Inducción del parto en gestaciones gemelares: estudio comparativo de oxitocina vs dinoprostona / Induction of labour in twin pregnancies: Comparative study of oxytocin vs. dinoprostone

Introducción: En los últimos años el número de gestaciones gemelares que alcanzan el término se ha incrementado. Aunque la vía vaginal ha demostrado ser una alternativa segura frente a la cesárea cuando el primer feto se encuentra en presentación cefálica, la evidencia disponible sobre los métodos de inducción aplicados a este tipo de gestaciones es limitada. Métodos: Estudio observacional retrospectivo realizado en un hospital de tercer nivel. Se incluyeron 44 gestantes gemelares, con edad gestacional superior a 34 semanas y con el primer gemelo en presentación cefálica, que fueron sometidas a inducción del parto. En 17 casos se utilizaron prostaglandinas vaginales (dinoprostona) y en 27, oxitocina intravenosa. La indicación se realizó aleatoriamente según la práctica clínica diaria. Se compararon los resultados de ambos grupos en seguridad y eficacia. Resultados: No se encontraron diferencias significativas en la tasa de cesárea por fracaso de inducción entre la oxitocina y las prostaglandinas (42,9% vs. 57,1%; p=0,3). Tampoco se encontraron diferencias en complicaciones neonatales ni maternas. Dos gestantes presentaron hemorragia obstétrica, única complicación materna descrita, ambas en el grupo de oxitocina. El 100% de las cesáreas realizadas fueron en gestantes con índices Bishop ≤6. Se encontró un mayor riesgo de cesárea en mujeres con IMC>30kg/m2 (p=0,001) e índice de Bishop previo a la inducción ≤6 (RR: 2,06; p=0,005). Conclusiones: Tanto las prostaglandinas vaginales como la oxitocina intravenosa resultan similares en eficacia, seguridad materna y neonatal, cuando se utilizan en gestaciones gemelares. Un índice de Bishop ≤6 y un IMC >30 se asocian con una mayor probabilidad de inducción fallida.

Introduction: In the last few years the number of twin gestations that reach term has increased. Although vaginal delivery route has proven to be a safe alternative to caesarean section when first foetus is in cephalic presentation, available evidence on induction methods applied to this type of pregnancies is limited. Methods: Retrospective observational study conducted in a tertiary hospital. Forty-four pregnant twins, with gestational age greater than 34weeks, and with the first twin in cephalic presentation, who underwent induction of labour, were included. Vaginal prostaglandins (dinoprostone) were used in 17 cases and intravenous oxytocin in 27 cases, indication was randomised according to daily clinical practice. Results of both groups were compared in terms of safety and efficacy. Results: No significant differences were found in the rate of caesarean section due to induction failure between oxytocin and prostaglandins (42.9% vs. 57.1%; P=.3). No differences were found either in terms of neonatal or maternal complications. Two pregnant women presented obstetric haemorrhage, the only maternal complication described, both in oxytocin group. Higher risk of caesarean section was found in women with BMI >30kg/m2 (P=.001) and pre-induction Bishop's index ≤6 (RR: 2.06) (P=.005). Conclusions: Both vaginal prostaglandins and intravenous oxytocin are similar in efficacy, maternal and neonatal safety when used in twin gestations. Bishop's index ≤6 and BMI >30 are associated with higher probability of induction failure.(AU)

Dolor pélvico en mujeres con episiotomía versus mujeres con desgarro perineal de segundo grado / Pelvic pain in women with episiotomy versus women with second-degree perineal tear

Introducción: El dolor pélvico es una de las disfunciones del suelo pélvico más comunes en el posparto, influyendo el grado de lesión y el momento en el que se valora. El grado de afección de una episiotomía medio-lateral es similar al desgarro perineal de segundo grado, por ello se decidió realizar un estudio que recogiera el grado de dolor referido mediante el Cuestionario de dolor de McGill. Material y métodos: Se realizó un estudio epidemiológico observacional, longitudinal prospectivo, de cohortes dinámicas, entre 384 mujeres, de las cuales 255 tuvieron un desgarro de segundo grado y a 129 se les practicó una episiotomía. Se realizó una valoración del suelo pélvico, junto con una recogida de datos (realización o no de masaje perineal, ejercicios musculares de suelo pélvico, presencia de Kristeller, tipo de sutura) así como el grado y tipo de dolor mediante el cuestionario de McGill, durante el puerperio inmediato, a las 6 semanas y a los 6 meses del posparto. Resultados: En el puerperio inmediato más del 50% de las mujeres refirieron algún tipo de sensación dolorosa, sin encontrar diferencias significativas entre ambas cohortes. Mientras que, a lo largo de la evolución del estudio, se produjo una disminución progresiva del dolor en ambas cohortes. Ya a las 6 semanas de posparto, menos del 33% de las mujeres refirieron alguna sensación dolorosa, considerándose como ausencia de dolor según los criterios del cuestionario de McGill. Conclusión:La presencia de episiotomía o desgarro perineal de segundo grado no ha tenido relación con el dolor perineal.(AU)

Introduction: Pelvic pain is one of the most common pelvic floor dysfunctions in the postpartum period, depending on the degree of injury and the time at which it is assessed. The degree of involvement of a mediolateral episiotomy is similar to that of a second degree perineal tear, therefore it was decided to conduct a study to collect the degree of pain reported using the McGill Pain Questionnaire. Material and methods: An observational, prospective longitudinal epidemiological study of dynamic cohorts was conducted among 384 women, of whom 255 had a second-degree tear and 129 had undergone an episiotomy. An assessment of the pelvic floor was carried out, together with data collection (performance or not of perineal massage, pelvic floor muscle exercises, presence of Kristeller, type of suture) as well as the degree and type of pain using the McGill Questionnaire, in the immediate puerperium, at six weeks, and six months of postpartum. Results: In the immediate puerperium more than 50% of women reported some type of painful sensation, without finding significant differences between both cohorts. However, as the study evolved, there was a progressive decrease in pain in both cohorts. By six weeks postpartum, less than 33% of women reported a painful sensation, considered as absence of pain according to the criteria of the McGill questionnaire. Conclusion: The presence of episiotomy or second degree perineal tear was not related to perineal pain.(AU)

Biomarkers for Pregnancy Latency Prediction after Preterm Premature Rupture of Membranes-A Systematic Review.

Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, ßhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.

Retinopathy of Prematurity among Preterm Newborn Admitted to the Neonatal Care Unit in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: World Health Organization has identified retinopathy of prematurity as an important cause of preventable childhood blindness. The presentation of retinopathy of prematurity is varied and differs in the developed and developing worlds. The study aimed to find out the prevalence of retinopathy of prematurity among preterm newborn admitted to the Neonatal Care Unit in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among preterm newborn admitted to the Neonatal Care Unit after receiving ethical approval from the Institutional Review Committee (Reference number: IEC/MGMEI/I/2021/66). The study was conducted from 15 December 2021 to 17 February 2022. Basic demographic data, risk factors, clinical characteristics, and prevalence of retinopathy of prematurity were noted. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 204 participants, retinopathy of prematurity was found in 118 (57.84%) (51.06-64.62, 95% Confidence Interval) in at least one eye. Early treatment retinopathy of prematurity type 2 in 82 (69.49%) was the commonest one severity-wise. Supplemental oxygen was given to 118 (100%) cases, and low birth weight was present in 109 (92.37%) cases. Conclusions: The prevalence of retinopathy of prematurity was found to be higher in other similar studies done in similar settings. The screening and treatment for the retinopathy of prematurity require a dedicated trained team of ophthalmologists, vitreo-retina specialists, paediatricians, and neonatologists with well-developed facilities for retinopathy of prematurity clinics. Keywords: blood transfusion; low birth weight; oxygen; preterm births; retinopathy of prematurity.

Association between excessive fetal growth and maternal cancer in Shanghai, China: a large, population-based cohort study.

The prevalence of high birth weight or large for gestational age (LGA) infants is increasing, with increasing evidence of pregnancy-related factors that may have long-term impacts on the health of the mother and baby. We aimed to determine the association between excessive fetal growth, specifically LGA and macrosomia, and subsequent maternal cancer by performing a prospective population-based cohort study. The data set was based on the Shanghai Birth Registry and Shanghai Cancer Registry, with medical records from the Shanghai Health Information Network as a supplement. Macrosomia and LGA prevalence was higher in women who developed cancer than in women who did not. Having an LGA child in the first delivery was associated with a subsequently increased risk of maternal cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.11). Additionally, in the last and heaviest deliveries, there were similar associations between LGA births and maternal cancer rates (HR = 1.08, 95% CI 1.04-1.12; HR = 1.08, 95% CI 1.05-1.12, respectively). Furthermore, a substantially increased trend in the risk of maternal cancer was associated with birth weights exceeding 2500 g. Our study supports the association between LGA births and increased risks of maternal cancer, but this risk requires further investigation.

Association between colonization of the respiratory tract with Ureaplasma species and bronchopulmonary dysplasia in newborns with extremely low gestational age: a retrospective study.

AIM: To ascertain the incidence of respiratory tract colonization in extremely low gestational age newborns (ELGANs) with Ureaplasma parvum and Ureaplasma urealyticum and determine if there is a difference in the severity of bronchopulmonary dysplasia (BPD) between ELGANs with and without Ureaplasma species (spp) colonization. METHODS: We reviewed the medical records of ELGANs 23 0/7-27 6/7 weeks of gestation, tested for U. parvum and U. urealyticum in our Center from January 1, 2009 to December 31, 2019. Ureaplasma spp were identified with the Mycofast Screening Revolution assay based on liquid broth cultures or with polymerase chain reaction. RESULTS: This study enrolled 196 preterm newborns. Fifty (25.5%) newborns had Ureaplasma spp respiratory tract colonization, with U. parvum being the predominant species. The incidence rate of respiratory tract colonization with Ureaplasma spp slightly increased in the studied period. The incidence rate for 2019 was 16.2 per 100 infants. BPD severity significantly correlated with Ureaplasma spp colonization (P = 0.041). After controlling for other risk factors for BPD in a regression model, preterm infants colonized with Ureaplasma spp had 4.32 times (95% confidence interval, CI 1.20-15.49) higher odds for developing moderate-to-severe BPD. CONCLUSIONS: U. parvum and U. urealyticum could be associated with the development of BPD in ELGANs.

Association of large for gestational age with cardiovascular metabolic risks: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to clarify the relationships among large for gestational age (LGA) and cardiometabolic risk factors. METHODS: PubMed, Web of Science, and the Cochrane Library databases were searched to identify studies on LGA and outcomes of interest, including BMI, blood pressure, glucose metabolism, and lipid profiles. Data were independently extracted by two reviewers. A meta-analysis was performed using a random-effects model. The Newcastle-Ottawa Scale and funnel graph were used to assess the quality and publication bias, respectively. RESULTS: Overall, 42 studies involving 841,325 individuals were included. Compared with individuals born appropriate for gestational age, individuals born LGA had higher odds of overweight and obesity (odds ratios [OR] = 1.44, 95% CI: 1.31-1.59), type 1 diabetes (OR = 1.28, 95% CI: 1.15-1.43), hypertension (OR = 1.23, 95% CI: 1.01-1.51), and metabolic syndrome (OR = 1.43, 95%; CI: 1.05-1.96). No significant difference was found in hypertriglyceridemia and hypercholesterolemia. Stratified analyses showed that, compared with individuals born appropriate for gestational age, individuals born LGA had higher odds for overweight and obesity from toddler age to puberty age (toddler age: OR = 2.12, 95% CI: 1.22-3.70; preschool: OR = 1.81, 95% CI: 1.55-2.12; school age: OR = 1.53, 95% CI: 1.09-2.14; puberty: OR = 1.40, 95% CI: 1.11-1.77). CONCLUSIONS: LGA is associated with increased odds of obesity and metabolic syndrome later in life. Future studies should focus on elucidating the potential mechanisms and identifying risk factors.

Trends in Resources for Neonatal Intensive Care at Delivery Hospitals for Infants Born Younger Than 30 Weeks' Gestation, 2009-2020.

Importance: In an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care. Objective: To examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital. Design, Setting, and Participants: This retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks' gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022. Exposures: Hospital of birth at 22 to 29 weeks' gestation. Main Outcomes and Measures: Birthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (<50 inborn infants at 22 to 29 weeks' gestation per year) and high-volume (≥50 inborn infants at 22 to 29 weeks' gestation per year) centers. High-volume level B and level C centers were combined, resulting in 3 distinct NICU categories: level A, low-volume B, and high-volume B and C NICUs. The main outcome was the change in the percentage of births at hospitals with level A, low-volume B, and high-volume B or C NICUs overall and by US Census region. Results: A total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B- or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B-level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B- or C-level NICUs decreased by 9.2% (95% CI, -10.3% to -8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks' gestation occurred at hospitals with high-volume B- or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B- or C-level NICUs decreased by 10.9% [95% CI, -14.0% to -7.8%) in the East North Central region and by 21.1% (95% CI, -24.0% to -18.2%) in the West South Central region. Conclusions and Relevance: This retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks' gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes.

Neonatal mortality in small for gestational age infants based on reference local newborn curve at secondary and tertiary hospitals in Indonesia.

BACKGROUND: Small for gestational (SGA) infants during the neonatal period have risks of mortality and sequelae for survival. Two - third of neonatal mortality occurs in the first weeks of life. Prevalence of SGA depends on the newbon curve used. Objectives of the study were to know the conditions that posed the risk of early neonatal and neonatal mortality, to identify preterm/full-term and SGA/appropriate gestational age (AGA) infants with cumulative mortality incident (CMI), to compare 5- year-period of early and neonatal mortality, and to investigate CMI on neonatal mortality of four categories during 5-year-period. METHODS: A retrospective cohort study on all live births, during 1998-2017, was conducted in Sleman and Sardjito hospitals, Yogyakarta, Indonesia. Based on the reference local curve, the eligible subjects were categorized into SGA and AGA infants. The analyses were based on preterm/full-term and SGA/AGA, thus resulting in 4 categories: preterm-SGA, preterm-AGA, full-term-SGA and full-term-AGA. Analysis was made with Unadjusted Hazard Ratio (HR) by Simple Cox Regression and Adjusted HR was calculated by Multiple Cox Regression, survival analysis to calculate CMI, and analysis mortality for 5-year period ( 1998-2002, 2003-2007, 2008-2012, 2013-2017). RESULT: There were 35,649 live births eligible for the study. Respiratory distress was the highest risk with HR 9,46, followed by asphyxia with HR 5,08, mother's death with HR 227, extra-health facility with HR 1,97, symmetrical SGA with HR 1,97, preterm-AGA with HR 1,75, low birth weight (LBW) with HR 1,64, primary health facility with HR 1,33, and boys with HR 1,16 consecutively. Early neonatal mortality in 4 categories by survival analysis revealed the highest CMI in preterm SGA. Similar result was found in neonatal mortality. Analysis of 5-year period unveiled the highest CMI during 1998-2002. The highest CMI based on the four categories, however, was found in preterm-SGA. CONCLUSION: Respiratory distress posed the highest HR in early and neonatal mortality. Survival analysis showing the highest CMI on early and neonatal mortality was identified in preterm-SGA. The 5 - year - period of neonatal mortality showed the highest CMI during 1998-2002 period, whereas based on 4 SGA categories, preterm-SGA demonstrated the highest CMI.

Molecular genetic screening of full-term small for gestational age.

OBJECTIVE: To examine the clinical application of genomic screening in newborns small for gestational age (SGA), hoping to provide an efficient technique for early discovery of neonatal diseases, which is necessary to elevate survival rates and the quality of life in infants. METHODS: Totally 93 full-term SGA newborns were assessed. Dried blood spot (DBS) samples were obtained at 72 h after birth, and tandem mass spectrometry (TMS) and Angel Care genomic screening (GS, using Targeted next generation sequencing) were carried out. RESULTS: All 93 subjects were examined by Angel Care GS and TMS. No children showing inborn errors of metabolism (IEM) were detected by TMS, while 2 pediatric cases (2.15%, 2/93) were confirmed as thyroid dyshormonogenesis 6 (TDH6) by Angel Care GS. Additionally, 45 pediatric cases (48.4%) had one or more variants conferring a carrier status for recessive childhood-onset disorders, with 31 genes and 42 variants associated with 26 diseases. The top three gene-related diseases with carrier status were autosomal recessive deafness (DFNB), abnormal thyroid hormone and Krabbe disease. CONCLUSIONS: SGA is tightly associated with genetic variation. Molecular Genetic Screening allows early detection of congenital hypothyroidism and may be a potent genomic sequencing technique for screening newborns.

Using Digital Tools to Study the Health of Adults Born Preterm at a Large Scale: e-Cohort Pilot Study.

BACKGROUND: Preterm birth is a global health concern. Its adverse consequences may persist throughout the life course, exerting a potentially heavy burden on families, health systems, and societies. In high-income countries, the first children who benefited from improved care are now adults entering middle age. However, there is a clear gap in the knowledge regarding the long-term outcomes of individuals born preterm. OBJECTIVE: This study aimed to assess the feasibility of recruiting and following up an e-cohort of adults born preterm worldwide and provide estimations of participation, characteristics of participants, the acceptability of questions, and the quality of data collected. METHODS: We implemented a prospective, open, observational, and international e-cohort pilot study (Health of Adult People Born Preterm-an e-Cohort Pilot Study [HAPP-e]). Inclusion criteria were being an adult (aged ≥18 years), born preterm (<37 weeks of gestation), having internet access and an email address, and understanding at least 1 of the available languages. A large, multifaceted, and multilingual communication strategy was established. Between December 2019 and June 2021, inclusion and repeated data collection were performed using a secured web platform. We provided descriptive statistics regarding participation in the e-cohort, namely, the number of persons who registered on the platform, signed the consent form, initiated and completed the baseline questionnaire, and initiated and completed the follow-up questionnaire. We also described the main characteristics of the HAPP-e participants and provided an assessment of the quality of the data and the acceptability of sensitive questions. RESULTS: As of December 31, 2020, a total of 1004 persons had registered on the platform, leading to 527 accounts with a confirmed email and 333 signed consent forms. A total of 333 participants initiated the baseline questionnaire. All participants were invited to follow-up, and 35.7% (119/333) consented to participate, of whom 97.5% (116/119) initiated the follow-up questionnaire. Completion rates were very high both at baseline (296/333, 88.9%) and at follow-up (112/116, 96.6%). This sample of adults born preterm in 34 countries covered a wide range of sociodemographic and health characteristics. The gestational age at birth ranged from 23+6 to 36+6 weeks (median 32, IQR 29-35 weeks). Only 2.1% (7/333) of the participants had previously participated in a cohort of individuals born preterm. Women (252/333, 75.7%) and highly educated participants (235/327, 71.9%) were also overrepresented. Good quality data were collected thanks to validation controls implemented on the web platform. The acceptability of potentially sensitive questions was excellent, as very few participants chose the "I prefer not to say" option when available. CONCLUSIONS: Although we identified room for improvement in specific procedures, this pilot study confirmed the great potential for recruiting a large and diverse sample of adults born preterm worldwide, thereby advancing research on adults born preterm.

Changes in perinatal management and outcomes of extremely preterm infants born below 26 weeks of gestation in a tertiary referral hospital in Sweden: Comparison between 2004-2007 and 2012-2016.

INTRODUCTION: Perinatal management of extremely preterm births in Sweden has changed toward active care from 22-23 gestational weeks during the last decades. However, considerable regional differences exist. This study evaluates how one of the largest perinatal university centers has adapted to a more active care between 2004-2007 and 2012-2016 and if this has influenced infant survival. MATERIAL AND METHODS: In this historical cohort study, women admitted with at least one live fetus and delivered at 22-25 gestational weeks (stillbirths included) at Karolinska University Hospital Solna during April 1, 2004-March 31, 2007, and January 1, 2012-December 31, 2016, were compared regarding rates of obstetric and neonatal interventions, and infant mortality and morbidity. Maternal, pregnancy and infant data from 2004-2007 were obtained from the Extreme Preterm Infants in Sweden Study while data from 2012-2016 were extracted from medical journals and quality registers. The same definitions of interventions and diagnoses were used for both study periods. RESULTS: A total of 106 women with 118 infants during 2004-2007 and 213 women with 240 infants during 2012-2016 were included. Increases between the study periods were seen regarding cesarean delivery (overall rate 14% [17/118] during 2004-2007 vs. 45% [109/240] during 2012-2016), attendance of a neonatologist at birth (62% [73/118] vs. 85% [205/240]) and surfactant treatment at birth in liveborn infants (60% [45/75] vs. 74% [157/211]). Antepartum stillbirth rate decreased (13% [15/118] vs. 5% [12/240]) and the proportion of live births increased (80% [94/118] vs. 88% [211/240]) while 1-year survival (64% [60/94] vs. 67% [142/211]) and 1-year survival without major neonatal morbidity (21% [20/94] vs. 21% [44/211]) among liveborn infants did not change between the study periods. At 22 gestational weeks, interventions rates were still low during 2012-2016, most obvious regarding antenatal steroid treatment (23%), attendance of a neonatologist (51%), and intubation at birth (24%). CONCLUSIONS: Both obstetric and neonatal interventions at births below 26 gestational weeks increased between 2004-2007 and 2012-2016 in this single center study; however, at 22 gestational weeks they were still at a low level during 2012-2016. Despite more infants being born alive, 1-year survival did not increase between the study periods.

[Establishment method and significance of birthweight curve and reference in single center].

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

Amniotic fluid CD36 in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study.

OBJECTIVE: The aim of this study was to evaluate CD36 concentrations in amniotic fluid in pregnancies complicated by spontaneous delivery with intact fetal membranes (preterm labor, PTL) and preterm prelabor rupture of membranes (PPROM) with respect to the presence of the intra-amniotic infection. METHODS: A total of 80 women with PPROM and 71 with PTL were included in the study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid CD36 concentrations were assessed by enzyme-linked immunosorbent assay. Microbial colonization of the amniotic cavity (MIAC) was determined by the cultivation and non-cultivation approach. Intra-amniotic inflammation (IAI) was defined as an amniotic fluid bedside interleukin-6 concentration ≥3000 pg/mL. Intra-amniotic infection was characterized by the presence of both MIAC and IAI. RESULTS: Women with PPROM with intra-amniotic infection had higher amniotic fluid CD36 concentrations than women without infection (with infection: median 346 pg/mL, IQR 262-384 vs. without infection: median 242 pg/mL, IQR 199-304; p = .006) A positive correlation between amniotic fluid CD36 concentrations and interleukin-6 concentrations was found (rho = 0.48; p < .0001). In PTL pregnancies, no statistically significant difference was found in the amniotic fluid level of CD36 between intra-amniotic infection, sterile IAI, and negative amniotic fluid. CONCLUSIONS: The presence of intra-amniotic infection is characterized by higher amniotic fluid CD36 concentrations in pregnancies complicated by PPROM. An amniotic fluid CD36 cutoff value of 252.5 pg/mL was found to be optimal for the prediction of intra-amniotic infection. In PTL pregnancies, no statistically significant change in CD36 concentration was found with respect to the presence of intra-amniotic infection.

PRELIMINARY FINDINGS OF TLR2 AND TLR4 EXPRESSION IN PRETERM NEONATES WITH NECROTIZING ENTEROCOLITIS.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants. Despite significant advances made in the prevention and treatment of disease so far, there has not been much change in the rate of mortality and morbidity associated with NEC. Although the factors affecting the development of necrotizing enterocolitis are not yet known precisely, prematurity is thought to be the most important risk factor for the development of NEC. This study aims to determine toll-like receptor (TLR) 2 and TLR4 expression levels in preterm neonates. A total of 50 preterm infants (patient: 42, control: 8) were included in the study. TLR2 and TLR4 expression levels were analysed by the RT-qPCR method. While there was no difference in infants' birth weight (g), gestational age (months), mother's age (years), father's age (years), and WBC (109/L); HGB (g/dL) and RBC (1012/L) were found to be significantly higher in the group with NEC (p<0.05). When TLR2 and TLR4 relative gene expression levels of neonates were evaluated (log2), it was determined that there was a significant difference between the two groups (below 1500 g) (p<0.001). TLR4 relative expression (2^-ddCt, above 1500 g) was higher in the NEC group than in the healthy group, while TLR2 relative expression (2^-ddCt, above 1500 g) was higher in the healthy group. TLR2 and TLR4 have been shown to have prominent roles in the development of NEC in experimental animal models and it would be significant to support this with human studies/animal models for a better understanding of the disease. Thus, it is recommended that future studies be carried out on experimental models that better replicate the human body, and dietary factors should be examined in detail.

Birth weight and large for gestational age trends in offspring of pregnant women with gestational diabetes mellitus in southern China, 2012-2021.

Background: With increasing prevalence of gestational diabetes mellitus (GDM) and changing management of GDM in pregnancy, it is imperative to understand the evolution of its current outcomes. The present study aimed to explore whether birth weight and large for gestational age (LGA) trends in women with GDM have changed over time in southern China. Methods: In this hospital-based retrospective study, all singleton live births for the period 2012 to 2021 were collected from the Guangdong Women and Children Hospital, China. GDM was diagnosed following the criteria of the International Association of Diabetes and Pregnancy Study Group. The cutoff points for defining LGA (>90th centile) at birth based on INTERGROWTH-21st gender-specific standards. Linear regression was used to evaluate trends for birth weight over the years. Logistic regression analysis was used to determine the odds ratios (ORs) of LGA between women with GDM and those without GDM. Results: Data from 115097 women with singleton live births were included. The total prevalence of GDM was 16.8%. GDM prevalence varied across different years, with the lowest prevalence in 2014 (15.0%) and the highest prevalence in 2021 (19.2%). The mean birth weight displayed decrease in women with GDM from 3.224kg in 2012 to 3.134kg in 2021, and the z score for mean birth weight decreased from 0.230 to -0.037 (P for trend < 0.001). Among women with GDM, the prevalence of macrosomia and LGA reduced significantly during the study period (from 5.1% to 3.0% in macrosomia and from 11.8% to 7.7% in LGA, respectively). Compared to women without GDM, women with GDM had 1.30 (95% CI: 1.23 - 1.38) times odds for LGA, and the ORs remained stable over the study period. Conclusions: Among offspring of women with GDM, there are decreased trends of birth weight in parallel with reductions in LGA prevalence between 2012 and 2021. However, the risk of LGA in women with GDM remains stable at relatively high level over the 10-year period, and efforts are still needed to address regarding causes and effective intervention strategies.

Management of the smaller twin with impending compromise in twin pregnancies complicated by selective fetal growth restriction: a questionnaire-based study of clinical practice patterns.

BACKGROUND: In twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician's perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR. METHODS: An online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates. RESULTS: A total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p < 0.001), but not with the limit of viability. However, the optimal gestational age of management transition for MC twin pregnancy was associated with both the limit of intact survival (p = 0.012) and viability with marginal significance (p = 0.062). CONCLUSIONS: Participants preferred to immediately deliver twin pregnancies complicated by sFGR with impending IUD of the smaller twin at the limit of intact survival (30 weeks) for DC twin pregnancies and at the midway between the limit of intact survival and viability (28 weeks) for MC twin pregnancies. More research is needed to establish guidelines regarding the optimal delivery timing for twin pregnancies complicated by sFGR.

The effect of maternal pregestational diabetes on fetal autonomic nervous system.

Heart rate variability assessment of neonates of pregestational diabetic mothers have shown alterations in the autonomic nervous system (ANS). The objective was to study the effect of maternal pregestational diabetes on ANS at the fetal stage by combining cardiac and movement parameters using a non-invasive fetal magnetocardiography (fMCG) technique. This is an observational study with 40 participants where fetuses from a group of 9 Type 1, 19 Type 2 diabetic, and 12 non-diabetic pregnant women were included. Time and frequency domain fetal heart rate variability (fHRV) and coupling of movement and heart rate acceleration parameters related to fetal ANS were analyzed. Group differences were investigated using analysis of covariance to adjust for gestational age (GA). When compared to non-diabetics, the Type 1 diabetics had a 65% increase in average ratio of very low-frequency (VLF) to low-frequency (LF) bands and 63% average decrease in coupling index after adjusting for GA. Comparing Type 2 diabetics to non-diabetics, there was an average decrease in the VLF (50%) and LF bands (63%). Diabetics with poor glycemic control had a higher average VLF/LF (49%) than diabetics with good glycemic control. No significant changes at p < 0.05 were observed in high-frequency (HF) frequency domain parameters or their ratios, or in the time domain. Fetuses of pregestational diabetic mothers exhibited some differences in fHRV frequency domain and heart rate-movement coupling when compared to non-diabetics but the effect of fHRV related to fetal ANS and sympathovagal balance were not as conclusive as observed in the neonates of pregestational diabetic mothers.

Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.

INTRODUCTION: Placental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function. MATERIAL AND METHOD: A nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles. RESULTS: Between 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed. CONCLUSION: Perinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted.