Successful outcomes in this case are consistent with the American College of Obstetricians and Gynecologist (ACOG) guidelines for preventing OASIS. The interprofessional birth care team (IBCT) model exemplified by this case focuses on best practice in promoting a family's preferences for physiologic birth and preventing recurrent OASIS. The first birth experience involved precipitous labor, obstetric anal sphincter injury (OASIS), and initiation of pelvic pain.Data regarding the incidence of recurrent grade III‐IV perineal lesions, also termed severe perineal trauma (SPT) or obstetrical anal sphincter injuries (OASIS), are limited and sometimes conflicting.The purpose of presenting this case is to describe a conceptual framework for factors associated with preventing recurrent OASIS in childbirth. The model is centered around support by an IBCT that includes continuous, non‐medical support. Continuous, nonmedical support has been recommended by international health organizations, including the World Health Organization (WHO), in promoting improved birth outcomes.22.1The mother in this single case study design was supported through four births by an IBCT led by a family practice physician and included labor nurses and continuous nonmedical support provided by a doula and the father. The mother is Asian American, 5’ 6” with a nonpregnant BMI of 28, and college educated. Her first birth experience involved precipitous labor at 37 weeks, OASIS, and initiation of pelvic pain. Before labor began, the patient was admitted for a nonreassuring fetal heart rate pattern, with an episode at the hospital where the fetal heart rate was 60 bpm for several minutes. This fetal heart rate pattern became reassuring with oxygen and change of position by the mother from reclined to frequently changing side to side.Nonreassuring heart rate patterns did not reoccur, and spontaneous labor began early the next day, progressing from 1 cm dilated, 50% effaced in a + 2 station to fully dilated, transition, and second stage in 25 minutes. The mother pushed during the second stage for 20 minutes. Membranes ruptured spontaneously during the second stage. During labor, the mother was unmedicated (no pain medicine or labor augmentation). Since the mother had expressed a preference prior to delivery of not birthing on her back, she was encouraged to be in a quadruped position during the pushing stage to promote labor progression. Per hospital policy, the mother pushed on command rather than with her own urge, and the mother held her breath when pushing. The newborn had an Apgar score of 9/10 at 5 minutes postdelivery, average weight at 3430.29 g (7 lbs 9 oz), and immediately initiated breastfeeding that continued for 36 months (including tandem feeding of the first and second born for 18 months). Immediate postbirth, the patient's perineum was repaired with sutures by the attending physician for what was documented at the time to be a second‐degree laceration of the perineum.During the postpartum period, the patient experienced persistent pelvic pain that increased with sitting, voiding, and intercourse. At her 6‐week follow‐up appointment, she was told these symptoms were normal. The mother sought a second opinion at 5 months when she began menstruating and the blood was coming from the rectum. She then received a diagnosis of OASIS involving grade III pelvic floor lacerations and two rectovaginal fistulas deep in the vaginal canal. The lacerations were promptly repaired, and there was no incontinence of flatus or stool following the repair. The patient participated in physical therapy upon wound closure to address her continued complaint of severe dyspareunia and perineal/pelvic pain. Physical therapy included scar mobilization, pelvic floor muscle strengthening, and relaxation training.After surgical repair, the patient continued to suffer from pelvic pain (reported as constant 2‐4/10), increased pain with intercourse lasting up to a day, and increased pain the week of and the week after menstruation. She reported the use of cloth hygiene pads during menstruation due to the irritation of the scar tissue with the use of other products. During this time, 10 months after the first birth and 5 months after the surgical repair, the patient became pregnant with her second child consistent with her desire for a larger family of 4‐5 children.2.2The urogynecologist who performed the OASIS repair at 5 months postpartum recommended that the mother plan to have a cesarean section (CS) at 35 weeks’ gestation to prevent recurrent OASIS with subsequent births. This plan was based on the provider's assumption that the patient would experience precipitous labor with subsequent births, an assumption that is not supported by best evidence. This family instead chose to continue to work with their interprofessional team that was skilled in and receptive to supporting the family's preference for expectant labor, continuous labor support from a doula, and perineal counter pressure during delivery. The mother performed a daily regimen of estrogen and perineal massage. In consultation with their IBCT, the family also chose to forgo epidural pain relief and allow the mother to labor in various positions, push with urge, and birth in her position of choice.Consistent with the family's desires, the mother gave birth to a second child vaginally and without the need for surgical interventions. The mother did not receive medical pain relief during this birth. This delivery occurred at 39 weeks +2 days gestation, that is, 19 months following the first birth and 13.5 months after surgical repair and rehabilitation of the OASIS. The labor progressed over 17 hours with slow, steady dilation. In consultation with the patient, membranes were ruptured at 9 cm dilation by the family practice physician. During the second stage, the mother often labored on her side to pace the progress of the labor and she gave birth in a supine position with perineal support applied during crowning. She also pushed in short bursts with urge in the second stage of labor and avoided breath holding. Oxytocin was infused immediately after the birth of the infant and continued after the birth of the placenta. Their second child was born average weight at 3042 g (6 lbs 11 oz) with an Apgar score of 9/10 at 5 minutes and immediately initiated breastfeeding that was continued for 22 months (including tandem feeding of the first and second born for 18 months). Notably, the persistent pelvic pain and dyspareunia the mother was experiencing after the birth of her first child resolved by 10 days postpartum, with only infrequent occasions of minor pain reported. A thorough pelvic examination postdelivery determined there were no recurrent lacerations of the perineum requiring repair.2.3The family's third birth occurred 25 months following the birth of their second child. In preparation for the delivery, the mother performed the same daily regimen of estrogen and perineal massage as with the second birth. The third birth involved precipitous labor that was even more rapid than the first birth experience, laboring for 25 minutes and pushing for 5 minutes. Membranes ruptured spontaneously during the second stage, and perineal support was provided with crowning. Shoulder dystocia occurred in the second stage and resolved in 20 seconds with suprapubic pressure. Their third child was born average weight of 3884 g (8 lbs 8 oz) with an Apgar score of 9/10 at 5 minutes and immediately initiated breastfeeding that was continued for 21 months. The mother experienced minor pubic symphysis pain that resolved by 3 months postpartum with a course of physical therapy. The physical therapist interventions included myofascial release and relaxation training along with progressive strengthening as the pelvic floor muscle spasms resolved and the scar tissue became functionally mobile. No perineal lacerations were noted with a thorough postdelivery pelvic examination.2.4The family's fourth birth occurred 27 months following the birth of their third child. The mother was induced at 39 weeks based on collaborative discussions between the mother and her family practice physician about avoiding a spontaneous, unassisted delivery and the suspicion of fetal macrosomia based on the 35‐week ultrasound. For this birth, a monitrice was included in the IBCT. A monitrice has a similar role as a doula in providing emotional labor support and can also provide services similar to a midwife by providing some monitoring and hands‐on support while the mother labors. Perineal massage was performed in the weeks prior to the birth without application of estrogen as the mother and physician both decided estrogen was not necessary.Labor started 35 minutes after induction by artificial rupture of membranes. The first stage of labor was approximately 3 hours, and the second stage of labor was approximately 1.5 hours. The mother pushed in various positions, mainly a squat position, and also side‐lying and quadruped, and then she gave birth in a right side‐lying position. Perineal support with warm compress was provided with crowning. The newborn experienced shoulder dystocia that was resolved in 40 seconds with manipulation maneuvers and maternal position changes. At birth, the infant's Apgar score was 9/10 at 5 minutes, and she weighed 4646 g (10 lbs 3 oz) and immediately initiated breastfeeding that has continued to the time of manuscript submission (the infant was four months at the time of submission). The mother experienced a second‐degree laceration requiring five sutures by the family practice physician. This laceration was not along the scar from the OASIS experienced with the first birth. The mother reported no pelvic floor‐related symptoms following this birth.3In light of conflicting evidence regarding primary and recurrent grade III perineal trauma,The model proposes four dimensions of care to be addressed across the cycle of childbearing from preconception to postpartum: medical, physical, spiritual, and psychosocial. The IBCT model places the mother, child, family, and their community at the center along with a variety of care providers and stakeholders.Consistent with the proposed model, the IBCT is bound by the Interprofessional Practice and Education Collaborative (IPEC) Core Competencies. The IPEC Core Competencies include four domains: (a) values and ethics, (b) roles and responsibilities, (c) communication, and (d) teams and teamwork.The three key elements, expectant labor, maternal mobility, and maternal self‐efficacy, work together to protect the perineum during birth. These key elements are supported by innate hormonal responses to labor, decreased use of medication for pain relief, and decreased use of forceps or vacuum extraction. The perineum is also protected by the use of perineal counter pressure during delivery.ACOG guidelines for management and prevention of obstetric lacerationsThe risk factors for OASIS listed in the ACOG guidelines include primiparity and Asian ethnicity and are consistent with the mother's race and first birth experience of OASIS. Modifiable risk factors include labor induction or augmentation, and epidural anesthesia, factors that were avoided with the first birth, yet the mother still experienced OASIS. The guidelines recommend restricting the use of operative vaginal birth techniques to only indicated cases. Operative vaginal birth techniques include vacuum extraction, use of forceps, and episiotomy. When these measures are necessary, the guidelines recommend advising the patient of the risks for perineal trauma and obtaining consent.The ACOG guidelines also include the need for adequate lighting, exposure, and anesthesia for diagnosing deep perineal lacerations such as those experienced by the mother with her first birth.The success of interprofessional birth care initiatives are well established in the literature.Grumbach & Bodenheimer pointed out a number of barriers to team formation, including relationship and personality conflicts.The mother in this case reported a resolution of her pelvic pain with her second vaginal birth. This is an important factor to note in this case since it is rational to conclude that vaginal birth might worsen pelvic pain. This case demonstrates that a vaginal birth does not necessarily aggravate pelvic pain conditions and could be a factor in resolving pelvic pain in some instances. Although the reason for pain resolution is not clear with this case, spontaneous release of scar tissue with vaginal birth seems to be the most likely explanation. The use of estrogen and perineal massage prior to subsequent deliveries could be another explanation for both the prevention of OASIS and pain resolution, though these measures are not supported by evidence and estrogen levels are already high prior to delivery.The resources for an IBCT were available to this family where the mother had a post‐secondary education, supportive family, and employer‐sponsored private health insurance. These factors are associated with favorable birth outcomes and are consistent with reports of disparities associated with race and socioeconomic status.4The favorable outcomes in this case and the limited evidence on best practices for preventing recurrent OASIS highlight the need to overcome barriers to comprehensive and cohesive interprofessional birth teams, even in emergent situations. Consistent implementation of best practices to prevent recurrent OASIS requires open dialogue between the family and an IBCT skilled in integrating those preferences. Evidence is needed to support funding and wide use of IBCTs that can include continuous labor support from nonmedical providers (doulas), regardless of family resources. Educational institutions have the challenge of developing birth simulations that are realistic enough to translate successful components of collaboration into practice, and include all the elements of a mobile patient during birth. Interprofessional research, practice, and education collaborations are tools for mitigating recurrent OASIS with childbirth and facilitating family‐centered care. This is an authentic case that can be used in healthcare education to promote interprofessional birth care practices, shape student perspectives related to the complexity of managing OASIS, and as a basis for research endeavors.None declared.All authors were involved in drafting or revising the content of this manuscript, providing intellectual content and critical analyses, and providing final approval. LT: the main author who provided primary development and revision of the manuscript. LT and JS: both physical therapists with specialty training in pelvic health, had full access to the original case data and were responsible for the initial concept. MM: provided input relative to expertise in perinatal nursing. DA: provided the perspective of a doula and doula trainer with a Master of Public Health degree. WH: the senior author, provided his perspective as an obstetrician and gynecologist.


Even if remarkable progress has been made in reducing preventable child deaths worldwide, neonatal mortality reduction has remained unsatisfactory. Low birth weight (LBW) is the major risk factor for child deaths during the neonatal period, yet only 5% of babies are weighed at birth in Ethiopia. The aim of the present study was to determine the magnitude and risk of dying among low birth weight neonates in rural Gedeo, Southern Ethiopia. Community-based mixed-method approach design was employed between September and October 2016 to identify and enroll study participants in rural Gedeo, Southern Ethiopia. Records of 17,503 live birth babies, of whom 2,065 (11.8%) had LBW, born in the last 12 months were screened to identify 885 (42.8%) biological mother–LBW neonate pairs from eight health centers. The study subjects were randomly selected using a multistage stratified cluster sampling technique. Cox proportional hazards regression model was used to predict maternal and neonatal risk factors associated with the risk of neonatal death. The overall neonatal mortality rate (NMR) among LBW infants was 110 per 1000 live births . Close to half, 374 (42.3%), of the LBW neonates died during the first week of life. The estimated hazard ratios of mortality were higher among neonates whose mothers did not attend antenatal care (ANC) , gave birth by assisted or cesarean delivery , and experienced some form of illness during pregnancy , respectively. Similarly, neonates born with very low (<2000gm) birth weight and born prematurely (before 37 weeks of gestation) carried a higher  risk of death. On the other hand, maternal formal education was found to be the single protective factor . Nearly one in every ten (11%) of neonates die before celebrating their firth month of life, mainly during the first week in rural Ethiopia. The risk of dying from LBW during the neonatal period is almost fourfold of the current estimated national NMR. Maternal obstetric characteristics and fetal maturity were predictors of mortality. Though remarkable progress has been made in averting preventable child deaths, the neonatal mortality rate remains too high –3. PromiLow birth weight (LBW) is one of the key drivers and indirect causes of neonatal death . It contHowever, little is known about community-level factors associated with the risk progress made to reduce LBW and the associated neonatal mortality, in spite of ample evidence relating to prevention of LBW using low cost, simple, and proven technologies/interventions , 18. A rIn Ethiopia, the latest 2015/16) estimate of neonatal mortality rate is 28 per 1000 live births and accounts for about half (47.5%) of the overall child mortality rate , 19. The15/16 estThe critical challenge of programs and interventions in Ethiopia remains to be a paucity of comprehensive community-based evidence as many of the neonatal deaths happen at home (not more than 5% of babies are weighted at birth) and left undetected . MoreoveTherefore, the present study aimed to generate and analyze community-based data on the magnitude and associated maternal and neonatal risk factors of neonatal death among LBW neonates in rural communities of Gedeo zone, Southern Ethiopia. The study findings will be used as inputs for policy makers and program implementers to design and implement context-based intervention to tackle the problem.We employed a community-based cross-sectional quantitative study design to collect data on magnitude and LBW related death risks between September and October 2016. The study was conducted in three randomly selected districts of the Gedeo zone in the Southern Nations, Nationalities, and People's (SNNP) Regional State of Ethiopia. The zone has six districts and two administrative towns  and is known for leading coffee producing areas in the country. We selected three districts and six clusters or kebeles  for the study.The study was approved by the Health Research and Ethics Review Committee of the College of Health Sciences of Dilla University. Written informed consent was obtained from the participants. The information obtained was kept anonymous, thereby ensuring confidentiality.The study population comprises pairs of mothers and LBW infants born alive 12 months prior to the data collection period. The infants were included only when they were living with their biological mothers, having birth certificates, apparently healthy, and born with a birth weight of <2500gm.A multistage cluster sampling technique was employed to select and enroll mothers in the study. The stratification was into urban and rural strata, followed by the use of simple random sampling to identify three districts and study clusters (kebeles). A total of six clusters (two from each district) were randomly selected and included to the study. Form the selected clusters, all neonates were included in the study; this yielded a total sample of 885 mother–LBW neonate pairs.Data were collected with face to face interview questionnaires. The questionnaires were designed and modified in comparison with previous studies , 8. DataThe dependent variable, neonatal death, was determined by recording the death of neonates within the first 28 days in the surveyed households and predicting variables from maternal and neonatal risk factors for neonatal death. Neonatal death is defined as death before 28 completed days. The date of death was recorded and infants who lived beyond 28 days were also censored at the time of data collection in completing of survival analysis.Data were entered using Epi INFO vision 3.5.1 and exported to SPSS V-20 for analysis. Cox proportional hazards model was used to investigate maternal and neonatal risk factors for neonatal death. Explanatory variables with a p < 0.20 in univariate Cox-regression analysis were further included in the multiple-Cox-regression analysis. Finally, the multiple-Cox-regression analysis was used to estimate hazard ratios (HR); corresponding with its 95 % confidence intervals (CI).Overall, 885 mother-neonate pairs were included in the study. Nearly half, 380 (43%), of mothers were 24-29 years old with a mean (± SD) and a median age of 28.5 (± 4.8) and 28.0 years, respectively. More than half, 518 (58.5%), of mothers did not attend formal education and 75.5% were housewives. Even though most, 688 (77.7%), of mothers reported to have at least one antenatal care (ANC) visit during their last pregnancy, less than one-fifth, 126(18.3%), had four or more ANC visits. The proportion of twin births was 4.4% .From the total 885 LBW neonates born during the study period, over one in every ten 97 (10.9%), 95% confidence interval (CI), 8.8-13.1) died before completing 28 days of life. A higher number of deaths were recorded during the first 41(4.6%), second 25 (2.8%), and third 24 (2.7%) weeks of neonatal life .A higher proportion of neonatal death was observed among mothers aged >30yrs, 46 (47.7%); married, 85 (87.6%); being unemployed/housewives, 61 (62.9%); attending fewer (<4) ANC visits, 47 (83.9%); having spontaneous vaginal delivery, 44 (45.4%); and experiencing some form of illness during pregnancy, 58 (59.8%) . SimilarA proportional Cox-regression analysis was employed to examine maternal and newborn factors affecting neonatal death, and results are presented in Tables During the multivariate-adjusted hazard analysis, maternal education , instrumental  or cesarean delivery , lack of ANC follow-up visits , and experiencing some form of illness during pregnancy  remained as independent maternal risk factors predicting higher risk of death among LBW neonates .In the same way, prematurity  and very low birth weight at birth  were neonatal conditions with independent predictors of higher risk of mortality of LBW infants.In this paper, we described the results of a community-based cross-sectional study that aimed to determine the magnitude and predictors of death among LBW neonates in rural districts of Gedeo, Southern Ethiopia. We found that nearly one in every ten (11%) (95 % CI: 17.5 - 22.8) LBW infants were dying before celebrating their first month of life . We observed that the risk of death was much higher during the first week of life. Both maternal and neonatal factors were significantly associated with the risk of death of an LBW neonate. Maternal obstetric characteristics like too few or no ANC follow-up visits, assisted/caesarian delivery, and experience of some form of illness during pregnancy and neonatal birth conditions like prematurity and having very low birth weight at birth were independent predictors of mortality among LBW neonates.The magnitude of neonatal death (110 per 1000 LB) observed among LBW neonates in the current study is almost a fourfold of the overall estimated national neonatal mortality rate (28 per 1000 LB) for Ethiopia  and exceThe main reason for such unacceptably high mortality among LBW neonates could be related to poor healthcare seeking behavior of mothers (caretakers) and/or families for neonatal and childhood health problems in such settings , 28. In Though we did not assess the causes of neonatal deaths using verbal autopsy, we could see that the leading predictors of death were related to maternal sociodemographic and obstetric characteristics that could be easily improved by providing a continuum of care to women during pregnancy, labor, immediate, and early neonatal periods . EvidencIn this study, higher neonatal deaths occurred in the first week of life 42.3 (95% CI: 33.0-51.5), compared to the second 25.8 (95% CI: 17.5-35.1), third 24.7 (95% CI: 16.5-33.0), and fourth weeks 7.2 (95% CI: 2.1-13.4), which was consistent with previous findings . The ratNeonates whose mothers attended formal education had a lower risk of death, which agreed with the studies done in Ethiopia  and NigeSimilar to previous findings –29, the Inadequate or lack of ANC visits and occurrence of maternal illness were other maternal predictors for early neonatal deaths among LBW neonates in the study area. Several previous studies –29 have LBW neonates born through assisted  delivery were also found to have two and four times added risk of dying compared to those born spontaneously. This could be related to elevated risk of infection and complications among nonspontaneous assisted deliveries as most are conducted after long-obstructed labor, usually referred from other facilities .The study has several strengths that should be appreciated. Firstly, it is among the very few studies conducted to assess prevalence and risk factors of death among LBW neonates. Secondly, unlike the existing evidence often based on facility-based studies, the resent study employed community-based study design in an area where a birth registry is very uncommon. The study also made use of available local evidence to strengthen evidence generated. On the other hand, the study also has limitations that should be taken into consideration while interpreting the findings. We used our own operational definition for very low birth weight (<2000g), unlike the conventional definition of a baby born < 1500g. This was made deliberately due to the fact that we have very few cases of the conventional definition leaving data analysis difficult or with poor meaningful interpretation. In addition, our study measured birth weight from health facility records which are not validated by concerned authorities for consistency and accuracyIn summary, the present study reported that the magnitude of neonatal mortality among LBW neonates was 11.0% (95% CI: 17.5-22.8), which is one of the highest in the world and a fourfold of the national estimated neonatal mortality rate. The first week of life is the riskiest period for survival of LBW neonates. The risk of dying among LBW neonates is determined by both maternal sociodemographic and obstetric characteristics, and neonatal birth conditions. Maternal antenatal care attendance, mode of delivery, and experience of illnesses during pregnancy were among the maternal independent predictors of mortality among LBW neonates. Very low (<2000gm) birth weight and prematurity are neonatal independent predictors of death among LBW neonates in rural settings of Southern Ethiopia.


The use of cumulative live birth rate (CLBR) per ovarian stimulation cycle is proving to be an accurate method to calculate the success of IVF; however, the cycle outcome is closely associated with the number of embryos transferred (ET). Our aim was to report CLBR after IVF according to the number of embryos required to achieve a live birth in women aged ≥35 years, considering age, body mass index (BMI), and ethnicity. We conducted a retrospective cohort study including 1344 patients who underwent IVF between January 2013 and June 2016 at the First Affiliated Hospital of Xinjiang Medical University. The cumulative probability of live birth for each couple was estimated using the Kaplan–Meier method, and survival curves were compared according to age, BMI, and ethnicity using the log-rank test. CLBR increased rapidly from 1 to 5 ETs, moderately from 6 to 10 ETs, and slowly thereafter. CLBR was significantly different across 4 categories based on BMI as well as across those based on age; low CLBR was significantly associated with the age of ≥42 years and obesity. The association between CLBR and number of ET provides realistic and precise information regarding the success of IVF and can be applied to guide clinicians and patients. The emergence of assisted reproductive technology (ART) has brought hope to infertile couples. Since the birth of the world's first “test tube baby,” Louise Brown, 40 years ago, 8 million babies have been conceived worldwide through ART . HoweverTypically, cumulative live birth rate (CLBR) and pregnancy rate are used as key indicators to assess the quality and success of IVF, and these are indispensable for patients to make decisions before starting the treatment , 4. CLBRThere is a growing tendency in some countries for couples to have children late in their life. This situation is obvious in China for several reasons, such as the two-child policy issued in 2015 [According to a recent study, nearly 57% of the couples of all ages in United Kingdom remained childless even after undergoing 6 complete IVF cycles [The aim of this study was to calculate CLBR per total number of ET required for achieving a live birth. This pragmatic method predicted outcomes considering each embryo as single opportunity to achieve a live birth. This approach is advantageous in that it can provide doctors and patients with a more accurate probability of live birth. Female age, BMI, and ethnicity were considered the key factors affecting the success of IVF.We performed a retrospective cohort study including 1344 women aged 35–45 years who underwent IVF/ET between January 2013 and June 2016 at the Reproductive Medicine Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China. The inclusion criteria were as follows: (1) women with a ≥1-year history of infertility and age of ≥35 years; (2) those undergoing the first cycle of IVF/ICSI; and (3) those in whom own oocytes were used and fresh or frozen-thawed embryos were transferred without preimplantation genetic screening for embryo aneuploidies. The exclusion criteria were as follows: (1) patients undergoing IVF cycles without ET for any reason; (2) those unsuitable for treatment because of severe disease; (3) those with unknown clinical outcome; (4) those aged >45 years; and (5) those with congenital uterine dysplasia. This study was approved by the Institutional Review Board (IRB) of the First Affiliated Hospital of Xinjiang Medical University, and all patients provided written informed consent before treatment.All patients were followed up for at least 2 years or until (1) they decided to discontinue the IVF treatment; (2) all embryos were transferred; (3) they decided to change to ovum donation; (4) had delivery of at least 1 live child surviving over 1 month; or (5) they were still receiving IVF treatment at the end of the study.2, moderate: <18.5–24.9 kg/m2, overweight: 25.0–29.9 kg/m2, and obese: >30 kg/m2); retrieved oocyte number; gonadotropin (Gn) dosage, Gn day, total number of ET (number of ET to achieve a live birth (ETRL); 1–3 ETRL, 4–6 ETRL, 7–9 ETRL, and >10 ETRL); number of metaphase II oocytes obtained; and outcomes in terms of pregnancy (include ongoing pregnancy), miscarriage, and live birth. The primary outcome was live birth, defined as any birth event in which at least 1 baby was born alive and survived for more than 1 month.Data were obtained from the ART records of the Reproductive Medicine Center without any patient identifier information. The following information was collected: maternal age ; ethnicity ; basal serum FSH level; basal luteinizing hormone level; infertility duration; body mass index  or median  and categorical variables were expressed as frequency (percentage). Categorical variables were compared using the P< 0.05 was considered statistically significant in all analyses. All analyses were performed using Stata 13 and R version 3.3.1 (http://www.r-project.org/).The cumulative probability of live birth for each couple undergoing IVF/ICSI treatment during the study period was calculated using the Kaplan–Meier method; this was according to the total ET in each cycle of treatments required to achieve a live birth. The probability of cumulative live birth and outcomes were estimated by the Kaplan–Meier method and compared using the log-rank, Breslow, and Tarone–Ware tests according to each categorical group. A two-tailedThe cohort included 1344 patients aged 35–45 years who underwent IVF/ICSI cycles involving 2596 ET. Demographical and clinical characteristic of patients are summarized in Tables  χ2 = 44.38, P < 0.0001).2. After 5 ETRL, CLBR was approximately 50%, 42%, 40%, and 25%, respectively. Obese women showed CLBR limited to 25% after 5 ETRL. CLBR was significantly different across BMI categories . χ2 = 0.53, P = 0.7674; CLBR was not significantly different across ethnicity categories (log-rank test:We evaluated outcomes of IVF treatment according to the total number of ET until a term live birth was achieved in women aged ≥35 years. Although the patients underwent the same number of treatment cycles, the total number of ET varied because the number of ET in each cycle varied from 1 to 3. Therefore, considering each embryo as a single opportunity for achieving a live birth can be a useful method to evaluate the outcomes of IVF/ICSI treatment, and it has the advantage of providing more accurate probability of treatment success to clinicians and patients. The cumulative probability of live birth was nearly 25% with 3 ET but only half of this rate with 6 ET. This indicates that the number of ET is a determinant of pregnancy and live birth achievements.The number of ET was an essential factor associated with CLBR. This is generally in agreement with other studies showing that the number oocytes retrieved was a contributing factor to live birth rate after IVF, with recent evidence indicating that CLBR increases with the number of oocytes retrieved –11. Not Female age is the main factor to achieve a successful live birth through ART. Natural aging may reduce fertility in a patient seeking IVF treatment . Women aOur results show that IVF overcomes infertility in women aged ≤41 years. Women at ≥42 years should be informed that IVF treatment cannot completely overcome reduced fertility due to age, which is consistent with reports of a previous study . The addStudies assessing the potential impact of female BMI on IVF outcomes have reported conflicting results. Multiple studies and a meta-analysis indicated that higher BMI was associated with fewer retrieved oocytes, higher cancellation rates, higher miscarriage rate, and lower pregnancy and live birth rates –36. MeanOur study has several strengths. We considered each embryo as a single opportunity for achieving live birth. The plots we produced are easy for clinicians and patients to understand and show the specific probability of treatment success according to patient characteristics. We did not restrict the treatment to 6 cycles as did other studies, [In summary, the present study provides the expected probability of having a child based on the number of ET. Clinicians can provide accurate probabilities to patients using visual graphics such as the Kaplan–Meier curves. This may assist patients to make difficult decisions regarding whether to pursue the IVF/ICSI treatment. Women aged ≥42 years may not experience any benefit with CLBR after 8 embryos are transferred; thus, they should be discouraged from continuing IVF treatment. Obese women seeking fertility treatment should be counseled on the detrimental effects of obesity and benefits of weight reduction, and they should be informed that weight loss via diet and exercise is associated with improved probability of becoming pregnant, with a trend toward improved live birth rate.


Although Denmark and Sweden have close cultural and historical ties, lifespans for Danes have generally been lower than those of Swedes. Recent improvements in Danish mortality after a period of stagnation have led to the suspicion that there may be positive trends at the very high ages at death within that population and that these trends could be quite different from those observed in Sweden. Although the mean ages at death for Danish and Swedish centenarians have been relatively constant at about 102 years for the cohorts born 1870–1904, the oldest-old in Denmark have been getting older, but no evidence has suggested any increase in lifespan for Swedes. Using quantile regression, we show that Danish centenarian lifespans in the 90th percentile have been lengthening, with those in 94th percentile  having a trend that is statistically significant at the 5 % level. We demonstrate that the increase observed is not due to the increasing sizes of birth cohorts and thus must be due to improving survival among this select top tier. We postulate that this super-select group in Denmark is best able to take advantage of the factors driving mortality reduction, whereas the majority of centenarians are not.The online version of this article (10.1007/s13524-018-0755-7) contains supplementary material, which is available to authorized users. Globally, human longevity has been on the rise. Empirically, this has been observed from increases in life expectancy, increases in ages at death, and declines in death rates at older ages. At the population level, life expectancy at birth has been steadily increasing and has more than doubled in the last two centuries Riley . The ratOne direct consequence of this is the rapid increase in—and accumulation of—the number of nonagenarians, centenarians, and supercentenarians  has been increasing steadily for more than one and a half centuries in Sweden, where high-quality data permit such observation . Life endurancy was found to increase substantially for both males and females in the United States between 1900 and 1990 and was projected to increase sharply by 2080  can be analyzed coherently within one framework. Given that our interest is in the tails, we can assess these directly by studying the high quantiles. By using high quantiles of the observed lifespan distribution, we avoid having to study the maximum ages at death, thereby sidestepping the use of more complicated inferential tools, such as extreme value theory. As far as we know, quantile regression has not previously been applied to the study of human lifespan trends.Centrale Person Register (CPR)) and the Swedish Total Population Register ). The Danish CPR was established in 1968, and all persons living in Denmark are registered for administrative use. It includes the name, gender, date of birth, place of birth, citizenship, unique personal identification number, and identity of parents; it also includes continuously updated information on vital status , place of residence, and spouses  are Swedish, and 5,976  are Danish. Some basic descriptive statistics for the ages at death  are presented in Table Y with probability distribution functionY is defined as the inverse function,Q0.5 is the median; Q0.75 is the third quartile, or 75th percentile.Koenker and Bassett  developeIn our particular case, we fit, for any choice of quantile τ, the following model:quantreg package of the R statistical software program  of the lifespan distribution.Figure It might be tempting to conclude that the upward trend in lifespan in Denmark could be due to a growing proportion of female centenarians over time. The proportion of female centenarians has been increasing over time in both countries, but this does not appear to have a serious impact on the results. When we control for sex  around the mean regression line envelops the horizontal line at 0, confirming the results of the linear regression: there is no trend in the mean. After the 85th percentile, the quantile regression coefficients show a continuous increase. However, only from the 94th percentile are they significantly different from 0 (at the 5 % level). Up to this point in the distribution, birth cohort is not a significant predictor of lifespan. Although the OLS regression coefficient may be a decent representation of how lifespan varies with birth year over most of the age range, it underestimates the strength of the relationship for the longest-lived centenarians in the Danish population. For the Swedish population, neither the mean nor the quantile regression coefficients are significantly different from 0, suggesting that centenarian lifespans have not been increasing in Sweden.In this article, we present a methodology that enables the analysis of lifespan trends over time, defined in our data as the calendar year of birth. A key advantage to this method is that it avoids trends in the maximum ages at death and their associated theoretical issues. Inference for the maximum of a random variable is nontrivial, and more sophisticated approaches using extreme value theory  having a statistically significant trend. Furthermore, the rate of increase rises as the percentile increases. For example, the rate of increase in lifespan at the 99th percentile (0.041 years per year) is more than 2.5 times that at the 95th percentile (0.016 years per year).Could these positive trends be driven by larger cohort sizes over time? To check this, we proceed as follows. First, we compute the conditional density function for the age at death from the values of the conditional quantile function, which we calculate in the quantile regression. We then repeat this procedure for several later birth cohorts. If the shapes of these densities are materially different from each other, it can be argued that the upward trend in the conditional quantiles Fig.  is driveAs an additional check of the influence of cohort size on the results, we rerun the quantile regression using larger cohorts comprising individuals randomly resampled from the existing data. We rerun the regression 5,000 times using bootstrapping and recalculate the coefficients. These results  to the lifespans and recalculate the regression coefficients. As expected, we see no change (figure not shown). This result adds further credibility to the observed quantile trends.It is often important in statistics to consider robustness to distributional assumptions. In this regard, quantile regression methods rank highly. They derive this robustness from the properties of basic sample quantiles. For example, given a data set that has some sample median, any data point above (below) the median can be changed to some other arbitrary value above (below) it without affecting the value of the median itself. So, given an estimate For the 1870–1904 birth cohorts, we find an increase in age at death among the longest-lived Danish centenarians but no increase for those in Sweden. Although these two Scandinavian countries are similar in many ways, Denmark has generally experienced higher mortality (lower lifespans) than Sweden, and this excess mortality has been attributed to smoking  in cohorts of female centenarians in Denmark


When a postoperative hepatic artery pseudoaneurysm develops after massive hepatectomy, both an intervention for the pseudoaneurysm and patency of hepatic artery should be considered because occlusion of the residual hepatic artery results in critical liver failure. However, the treatment strategy for a pseudoaneurysm of the hepatic artery after hepatobiliary resection is not well established.A 65-year-old woman underwent right hepatectomy, extrahepatic duct resection, and portal vein resection, for gallbladder cancer. Although the patient had an uneventful postoperative course, computed tomography on postoperative day 6 showed a 6-mm pseudoaneurysm of the hepatic artery. Angiography revealed the pseudoaneurysm located on the bifurcation of the left hepatic artery to the segment 2 artery plus the segment 3 artery and 4 artery. Stent placement in the left hepatic artery was not feasible because the artery was too narrow, and coiling of the pseudoaneurysm was associated with a risk of occluding the left hepatic artery and inducing critical liver failure. Therefore, portal vein arterialization constructed by anastomosing the ileocecal artery and vein was performed prior to embolization of the pseudoaneurysm to maintain the oxygen level of the remnant liver, even if the left hepatic artery was accidentally occluded. The pseudoaneurysm was selectively embolized without occlusion of the left hepatic artery, and the postoperative laboratory data were within normal limits. Although uncontrollable ascites due to portal hypertension occurred, embolization of the ileocolic shunt rapidly resolved it. The patient was discharged on postoperative day 45.Portal vein arterialization prior to embolization of the aneurysm may be a feasible therapeutic strategy for a pseudoaneurysm that develops after hepatectomy for hepatobiliary malignancy to guarantee arterial inflow to the remnant liver. Early embolization of arterioportal shunting after confirmation of arterial inflow to the liver should be performed to prevent morbidity induced by portal hypertension. Curative resection for biliary cancer often requires aggressive surgery with major hepatectomy and dissection of the hepatoduodenal ligament. After surgery, however, the remnant liver function is limited and the oxygen is supplied by only the residual hepatic artery . If a psThis case report describes successful multidisciplinary treatment of an aneurysm after hepatobiliary resection for gallbladder cancer.A 65-year-old woman with gallbladder cancer was referred to our hospital for surgery. The laboratory examination revealed obstructive jaundice and cholangitis. Computed tomography (CT) showed gallbladder cancer involving the hepatic hilum, including the portal bifurcation. Preoperative cholangitis developed several times, and the endoscopic biliary stent was exchanged three times. The indocyanine green clearance was 0.113. The estimated volume of the future liver remnant was 507 mL and 31%. Percutaneous transhepatic portal embolization of the right portal vein was performed. Two months later, right hepatectomy, extrahepatic duct resection, and portal vein resection were performed  6 revealed a pseudoaneurysm of the LHA with a diameter of 6 mm Fig. . AngiogrThis case report highlights two important clinical issues: portal vein arterialization prior to embolization of the aneurysm may be a feasible therapeutic strategy for a pseudoaneurysm that develops after hepatectomy for hepatobiliary malignancy to guarantee arterial inflow to the remnant liver, and early embolization of arterioportal shunting after confirmation of arterial inflow to the liver should be performed to prevent morbidity induced by portal hypertension.The remnant liver oxygenation must be cautiously considered when an intervention is performed for a pseudoaneurysm after hepatobiliary resection. Previous reports have shown that ligation of the hepatic artery to treat a pseudoaneurysm after hepatectomy results in fatal liver failure , 4. SeleThe arteriovenous shunt uses the mesenteric vessels and resolves the liver ischemia caused by thrombosis or ligation of the hepatic artery after hepato-biliary-pancreatic surgery or liver transplantation , 11–13. Arterioportal shunting is associated with postoperative complications of shunt occlusion and portal hypertension with significant ascites, hyperbilirubinemia, and gastrointestinal bleeding , 13. BhaIn our patient, the cause of the pseudoaneurysm was not known. Notably, our patient did not develop bile leakage, a pancreatic fistula, or an intra-abdominal abscess; thus, development of the pseudoaneurysm was not influenced by pancreatic juice, bile, or infection. The inflammation around the LHA was severe due to preoperative cholangitis, and dissection of the LHA was difficult. Therefore, we postulate that a retraction injury or thermal injury by the electrocautery device intraoperatively may have occurred.The patient in our case was asymptomatic, and dynamic CT revealed the pseudoaneurysm. It is vitally important to discover an asymptomatic aneurysm and perform a swift intervention to prevent mortality. Therefore, screening CT or ultrasonography is recommended after major hepatectomy with extrahepatic duct resection to check for the presence of an aneurysm.Portal vein arterialization prior to embolization of the aneurysm may be a feasible therapeutic strategy for a pseudoaneurysm that develops after hepatectomy for hepatobiliary malignancy to guarantee arterial inflow to the remnant liver. Early embolization of arterioportal shunting after confirmation of arterial inflow to the liver should be performed to prevent morbidity induced by portal hypertension.


Naphthalene is the simplest polycyclic aromatic hydrocarbon (PAH). It is easily emitted into the atmosphere, posing a significant risk to human health. However, limited studies have described the impact of naphthalene exposure on birth outcomes. In this study, we investigated the association between the maternal urinary metabolites of naphthalene, 2-hydroxynaphthalene (2-OH NAP), and birth outcomes.In the present study, four urinary PAH metabolites were measured in 263 pregnant women during late pregnancy. Multiple linear regression analysis was used to analyze the relationship between the concentrations of 2-OH NAP and birth outcomes, and restricted cubic spline models were further used to examine the shapes of the dose-response association.linear = 0.0293 for 2-OH NAP and BW; P linear = 0.0326 for 2-OH NAP and CI). Multiple linear regression data indicated that each 1 ln-unit increase in 2-OH NAP was significantly associated with a 2.09 g/cm increase in the CI. The associations among 2-OH NAP, BW, and CI were also observed in a subset of participants residing close to arterial traffic.General linear models showed that prenatal urinary 2-OH NAP was associated with lower birth weight (BW)  and higher cephalization index (CI) . These associations were linear and significant when 2-OH NAP was modeled as a continuous variable in restricted cubic spline models  contains supplementary material, which is available to authorized users. Naphthalene, the simplest polycyclic aromatic hydrocarbon (PAH), is a natural constituent of petroleum and a product of incomplete combustion of organic materials and petroleum products. Naphthalene is detected in cigarette smoke, in automobile exhaust and during combustion of petroleum products . It is eStudies demonstrate that exposure to naphthalene can destroy red blood cells and cause confusion, nausea, vomiting, and jaundice , 3. The Birth outcomes are objective and visual indicators that can reveal the nutritional and health status of infants and fetuses and predict the possibility and risks of adulthood diseases –15. ThisPregnant women who waited for delivery during the third trimester of pregnancy (≥ 35 weeks) in the Sixth Hospital of Shanxi Medical University and The Eighth People’s Hospital of Taiyuan were invited to participate in the Taiyuan Mother and Child Cohort Study. Pregnant women who had resided in Taiyuan for at least 1 year, were nonsmokers, were ≥ 18 years of age, and had a single gestational viable fetus were considered eligible for participation in the cohort study. A total of 287 pregnant women were included in the study. According to self-reported and medical record data, 17 subjects who had a chronic disease were excluded from the study. Urine samples and cord blood were collected for analysis from the 263 pregnant women included in the analysis. Prior to enrolling subjects, all participants gave written informed consent and the study was approved by the Research Ethics Committee of Shanxi Medical University.code for transport planning on urban road, which includes 40–60 km/h speed, more than 4 automobile lanes, 3.5-m lane width, and a separation zone  is similar to body mass index and is most commonly used in pediatrics [4] is a validated predictive indicator of intrauterine growth retardation that affects fetal brain development [We summarized information on birth outcomes from maternal and newborn medical records. The anthropometric indicators of the newborn in the present analyses included birth weight (BW) (in grams), birth length (BL), birth head circumference (BHC) (in centimeters), and two growth proportionality indices: ponderal index (PI) and CI. The PI [BW (g) / (BL (cm)) diatrics . The CI elopment . A higheelopment .p-value less than 0.05 was considered statistically significant. Continuous variables are expressed as the mean ± standard deviation (SD) or median and interquartile range (IQR). Categorical variables are presented as numbers and frequencies (%). Natural log transformation was applied to all the exposure metrics  to correct skewed distributions. The concentration of each PAH metabolite below the LOD was assigned a value corresponding to one-half the LOD. Spearman correlation analysis was used to evaluate the association between PAH metabolites and birth outcomes. General linear models and restrict cubic spline models were used to explore the dose-response association between PAH metabolites and birth outcomes after adjusting for potential confounders. Multiple linear regressions were used to estimate the effect of PAH exposure on birth outcomes. To assess the presence of collinearity and independence among the covariates, we ran the variance inflation factor (VIF), tolerance, and Durbin-Watson (DW) test on all linear regression models [The collected data were analyzed using SPSS 16.0  and SAS 9.4 . A bilateral n models –35. The r = − 0.15) and the PI (r = − 0.13) with P-values of < 0.05 for both. A similar pattern was observed for 2-OH FLU with an r  of − 0.15 (< 0.05) and − 0.18 (< 0.05) for BW and the PI, respectively. In contrast, maternal urinary 2-OH NAP and 2-OH FLU showed significant positive relationships with the CI , with P-values < 0.05 for both. The 9-OH PHE and 1-OH PRY levels were inversely associated with the PI  . These data suggested that naphthalene may serve as the primary PAH metabolite associated with the adverse effects of PAH, including decreased BW and increased CI. After eliminating the effect of multicollinearity, Tikhonov regularization also concluded that 2-OH NAP was positively associated with CI  . However, the association of 2-OH FLU and 9-OH PHE with birth outcomes disappeared after adjustments for parity, maternal BMI, maternal age, gender of newborn, gestational age, eating grilled meat, passive smoking, and levels of urinary phenol, cord blood lead, and the other three PAH metabolites. Additionally, maternal BMI and gestational age were correlated with birth outcomes, except for birth length , the distance from residence to arterial traffic (< 35 m or ≥ 35 m), heating system (collective or self-provided) and cooking experience during pregnancy (yes or no), we classified subjects into two groups and compared the levels of the four PAH metabolites between the groups. As shown in Table We demonstrated for the first time that naphthalene had an adverse effect on birth outcomes. The results showed a significant association of 2-OH NAP level with low BW and high CI. In the present study, we evaluated this dose-response association between 2-OH NAP and birth outcomes after adjusting for levels of 2-OH FLU, 9-OH PHE, and 1-OH PYR and other potential confounders. Further, multiple linear regressions were performed to test the relationship between 2-OH NAP and birth outcomes in different models. There was a consistent positive association between 2-OH NAP and the CI. According to the possible sources of naphthalene, linear regression analysis was performed to test the association in different subsets. The results indicated that one of the major sources of naphthalene may be automobile exhaust in Taiyuan city. A previous study showed that, aside from industrial sources, traffic pollution is the second largest source of naphthalene . The ratThe biological mechanism of naphthalene-associated adverse effects on birth outcomes remains unclear. Reviewing the related studies, we found that the possible mechanisms included the following aspects. First, naphthalene can destroy the red blood cell and induce fetus hemolytic anemia, especially when the fetus is deficient in glucose-6-phosphate dehydrogenase . Lower hWe recognize the following limitations in this study. First, there is no external exposure information, which can reflect the level of naphthalene in the environment. Due to the characteristics of naphthalene and complicated detection methods, we did not measure naphthalene concentrations in air. However, PAH metabolites are a validated internal exposure biomarker, and the level of 2-OH NAP can reveal the actual level of naphthalene in the body . Second,In summary, the present data documents that naphthalene exposure is associated with adverse effects on BW and CI. Therefore, naphthalene exposure from traffic and fossil fuel burning should be decreased during pregnancy to improve the health of newborns.Additional file 1:Additional file of maternal urinary 2-hydroxynaphthalene and birth outcomes in Taiyuan, China. (DOC 182 kb)


Antenatal care visits, gestational age, and female sex of newborn had statistically significant effect in determining the risk of low birth weight. Women who were living with large family members had a heavier newborn than counterparts. This might be due to the fact that pregnant women have better care and social support in Ethiopian context, so advising pregnant women to live with family members should be considered to enhance social support during pregnancy in Ethiopia. Maternal anthropometric measurements have no significant effect in determining birth weight in the city and we recommend similar studies where undernourished women are common.Low birth weight is a global public health problem for mortality and morbidity in any age group. The objective of this study is to investigate the effect of maternal anthropometric measurements on birth weight. A cross-sectional study was conducted from Nov 25, 2012, to Feb 25, 2013, in maternity public hospitals in Addis Ababa city, Ethiopia. The effect is investigated using correlation, linear regression, independent sample T-test, one-way ANOVA, and finally multivariate linear regression analysis. A total of 605 women and their newborns took part in this study and prevalence of low birth weight is 8.3%. On adjusted multivariate linear regression analysis, maternal anthropometric measurements did not have an effect on birth weight. Since maternal mid-upper arm circumference ≤ 20 cm and body mass index ≤18.5kg/m Low birth weight (LBW) is a weight at birth less than 2,500 grams irrespective of gestational age. A baby's low weight at birth is either the result of preterm birth  or the result of restricted fetal (intrauterine) growth . This coGlobally, more than 20 million 15%) infants are born with LBW and it is concentrated in two regions of the developing world: Asia and Africa. Seventy-two percent of LBW infants in developing countries are born in Asia and 22% in Africa, of which 13% to 15% found in Sub-Saharan Africa with little variation across the region as a whole 5% infant, 5. A si2) [The causes of LBW are multifactorial including complication during pregnancy, genetic, environmental, social-cultural, demographic, and nutritional variables , 8. Wome2) . The ris2) . Wealth 2) . Prenata2) , 14 wher2) .LBW is closely associated with fetal and neonatal mortality and morbidity, inhibited growth, and cognitive development. It is also a risk factor for chronic diseases later in life like adult-onset diabetes, coronary heart disease, high blood pressure, and intellectual, physical, and sensory disabilities .Anthropometry provides a simple, reliable, and low-cost method of assessing nutritional status by measuring maternal physical structure which can be universally applied at primary care level. Identification of the effect of those anthropometric parameters on birth weight is important in order to determine the level of care and priorities for a referral to centers where reasonable neonatal care is available. As such, the objective of this study is to investigate this to provide evidence-based information that can be used in the future to reduce birth weight-related complications.A cross-sectional study was conducted, in maternity public hospitals of Addis Ababa city, Ethiopia, and we used simple cluster sampling method. First the study participants were divided into four clusters: Tirunesh Beijing, Yekatit-12, Gahandi Memorial, and Zewditu Maternity Hospitals in the city. Yekatit-12 and Gahandi Memorial Maternity Hospitals were selected randomly and then consecutive sampling technique  was employed till the calculated sample was achieved in the three-month data collection. Hospitals average monthly client load was 100 and 175 deliveries/month for Yekatit-12 and Gahandi Memorial Hospitals, respectively. Based on this, samples were proportionally allocated 149 for Yekatit-12 Hospital and 456 for Gahandi Memorial Hospital and we finished data collection within three months.α/2)2 P(1-P) /d2 assuming a 17.1% proportion of LBW from previous study in Gondar Teaching Hospital, Ethiopia, at a 95% confidence level and 3% margin of error.The sample size of 605 was calculated using Open Epi, Version 2, and single proportion formula n= Z, and maternal age were exclusively taken during data collection by the study team. Weight gain during pregnancy, gestational age, date of birth, and history of diabetes mellitus during pregnancy were taken from medical record. Some women did not have antenatal care follow-up and some medical records were not filled correctly; in these cases data was taken by interviewing women by trained midwives within 72 hours of birth. Birth weight was taken using baby weight scales after checking the scale with known weight control. Adult MUAC measuring tape was used to measure maternal MUAC. The height of women was measured on barefoot in centimeter using standard height measuring board and recorded to the nearest 1 cm. Gestational age was taken in weeks starting from last menstrual period (LMP). In cases when women did not know their LMP, health provider's decision on medical records was taken.The objective of the study was just to see the effect of maternal anthropometrics measurement on birth weight and we tried to see the effect independent of potential factors that affect birth weight. Therefore, maternal diabetes, preterm, postterm, and unknown gestational age were exclusion criteria to reduce potential confounders and stillbirths also were excluded since we could not find outcome variable birth weight for still births.Data were entered, cleaned, and edited using Epi Info version 3.5.1 and then exported to SPSS version 15 for further analysis. After checking for the fulfillment of the assumptions needed to make inferences about the correlation coefficient, bivariate analysis was done using correlation, independent sample T-test, one-way ANOVA, and simple linear regression. Pearson correlation coefficient (r), unadjusted coefficient B, mean difference, and p-values less than 0.05 were used to fit into the multivariate linear regression model. All independent variables which had the association in bivariate analysis with the p-value of less than 0.05 were included in multiple leaner regression model to determine the independent predictors of birth weight. The variables with p<0.05 in multivariate linear regression analysis were considered as significant predictors of birth weight.The study was approved by the ethical review board of University of Gondar (UOG), Addis Continental Institute of Public Health (ACIPH) and City Government of Addis Ababa Health Bureau. All eligible study subjects were verbally invited and informed about the expected outcomes, benefits, and risks to take part in this study. They were informed of their right to refuse participating in the research and withdraw at any time they wished to, without losing any of their rights as a client of the hospital.Maternal gravidity, gestational age, and anthropometrics characteristics are shown in From a total of 603 newborns, 320 (53%) were males and 281 (47%) were females. The mean weight of the newborn is 3085gm and the prevalence of low birth weight is 8.3%. Independent samples T-test was done to see the association of newborn sex with birth weight. The analysis showed that the mean difference in birth weight between male and female was 91gm .In the first binary linear regression and correlation model maternal variable parameters, gravidity, gestational age, number of ANC, household family size, and maternal age were significantly associated with birth weight .Adjusted multivariate linear regression analysis is done for independent variables  which have significant association on bivariate analysis .2 and MUAC ≤ 20 cm were 0.7% and 1%, respectively) and it might be higher in rural population.Maternal anthropometric characteristics  had no significant effect to determine the risk of low birth weight. In India, short mothers had 2.74- and 9.0-fold greater risk of delivering LBW baby than average and tall mothers, respectively . Overwei First, when women have a higher family size they could have a higher number of previous pregnancies and older age than their counterparts. Being older and multiparous may determine the birth weight; because women who previously have a child were less likely to deliver a low birth weight (LBW) baby [ Second, pregnant women who are alone or with some family member might have depression and anxiety symptoms more than pregnant women who are living in large family, because depressive and anxiety symptoms were associated with low birth weight [ Third, social support is widely believed to affect health and feeding practice. Biological fathers and parents coresidence with pregnant mothers had been determinant factors for birth weight in rural South Africa women [Lower family size of women belonged has a significant risk of LBW. Even though the mechanism of action is not clear, this might be due to the following reasons:BW) baby , 10 and BW) baby , but both weight . Third, ca women .Low weight at birth is either the result of preterm birth or the result of restricted fetal (intrauterine) growth . This stMaternal anthropometric measurements have no significant effect in determining birth weight in the city. Since maternal MUAC less than 20 cm and BMI less than 18.5kg/m2 were almost nil in this study, generalization is difficult to sites where undernourished women are common, so we recommended similar study in such areas.


Which interventions under the domains of nutrition, deworming, maternal education, and water, sanitation, and hygiene can improve birth and linear growth outcomes during the first 1000 days of life in low-income and middle-income countries (LMICs)?This study used Bayesian network meta-analyses of 169 randomized clinical trials including 302 061 participants and showed that several nutritional interventions demonstrating greater associations with improved outcomes compared with standard of care, while other domains generally did not. Interventions provided to pregnant women generally demonstrated greater associations with improved outcomes than interventions provided to infants and children at later periods.The study findings suggest that it is important to intervene early for child development in LMICs, during pregnancy if possible, and combine interventions from multiple domains and test for their effectiveness. This study used Bayesian network meta-analyses to assess the magnitude of association of interventions provided to pregnant women, infants, and young children with child development birth and growth outcomes based on randomized clinical trials conducted in low-income and middle-income countries (LMICs). The first 1000 days of life represent a critical window for child development. Pregnancy, exclusive breastfeeding (EBF) period (0-6 months), and complementary feeding (CF) period (6-24 months) have different growth requirements, so separate considerations for intervention strategies are needed. No synthesis to date has attempted to quantify the associations of interventions under multiple domains of micronutrient and balanced energy protein and food supplements, deworming, maternal education, water sanitation, and hygiene across these 3 life periods with birth and growth outcomes.To determine the magnitude of association of interventions with birth and growth outcomes based on randomized clinical trials (RCTs) conducted in low-income and middle-income countries (LMICs) using Bayesian network meta-analyses.MEDLINE, Embase, and Cochrane databases were searched from their inception up to August 14, 2018.Included were LMIC-based RCTs of interventions provided to pregnant women, infants (0-6 months), and children (6-24 months).Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed for each life period. Effect sizes are reported as odds ratios (ORs) and mean differences (MeanDiffs) for dichotomous and continuous outcomes, with 95% credible intervals (CrIs). This study calculated probabilities of interventions being superior to standard of care by at least a minimal clinically important difference.The study compared ORs on preterm birth and MeanDiffs on birth weight for pregnancy, length for age (LAZ) for EBF, and height for age (HAZ) for CF.Among 302 061 participants in 169 randomized clinical trials, the network meta-analyses found several nutritional interventions that demonstrated greater association with improved birth and growth outcomes compared with standard of care. For instance, compared with standard of care, maternal supplements of multiple micronutrients showed reduced odds for preterm birth  and improved mean birth weight  but not LAZ during EBF . Supplementing infants and children with multiple micronutrients showed improved LAZ  and HAZ . The study found that pregnancy interventions generally had higher probabilities of a minimal clinically importance difference than the interventions for the EBF or CF in the first 1000 days of life.These analyses highlight the importance of intervening early for child development, during pregnancy if possible. Results of this study suggest that there is a need to combine interventions from multiple domains and test for their effectiveness as a package. These health and developmental issues can hamper personal, educational, and professional attainment.11Childhood stunting can have immediate and long-lasting negative consequences on both physical growth and neurodevelopment.13 This window also represents a key opportunity for stunting intervention delivery because stunting frequently begins during this time.13 The first 1000 days of life are often further divided into the following 3 key periods: pregnancy, the exclusive breastfeeding (EBF) period (0-6 months of age), and the complementary feeding (CF) period (6-24 months of age).14 Each of these periods deserves separate consideration with regard to the delivery of stunting interventions because growth determinants and requirements between them differ greatly.14The first 1000 days of life, a period spanning from conception to a child’s second birthday, are critical for child development.12 Similarly, comprehensive reviews have been limited to summarizing key findings of more focused review articles.12 No synthesis to date has attempted to summarize and quantify the effectiveness of multiple classes of interventions across the 3 key early-life periods of pregnancy, EBF, and CF.Over the last decade, several review articles of clinical trials or observational studies have rigorously investigated the consequences of interventions addressing stunting. However, all of these focused on a single class of interventions or investigated within a single early-life period  interventions. In this article, we report the magnitude of associations of the above interventions with birth outcomes and linear growth outcomes in the 3 key life periods across the first 1000 days of life.Network meta-analysis is an extension of conventional pairwise meta-analysis that allows for the comparison of interventions that have not been compared directly in head-to-head randomized clinical trials (RCTs).PRISMA) extension to network meta-analysis16 and report this study according to the JAMA users’ guides on network meta-analysis.17 The systematic reviews and NMAs conducted for this study were registered in PROSPERO.20We conducted this study according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses  articles , birth weight (continuous), and/or low birth weight (<2500 g) outcomes for pregnancy; length for age (LAZ), proportion stunted (LAZ less than −2 SDs), height/length, and/or head circumference for the EBF period; or HAZ and/or proportion stunted (HAZ less than −2 SDs) for the CF period. Trials that did not meet all the PICOS criteria were excluded. This review article presents the details and the results on the preterm birth, birth weight, LAZ, and HAZ; the details and the results of kangaroo care and other classes of interventions’ magnitude of associations with low birth weight, stunting, height/length, and head circumference will be published elsewhere.22Two reviewers (J.J.H.P. and M.L.F.) independently extracted the data into a standardized spreadsheet  and categorized results corresponding to the PICOS criteria for each of the systematic reviews. Cross-checking for consistency was conducted by other reviewers (L.D. and K.T.). For each eligible article, we extracted study characteristics , participant information , and outcome measures . In addition, 2 reviewers (J.J.H.P. and E.G.S.) assessed risk of bias in the included RCTs using the Cochrane Collaboration’s tool for assessing risk of bias.23 For pregnancy, the magnitudes of associations of interventions are measured using odds ratios (ORs) with associated 95% credible intervals (95% CrIs) for preterm birth and mean differences (MeanDiffs) with associated 95% CrIs for birth weight. For EBF and CF life periods, the interventions’ magnitudes of associations with LAZ and HAZ are measured using MeanDiffs with associated 95% CrIs.We applied Bayesian evidence synthesis models, as recommended by the National Institute for Health and Care Excellence in their Technical Support Document 2 (NICE TSD2).24 Accordingly, we defined the MCID threshold for birth weight as follows: 474 g ×0.15 = 71.1 g. As sensitivity analyses, we considered the MCID thresholds of 10% and 20% for preterm birth and 0.10 and 0.20 standardized MeanDiff improvement for LAZ, HAZ, and mean birth weight . These MCID thresholds have previously been used in the sample size calculations of several MNCH trials.34To allow for comparisons of interventions across multiple life periods, we calculated the posterior probability for achieving a minimally clinically importance difference (MCID) for preterm birth and birth weight (pregnancy), LAZ (EBF), and HAZ (CF) outcomes. Based on the recommendations of clinical experts, we determined the MCID threshold of 15% for preterm birth and 0.15 standardized MeanDiff improvement  for continuous outcomes for the primary analysis. The MCID for birth weight outcome was calculated using the WHO Child Growth Standards .35 for LAZ/HAZ and by Turner et al36 for preterm birth outcome, to stabilize the estimation of heterogeneity in the face of the low number of trials per comparison in the network. We used noninformative priors for mean birth weight outcome. We considered different random-effects model options with or without baseline adjustments or meta-regression based on baseline characteristics . Our model selection was informed by the deviance information criterion (DIC) and the deviance-leverage plots that could help identify outliers or lack of model fit. The final model selection was done according to recommendations of the NICE TSD2.23Because we anticipated heterogeneity between different trials, we used random-effects models for our NMAs. We used empirically informative priors for the heterogeneity variance, as suggested by Rhodes et al44 so we assumed a conservative value of 0.05 to adjust for the clustering consequences of the cluster trials in our analyses. The ICC was used to inflate variance accordingly for the continuous outcome and to down-adjust the sample sizes and the number of cases for the dichotomous outcome, as recommended by Uhlmann et al.45 We conducted sensitivity analyses for each outcome by excluding cluster RCTs. We conducted NMAs for each life period in a software program  using the R2WinBUGS 14 package.47 Full details of our statistical approaches, including inconsistency, are provided in the eAppendix in the Across the 3 early-life periods, our primary analyses included both cluster and individually randomized RCTs. Within the cluster trials included in our NMA, a mean value of intracluster correlation coefficient (ICC) of 0.0505 was reported,Among 302 061 participants comprised of 169 randomized clinical trials, the network meta-analyses found several nutritional interventions that demonstrated greater association with improved birth and growth outcomes compared with standard of care. For instance, compared with standard of care, maternal supplements of multiple micronutrients (MMN) showed reduced odds for preterm birth  and improved mean birth weight  but not LAZ during EBF . Supplementing infants and children with MMN showed improved LAZ  and HAZ . The study found that pregnancy interventions generally had higher MCID probabilities than the interventions for the EBFor CF in the first 1000 days of life.Our systematic search yielded publications that included 302 061 participants, of which 205 867 were pregnant women, 32 320 were mother-infant dyads, and 63 874 were children aged 6 to 12 months. The systematic search of databases and hand searching of bibliographies of published review articles yielded 22 738 abstracts  plus vitamin A, MMN, a single dose of deworming plus iron, and 118 kcal (20 g) of lipid-based nutrient supplementation . No important differences were observed for the remaining interventions for birth weight.The network diagram of evidence for the EBF is shown in The network for the CF is shown in Posterior probabilities of key interventions being superior to standard of care by at least the predefined MCID for preterm birth, mean birth weight, LAZ, and HAZ are shown in Similar to micronutrients, several balanced energy and protein supplements for pregnant women demonstrated higher probabilities of achieving an MCID consequence for preterm birth than mean birth weight, but their MCID probabilities were generally lower than those of the micronutrients. Maternal supplements of unfortified LNS 118 kcal had higher MCID probabilities for preterm birth and mean birth weight than fortified LNS 118-130 kcal, fortified LNS 372 kcal, and fortified flour 750 kcal. Fortified local food 597-850 kcal showed higher MCID probability for preterm birth, but its MCID probability for mean birth weight was low. Deworming and maternal education interventions showed low MCID probabilities.After birth, interventions under all domains generally did not show high MCID probabilities for either LAZ or HAZ. During the EBF period, maternal MMN and IFA supplements showed low MCID probabilities for LAZ. Provision of MMN directly to infants during this life period showed a slightly higher MCID probability. For the CF stage, IFA and MMN showed above-average MCID probabilities for HAZ. All other interventions were associated with low probabilities for this life period.For all of the 3 life periods, the results of the sensitivity analyses based on only individual RCTs were generally similar to the primary analyses. The results from these sensitivity analyses can be found in eFigure 4A to D and eFigure 6A to D in the Moreover, the sensitivity analyses with varying MCID thresholds generally showed similar trends as the primary analyses. When a lower threshold was used for the analyses, the MCID probabilities became larger for all interventions  to evaluate the magnitude of associations with preventive interventions under several domains, including micronutrients, balanced energy and protein and food supplements, maternal education, deworming, and WASH. We found several interventions that could improve birth outcomes and linear growth outcomes for infants and children living in LMICs. The MCID probabilities of interventions under the nutritional (micronutrient and food supplements) domains were generally greater than those of other domains. We also found that the magnitude of associations with interventions varies between different life periods. For instance, maternal supplementation of MMN during pregnancy was shown to be superior to standard of care, but provision of maternal MMN during the EBF period was not shown to be statistically superior to standard of care. Larger MCID probabilities were demonstrated for pregnancy compared with the life periods after birth, highlighting the importance of intervening early during the fetal growth.48 However, in our analysis on preterm birth, we found an OR of 0.54  for MMN compared with standard of care. This appears to disagree with the findings of a recently published Cochrane review on MMN that found a relative risk of 0.95  for preterm birth.48 However, in that Cochrane review, a pairwise comparison of MMN was made with “iron with or without folic acid,”48(p8) whereas our NMA compared MMN against IFA and iron alone separately. Our network analysis showed similar associations with preterm birth as the Cochrane review, with MMN showing an OR of 0.90  compared with IFA and an OR of 1.01  compared with iron.Our results are largely comparable to previously published review articles in terms of the precision of effect size estimates and trends of the associations.Some of the differences between our analyses and the previously published review articles can be attributed to the differences in PICOS criteria used to guide the study selection  was limited. However, we recognize the need for more investigation into these approaches to gain a better understanding of the social processes that contribute to linear growth faltering.5We opted to focus on micro-level interventions after reviewing the bibliographies of existing systematic reviews (eTable 1 in the In addition, few interventions have been assessed across 2 or more life periods, and there is a paucity of information on the consequences of combining interventions. While MMN is a combination of nutritional interventions, the component interventions potentially driving the results are, as yet, unknown. More trial research is needed to investigate the long-term and additive consequences of individual components of interventions.62 to reduce the number of children with stunted growth younger than 5 years by 2025, it is necessary and important to ensure that our assessment of interventions is comprehensive and appropriate for different settings.Generally, RCTs are known for being a costly, time and resource–intensive approach for determining treatment effectiveness. Most trials herein used a conventional trial approach with a fixed sample size design, where the assessment of effectiveness occurred only after the number of participants recruited reached the calculated sample size target. However, it is important to point out that the degree of clinical equipoise that could justify the initial trial design decreases as data accumulate during the trial. Applying a conventional trial approach to investigate several treatments across extended periods is often not efficient. While more clinical trials are needed to improve the quality of evidence, future trials will also require more efficient clinical trial designs. To achieve the 40% reduction target set forth by the World Health AssemblyThe findings of our study highlight the importance of intervening early to improve birth outcomes and counter childhood stunting. Our findings suggest that nutritional interventions, micronutrients, and food supplements generally showed greater associations with improved outcomes than interventions from other domains. Despite the numerous clinical trials that have already been conducted, more research targeting less explored areas, such as maternal education and WASH, appears to be needed. We believe that additional research that combines multiple intervention domains will also prove valuable for critical issues in global child development.


Different methods are used to assess the growth of preterm infants during neonatal hospital stay. The primary objective was to compare two methods for assessing growth velocity: g/kg/d according to the Patel exponential model (EM) and change in weight z-score (ZS) according to Fenton curves. The secondary objective was to highlight factors influencing the level of agreement between the two methods.Preterm infants born before 33 weeks were included. Growth velocity was computed by EM and ZS methods and linear regression was used to predict what growth velocity by EM method would be obtained using the ZS method. Differences between EM growth velocity and EM growth velocity predicted by ZS method were then used to assess the level of agreement between the two methods. A difference between -2 and +2 g/kg/day was considered as fair agreement, greater than ± 4 g/kg/day as poor agreement, and as disagreement otherwise.Among the 3954 children included, we observe a fair agreement in 2471 children (62.5%), a poor agreement in 1278 (32.3%) and a disagreement in 205 children (5.2%). Birth weight and gestational age explained 31% and 25%, respectively, of the variance in the difference between the two methods.In more than a third of enrolled children, the two methods for measuring growth velocity disagreed substantially. As variation of weight Z-score takes into account infant gestational age and gender, it could be more suitable to analyze a population of preterm infants with a wide range of gestational age. To compuGrowth velocity by ZS method = weight ZS at discharge–weight ZS at birth.Growth velocity calculated by ZS method was called ZS growth velocity.Because EM and ZS growth velocities are expressed in different units, linear regression was used to predict what the EM growth velocity would be, given the ZS method. Differences between EM growth velocity and EM growth velocity predicted by ZS method were then used to assess the level of agreement between the two methods.To compare differences between EM growth velocity and EM growth velocity predicted by ZS method, the 95% limits of agreement (1.96 standard deviation of the difference) as formalized by Bland and Altman  were comThe difference between the two methods was visually inspected according to gender, gestational age, and birth weight ZS. Multivariable regression analyses were then used to determine the adjusted relationships between the differences and 1) characteristics of the child  2) characteristics of the mother and her pregnancy  and 3) characteristics of the neonatal hospital stay  as independent variables.All the analyses were performed with the statistical software R. Significance level was set to p < 0.05. To describe the study population, medians and interquartile ranges (IQR) were computed for continuous variables and compared between groups using a Mann-Whitney test as well as proportions for categorical variables and chi-square tests for their comparisons.We included 4,652 children born < 33 weeks of gestational age between January 2003 and December 2015, who had been enrolled in the LIFT network. The study population consisted of the 3,954 children (85.0%) with no missing data concerning birth weight and weight at discharge.Table 1. In the 3,954 included preterm children, 2099 (53.1%) were male, 278 (7.0%) had a gestational age below 26 weeks of gestation and 1950 (49.3%) above 30 weeks of gestation. Median birth and discharge weights were 1320 g  and 2500 g , respectively, with an associated median EM growth velocity of 11.4 g/kg/day  and a median ZS growth velocity of -1.10  during hospital stay.The baseline characteristics of the patients are described in Fig 1 shows the observed relationship between EM and ZS growth velocity values as well as the 95% limits of agreement computed according to Bland and Altman. The mean difference between EM growth velocity and EM growth velocity predicted by ZS method was 0.0 g/kg/day with a standard deviation of 2.1 g/kg/day. These differences were observed in both directions and followed a Gaussian distribution. The calculated 95% limits of agreement was ± 4.2 g/kg/day meaning that the difference between EM growth velocity and EM growth velocity predicted by ZS method was in 95% of cases within ± 4.2 g/kg/day of the observed EM growth velocity. According to our predefined cut-offs, this observed agreement between the two methods was classified as disagreement.In the study population, 62.5% (n = 2471) of children had a difference of less than 2 g/kg/day, 32.3% (n = 1278) a difference of more than ± 2 g/kg/day, and 5.2% (n = 205) a difference of more than ± 4 g/kg/day between the two methods for measuring growth velocity.Fig 2 shows the density of the differences between EM growth velocity and EM growth velocity predicted by ZS method during neonatal hospitalization according to gender, gestational age and birth weight Z-score. Results of the multiple regression analysis are shown in Table 2. On multivariable analysis, child’s gender, gestational age, birth weight had a significant impact on the difference between EM growth velocity and EM growth velocity predicted by ZS method (p< 0.05). In this multivariable analysis, female gender, low gestational age, low birth weight Z-score increased the observed difference between the two methods. Birth weight and gestational age explained 31% and 25%, respectively, of the variance in the difference between EM growth velocity and EM growth velocity predicted by ZS method. All others included variables explained less than 1% of the variance.In this study, we highlight the very poor agreement between two methods commonly used for neonatal growth assessment, growth velocity by EM and ZS methods. In our population, a fair agreement between the two methods was found in only 62.5% of preterm children, 32.3% had a poor agreement and 5.2% a disagreement. The cut-offs of 2 and 4 g/kg/d are arbitrary but they seem to be relevant for clinical practice. Moreover, it corresponds to the change of weight gain quartiles in the study by Ehrenkranz et al  the curves are specific for boys and girls. Moreover, similar trends were however observed when using Olsen curves  . Preterm children with an antenatal corticosteroid treatment, bronchopulmonary dysplasia, and breastfeeding at discharge were indeed overrepresented in those included in the analysis. However, because 1) our study was based on a large number of children  with a good distribution in all studied variables 2) the number of not included children was relatively small , 3) no differences in anthropometric data were observed between included and not included children and 4) this restriction did not result in obvious selection bias (identified factors were indeed both positively and negatively correlated to observed differences), this bias was of limited impact.Our study suffered several limitations. First, when comparing children included and not included in the analysis, significant differences could be seen  Green points represent infants with agreement < 2 g/kg/day, yellow points agreement between 2 and 4 g/kg/day and red points agreement > 4g/kg/d.(JPG)Click here for additional data file.S2 FigZ-score growth velocity is the exponential model growth velocity predicted by weight Z-score change according to Olsen curves during neonatal hospital stay according to gender, gestational age and birth weight Z-score .(JPG)Click here for additional data file.S1 Table(XLS)Click here for additional data file.


Feynman lectures on Physics and the Introduction of Solid State Physics by Charles Kittel, which are routinely used to describe the quintessential ferroelectric phenomena such as the Curie-Weiss law and the emergence of spontaneous polarization below the Curie temperature. The model presented herein is overly simplified and ignores many of the complex interactions in real ferroelectrics; however, this model reveals an important insight: The polarization catastrophe phenomenon that is required to describe the onset of ferroelectricity naturally leads to the thermodynamic instability that is negative capacitance. Considering the interaction of electric dipoles and saturation of the dipole moments at large local electric fields we derive the full ‘S’-curve relating the ferroelectric polarization and the electric field, in qualitative agreement with Landau theory.The Landau theory of phase transitions predicts the presence of a negative capacitance in ferroelectric materials based on a mean-field approach. While recent experimental results confirm this prediction, the microscopic origin of negative capacitance in ferroelectrics is often debated. This study provides a simple, physical explanation of the negative capacitance phenomenon—i.e., ‘S’-shaped polarization vs. electric field curve—without having to invoke the Landau phenomenology. The discussion is inspired by pedagogical models of ferroelectricity as often presented in classic text-books such as the  Ferroelectric materials possess a spontaneous polarization that can be reversed by the application of an electric field. Because of their unique properties, ferroelectrics have been considered for a wide variety of applications ranging from infrared detection to non-volatile information storage. Recently, the use of negative capacitance in ferroelectrics was proposed to overcome the fundamental limits of power dissipation in integrated circuits . HoweverThe spontaneous polarization in a ferroelectric originates from its non-centrosymmetric crystal structure, below the Curie-temperature nsitions . Landau’nsitions  and Devonsitions  in the 1P and the electric field E is given by an ‘S’-shaped curve, which is the result of a symmetric double-well free energy landscape. Since this ‘S’-shaped P-E curve has a region of negative slope dP/dE < 0, it was originally argued by Landauer, that ferroelectric should possess a negative capacitance, which could in principle be stabilized , (2) and (4), we then obtainp is proportional to the local electric field p thereby resulting in a microscopic feedback loop. For positive values of In the Feynman model, the dipole moment Equation  describep with respect the applied electric field The dielectric susceptibility, T. Let C is the Curie constant.The polarizability At the Curie temperature, local electric field.A common misconception is that, in the negative capacitance region, the ferroelectric dipoles are aligned in the direction opposite to that of the electric field, which would be a violation of the fundamental laws of thermodynamics because the anti-parallel alignment corresponds to an energy maximum. However, as Equation  shows, tp or p and E in Equation (The Feynman model of ferroelectrics which we discussed so far would thus allow the system to spontaneously polarize for even the smallest deviation of either Equation , describp and To explain why the polarization eventually saturates and does not diverge to infinity, we have to introduce the polarizability as a non-linear function of the local electric field. In general, the application of an electric field increases the distance between the positive and negative ions of a dipole, thus increasing its dipole moment. However, the distance only increases until the attractive forces in the bond between the opposite charged ions balance the force due to the local electric field. Let p and For small values of Equation . CombiniUsing the identity, Equation , we can T. Let As we have established before, the linear polarizability Equation  simplifip-p-E curve is seen for Several Using the Taylor expansion in Equation  in the lp to the macroscopic polarization P, which is defined as the average dipole moment per unit volume V, i.e. We can now relate this expression for the microscopic dipole moments Equation . This yiU of one electric dipole, which can be generally defined as p from Equation (In a next step, we can calculate the electrostatic potential energy Equation , the eneHere the integration constant of the energy integral was set to zero. As can be seen from p and the local electric field p saturates at large values of P and the applied electric field An intuitive, microscopic description of the phenomenon of negative capacitance in ferroelectrics has been presented. It was shown that a positive feedback mechanism operates to align the electric dipole moments in the direction of the local electric field, which may also be in the direction opposite to the applied electric field, leading to a negative capacitance without any violation of fundamental thermodynamics. The positive feedback is set up because the electric field caused by the dipoles is larger than the applied electric field. The spontaneous electric dipole moment is bounded by a negative feedback loop due to attractive bonding forces in the atoms and the interaction with the electric field. By assuming a non-linear relation between the dipole moment It needs to be noted that the model presented herein is a toy model in one dimension, and does not represent any real ferroelectric material in three dimensions. As Feynman pointed out, having multiple instances of such one-dimensional chains close by in parallel will actually lead to antiferroelectricity, not ferroelectricity. An appropriate treatment of ferroelectrics negative capacitance in three dimensions was presented in ref. . HoweverFurthermore, it is rather intriguing that the single domain picture as originally proposed  and alsoBesides the recent progress in the basic theoretical understanding of negative capacitance, further investigations are necessary to prove that negative capacitance effects can also be utilized in application-relevant ferroelectric materials based on HfOand ZrO2 ,27. In tand ZrO2 . Therefo