The small number of studies examining the association of prenatal acetaminophen with birth outcomes have all relied on maternal self-report. It remains unknown whether prenatal acetaminophen exposure measured in a biological specimen is associated with birth outcomes.To investigate the association of acetaminophen measured in meconium with birthweight, gestational age, preterm birth, size for gestational age, gestational diabetes, preeclampsia, and high blood pressure.via multiple imputation and used inverse probability weighting to account for confounding and selection bias.This birth cohort from Sherbrooke, QC, Canada, included 773 live births. Mothers with no thyroid disease enrolled at their first prenatal care visit or delivery. Acetaminophen was measured in meconium for 393 children at delivery. We tested associations of prenatal acetaminophen with birthweight, preterm birth, gestational age, small and large for gestational age, gestational diabetes, preeclampsia, and high blood pressure. We imputed missing data Acetaminophen was detected in 222 meconium samples (56.5%). Prenatal acetaminophen exposure was associated with decreased birthweight by 136 g , 20% increased weekly hazard of delivery , and over 60% decreased odds of being born large for gestational age . Prenatal acetaminophen was not associated with small for gestational age, preterm birth, or any pregnancy complications.Prenatal acetaminophen was associated with adverse birth outcomes. Although unobserved confounding and confounding by indication are possible, these results warrant further investigation into adverse perinatal effects of prenatal acetaminophen exposure. Acetaminophen  is the only analgesic recommended by doctors for pregnant women, as prenatal exposure to other drugs commonly used to treat pain and fever such as aspirin and non-steroidal anti-inflammatory drugs  have previously been associated with birth defects, premature ductus arteriosus closure, and miscarriage –8. Accorvia adverse birth outcomes, such as reduced birthweight and preterm birth. For instance, birth cohort studies have shown associations of pre-pregnancy and prenatal acetaminophen exposure with low birthweight  cohort in Sherbrooke, QC, Canada. The cohort was initially designed to examine the effects of environmental contaminants on endocrine disruption. Women age ≥ 18 years without chronic medical conditions and with no known thyroid disease enrolled at the Research Center of the CHUS  from September 25, 2007, to September 10, 2009. Half of the cohort was enrolled at the beginning of pregnancy at their first prenatal care visit, and the other half was enrolled at delivery. Recruitment at delivery excluded very preterm births before 33 weeks completed gestation. Among the 800 women recruited, 37 were excluded due to loss to follow up or miscarriage and 10 gave birth to twins, resulting in 773 live births . All stuin utero, if the diaper was thrown in the trash before the technician was able to collect it, or if we were unable to finance technician time for collecting the sample. These potential sources of selection bias were addressed by weighting on the inverse probability of selection . Acetaminophen was measured with a recovery of 104% and repeatability of ±15%. The limit of detection (LOD) and limit of quantification (LOQ) were 2 and 5 ng/g, respectively.Meconium was collected from diapers of infants after delivery and stored within 10 mins at −80°C until analysis, which occurred in 2017–2018. Acetaminophen was extracted from <120 mg meconium and analyzed with ultraperformance liquid chromatography mass spectrometry following the methods described elsewhere . Among aData for birthweight and gestational age were obtained from CHUS medical records. Infants were weighed on Scale-tronix pediatrics scale 4802 by the obstetric team. Preterm birth was defined as birth before 37 completed weeks of gestation. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birthweights below the 10th percentile and above the 90th percentile for gestational age, respectively. We assigned SGA and LGA categories and computed birthweight for gestational age z-scores in accordance with the Fenton international growth chart . Data onCovariate data were obtained from CHUS medical records and questionnaires administered after delivery. Covariates were child sex, familial income, and maternal characteristics including age at delivery, education status (College/University vs. no College/University), pre-pregnancy BMI, smoking during pregnancy (yes/no), and alcohol during pregnancy (yes/no).Differences in baseline characteristics between (1) individuals with and without prenatal acetaminophen exposure, and (2) individuals with and without meconium collected at delivery were determined using chi-square goodness of fit tests for binary variables and two-sample t-tests for continuous variables. Using linear regression, we estimated associations of meconium acetaminophen detection (yes vs. no) with birthweight in grams and birthweight for gestational age z-score. Using logistic regression, we estimated associations of meconium acetaminophen detection with SGA, LGA, preterm birth, and maternal gestational diabetes, preeclampsia, and high blood pressure. Using cox proportional hazards models with birth as the event and gestational age as the time to event, we estimated the association of meconium acetaminophen detection with the hazard for giving birth. Because birth (the event) occurred for all individuals, increased hazards in these models indicate shorter gestational age (the time to event). Confidence intervals for cox models were calculated with robust standard errors. Coefficients from logistic regressions and cox models were exponentiated into odds ratios and hazard ratios, respectively. To account for missing covariate data, all models were employed on 10 datasets imputed using the “MICE” R package . Estimatp, the likelihood of detectable meconium acetaminophen) were estimated using logistic regression models in which exposure (meconium acetaminophen detected vs. not detected) was regressed on the covariates described above. Weights were estimated as 1/p for exposed individuals, and 1/(1 – p) for unexposed individuals. Covariate balancing propensity scores and weights were computed using the “CBPS” R package  using propensity scores –43. Prop package . This st package , 41, 43.We additionally addressed potential selection bias related to meconium collection by weighting models on both the inverse probability of exposure described above and the inverse probability of selection. We first created weights for the probability of selection using logistic regression models in which selection (meconium collected vs. not collected) was regressed on the covariates described above for the entire 810 individual cohort . Then we removed those without meconium data and created weights for the probability of exposure as described above before fitting weighted models of the effect of meconium acetaminophen exposure on birth outcomes. Weighting the 393 individual selected sample on the probability of selection creates a pseudo-population that is comparable on measured covariates to the entire 810 individual cohort.We computed E-values to assess the potential for unmeasured confounding . E-valueBaseline covariates stratified by meconium acetaminophen detection are presented in in utero compared to the unexposed group (39.0 vs. 39.3 weeks). Accordingly, prenatal acetaminophen exposure was associated with a 20% increased weekly hazard of delivery , indicating a higher likelihood for earlier delivery and thus reduced gestational age in exposed individuals (Infants with acetaminophen detected in meconium had a mean (range) birthweight of 3,338 g  and mean gestational age of 39.0 weeks  compared with 3,459 g  and 39.3 weeks  for unexposed infants . Accountividuals . Our datividuals . Resultsividuals . For outWe conducted sensitivity analyses for selection bias and unmeasured confounding. Mothers of children for whom meconium was collected were significantly older and more educated compared to those without meconium data , indicatMeconium acetaminophen was not associated with pregnancy complications including gestational diabetes, preeclampsia, or high blood pressure .In this Eastern Canadian birth cohort, detection of acetaminophen in meconium, which may indicate prenatal acetaminophen exposure during the 2nd and 3rd trimesters of pregnancy, was likely associated with decreased birthweight, decreased gestational age, and decreased odds of LGA. Although meconium was only collected for approximately half of our eligible births, we found no evidence that selection bias impacted effect estimation: associations of meconium acetaminophen with outcomes were nearly identical in both models adjusted and not adjusted for selection bias.Our study has several strengths. First, the high genetic and sociodemographic homogeneity in the GESTE cohort limits the likelihood of confounding by unknown genetic or sociodemographic factors. Second, the prospective nature of the cohort limits sources of bias common in retrospective designs, including selection and recall bias. Third, we explicitly controlled for known sources of confounding and selection bias. Finally, our measurement of prenatal acetaminophen exposure in meconium eliminates the possibility of recall bias.This study has limitations. First, while the homogeneity of the GESTE cohort may limit confounding, it also lowers the generalizability of results. Even within our own study, the magnitude of the association of meconium acetaminophen with birthweight was not entirely generalizable between individuals recruited during pregnancy and at delivery. This could be explained by differing distributions of unmeasured genetic and environmental effect modifiers in each group. Second, this study had a relatively small sample size of just under 400 mother child pairs. Consequently, there were few events for several outcomes, including early prematurity and severe preeclampsia. Third, our conclusions regarding preterm birth may be limited by the exclusion of some extremely preterm deliveries. Although unlikely, this could be a source of selection bias if there are different effects of prenatal acetaminophen exposure on the risk for preterm birth before 33 weeks versus before 37 weeks. Fourth, we lacked the information necessary to control for indications for acetaminophen use, such as chronic pain, fever, and infections during pregnancy. However, when controlling for indications for acetaminophen in the Danish National Birth Cohort study, Rebordosa and colleagues still observed associations of prenatal acetaminophen with increased risk of preterm birth . Howevervia questionnaires administered during pregnancy and postpartum. When self-report occurs in postpartum interviews, mothers of infants with adverse birth outcomes may rack their brains for an explanation, thereby overreporting exposures (A small number of studies have previously shown associations between maternal self-reported acetaminophen use during pregnancy and adverse birth outcomes. In the Danish National Birth Cohort, there was an increased risk of preterm birth among women using acetaminophen during the third trimester of pregnancy, but there were no associations of acetaminophen use with miscarriage, stillbirth, low birthweight, or SGA, or with common preterm birth complications including bronchopulmonary dysplasia, intracranial hemorrhage, retinopathy of prematurity, perinatal infections and anemia of prematurity . In the xposures –27. Our While the associations of prenatal acetaminophen exposure with adverse birth outcomes found here may be concerning, more studies in a diverse range of cohorts are needed before suggesting a change in clinical practice. Additionally, evolving patterns of both antenatal management and acetaminophen use in this population since the study began in 2007 likely impacts the relevance of our results. For instance, one study found a decline in acetaminophen use during pregnancy by 2.5% for each 2-year period between 2004 and 2018 .Mechanisms underlying the associations of prenatal acetaminophen exposure with adverse birth outcomes remain unknown. Acetaminophen may inhibit prostacyclin synthesis and thereby promote pre-eclampsia , which hWhile this study may add evidence in support of questioning the safety of acetaminophen use during pregnancy, more work is needed to rule out confounding by indication and to assess generalizability before a change in clinical practice is recommended.https://github.com/brennanhilton/acetaminophen-birth-outcomes.The original contributions presented in the study are publicly available. This code can be found here: The studies involving human participants were reviewed and approved by Institutional review boards of the University of Sherbrooke and Columbia University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.BB conceptualized and carried out the analyses, drafted the initial manuscript, reviewed, and revised the manuscript. HB conceptualized the analyses, reviewed, and revised the manuscript. TB, ABo, AL, and VG coordinated and supervised data collection, reviewed, and revised the manuscript. LT, J-PB, J-CP, and ABa designed the study, reviewed, and revised the manuscript. All authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In northern rural Malawi, the majority of households cook using open fires and there is also a high burden of adverse birth outcomes. The use of open fires or highly polluting cookstoves is associated with low birthweight in babies. There is mixed evidence on whether implementation of cleaner burning cookstoves reduces the number of babies born with low birthweight.N = 4010). A subset of data with stricter exposure definitions respecting the original randomized allocation was also analysed (N = 1050). A causal, forwards modelling approach was used.This is a secondary analysis of a cluster randomized control trial in Malawi, conducted over 2014–17. Households were randomized to receive improved cookstoves or to continue current practices. For this analysis, the primary outcome was low birthweight in households under routine demographic surveillance, among births occurring within the trial time frame (n = 2788). The subset analysis lacked power to provide evidence of association between improved cookstoves and low birthweight in the stricter exposure definition .The main dataset showed evidence of effect of the intervention on low birthweight [adjusted odds ratio (aOR) 0.69; 95% CI 0.48–0.99, This study provides some evidence that an improved cookstove intervention in rural Malawi reduced the number of babies born with low birthweight by 30%. This direction of the effect was also seen in the subset analysis. The analysis suggests that the intervention reduced the number of infants born prematurely or with intra-uterine growth restriction, indicating that improved cookstoves could be a useful maternal health intervention. Key MessagesAround 3 billion people worldwide cook using open fires or inefficient cookstoves, fuelled by biomass, coal or kerosene, accounting for 85% of particulate pollution in low-income countries.A growing body of evidence highlights the association with poor birth outcomes and household pollutants, with increases in risk for low birthweight, preterm birth and stillbirth.This secondary analysis in northern rural Malawi found evidence that a cleaner-burning, biomass-fuelled cookstove intervention reduced numbers of low birthweight babies born in this population by 31%.The intervention included user training, maintenance, two of most efficient stoves available and a solar panel: future programmes need to carefully consider sustainability and implementation.Further research on stillbirths, neonatal deaths and other birth outcomes in association with improved cookstoves would aid cost-benefit analysis.,Around 3 billion people worldwide cook using open fires or inefficient cookstoves, fuelled by biomass, coal or kerosene. This accounts for 85% of particulate pollution in low-income countries, causing an estimated 3.8 million premature deaths a year.,Worldwide, women and children are disproportionately exposed to household air pollution, due to traditional gender roles which include a larger volume of cooking and child care for women.In rural Malawi, gestational age is estimated without use of ultrasound scanning; therefore distinguishing premature birth from intra-uterine growth restriction (IUGR) can be challenging. It is estimated that 30–50% of babies who are born with a low birthweight will have been born prematurely; therefore in this analysis, low birthweight is used as a proxy for both pre-term birth and IUGR.,,,There is some evidence from observational studies that improved cookstoves reduce low birthweight.These findings have not been consistently replicated in the three intervention studies identified.This analysis aims to partially address the mixed evidence of whether an intervention of cleaner burning cookstoves would improve birthweight, through a secondary analysis of a large, small-area-level, cluster RCT in northern rural Malawi, which randomized clusters of over 4500 households either to a cleaner-burning biomass-fuelled cookstove or to continue standard cooking practices.In northern Malawi, the Karonga Health and Demographic Surveillance Site (HDSS) was established in 2002, within a 150-km² rural area.A subcluster randomized controlled trial [the Cooking and Pneumonia Study (CAPS)] was conducted in the Karonga HDSS in 2014–17. A total of 8626 households were allocated in geographically defined clusters to two arms of equal size, either to replace their usual cooking practices with two cleaner burning biomass-fuelled cookstoves with solar panels, or to continue cooking practices as normal.Cookstoves were maintained and replaced when necessary throughout the trial. In a randomly selected 10% of intervention households, monitors of temperature fluctuation were placed in one of the cookstoves as an objective measure of use. The mean number of times the cookstoves were used per day for the monitored cookstoves was 0.51 during the first year and 0.34 in the second year, demonstrating that the cookstoves continued to be used in the intervention arm.Participants in this secondary analysis were women participating in the Karonga HDSS who gave birth in from 2014 to 2018. Their exposure status was assigned according to whether they had a CAPS stove in their household for at least 1 week before the birth. The intervention arm included periods of observation from: (i) households in the CAPS intervention clusters who received a cookstove; and (ii) households in the CAPS control clusters who received a cookstove after completion of the trial from that point forward. The control arm periods of observation were: (i) households that were in CAPS control clusters for the period of the trial; and (ii) non-CAPS households from 2014 onwards. If a woman had more than one birth in the time period, only the first was used unless a subsequent birth had a greater intervention exposure time in pregnancy.Including control households in the intervention group after the trial ended increases the power of the analysis but could have resulted in a dilution of effect if households are less likely to use the cookstove if distributed without the training and support. Therefore, the same analyses were conducted on a smaller subset of the data which only included births in CAPS households during the trial itself, by the initial allocations as presented in The primary exposure was the cookstove intervention and the primary outcome was low birthweight (defined as weighing under 2.5 kg). When a birth is registered in the HDSS (which may be some time after birth), the midwife-recorded birthweight is transcribed from the patient-held health record of the infant , the mother is asked to report birthweight  and the weight of the baby is measured by study staff at the time of registration . No adjustment was made for the day the baby was weighed; however, both the intervention and the control groups had a similar distribution of babies weighed at the time of registration (control: 14.5% and intervention: 16.6%).P = <0.001), which suggested that analysing the recorded birthweight would be valuable: 51% of babies with an MUAC score of less than 11 had low birthweight, compared with 25% who did not. Further information on birth (i.e. location and method), the parents’ vital status (if known) and mother’s previous parity is collected during the registration of the birth.At the time of registration, mid upper arm circumference (MUAC) is also measured in the infants. MUAC scores are not used routinely under 6 months of age, but there is evidence that it has a strong correlation with birthweight.Potential confounders and effect modifiers were assigned from other population surveys in the demographic surveillance area, if the information was gathered within a certain time of the birth: mother’s marital status, household head’s schooling level and occupation reported within 1 year (before or after) of the birth, and cooking fire location within 2 years (before or after) of the birth.Stata (version 16.0) was used to perform the analysis. Although the data originate from an RCT, only households who had a child under 5 years were eligible for cookstoves and only households with births were included in this analysis. Therefore, as the intervention and control arms might be no longer balanced, confounders were adjusted for as necessary.P = 0.58) or trial arm (P = 0.7), so multiple imputation was used to allow inclusion of BMI in logistic regression models. As the BMI distribution was skewed, it was converted to the log scale prior to conducting the multiple imputation as this had a more normal distribution; 50 imputations were run, and the imputed BMIs were converted back prior to analysis. Logistic regression models were run with standard errors calculated to reflect that multiple imputation was used.A direct approach was used in line with a causal analysis: all confounders identified in the conceptual framework in ,Conceptually selected potential effect modifiers were tested for interactions. Maternal age, the sex of the baby and parents’ education were identified, as prior research has suggested these variables may determine vulnerability to household pollution: male neonates have been found to be more susceptible to pollutant exposure, younger or older women are more likely to have a low birthweight baby, and those who are at a social or economic disadvantage are more susceptible to negative exposures.The sample population consisted of 4340 births between 2014 and 2018. Of these births, 328 (8.3%) had a low birthweight (under 2500 g), 90 (2.1%) were neonatal deaths and 76 (1.8%) were stillbirths.The main dataset was made up of 4010 births from different women aged from 12 to 46, over 2014-17: 1201 (30.0%) mothers received the cookstove at least 1 week before birth, with the remaining 2809 women making up the control arm. In the intervention arm, 1041 (86.7%) women received the cookstove in their first trimester of pregnancy, 108 (9.0%) in their second and 52 (4.3%) in their third. In the control arm were 212 (78.2%) low birthweight babies.. The most common parity of birth was 1 or 2 (39.8%), with 84.3% of these births in the control arm. The largest proportion of women were in the age category of 20–24 (29.4%). The sex of the baby was equally distributed. Most births took place in a health facility (98.2%), with nearly all women receiving antenatal care during the pregnancy (99.9%). P = 0.14) or low birthweight (P = 0.41). Those who had missing marital status were more likely have a parity of 3–4 (P = 0.03). BMI had 55% missing data, with no association between missing BMI and low birthweight (P = 0.58) or trial arm (P = 0.70) found. Those with missing BMI were more likely to be younger (P <0.01) and unmarried (P <0.01). All other variables had less than 10% missing data.Marital status had 23% missing data. There was no evidence of an association between those who had marital status missing and trial arm  is made up of 1050 births from different women aged from 14 to 46, between 2014 and 2017. Differing from the main dataset, 551 (52.5%) of the mothers received the cookstove at least 1 week before birth, with 499 women in the control arm. P = 0.29) or trial arm (P = 0.62). Those with a missing BMI were more likely to be younger (P <0.01) and unmarried (P <0.01),There were less than 10% missing data in each variable, except 40% in BMI. There was no association between missing BMI and low birthweight , P = 0.34 for maternal age category  and P = 0.6 for sex of the baby .There was no evidence shown of effect modification by any pre-specified variable on the association between low birthweight and cookstove intervention in the main dataset: the likelihood ratio tests were ,,,We found some evidence that improved cookstoves reduced the odds of a baby being born with a low birthweight by 31%. This is the largest analysis on this topic to date, and was supported by a more restricted analysis of in-trial births: the same direction and similar magnitude of effect were found but there was weak evidence for this finding, likely reflecting a reduction in power due to fewer participants. This finding is consistent with one previous intervention study and all identified observational studies.One limitation of this study is birthweight measurement: 21.0% of birthweights were self-reported. Although birthweight was associated with MUAC measurements, the prevalence of low birthweight in Malawi is estimated to be 14.5% and in our sample it was 8.3%.Missing data for marital status in the main dataset is unlikely to have caused important bias: no key patterns of missingness or association were identified. Multiple imputation reduced possible bias and confounding due to missing data in BMI in the final models. Parity also remains partially unadjusted across both datasets: there were too few women in their first pregnancy to create a separate stratum, despite primiparity being known to increase the risk of low birthweight. This residual confounding may have biased towards the null, as more first-time mothers were in the control arm .This analysis found evidence that an improved cookstove intervention reduced the incidence of low birthweight in babies born in rural Malawi, either through a reduction in premature births or in IUGR. The findings highlight the importance of indoor air quality during pregnancy, specifically in low-income settings. Further larger-scale research is required to determine the effects of improved cookstoves on birth outcomes such as stillbirth and neonatal deaths, with longer data collection post-trial to consider the sustainability of this intervention. Understanding at which point in pregnancy the reduced pollutant exposure may be most beneficial could help target interventions.Qualitative work has shown that households do not view the higher costs of improved cookstoves as affordable or a worthwhile investment, especially when marketed as a health intervention.Ethics approval for the trial was granted from the Malawi College of Medicine Research Ethics Committee in Malawi (Ref P.11/12/1308), the Liverpool School of Tropical Medicine Research Ethics Committee in the UK (Ref 12.40) and, for the demographic surveillance, from the Malawi National Health Sciences Research Committee (#419/19).


Tailgut cysts or retrorectal cystic hamartomas are rare, congenital, development lesions arising from the remnants of the hindgut during embryogenesis. It is most often misdiagnosed due to its rarity, variable clinical presentation, and malignant potential. The following report describes an unusual case of a tailgut cyst in a 60-year-old male with a history of a perianal mass for 12 years. Surgical resection was done, and histopathological examination revealed a multiloculated cyst filled with brownish fluid, grossly, and a cyst lined by various epithelia such as stratified squamous epithelium, pseudostratified columnar epithelium, and flattened to cuboidal and mucin-secreting columnar epithelium along with cyst wall made up of bundles of smooth muscles, microscopically. Several lesions mimic a tailgut cyst and need to be excluded from the differentials. Although no malignancy was documented in this case, these cysts have been known to undergo malignant transformation into adenocarcinoma and neuroendocrine carcinoma, to name a few. This warrants a thorough and accurate histopathological assessment and mandatory follow-up. Tailgut cysts or retrorectal cystic hamartomas are rare, congenital, hamartomatous lesions that arise from the persistent embryological remnants of the postanal gut (hindgut) that fail to regress completely . They ocTailgut cysts are benign and need to be distinguished from other congenital malformations and benign and malignant neoplasms that occur in this location . Owing tThis case was previously presented as a poster at KAPCON 2021 Virtual Conference.A 60-year-old male patient presented with a painless, perianal lesion of 12 years in duration. No history of rectal bleeding/discomfort, constipation, urinary problems, or fever was reported. The physical examination revealed a polypoidal, skin-covered mass in the perianal region that was soft to touch, non-tender, and not adhered to surrounding structures. The patient underwent resection of the tumor with no significant intraoperative findings or intra-/postoperative complications. The specimen was sent for histopathological examination.Grossly, the resected skin-covered specimen measuring 5 × 3 × 1 cm showed a multiloculated cyst with trabeculations and expelled brownish material Figure -1C.Microscopically, the cyst was lined by various epithelia, including stratified squamous epithelium, pseudostratified columnar epithelium, and flattened to cuboidal and mucin-secreting columnar epithelium. The cyst wall contained bundles of smooth muscles. Areas of pigment-laden macrophages and chronic inflammatory cell infiltrates were noted. Skin adnexal structures, neuronal elements, bone, and cartilage were not identified in the cystic areas. No atypical/malignant cells were identified Figure -2F.Based on these findings, the case was diagnosed as a tailgut cyst.The origin of the tailgut cyst is hypothesized to arise from the remnants of the normally regressing hindgut tail around the eighth week of embryogenesis ,5.Tailgut cysts have various nonspecific clinical manifestations, making diagnosis difficult ,8. Most They may get secondarily infected and misdiagnosed as a pilonidal cyst, a perianal/anorectal fistula, or a recurrent retrorectal abscess . Signs oThe differential diagnoses of a tailgut cyst include anal gland cyst, duplication cyst, epidermal cyst, sacral meningocele, and teratoma/dermoid cyst . The locHjermstad and Helwig, the first authors to report a tailgut cyst, specified two histological criteria for the diagnosis of a tailgut cyst: (a) the epithelial lining of the cysts must contain transitional and/or glandular type (columnar) of epithelium, with or without a stratified squamous component, and (b) the underlying stroma must compose fibrous tissue with scattered and discontinuous smooth muscle bundle fibers, i.e., it must lack a well-defined muscular layer . Both thA large majority of tailgut cysts are benign; however, malignant transformation, although rare, has been reported in several cases. They include adenocarcinomas, carcinoid tumors, neuroendocrine carcinomas, endometrioid carcinomas, adenosquamous carcinomas, squamous cell carcinomas, and sarcomas, in decreasing order of frequency -6. EvideGiven the limitations of imaging techniques to make a definitive diagnosis, a preoperative biopsy could facilitate optimal surgical planning . HoweverComplete surgical excision followed by histopathological examination is a must to eliminate the risk of recurrence, hemorrhage, infection, compression, and malignant transformation ,12. PostTailgut cysts are rare, congenital lesions derived from vestigial elements of the embryonic hindgut. The clinical diagnosis is difficult because it is mostly asymptomatic or manifests with nonspecific mass effect symptoms or neurological symptoms. They are usually misdiagnosed and go into complications including malignant transformation. Complete surgical resection is mandatory upon diagnosis, followed by histopathological examination, and subsequent follow-up must be ensured.


Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants.The Japan Environment and Children’s Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <‐2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th–79th percentiles (204–260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <‐2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset.A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents’ heights, the odds ratio  of No-CU was 2.95 (1.28–6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU .High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism. Infants born small for gestational age (SGA) are at a high risk of long-lasting intellectual and psychological impairments such as low cognitive function, aggressive behaviors, and attention-deficit hyperactivity disorder –6. ApproSince the maternal supply of cholesterol to the fetus plays an important role in the development of the fetal nervous and vascular system –23, the Previously, we had shown that maternal TC levels in mid-pregnancy were associated with SGA or large for gestational age in the Japan Environment and Children’s Study (JECS), a Japanese nationwide birth cohort study . As a suThe JECS was established in 2011 with 15 Regional Centers located across Japan –38. ThisThe study protocol of the JECS was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and the ethics committees of all participating institutions. All participants in the present study provided written informed consent. Data for the current analyses were extracted from the dataset released in October 2019 (dataset -jecs-ta-20190930-qsn).The present study involved a total of 2,222 mothers with infants born SGA (length and/or weight <-2 SD) who were extracted from the original JECS cohort comprising a total of 104,062 fetal records. First, this study was restricted to 88,086 mother-and-infant pairs with singleton live births at term. Second, 2,235 mother-and-infant pairs were excluded because of missing or conflicting data for SGA diagnosis. As the present study focused on SGA infants, we excluded 83,281 mothers and non-SGA infants. Finally, 87 cases with congenital cerebral, heart, and/or chromosomal abnormalities were excluded, leaving 2,222 mother-and-SGA-infant pairs eligible for the present analysis Figure 1Non-fasting blood samples were collected from pregnant women at early and mid-pregnancy. A contract clinical laboratory  assayed and analyzed enzymatically serum blood TC levels at mid-pregnancy using a 7700 clinical chemistry/immunoassay hybrid analyzer  .Raw maternal TC values and gestational age (days) at the time of blood sampling were significantly positively correlated. Therefore, the analysis was adjusted for gestational age at the time of blood sampling by residual methods , 40. TheThe Co-operating health care providers and/or Research Coordinators in 15 Regional Centers transcribed gestational age at birth and data on neonatal anthropometric measurements from the medical records. To determine the gestational age in weeks and days, ultrasonography during early pregnancy and/or estimation from the last menstrual period were used. The Z-score of birth weight or length for gestational age was calculated based on Japanese neonatal anthropometric charts .We adopted two SGA definitions. First, SGA was defined as length and/or weight <-2 SD at birth according to the criterion of the global consensus statement for growth hormone (GH) treatment . As a seChildren’s height at 3 years was reported by their mothers in a self-administrated questionnaire which was distributed around the third birthday (3 years of age) of the children. In Japan, all municipal and regional administrative offices are legally required to provide a free medical health checkup for 1.5- and 3-year-old children, and approximately 95% of the eligible children are examined. In addition, the “Manual for evaluation of infant and child physical development” indicates that height of children aged 2 years or more must be measured by medical professionals in the standing position to the nearest 0.1 cm . Thus, aNo-CU was defined by a Z-score of height at 3 years <- 2 SD according to the growth standard charts for Japanese children , 43, sinSocioeconomic data and lifestyle-related information were self-reported during the early and mid-period of pregnancies . AnthropThe Z-score of birth weight, the mother’s age at delivery, and weight gain during pregnancy were used as continuous variables. Smoking status  was clasThese covariates were selected based on current biological and epidemiological knowledge related to postnatal growth or a strategy of selecting variables according to a certain level of statistical significance  in the univariable analyses. The accuracy of modeling was assessed using discrimination and goodness of fit. A fully adjusted model discriminated No-CU reasonably well, with a rate of correct classifications of 84.2% and p-value of 0.52 for goodness of fit by Hosmer–Lemeshow test.In total, 1,088 records of 2,222 subjects (49.0%) were incomplete. Missing values for mother’s height (0.1%), smoking status (2.7%), weight gain during pregnancy (2.4%), breastfeeding status (16.7%), meal frequency (21.4%) at 2 years, father’s height (15.1%), No-CU occurrence at 3 years (27.4%), and maternal TC categories at mid-pregnancy (16.5%) were imputed using the Missing Values option in SPSS. The results using the 20 imputed data sets were combined as average, and standard errors were adjusted to reflect both within-imputation variability and between-imputation variability . Because2 tests.The characteristics of participants according to the occurrence of No-CU are reported as means and SD for continuous variables. Differences in continuous data were tested using an analysis of variance. Categorical variables are described as frequency (%) and analyzed by χMultivariable adjusted odds ratios (ORs) and the 95% confidence intervals (CIs) of the gestational age-adjusted maternal TC categories for No-CU at 3 years were estimated using a logistic regression model. The first model was adjusted for Z-score of birth weight and maternal age at delivery (years) (model 1). The second model included variables adjusted for model 1 plus maternal weight gain during pregnancy (kg), smoking status during pregnancy , and study areas  (model 2). The third model additionally adjusted for breastfeeding status at 2 years  and the frequency of meals or snacks per day at 2 years  (model 3). The final model was further adjusted for maternal and paternal height (cm) (model 4).In an attempt to examine the dose–response relationship, we modeled each maternal TC percentile category as the following value provided in the parentheses and treated it as a continuous variable; <5th (-4), 5th–9th (-3), 10th–14th (-2), 15th–19th (-1), 20th–79th (0), 80th–84th (1), 85th–89th (2), 90th–94th (3), and ≥95th (4).Additionally, we constructed a restricted cubic spline model. In the model, maternal TC in mid-pregnancy was included as a restricted cubic spline using six knots at prespecified locations according to the percentiles of the distribution, the 5th, 10th, 25th, 75th, 90th, and 95th percentiles, and was adjusted for all covariates in model 4. The curves show ORs compared to the median value of the maternal TC (=227 mg/dl) in the present analysis dataset. In addition, tests for linear and quadratic trends were performed.http://cran.r-project.org/). Statistical significance was set at p < 0.05.All statistical analyses were performed using IBM SPSS Statistics for Windows software  and R  for Windows (The infants in the present study had a mean (SD) gestational age of 39.2 (1.1) weeks, length at birth of 45.3 (0.9) cm, and birth weight of 2436.9 (290.9) g; 42.2% of infants were males. The women in the present study had a mean (SD) age of 31.0 (5.1) years; 50.8% were nulliparous. The mean (SD) gestational age at the blood sampling of maternal TC was 22.8 (4.1) weeks.Compared to children with catch-up growth at 3 years, Z-score of birth weight, the maternal weight gain during pregnancy, parents’ heights, and the rate of children who had a meal or snack ≥3 times per day at 2 years were significantly lower in No-CU children. In addition, mothers of children with catch-up growth at 3 years tended to be nulliparous and practice breastfeeding, although these results were not significant. Smoking status during pregnancy did not significantly differ according to the occurrence of No-CU Table 1.A total of 362 (16.3%) children with No-CU at 3 years were identified. After adjusting for Z-score of birth weight, age of mother at delivery, smoking status, weight gain during pregnancy, and study area as well as breastfeeding status and meal frequency at 2 years, OR and 95% CI for No-CU was 2.88 (1.32–6.31) in TC ≥95th percentile (≥294 mg/dl), compared to the reference group. Further adjustment for parents’ heights did not alter the association  Table 2.The multiple-adjusted restricted cubic spline model using the complete data showed a non-linear trend of the association  Figure 2Secondary analysis using the Japanese clinical definition for the diagnosis of SGA  showed a total of 243 (18.7%) cases of No-CU at 3 years. The fully adjusted OR (95% CI) for No-CU was 3.71 (1.36–10.09) in the TC ≥95th percentile, compared to the reference group (table not shown).The present study focused on 2,222 mother-and-SGA-infant pairs in a large-scale birth cohort study that revealed a significant association between high maternal TC and No-CU among SGA infants. To our knowledge, this is the first study to report a relationship between higher maternal TC at mid-pregnancy and No-CU at 3 years among SGA infants. Commencing GH treatment at the appropriate period in infancy or early childhood can help to improve catch-up growth and intellectual performances –17. TherOur study showed that the cumulative incidence of No-CU at 3 years among full-term SGA infants was 16.3% using the global clinical definition of SGA for GH treatment: length and/or weight at birth <-2 SD . This isA key finding of this study is that higher maternal TC (≥294 mg/dl) at mid-pregnancy is significantly associated with No-CU at 3 years of age among SGA infants and the multiple-adjusted restricted cubic spline model showed a non-linear trend. Based on these results, we speculate the presence of a threshold effect in the association of high maternal TC with No-CU among SGA infants. A further large-scale prospective study is required to confirm this association, given the small number of SGA children without CU, among participants in the highest maternal TC group, in the present study.This is the first human study to report results that are consistent with those of previous animal experimental studies. A mini-review  reportedThere are several limitations in the current study. First, the study lacked control for dietary intake after birth because of the absence of related data. Second, due to the missing values in our data, we used multiple-imputation analysis. However, according to the assumption of missing at random mechanism, the sensitivity analysis by the completer dataset showed no substantial difference. Third, the outcome data, height of children at 3 years of age, was obtained from a self-administrated questionnaire completed by the mother, and this might have created a response bias.In conclusion, this study indicated that high maternal TC at mid-pregnancy was associated with No-CU among SGA infants. High maternal TC at mid-pregnancy among SGA infants could be an early alert for considering the need for GH treatment introduction. Furthermore, commencing GH treatment at the appropriate time may contribute to the improvement of long-lasting intellectual and psychological disabilities. This is the first human study to support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. This finding could be a clue to elucidate the mechanism of no catch-up growth among SGA infants that leads to future intellectual and developmental disabilities. Future studies should elucidate the detailed mechanism underlying the effect of maternal high fat diet on growth and development of SGA infants.jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies. Requests to access the datasets should be directed to Dr Shoji F. Nakayama, jecs-en@nies.go.jp.The datasets presented in this article are not readily available because data are unsuitable for public deposition due to ethical restrictions and legal framework in Japan. It is prohibited by the Act on the Protection of Personal Information  to publicly deposit the data containing personal information. Ethical Guidelines for Medical and Health Research Involving Human Subjects enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restricts the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: The studies involving human participants were reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and the Ethics Committees in Japan. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.Michihiro Kamijima , Shin Yamazaki , Yukihiro Ohya , Reiko Kishi , Nobuo Yaegashi , Koichi Hashimoto , Chisato Mori , Shuichi Ito , Zentaro Yamagata , Hidekuni Inadera , Takeo Nakayama , Tomotaka Sobue , Masayuki Shima , Hiroshige Nakamura , Narufumi Suganuma , Koichi Kusuhara , and Takahiko Katoh .KK conceptualized the design of the work, analyzed and interpreted the data, and drafted the manuscript. YI and HY contributed to the interpretation of data and revised the manuscript. TE, SK, TM, HT, HS, SS, MS-O, and JECS group members contributed to the acquisition of data and critically revised the manuscript for important content. MK led project administration and contributed to interpretation of data, and revising the manuscript. All authors provided final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors are in agreement with the content of the manuscript.This study was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors and do not represent the official views of the above government.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Infant-directed speech (IDS), the particular form of spontaneous language observed in interactions between parents and their infants, is a crucial aspect of the mother-infant interaction and an index of the attunement of maternal linguistic input to her infant communicative abilities and needs during dyadic interactions. The present study aimed to explore linguistic and pragmatic features of IDS during mother-infant interactions at 3-month of infant age. The effects of infant (birth status: preterm vs. full-term birth), maternal (perceived parenting stress) and dyadic (dyadic co-regulation) factors on IDS were explored. Results evidenced few differences between the groups on IDS linguistic characteristics. Moreover, observing the interaction of birth status and dyadic co-regulation, full-term mothers varied their IDS pragmatic features according to the quality of co-regulation while preterm mothers did not. Parenting stress was associated to specific linguistic IDS features independently from the birth status. Findings are discussed underling implications for the study of preterm dyads interactions and the importance to consider the interplay of several factors in affecting the quality of IDS. Infant-directed speech (IDS) is the particular form of spontaneous language observed in interactions between parents and their infants . CompareCharacteristics of IDS and associations with infant development have been studied extensively over the last few decades. The specific vocal patterns and linguistic features of IDS are an important part of mother-infant interactions, and play a role in regulating and attracting infant attention, making linguistic input more apparent and salient to infants, and helping infant interpretation of the emotional signals of adult speakers . DecadesPatterns of child-directed speech have been observed from infancy to childhood  infants (PT = 56 and FT = 55) participated in the study. Among those, 14 mothers of PT infants and 12 mothers of FT infants were excluded due to failure to complete study questionnaires . The final sample consisted of 86 dyads (PT = 42 and FT = 44).Preterm infants born <37 weeks gestational age were included. Exclusion criteria for both preterm and full-term groups were the presence of genetic abnormalities, severe neurodevelopmental impairment, and/or neurosensory disabilities .Most mothers  had a middle or high school level of education: 38.8% had a high school degree; 55.3% graduated college or had a master’s degree; 5.9% had less than a high school education. Preterm infants  and FT infants  had a mean gestational age of 30.71 (SD = 2.63) and 39.41 (SD = 1.18) weeks, and a mean birth weight of 1,379 (SD = 437.92) and 3,397 (SD = 406.97) grams, respectively. All infants were singletons.Mothers were invited to participate with their infant in a videotaped observational session when their infant was 3 months old (for preterm infants the corrected age was used). FT dyads were recruited via public services and advertisements, PT dyads were recruited by nurses and doctors of the hospital where they were born. All mothers completed and signed a consensus form before participation. The session consisted of 3 min of face-to-face interaction with the infant seated on an infant seat, and the mother seated directly in front of the infant, facing a mirror which was located behind the infant’s seat so that both partners’ faces could be clearly seen. After a brief introduction, mothers were asked to interact with their infants, as they would do at home.After the interactive episode, mothers were asked to complete the short version of the Parenting Stress Index. Each session was entirely transcribed according to the CHAT transcription system  of the CHILDES computational system (Child Language Data Exchange System) .The study was approved by the Ethical Committee of the Department.Mother–infant interactions were coded using the Revised Relational Coding System  to captusymmetrical co-regulation  and unilateral co-regulation .The coding system includes five global categories of communicative interactions: unilateral, asymmetrical, symmetrical, disruptive, and unengaged. In the present study we considered the global categories of The co-regulation patterns were coded every second from the videotapes by a trained coder, using the Mangold Interact 18 software. The relative total duration of each pattern was computed. An independently trained coder processed 25% of the sessions to compute inter-observer reliability. The Kappa values were 0.86 for symmetrical co-regulation and 0.94 for unilateral co-regulation.Mothers were asked to complete the PSI-Short Form questionnaire . The PSMaternal vocal productions were coded in order to analyze:-Verbosity: Rate per minute of utterances, word types and tokens .-TTR), which is a ratio of the number of types to tokens .-Control: Sentences used to re-orient infant attention, to direct infant attention toward something .-Preverbal: Sounds and sentences using typical baby-talk words, repetition of infant’s sounds.We first computed descriptive statistics and bivariate correlations among study variables in the full sample and separately in the two groups. The two birth groups were compared for mean values along the investigated variables. Afterward, to explore the single and additive role of birth status, dyadic co-regulation and parenting stress, and the interplay between dyadic co-regulation and parenting stress with birth status on IDS characteristics, we estimated and compared several multivariate models and then explored parameters of the best selected model More specifically, pertaining to predictors, first birth status was included in the model. Then, we considered the additive role of the psychological variables investigated (co-regulation and parenting stress). Finally, we included the interaction term between birth status and each of the dyadic/maternal variables considered to see if co-regulation and parenting stress differently predicted IDS depending on birth status. The Akaike Information Criterion (AIC) was used for model comparison, with lower values providing more support to a model against the others. The first group of multivariate models included as outcome variables IDS linguistic characteristics , and then we considered IDS pragmatic characteristics  Regression parameters were explored for the best fitting model. Analyses were run using the statistical software R, using Lavaan package.r = −0.56). Parenting stress was positively associated with TTR, and MLU .Means, SDs, and correlation values among variables of interest in the full sample are reported in r = −0.37) and demonstrated higher lexical variability and syntactic complexity . Similarly, IDS pragmatic characteristics were significantly associated with Unilateral and Symmetrical co-regulation only in the FT group. Mothers of FT infants pronounced less conversational and more controlled sentences when the dyad spent more time in unilateral co-regulation  and mothers used less control sentences when the dyad spent more time in symmetrical co-regulation (r = −0.44).Exploration of bivariate associations among investigated variables run separately for the two birth status groups see  suggesteF = 26.45, p < 0.001], demonstrated higher syntactic complexity , more conversational and less preverbal sentences  than FT mothers. Concerning parenting stress  and dyadic co-regulation , no differences emerged between the groups.The One Way ANOVA evidenced only few differences between PT and FT groups. When speaking to their infants, mothers of PT infants, talked less [verbosity: p < 0.05, except for the role of birth status on TTR. Results showed that mothers of PT infants spoke less , and with lower syntactic complexity  than mothers of FT infants. None of the parameters regarding the effect of unilateral co-regulation were significant.Comparison of multivariate regression models see  demonstrp < 0.05 for conversational  and control sentences  (see Comparison of multivariate regression models see  demonstr001) see . As repr001) see .p < 0.05, except for the role of birth status on TTR. Results showed that mothers of PT infants spoke less , and with lower syntactic complexity  compared with mothers of FT infants. None of the parameters regarding the effect of symmetrical co-regulation were significant.Comparison of multivariate regression models see  demonstrp < 0.05 for control  and preverbal sentences  (see Comparison of multivariate regression models see  demonstr042) see . As repr042) see .p < 0.05 except for the role of birth status on TTR. Results showed that mothers of PT infants spoke less , and demonstrated lower syntactic complexity  than mothers of FT infants. Moreover, for both PT and FT groups, mothers with higher levels of parenting stress spoke less , and demonstrated higher lexical variability  and higher syntactic complexity .Comparison of multivariate regression models see  showed mp < 0.05 except for the role of birth status on control sentences. Results showed that for mothers of PT infants, IDS was characterized by more conversational  and less preverbal  sentences compared with mothers of FT infants.Comparison of multivariate regression models see  demonstrThe present study aimed to explore the intra- and inter-individual differences of the linguistic and pragmatic features of IDS, directed to 3-month-old full-term and preterm infants. We found evidence of interactive effects between individual  and dyadic factors, on IDS characteristics. Recognizing that birth status  is an important condition affecting the infant, mother and dyad , we chosRegarding the role of dyadic co-regulation and IDS in PT versus FT infants, we found no differences between the groups concerning the quality of the dyadic, symmetrical and unilateral, co-regulation. Expressed differently, our results suggest that different patterns of IDS (between FT and PT) are not associated with fewer moments of co-regulated attention and affect. This is relevant because many studies considered the interactive qualities of PT mothers to be under- or over-stimulating, which was presumed to be suboptimal compared to what was observed in typical FT mothers . HoweverOne notable difference emerged between the groups when exploring how mothers vary their IDS with respect to the time spent in co-regulated interaction. We observed that the duration of shared versus un-shared moments was associated with different pragmatic features of IDS in FT, but not PT, mothers. In FT dyads, the greater time spent in moments of un-shared attention and affect  was associated with an IDS characterized by reduced conversational and increased control sentences. Conversely, the greater time spent in shared moments of attention and affect  was associated with increased use of preverbal, and decreased use of control sentences. Conversational sentences have, as its primary purpose, to keep open the communicative channels between two individuals when they are engaged in the same subject or are having a shared emotional experience. This is manifest by, for example, making comments, offering compliments, and asking open-ended questions. In contrast, control sentences are used to redirect, modify, and capture the attention of another when the other individual is focused on something different. This is manifested by, for example, calling or giving orders . ConsistConsistent with previous studies, we did not find differences in parenting stress between the two groups . The expWe would like to acknowledge some limitations of the current study. First, while our results were relevant, our sample sizes were not big and we included only 3-month-old infants. A larger sample followed longitudinally would have allowed us to explore additional interactive effects. An additional limitation is that our PT sample was quite homogeneous, composed of low-risk PT infants and of well educated low-risk mothers. Additional research should examine these associations in a more at-risk population of preterms to identify differential effects both at maternal, infant, and dyadic levels. With a larger and more at-risk sample, also the associations of IDS with the other co-regulation patterns, i.e., asymmetrical and unengaged, could be explored. Further studies should also consider the paternal dyadic communication and explore if these findings are replicable in father-infant dyads. Lastly, we did not explore infant vocal communication during the interaction. This information, as well as the inclusion of non-verbal infant and maternal cues, would help interpret our findings and should be the focus of future studies.Despite these limits, this study presents several strengths. To the best of our knowledge, this is the first study to examine infant, maternal, and dyadic factors and their associations with characteristics of IDS. This study highlights the need to go beyond exploring IDS effects on language development, and to consider its potential importance when exploring the quality of dyadic interaction and its role in sharing attention, affect and meaning between the mother and the infant . Our resThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Department of Neuroscience, Imaging and Clinical Sciences of the University G. d’Annunzio Chieti-Pescara. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MS and MF conceptualized the study and organized the data collection. MS and FL wrote the first draft of the manuscript. FL ran the analyses and wrote the results section. MG, ML, and SP conducted the data collection and coding. SD and PC coordinated preterm data collection. MF and PS revised the manuscript. All authors contributed to revision of the final version of the 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There is no standard birth weight curve for twins in Japan other than a prototype curve based on 1988–1991. Twins have a high perinatal mortality rate than singletons; therefore, we developed a new standard curve for twin birth weight using data from the 1995–2016 Vital Statistics and compared it with previous reports. We used 469,064 cases for analysis, excluding stillbirths and cases with missing values, and created a standard curve using LMS  method. In comparison with previous reports, the mean birth weight decreased by 100–200 g. The groups with the lowest neonatal death rates (NDRs) and infant death rates (IDRs) were those with a birth weight of 1,500–2,499 g  and those born at 34–36 weeks . Compared to these, the IDR was significantly higher in the 2,500–3,999 g group and the 37–39 weeks group (incidence rate ratio (IRR): 1.1 in the 2,500–3,999 g group, IRR: 1.3 in the 37w0d–39w6d group). In particular, the risks of neonatal mortality and infant mortality were higher in infants born at a birth weight above 3,500 g. Infants born at a birth weight above 3,500 g may include recipients of twin-to-twin transfusion syndrome. The most common causes of infant mortality are accidental death and sudden infant death syndrome (SIDS). We considered the possibility that infants treated as healthy newborns and whose mothers were discharged from the hospital without adequate twin care guidance may be more likely to experience unintentional accidents and SIDS at home. The present study suggested that creating a new twin birth weight standard curve and guidance on managing twins at home for full-term and normal birth weight infants may lead to a reduction in infant deaths. In Japan, the probability of multiple births, especially twins, has risen in recent years ,2. In thCompared to singletons, twin pregnancies are more susceptible to perinatal complications, such as hypertensive disorder of pregnancy, and fetal growth restriction (FGR) ,9, whichIn general, the anthropometric reference values at birth by the length of pregnancy published in 2011 are used in most of the clinical settings in Japan to assess the child’s growth at birth . This reKato et al. developed a birth weight standard curve for 32,232 sets of twins  born in Japan between 1988 and 1991 . The curWe used birth and death certificates issued by the Ministry of Health, Labor, and Welfare (MHLW), which maintains the Japanese population’s statistics for children born in Japan between January 1, 1995, and December 31, 2016. The birth certificate included the mother’s nationality, date of birth, pregnancy history, age at delivery, birth weight, and other characteristics of the mother and child. In contrast, the death certificate included information, such as the date of birth and date of death. Since the birth certificates were not listed for twins, we needed to extract the twin pairs and check whether the pairs were correct. The date of birth of the two children, the delivery date of mothers, and the number of gestational weeks were used to match the twin pairs, and if these matched, the pair was considered a twin pair. Stillborn babies were excluded from this analysis. Data that lacked maternal or infant information, such as birth weight, gestational age, mother’s date of birth, or pregnancy history, were also excluded. In this study, triplets or other multiples were excluded.th, 50th, and 90th percentile birth weight values from 22 to 41 weeks were plotted.The resulting matching rate of twin pairs was 96.6%. Neonates of foreign nationality were also excluded . Based oFor the mortality studies, the total number of early neonatal deaths, neonatal deaths, deaths between 29 days and one year of age, and infant deaths were calculated for each birth weight, week of delivery, and maternal age. Birth weight was classified as under 1000 g (defined as “extremely low birth weight” [ELBW]), 1000–1499 g, 1500–2499 g, 2500–3999 g, and over 4000 g. For maternal age, we also calculated the relationship between infant weight difference  and the number of weeks of delivery. Weight difference (discordance) was calculated using the following equation:The incidence rate ratio (IRR), 95% confidence interval (95% CI), and p-values for neonatal and infant mortality were calculated to identify the risk factors for neonatal and infant mortality. The analysis included birth weight, week of delivery, and maternal age. IRR, 95% CI, and p-values were evaluated using the chi-squared test.th percentile, 50th percentile, and 90th percentile), and X is the birth weight.When drawing the birth weight standard curve, it is still crude. We used LMS Chart Maker light version 2.54  . The LMSAll statistical analyses were performed using R Core Team 2018 . In this study, a p-value of <0.05 was considered statistically significant.The research plan for this study was reviewed and approved by the Ethics Review Board of St. Luke’s International University (Document No. 2021–775). Informed consent was not required for the secondary use of the survey that was conducted using anonymized demographic birth and death certificates without identifying individuals. Moreover, all the data were anonymized. Thus, the Ethics Review Board of St. Luke’s International University decided to waive the requirement for a written informed consent.Birth certificates from 1995–2016 were used for the analysis th percentile values were greater in boys than in girls at all weeks, for both first and second births. At 32 weeks, the difference in weight was over 200 g. Similarly, the difference in weight between males and females was 50–80 g until 30 weeks, but increased to more than 80 g at all weeks after 30 weeks.Standardized birth weight reference curves for 22–41 weeks for both sexes and each parity were constructed using the LMS method Figs . The 50tRegarding the relationship between mortality and the number of weeks of delivery, the IRR was significantly higher for both ND and ID when delivery occurred between 22 weeks, 0 days and 33 weeks, 6 days. The IRR was significantly higher in ID when delivery occurred after 37 weeks 0 days . Regarding maternal age, the under-25 group had significantly higher IRR in both END and ND .In this study, we investigated the increasing trend of twin births using data from the MHLW. We constructed standardized birth weight curves for male and female babies by menarche and first childbirth and identified the risk of ND and ID. The results showed that the birth weight of male babies was higher than that of female babies at all weeks, regardless of parity. The lowest frequency of ND and ID was observed in twins born at a birth weight of 1,500–2,499 g, late preterm deliveries, and maternal age at delivery of 25–29 years.th percentile values of that graph with the 50th percentile values of our birth weight reference curve for twins born between 22 and 41 weeks. Our 50th percentile values were smaller at all weeks, regardless of sex or pregnancy history. The birth weight of twins is smaller than that of singletons [The anthropometric reference values at birth by the length of pregnancy currently used in Japan were developed by including only singleton births . We compngletons , and ourth percentile values of our birth weight reference curve with those of a birth weight reference curve based on a survey of all births between 1988 and 1991 [We then compared the 50and 1991 . Our graand 1991 . Furtherand 1991 . Low BMIand 1991 ,22. In rand 1991 . Twins band 1991 ,25. TherThe higher frequency of deaths after 29 days of age in the 2,500–3,999 g birth weight group (0.3%) compared to the 1,500–2,499 g group (0.3%) is due to the large proportion of deaths in children with birth weights of 3,000 g and above, especially over 3,500 g. Children born large for gestational age have a higher mortality rate than those born appropriate for gestational age. Although we could not classify by sex, there is a high probability that MD twins are among those born at 3,500 g or more.In twins, late preterm delivery had the lowest frequency of ID. A comparison of neonatal outcomes between singleton and twin babies born in the late preterm showed that the duration of hospitalization was significantly longer in twins than in singletons. However, the neonatal epidemic and mortality rates remained the same . Twins mMothers younger than 25 years had the highest frequency of ND and ID. In general, mothers under 20 years of age are 1.78 times more likely to experience preterm labor than mothers aged 20–34 . In the A report published in 2018 stated that younger women were more likely to become pregnant with predominantly MD twins than older women ,31. In oOur study is reliable because we used data from all births and deaths recorded in the MHLW birth and death certificates for the past 22 years. Few studies have analyzed all births for such a long time. The birth weight of twins had decreased compared to 1988. We also found that neonatal and infant deaths were lower in deliveries with birth weights between 1,500–2,499 g and late preterm deliveries. The mothers of these infants likely received appropriate guidance during hospitalization, including guidance regarding sleeping on the back. The mothers of infants born at a birth weight of more than 2,500 g or born after 37 weeks should also receive appropriate guidance on SIDS prevention during hospitalization.This study had some limitations. Information not included in the birth and death certificates is missing from this study. For example, the chorionic and amniotic nature of the twins was not classified. As mentioned above, the risk of perinatal death differs greatly between DD and MD twins, and it is necessary to analyze them separately for more accurate risk analyses. Using the MHLW data, it was not possible to determine whether infants had anomalies. In addition, information regarding the maternal socioeconomic background and the use of fertility treatment was not available. In particular, the maternal background may affect the analysis of age risk. In recent years, a perinatal database has accumulated information on the maternal background, mainly in higher medical institutions. Because of the characteristics of twins, they are often managed by higher-order medical institutions, and therefore, more detailed information on twins can be covered by perinatal databases. In the future, we would like to use the perinatal database to examine the risk of infant mortality in twins, taking into account various other confounding factors into account.Standard birth weight curves for twins were generated. The birth weight of twins was found to be decreasing in both sexes, reflecting the social background of the mother and the transition to infertility treatment. At the same time, IDs were calculated by birth weight, week of delivery, and age, respectively. Twins have the best prognosis when delivered at a birth weight of 1,500–2,499 g and when born at late preterm. Home management guidance for twin full-term and normal birth weight infants may reduce infant mortality.S1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


The cyst of the canal of Nuck is an extremely rare female hydrocele, usually occurring in children, but also in adult women. It is caused by pathology of the canal of Nuck, which is the female equivalent to the male processus vaginalis. Due to its rarity and the lack of awareness among physicians, the cyst of the canal of Nuck is a seldom-encountered entity in clinical practice and is commonly misdiagnosed. We report on a case of cyst of the canal of Nuck in a 42-year-old woman, who presented with a painful swelling at her right groin. In addition, we conducted a review of the current available literature. This review gives an overview of the anatomy, pathology, diagnostics, and treatment of the cyst of the canal of Nuck. The aim of this review is not only to give a survey, but also to raise awareness of the cyst of the canal of Nuck and serve as a reference for medical professionals. A female hydrocele, namely cyst of the canal of Nuck, is an extremely rare entity that is not commonly encountered, especially in adults ,2. The oDue to the extremely rare occurrence of the condition, we conducted a literature review to understand the anatomical background, the diagnostics and treatment methods in order to highlight best practice in medical care of this phenomenon. The following databases were used to search for and identify the included literature: PubMed, Google Scholar, and MEDLINE. No date restriction was imposed on the search. The result of our review is presented in narrative form in addition to our case report.A 42-year-old female patient was referred to the surgical outpatient department by her general practitioner due to a small swelling on the right groin, with a suspected inguinal hernia. The patient had observed this swelling two months before, and was suffering dragging pain in the affected area. With the exception of a hysterectomy and a bilateral salpingectomy by reason of multiple myoma uteri two years ago, there was neither a history of abdominal or pelvic surgery nor trauma, and the patient was otherwise in good health, without the appearance of nausea or vomiting. On physical examination, a non-reducible deep-seated round tumor was detected and located in the right inguinal region with a size of approximately 15 × 10 mm, with no pressure pain. The remaining abdominal examination was inconspicuous, with soft abdominal wall conditions and regular peristaltic sounds. There was no complaint of lower extremity weakness.An ultrasound examination showed a hypoechoic cystic formation originated from the round ligament of the uterus in the right inguinal region without vascular flow or peristalsis. No changes in size or shape due to Valsalva maneuver could be determined. Magnetic resonance imaging (MRI) was obtained to further define the extent and nature of the cyst. The MRI revealed a 15 × 9 × 16 mm  well-defined, cystic formation with a peripheral contrast-enhancement within the medial border of her right inguinal ligament with no visible communication to the peritoneal cavity, compatible with a hydrocele of the Nuck canal. An axial T2-weighted MRI image of this hydrocele is displayed in The patient was admitted to the ward for preparation for open surgery. Due to the anatomical conditions, an open surgical procedure was determined. Pre-surgically, the cyst was detected by ultrasonography, followed by a para-inguinal incision over the verified cyst formation. Intrasurgically, a small cyst appeared, between the external abdominal oblique and the right inguinal ligament. The cyst was dissected from the round ligament , followeIn 1691, Anton Nuck, a Dutch anatomist, was the first to describe the canal of Nuck . The canAccording to the existing literature, only a few papers have reported the prevalence of the cyst of the canal of Nuck in children. Paparella et al. described a prevalence of 0.74% in 353 1–14-year-old female patients with inguinal swellings . A similThe commonly used classification was developed by Counseller and Black, who classified cysts of the canal of Nuck into three different types . The mosA recent classification was published by Wang et al. in 2021 , who subThe clinical presentation of a cyst of the canal of Nuck shows an inguinal or genital, painless or painful swelling, with no attending nausea or vomiting ,20,21,22Radiological imaging is of utmost importance in distinguishing from the differential diagnoses presented above. For initial imaging of suspect inguinal or genital swellings, sonography is the preferred investigative method. On ultrasound, the cyst of the canal of Nuck appears as a thin-walled anechoic or hypoechoic formation with no changes on Valsalva maneuver and lack of vascular flow on color Doppler ,15,16,21Due to the extreme rarity of cysts of Nuck’s canal, no standard therapeutic procedure as yet exists. Although conservative therapy options such as aspiration or sclerotherapy of female hydroceles are reported in the literature, hydrocelectomy is recommended, with or without ligation of the cyst, as treatment of choice ,21,22,56Recent therapeutic approaches consider laparoscopic intervention for the treatment of female hydroceles ,30,57,58A hydrocele in young females is a very uncommon disease, and it occurs even more rarely in adult women. Due to its infrequency, many health professionals are not even aware of its existence. Therefore, it is of utmost importance to raise awareness of clinicians, including surgeons and radiologists on the presence of the canal of Nuck as well as the possibility of a female hydrocele.The primary symptom of the cyst of the canal of Nuck is a painless or painful swelling in the groin or the labia majora ,10,11,22The treatment of choice is surgical excision of the cyst. Based on our literature research, only a few reports about surgical approaches are available. However, due to the rarity of a Nuck’s canal cyst, there is no defined standard method of intervention to date. In our opinion, the surgical approach should be adapted, based on the type of cyst of the canal of Nuck, the anatomical conditions, and the experience of the responsible surgeon. Although laparoscopic approaches have advantages such as reduced blood loss, less wound drainage, and a better aesthetic outcome, they are associated with higher risk for peri- and postoperative complications such as enterotomy, bowel injury, postoperative bleeding and ileus . Thus, iIn the available literature, only a few reports of cysts of the canal of Nuck have been published since its discovery ,20,21,22In conclusion, the cyst of the canal of Nuck in adult women is an extremely rare disease. If one is aware of its existence, it can be easily diagnosed using modern diagnostic methods and treated by adequate surgical approaches. A cyst of the canal of Nuck should always be considered as a possible cause in suspect inguinal and genital swellings in females.Due to the rare clinical occurrence and the lack of literature, a diagnosis of a cyst of the canal of Nuck is often difficult to make, not only for inexperienced surgeons, but also for medical experts. Thus, interdisciplinary collaboration in healthcare between various different fields, such as radiology and surgery, is necessary to prevent misdiagnosis as well as resultant errors in treatment. A focused physical examination followed by high-resolution sonography enables the diagnosis of a cyst of the canal of Nuck. To plan an adequate surgical intervention, cross-sectional imaging, preferably MRI, allowing clarification of the anatomical conditions is of utmost importance. Our review provides insight into the anatomical background, diagnostics, and surgical intervention of a cyst of the canal of Nuck. This article may serve as the foundation for raising awareness about the possibility of female hydroceles and provide guidelines for diagnostic and surgical methods.


Neonatal birth injury is the functional or structural damage of the new-born during child birth. Fetal related factors such as macrosomia, fetal height, fetal weight, and prematurity; maternal related factors such as overly young and old maternal age, parity, poor maternal health, and pelvic anomalies contribute to neonatal birth injury. Labor and delivery related factors including prolonged labor, fetal mal-presentation and mal-position, cesarean and instrumental deliveries also predispose the neonate to birth injury. This study was conducted to assess the prevalence and associated factors of birth injury among neonates admitted to the neonatal intensive care unit (NICU) in Governmental Hospitals of Southwest Ethiopia.To assess the prevalence and associated factors of birth injury among neonates admitted to the neonatal intensive care unit (NICU) in governmental hospitals in Southwest Ethiopia.Hospital-based cross-sectional study design was implemented at Mizan-Tepi University Teaching Hospital, Bonga Gebretsadik Shawo General Hospital, and Tepi General Hospital. A total of 1,315 neonates were included in the study using systematic random sampling techniques. Data was entered using Epi-Data version 4.2 and exported to SPSS version 21 for analysis. Logistic regression analysis was conducted to see the association between the dependent and independent variable.via instrumental delivery were 6.68, and 2.81 times more likely to develop neonatal birth injury compared to those whose age was greater than 34 years and neonates delivered through Cesarean section, respectively.The prevalence of neonatal birth injury was 16.7%. Predictors such as primipara, no formal education, mothers with no antenatal care, and mothers whose occupational status were unemployed were 12.27, 2.52, 2.40, and 4.26 times more likely to develop neonatal birth injuries than their counterparts, respectively. Whereas, maternal age within the age range of 25–34 years, and neonates delivered The magnitude of birth injury in the current study was significantly high. Primiparity, mothers with no history of antenatal care follow up, uneducated women, unemployed women, mode of delivery, and maternal age between 25 and 34 years were strong predictors associated with neonatal birth injury. Therefore, comprehensive maternal health care such as antenatal care follow up and health institution delivery should be promoted and well addressed to all reproductive age women and special attention should be given particularly to pregnant women in order to mitigate problems related to childbirth. Neonatal birth injury is the functional or structural damage of the newborn during child birth . Birth iWorldwide, an estimated 5.4 million children aged less than 5 years died. Of these deaths, 2.5 million 46%) occurred during the first 28 days of life (% occurreBirth injury (BI), commonly occurs in the 2nd stage of labor as a result of normal forces of labor, contraction, twisting, and traction of neonates through the birth canal or as a sequel of obstetric intervention . It variNeonatal birth injury was predisposed due to fetal related factors such as macrosomia, fetal height, fetal weight, and extreme prematurity and postdate; maternal related factors such as overly young and old maternal age, parity, poor maternal health, and pelvic anomalies contribute to neonatal birth injury –11. LaboNeonates who suffer from injuries and diseases associated with lack of quality of care during child birth, lack of skilled health care provider, and lack of treatment immediately after birth and within the first days of life are at risk of dying within the first 28 days of life . Preterm birth and intra-partum related complications such as birth asphyxia and lack of breathing at birth, infections, and birth defects caused the most neonatal deaths in 2017 .Despite advances in obstetric care and prenatal diagnosis that play a pronounced role in decreasing the frequency of BI among newborn babies, BI is still recorded even in uncomplicated deliveries with the presence of optimal diagnostic tools .The overall incidence of birth injuries in most developed countries has drastically declined due to improvements in obstetric care and prenatal diagnosis . HoweverA hospital-based multi-centered cross-sectional study was conducted from May 1st, 2021 to April 30th, 2022. These hospitals are Bonga G/tsadik Shawo General Hospital, Mizan Tepi University Teaching Hospital (MTUTH), and Tepi General Hospital. Currently, Mizan-Tepi University Teaching Hospital is expected to provide services to more than one million populations. Meanwhile, Bonga G/tsadik Shawo General Hospital and Tepi General Hospital are expected to provide care for more than 500,000 populations each. These hospitals provide health services and act as referral centers for other district primary hospitals and health centers. In 2020, the NICU in each hospital provided a service for a total of 1,200, 958, and 680 neonates in MTUTH, in Bonga Gebretsadik Shawo General Hospital and in Tepi General Hospital, respectively (Unpublished report).A multi-centered institutional based cross-sectional study design was conducted among neonates admitted in NICU in governmental hospitals of southwest Ethiopia from May 1st, 2021 to April 30th, 2022.Neonates aged 0–28 days admitted to neonatal intensive care unit of governmental hospitals, southwest Ethiopia region.Neonates with known major fetal anomalies (tumors) and neonates with severely ill mothers were excluded from the study.All neonates admitted to NICU in all public hospitals in southwest Ethiopia were the source population.All neonates admitted to NICU in selected public hospitals during the study period were the study population.p = 15.4%  = 1,315. Proportional allocation to size was performed and representative samples were drawn from each hospital.Sample size was determined using a single population proportion formula by considering the following parameters: Multistage sampling method was used in this study. First, the number of hospitals with NICU services in the Southwest Region was determined. Accordingly, five public hospitals with NICU service, such as Bonga Gebretsadik Shawo General Hospital, Tepi General Hospital, MTUTH, Tercha General Hospital and Masha General Hospital were determined in the region. Then, three hospitals  based on the order of time of admission .An interview administered structured questionnaire was adapted from reviewing different literature –18. The It is defined as functional or structural damage to the body of a new-born following labor/delivery.The data was checked for completeness and then the data was entered into Epi-Data Manager 4.2 and then transferred to the statistical package for social science (SPSS) version 21 for analysis. Descriptive statistics  were used to describe socio-demographic variables, neonatal and obstetrical related variables, and clinical and anthropometric measurements.p-value of <0.05 were included in a multivariable logistic regression model to identify the strong predictors significantly associated with neonatal birth injury.Binary logistic regression analysis was performed to determine the significant association between each predictor  and neonatal birth injury. Then, predictors with a p-value > of 0.05. Moreover, multicollinearity was checked using variance inflation factor (VIF) test and, the variance inflation factor (VIF) of less than 10 and tolerance of greater than 0.1 was considered as there was no multicollinearity. Finally, after adjusting for the confounding variables using multivariable logistic regression analysis, predictors with a p-value of <0.05 and a CI of 95% were considered as strong predictors associated with neonatal birth injury.The model fitness was checked with Hosmer and Lemeshow goodness of fit test at a A total of 1,315 neonates were involved in the study, with a 100% response rate. The mean (±SD) age of the study participants was 31.26 ± (8.88) years, with most of them, 544(41.4%) were aged greater than 34 years of old. The majority, of 787(59.8%) of women were rural residents. More than two thirds, 963(73.2%) of the total respondents were orthodox religious followers. From the total participants, 804(61.1%) and 542(41.2%) were employed and didn't attend formal education, respectively .From the total of 1,315 neonates admitted in NICU, 220 (16.7%) with a 9% CI of  have developed birth injury. Caput succedaneum and cephalhematoma were the major neonatal complications with an equal magnitude of 78 (35.4%), and followed by 11.36% and 6.82% of neonatal birth injury of Erbs's palsy and clavicle fracture, respectively .Regarding birth weight, majorities, 624 (47.5%) were below 2,500 g, 392 (29.8%) were within the range of 2,500–4,000 g, and 299 (22.7%) were above 4,000 g. Nearly half of the participants, 628 (47.8%) were preterm followed by term, 491 (37.3%), and post-term, 196 (14.9%). Out of the total number of study participants included in this study, almost all 1,267 (96.3%) were delivered at a health institution, and the remaining 48 (3.7%) of the participants were delivered at home.Out of the total number of neonates in NICU, 504 (38.3%) of them developed complications. Of those who developed complication, 120 (23.8%) and 204 (15.5%) of the neonates develop anemia and neonatal sepsis, respectively.Regarding obstetrical history, almost two thirds 999 (76%) neonates were delivered from mothers with a history of antenatal care follow up. More than half, 775 (58.9%) of neonates were delivered from multiparous mothers. Almost all of the mothers, 1,147 (87.2%) were referred from a health institution, while the remaining 168 (12.8%) were self-referred .Using bivariate logistic regression analysis, different variables such as gestational age, mode of delivery, antenatal care, educational status, occupational status, maternal age, birth weight, and parity were statistically associated with neonatal birth injury. But after adjusting for possible confounders using multivariate logistic regression analysis variables such as antenatal care, parity, educational status, occupational status, maternal age, and parity remained statistically significant predictors of neonatal birth injury.via instrumental delivery  were 6.68, and 2.81 times more likely to develop neonatal birth injury compared to those age were greater than 34 years and neonates delivered through cesarean section, respectively [Accordingly, women who were primipara , mothers with no formal education , mothers with no antenatal care (AOR: 2.40: 95% CI: 1.36–4.25), and mothers whose occupational status were unemployed , were 12.27, 2.52, 2.40, and 4.26 times more likely to develop neonatal birth injury than their counterparts, respectively. Whereas, maternal age with the age range of 25–34 years , and neonates delivered ectively .Worldwide, the incidence of neonatal birth trauma varies based on mode of delivery, fetal presentation, and fetal position, and is reported to be between 0.2 and 41.2 per 1,000 births , 19–21. via instrumental delivery (forceps/vacuum) are predisposed to develop injuries. This study was supported by studies conducted in Tikva, Israel, and Addis Ababa, Ethiopia, where caesarean delivery is a preventive factor for neonatal birth injury . Maternal age ranges from 25 to 34 years; neonates born from uneducated and unemployed mothers, prim parity, and mode of delivery  and mothers with no history of antenatal care follow-up during their pregnancy are statistically significant with neonatal birth injury. Thus, health education dissemination about antenatal care services for reducing neonatal birth injuries should be improved. Training should be provided to medical staff who attend laboring mothers regarding detecting abnormal progress in labor and also application of forceps and vacuum to assist vaginal delivery. Empowerment of women should be encouraged regarding education and health care services utilization. Primiparous women should also be well supervised during labor.