Introduction: Studies have shown that long-term positive behavioural and physiological changes are induced in connection with vaginal, physiological birth, and skin-to-skin contact after birth in mothers and babies. Some of these effects are consistent with the effect profile of oxytocin. This scoping review explores whether epigenetic changes of the oxytocin gene and of the oxytocin receptor gene (OTR) are involved in these effects. Methods: We searched Pubmed, Medline, BioMed Central, Cochrane Library, OVID, and Web of Science for evidence of epigenetic changes in connection with childbirth in humans, with a particular focus on the oxytocin system. Results: There were no published studies identified that were related to epigenetic changes of oxytocin and its receptor in connection with labour, birth, and skin-to-skin contact after birth in mothers and babies. However, some studies were identified that showed polymorphisms of the oxytocin receptor influenced the progress of labour. We also identified studies in which the level of global methylation was measured in vaginal birth and caesarean section, with conflicting results. Some studies identified differences in the level of methylation of single genes linked to various effects, for example, immune response, metabolism, and inflammation. In some of these cases, the level of methylation was associated with the duration of labour or mode of birth. We also identified some studies that demonstrated long-term effects of mode of birth and of skin-to-skin contact linked to changes in oxytocin function. Conclusion: There were no studies identified that showed epigenetic changes of the oxytocin system in connection with physiological birth. The lack of evidence, so far, regarding epigenetic changes did not exclude future demonstrations of such effects, as there was a definite role of oxytocin in creating long-term effects during the perinatal period. Such studies may not have been performed. Alternatively, the oxytocin linked effects might be indirectly mediated via other receptors and signalling systems. We conclude that there is a significant lack of research examining long-term changes of oxytocin function and long-term oxytocin mediated adaptive effects induced during physiological birth and skin-to-skin contact after birth in mothers and their infants. Animal experiments have shown that pregnancy, birth, and the early postpartum period were associated with adaptive physiological and behavioural adaptations ,2 StressStudies performed in humans have indicated that, on the one hand, normal stress (eustress) induced by physiological birth could be associated with beneficial and adaptive effects in both mother and infant . For exaOxytocin, sometimes popularly referred to as the love hormone, is a vital and integrative component of a comprehensive neurochemical system that regulates positive interaction and exerts powerful anti-stress and restorative effects. Oxytocin is a small peptide consisting of nine amino acids. It is produced in the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus. It is released into the circulation from the posterior pituitary to induce hormonal, peripheral effects. In parallel, oxytocin is released directly into the brain from the dendrites and axon collaterals (nervous extensions from the axons) of the oxytocin producing cells and also from oxytocinergic nerves originating from the PVN, where it regulates behavioural and physiological functions . The oxyOxytocin stimulates various kinds of social interactive behaviours including maternal behaviour and bonding ,15. It dThe central and peripheral actions of endogenous oxytocin are executed by its receptor, which is a G protein coupled receptor. In humans, the oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localised at 3p25-3p26.2 . The humOXT exposure has been implicated in “hormonal imprinting”, which is the process by which exposure to a hormone in early life produces an enduring effect in the developing organism . The perFrom a long-term perspective, oxytocin contributes to health by maintaining low levels of stress and inflammation, by stimulating restorative processes, and by inducing well-being and positive emotional engagement ,20,21. IExperiments in sheep have shown that maternal oxytocin, released in connection with birth, is of importance for the development of maternal behaviour and bonding . AdminisTaken together, these data support an important role of oxytocin in connection with the early postpartum period for promoting social interaction and for reducing anxiety and stress levels in the long term. Such effects of oxytocin may be exerted via oxytocin receptors or indirectly via other mechanisms activated by oxytocin. We are aware of epigenetic changes in animals. However, a mechanism which has been shown in animals might not necessarily be applicable to humans. We have not found any studies related to physiological birth in humans.Oxytocin plays a pivotal role in childbirth ,32. DuriDuring labour, oxytocin is also released in the baby; it is released into the circulation from the foetal posterior pituitary and into the brain from neurons within the brain. During labour, oxytocin in the foetus has been associated with pain relief and has been shown to counteract tissue damage caused by hypoxia due to its anti-inflammatory and restorative effects .Oxytocin has also been demonstrated to be released into the circulation in response to skin-to-skin contact immediately after birth in both mothers and their infants . The rolThere is evidence that oxytocin released in connection with childbirth and during skin-to-skin contact after birth, also plays an important role in shaping long-term features of physiology and behaviour in human mothers and their newborns. These effects are discussed in more detail later in this article.Given the long-term oxytocin-linked benefits regarding social interactive skills, stress levels, well-being, and health, one critical area for investigation is whether spontaneous vaginal birth followed by skin-to-skin contact could trigger epigenetic changes in the oxytocin system (the gene for oxytocin production or the gene for oxytocin receptors) in the mother and baby, which are, in turn, associated with optimal oxytocin function in the long term. The term epigenetics refers to changes in gene function that take place without a change in the DNA sequence. In most cases, these modifications turn genes on or off, permitting or stopping the gene from protein synthesis. Epigenetics encompass different mechanisms such as DNA methylation, histone modifications through acetylation, methylation or phosphorylation, and genomic imprinting .This paper aimed at synthesizing existing research demonstrating epigenetic changes in the expression of the oxytocin and oxytocin receptor gene in association with physiological childbirth and immediate maternal/neonatal skin-to-skin experiences. A second aim of the study was to identify literature reporting long-term impacts on the mother and infant in association with childbirth and immediate maternal/neonatal skin-to-skin contact.This was a scoping literature review where the primary question was whether epigenetic changes of oxytocin and its receptor mediate effects on the mother and infant during childbirth and skin-to-skin contact. We also searched the literature for evidence of other types of epigenetic changes in connection with childbirth. In addition, we searched for studies demonstrating the long-term effects of labour and skin-to-skin contact which were consistent with long-term effects of oxytocin.The following databases: Pubmed, Medline, BioMed Central, Cochrane Library, OVID, and Web of Science, were searched using the following search terms: “oxytocin”, “oxytocin gene”, “oxytocin receptor”, “oxytocin receptor gene”, “oxytocin effect”, “vaginal birth”, “caesarean section”, “genetic”, “epigenetic”, “skin-to-skin contact”, without putting a limit on the date of publication. There were 896 articles identified which were written in English, which, following in-depth reading, only 69 were included, as the rest were excluded because they did not contribute to the focus of this review.All articles were analyzed jointly by all the authors and the relevant data were extracted.The findings from the retrieved literature are summarised below.In contrast to our hypothesis, we failed to identify any articles showing that epigenetic changes of the oxytocin gene or oxytocin receptor gene were induced in connection with birth or in response to skin-to-skin in humans.We did, however, identify some studies that examined epigenetic mechanisms in relation to childbirth in humans. As mentioned above, epigenetics refer to changes related to gene function that take place without changing the existing DNA sequence. In most cases, these modifications turn genes on or off, permitting or blocking the gene from protein synthesis.Epigenetic mechanisms have been demonstrated to be activated during birth. Four articles compared the level of global methylation in newborns after spontaneous birth and after caesarean section ,36,37,38p < 0.001). The level of DNA methylation remained stable until three to five days later after vaginal birth, whereas it decreased in the caesarean section group (p = 0.01) and was no longer significantly different from that of vaginal birth.In one study conducted by Schlinzig et al. (2009), 37 newborn infants, of whom 21 were born spontaneously and 16 were delivered by elective CS, had blood sampled from the umbilical cord, three to five days after birth . Leucocyn = 407) in which global DNA methylation in infants born by caesarean delivery was compared with the DNA methylation level of infants born by vaginal birth [Virani et al. (2012) carried out a large birth cohort study , the influence of the mode of birth on the epigenetic state in neonatal hematopoietic stem cells (CD34þ) was investigated . In thisSimilar to the results of Schlinzig et al. (2009) who studied methylation in neonatal leukocytes, CD34+ cells of babies born via caesarean section, the CD34+ cells were globally more DNA methylated as compared with babies born vaginally . MaternaA locus-specific analysis of single genes was also performed, which identified 343 loci with a significant difference in the level of DNA methylation of 10% or greater between vaginal birth and caesarean section. A majority (76%) of the differentially methylated loci in neonatal CD34þ cells was actually found to be hypermethylated after vaginal birth, which was in contrast with the findings related to global methylation where the level of methylation was more pronounced after caesarean section. In addition, the degree of DNA hypermethylation in three of the identified loci correlated to the duration of labour. The functional relevance of these differently methylated loci involved processes such as regulation of glycolysis, response to food, ketone metabolism, and immunoglobulin biosynthesis .A prospective pilot study was carried out by Franz et al. (2014) on 41 newborn infants (23 with spontaneous birth and 18 delivered by elective caesarean section) . UmbilicTo summarise, global hypermethylation was shown in one study after caesarean section, but not in the other studies, including the larger study performed by Virani et al. (2012) . These fDespite the lack of studies examining methylation of the oxytocin gene and its receptor in relation to labour, birth, and postnatal skin-to-skin contact, there is some suggestion from the included studies that the mode of birth could affect the epigenetic state of some other specific genes in neonatal blood cells, linked to metabolism, inflammation, and immune response. There were, however, no long-term studies that examined if these changes persisted over time, and, if so, what the clinical implications might be.There are several polymorphisms of the oxytocin receptor in which different alleles may occur in some of the genes. Some of these minor structural differences in the oxytocin gene may be of clinical importance and have been shown to influence social interactive behaviours or stress reactivity. One example is a polymorphism in the rs53576 gene, where there can be either the G or A allele, which are linked to different psychological properties. Chen et al. (2011) showed that individuals with the G allele were able to deal more appropriately with stressors when given social support than those with the A allele .p = 0.022) and rs237888  [In addition, some studies suggested that the effect on uterine contractions and the length of latent and active labour could be influenced by polymorphisms of the oxytocin receptor. In addition to parity and birth weight, polymorphism of the oxytocin receptor is one of the main predictors regarding length of active labour. An in vitro study on human myometrial cells showed that there was a significant difference between the amount of OXT stimulation used among reference and variant groups for rs4686302  .p < 0.0001) as compared with the other polymorphisms. OTRrs2228485-T, OTRrs53576-A, ethnicity, and higher birthweight contributed independently to the longer latent phase [A secondary analysis of birth records from 1229 pregnant women, who participated in a study on the effect of genetics on preterm labour and who had a vaginal birth later than 34-week gestation, was conducted . Demogrant phase .A prospective study was performed on 187 women in order to investigate the occurrence of oxytocin gene receptor polymorphisms in women during childbirth requiring low (<4 mU/min) and high (>20 mU/min) oxytocin dosage. Thirty different OTR polymorphisms were identified, 10 of which were previously unknown and six of these were exclusive to women requiring high doses of oxytocin .The results from these studies suggested that there could be a genetic factor to oxytocin sensitivity of the uterus in women giving birth. We decided to include these studies because they showed that small differences in the structure of the OXTR had an important effect regarding the function of oxytocin.This may in part explain why some women take longer to give birth physiologically, and perhaps even why some require induction or augmentation. More and larger studies are needed to examine thoroughly the association among specific OTR polymorphisms and the progress of labour. This could include an examination of any association among OTR gene variations and the length of active labour or whether pregnancy-related factors may contribute to the effect. It would also be of interest to investigate if these polymorphisms influence behavioural and physiological changes that occur during labour.Although there were a few studies that examined physiological childbirth, and in spite of the negative findings regarding methylation of the oxytocin and oxytocin receptor gene in connection with birth, there was evidence of a disturbance of the oxytocin system in connection with caesarian deliveries, whether elective or emergency, as compared with spontaneous vaginal births.Several studies have shown that oxytocin levels postpartum were significantly lower in both mothers and newborns after elective caesarean section as compared with vaginal birth ,44. A smIn addition, mothers who have given birth by elective caesarean section did not exhibit the normal release of oxytocin in response to skin-to-skin contact and breastfeeding immediately after birth, nor did they show the mental changes  of decreased levels of anxiety and increased social interaction two days after birth. Interestingly, these effects were restored if the mothers received intravenous oxytocin postpartum . In factThe results of these studies support the important role of oxytocin release in connection with birth and postpartum, with consequences for the psychological adaptations and also for the release of prolactin, and thereby for breastfeeding. In addition, these studies point to a malfunction of the oxytocin system in mothers who have given birth by caesarean section. These results may explain why caesarean section, in particular elective sections, could be linked to breastfeeding problems, as has been demonstrated in several studies ,49,50,51Klaus et al. (1972) showed that early contact between a mother and their newborn promoted social interaction between the mother and infant for several months after birth and based on these observations the term “the early sensitive period” was coined, in this way describing a short period after birth during which closeness between mother and newborn influences the behaviour of the mothers and their newborn in a positive direction in the long term .On a similar note, a systematic review on early skin-to-skin contact for mothers and their healthy newborn infants, revealed that babies who were put skin-to-skin made more physical contact with their mothers and cried less, indicating decreased levels of pain and fear ,54. SkinBystrova and colleagues (2009) studied whether different labour ward routines, in particular, skin-to-skin contact and separation in the labour ward, as well as, during the maternity stay, rooming-in versus nursery care in the maternity ward, affected the mother–infant interaction one year postpartum. The effects of these interventions on mother-infant interaction one year postpartum were studied using the Parent Child Early Relational Assessment (PCERA). Findings from this study revealed that contact between the mother and the infant in the initial two hours following birth appeared to be noteworthy for maternal sensitivity, for mutuality in the dyad, and for infant’s self-regulation or ability to handle stress at the time when the infant was one year old as measured by PCERA. These effects seemed to be consequential to the skin-to-skin contact between mother and infant in the initial two hours (early sensitive period) . HoweverOxytocin is released during skin-to-skin contact after birth in both mother and baby  Figure . This reIn this literature review, no studies that demonstrated epigenetic changes of oxytocin and its receptor in connection with human childbirth, were identified. Data regarding global methylation of genes in connection with childbirth, were identified. In addition, some polymorphisms of the oxytocin receptor were identified.The hypothesis, put forward in this review, was that the function of the oxytocin system is influenced in connection with childbirth, in order to induce long-term beneficial adaptations for both mother and neonate . Labour,Oxytocin released in response to the Fergusson reflex in connection with birth and in response to activation of sensory nerves in the skin during skin-to- skin contact in human mothers and their foetuses/infants is likely to contribute to these short and long-term psycho-physiological adaptations . EpigeneWe did identify some studies that showed differences in the level of global methylation of genes as compared with caesarean section and vaginal birth, but these results were conflicting ,36,38. SOne reason for not picking up any epigenetic changes in the oxytocin gene or the oxytocin receptor gene might be that oxytocin often exerts its effects in the following two steps: first by activation of the oxytocin receptor, which in turn interacts with other signalling systems, such as the glucocorticoid (GC) receptor . TherefoOxytocin exerts effects on a mother and newborn during and following childbirth. Many of these effects are absent, or are less evident, in a mother and her neonate having had an elective caesarean section. The practice of skin-to-skin contact after birth increases the expression of the oxytocin-linked effects. In fact, skin-to-skin contact immediately after birth could be regarded as a part of birth, when stress levels, which are high during birth, are decreased. To date, it is still not clear by which mechanism oxytocin might beneficially induce its long-term effects. We speculate that the oxytocin system plays a major role, but the effect could be indirect as oxytocin is involved in the regulation of many other transmitter systems, including the HPA axis . This isGiven the positive effects of oxytocin, it is important to allow the oxytocin-induced effect in connection with physiological birth to be expressed. This is because oxytocin will stimulate social skills and decrease stress levels and inflammation, and therefore is linked to positive physical and mental health in the long term. These points of reflection are of importance when choosing the mode of birth and implementing possibly unnecessary interventions during birth, as many medical interventions are linked to a decreased amount of oxytocin release in connection with childbirth.This review was designed to locate and describe current evidence regarding epigenetic changes of the oxytocin gene and the oxytocin receptor gene in connection with childbirth in humans, and the potential consequences of any such changes for mother and baby in the short and long term. We did not find any specific studies regarding epigenetic changes of the oxytocin and the receptor gene in connection with childbirth or skin-to-skin contact. We did find some evidence that methylation might result from events during labour and birth, both globally and for specific genes, though this was not consistent among studies. Given that high amounts of oxytocin are released in connection with birth, there is a large body of evidence that supports the important role of oxytocin on effective labour; and there is strong evidence for oxytocin’s impact on pro-social behaviour and anti-stress effects in both mothers and newborns. This is a critical area for further investigation.


In efforts to reduce neonatal mortality, the World Health Organization (WHO) has included breastfeeding among its recommended packages of interventions. Early initiation of breastfeeding and avoidance of prelacteal feeding are key contributors to optimal feeding practices. This study aims to assess the prevalence and associated factors of early breastfeeding practices in Sudan.This study utilises the cross-sectional nationally-representative Sudan Multiple Indicator Cluster Survey (MICS) conducted in 2014. The sample includes women who had a live birth in the two years before the survey and their self-report on early breastfeeding practices, namely early initiation and prelacteal feeding. Percentages of these early breastfeeding practices indicators were estimated accounting for the complex survey design. Multivariable logistic regression analyses were used to examine the factors associated with these outcomes.Of 5622 mothers, 69% initiated breastfeeding within one hour of birth, 72% avoided prelacteal feeding in the first three days after birth, and 51% met the criteria for both . Optimal early feeding varied across regions of Sudan. Birth by caesarean section  and at a health facility  were negatively associated with optimal early feeding practice. Mothers with secondary education , those who desired their pregnancy at the time , those who were assisted by a skilled birth attendant at birth , and those who gave birth to female infants  had higher odds of use optimal early feeding practice. Similarly, the odds of optimal early feeding increased with parity and maternal age.Only half of Sudanese mothers practised optimal early feeding practice, with important differences between regions in the country. Early feeding practices in Sudan are associated with various maternal, child and community level factors. The findings suggest the need to develop breastfeeding promotion programs with consideration of regional variations and healthcare system interventions. Despite a substantial reduction in child mortality from 12.7 million in 1990 to 6.3 million in 2017, the proportion of child deaths attributable to neonatal mortality is increasing [Early or timely initiation of breastfeeding, ideally within the first hour after birth, is vital for both the mother and the infant. Despite the well documented health benefits of early initiation for maternal health , 5 and iThe introduction of prelacteal feeds (i.e. any food or drink other than breast milk) postpones the initiation of breastfeeding , potentiEarly feeding practices of infants are studied through two indicators developed by the WHO: early initiation within one hour and exclusive breastfeeding . In the A number of factors are associated with early breastfeeding practices, such as area of residence, region, socio-economic status, paternal education, maternal age at marriage, desire for birth, antenatal care, place of birth, attendance of birth by skilled personnel, mode of delivery, perceived size of infant, sex of infant, and birth order –19. Some2, a population of 40.53 million and diverse ethnic blend of Africans and Afro-Arabs. It is one of the least developed countries according to the United Nations classification with GDP per capita of 977.3 US dollars in 2018 [Sudan is one of the largest countries in Africa with an area of 1.886 million km in 2018 . Levels  in 2018 . The Bab in 2018 . In 2013 in 2018 .There is a lack of research on early feeding practices in Sudan, with previous studies with small samples and community-based , 25. TheThe 2014 Sudan Multiple Indicator Cluster Survey (MICS) is a representative survey designed to provide national-level data as well as state-level estimates for maternal and child health in the 18 states in Sudan. Sudan Central Bureau of Statistics (CBS) in collaboration with the Ministry of Health, conducted this survey as part of the global MICS programme . The webThis study utilises cross-sectional secondary data from the 2014 Sudan MICS. This survey utilised an updated 2008 population census and randomly selected 40 enumeration areas in each State. The survey design employed two-stage cluster sampling after stratifying by urban and rural areas within each State. In the first stage, within each stratum, enumeration areas were selected with probability proportional to size. In the second stage, 25 households were selected in each enumeration area. Paper-based questionnaires were used for data collection using the Arabic language. Data were collected using three questionnaires, collecting information at the household level, on all eligible ever-married women aged 15–49 years and on all eligible children under-5 years of age. The survey sampled 18,000 households of which 16,801 were interviewed; 18,302 eligible women and 14,081 mothers/caretakers of children under-5 were interviewed. Detailed reports on the survey design, methods and findings of the survey can be found on the MICS website .Data was collected from the three MIC questionnaires: breastfeeding information from the women questionnaire; child’s birth order from the children under-5 questionnaire and sociodemographic data from the household questionnaire, respectively. Analysis for this study was restricted to data from mothers with last-born children in the two years preceding the survey. The total sample size was 5622 mother-baby pairs.child’s name) to the breast?” Women responded by providing the number of hours or days. The outcome variable “early initiation” was defined by a binary variable reflecting the initiation of breastfeeding within one hour of birth (Yes/No). “No prelacteal feeding”, a binary (Yes/No) outcome variable, reflected the negative response to the question: “In the first three days after delivery, was (child’s name) given anything to drink other than breast milk?”. The “Optimal early feeding”, a binary outcome variable (Yes/No), was designed to capture children who both had early initiation within one hour of birth and did not have any prelacteal feeding in the first three days after delivery [To address the study objectives, three early feeding indicators were the outcome variables: (1) early initiation within one hour of birth, (2) no prelacteal feeding in the first three days after birth, and (3) optimal feeding (1 and 2). In the women questionnaire, mothers were asked: “How long after birth did you first put  were then eliminated from this model. Confounding was assessed; variables were included in the model if their coefficients changed by 20% or more. Identified a priori as a confounder, maternal age was included in all models. F-adjusted mean residual goodness-of-fit tests were used to assess any evidence to lack of fit of the final model [Svy commands using Taylor linearization for the variance estimation were used to account for the complex survey design using assigned weights, primary sampling units (clusters) and strata. The sample weights were the inverse of the probability that the observation was included because of the sampling design. Weighted sample sizes and percentage are reported unless otherwise indicated. Missing values in the outcome variables were handles similarly as in MICS methodology in order to produce similar indicators as in previously published reports [Percentages and 95% confidence intervals (95% CI) of the three breastfeeding outcome indicators were reported; overall and by explanatory variables. Logistic regression analyses were used to model the odds of the outcome variables. Crude logistic regression analyses were performed as initial steps of qualifying factors to be included in the multivariable logistic regression analyses. Potential factors with ed model . Using tal model . Odds ra reports . MultiplA total of 5622 observations of mothers/last-born child pairs within two years preceding the survey were included in this study. Around 96% of mothers reported ever-breastfeeding their child. The majority of the sample resided in rural areas (73.5%), in Darfur (27.9%), and Central 29.1%) regions  of women Table . It was Univariate logistic regression analyses revealed that early initiation was significantly associated with region of residence, household wealth, father’s education, place of birth, birth assisted by a skilled attendant, birth by caesarean section, and birth order (Supplementary Table Sp = 0.004). These odds were significantly higher with increasing father’s education. This result was similar for mother’s education up to secondary level where the adjusted odds of early initiation decreased for women with higher education compared to those with no education. The adjusted odds of early initiation was 34% higher among mothers whose births were assisted by a skilled attendant compared to unassisted mothers . Compared to mothers who gave birth by vaginal delivery, those who gave birth by caesarean section had 78% lower odds of commencing breastfeeding within the first hour after birth . Additionally, mothers of higher parity had higher odds of early initiation compared to mothers who had their first birth.Compared to the capital city of Khartoum, the adjusted odds of early initiation was lower among mothers who were residents in all other regions; the Eastern region was an exception Table . The adjNearly three-quarter of mothers did report not giving prelacteal feeds to their infants  , Eastern  and Darfur  regions. Maternal age and education up to secondary level were positively associated with avoiding prelacteal feeding. The adjusted odds of avoiding prelacteal feeding was lower among mothers who gave birth by caesarean section compared to those who gave birth by vaginal delivery . Likewise, the adjusted odds of avoiding prelacteal feeding was 1.51 times higher for mothers who planned pregnancy of their last child compared to those who did not .Compared to mothers who lived in Khartoum, the adjusted odds of avoiding prelacteal feeding in the first three days after birth was generally higher in almost all regions with significant odds ratio in Kordofan   and 43% lower in Northern region  when compared to Khartoum. Maternal age was significantly associated with optimal feeding with older women having about 25% higher odds of practicing optimal feeding related to the youngest women aged 15–24 years . Mothers who had secondary or higher education had a 62%  and 43%  increased odds of optimal early feeding respectively compared to those with no education. Mothers with a planned pregnancy had 1.33 times higher odds to optimally feed their infants . In comparison to home births, children who were given birth in a health facility were less likely to be fed optimally . Compared to vaginal delivery, caesarean section was significantly associated with a much lower odds of optimal feeding . On the contrary, skilled attendance at birth increased the odds of optimal early feeding . Sex of child was also significantly related to optimal feeding practice in this study with 16% higher odds of optimal feeding for mothers who had female vs male children . Moreover, compared to mothers with 1st.The adjusted odds of optimal early feeding practice was two times higher in the Eastern region  and , respectively.birth, the odds of optimal early feeding among mothers with 2nd and 3rd or higher birth order were  was relatively similar to Sudan national estimate in 2010  and leveThe results report that 72% of infants did not receive prelacteal feeds within the first three days of birth. Avoiding these feeds promotes the implementation of optimal breastfeeding practices. The observed avoidance prevalence in this study is higher than the overall level of 30 Sub Saharan African (SSA) countries , 36 and The results of this study found that despite the relatively high percentages of women breastfeeding their infants in the first hour after birth and refraining from giving their infants any prelacteal feeds in the first three days after birth, only half of them adhere to both good practices. This level of optimal early feeding is higher than overall levels reported by Oakley et al. (28%) but lower than several East African countries such as Malawi (93.2%), Mozambique (74.5%), Burundi (71.3%) and Rwanda (66.2%) . VariatiThe study found considerable regional variations in early breastfeeding indicators. Sudan consists of diverse ethnic tribes clustering in different regions with the capital Khartoum generally representing the whole country ethnic structure. Living situations across communities vary with access to health care facilities, media and health information. Previous studies conducted in different regions of Sudan also reported varying prevalence in breastfeeding behaviour , 43.After adjustment, this study found the following common factors as significant factors of the three early feeding practices indicators in Sudan: region, maternal education and birth by caesarean section. Maternal age was a significant factor for both no prelacteal and optimal feeding indicators. This study result of no prelacteal feeding was consistent with those reported in other studies , 44. ComCaesarean section has been consistently associated with lower odds of early initiation and a higher prevalence of prelacteal feeding , 47, 48.The finding that birth assisted by a skilled attendant is a significant factor associated with early initiation and optimal feeding practices is consistent with findings reported by Oakley et al. . The autThis study found no association between early initiation and no prelacteal feeding indicators with place of birth . This is in contrast to the overall findings reported by Bergamaschi et al.  associatAlmost three-quarters of births are delivered at home in Sudan, particularly in rural areas comprising three-quarters of the population Table . ImproveAbout two of three Sudanese mothers initiate breastfeeding early after childbirth. A similar number of Sudanese mothers avoid prelacteal feeding in the first three days after childbirth. Nonetheless, only half of these mothers follow both practices at the same time. The National Strategy for Infant and Young Child Feeding (IYCF) 2015–2024 established by the national nutrition program of Sudan Federal Ministry of Health address the challenges of the significant suboptimal IYCF practices in Sudan. The strategy calls for improvement of the implementation of BFHI and improvement of knowledge and skills of health service providers. This study provides evidence-based information to benefit the implementation of the strategy.This research is the first in Sudan to analyse a nationally representative sample to explore early feeding indicators. The data set was nationally representative with low levels of missing data. Another strength in this study is the use of a new optimal feeding indicator which captures two important early feeding practices . The study had some limitations that should be considered while interpreting the results. Firstly, although the MICS data provided the opportunity to control for several confounding factors, it did not allow to control directly for other important dimensions like social and cultural factors like the importance of advice from grandmothers and ethnic beliefs on infant early feeding , 40. NonOnly half of Sudanese infants received optimal early feeding practice, with notable differences between regions in the country. Early breastfeeding practices in Sudan are associated with various community levels, maternal and child factors. The findings suggest the need to develop breastfeeding promotion programs considering regional variations in the country. These programs should be targeted toward mothers giving birth by caesarean section and their health providers. The findings also suggest improving the knowledge and skills of health providers working at health facilities on IYCF education, and community-based health workers like traditional birth attendants to providing early postnatal visits and education to women who give birth at home. Further studies should be conducted to address the possible reasons for having better early breastfeeding indicators in mothers who give birth at home.Additional file 1: Supplementary Table S1: Univariate logistic regression modelling the likelihood of early feeding indicators (n = 5622).


A newborn male infant presented with multiple pustules and erosions with erythema involving his scalp and forehead at birth. One week after birth, new pustules continued to appear, forming crusted, ring-shaped plaques with pigmentation. Tests for possible pathogens were negative. Tzanck smear and skin biopsy revealed pustules beneath the stratum corneum at sites corresponding to hair follicles, which contained eosinophils and neutrophils. Taken together, a diagnosis of eosinophilic pustular folliculitis (EPF) was made. The pustules on the head disappeared rapidly with topical corticosteroid treatment, although new eruptions were still observed on the trunk about one month after birth. To our knowledge, only two cases of EPF since birth have been reported to date. Here, we also discuss the differential diagnosis of noninfectious pustular diseases at birth, including erythema toxicum neonatorum and transient neonatal pustular melanosis. These diseases, and EPF, may present with very similar clinical symptoms at birth, and the Tzanck test or biopsy may be required for differential diagnosis. Pustules are rarely present at birth. Regardless of the time of presentation, pustular diseases can be infectious or noninfectious. Infectious pustular diseases may be life-threatening and require a particularly early diagnosis. These diseases can be differentiated through the identification of bacteria, fungi, and viruses .Noninfectious pustular diseases include erythema toxicum neonatorum (ETN), transient neonatal pustular melanosis (TNPM), and eosinophilic pustular folliculitis (EPF). ETN and TNPM usually resolve spontaneously, whereas EPF often requires treatment. These diseases may present with very similar clinical symptoms at birth and must be differentiated for effective, targeted treatment. Here, we describe a rare case of EPF since birth, along with differential diagnosis from other diseases associated with pustules seen at birth.A male baby was born with numerous pustules on his scalp and forehead. His 35-year-old mother had a history of Graves’ disease and Moyamoya disease, which were treated with propylthiouracil and aspirin, and he was born by cesarean section at term. The perinatal period was uneventful, and the infant had a birth weight of 2700 g and Apgar scores of eight and nine at 1 and 5 min, respectively. At birth, multiple pustules measuring 1–5 mm and a few erosions with erythema were observed on his scalp and forehead . There wOne week after birth, new pustules continued to appear, forming crusted, ring-shaped plaques with pigmentation . BacteriFinally, we made a diagnosis of EPF based on a combination of clinical symptoms, Tzanck smear, and skin biopsy results. We treated the right side of the face with topical ketoconazole and the left side with topical corticosteroid. The pustules and erythema disappeared on the left side within about two days, although there were minimal effects on the right side . On the To diagnose noninfectious pustular diseases, infectious pustular diseases must be ruled out. Infectious pustular diseases include bullous impetigo, congenital cutaneous candidiasis, herpes simplex virus infection, varicella, etc. . These dETN is a transient physiological rash found in about 40% of newborn infants . Such raTNPM is common in black neonates, characterized by flaccid 1–3 mm pustules on the chin, neck, trunk, and thighs beginning at birth . These pAlthough a previous report proposed that TNPM and ETN may represent different points on the spectrum of the same disease , the patEPF in infancy is a rare disease first reported by Lucky et al. in 1984 . EPF is Our patient presented with many pustules but relatively minimal crusting at birth compared to typical infant cases of EPF. This may be because our case was bathed in amniotic fluid without exposure to air at the onset of EPF. However, one week after birth, our case exhibited typical crusting pustules. According to the clinical course over one month, the negative results of pathogen tests, the findings of the skin biopsy, and the response to treatment, we could differentiate EPF from the other infectious and noninfectious pustular diseases described above.Although the cause of EPF in infancy has not been clarified, the increased number of eosinophils in the peripheral blood during attacks is suggestive of an immunological pathomechanism . A cliniEPF develops within 24 h after birth in about 25% of affected infants under one year of age; however, the symptoms are rarely seen at birth ,11,14. T


Birth defects are the most serious causes of infant mortality and disability in sub-Saharan African countries with variable magnitude. Hence, this study was aimed to determine the pooled prevalence of birth defects and its associated risk factors among newborn infants in sub-Saharan African countries.A total of 43 eligible studies were identified through literature search from Medline (PubMed), EMBASE, HINARI, Google scholar, Science Direct, Cochrane Library and other sources. Extracted data were analyzed using STATA 15.0 statistical software. A random effect meta-analysis model was used.Twenty-five studies in 9 countries showed that the pooled prevalence of birth defects was 20.40 per 1,000 births . In the sub-group analysis, the highest prevalence was observed in southern Africa region with a prevalence of 43 per 1000 . The most prevalent types of birth defects were musculo-skeletal system defects with a pooled prevalence of 3.90 per 1000  while the least was Down syndrome 0.62 per 1000 . Lack of folic acid supplementation , presence of chronic disease  and intake of drugs  during pregnancy were significantly associated with the birth defects.The prevalence of birth defects is relatively high with high degree of regional variabilities. The most common types of birth defects were musculoskeletal defects. Lack of folic acid supplementation, presence of chronic disease and intake of drugs during pregnancy were significantly associated with birth defects. Birth defects (BD) are defined as a series of abnormalities of infants that occur during the pregnancy period. They are described by different terms like congenital disorders, congenital anomalies, congenital malformations and congenital abnormalities . These dWorldwide, the prevalence of birth defect varies from region to region. In the United States, it has been expected that birth defects occur in 2.76% of newborns . AccordiIdentification and study selection: published articles and unpublished research reporting the prevalence and associated risk factors of birth defects in sub-Saharan African countries were considered. Relevant studies were identified through a literature search of Medline (PubMed), EMBASE, HINARI, Google scholar, Science Direct, Cochrane Library and other sources. The references of each incorporated article were also searched manually to optimize the search strategy. The searching of the articles was performed from the 9th of September, 2018 to the 15th of November, 2018, and it was limited to English. Unpublished studies were also searched from Google and Google Scholar. The key terms used for the search were “Prevalence” OR “Epidemiology” AND “Congenital Abnormality” OR “Congenital Abnormalities” OR “Congenital Malformation” OR “Congenital Anomaly” OR “Congenital Anomalies” OR “Birth Defect” OR “Congenital Disorders”, AND “Each country in the sub-Saharan African region”. All the literatures accessible until November 15, 2018 were included in the systematic review and meta-analysis. The systematic review and meta-analysis was conducted in agreement with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline [Inclusion criteria: prevalence and associated factors of birth defects in sub-Saharan African countriesStudy area: only articles conducted in sub-Saharan African countries.Study design: all observational studies  that contain original data reporting the prevalence and associated risk factors of birth defects in sub-Saharan African countries were considered.Language: literatures published in the English language were incorporated.Population: studies conducted among newborn infants were considered.Publication condition: both published and unpublished articles which reported the prevalence of birth defects and associated risk factors among newborn infants in sub-Saharan African countries were considered.Exclusion criteria: non-accessible articles because of un-published, un-retrievable from the internet or failures of reply to correspondences made by e-mail were excluded. In addition, studies, which did not report our outcome of interest, were excluded after reviewing their full texts.Data abstraction: all the necessary data were retrieved using a consistent data extraction format made in Microsoft Excel. For the prevalence of birth defects, the data extraction format included first author, the country where the study was conducted, and the area of country where the study was carried out, publication year, study design, sample size, and prevalence of birth defects. For types of birth defects the prevalence of neural tube defects (NTD), oral-facial clefts defects (OFC), cardiovascular defects, urogenital defects, Down syndrome, gastrointestinal (GIT) defects and prevalence of unclassified birth defects were also included. For the associated risk factors, the data extraction format was prepared for each specific of the associated risk factor . We chose these variables because they are the most commonly reported associated risk factors in the studies included in this meta-analysis. In this systematic review and meta-analysis, the investigator considered variables as risk factors  if two or more studies have mentioned them as risk factors. For every associated risk factor, to compute the odds ratio, the data from the primary studies were extracted in the form of two by two tables.Outcome measurements: this systematic review and meta-analysis have two major outcomes. The primary outcome was prevalence of birth defects among newborn infants in sub-Saharan African countries. The second outcome of the study was risk factors of birth defects in the countries. The prevalence was calculated by dividing the number of infants born with birth defects to the total number of born infants in the study period who have been included in the study (sample size) multiplied by 1000.Quality assessment: to evaluate the quality of the studies included in this review, the researcher applied the Newcastle-Ottawa Scale tool as modified for cross-sectional studies´ quality assessment [sessment . The tooStatistical analysis: the required data were collected using a Microsoft Excel format and analyzed by using STATA Version 15.0 software. The original articles were presented using tables and forest plot. The researcher calculated the standard error of prevalence for each original article by the binomial distribution formula. Heterogeneity among the reported prevalence of studies was checked by using heterogeneity χ2 test, I2 test and the p-values [p-values . The abop-values , 19. TheSearch results: a total of 958 records regarding prevalence and associated factors of birth defects in sub-Saharan African countries were retrieved from the databases of Medline (PubMed), EMBASE, HINARI, Google scholar, Science Direct, Cochrane Library and other sources described above. From these preliminary records, 672 articles were excluded due to duplication. From the remaining 286 articles, 221 articles were excluded as they were found to be non-applicable to this review after assessing their titles and abstracts. The remaining 65 full text articles were then accessed, and assessed for eligibility based on the preset criteria, which resulted in further exclusion of 22 articles primarily due to the study population and outcome of interest. Among these, fourteen of the studies were conducted in countries other than sub-Saharan African countries: Indian, Iran, Brazil, Canada, China, Italy, Latin America, Pakistan, Spain, Saudi Arabia and Egypt. Three of the studies were conducted in: Tanzania, South Africa and Ugandan and excluded because their study population were not among newborn infants. The remaining five studies were conducted in different parts of Ethiopia and excluded because of the study population and unreported outcome of interest. Finally, 43 studies were found to be eligible and incorporated in the meta-analysis. Among the eligible studies, 25 studies were used for overall prevalence of birth defects. For prevalence of sub type of birth defects, 16 additional studies were included and 2 case control studies were also included for associated risk factors of birth defects  [4-23.77) , 20-42  followed by Central African 30.74 per 1000 , Eastern Africa 17.30 per 1000  and Western Africa, 9.17 per 1000   .Types of birth defects: among the types of birth defects in sub-Saharan African countries, the most frequent types of BD were musculoskeletal systems defects with a pooled prevalence of 3.90 per 1000 , followed by neural tube defects 2.98 per 1000 , cardiovascular system defects (CVSDs) 2.83 per 1000 , gastrointestinal defects 1.50 per 1000 , oro-facial clefts (OFCs) 1.27 per 1000 , unspecified birth defects 0.86 per 1000, urogenital system defects 0.69 per 1000  and Down syndrome 0.62 per 1000   .Factors associated with birth defects: the associations of maternal folic acid supplementation, maternal illness and maternal history of medication during pregnancy with birth defects were analyzed in four analyzable studies [ studies , 43-46. This meta-analysis is the first of its kind in sub-Saharan African countries to estimate the pooled prevalence and associated risk factors of birth defects among newborn infants. The study has found that the overall prevalence of birth defects in sub-Saharan African countries among newborn infants is 20.4 per 1000 . This finding is in line with a study in the northeast region of Cairo, Egypt, which has reported a BD prevalence of 20 per 1000  among neThe subgroup analysis of this study showed that the prevalence of birth defects among newborn infants significantly varies across regions of the sub-Saharan African countries. The highest prevalence of birth defects was observed in Southern Africa region, 43 per 1000  followed by the Central Africa region, 30.74 per 1000  and Eastern Africa 17.3 per 1000 , while the lowest prevalence was observed in the Western Africa region with a prevalence of 9.17 per 1000 . The present finding is in trajectory to the report of the study conducted on the prevalence of common birth defects in South African infants . This miThe most common types of birth defect were musculoskeletal systems defects followed by neural tube defects while the least frequent were urogenital system defects and down syndrome. Comparable sequence of the organ system defects have been described in a study conducted in southern Vietnam and where the most common types of BD were musculoskeletal system defects . HoweverInfants born from mothers who had no folic acid supplementation during pregnancy were 3.92 times more likely to have birth defects compared to those born from mothers who had folic acid supplementation. This finding is in line with a study which reported that folic acid supplementation lowers the risk of birth defects . The preInfants born from mothers who had a disease during pregnancy were 3.48 times more likely to have birth defects as compared to infants born from mothers who did not have diseases. The presence of maternal illness during pregnancy as a risk factor for birth defects is previously acknowledged by other study . The preStrength and limitations of the study: the strength of this meta-analysis is the first of its kind in sub-Saharan African country and it lies in the quest of existing and unpublished research and the use of several thoughts to digest the study. However, all articles found to have been cross-sectional in nature in this systematic review and meta-analysis. As a consequence, it is not possible to establish temporal relations between factors and outcome variables. Most of the research included in this review had a small sample size that could influence the final estimate. Furthermore, since this meta-analysis included accessible research recorded from a small region in sub-Saharan African countries, the various countries in the study area may be under-represented.The present review has revealed a relatively high prevalence of birth defects among newborn infants in sub-Saharan African countries. The most common types of birth defect were musculoskeletal defects, followed by neural tube defects, cardiovascular system defects, gastrointestinal defects and oro-facial clefts (OFCs). Lack of folic acid supplementation, presence of chronic disease and intake of drugs during pregnancy were significantly associated with birth defects. Therefore, based on the findings, it is recommended that efforts should be made to ensure that women use folic acid during the periconceptional period and during pregnancy. In addition, drugs should cautiously be prescribed to pregnant women, and chronic diseases of women must properly be managed so as to minimize the occurrence of birth defects. Furthermore, given the high prevalence of birth defects shown in this review, it is recommended that Fetal Medicine Unit maybe functional in the countries.Birth defects are a major public health challenge worldwide, especially in developing countries including Ethiopia;Different and few studies have been conducted in the study area;The problem is still higher and abundant discrepancy and inconstancy among sub-Saharan African countries.The prevalence of birth defects in sub-Saharan African countries among newborn infants is 20.4 per 1000;The most common types of birth defect are musculoskeletal systems defects;Maternal history of medication during pregnancy, lack of maternal folic acid supplementation and presence of chronic disease during pregnancy are the factors associated with birth defects.The authors declare no competing interests.


This study reviews the current status and future prospective of knowledge on the use of artificial intelligence for the prediction of spontaneous preterm labor and birth (“preterm birth” hereafter). The summary of review suggests that different machine learning approaches would be optimal for different types of data regarding the prediction of preterm birth: the artificial neural network, logistic regression and/or the random forest for numeric data; the support vector machine for electrohysterogram data; the recurrent neural network for text data; and the convolutional neural network for image data. The ranges of performance measures were 0.79–0.94 for accuracy, 0.22–0.97 for sensitivity, 0.86–1.00 for specificity, and 0.54–0.83 for the area under the receiver operating characteristic curve. The following maternal variables were reported to be major determinants of preterm birth: delivery and pregestational body mass index, age, parity, predelivery systolic and diastolic blood pressure, twins, below high school graduation, infant sex, prior preterm birth, progesterone medication history, upper gastrointestinal tract symptom, gastroesophageal reflux disease, Helicobacter pylori, urban region, calcium channel blocker medication history, gestational diabetes mellitus, prior cone biopsy, cervical length, myomas and adenomyosis, insurance, marriage, religion, systemic lupus erythematosus, hydroxychloroquine sulfate, and increased cerebrospinal fluid and reduced cortical folding due to impaired brain growth.  Preterm birth is a major cause of disease burden for newborns and children in the world ,2,3,4. P1H does not separate black and white circles while hyperplanes 2H and 3H separate the two groups. Here, the distance between the two groups is maximal for 3H and the support vector machine creates such a hyperplane.Recently, the words “artificial intelligence”, “machine learning”, and “deep learning” have gained strong interest around the world. For example, the Google trends for these keywords registered rapid growths from 10 to 100 from 2013 to 2018. The Merriam-Webster dictionary defines artificial intelligence as “the capability of a machine to imitate intelligent human behavior”. Machine learning (or data mining) is a branch of artificial intelligence to “extract knowledge from large amounts of data” . Six popAn artificial neural network is a network of input/output units  connected through weights . The artceteris paribus, i.e., “all the other variables staying constant”. For this reason, emerging literature started to employ artificial intelligence for various tasks and sectors, for example, classification, prediction and pattern recognition for business, finance, and medicine [Conventional studies covered only a limited range of factors for preterm birth, while centering on logistic regression with an unrealistic assumption of medicine ,19,20,21Seven articles were selected for review out of 107 articles in Google and PubMed with the search terms “artificial intelligence” and “spontaneous preterm labor and birth”. The following eligibility criteria were adopted: (1) the intervention(s) of a new deep learning method or several machine learning approaches addressed above ; (2) the outcome(s) of accuracy and/or the area under the receiver operating characteristic curve for the prediction of spontaneous preterm labor and birth; (3) the publication year of 2000 or later; and (4) the publication language of English. The following summary measures were employed: artificial intelligence method, sample size, data type, performance measures, and important predictors (independent variables). Here, accuracy denotes the proportion of correct predictions over all observations, whereas the area under the receiver operating characteristic curve represents the plot of the true positive rate (sensitivity) against the false positive rate (1-specificity) at various threshold settings. The artificial neural network and the random forest have been known for their performance that is comparable or superior to those of traditional methods such as logistic regression regarding the prediction of preterm birth ,19,20,21Another recent study made a rare attempt to compare popular machine learning methods for the analysis of preterm birth . Data foA more recent study used similar approaches for analyzing preterm birth, gastroesophageal reflux disease, and periodontitis . PreviouThe random forest (0.8681) registered similar accuracy with logistic regression (0.8736). The variable importance results of the random forest highlighted the significance of delivery and pregestational body mass index, age, parity, predelivery systolic and diastolic blood pressure, twins, below high school graduation, infant sex, prior preterm birth, progesterone medication history, upper gastrointestinal tract symptom, gastroesophageal reflux disease, Helicobacter pylori, urban region, calcium channel blocker medication history, and gestational diabetes mellitus. As a matter of fact, pregnant women often do not pay much attention to gastroesophageal reflux disease-related symptoms such as nausea and vomiting, given that these common symptoms do not look severe. A clinical implication of the statistical results above, however, states that more active care is essential for these common symptoms to prevent more severe outcomes including preterm birth. Another clinical implication from this study states that preventive measures for diabetes mellitus, hypertensive disorder, and gastroesophageal reflux disease would be useful for the prevention of preterm birth, together with effective management of body mass index and progesterone and calcium channel blocker medications.The most recent endeavor on this topic involved the use of machine learning for predicting early stillbirth, late stillbirth, and preterm birth . The traFour machine learning approaches  were applied for predicting early stillbirth, late still birth, and preterm birth in this study. The gradient boosting decision tree reduces the bias of a decision tree ensemble based on residual fitting in a sequential manner. The artificial neural networks with the activation functions of rectified and scaled exponential linear units were designed to solve the problem of gradient vanishing (the gradient of the loss with respect to the weight becomes 0 quickly). The respective sensitivity measures of the four methods were 0.22, 0.24, 0.24, and 0.24 for preterm birth. The respective areas under the receiver operating characteristic curves of the four methods were 0.62, 0.63, 0.64, and 0.64 for preterm birth . Based on the results of logistic regression for predicting preterm birth in this study, the coefficients of all independent variables except hepatitis B were statistically significant at 1%.Another notable attempt was made recently on the effective application of machine learning on the prediction of preterm birth using uterine electrohysterogram data . Data foAs defined above, deep learning is a sub-group of the artificial neural network whose number of hidden layers is larger than five, e.g., ten. Different types of deep learning have been designed for different types of data, e.g., the convolutional neural network for image data and the recurrent neural network for sequence data such as electronic health records. In the convolutional neural network, a feature detector (“kernel”) moves across input data and the dot product of its elements and their input data counterparts is calculated. This operation of “convolution” identifies certain characteristics of the input data, for example, the shape of a tumor compared to that of a normal cell . In the For example, a recent study used a recurrent neural network ensemble to predict extreme preterm birth  . Data foThe summary of review is presented in Existing literature on the early diagnosis of preterm birth based on artificial intelligence suffers from several limitations and more improvement is needed in these directions. Firstly, these studies used a cross-sectional design because of limited data availability. Expanding data with a longitudinal design is expected to improve the performance of artificial intelligence much more. Secondly, these studies did not consider possible mediating effects among variables. Thirdly, these studies used data with small sample sizes in single centers. Expanding these studies to big data  will be a good topic for future research. Fourthly, the areas under the receiver operating characteristic curves of machine learning methods in these studies (0.54–0.83) might not be optimal as diagnostic tests yet. Fifthly, binary categories  are common for preterm birth but their categories can be refined further, for example, previable (less than 24 weeks of gestation), very early (24–27 weeks), early (28–31 weeks), and late (32–37 weeks). Analyzing various factors of preterm birth based on more refined categories will be an interesting issue for future research. Sixthly, little investigation has been carried out and more study is needed on possible pathways between gastroesophageal reflux disease and preterm birth . SeventhThis article reviewed the existing literature and addressed the future perspectives regarding the application of artificial intelligence in early diagnosis of spontaneous preterm labor and birth. This review indicates that artificial intelligence provides a potential for a non-invasive tool and decision support system for early diagnosis of spontaneous preterm labor and birth.


This study aimed to investigate the predictors of maternal parenting self-efficacy when the children concerned are in the early years of life.A descriptive-analytical research study was carried out among 213 women who were in the early months of the postpartum period and attending healthcare facilities in Irbid, Jordan. The State Anxiety Inventory (SAI) and the Maternal Parenting Self-Efficacy (PMP S-E) tool were used to collect the data.A significant correlation was found between the scores in self-efficacy and the quality of marriage relations , family income , employment , education , and living with extended family .The findings of this study show that MPSE is significantly associated with various predictors. These predictors are the mother’s education, income, whether she lives with extended family, her quality of marriage, and her employment. Maternal anxiety was found not to be a predictor for MPSE and this may explain other factors such as social support and living with extended family.It is essential for nurses to understand maternal parenting self-efficacy, therefore, including the concept of maternal parenting self-efficacy in nursing curricula can help raise awareness of this important concept. Understanding maternal parenting self-efficacy is necessary for nurses to evaluate the mothers’ parenting self-efficacy. Maternal parenting self-efficacy (MPSE) is one of the critical elements of maternal transformation as a woman moves into parenthood. A mother’s self-efficacy as a parent not only affects her own mental health, it also influences the psychological development of her infant , 2.The pThus, to enable a seamless transition into parenting, it is essential to be aware of the factors that affect MPSE in order to facilitate the planning and delivery of comprehensive care to disadvantaged mothers. According to Bandura, MPSE refers to the perceptions that mothers have regarding their ability to accomplish particular duties in caring for newborns . MothersAccording to Yap, Nasir, Tan, and Lau, the level of MPSE is dependent on various factors, such as individual assets, society, and the environmental context . The facA review of eight quantitative studies on MPSE concluded that MPSE has a positive relationship with multiparty support, the support of society, parenting, and contentment in marriage, while it has a negative association with maternal stress and state of anxiety . Leahy-WNevertheless, irrespective of the apparent relationship between self-efficacy, social assistance, and postnatal stress, scant research has been conducted to investigate these interlinked elements in mothers during the early postpartum period . The limA descriptive cross-sectional approach was utilized in this research. This strategy seemed appropriate for achieving the research objectives since the aim of the study was to examine and define the association between all the factors of interest at a specific time without altering the associations between variables.The study was conducted in public tertiary health facilities in Irbid City in Jordan with an annual delivery of services to 30,000 mothers. Convenience sampling was employed to select suitable participants during the hospital discharge procedure. Convenience sample was achieved by visiting tertiary health centers in Irbid city and determine mothers that met inclusion criteria and invited them to participated.This type of sampling is especially beneficial when seeking to recruit subjects within a short duration of time, which is particularly relevant for the topic under study. The inclusion criteria for selecting the women were as follows: (a) age more than 18 years old, (b) mother to a child aged less than 3 years old, and (c) ability to read and write in Arabic. The exclusion criteria were designed to omit mothers who (a) were cognitively disabled according to their medical records, and (b) had suffered extreme intra-partum, ante-partum, or postnatal maternal difficulties, since these problems may impact the mother’s self-efficacy in negative ways. This is an indication that only women without any ante-natal complications were enrolled in the study.The estimation of the sample size relied on the use of a correlation assessment. This assessment suggested that in order to determine the association of MPSE with social assistance and other demographic factors, a minimum sample size of 200 was required. This figure was based on the need to have an effect of 0.25, and 80% power at a level of significance of .05 (two-sided). More than 250 were approached to participate in the study, but some of them did not participate for personal reasons. 220 surveys were returned, but seven were excluded since they were missing more than 20% of the data. A total of 213 women participated in the study.The instrument for this study consisted of three parts: a demographic questionnaire, the State Anxiety Inventory (SAI), and the Maternal Parenting Self-Efficacy (PMP S-E) tool. The researcher developed a questionnaire to obtain background information about the sample, such as age, gender, marital status, education level of the mother, living area , and the number of family members. See The SAI  was usedThe PMP S-E tool  was usedThe ethical endorsement to carry out this research was granted by the Ethical Committee of the Jordan University of Science and Technology (JUST) and the Institutional Review Board (IRB) of the Ministry of Health. The subjects were given information concerning the objectives of the study by the researcher, details of its benefits, the freedom to choose to participate, and the privilege of freely withdrawing from the survey. In addition, the subjects were given an assurance that their data would be confidential and that only the researcher could access the information.Data was only collected after the IRB of the Ministry of Health and the Ethical Committed of the JUST had given approval for the study to proceed. The mothers at the facilities who agreed to participate were interviewed to determine whether they met the criteria for inclusion. If they satisfied the criteria, they were asked to sign a consent form confirming that they wished to participate before they were issued with a folder. The folder contained an introduction letter, two consent forms (one for the researcher and one for the subject), a self-sealing envelope, and a survey form. The researcher gathered data from the subjects from the facilities. Every subject at the facilities was given approximately 20 minutes to finish the survey. This was in line with a pilot study that was conducted on a sample with a diverse range of education from which it was concluded that the survey instrument would take from 15 to 20 minutes to complete. The researcher’s assistants were present during the completion of the survey in order to respond to questions, and give clarifications.The descriptive statistics were analyzed using SPSS first according to mean, frequency, and distribution. Any discrepant or unusual data was identified and dealt with before this analysis. Surveys with more than 20% of the data missing were excluded from the study. A table format was used to display the descriptive information on the attributes and socio-demographics of the participating mothers. All the statistical procedures were subjected to an assumption trial. Normality was investigated for all the continuous-level data. The assumption trial for the multiple regression analysis was done to determine the predictors of MPSE. The significance level was determined to p≥ .05. The covariates factors were mother age, mother education, mother assistance, mother employment, mother experience with children, place of living, marital relation, family income, infant age, infant gender.n = 168) had completed a bachelor’s degree or higher. Over half were unemployed . The mean monthly income of the family was 887.2 Jordanian dinars. The age of the infant and toddlers ranged between 3 and 30 months, with a mean age of 17 months with just over half the infants and toddlers female  and the rest male . See The age of the mothers ranged between 19 and 37, with a mean age of 30.2 years. The majority of the mothers . This means that maternal anxiety does not predict MPSE and does not have any impact. See F = 2.930, P = 0.01) that indicated that MPSE was associated with the following factors: quality of marriage relations , as a higher quality of marriage meant an increased MPSE score, family income  as the increasing of income also caused an increase in the MPSE score. Employment is another factor that impacted MPSE and showed that working mothers did not exhibit more MPSE toward infants and toddlers . Education is another factor that impacted the MPSE score  and this means educated mothers exhibit more MPSE toward their infants and toddlers than uneducated mothers, and living with extended family  enhance the mother ability to exhibit greater MPSE. Hence, these factors were found to be key predictors of MPSE. The results of the multivariate regression analysis are shown in detail in Multiple regression analysis revealed a significant pattern (This study aims to investigate the relationship between maternal anxiety and the predictors of maternal parental self-efficacy when the children concerned are in the early years of life. Based on the outcomes of this study, it seems that environmental factors, including family factors, could have an impact on MPSE.Similar to previous studies by Ngai et al. and Salonen et al, our study found that maternal anxiety did not predict self-efficacy. However, there is a need for a longitudinal study to gauge the association between MPSE and maternal anxiety at different times during the postnatal period , 14. HowOur results showed that Jordanian mothers appreciate being in contact with their infant and toddlers, irrespective of the time taken to understand the needs of their infant and toddlers through the infant and toddlers’ expressions of temperament. In addition, Jordanian mothers with experience in caring for infants and toddlers before they had their own child and those living in a large family had an elevated level of MPSE. The above outcomes are in agreement with the results reported by Gharaibeh and Halman, who proposed that maternal background may work as precursors of self-efficacy. In the context of Arabic culture , these oThe findings of this study also showed that mothers with experience of caring for an infant and toddler before motherhood by living with extended family, being an aunt, and participating in childcare had a lot of confidence in their ability to take on caregiving responsibilities. Those who had watched others care for infants and toddlers or had received guidance, assistance, and words of encouragement perceived that they had high levels of self-efficacy. These outcomes are consistent with the results of Farkas and Valdés and Abuhammad et al, who stressed the significance of assistance in promoting self-efficacy and courage in caring for infants and toddlers , 22.According to Leahy-Warren and McCarthy , maternaAs for the impact of age, in contrast with previous Jordanian  and inteIt is essential for nurses to understand MPSE. Therefore, including the concept of maternal parenting self-efficacy in nursing curricula can help raise awareness of this important concept. Understanding maternal parenting self-efficacy is necessary for nurses to evaluate the mothers’ parenting self-efficacy. Certain anticipatory guidance and related interventions can be explored as required. Nurses can offer education to the mothers regarding parenting maternal self-efficacy, which will enable them to care for their children properly. For example, the nurses should teach mothers that parenting self-efficacy is modifiable. It is possible that maternal parenting self-efficacy and parenting practices may mutually influence each other over time.The findings of this study show that MPSE is significantly associated with various predictors. These predictors are the mother’s education, income, if she lives with extended family, her quality of marriage, and her employment. Maternal anxiety was found not to be a predictor for MPSE and this may explain other factors such as social support and living with extended family. Nurses may therefore wish to consider evaluating women who show a possible risk of low MPSE and assist them via training, assistance, and interventions to boost their parental self-efficacy. However, it should be noted that the theoretical technique applied in this study needs to be replicated in order to bolster these findings empirically. In addition, more studies on the impact of socio-demographic variables and other factors on MPSE are required to provide support to the outcomes of this study and deeper insight into this phenomenon.


In total, 58 preterm infants were included . No differences were identified at any predefined time point in terms of GA and delivery mode (p > 0.05). We, therefore, concluded that correction for these factors in this population is not warranted when performing fecal VOC analysis in the first three weeks of life.Fecal volatile organic compounds (VOC) reflect human and gut microbiota metabolic pathways and their interaction. VOC behold potential as non-invasive preclinical diagnostic biomarkers in various diseases, e.g., necrotizing enterocolitis and late onset sepsis. There is a need for standardization and assessment of the influence of clinical and environmental factors on the VOC outcome before this technique can be applied in clinical practice. The aim of this study was to investigate the influence of gestational age (GA) and mode of delivery on the fecal VOC pattern in preterm infants born below 30 weeks of gestation. Longitudinal fecal samples, collected on days 7, 14, and 21 postnatally, were analyzed by an electronic nose device (Cyranose 320 In recent decades, new diagnostic methods and therapeutic options in the care for preterm infants have resulted in improved outcomes, particularly after extremely preterm birth . NeverthTimely detection and prompt treatment are often impeded by lack of early and specific clinical signs and diagnostic tools ,13. MoreIn the past decade, metabolic research has pointed to new potential biomarkers for various medical conditions, including oncologic, inflammatory, endocrine, and infectious diseases in both adults and children ,30,31,32With the latter technology, the presented VOC are first ionized and subsequently transported toward a build-in sensor using a carrier gas. During the transport, the electric field is modulated, which makes the ions drift in a ‘zigzag-like’ pattern before reaching the sensor. As a result, a wide variety of different ionized molecules can be separated by (ion-specific) differences in mobility .In eNose devices, on the other hand, the odor sample is drawn across a sensor array, which results in a competitive interaction between the sensors and VOC upon exposure. Subsequently, reversible physical and/or chemical alterations in the sensing material occur, changing the electrical properties in each sensor. These changes are registered and result in a scent pattern .Specifically in neonatal care, eNoses have proven their potential in diagnosis of LOS, NEC, and bronchopulmonary dysplasia (BPD) in the clinical prodrome ,39,40,41®), are influenced by enteral feeding practice in preterm neonates born at GA < 30 weeks [Since part of excreted VOC are products of metabolic pathways of  micro-organisms, it is hypothesized that VOC in newborns would be affected by factors affecting the microbiota composition, such as mode of delivery, gestational age (GA), and feeding ,45,46,4730 weeks . The cur30 weeks ,45,49.The current study was part of an ongoing prospective multicenter cohort study in nine participating neonatal intensive care units (NICUs) in the Netherlands and Belgium in which infants born before 30 weeks of gestation are included . The aimFor the current study, infants born at four out of nine centers were included in order to limit center-specific variation in fecal VOC outcome: Emma Children’s Hospital , Máxima Medical Center , Wilhelmina Children’s Hospital , and University Hospital Leuven . Selection of participating centers was based on availability of fecal samples in the study biobank. Samples from infants born in the period between December 2014 and December 2016 were selected for further analyses. Probiotics were not administered routinely in any of the participating centers. Infants with congenital gastrointestinal malformations  and surgery of the gastro-intestinal tract were excluded. Additional exclusion criteria include the development of bacterial sepsis and/or meningitis ), diagnosis or suspicion for NEC (conform Bell’s criteria), and spontaneous intestinal perforation (SIP) . Infants1) vaginally born infants or (2) infants born by C-section. Infants were matched exclusively based on the birth center.Included infants were categorized according to the variables of interest: GA and mode of delivery. Cases and controls were defined as born 24–26 6/7 and 27–29 6/7 weeks of gestation, respectively. From epidemiological data, it is known that the morbidity and mortality of infants is inversely correlated with the gestational age at birth, with larger week-to-week variations at earlier GA . AssuminWe were not able to perform a sample size calculation due to lack of previous studies on this subject. Based on research on the effect of sampling conditions and enteral feeding type on VOC patterns, we assumed that a sample size of 15 subjects per group would suffice to identify clinically significant differences in VOC patterns ,52.1) predominantly consisting of mother’s milk , (2) predominantly consisting of formula milk  and (3) consisting of a combination of mother’s and formula milk (MM/FM). GA was defined as the number of weeks since the last maternal menstrual period. Age at full enteral feeding was defined as the first day of life at which infants were enterally fed > 120 mL/kg/day or did not receive parenteral feeding for over two consecutive days.The enteral feeding practice was categorized as , and subsequently stored at −20 °C within one hour after collection, until further handling. In case of multiple stool productions per day, the first fecal sample was stored. Sample collection was ceased in case of transfer to a referral hospital or decease before the postnatal age of 28 days. Fecal samples collected at 7 (t1), 14 (t2), and 21 (t3) (±2) days postnatally were selected for fecal VOC analysis.®, Smiths Detections, Pasadena, CA, USA). Approximately 150 mg sample mass was weighted on a calibrated scale  and transferred into a sealed vacutainer . Prior to analysis, samples were thawed to room temperature (18 °C) for 10 min, and subsequently connected to the eNose in an airtight loop system to prevent ambient air dilution . Distribution of the data was visually assessed. Categorical data are presented as numbers and percentages. A p-value < 0.05 was considered statistically significant.Statistical analyses of demographic and clinical data were performed using Statistical Package for the Social Science (SPSS) version 26.0 . Where considered appropriate, Mann-Whitney U-test, Student’s The statistical analyses of VOC profiles in relation to GA and mode of delivery were conducted using R version 3.6.3 packages ‘stats’, ‘gplot’, and ‘global test’. The R script is made available in ® polymer sensors, corrected by the previously mentioned linear regression model, were compared according to GA and mode of delivery. To do so, both an ANOVA  was applied per sensor to compare the measurements between groups as well as a global test to compare measurements of all sensors between groups. For this analysis, GA was categorized using 27 weeks as a cut-off, creating two groups, so that both it and the mode of delivery are binary variables. As such, the global test with a logistic link function was used. Including all 32 sensors’ data, this test allows for the assessment of changes in sensor data patterns between groups of GA on the one hand, and mode of delivery on the other hand. Results of the F-test from a one-way ANOVA were reported for the sensor with the lowest p-value on a given time point.In order to identify the association between fecal VOC profiles and the various study groups, the values representing the electrical resistance of each one of the 32 CyranoseFifty-eight infants were included in the study of which 29 were born at GA 24–26 6/7 weeks’ gestation and 24 were born vaginally . Birth w® eNose, did not differ significantly in the first three weeks of life between infants born at 24–26 6/7 weeks and those born at 27–29 6/7 weeks of gestation  ,58.The second aim of this study was to compare the longitudinal course of fecal VOC patterns between vaginal birth and birth via C-section in the same cohort. Our results suggest that mode of delivery does not affect VOC profiles significantly during the first weeks of life in infants born at GA <30 weeks. To our knowledge, no previous metabolic research has been conducted on this topic, but several microbiome studies are available ,60. In lThis is in contrast with studies on term infants, which show short- and long-term differences in the microbiome community structure and function after birth via C-section when compared to vaginally born infants ,61. It iThe first strength of this study is the prospective and standardized collection and handling of fecal samples by which we reduce the risk of potential pre-analytical errors ,52,54. AThere are several limitations that need to be addressed. First, within the group of mother’s milk-fed children, it was decided not to make a distinction between infants receiving raw own mother’s milk (OMM) and those receiving pasteurized own mother’s or pasteurized donor human milk (resp. pOMM and DHM). Based on previous studies, a (mildly) different microbiota, and potentially VOC profile, could be supposed . Yet, weAn additional limitation is that our exclusion criteria did not include non-infectious diseases with a potential effect on the infant’s metabolic state, such as BPD, severe IVH, and patent ductus arteriosus (PDA) ,58,63,64Our results show that VOC profiles, as measured by an eNose device, in preterm infants born at GA <30 weeks, are not influenced by GA or mode of delivery during the first three weeks of life. If reproduced in other cohorts, these results implicate that it would be methodologically appropriate not to correct for GA and mode of delivery when performing fecal VOC research in a preterm population born before 30 weeks’ gestation until three weeks postnatally. We hypothesized that environmental factors  and clinical conditions  are likely to influence fecal VOC outcome to a greater extent than GA and delivery mode in this particular population. When not yet investigated, these variables should be addressed in further research.