Diffusion magnetic resonance imaging (dMRI) studies report altered white matter (WM) development in preterm infants. Neurite orientation dispersion and density imaging (NODDI) metrics provide more realistic estimations of neurite architecture in vivo compared with standard diffusion tensor imaging (DTI) metrics. This study investigated microstructural maturation of WM in preterm neonates scanned between 25 and 45 weeks postmenstrual age (PMA) with normal neurodevelopmental outcomes at 2 years using DTI and NODDI metrics.n = 17 male) with median (range) gestational age (GA) 32+1 weeks (24+2–36+4) underwent 3 T brain MRI at median (range) post menstrual age (PMA) 35+2 weeks (25+3–43+1). WM tracts , inferior longitudinal fasciculus (ILF), optic radiations) were delineated using constrained spherical deconvolution and probabilistic tractography in MRtrix3. DTI and NODDI metrics were extracted for the whole tract and cross-sections along each tract to assess regional development.Thirty-one neonates  in the CST, fornix and optic radiations and neurite density index (NDI) in the cingulum, CST and fornix and negatively correlated with mean diffusivity (MD) in all tracts. A multilinear regression model demonstrated PMA at scan influenced all diffusion measures, GA and GAxPMA at scan influenced FA, MD and NDI and gender affected NDI. Cross-sectional analyses revealed asynchronous WM maturation within and between WM tracts.).We describe normal WM maturation in preterm neonates with normal neurodevelopmental outcomes. NODDI can enhance our understanding of WM maturation compared with standard DTI metrics alone.The online version of this article (10.1007/s00234-020-02584-9) contains supplementary material, which is available to authorized users. The incidence of preterm birth is increasing, impacting around 12–13% of all live births in the United States of America (USA) and 5–9% in other developed countries , 5, whicWM development begins in the foetal brain around 13–18 weeks post-conception with limbic, projection and commissural pathways, followed by thalamocortical and association pathways around 24–32 weeks and continues to rapidly develop during the first 2 years of life –11.Whilst histological studies describing WM maturation are informative, they can only be performed ex vivo. dMRI and tractography enable quantitative measures of WM tract microstructure to be determined through non-invasive, in vivo imaging methods. These measures include fractional anisotropy (FA) (a measure of how restricted water molecular motion is in one direction compared with other directions) and mean diffusivity (MD) . Previous neonatal dMRI tractography studies have reported a negative correlation between FA and MD , increasTo date, most studies assessing preterm brain development have used diffusion tensor imaging (DTI). However, there are two major drawbacks to DTI. First, DTI cannot resolve more than one fibre population in a voxel. To overcome this, high-angular resolution diffusion MR imaging (HARDI) tractography can be used in combination with constrained spherical deconvolution (CSD) to identify complex fibre configurations and orientations within each voxel and delineate WM tracts that traverse regions of crossing fibres . Second,NODDI and DTI metrics can be used to assess WM maturation along an entire WM tract; however, this may mask important spatial changes in WM maturation within the tract. Regional analyses can be performed at regular intervals along WM tracts in cross-sectional planes to examine the homogeneity of WM development within the tract . This coThe aim of this study was to investigate normal WM microstructural development between birth and term-equivalent age in a population of preterm infants with normal neurodevelopment in early childhood. We chose a range of WM tracts to represent limbic (cingulum and fornix), projection , optic radiations) and association ) tracts. We obtained DTI and NODDI metrics for each WM tract, as well as at regular cross sections within each tract to assess regional maturation. We investigated how DTI and NODDI metrics changed with postmenstrual age (PMA) at scan, the relationship between DTI and NODDI metrics, factors that influenced diffusion measures within the tract  and regional differences in WM maturation.+1 weeks (range 24+2–36+4) and median (range) PMA at scan of 35+2 weeks (25+3–43+1) . Participants were prospectively recruited from the neonatal unit, and written parental consent obtained. Participants were included in the study if they were born < 37 weeks GA and excluded if they were > 46 weeks PMA at scan; had congenital malformations; there was severe motion artefact or focal lesions on MRI. The study cohort included MR images from 31 participants with a median (range) GA at birth of 32b = 2500 s/mm2, 4 non-diffusion-weighted image (b = 0) with TR 9000 ms and TE 62 ms; 32 non-collinear directions, b = 750 s/mm2, 1 non-diffusion-weighted image (b = 0) with TR 9000 ms and TE 49 ms).Neuroimaging data were acquired using a 3-Tesla Philips Achieva system  situated in the neonatal intensive care unit using a 32-channel head coil. MRI sequences included T1-weighted 3D MPRAGE (repetition time (TR) = 17 ms, echo time (TE) = 4.6 ms, flip angle 13°, voxel size 0.82 × 0.82 × 0.8 mm); T2 weighted fast spin echo  and diffusion MRI . Neonates had continuous monitoring during the scan including pulse oximetry, temperature and heart rate monitoring. Auditory protection was provided using earplugs moulded from a silicone-based putty  placed in the external auditory meatus and neonatal earmuffs .T2-weighted images were bias corrected , brain eb = 0 volumes, and then the lower shell was rigidly registered to the averaged b = 0 volumes acquired with the higher shell. Gradient directions were rotated accordingly. All rigid registrations were performed with IRTK software.dMRI images were visually inspected for motion artefact, and corrupted volumes removed. Subjects included in the study had a maximum of 8 volumes  excluded from the higher shell, and 6 volumes  excluded from the lower shell. Volumes were corrected for EPI phase encoding distortions and eddy current–induced artefacts using FSL5.0 top up-eddy algorithm using a T2 volume rigidly registered to the b0 images and assuming a bandwidth of 0 (no phase encoding). This process was performed separately for the two acquired shells and their corresponding www.mrtrix.org) [To reconstruct the WM tracts, the higher shell data was used to estimate fibre orientation distribution (FOD) at each voxel using constrained spherical deconvolution (CSD) implemented in MRTrix3 (rix.org) . Whole-brix.org) , producib = 750 s/mm2). NODDI metrics (NDI and ODI) were obtained using the NODDI toolbox from a combination of the higher (b = 2500 s/mm2) and lower (b = 750 s/mm2) shells. Data were normalised by b = 0 volumes to account for differing TE/TR times between lower and higher shell [DTI metrics (FA and MD) were obtained using MRTrix3 from the lower shell , at a median (range) corrected age of 25.5 months (24–32.5 months). Participants were included in the study if they achieved a score of 85 or more on both cognitive and motor categories.p < 0.00125 was considered significant, given that there were 5 tracts × 2 sides × 4 diffusion measures (0.05/40).The relationship between PMA at scan with FA, MD, NDI and ODI in each tract was analysing using Pearson’s correlation in SPSS (v.24). Results were corrected for multiple comparisons using the Bonferroni correction for multiple significance testing; p < 0.05 were considered significant.To analyse the contribution of different covariates (extremely/very preterm (GA < 32/40) vs moderate/late preterm (> 32/40 but < 37/40 GA), PMA at scan, gender, side of the tract, type of tract) on diffusion measures , a multiple regression with bootstrap was performed in Stata v.13. Results with www.r-project.org/) and PowerPoint. Tractography images were created using MRTrix3 (www.mrtrix.org) and PowerPoint.Graphs were generated using R .The multiple regression model assessed the impact of different variables  on diffusion measures (Online Resources Tables p = 0.000), MD (p = 0.009), NDI (p = 0.012) and ODI (p = 0.008). GA also significantly influenced FA (p = 0.000), NDI (p = 0.000) and MD (p = 0.002) but not ODI (p = 0.442). The interaction between GA × PMA at scan significantly influenced FA (p = 0.000), MD (p = 0.002) and NDI (p = 0.000) but not ODI (p = 0.269).Increasing PMA at scan significantly influenced all the diffusion measures: FA (p = 0.014) and through interacting with PMA at scan (p = 0.009), but it did not affect any of the other diffusion measures. Side did not significantly affect any diffusion measures as a main effect  or through interacting with PMA .Gender influenced NDI, as a main effect (p = 0.006); MD (p = 0.004) and NDI (p = 0.022); fornix for MD (p = 0.040), NDI (p = 0.041) and ODI (p = 0.011) and ILF for NDI (p = 0.001). Post hoc tests provide further information about which tracts differ from each other  and right CST (r = 0.944) and between NDI and PMA at scan in the left (r = 0.796) and right (r = 0.794) CST. Our within-tract analysis of the CST demonstrated the greatest increase in FA and NDI, with a corresponding reduction in MD and ODI, at the level of the internal capsule. Early maturation and myelination within the CST at the level of the internal capsule have been reported in DTI [Rapid maturation  and earld in DTI , 58 and d in DTI .In contrast, the ILF is the least mature tract, based on dMRI metrics, with the lowest FA and greatest MD. Association fibres are among the last WM tracts to develop , 60, 61,In the cingulum, FA increased from the anterior cingulate gyrus towards the midsection, and this coincided with a rise in NDI and slight reduction in ODI, suggesting the midsection has the greatest neurite density, myelination and least dispersion. MD remained stable along the tract. Assessing the tractography images visually, the fibres were most cohesive in the centre but dispersed in the anterior and particularly posterior pole, consistent with the ODI results. Another DTI study in adults reported regional changes in WM maturation along the cingulum, supporting our findings that maturation is not uniform along the tract .The optic radiations had the greatest FA and NDI and lowest MD in the most anterior part of the tract, corresponding to the lateral geniculate nucleus of the thalamus, whilst ODI was greatest at the most posterior part of the tract at the level of the visual cortex. Again, suggesting that maturation of the tract proceeds from central to peripheral regions of the brain .Our model provided further information about the influence of different covariates on diffusion measures. Our model did not reveal a significant effect of lateralisation on diffusion measures. Visually inspecting the linear plots in Online Resources Gender influenced NDI but not FA, MD or ODI in our preterm cohort. Other studies have conflicting results regarding the impact of gender on diffusion measures, both in preterm infants , 73 and This study used cross-sectional data to investigate age-related differences in WM microstructure, whereas longitudinal data could provide more accurate data regarding changes over time. In addition, our study population was small, as we were investigating normal WM maturation in a population of preterm neonates with normal neurodevelopmental outcomes at 2 years. Whilst informative, our model only explains a part of the variation in the diffusion measures, and there are other covariates that we have not accounted for.WM maturation from the preterm to term period is associated with increasing FA and NDI and decreasing MD, as WM tracts become increasingly organised, myelinated and increase in density. WM maturation does not occur uniformly between WM tracts, with projection tracts maturing more rapidly than association tracts. Regional differences occur within WM tracts, with the most mature regions occurring centrally rather than peripherally  and inferiorly rather than superiorly (CST). Future studies should consider using NODDI or the recent extension to NODDI (multi-TE NODDI ) to provESM 1(DOCX 474 kb)


The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has been shown to have positive effects in promoting healthy birth outcomes in the United States. We explored whether such effects held prior to and during the most recent Great Recession to improve birth outcomes and reduce differences among key socio-demographic groups.n = 226,835) before (01/2005–03/2007) and during (12/2007–06/2009) the Great Recession. Interactions between WIC enrollment and key socio-demographic groupings were analyzed for binary and continuous birth weight outcomes.We used a pooled cross-sectional time series design to study pregnant women and their infants with birth certificate data. We included Medicaid and uninsured births from Washington State and Florida   and 58.0 g (recession) . For most groups this beneficial relationship was stable over time.This paper supports previous research linking maternal utilization of WIC services during pregnancy to improved birth weight (both reducing LBW and increasing infant birth weight in grams) among some high-disadvantage groups. WIC appears to have been beneficial at decreasing disparity gaps in infant birth weight among the very young, Black, and late/no prenatal care enrollees in this high-need population, both before and during the Great Recession. Gaps are still present among other social and demographic characteristic groups  for whom we did not find WIC to be associated with any detectable value in promoting better birth weight outcomes. Future research needs to examine how WIC  could be made to work better and reach farther to address persistent disparities in birth weight outcomes. Additionally, in preparation for future economic downturns it will be important to determine how to preserve and, if possible, expand WIC services during times of increased need.Not applicable, this article reports only on secondary retrospective data . The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is a government-funded nutritional supplementation and education program that has generally been shown to have positive effects in promoting healthy birth outcomes in the United States , 2. WIC The U.S. Department of Agriculture renews WIC services through annual discretionary funding by the U.S. Senate and House Appropriations Committee . FundingA robust body of research exists documenting socio-demographic disparities in maternal and child health outcomes in the U.S. , 16. OneWIC enrollment increased during the Great Recession of 2007–2009 and the WIC program received additional funding at the federal level through the American Recovery and Reinvestment Act –20. PrioThese changes in resource allocation and utilization, combined with previous research indicating differential WIC effects among race/ethnicity and other groups defined by social and demographic characteristics, suggest that associations between birth weight and maternal WIC enrollment may have changed during the Great Recession. In this paper we test the hypothesis that positive WIC effects on birth weight and birth weight disparities among key socio-demographic groups held just prior to (01/2005–03/2007) and during the Great Recession (12/2007–06/2009).Using secondary data and a pooled time series cross-sectional design, we tested whether maternal WIC enrollment had a differential association on birth weight by multiple social and demographic groups during the Great Recession. To do this we analyzed the interaction between maternal WIC enrollment with race/ethnicity and other groups defined by social and demographic factors, such as education level, on birth weight, within regression models representing pre- and intra-Recession periods. The first period (pre-Recession/baseline) was from January 2005–March 2007. The second period encompassed the official Recession dates (December 2007–June 2009) . Institun = 226,835).De-identified, individual-level birth certificate data were obtained from the state Departments of Health in Washington and Florida with relevant human subjects approvals from both Institutional Review Boards to carry out these analyses. Washington and Florida were chosen as study states based on the availability of uniquely comparable, longitudinal public health budget data and previous studies indicating relationships between public health expenditures and beneficial maternal and child health outcomes , 25, 26.We considered two outcome measures of birth weight—a binary LBW measure (yes/no) and a continuous measure of birth weight in grams. LBW was defined as a birth weight of less than 2500 g. Birth weight was selected as the outcome measure for this study because other studies show that WIC services have an impact on birth weight and constitute one of the more reliable pieces of birth certificate data , 14, 27.Linear regression models were specified for both time periods (pre- and intra-Recession) as well as for each birth weight outcome (a linear probability model for the binary LBW and continuous regression model for birth weight in grams). Models were estimated using STATA 12.0 . In all Table Regression models to test for interactions between WIC and various socio-demographic characteristics identified significant interaction effects during both periods (baseline and Great Recession). WIC enrollment was associated with reductions in birth weight disparities for both Black women and those who entered prenatal care late or not at all compared to White women and those who entered prenatal care in the first trimester Table . SpecifiWomen who entered prenatal care late without WIC enrollment had a greater probability of LBW outcomes of 0.005  baseline and 0.017  at baseline and during the Great Recession period respectively, compared to those without WIC but with appropriate first trimester prenatal care. The interaction shows that late or no prenatal care individuals with WIC reduced this gap by − 0.012  baseline and − 0.023  during the Recession such that they were less likely to have LBW outcomes compared to women with timely prenatal care.During the baseline period, WIC was also associated with a reduction in disparities for young mothers (age 14 years and under) compared with mothers who were age 30–34 years. Young mothers without WIC had a higher probability of LBW  compared with the referent group ; with WIC, young women reduced this difference between the two age groups by − 0.115 . During the Great Recession period, this age interaction with WIC was no longer significant for mothers age 14 years and under. However, in this period, education effects did have significant interactions with WIC. For those with less than a high school education and for those under age 20 years with their education unassessed, being enrolled in WIC reduced the difference observed for these categories compared to individuals with some college. .Figure Table Similarly to LBW, there were beneficial WIC interactions for infants of Black mothers and for those who entered prenatal care late or not at all during both periods. Among infants of Black mothers, WIC enrollment was associated with a decrease in the Black/White gap in birth weight. Specifically, among infants of Black mothers, WIC enrollment was associated with an increase in birth weight of 53.5 g  (baseline) and 58.0 g  (Recession), to 197.1 and to 197.2 less than White mothers using WIC during the same time periods. While these birth weights were still less than those of infants of White mothers, infants of Black mothers without WIC were 250.5  (baseline)/255.2  (Recession) grams less than comparable White mothers not enrolled in WIC.Among mothers with late or no prenatal care, WIC interaction effects were associated with an additional 37.0 95% CI = 21.3, 52.6) (baseline)/48.9  (Recession) grams which brought them up to 7.0 (baseline)/9.3 (Recession) grams higher than those infants of WIC participating women who entered prenatal care on time. During the baseline period, but not during the Great Recession, there was a positive WIC interaction among infants of young mothers (age 14 years and under). Those young mothers without WIC were associated with having infants 246.9 g  less than their referent group (women age 30–34 years) while those young mothers with WIC were associated with having infants only 51.4 g less than their referent group (WIC enrolled women age 30–34 years). Additional tables [see Additional files 1.3, 52.6This paper supports previous research linking WIC services to improved birth weights (both reducing LBW and increasing infant birth weight in grams) among some high-disadvantage groups –9. It isConsistent with previous studies, we found beneficial WIC interaction effects on birth weight between race and WIC, between prenatal care and WIC, and between age and WIC during the study period in Washington and Florida , 15, 17.Recent research has suggested that WIC recruitment efforts and program supports during the Great Recession were attenuated by cuts to local health department budgets/staffing , 23 —desWhile providing evidence for associations among birth weight, WIC, and other covariates, it is not possible to establish causal relationships with retrospective cross-sectional data, and findings must be interpreted with caution. Our study population may also limit generalizability of our results. For example, as described earlier we included only data from Washington and Florida. In this study we also limited inclusion to those with Medicaid or self-pay (uninsured) as the payer for their delivery, since we did not have maternal income or other specific information to be able to assess WIC eligibility. All Medicaid recipients are eligible for WIC services and, as found in other studies, it appears that WIC recipients were more likely to have disadvantaging characteristics , yet WIC was demonstrated to be particularly beneficial for some demographic and social groups . Those wThis paper adds to the evidence base linking WIC services to improved birth weight (both reducing low birth weight and increasing birth weight in grams) among some population groups. In particular, WIC appears to have been beneficial at decreasing disparity gaps in infant birth weight  among the very young, Black, and late/no prenatal care enrollees in this high-need population. It is encouraging that these benefits were present both before and during the Great Recession. However,clear gaps are still present among other social and demographic characteristic groups  for which we did not find WIC to be associated with any detectable value in promoting better birth weight outcomes. Additional research into how and why WIC is more effective for some groups than others will be essential to further narrowing and eventually eliminating disparities. Finally, recent research has suggested that WIC recruitment efforts and program supports during the Great Recession were attenuated by cuts to local health department budgets/staffing. In preparation for future economic downturns it will be important to preserve and, if possible, expand WIC services during times of increased need.Additional file 1. Word file, “Complete regression model results for low birth weight during baseline and Great Recession periods: Washington State and Florida, 2005-2009”.Additional file 2. Word file, “Complete regression model results for birth weight in grams during baseline and Great Recession periods: Washington State and Florida, 2005-2009”.


Birth weight (BW) is a strong predictor of neonatal outcomes. The purpose of this study was to compare BWs between global regions  prospectively and to determine if trends exist in BW over time using the population-based maternal and newborn registry (MNHR) of the Global Network for Women'sand Children's Health Research .The MNHR is a prospective observational population-based registryof six research sites participating in the Global Network (2013–2018), within five low- and middle-income countries  in threeglobal regions . The birth weights were obtained for all infants born during the study period. This was done either by abstracting from the infants' health facility records or from direct measurement by the registry staff for infants born at home. After controlling for demographic characteristics, mixed-effect regression models were utilized to examine regional differences in birth weights over time.The overall BW meanswere higher for the African sites (Zambia and Kenya), 3186 g (SD 463 g) in 2013 and 3149 g (SD 449 g) in 2018, ascompared to Asian sites , 2717 g (SD450 g) in 2013 and 2713 g (SD 452 g) in 2018. The Central American site  had a mean BW intermediate between the African and south Asian sites, 2928 g (SD 452) in 2013, and 2874 g (SD 448) in 2018. The low birth weight (LBW) incidence was highest in the south Asian sites (India and Pakistan) and lowest in the African sites (Kenya and Zambia). The size of regional differences varied somewhat over time with slight decreases in the gap in birth weights between the African and Asian sites and slight increases in the gap between the African and Central American sites.Overall, BWmeans by global region did not change significantly over the 5-year study period. From 2013 to 2018, infants enrolled at the African sites demonstrated the highest BW means overall across the entire study period, particularly as compared to Asian sites. The incidence of LBW was highest in the Asian sites (India and Pakistan) compared to the African and Central American sites.Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475. The weight of an infant at birth (BW) is a crucial anthropometric measurement associated with infant mortality –4. PopulA newborn is defined as having normal BW if weight at birth is ≥ 2500 g. Low birth weight (LBW), as defined by the World Health Organization (WHO),isa weight at birth that is less than 2500 g (up to and including 2499 g). Infants with BW < 2500 g are further categorized into low birth weight (LBW), 1500–2499 g; very low birth weight (VLBW), 1000–1499 g; and extremely low birth weight (ELBW) < 1000 g . In certIn the recent past, data from high-income countries such as the United States and the United Kingdom recorded an increasing trend in mean BW, with a concurrent decrease in the prevalence of LBW , 9. ThisA major challenge in monitoring the incidence of LBW is that about 60% of newborn babies in LMICs are not weighed nor have BWre corded . PopulatWe performed a longitudinal cohort analysis of all infants born to mothers enrolled in the MNHR of the Global Network between 2013 and 2018. For the analysis, all deliveries with a measured BW, obtained between day 0 and day 7 were included. We excluded multiple births, miscarriages, medically terminated pregnancies, and pregnancies of women living outside the predefined study cluster  for BW were computed by region and year. In addition, to account for possible demographic differences across the regions, we computed adjusted mean BWs by region and year, controlling for the following demographic characteristics: maternal age, education, parity, weight, height, infant sex, and time between birth and weight measurement. To compute the adjusted means, we fit a linear mixed-effect regression model of BWby region, year, and region by year interaction, controlling for demographic characteristics and including sampling cluster as a random effect. In addition, we tested for interactions between year and demographic characteristics to determine if birth weights changed for different demographic subgroups over time. In Kenya, maternal height was not routinely measured between 2013 and 2017, hence for this and other missing values on control variables , multiple imputation techniques was utilized. Analysis performed with and without imputations were similar. Given the large sample sizes, we had a high level of statistical power, and therefore, even very small effects were found to be statistically significant. To determine whether significant changes in mean birth weights from 2013 to 2018 were meaningful, we examined Cohen’s d as a measure of effect size for which values of 0.2–0.4 are considered small effects, 0.5–0.7 are medium effects, and 0.8 or higher are large effects.Allanalyses were conducted using SAS version 9.4.This study was reviewed and approved by all participating sites’ ethics review committees/boards including review boards at each U.S. partner university and the data coordinating center . All women provided informed consent for participation in the study, including data collection and the follow-up visits.Between 2013 and 2018, we enrolled 355,625 pregnant women in the MNHR. Of these, 1% (N = 3254) were lost to follow up. Of the 291,085 deliveries captured in the MNHR within the study period, 265,130 (91%) met inclusion criteria , hence the lowest percentage of all low BW categories  as compared to the other regional sites, of South Asia (India and Pakistan) and Central America . Across the study period, there were slight changes observed in the size of these disparities over time, with the gap between the African and Asian sites decreasing, and the gap between the African and Central American sites increasing. These observations, however, may not be generalizable to the regions on whole, since the presence of the registry in these clusters may have exerted an influence (Hawthorne effect) on pregnancy outcomes over time.The highest annual LBW rates were recorded in the Asian sites at 20.2%  and the Central American site at 15.6% . This is consistent with a 2019 UNICEF report, in which the LBW rate in south Asia was 28%. However, the prevalence of LBW in Latin American was report to be 8.7%, which was almost half of what our study reports , but difUsually,the causes of LBW deliveries are multifactorial. Genetic and environmental factors play a significant role. Parity, low socioeconomic status, marital status, maternal age, nutritional status, maternal body mass index (BMI), maternal health status, smoking, alcohol intake, and prevailing infections such as from malariahave all been associated with BW outcomes –19. TherSome studies report a direct relationship between maternal age and BW. This relationship was demonstrated in a large cohort study in the United Statesbetween 2005 and 2014 . The majOne limitation of our study is that not all BWs were measured on the same day, immediately after birth. The time a newborn weight is obtained may affect the recorded BW. However, in our study, this limitation is attenuated.The vast majority of all babies included in the analysis were weighed within 48 h of birth, and, for the entire sample, birthweights were acquired within one week of delivery. However, regional differences in time of weighing were also observed; African sites weighed the newborns closer to time of birth as compared to the Asian and Central American regional sites.An additional potential source of bias in the results is the population of women who were entered into the study, but were lost to follow-up before the birth of the infant and measurement of BW. Our rates for loss-to-follow-up were quite low (1%); however, it is possible that preterm and LBW infants are over-represented among infants lost to follow-up, resulting in bias towards larger infants in the measured and reported population. Also, stillbirth and early neonatal deaths were likely to have their birthweights estimated instead of measured.Observer errors have been reported in some studies of BW, as a result of digit preference. As an example, weights ending in 5 (five) or 0 (zero) tend to be preferred, as well as weights of multiples of 100. This is especially problematic when a continuous BW variable is categorized. For instance, an infant with a measured BW of 2492 g may be recorded as 2500, and hence categorized as a normal BW rather than LBW. Digit preference and rounding errors may result in over or underestimation, and therefore may affect observed BW trends . Some inA final limitation of our study is that the data were prospectively obtained from relatively small, discrete geographical areas (clusters) within each country. Hence, the data may not be representative of the country or region as a whole. However, as compared to other methods and data sources  we enrolled an extremely large number of participants, prospectively, and followed standard procedures in obtaining and documenting weight, across sites, throughout the study period.In a prospective, population-based, longitudinal cohort study of birthweight among three global regions, the observed BW meanshad no significant changeover time in aggregate or by region. In addition, theBWmeans recorded for African sites, as compared to the Asian sites, remained consistently higher.The LBWrate was consistently higher in the Asian sites as compared to the African sites. The incidence of LBW observed for the two African sites in the MNHR was lower than that reported for other global estimates.As compared to past regional estimates of BW, those obtained in the current study were determined from a very large sample of actual birthweights measured within sevendays of delivery. BW is impacted by a variety of complex maternal and environmental characteristics; future investigations should focus on determining the mechanistic underpinnings of regional and site differences in BW observed in this study.


Echinococcus granulosus, hydatidosis is frequently found in sheep-raising countries such as the Mediterranean countries. The disease usually involves the liver (75%) and lung (15%). We describe a case of hydatid cyst of the psoas muscle; we are reporting this case because of its rarity and its difficulty to diagnose clinically.Hydatid cyst is a zoonosis caused mainly by the larval stage of the cestode worm A 16 –year-old female from rural setting, presented to the department of surgery of our institution, with complaints of right flank pain. On abdominal examination, there was sensitization in the right lower quadrant, and there was no resistance or rebound.On abdominal ultrasonography, a 6 × 6 cm hydatid cyst was detected within the psoas muscle, which was confirmed by positive indirect hemagglutination, no other organ involvement has been detected by CT scan. A pericystectomy was performed; the intact intramuscular cyst was completely excised, Macroscopic and microscopic examination of the specimen confirmed Hydatid cyst. The patient was discharged from hospital on the fifth postoperative day. No local recurrence was detected during postoperative follow up.Hydatidosis should be considered in cases of a symptomatic swelling in musculoskeletal system without history of trauma and irradiation when patients belong to endemic area.Cyst or complex retroperitoneal tumors, cold or pyogenic abscess of psoas muscle are considered in differential diagnosis.In the light of this case and the literature data, we discuss the diagnosis and the therapeutic problems raised by hydatid cyst of the psoas muscle. •Hydatid cyst is a parasitic common disease in sheep breeding areas, especially in Mediterranean countries.•Hydatid cyst of the psoas muscle is important to know because of its rarity and its difficulty to diagnose clinically, especially in young people.•Hydatid cyst should be considered in the presence of any painless cyst mass of muscle in endemic regions. Unilateral and primitive forms are mainly reported.•Excision of the intact intramuscular cyst completely is required to avoid contamination and recurrence.•Cyst or complex retroperitoneal tumors, cold or pyogenic abscess of psoas muscle are considered in differential diagnosis. Dog is the primary host in echinococcal infestation while the intermediate hosts are sheep, cattle, horses, and occasionally man. For this reason, HD has its highest incidence in sheep and cattle-rearing regions, such as the Mediterranean countries. The human can incorporate to the parasitic life cycle as the intermediate host, role that is generally played by sheep. Organs affected by HD are the Liver (63%), Lungs (25%), Muscle (5%), Bones (3%), Kidney (2%), Brain (1%), and spleen (1%). Primary hydatidosis of skeletal muscle is therefore rare, with reported prevalence of 0.5–5% in the endemic areas Psoas muscle HD may cause ureteric compression and hydronephrosis , in our Ultrasonography (US) is particularly useful for the detection of cystic membranes, septa, and hydatid sand as well as the staging and follow-up of the cysts. Computed tomography (CT) best demonstrates cyst wall calcification and cyst infection as well as the passage of contents through a defect .CT scan facilitate diagnostic and therapeutic procedures in order to ensure complete surgical resection .Muscular hydatidosis should be always considered in patients with previous history of hydatid cyst , the resHAI, enzyme-linked immunosorbent assay, or Western blott are carried out for diagnosis, screening and postoperative follow up for recurrence; but these tests are often negative or inadequate for definitive diagnosis if the cyst is intact, calcified or sterile .After performing the pericystectomy and completely intramuscular cyst excision, posoperative prescription of Albendazole is not justified, Muscular hydatidosis should always be considered as secondary localization of the disease, especially in cases of previous surgical dissemination , post-opPartial pericystectomy and cyst drainage seems to be the best approach due to its minimal invasiveness. An alternative to surgery is the US-guided cyst puncture and injection of protoscolicide .We emphasise that HD should be taken into consideration in the differential diagnosis of a cystic painless mass in every anatomical location, especially when appearing in young patient from an endemic area.All authors declares that they have no conflict of interest.This case report is not funded by a specific project grant, authors received no financial support for the research, authorship, and publication of this article.Patient gave consentement for photos and publication, in accordance with ethical committee of our Hospital.Written informed consent was obtained from participant.Consent from legally authorized representatives parents.Personal details of patient in any part of the paper or supplementary materials were removed before submission.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Study concept and design Yassine Merad, Ahmed Zeggai.Writing paper: Yassine Merad, Hichem Derrar.Data collection Ahmed Zeggai, Yassine Merad.Manuscript review Zoubir Belmokhtar, Haiet Adjmi-Hamoudi.1.Name of the registry:2.Unique Identifying number or registration ID:3.Hyperlink to your specific registration (must be publicly accessible and will be checked):Yassine Merad, I am the principal author and I accept full responsibility for the work and the conduct of the study, and I control the decision to publish with agreement of co-authors.Not commissioned, externally peer reviewed.


Pig producers are required to supply consistent lean carcasses to the market. However, the pig production cycle contains seasonal variation in carcass fatness, such that pigs finished in spring have a greater carcass backfat thickness than those finished in summer. Our experiment showed that when sows were mated in summer they had an increased incidence of born-light progeny (≤1.1 kg), which when finished in spring, had increased fatness. This finding provides a novel explanation for the seasonal variation of carcass fatness and sets a research direction for future mitigation strategies.p < 0.001), lower average piglet birth weight , lower total litter weights  and lower average placental weight  than those mated in autumn, although litter sizes were similar. Feed intake and growth rate of progeny from 14 weeks of age to slaughter (101 kg live weight) were greater for the born-normal than born-light pigs within the progeny from sows mated in autumn, but there was no difference between the born-light and normal progeny from sows mated in summer, as evidenced by the interaction between piglet birth weight and sow mating season (Both p < 0.05). Only the born-light piglets from the sows mated in summer had a greater backfat thickness and loin fat% than the progeny from the sows mated in autumn, as evidenced by a trend of interaction between piglet birth weight and sow mating season (Both p < 0.10). In conclusion, the increased proportion of born-light piglets (0.7–1.1 kg range) from the sows mated in summer contributed to the increased carcass fatness observed in spring.The backfat of pig carcasses is greater in spring than summer in Australia. The unexplained seasonal variation in carcass backfat creates complications for pig producers in supplying consistent lean carcasses. As a novel explanation, we hypothesised that the increased carcass fatness in spring was due to a greater percentage of born-light progeny from sows that were mated in summer and experienced hot conditions during early gestation. The first part of our experiment compared the birth weight of piglets born to the sows mated in summer  with those born to sows mated in autumn , and the second part of the experiment compared the growth performance and carcass fatness of the progeny that were stratified as born-light (0.7–1.1 kg) and born-normal (1.3–1.7 kg) from the sows mated in these two seasons. The results showed that the sows mated in summer experienced hotter conditions during early gestation as evidenced by an increased respiration rate and rectal temperature, compared with those mated in autumn. The sows mated in summer had a greater proportion of piglets that were born ≤1.1 kg (24.2% vs. 15.8%,  Carcass fatness negatively affects the profitability of pig producers in some markets where a rigid specification on carcass fatness is imposed. In the Australian pig industry, backfat depth, an indicative measure of carcass fatness, is greater for pigs slaughtered in late winter and spring (July–October) than summer (January–March). The mechanisms for this phenomenon remain unclear. A study in Western Australia showed that less than 20% of the seasonal variation in backfat thickness was explained by the carcass weight . The seaPigs slaughtered during late winter and spring (July to October in the Southern Hemisphere) are the progeny born to the sows mated in summer (December to February in the Southern Hemisphere), and these sows usually experience hotter conditions during mating and early gestation. A recent climatically controlled study demonstrated that high environmental temperature occurring in the first half of gestation can increase fat deposition of the progeny of these sows . Also, eThe experiment consisted of two parts. Part 1 compared the birth weight of sows that were mated in summer with those mated in autumn. Part 2 followed a two by two factorial design to study the effects of the mating season of sows and the birth weight class  of their progeny on growth performance and carcass traits of progeny at a fixed slaughter weight. A flowchart of the experiment is illustrated in n = 119; parity 3.7 ± 1.45 for mean ± standard deviation) and autumn (May 2018 in the Southern Hemisphere)  in a commercial Australian piggery . The mated sows were housed in a pen of 40 until the sixth week of gestation, after which they were combined with another pen and housed in a pen of 80. All the sows were fed using electronic sow feeders while in the gestation pens, with each feeding station (40 pigs per feeding station) allowing individual feeding times. Sows were restrictively fed with an average of 2.2 kg diet per day until the 110th day of gestation to provide appropriate nutritional needs for their maintenance and pregnancy requirements. The sows mated in summer and autumn were housed in the same gestation pens using the same feeding system and allowance. The same gestation dietary formulation was used for the sows mated in the two seasons  . Respiration rate was monitored by visually counting the number of chest contractions during a 30-s duration. Skin injury score was counted once per week from the second day of entry to the gestation pen until the 110th day of gestation using a modified version of the method described by Karlen, et al. [n = 38 focal litters per mating season) were individually tagged, matched and weighed after birth.Behavioural signs  were used to predict farrowing time in the sows. A rubber mat was placed behind the sows to catch placentae when a sow was about to farrow. A technician frequently checked the farrowing process and quietly put a soft coloured cable tie around the intact umbilical cord when a piglet was born and had been expelled from the sow. Once the cable tie was tied securely, the umbilical cord was cut between the cable tie and the piglet using a pair of sterile scissors, then the umbilical cord with the fixed cable tie was retracted into the sow. The piglet was weighed using a digital scale and the body weight was recorded to match the colour of the cable tie which was used for tagging the placenta. Placentae with the tagged umbilical cords were expelled in the middle of the farrowing process or could be as late as the completion of the farrowing process. Individual placentae were separated using the necrotised tissue edge as the reference border, then the tagged placentae were weighed using the digital scale and recorded to match the individual piglet. On average, five placentae and five piglets from each focal litter . Plasma samples were harvested after centrifugation at 2000× g at 4 °C for five minutes. Plasma IGF-1 concentrations were determined in singlicate and completed in one assay .Blood samples were taken via jugular venepuncture at 24 h post-farrowing from piglets that had suckled sows and received colostrum . During the finisher phase (from 14 weeks of age to 101 kg live weight), pigs were individually housed . The sheds for grower and finisher phases were semi-climatically controlled and used fans, misting, water dripping system in summer and central gas heating in winter. Temperature loggers  recorded the air temperature inside the sheds. The average overall temperature between 9 weeks to 14 weeks of age was 22.6 ± 2.89 °C and 25.0 ± 2.78 °C (mean ± standard deviation) for progeny born to the sows mated in summer vs. autumn. The average overall temperature between 14 weeks of age and slaughter was 23.3 ± 2.96 °C vs. 24.9 ± 2.73 °C (mean ± standard deviation) for the progeny born to the sows mated in summer vs. autumn.In Part 2 of the experiment, 120 born-light  and 120 born-normal progeny piglets  from sows mated in each season were identified by individual birth weight. As a criterion for selecting the progeny pigs for Part 2 of the experiment, each litter contributed, at most, two born-light and two born-normal piglets. For evaluating growth performance of progeny pigs during the grower/finisher phase, pigs born to the sows mated in the two seasons were selected at 9 weeks of age based on similar body weight (20.4 ± 1.12 kg (mean ± standard deviation) for born-normal groups and 19.6 ± 1.12 kg (mean ± standard deviation) for born-light groups) as well as similar birth weight (1.5 ± 0.25 kg (mean ± standard deviation) for born-normal groups and 1.0 ± 0.25 kg (mean ± standard deviation) for born-light groups. Following the selection criteria, 56 born-light and 56 born-normal progeny pigs with balanced sexes were selected from each mating season and then housed in group pens during the grower phase (9–14 weeks of age)  has been validated to be able to accurately estimate muscle, fat and bone composition in pig primal cuts and carcasses . For carChi-squared analysis. Data on placental weight and piglet birth weight from focal new-born piglets were analysed for the main effects of mating season and parity of sows using sow’s ID (nested within mating season) as a random factor. Growth performance and carcass traits of progeny pigs were analysed using UNIVARIATE procedure with the main effects of mating season (summer vs. autumn), piglet birth weight class  and the interaction. A pen (a group of 4 pigs) was used as an experimental unit for measuring growth performance between 9 and 14 weeks of age. An individual pig was used as an experimental unit for measuring carcass traits and growth performance between 14 weeks of age and slaughter. All analyses were conducted in SPSS . Continuous variables are presented as mean ± standard error (SE), and binominal data are reported as a percentage of distribution. Means were considered to be significantly different when p ≤ 0.05, and a trend was considered to exist when p ≤ 0.10. Data on sow body conditions, total litter weight, piglet weight (average of each litter) and litter size were analysed using UNIVARIATE procedure with the main effects of mating season (summer vs. autumn) and parity of sows . Data on rectal temperature, respiration rate, and number of skin injuries of gestating sows were analysed using Repeated Measures with the day of measurement as a within-subject factor and mating season as a between-subject factor. Farrowing rates of sows were analysed by Pearson’s p = 0.003) but gained more weight by the 110th day of gestation than those mated in autumn  so that sow body weight at the 110th day of gestation was similar between the two mating seasons (p = 0.080), and the backfat thickness of sows mated in summer was significantly lower than those mated in autumn  by the 110th day of gestation. The change of backfat thickness between the 2nd and 110th day of gestation did not differ (p = 0.75) between sows mated in summer and autumn. The average daily feed intake during gestation was controlled to the same amount between the sows mated in summer and autumn.Sows that were mated in summer were lighter on the second day of gestation (250 kg vs. 270 kg  seasons . Backfatp < 0.001). The number of total born, born alive, stillborn and mummified piglets were all similar between the two mating seasons. Litter birth weights were lighter in the sows mated in summer than those mated in autumn . Average piglet birth weight was lighter for the sows mated in summer than those mated in autumn ; 1.37 kg vs. 1.54 kg, p < 0.001 (stillborn piglets were included)). The percentage of born-alive pigs weighing less than 1.1 kg was greater in the sows mated in summer than in autumn .Sows with a similar average parity were compared between summer and autumn mating seasons for farrowing outcomes . The sowp < 0.001; p < 0.001). The ratio between piglet birth weight and its matched placenta weight tended to be greater in the sows mated in summer than those mated in autumn .The focal sows from which placental weights were measured had a similar average parity . The nump < 0.001). The number of fresh scars was significantly greater in the sows mated in summer than in those mated in autumn in the first three weeks of gestation , regardless of the mating seasons of sows. The interaction between mating season and progeny birth weight class was not significant.New-born piglets from sows mated in summer and autumn had similar plasma IGF-1 concentrations . The borp < 0.001) at selection. Between 9 and 14 weeks of age, pigs that were born to the sows mated in summer had a greater ADFI , grew faster , and were heavier at 14 weeks of age  than those born to the sows mated in autumn. The FCR was not affected by mating season or birth weight class. The ADFI, ADG and FCR did not differ significantly between born-light and born-normal pigs during 9–14 weeks of age. The interaction between mating season and birth weight class was not significant in those measurements.Progeny pigs were selected into a grower shed at 9 weeks of age with a similar body weight between mating seasons . Born-lip < 0.001), ADG , and took fewer days to reach the 101 kg slaughter weight  than the pigs born to the sows mated in autumn. The interaction between mating season and birth weight class was significant for ADFI (p = 0.008), such that the born-light progeny pigs had lower ADFI than born-normal piglets among the progeny born to the sows mated in autumn but not in summer. Born-light pigs had lower ADG than born-normal pigs , regardless of mating seasons. The interaction between birth weight class and mating season was significant (p = 0.039) for ADG, such that the difference in ADG between born-light and born-normal pigs was smaller in the progeny born to the sows mated in summer than in those born to sows mated in autumn. The FCR was higher in the born-light progeny than in the born-normal ones , whereas it was not affected by mating seasons. Born-light pigs took longer to reach 101 kg weight than born-normal pigs . End-point slaughter weight was controlled to be similar between mating seasons and birth weight classes.Between 14 weeks of age and growth to 101 kg live weight, the pigs that were born to the sows mated in summer had a greater ADFI . Born-light progeny had a greater carcass backfat thickness than born-normal progeny at slaughter . The interaction between mating season and birth weight class on carcass backfat thickness tended to be significant (p = 0.073), indicating it was the born-light progeny  that had a greater backfat thickness when born to the sows mated in summer vs. autumn. Loin depth tended to be greater in born-light than the born-normal progeny that were born to the sows mated in autumn, but this effect was not seen in the progeny born to the sows mated in summer, as evidenced by a trend between mating season and birth weight class (p = 0.066). Neither mating season nor progeny birth weight class affected the dressing percentage. The head weights of progeny pigs were not affected by the mating season of sows or the birth weight class.Hot standard carcass weight was similar for the progeny born to the sows mated in summer and autumn, which is an expected outcome after slaughtering at a fixed live weight . Pigs bop = 0.023) than those born to the sows mated in autumn (p = 0.054) than born-normal progeny. The interaction between mating season and birth weight class on loin fat% tended to be significant (p = 0.087), such that it tended to be only the born-light  progeny that had increased loin fat% when born to the sows mated in summer vs. autumn. Pigs born to sows mated in summer tended to have less loin lean%  than those born to the sows mated in autumn. Born-light pigs tended to have less loin lean%  than born-normal counterparts. The interaction between mating season and birth weight class on loin lean% tended to be significant (p = 0.10), such that it was only the born-light  progeny that had reduced loin lean% when born to the summer vs. autumn mated sows. Similarly, the fat: lean ratio was greater in the pigs born to the sows mated in summer  than those born to the sow mated in autumn. Born-light pigs had a greater fat: lean ratio  than born-normal counterparts. The interaction between mating season and birth weight class for fat: lean ratio tended to be significant (p = 0.058), such that the born-light but not the born-normal progeny tended to have a greater fat: lean ratio when born to the sows mated in summer vs. autumn. Pigs born to the sows mated in summer had less bone%  than the progeny born to the sows mated in autumn. Born-light piglets tended to have less bone% . The interaction between mating season and birth weight class on bone% tended to be significant (p = 0.095), such that born-light progeny had less bone% than born-normal progeny only when they were born to the sows mated in summer.Pigs born to the sows mated in summer had greater loin fat%  in the half carcass than those born to the sows mated in autumn. The effect of birth weight class or the interaction between mating season and birth weight class was not significant on bone% of the half carcass.Tissue composition or fat: lean ratio in shoulders, bellies or legs was not affected by the mating season, birth weight class or their interaction. Fat% or lean% of the half carcasses were not affected by mating season, birth weight class or their interaction. Progeny born to the sows mated in summer had less bone%  than those mated in autumn (24.2% vs. 15.8%). Second, the progeny born-light  from sows mated in summer had greater carcass backfat thickness (15.6 mm vs. 14.4 mm for the born-light progeny born to sows mated in summer vs. autumn) and loin fat % than the progeny born to the sows mated in autumn. Based on the above results, we estimate that the greater percentage of born-light progeny and the higher carcass backfat would increase the populational average of backfat of the finisher progeny from 14.06 mm to 14.39 mm (101 kg live weight at slaughter). This estimated magnitude of increase in the populational carcass backfat was similar as the multiple-year data collected from Western Australia  [.1 kg thaThe sows mated in summer had 16% lower average placental weight and 9% lower average piglet birth weight compared with those mated in autumn, suggesting an inferior placental and fetal development. The compromised placental and fetal development for the sows mated in summer is suspected to be partially associated with the hotter environmental conditions during early gestation. In the current experiment, the sows mated in summer experienced hotter conditions during the first half of gestation than those mated in autumn, as evidenced by greater rectal temperatures and respiration rates. Effects of gestational heat stress on pig fetal development remain unclear due to the limited number of published studies and small sample sizes often used. A recent study showed that exposing pregnant gilts to artificially hot conditions during the whole of gestation reduced average piglet birth weight by 16% without affecting the number of piglets born alive (published as an abstract) . AnotherUnlike sheep, sows always produce numerous fetuses, and there has been no evidence from climatically controlled studies on whether the impacts of heat stress on gestating sows is homogenous on all the fetuses or are expressed as increased frequency of born-light progeny. Our experiment showed that in summer-mated sows, there was an increased proportion (from 15.8% to 24.2%) of born-light progeny (≤1.1 kg) in a litter. Blood IGF-1 (measured at 24 h post-farrowing) in either birth weight class did not differ between summer and autumn mating seasons, but it was markedly lower in the born-light than born-normal piglets. The reduced IGF-1 in blood and tissues has been reported previously in the neonatal piglets identified as being intrauterine growth restricted ,17. CombAnother important finding is that only the born-light progeny from the sows mated in summer had greater backfat and loin fat composition when compared with the progeny born to the sows mated in autumn. The born-normal progeny born to the sows mated in summer had a similar carcass backfat thickness and carcass fat composition as the born-light and born-normal progeny from the sows mated in autumn. This finding suggests that it is the increased proportion of born-light progeny that contribute to the greater carcass fatness observed in spring in the Australian pig industry. The current seasonal comparison design did not allow us to distinguish if the greater carcass fatness of born-light progeny from sows mated in summer was due to the prenatal or postnatal environment. The progeny that were born to the sows mated in summer and finished in spring had an overall 9% and 12% greater feed intake for 9–14 weeks of age and 14 weeks of age to slaughter respectively compared with the progeny that born to sows mated in autumn and finished in summer. Similarly, a survey in an Australian piggery between 2006 and 2008 showed that ADFI of pigs finished in the spring season was 7% greater than that of pigs finished in summer ,21,22, wIn addition to the hot conditions during early gestation, we also found other factors may potentially contribute to the reduced birth weights of progeny that were born to the sows mated in summer. The effects of these factors on fetal development warrant further investigations in controlled studies. First, the negative energy balance of sows during summer lactation may jeopardise the body conditions of sows at subsequent mating and have carry-over effects on fetal development. We found that sows mated in summer were 20 kg lighter at mating than those mated in autumn, which is likely to be a consequence of negative energy balance during summer lactation ,31. SimiThe limitation of the current seasonal comparison experiment was that the data was only collected from one year. Ideally, the individual progeny birth weight, growth performance and body composition data collected from multiple years are required for validating the seasonal effects discovered in the current study.Sows mated in summer produced an increased proportion of born-light piglets (≤1.1 kg), which may be associated with the hotter environmental conditions experienced during the first half of gestation. The born-light but not born-normal progeny from the sows mated in summer had an increased carcass backfat thickness and loin fat composition at slaughter, possibly due, at least in part, to the increased feed intake during a cooler grower/finisher phase, when compared with the progeny from sows mated in autumn. Future experiments are required to understand the exact mechanism for the increased proportion of born-light progeny born to the sows weaned and mated in hot conditions so that mitigation strategies can be developed.


Birth registration is a child’s first right. Registration of live births, stillbirths and deaths is foundational for national planning. Completeness of birth registration for live births in low- and middle-income countries is measured through population-based surveys which do not currently include completeness of stillbirth or death registration.The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017–2018). In four African sites, we included new/modified questions regarding registration for 1177 stillbirths and 11,881 livebirths . Questions were evaluated for completeness of responses, data quality, time to administer and estimates of registration completeness using descriptive statistics. Timing of birth registration, factors associated with non-registration and reported barriers were assessed using descriptive statistics and logistic regression.Almost all women, irrespective of their baby’s survival, responded to registration questions, taking an average of < 1 min. Reported completeness of birth registration was 30.7% (6.1-53.5%) for babies surviving the neonatal period, compared to 1.7% for neonatal deaths (0.4–5.7%). Women were able to report age at birth registration for 93.6% of babies. Non-registration of babies surviving the neonatal period was significantly higher for home-born children (aOR 1.43 (95% CI 1.27–1.60)) and in Dabat (Ethiopia) (aOR 4.11 (95% CI 3.37–5.01)). Other socio-demographic factors associated with non-registration included younger age of mother, more prior births, little or no education, and lower socio-economic status. Neonatal death registration questions were feasible , revealing extremely low completeness with only 1.2% of neonatal deaths reported as registered. Despite > 70% of stillbirths occurring in facilities, only 2.5% were reported as registered.Questions on birth, stillbirth and death registration were feasible in a household survey. Completeness of birth registration is low in all four sites, but stillbirth and neonatal death registration was very low. Closing the registration gap amongst facility births could increase registration of both livebirths and facility deaths, including stillbirths, but will require co-ordination between civil registration systems and the often over-stretched health sector. Investment and innovation is required to capture birth and especially deaths in both facility and community systems. Despite the right to an identity being enshrined in the UN convention on the rights of the child  as well Investment in CRVS systems in many low- and middle-income countries (LMICs) is increasing . ParticuDeath registration systems lag behind birth registration . Only 60Estimates of the completeness of registration data in LMICs rely on nationally representative household surveys such as demographic and health surveys (DHS) and multiple indicator cluster surveys (MICS) . In the Survey question performance: Evaluate new and modified questions on birth, stillbirth and neonatal death registration addressed to women in a population-based survey, including completeness of responses and time implications.Data utility: Assess the information obtained through the survey regarding birth, stillbirth and neonatal death registration including estimates of completeness and timing of registration, factors associated with non-registration and reported barriers to registration.This paper is part of a series of papers from the Every Newborn-International Network for the Demographic Evaluation of Populations and their Health (EN-INDEPTH) study in five health and demographic surveillance system (HDSS) sites in Africa and Asia. This paper aims to improve understanding of the measurement of birth, stillbirth and death registration in population-based household surveys through the following objectives:The EN-INDEPTH study was a cross-sectional multi-site study conducted between July 2017 and August 2018, including a survey of 69,176 women aged 15–49 years undertaken in five HDSS sites: Bandim in Guinea-Bissau, Dabat in Ethiopia, IgangaMayuge in Uganda, Matlab in Bangladesh and Kintampo in Ghana  under study and the previous question. Missing data and responses that took 30 min or more were excluded.Completeness of birth registration and mean time from birth to registration were calculated overall and by HDSS site for babies who died before the 28th day after birth  and those surviving the neonatal period separately. As specific questions regarding stillbirth registration were not asked, babies who were stillborn (stillbirths) were classified as registered if the mother reported that the baby was registered through either the birth or the death registration questions.Reported reasons for non-registration of children surviving the neonatal period are presented graphically using descriptive statistics. Factors associated with non-registration of these children were explored using logistic regression, with registration status as the dependent variable. A gap analysis comparing the coverage of facility births to completeness of birth, stillbirth and neonatal death registration was undertaken to examine potential missed opportunities for registration for facility births.All data management and quantitative analyses were undertaken using Stata 15.1. Results are reported in accordance with STROBE Statement checklists for cross-sectional studies  Additio.Information on birth and death registration was collected for 13,058 babies and children born to 12,462 surveyed women: Bandim (2065 women), Dabat (3606), Iganga (2254) and Kintampo (4537). These included 1177 stillborn and 11,881 liveborn babies, of whom 1333 died in the neonatal period and 10,548 survived to the 28th day of life  have a birth certificate?’ was low overall  (Tables Has (name)'s birth been registered with the civil authorities?’ resulted in a 4-percentage point increase in the estimated proportion of babies registered for children surviving the neonatal period and 0.5-percentage point increase for stillbirths and neonatal deaths (Tables A response of ‘don’t know’ for ‘) Tables . The adds Tables . Howeverp < 0.001).Most women were able to provide details of the time since birth to registration for their baby  (Table Most women (> 95%) reported that they had not registered the death of their baby, with 1.2% of women with a neonatal death and 1.8% with a stillbirth responding that they did not know if the baby’s stillbirth or death had been registered Tables  and 4B.Reported median time from birth to registration did not vary by child’s sex but did by site from just over 7.5 months in Dabat and to 1 month in IgangaMayuge. The few neonatal deaths that had their births registered were registered sooner after birth than children surviving the neonatal period , 0–3)), children surviving the neonatal period 3 months  .Overall, 30.7% of children surviving the neonatal period and 1.7% of neonatal deaths were reported to have had their births registered with the civil authorities. For children surviving the neonatal period, completeness of birth registration was the highest in Kintampo 53.5%), compared to 6.1% in Dabat Fig. . Reporte3.5%, comFewer than 2% of neonatal deaths had their deaths registered in all sites Table . 9.2% ofThe majority of registered surviving babies were registered during the first few months of life, with some evidence of catch up registration especially in the Dabat and Bandim sites Fig. .Fig. 3AFor children surviving the neonatal period, being under 1 year of age at the time of the survey, born at home and maternal socio-demographic factors including younger age, higher parity, lower levels or no education and lower socio-economic status were associated with non-registration in both crude and adjusted analyses. Non-registration was not associated with the sex of the child  of women with a non-registered child surviving the neonatal period provided information on barriers to registration. Amongst these, 36.1% of women reported that the birth registration process was too complicated to understand. Other commonly reported barriers included cost (28.4% of respondents) and distance to a registration facility (16.1%). Lack of the required documentation, father’s support and a name for the baby were less frequently reported as barriers , compared to birth registration for just 1.7% of neonatal deaths. Lower completeness of birth and death registration was expected in Dabat because Ethiopia’s first permanent, compulsory and universal registration and certification system for vital events throughout the country is very new, only launched in August 2016 , and consistent with the World Health Organization's estimate that fewer than 5% of neonatal deaths globally are registered . A studyClosing the gap for registration of facility births and also deaths around the time of birth, notably stillbirths, could address common reasons for non-registration and lead to large increases in completeness of birth, stillbirth and neonatal death registration in all sites. This is feasible to achieve. UNICEF, WHO and the Global Vaccine Alliance (Gavi) have provided successful examples for integrating CRVS and health systems, in particular immunisation systems, in recent reports including creating awareness of the importance of registration during antenatal and delivery care; ensuring all births and deaths occurring in health facilities are notified to the civil registrar, with death notification including cause of death; increasing the potential co-location of registration facilities within hospitals and other delivery facilities; notifying home births and deaths by community health workers; notifying unregistered children when presented for immunisation and other health services; promoting community outreach for creating demand for birth and death registration; and sensitising health workers on the importance of registration of births and deaths , 34–36. This study has strengths, notably being undertaken across four different settings in sub-Saharan Africa, including information on a large number of children . However, we note that whilst women were able to provide plausible responses to these questions, we were unable to verify accuracy by comparing responses to actual birth or death registration records. Since this study was undertaken in HDSS sites amongst populations under surveillance, it is possible that this may affect women’s responses, although in none of these sites are women routinely asked about birth or death registration of their children. Potential confusion between ‘registration’ with the HDSS, religious institutions or other groups and registration with the civil authorities, as highlighted in a UNICEF report , may havReliable measures in surveys are crucial to track progress for birth and death registration. Surveys have the advantage of providing data that can be disaggregated by different categories such as place of residence, sex, maternal education, or socio-economic status to identify which children are being left behind. This study found that questions on both birth and death registration were feasible to ask in a household survey, with minimal additional time implications. Whilst asking birth registration questions for surviving children in the household or the child’s questionnaire has the advantage of capturing information on all children regardless of whether the mother is in the household or eligible to be interviewed, children who are stillborn or who have died are missed. Asking additional questions on birth registration for non-surviving children in the woman’s questionnaire could provide information on deceased children who may be at higher risk of not being registered.Given that around 80% of the world’s births are now in facilities, closing the gap between facility birth and registration for these babies would increase birth and stillbirth registration completeness and enable timely tracking through routine facility data and annual vital statistics reports, instead of relying only on 5-yearly surveys. However, facility registration alone will leave behind 20% of all babies who are born outside facilities, who are often the poorest and at highest risk of stillbirth and neonatal mortality. Therefore, surveys remain crucial to track overall population-level progress for birth registration and to identify who is left behind in this marker for child rights.There is a larger gap for death registration, with only 1.2% of neonatal deaths and 2.5% of stillbirths reported to be registered. More attention is required to capture these deaths in facility and community systems, count them through death certificates and improve cause of death data to count and end these deaths, which will be crucial for all governments if SDG targets are to be measured and met.Additional file 1. Background overview of the four HDSS sites.Additional file 2. Selection of women with a livebirth surviving the neonatal period.Additional file 3. STROBE guidelines checklist.Additional file 4. Additional results.Additional file 5. Gap analysis for birth registration in EN-INDEPTH survey, by site.Additional file 6. Ethical Approval of local Institutional Review Boards.