Limited evidences were reported about the risk of pre-pregnancy hair dye use or irregular menstruation with abnormal birth weight during pregnancy, and their joint effects were also unknown. The aim of our study was to explore whether the pre-pregnancy exposure of hair dye and irregular menstruation were associated with the risk of abnormal birth weight.We conducted a nested case-control study from a prospective cohort of 6203 pregnant women. Low birth weight study included 315 mother-infant pairs (105 LBW cases and 210 matched controls), and macrosomia study included 381 mother-infant pairs (127 macrosomia cases and 254 matched controls). Meanwhile, lifestyle information including hair dying custom and menstrual history were collected by face-to-face questionnaires and birth outcomes were extracted from the medical records. The logistic regressions models were used to analyze the join effect of irregular menstruation and hair dye use.P = 0.048). Irregular menstruation had high risk of LBW  and macrosomia . Additionally, in the LBW study, women who used hair dye with pre-pregnancy BMI < 18.5 kg/m2 had higher OR than those with only one risk factor , and women with both hair dye use and irregular menstruation also had higher risk than those with only one factor . Moreover, in macrosomia study, women with irregular menstruation and pre-pregnancy BMI ≥ 24 kg/m2 had higher risk than those with one factor .Pre-pregnancy hair dye use was associated with increased risk of LBW (adjusted OR = 1.71, 95% CI: 1.01–2.92, Our study showed that either pre-pregnancy hair dye use or irregular menstruation was associated with abnormal birth weight, especially, their joint effects could furthermore increase the risk of low birth weight infants when these two factors existed simultaneously. Abnormal birth weight is an important issue which could reflect fetal growth and maternal health, including low birth weight (LBW) infant  and macrosomia  . Low birThe etiology of abnormal birth weight is not entirely clear now, previous studies reported maternal pre-pregnancy body mass index (BMI), life style, dietary and infection during pregnancy, et al. may have effects on abnormal birth weight , 13, 14.Our present study used the nested case-control design including 4,978 pregnant women in Guangxi, China, and investigated associations between pre-pregnancy hair dye use, irregular menstruation and the risk of abnormal birth weight.The nested case-control study is based on an ongoing collaborate prospective of Guangxi Birth Cohort Study (GBCS), which contains seven Maternal & Child Health Hospitals and aims to investigate the effects of genetic and environmental factors on pregnancy outcomes. The inclusion criteria of GBCS required the volunteers to be 18–45 years old, born in and live in the study areas and have comprehensive ability to complete a face-to-face interview questionnaire. A total of 6, 203 pregnant women were recruited during prenatal examination at those hospitals from July to September in 2015. In the end, 5, 541 pregnancies were followed-up after they completed the delivery.In the nested case-control study, the exclusion criteria were: (1) Preterm delivery , multiple birth, unknown infant gender, abortion, stillbirth and birth defect. (2) Women who used birth control pills or contraceptive injection less than few months prior to pregnancy or did any fertility treatment were excluded. After exclusions, 4, 978 single live full-term infant-mother pairs were selected for the final study, contained 105 LBW infants and 127 macrosomia. The selection of the controls was as follows: (1) Mothers delivered a singleton live full-term infant with normal birth weight. (2) For each case, two controls were randomly selected from the normal birth-weight subjects based on the matching variables as fetal gender, approximate gestational age at conception , maternal age  and recruitment area According to the matching constraints, separately 210 normal birth-weight births were matched for low birth weight cases and 254 controls were matched for macrosomia cases...), personal lifestyle , pregnancy history (gravidity and parity), pregnancy complications, medication history (pre-pregnancy use and during pregnancy use), physical activity, dietary, psychological factors and the menstrual history. Pregnant women were followed-up until delivery, and the information of pregnant women  and infants  were obtained from the Guangxi Maternal and Child Health Information System.The detailed questionnaire collected information, regarding demographic factors ). All patients consented to participate in the research, and written informed consent was obtained from each patient.P value < 0.05 in 2-tailed tests was considered statistically significant. Statistical analysis was performed using SPSS version 21.0 (IBM).Significant differences were assessed by t-test for continuous variables (means with 1 SD) or chi-square tests for categorical variables (frequency and percentage). Binary logistic regression analyses were used examine the risk of dichotomized exposures associated with abnormal birth weight. Crude and adjusted Odds ratios (ORs) were calculated and 95% confidence intervals (CIs) were given. The pre-pregnancy hair dye use and maternal irregular menstruation were analyzed as categorical variables. A The nested case-control study contained two sub-studies, which were low birth weight (LBW) study and macrosomia study, respectively. General characteristic of maternal and neonatal are presented in Tables P < 0.05 , all 2.9%, allIn the macrosomia study, compared to controls, the pregnant women had higher maternal age, pre-pregnant height, and weight, and a higher proportion of first parity (55.9% vs 42.9%), menstrual irregularity 27.6% vs 16.2%) and low education level (≤9 years) (53.5% vs 33.5%) (Table 6.2% and P > 0.05)  Tables  and 2.P < 0.001) and macrosomia , respectively compared to the pregnant women with regular menstruation. After adjusted by maternal age, education level and pre-pregnant BMI, the associations were still statistically significant .Table P < 0.05). However, there were no statistical significance in macrosomia study .The confounding factors including maternal age, maternal education level and pre-pregnant body mass index were adjusted in the logistic regression analysis . Meanwhile, when combined with BMI < 18.5 kg/m2 and hair dye use, the odds of having a LBW infant had a little higher  . After adjusted by maternal age, maternal education level, parity and pre-pregnancy hair dye use, the risk was still striking (OR adjusted: 13.31 vs 2.09) .As society develops, hair dye using is rapid increasing and becoming common during women. Recent studies focused on the effects of occupational exposure to chemical substances which persist in hair care products on abnormal birth outcome and maternal complications in hairdressers , 26–29 aThe use of hair dye is popular between women however different components of chemical substance can be found on it. A Canadian study found the hair dye production contained at least one phthalate at a detectable level . Based oIrregular menstruation may be the other risk factor for abnormal birth weight infant. Our study reported that women with irregular menstruation had significant association of LBW  and macrosomia . The results were consistence with previous studies , 38-41, Irregular menstruation may indicate ovulation disturbances which associated with sub-fertility. Women with sub-fertility were spontaneously considered to have a risk of abnormal birth outcomes, such as preeclampsia, low birth weight, preterm birth, abortion and stillbirth . DysfuncInterestingly, when we combined hair dye use with irregular menstruation, the risk of LBW was significantly higher than those had only one risk (OR: 4.58 vs 2.16), which indicated that two factors simultaneously existed would highly strengthen the risk of LBW. As we knew, this is the first report about the joint effect of hair dye use and irregular menstruation on low birth weight infant. A Japanese study showed that the frequently use of hair dye was associated with an increased risk of abnormal circulating testosterone levels , which c2 had higher risk of low birth weight infants than those had one factor , irregular menstruation women with BMI ≥ 24 kg/m2 had higher risk of macrosomia than one factor existed . This indicated that women with abnormal pre-pregnancy BMI with irregular menstruation or hair dye use could further strengthen the risk of abnormal birth weight infants.Pre-pregnancy BMI may be other risk factors of abnormal birth weight infants. Previous studies showed that women either underweight or overweight and obese had unhealthy impacts on birth weight –54.Our sThe advantage of this study was the prospective design in a large sample aimed to investigate the relationship of hair dye use or irregular menstruation with infant birth weight. In addition, there were several limitations in our study. First, the information of irregular menstruation was collected by women self-reported, retrospective bias was inevitable. In future study, we could consider combine ultrasound examination-based gestational age and self-reported. Second, the detailed information of pre-pregnancy hair dye use, including the frequency and name or types of products, were not collected, which limited the quantity study of hair dye use with abnormal birth weight. This will be considered in future studies. Third, our nested case-control study did not have a large number of subjects even though the birth cohort study sample was a good number. In addition, we will do further studies because the evidences of reporting the risk of pre-pregnancy hair dye use or irregular menstruation with abnormal birth weight are limited at present.From this nested case-control study, we found that either pre-pregnancy hair dye use or irregular menstruation was associated with abnormal birth weight in China, indicating that pre-pregnancy exposure to hair dye and irregular menstruation may be risk factors for abnormal birth weight infants.


Little is known about the epidemiology of congenital hydrocephalus (CH) in China. This study aimed to depict recent changes in CH prevalence and perinatal outcomes of the affected newborns.–2012 were analyzed. Poisson regression was used to calculate prevalence ratios (PR) and 95% confidence intervals, and linear chi-square test was used to examine time trend of CH prevalence.Data were obtained from the Chinese Birth Defects Monitoring Network (CBDMN), which collects demographic information on all newborns above 28 weeks of gestation, and clinical information on neonates with congenital anomalies. CH cases delivered during 2005P < 0.001). Higher prevalence was found in both younger  and older  maternal-age groups in comparison with the maternal-age group of 20 to 24 years. Higher prevalence was also found in infants born to mothers resided in rural areas, male infants, and multiple births. Of non-aborted infants with congenital hydrocephalus, 38.11% were born with low birth weight, 37.53% were preterm birth, and 20.69% died within 7 days after birth.Five thousand two hundred forty-five isolated and 1245 associated CH cases were identified among 10,574,061 newborns, yielding the prevalence of 4.96, 1.18 and 6.14 per 10,000 births for the isolated, associated and overall hydrocephalus, respectively. The annual prevalence of CH presented a decreasing trend (from 7.52 to 5.98 per 10,000 births, Our findings present a relatively high prevalence and poor perinatal outcomes of CH in China, which can serve as a baseline for future study. National Regulation on the Administration of Prenatal Diagnosis Techniques took effect in 2003 [Congenital hydrocephalus (CH) is a group of neurological disorders caused by various reasons that all result in imbalance between the production and absorption of cerebrospinal fluid (CSF) . The mai in 2003 , which l in 2003 , 18. HowData on CH cases and newborns in the study were abstracted from CBDMN, a nationwide hospital-based birth defects surveillance program in China, with monitoring period from 28 weeks of gestation to 7 days after birth. The procedure of data collection, case ascertainment and data quality management has been described in detail elsewhere , 20. In Maternal age , residential area , gender, and plurality of pregnancy were obtained for all births and CH cases. Residential areas were classified into urban (cities and towns) and rural (villages and countryside) areas based on mother’s last residence address where she lived for at least 1 year [The prevalence of CH was calculated as the number of CH cases, divided by the total number of live birth and stillbirth in CBDMN database during the 8-year period of the study. The changes in prevalence over the study period were analyzed by linear chi-square test . CH prevP < 0.001) and isolated CH , but not in the prevalence of associated CH  were identified among 10,574,061 births, yielding a prevalence of 6.14, 4.96, and 1.18 per 10,000 births for the overall, isolated, and associated CH, respectively. There was a downward trend in the annual prevalence of overall CH  cases were diagnosed prenatally, 4942 (76.15%) cases were terminations of pregnancy (TOP). Characteristics of 1548 non-aborted CH cases were shown in Table P < 0.001) [By analyzing almost 10 million birth data in CBDMN, we identified an overall prevalence of 6.14/10,000 for CH during 2005 to 2012, which was significantly lower than the rate of 7.03/10,000 during 1996–2004 (< 0.001) –13. In c< 0.001) . Notably< 0.001) . The pre< 0.001)  and seveNational Regulation on the Administration of Prenatal Diagnosis Techniques since 2003. According to the regulation, pregnant women are recommended to have systemic ultrasound examination to screen for birth defects in the second trimester, and pregnancy affected by severe birth defects is legally allowed to be terminated through a standardized process. Reasonably, a portion of fetuses with severe hydrocephalus could be diagnosed and terminated before 28 weeks of gestation along with the widespread use of prenatal sonography, which might result in the decrease of CH prevalence to some extent. Nevertheless, the contribution of improved maternal nutrition status and prenatal health care should not be neglected.Similar to previous findings of studies in the United States , Sweden In the current study, higher prevalence was found in both younger (<20 years) and advanced (≥ 35 years) maternal age groups. Data from Czech Republic showed that significantly higher risk of hydrocephalus was in women above 37 years of age . A DenmaThere are substantial urban-rural differences in the residents’ education level, health literacy, occupational exposure, lifestyle, and access to health care in China . The obsIn our study, about one third of non-aborted hydrocephalus cases were low birth weight and preterm births. Given that CH cases secondary to intraventricular haemorrhage were excluded from the current analysis, the high portion of low birth weight and preterm births are likely due to impaired physical development. In another word, though preterm birth is risk factor of neonatal hydrocephalus, congenital hydrocephalus may increase the risk of preterms. In low resource setting, 47.8% of severe hydrocephalus and 55.6% of Dandy-walker syndrome cases died prior to 1 year of age . HoweverBased on a large-sample-size database with extensive geographic coverage and good data quality management, our findings represent the current status of CH in Chinese population, which can provide valuable references for future intervention in China as well as in other developing countries. Considering the possible ascertainment bias due to variation in the diagnosis between different member hospitals and the short monitoring period, the observed CH prevalence and mortality rate in this study might be underestimated. Due to data limitation, we can not make further cause-specific analysis.In conclusion, our analyses found a downward trend in birth prevalence of CH in China since 2005, and the prevalence varied significantly by maternal age, gender, residential area and plurality of pregnancy. The findings of relatively high prevalence and poor perinatal outcomes of infants with hydrocephalus are of great value for future study.


Eutropis rugifera is a secretive, forest adapted scincid lizard that ranges across the Sunda Shelf. In this study, we sequenced one mitochondrial (ND2) and four nuclear  markers and generated a time-calibrated phylogeny in BEAST to test whether divergence times between Sundaic populations of E. rugifera occurred during Pleistocene sea-level changes, or if they predate the Pleistocene. We find that E. rugifera shows pre-Pleistocene divergences between populations on different Sundaic land-masses. The earliest divergence within E. rugifera separates the Philippine samples from the Sundaic samples approximately 16 Ma; the Philippine populations thus cannot be considered conspecific with Sundaic congeners. Sundaic populations diverged approximately 6 Ma, and populations within Borneo from Sabah and Sarawak separated approximately 4.5 Ma in the early Pliocene, followed by further cladogenesis in Sarawak through the Pleistocene. Divergence of peninsular Malaysian populations from the Mentawai Archipelago occurred approximately 5 Ma. Separation among island populations from the Mentawai Archipelago likely dates to the Pliocene/Pleistocene boundary approximately 3.5 Ma, and our samples from peninsular Malaysia appear to coalesce in the middle Pleistocene, about 1 Ma. Coupled with the monophyly of these populations, these divergence times suggest that despite consistent land-connections between these regions throughout the Pleistocene E. rugifera still faced barriers to dispersal, which may be a result of environmental shifts that accompanied the sea-level changes.Episodic sea level changes that repeatedly exposed and inundated the Sunda Shelf characterize the Pleistocene. Available evidence points to a more xeric central Sunda Shelf during periods of low sea levels, and despite the broad land connections that persisted during this time, some organisms are assumed to have faced barriers to dispersal between land-masses on the Sunda Shelf.  Throughout the Pleistocene and late Pliocene, glaciation cycles caused sea level fluctuations that repeatedly led to land connections between islands that today are separated by ocean channels . With thThe historic sea level fluctuations on the Sunda Shelf represent a dramatic case of an ever-changing Pleistocene landscape. Sea levels dropped 120 m below present levels and caused land area on the Sunda Shelf to expand up to twice the present area, leading to concomitant climatic and environmental changes . Sea levEutropis rugifera , is a secretive, semi-arboreal skink, distributed over mainland Southeast Asia , as well as on the islands of Borneo, Sumatra, Java, Bali, the Nicobar Islands, the Mentawai archipelago, and the southwest Philippines , it represents an ideal biological system for testing hypotheses of divergence and diversification on the Sunda Shelf. Sea level and climatological shifts have impacted the landscape dramatically. It is estimated that Borneo was connected to the Malay Peninsula throughout the Miocene, and to Java and Sumatra as well after their emergence in the mid-Miocene (∼10–15 Ma). These broad land connections on the Sunda Shelf persisted until the early Pliocene (∼5 Ma) when sea level shifts caused fragmentation of these islands to near-present configurations, though there is likely to have been occasional land connections due to sea-level shifts throughout the Pliocene  from a population in the Zamboanga Peninsula of Mindanao in the Philippines. This result suggests that the population in the Philippines represents a hitherto undescribed species within the group.Previous phylogenetic studies have included broad enough geographic sampling for ndonesia . Adding E. rugifera correspond to periods of land connections across the Sunda Shelf during the Pleistocene, suggesting that these land bridges allowed for dispersal across the Sunda Shelf, or if they predate the late-Pliocene and Pleistocene climatic shift, indicating that E. rugifera faced barriers to dispersal on the Sunda Shelf despite land connections. The result has implications for the role historical climatic and geographic processes have played in the evolutionary history in Eutropis rugifera and other taxa on the Sunda Shelf.In this study, we test whether divergence times between Sundaic populations of ND2 , and nuclear BRCA1 (969 bp), BRCA2 , MC1R (660 bp) and RAG1  amplified using polymerase chain reaction. Corresponding primers and annealing temperatures are shown in E. rugifera, with the Philippine samples treated as an outgroup  on the nuclear substitution rates, and by sampling the ND2 rates from a normal distribution with a mean of 0.00895 and a standard deviation of 0.0025 -68 and Export Permit 15530). Collection and euthenization protocols were approved by the Villanova University Institutional Animal Care and Use Committee (AS FY13-14 and AS FY17-02).E. rugifera from Sundaland as monophyletic and divergent from populations from Mindanao in the Philippines, as previously reported by The concatenated BI and ML topologies were nearly identical, except for one node within the north Borneo clade . SupportE. rugifera in north Borneo, one in central Sarawak from Bintulu to Gunung Mulu National Park, one in far southwest Sarawak, in Kuching, and a third in Sabah. The relationship between these clades is not well supported, but is consistent among all analyses in showing the sample from Kuching sister to the central Sarawak clade, and the sample from Sabah sister to all the Borneo samples. Divergence time estimates place the split between these clades at well over 2 Ma. The BI analysis places the Kuching and the Danum Valley specimens together as sister to the central Sarawak clade. The BI and ML topologies do not recover strong support for these relationships, but the timetree shows some support for these relationships : (1.) Sumatra + Nicobar Islands; (2.) Mentawai Archipelago; (3.) Peninsular Malaysia; (4.) Borneo; (5.) Bawean Island; and (6.) Bali. Further genetic sampling may show close relationships between some of these clades  and will shed light on the phylogeography and evolutionary history of this species across the entire Sunda Shelf.Our phylogeographic results are consistent with E. rugifera, which are relatively difficult to target when conducting fieldwork, will only be fully understood once a larger body of genetic samples have accumulated from repeated surveys across Indonesia. In particular, samples from Kalimantan are necessary to investigate the geographic structuring observed in Borneo, and collections across the entire range of E. rugifera, especially from the Nicobar Islands, Sumatra, and Java will help to fully understand the phylogeography of this species. The divergent and geographically isolated lineages of E. rugifera uncovered here both within Borneo and across the Sunda Shelf suggest that this species may be particular susceptible to divergence from biogeographic forces, and further study of this species may lead to further insights into the evolutionary processes causing cladogenesis on the Sunda Shelf.Modern herpetological collections in Indonesia have been sparse and large portions of the country remain to be surveyed. Secretive species like 10.7717/peerj.3762/supp-1Figure S1Support for the ML phylogeny indicated by bootstrap values  and for the BI tree by posterior probabilities.Click here for additional data file.10.7717/peerj.3762/supp-2Figure S2Click here for additional data file.10.7717/peerj.3762/supp-3Table S1Click here for additional data file.10.7717/peerj.3762/supp-4Supplemental Information 1Click here for additional data file.


A combination of a solution process and the control of the electric potential for magnetism represents a new approach to operating spintronic devices with a highly controlled efficiency and lower power consumption with reduced production cost. As a paradigmatic example, we investigated Co/Pt(111) in the Bloch-wall regime. The depression in coercive force was detected by applying a negative electric potential in an electrolytic solution. The reversible control of coercive force by varying the electric potential within few hundred millivolts is demonstrated. By changing the electric potential in ferromagnetic layers with smaller thicknesses, the efficiency for controlling the tunable coercive force becomes higher. Assuming that the pinning domains are independent of the applied electric potential, an electric potential tuning-magnetic anisotropy energy model was derived and provided insights into our knowledge of the relation between the electric potential tuning coercive force and the thickness of the ferromagnetic layer. Based on the fact that the coercive force can be tuned by changing the electric potential using a solution process, we developed a novel concept of electric-potential-tuned magnetic recording, resulting in a stable recording media with a high degree of writing ability. The increasing use of the cloud for the storage of digital information involves the use of hard disk drives which use magnetism for the storage and retrieval of digital information11246781012131416176HC) could be enhanced by about 4.5% by varying the electric potential between −1000 and −400 mV242527HC was observed to be reproducible for the case of an electrochemically etched specimenBecause of the higher storage density1920222324242526270.93Mn0.07As increases as the gate voltage sweeps from positive to negative valuestFM) affect electric potential tuned magnetic phenomena is still unclear.Exploring the possible mechanisms responsible for developing electric potential tuned magnetic phenomena is an important issue in terms of developing more efficient magnetic recording devices. From the literature, the mechanisms of the electric potential tuned magnetic phenomena are mainly related to the Curie temperature2427303132HC is detected by applying a negative electric potential in an electrolytic condition. The electric potential tuned HC and tFM shows an inverse square relation that can be successfully explained using an electric potential tuning-magnetic anisotropy energy (EPT-MAE) model. For a smaller tFM, the electric potential induced change of the HC is larger, while the electric potential induced change of the MAE is again magnified. A higher controlling efficiency of the tunable HC in thinner ferromagnetic layers was demonstrated using our apparatus. Based on the characteristics of a tunable HC produced by changing the electric potential using a solution process, we propose a novel technique for achieving electric-potential-tuned magnetic recording (EPTMR). A schematic plot of the EPTMR with storage and writing processes is shown in C is tunable by a negative electric potential, and ranged from a storage area of high HC to a writing area of relatively small HC within an available head field range. In additional, the patterned pillars are isolated in write or read process because of the parallel potential channel design. The parallel potential channel is designed to switch the write and read process by changing the supplied electric potential for each pillar that can avoid the exchange coupling between pillars. In these design, the potential controllable magnetic pillars can be structured as three-dimensional stacking like many electronic devicesIn this letter, tuning the magnetic properties by an electric potential for Co/Pt(111) of nanometer thickness in the Bloch-wall regime was investigated for a solution process. For Co/Pt(111) in the Bloch-wall regime, the depression of the V = −500 mV for a Co/Pt(111) layer thinner than 18 nm. No hysteresis is detected in the polar configuration. Hysteresis occurs only in the longitudinal configuration. This shows that the easy axis of magnetization lies on the surface plane. Shape anisotropy is dominant for the Co/Pt(111) in this thickness range36After waiting for a certain time at a suitable potential for Co deposition, a linear potential scan in the positive potential direction is performed to strip off the Co from the film. Anodic peaks from cyclic voltammograms (CV) for strip off measurements for Co/Pt(111) thinner than 18 nm are shown in 28tCo). As the tCo increases, the saturated Kerr intensity in the longitudinal configuration increases between 4.5 and 18 nm, due to the relation between the magnetization and the thickness of the ferromagnetic layersMS) and tFM can be expressed bytCo is shown in HC increases rapidly with increasing tCo below 6.8 nm. From the literature, Bloch wall energy density decreases with increasing film thickness because of the increased magnetostatic energy due to the appearance of charged surface above and below the wall, while the Néel wall energy shows opposite trend because of the proportional relation with the area of the charged surface inside the filmHC by increasing the film thickness4443444546HC decreases monotonously which follows Bloch wall behavior3544tFM, the increase in HC to a maximum at around several nanometers followed by a monotonous decrease for thicker films has been previously reported and can be described by changing the domain wall type from a Néel wall to a Bloch wallby considering the amount of magnetic moments in a ferromagnetic layer38394041tCo = 4.5 nm), no significant change in HC is detected at different electric potentials. The Néel-wall is related to the film thickness in order to minimize the magnetostatic energy. At a sufficiently small film thickness, the magnetostatic energy is no longer significant and the Néel-wall is stabilized. In addition, the energy density of the Néel-wall is related to its magnetization and film thicknesstCo = 6.8 nm), an electric potential induced change in HC occurs. For a larger negative electric potential (V = −500 mV), the value for HC is smaller. This result provides strong evidence for the negative electric potential induced depression in HC for Co/Pt(111) in the Bloch-wall regime. Variations in HC are shown in V = −500 and −400 mV. The jump in HC between 0.42 and 0.48 kOe is highly reproducible within hours of the start of the experimental tests. At this electric potential range, the typical current is around few μA/cm2. The heating power density by the electric current is less than a few μW/cm2and therefore the effects of thermal annealing can be neglected. In additional, in the Bloch-wall regime, the films are robust against variations in the electric potential for magnetic switchingHC by means of the electric potential for magnetic films in the Bloch-wall regime represents a possible route for preparing spintronic switching devices. In the following discussions for the electric potential induced phenomena, we focus on Co/Pt(111) in the Bloch-wall regime.In order to elucidate the role of the electric potential on the magnetic properties of Co/Pt(111) in Néel-wall and in Bloch-wall regimes, tCo between 7 and 18 nm, the HC measured at both V = −500 and−400 mV decrease monotonously with increasing tCo. At V = −500 mV for an individual tCo, the reduction in HC is more pronounced. By tuning the electric potential V, the electric field E applied to the specimen can be adjusted. The change in the coercive force (ΔHC) at electric fields E1 and E2 can be defined asAs shown in HC versus tCo where the electric fields E1 and E2 correspond to the electric potentials V1 = −500 mV and V2 = −400 mV, respectively. The value for ΔHC decreases with increasing tCo. In a further analysis of the data in HC and tCo, a well linear relation between ln(ΔHC) and ln(tCo) is observed, as shown in HC is proportional to the inverse of the square of tCo. Based on the above experimental evidence, we proposed an EPT-MAE model to explain the inverse square relation between the electric potential tuned HC and the thickness of the ferromagnetic layer. Detailed discussions are below.HC, an easy-axis magnetization process results in a square M-H loop, and is characterized in the single domain behavior or pinned wall limit by rotational hysteresis, i.e.,Both the magnetic anisotropy and the imperfections in ferromagnetic materials give rise to hysteresis loss and an increase in the coercive forceKu is the MAE of the ferromagnetic layerwhere n is the amount of pinning sites and ε is the pinning energy for a domain wall motionwhere p (0 ≤  p ≤ 1) is the percentage of the contribution of the magnetic anisotropy energy. By tuning the electric potential applied to a ferromagnetic film, previous investigations indicate that the corresponding magnetoresistance49511023102328495051HC. Therefore, from HC can be expressed bywhere MS is proportional to tFM as shown in tFM and the ΔHC can be expressed byBecause the E is increasedxy, dyz, dxz, dz2, and dx2 − y2) in the presence of electric field+, OH− and CO on the top of Co can influence the interface MAE via controllable electric field effect54+ and K+ in the electrolyte while the large electric field created by the electrical double layer near the electrode surface is responsible to the change of the MAE of the magnetic system. The electric field applied on the specimen can be adjusted by tuning the electric potential V. The change in the electric field (ΔE) can be defined asIn previous reports, the first principle calculations for Fe and Co films on Pt(111) show that the MAE is enhanced when the electric field V1 = −500 mV and V2 = −400 mV. By further considering the thickness of the ferromagnetic layer, the relation between the change in magnetic anisotropy energy ΔKu at the electric fields E1 and E2  and the change in the electric field ΔE can be expressed asUnder different electric fields, the MAEs are different. In this study, the magneto-optical Kerr effect (MOKE) measurements were carried out at electric potentials β is the interfacial magnetic anisotropy energy coefficientHC on layer thickness can be expressed aswhere HC versus tFM shows an inverse square relation, as shown in HC) versus ln(tCo) is −2.00 + 0.06. This result shows that combining MAE and electric field effects can successfully explain the inverse square relation between the ΔHC and the tFM.From the discussions of the electric field induced change of MAE, the ΔHC and tFM is proposed and is schematically illustrated in tFM, the electric potential induced change in HC is larger, as indicated in HC as suggested in HC and tFM in HC. Compared to the right panel of tFM, the electric potential induced ΔHC is enhanced by four times. This shows that the electric potential induced ΔHC is much more pronounced for thinner ferromagnetic layers. From a technological point of view, by changing the electric potential in ferromagnetic layers with smaller thicknesses, a higher controlling efficiency of the tunable HC is demonstrated in our apparatus. The establishment of the EPT-MAE model provides insights into our knowledge of the relation between electric potential tuning HC, the ferromagnetic layer thickness, and associated mechanisms.Based on KuV/kBT needs to be larger than 70 for a commercial deviceV is the volume of a nanoparticle; kB is the Boltzmann constant; and T is the sample temperature. To enhance the areal density of a magnetic recording disc, increasing the MAE is the key point. When using a material with a higher MAE, a higher writing field is necessary, but this is a disadvantage for real applications. By employing an electric potential tuned mechanism, the findings reported here show that 100 mV can reduce the coercive force by 15% for thin magnetic films (6.8 nm Co/Pt(111) as an example) in the Bloch wall regime. In practice, by using EPTMR, it is possible to create stable recording media with a high writing ability.For magnetic recording applications, superparamagnetic behavior is the limitation for further reducing the volume of a magnetic bit, but EPTMR is a possibility, as shown in HC is detected when a negative electric potential is applied in an electrolytic condition. For Co/Pt(111) under conditions of a continuously changing electric potential, the increase in HC between two states is highly reproducible. As the value for tFM increases, both the HC measured at V = −500 and −400 mV decrease monotonously. The reduction of HC for an individual tCo is more pronounced at a more negative potential. An electric potential tuned HC and tFM have an inverse square relationship with one another. By changing the electric potential in ferromagnetic layers with smaller thicknesses, a higher controlling efficiency of tunable HC is achieved. Assuming that the pinning domains are independent of the applied electric potential, an EPT-MAE model in which the MAE and the electric field effects are combined is established. This provides insights into our knowledge of the relation between electric potential tuning HC and the thickness of the ferromagnetic layer. The implementing of EPTMR is a potentially promising route for applications combining a solution process and electric potential control in magnetic data storage.In conclusion, for Co/Pt(111) of nanometer thickness in the Bloch-wall regime, a depression in 2) and ultra-pure water(>18 MΩ cm). To avoid contamination by oxygen, the solutions were purged with high purity argon for 1 hr before the experiments. The electrochemical cell used for the CV and MOKE measurements was developed and built in our laboratory343456602 additive are shown in the 2, the electric potential range that is suitable for the electrodeposition of Co/Pt(111) was determined. The Co layer was electrodeposited at an electric potential more negative than −700 mV for a pre-determined time, depending on the thickness of the layer. The potential range for MOKE measurements was chosen to be between −400 and −600 mV to avoid the possible deposition/dissolution of the Co deposits. A He–Ne laser with a wavelength of 632.8 nm was used as the light source for the MOKE measurements. The Kerr signals as a function of magnetic field were measured by a photodiode and recorded by a computer-controlled multimeter to generate the hysteresis loops.A platinum crystal was oriented within 0.5° of the [111] direction as checked by x-ray diffraction. The diameter of the crystal is 8 mm while the thickness is 2 mm. This specimen size is suitable for the designed apparatus for the MOKE measurements in electrochemical environments28352857588 V/m25HC. Surface species are different in different electrolytes, and the effects of point of a zero charge (PZC) need to be taken into consideration. In this report, we used the same electrolyte and the same electrochemical conditions, the PZC was not altered. Discussions of the EDL as well as the PZC can be found in the By applying an electric potential, an electrical double layer (EDL) near the electrode surface was establishedHow to cite this article: Chang, C.-H.-T. et al. Tuning coercive force by adjusting electric potential in solution processed Co/Pt(111) and the mechanism involved. Sci. Rep.7, 43700; doi: 10.1038/srep43700 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


To investigate the incidence, severity and risk factors of retinopathy of prematurity (ROP) in triplets.The medical records of consecutive premature triplets who had been screened for ROP in a single maternity hospital were analyzed and presence and severity of ROP; birth weight, gender, gestational age of the infant; route of delivery and the mode of conception were recorded.A total of 54 triplets  who were screened for ROP between March 2010 and February 2013 were recruited for the study. All triplets were delivered by Caesarean section and 36 (66.7%) were born following an assisted conception. During follow-up, seven (13%) of the infants developed ROP of any stage and two (3.7%) required laser photocoagulation. The mean gestational age of triplets with ROP was 27.6±1.5 (27-31) weeks whereas it was 32.0±1.5 (30-34) weeks in those without ROP (p=0.002). The mean birth weights of triplets with and without ROP were 1290.0±295.2 (970-1600) g and 1667.5±222.2 (1130-1960) g, respectively (p<0.001). The presence of ROP was not associated with gender (p=0.358) or mode of conception (p=0.674).ROP in triplets seems to be mainly related to low gestational age and low birth weight. Further prospective randomized studies are necessary to demonstrate risk factors of ROP in triplets and to determine if and how gemelarity plays a role in the development of ROP. Prior to examination, pupillary dilation was induced with 2.5% phenylephrine and 0.5% tropicamide, after which the topical anesthetic proparacaine was instilled and an eyelid speculum was applied. Each infant underwent a binocular indirect ophthalmoscopy examination for each eye with a 28 D condensing lens and scleral depression. Treatment decisions were made according to ‘The Early Treatment of Retinopathy of Prematurity study’ criteria.10 Statistical analysis was performed using SPSS software for Windows 15.0 . Median and range were given as descriptive statistics for quantitative data. Categorical data were summarized using frequency and percentages. Independent samples t test was used to compare two independent groups with normal distribution of quantitative data and Mann-Whitney U test was used for abnormal distributions. Results were accepted as statistically significant when p was <0.05.This retrospective study was carried out in a single maternity and research hospital in full accord with the principles laid out in the Declaration of Helsinki, upon approval of Institutional Review Board. The data was obtained by chart review. The medical files of premature infants admitted for routine ROP screening examination were reviewed and consecutive triplets who were followed for at least 6 months were recruited to the study. The rendered data included the presence and severity of ROP; birth weight, gender, gestational age of the infant; route of delivery and the mode of conception . The timing of the initial screening examination, frequency of follow-up examinations and when to discontinue screening examinations was determined according to the recommendations of the American Academy of Pediatrics, American Academy of Ophthalmology, and American Association for Pediatric Ophthalmology and Strabismus.A total of 54 triplets  who were screened for ROP between March 2010 and February 2013 were included in the study. Gestational age of the infants at birth ranged from 27 to 34 weeks with a mean gestational age of 31.4±2.1 weeks. Birth weight ranged from 970 to 1.960 g with a mean of 1.618.5±262.9 g. All triplets were delivered by Caesarean section and 36 (66.7%) were born following an assisted conception. Seven (13%) of the infants developed ROP of any stage and two (3.7%) required transpupillary diode laser photocoagulation during follow-up. The two infants who required laser treatment were siblings. Their third sibling had zone II stage 2 ROP which spontaneously regressed without any treatment. Infants requiring treatment for ROP were those with the lowest gestational age (27 weeks) and lowest birth weight (970 and 980 g) among the whole study population. The distribution of ROP according to gestational age groups are shown in 11 These are known to be associated with maternal and neonatal complications which are directly related to the number of fetuses in utero. A large study reported that 15% of singletons, 48% of twins and 78% of higher order multiples require neonatal intensive care unit (NICU) admission.12 The higher rate of neonatal complications is mostly due to prematurity. However, the relationship between multiple pregnancies and ROP is still controversial.13 Some investigators assume multiple gestation is an independent risk factor for ROP,15 but others do not.16The incidence of multiples pregnancies has increased, possibly because of higher maternal age and the increased use of assisted conception methods such as ovulation induction and in vitro fertilization.17 In a study investigating NICU admissions, the proportion of triplets reported to be decreased from 5.0 to 3.3 per 100 NICU admissions.18 Preterm labor and prematurity were the commonest complications of triplet gestations. Chibber et al.19 reported the rate of prematurity as 84% in their large triplet series. In a study investigating fetomaternal outcome in triplet pregnancy, mean birth weights of 1st, 2nd and 3rd triplets were 1.651, 1.640 and 1.443 g respectively.20 Zanconato21 reported the incidence of preterm labor as 78.6% and ROP as 6.5% in triplet pregnancies. The incidence of any stage of ROP was 13% and the rate of ROP requiring treatment was 3.7% in our series.Triplet birth is a rare occurrence. The incidence of triplets increased after the introduction of assisted conception methods, but started to decline again after limitation of the number of embryos transferred.8 found no increased risk for ROP when they compared premature triplets with premature singletons, and concluded that multiple gestation adds no risk beyond that due to prematurity. Assisted conception methods also did not appear to be an independent risk factor for ROP in our study, similar to previous studies in the literature.19 Nevertheless, gynecologists should be aware of possible neonatal outcomes of triplet pregnancies and the higher risk of prematurity in order to follow proper infertility management strategies and avoid iatrogenic multiple gestations.The relationship between triplet pregnancies and ROP is also controversial. Tomazzoli et al.16 compared triplet and singleton preterm infants and found no differences between two groups in terms of perinatal parameters, respiratory parameters and neonatal complications, including ROP. We did not investigate some other proposed risk factors such as respiratory distress syndrome, septicemia, number of blood transfusions and duration of mechanical ventilation.We evaluated triplets for certain clinical and demographical features including birth weight, gestational age, gender, route of delivery and mode of conception, and found birth weight and gestational age were related to ROP. The two siblings who required treatment for ROP in our study population were extremely premature . Gender, route of delivery and mode of conception were not associated with ROP. Maayan-Metzger et al.The present study should be viewed in context of some limitations. First of all, the limited number of triplets may influence the power of statistical outcomes. Regression analysis for risk factors could not be performed because of the small number of infants with ROP. Secondly, other ROP risk factors such as respiratory distress syndrome, duration of mechanical ventilation, septicemia, and blood transfusion were not included in the study parameters. Thirdly, the study was retrospective, which limited the data available. Finally, there was a lack of control group such as singleton or twin gestations for comparing outcome data. Despite these limitations, the current study has important implications regarding the incidence, severity and risk factors of ROP in triplets. In light of the present data, as the most important risk factors are low birth weight and low gestational age for ROP in triplets, we can suggest that an ROP screening protocol similar to that used for singletons can be applied in triplets.Triplet pregnancies usually result in prematurity. ROP in triplet infants seems to be mainly related to low gestational age and low birth weight. Larger prospective randomized studies are necessary to demonstrate risk factors of ROP in triplets and to determine if and how gemelarity plays a role in the occurrence of ROP.Ethics Committee Approval: The study was approved by the Zübeyde Hanım Gynecology Training and Research Hospital of Local Ethics Committee, Informed Consent: Consent form was filled out by all participants.Peer-review: Externally peer-reviewed.


Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites. RNA stability assays showed that Sam68-deficiency decreased the half-life of Hotair, and increased the half-lives of Mir155hg and SR-lncRNA-2, while the stability of SR-lncRNA-1 was unaffected. Depletion of Hotair and SR-lncRNA-1 in wild type 3T3-L1 cells led to defects in adipogenesis, whereas depletion of SR-lncRNA-2 in Sam68-deficient 3T3-L1 cells partially rescued the adipogenesis defect observed in these cells. Collectively, our findings define a new role for Sam68 as a regulator of lncRNAs during adipogenic differentiation.The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis. Of the lncRNAs, we identified  With the soaring prevalence in obesity and diabetes, understanding the molecular mechanisms of adipogenesis has become an area of immense interest, and much of our current knowledge has emphasized on the transcriptional cascade that governs adipocyte differentiation . SpecifiSam68-/-) mice are lean due to increased energy expenditure, decreased commitment to early adipocyte progenitors, and defects in adipogenic differentiation , 30HotaiMir155hg, which is the primary sequence of miR-155, a known inhibitor of adipogenesis [SR-lncRNA-1 and SR-lncRNA-2, with positive and negative roles in adipocyte differentiation, respectively. Given the versatility and ubiquitous nature of Sam68 [Moreover, we also identified ogenesis . Althougogenesis , 11. In of Sam68 , 4, it wHotair, it increased the half-lives of Mir155hg and SR-lncRNA-2. Given that spliced lncRNAs are more stable than single exon transcripts [One aspect of Sam68 that we have yet to investigate is its possible transcriptional role in preadipocytes. Indeed, previous studies have identified Sam68 as a co-regulator for a number of transcription factors, including the androgen receptor (AR) , NF-κB , and p53nscripts , it can To date, several mechanisms of action have been elucidated for lncRNAs in gene regulation. Most lncRNAs are nuclear, and function by modifying chromatin structures , 33, wheIn summary, our study demonstrates a previously unappreciated role for Sam68 as a regulator of lncRNAs during adipogenesis. This feature of Sam68 can be potentially harnessed as a therapeutic target for treating obesity and its related metabolic disorders, possibly by inhibiting the activity of Sam68 . Howeverp-value < 0.05. Gene ontology (GO) analysis was performed with GOrilla tools [p < 0.05) [Total RNA was isolated from undifferentiated Sam68 wild type (pRetroSuper) and Sam68-deficient (Sam68sh) 3T3-L1 preadipocytes using TRIzol reagent according to the manufacturer’s instructions. RNA integrity and quality were checked as previously described , and biola tools . Differe < 0.05) , 43.Sam68 wild type (pRetroSuper) and deficient (Sam68sh) 3T3-L1 cells were previously described . AdipogeTotal RNA was extracted at the indicated time points as described above. Reverse transcription (RT) was performed with the M-MLV reverse transcriptase (Promega). Real-time PCR (qPCR), including primer design and efficiency tests, was performed according to the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines . qPCR exHotair, SR-lncRNA-1 (2610035D17Rik), and SR-lncRNA-2 (4930461G14Rik). Transfection of siRNAs was performed with RNAiMAX reagents (Invitrogen) according to the manufacturer’s instructions. Cells were recovered and grown to confluence before induction of differentiation. Total RNA was harvested as described above.The following siGENOME SMARTpool small interfering RNAs (siRNAs) were purchased from Dharmacon:


Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation.Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation.Prevalence of all birth defects was 18.9/1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term.Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects. However, it is now recognized that there are birth defects known to be caused by hazardous epidemics, such as thalidomide exposure during pregnancy. To investigate and prevent birth defects, surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) are underway.3,4Birth defects, including malformations, deformations, and chromosomal abnormalities, are major causes of neonatal mortality.3 Data regarding the prevalence of all birth defects, and cases observed before 22 weeks of gestation, could be captured via prospective cohort studies of pregnant women. In this report, we described birth defects observed beginning at 12 weeks of gestation during the pre-natal care of pregnant women in a prefecture-wide hospital-based birth cohort study, the Hokkaido Study on Environmental and Children’s Health.5,6 Furthermore, we examined parental risk factors for birth defects, and the association between the birth defects and the risk of growth retardation. We analyzed and presented the differences in these estimations between those birth defect cases included in the ICBDSR and those cases not included.Incidence of birth defects cannot be accurately estimated because fetal death cases before diagnosis of the pregnancy are unknown. The Japan Association of Obstetricians and Gynaecologists (JAOG) reports observed birth defect cases via the nation-wide hospital-based monitoring program to the ICBDSR. However, mortality cases before 22 weeks of gestation have not been reported.5,6 We enrolled women in early pregnancy , who visited one of the 37 associated hospitals or clinics  in the Hokkaido Prefecture, from February 2003 through March 2012. These hospitals and clinics are evenly distributed throughout Hokkaido Prefecture. We obtained written informed consent from all subjects. The institutional ethics board of the Hokkaido University Center for Environmental and Health Sciences  and the Hokkaido University Graduate School of Medicine  approved the study protocol.The primary goal of the Hokkaido Study on Environmental and Children’s Health was to examine the effects of perinatal environmental chemical exposures on birth outcomes, including birth defects. The details of this cohort study have been described previously.Follow-up with the pregnant women enrolled in the study and their offspring is on-going. In this report, we used the dataset of the fixed cohort as of the end of 2015, which included 20,805 women. The number of study participants with a birth record was 19,579. The follow-up rate at birth was 94.1%. Data from 5.9% of participants were missing because the participants were lost to follow-up.7 The ICBDSR monitoring list, which physicians also complete, lists 35 malformations.3The number of subjects in this report who had birth outcome data and gestational week data was 19,244. According to the standardized manual provided by the principal investigator of the Hokkaido University (R.K.), each physician in charge of each woman in the delivery units of the participating hospitals or clinics filled the unified sheet by referring to the medical records, within 7 days of delivery or at the termination of pregnancy. Whether the diagnosis of birth defects was made during the antenatal period (using ultrasound or via some other means) or during the postnatal period was recorded. However, the date of diagnosis was not recorded. The physicians selected from a list of 55 disease names to record the birth defect, or if the disease was not on the list, described disease names in the unified sheet. These 55 birth defects listed on the unified sheet are possible effect markers of environmental exposure. We encoded the birth defects according to the International Statistical Classification of Diseases and Related Health Problems (ICD), 10th revision.8Medical records of the parents and offspring at delivery or termination, including gestational age and birth weight, were also recorded on the same sheet. A miscarriage was defined as the presence of a dead fetus between 12 and 21 weeks of gestational age. A stillbirth was defined as the birth of a dead fetus at 22 weeks of gestation or later. Preterm birth was defined as birth between 22 and 36 weeks of gestation. Very low birth weight (VLBW) was defined as birth weight <1,500 g. Small for gestational age at term (term SGA) was defined as birth weight below the 10th percentile reference point for birth weight, according to gestational age, sex, and parity. We used the database of birth weight published by the Japan Pediatric Society as a reference.The baseline data regarding information on parental reproductive history and lifestyle factors, including age at the entry of this study, body mass index before the pregnancy, parity, drinking habit in the first trimester, smoking during the pregnancy, and any usage of assisted reproductive technologies, were collected using a self-administered questionnaire.Differences between expected and observed frequencies by gestational week (before week 22 or from week 22 of gestation), sex , and the number of births (singletons or multiples) for each category or defect were tested using the Fisher’s exact test.P values <0.05 were considered as statistically significant. Statistical analyses were calculated using Stata 14 .We calculated risk ratios (RRs) for all kinds of birth defects, and birth defects included or not included in the ICBDSR, in singleton fetus or infants, according to maternal and paternal factors, including maternal age at entry (<35 or ≥35 years old), maternal body mass index, parity (0 or ≥1), assisted reproductive technology (used or unused), age of the partner at the entry (<35 or ≥35 years old), maternal alcohol use in early period of the pregnancy (used or unused), and maternal smoking during pregnancy (smoking or nonsmoking). We estimated RRs of birth defects by preterm birth, VLBW, and term SGA. We calculated RRs using log-binomial regression analysis, with and without adjustment for the above maternal and paternal factors. We show the distribution of mother and singleton child pairs according to gestational week and birth outcomes in Figure P < 0.0001). Prevalence of malformations of the nervous system; malformations of the eye, ear, face, or neck; malformations of the urinary system; malformations and deformations of the musculoskeletal system’ and chromosomal abnormalities was higher before 22 weeks of gestation compared to at 22 weeks of gestation or later. Among patients with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. The total prevalence was not significantly different between males and females: 19.6/1,000 births in males and 17.6/1,000 births in females (P = 0.48). Malformations of the eye, ear, face, or neck and malformations of the circulatory system were found more in females than males, but the differences were not statistically significant . Malformations of genital organs and the urinary system occurred significantly more in males than females . The total prevalence was not significantly different between singleton  and multiple birth infants  (P = 0.70). In multiple births, triplet births occurred only in nine pregnancies. No birth defects were observed in the triplet births. Most birth defect cases were identified before birth. All cases of malformation of the nervous system, malformations of the digestive system except for the oral cavity, and malformations of the genital organs were identified before birth. Malformations of the respiratory system showed the lowest percentage of identification before birth (50.0%).The prevalence of birth defects classified by major ICD-10 categories according to gestational week, sex, and number of births is shown in Table n = 8), followed by malformations of the circulatory system and other malformations (n = 5) and cleft lip/cleft palate and malformations and deformations of the musculoskeletal system (n = 5).There were 32 cases of multiple defects. The most frequent combination of multiple defects was malformations of the circulatory system and chromosomal abnormalities  is unknown, this study omitted observations before 12 weeks of gestation. The ICBDSR surveillance programs omit observations before 22 weeks of gestation. Observation before 22 weeks of gestation are included in this report.3 Using the same denominator and numerator, the prevalence of birth defects included in the ICBDSR was found to be 0.8% in our study. The prevalence in our study is lower than that reported in the nation-wide hospital-based monitoring project. One possibility is that the ICBDSR monitoring project consists of core hospitals in each area, such as university hospitals and specified children’s hospitals . High-risk pregnant women might tend to visit such hospitals, and severe birth defect cases are usually transferred to such core hospitals before delivery. Moreover, only 10 institutions participated in the monitoring project in the Hokkaido area. Our 37 associated hospitals or clinics, including 3 university hospitals, were evenly distributed throughout Hokkaido Prefecture and accounted for approximately 40% of the institutes with delivery units in this prefecture.9 Therefore, we assume that our study participants represented the population of women in general in the Hokkaido area. Another possibility might be that our participants were relatively healthy pregnant women who had an interest in environment and health in communities.The Japanese data reported in the ICBDSR showed that the prevalence of birth defects  was 1.6% per year during 2007–2011.We found that patients with birth defects delivered before 22 weeks of gestation comprised approximately 10% of all patients with birth defects. However, the proportion of birth defects in this early gestational period was very high. Therefore, this finding confirmed that a large proportion of stillbirths and terminations were caused by birth defects. Pregnancies with major structural defects tend to be terminated. Information on termination of pregnancy is difficult to obtain in general; however, prospective birth cohort studies provide an opportunity to obtain information on termination.10 We did not observe significant differences in prevalence between males and females. Higher prevalence of malformations of genital organs and urinary system in males, and malformations of ear, face, and neck in females were consistent with data in the United States. However, we found a difference regarding malformations of the circulatory system, with higher prevalence in females in our study. The mechanisms of a sex-based difference in prevalence are unknown. However, race-based difference in prevalence suggests involvement of differences in susceptibility genes.11Regarding differences by sex, a population-based study in the United States observed that the overall prevalence of major defects in live births was 3.9% among males and 2.8% among females during 1968 to 1995.12 Although the prevalence is low, a study of multiple births would be necessary to elucidate the cause of birth defects.Concerning multiple gestations, the total prevalence of birth defects was not different between singleton and multiple-birth infants in this study. However, there were congenital malformations observed only in twins. Additional etiological factors appeared to be a factor in multiple births.11,13 However, the causes of most birth defects remain unknown. The increased risk from high maternal age in our study was consistent with previous studies.14 In previous studies, there was less evidence that high paternal age affected risk.15 We observed increased risk due to high age of the partner in birth defects included in the ICBDSR, although the RR was not statistically significant. Increased risk of birth defects not included in the ICBDSR due to usage of assisted reproductive technologies was comparable finding to previous studies.16 The risk of alcohol use and smoking has been reported in previous studies; however, we did not observe a significant risk.17,18 Future studies need to further examine parental and environmental factors, including passive smoking,19 endocrine disrupting chemicals,20 indoor air pollution,21 folate,22,23 supplemental vitamins,24–26 and stress.27,28Our study findings suggest a different pattern of parental risk factors between those birth defects included in the ISBDSR and those not included. Various risk factors for birth defects have been suggested, including environmental exposures.29 We observed an increased risk of preterm birth in birth defects included in the ICBDSR. In contrast, we observed an increased risk of term SGA in birth defects not included in the ICBDSR. Both low gestational age at birth and SGA result in low birth weight. However, their risk factors and health effects were different between preterm SGA and term SGA infants, a finding which is consistent with previous studies.13,30,31 Therefore, our findings might suggest that there were different etiological factors between birth defects included and those not included in the ICBDSR. Our observations of birth defects not included in the ICBDSR also suggest that the same etiology, such as usage of assisted reproductive technologies, might be involved in fetal growth and in birth defects. Because of future morbidity of children associated with growth retardation,32,33 our findings emphasize that prospective birth cohort studies play an important role in the prevention of childhood illness.It was indicated in a previous study that structural birth defects contributed to a substantial proportion of preterm birth.11 Although the rarity of specific anomalies often limits the design of epidemiologic studies, the data from prospective studies are still valuable.Birth defects are rare outcomes. In addition, it is often not possible to conduct prospective studies for the investigation of birth defects. Therefore, researchers usually select a case-control study design, which is appropriate for rare disease outcomes, in order to elucidate the relationship between birth defects and parental and environmental factors. However, in case-control studies, an underlying recall bias of exposure is not avoidable.The potential disadvantages of our study data should be considered. The findings concerning the lost-to-follow-up group suggest the existence of ‘bias due to withdrawal’, although the reasons for dropout were speculative. Participants from certain backgrounds might tend to withdraw from this or similar studies. However, the effect of the withdrawal was considered to be small because our follow-up rate was sufficiently high.13 In this study, the term ‘birth defects’ was used.Malformations, deformations, and chromosomal abnormalities were previously thought to be idiopathic; therefore, they were frequently termed congenital anomalies. However, more recent research indicates that such abnormalities have been caused in part by parental conditions and environmental factors, such as drug usage and environmental pollution. The term ‘congenital anomalies’ is no longer used as the general term.11 In our study, most birth defects were diagnosed before birth. However, some birth defects, such as malformations of the respiratory system, showed low percentage of ascertainment before birth. We continue to collect data regarding birth defects using a self-administered questionnaire administered at 1, 2, 3, 4, and 7 years after delivery. Because there are birth defects that may not be identified until the later years of follow-up, it is anticipated that the number of birth defect cases will increase over time. Future studies investigating the association of risk factors with birth defects and the long-term impacts of birth defects, using the existing and future data of this cohort study, will provide valuable insights.Previously, observation of birth defects began at birth. However, timing of ascertainment has begun earlier as technology advances, especially through the use of ultrasound.In conclusion, we reported the prevalence of birth defects in the general population of Japanese women in our cohort study. Although the monitoring system based on the ICBDSR is an excellent nation-wide monitoring system to survey longitudinal trends, the birth defects not included in the ICBDSR should also be analyzed to elucidate the etiology of birth defects. Prospective studies will contribute to the elucidation of the prevalence and etiology of birth defects using the framework of epidemiology.


The first years of life are the most dynamic period for childhood growth. There are limited data available on growth patterns of infants and children living in rural Latin America. The aim of this study was to describe the growth patterns from birth to 5 years in children living in a rural District of tropical coastal Ecuador using data from a birth cohort of 2404 neonates. We hypothesize that there would be growth differences according to ethnicity and sex. Evaluations were conducted at birth or until 2 weeks of age and at 7, 13, 24, 36 and 60 months during clinic and home visits. Individual growth trajectories for weight-for-age, height-for-age and weight/height-for-age Z-scores were estimated using multilevel models. Girls were lighter and shorter than boys at birth. However, Afro-Ecuadorian children (versus mestizo or indigenous) were longer/taller and heavier throughout the first 5 years of life and had greater mean trajectories for HAZ and WAZ independent of sex and socioeconomic factors. Our data indicate that ethnicity is a determinant of growth trajectories during the first 5 years of life independent of socioeconomic factors in a birth cohort conducted in a rural region of Latin America. This period of growth is an important determinant of future health but is vulnerable to social and environmental injuries Patterns of growth in the uterine environment may determine future health and wellbeing. Rapid weight gain during the first year of life is considered to be a risk factor for obesity and chronic diseases in childhood The limited available data on growth patterns of Ecuadorians infants and children are from small cross-sectional studies comparing children between the Andes and Coast The nutritional transition in Latin America from more traditional to more Western diets has been accompanied by a decline in malnutrition, stunting and underweight, in all age groups and an increase in overweight and obesity. Nutritional interventions deserve greater attention as a means to prevent and treat chronic diseases even in countries where malnutrition was previously extremely common Stunting is a prevalent problem in Latin American and more frequent among children of low socioeconomic status 22.1The study was a birth cohort, the ECUAVIDA cohort, of 2404 neonates recruited at the Hospital “Padre Alberto Buffoni” (HPAB) over the period November 2005 to December 2009, in the District of Quinindé, Esmeraldas Province in Northern coastal Ecuador. The main objective of the ECUAVIDA cohort was to investigate the potential effects of intrauterine and postnatal exposures to geohelminth parasites on vaccine immune responses in infancy, and the development of allergic sensitization and allergic inflammatory diseases in childhood. The methodology of the cohort study, including power and sample size estimations for primary outcomes, has been described previously in detail 2.2Quinindé is a rural District in the Province of Esmeraldas with an estimated total population of 150 000 that includes three towns with populations greater than 10 000 inhabitants: Quininde, La Union and La Concordia (now re-assigned to the Province of Santo Domingo following a recent plebiscite). About 70% of the cohort lives in rapidly expanding urban and peri-urban neighborhoods of these three towns, and the remainder in rural settlements. The main sources of income are derived from African palm oil and fruit cultivation, cattle, and extraction of timber. The Province is one of the poorest regions of Ecuador, with a per capita income of less than USD$2000 in 2005. The District has an ethnically mixed population of mestizos (90%), Afro-Ecuadorians (7%), and indigenous Amerindians (term used interchangeably with native) (3%) 2.3Formal recruitment into the cohort occurred around the time of birth. Entry criteria into the study were: 1) healthy normal baby less than 14 days old; 2) at least one stool sample collected from the mother; 3) the family had lived in the District for, at least, the last 2 years and did not plan to move out from the District over the following 3 years; 4) accessible home; and 5) maternal age of 17 years or older 2.4First measurements of weight and height were done between birth and 2 weeks of age and then repeated periodically as close as possible to 7, 13, 24, 36 and 60 months during clinic and home visits. At each observation time, length (if less than 24 months of age) or height, in centimeters, and weight, in kilograms, measurements were taken in duplicate by trained members of a team of health professionals, and the mean of two measurements was considered as the final measurement Data on socioeconomic and environmental factors were obtained using standardized questionnaires administered to the child's mother or primary care giver.2.5Individual growth trajectories for WAZ, HAZ and WHZ Z-scores were estimated from birth to 60 months of age using WHO standards and multilevel linear models. Four specifications of the multilevel models for the trajectories were used 3Of the 2404 children recruited at baseline, anthropometric data to five years of age following the initial measurement within the first 2 weeks of life were available for 1907 (79.3%) . The preAnthropometric characteristics of study children are shown in P > .20 were then excluded from a second model (Model 2). Among the Afro-Ecuadorian, z-scores were on average 0.25 (HAZ) and 0.17 (WAZ) higher than those observed for Mestizo/native children and this difference persisted after adjusted for all other variables in the model including heterogeneity of subjects (taken into account by random effects), which can be considered to represent unmeasured variables such as genetic predisposition, social, and environmental factors. Boys had on average 0.10 higher WHZ Z-scores than girls.We also fitted multilevel quadratic models for HAZ, WAZ and WHZ  and weight-for-age (WAZ) during the first five years of life. The latter observation was independent of sex and socioeconomic factors with the exception of number of children living in the household that was associated with greater deficits in HAZ. These findings contribute to our understanding of anthropometric trajectories and ethnicity in Latin America.The stunting rates observed in our study were consistent with the findings of previous studies in Latin America Studies of heritability have indicated genetics may account for up to 60% of adult height Recent population based studies in Ecuador Several studies have shown a clear relationship between birth weight and later childhood growth - children with low birth weight having accelerated growth during the first two years of life while heavier children had slower growth Previous studies have shown differences in height and weight between Afro-Ecuadorian and mestizo women, and that infants of Afro-Ecuadorian mothers were heavier Our data show that children aged around 36 months were at greater risk of stunting particularly non Afro-Ecuadorian children. Short period of breastfeeding, inadequate introduction of complementary foods and low coverage and quality of public health interventions may explain the greater vulnerability at this age The findings from this study should be interpreted in light of its limitations and strengths. A major strength of this study is the availability of six direct measurements of growth parameters taken prospectively between birth and 5 years of age by a trained team using standardized methods. However, first measurements of weight and height were done between birth and 2 weeks of age. Residual confounding is a potential weakness given that the study is observational.Many lower and middle-income countries, such as Ecuador, have seen alterations in feeding practices and energy expenditure in children over the last decade as a consequence of changes in economic, social, demographic and health structures. These changes are known as the ‘nutrition transition’ and provide an opportunity to investigate the role of nutrition in the causation of chronic diseases such as type-2 diabetes that has reached epidemic levels in many Latin American countries. The main consequence of the nutrition transition has been a predominance of diet-related chronic diseases and increases in weight. Further studies on growth in early life will be important, especially in developing countries, which are experiencing such a transition and which is likely to be associated with increases in the occurrence of overweight/obesity, particularly among the socially vulnerable.


Uterine artery pseudoaneurysm is an uncommon cause of secondary postpartum hemorrhage, although it carries a high mortality rate. The etiology includes vascular trauma during cesarean section, vaginal delivery, curettage or hysterotomy. We present a post-cesarean female who developed delayed hemorrhage and was diagnosed with left uterine artery pseudoaneurysm. Selective transcatheter arterial embolization was performed and the pseudoaneurysm was successfully obliterated. Angiographic embolization is a safe and efficient method of treatment of postpartum hemorrhage due to pseudoaneurysm in hemodynamically stable patients. Thus, it should be considered as a treatment option before opting for surgery in favorable cases. Pseudoaneurysm is anextra-luminal collection of blood which is contained by the adventitia or surrounding perivascular soft tissue. It communicates with the flowing arterial blood through a defect in the arterial wall. It causes recurrent hemorrhage when it connects with the uterine cavity . The absDiagnosis is based on both Doppler sonography and arteriography . TranscaA 26-year-old gravida 1 para 1 was transferred to our institution 32 days post-partum with symptoms of excessive bleeding per vagina. She had undergone an emergency c-section for prolonged second stage. Intraoperatively there was an extended tear at the left side, 3 cm downwards to the bladder base, which was secured. She was apparently asymptomatic for seven days post operation. She later developed excessive bleeding per vagina and was readmitted twice on Day 8 and Day 25 post-cesarean section and was managed by suction and curettage on both admission and tissues sent to pathology. Histopathological examination results, however, showed no evidence of retained pregnancy products. The patient presented again with excessive bleeding per vagina on Day 32 post-cesarean section. She had a healed Pfannenstiel scar, bulky and soft uterus, and the cervical os was closed. Her hemoglobin level was 7.4g/dl. She was stabilized with crystalloids, four units packed red blood cells, and started on broad-spectrum antibiotics.Transabdominal ultrasonography revealed a postpartum uterus with blood clots within the uterine cavity. Hypoechoic lesion seen at the left wall of uterus and color flow Doppler sonography showed swirls of colors, which represents the opening of the pseudoaneurysm and its supplying artery Figure . Pelvic To preserve the fertility of this young patient, a transcatheter arterial embolization of this pseudoaneurysm was planned. She underwent digital subtraction angiography. Arteriography revealed a pseudoaneurysm from the terminal part of the left uterine artery, in addition, the left uterine artery was tortuous Figure , 3B. ThePostpartum hemorrhage is a leading factor in maternal mortality and morbidity in developing countries. Secondary postpartum hemorrhage is excessive bleeding from 24 hours after delivery, up to six weeks postpartum. Causes include retained products of conception, endometritis, and placental bed subinvolution, pseudoaneurysm of uterine artery, arteriovenous malformations, and choriocarcinoma .On ultrasound, pseudoaneurysms appear as an anechoic sac which shows turbulent arterial flow on Doppler. Doppler demonstrates to-and-fro sign in the neck of the pseudoaneurysm and yin-yang sign in the body of the pseudoaneurysm which is pathognomonic of pseudoaneurysm with a narrow neck. During systole, with higher arterial pressure, there is an influx of blood into the pseudoaneurysm. In diastole, the pressure in the artery drops and blood flows back through the pseudoaneurysm neck. This Doppler sign at the neck of the pseudoaneurysm together with turbulent flow helps to confirm the diagnosis .Precise diagnosis of vascular causes of delayed postpartum hemorrhage helps to avoid unnecessary curettage for suspected retained products of conception and may avoid life-threatening blood loss. With the introduction of latest imaging modalities, the diagnosis of uterine artery pseudoaneurysm has become effortless . UltrasoIn 1979, Brown, et al. reported the first successful case of selective arterial embolization for treatment in an extra-uterine pelvic hematoma after three failed surgical attempts. Since then, arterial embolization has been used widely to control postpartum bleeding with the success rate following embolization around 97% . In a stFor a woman with unexplained vaginal bleeding after C-section delivery, pseudoaneurysms are potentially life-threatening complications and should be considered in the differential diagnosis of secondary postpartum hemorrhage. Angiographic embolization should be considered as a treatment option before resorting to surgery in these cases.


To compare fertility-sparing therapies including oral progestogens, hysteroscopic resection (HR), and the levonorgestrel- releasing intrauterine system (LNG-IUS) in achieving disease regression, recurrence and live birth rate in well differentiate early-stage endometrial carcinoma (eEC) and complex atypical hyperplasia(CAH).This was a meta-analysis of previous studies focus on the fertility-sparing therapy for well differentiate early-stage endometrial carcinoma (eEC) and complex atypical hyperplasia (CAH).Medline, the Cochrane Library and Embase was searched with the terms and Synonyms: words similar to eEC and CAH with therapies associated with fertility-sparing.The number of all patients accepted fertility sparing therapies, patients got regressed, relapsed and delivered were extracted from each study, and the regression, recurrence, and live birth rate of each study were calculated. The regression, recurrence and live birth rates between each two interventions were compared with the aid of meta-regression in packages of “meta” and ”meta for” written in R.P < 0.0001) and live birth rate  and a lower recurrence rate compared with oral progestogens alone (4.79% vs 32.17% P = 0.0004). At the same time, the pooled live birth rate (52.57% vs 18.09% P =0.0399) of HR followed by progestogens are significantly higher than the LNG-IUS alone. Which no statistical difference in regression  and recurrence rates (4.79% vs 3.90% P = 0.8561) was seen.Fifty-four studies reported fertility sparing therapies in young women with eEC and CAH were included. Meta-analysis showed that HR followed by progestogens achieved a higher pooled regression (98.06% vs 77.20% Of the available fertility-sparing therapeutic options, HR followed by progestogens may be a more effective one. Endometrial carcinoma (EC), the most common malignancy of the female genital tract, and complex atypical hyperplasia (CAH), its precursor lesion, most frequently affects peri- and post-menopausal women. It is reported that the incidence of EC among women 40 years or younger comprised 14.4% of all patients diagnosed with EC between 1976–1983 , but in The electronic search identified 2047 citations in Medline, the Cochrane Library and Embase. Of these, 1919 were excluded as the title and abstracts not meet the inclusion criteria. One hundred and twenty-eight publications were obtained, and another 74 were excluded for not meeting the inclusion criteria after thorough reading of the paper. In the final analysis, 54 articles , 10–62 wP < 0.0001)  though without statistical sense   with or without another methods such as progestogens or GnRH agonist showed a pooled regression, recurrence and live birth rate of 98.06% , 4.79% , and 52.57% , respectively. Studies focusing on oral progestogens alone found a pooled regression, recurrence and live birth rate of 77.20% , 32.17% , and 33.38 % , respectively. Meta-analysis showed that HR with or without progestogens achieved a statistical significantly higher pooled regression rate (P = 0.0399) (See P = 0.4098) (See P = 0.8561) , 3.90%  and 18.09% , respectively. The pooled live birth rate (399) See  for eEC 098) See  and recu561) See  rate bet561) See .P = 0.0417) and a relatively lower recurrence rate (P = 0.0044) but no difference in live birth rates (P = 0.7247) when treated with oral progestogens , 27.34%  and 32.28% , respectively. A pooled regression, recurrence and live birth rate of 88.74% , 9.20%  and 28.74 % , respectively, was achieved in patients with CAH who were treated with oral progestogens only. Compared to those with eEC, women with CAH achieved a statistically significant higher regression , and another recent meta-analysis showed a response rate of 72% (95% CI 62–80%) [The overall complete response rate for both eEC and CAH ranges from 62.5 to 89% , 53, 64. 62–80%) . It is r 62–80%) . A poole 62–80%) .The recurrence rates for eEC and CAH in Gallos’ meta-analysis was 40.6% and 26%, respectively . A lowerP = 0.03). A higher regression rate  was also seen in a randomized, multicenter study carried out by Orbo et al. [P = 0.0010) for LNG-IUS compared to oral progestogens. This is similar to a study by Kim et al. [The LNG-IUS acts on the progesterone receptors in the endometrium directly, thus the concentration of progesterone has been found to be much higher in the endometrial mucosa . Studieso et al. . Similarm et al.  in whichm et al. .P = 0.0001). The live birth rate is 18.09% without significant difference with oral progestogens (P = 0.1242)See  suggestiHysteroscopic resection (HR) as a fertility-sparing treatment for eEC and CAH is less frequently used. Most articles report on HR followed by oral progestogens or GnRH agonists. A recent updated meta-analysis reported the regression rates of hormones only, surgery only, and hormones and surgery combined as 49.6% (111/224), 75% (3/4), and 100% (3/3), respectively . The supHR consisted of three steps: excluding the lesion areas, the nearly endometrium and the myometrium under the lesion , 32, 71.The standard therapy for women with eEC and CAH still TH and BSO, so definite surgery is strongly suggested once a persisted or progression disease was found or after finishing delivery. We extracted the patients who undergone definite surgery and the final pathology. A total of 381 patients accepted standard therapy of which 37 patients (9.7%) showed no residual lesion, while persistent disease was seen in 219 women (57.5%). Unfortunately, ninety patients (23.6%) were diagnosed with progression when TH and BSO was operated and 6.5% (25) women with concurrent ovarian cancer. A recent study aimed at the EC developing risk between young women with CAH accepted fertility-sparing therapy and primary hysterectomy, finding that fertility-sparing therapy delays the occurrence of EC without increasing its risk . The incThe limitations of this study take into account the publications on which they were based. Publication bias exists due to possible overestimation of reported success rates. Insufficient studies on HR and LNG-IUS is another defect. Many of these reports are retrospective and include small sample sizes with limited follow up. Although fertility-sparing therapy does appear to be effective for women with eEC and CAH, with satisfactory regression and live birth rates, the recurrence rate is still concerning. Close, long-term surveillance should be performed.In conclusion, hysteroscopic resection followed by progestin as fertility-sparing therapy may be a more effective option for women with CAH or EC. Further studies are needed to evaluate HR with or without hormonal therapy or a LNG_IUS, as well as the combination of LNG-IUS and oral .The population of interest is young women aged 44 years or younger with early stage  Grade 1 EC or CAH, who underwent fertility-sparing therapy including MA and MPA, the LNG-IUS, and hysteroscopic resection(HR) followed by progestogens. The outcome of interest was incidence of disease regression, recurrence and live birth . We searched Medline, the Cochrane Library and Embase (from January 1950 to December 2016) with the following Medical Subject Headings (MeSH) and text words: i) Words with sense of EC: “cancer” or “carcinoma” or “adenocarcinoma” or “malignant” or “neoplasm” AND “endometrial” or “endometrium” or “corpus uteri”. ii) Words with a similar meaning to CAH: “precancer” or “precursor” or “premalignant” or “precancerous” or “atypical hyperplasia” AND “endometrial” or “endometrium” or “corpus uteri”. iii) Therapies associated with fertility-sparing treatment: “fertility sparing” or “fertility preserve” or “fertility preserving” or “fertility preservation” or “conservative” or “hysteroscopic resection” or “GnRH analogue” or “hormone therapy” or “progesterone” or “progestin” or “levonorgestrel-releasing intrauterine system”. The following words were used to generate a subset of citations “humans and female” “age between 19–44 years old” and “language in Chinese and English”.Inclusion criteria were defined as: 1) Women between 19 and 44 years old;2) patients who desire fertility; 3) diagnosis of stage I grade I EC or CAH ; 4) treatment with fertility-sparing therapy and 5) articles written in English and Chinese. Exclusion criteria consisted of: 1) Women aged 45 or older; 2) those who underwent conservative treatment due to high perioperative risks; 3) patients with greater than stage IA disease(invading deep myometrium or distant metastasis) or pathology other than endometrioid adenocarcinoma; 4) patients with simple hyperplasia or complex hyperplasia without atypia; 5) case reports and small studies with fewer than five patients; 6) articles written in languages other than English and Chinese; 7) data was unable to be extracted.Studies were selected in two stages. Firstly, the titles and abstracts of the articles searched from Medline, the Cochrane Library and Embase were independently assessed by two reviewers. Secondly, full articles meeting the inclusion criteria according to the first step were obtained and evaluated. Any disagreements about inclusions were arbitrated by a third reviewer. Two reviewers performed the quality assessment and adhered to the Methodological Index for Non- Randomized Studies (MINORS), a widely accepted tool used to assess the quality of the included studies .Disease regression was defined as eEC or CAH returned to normal endometrium or hyplasia without atypical during follow-up. Disease recurrence was defined as eEC or CAH reoccurred during follow-up in patients initially showed disease regression. Live births was the birth of healthy infants during the follow-up period, and its rate was calculated as the number of women who gave birth of healthy infants divided by the number of women accepted fertility-sparing therapy and wanted to pregnant immediately. We defined appropriate follow-up time to be at least 5 years.Q test and I2 test [After data extraction, regression, recurrence and live birth rates were calculated separately. Both a fixed and random effects model was used to obtain pooled rates . Heterog I2 test . The for I2 test . The reg I2 test .