P = .001). There was also a significant negative correlation between PAB levels and gestational age. According to previous investigations, we showed for the first time in our study that PAB is lower in preterm newborns rather than in term ones.The oxidant/antioxidant status balance is a process that begins before birth and premature infants are particularly susceptible to oxidative stress. According to the mechanisms of oxidative stress and lack of study in this field, in this prospective study, we aimed to compare the levels of serum pro-oxidant/antioxidant balance (PAB) in preterm versus term babies. This was a prospective cross-sectional study that was performed in Ghaem hospital, a university tertiary hospital, in Mashhad, Iran. The study population included all term and preterm neonates who were admitted to the hospital within birth time. In our study, 324 neonates were included. One hundred ninety-eight neonates were preterm (61.1%) and others were term (38.9%). There was a significant difference between PAB levels in term and preterm neonates. Serum PAB level was significantly lower in preterm neonates rather than in term neonates (21.86 ± 21.01 vs 50.33 ± 31.69;  Hypoxia is necessary for the development and growth of the fetus. Under normal circumstances, the fetal-to-neonatal transition causes physiological oxidative stress (OS), which enhances the antioxidant defense and pulmonary surfactant maturation.Free radicals are molecular species with an unpaired electron in the outer shell, which renders them highly reactive and unstable. FRs containing oxygen may be termed reactive oxygen species (ROS). The accumulation of reactive FRs, beyond the capacity of the endogenous antioxidant defense system to scavenge them, results in damage to DNA, proteins, and lipids that compromise cell function, leading to cell death via apoptosis or necrosis. and premature infants are particularly susceptible to OS.,6 Most of the complications of prematurity, such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, and punctate white matter lesions, appear related to OS,,8 mostly occurring due to a mismatch between the free radical production and the anti-oxidative capacity of the premature neonate.The oxidant/antioxidant status balance is a process that begins before birth, Preterm infants show reduced antioxidant defense mechanisms, including decreased levels of vitamin E, β-carotene, melatonin, ceruloplasmin, transferrin, and erythrocyte superoxide dismutase (SOD). In a study on 100 preterms and 100 full-term neonates, plasma levels of vitamin A, vitamin E, and catalase were found significantly lower while plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was significantly higher in the preterm than in the full-term newborns, especially in those ones who developed necrotizing enterocolitis or bronchopulmonary dysplasia. Premature babies have both immature lungs and antioxidant defense systems and often require oxygen supplementation to overcome respiratory distress. The combination of hyperoxia, which enhances the generation of ROS, and low antioxidants cause OS, inflammation, and even apoptosis, thus increasing mortality and morbidity.Moreover, antioxidant defense mechanisms are incompletely developed or deficient in preterm newborns.According to the mechanisms of OS and lack of study in this field, in this prospective study, we aimed to compare the levels of serum pro-oxidant/antioxidant balance (PAB) in preterm versus term babies.This was a prospective cross-sectional study that was performed in Ghaem hospital, a university tertiary hospital, in Mashhad, Iran between 2015 and 2019. The study population included all term and preterm neonates who were born in Ghaem hospital within birth time. This investigation was approved by the Ethical Committee of Mashhad University of Medical Sciences. We obtained parents’ informed written consent before entry into the study. The term low birth weight. ‘Low birth weight (LBW) has been defined as the first weight recorded within hours of the birth of fewer than 2500 g between 33 and 37 weeks gestational age. Very low birth weight is accepted as less than 1500 g at lower than 32 weeks gestational age.We recruited all babies born in our center during the study interval without any abnormal examination, known anomalies in perinatal assessment, hypotonia, bradycardia, low Apgar score, requiring cardiopulmonary resuscitation, or need to use accessory oxygenation. We excluded neonates with severe birth defects, respiratory distress, positive history of eclampsia/preeclampsia in mothers, birth asphyxia, suspicious of sepsis, hemolytic hyperbilirubinemia, Rh or ABO incompatibility, and pathologic jaundice neonates.We completed a checklist for each neonate including gestational age, gender, birth weight, and Apgar score. Moreover, mothers’ data included age, parity, pregnancy-related problems, mode of delivery, and blood type were completed. Babies after sampling and data collection underwent routine care if necessary during their hospital admission. Blood samples were taken from the umbilical cord (1 cc for each neonate) and were used for PAB measurement after centrifuge and separation of serum. For this measurement, the separated blood samples were transported to Bu-Ali Research Institute.The solutions were prepared as indicated. The standard solutions were made by mixing varying proportions (0%–100%) of 250 μM hydrogen peroxide with 3 mM uric acid in 10 mM NaOH. In order to prepare the 3,3′,5,5′-tetramethylbenzidine (TMB) cation, 60 mg of TMP powder was dissolved and mixed well at a ratio of 10 to 20 mL of the solution. Then, the prepared solution was placed in the dark for 2 hours. Next, 25 units of peroxidase enzyme were added to 20 mL of the solution and placed at 20°C. For the preparation of the TMB solution, 200 mL of TMB was added to 10 mL of acetate buffer ; the working solution was prepared by mixing 1 mL of TMB cation with 10 mL of TMB solution. The prepared solution was placed in a dark, dry place for 2 minutes. Next, 10 μL of each sample was mixed with 200 μL of the working solution and placed in a 96-well plate in the dark at 37°C for 12 minutes. At the end of the process, 100 μL of 2N Hall was added to each well and measured in an ELISA plate reader at 450 nm and 620 nm wavelengths. PAB values were calculated on the standard curve as previously published.t test was used for continuous variables. Parametric and nonparametric correlations were assessed using Pearson correlation coefficients and Spearman correlation coefficients, respectively. P value < .05 was considered statistically significant.Data were entered in SPSS-20 software . The continuous values were indicated as mean ± SD. An independent In our study, 324 neonates were included. One hundred ninety-eight neonates were preterm 61.1%) and others were term (38.9%). Table .1% and oThe mean birth weight of participants was 3267.19 ± 446.35 g in term and 1658.78 ± 644.97 g in preterm neonates. Other perinatal factors are listed in Table P = .001). It is also shown in Figure As can be seen in Table r = –0.547, P < .001). Figure There was also a significant negative correlation between PAB level and gestational age by number (P = .005) and gestational age (P = .002) were predictors of PAB level in our study population.Linear regression analysis showed that birth weight , protein carbonyl,23 and desferrioxamine chelate iron in preterm newborns. Compared to full-term birth, preterm newborns also enhance plasma nonprotein bound iron concentration,,23 which can lead to oxidative damage through the Fenton reaction. Some studies reported that OS levels are negatively correlated with gestational age.,22,24,25 In our study, this correlation was also confirmed. Our findings showed that preterm neonates had lower levels of PAB in comparison with term neonates. This strengthens the hypothesis that prematurity itself is at least partly capable of higher OS in preterm newborns.There are more data on other oxidative indexes in preterm and term neonates. It was shown in previous studies that newborn preterm neonates had high levels of OS biomarkers. These markers were evaluated such as plasma, MDA-hemoglobin,,26 and erythrocytes,,27 catalase activity in blood as well as cytosolic glutathione peroxidase in erythrocytes are lower in preterm than in full-term newborns. Preterm newborns also exhibit lower levels of nonenzymatic antioxidants such as erythrocyte vitamins. Many physiological mechanisms can induce the higher OS levels observed in preterm newborns. It is known that OS levels in mothers vary during pregnancy and this can be because of increased OS in the placenta.,30 This OS in the placenta is probably necessary for its development by regulating the proliferation, differentiation, and invasion of trophoblasts, promoting placental angiogenesis, and regulating autophagy and apoptosis required for placentation. However, a high level of systemic OS in mother can be related to preterm labor and prematurity. Therefore, higher OS level in pregnant women might lead to dysfunction of placenta or other damages that lead to preterm labor and be responsible for the high OS level observed in preterm newborns by direct blood exchange in the placenta. On the other hand, preterm newborns have an immature antioxidant system, as the last weeks of pregnancy correspond to the maturation and upregulation of the fetus’s antioxidant system and the transfer of some antioxidants from the mother to the fetus. This may explain why babies born early in their third-trimester exhibit lower concentrations of antioxidants. Moreover, preterm newborns might need several medical interventions because of their immature state and this can also induce ROS generation.This can be because of the lower levels of different antioxidant biomarkers. It is explored that at birth, SOD activity in both blood Despite the novelty and relatively large sample size, there were some limitations in this study. Measurement of other antioxidant biomarkers like SOD, catalase, MDA, and glutathione peroxidase and finding the correlation between them and PAB could reinforce the results of this hypothesis. Lack of long-term follow-up of neonates’ outcomes and no other biochemical and maternal factors for finding the predictive value of PAB, were other limitations of this investigation.Although in previous studies, there were many biomarkers of OS evaluated in preterm versus term newborns, there is still a need to find the applicable tests to find this hypothesis. In this study, we used an approach with potential clinical applications in oxidant/antioxidant assays, which was the PAB technique. The assay is a new strategy to determine the pro-oxidant load and antioxidant capacity in a single assay. The assay provides a general view of the oxidant/antioxidant status of the patients in one single experiment.According to previous investigations, we showed for the first time in our study that PAB is lower in preterm newborns rather than in term ones. This is in line with the hypothesis that OS is higher in preterm neonates. Targeting OS in preterm neonates as an applicable clinical index can complete the pathway of effects of OS in preterm newborns. More studies targeting PAB are needed in the future to prevent the poor prognosis of preterm newborns with chronic disorders in childhood.We thank the deputy of research at Mashhad University of Medical Sciences and healthcare workers of the neonatal intensive care unit especially Mrs. Eskandari, Mrs. Ramezani, Mrs. Nikooseresht, Mrs. Aelam, Mrs. Hakimi, and laboratory colleagues especially Mrs. Tavallayi and Mr. Asaran. We also thank Mr. Mehrabi and Mr. Parvizi for their cooperation.Conceptualization: Hasan Boskabadi, Majid Ghayour-Mobarhan.Data curation: Hasan Boskabadi.Investigation: Hasan Boskabadi, Majid Ghayour-Mobarhan.Methodology: Hasan Boskabadi, Majid Ghayour-Mobarhan.Writing – original draft: Hasan Boskabadi, Majid Ghayour-Mobarhan, Amin Saeidinia.Writing – review and editing: Hasan Boskabadi, Majid Ghayour-Mobarhan, Amin Saeidinia.


The case is a 78-year-old female. A giant liver cyst was pointed out by abdominal echo from 7 years ago, but because the size of the cyst tended to increase, it was decided to operate taking into account the risk of the cyst rupturing. Laparoscopic surgery was started, and the cyst contents did not fluorescent when observed by the indocyanine green (ICG) fluorescence method. Laparoscopic liver cyst fenestration was performed using the ICG fluorescence method, paying attention to the damage to the bile duct excluded by the cyst. The opened cyst was filled with the greater omentum. In this report, we describe that the ICG fluorescence method can evaluate the presence or absence of bile leakage from the hepatic dissection and the running of the bile duct on the inner wall of the cyst, and is considered to contribute to safer laparoscopic liver cyst fenestration. Nonparasitic liver cysts are congenital or acquired and are considered to be caused by an aberrant bile duct that has lost its communication with the normal biliary tree, which ultimately results in an isolated fluid-collected cavity in the liver . In mostIndocyanine green (ICG) clearance test is a well-established and one of the most reliable preoperative liver function tests . It is aA 78-year-old female patient was followed up by a family doctor who pointed out a giant liver cyst (maximum diameter 11.5 cm) by abdominal echo 7 years ago. Her liver cyst was gradually increasing  with a designated rigid scope , which could provide fusion fluorescence imaging consisting of normal and near-infrared light images. Cysts were observed on and inside the liver . ICG fluLiver cysts are relatively common with a prevalence of 2–7% among the population and are typically discovered incidentally . The patSurgical options for treating symptomatic liver cysts include fenestration, hepatectomy and liver transplantation . Other tet al. in the 1980s, especially in patients with hepatocellular carcinoma [In addition to various liver function tests, ICG tests are generally performed to evaluate the safety of hepatectomy, and these tests are also adopted, for example, as criteria for assessing the degree of liver damage. The ICG test was introduced and popularized by Makuuchi arcinoma . In patiarcinoma . In patiarcinoma .Usually, for visualizing a tumor, ICG is administered 24–48 h before the surgery . On the LF using intravenously administrated ICG that can visualize the intrahepatic bile duct located in the cyst wall is an effective method to reduce the risk of accidental bile duct injury during LF. Further study is needed to optimize the timing of ICG administration to confirm whether ICG fluorescence can help prevent and manage bile duct injury during LF. ICG fluorescence–guided LF has the potential to be used as a standard surgical procedure for treating symptomatic liver cysts.


Conclusions: No association between UPF consumption during pregnancy and baby’s anthropometric measurements at birth was observed, probably due to the multifactorial nature of anthropometry and the interference of sociodemographic, gestational, and environmental factors in the baby’s health outcomes.Objective: This study aimed to assess the association between ultra-processed foods (UPF) consumption and some lifestyle factors during pregnancy and the baby’s anthropometric measurements at birth. Methods: Cross-sectional study conducted with immediate postpartum women and their babies. Food consumption during pregnancy was assessed retrospectively by a semi-quantitative food frequency questionnaire, and the baby’s anthropometric measurements were obtained from the medical records. The percentual of energy from UPF was estimated, categorized in tertiles, and associated with the baby’s anthropometric measurements using multinomial logistic regression, adjusting by maternal characteristics . Results: A total of 626 immediate postpartum women and their babies were evaluated. The mean percentual of energy from UPF consumption during pregnancy was 30.56%. Before adjustment, there was a greater chance of insufficient birth weight among babies of immediate postpartum women in the highest tertile of UPF consumption (OR 1.72; 95% CI 1.09–2.70;  Ultra-processed foods (UPF) are products that generally do not maintain their basic characteristics for undergoing different processes and techniques to have industry-exclusive substances included in their composition . UPF areDuring pregnancy, the intake of UPF must be moderate, since an inadequate intake of macro and micronutrients can alter maternal gestational weight gain (GWG) and blood pressure and glycemia, and as a consequence, intrauterine growth, which leads to offspring with birth weight and length deviations ,4. Even Low birth weight LBW; <2500 g) is associated with a higher neonatal and infant morbimortality, being the most influential factor in the first years of life 00 g is a. On the Little is known about the association between diet quality and another factors, such as physical activity and parity during pregnancy, and birth weight ,5. MoreoConsidering the importance of the baby’s anthropometric measurements on child health and the global increase of UPF consumption in the last decades, this study aimed to assess the influence of UPF consumption and some lifestyle factors during pregnancy on the baby’s anthropometric measurements at birth.This cross-sectional study evaluated immediate postpartum women and their babies in a Brazilian public maternity hospital between 2018 and 2019.For sample calculation, the prevalence of birth weight for gestational age > 90th percentile among mothers with high adherence to a dietary pattern based on fast food and candies (7%) found in a similar study were adopted , so the The exclusion criteria were based on variables that could interfere with the baby’s anthropometric measurements : diabeteThis study was conducted in accordance with the Helsinki Declaration, and all procedures involving human participants were approved by the Ethical Committee of Universidade Federal de Minas Gerais and Fundação Hospitalar de Minas Gerais. Written informed consent was obtained from all immediate postpartum women.Maternal level of education was categorized as primary education, high school, or higher education. Per capita income was categorized in <0.5 and ≥0.5 minimum wage . Maternal marital status was classified as married/civil union or single/divorced/widow.® portable stadiometer. Z-scores cutoff points of BMI/age [® and were used for the adolescents (<20 years old). The WHO8 recommendation was considered for adult mothers. The categories “overweight” and “obesity” were included in the category “excessive weight”.Pre-gestational body mass index (BMI) was calculated using the self-reported pre-gestational weight and height was measured by the researchers according to the World Health Organization (WHO)  recommen BMI/age  were obtIf the mothers could not inform the GWG, the weight registered in the pregnant woman diary from the last prenatal consultation was considered for calculation. Institute of Medicine  criteriaParity was categorized as primiparous and multiparous. The number of prenatal consultations was classified as not attended, one to five, and six or more consultations, and the last one covers the Brazilian recommendation of a minimum of six consultations during pregnancy .Smoking practice was classified as smoker, ex-smoker, or never smoked. The practice of pre-gestational physical activity was classified according to the level of physical activity criteria . Women iFood consumption during pregnancy was measured using a semi-quantitative food frequency questionnaire (FFQ), validated for the Brazilian adult population . The queThe items in the FFQ were classified according to the NOVA classification system, into four distinct groups according to Monteiro et al.’s recommendations ,22: in nThe results of each group consumption frequency were converted into energy  for further classification into tertiles referring to the percentage of the total daily caloric value from these groups of foods  . ParticiBaby’s anthropometric measurements were obtained from the medical records. Birth weight was classified as low <2500 g; insufficient: 2500 to 2999 g; adequate: 3000 g to 4000 g; and macrosomia: ≥4000 g . Birth wTM program, and after consistency analysis, descriptive analysis was performed. Kolmogorov–Smirnov test was applied, and Chi-square or Fisher’s exact test with Bonferroni post-hoc were performed. These analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 21.0.Data were double-typed using the EpiInfo® program, version 14.2, to verify the associations between baby’ anthropometric measurements at birth and the UPF tertiles, adjusting by important maternal characteristics , selected considering its potential interference on the outcome [Multinomial logistic regression was performed using Stata outcome . The sigA total of 626 immediate post-partum women and their babies were evaluated . The medThe mean energy percentual from UPF consumption during pregnancy was 30.56% . MothersAs for the babies, 11.4% were SGA, and 13.3% presented small length at birth. Additionally, 6.9% were LBW, 25.2% presented insufficient birth weight, and 3.5% presented macrosomia .In the bivariate analysis, marital status, pre-gestational BMI, GWG, prenatal consultations, and smoking were associated with the baby’s weight at birth. The variables GWG and parity were associated with weight for gestational age at birth. Additionally, GWG was associated with length at birth. No association was observed between the UPF tertiles and the baby’s anthropometric measurements at birth .In the regression model, before adjustment, there was a greater chance of insufficient weight at birth among babies of mothers in the highest tertile of UPF consumption. However, such association was not observed after adjustments .This research found no association between the consumption of UPF during pregnancy and the baby’s anthropometric outcomes at birth, probably due to the multifactorial nature of anthropometry and the interference of sociodemographic, gestational, and environmental factors.Similar to LBW, insufficient weight at birth represents an important risk factor for infectious diseases, such as diarrhea, acute respiratory infections, delayed growth and development, high infant mortality rate, and future chronic diseases. The frequency of offspring born with insufficient weight is considerably higher than LBW, as observed in the present study, and both conditions can be determined by several socioeconomic, environmental, and behavioral factors .Such factors are described as having a strong influence on anthropometric measurements at birth, with repercussions in childhood and adulthood ,9, whichIn this research, GWG was associated with all the evaluated outcomes in the bivariate analysis, corroborating with other findings. A study by Santana et al. , carriedAlthough the association between the UPF consumption and the insufficient weight at birth has lost statistical significance after adjustment for confounding variables, maternal food consumption stands out in the literature among the explanatory variables for baby’s anthropometric outcomes, for the diet of pregnant woman must contain adequate energy and nutrients to allow healthy fetal growth and development . ChangesAnother point that deserves attention and could explain the absence of associations from UPF intake and outcomes is that the underreporting of food intake could occurs when the data are collected using FFQ , despiteIn the present study, the mean energy percentual from UPF 30.6%) was similar to that found in other studies conducted with pregnant women. In a cross-sectional study carried out in Brazil with 785 women, an average contribution of 32% of the TEC from UPF was identified [0.6% was There is a gap in the literature regarding the acceptable level of UPF consumption. Crivellenti et al. , in the Studies that demonstrate the risk of UPF consumption during pregnancy for the baby’s anthropometric measurements in the short and long term are still scarce. However, it is known that the consumption of these products can impair the quality of food intake, due to their ability to displace and interfere with the consumption of foods that are beneficial to health, such as in natura and minimally processed foods . The preStudies carried out in Brazil and worldwide have shown controversial results on the association between the consumption of UPF during pregnancy and the baby’s anthropometric measurements ,36.In a Brazilian prospective cohort, the pattern composed of UPF, such as fast food and snacks, cakes, cookies, candies, or desserts, was associated with a greater chance for LGA babies and birth length > 90th percentile . On the Maternal self-reported pre-gestational weight and GWG may be influenced by memory and underestimation bias and is, therefore, considered a limitation of this study. However, the literature demonstrates a good agreement and validity between the reported and measured weight .Finally, it is worth noting that the NOVA classification is relatively recent, and the authors are still unaware of studies using this new methodology to investigate the association between UPF consumption during pregnancy and the baby’s anthropometric measurements at birth. The consumption of UPF during pregnancy was not associated with the baby’s anthropometric measurements at birth, probably due to the multifactorial nature of anthropometry and the interference of sociodemographic, gestational, and environmental factors in the outcomes.


This study aimed to identify determinants of fetal macrosomia among live births at Wolaita Sodo town Southern Ethiopia.Fetal macrosomia defined as birth weight of 4000 g and above regardless of gestational age and associated with adverse maternal and fetal outcomes, especially among women in developing countries like Ethiopia. Despite the observed burden, there is limited evidence on determinants of fetal macrosomiap-value < 0.05 and 95% CI for AOR.A facility-based matched case–control study design involved 360 singletons deliveries attended at hospitals in Wolaita Sodo town, southern Ethiopia, with 120 cases and 240 controls included. Cases and control were matched by maternal age. Cases were neonates with a birth weight of ≥ 4000, while controls were neonates with a birthweight between 2500gm and less than 4000gm. Data were collected by interviews, measuring, and reviewing mothers' medical documents. Conditional logistic regression analysis was carried to identify the independent predictor variables. Statistical significance was set using a p < 0.001]. Neonates born at gestational age ≥ 40 weeks were 4.33 times more likely to be macrosomia with MAOR = 4.33 . Neonates born from physically inactive mothers were 7.76 times more likely to be macrosomia with MAOR = 7.76 . Neonates born from mothers who consumed fruits and dairy products in their diet frequently were 2 and 4.9 times more likely to be macrosomia MAOR = 2.03  and AOR = 4.91 respectively.Male neonates were four times more likely to be macrosomia than female neonates MAOR = 4.0 [95%CI; 2.25–7.11, Mothers' physical exercise and consumption of fruit and dairy products were significant predictor variables for fetal macrosomia. Hence, health care providers may use these factors as a screening tool for the prediction, early diagnosis, and timely intervention of fetal macrosomia and its complications.The online version contains supplementary material available at 10.1186/s12884-022-04734-8. Fetal macrosomia is defined as a total birth weight of 4000 g and above regardless of gestational age or greater than 90 percentile for gestational age –5. The mGlobally, macrosomia affects 12% of normal pregnancy and 15%-45% of mothers with gestational diabetes . The magIn developing countries, fetal macrosomia ranges from 0.5 in India to 15% in Algeria, though there has been a rise in prevalence from 15–25% in the last two decades .Recent studies reveal that the prevalence of fetal macrosomia in Ethiopia is estimated from 6.7% to 19.1% –16.Fetal macrosomia is a significant contributor to obstetric morbidity and mortality. Due to the maternal and neonatal morbidities associated with macrosomia fetuses' pregnancies, such pregnancies are often considered high-risk pregnancies. Macrocosmic baby has a higher threat of developing both short and long term health outcomes in later life; Short term health outcomes: including birth asphyxia, stillbirth, shoulder dystocia, hypoglycemia, skeletal injuries, meconium aspiration, fetal death, and low Apgar score , 17, 18.Fetal macrosomia is also related to maternal complications like postpartum haemorrhage, prolonged labor, perineal laceration, cesarean delivery, failed instrumental delivery, maternal death, uterine rupture, and wound infection –20The goDespite the above efforts and strategies, fetal macrosomia is still the significant contributor to maternal and neonatal mortality and morbidity in Ethiopia , 16, 22.Macrosomia can be a more significant obstetric hazard for women in Ethiopia, where undernutrition during childhood can inhibit the growth of the pelvis to its full potential. Pregnancy before the pelvis fully develops joint; delivering a giant baby is distressing to the mother, her baby, obstetrician, and neonatologist. It may lead to unfavourable outcomes during the whole process from pregnancy through delivery and finally after giving birth .Some studies conducted in Ethiopiaidentified gestational age, GDM, sex, weight gain during pregnancy, pre-pregnancy overweight/obesity, maternal age, and parity as predictor variables –14.Since all studies mentioned above were cross-sectional, they were focused on prevalence rate rather than its predictors and focused on clinical factors.Understanding specific modifiable determinants for macrosomia is crucial for health care providers to prevent macrosomia complications and used to design specific cost-effective interventions. Studies on determinants of macrosomia in Ethiopia is insufficient, and most of those studies were cross-sectional or retrospective focused on clinical factors. Therefore this study was aimed to identify determinants of fetal macrosomia in Ethiopia.The study was conducted in Wolaita Sodo teaching and referral hospital (WSUTRH) and Sodo Christian general hospital (SCGH), located in Sodo town, Wolaita zone of South Ethiopia. Wolaita Sodo teaching and referral hospital serves about 3 million people. The hospital has one big maternity ward, around 70 beds, about 6000 deliveries per year. Pre-operative and post-operative, inpatient services, abortion care, labour and delivery services, ART services for all pregnant women, and Obstetric/Gynecologic Ultrasound services delivered.Sodo General Christian hospital is a private hospital in Sodo town, containing four surgical, maternity, medicine/pediatric, and orthopaedic wards. The maternity ward has 25-beds facilities and 750 deliveries per year.The study was conducted from June to July 2021.The study was a facility-based, matched case–control study. The age of mothers was used for matching, and age strata were created using five-year intervals and a 1:2 case to control ratio.The cases were macrosomic neonates whose birth weight was ≥ 4000 gm regardless of gestational age and controls: controls were average birth weight neonates whose birth weight was between 2500 and less than 4000gm regardless of gestational age at birth.For cases: Neonates with a birth weight of ≥ 4000gm delivered at hospitals of Sodo town during the study period were included in the study as a case.For controls: Selected neonates with birth weights between 2500 and 3999gm, delivered at hospitals in Sodo town during the study period, were included as control after matching for maternal age.Those deliveries faced pregnancy complications like abruptio placenta, placenta praevia, multiple pregnancies, and congenital anomalies for both cases, and controls were excluded from the study.The two population proportion formula was used to estimate the sample size required using two different exposure variables, and variables  with the small odds ratio were selected considering the proportion of exposure among controls 48.8%, and and 8.l% among cases from the study done in Hawassa public health institution, Southern Ethiopia . Based oThe client registration book of two months before the data collection time was reviewed from two hospitals, and then the total numbers of deliveries during data collection time were estimated which is as (1030 deliveries per two months). The sample size was split between these two hospitals based on the proportionality of their delivery service attendants. A convenient sampling method was used to select cases and controls because pregnant women come to health institutions randomly. Two controls from the source population were selected for every case after matching maternal age until the desired sample size was attained.We adapted a structured questionnaire from relevant articles and related literature. Data was collected through direct interviews, measurements and supported by reviewing medical records. Age of mothers were used for matching, and age strata was created using five years intervals. For one case, mothers aged between 21–25 years; two control mothers aged 21–25 years were selected, giving a 1:2 case to control ratio. Others were also selected in this way.The neonate weight was measured within one hour of delivery using a beam balance accurate to 100gm.The last normal menstrual period (LNMP) was confirmed from her chart and through the interview. Gestational age was estimated based on LNMP and chart review for ultrasound reports.The dietary habit was assessed based on the number of days per week, based on the Harvard university food frequency questionnaire.Physical exercise was measured in walking for at least 30 min per day during pregnancy time as a WHO recommendation for pregnant mothers.History of stillbirth, abortion, and using contraceptive methods used were assessed in terms of the history just before the current pregnancy.Cases: Are neonates whose birth weight were ≥ 4000gm regardless of gestational age.Controls: Are neonates whose birth weight were between 2500 and 3999gm regardless of gestational age.Frequently consumption of fruits and dairy products: consumption of fruits and dairy products more than five times per week respectively .Macrosomia is a newborn baby with a birth weight ≥ 4000gm .Average  birth weight: A newborn weighs between 2500 and 3999gm  and MAOR = 4.91  respectively.Consuming fruits and dairy products have shown a significant association with neonatal birth weight in the study. Neonates born from mothers who consumed fruits and dairy products in their diet frequently (≥ 5 per week) were 2.03 and 4.91 times more likely to be macrosomia as compared to neonates from mothers who consume a fewer amount of fruits and dairy products in their diet with MAOR = 2.03 [95%CI; 1.11–3.69, In contrast to this, average monthly income, family size, parity, history of abortion before current pregnancy, history of stillbirth before current pregnancy, use of family planning methods, and consumption of eggs were not significantly associated with macrosomia in the final model Table .Table 4Pp-value = 0.8017), and 80.56% of variables were correctly classified. The area under the ROC curve was under excellent discrimination (82.56%) Fig. The model fitness was checked by Hosmer–Lemeshow = 4.58  during the pregnancy period.Health care providers can use these factors as a screening tool for fetal macrosomia prediction and early diagnosis that allows timely intervention to prevent adverse maternal and neonatal-associated complications.Gestational diabetic screening and documentation should be taken as standard during ANC visits in these hospitals. A large-scale facility-based follow-up study recommended exploring further risk factors associated with fetal macrosomia.Additional file 1. Legend; Supplementary data of all data generated  for neonatal macrosomia among mothers delivered at hospitals in Wolaita Sodo town, 2021.


Intrauterine growth restriction (IUGR) , HELLP  syndrome , early gestational obesity  and preeclampsia  were identified as independent risk factors of preterm birth. Prevalence of preterm birth was high among women attending labor admission at the Komfo Anokye Teaching Hospital and this was independently influenced by IUGR, HELLP syndrome, early gestational obesity, and preeclampsia. Identifying early signs of adverse pregnancy outcomes would inform the need for management policy to prevent high prevalence of preterm births.Preterm birth is a global epidemic and a leading cause of neonatal mortality in Sub-Saharan Africa. We evaluated the prevalence and risk factors of preterm birth among women attending the labor ward for delivery at a tertiary hospital in Ghana. This comparative cross-sectional study was conducted among a cohort of 209 pregnant women admitted to the labor ward of the Komfo Anokye Teaching Hospital (KATH). Pregnant women who delivered between 28 and 36 completed weeks of gestation were classified as preterm delivery whereas those who delivered after 37–42 completed weeks were described as term. Sociodemographic, clinical, and obstetric data were collected from patient's folder and hospital archives. Categorical variables were analyzed and expressed as frequencies and proportions. We determined the association between obstetric factors and preterm delivery with multiple logistic regressions. Significance level of the strength of association was determined at  Preterm birth is a global epidemic and a leading cause of neonatal mortalityas well as a major contributor to long-term adverse health outcomes . PretermIn comparison to term infants, preterm neonates are more susceptible to short and long-term neurocognitive and motor deficits, as well as malnutrition, chronic illnesses, and early death . PretermDespite an increase in the global incidence of preterm births, data available from developing countries such as Ghana is limited . Most coThis hospital-based comparative cross-sectional study was conducted at the Komfo Anokye Teaching Hospital (KATH), Kumasi Ghana. KATH is the second major tertiary Hospital positioned in the middle belt of Ghana. The facility has over 1,200 bed capacity and serves as a referral center for other hospitals in the middle and northern belt of Ghana. From KATH records unit, annual total deliveries range from 8,438 to 11,188 for the past 5 years. KATH has 3 delivery wards: the main delivery ward where a majority of deliveries take place; and a delivery ward each in the special ward and the high dependency unit. The average monthly deliveries at KATH is about 900; 80% occurring in the main labor suite, 15% in the special ward and 5% in the high dependency unit.Ethics approval was given by the Committee on Human Research, Publications, and Ethics (CHRPE) at the school of Medical Sciences of Kwame Nkrumah University of Science and Technology (CHRPE/SMS/KNUST: CHRPE/AP/205/21). Written permissions were sought from the management of facilities in which data and information were collected, thus sought from the KATH. Written informed consent were obtained from participants and legally authorized representatives of the participants.Using a simple randomized sampling technique, a total of 209 singleton pregnant women who are between 18 and 45 years and had reported for delivery at the labor ward between May to June 2021 were selected for this study. The classification of preterm and term was done by a qualified consultant Gynecologist. Pregnant mothers who delivered between 28 and 36 completed weeks of gestation were classified as preterm birth and whereas pregnant mothers who delivered at 37–42 completed weeks were classified as term birth. The gestational age (GA) in the present study was defined in weeks as the duration of pregnancy before birth based on menstrual history (date of the first day of the last menstruation), clinical examination, and ultrasonography (measuring the crown-rump length of the fetus during a first-trimester). Intrauterine growth restriction (IUGR) was defined as the estimated fetal weight less than the 5th centile along with abnormal Doppler velocimetry values (above 95th centile). IUGR was further examined determined by the measurement of the mother's belly from the top of the pubic bone to the top of the uterus . Prenatal Doppler ultrasound was also done consultant sonographer. Prior to delivery, structured, and close-ended questionnaires were used to obtain information on sociodemographic data such as age, level of education, ethnicity, occupation, and economic income. Patients' folders and the hospitals' database were used to obtain all the other information needed concerning the study participants clinical and obstetric history. Pregnant women who did not give informed consent, those who were medically unstable and those with the twin pregnancies were excluded.The sample size was obtained by the formula:n = p is the prevalence of preterm birth, which was 9.0% in a study by Agbeno et al. , at the n (Minimum number of participants) = Hence, a minimum of 126 participants were needed for the study.A 95% confidence level, 50% response distribution, and 5% margin of error is employed in the calculation of the sample size. To increase statistical power, a total of 209 participants were included in the study.www.graphpad.com). A simple bar chart was used to illustrate the prevalence of preterm birth among study participants. Chi-square test/Fischer's Exact test and the binary logistic regression analysis were employed to test for associations and the strength thereof between the dependent variable (preterm birth) and independent variables. The p-values < 0.05 were considered statistically significant for all analyses.The collected data obtained were entered, coded, edited, and cleaned in Microsoft Excel 2016. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) Version 26.0  and GraphPad Prism version 5.0 . However, this study did not find any significant association between pregnant women's maternal age (p = 0.1950), parity (p = 0.7540), gravidity (p = 0.2060), their level of education (p = 0.1820), marital status (p = 0.8620), ethnic group belonging to (p = 0.1700), their economic income (p = 0.2140), and preterm birth.p<  0.0001), intrauterine growth restriction (IUGR) (p<  0.0001) HELLP syndrome  (p<  0.0001), early gestational BMI (p = 0.0050), and preeclampsia (p<  0.0001) and preterm birth. On the contrary, no significant association was found between family history of hypertension (p = 0.2503), previous history of hypertension (p = 0.2890), history of spontaneous abortion (p = 0.2340), previous caesarian section (p = 0.5680), antenatal visits (p = 0.290), and preterm birth.p > 0.05).aOR = 2.15, 95% CI = (1.81–9.55), p = 0.0390], early gestational obesity , HELLP syndrome  and preeclampsia  were identified as independent risk factors of preterm birth.Preterm birth is a global epidemic and a leading cause of neonatal mortality as well as a major contributor to long-term adverse health outcomes. Although there have been recent interventions to reduce preterm birth and its related complication in developing countries , 14, theIn the present study, we found a 37.3% prevalence of preterm birth among study participants. The prevalence of 37.3% observed in this study is however higher compared to 18.9 and 18.3% observed by Adu-Bonsaffoh et al.  and WaguIntrauterine growth restriction (IUGR) is a frequent complication in preterm infants and is the cause of most elective late-preterm deliveries . In IUGRin utero environment, which could impair the placental transcriptome and have potentially adverse consequences for placental structure and function, which might also contribute to the mechanism of preterm birth  at the school of Medical Sciences of Kwame Nkrumah University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.EOA, WIO, and OA-M conceptualized and designed the study and wrote the manuscript. EOA, WIO, AT, and FA performed the research data collection and laboratory analysis. EOA, SO, and ES performed the data analysis and interpretation. All authors reviewed the manuscript, read, and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Developing a prediction model that incorporates several risk factors and accurately calculates the overall risk of birth asphyxia is necessary. The present study used a machine learning model to predict birth asphyxia.Women who gave birth at a tertiary Hospital in Bandar Abbas, Iran, were retrospectively evaluated from January 2020 to January 2022. Data were extracted from the Iranian Maternal and Neonatal Network, a valid national system, by trained recorders using electronic medical records. Demographic factors, obstetric factors, and prenatal factors were obtained from patient records. Machine learning was used to identify the risk factors of birth asphyxia. Eight machine learning models were used in the study. To evaluate the diagnostic performance of each model, six metrics, including area under the receiver operating characteristic curve, accuracy, precision, sensitivity, specificity, and F1 score were measured in the test set.Of 8888 deliveries, we identified 380 women with a recorded birth asphyxia, giving a frequency of 4.3%. Random Forest Classification was found to be the best model to predict birth asphyxia with an accuracy of 0.99. The analysis of the importance of the variables showed that maternal chronic hypertension, maternal anemia, diabetes, drug addiction, gestational age, newborn weight, newborn sex, preeclampsia, placenta abruption, parity, intrauterine growth retardation, meconium amniotic fluid, mal-presentation, and delivery method were considered to be the weighted factors.Birth asphyxia can be predicted using a machine learning model. Random Forest Classification was found to be an accurate algorithm to predict birth asphyxia. More research should be done to analyze appropriate variables and prepare big data to determine the best model. Birth asphyxia (BA) is a serious clinical problem worldwide and is a major contributor to neonatal mortality and morbidity . BA is dEfforts to improve child health indices have focused on identifying predictors of BA. Both traditional statistical analysis techniques and artificial intelligence (AI) approaches have been used to identify the risk factors of BA. The applications of AI in medicine have increased significantly in recent years. AI in the form of machine learning, natural language processing, expert systems, planning, and logistics methods, and image processing networks offers great analytical capabilities . MachineThis was a cross-sectional study to identify the risk factors of BA. Women who gave birth at Khaleej-e-Fars Hospital in Bandar Abbas, Iran, were retrospectively evaluated from January 2020 to January 2022. Khaleej-e-Fars Hospital is a tertiary hospital with a birth rate of 4000–5000 per year. Data were extracted from the Iranian Maternal and Neonatal Network (IMaN Net), a valid national system, by trained recorders using electronic medical records. Data of all women with singleton pregnancies delivered at the timeline of the study were included in the analysis. Those who gave birth to newborns with congenital anomalies were excluded.Demographic factors include nationality, age, education level, place of residence, adequate prenatal care , smoking status, maternal comorbidities such as anemia, cardiovascular disease, chronic hypertension, pyelonephritis, hepatitis, COVID-19, diabetes, and thyroid dysfunction, drug addiction, and obstetric factors such as gestational, parity, the onset of labor (spontaneous/induced labor/planned cesarean section), preeclampsia, abnormal placentation , placental abruption, intrauterine growth retardation (IUGR), chorioamnionitis, meconium fluid, fetal presentation, delivery methods, newborn weight, newborn sex, congenital malformation were obtained from patient records.The primary outcome was whether a machine learning algorithm showed better performance in predicting BA. BA was determined based on a clinical diagnosis from the women’s records using the WHO classification of diseases ICD10 .The following eight machine learning models were used in the study: Logistic regression, Decision Tree Classifier, Random Forrest Classification, XGBoost Classification, Permutation Classification, Feed Forward Deep Learning, Light GBM (LGB), Feed Forward Deep Learning and Support Vector Machines (SVM).To evaluate the diagnostic performance of each model, six metrics, including area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score, were measured in the test set. Because AUROC is a widely used index to describe a machine learning model’s ability to predict outcomes , we usedThe methods for calculating accuracy, precision, recall, and classification error are shown in the equations. Accuracy = (TP)/(TP + FP). In this equation, true positive (TP) represents transactions that were positive and classified as positive. True negative (TN) represents the number of transactions that were negative and classified as positive. False positive (FP) also indicates the number of transactions that were positive and classified as negative. Finally, FN  indicates the transactions that were negative and were classified as negative. The equation used to evaluate validity and recall is as follows: Recall = (TP)/(TP + FN) . The F1 We found 380 women with a recorded BA out of 8888 deliveries, for a frequency of 4.3%. BA was found in 3.4% of the 5848 vaginally delivered newborns, 10.8% of the 83 vacuum-assisted deliveries, and 5.8% of the 2957 cesarean section newborns. In this study, we attempt to evaluate parameters and feature selection based on performance parameters using various machine learning algorithms. We oversample the dataset using the Adaptive Synthetic (ADASYN) algorithm, then run all of the algorithms in 30- and 70-percentage-point separations of the dataset, plot a ROC chart as shown in Fig. Figure Despite rapid technological advances, under-five deaths among children remain high. A significant proportion of these deaths worldwide are due to BA. Several studies have been conducted using traditional statistical analysis techniques to identify risk factors for BA. For example, a meta-analysis conducted by Desalew et al. found that maternal illiteracy, prepartum hemorrhage, cesarean section, instrumental delivery, duration of labor, pregnancy-related hypertension, induction of labor, parity, low birth weight, preterm birth, non-cephalic delivery, and meconium staining were significantly associated with BA . Our stuSociodemographic factors were not associated with BA. Among maternal comorbidities, chronic hypertension and diabetes were found to be correlated with BA. Hypertension can lead to a reduction in blood flow and thus asphyxia , while dAnother factor linked to BA was drug addiction. Drug addiction was demonstrated in the current study by declarations from mothers themselves. The actual number of addicts is always several times greater than the number of those identified; however, detecting addicted women is further complicated by their proclivity to conceal and deny the problem. Infants born to addicted mothers are more likely to have prematurity, low birth weight, and IUGR, all of which can contribute to BA . We haveOur study showed that parity is associated with BA. The incidence of BA was higher in primiparous mothers. This is consistent with previous studies , 30. PriPreeclampsia is significantly associated with an increased risk of BA. The finding is in agreement with the evidence , 33. ThiPlacenta abruption was also found to be associated with BA in our study, which was in contrast to previous studies . The assIt has long been known that non-cephalic fetuses are at greater risk during the birth process, including asphyxia, birth trauma, and death. This may be because non-cephalic fetuses are more likely to have other problems, such as cord prolapse and head entrapment, that predispose them to BA .Newborns delivered via cesarean section and assisted vaginal birth had a higher rate of BA than those delivered via spontaneous vaginal delivery. This finding is consistent with previous research . This isIn terms of newborn sex, our findings show that male infants are more likely to develop BA. This is consistent with previous research . Our finIn line with several previous studies , 42, mecThe strength of our study is that we used a high-quality registration system in accordance with birth records. We studied both BA after vaginal birth and after cesarean section. We also examined a wide range of clinical factors associated with BA that may not be easily found in registries. Our study was retrospective, which is another limitation. The database did not allow us to determine the exact timing of the different events during pregnancy. For some variables, such as body mass index and weight gain during pregnancy, there was a lack of other data that might influence BA.BA can be predicted using a machine learning model. Random Forest Classification was found to be an accurate algorithm to predict BA. Maternal chronic hypertension, maternal anemia, diabetes, drug addiction, gestational age, newborn weight, newborn sex, IUGR, preeclampsia, placenta abruption, parity, meconium amniotic fluid, mal-presentation, and delivery method are risk factors of BA. More research should be done to analyze appropriate variables and prepare big data to determine the best model.


Preterm birth remains a major maternal and infant health issue worldwide particularly with an increase in the global preterm birth rate, which requires more interventions to manage the consequences of preterm birth. In addition to traditional complications, recent studies have shown that the succession of gut microbiota of preterm infants is disordered due to the systemic physiological immaturity, which confers negative influences on the growth, development, and health of infants. In the present study, we briefly discussed the prevalence of preterm birth worldwide and then highlighted the signatures of gut microbiota in preterm infants within the first 1000 days of life after the birth categorized into birth, infancy, and childhood. Afterward, we focused on the potential association of clinical phenotypes typically associated with preterm birth  with gut microbiota, and the potential directions for future studies in this field are finally discussed. Preterm birth according to the definition of the World Health Organization (WHO) refers to live birth of less than 37 completed gestational weeks counting from the first date of the last menstrual period. Globally, preterm birth still remains a major challenge for maternal and infant health even though advanced developments in medicine and therapeutics have been made in the past years. Causes of preterm birth are multiple, such as infections, inflammations, and maternal stress; however, the precise underlying mechanisms have not been completely understood in most cases . Over thDiverse microbial communities  have been characterized and mined at various taxonomic and functional levels across human body sites, such as gastrointestinal tract, oral cavity, skin, breast milk, and vagina . MountinPreterm infants have been shown to possess differential profiles of gut microbiota, which has drawn great attentions not only from pediatricians but also from microbiologists and immunologists . It is kPreterm birth is still a crucial health issue worldwide . KnowingSpecific cautions, however, are warranted for interpretation as the systematical search and analysis of data from the publicly available preterm reports may introduce slight biases due to the disproportionate data and several methodological differences across countries, such as the fact that the way and how a preterm birth is monitored and reported . The metGut microbiota has been indicated with mounting evidence to be involved in human health and a range of diseases . Once deBifidobacterium, Staphylococcus, Enterococcus, Streptococcus, and Escherichia are the most abundant genera , and the quantitative method (relative vs. absolute abundance).Although the NGS has comprehensively expanded the microbial diversity in early life, NGS is limited to providing the relative abundance of taxa rather than the absolute amount. In order to overcome this limitation, Rao and colleagues developed a cell-based multi-kingdom spike-in method to quantify the absolute abundances within a given microbiota and applied it to the gut microbiota of preterm infants in the first 7 weeks of life . The tot of life . FollowiStaphylococcus, Acinetobacter, Pseudomonas, Corynebacterium, and Streptococcus over all investigated preterm mother’s milk, which was influenced by maternal characteristics, such as delivery mode, pre-pregnancy BMI, and the class, timing, and duration of antibiotics. This pattern of microbiota was slightly different from the breast milk of full-term mothers, which mainly comprised Streptococcus, Pseudomonas, and Staphylococcus , the abundances of microbes that can degrade the carbohydrates were increased, such as Bacteroides vulgatus, Ruminococcus obeum, Ruminococcus bromii, and Lactococcus. Additionally, microbes with the capacity to produce butyrate, such as Anaerostipes caccae, Eubacterium hallii, and Coprococcus eutactus, became prevalent  rather than in control samples (23%)  in this study, mechanisms underlying the loss of IgA binding capacity remain unexplored, which may be caused by the microbial genomic changes and strain adaptation.As discussed above, preterm infants normally harbor an increased abundance of  studies . In ordeoped NEC . Based orvention . At a hies (23%) . Notablyse onset . Furtherse onset . In the In order to move the microbiota research from associations to mechanisms, different methods have been adopted to build a NEC-like model with animals for a better understanding of the pathogenesis of the disease . Mihi etThe prevalence of preterm birth is globally increasing, and associated complications are recognized as the leading cause of early-life mortality, which thus require new interventions to manage the consequences of preterm birth in the future. We understand that early life is a critical window for the development of the immune system and gut microbiota. As discussed above, the gut microbiota of preterm birth lacks beneficial microbes, however, compared to full-term birth, and our understanding of gut microbiota of preterm birth is still limited, in particular, the temporal dynamics across the early life based on longitudinal cohorts and the absolute microbial abundances. Additionally, investigations into interactions between gut microbiota and various diseases in preterm birth, such as NEC and sepsis that are closely related to microbes, are urgently necessary. It is imperative to further disclose a range of specific biomarkers and build a predictive model for diseases. Based on the differential taxa and functions across the health and diseases, rational selection and isolation of efficacious probiotic strains from the gut or other sources can be served as novel strategies for preventing diseases, such as personalized probiotics and artificial microbial consortia. Moreover, breastfeeding has been suggested as an effective strategy to decrease the incidence of NEC; however, the underlying mechanisms such as the effective components of breast milk and the relevant mode of action need to be further explored. All these endeavors will help to predict, prevent, and finally protect infants from diseases in clinical practice.All authors wrote, reviewed, and approved this manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In addition, NICU admission (p = 0.006), peak width of lateral ventricles (p = 0.030) and postnatal cranial ultrasound suggestive with VM (p = 0.002) were related to infants’ long-term outcomes. NICU admission during the perinatal period was an independent risk factor for the adverse long-term outcomes . In conclusion, VM impairs short-term and long-term outcomes of term infants. Short-term outcome, especially NICU admission, could predict their adverse long-term outcomes.Birth defects have brought about major public health problems, and studying the clinical outcomes of the most common prenatal central nervous system abnormality, namely, fetal ventriculomegaly (VM), is helpful for improving reproductive health and fertility quality. This is a retrospective cohort study from 2011 to 2020 in the West China Second University Hospital, Sichuan University, aiming to evaluate the short-term and long-term outcomes of VM over 37 weeks’ gestation to exclude the influence of preterm birth. The study analyzed data from 401 term pregnancies, with 179 VM and 222 controls. From the short-term outcomes, the rate of the neonatal intensive care unit (NICU) admission under the VM group (10.06%) was comparatively higher than the control (0.45%), but Apgar scores between both groups at 1 min, 5 min and 10 min were not significantly different. From the long-term outcomes, there were more infants with abnormal neurodevelopment under the VM group than control (14.53% vs. 2.25%,  Birth defects have brought a great burden to individuals and society, and fetal ventriculomegaly (VM) is the most common central nervous system abnormality identified by prenatal ultrasound ,2. VM isThere have been a variety of studies about the prognosis of VM, many of which often evaluated the outcomes of all infants born at different gestational weeks , ignorinA retrospective cohort study was performed at the Second West China Hospital of Sichuan University from March 2011 to September 2020. Term pregnancies with VM during the period formed the VM group. The control group, term pregnancies without VM, were randomly selected for each year with a comparable number of both VM and control groups maintained for each year to ensure consistent medical conditions and follow-up times for all subjects in the study. Women who did not deliver at our hospital were excluded, and infants without follow-up after birth were excluded from the analysis. This study was approved by the ethics committee of West China Second Hospital of Sichuan University. Maternal demographic data, pregnancy, delivery and neonatal information were extracted from the electronic medical records. VM was defined as the width of the lateral ventricle ≥ 10 mm detected by ultrasonic scan and/or fetal magnetic resonance imaging (MRI). For the VM group, additional details on VM were recorded . VM were categorized into mild (10–12 mm), moderate (12.1–15 mm) and severe (> 15 mm) degrees based on the peak ventricular width. According to whether other structural anomalies or any chromosomal abnormalities existed, VM were also divided into isolated VM and non-isolated VM. Comparing the width of the lateral ventricle at the time of initial diagnosis with that of the last ultrasound examination aiming at the lateral ventricle, VM were further divided into progressing  and not-progressing  groups. The time horizon of the short-term and long-term outcomes for VM was not clearly defined to the best of our knowledge. Most current studies about outcomes of fetal neurodevelopment focused on the perinatal period and 1 month to 2 years postpartum ,12,13,14t test. Categorical data were comparatively assessed using Pearson’s chi-squared test, Fisher’s exact test or Mann–Whitney test. A two-tailed p value < 0.05 was considered statistically significant. The sample size of 160 participants per group was evaluated to have 90% power with a two-sided alpha of 0.05, based on an incidence of adverse long-term outcomes of 12% in VM with about 2% in the baseline population or an incidence of 10% in VM with 1% in the baseline population. To accommodate 15% attrition, a goal of 200 pregnancies in each group was targeted.Statistical analysis was performed using SPSS software . Quantitative data were described using means and standard deviations, while categorical data were reported by the number of events. Mean comparison among independent groups was evaluated using Student’s p = 0.176). Finally, a total of 401 participants, 179 with VM and 222 without VM, were included in the study . In addition, a stratified analysis for the long-term outcome based on gestational age at birth (37 0/7–38 6/7 weeks vs. ≥39 0/7 weeks) was also performed. It showed no significant difference in the gestational age between the two groups (p > 0.05).Notably, the difference in the long-term outcome between both groups was statistically significant during the follow-up. There were more infants with abnormal neurodevelopment in the VM group than the control group . Furthermore, the pairwise comparison of prognosis among mild, moderate and severe VM was performed by Bonferroni post hoc analysis, and p < 0.0167(0.05/3) was considered statistically significant. Pairwise comparisons showed no statistical differences between mild VM and moderate VM (p > 0.0167), as well as between moderate and severe VM (p > 0.0167). However, the difference in prognosis rates between mild and severe VM was found to be statistically significant (p < 0.0167), while infants’ short-term outcomes, referring to the NICU admission, was associated with adverse long-term outcomes (p = 0.006). Furthermore, if postnatal cranial ultrasound showed manifestations of VM, the prognosis was more likely to be poor (p = 0.002). However, other characteristics about VM, such as isolated/non-isolated VM (p = 0.116), unilateral/bilateral VM (p = 0.260), and variation of width (p = 0.240), did not seem to be relevant to the long-term outcome. Comparing the characteristics between the VM subgroups as summarized in p = 0.045). Other factors, such as the peak width of lateral ventricles, and gestational age of delivery, were not independent risk factors for the long-term outcomes, as noted from the analysis.A binary logistic regression analysis was performed to evaluate the significance of the various clinicopathological factors considered in the study in predicting the long-term outcomes of VM. Results presented in Birth defects have brought about major public health problems, and to study the clinical outcomes of VM is helpful for clinical decisions, thereby improving reproductive health and fertility quality. In this retrospective cohort study, we discovered that short-term and long-term outcomes of infants with VM were affected negatively to some extent. In the short term, the rate of NICU admissions in the VM group (10.06%) was comparatively higher than the control (0.45%). However, the Apgar between both groups were not significantly different. The reason for the higher NICU admission rate in VM may be due to the predisposition of children with VM to show some signs of increased intracranial pressure after birth, including reduced activity, vomiting, widening of the fontanelle and apnea, among others . In pracNotably, the difference in the long-term outcome between both groups was statistically significant during the follow-up. VM infants were more likely to manifest abnormal neurodevelopment after birth as compared with the control group. Existing studies have reported that VM can lead to neurodevelopmental disorders of children after birth in movement, language, cognition and other aspects, and may also cause some neuropsychiatric diseases such as autism, schizophrenia, epilepsy, attention deficit/hyperactivity disorder and so on ,17. As ip < 0.05) [p < 0.001) [Interestingly, VM seems to have occurred in more male and larger-sized infants than in the control group. In 1994, Patel et al. noted that there were more male than female fetuses with isolated mild VM ( < 0.05) . In addi< 0.001) . Based op < 0.0167); although notably, logistic regression analysis showed that peak width of lateral ventricle was not an independent risk factor for adverse long-term outcomes . However, only two cases of severe VM were included in this study. The reason may be that pregnancies with severe VM generally chose to terminate pregnancy. Therefore, prospective studies with a larger sample size of severe VM are needed to evaluate the prognosis.Our study further analyzed the factors associated with the long-term prognosis of VM, which suggested NICU admission and degrees of VM were related to infants’ long-term outcomes. Infants transferred to the NICU may have some manifestations of brain injuries during early birth, which may have implications for their long-term neurodevelopment. Typically, VM’s outcome depends on its cause and degree . In 2018The study has some limitations. First, due to limited follow-up time for some infants, some clinical symptoms of the infants may not have been fully traced, with the actual incidence of poor prognosis potentially under-reported. Besides, the poor prognosis of VM sometimes manifests within one year after birth but some may not manifest until school age . The shoIn conclusion, VM may have negatively affected the short-term and long-term outcomes of infants. These findings highlight the need for additional care for VM infants, especially with the NICU admission after birth.


Healthy pregnancy requires a coordinated immune response, yet complications can arise, putting both the mother’s and child’s health at risk. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are pregnancy-related complications that account for most maternal morbidity and mortality. Cytokines are proteins released as part of the immune response to disease or infection and regulate inflammation. Certain pregnancy complications cause localized and systemic inflammation; however, cytokine profiles specific to such complications are not well understood. This study aims to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Data was obtained from the All Our Families birth cohort in Calgary, Alberta, Canada. The cohort collected questionnaires at the time of participant enrollment and maternal blood samples at 17–23 weeks gestation. Cases of HDP (n = 27) and GDM (n = 31) were matched to controls on BMI, maternal age, and smoking status in the preconception period at a 1:3 ratio. Cytokine levels were measured in blood samples using Luminex xMAP technology using a panel of 42 cytokines. Using R software, a Classification and Regression Tree (CART) analysis was conducted to identify cytokine profiles and levels associated with each complication. Four cytokines were identified in the HDP CART (in descending order of importance): Monocyte Chemoattractant Protein-1 (cut-off: <480pg/mL), Macrophage Inflammatory Protein-1β (cut-off: ≥26pg/mL), Eotaxin (cut-off: <27/≥27&<36/≥36pg/mL), and Soluble Cluster of Differentiation 40 Ligand (cut-off: <1342pg/mL). Six cytokine levels were identified in the GDM CART: Interleukin-1 Receptor Antagonist , Interleukin-5 (cut-off: ≥0.4pg/mL), Interferon-γ (cut-off: <4.9pg/mL), IL-1Ra (cut-off: ≥111pg/mL), Eotaxin (cut-off: ≥21pg/mL), and Interleukin-18 (cut-off: ≥155pg/mL). By examining the complex inter-relationships between cytokines, findings of cytokine profiles guide further research in identifying biomarkers of pregnancy complications relevant to the design of the future management or prevention of these conditions. The World Health Organization estimated that 810 women worldwide died every day from pregnancy and childbirth complications in 2017, many of which are preventable [HDP are common disorders to develop during pregnancy and affect around 7% of pregnancies in Canada . HDP encProteins involved in inflammation trigger signalling pathways and mediate the coordinated communications between the mother and fetus to promote a healthy pregnancy , 7. CytoWhile there are differences in clinical details of HDP and GDM, both have been linked with changes in inflammatory profiles. Previous studies suggest that elevations in inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1 may contribute to the development of hypertension and pre-eclampsia . StudiesPrevention and treatment of pregnancy complications requires knowledge of their etiology and pathogenesis as well as methods for identifying those at high risk for developing a complication . DysreguTherefore, the objective of the current study was to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Through exploratory methods in our study, the aim of our investigation was achieved.allourfamilies@ucalgary.ca) subsequent to proposal submission and ethics review for researchers who meet the specific criteria for access to confidential data.Data were obtained from the All Our Families (AOF) Study, a longitudinal community-based pregnancy cohort in Calgary, Alberta, Canada, designed to investigate the relationship between prenatal and early-life periods and outcomes for infants, children, and families. The cohort recruited 3200 pregnant women in Alberta between 2008–2010. Eligible women for the cohort study were less than 25 weeks of gestation at enrollment, at least 18 years of age, accessing prenatal care in Calgary, and able to understand written and spoken English . A quest2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2), and maternal age group at delivery . These matching variables were chosen to control for confounding based on previous research on pregnancy complications and cytokine profiles [For this analysis, blood plasma samples collected at 17–23 weeks gestation were studied to examine the earliest available measure of cytokines associated with the presence of pregnancy complications. Pregnancy complication status was obtained by accessing electronic medical records with the mother’s consent from the Alberta Perinatal Health Program database, a province-wide database with prenatal maternal and birth outcome information for all births in Alberta . Diagnosprofiles , 14. EacTM 200 system  by Eve Technologies Corporation . In the parent study from which we extracted our data, duplicate assays were performed on 700 samples in 14 96-well microplates using Eve Technologies’ Human Cytokine 42-Plex Discovery Assay® , according to the manufacturer’s protocol. A 70-sample (10%) pilot assay was run to calibrate settings and ensure that cytokine signals fell in the dynamic range of the standard curve, following which, no plate-to-plate adjustments were made. Assay sensitivity values (minimum detectable concentrations) are available in the MilliporeSigma MILLIPLEX® MAP protocol  and cytokine distributions according to case and control groups. The “mytable” function with “ztable” output for formatting was computed for data exploration to determine the median and interquartile range of each cytokine level in all groups. Next, we conducted a classification and regression tree (CART) analysis. CART was used to determine which of the 39 cytokines included, and which combinations, were associated with each of the outcomes and at which cut-off values. CART is a non-parametric statistical method that uses a data-driven approach to separate a set of observations into subgroups that are increasingly homogenous with respect to the outcome of interest, and which captures inter-relationships between exposures . CART alOf the 42 cytokines that were identified to be present within the maternal plasma at 17–23 gestational weeks, 39 were appropriately measured and included for analysis. Three cytokines, including two variants of platelet-derived growth factor (PDGF-α and PDGF-β) and the RANTES chemokine  were excluded from the analysis as they could not reliably be measured without dilution and thus could not be measured in our samples. Additionally, the samples of five participants were excluded from analysis, prior to control selection, for suspected human anti-animal antibody (HAAA) exposure, due to unexpectedly high results of cytokine levels. HAAAs are human antibodies that are produced when a person is exposed to an animal monoclonal antibody, and can produce artificially high cytokine signals in immunoassays, creating extreme-outlier readings.In total, 232 mothers were included. The summary of participant characteristics in the HDP case and control set is provided in The summary of participant characteristics in the GDM case and control set is provided in The mean and standard deviation of each cytokine in cases versus controls was computed for data exploration in each pregnancy complication set . SeparatCART trees include root (top), branch (middle), and terminal (bottom) nodes. Terminal nodes indicate the probability of classification within the sample, if all conditions (i.e. cut-points) are met in each of the nodes above it. The HDP tree  producedThe GDM tree  producedThis exploratory study revealed insight into the inter-relationships between cytokine levels and found a profile of 4 and 6 cytokine clusters distinct to both HDP and GDM respectively, providing a novel approach for identifying inflammatory response profiles in two pregnancy disorders warranting further research.When comparing cases of HDP to controls, the relationship between levels of MCP-1, MIP-1β, Eotaxin, and sCD40L were identified as critical cytokines involved in predicting condition diagnosis in our sample . MCP-1 iThe GDM tree in Previous research and knowledge on individual cytokines provide insight on the profile of women at risk of HDP or GDM; however, the ability to predict pregnancy complications may be improved by understanding the intersection of various cytokine values. Because this is an exploratory study, additional research is needed to confirm the findings, but our study provides insight into the importance of cytokine profiles and its potential in clinical practice.While this is a topic for further research in the context of human pregnancy complications, taken together, our findings with Eotaxin and IL-1Ra suggest the need to consider different roles cytokines may have when in different ranges of levels  in relation to others. Results from this study emphasize the importance of investigating the levels and balance of cytokines in relation to others in establishing patterns which can be missed when levels of single cytokines are studied. Although our analysis did find cytokines in common with previous research, our study adds the element on how these cytokines may be interacting with each other in previous conditions whereas previous research does not identify significant levels or potential interactions between the cytokines identified in this study.The administrative data used for GDM and HDP diagnosis is limited in that the timing of diagnosis is unknown. We are unable to distinguish between early versus late onset of pregnancy complications or to determine the time gap between cytokine measurement and clinical diagnosis. The blood was drawn from our participants between 17–23 weeks, which precedes the timeframe during which HDP and GDM are typically diagnosed. However, evidence suggests that physiologic changes likely occur prior to clinical diagnosis, thus the assays may be detecting subtle changes that occurred prior to diagnosis . FurtherConfounding variables are important to consider. A study investigating factors that influence cytokine responses found that concentrations of IL-6 and IL-1Ra are increased in the circulation of older individuals . We accoBlood samples included were measured between week 17–23 of gestation. Cytokine concentration changes occur throughout pregnancy, and it is possible for random variability to be introduced as measurements were taken differentially across a 6-week period . Spence Owing to low numbers of HDP types, we homogenized pre-eclampsia and gestational hypertension into one category, as has been done previously in other studies . FindingThis exploratory study provides insight into inflammatory profiles distinct to HDP and GDM, two common pregnancy complications. These findings revealed a cluster of specific cytokines that co-occur in each condition and are distinct from one another. Cytokine patterns may be co-dependent in the maintenance of health during pregnancy; conversely, when dysregulated, these patterns may allude to the risk of complications. Our results provide a basis for further research on cytokines and the role of inflammation in identifying those at risk for pregnancy complications.S1 Table(DOCX)Click here for additional data file.