[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

High threshold of total developmental quotient at 3 years for follow-up in extremely preterm infants.

AIM: To investigate the relationship between the developmental quotient (DQ) at age 3 years and the need for educational support at school age in extremely preterm infants. METHODS: A total of 176 infants with a gestational age of <28 weeks were analyzed. The total DQ and subscales were evaluated using the Kyoto Scale of Psychological Development (KSPD) test. Neurodevelopment at age 3 years was stratified using total DQ in a conventional (DQ < 70 as developmental delay, DQ 70- <85 as subnormal, DQ ≥85 as normal) and a modified way (subdividing normal into DQ 85- <93 as low-normal and DQ ≥93 as high-normal). The prevalence of future educational support was compared for each stratum. Additionally, subscales were compared between those with and without educational support in each total DQ stratum. RESULTS: In conventional stratification, the prevalence of educational support was 32 (63 %) for developmental delay, 14 (24 %) for subnormal, and 10 (15 %) for normal. In modified stratification, the prevalence was 8 (26 %) for low-normal and 2 (5 %) for high-normal. While there was no significant difference in the odds of educational support between the normal and subnormal, the low-normal had significantly higher odds compared to the high-normal (OR 6.00; 95 % CI, 1.16-30.95, p = 0.03). Among the low-normal stratum, the language-social subscale was significantly lower in those with educational support. CONCLUSION: Setting high thresholds for total DQ and evaluating detailed subscales at age 3 years may be useful for developmental follow-up in extremely preterm infants.

Parental views on prospective consent: Experience from a pilot randomised trial recruiting extremely preterm infants during the perinatal period.

AIM: To explore parental perceptions of the consenting process and understanding of the study in a pilot randomised controlled trial wherein extremely premature infants (<29 weeks' gestation) were recruited either antenatally or by 4 h of life. METHODS: We prospectively surveyed parents who had consented, declined consent or were eligible infants in the Positioning Preterm Infants for Neuroprotection study, a low-risk intervention study in the first 72 h of life. Structured interview questions explored the process and acceptability of the consenting approach by the parents and their knowledge of the study. Additional comments made by the parents were transcribed verbatim. RESULTS: Sixty-two parents participated in the surveys; of those, 41 had provided their consent, 8 declined consent and 13 were parents of missed eligible infants. Overall, most parents reported they understood the study well before providing their consent and approaching them for consenting did not create a burden for them. A verbal explanation of the study by the study team, especially by the medical practitioners, was viewed as beneficial. Where consent was obtained in the birthing unit (imminent births and within 4 h of birthing), it was suggested that the 4-h period for obtaining post-natal consent may be too short. A deferred consent with a follow-up opportunity for obtaining informed consent could be a suitable alternative. CONCLUSION: Parents found the consenting process acceptable and indicated they had sufficient understanding of the study to provide an informed consent. Deferred consent should be explored for future, low-risk intervention studies as an alternative to prospective consent where extremely preterm infants need to be recruited in the immediate neonatal period.

A Volume-Adjustable Artificial Womb for Extremely Preterm Infants.

More than 13 million children are born preterm annually. Prematurity-related mortality accounts for 0.9 million deaths worldwide. The majority of those affected are Extremely Preterm Infants (gestational age less than 28 weeks). Immaturity causes organ failure and specific morbidities like germinal matrix hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. Artificial womb and placenta technologies address these issues. As a bridge-to-life technology, they provide a liquid environment to allow organ maturation under more physiological conditions. The proposed artificial womb can adapt to fetal growth. Volume adjustment is achieved by removing fluid from the interspace between an inner and outer chamber. Results of the in vitro tests showed a temperature constancy of 36.8°C ± 0.3°C without pressure loss over 7 days. The volume of the inner sac was variable between 3.6 and 7.0 L. We designed a filtration and disinfection system for this particular purpose. This system has proven strong disinfection capabilities, effective filtering of metabolic waste, and the ability to avoid phospholipid washout. The presented artificial womb has sufficient volume variability to adapt to the physiologic growth of an extremely preterm neonate over a 4-week period. We regard this as an important step in the development of this bridge-to-life technology.

Clinical phenotype of pulmonary vascular disease requiring treatment in extremely preterm infants.

BACKGROUND: Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment. METHODS: This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups. RESULTS: Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment. CONCLUSIONS: This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.

Randomized Controlled Trial of Enteral Vitamin D Supplementation (ViDES) in Infants <28 Weeks Gestational Age or <1000 Grams Birth Weight: Study Protocol.

Background: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. Methods: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 grams birth weight at a large academic center in the United States.Infants are stratified by birth weight and randomized within 96 hours after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth.We hypothesize that the higher and early vitamin D dose (800 IU/d with early feeding) compared to placebo plus routine dose (400 IU/d with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at one month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes) and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes.The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. Discussion: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterminfants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. Trial registration: ClinicalTrials.gov registered on July 14, 2022 (NCT05459298).

Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. DISCUSSION: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. RESULTS: This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

[Moxifloxacin treatment for Mycoplasma hominis meningitis in an extremely preterm infant]. / èŽ«è¥¿æ²™æ˜Ÿæ²»ç–—è¶ æ—©äº§å„¿äººåž‹æ”¯åŽŸä½“è„‘è†œç‚Ž1例.

The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

[A cross-sectional survey of delivery room transitional care management for very/extremely preterm infants in 24 hospitals in Shenzhen City]. / 深圳市24家医院极/è¶ æ—©äº§å„¿äº§æˆ¿è¿‡æ¸¡æœŸç®¡ç†çš„æ¨ªæ–­é¢è°ƒæŸ¥.

OBJECTIVES: To investigate the current status of delivery room transitional care management for very/extremely preterm infants in Shenzhen City. METHODS: A cross-sectional survey was conducted in November 2022, involving 24 tertiary hospitals participating in the Shenzhen Neonatal Data Network. The survey assessed the implementation of transitional care management in the delivery room, including prenatal preparation, delivery room resuscitation, and post-resuscitation management in the neonatal intensive care unit. Very/extremely preterm infants were divided into four groups based on gestational age: <26 weeks, 26-28+6 weeks, 29-30+6 weeks, and 31-31+6 weeks. Descriptive analysis was performed on the results. RESULTS: A total of 140 very/extremely preterm infants were included, with 10 cases in the <26 weeks group, 45 cases in the 26-28+6 weeks group, 49 cases in the 29-30+6 weeks group, and 36 cases in the 31-31+6 weeks group. Among these infants, 99 (70.7%) received prenatal counseling, predominantly provided by obstetricians (79.8%). The main personnel involved in resuscitation during delivery were midwives (96.4%) and neonatal resident physicians (62.1%). Delayed cord clamping was performed in 52 cases (37.1%), with an average delay time of (45±17) seconds. Postnatal radiant warmer was used in 137 cases (97.9%) for thermoregulation. Positive pressure ventilation was required in 110 cases (78.6%), with 67 cases (60.9%) using T-piece resuscitators and 42 cases (38.2%) using a blended oxygen device. Blood oxygen saturation was monitored during resuscitation in 119 cases (85.0%). The median time from initiating transitional care measures to closing the incubator door was 87 minutes. CONCLUSIONS: The implementation of delivery room transitional care management for very/extremely preterm infants in the hospitals participating in the Shenzhen Neonatal Data Network shows varying degrees of deviation from the corresponding expert consensus in China. It is necessary to bridge the gap through continuous quality improvement and multicenter collaboration to improve the quality of the transitional care management and outcomes in very/extremely preterm infants.

Prolonged renal function impairment in infants born during the peri-viable period: A retrospective longitudinal cohort study.

BACKGROUND: The number of infants born during the peri-viable period who survive has been increasing. AIM: To clarify renal function in infants from the time of birth during the peri-viable period until their due date. STUDY DESIGN: This retrospective cohort study was conducted at a single center. SUBJECTS: We reviewed the data of infants born at ≤28 weeks of gestation between 2018 and 2022 at our hospital. The infants were divided into the following groups: born at 22-24 weeks vs. 25-28 weeks (appropriate-for-gestational age [AGA] infants), and AGA infants vs. small-for-gestational age (SGA) infants (born at 22-28 weeks). OUTCOME MEASURES: We compared the perinatal data and renal function of the infants from birth until their due date. RESULTS: Eighty-one infants were included. Their serum creatinine, fractional excretion of sodium, and urine glucose levels were high or positive soon after birth but gradually improved. The urine albumin level was significantly higher among AGA infants born at 22-24 weeks, even at term equivalent age, than among those born at 25-28 weeks. CONCLUSIONS: Persistent renal insufficiency was observed even around the term equivalent age in peri-viable infants. Follow-up data collected after the neonatal period should be investigated in these infants.

International Online Survey on the Management of Patent Ductus Arteriosus.

INTRODUCTION: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. MATERIALS AND METHODS: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. RESULTS: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6-6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5-2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7-3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2-9.8; p < 0.001]). DISCUSSION/CONCLUSION: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.

Postnatal longitudinal analysis of serum Nitric oxide and eosinophil counts in extremely preterm infants.

BACKGROUND: Nitric oxide (NO) may be related to the pathogenesis of several morbidities in extremely preterm infants, including late-onset adrenal insufficiency. However, eosinophilia is observed under pathological conditions with adrenal insufficiency. Therefore, this study explored postnatal changes in NO levels and eosinophil counts in extremely preterm infants with and without morbidities. METHODS: Nineteen extremely preterm infants with a median gestational age of 27.0 weeks and median birth weight of 888 g were enrolled in this study. Serum levels of nitrogen oxides (NOx) and peripheral blood eosinophil counts were measured at birth and every 2 weeks thereafter. Morbidities of the study group were diagnosed using a single criterion. RESULTS: Serum NOx levels (mean ± standard deviation) were 22.5 ± 14.9 µmol/L, 51.2 ± 23.7 µmol/L, 42.4 ± 15.2 µmol/L, and 33.8 ± 9.4 µmol/L at birth and 2, 4, and 6 weeks of age, respectively. The serum NOx level at 2 weeks of age was significantly higher than that at birth and 6 weeks of age. Eosinophil counts, which increase with adrenal insufficiency, were measured simultaneously and were 145 ± 199/µL, 613 ± 625/µL, 466 ± 375/µL, and 292 ± 228/µL at birth and 2, 4, and 6 weeks of age, respectively. These values showed that the eosinophil count was significantly higher at 2 weeks of age than at birth and 6 weeks of age. The serum NOx level of infants without chorioamnionitis was significantly increased at 4 weeks of age, and the eosinophil count of infants with necrotizing enterocolitis was significantly increased at 2 weeks of age. No correlation with the NOx level or eosinophil count was observed in infants with late-onset circulatory collapse. CONCLUSION: The postnatal serum NOx level and eosinophil count were significantly correlated with each other and peaked at 2 weeks of age.

[Comparison of unfavorable perinatal outcomes in primiparous adolescents and adults]. / Comparación de resultados perinatales desfavorables en primigestas adolescentes y adultas.

Background: Adolescent pregnancy may be associated with medical complications related to the biological immaturity of the mother, and adult primiparous mothers may present perinatal outcomes associated with pre-existing age-related chronic changes. Objective: To compare unfavorable perinatal outcomes in adolescent and adult primiparous women. Material and methods: Observational, cross-sectional, retrospective and analytical study. Records of adolescent women from 12-19 years and adult women from 20-40 years in their first pregnancy, with a gestation of more than 20 weeks, who entered the Obstetrics Area of a third level hospital for pregnancy resolution were included. Perinatal outcomes were compared using chi-squared, Fisher's exact test, or Mann-Whitney U test. Results: 220 records of primiparous women, 110 adolescents aged 18 (16-19) and 110 adults aged 24 (21-25) were included. Adolescent mothers presented as unfavorable perinatal outcomes newborns (NB) small-for-gestational-age (SGA): odds ratio (OR) 2.95 (95%CI 1.10-7.85), p = 0.04. Adult pregnant women presented more comorbidities (gestational hypertension [11.82 vs. 3.64%] and preeclampsia [10.91 vs. 4.55%], gestational diabetes [6.36 vs. 0.91%], [p = 0.006]) that were associated with prematurity (p = 0.018) and with hospitalization in the NB (p = 0.008). Conclusions: Adolescent mothers presented twice more SGA NB. Prematurity and hospitalization of the NB was associated with the presence of comorbidities in adult mothers.

Introducción: el embarazo en la adolescencia puede estar asociado a complicaciones médicas relacionadas con la inmadurez biológica de la madre y las madres primigestas adultas pueden presentar resultados perinatales asociados a alteraciones crónicas preexistentes relacionadas con la edad. Objetivo: comparar los resultados perinatales desfavorables en primigestas adolescentes y adultas. Material y métodos: estudio observacional, transversal, retrospectivo y analítico. Se incluyeron expedientes de mujeres adolescentes de 12-19 años de edad y mujeres adultas de 20-40 años primigestas, con gestación mayor de 20 semanas, que ingresaron al área de Obstetricia de un hospital de tercer nivel para resolución del embarazo. Los resultados perinatales se compararon con chi cuadrada, prueba exacta de Fisher o U de Mann-Whitney. Resultados: se incluyeron 220 expedientes de mujeres primigestas, 110 adolescentes de 18 (16-19) años y 110 adultas de 24 (21-25) años. Las madres adolescentes presentaron como resultados perinatales desfavorables a recién nacidos (RN) con peso bajo para edad gestacional (PBEG): razón de momios (RM) 2.95 (IC 95% 1.10-7.85), p = 0.04. Las embarazadas adultas presentaron más comorbilidades (hipertensión gestacional [11.82 frente a 3.64%] y preeclampsia [10.91 frente a 4.55%], diabetes gestacional [6.36 frente a 0.91%], [p = 0.006]) que se asociaron con prematurez (p = 0.018) y con la hospitalización en el RN (p = 0.008). Conclusiones: las madres adolescentes presentaron dos veces más RN con PBEG. La prematurez y la hospitalizacion del RN se asoció a la presencia de comorbilidades de las madres adultas.

Opportunities and Challenges of Prognostic Models for Extremely Preterm Infants.

Predicting the short- and long-term outcomes of extremely preterm infants remains a challenge. Multivariable prognostic models might be valuable tools for clinicians, parents, and policymakers for providing accurate outcome estimates. In this perspective, we discuss the opportunities and challenges of using prognostic models in extremely preterm infants at population and individual levels. At a population level, these models could support the development of guidelines for decisions about treatment limits and may support policy processes such as benchmarking and resource allocation. At an individual level, these models may enhance prenatal counselling conversations by considering multiple variables and improving transparency about expected outcomes. Furthermore, they may improve consistency in projections shared with parents. For the development of prognostic models, we discuss important considerations such as predictor and outcome measure selection, clinical impact assessment, and generalizability. Lastly, future recommendations for developing and using prognostic models are suggested. Importantly, the purpose of a prognostic model should be clearly defined, and integrating these models into prenatal counselling requires thoughtful consideration.

[Risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants]. / è¶ æ—©äº§å„¿ç”ŸåŽ72 hå† ä½Žè¡€åŽ‹å‘ç”Ÿçš„å±é™©å› ç´ åŠé¢„åŽåˆ†æž.

OBJECTIVES: To investigate the risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants. METHODS: A retrospective analysis was conducted on clinical data of extremely preterm infants admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2019 to April 2022. Based on the presence of hypotension within 72 hours after birth, the eligible infants were divided into a hypotension group (41 cases) and a normotension group (82 cases). The clinical characteristics, echocardiographic parameters within 72 hours after birth, and early complications were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors for hypotension within 72 hours after birth, and receiver operating characteristic curve analysis was performed to evaluate the predictive value of relevant indicators for the occurrence of hypotension within 72 hours after birth in the preterm infants. RESULTS: The proportion of infants who required medication or surgical closure of patent ductus arteriosus (PDA), the proportions of infants with intraventricular hemorrhage ≥ grade III and severe pulmonary hemorrhage, and the mortality rate within 7 days in the hypotension group were significantly higher than those in the normotension group (P<0.05). Multivariate logistic regression analysis showed that lower birth weight, larger PDA diameter, and hemodynamically significant PDA were risk factors for the occurrence of hypotension within 72 hours after birth in extremely preterm infants (P<0.05). The receiver operating characteristic curve analysis showed that the combination of birth weight, PDA diameter, and hemodynamically significant PDA had an area under the curve of 0.873 (95%CI: 0.802-0.944, P<0.05) for predicting hypotension within 72 hours after birth, with a sensitivity of 73.2% and specificity of 91.5%. CONCLUSIONS: Hypotension within 72 hours after birth is closely related to birth weight and PDA, and increases the risk of early severe complications and mortality in extremely preterm infants.

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth.

Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.

Artificial placenta technology: History, potential and perception.

As presently conceptualised, the artificial placenta (AP) is an experimental life support platform for extremely preterm infants (i.e. 400-600 g; 21-23+6 weeks of gestation) born at the border of viability. It is based around the oxygenation of the periviable fetus using gas-exchangers connected to the fetal vasculature. In this system, the lung remains fluid-filled and the fetus remains in a quiescent state. The AP has been in development for some sixty years. Over this time, animal experimental models have evolved iteratively from employing external pump-driven systems used to support comparatively mature fetuses (generally goats or sheep) to platforms driven by the fetal heart and used successfully to maintain extremely premature fetuses weighing around 600 g. Simultaneously, sizable advances in neonatal and obstetric care mean that the nature of a potential candidate patient for this therapy, and thus the threshold success level for justifying its adoption, have both changed markedly since this approach was first conceived. Five landmark breakthroughs have occurred over the developmental history of the AP: i) the first human studies reported in the 1950's; ii) foundation animal studies reported in the 1960's; iii) the first extended use of AP technology combined with fetal pulmonary resuscitation reported in the 1990s; iv) the development of AP systems powered by the fetal heart reported in the 2000's; and v) the adaption of this technology to maintain extremely preterm fetuses (i.e. 500-600 g body weight) reported in the 2010's. Using this framework, the present paper will provide a review of the developmental history of this long-running experimental system and up-to-date assessment of the published field today. With the apparent acceleration of AP technology towards clinical application, there has been an increase in the attention paid to the field, along with some inaccurate commentary regarding its potential application and merits. Additionally, this paper will address several misrepresentations regarding the potential application of AP technology that serve to distract from the significant potential of this approach to greatly improve outcomes for extremely preterm infants born at or close to the present border of viability.

Parental Narratives of Bonding and Relational Experiences with Preterm Infants Born at 23 to 24 Weeks-A Qualitative Descriptive Study.

(1) Background. The birth of an infant at 23 to 24 weeks poses a significant challenge to healthy parent-infant bonding because of the high risk of infant loss and the prolonged separation. The aim of this study was to retrospectively explore the narratives of parents with children born at 23-24 weeks about their bonding formation and relational experiences. (2) Methods. This was a qualitative descriptive study conducted with Finnish parents of children born at 23 or 24 weeks of gestation. Twenty-nine mothers and eight fathers were retrospectively interviewed using a semi-structured interview about the bonding process with their infant during the period in the neonatal intensive care unit (NICU) and their later parent-child relationship. Parents' narratives were deductively analysed according to a framework previously developed for studying parental bonding. (3) Results. Our results showed that several parents described the bonding process as natural or even easy despite the traumatic start to parenthood. Support from NICU staff and providing opportunities for participation in infant care and parent-infant physical closeness were reported to enhance the bonding process. Our study identified earlier parenting experience as a new element supporting bonding. (4) Conclusions. According to our results, essential elements enhancing parent-infant bonding in NICU settings seem to be supporting parents psychologically, promoting parent-infant closeness, and encouraging parental participation in the infants' care, even with the most immature infants.