95th Centile Research Articles

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study

BackgroundThe aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. MethodsThis was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000–2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests.Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. FindingsThe final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0·19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13·2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0·74%), with the highest rate (19·6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7·59% livebirths), with the peak incidence occurring in the <1st centile category (12·3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10–90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. InterpretationAlthough the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently “appropriately grown” (i.e., birthweight 10th - 90th centile). FundingNational Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women’s Health Foundation – Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Pharmacovigilance of nephrotoxic drugs in neonates: the Pottel method for acute kidney injury detection in ELBW neonates

BackgroundExtremely low birth weight (ELBW) neonates (birth weight ≤ 1000 g) are at high risk to develop drug-induced acute kidney injury (AKI). However, we lack a pragmatic detection tool to capture their time-dependent (patho)physiologic serum creatinine (Scr) patterns. Pottel et al. suggested rescaling Scr by dividing Scr with the mean Scr value of the age- and sex-specific reference population. We explored if this Pottel method can detect drug-related nephrotoxicity in ELBW neonates.MethodsA previously reported dataset on Scr changes in ELBW neonates exposed to ibuprofen, amikacin, or vancomycin was updated to calculate Pottel scores for every available Scr value in the first 28 postnatal days. We hereby used previously published postnatal age-specific 50th centile values in an ELBW population. Linear mixed models were applied, analyzing Pottel scores as response variable and continuous time (day), drug exposure, and interaction thereof in the explanatory model.ResultsSerum creatinine (n = 3231) observations in 201 ELBW neonates were collected. A statistically significant rise of Pottel scores was observed with ibuprofen starting from postnatal day 4. In addition, a cumulative effect of treatment with mean Pottel scores on day 0 of 1.020 and on day 3 during treatment of 1.106 (95% CI 1.068–1.145, p < 0.001) was observed, corrected for effect of antibiotics. Antibiotic administrations showed a small but statistically significant difference up to postnatal day 5.ConclusionsAs rescaled Scr biomarker, the Pottel method showed a clear association with ibuprofen-exposed ELBW neonates, suggesting its applicability as a pragmatic bedside alternative tool to assess nephrotoxicity.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Predicting Time to Delivery in Hypertensive Disorders: Assessing PlGF and sFlt-1 with the Novel Parameter 'Mtp-Multiples of a Normal Term Placenta'.

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio.

Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p=1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p<0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39weeks in neither the cohort (38.7weeks) nor the pooled literature (37.6weeks). An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39weeks of gestation. After 39weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.

Lifespan development of thalamic nuclei and characterizing thalamic nuclei abnormalities in schizophrenia using normative modeling.

Thalamic abnormalities have been repeatedly implicated in the pathophysiology of schizophrenia and other neurodevelopmental disorders. Uncovering the etiology of thalamic abnormalities and how they may contribute to illness phenotypes faces at least two obstacles. First, the typical developmental trajectories of thalamic nuclei and their association with cognition across the lifespan are largely unknown. Second, modest effect sizes indicate marked individual differences and pose a significant challenge to personalized medicine. To address these knowledge gaps, we characterized the development of thalamic nuclei volumes using normative models generated from the Human Connectome Project Lifespan datasets (5-100+ years), then applied them to an independent clinical cohort to determine the frequency of thalamic volume deviations in people with schizophrenia (17-61 years). Normative models revealed diverse non-linear age effects across the lifespan. Association nuclei exhibited negative age effects during youth but stabilized in adulthood until turning negative again with older age. Sensorimotor nuclei volumes remained relatively stable through youth and adulthood until also turning negative with older age. Up to 18% of individuals with schizophrenia exhibited abnormally small (i.e., below the 5th centile) mediodorsal and pulvinar volumes, and the degree of deviation, but not raw volumes, correlated with the severity of cognitive impairment. While case-control differences are robust, only a minority of patients demonstrate unusually small thalamic nuclei volumes. Normative modeling enables the identification of these individuals, which is a necessary step toward precision medicine.

Creatinine as a predictor of muscle mass deficiency in patients with severe cerebral palsy

Energy processes in muscles can be reflected by the creatine phosphokinase system of ATP resynthesis from ADP and creatine phosphate. The product of non-enzymatic degradation of creatine (creatine phosphate) is creatinine, which accumulates in the blood serum, and its concentration correlates with the volume of the patient’s muscle tissue, subject to the normal functioning of the kidneys. Purpose. To assess the perioperative serum creatinine level as a biological marker of muscle mass in patients with severe forms of cerebral palsy, IV–V level according to GMFCS, during orthopedic interventions on the hip joint. Material and methods. A prospective clinical observational study included 82 patients with severe forms of cerebral palsy, spastic dislocations (subluxations) of the hips, for which reconstructive or palliative interventions were performed on the hip joints. The trophological status of children was assessed before surgery, the level of serum creatinine was determined in the intraoperative period, on the first postoperative day, and on the fifth day after surgery. Results. The circumference of the middle third of the shoulder in 28 % of patients, as well as the thickness of the skin-fat fold over the triceps in 61 % of children were below the 10th centile, which was regarded as malnutrition. The calculated proportion of body fat equal to 10 [8; 20] % in combination with the circumference of the muscles of the middle third of the shoulder suggest a combination of protein-energy deficiency and muscle mass deficiency in 1/5 of the patients. Creatinine indicators at all stages of observation corresponded to the minimum age norm or were below these values, tended to decrease and had a random agreement (W = 0,129). Conclusion. The level of creatinine in the blood serum correlates with the «shoulder muscle circumference» parameter in children with severe forms of cerebral palsy, severe movement disorders of IV–V level according to GMFCS. Plasma creatinine can be used as a biological marker of skeletal muscle mass in patients with severe cerebral palsy.

Generation of South Indian Data for Normal Clitoral Dimensions and Anogenital Ratio in Term Neonates.

Assessment of genitalia is an important part of the neonatal examination. Regional, racial, and ethnic variations in phallic length have been documented. Clitoral dimensions may also show similar variations. Normal values for neonatal clitoral measurements may help the pediatrician/neonatologist to accurately diagnose clitoromegaly and underlying etiology to guide appropriate investigations. Data on clitoral measurements is limited with only one study from India (Kolkata). Hence we aimed in this study to generate south Indian data on neonatal clitoral dimensions, anogenital distance, and anogenital ratio. Two hundred and fifty two hemodynamically stable term female neonates without ambiguous genitalia/vulval masses born in a community hospital. Hospital-based cross-sectional study. 1. To measure clitoral dimensions, anogenital distance, and anogenital ratio in female neonates. 2. To correlate clitoral dimensions, anogenital distance, and ratio with anthropometric measurements, gestational age, and maternal comorbidities. Measurements were recorded using a digital vernier caliper, under strict aseptic precautions with labia majora gently separated and the baby held in a frog-leg position. Clitoral length, width, and anogenital distance were measured and anogenital ratio and clitoral index were calculated. In term neonates, the mean ± SD of clitoral length (CL), clitoral width (CW), anogenital ratio (AGR) were 6.34 ± 1.75 mm, 6.39 ± 1.27 mm and 0.39 ± 0.05, respectively. The 3rd and 97th centiles for mean clitoral length were 3.55 and 9.93 mm, for mean clitoral width were 3.37 and 8.35 mm, and for AGR were 0.28 and 0.48, respectively. These clitoral dimensions in south Indian neonates were higher than those from East India (Kolkata), lower than Nigerian babies, and similar to Israeli neonates. Mean CL and CW had no statistical correlation with birth weight, gestational age, head circumference, or length in term neonates. A significant correlation was noted between pregnancy-induced hypertension and mean clitoral width, and between gestational diabetes and AGR. Normative values for clitoral dimensions (length and width) and AGR for south Indian term female neonates have been established. 97th centiles of 9.93 mm (CL) and 8.35 mm (CW) and 0.48 mm (AGR) may be used as practical cut-offs to diagnose clitoromegaly and virilization. Clitoral measurements had no statistical correlation with birth weight, gestational age, or anthropometry. Clitoral measurements exhibit ethnic and racial differences, thus emphasizing the importance of regional cut-offs and need for more studies from different parts of India on CL.

Placentae of small appropriately-grown-for-gestational-age neonates exhibit sexually dimorphic transcriptomic changes representative of placental insufficiency

IntroductionPrevious studies have reported that neonates less than the 25th BWC especially if they were male, were more likely to be associated with birth complications suggesting small neonates often identified as appropriately grown are at risk of adverse outcomes. We have questioned whether smaller neonates not typically categorized as “small for gestational age” may not reach their genetically determined growth due to placental insufficiency. MethodsRNA-Seq was performed on the Illumina NovaSeq 600 using term placentae from neonates that were less than the 10th birthweight centile (BWC) (n = 39), between the 10th and the 30th BWC (n = 15) or greater than the 30th BWC (n = 23). Bioinformatic analyses were conducted and statistical significance was assessed at a level of P < 0.05 for single comparisons or FDR <0.05 unless otherwise noted. ResultsGene set enrichment analysis revealed differences between BWC groups and in relation to the sex of the placenta. Genes associated with hypoxia, inflammatory responses, estrogen responsive genes, and androgen responsive genes were enriched (FDR <0.1) for in placentae of neonates <10th BWC regardless of sex and also in male placentae of neonates between the 10th-30th BWC. Female placenta of neonates between the 10th-30th BWC were comparable to placentae of neonates >30th BWC. DiscussionThese findings provide evidence that small male neonates may be at a greater risk of an adverse outcome than females due to changes in gene expression that are associated with placental dysfunction. The current data raises questions of whether placental pathology for smaller appropriately grown neonates should be scientifically and clinically examined in more depth.

A286 MYO5B MUTATIONS AS A CAUSE OF CHOLESTASIS IN A CHILD WITHOUT MICROVILLOUS INCLUSION DISEASE

Abstract Background Biallelic Myosin Vb (MYO5B) mutations are identified in the majority of patients with microvillus inclusion disease (MVID) that requires life-long parenteral nutrition and eventually cholestatic liver disease. Biallelic MYO5B mutations have also been reported in a few children with predominant early-onset cholestatic liver disease. Aims To report on a patient with MYO5B mutations and progressive familial intrahepatic cholestasis PFIC-like phenotype and normal serum GGT without intestinal disease. Methods We describe a 2-year and 8-month-old girl, who is the first child of healthy non- consanguineous parents from the Phillipines with no family history of liver disease. She presented at the age of 10 months for evaluation of mild jaundice, which was noticed at the age of 6 months. Other symptoms included pruritus, slowly weight gain, intermittent pale stools and dark urine. Laboratory investigations revealed AST 99, ALT 87, GGT 27, conjugated bilirubin 13 and INR 0.8. Fasting abdominal ultrasound was normal apart from a possibly hypoplastic gallbladder and mild splenomegaly. Additional investigations revealed normal thyroid-stimulating hormone, cortisol, galactosemia screening and sweat chloride, but bile acids were elevated 391.6 umol/L. A liver biopsy was performed and a cholestasis genetic panel sent. The patient was started on ursodiol, hydroxyzine, rifampicin and vitamin D. Results Liver biopsy revealed moderate hepato-canalicular cholestasis, bile duct injury without prominent ductopenia, small caliber bile ducts with no features of obstructive cholangiopathy, mild periportal and pericentral fibrosis stage 1-2/ 4. Electron microscopy demonstrated cytoplasmic and canalicular bile accumulation. The bile canaliculi were variably distended by coarse granular bile. Immunohistochemical staining for BSEP and MDR3, showed canalicular staining in zones 1 and absence of staining in zones 2 and 3. Genetic analysis revealed one pathogenic variant and one variant of uncertain significance in MYO5B. No mutations in ABCB11 or ATP8B1 genes were identified. On follow-up, the jaundice improved, pruritus was managed with the medications described above. Her growth has improved and she is growing on the 25th centiles. She has not developed any gastrointestinal symptoms. Conclusions We present a patient with MYO5B mutations who presented with normal GGT cholestasis and a liver biopsy consistent with PFIC, without any evidence of intestinal disease. Because MYO5B mutations disrupt the intracellular trafficking of brush border proteins in the intestine, it has been assumed that it similarly disrupts the trafficking of the canalicular bile acid transporting and bilirubin transporting proteins in the liver. This case highlights the broad phenotype associated with MYO5B variants. Funding Agencies None

Late selective termination in dichorionic twins: comparing late second and third trimester procedures

Research questionDo perinatal outcomes of selective termination performed in the late second versus third trimester differ and what risk factors are associated with subsequent preterm birth? DesignThis is a retrospective cohort study of late selective terminations performed in dichorionic twins between 2009 and 2021. Perinatal outcomes were compared between two groups: group A, late second trimester (20.2 to 24.2 weeks, n = 26), and group B, third trimester (≥28.2 weeks, n = 55) selective terminations. Univariate and multivariate analyses were conducted to identify factors associated with post-procedure preterm birth. ResultsIn total, 81 dichorionic twin pregnancies were included. There were no pregnancy losses but 16% (13/81) of cases experienced complications. Group A had a higher median birthweight centile (36.5th versus 15th centile, P = 0.002) and lower rates of intrauterine growth restriction (IUGR) and Caesarean delivery (11.5% versus 32.7%, P = 0.04; and 26.9% versus 61.8%, P = 0.003) than group B. Preterm birth rates were similar (46.2% versus 63.6%, P = 0.15). Multiple regression revealed that reduction of the presenting twin and cervical length ≤35 mm were independently associated with post-procedure preterm birth (odds ratio [OR] 8.7, P = 0.001, 95% confidence interval [CI] 2.5–29.8; OR 3.8, P = 0.015, 95% CI 1.3–11). ConclusionsLate second trimester selective termination is associated with a higher birthweight centile and lower rates of IUGR and Caesarean delivery, compared with third trimester selective termination. Cervical length 35 mm or less and reduction of the presenting twin are independent risk factors for post-procedural preterm birth. These findings may help determine the optimal time to perform a late selective termination.

Doppler ultrasound of umbilical and middle cerebral artery in third trimester small-for-gestational age fetuses to decide on timing of delivery for suspected fetal growth restriction: A cohort with nested RCT (DRIGITAT).

To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small-for-gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Multicentre cohort study with nested randomised controlled trial (RCT). Nineteen secondary and tertiary care centres. Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Women were classified: (1) RCT-eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT-eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. The cohort consisted of 690 women. The study was halted prematurely for low RCT-inclusion rates (n = 40). In the RCT-eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59-0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near-significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre-eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67-0.76). Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34-36 weeks should only be performed in the context of clinical trials.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

New definitions, old complications: The association between duration of transition from latent to active labor and adverse obstetrical outcomes.

To explore the relationship between the duration of transition from latent to active labor and various obstetric, maternal, fetal, and neonatal outcomes. A retrospective cohort study was conducted on term, singleton deliveries at Soroka University Medical Center from 2013 to 2018. Data were extracted from electronic medical records. The exposure variable was defined as prolonged transition, which was itself defined as the upper 10th centile of dilation duration from 4 to 6 cm. Clinical and demographic characteristics were compared using χ2 test. Multivariate logistic regression was used to estimate the contribution of a prolonged transition with each adverse outcome adjusting for potential confounders. In all, 12 104 deliveries met the inclusion criteria. The mean ± standard deviation of duration of dilation from 4 to 6 cm was 03:07:58 ± 03:03:42 (hours:minutes:seconds). Progress curves varied significantly among patients with different obstetrical and demographic characteristics. Prolonged transition was significantly linked to an increased risk of cesarean delivery (adjusted odds raito 2.607, 95% confidence interval 2.171-3.130, area under the curve 0.689) and higher rates of maternal and neonatal morbidity. Patients experiencing transition phases exceeding the 90th centile faced an elevated risk of cesarean delivery and postpartum complications. Future studies should focus on interventions during the transition phase to improve pregnancy outcomes and enhance patient safety.

Effects of uterine Doppler on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study

Objective To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values. Methods This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33–44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. Results The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49–45.53) vs abnormal UtA PI 25.31(19.76–35.13) mm; p < 0.0022), CV (normal 25.78 (18.19–29.35) abnormal UtA PI 17.03 (14.07–24.16)mm; p = 0.0067); SF (normal 10.58 (8.99–11.97)vs abnormal UtA PI 7.44 (6.23–8.46) mm; p < 0.0001), POF (normal 6.85 (6.35–8.14) vs abnormal UtA PI 4.82 (3.46–7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85–5.41) vs abnormal UtA PI 2.33 (2.49–4.01)); p < 0.0382). Conclusions Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

Nomogram for fetal limb bones in Chinese ethnicity

Objective To construct fetal limb bone nomograms in the Chinese ethnic population. Methods This was a prospective cross-sectional study on singleton pregnancies between 12 and 37 weeks of gestation. Femur, tibia, fibula, humerus, ulna, radius, and foot length were measured in a standardized manner by one of the three sonographers. Each fetus’s measurements were only included once and those who developed maternal or fetal complications were excluded. Fractional polynomial regression model was used to obtain the 3rd, 10th, 50th, 90th, and 97th centiles for each of the limb measurement. Z-score for the 50th centile of each fetal limb measurement was then compared with published nomograms derived from other populations. Results Of the 843 scans performed, 775 were included in analysis after excluding conditions such as pre-eclampsia, chromosomal abnormalities, single umbilical artery and skeletal dysplasia. Comparison with other populations showed that Chinese had shorter fetal limb bone lengths than the Caucasian and Afro-Caribbean populations. Conclusion This study established nomograms for all the fetal limb bones in the Chinese ethnic population, which showed lengths comparatively shorter than Caucasian and Afro-Caribbean nomograms. This would reduce the false alarm of short fetal limb bone lengths and its consequent anxiety and intervention.

Risk Stratification of Foetuses based on Estimated Foetal Weight less than the 40th Percentile and Evaluation of Perinatal Outcomes using Third-trimester Obstetric Ultrasound: A Prospective Cohort Study

Introduction: Perinatal mortality and morbidities constitute a burden on society and healthcare system. One of the major identifiable causes of these conditions in India is Low Birth Weight (LBW) and preterm births. Small for Gestational Age (SGA) infants account for almost 46.9% of LBW infants. They are prone to the morbidities of preterm birth and are the second major contributor to perinatal mortality. Recent studies have reported that higher screening performance for SGA can be achieved through ultrasonographic foetal biometry and Doppler studies during the third trimester. Aim: To stratify foetuses with Estimated Foetal Weight (EFW) below the 40th centile, as determined by obstetric ultrasound, into three categories (low, intermediate, and high-risk), and study the perinatal outcomes in each category. Materials and Methods: The present prospective cohort study was conducted in the Department of Obstetrics and Gynaecology at Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India from November 2020 to April 2022. A total of 280 antenatal women, at a gestational period between 35 to 36+6 weeks with singleton pregnancies, were studied and based on the foetal biometry and Doppler parameters, women were classified into low (Group A), intermediate (Group B) and high risk (Group C) categories. Risk categorisation was based on EFW and Doppler indices. The low-risk group underwent an ultrasound Doppler scan after four weeks, the intermediate-risk group after two weeks, and the high-risk group was scanned weekly. The high-risk group was delivered at 39 weeks of gestation. Perinatal outcomes, neonatal weights, adverse neonatal outcomes {such as Neonatal Intensive Care Unit (NICU) admissions exceeding 48 hours}, stillbirths, and neonatal deaths were recorded. The Area under Curve (AUC) cut-off for EFW percentiles on ultrasonography was calculated as a predictor for SGA foetuses requiring NICU admissions. Concurrent admissions in the NICU of neonates delivered to unregistered pregnant mothers, who were not screened during the antenatal period, were also recorded. The Chi-square test was used to compare categorical data between groups. The receiver operating characteristic curve was used to determine the cut-off for foetal weight to predict NICU admission. A p-value of &lt;0.05 was considered statistically significant. Results: Among the study population, 231 (82.6%) were between 21-30 years of age, and 250 (88.87%) had a normal Body Mass Index (BMI) with a mean age of 25.78±3.90 years. On risk categorisation, 71 (25.1%), 82 (29%), and 127 (45.9%) women were in the high, intermediate, and low-risk categories, respectively. All the neonates in the high-risk group were classified as SGA according to the INTERGROWTH 21st growth chart. Among the neonates, 18 (6.4%) weighed below 2100 g, 35 (12.4%) weighed between 2101 to 2200 g, 62 (22.3%) weighed between 2201 to 2400 g, and 165 (59%) weighed above 2401 g. NICU admissions occurred in 25 (35.2%), 10 (12%), and 5 (3.8%) neonates in the high, intermediate, and low-risk groups, respectively (p-value &lt; 0.001). At a cut-off of EFW (g) less than or equal to 2122 g (between the 10th and 20th centile) during the first ultrasound, it predicted SGA neonates requiring NICU admissions with a sensitivity of 80% and a specificity of 70%. No stillbirths or neonatal mortality occurred in the study group. Conclusion: A single third-trimester obstetric ultrasound, along with Doppler measurements, should be performed at 35 to 36 weeks as an important adjunct for identifying and stratifying the risk of singleton foetuses. Close monitoring and timely delivery can help reduce adverse perinatal outcomes in SGA foetuses.

Assessing the external validity and clinical relevance of umbilical doppler resistance index references in daily practice

ObjectiveTo assess the external validity and clinical relevance of current references for umbilical artery resistance index (UA RI) in daily practice. MethodsRetrospective cross-sectional single center study including all UA RI measurements between 22 and 40 gestational weeks (GW) from distinct patients between 2014 and 2022. Patients with normal pregnancies and normal neonatal outcomes that had an UA RI measurement between 2014 and 2019 were used to calculate reference ranges. The established reference for the 95th centile was compared to two current references. The clinical relevance of the established reference was tested by comparing neonatal outcomes according to the 95th percentile among the consecutive distinct patients between 2020 and 2022. ResultsAmong the 13342 consecutive distinct patients with a singleton pregnancy that had an UA RI measurement between 22 and 40 GW between 2014 and 2022, 5298 patients were included to establish the reference ranges, and 3634 patients to validate these ranges. For each gestational age, the established references were similar to current references. Using the established references, the proportion of patients presenting an UA RI>95th percentile among the patients with normal pregnancies in the validation population was comparable to the proportion when using the two current references. Among the validation population, 268 patients (7.4 %) (95%CI[6.5-8.2]) presented an UA RI ≥ 95th percentile. Of these 268 patients, 67.9% had a SGA newborn (versus 19.2%, p<0.001) and 59% a preterm birth (versus 13.9%, p<0.001). ConclusionsThe reference range obtained from daily practice is clinically relevant and similar to current references.

Inequalities in adiposity trends between 1979 and 1999 in Guatemalan children.

Guatemala suffered from civil war and high levels of inequality and childhood stunting in the second half of the 20th century, but little is known about inequalities in secular trends in adiposity. To investigate differences in childhood body mass index (BMI) and skinfold thickness trajectories from 1979 to 1999 between three groups of children: High socioeconomic position (SEP) Ladino, Low SEP Ladino, and Low SEP Indigenous Maya. The sample comprised 19 346 children aged 7-17 years with 54 638 observations. The outcomes were height, BMI, triceps skinfold thickness (TST), and subscapular skinfold thickness (SST) Z-scores according to the Centers for Disease Control and Prevention (CDC) references. Sex-specific multilevel models were used to estimate and compare mean trajectories from 1979 to 1999 between the three groups. Mean Z-scores were always highest for High SEP Ladino children and lowest for Low SEP Maya children. Despite their very short stature, the Low SEP groups had SST trajectories that were above the 50th centile. The BMI trajectories were relatively flat and within one major centile band of the CDC median, with differences between the three groups that were small (0.2-0.3 Z-scores) and did not attenuate over time. Conversely, the TST Z-score trajectories demonstrated larger positive secular trends (e.g., from -1.25 in 1979 to -0.06 in 1999 for Low SEP Maya boys), with differences between the three groups that were large (0.5-1.2 Z-scores) and did attenuate over time (in boys). Secular trends and between-group difference in the SST Z-score trajectories were less pronounced, but again we found stronger evidence in boys that the estimated inequalities attenuated over time. Secular trends and inequalities in skinfolds differ from those for BMI in Guatemalan children. Differences between groups in skinfolds attenuated over time, at least in boys, but whether this is good news is questionable given the very short stature yet relatively large subscapular skinfolds of the Low SEP groups.

Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach nearterm.

Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.