3rd Percentile Research Articles

Postneonatal mortality of severely small for gestational age extremely low birth weight infants

Infants born with weights below the 10th percentile of the expected birth weight for gestational age, defined as small for gestational age (SGA), have an increased risk of neonatal mortality and prematurity-related complications. However, the relationship between SGA and postneonatal (28 days to <1 year) mortality among extremely low birth weight infants (ELBWIs) remains uncertain. Hence, this study aimed to investigate the association between birth weight percentiles and postneonatal mortality in ELBWIs. A cohort of ELBWIs with a gestational age greater than 23 weeks who were admitted to Osaka Women's and Children's Hospital between 2008 and 2019 were considered eligible. Infants with major congenital anomalies, those large for their gestational age, or those who died within 28 days of birth were excluded. Baseline characteristics and outcomes of the three groups of ELBWIs-severe SGA (sSGA; birth weight, <3rd percentile), moderate SGA (mSGA; birth weight, 3rd to <10th percentile), and appropriate for gestational age (AGA; birth weight, 10th to <90th percentile)-were compared. Logistic regression analysis was used to identify perinatal factors associated with postneonatal mortality in sSGA infants. sSGA ELBWIs demonstrated higher incidence of meconium obstruction (25% vs. 8.3% vs. 7.6%, P<0.001), cholestasis (21% vs. 4.2% vs. 9.7%, P<0.003), and postneonatal mortality (7.3% vs. 0% vs. 0.7%, P<0.004) than mSGA and AGA ELBWIs. In the logistic regression analysis, cholestasis (odds ratio, 30.1; 95% confidence interval, 2.98-304) and sepsis (odds ratio, 13.5; 95% confidence interval, 1.06-173) were significantly related to postneonatal mortality among ELBWIs with sSGA. The leading cause of postneonatal mortality in sSGA ELBWIs was liver failure (55.5%). sSGA ELBWIs exhibited a higher rate of postneonatal mortality compared to mSGA and AGA ELBWIs. Therefore, strategies aimed at preventing liver dysfunction in severely cholestatic ELBWIs with sSGA are necessary.

Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions.

Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.

Deep learning-based segmentation of whole-body fetal MRI and fetal weight estimation: assessing performance, repeatability, and reproducibility.

To develop a deep-learning method for whole-body fetal segmentation based on MRI; to assess the method's repeatability, reproducibility, and accuracy; to create an MRI-based normal fetal weight growth chart; and to assess the sensitivity to detect fetuses with growth restriction (FGR). Retrospective data of 348 fetuses with gestational age (GA) of 19-39weeks were included: 249 normal appropriate for GA (AGA), 19 FGR, and 80 Other (having various imaging abnormalities). A fetal whole-body segmentation model with a quality estimation module was developed and evaluated in 169 cases. The method was evaluated for its repeatability (repeated scans within the same scanner, n = 22), reproducibility (different scanners, n = 6), and accuracy (compared with birth weight, n = 7). A normal MRI-based growth chart was derived. The method achieved a Dice = 0.973, absolute volume difference ratio (VDR) = 1.8% and VDR mean difference = 0.75% ([Formula: see text]: - 3.95%, 5.46), and high agreement with the gold standard. The method achieved a repeatability coefficient = 4.01%, ICC = 0.99, high reproducibility with a mean difference = 2.21% ([Formula: see text]: - 1.92%, 6.35%), and high accuracy with a mean difference between estimated fetal weight (EFW) and birth weight of - 0.39% ([Formula: see text]: - 8.23%, 7.45%). A normal growth chart (n = 246) was consistent with four ultrasound charts. EFW based on MRI correctly predicted birth-weight percentiles for all 18 fetuses ≤ 10thpercentile and for 14 out of 17 FGR fetuses below the 3rd percentile. Six fetuses referred to MRI as AGA were found to be < 3rd percentile. The proposed method for automatic MRI-based EFW demonstrated high performance and sensitivity to identify FGR fetuses. Results from this study support the use of the automatic fetal weight estimation method based on MRI for the assessment of fetal development and to detect fetuses at risk for growth restriction. • An AI-based segmentation method with a quality assessment module for fetal weight estimation based on MRI was developed, achieving high repeatability, reproducibility, and accuracy. • An MRI-based fetal weight growth chart constructed from a large cohort of normal and appropriate gestational-age fetuses is proposed. • The method showed a high sensitivity for the diagnosis of small fetuses suspected of growth restriction.

A Comparison of Magnesium Levels in Obese Versus Normal-Weight Children.

Introduction One of the world's most pressing problems right now is childhood obesity. After potassium, magnesium (Mg) is the second most prevalent intracellular cation and the fourth most prevalent mineral in the human body. Numerous symptoms of magnesium insufficiency can include hypocalcemia, hypokalemia, as well as cardiac and neurological symptoms. Additionally, chronically low Mg levels have been associated with a number of chronic diseasessuch as diabetes, hypertension, coronary heart disease, and osteoporosis. Objectives This study aimed to compare the magnesium (Mg) level between normal-weight and obese children in a tertiary center in Saudi Arabia over the past seven years and evaluate the vitamin D and phosphorus between the two groups as a secondary objective. Methods This is a single-center, case-control study conducted on patients followed up in our center from January 2016 to December 2022. All pediatric patients were between two and 14 years of age. They were divided into two groups: one with children whose body mass index (BMI) was over the 85th percentileand the other with children whose BMI was between the 3rd and 85th percentiles. Results Mean serum Mg levels showed no significant correlation between the obese group (0.82 mg/dl) and the normal-weight group (0.83 mg/dl). However, vitamin D and phosphorus demonstrate a significant difference between the two groups. The obese group revealed a vitaminD of 1.6±0.24 and phosphorus of 4.2±0.46. On the other hand, the normal group had a vitamin D of 44.0±28.2 andphosphorus of 1.5±0.26. Conclusion There was a negative correlation between Mg levels and weight in pediatric patients. However, a positive relationship was observed between the Mg intake and Mg levels. Moreover, sodium, phosphorus, and vitamin D levels showed significant differences.

Shortened fetal long bones: A notable intrauterine phenotypic feature in SHOX-associated skeletal dysplasia.

To explore the intrauterine phenotypic spectrum of short stature homeobox-containing (SHOX) gene-associated skeletal dysplasia and provide genetic counseling at-risk pregnancies. We analyzed the fetuses with SHOX-microdeletions identified by single nucleotide polymorphism (SNP)-array. The intrauterine phenotypes and outcomes were further elaborated. Nine fetuses carrying a single SHOX-microdeletion were reported, with deletion sizes ranging from 0.134 to 1.35 Mb. Shortened long bones were observed in all fetuses, varying from -2.0 standard deviation (SD) to -5.3 SD. Moreover, all cases had a femur length/foot ratio less than 0.87 and a femur/abdominal circumference ratio greater than 0.16, suggesting that non-lethal skeletal dysplasia may be involved. Two fetuses showed intrauterine growth restriction, and two had nasal bone hypoplasia. Prenatal ultrasonography did not reveal other obvious anomalies, including the Madelung deformity. Five microdeletions were inherited and one was de novo. Five terminations and four newborns were recorded. Two newborns had normal stature, and two were short-statured (height <3rd percentile), with one having inflexible wrists. SHOX haploinsufficiency may manifest with shortened fetal long bones. The combination of history taking, prenatal ultrasonography, and SNP-array can prompt early prenatal diagnosis and timely postnatal treatment of SHOX-associated skeletal dysplasia.

Corpus callosum-fastigium and tectal lengths in late-onset small fetuses.

To investigate measurements on neurosonography of midbrain morphology, including corpus callosum-fastigium length and tectal length, in late-onset small fetuses subclassified as small-for-gestational-age (SGA) or growth-restricted (FGR). This was a case-control study of consecutive singleton pregnancies delivered at term at a single center between January 2019 and July 2021, including those with late-onset smallness (estimated fetal weight (EFW) < 10th centile) and appropriate-for-gestational-age controls matched by age at neurosonography. Small fetuses were further subdivided into SGA (EFW between 3rd and 9th centile and normal fetoplacental Doppler) and FGR (EFW < 3rd centile or EFW < 10th centile with abnormal cerebroplacental ratio and/or uterine artery Doppler). Transvaginal neurosonography was performed at a mean ± SD gestational age of 33 ± 1 weeks in all fetuses to evaluate corpus callosum-fastigium length and tectal length in the midsagittal plane. Intra- and interobserver agreement was evaluated using the intraclass correlation coefficient and Bland-Altman plots. A total of 70 fetuses with late-onset smallness (29 with SGA and 41 with FGR) and 70 controls were included. Compared with controls, small fetuses showed significantly shorter corpus callosum-fastigium length (median (interquartile range), 44.7 (43.3-46.8) mm vs 43.7 (42.4-45.5) mm, P < 0.001) and tectal length (mean ± SD, 10.5 ± 0.9 vs 9.6 ± 1.0 mm, P < 0.001). These changes were more prominent in FGR fetuses, with a linear trend across groups according to severity of smallness. Corpus callosum-fastigium length and tectal length measurements showed excellent intra- and interobserver reliability. Small fetuses exhibited shorter corpus callosum-fastigium length and tectal length compared with controls, and these differences were more pronounced in fetuses with more severe smallness. These findings illustrate the potential value of midbrain measurements assessed on neurosonography as biomarkers for brain development in a high-risk population. However, further studies correlating these parameters with postnatal functional tests and follow-up are needed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

External validation of Fetal Medicine Foundation competing-risks model for midgestation prediction of small-for-gestational-age neonates in Spanish population.

To examine the external validity of the new Fetal Medicine Foundation (FMF) competing-risks model for prediction in midgestation of small-for-gestational-age (SGA) neonates. This was a single-center prospective cohort study of 25 484 women with a singleton pregnancy undergoing routine ultrasound examination at 19 + 0 to 23 + 6 weeks' gestation. The FMF competing-risks model for the prediction of SGA combining maternal factors and midgestation estimated fetal weight by ultrasound scan (EFW) and uterine artery pulsatility index(UtA-PI) was used to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. The predictive performance was evaluated in terms of discrimination and calibration. The validation cohort was significantly different in composition compared with the FMF cohort in which the model was developed. In the validation cohort, at a 10% false-positive rate (FPR), maternal factors, EFW and UtA-PI yielded detection rates of 69.6%, 38.7% and 31.7% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks' gestation, respectively. The respective values for SGA < 3rd percentile were 75.7%, 48.2% and 38.1%. Detection rates in the validation cohort were similar to those reported in the FMF study for SGA with delivery at < 32 weeks but lower for SGA with delivery at < 37 and ≥ 37 weeks. Predictive performance in the validation cohort was similar to that reported in a subgroup of the FMF cohort consisting of nulliparous and Caucasian women. Detection rates in the validation cohort at a 15% FPR were 77.4%, 50.0% and 41.5% for SGA < 10th percentile with delivery at < 32, < 37 and ≥ 37 weeks, respectively, which were similar to the respective values reported in the FMF study at a 10% FPR. The model had satisfactory calibration. The new competing-risks model for midgestation prediction of SGA developed by the FMF performs well in a large independent Spanish population. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

New bioelectrical impedance vector references and phase angle centile curves in 4,367 adults: The need for an urgent update after 30 years

The bioelectrical impedance vector analysis (BIVA) represents a qualitative analysis of body composition. The vector, defined by resistance (R) and reactance (Xc) standardized by stature, can be evaluated compared to the 50%,75%, and 95% tolerance ellipses representative of the reference populations. The tolerance ellipses for healthy adults have been provided in 1995 and were developed by mixing underage, adult, and elderly subjects, possibly misrepresenting the actual adult population. The current multicentric, cross-sectional study aimed to provide new tolerance ellipses specific for the general adult population and as a secondary aim to present centile curves for the bioelectrical phase angle. R, Xc, and phase angle were measured in 2137 and 2230 males and females using phase-sensitive foot-to-hand analyzers at 50kHz. A minimum of 35 subjects were included for each sex and age category from 18 to 65 years. The new mean vectors showed a leftward shift on the R-Xc graph with respect to the former reference values (males: F=75.3; p<0.001; females: F=36.6, p<0.001). The results provided new 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97th percentile curves for phase angle, identifying time point phases of decrement (males:-0.03° per year at 33.0-51.0 years and-0.05° per year after 51 years; females:-0.03° per year from 37.2 to 57.9 years). Compared to the original references, the new data are characterized by a different distribution within the R-Xc graph with a higher phase angle. Thirty years after the BIVA invention, the current study presents new tolerance ellipses and phase angle reference values for the adult population.

Predictive factors of catch-up growth in term, small for gestational age infants: a two-year prospective observational study in Algeria.

Most small for gestational age (SGA) infants show catch-up growth but the minority who do not may benefit from growth-promoting treatment. We determined the prevalence of, and risk factors for, failure to show catch-up growth in term SGA infants. Prospective observational study of infants born at 37-42 weeks gestation between December 2012 and March 2014 with birth weight <10th percentile. Length, weight and head circumference were measured from birth to 2 years. Of 457 (3.9 %) term infants with SGA, 446 (97.6 %) were followed up until 2 years. At 24 months, supine length, weight and head circumference were ≥-2 standard deviation score (SDS) in 87.9 , 96.4 and 97.1 % subjects, with persistent short stature in 12.1 %. In a multivariate analysis, the independent predictors of failure to show catch-up growth at 24 months were: maternal height <150 cm, difference between mid-parental height and birth length of ≥2.2 SDS, height at 24 months <-2 SDS below mid-parental height SDS, history of SGA, ponderal index <3rd centile and duration of breast feeding <3 months. This study provides data concerning the epidemiology of SGA in Algeria and the factors associated with post-natal growth. Establishing which children remain short at 2 years has identified a cohort of patients requiring continuing follow up, with a view to instituting growth hormone therapy in selected cases. These results favour the setting up of an integrated national program to register SGA infants at birth, with re-evaluation at 2 years. (250 words).

Risk of adverse pregnancy outcome in isolated single umbilical artery diagnosed at the mid-trimester anomaly scan: a large Danish retrospective cohort study

Objective To examine the association of isolated single umbilical artery (iSUA) confirmed at the mid-trimester anomaly scan and adverse pregnancy outcome and congenital malformations with up to 10 years postnatal follow up. Methods This retrospective cohort study included 116,501 singleton pregnancies consecutively enrolled in first trimester screening for aneuploidies and mid-trimester anomaly scan at three University Hospitals in the Capital Region of Copenhagen, Denmark. Data from the Danish Fetal Medicine Database (2008–2017) were verified by manually scrutinizing pre- and postnatal records. The main outcomes of interest were intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, cesarean section and unrecognized pre- and postnatal congenital malformations. Results In total, 775 pregnancies with iSUA were identified. Isolated SUA were associated with a significantly increased risk of IUFD (OR 4.16, 95% CI 2.06–8.44), SGA < 3rd centile (aOR 2.41, 95% 1.85–3.14) and SGA < 10th centile (aOR 1.84, 95% CI 1.53–2.21), but not with preterm delivery or cesarean section. The laterality of the missing artery was not associated with SGA. In total, 4.3% of pregnancies with iSUA had unrecognized congenital malformations. 1.5% with iSUA had congenital cardiovascular malformations, which were considered minor. Conclusion Isolated SUA is associated with IUFD and SGA, supporting surveillance during third trimester. If, during the mid-trimester scan, the sonographer achieves thorough, extended cardiac views and finds no additional malformation other than SUA, fetal echocardiography seems not to be needed.

Shunt fracture as ventriculoperitoneal shunt complication in pediatric: a case series

Link of Video Abstract: https://youtu.be/7m2n6og9EUIBackground: Shunt fracture is a ventriculoperitoneal (VP) complication requiring shunt revision. The author discusses the experience of treating 5 cases of hydrocephalus patients with shunt fracture, including a clinical manifestation, nutritional status, and age of VP shunt insertion as a risk factor of shunt fracture will be discussed further in this case series report. Case Presentation: This study analyzed all cases treated in 6 years from 2016 to 2021, with an inclusion criterion of all pediatric patients with shunt fractures. This study is a retrospective report of the clinical manifestations and diagnoses assessed for pre-procedural and post-procedural conditions. Eight hundred fifty-two patients with hydrocephalus with VP shunt insertion and 5 patients with shunt fracture were reported. Headache, lump in the shunt line, vomiting, and seizure were the main complaints of all patients. Four of the five patients had poor nutritional status (&lt;50th and &lt;3rd percentile). One patient had a shunt removal, two had a shunt revision, and two had a laparoscopic shunt extraction and VP shunt insertion. All patients had improved clinical outcomes. Conclusion: Knowing the process of shunt fracture is essential as a modality to determine the subsequent management. A comprehensive clinical and radiological examination is mandatory to rule out a shunt fracture. Monitoring patients with VP shunt is an important thing that must be done to prevent further complications.

Fetal Heart Rate < 3rd Percentile for Gestational Age Can Be a Marker of Inherited Arrhythmia Syndromes.

Repeated fetal heart rates (FHR) < 3rd percentile for gestational age (GA) with 1:1 atrioventricular conduction (sinus bradycardia) can be a marker for long QT syndrome. We hypothesized that other inherited arrhythmia syndromes might present with fetal sinus bradycardia. We reviewed pregnancies referred with sinus bradycardia to the Colorado Fetal Care Center between 2013 and 2023. FHR/GA data, family history, medication exposure, normalized isovolumic contraction times (n-IVRT), postnatal genetic testing, and ECGs at 4-6 weeks after birth were reviewed. Twenty-nine bradycardic subjects were evaluated by fetal echocardiography. Five were lost to follow-up, one refused genetic testing, and one had negative genetic testing for any inherited arrhythmia. Six had non-genetic causes of fetal bradycardia with normal prenatal n-IVRT and postnatal QTc. Thirteen carried pathogenic variants in RYR2 (n = 2), HCN4 (n = 2), KCNQ1 (6), and other LQTS genes (n = 4). The postnatal QTc was <470 ms in subjects with RYR2, HCN4, and two of those with KCNQ1 mutations, and >470 ms in subjects with CALM 2, KCNH2, SCN5A, and four of those with KCNQ1 mutations. LQTS and RYR2 mutations were associated with prolonged n-IVRT, but HCN4 was not. Two fetuses died in utero with variants of uncertain significance (CACNA1 and KCNE1). Cascade testing uncovered six affected but undiagnosed parents and confirmed familial inheritance in five. In addition to heralding LQTS, repeated FHR < 3rd percentile for GA is a risk factor for other inherited arrhythmia syndromes. These findings suggest that genetic testing should be offered to infants with a history of FHR < 3rd percentile for GA even if the postnatal ECG demonstrates a normal QTc interval.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Management of late-onset fetal growth restriction: pragmatic approach.

There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus

Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

P-622 Age-specific reference intervals for anti-müllerian hormone in Mexico: A population-based study. implications for Latin America

Abstract Study question To determine the age-specific normal range of antimullerian hormone (AMH) levels in a female Latin American population. Summary answer Age-related nomograms for general population for the 3rd-97th percentiles were produced. These nomograms could provide a reference guide for clinicians to consult women with infertility. What is known already The variation of AMH levels among different races and ethnicities has been well documented (Seifer et al., 2009). Despite the wide use of AMH measurements in clinical assessment of ovarian reserve, a population-based estimate for its reference range in Latin America is not available. Study design, size, duration A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed from January 2017 to December 2018 at a large clinical laboratory network in the Mexico City area, encompassing 35 locations. A total of 6444 AMH measurements were included. Participants/materials, setting, methods AMH was assayed using either the cobas or ELISA methodologies. All AMH measurements from women 25-45 years were included. The Kolmogorov-Smirnov test was used to confirm that AMH levels between patients assayed with cobas were comparable to those assayed with ELISA at every age. Main results and the role of chance In total, 6444 measurements were identified and available for analysis. Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. The overall rate of AMH decline accelerated after 40 years of age. In women 25-30 years, 11.4% (63/554) had an AMH &amp;lt;1.0ng/mL. In women 30-35 years, 18.6% (276/1484) had an AMH &amp;lt;1.0ng/mL. In women 35-40 yeras, 35.8% (830/2319) had an AMH &amp;lt;1.0ng/mL. In women 40-45 years, 58.0% (1120/1932) had an AMH &amp;lt;1.0ng/mL. Limitations, reasons for caution The lack of medical history for patients precluded identification and exclusión of patients with iatrogenically abnormal AMH levels (e.g. due to oophorectomy). Patients undergoing measurement of AMH were primarily referred through fertility clinics, limiting the potential for extrapolation to the general population. Wider implications of the findings The study reports age-specific AMH levels drawn from a large sample of women around Mexico City. The study includes the largest dataset to date. Latin American patients considering fertility preservation should be aware of the high prevalence of diminished ovarian reserve in this large cohort, including among women 35-39. Trial registration number Not Applicable

Correlation of placental lesions in patients with systemic lupus erythematosus, antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and adverse perinatal outcomes

IntroductionWe aimed to describe the pattern of placental injuries in women with systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) and non-criteria obstetric APS (NC-OAPS), and to correlate the placental findings with the occurrence of adverse perinatal outcomes. MethodsThe perinatal outcomes and placental findings of pregnancies of women with SLE, APS, and NC-OAPS and gestational-age matched healthy controls were analyzed and classified according to the 2015 Redline - Classification of placental lesions. Results91 women with SLE, APS, and NC-OAPS and 91 controls were included. Mean values of placental weight differed between groups, being significantly lower in NC-OAPS and APS groups compared to controls. Furthermore, 14.3% of placentas in the APS group were under the 3rd percentile, which was significantly higher in comparison with other groups.Regarding histopathological placental findings, maternal-side malperfusion was significantly increased in APS (46.4%) compared to NC-OAPS (14.3%) and SLE (9.5%). Fetal-side maldevelopment was significantly increased in NC-OAPS (19.1%) compared to controls (1.1%) and SLE (2.4%). A significantly increased prevalence of adverse perinatal outcomes (APOs) was observed in all studied groups compared to healthy controls (controls 3.3%, SLE 52.4%, NC-OAPS 57.1%, APS 64.3%). Overall, both maternal (OR 6.8, 95%CI 2.1–22) and fetal-side (OR 4.1, 95%CI 1.3–13.5) lesions were significantly associated with APO. Maternal malperfusion and fetal maldevelopment were the lesions most strongly associated with APOs. DiscussionPregnant women with SLE, APS, or NC-OAPS showed a different pattern of histopathological findings. Compared to controls, SLE, APS, and NC-OAPS conferred an increased risk of APOs that was strongly associated with placental maternal-side malperfusion and fetal-side maldevelopment.

Fetal growth restriction and small for gestational age as predictors of neonatal morbidity: which growth nomogram to use?

Fetal growth nomograms were developed to screen for fetal growth restriction and guide clinical care to improve perinatal outcomes; however, existing literature remains inconclusive regarding which nomogram is the gold standard. This study aimed to compare the ability of 4 commonly used nomograms (Hadlock, International Fetal and Newborn Growth Consortium for the 21st Century, Eunice Kennedy Shriver National Institute of Child Health and Human Development-unified standard, and World Health Organization fetal growth charts) and 1 institution-specific reference to predict small for gestational age and poor neonatal outcomes. This was a retrospective cohort study of all nonanomalous singleton pregnancies undergoing ultrasound at ≥20 weeks of gestation between 2013 and 2020 and delivering at a single academic center. Using random selection methods, the study sample was restricted to 1 pregnancy per patient and 1 ultrasound per pregnancy completed at ≥22 weeks of gestation. Fetal biometry data were used to calculate estimated fetal weight and percentiles according to the aforementioned 5 nomograms. Maternal and neonatal data were extracted from electronic medical records. Logistic regression was used to estimate the association between estimated fetal weight of <10th and <3rd percentiles compared with estimated fetal weight of 10th to 90th percentile as the reference group for small for gestational age and the neonatal composite outcomes (perinatal mortality, hypoxic-ischemic encephalopathy or seizures, respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, hyperbilirubinemia or hypoglycemia requiring neonatal intensive care unit admission, and retinopathy of prematurity). Receiver operating characteristic curve contrast estimation (primary analysis) and test characteristics were calculated for all nomograms and the prediction of small for gestational age and the neonatal composite outcomes. We restricted the sample to ultrasounds performed within 28 days of delivery; moreover, similar analyses were completed to assess the prediction of small for gestational age and neonatal composite outcomes. Among 10,045 participants, the proportion of fetuses classified as <10th percentile varied across nomograms from 4.9% to 9.7%. Fetuses with an estimated fetal weight of <10th percentile had an increased risk of small for gestational age (odds ratio, 9.9 [95% confidence interval, 8.5-11.5] to 12.8 [95% confidence interval, 10.9-15.0]). In addition, the estimated fetal weight of <10th and <3rd percentile was associated with increased risk of the neonatal composite outcome (odds ratio, 2.4 [95% confidence interval, 2.0-2.8] to 3.5 [95% confidence interval, 2.9-4.3] and 5.7 [95% confidence interval, 4.5-7.2] to 8.8 [95% confidence interval, 6.6-11.8], respectively). The prediction of small for gestational age with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 6.3 to 8.5 and an area under the curve of 0.62 to 0.67. Similarly, the prediction of the neonatal composite outcome with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 2.1 to 3.1 and an area under the curve of 0.55 to 0.57. When analyses were restricted to ultrasound within 4 weeks of delivery, among fetuses with an estimated fetal weight of <10th percentile, the risk of small for gestational age increased across all nomograms (odds ratio, 16.7 [95% confidence interval, 12.6-22.3] to 25.1 [95% confidence interval, 17.0-37.0]), and prediction improved (positive likelihood ratio, 8.3-15.0; area under the curve, 0.69-0.75). Similarly, the risk of neonatal composite outcome increased (odds ratio, 3.2 [95% confidence interval, 2.4-4.2] to 5.2 [95% confidence interval, 3.8-7.2]), and prediction marginally improved (positive likelihood ratio, 2.4-4.1; area under the curve, 0.60-0.62). Importantly, the risk of both being small for gestational age and having the neonatal composite outcome further increased (odds ratio, 21.4 [95% confidence interval, 13.6-33.6] to 28.7 (95% confidence interval, 18.6-44.3]), and the prediction of concurrent small for gestational age and neonatal composite outcome greatly improved (positive likelihood ratio, 6.0-10.0; area under the curve, 0.80-0.83). In this large cohort, Hadlock, recent fetal growth nomograms, and a local population-derived fetal growth reference performed comparably in the prediction of small for gestational age and neonatal composite outcomes.

Effects of antenatal dexamethasone on postnatal serum cortisol levels in late preterm infants

Objectives To explore whether antenatal dexamethasone impacts postnatal serum cortisol levels in stable late preterm (LPT) infants. Secondary outcomes were to identify short-term hospital outcomes related to antenatal dexamethasone exposure. Methods A prospective cohort study of serial serum cortisol levels in LPT infants within 3 h of birth, and at 1, 3, and 14 postnatal days. Serum cortisol levels were compared between infants exposed to antenatal dexamethasone >3 h and <14 days prior to delivery (aDex) and those who either did not receive dexamethasone or were exposed < 3 h or >14 days prior to delivery (no-aDex). Results Thirty-two LPT infants (aDex) were compared with 29 infants (no-aDEX). Group demographic characteristics were similar. Serum cortisol levels were identical between the groups at all 4-time points. Cumulative antenatal dexamethasone exposure ranged from 0 to 12 doses. Post-hoc analysis of the 24-hour serum cortisol levels indicated a significant difference between 1 to 3 cumulative doses versus 4 or more doses (p = .01). Only 1 infant in the aDex group had a cortisol level <3rd percentile of the reference value. Rates of hypoglycemia (absolute difference [95% CI] − 1.0 [–16.0,15.0]; p = .90) and mechanical ventilation were similar in both groups (absolute difference [95%CI] − 0.3 [–9.3,8.7]; p = .94). No deaths occurred. Conclusion Antenatal dexamethasone administered 14 days prior to delivery did not affect serum cortisol levels and short-term hospital outcomes in stable LPT infants. Exposure to low cumulative doses of dexamethasone resulted in transient low serum cortisol levels compared to 4 or more doses only at 24-hours.

Establishment and validation of a prognostic risk classification for patients with stage T1-3N0M0 esophageal squamous cell carcinoma

IntroductionAt present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model.MethodsStage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses.ResultsThe Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders.ConclusionsWe combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients.