In this paper, diamond-based vertical p-n junction diodes with step edge termination are investigated using a Silvaco simulation (Version 5.0.10.R). Compared with the conventional p-n junction diode without termination, the step edge termination shows weak influences on the forward characteristics and helps to suppress the electric field crowding. However, the breakdown voltage of the diode with simple step edge termination is still lower than that of the ideal parallel-plane one. To further enhance the breakdown voltage, we combine a p-n junction-based junction termination extension on the step edge termination. After optimizing the structure parameters of the device, the depletion regions formed by the junction termination extension overlap with that of the p-n junction on the top mesa, resulting in a more uniform electric field distribution and higher device performance. A diamond diode presents a wide range of applications for the high-power electronic devices and high-frequency, high-power microwave devices [onR) and less static power loss in high-voltage applications thanks to the conductivity modulation effect [Diamond-based devices are promising for high-frequency and high-power applications and can be worked under harsh conditions  ,2,3. Dia devices . In addi devices . Compare devices , the bip devices ,10,11. In effect . HoweverBDV) of 4.8 kV [For the PNDs, various advanced ET techniques have now been adopted to alleviate electric field crowding, including field plates (FPs), guard rings (GRs), junction termination extension (JTE), and ion implantation, as well as beveled/step mesa ,14,15,16f 4.8 kV ,24,25.Generally, it is not easy to etch diamond deeply due to its high hardness and high atomic density. Therefore, a multi-step structure with shallow steps is regarded as more suitable for diamond-based diodes. However, the development of diamond PNDs with a mesa structure is rarely reported. Herein, we perform a comprehensive optimization of a mesa-based termination structure for diamond PNDs by using the Silvaco technology computer-aided design (TCAD) software (Version 5.0.10.R). A combined structure of step mesa and JTE is proposed to balance the electric performance and device fabrication. This work can provide a reference for the future development of high-power and high-voltage diamond bipolar power devices.+-diamond, 5 μm of a lightly doped p−-diamond drift layer, and 500 nm of a n-type doped diamond from bottom to top of the surface. The carrier concentrations of p+, p−, and n-type diamond were set to 2 × 1020 cm−3, 1.5 × 1015 cm−3, and 2.5 × 1020 cm−3, respectively. BDV depends only on the thickness of the p−-diamond drift layer. The PND with a simple step ET structure is shown in The electric performances of diamond PNDs were simulated by the commercial Silvaco TCAD software. Four kinds of diamond PNDs with different ET structures were designed for comparison . All the15 cm−3, 2 × 1020 cm−3, and 2.5 × 1020 cm−3 for the p−, p+, and n+ layers, respectively. When the temperature increases from 250 K to 650 K, the resistance rapidly decreases and nearly remains constantly higher than 500 K. Considering the actual working conditions, we think that 550 K is the suitable temperature used for simulation to obtain small resistance. The current-voltage (I-V) curve is used to calculate the current density, turn-on voltage , and onR (deduced by the differentiation of the I-V curve), while the electric field distribution is used to determine the BDV. It is worth noting that the critical breakdown electric field for diamond is set to be 6 MV/cm. The reason is that the ionization coefficient values are different in many previous works due to the immaturity of the diamond material and device [During the TCAD simulation, a common phonon-assisted tunneling model, the Parallel-Electric-Field-dependent mobility model, Selberherr’s ionization model, and the incomplete ionization model were added . The actd device .BDV of the PNDs. It demonstrates that the ideal diamond PND presents a high BDV of approximately 3000 V , presenting a comparable onV of 5.4 V and onR of approximately 0.28 mΩ·cm2. It is worth noting that the device is fully turned on when the forward voltage is 10 V and the onR is relatively stable. The corresponding Baliga’s figure of merit (BFOM = BDV 2/onR) values are 30.0, 2.9, 2.42, and 6.24 GW/cm2 for the ideal PND, conventional PND, step mesa PND, and deeply etched mesa PND, respectively. It demonstrates that the deeply etched mesa is a more effective termination structure than the step mesa. However, it is not easy to etch diamond deeply due to its high hardness and high atomic density. Taking into account the device performance and the fabrication process, the step mesa with a relatively smaller etching depth in each process is chosen for further evaluation. This is almost in agreement with the values of Von, Ron, and BFOM reported by Traoré et al. [Firstly, we simulated the electrical performance of the diamond PNDs with different termination structures. pe layer b. TherefBDV of 1100 V, while the increase in W or D will decrease the BDV. By comparing the electric field distributions at the BDV in BDV. The variation of BDV is consistent with the electric field profile along the maximum electric field. When the reverse voltage is 900 V, the device’s electric field distribution is basically the same, both at the edge of the p-n junction where the electric field is concentrated. The difference is that the device electric field is obviously effectively dispersed when W, D is 0.5, 0.5, and, thus, the  BV is relatively high , , , and , respectively. Therefore, the relatively smaller W and D are beneficial to provide a wider and more uniform electric field distribution in the drift layer for the PND with the step mesa. It can be seen that the reverse BV and BFOM values of the device when using  of  are close to the 1550 V, 2.64 GW/cm2 reported by Lin et al. [The dimensions of W and D are the key parameters for the PND devices with a two-step mesa structure. In this section, four sets of W and D are adopted as , , , and , respectively. As summarized in ely high d. Similaely high e, presenn et al. . This alBDV versus W is more obvious than that versus D. Therefore, we keep the D and adopt four sets of Ws as , , , and  for further optimizations. BDV as well as the corresponding BDV and onR for the PNDs. It is found that the drift layer locals beneath the step (marked as region C by the white arrow) contribute to sustaining the reverse bias, but the electric field distribution tends to crowd around the bottom corner (marked as region D by the black arrow) of the step when the W is 0.1 μm. In the reverse voltage of 1100 V, the breakdown location is due to the different devices and leads to a slight difference in the distribution of the electric field. When W = 0.1 μm, the device breakdown location for the right-angle region is close, so the size of the step under result did not play a role in mitigating the role of the electric field density, resulting in a relatively low BV. When W is more than 0.2 μm, the step away edge of the p-n junction is relatively far, resulting in the weak dispersion of the electric field ability. Therefore, the BV decreases. When W increases to 0.2 μm, the electric field distributions around the p-n junction interface and the bottom corner become more uniform, resulting in the suppression of the crowding point and reaching a maximum BDV of 1200 V , , , and , respectively. It can be seen that when the  of the device is , the BFOM of the device is the maximum, but it is only 10% of the ideal device, which makes it difficult to be commercially applied.As summarized in f 1200 V f. Howevef 1200 V a–d, presBDV value is far away from the theoretical one. Previous works report that the JTE structure with a proper doping concentration also can effectively reduce the electric field crowding and enhance the BDV of the device [18 cm−3 and an optimal concentration of 2 × 1022 cm−3, to reveal the variation of the electrical properties. It is worth noting that the JTE on the mesa presents a relatively smaller device area compared with the conventional planar JTE. As shown in 18 cm−3. The possible reason is attributed to that the depletion effect of the JTE is much weaker than that of the p-n junction. However, the JTE can introduce an extra depletion region around the step bottom to expand the electric field distribution in the drift layer locals beneath the step bottom. Then, all the PNDs with different  show a slightly enhanced BDV compared with the PNDs that only possess a step mesa  have a stronger ability to mitigate the electric field concentration effect and are significantly lower than the devices with  and . When using a JTE with a doping concentration of 2 × 1022 cm−3, it can be seen from the electric field distribution that the devices with a W, D of  have a stronger ability to mitigate the electric field concentration effect and are significantly lower than the devices with . The electric field concentration effect mitigation is stronger and significantly lower than the devices with  and   of , step mesa, and JTE  of  structure after the introduction of JTE.The electric field distribution of PNDs can be divided into three regions and labeled into Ⅰ, Ⅱ, and Ⅲ e, which VBD f. In addVBD  k,l. Comb and JTE g. On the022 cm−3 i,j for cBDV for the PNDs with different etching depths are shown in BDV, a maximum BDV of 2300 V (D = 0.5 μm). This value is comparable to that of the step device with . Most of the electric field distribution shifts downward to the ohmic contact electrode when the etching depth is increased. Furthermore, the drift region that does not sustain the reverse bias becomes broad around the p-n junction interface with an increasing depth. Therefore, the degradation of BDV is ascribed to the suppressed effective drift layer thickness that sustains the bias. Also, we observe that the forward conduction current of the device decreases slightly with the increasing etching depth, which is attributed to the gradually suppressed conduction path. It can be seen that as the depth of etching increases, the electric field at the corners of the device gradually concentrates with a fixed reverse withstand voltage of 1100 V, which leads to a decrease in the withstand voltage performance  of  step mesa, the electric field distributions introduced by the p-n junction on the top mesa and the JTE around the bottom mesa overlap each other, resulting in a more uniform electric field distribution and higher BDV. Finally, a device with a onR of 0.415 mΩ·cm2, BDV of 2200 V, and BFOM of 12.74 GW/cm2 is obtained.On the other hand, we propose a novel structure to improve the voltage resistance by combining the JTE and step. The electric field distributions are similar with the PNDs without ET when the concentration of JTE is lower than that of the n-diamond layer, which is attributed to that the depletion effect of the JTE being much weaker than that of the p-n junction. When the concentration of JTE reaches 2 × 10


Bariatric surgery (BS) increases the risk of small for gestational age (SGA) neonates. Guidelines recommend postponing pregnancy for 12–24 months, but optimal surgery-to-conception interval (BSCI) remains uncertain. We aimed to evaluate the impact of BSCI on birth weight and SGA.th percentile. Optimal BSCI was obtained from the analysis of ROC curves, and pregnancies were compared by that cut-off.Retrospective cohort study of 42 pregnancies following BS, including Roux-en-Y gastric bypass, gastric sleeve, adjustable gastric banding and biliopancreatic diversion. Neonates were classified as SGA if birth weight < 10There was a linear association between BSCI and birth weight and an inverse association with SGA, with each additional month of BSCI translating into additional 4.5 g (95%CI: 2.0–7.0) on birth weight and -6% risk of SGA (95%CI: 0.90–0.99). We established a cut-off of 24.5 months of BSCI for lower risk of SGA. Pregnancies conceived in the first 24 months had a more than tenfold increased risk of SGA , even when adjusted for maternal age, gestational diabetes and inadequate gestational weight gain.BSCI was associated with birth weight and SGA. Our results are in line with the recommendations of BSCI of at least 24 months to reduce the risk of SGA. Obesity is a major public health problem and its prevalence is increasing steadily among women of reproductive age . ObesityTherefore, our purpose in this study was to evaluate the impact of BSCI on birth weight and on the risk of SGA. Additionally, we aimed to determine the ideal BSCI to reduce the risk of SGA in our population.2), 7.0–11.5 kg in overweight (BMI 25.0–29.9 kg/m2) and 5.0–9.0 kg in women with obesity (BMI ≥ 30 kg/m2)  2780-3361 g); 10 neonates were SGA (28.3%) and one was LGA (2.4%). All SGA neonates were born at term, with median gestational age of 38 weeks (IQR 38–39 weeks) and mean birth weight of 2498 ± 233 g. Most neonates (87.5%) had birth weight inferior to the 50th percentile (P): 28.3% inferior to P10, 19.0% between P10-P25 and 40.5% between P25-P50; 11.9% had birth weight between P50-P75, 2.4% between P75-P90 and 2.4% above P90. There was no association between SGA and bariatric procedure type, and there was no significant difference in maternal age or pre-gestational BMI in SGA and non-SGA neonates. GWG was adequate in 30.0% of all pregnancies, inadequate in 32.5% and excessive in 37.5%. The prevalence of SGA was 30.8% in pregnancies with inadequate GWG versus 8.3% in pregnancies with adequate GWG, but this difference did not reach statistical significance (p = 0.70).From a total of 47 singleton pregnancies with complete follow-up, four (8.5%) resulted in spontaneous abortion and one 2.1%) in fetal demise at 30 weeks. Excluding these, we obtained a total of 42 pregnancies that lead to 39 term births and 3 preterm births: 1 extremely preterm and 2 moderate to late preterm. As presented in Table % in feta2a = 66.1%). Comparing BSCI across birth weight percentiles there was a similar association, with progressively higher birth weight percentiles (< P10 to P75) showing progressively longer mean BSCI . Logistic regression confirmed an inverse association between BSCI and SGA, in which for every additional month of BSCI there was a decrease of 6% on the risk of SGA .BSCI showed a linear relationship with birth weight. By multiple linear regression, we estimated a birth weight increase of 4.5 g for each month of BSCI (95% CI 2.0–7.0), adjusting for gestational age R2a = 66.%. Comparp = 0.389) or multivariate analysis adjusted for BSCI (p = 0.501). Excluding the 6 pregnancies that were conceived on the first 12 months after BS, the association between BSCI and SGA remained significant, with a higher prevalence of SGA in those who conceived between 12 and 24 months after surgery, when compared to those who conceived after 24 months .By the analysis of ROC curves, we established a cut-off of a minimum of 24.5 months of BSCI for lower risk of SGA neonates  [Fig. p = 0.153).There was no correlation between BSCI and BMI reduction from surgery to conception and BMI reduction was similar in pregnancies with BSCI of up to 24 months or longer than 24 months. Additionally, pregnancies conceived after the first 24 months following BS showed a greater prevalence of adequate GWG (42.9% vs 0.0%) and no significant difference in the prevalence of excessive GWG (28.6% vs 58.3%, In this study, we show an association between time from BS to conception and birth weight and risk of SGA. More than a quarter of neonates were SGA and the vast majority had a birth weight percentile of less than 50. BSCI showed a linear association with birth weight and an inverse association with the risk of SGA. Furthermore, we obtained an optimal cut-off of at least 24.5 months from BS to conception to reduce the risk of SGA, independently of BS type. Women who conceived in the first 24 months after BS had a high prevalence of both inadequate and excessive GWG, and displayed a 13 times higher risk of having an SGA neonate.Parent et al. analysed a cohort of 1859 pregnancies and reported a higher risk of SGA in those conceived within the first 2 or 2–4 years after BS, compared to those conceived after more than 4 years [Rasteiro et al. described a lower fetal growth percentile in pregnancies conceived before 24 months [Heusschen et al. showed a progressive increase in birth weight and decrease in SGA prevalence from BSCI of less than 12 months to BSCI of more than 24 months [Heusschen et al. [As described in previous studies, despite significant weight loss, the prevalence of obesity remained elevated among women who underwent BS , 22, but 4 years , Rasteir4 months , and Heu4 months . Regardin et al. . Addition et al. , 18, thaOur study has several strengths. We analysed a cohort that included several pregnancies with considerably long intervals from BS to conception; the characteristics of pregnancies conceived before and after the first 24 months following BS were homogeneous with respect to maternal age, surgery type, BMI reduction and pre-gestational BMI. We proposed an “ideal cut-off” for BSCI, with elevated sensitivity and specificity, in order to minimize the risk of having an SGA neonate; the obtained cut-off is in line with current recommendations.However, our study has several important limitations. It was a retrospective analysis, which relied on the availability of clinical registries. Data on nutritional deficiencies were limited and, therefore, not included in the analysis, which represents a possible confounding factor. GWG was heterogeneous between BSCI groups, with pregnancies conceived before 24 months showing a higher prevalence of inadequate GWG. Additionally, pregnancies with inadequate GWG had more SGA. Thus, although we did not find a statistically significant impact of inadequate GWG in SGA, the limited sample size does not allow us to overrule a confounding effect of GWG in our study. Also, our analysis does not allow to discriminate between pathological and constitutional SGA, as ultrasound assessment of fetal growth during pregnancy was not investigated, neither did we use customized charts that adjust birth weight for parent’s characteristics. Different types of BS were included, but with small sample size. Moreover, given the limited sample size and small number of pregnancies with a BSCI of less than 24 months, the study has insufficient statistical power to allow the generalization of the obtained results and recommendations. Therefore, we emphasize the need for larger studies, with a sufficient number of pregnancies within each type of BS and within each BSCI interval category, in order to confirm the ideal cut-off of time between surgery and conception.In conclusion, our results support the association of shorter BSCI with lower birth weight and increased risk of SGA, and suggest delaying conception for 24 months to minimize this risk for most women. However, we recognize that frequent follow-up and monitoring may allow for the individualization of BSCI in each woman.


Our objective was to analyze a prospective population-based registry including five sites in four low- and middle-income countries to observe characteristics associated with vaginal birth after cesarean versus repeat cesarean birth, as well as maternal and newborn outcomes associated with the mode of birth among women with a history of prior cesarean.Maternal and perinatal outcomes among vaginal birth after cesarean section will be similar to those among recurrent cesarean birth.A prospective population-based study, including home and facility births among women enrolled from 2017 to 2020, was performed in communities in Guatemala, India (Belagavi and Nagpur), Pakistan, and Bangladesh. Women were enrolled during pregnancy, and delivery outcome data were collected within 42 days after birth.We analyzed 8267 women with a history of prior cesarean birth; 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a repeat cesarean birth. Having a repeat cesarean birth was negatively associated with a need for curettage  but was positively associated with having a blood transfusion . Having a repeat cesarean birth was negatively associated with stillbirth  and, breast-feeding within an hour of birth , but positively associated with use of antibiotics .In select South Asian and Latin American low- and middle-income sites, women with a history of prior cesarean birth were 5 times more likely to deliver by cesarean birth in the hospital setting. Those who delivered vaginally had less complicated pregnancy and labor courses compared to those who delivered by repeat cesarean birth, but they had an increased risk of stillbirth. More large scale studies are needed in Low Income Country settings to give stronger recommendations.https://clinicaltrials.gov/ct2/show/record/NCT01073475.NCT01073475, Registered February 21, 2010,  Repeat cesarean birth in select Latin American and South Asian sites was the more common mode of birth and was associated with reduced stillbirth but also with reduced postpartum breastfeeding, and increased infant antibiotic and oxygen use compared to vaginal birth after cesarean.Cesarean birth rates are rising globally –3. WomenIn low- and middle-income countries, mode of birth among women with a history of prior cesarean varies by region , 8. In sThis topic is of interest because as cesarean birth rates rise, accompanied by the adverse outcomes associated with major abdominal surgery, safely attempting vaginal birth after cesarean with trained providers in an appropriate setting may be one method of curbing rising global cesarean birth rates . Our objThe novel aspect of our research is rooted in the inclusion of data from a prospective population-based maternal registry in low- and middle-income countries with limited data, which offers a unique perspective on the topic. While our study acknowledges the existing body of research on this topic, it seeks to provide a fresh and valuable contribution to the field.This secondary analysis was conducted using data from a prospective study conducted in communities at eight sites in seven low-income countries on births 2017 through 2020 in the sites of the Global Network for Women’s and Children’s Health Research (GN), which is a NICHD-funded network studying pregnancy outcomes in low- and middle-income settings . Data inThe GN’s prospective registry, the Maternal and Newborn Health Registry (MNHR), includes outcomes from sites that generally include between 6 and 12 communities. About 300 to 500 births take place annually in each community, which is usually served by a primary healthcare center. The intent of designing the MNHR was to enroll pregnant women and to obtain data on pregnancy outcomes for all deliveries of registered women, regardless of delivery location.MNHR staff primarily comprise community workers and nurses who are assigned specific geographical areas. Their responsibilities involve conducting three crucial visits: The first visit, known as the enrollment visit, is ideally scheduled during the first trimester of pregnancy. During this visit, they meticulously gather essential pregnancy-related data. The second visit is conducted within the first 48 h postpartum, where they collect comprehensive birth-related data, ensuring timely and accurate documentation and finally, the third visit takes place 42 days postpartum, during which they focus on gathering morbidity and mortality data .The population studied included women screened for the MNHR who were eligible, consented, and delivered between 2017 and 2020. Data were excluded for women who were enrolled but lost to follow-up prior to delivery, maternal deaths prior to labor and delivery, miscarriages, medically terminated pregnancies, pregnancies complicated by breech or other malpresentations, and those with missing data for delivery.p < 0.1. All statistical comparisons were performed using robust Poisson regressions, adjusting for the correlation within cluster. Statistical analyses were performed using SAS software version 9.4 .Data were collected and transmitted through secure methods to a central data-coordinating center . Counts and percentages of modes of birth were obtained using standard contingency table techniques. Bivariate comparisons of women achieving vaginal birth after cesarean compared to RCB were assessed. A multivariate model of VBAC compared to RCB was assessed with a priori selected covariates of delivery location, maternal hypertensive disease, dysfunctional labor, maternal schooling, and maternal age. Subsequently, individual models of maternal and perinatal outcomes were fit to determine which outcomes were more and less common among women pursuing RCB as compared to vaginal birth after cesarean. Each of these models was adjusted for the characteristics that were predictive of RCB compared with vaginal birth after cesarean at The appropriate institutional review boards/ethics research committees of the participating institutions approved the MNHR study. Individual informed consent for study participation is requested and obtained from each study participant. A Data Monitoring Committee, appointed by the NICHD, oversees, and reviews the study semi-annually.n = 8267), 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a RCB. The VBAC rate ranged from 4.2% in Bangladesh, 15.5% in Belagavi, 17.3% in Nagpur, 16.5% in Pakistan, up to 21.2% in Guatemala.Figure Compared to those who underwent RCB, women in these selected GN sites who achieved VBAC have differed in terms of education (7.8% vs. 13.8% achieved higher education), parity (29.1% vs. 9.4% had parity > 2), body mass index (BMI) (35.7% vs. 40.3% had BMI ≥ 25), median inter-delivery interval (32 vs. 37 months), number of antenatal care visits (59.1% vs. 72.7% had ≥ 4 visits), experiencing obstructed labor or failure to progress (2.9% vs. 8.7%), experiencing hypertensive disorders (2.2% vs. 5.7%), undergoing induction of labor (3.6% vs. 0.5%), choice of delivery location , and preterm birth rates (20.0% vs. 16.6%) ; having a hypertensive disorder ; experiencing obstructed labor or failure to progress ; and having schooling versus no formal education or being illiterate   where no fetal monitoring was available, compared to women with RCB (2.8%).Lower rates of breastfeeding initiation within the first hour after delivery were observed for those with RCB, an outcome with implications for both maternal and infant health.Our findings are consistent with prior studies , 7–19, wWhile these findings are consistent with other literature, it is notable that the rate of VBAC in Bangladesh is less than 5%. This is even lower than the rate in high-income settings and is certainly an outlier even among our study sites with lower cesarean birth rates. Recent data show that our findings are consistent with the rise of cesarean rates –24, and It is known that babies born by RCB have a higher risk of needing supplemental oxygen due to transient tachypnea of the newborn. Also, significantly greater usage of antibiotics has previously been reported for infants born via cesarean delivery , 11, 25,The impact of cesarean delivery on delayed initiation of breastfeeding has been previously reported for low- and middle-income countries –30. The The high prevalence of RCBs in some countries, such as Bangladesh, highlights the need for research on ways to safely and successfully promote vaginal birth after cesarean (VBAC) in low-resource settings. The increasing rates of cesarean birth can strain the healthcare system and have negative impacts on the health and well-being of women and their offspring. This is especially concerning in settings where there may be limited resources and higher rates of morbidity and mortality. The findings of this analysis align with existing literature and enhance the external validity of the data collected in the GN registry. Our findings lead us to propose areas that warrant further research, which, in turn, could contribute to the promotion of policies aimed at reducing the rate of cesarean sections. This, in turn, may play a positive role in decreasing complications associated with VBAC and RCB.This analysis has some limitations due to its reliance on the secondary analysis of quantitative data, lacking additional context regarding women’s preferences for their mode of birth and their labor experiences in cases of failed trial of labor after cesarean, also to discuss the complications related to VBAC and RCB. However, the study’s strengths lie in its utilization of large sample sizes drawn from diverse global populations, reflecting the increasing rates of C-sections. Moreover, the study’s unique contribution emerges from its broader scope, standing in contrast to narrower, single-site, or regional analyses.


Involvement of women in the decision-making process during childbirth plays an important role in their physical and psychosocial preparation. A birth plan allows the woman to express her expectations and facilitates her participation in her own care. The present study is the first to assess the implementation of birth plans integrated into childbirth preparation classes in Tehran, Iran.t-test, Mann–Whitney U-test, Chi-square test, Fisher's exact test, and logistic regression were used for data analysis.This study is a randomized controlled clinical trial performed on 300 pregnant women at 32–33 weeks of gestation referring to four public health centers in Tehran, Iran. The participants were randomly allocated into intervention and control groups using block randomization method. A training session on the items of the birth plan checklist was held in the fifth session of childbirth preparation classes for the participants in the intervention group. Accordingly, a birth plan was prepared according to the requests of mothers. The birth plan was implemented after the women were admitted to the maternity ward. The primary outcomes were frequency of vaginal birth, mean duration of labor stages, and mean score of childbirth satisfaction. We used a checklist of maternal and neonatal outcomes, Mackey's childbirth satisfaction questionnaire, and a partogram form for data collection. Independent p < 0.001). Also, the lengths of the first and the second stages of labor were significantly shorter in women having a birth plan (p = 0.02). Women in the birth plan group were significantly more satisfied with the process of labor and childbearing (p < 0.001), and started breastfeeding after birth earlier than those in the control group (p < 0.001).Vaginal birth rates were significantly higher in women who had birth plans compared with those without (81.9% vs. 48.7%, Having a birth plan and attending childbirth preparation classes can increase the rate of normal vaginal birth. Also, according to our results, women's participation in the decision- making process and fulfilling their preferences during birth can improve maternal and neonatal outcomes and childbirth satisfaction.Trial registration: IRCT20190415043283N2. 2020-12-07. Childbirth is a major life event for women so much so that it can create memories which will probably stay with them for a lifetime . NowadayOver the past decades, there has been an unprecedented and significant rise in cesarean birth rates across the world . TherefoIn addition to childbirth educational classes, birth plan is one of the philosophies advocating the de-medicalization of natural processes of labor and birth . Using bPlanning birth during the antenatal period promotes health education and fosters communication between women and health professionals . The WorDespite the fact that around 90% of Iranian women give birth at hospital, unnecessary medical interventions are still very common during normal labor and childbirth, compared to developed countries . It is wThe high rate of cesarean section has raised serious concerns among health policy-makers and decision-makers in Iran , and theThis randomized controlled trial which included two parallel groups was conducted on 300 pregnant women at gestational age of 32–33 weeks in Tehran, Iran. This study was carried out in four public health center of Tehran from December 2020 to the end of June 2021.were also recruited. Women with any contraindications to vaginal birth, history of abortion, multiple pregnancy, pre-eclampsia or eclampsia, placenta previa, placental abruption, history of infertility, history of medical disorders such as cardiovascular, renal, liver, brain diseases, and abnormal fetus were excluded from the study.Eligible women to participate in the study were primiparous or multiparous women who were married and aged ≥18 years, had low-risk singleton pregnancy, were at gestational age of 32–33 weeks, had basic literacy, were planning to have normal vaginal birth, and attended the fifth session of child birth preparation classes. Women with previous cesarean section who were willing to have vaginal birth This study was conducted in four public health centers  affiliated to Tehran University of Medical Sciences. Tehran is the capital of Iran which is also known as the most populous city in this country . These hTwo private hospitals and one hospital affiliated to the armed forces in Tehran  were designated for the participants’ childbirth. Although birth plan is not routinely implemented in Iran, these hospitals were chosen because they allowed pregnant women to give childbirth in maternity wards based on their birth plan. In the study period, the childbirth rates were about 2,000, 3,000, and 5,000 births annually in Omid, Ansari, and Najmiyeh hospitals, respectively. In these hospitals, obstetricians had direct responsibility for prescriptions during labor and birth. The vaginal births were carried out by midwives or obstetricians. Eligible pregnant women were selected from the above-mentioned educational classes. The first investigator  briefed the women on the study objectives and methods, and written informed consent was obtained from those who were willing to participate. Then, a demographic questionnaire was completed for each eligible woman through interview.After assigning the participants into study groups, the researcher (ZM) held a training session for the intervention group in the fifth session of childbirth preparation classes, and all items of the birth plan checklist were explained. Training on the birth plan was held in groups, and an average of 8–10 women participated in each group. Childbirth preparation classes were held by a designated midwife, and the researcher only introduced and taught the birth plan.Birth plans were prepared from this session up to several weeks prior to labor. In these sessions, the researcher, the pregnant women, and her husband discussed various aspects of labor and birth along with personal expectations and concerns. The specific issues that were considered and documented in each birth plan included woman's expectations and preferences , care during the first stage of labor , care during the second stage of labor , and care after delivery . Apart from predetermined items, any further needs or expectations were described in a blank space. The birth plan checklist was filled out by the women themselves. In addition, a phone number was provided to the women so that they could contact the first investigator in case they had any question. From the time the birth plan was developed until the time of birth, ZM was in contact with the participants by telephone, and she answered any question the participants had about birth plan. The women were requested to call one of the researchers (ZM) once they were admitted to the hospital for labor and birth. Upon admission to the hospital, the women brought their documented birth plans to the maternity ward and handed it to the midwife, who had already been instructed to use the plan as a basis for care. In addition, the women's birth plan was shared with an obstetrician who was responsible for the care of these women. Labor and birth management were based on the mother's requests in her birth plan.Women in the control group received only routine care according to the hospital policy. They attended childbearing preparation classes without any birth plan. Due to the COVID-19 pandemic, some sessions of educational classes for both groups were held virtually. During the childbirth process, birth information, partogram form, and maternal and neonatal outcomes were recorded for all participants by two research assistants who were blinded to the grouping. Also, women's satisfaction with childbirth was assessed according to Mackey's Childbirth Satisfaction Rating Scale, 12–24 h after birth and before discharge from hospital. In both groups, vaginal births were attended by midwives or obstetricians in the maternity wards of the mentioned hospitals, and the researchers were not involved in providing any care during pregnancy, labor, birth, and postpartum periods.The primary outcomes were (1) comparison of birth mode in the studied groups (2) comparison of the mean duration of the labor stages in the studied group (3) comparison of the mean score of child birth satisfaction in the studied groups.Secondary outcomes were (1) frequency of labor augmentation, perineal tears, and maternal outcomes (2) neonatal admission to neonatal intensive care units (NICU) (3) neonatal Apgar score in the first and fifth minutes (4) initiation of breastfeeding within 1 h after birth.α = 0.05 and power = 90%, the sample size in each group was calculated to be 127. Considering 15% potential attrition rate, 150 participants were considered for each group.The sample size was calculated according to the predicted reduction of cesarean section rate from 50.57% to 30% according to the instruction of the Iranian health care reform-executive . With thRandomization was performed using the “blockrand” package of R software, with block sizes of four and six and an allocation ratio of 1: 1 for the intervention and control groups.For allocation concealment, the type of intervention was written on a piece of paper and was placed inside consecutively numbered opaque envelopes which were kept by a person who was not aware of the objectives of the study. Therefore, neither the researchers nor the participants were aware of grouping until the commencement of the study. After informed consent was obtained from eligible women, the envelopes were opened, and the intervention started.The allocation sequence was determined by a person who was neither involved in the sampling and data collection nor aware of the study process.Due to the nature of the study, the participants and researchers could not be blinded; however, outcome assessors and data analyzer were blinded to grouping.The demographic questionnaire included questions about age, educational attainment, occupation, ethnicity, and body mass index. Some obstetric characteristics such as gravidity, parity, mode of pervious birth, history of prenatal care, and history of childbirth preparation classes were also recorded. The validity of this questionnaire was confirmed through content and face validity methods. The face validity was determined based on the opinions of 10 experts in the field of midwifery and reproductive health specialists. Also, the specialists reviewed the questionnaire items in terms of difficulty level, irrelevancy, and ambiguity. If necessary, the items were modified based on the given recommendations , and forBirth plans have different formats including a list of options that women can choose during labor and birth, and include a few open-ended questions that women may not find in the checklist .Since birth plan has not been yet established in Iran, the birth plan checklist in the present study was prepared based on available evidence and clinical experience. The birth plan checklist included 13 questions. It was later reviewed by 14 experts in the field of midwifery and obstetrics, and its content validity ratio (CVR) and content validity index (CVI) were assessed. CVI values were calculated by determining the simplicity, relevance, and clarity of the items, and were scored according to a four-point Likert scale. A CVI value higher than 0.79 was considered acceptable. To determine CVR scores, the specialists were asked to comment on the necessity of each item based on a three-point Likert scale. Based on the Lawshe Table , the minPartogram is a valuable tool used by midwives and obstetricians for recording labor details. The application of partogram in developed and developing countries led to its worldwide recognition . In ordeThe maternal and neonatal outcome checklist included information about mode of birth, reasons of cesarean section, admission to NICU, intrauterine growth retardation (IUGR), breastfeeding initiation, Apgar score, and neonate's weight, height, and head circumference. The content and face validity of this checklist was assessed. The face validity was confirmed based on the opinions of faculty members who were midwifery and reproductive health specialists. They reviewed the tool items based on the difficulty level, irrelevancy, and ambiguity criteria. If necessary, the items were modified based on the recommendations provided , and forThis scale which consists of 40 questions was developed to measure women's satisfaction from childbirth. A five-item Likert scale was used for scoring this scale in the present study. For questions 1–34, the responses were scored from 1 (very dissatisfied) to 5 (very satisfied).For questions 37–40, a four-item Likert scale was used for scoring, which ranged from (1): very negative, to (4): very positive. A total score ≥12 indicated positive experiences and scores <12 indicated negative experiences . A totalU-test. However, for data with normal distribution, the independent t-test was used. Chi-square test or Fisher's exact test was used for comparing categorical data. Logistic regression was used to estimate the effect of birth plan on gestational outcomes after adjusting for potential confounders . In all analyses, p < 0.05 was considered statistically significant.The data were analyzed using SPSS version 22 . The Kolmogorov–Smirnov test was used for testing normality of data. The gestational age at birth, birth weight, and length of labor did not have normal distribution and were compared using the Mann–Whitney n = 150) or control (n = 150) groups  groups .p = 0.708). The majority of women in both groups were housewives . Significantly more women in the birth plan group had university education compared to the control group (p < 0.001). The obstetric history showed that 22.7% and 32% of women in the intervention and control groups were primigravidae, respectively (p = 0.106).Baseline characteristics of the participants are described in Mean gestational week at the first prenatal care was 9w + 3d in both groups. Also, there was no difference between the two groups in terms of gestational age at birth .p < 0.001). Also, women with a birth plan were more likely to have vaginal birth after cesarean section (VBAC) . Among those undergoing vaginal birth, the majority of women who had birth plan (70.7%) and women without birth plan (71.2%) were attended by midwives (p < 0.94).p = 0.02). Women with a birth plan were also less likely to have episiotomy  or receive oxytocin as an augmentation compared to the control group . There were no differences between the two groups in terms of other pregnancy outcomes such as postpartum hemorrhage, preeclampsia, eclampsia, or preterm labor , and they consistently received higher scores on all dimensions of the satisfaction scale. Specifically, women with a birth plan had a higher satisfaction with their birth experience (p < 0.001)  .p = 0.163, p = 0.483). Although the neonatal admission to NICU was fewer in the birth plan group , the difference was not significant (p = 0.19). Women in the intervention group started breastfeeding after birth sooner than those in the control group (p < 0.001).This study assessed the effect of birth plans along with childbirth preparation classes on maternal and neonatal outcomes of Iranian pregnant women. Birth plans increased the frequency of vaginal childbirth, reduced unnecessary medical interventions such as induction and episiotomy, and reduced the duration of active, second, and third phases of labor. It also improved the childbirth experiences of mothers, as well as their childbirth satisfaction. However, there was no significant difference between the two groups in terms of first- and fifth-minute Apgar scores, and frequency of admission of a newborn in NICU.This intervention was the first of its kind to be conducted in Iran. According to the results, women with a birth plan had a significantly higher rate of vaginal birth and vaginal birth after C-section (VBAC), compared with the control group. Also, after using the adjusted model of regression, our results revealed that birth plan can increase the rate of vaginal birth . These findings suggest that educating women and involving them in decision making and planning for their childbirth can increase the normal vaginal birth rate. There are, however, conflicting data in the literature on the correlation between birth preparation and mode of birth. Our findings are consistent with those of Wu et al. who reported that the rate of vaginal birth in women with a stronger preference for vaginal birth was significantly higher . Also, oOur results, however, are in contrast with those of Pennell et al. who found that women with a birth plan had an increased rate of cesarean births . This isp < 0.001). They had an active role in managing their labor and birth, with pervious preparation and awareness. The majority of our participants were admitted to hospital when they were in the active phase and had better dilatation and effacement compared to the women without birth plan.The current study showed that having birth plan is associated with less frequent use of oxytocin for augmentation, which is in agreement with Afshar et al. , and Pedp < 0.001) (p = 0.83)  . Deering = 0.83) . This fiOur findings demonstrated that having a birth plan may reduce the length of different stages of labor, which is not consistent with Farahat et al., who found no difference between the studied groups in terms of the length of the first and third stages of labor. They also reported that length of the second stage of labor was longer in women having a birth plan . The finA possible explanation for this finding may be that prenatal training and involving women in decision making about their values in labor and birth can reduce their fear and anxiety . ReducinChildbirth is one of the most important psychological events in a mother's life. Support and communication during labor increase a “woman's childbirth satisfaction” . This efResults of the present study showed that women with a birth plan are more likely to start breastfeeding earlier after birth. Furthermore, their neonates were found to be less likely to be admitted to the NICU. These findings are in agreement with those of Lundgren et al.'s study in which having a birth plan was found to have a beneficial effect on neonatal outcomes . These fThe present study was performed in hospitals where more than 70% of the deliveries are performed by cesarean section. The surprising results of this study suggest that Iranian women need more midwifery services, and that by fulfilling the preferences of a pregnant woman during childbirth, the possibility of vaginal birth will increase accordingly. Childbirth education alongside a birth plan can play an effective role in empowering women. Therefore, health policymakers need to change their strategies to support women's health during childbirth. Also, government support for the implementation of women's preferences during labor and birth can be an appropriate solution against the increased cesarean section rate in Iran.The main limitation of this study is that it was conducted in private hospitals; therefore, the results of this study may not be generalized to all hospitals including public hospitals. However, this study has several strengths such as random sampling, and it is the first study to the best of our knowledge to investigate the effects of birth plan integrated into childbirth preparation classes in Tehran, Iran.Birth plans along with childbirth preparation classes are an appropriate strategy for reducing the rate of cesarean section and improving women's satisfaction. Involving pregnant women in decision making about their preferences during labor can improve health outcomes and satisfaction.


Neurenteric cysts are rare benign lesions that are usually located in the lower cervical and upper thoracic spine and extremely rare in the craniovertebral junction. It is generally challenging to completely remove the neurenteric cysts of the craniovertebral junction. We report the cases of 2 patients with neurenteric cyst in the ventral craniovertebral junction managed using different treatment strategies.The first patient was a 64-year-old man. He man was admitted with headache, posterior neck pain, and a tingling sensation in both the forearms. The second patient was a 53-year-old woman. She was admitted with tingling sensations and numbness in both the hands and feet.Cervical spine magnetic resonance imaging showed 2 intradural extramedullary cystic lesions in case 1 and a C2 to C3 intradural extramedullary cystic mass in case 2.The patient of the case 1 underwent a left C1 to C2 hemi-laminectomy and the cysts were completely removed. Eleven years after the surgery, there was no recurrence. In case 2, we performed a left C2 to C3 hemi-laminectomy and removed only a part of the outer membrane to enable sufficient communication with the surrounding normal subarachnoid space. After removing the cyst wall, the patient underwent C1 to 2 trans articular screw fixation to prevent cervical instability. Ten years after surgery, there was no recurrence of the cyst or new lesions.Clinicians should consider neurenteric cyst in the differential diagnosis of arachnoid cyst or epidermoid cyst. If performing a complete surgical removal is difficult, partial surgical removal, using a cysto–subarachnoid shunt and stabilization, such as screw fixation, could be an alternative treatment option to reduce the risk of mortality and morbidity. There were no neurological deficits, including gait disturbance, motor weakness, or sphincter dysfunction. Cervical spine magnetic resonance imaging (MRI) revealed 2 intradural extramedullary (IDEM) cystic mass lesions. The spinal cord at the C2 level showed poorly defined hyperintensity on T2-weighted images. One lesion was a 1.5-cm mass dorsal to the spinal cord from the craniovertebral junction to C1; the other was a 2.5-cm mass ventral to the spinal cord from C2 to C3 (Fig. We performed a left C1 to C2 hemi-laminectomy. intraoperatively, 2 white-colored cysts with thick membranes compressing the spinal cord and the right C2 nerve root were exposed. There was no connection between the 2 cysts, and they could be dissected away from the spinal cord and nerve root. The cysts were completely removed without injuring the surrounding neurovascular structures. Tissue was obtained from the cystic wall of the lesion at C2 to C3 for biopsy. After surgery, his symptoms improved, and he returned to daily life with reduced medication. The cysts were diagnosed as neurenteric cysts. Histopathological findings revealed that the tissue we thought was a cyst membrane was an inflammatory component, and the inner fluid was mucin-like material. Overall, the cyst was more likely to be a neurenteric cyst than an arachnoid cyst.Postoperatively, cervical spine MRI revealed no residual or recurrent cystic masses. Follow-up cervical spine MRI performed 6 months after surgery revealed no recurrence; 11 years later, no recurrence was observed.A 53-year-old woman presented with a 1 year history of tingling sensations and numbness in both hands and feet. She had no neurological deficits, including gait disturbance, motor weakness, or sphincter dysfunction. A C2 to C3 IDEM ventral spinal cord cystic mass was evident on cervical spine MRI scans, exhibiting isointense to low-intensity signals on T1-weighted images (Fig. We performed a left C2 to C3 hemi-laminectomy. Intraoperatively, white-colored cysts within a transparent gelatin-like material were found compressing the spinal cord. The transparent inner material of the cyst was easily removed using suction. Complete surgical resection of the cystic wall was difficult due to the spinal cord; therefore, we removed only part of the outer membrane to enable sufficient communication with the surrounding normal subarachnoid space. Biopsy of the cyst membrane was performed. After removing the cyst wall, we performed a C1 to 2 trans articular screw fixation to prevent cervical instability Fig. . After sHistological examination revealed that the mucin and cyst wall were lined by simple columnar and cuboidal epithelium with isolated goblet cells. Considering the overall features, the patient was diagnosed with a neurenteric cyst Fig. . Ten yea,7Neurenteric cysts are rare benign lesions of the central nervous system. Over 90% of such lesions are IDEM lesions whose locations can cause pain, myelopathy and radiculopathy due to spinal cord and nerve root compression. These lesions are usually located ventral to the lower cervical and upper thoracic spinal cord but can occur rarely in the craniovertebral junction.,8 Several theories have been suggested to explain their origin; the most widely accepted theory is that, during the embryogenic phase, abnormal communication between endodermal and ectodermal tissue is the main cause of cyst formation.,7Typical MRI findings of neurenteric cysts are isointense on T1-weighted images and hyperintense on T2-weighted images. However, they can appear differently on T1 weighted images, depending on protein content of the cysts. The cysts exhibited no contrast enhancement after gadolinium administration, however the cystic wall sometimes exhibited slight contrast enhancement. Cysts are mostly filled with fluid and have no solid component.,5,8 In general, confirmation of cysts is based on pathological findings; however, we did not obtain any characteristic pathological tissues in case 1. In this case, other diseases, including arachnoid cysts, could be ruled out because the cyst contained sticky gelatin-like material and not cerebrospinal fluid, and the cyst contained inflammations. Based on these findings, we concluded that the diagnosis was neurenteric cyst.Due to its embryological origin, the cyst wall pathologically resembles gastrointestinal and respiratory tissue. Hematoxylin-eosin staining showed that the cysts were lined by cuboidal or simple columnar epithelium with or without cilia containing frequent goblet cells, which produce secretions such as mucin. This secreted material, which it is thought to be the main cause of cyst growth, is mostly transparent and viscous or milky.,8,9 Therefore treatment method was determined according to the operator’s clinical judgment without definitive guidance.Some articles have reported on patient symptoms, diagnoses, and surgical management to reduce recurrence; the cases of neurenteric cyst at the craniovertebral junction are summarized in Table ,11 Therefore, we performed partial surgical removal using a cysto–subarachnoid shunt with posterior screw fixation to prevent recurrence.Clinicians should perform complete surgical removal if possible. However, complete removal of a neurenteric cyst in the craniovertebral junction is difficult; many important structures are located in the craniovertebral junction, including the vertebral artery and the lower cranial nerve. Moreover, the surgical field is usually narrow, because the amount of bone exposure should be tailored to avoid unnecessary bone drilling and reduce craniovertebral instability; retraction of the cerebellum, brainstem, and spinal cord should also be minimized to prevent neurological injury.,13 Based on this, we assumed that instability is a factor that triggers inflammatory reactions. Instability causes mucin secretion to become more active, which increases the size of the cysts as goblet cells secrete mucin. Therefore, in Case 2, we thought that the cyst would not recur if mucin secretion was reduced and the cyst wall was sufficiently removed so that the remnant cyst wall did not block communication. For these reasons, we suggest that partial removal of a cyst and stabilization through screw fixation are sufficient treatments to eliminate the cause of the cyst growth.The generally accepted hypothesis is that some inflammatory/immune-response mediators initiate mucin hypersecretion in the respiratory system and gastrointestinal tract by activating a secretory cascade that results in the rapid release of mucin from the secretory granules in goblet cells.Partial removal and stabilization are an alternative treatment option for a neurenteric cyst in the craniovertebral junction, where complete surgical removal is difficult, and are thought to reduce the risk of mortality and morbidity. Although no recurrence was observed in case 2 during the 10-year follow-up period, the cyst could not be considered completely cured. More cases of these rare cysts, exploring other treatment options, should be reported to help define evidence-based recommendations for patients with neurenteric cysts in the craniovertebral junction.Neurenteric cysts are rare benign cysts; until recently, complete surgical removal has been considered an effective treatment for reducing the risk for recurrence after surgery. However, it is often difficult to approach and completely remove neurenteric cyst surgically. We suggest that partial surgical removal, using a cysto–subarachnoid shunt and stabilization, such as screw fixation, could be an alternative treatment option for patients for whom complete surgical removal is difficult or whose cysts have severe adhesion to the surrounding neurovascular structures.Conceptualization: Jung-Kil Lee.Data curation: Sue-Jee Park, Jong-Hwan Hong, Bong Ju Moon, Joo-Yeon Koo.Methodology: Jung-Kil Lee, Moon-Soo Han.Software: Sue-Jee Park.Supervision: Jung-Kil Lee.Writing – original draft: Sue-Jee Park, Moon-Soo Han, Joo-Yeon Koo.Writing – review & editing: Sue-Jee Park, Jung-Kil Lee, Moon-Soo Han.


Moreover, the odds of LGA increased by nearly 11% for each one-unit increase in pregestational BMI . To our knowledge, the present study is the first to highlight a relationship between adherence to an unhealthy dietary pattern and the likelihood of giving birth to a LGA newborn. This evidence adds to the current knowledge about the effects of diet on birth weight, which, however, remains limited and controversial.Limited evidence exists on the effects of maternal dietary patterns on birth weight, and most studies conducted so far did not adjust their findings for gestational age and sex, leading to potentially biased conclusions. In the present study, we applied a novel method, namely the clustering on principal components, to derive dietary patterns among 667 pregnant women from Catania  and to evaluate the associations with birth weight for gestational age. We identified two clusters reflecting distinct dietary patterns: the first one was mainly characterized by plant-based foods , fish and white meat, eggs, butter and margarine, coffee and tea; the second one consisted mainly of junk foods , pasta, white bread, milk, vegetable and olive oils. Regarding small gestational age births, the main predictors were employment status and primiparity, but not the adherence to dietary patterns. By contrast, women belonging to cluster 2 had higher odds of large for gestational age (LGA) births than those belonging to cluster 1 (OR = 2.213; 95%CI = 1.047–4.679;  Globally, about 140 million births take place every year. Deaths from complications during pregnancy and childbirth have declined by 38% in the last two decades, but at an average reduction of just 3% per year ,6,7. SimDuring the entire reproductive period—but especially in pregnancy—both environmental exposures and lifestyles can affect physiological and pathological conditions in mothers and in future generations ,15,16. MTwo independent systematic reviews have tried to understand the effects of maternal dietary patterns on birth outcomes ,61. TherLimited conclusions, instead, can be drawn on the effects of maternal dietary patterns on birth weight ,61. A grAmong data-driven methods used in nutritional epidemiology, two multivariate techniques have been widely applied to derive dietary patterns: principal component analysis (PCA) and cluster analysis  ,64,65,66The present analysis was conducted on data from the “MAMI-MED” cohort, an ongoing prospective study on mother–child dyads from Catania , which has been established in December 2020. The general aim of the study is to evaluate the effects of social, environmental, behavioral, and molecular factors on maternal and child health. The MAMI-MED cohort shares the same study protocol and methods used for the “Mamma and Bambino” cohort, established in 2015 ,69,70,71At recruitment, each woman was administered a structured questionnaire for the collection of socio-demographic characteristics and behaviors. Maternal education was categorized into two levels: low educational level if women had ≤ 8 years of school; high educational level if women had > 8 years of school. Mothers were also classified as unemployed (which included students and housewives) or employed. Regarding the smoking status, they were classified as current or non-current smokers (including ex-smokers). Women were asked about their height and weight before pregnancy at the time of recruitment; this information was then used to calculate and categorize pre-pregnancy BMI according to the WHO criteria . In ordehttp://ndb.nal.usda.gov/ (accessed on 1 January 2014)) adapted to Italian foods. Daily dietary intakes were adjusted for total energy intake according to the residual method [At recruitment, the assessment included a 95-item semiquantitative Food Frequency Questionnaire (FFQ) referred to the previous 30 days ,76,77,78l method .To derive distinct dietary patterns, we applied a novel approach defined as clustering on principal components (PCs) that is fully described elsewhere . Brieflyt-test. Multivariable logistic regression analyses were applied to evaluate the association of dietary patterns and birth weight for gestational age (SGA or LGA versus AGA), adjusting age (continuous), pre-pregnancy BMI (continuous), GWG (continuous), educational level (high vs. low-medium), employment status (employed vs. unemployed), primiparity (primiparous vs. non-primiparous), smoking status (smoker vs. non-smoker), and total energy intake (continuous). Results from the logistic regression were reported as Odds Ratios (ORs) and their 95% Confidence Intervals (95%CIs). All statistical tests were two-sided and performed at a significance level α = 0.05.Statistical analyses were performed using SPSS v. 26.0 . Univariate analysis was conducted to describe the characteristics of the study population, in terms of median and interquartile range (IQR) or frequencies . The Kolmogorov–Smirnov test was used to check the distribution of quantitative variables. Bivariate analysis was conducted using the Mann–Whitney U-test was used for quantitative variables or the Chi-squared test for categorical variables. Z-scores of food and nutrient intakes were compared between clusters using Student’s The study population consisted of 667 women who completed pregnancy and satisfied inclusion criteria. The median age was 31 years (IQR = 7), and 51.1% of women were primiparous. Regarding socioeconomic factors, 24.9% reported a high level of education and 50.7% of women were employed. Almost all of them reported not being a smoker during pregnancy (91%), and they reported a median total energy intake of 1703 kcal (IQR = 508). Before pregnancy, the median BMI was 23.2 kg/m2 (IQR = 5.8), and over half of the women were normal weight (60.4%). According to the GWG , 38.5% of women reported a reduced weight gain, and 28.7% reported an excessive weight gain. The median gestational week at delivery was 39 (IQR = 2), and 94% of births were at term. Regarding birth sizes, the median values were 3.3 kg (IQR = 0.6) for birth weight and 50 cm (IQR = 2) for birth length. As a result, 81.9% of newborns were AGA, 7.1% were SGA, and 11.0% were LGA.p-value for the Bartlett’s test < 0.001), the PCA was applied to standardized and energy-adjusted dietary data. The PCA produced 16 PCs with eigenvalue greater than 1. Through inspection of the scree plot and in accordance with the elbow method (n = 158) were characterized by higher intake of potatoes, cooked and raw vegetables, legumes, fruits, nuts, yogurt, rice, wholemeal bread, white meat, offal, fish, eggs, butter and margarine, coffee, tea, and soup. Those in cluster 2 (n = 509) were characterized by higher intake of milk, pasta, white bread, shellfish, vegetable and olive oils, sweets, fruit juices, dipping sauces, salty snacks, and fries. Regarding nutrients, participants in cluster 1 were characterized by higher intakes of folate, magnesium, and vitamins A, B6, and C, while those belonging to cluster 2 had higher intakes of saturated and unsaturated fatty acids, calcium, and vitamin B1  and had a lower level of education (p = 0.018) than those belonging to cluster 1. Furthermore, they reported a higher total energy intake (p < 0.001). No other statistically significant differences were evident between the clusters. Likewise, there were no differences between the clusters regarding birth outcomes, including gestational week at delivery, proportion of preterm birth, birth weight, and birth length . Conversely, primiparous women had higher odds of SGA than women who have already had one or more pregnancies . Regarding LGA, the main associated factors were cluster membership and pre-pregnancy BMI. Specifically, women belonging to cluster 2 had higher odds of LGA than those belonging to cluster 1 . Moreover, the odds of LGA increased by nearly 11% for each one-unit increase in pregestational BMI .Finally, we evaluated which were the main factors associated with birth weight for gestational age . RegardiTo our knowledge, this is the first study applying the clustering on PCs to derive dietary patterns during pregnancy and to evaluate their associations with pregnancy and birth outcomes, with a particular focus on the effect on birth weight for gestational age. By applying this method, we first obtained two clusters reflecting dietary patterns that were popular among pregnant women. The identified dietary patterns were similar to those derived in previous studies on similar populations from the same region ,77,80,81From the comparison of maternal characteristics between dietary patterns, it was evident that younger and less educated women adhered more to the western diet. These findings were in line with previous evidence showing that younger people with lower level of education are moving away from traditional healthy habits and instead adopting western behaviors ,82,83,84In our study, there were no differences between dietary patterns in terms of gestational week at delivery and PTB. This finding differed from those obtained by previous meta-analyses and interventional studies ,61,89, aThe absence of the relationship with the risk of SGA was not surprising. As Raghavan and colleagues reported in their previous systematic review, only half of the studies found an association between dietary patterns and birth weight outcomes . FurtherThe main strength of our study is the application of an innovative method for analyzing dietary patterns during pregnancy. This approach overcomes the limitations of PCA (which does not provide distinct dietary patterns but scores for different components) and provides a better solution than simple clustering . In addiDespite these limitations, the present study is the first to highlight a relationship between the adherence to an unhealthy dietary pattern and the likelihood of giving birth to an LGA newborn. This evidence adds to the current knowledge about the effects of diet on birth weight, which, however, remains limited and controversial. Although far from drawing definitive recommendations based on evidence, these findings are important to guide future research in this field. In particular, our work proposes an alternative method for analyzing nutritional profiles, which could be used in future studies during pregnancy and throughout the periconceptional period.


Fetal cerebral aneurysm other than aneurysm of vein of Galen aneurysmal malformation (VGAM) is extremely rare. This report describes prenatal features of aneurysm of the posterior cerebral artery (APCA) with rapid progression and its natural intrauterine course of the disease, which has never been reported.This is the first report of prenatal features of APCA, detected at 34–36 weeks of gestation, simulating choroid plexus cyst or arachnoid cyst. The diagnosis was based on color flow ultrasound with tracing along the course of cerebral arteries. Also, rendered 3D color flow ultrasound was helpful in demonstrating course of the vessels feeding the aneurysm and supporting the diagnosis. The aneurysm showed nature of rapidly progressive changes, leading to leakage resulting in intracerebral and intraventricular hemorrhage as well as high output state associated with anemia. Prenatal diagnosis and management are very challenging. This case ended up with planned delivery at 37 weeks, giving birth to a surviving male newborn, weighing 2600 g. The neonatal CT brain scans and CTA confirmed the prenatal findings. The prognosis was relatively poor because of extensive intracerebral hemorrhage with severe hydrocephalus and brain midline shift. The couple opted for neonatal palliative care without neurosurgical correction.This study demonstrate that the most important tool for prenatal diagnosis is color Doppler ultrasound, which will demonstrate turbulent blood flow. Three-dimension color Doppler ultrasound is helpful in supporting the diagnosis. The case presented here suggests that the disease has a natural course of rapid progression and massive brain destruction or high output congestive heart failure can be expected.The online version contains supplementary material available at 10.1186/s12884-023-06056-9. Fetal cerebral aneurysm is a rare but very challenging. Nearly all cases of prenatal diagnosis of cerebral aneurysm ever reported were vein of Galen aneurysmal malformation (VGAM), with the estimated incidence of 1 in 10,000 to 1 in 25,000 births . Though +5 weeks at our hospital, the size of lateral ventricles, third ventricle and fourth ventricle were relatively the same. The round -shape anechoic cyst at the left parieto-occipital lobe was increased in size, 32 × 27 × 25 mm, with expanding hyperechoic area surrounding the cyst, representing pericystic hemorrhage. The left lateral ventricle was filled with hyperechoic irregular mass (hemorrhage) in most part. Color and spectral Doppler ultrasound showed turbulent flow in the cyst. The originating point of arterial jet arose from the left posterior cerebral arteries at left lateral border of temporal-parietal area of the hemisphere  were also documented. Peak systolic velocity of the middle cerebral artery was 103.5 cm/s (greater than 1.5 MoM). After multidisciplinary consensus  and patient counseling about poor prognosis in case of no intervention, planned delivery for postnatal management was performed by induction of labor at 37 weeks of gestation. However, cesarean section was performed due to failure of induction, giving birth to a male newborns, weighing 2,600 gm with Apgar scores of 9, 10 and 10 at 1, 5 and 10 min, respectively. Grossly, the newborn was not obviously abnormal except for pale skin. The occipitofrontal circumference was 37 cm. The fetal movement was normal. Neonatal CT brain scans on day 1 , third ventricle and fourth ventricle, and a round shape, anechoic cyst (13 × 10 mm), at the left parieto-occipital lobe adjacent to the left lateral ventricle  Because of no anomaly seen at mid-pregnancy screening and first detection as a small cyst at 34 weeks, it suggests that APCA likely occur in the third trimester, as commonly seen in VGAM . 2) APCAThe differential diagnosis of a fetal intracranial vascular mass includes hemangioma, Kaposiform hemangioendothelioma, angioblastoma, angiosarcoma, congenital hemangiopericytoma, and arteriovenous malformation / aneurysm . DopplerNatural course of progression of the aneurysm in utero has never been studied. Nevertheless, our evidence supports the progressive nature as described in postnatal life. In adults, most cerebral aneurysms develop rapidly in hours, days or weeks, to achieve a size, of which elasticity in the aneurysmal wall can no longer expand, leading to either rupture or undergoing stabilization and hardening –11. ThisIn summary, fetal aneurysm of the APCA is extremely rare, possibly occurring in the third trimester of pregnancy as commonly seen in aneurysm of the vein of Galen. This disorder must be differentiated from other cystic brain anomalies. The most important tool for prenatal diagnosis is color Doppler ultrasound, which will demonstrate turbulent blood flow. Three-dimension color Doppler ultrasound is helpful in supporting the diagnosis. The case presented here suggests that the disease has a natural course of rapid progression and massive brain destruction or high output congestive heart failure can be expected. However, more several case reports/series are warranted to establish the true natural intrauterine course and prognosis.Additional file 1.


Since December 2012, the prophylactic use of caffeine to treat AOP in preterm infants has been approved in China. This study aimed to investigate the relationship between early caffeine treatment initiation and the incidence of oxygen radical diseases in neonatology (ORDIN) in Chinese preterm infants.A retrospective study was conducted at two hospitals in South China, involving 452 preterm infants with gestational ages less than 37 weeks. The infants were divided into early  and late  caffeine treatment group. Logistic regression analysis and Receiver Operating Characteristic (ROC) curves were used to evaluate the association between early caffeine treatment and the incidence of ORDIN.P = 0.02; ROP, 70.8% versus 89.9%, P = 0.025). Very preterm infants in the early treatment group had a lower incidence of BPD and PIVH compared to those in the late treatment group . Moreover, VLBW infants who received early caffeine treatment exhibited a decreased incidence of BPD , PIVH , and ROP  compared to those in the late treatment group. Infants in the early caffeine treatment showed a reduced likelihood of PIVH  but did not exhibit a significant association with other terms of ORDIN. ROC analysis revealed that early initiation of caffeine treatment was associated with lower risk of BPD, PIVH, and ROP in preterm infants.The results showed that extremely preterm infants in early treatment group had a lower incidence of PIVH and ROP compared to those in the late treatment group (PIVH, 20.1% versus 47.8%, In conclusion, this study demonstrates that early initiation of caffeine treatment is associated with a decreased incidence of PIVH in Chinese preterm infants. Further prospective investigations are necessary to verify and elucidate the precise effects of early caffeine treatment on complications in preterm Chinese infants. However, due to their immature organ development, extremely or very preterm infants are at high risk for preterm-related diseases in various organs or systems, including bronchopulmonary dysplasia (BPD), periventricular–intraventricular hemorrhage (PIVH) , perivenMethylxanthines have been used for several decades to prevent apnea of prematurity (AOP) in preterm infants. Caffeine is one of the most common methylxanthines widely used in neonatal intensive care units (NICU) due to its longer-lasting effects, greater safety, and lower cost compared to other methylxanthines. Studies have shown that caffeine significantly reduced the duration of mechanical ventilation and the incidence of BPD, intraventricular hemorrhage (IVH), and other terms of ORDIN –6. The pThe timing and dose of caffeine administration can have varying effects on preterm infants, and there is currently no consensus on standardized protocols for caffeine treatment till now in the NICU . Early iCompared to the long history of caffeine application in preterm infants, the use of caffeine for the management of AOP has only been approved in China since December 2012. There is a shortage of research on the timing and outcomes of caffeine treatment for ORDIN. In this study, data from two hospitals in Guangzhou, China, were retrospectively analyzed to investigate the association between early treatment of caffeine and outcomes of ORDIN in different subgroups of preterm infants.2.2.1.t inherited metabolic diseases.We conducted a retrospective study of those preterm neonates who were admitted to the Neonatology Department at the Third Affiliated Hospital of Guangzhou Medical University and the Third Affiliated Hospital of Sun Yat-sen University between January 2017 and December 2019. The study subjects were enrolled based on the following inclusion criteria: (1) gestational age (GA) less than 37 weeks at birth; (2) birth weight (BW) less than 2,500 g; (3) admission to the hospital within 24 h after birth; and (4) receiving caffeine citrate during hospitalization. Neonates who met any of the following exclusion criteria were excluded from the study: (1) death within 24 h after admission; (2) severe congenital malformation; and (3) n = 227), and the late caffeine treatment group (LCT), comprising those who received caffeine citrate over 48 h after birth (n = 225). Caffeine treatment was administered in two scenarios: (1) Immediate use following an episode of apnea, which is defined as the cessation of airflow for more than 20 s accompanied by a heart rate of <100 beats per minute, cyanosis, or a decrease in oxygen saturation. The decision to initiate caffeine treatment was made by clinicians or nurses accordingly. (2) Prior to the removal of mechanical ventilation during extubation, all preterm infants received a loading dose of caffeine citrate (20 mg/kg) through intravenous drip for 30 min, followed by a maintenance dose of 5–10 mg/kg daily, which started 24 h after the loading dose. Caffeine administration continued until the apnea symptoms disappeared. Both groups received the same routine treatments, including electrocardiograph monitoring, being kept in a warm environment, and keeping the airway open. The duration of caffeine treatment in earliest completion time (ECT) and latest completion time (LCT) were 16.7 ± 12.5 days and 17.0 ± 13.8 days, respectively, with no significant difference (P > 0.05).The eligible preterm neonates were divided into two groups: the early caffeine treatment group (ECT), comprising those who received caffeine citrate within 48 h after birth  thePreeclampsia was diagnosed when there is an elevation in blood pressure and the presence of proteinuria (excess protein in the urine) after 20 weeks of pregnancy, along with accompanying symptoms such as headaches, dizziness, nausea, vomiting, and upper abdominal discomfort. Eclampsia is diagnosed when individuals with preeclampsia develop more severe symptoms, including seizures or a state of coma. Fetal growth retardation, also referred to as intrauterine growth restriction (IUGR), was diagnosed through the use of fetal ultrasound. Fetal distress is a recognized term utilized to denote the occurrence of hypoxia in the uterine environment. It was determined through observed changes in fetal heart rate, anomalous fetal movements, and alterations in the composition of amniotic fluid. Premature rupture of membranes was diagnosed when there is a spontaneous rupture of the fetal membranes prior to the onset of labor or delivery. Gestational diabetes mellitus refers to the condition in which normal glucose metabolism or impaired glucose tolerance is present before pregnancy or develops and was diagnosed during pregnancy. Cholestasis is characterized by pruritus of the skin without apparent lesions during the later stages of pregnancy, occasionally accompanied by mild jaundice and limited additional symptoms. Serum biochemical markers reveal a mild to moderate elevation in transaminase and bilirubin levels, as well as an increase in glycocholic acid. The diagnosis of acute chorioamnionitis involves the identification of inflammation caused by the infiltration of pathogens in the chorionic and amniotic membranes of the placenta. Placenta previa is defined as the abnormal attachment of the placenta to the lower segment of the uterus after 28 weeks of pregnancy, with the possibility of the placenta's lower edge reaching or partially covering the cervical opening, which is positioned lower than the fetal presentation. Placental abruption was defined as the partial or complete separation of the normally located placenta from the uterine wall, which occurs after 20 weeks of pregnancy or during the delivery process, before the fetus is expelled. Antepartum hemorrhage is defined as the occurrence of vaginal bleeding after 28 weeks of pregnancy. Vaginitis is defined by the presence of external symptoms in the vaginal area, such as itching, burning pain, irritation, and abnormal vaginal discharge. Neonatal respiratory distress syndrome is characterized by acute respiratory failure resulting from extensive alveolar collapse, lung damage, and exudation in both lungs, which can be attributed to an insufficient production of pulmonary surfactant. Neonatal infection is defined as the presence of pathogenic microorganisms causing infection in newborns. Intrauterine infection refers to the transmission of pathogens from an infected pregnant woman to the fetus through the placenta during pregnancy. Neonatal infectious pneumonia encompasses pneumonia acquired prior to birth, during the birthing process, or after birth. Neonatal sepsis is defined as a systemic inflammatory response resulting from the invasion, growth, reproduction, and toxin production of pathogens within the bloodstream of newborn infants. Pulmonary arterial hypertension in neonates is characterized by the sustained elevation of pulmonary vascular resistance following birth. Fetal arterial catheterization enables blood circulation, but after birth, as the lungs expand and assume gas exchange function, the catheters naturally close. If the ductus arteriosus remains open, it is known as patent ductus arteriosus. Intracerebral hemorrhage refers to the rupture of cerebral arteries, veins, or capillaries resulting in bleeding within the brain tissue. Asphyxia refers to the condition in which a newborn is unable to initiate normal spontaneous breathing after birth, resulting in hypoxemia, hypercapnia, and potential damage to multiple organs. Small for gestational age (SGA) infants are defined as newborns whose birth weight falls below the 10th percentile of the average birth weight for infants of the same gestational age.For the assessment of patent ductus arteriosus (PDA), a routine cardiac ultrasound examination was conducted within one week of birth and prior to discharge. However, if clinical manifestations such as apnea, increased oxygen or ventilator requirements, metabolic acidosis, tachycardia, heightened precordial pulsation, hypotension, an increased pulse pressure difference (>25 mmHg), or the presence of murmurs were observed, an immediate cardiac ultrasound examination was performed.Neonatal infection encompasses various types of infections, such as sepsis, intrauterine infection, infectious pneumonia, and others . Diagnostic criteria for sepsis include the isolation of pathogenic bacteria from blood culture or sterile body cavities. Clinical manifestations, along with specific examination results or positive pathogen antigen/DNA detection in blood samples, are used for diagnosis.The diagnosis of ORDIN was performed according to Practical Neonatology (fifth version). Preterm infants requiring oxygen therapy for 28 days or longer were diagnosed with BPD. ROP was diagnosed and classified by an ophthalmologist according to the International Classification of Retinopathy of Prematurity (ICROP). PIVH and PVL were diagnosed based on the results of craniocerebral ultrasound or MRI and were graded according to the Volpe method (2008) and De-Vries criteria, respectively. The diagnosis of NEC was based on symptoms such as abdominal distension, hematochezia, and absence of bowel sound, as well as x-ray images.2.3.The study collected baseline demographics and clinical information of both mothers and infants, including the gender of preterm infants, gestational age, BW, maternal age, delivery mode, antenatal steroid treatments, and perinatal conditions . Additioχ test, while continuous variables were analyzed using either Student's t-test or the Wilcoxon rank test.The demographic and clinical characteristics of both the maternal and preterm neonates were described and compared between the early and late caffeine treatment groups. Categorical variables were analyzed using the Pearson The dataset was randomly divided into a training set and testing set at a ratio of 7:3. To make the most of the available information on complications and birth status in a relatively small sample, the researchers first established four comprehensive disease scores (Discore) by using least absolute shrinkage and selection operator (LASSO) regression to summarize the complex complications for the four outcomes of interest  (excluding PVL due to non-convergence) . The ris3.3.1.P = 0.439). There were no significant differences in the rates of natural conception or common perinatal complications between the two groups (P > 0.05), including preeclampsia, gestational diabetes, premature rupture of membrane, acute chorioamnionitis, placenta previa, placenta abruption, eclampsia, cholestasis, antepartum hemorrhage, and vaginitis. Additionally, there were no significant differences in the gender ratio of preterm neonates, the number of SGA neonates, or the incidence of fetal growth retardation, intracerebral hemorrhage, and distress between the ECT and LCT groups (P > 0.05). However, a higher proportion of preterm neonates with a gestational age of less than 28 weeks were found in the LCT group (P < 0.001), and the proportion of low-birth-weight neonates in the LCT group was also higher than that in the ECT group (P < 0.001). Notably, the incidence of PDA, intrauterine infection, septicemia, neonatal infection, infectious pneumonia, and ventilation rate was higher in the LCT group than that in the ECT group (P < 0.001). The preterm infants in the LCT group exhibited a longer duration of oxygen supplementation and invasive ventilation (P < 0.001). Further details of complications of maternal and preterm neonates are listed in A total of 452 preterm infants were included in this study, with 227 in the ECT group and 225 in the LCT group. The demographic characteristics of the mothers and preterm infants in the two groups were compared as shown in 3.2.P < 0.05, P > 0.05, The differences in GA, BW, and the incidence of PDA, intrauterine infection, and septicemia between the ECT and LCT groups could potentially confound the analysis results regarding the outcomes of caffeine treatment. The incidence of ORDIN was compared among different GA/BW subgroups of patients. The patients were classified into three subgroups based on GA: (1) extremely preterm birth subgroup ; (2) very preterm birth subgroup ; and (3) moderate to late preterm . P = 0.000), ROP , and PIVH . However, there were no significant differences in the incidence of PVL  and NEC  between the two groups. For infants with a birth weight between 1,500 g and 2,500 g, the incidence of the indicated terms of ORDIN was comparable between the ECT and LCT groups .3.4.3.5.P values) for PIVH, ROP, and NEC showed that the factors of ventilation and oxygen supplementation did not significantly affect the fit of the primary model. However, the coefficient for BPD increased after adding these factors (P < 0.001), suggesting an impact on the fit of the primary model. Nevertheless, the 95% CI for the odds ratio indicated no significant association between early caffeine treatment and the incidence of BPD. Importantly, the 95% CI for the odds ratio revealed that early caffeine treatment only reduced the risk of PIVH, consistent with the findings in We conducted a sensitivity analysis  by inclu3.6.t other time points and the cutoff time point (P > 0.05). Despite smaller ORs being observed under the definition of 24, 30, and 36 h after delivery, f larger sample sizes or randomized controlled trials are necessary to determine the optimized initiating time point of caffeine treatment.To further assess the impact of treatment time on the PIVH risk, we redefined the start time of ECT as 12 h, 18 h, and up to 120 h. We used the same multivariable models as in the previous section to examine the effects of ECT on PIVH incidence risk under different time definitions . Our res4.In this retrospective study, the LASSO regression model demonstrated that early caffeine treatment was associated with a decrease in PIVH, but no other terms of ORDIN, after adjusting with gestational age, birth weight, asphyxia, and Discore. Additionally, ROC curves of multivariable analysis further illustrated that early caffeine treatment was linked to a reduced risk of BPD, PIVH, and ROP in preterm infants.Our univariable logistic analysis indicated that early caffeine treatment was associated with a low risk of BPD. However, after adjusting with factors including gestational age, birth weight, asphyxia, and Discore in the multivariable regression analysis, this association was not supported. The results of subgroup analyses, which showed early caffeine treatment reduced the incidence of BPD in preterm infants, especially in VLBW or very preterm infants, suggest that the confounding factors in the retrospective study greatly influenced the evaluation of caffeine treatment with different initiation times. Previous research has also reported that early caffeine administration can reduce the risk of BPD in infants <29 weeks' GA, with an adjusted OR of 0.61  . HoweverPreterm infants are particularly vulnerable to brain injuries due to the immaturity of their brains, with the “periventricular” area being critically susceptible. This area is at high risk of injury because of the dense network of thin and fragile capillaries that can easily be damaged. When these vessels rupture, it can lead to periventricular hemorrhage, which can develop into PIVH. PIVH mostly occurs in infants who are born before 33 weeks of GA .Our study showed that the incidence of PIVH decreased in extremely and very preterm infants who received caffeine early (<48 h after birth) compared to that of those who received late caffeine treatment. We also found that VLBW infants had a lower incidence of PIVH when they received caffeine treatment earlier. Furthermore, both univariable and multivariable regression analysis after adjusting indicated clinical factors strongly suggested that early caffeine treatment is associated with a lower risk of PIVH in preterm infants. Additionally, ROC analysis in our study further showed that early caffeine treatment could predict the incidence of PIVH in preterm infants.Our results differ from a previous clinical trial where there was no significant difference in the occurrence rate of PIVH in preterm infants with a GA of 25–35 weeks between early and late caffeine treatment groups . This diRegarding the optimal initiating time of caffeine treatment, our findings suggest that a window between 12 h and 120 h after birth could significantly reduce the risk of PIVH, with smaller odds ratios between 24 h and 36 h. However, further research with a larger sample size or randomized controlled trials is necessary to determine the most effective timing for initiating caffeine treatment.PVL is a complication that can arise from PIVH. However, in our study, we did not observe a significant difference in the gross incidence of PVL or in subgroups between the early and late caffeine treatment groups. This finding is consistent with a retrospective study reported by Yang et al. .Our study showed that the extremely preterm and VLBW infants who received early caffeine treatment had a lower incidence of ROP. The incidence of ROP is inversely correlated with GA and BW and is more common in extremely preterm and VLBW infants . CaffeinThe effect of early caffeine treatment on the risk of NEC remains controversial. Taha et al.  reportedThe pathogenic mechanisms of various terms of ORDIN are distinct from one another. For instance, BPD is characterized by insufficient vascular development , while PThe effects of caffeine on angiogenesis vary in different tissues/organs and diseases. Studies have shown that caffeine treatment can attenuate BPD by improving angiogenesis in the lungs. For instance, postnatal use of caffeine (20 mg/kg/day) significantly improved pulmonary microvasculature by regulating angiogenic gene expression in male mice, such as VEGF and hypoxia-inducible factor (HIF)-1alpha . AR are A limitation of this study is its retrospective nature, which makes it vulnerable to confounding factors. Gestational age and birth weight are known to affect the outcomes of caffeine treatment in preterm infants. To minimize their impact, we performed stratified analyses in different gestational age and birth weight subgroups and used logistic regression with multivariate analysis. After adjusting with gestational age, birth weight, asphyxia, and Discore, preterm infants in the ECT group only had decreased odds of PIVH but no other terms of ORDIN, indicating that factors such as asphyxia, PDA, intrauterine infection, and septicemia may also affect the outcomes of caffeine treatment.In conclusion, our retrospective study suggests that early initiation of caffeine treatment in Chinese preterm infants is associated with a reduced risk of PIVH. However, in our retrospective study, the findings are limited by potential confounding factors. Therefore, future prospective investigations are needed to verify and elucidate the precise effects of early caffeine treatment on complications in preterm infants. Overall, our study provides insights into the potential benefits of early caffeine treatment for preterm infants in Chinese neonatal intensive care units.