Birth registration, an essential component of the civil registration system, is expected to be complete and universal. This study assesses the progress made in recent years and identifies gaps in birth registration in Nepal. Data from the Multiple Indicator Cluster Surveys undertaken in 2014 and 2019 are used for the analysis. The two surveys included a total of 12,007 children under five years of age living with their mothers at the time of the surveys. The survey respondents were 11,821 mothers and 186 caretakers (in the case of those without mothers) of the children. The variations in the proportion of births registered among various subgroups of the children are assessed by performing bivariate analysis and binary logistic regression. Birth registration increased considerably, from 58% (95% CI: 57–59%) in 2014 to 77% (95% CI: 76–78%) in 2019. Several of the disparities between and among the various population subgroups that were evident in the 2014 survey had been considerably reduced or eliminated by 2019. The disparities in registration between boys and girls attenuated over time. Although birth registration increased for all children (ages 0–59 months old), infants still had comparatively lower levels of registration. The relatively disadvantaged provinces showed significant progress between the two survey periods. Considerable and significant progress has been made in birth registration in recent years. However, achieving universal and complete birth registration would require sustaining recent achievements and applying proven strategic interventions to ensure the inclusion of the unregistered births. Civil registration is defined as the “universal, continuous, permanent and compulsory recording of vital events provided through decree of regulation in accordance with the legal requirement of each country” . Vital eAs defined, birth registration is an essential component of the civil registration system, and therefore, obtaining a birth certificate is recognized as one of the rights of every child . DespiteVarious factors have been found to account for the variations in the coverage of birth registration across countries. A few studies have examined the determinants of birth registration at the individual, household, and community levels. At the individual level , those with higher socioeconomic status, higher levels of education, exposure to mass media, higher mobility, and having had an institutional delivery are likely to register their child’s birth , 7–10. ATo our knowledge, no such studies have been undertaken for Nepal. As a signatory to the United Nations Economic and Social Commission for Asia and Pacific (UNESCAP) Ministerial Declaration, Nepal is committed to achieving its three goals–attaining universal civil registration; accepting civil registration as legal documentation to claim identity, civil status and ensuring rights to all individuals; and the production and dissemination of timely and complete vital statistics . Based oNepal’s 2011 census recorded the total population as 26.5 million, with 595,000 annual births  . As per The history of registering vital events in Nepal goes back to the 1950s and has been systematically documented by Gautam . He has The current (2015) Constitution of Nepal recognizes birth registration as a right for every child, and has given authority to all three levels of the government–federal, provincial, and local–for registration of vital events . AccordiAs of 2020, a total of 6,743 local registrars have been deployed in 753 municipalities for registration and issuance of birth certificates . The locAside from the structural and organizational set up, some significant policy and program interventions have been launched that have bearing on the program’s effectiveness and improvements in birth registration. Beginning in 2009, the Government of Nepal introduced a cash transfer incentive program to parents to register their children, particularly in comparatively socioeconomically disadvantaged provinces . AdditioThese steps seem to have paved the way for steady progress in recent years. Nationally, birth registration increased from 35% in 2006, to 42% in 2011, to 53% in 2014, to 56% in 2016, and to 77% in 2019 –31. ThusThe data analyzed are from the Nepal Multiple Indicator Cluster Surveys (NMICS) undertaken in 2014 and 2019. The NMICS are standardized cross-sectional and nationally representative household surveys conducted by the government’s Central Bureau of Statistics (CBS) in partnership with UNICEF/Nepal , 31. TheThe surveys ascertained the birth registration status of each child under five years of age living with a mother or caretaker in the household on the day of the interview. In the 2014 survey, there were a total of 5,279 mothers and 70 caretakers . Similarly, in the 2019 survey, there were 6,542 mothers and 116 caretakers. They were the respondents in the survey who provided information relating to the birth registration of children– 5,349 in the 2014 survey and 6,658 in 2019 survey. These under-five living children are defined as the ‘study population’ for this analysis. In view of the fact that the caretakers represent only a small proportion (1.3% in the 2014 survey and 1.7% in the 2019 survey), we refer to all the respondents as ‘mothers’ for convenience.The outcome variable is the registration/non-registration status of each study population. A child is considered registered as per the verbal reporting–yes or no–of the respondent, regardless of whether the child had a birth certificate or not. The individual-level variables used as the explanatory variables are: age of the child (0–59 months), sex of the child, and the mother’s highest level of education. The household-level variable is represented by the wealth (household) index. The index includes household amenities, assets and durables that are grouped into five quintiles, from the poorest to the richest .Nepal is known to have many ethnic groups intertwined in religious affiliation, specific geographic location, traditional caste, tribal practices, and other considerations , 34. ForAside from the six independent factors (variables), additional variables of interest for inclusion could be urban-rural place of residence, mass media exposure, mother’s age, parity, and birth order. In a preliminary analysis, urban-rural place of residence did not show any significant difference. This was probably due to the fact that in recent years many areas that are principally rural in characteristics have been designated as urban areas for political and budget allocation purposes. For example, the 2014 survey reported that 58% of the respondents were living in an urban area, and that number increased to 65% in 2019.  As regards the mass media variable, the composite index variable ‘wealth status’ includes the household’s possession of radio and television. Because of the low fertility level, as noted earlier, we excluded birth order or number of live births variables from the analysis. In a preliminary analysis, we also included the mother’s age as an additional variable . The inclusion of this variable did not make any significant contribution to the overall results. This variable is, therefore, not included in the results presented in the paper. We adapted the strategy of parsimony in the data analysis and modeling. Also, more importantly, the study is focused on testing how certain interventions may have influenced the higher level of registration, and also, evaluating how some of the factors identified here influenced the level of registration.To the extent that the recent policy and program interventions (mentioned earlier) have contributed to the improvement in birth registration in recent years, we expected to find a strong significant influence on the participation of the Dalit ethnic group in the program in particular, especially those living in the most disadvantaged provinces in the country. Further, the effect of the ‘child grant’ intervention program is expected to be evident in the birth registration based on the socio-economic class of the household where the child resides. Additionally, the child’s age is expected to be strongly and significantly associated with birth registration. More specifically, because a birth registration card is required for children for admission to school, a higher level of uptake birth registration is expected around age five.As noted earlier, the fairly high level of birth registration– 77% as of 2019 –should necessarily encompass the registration of diverse population subgroups, and not be limited to certain more affluent population subgroups. A similar pattern has been found with respect to the vitamin A supplementation provided to children in ages 6–59 months, when the percentage of children receiving the supplementation progressed to a higher level . In viewBivariate analysis is performed to examine the association between the outcome variable and the background characteristics. Binary logistic regression is applied to assess the net effect of each of the background variables (covariates) on the outcome variable . The log0 + β1X1 + … + βkXk, which states that the  logarithm of the odds of outcome variable is a linear function of the X variables (covariates), and is often called the log odds. This is also referred to as the logit transformation of the estimated probability of outcome variable, P. The outcome variable is binary: ‘1’ if the index child has had a birth registration, and ‘0’ if no. We considered a p-value of 0.05 or better to indicate a statistically significant association for interpretation and drawing inferences and conclusions based on the results.Logit (P) = log (P/1−P) = βThe percent distribution of the variables included in the analysis for the two surveys are presented in Of the total of 12,007 children included in the two surveys, about one-fifth belong to each of the five age groups. There are more male than female children, with a male-to-female ratio of 110 (per 100). Unlike other characteristics, the two surveys recorded large differences in the proportion of the children’s mothers based on the education categories: whereas the 2014 survey reported 42% of the mothers having no education, it was only 26% in the 2019 survey. Similarly, the 2014 survey recorded 17% of the mothers as having had a basic education (1–8 grades), while it was 32% in the 2019 survey. . Slightly over one-fourth of the respondents belonged to the Brahmin/Chhetri group, about one-third of the women belonged to the Janajati group, and 16% were in the Dalit group. Nearly one-fourth of the women belonged to the poorest household wealth group, and 16% belonged to the richest group.Regarding the place of residence, Province 2 had the largest proportion (24%) of the children, while Provinces 4, 6 and 7 had the smallest proportion (7–10%). Province 3, where the federal capital is located, had 17% of the total children residing at the time of the survey. Province 3 also showed a slight increase in the proportion between the two surveys.Compared to the other age groups, the registration of infants in particular  increased sharply from 33% to 59% between the two time periods. Still, the absolute proportion registered among infants was proportionately less than other age groups. The registration of female children in particular increased proportionately over time, and by 2019, the difference in birth registration between the boys and girls had attenuated.The increase in the birth registration of children was higher than the overall average, particularly among women with higher levels of education. Among the five broad ethnic groups, as of 2019, the Dalit had the highest proportion (85%) of children registered; even higher than among the Brahmin/Chhetri group. The poorest household group had proportionately the highest gain (46%) in birth registration, while the richest group experienced only a modest gain (29%). But the coverage across all the five groups remained high—between 74% and 80%.Two of the seven provinces experienced a considerable gain in registration over time. Province 7 showed the largest gain (107%) followed by Province 3 (61%). Province 6 showed the smallest gain (12%). This was, however, also due to an already high level of coverage in the base year (2014). Overall, all of the provinces except for Province 3 had reached coverage levels between 74% and 89% as of 2019.We performed a multivariate binary logistic regression to assess the net effects of the six covariates (variables) on birth registration. The results  indicateIn both the survey periods, birth registration increased consistently for all children in ages 0 to 59 months. However, compared to the children more than 12-months old, infants had persistently lower odds of being registered. The lower registration of female children that existed in 2014 had also subsided by 2019, indicating that the sex disparity in birth registration attenuated considerably over time.Educated mothers still have a slightly higher advantage in having their child’s births registered compared to their counterparts with less education. Among the ethnic groups, Dalit showed higher odds of having their births registered (compared to Brahmin and Chhetri). The poorest households did just as well as the other households. More importantly, the large differentials and disparities in birth registration that existed across the provinces as of 2014 had been minimized by 2019. A similar pattern of change occurred across all the provinces of residence. Provinces 6 and 7, known to be relatively the most disadvantaged in terms of socio-economic indicators, actually experienced a significant likelihood of having under-five children registered .Higher birth registration, particularly among the Dalit , and in comparatively worse-off provinces, seems to be the result of specifically targeted policy and program interventions , 39. BegThe ‘child grant’ program comprised a cash transfer to the child’s family to inform, empower, and encourage them toward the birth registration of the child. This program most likely affected the household economic situation, particularly for the poorest families, as was also evident from the 2019 survey results. The impact of the cash transfer intervention program ─ in the form of child grant or social security programs ─ has been documented in several other countries as well , 41–44, The data indicated that the proportion of children registered increased rapidly with the child’s age, and reached nearly 90% by age five. This pattern is most likely linked to the school-going time of the child, as a birth certificate is required for admission to school. The age-related pattern of birth registration has also been found in other countries –47. Thisth grade education are more likely register their children may indicate a higher level of awareness, realization of the importance of birth registration, and self-efficacy.As noted in the preceding section, the data on the mother’s education between the two time periods are difficult to explain . We know of no specific interventions targeting the education of the mothers. However, it is possible that some of the women who were ‘literate but had no formal education’ may have been misclassified. Notwithstanding this, the results showing that the mothers with a higher than 8The data also clearly indicate that the typical biases against girls that are known to prevail in patrilocal and patriarchal societies such as in Nepal are not as pronounced as they might have been in the past. As a matter of fact, with respect to their birth registration, the differences between boys and girls had diminished by 2019. Similar findings also existed with respect to vitamin A supplementation for under-five children in Nepal . Part ofFurther, underpinning the evidence of progress indicated by the individual level data is the fact that the basic organizational infrastructure warranted for a functioning civil registration system that necessarily includes birth registration is gaining a foothold in the country. In this context, the Department of National Identity and Civil Registration (DoNICR) appears to be functioning increasingly effectively. Policies and programs initiated by the DoNICR include building the capacity of local government bodies, raising awareness, addressing perceived or actual barriers to registration, and other related activities towards achieving complete and universal birth registration have been launched with periodic supplementary activities , 27, 40.de facto surveys , it excluded those who may have been away or traveling at the time of the survey, although this is likely to be a small proportion. Third, all the births that were reported and considered as registered in the surveys may not necessarily have had a birth certificate. Finally, the survey data analyzed do not include several factors such as distance, convenience and ease of registration, availability of trained and skilled human resources, and access to healthcare contacts. These factors have been found to be important enabling or restricting factors associated with higher coverage of birth registration [A major limitation of the data analyzed here is that no birth registration information was ascertained for children who may have died among the live born during the five years immediately preceding the survey time. Based on the under-five mortality estimates from the same surveys, this implies missing information on 3.8% and 2.8% of live births in the 2014 and 2019 surveys , 31. Howstration , 8, 11. stration .The analysis of the data on birth registration, based on the surveys from the two time periods– 2014 and 2019 –unequivocally indicate that there have been significant gains in the registration of births of children under five years of age immediately preceding each survey. Thus, the two surveys provide a snapshot of an approximately 10-year period. As of 2019, more than three-fourths (77%) of births are registered, and this should be considered a remarkable achievement. This record of achievement has placed Nepal ahead of some other countries within the South Asia region.The data also clearly indicate that the typical differences between boys and girls are no longer prevalent as regards birth registration. Similarly, the other large disparities based on household wealth status have been considerably minimized. At the same time, some other disparities remain and need attention. A large proportion of infants remain unregistered, and this warrants socio-culturally appropriate interventions. The mothers with little or no education also need attention. Additionally, respondents living in better-off geographical areas  actually have lower birth registration rates than those living in relatively more disadvantaged areas. On the other hand, the evidence from relatively disadvantaged provinces indicates that it is feasible to increase the coverage if focused interventions are initiated. To this end, the evidence analyzed in this paper could provide guidance towards understanding where the disparities exist so that targeted interventions could be designed, implemented, and evaluated.


Dear Editor1. The detection of prenatal choledochal cysts is increasing with the improvements in antenatal detection, but the timing of surgery after birth remains controversial. If the cyst size increases significantly or repeated inflammation occurs during observation, early surgery is considered necessary2. With the development of minimally invasive technology, the invention and application of a robotic surgical system has created a new era of surgery3. Ihn et al.4 reported that a bodyweight of 6 kg was one of the exclusion criterion for robot-assisted surgery, whereas Xie et al.5 suggested that robotic surgery was not recommended in children aged less than 6 months. This retrospective study aimed to verify the feasibility of this procedure for patients weighing less than 6 kg.Choledochal cyst is a congenital dilatation of the biliary system. The current treatment for this is cyst excision with Roux-en-Y hepaticoenterostomyTable 1).A total of 10 patients weighing less than 6 kg with choledochal cysts who had undergone robot-assisted surgical resection between April 2020 to April 2022 were studied retrospectively . The jejunal Roux limb was fashioned extracorporeally through the enlarged umbilical incision, then the umbilical wound was partially closed to refit the 8-mm trocar. Adjusting the patient’s position to head high and feet low, after setting the upper abdominal operation mode of the machine, the no. 3 robotic arm was connected to the umbilical trocar and robotic arms no. 2 and 4 were connected to the right lower and left upper abdominal trocars. Suspending the gallbladder fossa and ligamentum teres hepatis through the abdominal wall, the gallbladder was removed from the gallbladder fossa with the electric hook. If the cyst was large, decompression was performed first to increase the operating space, then the cysts were dissected using an electric hook, keeping close to the cyst wall and away from the portal vein and hepatic artery . The dissection continued down to the distal aspect of the choledochal cyst to the point where it tapered, then the distal end was ligated with Hem-o-Lok®  polymer clips . The proximal end of the cyst was dissected in reverse along the cyst wall to the hepatic duct of the hilar part . A 4/0 absorbable suture was used for end-to-side hepaticojejunostomy . After the surgery, a drainage tube was placed around the anastomotic site, then the choledochal cyst and gallbladder were removed through the umbilical incision. All 10 patients recovered well after the operation with no complications.The patient was placed in the supine position and, after endotracheal intubation under general anaesthesia, pneumoperitoneum was established through the umbilicus. An 8-mm trocar was inserted into the umbilical incision. Another two 8-mm trocars were placed in the left upper and right lower abdomen between 3 and 8 cm from the umbilical incision, and a 5-mm laparoscopic trocar was placed in the left abdomen as an auxiliary port (


Decades of research have established that the home language environment, especially quality of caregiver speech, supports language acquisition during infancy. However, the neural mechanisms behind this phenomenon remain under studied. In the current study, we examined associations between the home language environment and structural coherence of white matter tracts in 52 typically developing infants from English speaking homes in a western society. Infants participated in at least one MRI brain scan when they were 3, 6, 12, and/or 24 months old. Home language recordings were collected when infants were 9 and/or 15 months old. General linear regression models indicated that infants who heard the most adult words and participated in the most conversational turns at 9 months of age also had the lowest fractional anisotropy in the left posterior parieto-temporal arcuate fasciculus at 24 months. Similarly, infants who vocalized the most at 9 months also had the lowest fractional anisotropy in the same tract at 6 months of age. This is one of the first studies to report significant associations between caregiver speech collected in the home and white matter structural coherence in the infant brain. The results are in line with prior work showing that protracted white matter development during infancy confers a cognitive advantage. These gains are supported in part by the home language environment, specifically how much and the manner in which caregivers speak to their children . Recent Traditional models of language neurobiology focus on the arcuate fasciculus, or dorsal pathway, a tract which connects Broca’s area in the frontal lobe and Wernicke’s area in the posterior superior temporal gyrus. The arcuate fasciculus can itself be separated into three distinct segments: 1) the direct segment which provides a continuous connection between Broca’s and Wernicke’s areas, 2) the anterior indirect segment which connects Broca’s area to the inferior parietal cortex, and 3) the posterior indirect segment which connects the inferior parietal cortex to Wernicke’s area . The arcWhile traditional models of language neurobiology are based on the adult brain, some studies have shown that infants have “adult-like” language networks . Dubois To date, investigations aiming to understand the neurobiological mechanism by which caregiver speech supports child language skills have been largely focused on functional brain development. For example, studies have reported negative associations between language input and resting state activation and functional connectivity during infancy . InvestiThe current exploratory study of typically developing infants aimed to investigate the associations between the home language environment, at 9 and 15 months , and white matter microstructure, at 3, 6, 12, and 24 months of age . The following tracts were examined: arcuate fasciculus . Given the inconsistencies in the previous literature, the current study took an exploratory approach. We examined the home language environment for associations with both concurrent white matter microstructure and the development of white matter microstructure in language production-related white matter tracts. Results from this study could inform future work on the potential mechanistic role that white matter plays in how caregiver speech supports language production skills during infancy.22.1The present study included fifty-two infants from the Infant Brain Imaging Study (IBIS). IBIS is a prospective longitudinal study conducted at four clinical data collection sites: University of North Carolina at Chapel Hill (UNC), the Children’s Hospital of Philadelphia (PHI), University of Washington (SEA), and Washington University in St. Louis (STL). Data coordination was provided by the Montreal Neurological Institute at McGill University using the LORIS data management system , and datTypical Development Status).IBIS includes infants determined to have (based on family history) either a low- or high-likelihood for autism spectrum disorder (ASD). Infants with a high-likelihood for ASD had at least one older sibling with autism, therefore, approximately a 20% recurrence likelihood of ASD  Infants Typical Development Status).Infants were included in this study if they contributed at least one home-language recording at either 9 or 15 months (> 8 h in duration), at least one diffusion-weighted MRI scan at 3, 6, 12, or 24 months, and completed behavioral and diagnostic assessments at 24 months. All infants were determined to be typically developing . The MSEL ELC and MSEL VDQ are provided to characterize participant language skill  is a standardized assessment of cognitive development normed for children from birth to 68 months . The MSEge skill . Charactge skill  and Autige skill  at 24 moge skill  was admi2.3t-score < 35, (c) no MSEL subtest t-score < 30, and (d) no clinical best estimate diagnosis of ASD at 24 months. Clinical best-estimate diagnoses were made by licensed clinicians based on DSM-IV-TR criteria using all available assessment data including the ADOS, ADI-R, MSEL, and the Vineland Adaptive Behavior Scales II.All infants in the current study were determined to be typically developing. Infants at a high-likelihood for ASD met the following criteria for typical development : (a) ADO2.4Day long audio recordings were collected when infants were 9 and/or 15 months of age. Infants wore a small recording device  designed to capture up to 16 h of home language audio data. Families were instructed to record two full days of audio, turning on the recorder when the infant woke up, and leaving it on throughout the day and into the night. Full recording procedures are available in Software automatically extracted infant and adult vocalizations from the home language recordings  were extracted via LENA software for further analysis. AWC is the number of words spoken by an adult near the infant wearing the recorder. CVC is the number of speech-like vocalizations produced by the infant wearing the recorder. Speech-like vocalizations produced by an infant can include words, babbles, or pre-speech communicative sounds  equipped with 12-channel head coils. Scans were collected during natural sleep. DWI scans were acquired using an ep2d_diff sequence with a field of view of 190 mm  or 209 mm (24 months), 75–81 transversal slices, slice thickness of 2 mm isotropic, 2 ` 2 ` 2 mm2.6Both automated and manual quality control measures were implemented to correct for infant motion and common artifacts in all generated diffusion weighted images (DWI). DTIPrep  was util2.7DTI images were co-registered to create an unbiased DTI atlas using DTI-AtlasBuilder. First, DTI images were affinely registered to a previously generated infant T2 weighted template. Next, an unbiased diffeomorphic atlas was created via affine, followed by deformable diffeomorphic registration. The displacement fields created in this procedure mapped the study-specific atlas space to individual subject spaces through a nonlinear, invertible transformation. Tensor maps were transformed into the atlas space and averaged to produce the final DTI atlas . In this2.83D Slicer (www.slicer.org) was used to create seed label maps in the DTI atlas. Further post-processing based on known fiber tract anatomy was performed using FiberViewerLight (http://www.ia.unc.edu/dev/) to further delineate fibers of interest from erroneous fibers. Label map tractography was conducted for each white matter tract. Label map tractography of the arcuate fasciculus yielded two segments for the left arcuate  and one segment for the right arcuate . The arcuate is highly variable in humans and is late to myelinate; given these two factors, quantitative fiber tracking in the atlas space may result in asymmetric segmentations of the arcuate. The corpus callosum was segmented based on the Fractional Anisotropy (FA) is a measure of the degree of anisotropy along a given axon with values ranging from 0 to 1; a value of 0 indicates isotropic diffusion, while a value of 1 is indicative of anisotropic diffusion, and highly organized axonal structure. Average FA values were generated across each of the following bilateral tracts: corticospinal tract, inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. FA values were generated across the remaining tracts: left direct fronto-temporal arcuate fasciculus, left posterior parieto-temporal arcuate fasciculus, right anterior fronto-parietal arcuate fasciculus, and splenium of the corpus callosum. Other DTI measures were also studied, including radial diffusivity (RD), a measure of diffusivity perpendicular to axonal fibers, and axial diffusivity (AD), a measure of diffusion parallel to fiber tracts.2.9N = 25, high-likelihood, N = 27). All analyses were performed using R, version 4.1.1 .As of April 26th, 2021, data were available for 52 infants who completed at least one DTI scan and one home-language recording . This multivariate statistical approach is particularly useful when the original dataset contains inter-correlated variables (as in here), because, in this case, only a few principal components can extract most of the variability in the dataset.To optimize power and identify potential covariates impacting FA measurements we used principal component analysis PCA, see . To analN = 34) was selected for PCA and a data matrix was created with the rows being participants and columns being FA values of the a priori tracts of interest (P = 14). The analysis was performed using the epPCA and epPCA.inference.battery functions from the ExPosition and InPosition R-packages . To evaluate the effect of one variable, the mean of each group of this variable was computed (and projected on the component plots) and a 95% confidence interval of each mean computed using a bootstrap resampling procedure see,  was draw05 level . The folp-values are presented as q-values. Significant models were followed up with tests of convergent validity using AD and RD values and tests to examine associations between home language recording variables and individual arc lengths along the fiber tracts.FA values for all tracts were determined to approximate a normal distribution via visual inspection of histograms. Thus, classic regression models were used to examine the cross-sectional associations between FA values at 3, 6, 12, and 24 months and home language environment variables at 9 and 15 months separately. Participant’s age at MRI scan was selected a priori to be included as a covariate in all models. False Discovery Rate (FDR) corrections were implemented for all tests conducted using the same response variable to correct for multiple comparisons using the one-step model described by Mixed models were used to model the longitudinal association between FA and the home language environment across time. All models had longitudinal FA as the response variable with home language environment variables serving as the fixed effect. Participant identification number was included as a random intercept in all longitudinal models.33.1N = 170) recording days having full 16 h of data, and the remainder having between 8- and 16-hour recordings. The shorter recordings were generally a consequence of the parents turning the recorder off during bedtime and hence the data was not adjusted for recording time , indicating that infants who produced more speech-like vocalizations had less coherent white matter organization. Significant negative associations were also found between AWC and CTC at 9 months and FA in the left posterior parieto-temporal arcuate at 24 months . q =.007, q =.004, respectively). The remaining RD models did not yield statistically significant results. We also examined associations between AD and home language recording variables, but none of the models were significant prior to FDR correction.Results  showed ap-values along the arc lengths were generated using the FADTTS  toolbox and its corresponding graphical user interface, FADTTSter  ; While automated measures of the home language environment offer the convenience of processing large amounts of data quickly, they are not devoid of limitations. The main limitation of this approach is the reliability of the automated tool to perform correct diarization of the data . While initial validation results by the LENA Research Foundation indicated acceptable sensitivity of their software  contribute to the estimate. Additionally, regions of crossing fibers may result in areas of signal drop out due to poor model fit . The cur4.3Advancements in DTI since the collection of the current dataset include scan sequences that are efficient at handling crossing fibers which are known to make fiber tracking of infant temporal lobe tracts a particular challenge. One notable example, is High Angular Resolution Diffusion-Weighted Imaging HARDI; . HARDI sThe current study adds to the body of research showing that caregiver speech is a protective factor for productive language development, because this study provides initial insights into potential structural brain mechanism in infants. However, the current sample is underpowered to determine how caregiver speech, infant brain development, and infant language skills are all interconnected across early development. Such integrated biobehavioral environmental approaches will be essential to a fuller understanding of how to best support infant brain and language development. For example, such approaches would yield important information on the timing of when caregiver speech has the greatest influence on brain development. Filling this gap in the literature would increase the effectiveness of interventions designed to support school readiness through right home language environments.infancy is associated with both brain and behavior in the toddler years. The timing of this developmental cascade is important for clinical and public health research that targets caregiver speech as a way to close the achievement gap and support kindergarten readiness. Providing supports for caregivers during the earliest months of life may results in optimal outcomes as infancy is a period of high brain plasticity and a sensitive period for language development.In conclusion, the current research study found that infants who heard more caregiver speech, exchanged more conversational turns, and used more speech-like vocalizations also had lower white matter coherence in language production-related white matter tracts. This research contributes to a small but growing body of infancy research showing that protracted white matter development is associated with better cognitive skills. The results of this study also contribute important information on developmental cascades; namely that the home language environment during The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The COVID-19 pandemic has taken a large toll on population health and well-being. We examine the consequences of prenatal exposure for infant health, through which the pandemic may have lasting intergenerational effects. We examine multiple pathways by which the pandemic shaped birth outcomes and socioeconomic disparities in these consequences. Analysis of more than 3.5 million birth records in California with universal information on COVID infection among persons giving birth at the time of delivery reveals deep inequalities in infection by education, race/ethnicity, and place-based socioeconomic disadvantage. COVID infection during pregnancy, in turn, predicts a large increase in the probability of preterm birth, by approximately one third. At the population level, a surprising reduction in preterm births during the first months of the pandemic was followed by an increase in preterm births during the surge in COVID infections in the winter of 2021. Whereas the early-pandemic reduction in preterm births benefited primarily highly educated mothers, the increase in pre term births during the winter infection surge was entirely concentrated among mothers with low levels of schooling. The COVID-19 pandemic is expected to exacerbate U.S. inequality in multiple ways. Our findings highlight a particularly enduring pathway: the long-term legacy of prenatal exposure to an unequal pandemic environment. The COVID-19 pandemic has had an unprecedented impact on population health and well-being in the United States, where almost 100 million cases of the SARS-CoV-2 virus that causes COVID disease have been recorded by October 2022 and 1.09 million deaths have been attributed to the disease. The impact on health and well-being has not been equally distributed. Cases, hospitalizations, and deaths have been higher among socioeconomically disadvantaged populations  and raciin utero exposure to COVID and infant health could have direct implications for inequality and the intergenerational transmission of disparities  a novel health threat that (2) may be at least partially prevented by behavioral and locallevel structural modifications to reduce risk, which (3) causes broader disruption to family arrangements and economic well-being and (4) poses disparate risks based on cumulated health disadvantage. We rely on two theoretical approaches—fundamental cause theory and cumulative disadvantage approaches—to formulate testable hypotheses linking this type of exposure to unequal outcomes.Fundamental cause theory suggests that socioeconomic inequality in health persists over time because socioeconomic advantage comprises multiple resources, such as money, prestige, power, and social connections . These rThe fundamental cause approach predicts that socioeconomic position will be more salient when the factors affecting health are, as in the case of COVID, preventable and therefore allow for resources to be deployed . Even inObserved stratification patterns of COVID infection for the general population are consistent with fundamental cause theory. Socioeconomically disadvantaged and racially minoritized persons were more likely to be exposed to COVID-related risk factors: they were more likely to live in crowded conditions, to hold jobs that could not be performed remotely, and to be concentrated in public-facing occupations, all of which make maintaining social distancing difficult to afford . Risk-reNot surprisingly, given the stratification of risk factors, research suggests socioeconomic disparities in COVID infection among pregnant populations. Pregnant persons with low educational attainment, racial/ethnic minorities, and those living in disadvantaged neighborhoods have been found to be more likely to be infected or have COVID symptoms during pregnancy .Indirect pathways linking the COVID pandemic to infant health emerging from economic and family disruption also suggest marked socioeconomic stratification. Early in the pandemic, risk factors such as employment loss, food insecurity, and heightened anxiety were much more likely to disrupt the lives of individuals in vulnerable communities, including those with low levels of education and racial/ethnic minorities . In contSupplementing fundamental cause theory, the cumulative disadvantage approach suggests that disparities in exposure to infection may be compounded by disparate vulnerability to its consequences for maternal and infant health. Diverse strands of this approach, including allostatic load  and weatThe fundamental cause and cumulative disadvantage approaches are theoretically distinct. However, they offer similar predictions about the unequal impact of the COVID pandemic on infant health: the same groups of people who faced disproportionate exposure to pandemic risks and fewer resources to manage those risks also began the pandemic with a larger burden of health risks accumulated over their lives.On the basis of these theoretical approaches, we formulate the following hypotheses:Socioeconomically disadvantaged persons are more likely to be infected with COVID during pregnancy because of a higher prevalence of risk factors and reduced ability to reduce risk.Disadvantaged pregnant persons with a COVID infection during pregnancy are more likely to experience preterm birth because of a heavier burden of comorbidities and differential treatment by the health care system.The populationlevel impact of COVID on infant health will be stratified by socioeconomic advantage as a result of both direct (infection among pregnant persons) and indirect (economic and family disruptions and policy responses to the pandemic) mechanisms.The populationlevel impact of the pandemic might even vary in direction across groups defined by socioeconomic advantage, with direct and indirect pathways potentially increasing preterm births among disadvantaged groups and the positive externalities of the pandemic potentially benefiting advantaged groups and reducing preterm births.We rely on detailed birth records for all infants born in California between January 2014 and November 2021. We obtained early-release restricted-access natality microdata based on birth certificates from the California Department of Public Health. The natality data set contains information about the date of birth, infant characteristics , and mother’s characteristics . The total sample size is 3,667,903. To the natality data, we merged sociodemographic information from the ZIP code tabulation area of the pregnant person’s residence obtained from the American Community Survey 2015–2019.1Starting in June 2020, California birth certificates recorded both confirmed and presumptive cases of COVID infection among all persons giving birth. Confirmed cases are indicated by tests verified by the CDC laboratory, whereas presumptive cases result from tests conducted by a state or local laboratory but not yet confirmed by the CDC at the time the birth certificate was recorded. Following CDC guidelines, both presumptive and confirmed cases are considered a diagnosis of COVID.2 and ascertained whether universal testing on admission was administered and if so when it started for 75% of births occurring since June 2020, when birth certificates started including this information. Of these births, 72% occurred in a facility with confirmed universal testing. We use this data set to test the robustness of results by limiting the sample to births that occurred in a facility with confirmed universal testing . The analysis considers the period when COVID infection status among persons giving birth was first recorded on California birth certificates  to the most recent date available at this writing . We restrict the observations to singletons to limit the influence of other determinants of preterm birth that accompany multiple-birth pregnancies. Fixed effects for birth facility account for differences in COVID testing protocols, labor and delivery protocols, and other institutional characteristics that might shape preterm birth. Fixed effects for calendar week account for trends in COVID infection and temporal changes in testing shared across facilities.The sociodemographic predictors included in the models are mother’s race/ ethnicity , educational attainment , and socioeconomic disadvantage of the ZIP code of mother’s residence. We construct this latter measure with information on the proportion of adult residents in the ZIP code with a high school diploma or less, median household income, the proportion Hispanic, the proportion Black, the Gini index, the proportion foreign-born, the proportion of households below the poverty line, and the proportion of individuals without health insurance. We used principal component analysis to calculate the ZIP code disadvantage index, extracting the first component and dividing it into quartiles.Prior scholarship suggests that socioeconomic gradients in maternal and infant health vary across racial/ethnic groups . To exam3 The preferred ARIMA specification for the entire population and educationspecific groups is a seasonal multiplicative model with one firstdifference term, one moving average term, and one seasonal 52-week difference parameter capturing annual seasonality .To assess population-level trends in preterm birth during COVID, we aggregate individual-level data into a weekly time series of preterm birth rates from January 1, 2014, to November 28, 2021. We create time-series data sets for all singleton births and across levels of mother’s educational attainment. Time-series data contain sources of temporal autocorrelation, including trend, seasonality, and the tendency for high and low values to persist over several periods, which can confound the effect of exposure . We estiCOVID cases in California exhibited a gradual increase through the summer of 2020, a reduction in the fall, and a large spike in the winter of 2021 . After aBetween June 22, 2020, and November 28, 2021, 2.6% of pregnant persons tested positive for SARSCoV2 infection. Infection risk was highly stratified by socioeconomic resources. Our fixedeffects analysis shows a marked gradient by educational attainment and ZIP code socioeconomic disadvantage , panel aPrior scholarship suggests that educational and other socioeconomic gradients in maternal and infant health may vary across racial/ethnic groups . We therMaternal COVID infection at the time of labor and delivery predicts a large increase in the probability of a preterm birth .p > .05 for all pairwise comparisons). In sum, our analysis shows that mothers with low levels of education, living in disadvantaged ZIP codes, and who are Hispanic experienced an elevated risk of preterm birth during the COVID pandemic. This excess risk is due to a higher probability of COVID infection rather than to a more detrimental impact of infection on preterm birth.The stratification of COVID infection risk during pregnancy might be compounded by disparities in the association between maternal infection and preterm birth. As the fundamental cause and cumulative disadvantage approaches predict, the impact of infection on infant health might be more acute among disadvantaged populations because of a stronger burden of comorbidities, reduced access to medical technologies, and dissimilar standards of care. We do not find evidence supporting a stronger negative association between COVID infection and preterm births among disadvantaged groups defined by maternal race/ethnicity and educational attainment  that evolved alongside social distancing policies. Earlier studies attributed postpandemic changes in birth outcomes to policy responses, but such responses cannot be considered exogenous. Evidence indicates that people adjusted their behavior and hospitals altered health care protocols to reduce the risk of COVID infection independent of social distancing policies .The evidence here indicates key avenues for future research. Although the mortality costs of the COVID pandemic are unambiguously clustered among the elderly, pregnant populations—and, by extension, those of reproductive age—warrant serious public health attention. Further, the longer run outcomes for children born during the pandemic, particularly those born into low-resourced families with a higher risk of COVID exposure, require special attention and monitoring over time. Several safety-net programs have been tested during the pandemic, and attention to their inequality-mitigating effects will be important as the cohorts that were prenatally exposed age. Finally, the study underscores that attention to population heterogeneity during large-scale health crises is critical. Although aggregate data provide early surveillance, they likely mask substantial variation, ranging from harmful effects for some groups to neutral or even positive effects for others. As we have shown, early-release administrative data with key information on socioeconomic heterogeneity provide a critical resource for developing strategies to support infant health in the context of health crises.Appendix


Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population.The study included an unselected series of 113 patients aged 2–18 years , referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible.23 IBD patients  were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern  and mesenteric hypertrophy  accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%.Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation. Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBD-U), are characterized by chronic inflammation of the gastrointestinal (GI) tract. Their incidence and prevalence have dramatically increased worldwide over the past 50 years . In up tTherefore, prompt investigations, are recommended in all children with strong suspicion of IBD, in particular ileocolonoscopy . HoweverThe accuracy of IUS in the detection of IBD has been well established by systematic reviews, meta-analysis and international guidelines, but data on its accuracy rely only on one parameter such as the presence of an abnormal bowel wall thickening (BWT), namely a BWT more than 3 or 4 mm , 8. HoweTo date, no data are available on the usefulness of combined IUS finding to discriminate children at high risk for IBD. Moreover, the relevance of increased BWT and the additional value of other IUS parameters in the diagnosis of IBD have not been investigated so far. This study aims at investigating the diagnostic accuracy of several US parameters in detecting IBDs in a paediatric population.This is a retrospective study including a consecutive series of children aged 2–18 years, referred to our paediatric gastroenterology clinic from 2007 to 2013 for recurrent abdominal pain and/or altered bowel habits (diarrhoea or/and constipation) for whom the decision to proceed with endoscopy was not already definite.Children were eligible for the study if they had undergone IUS because of altered laboratory tests including faecal calprotectin (FC) and biochemical inflammatory indexes (BII), in particular C-reactive protein (CRP), within 1 week following the initial outpatient visit, as part of a scheduled diagnostic work-up used in our paediatric gastroenterology unit since 2007. Indeed, since 2007 a work-up algorithm based on IUS, BII and FC is used for every child who present symptoms like recurrent abdominal pain and/or altered bowel habits (diarrhoea and/or constipation) and/or history of weight loss with fever.Exclusion criteria were: (i) known organic diseases (e.g. previously known IBD or celiac disease), (ii) highly suspected IBD , which would have required a digestive endoscopy anyway, or, (iii) a recent (within 6 months) instrumental diagnostic investigations (e.g. upper or low\er endoscopy).Reference gold standard for IBD diagnosis was the confirmation by endoscopic and/or radiologic investigations performed within 1 year from initial non-invasive diagnostic work-up, according to ESPGHAN revised Porto criteria . ConversBeing a retrospective study, a formal approval by our local Ethical Committee was not need, but only an informative letter of intent.Faecal calprotectin (FC) was measured using a quantitative immunochromatographic point-of-care test. Calprotectin concentration < 200 μg/g was considered normal reference value.IUS was performed by the same expert gastroenterologist , after a 6-h fasting, without any specific bowel preparation. All examinations were performed with the same equipment  using a broadband convex probe with a frequency of 3.5–5 MHz for a panoramic view of the abdomen and then a high frequency (4–8 MHz) microconvex transducer for detailed bowel evaluation. Despite BWT > 3 mm is the main variable considered for IBD , in our Therefore, BWT was measured perpendicular to the wall from internal interface between the lumen and mucosa to the external interface between serosa and muscularis propria, both in longitudinal and transverse sections, in the most affected intestinal segments, taking the average measurement and considering it pathological if > 3 mm , 9Fig. . Bowel wU test for continuous variables and the chi-square or Fisher’s exact test for categorical variables. Univariate binary logistic regression was used to evaluate variables predictors of the presence of IBD [P value < 0.05 was considered statistically significant.The statistical analysis was performed by a biomedical statistician (AD) using IBM SPSS statistics version 26 . Data are reported as frequencies or means ± standard deviation (SD). Comparisons between groups were made by Mann–Whitney e of IBD . The assOne hundred thirteen patients were enrolled . Demographic data are shown in Table p < 0.0001).As expected, IBD patients showed a greater prevalence of abnormal biochemical tests, especially high levels of FC, compared with patients without IBD , while increased BWT, altered bowel echopattern and mesenteric hypertrophy (MH) were found far more frequently in IBD patients compared to non-IBD patients . Finally, the finding of abdominal free fluid was higher in IBD patients .As regards IUS, IBD patients showed a significantly higher rate of abnormal findings compared to non-IBD patients, with a degree of variability among different parameters Table . EnlargeTherefore, the main and more frequently found IUS parameters at univariate binary logistic analysis and confirmed at multivariate binary logistic analysis were altered bowel patter  and mesenteric hypertrophy  with a borderline value for the increased BWT  Table .Table 3UAs a consequence, the diagnostic accuracy of IUS in discriminating children with IBD from those without IBD showed that BWT > 3 mm had the greatest positive predictive value , while the absence of altered bowel pattern  shows the greatest negative predictive value . Overall, intestinal ultrasonography bowel pattern (IUS-BP), MH and BWT > 3 mm had a sensitivity value of 78.3%, 65.2% and 69.6%, and a specificity value of 93.3%, 92.2% and 96.7%, respectively. The combination of these three parameters increased the positive predictive value (PPV) up to 100%, whilst the absence of any of these IUS findings showed the greatest negative predictive value (NPV)   and 100% (95% CI 66–100), respectively, in an Italian study conducted on 21 children .Among several IUS parameters, the BWT is the most reliable and usually considered for the diagnosis of IBD and CD in particular , 8. HoweThe usefulness of the combination of non-invasive tests and IUS has been already demonstrated . A recenThe values in our study were slightly higher. However, we used these parameters for the diagnosis of IBD, and not for not for the evaluation of activity in patients with a known diagnosis of CD. In our study, at the multivariate we have found OR for BWT > 3 mm 5.4 (95% CI 0.7–40.1), for altered US-BP 9.8 (95% CI 1.6–59.0) and MH 5.2 (95% CI 1.1–25.1).. showed that abdominal free fluid and enlarged mesenteric lymph nodes showed a specificity of 96% and 97%, respectively, whereas dilated small bowel loops with increased fluid content and increased peristalsis had a sensitivity of 92% and 83%, respectively [The diagnostic weight of a single IUS parameter and of their combination has already been investigated in celiac disease. Fraquelli et alectively .We found that mesenteric lymph nodes were the commonest IUS findings in children complaining abdominal symptoms. However, along with abdominal free fluid likely the less specific, as it has been observed also in a greater proportion of non IBD patients. These findings are in keeping with the data of the literature showing that, although more frequently encountered in inflammatory conditions, enlarged lymph nodes and small amounts of abdominal free fluid are common, unspecific and sometimes clinically insignificant findings in children  but may On the contrary, increased BWT, altered bowel pattern and mesenteric hypertrophy were found far more frequently in IBD patients and could be considered more specific of an inflammatory disorder like IBD, as also confirmed by our multivariate binary logistic analysis. However, their specific weight in IBD diagnosis is still debated. Most studies carried out in paediatric populations considered BWT as the main parameter for assessing IBD and its course after treatment  althoughThe main strength of our study is the evidence that the combination of IUS findings may increase the PPV and the NPV of the IUS. In particular, the combination of these three alterations increased the PPV up to 100%, whilst the absence of any of these IUS findings showed the greater NPV. This could be crucial in children where the setting for colonoscopy could be difficult.Our study includes several limitations. Firstly, it is a retrospective study, and it has a non-univocal reference gold standard as a comparison. Secondly, the assessment of one parameter may be inevitably influenced by the detection of the others. Finally, it has not been included neither colour Doppler or small intestine contrast ultrasonography (SICUS), now considered relevant methods for assessing IBD both in children  and in aIUS could be used for the diagnosis of IBD with high sensitivity and specificity in a large retrospective cohort of children. The combination of BWT > 3 mm, US-BP and MH had a positive predictive value of 100% in our cohort. Therefore, the key massage of the study is that sonographic diagnosis of IBD—or better the “suspected diagnosis of IBD” as the true “diagnosis relies of clinical, biochemical, radiological, endoscopic and histological parameters —is betteWe believe that our findings could be of value for clinical practice and research, in particular to plan new studies in adults, in order to investigate the exact role of intestinal ultrasound in patients with abdominal complaints especially those with lower pre-test probability of IBD.


Published guidelines on decision-making and resuscitation of extremely preterm infants primarily focus on high-income countries. For rapidly industrializing ones like China, there is a lack of population-based data for informing prenatal management and practice guidelines.The Sino-northern Neonatal Network conducted a prospective multi-centre cohort study between 1 January 2018 and 31 December 2021. Infants with a gestational age (GA) between 22  and 28  admitted to 40 tertiary NICUs in northern China were included and evaluated for death or severe neurological injury before discharge.For all extremely preterm infants (n = 5838), the proportion of admission to the neonatal was 4.1% at 22-24 weeks, 27.2% at 25-26 weeks, and 75.2% at 27 and 28 weeks. Among 2228 infants admitted to the NICU, 216 (11.1%) were still elected for withdrawal of care (WIC) due to non-medical factors. Survival rates without severe neurological injury were 6.7% for infants at 22-23 weeks, 28.0% at 24 weeks, 56.7% at 24 weeks, 61.7% at 25 weeks, 79.9% at 26 weeks, and 84.5% at 27 and 28 weeks. Compared with traditional criterion at 28 weeks, the relative risk for death or severe neurological injury were 1.53  = 1.26-1.86) at 27 weeks, 2.32 (95% CI = 1.73-3.11) at 26 weeks, 3.62 (95% CI = 2.43-5.40) at 25 weeks, and 8.91 (95% CI = 4.69-16.96) at 24 weeks. The NICUs with higher proportion of WIC also had a higher rate of death or severe neurological injury after maximal intensive care (MIC).Compared to the traditional threshold of 28 weeks, more infants received MIC after 25 weeks, leading to significant increases in survival rates without severe neurological injury. Therefore, the resuscitation threshold should be gradually adjusted from 28 to 25 weeks based on reliable capacity.China Clinical Trials Registry. ID: ChiCTR1900025234. Preterm birth and ensuing complications are the primary causes of death among children under five years of age globally . AlthougAs the largest developing country, China has over 1.17 million premature infants, the second largest number of premature babies globally . PreviouWe prospectively defined the mode of death and analysed the results of the Care-Preterm Cohort study (2018-2021), a regional cohort of infants born at a gestational age between 22  and 28  weeks based on the Sino-northern Neonatal Network. We aimed to provide the updated mortalities and morbidities for each GA group in the real world to discuss the recovery threshold of extremely preterm infants.The Care-Preterm study was based on the Sino-northern Neonatal Network (SNN), which collected data both prospectively and continuously. The Network was established to report on survival and outcomes in very preterm and very low birth weight infants born in this geographical region in order to conduct quality improvement. It is based in Shandong and covers a total of six provinces  comprising 40 NICUs covering 29 general hospitals and 11 maternity hospitals . Health insurance coverage is at more than 95% in the included provinces. Per the Maternal Health Handbook, pregnant women <32 weeks of gestation are intrauterine transferred to a tertiary maternal or general hospital equipped with a tertiary NICU. Newborns are transferred at the county, prefectural, and provincial levels on a tiered basis . We implWe included infants born at GA between 22  and 28  and admitted to participating NICUs between 1 January 2018 and 31 December 2021. We excluded infants who had known congenital anomalies or who were moribund (those in whom a decision was made at the time of birth not to provide resuscitative care).We determined GA by the best estimate based on early prenatal ultrasound examination, the last menstrual period, and the physical examination of infants at birth, in this order. We included the date of embryo transfer to determine GA for in vitro fertilization. Mortality was defined as death due to any cause prior to discharge from the NICU. We defined severe neurological injury (SNI) as intraventricular haemorrhage (IVH) (grade 3 or 4) and/or porencephalic ventricular leukomalacia (PVL) . The staWe defined a composite outcome of mortality or any major morbidity as death before discharge or survival with any of four major morbidities: bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP), SNI (IVH ≥grade 3 and/or PVL), stage 2 or 3 necrotic enterocolitis of newborn (NEC). We defined BPD as respiratory support given at 36 weeks’ post menstrual age or at discharge (if earlier than 36 weeks’ PMA) to level 2 centres , severe We defined normothermia as a recorded admission temperature between 36.5 and 37.5°C  taken within the first hour of admission and representing the first set of vital signs recorded after NICU admission .2 or Fisher exact test to compare between groups. For internal comparison, we divided units with more than 20 cases into four groups, according to the proportion of WIC according to quartiles, descriptively compared the incidence of mortality or SNI after MIC after standardisation of potential confounders including male gender, antenatal corticosteroids, the Score for Neonatal Acute Physiology with Perinatal Extension II (SNAPPE-II) >20, and multiple births. We evaluated the associations between GA and mortality or SNI on a continuous scale, with restricted cubic spline curves based on logistic models with three knots at the 25th, 50th, and 75th percentiles of the distribution. We selected covariables that could be potential confounders of the associations between GA and infant outcome based on literature [We summarised demographic and clinical characteristics using counts and percentages for categorical and medians and interquartile ranges (IQRs) for continuous variables. We used the χterature ,24 and cIn the 40 hospitals included in the SNN, 5838 pregnancies at 22  and 28  weeks resulted in 2579 live births (Table S1 in the P = 0.001) and male infants  underwent WIC. The maternal age was higher in the MIC (md = 32 (IQR = 29-36)) than the WIC group (md = 31 (IQR = 28-35)). The Apgar at five minutes and SNAPPE-II revealed no statistical significance between the two groups.For 2228 extremely preterm infants, 1185 (56.6%) were male (median (md) GA = 27 (IQR = 27-28) weeks; md bodyweight (BW) = 1030 grams (IQR = 880-1200)). Among the 575 (26.6%) infants who died before discharge, 216 (37.6%) died following a decision of WIC. The proportion of WIC was the highest in the 24-26-week group (13.7%) instead of the 22-23-week group (6.3%); the highest proportion of WIC was in the 501-750-gram group (16.2%) and was at 14.3% in the 751-1000-gram group, while infants <500 g did not undergo WIC  accounted for 70.7% (n = 522/688) of all deaths. How small is not too small in present-day China, however, still warrants further exploration.We found that a more aggressive prenatal preparation and resuscitation for preterm infants at 25-27 weeks before delivery, rather than a postnatal decision for further care, may benefit a larger absolute number of infants in China. Although our study is not based on a national cohort, its geographic area covers a quarter of China's population and is representative of those with similar levels of medical care. Countries or regions shoulds analyse baseline data to inform physicians to reduce death caused by medical and non-medical reasons.The workable recommendations can be beneficial in improving outcomes for preterm infants. For example, the publication of the Swiss guidelines was followed by a significantly improved survival of infants born extremely preterm . The optWe found China has a similar mortality rate to networks in developed countries with relatively higher mortality rate, such as the Spanish Neonatal Network (23.4%) or the United Kingdom Neonatal Collaborative (15.8%), but not with others like the Finnish Medical Birth Register (9.6%) and the Neonatal Research Network of Japan (7.0%) . HoweverFor industrialised countries, the resuscitation threshold constantly changed from the 1960s to 1970s; it included infants with GA>28 weeks and BW>700 g, but now, there is general agreement for comfort care at 22 weeks’ GA and active care at 25 weeks’ GA -34. ThisThis study has several limitations. In China and other developing countries, where the neonatal collaborative network has only recently been established, data on long-term follow-ups are not yet available , thus thDescriptive data and statistical analyses demonstrated that the rescue limit should be adjusted from 28 to 25 weeks, which may help make appropriate decisions. Future studies must assess the impact of this change, including the long-term outcomes of infants, the societal and economic burden on families, and cost and services utilisation of the health care system.


Z-score loss between birth and discharge was higher than 1. Body composition was assessed between 35 and 41 weeks of PMA. Among the 310 ELBW infants included, the gestational age of birth was 26.7 ± 1.8 weeks, and the birth weight was 800 ± 128 g. The mean Z-score difference between birth and discharge was moderately negative for the weight (−0.32), more strongly negative for length (−1.21), and almost nil for head circumference (+ 0.03). Only 27% of infants presented PNGF. At discharge, fat mass was 19.8 ± 3.6%. Multivariable analysis showed that the proportion of preterm formula received and gestational age at birth were independently associated with the percentage of fat mass.This cohort study aimed to evaluate the impact of an individualised nutritional care approach combining standardised fortification with adjustable fortification on postnatal growth and body composition in extremely low birth weight (ELBW) infants. We included ELBW infants admitted to a neonatal intensive care unit and still hospitalised at 35 weeks postmenstrual age (PMA). The fortification of human milk was standardised (multicomponent fortifier) between 70 mL/kg/day and full enteral feeding, and then individualised using adjustable fortification. When weight gain was below 20 g/kg/day, protein or energy was added when serum urea was below or above 3.5 mmol/L, respectively. Postnatal growth failure (PNGF) was defined as being small for gestational age at discharge and/or when the   Conclusion: The individualised nutritional care approach applied herein prevented postnatal weight loss in most infants, limited length growth deficit, and supported excellent head circumference growth. Z-scores for body weight were −0.66 at birth and −1.84 at 36 weeks PMA. Importantly, 44% of these infants had a Z-score below -2 standard deviation (SD) at discharge . The search for factors potentially associated with FM% was carried out using univariable and multivariable linear regression analyses. Variables with p < 0.05 in univariable analysis were retained in the multivariable model. Results are presented as an estimate with [95%CI]. The alpha-risk significance level for all analyses was set at 0.05. All analyses were performed using R software version 3.5.3 .For statistical analysis, continuous variables were described by their means and SD, and comparisons were performed using Welch’s The study was approved by the ethics committee Comité de Protection des Personnes Sud-Est IV (IRB: 00009118), and the institutional review board  was registered in Clinicaltrials.gov (NCT02686801). infants , moderately negative for the weight (−0.32 ± 0.75), and more strongly negative for length (−1.21 ± 0.92)  presented PNGF . FM% was significantly higher in infants with optimal growth compared to those with PNGF . Factors influencing FM% were the proportion of milk intake as preterm formula and GA at birth. Those influencing FFM were GA at birth and sex , despite the fact that the infants herein were less mature [Z-score loss recently proposed as acceptable [Z-score for body weight below −2 at discharge than in the EXPRESS cohort [Z-score for body weight below −1.28 at discharge, which is lower than previously reported in even more mature very low birth weight infants [Z-score loss of 0.82 [Z-score for length during hospitalisation [The postnatal growth observed in this cohort closely followed that of foetal growth, at least for body weight and HC. The present individualised nutritional care approach helped to avoid the postnatal weight deficit as demonstrated by a s mature . This deceptable , 21. In S cohort . Moreove infants . The obs infants . In a si of 0.82 . In the  of 0.82 . Althoug of 0.82 . Surpris of 0.82 , 27, andlisation . It is wlisation . Furtherlisation . The fewlisation . This relisation –34.Of note, PNGF might be a more relevant marker of growth deficit than just SGA at discharge . When usCurrently, there is no consensus regarding the body composition objective at the end of hospitalisation. Due to the metabolic adaptation to extrauterine life needed to increase energy storage and improve thermoregulation, the foetal body composition cannot serve as a reference . Given tA deficit in FFM at discharge has been associated with neurological impairment at 2 years of age , 40. HerA limitation of this study is its single-centre design, although this did not prevent the data from a significant number of ELBW infants to be analysed. Furthermore, it avoided the impact of potential inter-centre differences in practices other than nutritional management, which could impact postnatal growth. Moreover, only a subgroup of infants could benefit from the body composition assessment herein. They had less bronchopulmonary dysplasia and therefore, less postnatal steroid treatment. However, even though the most severely ill infants did not undergo a body composition measurement, those who had it still represented a population of very high-risk ELBW infants.In conclusion, an individualised nutritional care approach using standardised fortification followed by adjustable fortification limited body weight and HC postnatal growth deficits. FM% was higher than that of foetuses of the same GA, possibly representing a necessary adaptation to extrauterine life. Further studies are still needed to determine the growth and body composition objectives in ELBW infants according to their impact on later development.


The dentigerous cyst is a developmental odontogenic asymptomatic cyst, that is associated with the crown of an unerupted or impacted tooth. Early diagnosis is important to avoid any future complications and choose the best treatment option. The purpose of this case report is to describe the management of a dentigerous cyst related to lower second molar in a young female patient using orthodontic traction as a conservative treatment approach. This procedure helps to spare the patient an unnecessary surgical excision procedure and the associated excessive bone removal for a safety margin, stimulates bone healing and promotes the eruption of the cyst-associated tooth. The presence of an impacted, unerupted, embedded tooth, a tooth under development, odontome or a supernumerary tooth, carries the risk of development of one of the most common types of odontogenic cysts; the Dentigerous cyst or follicular cyst . It was The dentigerous cyst surrounds the crown of the unerupted tooth and is attached to its cervical region. It develops from accumulation of fluid between the remnants of the reduced enamel epithelium and the subjacent tooth crown shortly after complete formation of the crown . The natRadiographically, the Dentigerous cyst is usually characterized by a unilocular radiolucent lesion around the unerupted tooth, with a distinct dense periphery of condensed bone . An enlaThe classical treatment decision of the Dentigerous cyst is total enucleation with a safety margin of bone removal, to avoid recurrence together with extraction of the associated impacted tooth . HoweverThis article presents a clinical case with a Dentigerous cyst surrounding the crown of an unerupted lower right second molar that has been treated by orthodontic traction of the unerupted tooth.A fourteen-year-old female presented to our orthodontic clinic with a chief complaint of unpleasant appearance of her teeth. The pre-treatment records including clinical intra-oral and extra-oral examination, photos, panoramic radiograph, lateral cephalometric radiograph, upper and lower impressions were taken. Intraoral examination showed the patient had a full set of erupted permanent teeth up to the first molars in all quadrants. A single cusp tip of the lower left second molar was erupting, while the lower right second molar was unerupted. The patient showed an Angle class I malocclusion with moderate and mild crowding in the upper and lower arches respectively, and anterior deep bite Fig. . ExtraorThe case was referred to the maxillofacial surgeon for consultation. Based on the clinical, radiological and CBCT findings, a diagnosis of dentigerous cyst was concluded.The treatment option recommend by the surgeon was extraction of the associated impacted tooth and the third molar, cyst enucleation and bone removal with a proper safety margin in order to minimize the possibility of recurrence and allow the regeneration of healthy bone.Considering the age of the patient, size of the cyst, the position of the cyst close to the oral mucosa, the dental deep overbite, the possibility of resolution of the cyst with the eruption of the second molar, the approach of enucleation and tooth extraction was considered to be aggressive for the current case. Hence, a more conservative approach for the sake of conservation of the natural permanent tooth was agreed upon with the surgeon. Orthodontic traction which will be accompanied by spontaneous decompression and marsupialization of the cyst will be done. Accordingly, a CBCT was captured Fig. , which cThe treatment strategy depends on surgical exposure of the impacted second molar, bonding orthodontic attachment and orthodontic traction until the cyst lining attached at the cervical margin gets exposed in the oral cavity and blends with the oral mucosa, with no future risk of fluid accumulation and re-formation of the cyst. The critical stage in this procedure is the ability to maintain the decompression and cyst opening exposed in the oral cavity without healing until eruption of a part of the tooth.Orthodontic treatment was initiated on the lower arch, comprising bonding of fixed orthodontic appliance, Roth prescription, 0.018 inch slot Roth brackets, with bonding of a double tube on the lower right first molar to help orthodontic traction of the lower second molar. Levelling and alignment was initiated until an archwire of 0.017 × 0.025 inch stainless steel archwire was reached. Surgical exposure of the second molar and bonding of an orthodontic tube to the exposed part of the buccal surface was done. An initial auxillary archwire 0.012 inch nickel titanium archwire attached between the auxillary tube of the first and second molars is used for occlusal traction of the second molar. In the monthly recall of the patient, the gauge of the wire was increased until the tooth is totally erupted on the oral cavity and an archwire of 0.017 × 0.025 inch stainless steel archwire could be inserted as a main archwire. At this stage, intraoral photographs and a panoramic radiograph were taken Fig. , which sThe threat the dentigerous cyst presents is reverted back to its asymptomatic, incipient, and expanding nature. The early diagnosis is of paramount importance prior to the expression of the aggressive form of the lesion. This aggressive form has the potential to expand the bone of the mandible, with the subsequent displacement of teeth, malocclusion, pain, inferior alveolar nerve paresthesia and root resorption .The intraoral observation of any altered eruption patterns, besides the proper examination of the pre-orthodontic panoramic radiograph to detect the presence of such cyst can be of significant help for early intervention. However, the differential diagnosis should be considered for identification of the Dentigerous cyst. When the follicular space exceeds 3–4 mm, Dentigerous cyst is suspected .The most convenient treatment option for the dentigerous cyst should be chosen to suit the clinical situation. Surgical enucleation is a common modality for treatment of the Dentigerous cyst . It encoThe other treatment option is decompression; which is elected in the currently presented case and in other previously reported cases . It encoIn the current case, the young age of the patient with the strong healing and eruptive power of the teeth, besides the favorable position of the cyst and the vertical impaction of the second molar privileged decompression and orthodontic traction of the embedded second molar. Besides, the preservation of the second molar could have a favorable functional and psychological impact on the patient . This prThe bonding of the impacted second molar on the day of incising the cyst wall and decompression and the early occlusal traction of the second molar gave chance for maintaining the intact and the fast eruption of the impacted tooth. After few months of released pressure on the bone, the panoramic radiograph showed complete disappearance of the cyst, increased radio-opacity of the surrounding bone with the full eruption of the second molar. These same findings were confirmed in the panoramic radiograph taken 3 years after finishing the orthodontic treatment, with no evidence of recurrence Fig. .The chosen treatment option of decompression of the developing dentigerous cyst simultaneously with guided eruption of the associated second molar showed acceptable results with such a case.The post-treatment panoramic radiograph showed complete radiographic healing of the cyst and uneventful eruption of the impacted second molar, which credits the treatment modality elected to save the involved tooth.