Birth registration remains limited in most low and middle-income countries. We investigated which characteristics of birth registration facilities might determine caregivers’ decisions to register children in Ethiopia.We conducted a discrete choice experiment in randomly selected households in Addis Ababa and the Southern Nations, Nationalities, and People’s Region. We interviewed caregivers of children 0–5 years old. We asked participants to make eight choices between pairs of hypothetical registration facilities. These facilities were characterised by six attributes selected through a literature review and consultations with local stakeholders. Levels of these attributes were assigned at random using a fractional design. We analysed the choice data using mixed logit models that account for heterogeneity in preferences across respondents. We calculated respondents’ willingness to pay to access registration facilities with specific attributes. We analysed all data separately by place of residence .Seven hundred and five respondents made 5614 choices. They exhibited preferences for registration facilities that charged lower fees for birth certificates, that required shorter waiting time to complete procedures and that were located closer to their residence. Respondents preferred registration facilities that were open on weekends, and where they could complete procedures in a single visit. In urban areas, respondents also favoured registration facilities that remained open for extended hours on weekdays, and where the presence of only one of the parents was required for registration. There was significant heterogeneity between respondents in the utility derived from several attributes of registration facilities. Willingness to pay for access to registration facilities with particular attributes was larger in urban than rural areas.In these regions of Ethiopia, changes to the operating schedule of registration facilities and to application procedures might help improve registration rates. Discrete choice experiments can help orient initiatives aimed at improving birth registration. Birth registration is incomplete in most low and lower-middle income countries.This limits access to rights, protections and services for children.It also prevents the establishment of reliable vital statistics about fertility and mortality.In two regions of Ethiopia, there were important barriers to birth registration related to costs, distances and wait times.Caregivers of young children also expressed strong preferences for registration facilities that had convenient opening schedules , and delivered birth certificates in a single visit.In urban areas, only requiring one of the parents to be present at the time of registration might also help improve registration rates.Interventions that modify the opening schedule of registration facilities, as well as registration procedures, might complement current initiatives to improve birth registration.Discrete choice experiments have the potential to help inform the development of birth registration systems in low and middle-income countries.Birth registration is the process of recording a child’s birth in governmental registers or databases. It is necessary to establish a birth certificate, which gives each child a number of rights and protections.3 6 7The coverage of birth registration varies greatly throughout the world.8–10Reaching universal birth registration in low income and lower-middle income countries (LLMIC) has recently become a key objective of LMICgovernments and various global actors.Improving the coverage of birth registration in LMICs also requires stimulating the demand for, and removing barriers to, birth registration among local populations, particularly in settings where significant numbers of births occur at home. This is so because CRVS systems are predominantly ‘passive’: the caregiver(s) of a child must contact a CRVS agent to report the occurrence of the birth and complete the required paperwork.We investigated the preferences of caregivers for the registration of births in two regions of Ethiopia, a country with some of the lowest birth registration rates worldwide.This study is part of Performance Monitoring for Action (PMA), a multicountry project that collects survey data on key health indicators.27 28Several months after the sixth round of PMA data collection (‘R6 survey’ thereafter), we conducted a follow-up study of birth registration (‘Birth registration study’ thereafter) in two regions: Addis Ababa and Southern Nations, Nationalities, and People’s Region SNNPR; . Addis A15In Ethiopia, the Vital Events Registration and National Identification proclamation of 2012 (revised in 2017) is the law that regulates the administrative process of birth registration. The federal Vital Events Registration Agency (VERA) was established in 2014 to oversee this process. The implementation of civil registration (including births) under the new law began nationwide in 2016.29Health facilities, as well as health extension workers who routinely visit households, are expected to produce notification forms for births. These forms contain information about the child . They do not replace the forms and certificates that must be obtained from the registration offices located in each kebele, that is, the lowest administrative unit in the country.There are more than 18 000 kebeles in Ethiopia, the large majority of which now offer birth registration services.Birth registration is free in Ethiopia, but families might be charged a fee to obtain their child’s birth certificate, with the amount of the fee set by each administrative region. Birth registration is mandatory and should be accomplished within 90 days of birth. After that delay, penalties might be incurred but are rarely enforced in practice. The parents of a child must both be present at the registration office, and they must show their identification card to register the birth of their child. If one or both parents cannot be present to register a birth, additional procedures  are required to allow the available parent, or a guardian, to carry out birth registration.For the birth registration study that included the DCE, we selected a subset of households that had participated in the R6 survey. The R6 survey was conducted in June and July 2018. It used a two-stage cluster design, with urban-rural and administrative regions as strata. In the first stage, 44 EAs were selected in the SNNPR, and 22 EAs in Addis Ababa. Urban EAs were oversampled in the SNNPR. In the second stage, 35 households were selected at random within each EA. In total, 1617 households in the SNNPR, and 761 households in Addis Ababa, participated in the R6 survey.Households were eligible for the birth registration study if they had a child aged 0–5 years among their members. We revisited selected households between December 2018 and March 2019. At that time, we confirmed the presence of children 0–5 years old using a household roster. We determined which household member was the primary caregiver of each listed child, that is, the parent or legal guardian. We selected study participants among adult caregivers. If there was only one primary caregiver in the household, he/she was automatically selected. If there were multiple primary caregivers in a household, we selected one at random. Households in three rural EAs in SNNPR could not be included due to security reasons.The birth registration study consisted of a face-to-face interview with selected caregivers. In addition to the DCE module, the questionnaire ascertained a caregiver’s demographic characteristics, his/her knowledge of birth registration, the registration status of the children he/she cares for and exposure to messages stressing the need to register births.The DCE was designed to estimate the relative value that caregivers assign to attributes of birth registration facilities in considering whether and where to register their child(ren). We first conducted a review of the literature on the barriers to birth registration in LMICs. The protocol of this review is provided in 10.1136/bmjgh-2019-002209.supp1Supplementary dataThis process yielded six DCE attributes : (1) theThere were 324 potential combinations of the attributes and levels described in 34 35In addition, the DCE included two practice choice sets, during which interviewers demonstrated DCE procedures, verified respondents’ understanding of DCE procedures and addressed questions. We also added a choice set that contained a ‘dominant’ alternative, that is, one of the two hypothetical facilities was preferable to the other facility on all attributes.19 20 37We determined the sample size of the birth registration study to estimate indicators of CRVS coverage with a desired level of precision. For analyses of DCE data, given large differences between urban and rural areas in (A) characteristics of respondents, and (B) accessibility and equipment of kebele offices, we sought to elicit caregivers’ preferences separately by place of residence. According to formulas of the statistical power of DCEs,We administered the questionnaire with Open Data Kit, a data collection platform frequently used in LMICs.We built automated quality checks into the DCE module. We flagged instances where a respondent opted out , or selected the same facility , in each choice set. Field supervisors were alerted to those occurrences and were asked to provide feedback to interviewers. In some cases, they revisited respondents for verification and corrections, if needed.2 tests.We tabulated the characteristics of caregivers, by place of residence . These included descriptions of their gender, age group, educational level, marital status and religion. We also included an assessment of their household wealth based on ownership of assets. This variable was constructed from R6 survey data, with methods similar to those used in Demographic and Health Surveys.U that a DCE respondent r derives from selecting alternative i in a choice set t was specified as:Our analyses of DCE data relied on the assumption that caregivers are rational actors, who make choices that maximise their individual utility.βr is a vector of coefficients that represent the marginal utility that respondents derive from each level of these attributes (their ‘preferences’); and εr, i, t is an unobserved error term that is assumed to be independent of individual preferences and attribute levels.i among a set of J alternatives in a choice set is described by a logit modelwhere b, and a term DCE data have often been analysed using conditional logit models,b) and their SDs, along with 95% CIs. We also tested the null hypothesis that all SDs were jointly equal to 0 (likelihood ratio test).In our models, the Despite the stratified sampling scheme of the R6 survey, we report unweighted analyses of DCE data. We do so because our analyses were stratified by urban versus rural place of residence, which were the main domains for which estimates were sought in the R6 survey. In addition, the survey weights are not related to the dependent variable in our mixed logit models . Unweighted estimates are thus unbiased and more efficient than weighted estimates.47To further understand respondents’ preferences for various attributes of registration facilities, we conducted a willingness-to-pay (WTP) analysis. We divided the coefficient of each variable obtained using mixed logit models by minus one times the coefficient associated with registration costs.We selected 840 caregivers for the birth registration study and 715 consent to participate (response rate=85.1%). Among those, 705 completed the DCE section of the interview. Four hundred and fifty-nine DCE respondents resided in urban areas 65.1%,  versus 2In urban areas, approximately 4 out of 10 respondents resided in Addis Ababa . All rural respondents resided in the SNNPR. There were large differences in background characteristics by place of residence. Urban respondents were younger, more educated and often members of wealthier households than rural residents. Only 10.9% of urban respondents (50/459) had never been to school versus 49.6% of rural respondents (122/246). Similarly, more than two-thirds of urban respondents resided in a household that belonged to the wealthiest quintile of the Ethiopian population , whereas this was the case for <1% of rural respondents . A larger proportion of urban respondents had ever heard messages about birth registration (49.9% vs 16.7%). DCE participants were predominantly women , who were currently married .Participants failed to complete 26 of the 5640 total DCE choices they were asked to make (0.45%). Among valid DCE answers, respondents opted out of the choice between the two hypothetical facilities 726 out of 5614 times (12.9%).This proportion was slightly higher in rural areas  than in urban areas . Two-thirds of respondents never opted out of the choice they were asked to make . This proportion was higher among urban respondents than among rural respondents (69.5% vs 61.4%). Only six respondents (0.85%) opted out of every choice. Among those, five resided in urban areas and one resided in rural areas. In the choice set with a dominant option, 656 respondents selected the objectively most desirable registration facility . There were no differences in the likelihood of selecting the dominant option between urban and rural respondents .The parameter estimates for the effects of registration facility attributes on utility are shown in β=−0.130 in urban areas, and β=−0.127 in rural areas), or were located further away from their residence . They preferred facilities that completed all registration procedures and delivered birth certificates in a single visit  and facilities that were open on weekends .In both urban and rural areas, respondents were less likely to select facilities that had longer waiting times . However, the disutility resulting from higher costs was larger in rural areas. Respondents in urban areas expressed preferences for facilities that were open for extended hours on weekdays (β=0.205), and that only required one of the parents to be present for registration (β=0.427). Respondents in rural areas did not display similar preferences in their choices.Higher costs of birth certificates negatively affected the utility of caregivers in both urban and rural areas  in a population-based sample. The DCE confirmed the existence of significant barriers to birth registration in these two regions. DCE participants were less likely to opt for registration facilities that were further away from their homes, that had longer wait times to obtain services and/or that charged a fee for the acquisition of the birth certificate. This is consistent with findings from other studies that have investigated barriers to birth registration in other settings, using an array of other methodologies.49 50We found strong preferences for registration facilities that deliver a birth certificate in a single registration visit. The current CRVS policy in Ethiopia requires that the administrative facilities implementing birth registration deliver the birth certificate immediately to the parents/caregivers. However, in our survey, more than a third of caregivers who had registered the birth of their child reported having to return to the registration facility several times to complete that process. More consistently implementing the current policy might help improve registration rates.DCE respondents in urban areas also preferred registration facilities that only required one of the two parents to be present at the time of registration. The main procedure outlined by the current legal framework in Ethiopia however requires both parents to be present at the registration facility in order to register a birth. This might constitute a barrier to birth registration, as also indicated by prior studies that have investigated reasons reported by caregivers for not registering a birth in other settings.Our study highlighted other characteristics of registration facilities that might play a key role in the registration-related behaviours of caregivers. In particular, choices were influenced by the opening schedule of the facility: DCE participants expressed consistent preferences for registration facilities that remained opened on weekends. In urban areas, they also expressed preferences for facilities that remained opened for extended hours on weekdays. This might be because the current opening schedule of registration facilities conflicts with work schedules or with times during which economic activities of caregivers are ongoing.There were differences in the preferences revealed by the DCE between residents of urban and rural areas. In particular, the effects of costs on patterns of choices were larger in rural areas than in urban areas. This is likely due to the fact that rural residents were much poorer than urban residents. As a result, WTP estimates were lower in rural areas. For example, caregivers in urban areas were willing to pay more than 55 birr  to access a registration facility that was opened on weekends, whereas caregivers in rural areas were willing to incur only half of that implicit price (27.02 birr or US$0.99).Our DCE has several limitations. First, we only investigated the main effects of each attribute of registration facilities, without considering potential interactions between attributes. This is problematic because the effects of an attribute might depend on the levels of another: for example, facilities that remain open on weekends might be particularly attractive in settings where both parents are required to be present at the time of registration, because it is more likely that both parents will be available on weekends. Investigating interactions between attributes would however require respondents to make a larger number of choices during the DCE than we deemed feasible in this setting.51Second, due to limited sample sizes, we only investigated whether preferences for birth registration varied between urban and rural areas. We did not investigate whether preferences varied across other subgroups, for example, by poverty or educational level. In urban areas, we also did not investigate whether preferences varied between Addis Ababa and the smaller cities of the SNNPR. Third, we only presented DCE respondents with choices that were characterised by a limited set of attributes. Other aspects of the registration facilities/process might affect registration choices, for example, whether the registration office is located in an administrative setting or in a healthcare setting.Fourth, some of the choice patterns in our DCE indicated that some respondents might not have fully understood the choices they were asked to make, or experienced fatigue. A small fraction of the respondents consistently opted out of the choices they were presented (<1%); whereas others (6.7%) failed to select the objectively most appealing alternative in a dominant choice set. However, these proportions were consistent with the experience of other high-quality DCEs,10.1136/bmjgh-2019-002209.supp2Supplementary dataFifth, the caregivers we interviewed were in large majority women (>96%). However, as for other services , men likely play important roles in the decision process about birth registration, in particular in settings where their presence is required for registration. Future studies should thus ensure that men are included in DCEs designed to elicit preferences towards birth registration. Sixth, our statistical analyses of DCE data made several assumptions that might have impacted our results. For example, we used mixed logit models to represent heterogeneity in preferences within the population. Other recent work has used latent class models to represent such heterogeneity.34Finally, our work was limited to two regions of Ethiopia, and thus does not represent the preferences of residents of other regions of the country where birth registration is also low. Furthermore, Ethiopia is a country where birth registration has only recently been reorganised and implemented nationwide. Preferences for birth registration might differ in countries with higher background rates of event registration .Despite these limitations, our work indicates several strategies that might help further accelerate the scale-up of birth registration in Addis Ababa and in the SNNPR. It appears warranted to explore whether altering the opening schedule of registration facilities to allow evening and weekend openings might help improve birth registration rates. This is feasible within the current legislative framework for birth registration in Ethiopia and could thus be tested during a cluster-randomised trial in those two regions. Such a change might stimulate the demand for birth registration and complement initiatives that aim to strengthen and streamline the administrative systems that implement civil registration.


There was a fast improvement of twin's birth outcomes in the past decade, but it was average in developing countries. Stillbirth, preterm birth, low birth weight, and birth asphyxia are the major contributors to poor twin birth outcomes. This study was crucial to address the gaps and clarify the outcome of twin delivery.  To assess the birth outcome of twin delivery and associated factors among newborns who were delivered in Dessie Referral Hospital, Ethiopia, 2019. p value < 0.20 in bivariable logistic regression analysis were considered for multivariable logistic regression analysis; adjusted odds ratio with 95% confidence interval was used to measure the association variable with p value < 0.05 which was statistically significant.  Institutional-based retrospective cross-sectional study was employed among 385 maternal records from Nov 10/2013 to Dec 10/2019. Data were selected by using a random sampling technique. Frequencies, proportion, and summary statics were used to describe the study population. The data were entered into Epi Info and exported in the SPSS version 20 for analysis. All variables with Conclusions and Recommendations. Magnitude of twins' adverse birth outcome was 23.4%. Hypertension disorder, rural residence, PROM, and no ANC follow-up were significant variables for twins' adverse birth outcome. Therefore, all healthcare providers should give sustainable educations and instructions about the importance of sticking with the recommended ANC follow-up. This finding showed that the prevalence of twin birth outcome accounts 23.4% . Low birth weight 9.1%, stillbirth 4.2%, Apgar score < 7 9.1%, and neonatal death 1 % were accounted. Hypertension disorder ), rural residence (95% CI 2.46(1.39–4.37)), PROM (95% CI 6.39(2.52–16.16)), and no ANC follow-up ) were significantly associated with adverse twin birth.  Twin birth is a type of multiple births when the mother gives birth to two offspring from the same pregnancy. It can be either dizygotic or monozygotic. Twin pregnancies are risks during pregnancy, labour, and delivery as well as during postnatal period as the result of preterm delivery, antepartum haemorrhrage, chronic disease, and postpartum haemorrhage . AdverseIn Ethiopia, National Reproductive Health Strategy adopted in Ethiopia showed that increased number of midwives and surgeon prepare health center with basic obstetric and new born equipments, equip all hospitals to deliver comprehensive obstetric and new born care, improve antinatal care and promote institutional delivery, ensure availability of medicine, postpartum and new born care, improve referral and health care financing systems to expand positive birth outcome during labour delivery , 4.Twin pregnancy is among the obstetric conditions with accounts of 2 to 4% of total births, with a prevalence ranging from 0.9 to 2.4% in Brazil. It is one of the increasing risks of perinatal mortality, a well predictable factor. Twin pregnancy is negative impact from a complex interaction of genetic and environmental determinants occurring in approximately 2–4% of live births and remarkably rates are highest in some parts of Africa, especially in Ethiopia, where health care is not well established. However, its prevalence increased more than 70% globally in the last three decades mainly in high- and middle-income countries , 5, 6.Adverse birth outcomes among twin deliveries, such as prematurity, low birth weight, and birth defects, represent significant problems in both developing countries. Each year, about 15 million babies in the world, more than one in 10 births, are born too prematurely –9. More Adverse birth outcome for twin delivery is a critical health issue in developing countries such as Ethiopia. It resulted in many bad consequences, neonatal and infant morbidity and mortality. More than a million of them die immediately after birth; many others suffer from lifelong physical, neurological, or educational disabilities. According to Ethiopian Demographic and Health Survey in 2016, there were high rates of twin prenatal mortality during parturition period. From the total deliveries, thirty-three deaths per 1000 live births were reported –15.There are factors to increase the negative birth outcome of twin delivery; from these, some of them are associated with increased maternal age, primiparity, low birth weight, chronic disease, low ANC follow-up, and PROM , 17.Twin pregnancy has increased the rate of obstetric and perinatal complications such as preterm labour, preachalasia, and postpartum haemorrhage, and therefore, the aim of this study is to assess the adverse birth outcome of twin deliveries and its determinant factor, the birth outcome in Dessie Referral Hospital during the study period.The study was conducted from Nov 10–Dec 10, 2019, in Dessie Referral Hospital which is located in Amhara region, Ethiopia, 401 km far from the capital city of Addis Ababa. Based on 2007 Ethiopian Census conducted by Central Statistical Agency, Dessie has the total population of 250,536. Of them, 117,060 are men and 78,242 are women . Dessie Institutional-based retrospective cross-sectional study design was employed among 385 maternal records from Nov 10/2013 to Dec 10/2019.The source of population of this study was total twin delivery records of Dessie Referral Hospital from November 10/2013 to December 10/2019.The study population of this research was all-twin delivery recorded in Dessie Referral Hospital from September 01/2013 to September /01/2019. Maternal medical record sheet was used to review this study in 6 years recorde sheet before the study period.The study included all twin deliveries recorded from September 01/2013–September 01/2019.Twin deliveries were recorded with incomplete recorded information sheets.n = minimum sample size, z (a/2) = desired level of confidence interval 95% (1.96) P=50% proportion rate, and d = margin of error 5% (0.05). The total sample size becomes n = 384.The sample was calculated by using single population formula, 95% confidence interval, and 5% margin of error and proportion rate of 50% of adverse twin birth outcome rateThe eligible record was selected by the investigator and the health management information system (HMIS) focal person of Dessie Referral Hospital before data collection. The records were selected by using simple random sampling technique (lottery method) to gather the exact sample size. From September 2013–September 2019, the total deliveries of Dessie Referral Hospital were 24561. Among them, 748 were twins; therefore, by using the simple random sampling method, 384 maternal records were selected to conduct this research.Pretest was performed at Borumeda Hospital and structured checklist was developed after reviewing relevant literatures. The checklist was designed to obtain relevant information on the predictor variables such as demographic, obstetric, maternal complication, intervention, and component of modified WHO partograph The conditions of the baby such as Apgar score were assessed and Apgar score = 7 was considered as satisfactory by this study . Five miDependent variables were twin birth outcomes.(1) Demographic Factors. Age, gravidity, parity, and residence.(2) Obstetric Factors. NC history, mode of delivery, gestational age at onset if labour, outcome of delivery, and sex of the new born.(3) Partograph-Related Factors. Quality of the partograph , time of action line closed, and time of action taken based on the partograph result.For data collectors and supervisors, 1 and a halve day training was given about data collection system. The data collectors were supervised by a supervisor daily and reported to the principal investigator every day; before the actual data collection, the checklist was pretested on 5% of the sample size, which are 20 maternal medical records in Borumeda Hospital, after that unclear questioners were revised, and the actual questioner was prepared in English and translated into Amharic and then translated back into English to check the exact adjustment of the questioner.All checklists were checked for their completeness and consistency, and double data entry was made using Epi Info 7 software. Then, the data were exported into SPSS version 20 for analysis.Frequencies, proportion, tables, and summary statistics were used to describe the study population in relation to the relevant variable.Bivariable analysis was carried out and the variable with P value less than 0.20 was titled to multivariable logistic regression significantly associated with twin birth outcome. Finally, adjusted odds ratio with its 95% confidence interval was used to measure the association variable with P value less than 0.05 statistical associations.Ethical clearance was obtained from the review committee of Wollo University, College of Health and Medical Science. The permission and agreement consent were obtained from Dessie Referral Hospital before starting of the study. Mandatory information was collected by the trained data collector with keeping the confidentiality of the maternal medical history.In this study, a total of 385 study participants/maternal record were involved. From the total number of maternal records, mean age was 29.78 with Std. deviation of ±6.53. Regarding the sex of fetus, 195 (50.6%) were female. Majority of respondents, 371 (96.4%) of the study participants, were married. From the total records, 131 (34.0%) of participants, were Muslim religion followers and regarding residence, more than half (58.2%) of the participant residence was rural .This finding showed that only 34 (8.8%) respondents have intact membrane status. Majority of mothers have regular ANC follow-up, 369 (95.8%). Regarding gestational age at onset of labour, 327 (84.9%) of mothers were found between weeks of 37–42. Majority of the mothers about previous index pregnancy were good 306(79.5%). Regarding bleeding disorder during pregnancy and after delivery, APH accounts for 18 (4.7%) and 11 (2.9%) were affected by PPH, respectively .About two-third of respondents, 263 (68.3%), have got action according to line. Based on WHO partograph standard ,311(80.8) did not fulfill the partograph recording criteria. Almost three-fifth, 313 (81.3%), of the respondents' duration of labour were normal based on the partograph standard.Out of 385 participants, 90 (23.4%)  of them have adverse birth outcome of twins while the remaining 295 (76.6%) had good birth outcome. From the total finding, low birth weight 35(9.1%), still birth 16 (4.2%), Apgar score < 7 35 (9.1), and neonatal death 1% were accounted .Bivariable analysis result showed that hypertension disorder, residence, age, ANC, membrane status, APH, and PPH were significantly associated with adverse birth outcome.In multivariable analysis, hypertension disorder, residence, PROM, and regular ANC follow-up were identified to be significantly associated with adverse birth outcome.Mothers who had hypertension disorder were ) six times more likely to develop adverse birth outcomes compared to mothers who had no hypertension disorder. Mothers who come from rural areas were two times more likely to develop adverse birth outcome as compared to mothers who come from urban areas ). Mothers who follow ANC regularly were thirteen times more likely to have adverse birth outcome as compared to their counterpart ((AOR = 13.4795% C (2.49–72.85)).Mothers who had normal membrane status were six times more likely to develop adverse birth outcome as compared to mothers who had normal membrane status ) .The findings of this study showed that adverse birth outcome of twin's delivery was nearly one-fourth (23.4%) . Low birth wt. 9.1%, still birth 4.2%, Apgar score < 7 9.1%, and neonatal death 1 % were accounted. Among factors, hypertension disorder, rural residence, PROM, and no ANC follow-up were identified to be significantly associated with adverse birth outcome. The prevalence of adverse birth outcome in this study is in line with the result of the studies conducted in Hosanna (24.5%) , but theIn this study, mothers who had hypertension disorder were six times more likely to be associated with adverse birth outcome as compared to mothers who had no hypertension disorder. This finding was in line with other studies done in Hawasa  and low-Mothers who come from rural areas were two times more likely to be associated with adverse birth outcome as compared to mothers who come from urban areas. This might be due to the different educational level and in-depth of knowledge of the patient, it is clearly known that living in rural areas lead to decrease in exposure to information that is unable to understand the disease process and effect of adverse outcome. The finding of this study vary with study conducted in Suhul Shire Hospital. This difference is due sociodemographic characteristics of the participants . The varMothers who do not have regular ANC follow-up were thirty times more likely to have adverse birth outcome as compared to their counterpart; this finding was in line with the study done in Gonder University  and HawaThis finding showed that the mothers becoming PROM neonatal outcome were six times more likely to be associated with adverse birth outcome as compared to mothers who had normal membrane status, the finding of this study was a similar study done in Suhul Hospital Shire . The rea


We evaluated the incidence and factors associated with PGF among preterm infants managed at a rural hospital in Uganda.Prematurity is the leading cause of mortality in children under 5 years of age globally and is also frequently associated with postnatal growth failure (PGF). Although most preterm births occur in low resource settings, little is known about their postnatal growth outcomes especially in rural areasRetrospective cohort study of preterm infants discharged from Kiwoko Hospital neonatal intensive care unit (NICU) from July 2017 to June 2018. Inclusion criteria included gestational age 26 up to but not including 37 weeks, admission within 24 h of birth and at least 7 days hospital stay. Exclusion criteria included major congenital anomalies and missing gestational age or birth weight. Birth and discharge weights from clinical notes were plotted on Fenton 2013 growth charts. Gestation age was determined by last normal menstruation period (LNMP), extracted from the mother’s antenatal card or early obstetric ultrasound scan reports. Postnatal growth failure was diagnosed if discharge weight was less than the 10th percentile for estimated gestational age. Other data from the clinical notes included demographic characteristics, neonatal morbidities as assigned by the attending physician and infant feeding practices. Multivariable logistic regression was used to explore factors associated with PGF.A total of 349 preterm infants with a mean gestational age of 31 (range 26 to 36) weeks were included. The incidence proportion of PGF was 254/349 (73%). Factors significantly associated with postnatal growth failure included: delayed initiation of enteral feeds , sepsis , multiple gestation  and male gender [AOR = 1.71 95% (CI 1.01 to 2.91)].Nearly three quarters of preterm infants managed at a rural hospital in Uganda had postnatal growth failure. Delayed initiation of enteral feeds and sepsis were highly associated with postnatal growth failure. Enteral feeds should be initiated as soon as possible in these infants to reduce early protein deficits and hence postnatal growth failure. Preterm birth is increasing worldwide, with 60% of these births occurring in middle to low income countries of South Asia and Sub-Saharan Africa. In Uganda, preterm infants make up 14% of all live births and Uganda ranks at 13th out of 184 countries in rates of preterm births  growth lEarly growth deficits amongst preterm infants results from protein and energy deficits after birth  and are We evaluated the incidence and factors associated with postnatal growth failure amongst preterm infants managed at Kiwoko Hospital- a rural district hospital in central Uganda.This was a retrospective cohort study using in-patient records of preterm infants for a 1 year period .The study was carried out at Kiwoko Hospital, a rural faith-based hospital in Nakaseke district. The neonatal unit opened in 2001 and is supported by Adara Development an international non-governmental organisation. The unit is well-established and recognised in Uganda as a centre of excellence in newborn care. Services are offered at subsided prices to mainly three rural districts of central Uganda; Nakaseke, Luwero, Nakasongola as well as a few cases from other surrounding districts. With an official bed capacity of 38, the unit admits over 100 neonates per month, 1200 per year of which prematurity accounts for 40% of admissions. It is run by a paediatrician supported by one medical officer and a team of nurses. Unit resources include constant electricity, incubators, radiant warmers, intermittent pulse oximetry, phototherapy, intravenous pumps, and continuous positive airway pressure (CPAP). The neonate: nurse ratio per shift is on average 5:1.On admission to the unit, maternal and infant demographic data are recorded on a specified admission sheet by the admitting nurse who also takes anthropometric measurements. Weights are taken using Seca weighing scales with the infants fully undressed. Gestational age is estimated mostly by LNMP from the mother’s antenatal card, few by first trimester scan and rarely Ballard score done by the admitting doctor. Further assessement is done by both the admitting and unit doctor who makes a clinical diagnosis and recommends appropriate investigations and treatment.For all infants, intravenous fluids with 10% dextrose at 80-100 ml/kg/day are initiated on admission and electrolytes added on day 3. Each infant is reviewed on a daily basis by the unit doctors and a decisions is made on when to start enteral feeds. Expressed breast milk (EBM) is given initially at 10 - 20 ml/kg/day and increased gradually by 10 - 20 ml/kg/d depending on tolerance by the infant as well as the availability of the milk by the mother. Preterm formula is rarely used when mataernal human milk will not be available. There is no donor milk at the facility. For very low birth weight (VLBW) preterm infants feeding is done by nasogastric tube (NGT). More mature and stable infants may feed via cup or at the breast as soon as possible. For breast feeding infants, fluids are stopped once the neonate is breast feeding well and the mother has enough breast milk. For those feeding by cup or nasogastric tube fluids are stopped once the infant can tolerate 15 ml per feed or 150 ml/kg/day whichever comes first. The mother works closely with the nurses on duty to ensure she gives the prescribed feeds and report any feeds intolerence. This information is recorded in a specified feeds monitoring chart kept in the patients’ file and is reviewed daily by the clinician. Neither fortification of human milk nor total parenteral feeding is available at the unit.Weights are taken on alternate days and feeds are adjusted according to the weight once the neonate starts gaining weight. Supplementation with multivitamins (Grovit drops) and iron (Haemoforte syrup) is started once the neonate is on full enteral feeds. The VLBW and extremely low birth weight (ELBW) infants are discharged once they attain 1.5 kg, with no recorded apneic spells in the past 5 days and have stable vitals in a cot. On discharge, their corrected gestation in weeks, discharge weight and head circumference are recorded.Files of discharged preterm infants are stored in the records department and data on demographics and clinical variables stored electronically for quality improvement use.Neonates with a gestation age between 26 and 36 completed weeks and 6 days  who were admitted to the unit within 24 h of life and spent 7 or more days in hospital were included into the study. Preterms with major congenital abnormalities and those with missing birth weight or recorded gestation age were excluded from the study. The former were excluded as they were expected to have PGF from other abnormalities.Perinatal factors: Date and time of birth, date of admission, estimated gestational age at birth , birth weight, sex, discharge weight. Preterm infants were classified as: extremely preterm (< 28 weeks), very preterm (28 to 32 weeks) and moderate to late preterm (> 32 to < 37 weeks) [Using a structured and pretested data collection tool, we obtained demographic, nutritional and clinical data relevant to the study from patient files that fulfilled the inclusion criteria. This information included: 1) rm 28 to 2 weeks aMorbidity during hospitalization: Need for CPAP, sepsis or necrotizing enterocolitis (NEC) and oxygen requirement after 28 days. These were diagnoses made by the attending clinician and extracted from patient files. Maternal characteristics: Age, parity, morbidities like hypertension (HTN) and HIV sero status. 2) Need for CPAP. Preterm infants with a respiratory severity score of 5 and above (using the Silverman-Anderson score) were started on CPAP. Chest X-rays are not routinely performed. CPAP is the treatment modality used for RDS at the unit sincce surfactant and ventilators are not available.Sepsis: Clinical diagnosis with abnormal axillary temperature (> 38.5° or < 36 °C), fast respirations (above 60 breaths per minute) with refusal to breastfeed or new apnoea/ oxygen requirement in one who was previously stable and in the absence of anaemia. Blood cultures are not available.PDA: A continuous murmur most prominent at the upper left sterna border in a preterm infant with significant cardiovascular compromise .NEC: Increased gastric residues/ emesis/ bloody stools with abdominal distention, unstable vitals  plus or minus abnormal abdominal radiographs.Apnea: Cessation of breathing for 20 s or longer, or a shorter respiratory pause associated with bradycardia and desaturations.Anaemia: Haemoglobin count of < 8 g/dL if asymptomatic and off oxygen, < 10g/dL if on oxygen, or < 12g/dL if having apnoeas.Definitions of neonatal morbidities in this study were as follows;) Nutrition information: Dates and time of initiating enteral feeds, any documented feeds intolerance (increased gastric residue with or without vomiting of feeds) and date of attaining full enteral feeds. Delayed initiation of enteral feeding in this study was if feeds were started after 48 h of life.3Birth and discharge weight for each preterm were plotted on Fenton growth charts 2013 , 10 and Statistical data analysis was done using STATA version 14 . Continuous data were expressed as mean and standard deviation if normally distributed, median and interquartile range if non-normal. Categorical data were expressed as frequencies and proportions. We used Chi square and Fischer’s Exact test to test for presence of association between PGF and the categorical independent variables. The Student’s t- test was used for normally distributed continuous variables and Mann-Whitney U test for those with a skewed distribution.The cumulative incidence of PGF among preterm infants was determined as the number of new cases of PGF out of the total number of infants at risk in the sample.p-value of less than 0.25 at bivariable analysis and those with biological plausability including gestational age and maternal morbidities (HIV and hypertension) were inserted into a multivariable logistic model. Hosmer-Lemeshow test was used to test the goodness of fit for the model. Adjusted odds ratios and their 95% confidence intervals were obtained to assess for strength of association and the level of significance was set at 5%.We used binary logistic regression to find out the association between the independent variables with PGF. Factors that achieved a A total of 494 preterms were admitted to the unit from July 2017 to June 2018. Of these 130 didn’t meet the inclusion criteria and 15 had exclusion criteria. This left a total of 349 preterm infants with a mean gestational age of 31 (range 26 to 36) weeks that were eligible and these were included into the study. The 130 preterm infants who did not meet inclusion criteria included 40 pretems who died within the first week of life, 88 who were discharged before 7 days of life and 2 was was transferred to other units. The 15 preterm infants meeting the exclusion criteria included 5 who had congenital abnormalities, 7 with missing records of gestation age or birth weight, 2 admitted at 2 weeks of age and 1 who was born to a diabetic mother.One hundred eighty eight preterm infants were female (53.9%). Majority were moderate to late preterms 167 (47.9%) and very preterm 168 (48.1%). The median length of hospital stay was 14 days (interquatile range (IQR) =23). Majority of the mothers were aged 20–24 (33%), 106 (30.5%) mothers had a parity of one and the prevalence of HIV among the mothers was 8.3%  with 121/349 (34.7%) requiring CPAP and 47/349 (13.5%) were managed for sepsis. Enteral feeds were initiated within the first 48 h in 80.1% of these preterm infants (Table In this study 73% 254/349) preterm infants had PGF at discharge Fig.  and the 54/349 prFactors associated with PGF at bivariable analysis are shown in Table We evaluated the incidence of and factors associated with PGF in hospitalized preterm infants in a neonatal care unit in a rural population in Uganda. We found a very high incidence of PGF- 73% of the preterm infants were below the 10th percentile for weight at discharge. PGF was not only found in the extremely preterm infants but also in the moderate to late preterms. The findings are consistent with other studies that show that PGF is common in hospitalized preterm infants worldwide. Kumar et al. in a prospective observational study in a level III NICU at a tertiary care teaching hospital in India found the incidence of PGF to be 64.8% from a study population of 111 preterm infants . In AfriPoor post-natal growth  is primarily due to inadequate nutritional intake . This eaThis study showed that delayed initiation of enteral feeds that is after 48 h of life was 3.7 times more associated with PGF compared to when feeds were started within the first 48 h of life. A South African study on growth of 92 extremely low birth weight preterm infants at a tertiary hospital also found that being kept nil per os beyond the first day of life was significantly associated with poor growth . EarlierAlthough the American Academy of Paediatrics suggests that postnatal growth in preterms should mimic their intrauterine foetal growth rates at the same estimated gestational age, this growth trajectory was not reflected in this study population. Embleton et al. in 2001 related this growth lag to the cumulative energy and protein deficits that occur in the postnatal period . It takeIn this study, preterm infants with sepsis were 6.76 more times likely to have PGF compared to those without sepsis. Being ill increases the basal metabolic requirements and yet the sick preterms are in most cases fed less due to concerns of  instability and ability to digest feeds. This creates protein and energy deficits consequently leading to poor growth as has been reported by Bertino et al. 2006 in Italy, Lee et al. 2018 in Korea, and Mabhandi et al. 2019 in South Africa , 12, 18.The incidence of PGF has been shown in some studies to increase as gestational age and birth weight decrease because smaller preterm infants lose more weight and take longer to regain it. Also as gestation age decreases, nutritional requirements increase and achieving satisfactory growth rate become less likely , 19. In This study had a number of limitations. Given that it was a retrospective chart review, there was missing information from the files that resulted in some patient files being excluded from the study. Weight measurements are subject to errors and some may been incorrectly done leading to misclassification. LNMP was the most commonly used method for estimating gestational age in this population and is less precise than a first trimester ultra sound scan. We were unable to quantify the actual nutrition intake for these preterms using patient files.The major strength of this study was the good quality data, carefully recorded weights and patient information in a reasonably well organized model neonatal unit in rural Uganda that enabled us to compile this data and report an important topic. To our knowledge, this was the first study in Uganda to investigate PGF among preterm infants.Nearly three quarters of preterm infants managed at a rural hospital in Uganda had postnatal growth failure. Initiating enteral feeds after 48 h of life and sepsis during hospitalization were significantly associated with PGF. Enteral feeds should be initiated as soon as possible in these infants to reduce early protein deficits and hence postnatal growth failure.


Background: Amino acid (AA) metabolic patterns have emerged as an analytical technique to characterize biomarkers compromising normal growth and elucidate underlying nutritional exposure. This study aimed to identify AA metabolites most likely associated with poor growth and examine the association between AA metabolites and nutrition regimens in preterm infants during transition from parenteral nutrition (PN) to enteral nutrition (EN), using gas chromatography-mass spectrometry (GC-MS).Methods: This observational cohort study was conducted in infants born at <32 weeks' gestation with birth weight of <1,500 g. The outcome of extrauterine growth retardation (EUGR) based on whether the weight was <10th percentile for post-menstrual age, was evaluated when full EN reached. Samples were collected at four sampling points according to nutritional status. AA profiles in dried sampling point spots (DBS) were quantified using GC-MS; and were compared simultaneously. The correlation of AA concentration with growth and nutritional parameters was examined using multivariate analysis.Results: We identified 40 eligible infants: 20 in the EUGR group and 20 in the non-EUGR group. AA deficiency progressively emerged during the transition. Lower concentrations of four AAs, including citrulline (Cit), were associated with increased risk of EUGR when adjusted for gestational age, birth weight z-score, age when trophic EN was started, as well as average energy and protein intakes in synchronous nutritional period. Moreover, a lower Cit concentration was positively correlated with the compromised protein and energy deficits in EN during early transition.Conclusion: A low Cit concentration during transition from PN to full EN should be noticed by the clinician to more closely examine nutrition practices to prevent EUGR. Preterm infants are at a high risk of extrauterine growth retardation (EUGR) in the early months of life, and this is significantly associated with adverse neurodevelopmental outcomes during childhood –3. ProteAA concentrations are biomarkers of protein metabolism, and examining their patterns in preterm infants may disclose metabolic changes associated with particular conditions , 13. To https://www.clinicaltrials.gov/ (NCT03100305). The exclusion criteria were as follows: infants with major or digestive congenital anomalies, infants with BW of ≥1.5 kg, and infants who transferred from the NICU before reaching total EN. GA was estimated based on obstetric records obtained during early-pregnancy ultrasound. Body weight was measured three times weekly using an electronic digital scale. The EUGR group was defined as infants with body weight below the 10th percentile for postmenstrual age, as plotted on the 2013 Fenton growth curves, when total EN is stable.This prospective observational study was conducted in preterm infants born at <32 weeks' gestation and with BW of <1,500 g, and admitted to the neonatal intensive care unit (NICU) of Xinhua Hospital from December 2016 to 2017. The protocol was approved by the medical ethics committee of Xinhua Hospital, which is affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-2016-139), and was registered on Individualized PN was prescribed daily by nutritionists depending on infant metabolic status and medical criteria, validated by pharmacists, and prepared by nurses at the pharmacy department following good manufacturing practices. Guidelines for nutrition support in neonates in China (2013) were used in the neonatal unit. PN initiation was recommended within 24 h of birth at 80 ml/kg/d and increased by 20 ml/kg/d as infusion, containing dextrose infusion at a rate of 4–8 mg/kg/min; amino acids infusion  initiated at 1.5–2 g/kg/d, and increased at a rate of 0.5–1.g/kg/d to the goal of 3.5–4.0 g/kg/d; and lipid infusion  initiated at 1 g/kg/d, increased at a rate of 0.5–1 g/kg/d to the goal of 3 g/kg/d. Since daily PN was only available after 15:00, some newborns could not receive individualized PN within 24 h after birth.Enteral feeding was initiated when the baby showed tolerance as soon as possible after birth. The mean human milk content was assumed to be 68 kcal/dL with 1.5 g/dL of protein. Various infant formula compositions provided by the manufacturers were listed in Sampling pointSamples were collected dynamically at four sampling points:Sampling point 1: within 24 h after birth;Sampling point 2: when stable PN reached and before EN started, AA infusion in PN increased to the goal of 3.5–4.0 g/kg/d or be stable for 2–3 days;Sampling point 3: EN energy intake reached 50% of the total energy intake;Sampling point 4: full intestinal feeding was reached.Then the nutrition regimens were divided into three phases from PN to EN based on the sampling point: (1) Phase 1: the total PN phase, which started from sampling point 1–2, (2) Phase 2: the early nutrition transitional phase, which started from sampling point 2–3, (3) Phase 3: the later nutrition transitional phase, which started from sampling point 3–4.AA profiles were collected from the infants' heels as spots, which were dried at room temperature, stored at −20°C, and quantified using gas chromatography-mass spectrometry (GC-MS) with the Waters Xevo-TQ. The AA profiles included essential amino-acid (EAA): threonine (Thr) arginine (Arg), methionine (Met), phenylalanine (Phe), leucine (Leu), tryptophan (Trp) and valine , as well as non-essential amino-acid (NEAA): citrulline (Cit), tyrosine (Tyr), proline (Pro), alanine (Ala), aspartic acid (Asp), glutamine (Gln), glutamate (Glu), glycine (Gly), histidine (His), ornithine (Orn), and serine (Ser). The internal isotope standard for tandem mass spectrometry was NSK-A from Cambridge Isotope Laboratories.Data for each eligible infant were collected: antenatal characteristics including steroid administration, preeclampsia, diabetes, and thyroid abnormalities; delivery history including sex, BW and its z-score, GA, Apgar score at 1 and 5 min; and clinical factors such as bronchopulmonary dysplasia , sepsis (confirmed by positive sampling point or urine culture), and severe intraventricular hemorrhage , and pulmonary hypertension (PH).t-test or Mann-Whitney U-test was conducted for continuous variables, and the chi-square test was used for categorical variables. Spearman correlation was administered to reveal the association between AAs concentration with nutritional parameters. Multivariate regression analysis was used to validate the independent association of the AA concentrations with the risk of EUGR, and the nutritional parameters. Statistical significance was assumed at p < 0.05. Variables that reached statistical significance on univariate analysis for EUGR were included in the model.The SPSS 22.0  was performed as Statistical analysis. The normality analysis was used with Shapiro-Wilk test. The A total of 44 preterm infants with a BW of <1,500 g and a GA of <32 weeks were consecutively selected for this registered observational cohort study. We excluded four small-for-gestational-age (SGA) infants with a BW < the 10th percentile. Finally, this study included 20 infants in the EUGR group and 20 infants in the non-EUGR group .p < 0.05), even though there was no difference in gestational age and birth weight. There were no significant differences in sex, multiple birth, antenatal steroid use, complications of maternal pregnancy, and delivery history between groups. Postnatal age and actual weight of infants at sampling points 2, 3, and 4 were comparable between the two groups. Moreover, there was no significant difference in incidences of BPD, severe IVH, PH, and sepsis between both groups. The demographics and clinical factors are summarized in A distinctive difference in birth weight z-score was observed between both groups. Infants in the EUGR group had lower birth weight z-score than those in the non-EUGR group, with statistically significant difference . Besides, there were no significant differences in age when PN was started, in average intakes of AAs, or in energy in PN at all three phases .Spearman analysis showed a positive correlation between the Cit level at sampling point 3 and average energy intake . Given a power of 0.80 and a two-tailed alpha error probability of 0.05, 15 infants in each group is necessary to obtain significant difference between the two groups.This study described the AA metabolomic profiles of preterm infants during different nutritional phases. Based on the findings, concentrations of Cit and Thr at sampling point 3 and Met and Pro at sampling point 4 were compromised in the EUGR group and were associated with a higher risk for EUGR when full EN started. Furthermore, a deficiency in Cit concentration at sampling point 3 was positively correlated with energy deficit and, protein deficit in EN during the early transitional phase.Due to immaturity and intolerance, most preterm infants are indicated for initial PN and subsequent enteral feedings which are frequently interrupted. To examine the association between AA metabolic patterns and nutrition regimens during the nutritional transition, we used neonatal data by nutritional phases as described by Miller et al. , but ratIn this study, there was no significant difference in AA patterns at birth between the two groups, except for Thr, which was higher at sampling point 1 and had lower concentration in the EUGR group at sampling points 3 and 4.The high Thr level after birth soon may be related to mother' metabolic condition, It hadn't been reported before that Thr was higher after birth in EUGR infants yet. Moreover, threonine kinetics studies indicated a high obligatory visceral need for threonine, presumably for the purposes of synthesis . The higPrevious studies have raised concerns about the effect of AAs on growth and development, but such effect remains inconsistent and undefined. In this study, the multivariate regression analysis showed the correlation of lower concentrations of Cit and Thr at sampling point 3 as well as Met and Phe at sampling point 4 with the high risk of EUGR after adjusted for GA, birth weight z-score, age when trophic EN was started, as well as average energy and protein intakes in synchronous nutritional period. Of particular interest was Cit and Thr at sampling point 3, which occurred ahead of sampling point 4 and could effectively predict EUGR in advance. Animal studies have raised concerns about the effect of hyperthreoninemia on the developing brain, however, its effect on growth is blurry. Neonatal Cit administration would enhance growth and prevent the metabolic consequences of intrauterine growth retardation through an “imprinting” effect on the liver lipidome and fat metabolism , 26. We Our study has some limitations. First, it has a observational design. However, to better examine the associations between metabolism, growth, and contemporaneous nutrition regimens, we defined EUGR as weight below the 10th percentile, when total EN is stable, rather than discharge commonly used. Second, time frames for growth rates were not included in this study. Lastly, although there were no differences in major medical conditions between the two groups, all nutritional phases may not have been excluded uniformly, creating a potential bias. No consensus exists for a normative AA profile in preterm infants, which may be related to the different immaturity, clinical status, and nutritional support and the like. Studies have revealed a dynamic fluctuation in AA patterns, but it is not yet to determine whether it is physiological or not. Previous studies have revealed different factors that influenced the AA profiles, including mothers' condition, GA, BW, age of sampling, and disease status, etc. More studies are needed to further reveal the metabolism of AAs in preterm infants.In conclusion, we found that a lower Cit concentration during the transitional phase was associated with an increased likelihood of EUGR in infants, and positively correlated with contemporaneous nutrition intake. It should prompt the clinician involved in neonatal nutrition management to more closely examine nutrition practices to prevent the incidence of EUGR. More aggressive PN management during the early transitional phase could be encouraged to minimize nutrient deficit. Furthermore, the follow-up study is necessary about AA metabolic patterns on the long-term growth and development.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the medical ethics committee of Xinhua Hospital, which is affiliated to Shanghai Jiao Tong University School of Medicine (XHEC-2016-139). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.ZH, YW, and LH contributed to the conception and design of the research. DL, LW, and HS contributed to the acquisition of the specimen and data. LW contributed to the analysis, and interpretation of the data. All authors drafted the manuscript, critically revised the manuscript, agreed to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Mage = 11.75, SD = 1.27) were recruited to complete three self-reported questionnaires. The results showed that compromising thinking predicted decisional forgiveness but not emotional forgiveness. Furthermore, self-esteem was identified to moderate the conditional effects of compromising thinking on decisional and emotional forgiveness. These findings advance a better understanding of the construct and mechanism of forgiveness, which can provide insights for targeted forgiveness interventions among early adolescents, such as compromising thinking instructions and self-esteem enhancement programs.Forgiveness contributes to positive social relationships, which is critical for individual development, particularly for early adolescents. Most previous studies focused on the unique roles of cognitive factors  and personality traits  in the process of developing forgiveness. However, sporadic research has examined their interactive effect on forgiveness from an integrated perspective. Given that forgiveness has been categorized into decisional and emotional forgiveness, this study aimed to examine the effects of compromising thinking on two types of forgiveness, and the moderating effects of self-esteem on the association between compromising thinking and forgiveness among early adolescents. A total of 1,009 Chinese primary and secondary school students (50.4% males;  Early adolescence is a developmental period in which social relationships become increasingly important and complex , and intdecisional forgiveness and emotional forgiveness. The former refers to the behavioral intention to resist an unforgiving stance and to respond differently toward a transgressor; the latter refers to reduction of unforgiving-related negative emotions and replacement with positive prosocial emotions. These two processes have an essential distinction and interactively explain the process of forgiveness , and/or there may be reciprocity  . In thisH1a: Compromising thinking is positively associated with decisional forgiveness.H1b: Compromising thinking is positively associated with emotional forgiveness.Despite the potential role compromising thinking plays in explaining the process of forgiveness, the extent of association may vary with individual differences, such as how an individual feels about and interprets a situation after experiencing a transgression . As statSpecific to transgression contexts, people with low self-esteem feel insecure and have low self-confidence and fragile self-worth; they also show high interpersonal sensitivity and possibly treat being offended as a threat to self-worth . After eIn contrast, people with high self-esteem have stable self-cognition and are less influenced by the external environment ; they arH2a: Self-esteem moderates the effect of compromising thinking on decisional forgiveness. That is, compromising thinking has a stronger association with decisional forgiveness with high self-esteem compared with those with low self-esteem.H2b: Self-esteem moderates the effect of compromising thinking on emotional forgiveness. That is, compromising thinking has a stronger association with emotional forgiveness with those who have high self-esteem compared with those with low self-esteem.By reviewing the existing literature, cognitive factors and personality traits have been argued to interactively influence the process of forgiveness . CompromM = 11.75, SD = 1.27). Participants consisted of 24.7% fourth graders, 33.0% fifth graders, 24.2% sixth graders, 13.1% seventh graders, and 5.0% eighth graders.Participants were 1,009 students  who were recruited from two ordinary primary and secondary schools in Beijing, China, with an age range from 10 to 15 years . This process helped to clarify the words, statements, and instructions that were fit for students, especially for those in lower grades, which could avoid possible result bias . Studentstrongly disagree) to 7 (strongly agree). Higher scores indicated higher tendencies to engage in compromising thinking. The results of confirmatory factor analysis (CFA) supported the one-dimension construct validity, chi-square values, χ2 (4) = 47.75, the comparative fit index (CFI) = 0.97, the Tucker-Lewis fit index (TLI) = 0.93, the root mean square error of approximation (RMSEA) = 0.10, and the standardized root-mean-square residual (SRMR) = 0.03. Validity evidence showed moderate correlations with relevant measures such as the Global Style Scale and the Rahim Organizational Conflict Inventory–II , with higher scores indicating higher levels of self-esteem. The results of CFA showed that the validity of this scale was acceptable, χ2 (28) = 114.88, CFI = 0.99, TLI = 0.98, RMSEA = 0.06, SRMR = 0.03. The scale was moderately correlated with the scale of assessing self-consistency and congruency , with higher scores indicating higher tendencies to engage in decisional and emotional forgiveness. The results of CFA supported the two-dimension construct validity of the Decisional Forgiveness Scale, χ2 (17) = 137.48, CFI = 0.96, TLI = 0.93, RMSEA = 0.08, SRMR = 0.05, and the Emotional Forgiveness Scale, χ2 (16) = 119.17, CFI = 0.96, TLI = 0.93, RMSEA = 0.08, SRMR = 0.06. The Decisional and Emotional Forgiveness Scales were both strongly correlated with other measures of interpersonal forgiveness, trait, and state forgiveness  in Mplus 7.1. Moreover, the missing data were handled by maximum likelihood (ML) estimates in the analyses. The model fit was evaluated by χodel fit .Means, standard deviations, and Pearson correlations for all variables are presented in 2 (4) = 11.00, CFI = 0.99, TLI = 0.97, RMSEA = 0.04, SRMR = 0.02. The model indicated that compromising thinking positively predicted decisional forgiveness  but failed to predict emotional forgiveness (p = 0.89 > 0.05) after controlling for the effect of age. The finding indicated compromising thinking was associated with decisional forgiveness but not with emotional forgiveness, supporting H1a, but not supporting H1b.Compromising thinking and self-esteem can be handled as manifest variables because they have a one-dimensional and homogeneous construct. Decisional and emotional forgiveness have multiple dimensions, they thus can be parceled as latent variables according to subordinated dimensions in SEM analyses . To test2 (8) = 23.93, CFI = 0.98, TLI = 0.94, RMSEA = 0.05, SRMR = 0.02. As shown in In regard to the hypotheses of self-esteem , the moderating model had a good model fit, χM + SD; Low = M−SD) on the basis of the levels of the moderator. As shown in To further clarify the essence of the interaction effect, a simple slope analysis was conducted. Specifically, participants were divided into two counterparts  and personality traits  on decisional and emotional forgiveness among primary and secondary school students. Based on a large sample of early adolescents, the results revealed slightly negative correlations between age and two types of forgiveness. Furthermore, compromising thinking positively predicted decisional forgiveness, but it did not directly predict emotional forgiveness. More importantly, the conditional predictions were moderated by individual difference in self-esteem. In sum, these findings contribute to further understanding of the construct and mechanism of forgiveness within Chinese contexts, which can lend credence to prosocial development interventions among young people.r = 0.06) was so small that it can be nearly negligible (This study showed weak and negative correlations between age and decisional forgiveness/emotional forgiveness among primary and secondary school students. The negative relation was consistent with the findings among fourth, seventh, and ninth grader samples . Althouggligible . Future The results showed that compromising thinking positively predicted decisional forgiveness after the effect of age was controlled, consistent with the previous research . InfluenFurthermore, self-esteem moderated the effect of compromising thinking on decisional forgiveness. That is, compromising thinking did not predict decisional forgiveness among early adolescents with low self-esteem, but it positively predicted decisional forgiveness among early adolescents with high self-esteem. Consistent with the previous research, the role of social-cognitive factors in predicting forgiveness strengthened with increased self-esteem . Early aAlthough compromising thinking did not directly predict emotional forgiveness after the effect of age was controlled, self-esteem moderated the association between compromising thinking and emotional forgiveness. That is, compromising thinking negatively predicted decisional forgiveness among early adolescents with low self-esteem, whereas it positively predicted decisional forgiveness among early adolescents with high self-esteem. As stated earlier, self-esteem to some extent influences the perceptions of external and subsequent behaviors . In turnIn contrast, early adolescents with high self-esteem have sufficient psychological resources; they may appraise the incident as a challenge for self-enhancement and believe in prosocial changes as a way of spirituality-shaping and personal growth . In thisSeveral limitations of this study should be noted. First, a cross-sectional design cannot make causal inferences; thus, future researchers might use an experimental design to further examine its effect on forgiveness. For example, compromising thinking can be primed by relevant materials , and forDespite these limitations, several theoretical and practical implications of this study should be noted. This study found a slightly negative relationship between age and forgiveness, which complements the previous research that mainly focused on adolescence and adulthood. Moreover, this study was, to date, the first piece of research to examine the effects of compromising thinking on decisional and emotional forgiveness, and the moderating effects of self-esteem on the association. On the one hand, these findings supported the unique and distinct constructs of forgiveness . On the In regards to targeted forgiveness interventions for early adolescents, compromising thinking can be improved by naïve dialecticism training, which may be instrumental in reconciling non-constructive cognitions and alleviate non-adaptive emotions, thereby further avoiding social conflicts, fostering forgiveness, reducing somatic symptoms, and increasing psychological well-being . To be sThe datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by the Academic Ethics Committee of the Faculty of Psychology at Beijing Normal University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.WH and R-DL designed the study, analyzed the data, and drafted the manuscript. WH, YD, and TO revised the manuscript. XF, RJ, and SJ collected the data. All co-authors participated in the discussion of the results.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Observational studies have identified associations between periodontitis and adverse pregnancy outcomes, but randomised controlled trials evaluating the efficacy of periodontal therapy have yielded inconsistent results. Few studies have explored relationships between gingival inflammation and these outcomes or been conducted in rural, low-income communities, where confounding risk factors differ from other settings.We conducted a community-based, prospective cohort study with the aim of estimating associations between the extent of gingival inflammation in pregnant women and incidence of preterm birth in rural Nepal. Our primary exposure was gingival inflammation, defined as bleeding on probing (BOP) ≥10%, stratified by BOP <30% and BOP ≥30%. A secondary exposure, mild periodontitis, was defined as ≥2 interproximal sites with probing depth (PD) ≥4 mm (different teeth) or one site with PD ≥5 mm. Our primary outcome was preterm birth (<37 weeks gestation). We used Poisson regression to model this relationship, adjusting for potential confounders.Of 1394 participants, 554 (39.7%) had gingival inflammation, 54 (3.9%) mild periodontitis and 197 (14.1%) delivered preterm. In the adjusted regression model, increasing extent of gingival inflammation was associated with a non-significant increase in risk of preterm birth (BOP ≥30% vs no BOP: adjusted relative risk (aRR) 1.37, 95% CI: 0.81 to 2.32). A secondary analysis, stratifying participants by when in pregnancy their oral health status was assessed, showed an association between gingival inflammation and preterm birth among women examined in their first trimester , but not later in pregnancy .Gingival inflammation in women examined early in pregnancy and poor oral hygiene behaviours were risk factors for preterm birth. Future studies should evaluate community-based oral health interventions that specifically target gingival inflammation, delivered early in or before pregnancy, on preterm birth.NCT01177111.Nepal Oil Massage Study,  This study collected data through a large, community-based, prospective cohort in a rural, low-resource setting.The study population had low prevalence of some established confounders of the relationship of interest, which are common in other populations.Some clinical periodontal measures were not collected due to visit time constraints, for example, recession on interproximal sites or gingival index score.Preterm birth classification was based on maternal self-report of last menstrual period instead of the gold standard, ultrasound examination.Annually, 2.5 million babies die prior to 28 days of life, and preterm birth is the leading cause of these deaths.3Porphyromonas gingivalis.7 8Periodontal disease includes several inflammatory conditions, typically initiated by oral bacteria, beginning with reversible accumulation of plaque and inflammation of gingival tissue (gingivitis) and progressing to irreversible breakdown of the supportive tissues of the teeth and tooth loss (periodontitis).Periodontal disease in pregnant women has been associated with preterm birth and other adverse pregnancy outcomes.20Alternatively, the observed relationship between periodontal disease in pregnant women and adverse pregnancy outcomes could be the result of unmeasured and uncontrolled confounding factors. Previously described confounders of this relationship, which are commonly controlled for in studies, include age, smoking, multiple birth, previous adverse pregnancy outcomes, ethnicity and socioeconomic factors.21Few studies have evaluated whether gingival inflammation is associated with risk of preterm birth or other adverse pregnancy outcomes. Further, studies of this association have been nearly universally facility-based, whether in high-income or low-income settings. Understanding this relationship from a population-based perspective in low resource communities can offer certain benefits from an epidemiological perspective. Many populations in LMICs have lower prevalence of important confounding factors of this relationship, such as smoking, alcohol use and chronic diseases . Community-based studies can avoid selection bias associated with hospital-based studies, particularly in populations where home delivery remains common, as is the case in much of South Asia. Given these potential benefits, we conducted a community-based, prospective cohort study to estimate the association between gingival inflammation and preterm birth among women in a rural community in the Terai (plains) region of Nepal.NCT01177111), which was actively enrolling a population-based sample of pregnant women in this study area.We conducted a community-based, prospective cohort study of maternal gingival inflammation and adverse pregnancy outcomes across nine village development committees in Sarlahi District, Nepal. Eligible participants included married pregnant women between the ages of 15 and 40 who were <26 weeks gestation at the time of enrolment. Participants were identified and determined eligible between January and November 2016 using the infrastructure of a large community-based randomised trial of topical applications for newborn massage, the Nepal Oil Massage Study (NOMS)  at the Department of Dentistry, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. We estimated the validity of probing depth (PD) measurements of the auxiliary nurse midwives relative to the dentist (NKA), finding per cent agreement, weighted kappa scores and intraclass correlation coefficients, with an allowance of PD ±1 mm, exceeded 99%, 0.7 and 0.9, respectively.22Auxiliary nurse midwives used portable dental equipment to conduct a full mouth examination. Periodontal measurements were made using a colour Williams probe . PD was measured on six sites per tooth , and the cemento-enamel junction to gingival margin (CEJ-GM) distance was measured on two sites per tooth , excluding third molars. Presence or absence of bleeding on probing (BOP) was recorded for any buccal or lingual probing site of each tooth. PD values were recorded in millimetres rounded to the next higher whole number. CEJ-GM distances were recorded similarly. If the free gingiva was coronal to the CEJ, the CEJ-GM measurement was recorded as 0. Clinical attachment loss (CAL) was calculated by summing PD and CEJ-GM distances.Our primary exposure definition, gingival inflammation, was defined according to a classification scheme developed by the American Academy of Periodontology (AAP) and European Federation of Periodontology to update the 1999 classification of periodontal diseases and conditions.24–29We defined secondary exposure definitions for mild and moderate periodontitis based on a modified version of Centers for Disease Control and AAP updated 2012 case definitions for population-based surveillance of periodontitis.31Gestational age was calculated using the last menstrual period (LMP) method as recalled by the mother at 5-weekly pregnancy surveillance home visits. Our 5-weekly pregnancy surveillance approach has several benefits, including short recall (≤5 weeks) and pregnancy testing, as compared with traditional LMP approaches, which often rely on LMP recall later in pregnancy or at time of delivery. Preterm birth was defined as a live birth or stillbirth <37 completed weeks of gestation at the time of delivery.Bivariate analyses between participant characteristics and the outcome, preterm birth, were evaluated using t-tests and Poisson regression for continuous and binary and categorical variables, respectively. We calculated unadjusted relative risks and adjusted relative risks (RR and aRR) of preterm birth and associated 95% CIs using Poisson regression with robust variance, which was used due to occurrence of convergence issues with other regression methods. Given our sample size (n=1394) and assuming a power of 80%, type I error of 0.05, and our pre-study estimates of population prevalence of preterm birth (17%) and gingival inflammation (40%), we estimated that we could detect a relative risk of preterm birth of roughly >1.5.Multivariable models were constructed by sequentially adding groups of covariates, including maternal characteristics, oral hygiene behaviours and socioeconomic factors. Covariates associated with preterm birth at the p<0.10 level in bivariate analyses were considered in these regression models. Additional variables, known through previous studies to be confounders of the periodontal disease and preterm birth relationship, were also included in regression models .In an effort to remove a possibly attenuating effect of including cases of transient pregnancy-induced gingival inflammation, we examined the relationship stratified by timing of the oral exam. Women were categorised into two trimester groups (<13 weeks and ≥13 to <26 weeks gestation). Similar to the primary analysis, for each trimester group we calculated aRR of preterm birth and associated 95% CIs using Poisson regression with robust variance.All statistical analyses were performed in Stata 14.2 . All participants provided written consent for this study.There was no patient or public involvement in this study.Between 11 January 2016 and 26 November 2016, among 2821 pregnancies in the study area, 2291 (81.2%) participants were identified by the parent trial as eligible for enrolment (<26 weeks gestation) . Among eBirth outcomes for the 1474 women followed until the end of pregnancy were recorded as 1345 single live births, 14 twin live births, 33 single stillbirths, 1 twin stillbirth, 1 set of twins where 1 was live born and 1 stillborn, 74 miscarriages and 6 abortions. As our primary outcome was preterm birth, pregnancy was selected as the unit of analysis . There were 1394 total pregnancies for analysis, of which 197 (14.1%) were preterm. Preterm deliveries included 163 (11.7%) moderate preterm (<37 to ≥32 weeks), 27 (1.9%) very preterm (<32 to ≥28 weeks) and 7 (0.5%) extremely preterm (<28 weeks). Over three-quarters of participants  were full-term (≥37 weeks) and 144 (10.3%) were post-term (≥42 weeks).Baseline demographic, periodontal, oral hygiene and dental healthcare seeking characteristics of participants by extent of gingival inflammation were previously reported.According to our definition, 554 (39.7%) participants had gingival inflammation and 840 (60.3%) were healthy . Of thosSeveral poor oral hygiene behaviours were associated with increased risk of preterm birth, including extended teeth cleaning time  and use of a non-traditional dentifrice  . Teeth cleaning episodes per week  was associated with decreased risk of preterm birth. Risk of preterm birth increased with a dose response pattern for women who practiced multiple poor oral hygiene behaviours, defined as extended cleaning time per episode (≥5 min), infrequent cleaning episodes (<7 times per week) and use of a traditional dentifrice. Incidence of preterm birth was 17/208 (8.2%) for women with no poor behaviours, 155/1098 (14.1%) for women with one and 25/88 (28.4%) for those with two.Incidence of preterm birth by periodontal status was 113/840 (13.5%) for health and 84/554 (15.2%) for gingival inflammation. Incidence of preterm birth increased from 120/890 (13.5%) for women with either health (no sites BOP) or BOP <10% to 59/395 (14.9%) for women with localised gingival inflammation (BOP ≥10% and <30%) to 18/109 (16.5%) for women with generalised gingival inflammation (BOP ≥30%).Our binary definition of gingival inflammation (BOP ≥10%) was not associated with preterm birth in the crude model  or after adjusting for confounders . In the final adjusted model, increasing extent of gingival inflammation was associated with a non-significant increase in risk of preterm birth  . In thisIn a secondary analysis, participants were stratified by their trimester at the time of the periodontal examination . Among women with dental exams in the first trimester, incidence of preterm birth increased from 47/381 (12.3%) for women with either health (no sites BOP) or BOP <10% to 28/158 (17.7%) for women with localised gingival inflammation (BOP ≥10% and <30%) to 8/35 (22.9%) for women with generalised gingival inflammation (BOP ≥30%). Our binary definition of gingival inflammation (BOP ≥10%) in the first trimester was associated with preterm , but not in the second trimester , after adjusting for confounders. In the final adjusted model stratified by trimester, there was a positive relationship between gingival inflammation and risk of preterm birth among women in the first trimester , but not among women in their second trimester  .Our secondary exposure definition for mild periodontitis was not associated with preterm in a binary comparison or the crude or adjusted regression models for our primary or secondary analyses. These analyses were not conducted for moderate periodontitis given the low prevalence of the condition in this study population.In our community-based, prospective cohort study, gingival inflammation was an independent risk factor for preterm birth among women examined during their first, but not second, trimester, after adjusting for potential confounding risk factors. Our finding suggests that gingival infection and inflammatory burden early in pregnancy, potentially originating prior to conception, could be responsible for the observed relationship, which becomes obscured in the second trimester by the presence of women with initially healthy periodontal conditions who develop pregnancy-induced gingival inflammation. This result is consistent with studies that have reported that active, and especially progressive, periodontal infection is most harmful early in pregnancy.33Most previous studies have considered the relationship between varying definitions and severities of periodontitis and preterm birth. A meta-analysis of seven cohort studies estimated a pooled relative risk of preterm of 1.70 (95% CI: 1.03 to 2.81) for pregnant women with periodontitis versus health.et alet alet alFew observational or interventional studies have considered gingival inflammation as the primary exposure definition when investigating the relationship between periodontal disease and preterm birth. A cohort study by Kruse Extent and severity of gingival inflammation, independent of traditional clinical measures of periodontitis, such as CAL or PD, have been associated with magnitude of bacteraemia.41Poor oral hygiene behaviours, including extended teeth cleaning time (≥5 min), infrequent teeth cleaning (<7 times per week) and use of traditional dentifrice  or datiwan, were also associated with increased risk of preterm birth in our analysis. Studies have shown that the mechanical manipulation involved in brushing, particularly frequent or forceful brushing or use of brushes with hard filaments, can lead to gingival abrasion, recession and bacteraemia.et al,45An important strength of our study was that we used a population-based sample, compared with previous observational studies of this relationship, which were primarily conducted in health facility settings, introducing risk of selection bias associated with the likelihood of women in the target population delivering in a particular facility. The potential for selection bias to influence the measure of association in a facility-based study is especially high in populations where a substantial proportion of women deliver at home, as is the case in this area of rural Nepal, where roughly half of women deliver in a facility. In the unpublished review conducted by our research team, we found one study of this association, by Mobeen A limitation of this study was the collection of clinical recession measures from only the direct buccal and lingual surfaces. In the absence of these data, we likely underestimated the burden of periodontal disease among pregnant women in this study, potentially attenuating our measure of association. We were unable to control for some confounders of this relationship, including previous preterm birth, certain chronic diseases , and we only used a proxy (self-reported symptoms) for urinary tract and vaginal infections. Conducting periodontal exams in participant homes, where light and other conditions are variable, may have introduced a level of measurement error in our exposure that could not be quantified or controlled for given the setting and logistical constraints of our study. Lastly, preterm birth was based on maternal self-report of LMP instead of ultrasound examination. If our LMP estimates were less accurate among women examined later in pregnancy, due to longer maternal recall relative to women examined earlier in pregnancy, this could have resulted in non-differential misclassification of our binary outcome, preterm birth, which would tend to attenuate observation of a true relationship among women examined in the second trimester.Our study identified gingival inflammation as an independent risk factor for preterm birth among women examined early in pregnancy. Women non-compliant with oral hygiene care recommendations were at substantially increased risk of preterm birth. These findings highlight the importance of adherence to proper home oral self-care in pregnant women and women expecting to become pregnant. Oral health policies and education programmes should include tailored approaches to encourage improved self-care practices in this important population. Future studies should evaluate the effectiveness of community-based oral health interventions that specifically target gingival inflammation—delivered to women early in or prior to pregnancy—on the incidence of preterm birth and other adverse pregnancy outcomes in low-income countries with high risk for these outcomes.