SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD)  and higher rate of late-onset sepsis compared with intralipid . SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis—it is a double-edged sword.The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid–LE group had a lower Δ weight z-score compared to those in the intralipid group ( Very preterm infants are born with insufficient energy stores and underdeveloped gastrointestinal tract and immune systems . They reA new generation of lipid emulsions has been widely introduced. It comprises a mixture of 30% soybean oil, 30% medium-chain triglycerides (MCTs), 25% olive oil, and 15% fish oil: the so-called SMOFlipid (Fresenius Kabi). The major target of SMOFlipid is to reduce the soybean oil’s detrimental effects. A recent meta-analysis showed that SMOFlipid reduces the liver injury and hyperlipidemia and shortens the period of hospital stay; however, it could not reduce the important inflammatory markers in adults who are admitted for surgical reasons . AnotherIn the pediatric population, the Congress of Intestinal Rehabilitation and Transplantation showed that the trend of SMOFlipid use is moving up as the first-line choice for pediatric patients . A recenDespite limited evidence, use of SMOFlipid is increasing globally. A recent randomized controlled trial found that the antioxidant capacity was lower in preterm infants who received SMOFlipid than in other infants who received another intralipid form (ClinOleic) . It alsoThe aim of our study is to investigate the SMOFlipid impact on growth velocity, major neonatal outcomes, and preterm infants’ mortality.This retrospective chart review included a cohort of preterm infants who were admitted to the neonatal intensive care unit (NICU) of the King Saud Medical City (KSMC) tertiary referral center between January 2015 and January 2022.Including level 3, the NICU at KSMC has an average annual admission of 1100 patients. This study was conducted in accordance with the Declaration of Helsinki and Good Pharmacoepidemiology Practice Guidelines and was approved by the medical ethical review committee of KSMC. The requirement for consent was waived.We included very preterm infants who were born at KSMC at ≤32 weeks of gestation, had a birth weight of <1500 g, and were admitted to the NICU. All infants who received total PN plus lipid emulsion within the first 24 h of birth were included in our study. We excluded infants with major congenital anomalies or congenital infection, inborn errors of metabolism, those who did not receive PN, those who were not born at KSMC or were transferred to another hospital or died within the first 7 days, and those whose data could not be retrieved.The infants’ charts from NICU admission until discharge or death were reviewed. Demographic, clinical, and outcome data, including the major morbidities associated with prematurity, were obtained. Maternal data, including gestational diabetes mellitus, maternal hypertension, antenatal steroid treatment, and mode of delivery, were also retrieved. The details about the measurement of body weight, head circumference (HC), and lipid profile are provided in The primary outcome of this study was the change in weight z-score (weight Δ z-score) from birth to 36 weeks of post-menstrual age (PMA) or at discharge, whichever one came first during two different period changes when SMOFlipid was routinely included in PN formulation.Secondary outcomes were the change in HC z-score (HC Δ z-score) from birth to 36 weeks of PMA or at discharge, discharge weight, z-score of discharge weight, days of PN and lipid emulsion (LE), and length of hospital stay, as well as the incidence of mortality and preterm neonatal morbidities including BPD, late onset of sepsis (LOS), ROP, any or severe intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC).Parenteral nutrition (PN): The PN was started early after birth using starter PN. Individualized PN was prescribed daily. Starter PN contains dextrose 10%, amino acids 4%, and calcium gluconate 0.01 mmol/mL. Individualized PN solution containing amino acids, glucose, minerals, trace elements, water-soluble vitamins, and fat-soluble vitamins was started within the first 24 h of life and infused continuously for 24 h.The subjects were categorized into two groups of LE—(1) SMOFlipid : infants were given parenteral multi-oil emulsions, containing soybean oil, MCT, olive oil, and fish oil; and (2) intralipid 20% medium-chain and long-chain fat injection: containing soybean oil and MCT.The initial LE dose was 0.5 to 1.0 g per kg per day early after birth and was increased by 0.5 to 1.0 g per kg per day every 24 h with a maximum of 3.0 g to 3.5 g lipids per kg per day. Triglyceride level was not measured in the routine investigation. Minimal enteral nutrition was started as soon as possible after birth if possible. A preterm formula or expressed breast milk was administrated through an orogastric tube intermittently according to the feeding protocol, which depends on birth weight.Preterm formula was administered when human milk was not available or sufficient.The body weight and HC were recorded when entering the neonatal unit. Body weight and HC was measured by NICU nurses. The body weight was measured with an electronic scale calibrated to 0.05 kg. The HC measurement was obtained weekly with a measuring tape, which is precise to the nearest millimeter. The change in body weight was recorded daily, with HC weekly records. For the z-score calculation, the 2013 Fenton growth chart was used . PostnatDiagnoses of IVH, BPD, NEC, as well as sepsis were retrieved from clinical records. Severe IVH was defined as grade III–IV IVH on Papile classification . BPD wasBefore performing the analysis, we checked the dataset for missing data. Data were analyzed using a statistical software package .t-test was used for normally distributed data, and the Mann–Whitney U test was used for non-normally distributed data. The Kolmogorov–Smirnov test and a visual inspection of histograms were performed to evaluate the distribution of quantitative variables.Data regarding maternal and infant variables were presented using descriptive statistics, including median, interquartile range (IQR), frequency, and percentage. Fisher’s exact test was used to determine the association between categorical variables. The Mann–Whitney U test was used for between-group comparisons of ordinal qualitative variables. For between-group comparisons of continuous variables, the unpaired Student’s p value of <0.05 in the univariate analysis were included in the final multivariable regression model. Linear regression analysis was conducted to analyze the association between type of LE and growth anthropometrics after checking for collinearity with a correlation matrix. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied for univariate relative risk analysis and to the models to adjust the relative risk for neonatal morbidities and mortality. The BPD mediation effect and grades 3 or 4 IVH on weight velocity and weight, length, and HC at 36-week PMA were evaluated using a causal mediation analysis. All statistical tests were two-tailed, and p values of <0.05 were considered statistically significant.To analyze the association between type of LE and outcomes, we first conducted a univariate relative risk analysis on the recorded variables  because we considered them to be potential confounders. All factors with a During the study period, 1976 preterm infants with ≤32 gestational weeks and birth weight <1500 g were admitted to the NICU (level 3). Of them, 858 met the inclusion criteria and were eligible for inclusion in the final analysis .Among 858 infants, 238 received SMOFlipid and 620 were in the intralipid group. Maternal and neonatal characteristics are summarized in p < 0.001). In contrast, the median of parenteral carbohydrate intake, either the total intake or the first postnatal week (mg/kg/min), was lower in the SMOFlipid compared with intralipid group (p < 0.001). We observed no association between energy intakes and type of LE. Infants who received expressed breast milk were higher in SMOFlipid compared with the intralipid group (p < 0.001)  and protein (g/kg/day) either the total intake or in the first postnatal week was significantly higher in the SMOFlipid group compared with the intralipid group (< 0.001) .p < 0.001). In addition, the growth rate and z-score at discharge weight were significantly higher in infants who received intralipid compared with infants who received SMOFlipid (p = 0.02) (p < 0.001)  . The per< 0.001) .p = 0.001). Males in the SMOFlipid–LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82) . However, grade 3 or 4 IVH did not have a mediating effect for either male and female infants .The multivariable regression analysis performed after adjusting the variables that were significant in the univariate analysis revealed that the SMOFlipid administration had a negative impact on Δ weight z-score compared with intralipid  . The SMO = 0.82) . Causal Furthermore, the SMOFlipid administration compared to the intralipid group significantly reduced the BPD . However, infants who received SMOFlipid had significantly higher LOS compared with those who received intralipid .However, aRR revealed that there was no association between SMOFlipid and neonatal morbidity  as well as neonatal mortality.Our study indicates that SMOFlipid is associated with low growth velocity in very preterm male infants. In addition, it is associated with increased proportion of late onset of sepsis and decreased rate of BPD.In terms of growth velocity, the main target of PN is to meet the nutritional requirements in preterm infants and achieve weight gain like a normal fetus . Lipid iOur resulted showed increased risk of late-onset sepsis. A decade ago, meta-analysis showed that SMOFlipid emulsions are weakly associated with fewer episodes of late onset of sepsis compared with soybean oil emulsions  . They exOur study showed that preterm infants who received SMOFlipid as part of their PN in their early life have a lower BPD rate. The DHA, as part of SMOFlipid, stimulates surfactant production and minimizes the inflammatory process in animals’ lungs ,40,41,42With regard to other neonatal morbidities, such as ROP, IVH, NEC, and mortality, our study did not find any potential benefit of SMOFlipid in reducing their incidence rates. Previous studies demonstrated conflicting results. The recent meta-analysis found that DHA supplements do not make any significant changes in NEC, IVH, and severe ROP . HoweverCurrent studies present conflicting data regarding the short-term and long-term impacts of SMOFlipid in preterm infants. These differences might be attributed to the population enrolled in each study, the quantity of the supplements, and the method of preparation and giving they received, such as whether they received DHA only or lipid that is enriched with DHA, in addition to other components.Several limitations are present in the current study. Our study is retrospective in nature and not all confounding factors may have been adjusted for. We did not measure the essential fatty acid levels, as it is not a routine test, and we perform it for preterm infants unless there are indications of metabolism inborn error. Furthermore, long-term follow-up would have strengthened the study. We have good sample size, and we were able to investigate the important neonatal outcomes and controversies at the same time. We were able to highlight the present conflict in the current practice of SMOFlipid in preterm infants.In conclusion, our study revealed that none of the studied lipid emulsions were proven to be superior to the others for very preterm infants. SMOFlipid may reduce the risk of BPD but increases the risk of late onset of sepsis and postnatal growth failure. A large randomized controlled trial is required to identify effects of SMOFlipid on neonatal morbidities.


Arthroscopic reconstruction of the anterior cruciate ligament has been modernized through new materials and novel surgical techniques. The usage of bioabsorbable screws for tibial fixation may potentially lead to complications, such as formation of a tibial tunnel or pretibial cysts. This is a relatively rare complication, but it has been described in the literature. The pathomechanism of cyst formation, however, still remains poorly understood. In this case report, we present a case of a healthy 23-year-old gentleman who had left tibia vara, which was treated surgically with proximal tibia corrective osteotomy with plate and screw fixation and subsequent hardware removal. Later in his life, he injured his anterior cruciate ligament, which required arthroscopic reconstruction. Years after, he developed a pretibial synovial cyst, which was visualized on magnetic resonance imaging. We reviewed previously published cases with similar presentations to help describe the possible etiology of intraosseous  cysts. Arthroscopic reconstruction of the anterior cruciate ligament (ACL) has been modernized through new materials and novel surgical techniques. The usage of bioabsorbable screws for tibial fixation may lead to potential complications, such as formation of a tibial tunnel or pretibial cysts . This isA 23-year-old gentleman sustained a twisting injury to his left knee in 2017. He had a history of left tibia vara treated with a proximal tibial osteotomy (2007) with subsequent hardware removal (2010). Examination revealed positive Lachman’s test and laxity, intact posterior drawer test, and stable collateral ligaments. MRI confirmed an anterior cruciate ligament tear. In 2018, he underwent arthroscopic left knee ACLR with hybrid grafting , as semitendinosus adhered to the medial collateral ligament. Proximally adjustable end button and distal fixation were obtained using a bioabsorbable poly-D-L-lactide (PDLLA) 10 mm interference screw . A stable knee was obtained after fixation. The two-week postoperative visit revealed a clean healing wound.In 2020, he presented with pain, redness, and swelling of the overlying skin around his previous arthroscopic surgical site. We suspected cellulitis and ordered a septic workup, X-ray, MRI, and prescribed amoxicillin with clavulanic acid in addition to analgesia. His septic workup came back negative and his X-ray showed a pretibial cystic lesion over the proximal tibia Figure .His MRI revealed a bright lesion with graft mucoid degeneration and tibial tunnel widening. Within the tibial tunnel lied a ganglion cyst communicating with the pretibial area. Surrounding the tunnel, significant bone marrow signal alterations involving the proximal tibial epiphysis and metaphysis were noted. The posterior cruciate ligament was intact. There was a complex tear involving the posterior aspect of the medial meniscus Figure .Inflammatory markers were normal, making osteomyelitis unlikely.He was admitted the following day for cyst curettage and bone grafting. Intraoperatively, ACL testing was done showing an intact reconstructed ligament. The previous incision was utilized and clear fluid with remaining screw particles was produced from the cyst. It did not communicate with the joint despite the MRI finding Figure .Tissue samples were sent for histopathology and cultures. Debridement was done and the bony defect was impacted with cancellous bone chips. Closure was done. Wound and tissue cultures were negative. He was advised to practice non-weight-bearing, provided with analgesia and antibiotics, and discharged. The histology result slowed vascularized fibroadipose tissue with focal synovial lining, which is consistent with synovial cysts. It showed foci of chronic inflammation and bone fragments. The sample stained positive for CD163. Pan-cytokeratin (pan-CK) was negative in the lining cells.Upon wound inspection, swelling and oozing of serosanguinous fluid were noted therefore, manual evacuation was performed. Samples were not sent for microbiology.He was given a close follow-up with imaging and prescribed additional antibiotics Figure .During such, pain improved and the wound stopped producing discharge. He was allowed to bear weight as tolerated. He was allowed to progress to full weight-bearing six weeks after the procedure, and since then he has been doing well with a healed wound and good range of motion (ROM) and mobilization. We were not able to secure a clinical picture of his healed wound at the time. He complains of occasional mild anterior knee pain over the tibial tubercle and is still being followed up in the clinic. No additional radiological investigations were done to objectively assess the healing of the lesion. He’s currently continuing physical therapy, strengthening exercises, and avoiding vigorous activity. The patient’s informed consent was sought and granted.Arthroscopic reconstruction of the ACL has been modernized through novel materials and surgical techniques. Usage of bioabsorbable screws for tibial fixation may potentially lead to complications, such as tibial tunnel or pretibial cysts, mostly occurring 1-5 years postoperatively -5. In puSynovial cysts are fluid-filled juxta-articular cysts lined by synovial cells that may or may not communicate with the joint fluid . Some suOn MRI, cysts appear as well-defined uni/multilocular cystic masses . There mThere were a variety of graft materials and several tibial fixation devices utilized . DespiteThe occurrence of non-communicating cysts has been most prominently linked to a bony reaction to fixation devices (which may cause communicating or non-communicating) and breakdown of bioabsorbable interference screws ,2,10. SeCommunication of cysts to the joint may not be easily demonstrated, therefore, the presence of chondroitin sulfate in cyst analysis may indicate that the fluid came from the joint . CommuniTsuda et al. theorized that cyst occurrence was due to leakage of articular fluid through the tibial tunnel . This waSimonian et al. described incomplete autograft incorporation . When exAhn et al. described an incidental cyst after posterior cruciate ligament reconstruction. They theorized that fluid leakage and cyst formation was due to failed osteointegration of the graft into the tibial tunnel . It was Fewer studies believed the occurrence of cysts may be due to using nonabsorbable sutures, drilling oversized tunnels, or tunnel-graft size mismatch . This isBioabsorbable screws fragment once they are hydrolyzed, producing a phagocytic reaction by macrophages, which may elicit an inflammatory foreign body reaction ,13. DegrWe believe the etiology is multifactorial. In our patient, several causes can be attributed to the formation of the cyst. We used a bio-absorbable screw, and a hybrid graft . Both have been documented to carry the rare potential risk of cystic formation years after the procedure. The MRI showed a communicating cyst, in contrast to intraoperative assessment, as well as a significant tunnel widening, favoring the theory of an inflammatory reaction due to the screw breakdown, as this takes years to occur. In our case, the cyst presented 2 years postoperatively. Furthermore, histologic results of chronic inflammatory signs support the theory of a foreign body reaction occurring while the screw was breaking down. Remaining screw particles were found intraoperatively, possibly indicating that the screw was undergoing resorption at the time of surgery. Second, lack of complete osteointegration of the graft into the tunnel could lead to the MRI findings. This can be supported by using a hybrid reconstruction, as we know little about how allografts integrate and whether they may induce an immunological reaction, which may explain the chronic inflammatory changes seen on histology. Third, this could lie in the patient’s history of having a corrective osteotomy years earlier, allowing for the focal bone to become weaker, owing to the occurrence of the cyst in the same area of the proximal tibia. The latter theory does not explain the chronic inflammatory reaction, but it does explain the cyst lining being that of a synovial cyst. To add, we have not taken a sample of the femoral aspect of the tunnel for biopsy, to concur whether or not there were chronic inflammatory changes there as well. Therefore, we are unable to attribute this complication to a single theory.Despite the perceivable advantages of bioabsorbable screws, awareness of their complications is essential. Given the infrequency of cyst formation compared to the number of ACL reconstructions being performed with bioabsorbable screws, it raises the possibility of a patient-related factor. It was proposed that this may be due to a sensitivity to larger foreign bodies .There are several limitations. First, as a case report, we are unaware of other cases that were not evaluated further. Second, we used a hybrid graft and have no other cases to infer from in terms of rates of occurrence in such grafts. Moreover, our sample was only investigated by light microscopy and immunohistochemistry, without biochemical analysis of the fluid. Despite this, up to our current knowledge, no cases have been published from Saudi Arabia.Due to the limited number of published cases and poor understanding of the mechanism of cyst development and the long-term outcomes, and the many variables mentioned, it is challenging to narrow down the direction of prospective studies. It will be difficult to find an adequate sample size, due to rare occurrences and lack of symptoms. Areas worthy of addressing are the different surgical techniques, graft preparations, and types of grafts utilized. We would also recommend addressing individual-to-individual variations in biodegradation and immunological mechanisms.The occurrence of the tibial tunnel and pretibial cysts after ACLR is infrequent, with a limited number of cases reported in the literature. Our current case is interesting as our patient had a history of undergoing tibial corrective osteotomy for tibia vara years before undergoing ACLR. It is likely that the etiology behind his developing this pretibial cyst is multifactorial, as several causes can be attributed to the formation of this cyst, including the usage of a bioabsorbable screw and hybrid graft, the possible inflammatory reaction due to the screw breakdown, the possibility of incomplete osteointegration of the graft, or the possibility of a patient-related factor as he had a corrective osteotomy years earlier in the same location of the proximal tibia. We highlight the importance of the awareness of the potential complications of bioabsorbable screws, despite their perceivable advantages.


Transcranial direct current stimulation (tDCS) is a promising tool to enhance therapeutic efforts, for instance, after a stroke. The achieved stimulation effects exhibit high inter-subject variability, primarily driven by perturbations of the induced electric field (EF). Differences are further elevated in the aging brain due to anatomical changes such as atrophy or lesions. Informing tDCS protocols by computer-based, individualized EF simulations is a suggested measure to mitigate this variability.While brain anatomy in general and specifically atrophy as well as stroke lesions are deemed influential on the EF in simulation studies, the influence of the uncertainty in the change of the electrical properties of the white matter due to white matter lesions (WMLs) has not been quantified yet.A group simulation study with 88 subjects assigned into four groups of increasing lesion load was conducted. Due to the lack of information about the electrical conductivity of WMLs, an uncertainty analysis was employed to quantify the variability in the simulation when choosing an arbitrary conductivity value for the lesioned tissue.The contribution of WMLs to the EF variance was on average only one tenth to one thousandth of the contribution of the other modeled tissues. While the contribution of the WMLs significantly increased (Our results suggest that WMLs do not perturb the EF globally and can thus be omitted when modeling subjects with low to medium lesion load. However, for high lesion load subjects, the omission of WMLs may yield less robust local EF estimations in the vicinity of the lesioned tissue. Our results contribute to the efforts of accurate modeling of tDCS for treatment planning. During To investigate the influence of WMLs on the electric field by means of a simulation study, they must be representable geometrically and physically in a head model. A segmentation of WMLs from MR images can be performed automatically , allowinAn uncertainty analysis is a promising tool to model tDCS simulations with uncertain inputs. The physical properties of the head model are represented by a multi-dimensional input space instead of a set of fixed conductivity values. A relation between this input space and the output quantities (i.e. the electric field) is established and statistics such as the mean electric field magnitude, its variance, and the contribution of each tissue to that variance can be derived.This process is a computationally expensive task. The input space must be sampled sufficiently enough, performing a complete, standard tDCS simulation on each sampling iteration to determine the relation to the output quantity reliably. One technique to mitigate this computational effort is the so-called generalized polynomial chaos expansion, which efficiently determines a surrogate model of the output quantity based on fewer samples, requiring much less computational resources .This technique was previously introduced in tDCS and TMS case studies in a single young, healthy adult . McCann Here, the influence of white matter lesions on the electric field distribution during tDCS with two different electrode setups is investigated by means of a computational uncertainty analysis using the generalized polynomial chaos expansion. We expected an elevated total variance of the electric field induced by an increasing contribution of the WMLs to the variance proportional to the lesion load. To systematically assess the influence of the lesion load on the electric field and to account for the spatial variability of the lesions, simulations were performed using the imaging data of in total 88 subjects. They were assigned to one of four groups according to their Fazekas score  with a p22.1T1-weighted magnetization prepared rapid gradient echo (MPRAGE) and T2-weighted fluid-attenuated inversion recovery (FLAIR) head images of each subject were selected from a pool of 2029 datasets. These imaging data were collected previously on a MAGNETOM Verio scanner  using a 32-channel head receiver coil and a body transmitter coil as part of the large cross-sectional imaging study of the Leipzig Research Centre for Civilization Diseases (LIFE study) . Detaile2.2Imaging data of 88 subjects, gender  and age-matched , were selected from the database of the LIFE study. Subjects were assigned to four groups according to their Fazekas score , which q2.3checkMesh, which acknowledged the generated meshes to be suitable for the subsequent FVM-simulations in terms of mesh non-orthogonality, element skewness, element aspect ratio, element volume, and face area in all cases. The T1-weighted head images were segmented using our segmentation pipeline   and reme2.3.1-15 S/m, acting as an insulator. Two electrode setups were simulated, each using quadratic 25 cm2 pad electrodes , gray matter (GM), white matter (WM), and the WMLs. As part of the sensitivity analysis, their homogenous, isotropic electrical conductivity values were not fixed but modeled as random variables y values  based ony values . A beta ectrodes . In setuectrodes . This seectrodes . The ele2.4In general, an uncertainty analysis aims to determine the variation of the output quantity The generalized polynomial chaos expansion (gPC) is an established approach to drastically reduce the number of simulations by constructing a surrogate of the computationally expensive original model of the output quantity. The surrogate model is represented by joint polynomial basis functions The degree of the polynomials is denominated by the multi-index The polynomial series with its coefficients ut space  at the lConsequently, the input space can be sampled more efficiently since it merely involves evaluating a polynomial function instead of evaluating the modeled problem. Finally, to establish the surrogate model, far fewer samples are required than for the setup of the actual output PDF by the Monte Carlo method.2.4.1For our tDCS simulations as the system under investigation, the electric field magnitude us study , the eleCalculating one sample of the output quantity for a tDCS simulation-based uncertainty analysis implies performing a full simulation with a randomly (according to the input PDFs) selected fixed conductivity for each tissue compartment. Every simulation pass, thus, represents a mapping from the input space (conductivities) onto the output space  coefficients  for each2.4.2On an Intel Core i7 6700 workstation equipped with an SSD drive and 32 GB RAM, the simulation time for one simulation pass per subject was approximately 8 min. Between 51 and 96 simulations were necessary per subject to expand the gPC series with a residual of The average relative error across all test cases between the electric field magnitude computed by the polynomial series and the actual simulated value was 0.56% (sd: 0.2%).2.5The uncertainty analyses focused on determining the mean electric field magnitude, the associated variance, and the Sobol indices as result quantities. We distinguish between two levels of means and variances of the electric field magnitude. The first level is the mean electric field magnitude mean were defined at four locations on the cortical mid-layer and by four deep structures. The cortical mid-layer ROIs were chosen as the cortex represented the primary target site for tDCS. The selected deep brain regions were reported to likewise receive a pronounced electric field magnitude . Further2.5.2t-test was used as a post-hoc test. Non-normally distributed samples were tested with the Kruskal-Wallis (KW) rank test and corrected for multiple comparisons. Subjects were again grouped according to their Fazekas score. A post-hoc test was conducted using the Bonferroni-corrected Dunn’s test. The effect size measure Statistics of the spatially averaged results of the uncertainty analysis were computed in R v.3.4.4  for the tatistic .3The electric field magnitude is analyzed in terms of its mean, mean and, thus, on average the lowest contributor to the electric field variance. However, the contribution was modulated by the lesion load. As expected, the Sobol index of WML from all three groups was consistently the highest in the Fazekas 3 group across all conditions and decreased with decreasing lesion load. Overall, the difference in the Sobol index of WML tissue between the Fazekas 1 and Fazekas 3 group was at least one order of magnitude (i.e. a factor of ten) in both electrode setups. Consequently, the group average WML Sobol indices differed significantly between the high and medium lesion load group  . Similar p≪.001) .The strongest influence on a single-subject level on the mid-layer was found in a location within the right Electrode ROI in the bihemispheric setup in a Fazekas 3 subject with a contribution of 11.25% to the total variance. In the deep ROIs, the 99th-percentile highest, single-subject WML Sobol index reflected a contribution of 91.8% to the total electric field variance at a distinct location in the right thalamus in a Fazekas 3 subject when using the bihemispheric electrode montage. Notably, the white matter lesions of this subject were directly adjacent to the right thalamus.4In this work, the impact of white matter lesion (WML) tissue on the electric field magnitude during the application of transcranial direct current stimulation was assessed using a group-level computational uncertainty analysis. Two electrode montages were simulated, a bihemispheric setup targeting the motor cortex and a frontal-occipital setup targeting deeper, subcortical structures. The mean electric field magnitude, its associated total variance, and decomposition of this variance into the contributions of each tissue by means of Sobol indices were analyzed at the cortical midlayer and in superficial cortical and deeper regions of interest in four groups with increasing lesion load. A consistent pattern for both electrode montages was a significant increase in the contribution of white matter lesion tissue to the variance of the electric field magnitude in the high lesion load group compared to the low lesion load group. This increase could be detected in all analyzed regions of interest but varied in strength. However, the contribution of the white matter lesion tissue to the electric field variance was on average the lowest compared to the other tissue classes within all ROIs. Data on a single-subject level from a sampling line through the intracranial compartment suggested that a major part of the electric field variance was accounted for by WMLs only directly within the lesioned tissue and its immediate surroundings with the highest radius in a Fazekas 3 subject. Concludingly, WMLs could be omitted in most head models. Still, additional modeling effort may be required for an accurate simulation of subjects with a high lesion load if the lesion location is close to the stimulation site or when deeper subcortical structures are targeted.White matter lesions, also known as leukoaraiosis, are characterized by the absence of apparent clinical symptoms. However, they may co-occur with several neurological diseases that develop in the aging brain, such as Parkinson’s disease (PD), Alzheimer’s disease, or stroke. TDCS interventions for improving gait in PD , for sloAn entirely different approach to investigate the influence of WMLs on the electric field during tDCS was taken recently by Despite the significantly higher contribution of WMLs to the total variance of the electric field magnitude in the Fazekas 3 group in both electrode setups, this variance was not increased across all conditions and ROIs. Instead, the contribution of healthy white matter tissue decreased in the Fazekas 3 group in all ROIs of both electrode montages. This indicates 1) that the WMLs did not cause a global perturbation of the electric field and 2) that healthy and lesioned white matter share their contribution to the total variance. The shared volume of healthy and lesioned white matter in the brain may be a possible explanation for their shared contribution to the total variance — a higher lesion load results in a lower volume of healthy white matter.The local influence of the WMLs on the electric field variance is further supported by three observations: 1) elevated levels of the WML Sobol index could only be found up to 4.3 mm distant from WML areas on the intracranial volume sampling line , 2) the From both electrode setups, general conclusions concerning the influence of white matter lesions on the electric field could be drawn. However, a few differences between both setups were apparent. Whereas in the mid-layer ROIs, no significant difference in the spatially averaged mean electric field magnitude between the groups could be identified in the bihemispheric electrode montage, there was a significant difference between the Fazekas 3 group and both the Fazekas 2 and Fazekas 0 groups in the M1 ROIs and on the whole brain level in the frontal-occipital setup . As a reBy quantifying the contribution of the distinct tissue classes to the variance of the electric field magnitude due to their uncertainty in electrical conductivity, our results provide an estimate of the robustness of the results derived from tES simulations when choosing an arbitrary conductivity value from the analyzed ranges. In this study, the influence of uncertainty in the electrical conductivity of WML tissue was of particular interest. We consider the influence of the lesioned tissue on the electric field in Fazekas 1 and 2 subjects virtually negligible in superficial, cortical targets for both electrode configurations. No significant difference between the two groups was found and the WML Sobol index was, on average, approximately only a thousandth of that of the skin tissue class . We founIn this study, we selected an electrode montage that is commonly used for motor cortex stimulation , and a mOne limitation of the presented work might be that white matter anisotropy was not included in the physical properties of the head models because of lacking suitable diffusion-weighted imaging data. The imaging data were obtained from the existing pool of data of a large cross-sectional study, the LIFE-Adult study . ModelinTo verify our entire workflow, we compared the previous work of The presented results were obtained in participants with subcortical lesions of vascular origin. The electrical conductivity of these lesions was modeled highly uncertain in the sensitivity analysis. For this reason, these results might also apply to other patient populations with other types of subcortical lesions caused by diseases such as multiple sclerosis, infectious encephalitis, and leukodystrophy.Our study systematically examined the influence of pathological brain structures on a group level in an uncertainty analysis. With 88 individual head models of both sexes, a wide range of phenotypes was covered. By leveraging a sensitivity analysis, the limitation of unknown conductivity of the structure under investigation, namely white matter lesions, was overcome. Our results support that white matter lesions must only be considered on an individual level in the case of a high lesion load and if the lesions occur in the vicinity of the stimulation site when conducting a tDCS intervention.B. Kalloch was supported by FAZIT Stiftung and the International Max Planck Research School on Neuroscience of Communication.Benjamin Kalloch: Conceptualization, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft. Konstantin Weise: Conceptualization, Methodology, Software, Validation, Writing – review & editing. Leonie Lampe: Resources, Data curation, Writing – review & editing. Pierre-Louis Bazin: Methodology, Software, Writing – review & editing. Arno Villringer: Funding acquisition, Resources, Supervision, Writing – review & editing. Mario Hlawitschka: Conceptualization, Project administration, Supervision, Writing – review & editing. Bernhard Sehm: Conceptualization, Project administration, Supervision, Writing – review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The aim of this paper was to investigate whether two freeze-thaw cycles before embryo transfer may affect perinatal and neonatal outcomes. N = 96) and the control group (N = 7932). Propensity score matching (PSM) was used to adjust the baseline characteristics of the two groups at a proportion of 1 : 4. There were 96 patients in the OC group and 369 patients in the control group after PSM. The pregnancy-related complications and neonatal conditions after delivery of the two groups were compared.  A total of 8,028 frozen-thawed embryo transfer patients who became pregnant between March 2013 and September 2019 were included. The patients were divided into two groups: the oocyte cryopreservation (OC) group (P = 0.029) than the control group after PSM. Moreover, a slightly higher pregnancy defect rate was found in the OC group. There was no significant difference in the rates of diabetes mellitus, hypertension during pregnancy, cesarean section, multiple births, low birth weight (LBW), or premature birth defects between the two groups.  The OC group had a higher stillbirth rate  with cryopreserved oocytes was associated with a higher rate of stillbirth than FET with fresh oocytes. The incidences of diabetes, gestational hypertension, cesarean section, multiple births, LBW, premature birth, and birth defects of the two groups were not significantly different. Cryopreservation technology has been widely used for embryo and gamete cryopreservation in assisted reproductive technology (ART), and the cryopreservation of oocytes and embryos is a major component of ART. The first successful birth from cryopreserved embryos was reported in 1983, and the first successful birth from cryopreserved oocytes was reported in 1986 . Early oFrozen-thawed embryo transfer (FET) can be used to store surplus embryos, increase the cumulative pregnancy rate, and reduce the risk of OHSS . Many stOC was originally used for females who needed to preserve their fertility due to medical conditions , who could not obtain sperm on the day of oocyte retrieval, who needed to postpone childbirth, or who wished to become egg donors , 10. It To date, there have been few studies on pregnancy outcomes after OC. In recent years, research results have been inconsistent and controversial regarding whether cryopreserved oocytes have a lower success rate than fresh oocytes , 12. HowPatients are often concerned about whether FET or OC poses a risk to offspring perinatally or after birth. Regarding FET, there are consistent findings of an increased risk of hypertensive disorders of pregnancy and large for gestational age after FET, but the specific reasons for this are not clear –18. SomeFor each OC patient, more than one oocyte is thawed in every cycle to maximize cost-effectiveness. Therefore, some patients with OC may have extra embryos to be frozen, while others with OC may need to have frozen embryos transferred for medical and personal reasons. Thus, these embryos would undergo two freeze-thawing cycles: freezing and thawing of the oocyte and freezing and thawing of the embryo. It is not clear whether two freeze-thaw cycles affects maternal or infant outcomes. To address this, we searched and screened the literature but were unable to retrieve relevant literature. Thus, we designed this study to explore this issue. The goals of our study were to determine whether twice freezing affects perinatal and neonatal outcomes and to help clinicians make informed decisions.We selected all frozen-thawed embryo transferred patients at the Affiliated Reproductive Hospital of Shandong University who became pregnant from March 2013 to September 2019. All frozen-thawed oocytes were subjected to intracytoplasmic sperm injection (ICSI) and blastocyst transfer. To reduce potential confounding factors and improve the efficiency of propensity score matching (PSM), the inclusion criteria were as follows: (1) pregnancy ≥24 weeks; (2) underwent an ICSI cycle; and (3) transferred D5/D6 blastocysts. The exclusion criteria were as follows: (1) donated eggs; (2) preimplantation genetic testing; (3) uterine abnormalities; and (4) missing data. The patients were divided into two groups: the OC group and the control group. The patients in the OC group first underwent oocyte freezing and thawing and later underwent FET. The control group underwent FET only with fresh oocytes. After strict screening, we finally identified 8028 patients with frozen-thawed embryos transferred, including 96 patients in the OC group and 7932 patients in the control group. This study was carried out according to the Helsinki Declaration. Ethical approval was obtained from the ethical committee of the Center for Reproductive Medicine affiliated with Shandong University. Based on the condition of each patient, medical staff developed different ovulation protocols. Ovulation induction programs included a long gonadotropin releasing hormone (GnRH) agonist regimen, short GnRH agonist regimen, GnRH antagonist regimen, mild stimulation protocol, and natural regimen. Ovulation induction programs have been published in previous studies –26. In tEndometrial preparation was performed using a natural cycle regimen, hormone replacement cycle regimen, or ovarian stimulation cycle. Natural ovulation cycles were adopted for patients with regular ovulation, and hormone replacement or ovarian stimulation cycles were used for patients with anovulatory or irregular menstruation. Upon ovulation or when endometrial thickness exceeded 7 mm, the luteal phase support regimen was added according to the endometrial preparation protocol. The blastocysts were transferred on the fifth day after ovulation or progesterone injection. Luteal phase support lasted until 10 weeks of gestation. Follow-up of the patients was conducted regularly through telephone or outpatient visits during pregnancy and the perinatal period, with neonatal outcomes obtained.The evaluation results included mainly pregnancy-related complications and the neonatal condition after delivery. Complications during pregnancy included stillbirths, multiple pregnancies, gestational diabetes mellitus, and gestational hypertension. Neonatal condition included gestational age, birth weight, and gender. Low birth weight was defined as birth weight < 2500 g, and macrosomia was defined as birth weight > 4500 g. All deliveries included live born and stillborn infants. Babies born included all live born infants. Birth defects were determined per the International Classification of Diseases (ICD) version 10 code.P < 0.05 indicated a significant difference. To reduce selection bias and eliminate the interference of confounding factors, the PSM method was used in this study, and the nearest neighbor PSM was employed to match the two groups. PSM was used mainly to match the baseline variables of the two groups, including age, body mass index (BMI), follicle stimulating hormone (FSH), luteinizing hormone (LH), number of oocytes retrieved, polycystic ovary syndrome (PCOS), endometrial preparation scheme for FET, natural cycle, program cycle, ovarian stimulation cycle, number of transferred embryos, endometrial thickness, endometrial thickness on HCG trigger day, and previous conception. The matching ratio for PSM was 1 : 4 within a caliper width of 0.1 for a satisfactory match.All data were statistically analyzed using SPSS 26.0 . Categorical variables are expressed as percentages, and the chi square test and Fisher's exact test were used for analysis. As the data did not meet the assumption of a normal distribution, continuous variables are expressed as the median (25th percentile–75th percentile), and a nonparametric test was used. A total of 8,028 FET cycles undergoing ICSI, blastocyst transfer, and final deliveries between March 2013 and September 2019 were included in the analysis. There were 96 patients in the OC group and 7,932 patients in the control group. Before PSM, there were statistically significant differences in baseline characteristics between the two groups . To addrP = 0.029). The rates of gestational diabetes mellitus, hypertension during pregnancy, cesarean section, multiple births, birth weight, and gestational age were comparable between the two groups.The pregnancy outcomes of all deliveries (stillbirth and live birth) ≥24 weeks are shown in P > 0.05)  cases (live and stillbirth) were diagnosed with the following major birth defects at birth : neurolo.05) see .The results of this retrospective study showed that performing FET with cryopreserved oocytes was associated with a higher rate of stillbirth than performing FET with fresh oocytes. There was no significant difference between the two groups in the incidence of diabetes, gestational hypertension, cesarean section, multiple births, low birth weight (LBW), preterm birth, or birth defects.The development of cryopreservation technology enables the long-term preservation of gametes. With the increasing popularity of cryopreservation of gametes, although the clinical effect is excellent, its safety is still controversial. Patients and doctors are most concerned about the health of mothers and newborns in ART. It has been suggested that frozen-thawed embryos or oocytes may be associated with increased genetic and epigenetic risks . For ethMany studies have demonstrated that FET has increased risks in terms of gestational age babies and hypertensive disorders of pregnancy –18, 40. Clinical research data on cryopreserved oocytes are limited. However, the perinatal outcome data of cryopreserved oocytes are reassuring. Almost all the literature has reported that the vitrification of oocytes cannot increase the risk of adverse obstetric and perinatal outcomes , 41, 42.The results of this study showed that the stillbirth rate of frozen oocyte FET patients was higher than that of fresh oocyte FET patients. Early studies did not find any difference in perinatal mortality between the OC cycle and fresh oocyte cycle or between the fresh embryo cycle and FET cycle , 43. We There was no significant difference in the incidence of gestational diabetes mellitus, gestational hypertension, cesarean section, multiple births, LBW, or premature birth between the OC group and the control group. However, our results may be affected by the low numbers of related outcome events. Therefore, further large RCTs are needed to confirm the above hypothesis.To the best of our knowledge, there is currently no similar study on the use of two freezing and thawing cycles. Our study also provides guidance for the clinical application of FET with cryopreserved oocytes. We suggest that caution be used in the selection of frozen-thawed embryos transplanted with cryopreserved oocytes. The advantage of this study is the use of PSM to control for confounding factors in a nonrandomized study and avoid confounding bias. However, there are a few limitations in this study. First, the number of patients in the OC group was relatively limited because the included patients comprised all deliveries and the inclusion criteria were strict. Second, due to the limited number of patients, we did not evaluate all pregnancy complications. Third, although PSM was used to minimize bias, we could not cover all relevant confounding factors. Therefore, there is still a risk of selection bias. More multicenter, large RCTs, and expanded sample sizes are needed to verify our results in the future.In this study, we found that FET after cryopreservation of oocytes was significantly correlated with a higher stillbirth rate than FET with fresh oocytes. The incidences of diabetes, gestational hypertension, cesarean section, multiple births, LBW, premature birth, and birth defects between the two groups were not significantly different.


The scientific community is making significant efforts to be inclusive and to promote diversity and equity. The microbial sciences are not the exception, and organizations, such as the American Society for Microbiology (ASM), are implementing strategic plans to advance these initiatives. However, one unexplored topic is whether the recruitment of minoritized microbiologists should use tailored programs for the success of trainees and faculty. Some challenges and opportunities are presented for consideration while developing recruitment, retention, and advancement programs in the microbial sciences. Microbiology departments across the United States, as parts of major universities, colleges, and institutes, are joining a growing national movement to diversify their institutions and to advance their inclusion and equity missions. However, one major, common concern by search committees that recruit students and faculty is that is exceedingly difficult to find qualified individuals, particularly those that belong to minoritized groups . Although this concern represents a common bias permeating academia, it does not reflect the available qualified candidates that can occupy those positions, and search committees need to consider the challenges of this group of applicants while recruiting them. Schools continue to develop strategic plans to recruit these microbiologists, but they do not consider that trainees and/or faculty candidates belonging to these ethnic and racial groups might require different strategies to be incorporated in their scientific/academic communities or that there is a need to create a change in the academic culture that can support their careers and their advancement in the microbial sciences , 2. HereIt is well-documented that Black scientists are historically excluded in microbial education, training, and research , 4; howeASM has recognized the value of the Black community of microbiologists by having the only Black President of the Society on Clifford Houston of the University of Texas Medical Branch, who was a microbiologist who advanced the educational mission of ASM and founded the Annual Biomedical Research Conference for Minority Students (ABRCMS). Unfortunately, the recent ASM Diversity, Equity and Inclusion Task Force Report  showed tHispanics are the fastest growing minoritized group in the United States, but they remain a significantly underrepresented group in the microbial sciences, comprising 6% of the total workforce of microbiologists in the United States , 12, 13.In general terms, the first subgroup consists of individuals that were born and educated in the United States, and microbiologists from this group are mainly distributed in Hispanic-serving institutions  or in st18–https://www.cienciapr.org/) and networks for professional development as part of the Puerto Rico Society of Microbiologists (https://www.micropr.org/). However, the economic challenges of the island lead many microbiologists to migrate to the mainland and hinder their direct participation in these networks.Finally, a third subgroup consists of microbiologists with a strong link to Puerto Rico, either because they trained there and are part of the academia of the island or because they are Puerto Rican trainees or faculty members on the mainland. These microbiologists have a long tradition of training excellent students who are frequently recruited by different institutions to be part of their graduate programs, but they are less often recruited to become faculty members. Interestingly, Puerto Rico is the place that has the most ASM branches housed at its academic institutions, serving as a forum for microbiology trainees to collaborate and to organize local scientific meetings. Further, the Puerto Rican microbiologists have established support networks in the form of “Ciencia Puerto Rico” , recently renamed the Annual Biomedical Research Conference for Minoritized Scientists, has been the place for minoritized individuals from community colleges as well as undergraduate, graduate, and postbaccalaureate students to display their talents in STEM. This conference also brings together many minoritized faculty members that serve as mentors, judges, speakers, and recruiters of all of the students who attend the conference. ASM has sponsored this conference from the beginning, with the goals being to promote microbiology and other STEM fields and to use this platform to empower the next generation of microbiologists. Academic institutions that are trying to diversify their research programs or faculty pools at large and cannot find sufficient candidates for their graduate programs should consider attending this conference and developing long term strategic plans to support these minoritized scientists in training, with the goal being to recruit those who demonstrate excellence in their research and can eventually occupy faculty positions at academic institutions.Many conferences and scientific meetings are constantly highlighting the nonbiomedical efforts to build a diverse and welcoming community for professionals in various STEM fields. Venues that include basic and/or applied microbiology topics are trying to diversify their panels of speakers and participants; however, sometimes the pool of participants from minoritized groups seems exceedingly small. For 20 years, the Annual Biomedical Research Conference for Minority Students . Fourth, representing the most vital component of any institutional DEI plan, which is commonly ignored, is that when minoritized microbiologists become successful, they will be heavily recruited by other programs. Therefore, the home institutions that have created a more inclusive culture and environment for trainees and faculty will be more successful in retaining their talented minoritized microbiologists. Finally, it is always important to emphasize that recruiting minoritized individuals just to fulfill a quota established by the institution, without a well-designed DEI strategic plan, is a disservice to the microbiological community at large and to those minoritized microbiologists who deserve more opportunities to display their talents.This commentary is not intended to be a comprehensive review of all of the challenges and opportunities faced by minoritized microbiologists. Instead, this commentary is a series of personal observations that could be useful for academic institutions and microbial societies that are trying to diversify their microbiology programs by having a better understanding of the existing networks supporting these individuals and the potential mechanisms that can be established to support the recruitment, retention, and advancement of minoritized microbiologists. It is evident that recruiters of different institutions need to consider establishing collaborations with some of these networks so that equity in the pool of applicants can be created . Here ar


The INTERGROWTH‐21st sex and gestational age (GA) specific newborn size standards (IG‐NS) are intended to complement the World Health Organization Child Growth Standards (WHO‐GS), which are not GA‐specific. We examined the implications of using IG‐NS at birth and WHO‐GS at postnatal ages in longitudinal epidemiologic studies.The aim of this study was to quantify the extent to which standardised measures of newborn size and growth are affected when using WHO‐GS versus IG‐NS at birth among term‐born infants.n = 755) and The Gambia (n = 522) were used to estimate and compare size at birth and growth from birth to 3 months when using WHO‐GS only (‘WHO‐GS’) versus IG‐NS at birth and WHO‐GS postnatally (‘IG‐NS’). Mean length‐for‐age (LAZ), weight‐for‐age (WAZ) and head circumference‐for‐age (HCAZ), and the prevalence of undernutrition  were estimated overall and by GA strata . We used Bland–Altman plots to compare continuous indices and Kappa statistic to compare categorical indicators.Data from two prenatal trials in Bangladesh (At birth, mean LAZ, WAZ and HCAZ, and the prevalence of undernutrition were most similar among newborns between 39 and 40 weeks of GA when using WHO‐GS versus IG‐NS. However, anthropometric indices were systematically lower among early‐term infants and higher among late‐term infants when using WHO‐GS versus IG‐NS. Early‐term and late‐term infants demonstrated relatively faster and slower growth, respectively, when using WHO‐GS versus IG‐NS, with the direction and magnitude of differences varying between anthropometric indices. Individual‐level differences in attained size and growth, when using WHO‐GS versus IG‐NS, were greater than 0.2 SD in magnitude for >60% of infants across all anthropometric indices.Using IG‐NS at birth with WHO‐GS postnatally is acceptable for full‐term infants but may give a misleading interpretation of growth trajectories among early‐ and late‐term infants. Therefore, the IG‐NS have been promoted for use in conjunction with WHO‐GS in clinical and research settings.30/7–406/7 weeks) but gives a misleading interpretation of size and growth trajectories of early‐term (370/7–386/7 weeks) and late‐term (410/7–430/7 weeks) infants.Using IG‐NS at birth and WHO‐GS postnatally is acceptable for full‐term infants  are the most widely used normative tool to evaluate postnatal child growth.z‐scores for birth size derived using the two standards should be very similar. The IG‐NS investigators demonstrated that the medians of the IG‐NS and WHO‐GS standards align for infants at 40 weeks of GAz‐scores across the distribution of newborn weights or lengths similarly align between the two standards. If the standards are not well aligned across their entire distributions, then the combined use of IG‐NS  with WHO‐GS  may result in artefactual, rather than biological, within‐child changes in z‐scores between birth and a postnatal time point in clinical assessments and in longitudinal studies of child growth.The IG‐NS have been promoted to replace previous newborn size references and complement the WHO‐GS in clinical settings and in epidemiologic research.z‐scores (HCAZ), and the prevalence of anthropometric indicators, including stunting (LAZ < −2 SD), underweight (WAZ < −2SD) and microcephaly (HCAZ < −2SD). Second, we estimated the changes in LAZ, WAZ and HCAZ from birth to 3 months of age when using IG‐NS at birth in conjunction with WHO‐GS postnatally compared with using WHO‐GS both at birth and postnatally.The aim of this study was to quantify the extent to which standardised measures of newborn size and growth in early infancy are affected when using different standards at birth in two birth cohorts from Bangladesh and The Gambia. First, we compared the use of WHO‐GS versus IG‐NS to estimate mean anthropometric indices at birth, including length‐for‐age (LAZ), weight‐for‐age (WAZ) and head circumference‐for‐age 22.1n = 1298) were randomly assigned at mid‐gestation (17–24 weeks of GA) to one of the five groups of vitamin D supplementation. The ENID trial was a 2 × 2 × 2 factorial design randomised controlled trial conducted in the West Kiang region of the Gambia in which women (n = 875) who were between 10 and 20 weeks of pregnancy were randomly assigned to one of four prenatal nutrition interventions arms. Mothers and infants were followed at multiple time points throughout pregnancy and in the postpartum period in both trials. We used data from these two studies to assess the consistency of inferences across populations with differing nutritional status.This is a secondary analysis of data from term‐born infants in the Maternal Vitamin D for Infant Growth (MDIG) trial  and the Early Nutrition and Immune Development (ENID) trial .Because variation in GA at birth is most likely to influence growth trajectories in early life and has diminishing impact over time,2.2In both MDIG and ENID studies, ultrasound‐based assessments were used to measure GA.2.3z‐scores according to IG‐NS or postnatal age‐ and sex‐standardised z‐scores using the WHO‐GS. At 3‐month postnatal age, only the WHO‐GS were used to derive age‐ and sex‐standardised z‐scores for anthropometric measures.Anthropometry was assessed using standardised procedures by trained personnel at birth and 3 months.2.4In cross‐sectional analyses of birth size measurements, we estimated and compared mean LAZ, WAZ or HCAZ and the proportion of newborns classified as being undernourished  using WHO‐GS versus IG‐NS (whereby the latter was considered the reference for comparison as it accounts for variations in GA at birth). We used Bland–Altman plots to assess the distribution of individual‐level differences in LAZ, WAZ or HCAZ and the Kappa statistic to estimate the degree of within‐infant concordance in stunting, underweight or microcephaly classification when using WHO‐GS versus IG‐NS at birth. We also estimated sensitivity and specificity of indicators of undernutrition at birth using WHO‐GS versus IG‐NS.z‐scores from birth to 3 months and mean conditional measures of size at 3 months using Bland–Altman plots to visualise the distributions of individual‐level differences between WHO‐GS and IG‐NS.Using WHO‐GS at birth and postnatally (‘WHO‐GS’) or IG‐NS at birth combined with WHO‐GS postnatally (‘IG‐NS’), we estimated infant growth in the first 3‐month postnatal age by quantifying: (i) mean change in LAZ, WAZ or HCAZ from birth to 3 months, referred as to ΔLAZ, ΔWAZ and ΔHCAZ, respectively; and (ii) mean LAZ, WAZ or HCAZ at 3 months conditional on size at birth, respectively. The latter, ‘conditional measures’ of growth, were the infant‐level model residuals from the linear regression of size at 3 months on size at birth. A positive residual indicates greater than expected growth given size at birth, whereas a negative residual indicates lower than expected growth given size at birth, relative to other infants in the cohort. For any index based on conditional growth, the overall group mean is always zero; therefore, mean conditional measures are only reported by GA strata. We compared WHO‐GS and IG‐NS with respect to mean changes in z‐scores at birth derived using WHO‐GS versus IG‐NS; or (b) differences in ΔLAZ, ΔWAZ and ΔHCAZ using WHO‐GS versus IG‐NS at birth. Classifications were based on whether the absolute value of the difference exceeded a priori thresholds of 0.20 SD, 0.32 SD and 0.50 SD. An effect size of 0.2 SD is a commonly observed magnitude of change in anthropometric indices (namely LAZ) due to nutrition‐specific interventions.z‐score difference between the 5th (1.64 SD) and 2.5th (1.96 SD) percentile of a normal distribution, which was the stricter criterion used to assess comparability of data across sites by the INTERGROWTH‐21st consortium.z‐scores to assess acceptability of pooling data from different sites.In further analyses, we classified infants according to (a) individual‐level differences in 0/7 to 386/7 weeks), full‐term (390/7 to 400/7 weeks) and late‐term (410/7 to 430/7 weeks)] within the broad category of ‘term’ gestation to assess the extent to which overall heterogeneity in early postnatal growth trajectories may be due to variation in GA at birth. Analysis for each cohort was conducted independently using Stata version 14.0 and R package.All analyses were stratified by GA [i.e. early‐term  for primary comparisons of anthropometric indices and indicators using WHO‐GS versus IG‐NS.2.6Ethics approval for the use of de‐identified secondary data from the two trials was obtained from the Hospital for Sick Children Research Ethics Board, Toronto, Canada (Protocol # 1000057464).3n = 28 in MDIG), preterm‐born infants (n = 53 in MDIG and n = 9 in ENID) and infants for whom birth anthropometry was taken after 48 h (n = 150 in ENID), data from 755 infants from the MDIG study and 522 infants from the ENID study were included in the final analytical sample. Baseline maternal characteristics of infants included in this study differed between the cohorts , the prevalence of underweight was similar in MDIG (18% vs. 17%) but lower in ENID (7.5% vs. 12%), and the prevalence of microcephaly was higher in MDIG (10% vs. 7.6%) but the same in ENID , highlighting the major effect of the choice of birth size standards on the assessment of an individual infant's growth trajectory, beyond its effects on population‐level inferences.In two longitudinal birth cohorts from Bangladesh and The Gambia, mean LAZ, WAZ and HCAZ, and the prevalence of undernutrition at birth among term‐born children were most similar when using WHO‐GS compared with IG‐NS among infants born between 39 and 40 weeks of GA. Mean anthropometric indices were systematically lower among early‐term infants and higher among late‐term infants when using WHO‐GS compared with IG‐NS at birth. The relatively slow growth of early‐term infants and relatively faster growth of late‐term infants observed when using IG‐NS at birth was not evident when using WHO‐GS as the only growth standard in longitudinal analyses. Importantly, the magnitude of changes in 4.2The strengths of the study are the use of data from two birth cohorts—one from South Asia and the other from sub‐Saharan Africa—to assess the consistency of inferences across populations with differing nutritional status. While this study could have been performed with simulated data, the use of two cohort datasets provides a real‐world illustration of the discrepancies between the two standards. In addition, ultrasound‐based assessments were used in both MDIG and ENID studies, which is the gold‐standard method for determining GA. Newborn and infant anthropometric measures were collected using robust methods in both studies.4.3Although ultrasound assessments were used to confirm GA, these were not solely based on first trimester ultrasounds assessments, which are most reliable for GA dating. We restricted our analysis to only include data from liveborn infants at term gestation with no congenital anomalies, available GA and at least one available anthropometric measure collected within 48 h of birth to allow for robust methodological comparisons with high‐quality anthropometric data. Therefore, the sample population in this study may not be reflective of the general population in Bangladesh and The Gambia, yet inferences regarding the comparisons of anthropometric indices and indicators between WHO‐GS versus IG‐NS remain valid. Furthermore, the distribution of infants born across GA strata of early‐term, full‐term and late‐term was not equal which may have affected the ability to detect differences between anthropometric indices and indicators when using WHO‐GS versus IG‐NS within GA strata.4.4The INTERGROWTH‐21st newborn size standards (IG‐NS) were intended to replace previous size‐at‐birth references and to complement the WHO‐GS to enable the evaluation of the growth of a child or a group of children across a ‘continuum from the womb to the classroom’.z‐scores between birth and a postnatal time point when using IG‐NS at birth and WHO‐GS postnatally. This is particularly relevant in the first few months of life when variation in GA at birth is most likely to affect size and growth.The present study focused on examining the implications of variations in GA on newborn size and early growth among term infants only. Previous studies have consistently shown that perinatal and newborn mortality, morbidity and child development vary by week of GA even within the relatively narrow term duration of 37 to 42 weeks of GA.5z‐scores that are an artefact of combining two different standards, particularly among early‐ and late‐term infants. Therefore, researchers should carefully evaluate the interchangeability of z‐score values when using IG‐NS compared with the WHO‐GS at birth among term‐born children, and explicitly assess the potential implications for summarising early life growth trajectories and robustness of inferences for epidemiologic associations.The INTERGROWTH‐21st newborn size standards and the WHO‐GS are not interchangeable at birth for all the GAs in the range in which they overlap (i.e. 37to 42 weeks), especially for children born at <39 weeks or >40 weeks of GA. Using IG‐NS at birth in conjunction with WHO‐GS at a postnatal time point in the same analysis may yield within‐child changes in anthropometric None to declare.NP and DER conceptualized the study; NP, EOO, AMP, PSS, SEM, and DER contributed to the study design; AM, AMP, SEM, and DER contributed to acquisition of the data used in the study; EOO contributed to the analysis; NP led the analysis and interpretation of the data and drafted the manuscript. All authors revised the manuscriptcritically for important intellectual content and provided their final approval of the version to be published.Supinfo S1Click here for additional data file.


This study aimed to determine the relationship between estimated fetal weight discordance by ultrasonography and maternal and neonatal outcomes in dichorionic diamniotic twin pregnancies. We conducted a retrospective review of the medical records of 106 twin pregnancies delivered at a single tertiary center between January 2011 and February 2020. At 20–24 and 28–32 weeks of gestation, participants were divided into two groups: discordant twins with an estimated fetal weight difference of more than 20% and concordant twins with a weight difference of less than 20%. Maternal complications and neonatal outcomes were compared between the two groups. Although the incidences of preeclampsia and placenta previa were significantly higher in discordant twins measured between 20 and 24 weeks, no statistical significance was found in neonatal outcomes. Delivery times were earlier, and neonatal weights were lower in discordant twins measured between 28 and 32 weeks. Neonatal outcomes such as ventilator use and neurodevelopment were also significantly different. Discordance in estimated fetal weight measured using ultrasonography between 20 and 24 weeks can be a risk factor for maternal preeclampsia and placenta previa, whereas discordance at 28–32 weeks may predict poor neonatal outcomes. Increasing maternal age and pregnancy through assisted reproductive techniques (ART) contribute to increased twin births3. The incidences of maternal pregnancy-related complications, neonatal morbidities, and mortality are higher in twin pregnancies than in singleton pregnancies. Preeclampsia occurs 2.6 times more frequently in twin pregnancies, which increases the risk of placental abruption and preterm delivery4. Twin pregnancies also increase maternal morbidity, such as gestational diabetes mellitus (GDM), postpartum hemorrhage (PPH), and operative delivery8. In neonates, twin pregnancies increase the risk of stillbirth by approximately five times9. In addition, neonatal morbidity and mortality increased, including a 6-fold increase in preterm births before 34 weeks10. Moreover, risks such as preterm birth (PTB) and stillbirth, congenital fetal anomaly, intrauterine growth restriction (IUGR), umbilical artery acidosis, neonatal intensive care unit (NICU) admission, and respiratory distress (RDS) are increased in discordant twins whose birth weights differ by more than 20%11. Neonatal morbidity increases by approximately 7.7 times in discordant twins and small-for-gestational-age (SGA) babies2. Fetal weight discordance after birth has been used to predict prognosis. The purpose of this study was to determine whether discordance of the estimated fetal weight (EFW) could predict neonatal outcomes of twin babies based on sonographic findings of the fetus performed during the prenatal examination. Additionally, the relationship between weight discordance and maternal pregnancy complications was investigated. This study used the EFW between 20–24 weeks and 28–32 weeks of gestation in twin pregnancies and compared maternal and neonatal outcomes between the discordant and concordant fetal weight groups.The incidence of multifetal pregnancies, including twins and triplets, is increasing worldwide. In the United States, approximately 33.3 births per 1000 pregnancies were twin pregnancies in 2009, a 76% increase since 1980This study included 106 twin pregnancies and 212 neonates. When weight discordance developed in twins between 20 and 24 weeks of pregnancy and between 28 and 32 weeks of gestation, the obstetric and neonatal outcomes were analyzed. Based on EFW between 20 and 24 weeks of gestation, pregnancies were divided into 95 concordant and 11 discordant weight twin pregnancies. According to EFW, between 28 and 32 weeks of gestation, pregnancies were divided into 90 concordant and 16 discordant weight twin pregnancies.p = 0.095) and body mass index (BMI) . However, in the concordant group, significantly more nulliparous cases  and pregnancies through ART  were confirmed. No significant differences in GDM , threatened preterm labor (PTL) , premature rupture of the amniotic membrane (PROM) , and PPH  were observed between the two groups. However, the frequencies of preeclampsia  and placenta previa  were significantly higher in the discordant group than in the concordant group. No differences in the causes of delivery were observed between the two groups.Table p = 0.778), sex , and birth weights . Moreover, no differences were observed in the 1- and 5-min Apgar scores of 7 or less  and NICU hospitalization . The frequency of actual weight discordance at delivery  and developmental delay  were higher in the discordant group, whereas oxygen supply treatment  was higher in the concordant group. No significant differences were observed in neonatal morbidity, intubation, ventilator use, RDS, sepsis, patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP). There was no statistically significant difference in neonatal outcomes between the discordant large and small, measured by ultrasonography between 20 and 24 weeks.Table p = 0.041) were performed, but no significant differences in maternal age, parity, or BMI were observed. Although preeclampsia was more prevalent in the discordant group , no significant difference in the frequency of placenta previa  was detected. Moreover, the frequency of iatrogenic cause of delivery was higher in the discordant group . No significant differences in the incidences of GDM, PROM, or threatened PTL were detected between the two groups.Table p < 0.001), lower birth weights , and higher NICU admission . Moreover, discordant twins required intubation , ventilator use , oxygen supply therapy , and phototherapy due to hyperbilirubinemia  more often than concordant twins. Moreover, developmental delays between 1 and 2 years after birth were more frequent in the discordant group . In the discordant group, there was no statistically significant difference in neonatal outcomes between the discordant large and discordant small neonates. However, in discordant small babies, lower 1 min Apgar scores and higher NICU admission rates were observed.Table p = 0.005) for discordance between 20 and 24 weeks of gestation and an OR of 2.961  for discordance between 28 and 32 weeks of gestation. Moreover, placenta previa was predicted by an OR of 7.400  for discordance between 20 and 24 weeks of gestation, and an OR of 2.087  for discordant twins between 28 and 32 weeks.Figure p = 0.154) and the OR of discordance between 28 and 32 weeks as 1.232 . Developmental delay was predicted by an OR of 8.047  for discordance between 20 and 24 weeks and an OR of 11.113  for discordance between 28 and 32 weeks.Figure 13. The reasons for the discordance in twin pregnancies differ depending on chorionicity. In dichorionic twins, discordance is due to potential differences in genetic growth and placental dysfunction, which account for the demands for oxygen and nutrition, which increase as the fetus grows. Incomplete conversion of uteroplacental circulation induces ischemic changes in placental tissue, which induces oxidative stress, apoptosis, and, subsequently, fetal growth differences20. In monochorionic twins, discordance arises because of the differences in the sharing of one placenta20. The earlier the onset of discordance, the lower the long-term survival of the fetus due to the occurrence of twin-to-twin transfusion syndrome (TTTS)22. Twin discordance is related to poor neonatal prognoses such as respiratory complications, stillbirths, SGA, and maternal morbidity. However, to our knowledge, few studies have investigated the weight discordance between two fetuses using ultrasonography measured during pregnancy and determined the relationship between weight discordance and maternal pregnancy-related complications and neonatal morbidities. The maternal and neonatal outcomes of concordant and discordant twins were compared at both gestational periods.Twin discordance, a twin-specific condition, has a total incidence of 10–15%, and the prevalence does not differ according to chorionicity23. Among dichorionic twins, the incidence of preeclampsia was higher in discordant birth weight twins than in concordant twins. In addition, studies have shown that the more severe the weight discordance, the greater the occurrence of preeclampsia and gestational hypertension24. These findings are consistent with the results of this study: discordance during pregnancy predicted the occurrence of maternal preeclampsia. The pathophysiology of the relationship between discordance and preeclampsia during pregnancy is unknown. However, there are several possible explanations. Discordance during pregnancy is either a cause or effect of placental ischemia or hypoxia25. Placental hypoperfusion caused by hypoxia may activate maternal endothelial dysfunction, which manifests as symptoms of vascular constriction and high blood pressure26. In addition, placental hypoperfusion affects maternal angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor, which are related to the development of preeclampsia27. Placental abnormalities such as location and weight of the placenta may also affect twin discordance and fetal growth28. A previous meta-analysis of singletons showed an association between fetal growth and placenta previa29. Most cases of placenta previa diagnosed on ultrasonography in the routine mid-trimester resolve before late gestation. However, placenta previa persisting until delivery may be related to placental hypoperfusion. Abnormal placentation such as placenta previa may induce placental hypoperfusion, which may cause discordance.Discordant twins between 20 and 24 weeks of gestation were found to have more complications related to maternal abnormal placentation, such as preeclampsia and placenta previa, compared with concordant twins. Preeclampsia is more common in twin pregnancies than in singleton pregnancies28. This study is different from other studies in that the study was limited to cases that were delivered after 32 weeks of gestation, and the predicted weight during pregnancy, not the actual birth weight, was used. Weight discordance after the third trimester of pregnancy is not due to the abnormal placentation of the mother, but rather the cause and effect of stress or insult to the fetus in the uterus due to various factors. Thus, the long-term intrauterine environment affects not only short-term outcomes such as oxygen therapy, which may appear immediately after delivery, but also long-term outcomes, such as developmental delay, that may appear 1–2 years after the birth of the fetus. In addition, weight discordance that occurs between 28 and 32 weeks of gestation is considered a sign that delivery is required and may lead to preterm births, which may affect short and long-term perinatal outcomes of the fetus.When comparing concordant and discordant twins using weight discordance between 28 and 32 weeks of gestation, discordant twins had a higher tendency to develop preeclampsia, but no significant differences were observed in the incidence of placenta previa. There were no significant differences in the incidence of GDM, PTL, or cause of delivery. No significant differences in gestational age at delivery and birth weight were observed when discordance was measured at 20 and 24 weeks of gestation. Except for developmental delay 1–2 years after birth, neonatal morbidities and complications also showed no significant differences. However, when comparing concordant and discordant twins using weight discordancy between 28 and 32 weeks of gestation, worse neonatal outcomes were observed in discordant twins. In the discordant group, the average GA at delivery was approximately 1 week earlier, and the fetuses tended to have lower birth weights. Delivery was more likely to be an induction delivery or cesarean section for medical reasons rather than an elective or scheduled delivery for discordant twins. Neonatal outcomes were worse, resulting in more NICU hospitalizations, and the presence of complications, such as morbidities, need for intubation, use of a ventilator, and phototherapy, tended to be higher in discordant twins. Developmental delays between 1 and 2 years of age also tended to be higher in the discordant group. Halling et al. reported that smaller discordant twins have more developmental disorders in cognition, language, and motor skills than larger twins do. However, PTB before 33 weeks of gestation had a greater effect on developmental delay than did discordanceAccording to the regression analyses of fetal weights at 20–24 weeks, preeclampsia is 5.5 times more likely to occur, and placenta previa is 7.4 times more likely to occur in discordant weight twins than in concordant weight twins. However, the discordance between 28 and 32 weeks was less significant as a diagnostic predictor. Therefore, sonographic findings in the second trimester of pregnancy may predict an abnormal placenta. In contrast, discordant weight fetuses measured between 28 and 32 weeks are 1.2 times more likely to use a ventilator and 11 times more likely to have developmental delays after birth after adjusting for confounding factors. Thus, discordance at 28–32 weeks was a predictor of short and long-term neonatal outcomes. In the discordant twin between 20 and 24 weeks, GA at delivery, birth weight, and short-term outcomes were similar to those of the concordant twin. However, there was a significant difference in the developmental delay. Intrauterine insult, which can induce discordance in early pregnancy, affects fetal neurodevelopment, but more research is needed.This study has several limitations. First, ultrasonography was subjective. However, to reduce intra-observer bias, sonographic values were measured three or more times in a row. Moreover, to reduce interobserver bias, one obstetrician performed sonographic measurements continuously according to the number of weeks of pregnancy. An expert reviewed the sonographic images and re-evaluated whether the images were appropriate. Second, the sample size was small. The study included only healthy dichorionic diamniotic (DCDA) twin mothers who had complete medical records and did not have fetal death, fetal anomalies, or twin-specific complications. Further research with a larger sample size is warranted. Finally, selective IUGR was not considered in this study. In this study, only the weight difference between the two fetuses of DCDA twins was analyzed, and the effect is unknown; therefore, it should be further addressed in future studies.In twin pregnancies, discordance using the estimated weight of the fetus between 20 and 24 weeks of gestation can predict the possibility of abnormal placentation, such as preeclampsia or placenta previa, whereas discordance between 28 and 32 weeks of gestation can predict a higher risk of short and long-term poor neonatal outcomes.30. This was done to minimize the impact of neonatal outcomes due to prematurity. An additional 29 women were excluded because of major fetal anomalies, chromosomal abnormalities, or fetal death in utero. Four women with unclear chorionicity, 3 with monochorionic monoamniotic (MCMA) twins, 23 with monochorionic diamniotic (MCDA) twins, and 10 with TTTS were also excluded. When chorionicity in the medical records and placental pathologic findings after delivery were different, the pathologic result was followed. Thus, 117 pregnancies were excluded, and 203 twin pregnancies were reviewed. Fetal ultrasonography  reports between 20 and 24 weeks of gestation and 28 and 32 weeks of gestation were reviewed. The weight was measured three times per fetus, and the average value was taken as the EFW. Ninety-seven pregnancies were delivered; however, sonographic measurements were not performed between 20 and 24 weeks of gestation or 28 and 32 weeks of gestation and were excluded from the study. Thus, the final number of pregnancies included in the analysis was 106. A flowchart illustrating the study plan is shown in Fig. The medical records of 320 patients with twin pregnancies who delivered at Kyungpook National University Chilgok Hospital in Daegu, South Korea between January 2011 and February 2020 were retrospectively reviewed. Based on 32 weeks of gestation, when lung maturation was expected in twins, 48 pregnancies delivered before 32 weeks of gestation were excluded3. If the value was > 20%, the fetuses were classified as discordant twins, and if the value was less than 20%, the fetuses were classified as concordant twins according to the consensus of the American College of Obstetricians and Gynecologists (ACOG) and the International Society of Obstetrics and Gynecology (ISUOG)31. In DCDA twins, discordance was distinguished only by weight difference, and selective fetal growth restriction (sFEG), which is IUGR in one of the two fetuses, was not considered32. Maternal characteristics such as age at delivery, parity, pre-pregnancy BMI, use of ARTs, and pregnancy-related complications such as preeclampsia, placenta previa, GDM, threatened PTL, and PPH were compared. According to the International Society for the Study of Hypertension in Pregnancy, preeclampsia was defined as a blood pressure of 140/90 mmHg or higher and proteinuria of 300 mg or higher for 24 h after 20 weeks of gestation33. A 50-gm glucose tolerance test was performed as a screening test for GDM between 24 and 28 weeks of gestation, and a 100-gm glucose tolerance test was performed when the value was > 140 mg/dL. GDM was diagnosed according to the Carpentre–Coustan criteria34. Placenta previa was defined by evaluating the location of the placenta through ultrasonography immediately before delivery, including placenta previa totalis, placenta previa partialis, placenta previa marginalis, and a low-lying placenta. Threatened PTL was defined as inpatient conservative treatment before 37 weeks of gestation owing to regular uterine contractions and a short cervical length of less than 25 mm. PPH was defined as bleeding of more than 1 L or getting a transfusion after delivery because of anemia. Deliveries scheduled on a non-event date were classified as elective, deliveries due to labor pain as spontaneous, and emergency deliveries due to preeclampsia or poor fetal condition as iatrogenic. A comparison was made between the 20th and 36th weeks of pregnancy, divided into 4-week intervals. The 32–36 weeks of gestation, where there was no significant difference between EFW and birth weight, were excluded. There was no difference in EFW between 24–28 and 28–32 weeks of gestation. The early gestational weeks could be affected by genetics, and hence, 24–28 weeks of gestation were excluded from the analysis. Maternal complications and neonatal outcomes were analyzed at 20–24 and 28–32 weeks of gestation. To compare the neonatal outcomes of discordant and concordant pregnancies, GA at delivery, neonatal birth weight, 1-min and 5-min Apgar scores, NICU admission, neonatal morbidity, and mortality were analyzed. The morbidities included RDS, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), and sepsis. We reviewed the rate of developmental delay in cases that had fine and gross motor disturbances observed through physical examination and the Bayley Scale, and in those that required rehabilitation 1–2 years after birth. This study was approved by the Institutional Review Board (IRB) of Chilgok Kyungpook National University Hospital (IRB No. KNUCH 2020–06-015). All methods were performed in accordance with the relevant guidelines and regulations. The requirement for informed consent was waived by Institutional Review Board (IRB) of Chilgok Kyungpook National University Hospital because of the retrospective nature of the review of medical records. This study was approved by the Institutional Review Board (IRB) of the Chilgok Kyungpook National University Hospital.Weight discordance was measured using the EFW of the two fetuses using the Hadlock formula, which was multiplied by 100 after dividing the difference between the weights of the two fetuses by the expected weight of the large fetus, as defined in previous studieswww.r-project.org/). The results of the concordant and discordant groups were compared using the Mann–Whitney U test for continuous numerical data, whereas the χ2 test was used for binary categorical data. Data is presented as mean ± standard deviation for continuous variables with normal distributions and numbers (percentages) for binary categorical data. A p value of < 0.05 was considered to be statistically significant. Logistic regression analyses were conducted to identify independent variables predictive of maternal complications and neonatal outcomes among concordant and discordant twins. ORs and 95% confidence intervals (CIs) were calculated.All data were analyzed with IBM SPSS Statistics for Windows, version 26.0,  and R version 4.0.0  of Chilgok Kyungpook National University Hospital (IRB No. KNUCH 2020-06-015). Informed consent was not obtained from the study participants due to the retrospective nature of the review of medical records.