Extreme Prematurity Research Articles

Immediate postnatal prediction of death or bronchopulmonary dysplasia among very preterm and very low birth weight infants based on gradient boosting decision trees algorithm: A nationwide database study in Japan.

Bronchopulmonary dysplasia (BPD) poses a substantial global health burden. Individualized treatment strategies based on early prediction of the development of BPD can mitigate preterm birth complications; however, previously suggested predictive models lack early postnatal applicability. We aimed to develop predictive models for BPD and mortality based on immediate postnatal clinical data. Clinical information on very preterm and very low birth weight infants born between 2008 and 2018 was extracted from a nationwide Japanese database. The gradient boosting decision trees (GBDT) algorithm was adopted to predict BPD and mortality, using predictors within the first 6 h postpartum. We assessed the temporal validity and evaluated model adequacy using Shapley additive explanations (SHAP) values. We developed three predictive models using data from 39,488, 39,096, and 40,291 infants to predict "death or BPD," "death or severe BPD," and "death before discharge," respectively. These well-calibrated models achieved areas under the receiver operating characteristic curve of 0.828 (95% CI: 0.828-0.828), 0.873 (0.873-0.873), and 0.887 (0.887-0.888), respectively, outperforming the multivariable logistic regression models. SHAP value analysis identified predictors of BPD, including gestational age, size at birth, male sex, and persistent pulmonary hypertension. In SHAP value-based case clustering, the "death or BPD" prediction model stratified infants by gestational age and persistent pulmonary hypertension, whereas the other models for "death or severe BPD" and "death before discharge" commonly formed clusters of low mortality, extreme prematurity, low Apgar scores, and persistent pulmonary hypertension of the newborn. GBDT models for predicting BPD and mortality, designed for use within 6 h postpartum, demonstrated superior prognostic performance. SHAP value-based clustering, a data-driven approach, formed clusters of clinical relevance. These findings suggest the efficacy of a GBDT algorithm for the early postnatal prediction of BPD.

Morbidity and Mortality Profile of Neonates Admitted in Neonatal Intensive Care Unit.

The neonatal period faces the greatest risk of death as they are vulnerable to sepsis, birth asphyxia, hypoxic injuries etc. A substantial disparity exists in NMR between Nepal and other developed countries and among different provinces of Nepal as well. This study was conducted to describe the pattern of neonatal admission, and immediate hospital outcomes from NICU located in a remote part of Nepal. This prospective study was conducted in The Province Hospital, Karnali, Nepal over a period of six months (June 2021 to Dec 2021 AD). The variables used were neonatal age, sex, gestation, birth weight, maternal age, mode and place of delivery. Neonatal morbidities and final outcomes at discharge were recorded in a predesigned proforma. A total of 396 neonates included, the majority were inborn 283(71%), male 241(61%), term 301(76%) and had normal birth weight 279 (70.4%). Neonatal sepsis 188(37.2%), prematurity 95(24%), and birth asphyxia 55(15.2%) were main indications for hospitalization. The majority 337(85%) improved after treatment, while 33(8.3%) died, 12 (3%) left against medical advice and 14(3.5%) cases were referred. Preterm neonates had thrice the risk of mortality than term neonates (OR =3.27). Low birth weight (< 2500 grams) had higher odds of poor outcomes (OR =3.5). Low maternal age (<20 years), prematurity, LBW, mechanical ventilation and inotrope use were predictors of poor outcomes. Neonatal sepsis, prematurity and perinatal asphyxia were the most common causes of NICU admissions. Mechanical ventilation, inotropes use, extreme prematurity, low birth weight and younger age of the mother were predictors of poor outcome.

Pain Exposure and Brain Connectivity in Preterm Infants

Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown. To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants. This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023. Pain was quantified in the initial weeks after birth as the total number of invasive procedures. Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education. A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, -0.46; 95% CI, -0.78, to -0.15; P = .004) and local efficiency (coefficient, -0.57; 95% CI, -1.04 to -0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes. In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.

Circadian characteristics of term and preterm labors

The labor is a physiological event considered to have its own circadian (diurnal) rhythm, but some of the data remain conflicting, especially for preterm births. In this retrospective study, we analyzed the circadian trends of labor onset times in the Slovenian birth cohort from 1990 to 2018 with over 550,000 cases of singleton births. The number of term and preterm labor onsets was calculated for each hour in a day and circadian trends were evaluated for each of the study groups by modeling with a generalized Poisson distribution linked with the cosinor regression model using logarithmic link function. The induced labors were taken as the control group since the timing of labor depends mostly on the working schedule of personnel and not on the intrinsic rhythmic characteristics. For induced labors, the main peak in the number of labor cases was observed in the late morning hours (around 10 AM) for all gestational ages. The prominence of this peak becomes smaller in spontaneous premature labors with gradually disrupting rhythmicity in very preterm and extremely preterm cases. Labors starting with spontaneous contractions peak between 6 and 7 AM and lose the rhythmicity at 35 weeks of gestation while labors starting with a spontaneous rupture of membranes peak at 1 AM and lose the rhythmicity at 31 weeks of gestation, suggesting differences in underlying mechanisms. According to our knowledge, this is the first study that shows differences of circadian trends between different types of spontaneous labors, i.e., labors initiated with contraction and labors initiated with a spontaneous rupture of membranes. Moreover, the obtained results represent evidence of gradual disruption of rhythmicity from mild to extreme prematurity.

Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD. 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise. Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely. In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.

Percutaneous retrieval of embolized umbilical arterial catheter in extreme premature infant

Background: Umbilical arterial catheterization is a common procedure performed on critically ill neonates, especially those with extreme prematurity. Various complications have been described following umbilical artery catheter (UAC) placement including thrombosis, embolism, vasospasm, vascular perforation, hemorrhage, and infection. However, treatment of these complications is challenging due to the small size of this very fragile subset of patients. Methods: A 3-day old extremely preterm infant was referred to our institution for percutaneous removal of a fragmented and embolized umbilical arterial catheter. Results: Catheter retrieval was successful via a carotid approach utilizing techniques from percutaneous closure of PDA in preterm infants and trans-carotid access for PDA stent and aortic interventions. Conclusion: This case report describes the successful percutaneous retrieval of an embolized UAC fragment in an extremely preterm infant, the smallest documented in literature to date.

Advice to Clinicians From Expectant Parents at Extreme Prematurity: A Multimethod Study.

Despite recommendations for patient-centered counseling on extreme prematurity, clinicians often miss opportunities to communicate in a way that facilitates parental knowledge, decision-making, and emotional support. In this study, we aimed to determine empirical, parent-derived recommendations and advice for clinicians counseling on extreme prematurity. Pregnant women (and their partners) admitted at 22 0/7 to 25 6/7 weeks' estimated gestation participated in postantenatal counseling semi-structured interviews or questionnaires to explore parental preferences in the counseling process, including advice to clinicians. Thematic analysis was performed. A total of 39 interviews and 47 questionnaires, representing 62 total prenatal consultations, were completed. Thematic analysis of participants' advice to clinicians from both interview and questionnaire data resulted in 14 parent-derived recommendations to clinicians who counsel expectant parents at extreme prematurity. Parental recommendations related to compassionately engaging, supporting, and communicating with families, as well as aligning teams and following up. We present an empirical parent-derived, family-centered, and practical approach for clinicians counseling on extreme prematurity. Future studies should include a more diverse patient population and assess the impact of these recommendations on the counseling process and outcomes.

Interactive sequences in the mother–baby dyad: a dyadic and longitudinal communication pattern between mothers and babies with extreme and moderate prematurity /Secuencias interactivas en la díada madre-bebé: un patrón de comunicación diádico y longitudinal entre la madre y el bebé con prematuridad extrema y moderada

The goal of this study was to detect communicative sequences in mother–baby dyads according to the degree of prematurity, comparing them in three corrected ages (two, four and six months). The observational methodology was used from the mixed methods perspective, and the design is nomothetic/follow-up/multidimensional. Fifteen mother–baby dyads with extreme prematurity and 15 mother–baby dyads with moderate prematurity participated. An observation instrument was constructed combining an observation instrument and category systems to code the dyads’ behaviours. Fifteen minutes of free interaction were recorded and Type IV data were logged. The programs HOISAN and SDIS-GSEQ/GSEQ were used to analyse the results. The results detected different behavioural patterns related to the interaction in both the expression of communicative behaviours and in the time when they were deployed in the ages evaluated.

Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature—An Exploratory Study

PurposeNeonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates.MethodsT1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson’s correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes.ResultsCognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = −0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = −0.408; p = 0.018) and pontine tegmentum (r = −0.414; p = 0.017)); and FA (pontine tegmentum (r = −0.352; p = 0.045)).T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes.ConclusionThere are relationships between relaxometry‑/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

Extreme prematurity: Factors associated with perinatal management and morbi-mortality in western Normandy, France

BackgroundExtreme prematurity (birth before 26 weeks of gestation), presents complex challenges and can lead to various complications. Survival rates of extremely preterm infants are lower in France than in other countries. The choice between active and palliative care is decisive in managing these births. ObjectiveTo conduct an observational study focused on factors associated with perinatal management, mortality, and morbidity outcomes among extremely preterm births in a regional perinatal network. MethodsWe undertook a retrospective, multicenter study within the western Normandy perinatal network, encompassing live births between 230/6 and 256/6 weeks from 2015 to 2019. Data were extracted from the perinatal network database and medical records. ResultsOne hundred and seven infants born from 94 women were included. In the antenatal period, 79 were exposed to corticosteroids, 66 to magnesium sulfate, and 67 to antibiotics. Active care at birth was provided to 84 neonates of whom 42 survived. In total, 65 infants died. Among the 42 surviving neonates, 9 experienced no severe morbidity, 29 displayed one and 4 exhibited two criteria of severe morbidity. Active care was associated with gestational age. Neonatal survival was correlated with antenatal exposure to antibiotics and magnesium sulfate as well as with postnatal corticosteroids. We found no significant association between mortality and gestational age at birth. ConclusionPrognostic factors must be weighed to discuss active antenatal care which is crucial for survival of extremely preterm neonates. Cooperation between obstetricians and neonatal caregivers is a cornerstone on a regional perinatal network scale.

Cardiopulmonary exercise testing in adolescence following extremely premature birth.

Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited. What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era? We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years). Thirty-sevenchildren aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O2 peak of 91% predicted. The BPD and non-BPDsubgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021). In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time.

Identification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome

BackgroundAntenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported.MethodsIn our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.ResultsOur findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.ConclusionsOur results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.

Breastfeeding premature infants affects the microbiota composition of breast milk.

To determine whether and how breast feeding of premature infants influences the human milk (HM) bacterial communities. HM samples before and after breastfeeding were collected from 40 preterm infant mothers at 24-366/7 weeks of gestational age in the neonatal intensive care unit of our hospital. Of these 40 babies, 11 at 24-276/7 weeks of gestational age and 12 at 28-316/7 weeks were grouped into an extremely premature (EPM) group and a very premature (VPM) group, respectively. In addition, 11 with a birth weight (BWT) of 1000 g ≤ BWT < 1500 g were classified as a very low birth weight (VLBW) group and 12 with BWT < 1000 g an extremely low birth weight (ELBW) group. Breast feeding and kangaroo mother care were given once a day for 7 days, from 14 to 21 days of age. The bacterial composition of HM was analyzed using high-throughput sequencing before and after feeding. Linear discriminant analysis effect size of HM samples before and after feeding showed that Bacillus, Prevotella and Fusobacterium were significantly enriched in HM before breastfeeding (P < 0.05). Post-feeding HM for the EPM group showed significant enrichment in Lactobacillales, Streptococcus, Desulfuromonadales, Ruminococcus, Geobacteraceae, Geobacter and Elizabethkingia_meningoseptica (P < 0.05). Bacillus was significantly enriched in the HM for EPM group before feeding (P < 0.05). For mothers with VLBW infants, Bacillus was enriched before feeding, while Lactobacillales was predominant after feeding (P < 0.05). There was a moderate correlation between the diversity of HM bacteria and infant development and immune outcomes. Breastfeeding of preterm infants can significantly affect the bacterial diversity in HM.

A Case of Extremely Premature Baby with Persistent Metabolic Acidosis, Hypoglycemia and Dyselectrolytemia Induced by Liposomal Amphotericin B

Amphotericin B is widely used in the treatment of neonatal invasive fungal disease. Liposomal amphotericin B (LAmB) is now preferred over conventional amphotericin B deoxycholate due to its lower kidney toxicity. However, it is essential to monitor the possible side effects of LAmB when treating extremely premature infants. Herein, we present a case of an extremely premature infant who exhibited persistent metabolic acidosis, hypoglycemia, and dyselectrolytemia after administration of LAmB for a suspected fungal infection.

Disruption of Cerebellar Granular Layer as a Consequence of Germinal Matrix Intraventricular Hemorrhage in Extreme Prematurity: An Acute Direct Mechanism Too?

Cerebellum is an important brain structure for the future development of motor, cognitive, and behavioral abilities in children. This structure undergoes its most significant growth during the third trimester of pregnancy. Prematurity gathers several risk factors for cerebellar impairment and underdevelopment, and among them is ventricular dilatation following germinal matrix intraventricular hemorrhage (GMH-IVH). In this report, we illustrate how this prevalent complication associated with prematurity may induce secondary cerebellar cortical damage. A premature male born by an emergency Caesarean section displayed massive GMH-IVH at brain ultrasound performed after three hours of extrauterine life and died after 18 hours of life, despite maximized vital support. We report a postmortem histopathological specimen of the cerebellar cortex showing the disruption of the external granular layer (EGL) by hemorrhagic content flowing from the supratentorial ventricles into the fourth ventricle and cisterna magna. The expansion of the ventricular system and the presence of blood in the lateral ventricles can cause inflammation and damage to the cerebellar gyri. Experimental models have shown a thinning of the EGL, suggesting that blood surrounding the cerebellum has a harmful action. Additionally, a sudden influx of cerebrospinal fluid from the lateral ventricles may directly contribute to cerebellar damage, indicating that this may be another way in which the cerebellar gyri are impaired during acute severe GMH-IVH. This is the first histopathologically confirmed case of acute disruption in the cerebellar cortex during a GMH-IVH in a premature baby.

Outcomes of Ultrasound or Physical Examination-Indicated Cerclage according to the Degree of Cervical Dilation.

Pregnancy outcomes of individuals receiving cervical cerclage when the cervix is dilated are not well known. We sought to examine preterm birth rates after ultrasound or physical examination-indicated cerclage placement according to the degree of cervical dilation. This was a retrospective cohort study of individuals with singleton pregnancies undergoing ultrasound or physical examination-indicated cerclage before 240/7 weeks of gestation from 2004 to 2018. Individuals were categorized based on the degree of cervical dilation at the time of cerclage. Our primary outcome was preterm delivery at less than 37 weeks of gestation. Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) with 95th confidence intervals (95% CI), controlling for predefined covariates. Of 147 individuals undergoing ultrasound or physical examination-indicated cerclage, 90/147 (61%) had a closed or 0.5 cm dilated cervix at the time of cerclage placement, 45/147 (31%) had a cervical dilation of 1 to 2.5 cm, and 12/147 (8%) had a cervical dilation of 3 to 4 cm at the time of placement. Individuals with a cervical dilation of 1 to 2.5 cm compared with those who had a closed cervix did not have increased odds of preterm delivery (58 vs. 42%; aOR: 1.95; 95% CI: 0.93-4.07). However, individuals with a cervical dilation of 3 to 4 cm compared with individuals who had a closed cervix had significantly increased odds of preterm delivery (75 vs. 42%; aOR: 4.33; 95% CI: 1.05-17.77). The rate of preterm birth increases with increasing cervical dilation at the time of cerclage placement. However, individuals who have a cerclage placed when the cervix is 1 to 2.5 cm can achieve an outcome that is not significantly different from those who had a cerclage placed when the cervix is closed. · Time from cerclage placement to delivery decreases as cervical dilation increases.. · Individuals 1 to 2.5 cm dilated at the time of cerclage can achieve a favorable outcome.. · A cervical dilation of ≥3 cm at cerclage placement was associated with extreme prematurity..

Study of Childbirth with A Single Scar Uterus at the "Major Moussa Diakite" Reference Health Center in Kati, Mali

The management of childbirth in a scarred uterus is one of the most debated subjects in modern obstetrics, due to the considerable increase in caesarean section rates and many other risks of complication such as disunion of the old scar. Objective: To study childbirth with a single scar uterus at the Kati Reference Health Center. Method: This was a prospective cross-sectional study, which ran from 1 January to 31 December 2021. It focused on parturients with a single myometrial scar, a vertex presentation of the foetus, a clinically normal pelvis, a uterine height of less than 36 centimeters, a single foetal pregnancy and an intergenesic interval of more than one year. Results: Out of a total of 2521 deliveries, seventy (70) women met the criteria of our study, or a frequency of 28%. The average age of parturients was 30, with extremes ranging from 18 to 42. Only 20% of our parturients had completed four antenatal consultations. They were carried out in 78.5% of cases by qualified staff. Eight out of ten of our parturients (81.4%) came on their own, and in seven out of ten cases (70.0%) in the active phase of childbirth. Delivery was by natural route in almost seven out of ten cases (65.7%), compared with caesarean section in 34.3% of cases. The indications for caesarean section were dominated by dynamic dystocia (66.7%), followed by failure to engage (12.5%), acute foetal distress (12.5%) and umbilical cord prolapse (8.3%). Previous vaginal delivery prior to caesarean section was associated with a successful uterine test (P=0.019). Maternal complications were haemorrhage due to uterine atony (1 case) and disunion of the old caesarean scar (1 case). We recorded two macerated stillbirths and one case of early neonatal death linked to extreme prematurity, and six cases of neonatal suffering. Conclusion: Childbirth in a scar uterus is a high-risk delivery, and strict adherence to the conditions under which it is carried out is essential to improve the maternal and ....

Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option. This study evaluated the minimum effective dose of prophylactic acetaminophen to close the ductus and assessed the safety and tolerability profile in extremely preterm infants at 23-26 weeks of gestation. A dose finding trial with Bayesian continual reassessment method was performed in a multicenter study with premature infants hospitalized in neonatal intensive care unit. Infants of 23-26 weeks of gestation and post-natal age ≤ 12 h were enrolled. Four intravenous acetaminophen dose levels were predefined. The primary outcome was the ductus arteriosus closing at two consecutive echocardiographies or at day 7. The main secondary objectives included the safety of acetaminophen on hemodynamics and biological hepatic function. A total of 29 patients were analyzed sequentially for the primary analysis with 20 infants assigned to the first dose level followed by 9 infants to the second dose level. No further dose level increase was necessary. The posterior probabilities of success, estimated from the Bayesian logistic model, were 46.1% [95% probability interval (PI), 24.9-63.9] and 67.6% (95% PI, 51.5-77.9) for dose level 1 and 2, respectively. A closing or closed pattern was observed among 19 patients at the end of treatment [65.5% (95% confidence interval (CI), 45.7-82.0)]. No change in alanine aminotransferase values was observed during treatment. A significant decrease in aspartate aminotransferase values was observed with postnatal age. No change in systolic and diastolic blood pressures was observed during treatment. Minimum effective dose to close the ductus was 25 mg/kg loading dose then 10 mg/kg/6 h for 5 days in extremely preterm infants. Acetaminophen was well tolerated in this study following these doses. ClinicalTrials.gov Identifier: NCT04459117.

Leveraging transcriptomics to develop bronchopulmonary dysplasia endotypes: a concept paper

ImpactBronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes.IntroductionBronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease.MethodsAn unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics.ResultsFour BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value < 0.05 after multiple comparison testing. Endotype A consisted of neonates with a higher gestational age and birthweight. Endotypes B-D included neonates between 25 and 26 weeks and a birthweight range of 640 to 940 g. Endotype D appeared to have a protective role against BPD compared to Endotypes B and C (36% vs. 62% vs. 60%, respectively). The most significant pathway focused on T helper 17 cell differentiation.ConclusionBioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD.

Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study

The administration of dexamethasone has been associated with suboptimal neurodevelopment. We aimed to compare the development of extremely premature infants treated or not with alternatives to dexamethasone: betamethasone, hydrocortisone hemisuccinate. This retrospective cohort study included infants born before 29 weeks of gestational age, treated or not with late (day ≥ 7) postnatal steroids (betamethasone, hydrocortisone hemisuccinate). The neurodevelopment outcome was evaluated at 24 months corrected age, after adjustment on comorbidities of extreme prematurity. In order to analyse their overall development, data about growth and respiratory outcomes were collected. Among the 192 infants included, 59 (30.7%) received postnatal steroids. Suboptimal neurodevelopment concerned 37/59 (62.7%) postnatal steroid-treated and 43/133 (38.1%; p = 0.002) untreated infants. However, in multivariable analysis, only severe neonatal morbidity (p = 0.007) and male gender (p = 0.027) were associated with suboptimal neurodevelopment outcome at 24 months. Conclusions: Betamethasone or hydrocortisone hemisuccinate treatment was not an independent risk for suboptimal neurological development, growth and respiratory outcomes assessed at 24 months corrected age in extremely premature infants. Registration number: The study was registered on the ClinicalTrials.gov register: NCT05055193.What is Known:• Late postnatal steroids are used to treat bronchopulmonary dysplasia• Meta-analyses warned against the neurological risk of dexamethasone use during neonatal period. Early or late hydrocortisone hemisuccinate has been evaluated in multiple studies, none of which have reported an adverse effect on neurodevelopment at least to 2 years. Data about the use of betamethasone are scarce.What is New:• The risk of suboptimal neurodevelopment was higher among extremely premature infants who received postnatal steroids when compared to those who did not.• Betamethasone and hydrocortisone hemisuccinate treatment was not an independent risk factor for suboptimal neurodevelopment at 24 months corrected age.