total of 400 participants with gestational diabetes mellitus who had a late preterm delivery within the study period. Of these women, 196 (49%) received late preterm antenatal corticosteroid treatment. Main outcomes showed no difference. Decreasing gestational age at birth was identified as an independent risk factor predicting both composite respiratory outcome and composite neonatal outcome in multivariate logistic regression analysis.

Antenatal corticosteroid treatment at or after 34 0/7 weeks of gestation in women with gestational diabetes mellitus who had a late preterm delivery was not associated with improvement in adverse neonatal outcomes. Decreasing gestational age at birth was the only independent risk factor predicting composite neonatal and composite respiratory outcomes.

Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

To investigate recent trends in the cumulative incidence and treatment patterns of retinopathy of prematurity (ROP) in Japan.

A retrospective multicenter cohort was conducted from 2011 to 2020 using the Diagnosis Procedure Combination inpatient database. Preterm newborns with birth weight <2,500 g were categorized by birth weight. The cumulative incidence of ROP, treatment patterns, and association between treatment and birth weight were investigated.

A total of 82,683 preterm infants were identified, of whom 9,335 (11.3%) were diagnosed with ROP. The cumulative incidence of ROP increased by 15% in those with birth weight <500 g over the study period. Among the ROP infants, 20.2% received treatment, including laser photocoagulation (94.8%), intravitreal injection (3.8%), or both (1.8%). The proportion receiving laser photocoagulation decreased followed by an increase in intravitreal injection. This shift in intervention pattern was most conspicuous for those with birth weight 750 to 1,249 g. The risk ratio of receiving laser and intravitreal injection for those weighing <500 g was 24.7 (95% confidence interval, 10.5-58.2) and 28.4 (5.8-138.1), respectively, as compared with infants weighing >1,500 g.

The cumulative incidence of ROP increased in infants with birth weight <500 g. A shift from laser photocoagulation to intravitreal injection was observed in the more recent years.

Neonates born at the cusp of viability are at particularly high risk of severe morbidity and mortality. With advances in medicine and technology, the ability to resuscitate smaller, more premature neonates has become possible, and survival as early as 21 weeks of gestation has been reported. Although administration of antenatal corticosteroids has been shown to reduce the risk of morbidity and mortality at later gestational ages, neonates born before 24 weeks of gestation have not been included in randomized clinical trials. Changing clinical practices surrounding neonatal resuscitation with intervention offered after birth at earlier gestational ages has prompted re-evaluation of the use of antenatal corticosteroids at these very early gestational ages. Recent observational data demonstrate that antenatal corticosteroids administered before deliveries at or after 22 weeks of gestation are associated with lower risks of neonatal mortality, although survival with severe morbidity remains high. Future research is needed to determine the efficacy of antenatal corticosteroids for deliveries before 22 weeks of gestation and should evaluate the timing of corticosteroid administration. Furthermore, efforts should be made to include diverse populations and clinically meaningful long-term outcomes. At this time, the decision surrounding antenatal corticosteroids for threatened periviable deliveries should incorporate multidisciplinary counseling with the goal of achieving concordant prenatal and postnatal management aligned with the patient's desires.

The effectiveness of antenatal corticosteroids (ACS) in significantly reducing respiratory distress syndrome (RDS) depends crucially on the timing. It is successful if delivery takes place between 24 hours and seven days following administration; after this period, the side effects seem to predominate. In addition, an increased rate of mental impairment and behavioral disorders are observed in children born full-term after ACS administration. The optimal timing of ACS administration depends crucially on the given indication; to date, it has been achieved in only 25-40% of cases. ACS administration is always indicated in PPROM, in severe early pre-eclampsia, in fetal IUGR with zero or reverse flow in the umbilical artery, in placenta previa with bleeding, and in patients experiencing premature labor with a cervical length < 15 mm. The risk of women with asymptomatic cervical insufficiency giving birth within seven days is very low. In this case, ACS should not be administered even if the patient's cervical length is less than 15 mm, provided that the cervix is closed and there are no other risk factors for a premature birth. The development of further diagnostic methods with improved power to predict premature birth is urgently needed in order to optimize the timing of ACS administration in this patient population. Caution when administering ACS is also indicated in women experiencing premature labor who have a cervical length ≥ 15 mm. Further studies using amniocentesis are needed in order to identify the patient population with microbial invasion of the amniotic cavity/intra-amniotic infection (MIAC/IAI), and to define threshold values at which delivery is indicated. ACS administration is not performed as an emergency measure, usually not even before transfer to a perinatal center. Therefore, whenever possible, the indication for ACS administration should be determined by a clinician who is highly experienced in perinatology.

To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.

Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions.

One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined.

977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4).

Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

In 2014, the leading obstetric societies published an executive summary of a joint workshop to establish obstetric interventions to be considered for periviable births. Antenatal corticosteroid administration between 220/7 and 226/7 weeks was not recommended given existing evidence. We sought to evaluate whether antenatal steroid exposure was associated with improved survival among resuscitated newborns delivered between 22 and 23 weeks of gestation.

We conducted a population-based cohort study of all resuscitated livebirths delivered between 220/7 and 236/7 weeks of gestation in the United States during 2009 to 2014 utilizing National Center for Health Statistics data. The primary outcome was rate of survival to 1 year of life (YOL) between infant cohorts based on antenatal steroid exposure. Multivariable logistic regression estimated the association of antenatal steroid exposure on survival outcomes.

In the United States between 2009 and 2014, there were 2,635 and 7,992 infants who received postnatal resuscitation after delivery between 220/7 to 226/7 and 230/7 to 236/7 weeks of gestation, respectively. Few infants born at 22 (15.9%) and 23 (26.0%) weeks of gestation received antenatal corticosteroids (ANCS). Among resuscitated neonates, survival to 1 YOL was 45.2 versus 27.8% (adjusted relative risk [aRR]: 1.6, 95% confidence interval [CI]: 1.2-2.1) and 57.9 versus 47.7% (aRR: 1.3, 95% CI: 1.1-1.5) for infants exposed to ANCS compared with those not exposed at 22 and 23 weeks of gestation, respectively. When stratified by 100 g birth weight category, ANCS were associated with survival among neonates weighing 500 to 599 g (aRR: 1.9, 95% CI: 1.3-2.9) and 600 to 699 g (aRR: 1.7, 95% CI: 1.1-2.6) at 22 weeks.

Exposure to ANCS was associated with higher survival rates to 1 YOL among resuscitated infants born at 22 and 23 weeks. National guidelines recommending against ANCS utilization at 22 weeks should be re-evaluated given emerging evidence of benefit.

· Exposure to antenatal steroids was associated with higher survival rates at 22 and 23 weeks of gestation.. · Women exposed to antenatal steroids were more likely to have an adverse outcome.. · The association between steroids and survival was observed among infants with birth weights > 500 g..

Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes.

A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32 weeks of gestation and weighing ≤ 1500 g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value.

The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes.

Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes.

To investigate whether gestational age (GA)-related intelligence outcomes of children born very preterm improved over time.

A multicenter cohort study recruited 4717 infants born at GA <31 weeks and admitted to neonatal intensive care units between 2001 and 2015 in Taiwan. Intelligence outcomes at age 5.5 years were classified by intelligent quotient (IQ) into no cognitive impairment (IQ > -1 SD), mild cognitive impairment (IQ = -1∼-2 SD), and moderate/severe cognitive impairment (IQ < -2 SD). Trends were assessed for neonatal morbidities, mortality, and intelligence outcomes by birth epoch (2001-2003, 2004-2006, 2007-2009, 2010-2012, 2013-2015) and GA (23-24, 25-26, 27-28, 29-30 weeks).

Maternal education levels increased and rates of brain injury and mortality decreased over time. Among the 2606 children who received IQ tests, the rates of no, mild, and moderate/severe cognitive impairment were 54.5%, 30.5%, and 15.0%, respectively. There were significant trends in the increasing rates of no cognitive impairment and declining rates of mild and moderate/severe cognitive impairment in all GA groups across the 5 birth epochs. Relative to the occurrence in 2001-2003, the odds were significantly reduced for moderate/severe cognitive impairment from 2007-2009 (aOR 0.49, 95% CI 0.30-0.81) to 2013-2015 (0.35, 0.21-0.56) and for mild cognitive impairment from 2010-2012 (0.54, 0.36-0.79) to 2013-2015 (0.36, 0.24-0.53).

For children born very preterm between 2001 and 2015 in Taiwan, the improvement of maternal education levels and improvements in neonatal brain injury and mortality were temporally associated with trends of decreasing intellectual impairment at school age across all GA groups.

Children of mothers with hypertensive-disorders-of-pregnancy (HDP) have high rates of preterm-birth (<37 weeks' gestation) and small-for-gestational-age (SGA), both of which are risk factors of intellectual disability (ID).

To test the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ID hazards, and HDP might not have independent effects.

This population-based cohort study enrolled 1,417,373 mother-child pairs between 2004 and 2011. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for ID outcome until 6-13 years of age. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and ID hazards were assessed with adjusted hazard ratios (aHR) and 95 % confidence intervals (CI), and the effects of preterm-birth and SGA on the associations were examined.

The HDP group had higher cumulative rates of ID (1.6 %) than the normotensive group (0.9 %), particularly the subgroup of preeclampsia-with-chronic-hypertension (2.4 %), followed by preeclampsia (1.7 %), chronic-hypertension (1.5 %) and gestational hypertension (1.0 %). Preterm-birth and SGA exerted aggravating effects on ID hazards in children exposed to any HDP. After adjustments, maternal chronic-hypertension (aHR 1.59, 95 % CI 1.28-1.97), preeclampsia (1.52, 1.26-1.83), and preeclampsia-with-chronic-hypertension (1.86, 1.38-2.51) independently contributed to ID outcome.

Maternal HDP other than gestational hypertension increased offspring's ID hazards independently from the potentiating hits of preterm-birth and SGA, implicating long-lasting influence of in-utero HDP exposure on children's cognitive development.

Preterm birth is associated with an increased risk of neurodevelopmental and neurobehavioral impairments including attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. In this narrative review, we examine the known associations between prematurity and ADHD and highlight the impact of both prematurity and ADHD on multiple domains across the pediatric life-course. We develop a framework for understanding the health services journey of individuals with ADHD to access appropriate services and treatments for ADHD, the "ADHD Care Cascade". We then discuss the many racial and ethnic inequities that affect the risk of preterm birth as well as the steps along the "ADHD Care Cascade". By using a life-course approach, we highlight the ways in which inequities are layered over time to magnify the neurodevelopmental impact of preterm birth on the most vulnerable children across the life-course.

To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1).

A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI.

Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003).

The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Outcomes for extremely low gestational age newborns (ELGANs), defined as <28 weeks estimated gestational age (EGA), remain disproportionately poor. A radical paradigm shift in the treatment of prematurity is to recreate the fetal environment with extracorporeal support and provide an environment for organ maturation using an extracorporeal VV-ECLS artificial placenta (AP) or an AV-ECLS artificial womb (AW). In this article, we will review clinical indications, current approaches in development, ongoing challenges, remaining milestones and ethical considerations prior to clinical translation.

Preterm birth, typically defined as birth between 20 0/7 weeks and 36 6/7 weeks of gestation, is a major cause of neonatal morbidity, and rates of preterm birth continue to rise. Antenatal corticosteroids have demonstrated benefit for reduction of morbidities and mortality associated with preterm birth, with few observed maternal risks. As such, antenatal corticosteroids have become the standard of care for treating pregnant people at risk of preterm birth. Tocolytics may be beneficial in temporarily slowing uterine contractions to prolong pregnancy long enough for the administration of corticosteroids or stabilization and transfer of a parturient in preterm labor.

Early assessment of the prognosis of preterm newborns is crucial for accurately informing parents and making treatment decisions. The currently available prognostic models rarely incorporate functional brain information from conventional electroencephalography (cEEG).

To examine the performance of a multimodal model combining (1) brain function information with (2) brain structure information (cranial ultrasonography), and (3) perinatal and (4) postnatal risk factors for the prediction of death or neurodevelopmental impairment (NDI) in extremely preterm infants.

Preterm newborns (23-28 weeks' gestational age) admitted to the neonatal intensive care unit at Amiens-Picardie University Hospital were retrospectively included (January 1, 2013, to January 1, 2018). Risk factors from the 4 categories were collected during the first 2 weeks post delivery. Neurodevelopmental impairment was assessed at age 2 years with the Denver Developmental Screening Test II. No or moderate NDI was considered a favorable outcome. Death or severe NDI was considered an adverse outcome. Data analysis was performed from August 26, 2021, to March 31, 2022.

After the selection of variables significantly associated with outcome, 4 unimodal prognostic models (considering each category of variable independently) and 1 multimodal model (considering all variables simultaneously) were developed. After a multivariate analysis for models built with several variables, decision-tree algorithms were run on each model. The areas under the curve for decision-tree classifications of adverse vs favorable outcomes were determined for each model, compared using bootstrap tests, and corrected for type I errors.

A total of 109 newborns (58 [53.2% male]) born at a mean (SD) gestational age of 26.3 (1.1) weeks were included. Among them, 52 (47.7%) had a favorable outcome at age 2 years. The multimodal model area under the curve (91.7%; 95% CI, 86.4%-97.0%) was significantly higher than those of the unimodal models (P < .003): perinatal model (80.6%; 95% CI, 72.5%-88.7%), postnatal model (81.0%; 95% CI, 72.6%-89.4%), brain structure model (cranial ultrasonography) (76.6%; 95% CI, 67.8%-85.3%), and brain function model (cEEG) (78.8%; 95% CI, 69.9%-87.7%).

In this prognostic study of preterm newborns, the inclusion of brain information in a multimodal model was associated with significant improvement in the outcome prediction, which may have resulted from the complementarity of the risk factors and reflected the complexity of the mechanisms that interfered with brain maturation and led to death or NDI.

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing.

This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6 years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders.

A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28 weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31).

Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders.

To explore providers' perspectives about decisional authority, conflict resolution, and diverse family structures within the context of periviable delivery (eg, between 22 and 25 weeks of gestation), with the ultimate goal of helping practitioners support, engage, and navigate conflict with parents facing periviable delivery.

Qualitative interviews with 30 neonatologists and obstetricians sought opinions about whether and how a pregnant person's partner should be involved in making periviable treatment decisions and how health care teams should proceed when parents do not agree on a treatment plan. Physicians were asked to consider whether their opinions changed under different scenarios involving marriage, biological relationship, adoption, and surrogacy.

Interviews revealed 4 main themes corresponding to providers' perspectives regarding partner involvement and decisional authority: providers care; involvement matters; mom is the priority; and uncertainty and guidance needed. Unique themes arose when discussing diverse family structures.

Shared decision making is optimal in the setting of periviable delivery, where decisions are both preference sensitive and value laden. Our interviews suggest that incorporating the dynamics and impact of partners' involvement in periviable resuscitation decision-making may facilitate more shared, equitable, and high-quality decision-making tailored to the needs of both pregnant people and their partners.

Infants born preterm and with low birth weight have increased risk for neurodevelopmental challenges later in life compared to term-born peers. These include functional motor impairment, cognitive and speech delays, neurobehavioral disorders, and atypical social development. There are well-documented inequities in the population distributions of preterm birth and associated short-term morbidities by race, ethnicity, language, and nativity. Far less is known about how these inequities affect long-term outcomes, though the impact of unequal access to post-discharge support services for preterm infants raises concerns about widening gaps in health, development, and functioning. In this review, we describe what is currently known about the impact of race, ethnicity, nativity, and language on long-term outcomes. We provide a framework for understanding inequities in social, political, and historical context. And we offer guidance for next steps to delineate mechanistic pathways and to identify interventions to eliminate inequities in long-term neurodevelopmental outcomes through research, intervention, and advocacy.

Recent contributions of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) regarding obstetrical perinatal interventions and neonatal delivery room practices include the following: the impact of multiple antepartum factors including maternal diabetes, hypertension, obesity and mode of delivery on outcomes of extremely preterm newborns, effects of delayed delivery interval for extremely preterm multiples, effects of antenatal steroids on preterm newborn outcomes and the impact of antenatal magnesium sulfate therapy on neurodevelopmental outcomes for extremely preterm infants. NRN studies also contribute important evidence for neonatal delivery room resuscitation guidelines including umbilical cord management and maintenance of euthermia immediately after birth. The updated NRN outcome calculator helps better counsel families regarding possible outcomes for the most immature newborns if resuscitation is attempted at birth. Thus, the NRN provides substantial information regarding effects of perinatal management on newborn infants.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.

To determine the rate and trend of active treatment in a population-based cohort of infants born at 22-25 weeks of gestation and to examine factors associated with active treatment.

This observational study evaluated 8247 infants born at 22-25 weeks of gestation at hospitals in the California Perinatal Quality Care Collaborative between 2011 and 2018. Multivariable logistic regression was used to relate maternal demographic and prenatal factors, fetal characteristics, and hospital level of care to the primary outcome of active treatment.

Active treatment was provided to 6657 infants. The rate at 22 weeks was 19.4% and increased with each advancing week, and was significantly higher for infants born between days 4 and 6 at 22 or 23 weeks of gestation compared with those born between days 0 and 3 (26.2% and 78.3%, respectively, vs 14.1% and 65.9%, respectively; P < .001). The rate of active treatment at 23 weeks increased from 2011 to 2018 (from 64.9% to 83.4%; P < .0001) but did not change significantly at 22 weeks. Factors associated with increased odds of active treatment included maternal Hispanic ethnicity and Black race, preterm premature rupture of membranes, obstetrical bleeding, antenatal steroids, and cesarean delivery. Factors associated with decreased odds included lower gestational age and small for gestational age birth weight.

In California, active treatment rates at 23 weeks of gestation increased between 2011 and 2018, but rates at 22 weeks did not. At 22 and 23 weeks, rates increased during the latter part of the week. Several maternal and infant factors were associated with the likelihood of active treatment.

Advances in ventilation strategies for infants in the NICU have led to increased survival of extremely preterm infants. More than 75% of infants born at less than or equal to 27 weeks' gestation require initial mechanical ventilation for survival due to developmental immaturity of their lungs and respiratory drive. Various ventilators using different technologies and involving multiple management strategies are available for use in this population. Centers across the world have successfully used conventional, high-frequency oscillatory and high-frequency jet ventilation to manage respiratory failure in extremely preterm infants. This review explores the existing evidence for each mode of ventilation and the importance of individualizing ventilator management strategies when caring for extremely preterm infants.

The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.

To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids.

This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded.

Infants were classified as having no, partial, or complete exposure to antenatal steroids.

The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center.

A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]).

In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.