The under-reporting of Aboriginal and Torres Strait Islander people on routinely collected health datasets has important implications for understanding the health of this population. By pooling available information on individuals’ Aboriginal or Torres Strait Islander status from probabilistically linked datasets, methods have been developed to adjust for this under-reporting. To explore different algorithms that enhance reporting of Aboriginal status in birth data to define a cohort of Aboriginal women, examine any differences between women recorded as Aboriginal and those assigned enhanced Aboriginal status, and assess the effects of using different reported populations to estimate within-group comparisons for Aboriginal people.Three algorithms, with different levels of inclusiveness, were used to establish different study populations all of which aimed to include all singleton babies born to Aboriginal or Torres Strait Islander women residing in New South Wales, Australia between 2010 and 2014 and their mothers. The demographics of the four study populations were described and compared using frequencies and percentages. In order to assess the impact on research outcomes and conclusions of using study populations derived from different algorithms, estimates of the associations between smoking during pregnancy and selected perinatal outcomes were compared using rates and relative risks.Women included in the study population through enhanced reporting were older, less disadvantaged and more commonly resided in urban areas than those recorded as Aboriginal in the birth data. Although rates of smoking and some perinatal outcomes differed between the different study populations, the relative risks of each outcome comparing smoking and non-smoking Aboriginal mothers were very similar when estimated from each of the study populations.This work provides evidence that estimates of within-group relative risks are reliable regardless of the assumptions made for establishing the study population through the enhanced reporting of indigenous peoples. Aboriginal and Torres Strait Islander Australians are under-reported on routinely collected health datasets nationwide , usuallyFor the purposes of this study, Aboriginal and Torres Strait Islander people were grouped together because of the small proportion of Torres Strait Islander people living in NSW  and somWith the increasing availability of timely linked datasets, many research groups enhance reporting by pooling available information on an individual’s Aboriginality from linked datasets to assign an enhanced Aboriginal status. This technique has been coined the Enhanced Reporting of Aboriginality (ERA) . Many alAlthough it is important to understand the health disadvantage experienced by Aboriginal people, there is growing opinion that comparisons to Non-Aboriginal Australians are not always helpful and comparisons among Aboriginal people may be more constructive , 13. CurThree algorithms were used to establish different study populations, all of which aimed to include all singleton babies born to Aboriginal or Torres Strait Islander women residing in NSW between 1 January 2010 and 31 December 2014 and their mothers. This date range was chosen in order to have a full five years of data for all datasets in the study, to ensure adequate population size and also have the most up-to-date data available at the time. Each algorithm assessed the evidence available in each dataset and, based on predefined constraints, assigned each mother an enhanced Aboriginal status.All datasets used in this study are held by the NSW Government and routinely collected for administrative and/or surveillance purposes. The study population was identified from all records in the NSW Perinatal Data Collection (‘birth data') for the period 1 January 2010 to 31 December 2014. This surveillance system  includes all live births and stillbirths of at least 400 grams birthweight or at least 20 weeks gestation, including births at NSW public and private hospitals and home births [Public and private hospital admission records were drawn from the Admitted Patient Data Collection  for admission dates from 1 January 2001 to 31 December 2015. Diagnoses coded in the hospital data are applied according to the International Classification of Diseases, Australian Modification (ICD-10-AM). Information on all visits to a public emergency department was taken from the NSW Emergency Department Data Collection (‘emergency data’) between 1 January 2005 and 31 December 2015. The collection of emergency data in NSW commenced in 1994, and became an organised collection from July 1996, with the number of participating emergency departments increasing each year to around 90 in 2010, covering the majority of the NSW population .Records within and across all datasets were probabilistically linked using personal identifiers such as name, address and date of birth, by the NSW Centre for Health Record Linkage (CHeReL). The CHeReL uses the Choicemaker software for linkage, which uses blocking and machine learning to assign weights to potential matches , and hasenhance the reporting of Aboriginality among those assessed for eligibility, all women recorded as Aboriginal on the birth data were assumed eligible for inclusion in all study populations regardless of their Aboriginal status on other linked records. Thus the following algorithms were only applied to those women who were not recorded as Aboriginal on the current birth data.All women with a birth record in the NSW birth data in the study period were potentially eligible for inclusion in the study, either in the baseline population or in one of the enhanced populations. Due to the previously noted under-reporting of Aboriginal mothers in the birth data, a number of ERA algorithms were applied to increase ascertainment of eligible participants, resulting in different reported populations. Since we wanted to Study population 1 was established using the least inclusive algorithm and inclusiveness increased with population number. Study population 1 consisted of just those mothers who were recorded as Aboriginal on the birth data and their babies, thus providing a lower bound on all study populations.Study population 2 was established using only the data surrounding the birth; this included the birth data and, where available, the corresponding hospital birth record and birth registration. The recording of any woman without a corresponding hospital birth record or registration  could not be further enhanced and was thus not included in study population 2. Where the hospital birth record and birth registration were available, both needed to indicate that the mother was Aboriginal for enhanced inclusion in study population 2. If the mother only had one linked record , that record needed to indicate she was Aboriginal for enhanced inclusion in the study population. A flow diagram outlining the logic of this algorithm is given in In the case where multiple records were identified as hospital birth records and where Aboriginality differed on these records, a relatively conservative method was used to collapse these into one hospital stay for use in the algorithm:and non-Aboriginal on at least one hospital birth record respectively, then she was excluded from the enhanced population;if the mother was recorded as Aboriginal if at least one hospital birth record for the mother was recorded as Aboriginal and all remaining hospital birth records were missing or Aboriginal status was recorded as unknown, these records were collapsed into one that reported the mother as Aboriginal.Babies born from a multiple birth who were assigned Aboriginal status from the ERA but their twin was not (‘lonely twins’) were excluded from the enhanced population.To establish study population 3 a Multistage-Median algorithm was applshe had one or two linked records and at least one recorded her as Aboriginal,she had three or more linked records and at least two recorded her as AboriginalA comparable algorithm using dataset-specific statuses instead of records was used to assign an overall status and thus determine the inclusion of each woman in study population 3. A flow diagram outlining the logic of this algorithm is given in Where a mother had multiple records for one stay in the hospital data and where Aboriginality differed on these records, these records were collapsed into one hospital stay for use in the algorithm. An algorithm with the same logic used to establish each data-set specific status was used to assign an individual status for one hospital stay where a mother had multiple hospital birth records from one birth.Study population 4 included all mothers that were recorded as Aboriginal on at least one record from the birth, hospital, emergency or birth registration data. For the hospital data, this included all linked records, not just the linked birth record.The study exposure was maternal smoking status. The birth record and the mother’s hospital birth data were used to assign smoking status. If the birth data indicated that a mother smoked at any time during her pregnancy and/or if she was recorded as a current smoker on her hospital birth record(s) (ICD-10-AM diagnosis codes Z72.0 and F17) then she was considered to be a smoker. Smoking is self-reported in both datasets and is known to be under-reported with an estimated sensitivity and specificity of 58.5% and 98.4% respectively in the hospital data .The outcomes of interest included perinatal death , preterm birth (<37 completed weeks of gestation), and small-for-gestational age (birthweight <10th percentile for sex and age ).Study covariates included maternal age, any hypertension, any diabetes, parity and socio-economic status. Maternal age and parity were reported according to the birth data. The mother’s chronic conditions , hyperteThe demographics of each of the four study populations and separately for those included via the ERA algorithms were described and compared using frequencies and percentages. The additional women included through the ERA in study population 2, 3 and 4 are referred to as ERA 2, 3 and 4 respectively.In order to assess the effects on health outcomes and comparisons of using study populations derived from different algorithms, estimates of the associations between smoking during pregnancy and selected perinatal outcomes were compared using rates and relative risks. To estimate the unadjusted and adjusted relative risk of each binary outcome while accounting for the correlation within the data (some mothers had more than one baby during the study period), an extension to the modified Poisson regression  was usedFollowing exclusion of duplicates (n=76), a total of 487,388 babies were born to 379,116 mothers in NSW and were assessed for inclusion in this study. Aboriginal status was not stated for 623 mothers . All 470,484 babies born to mothers not recorded as Aboriginal in the birth data  were assessed for inclusion using each of the ERA algorithms.Birth data records indicated that 16,904 babies were born to 12,720 Aboriginal mothers between 2010 and 2014 in NSW. After excluding all babies from multiple births, those born to mothers who were interstate residents at the time of birth or those not recorded as Aboriginal, study population 1 consisted of 16,306 singleton babies born to 12,504 Aboriginal mothers .885 babies born to 779 mothers were assigned enhanced Aboriginal status using this algorithm; making a total population of 17,789 babies born to 13,267 Aboriginal mothers . Almost Almost all mothers not recorded as Aboriginal on the birth data were assigned dataset-specific statuses regarding Aboriginality for the hospital (99.7%) and birth registration data (99%) and 67% were assigned a dataset-specific status for the emergency data . 1,921 bAlmost all mothers not recorded as Aboriginal on the birth data had at least one record in the hospital (99.7%) and birth registration data (99%) and 67% had at least one record in the emergency data . 8,143 bThe number of births to mothers recorded as Aboriginal on the birth data increased from 2011  to 2014 . The increase in births when applying the ERA was not consistent over the study period; falling from a 6% to 3% increase for population 2, a 16% to 6% increase for population 3 and a 58% to 36% increase for population 4 . SimilarWomen reported through the ERA tended to be older, less disadvantaged and more commonly resided in urban areas than study population 1 . A materRegardless of the study population, adverse perinatal outcomes occurred less frequently among babies born to non-smoking mothers . Each esWe applied a number of algorithms to enhance the reporting of Aboriginality in the NSW birth data, thus increasing the size of the study population for subsequent analysis. As expected, the size of the study population increased with the inclusiveness of the algorithm used. The population size ranged from 16,306-24,107 babies born to 12,504-17,947 Aboriginal mothers respectively. Interestingly, the increase in women reported as Aboriginal through the ERA dropped over the study period for all algorithms and conversely the level of reporting increased. The percent increase in births observed when applying the different ERA algorithms also decreased over time. This could be due to measures that have been taken to improve recording in hospitals and observed increases in the propensity to identify as Aboriginal, meaning there is less potential for the ERA to add more information.The demographics of women assigned enhanced Aboriginality from the three ERA algorithms differed from each other and those recorded as Aboriginal on the birth data. Generally, women recorded through the ERA were older, less disadvantaged, lived in less remote areas and were less likely to smoke or have diabetes than women recorded as Aboriginal on the birth record. Overall, these differences increased with the inclusiveness of the ERA algorithm. These findings are consistent with a similar NSW study which found that ERA tended to capture more women from urban areas than rural areas (but did not report on other demographics) and a study from Western Australia which concluded that Aboriginal or Torres Strait Islander babies reported through the ERA were less disadvantaged , 25. TheIt is important that every individual has a choice whether or not to identify themselves as Aboriginal or Torres Strait Islander, and only an estimated 8% of Aboriginal people in NSW report never identifying themselves as such. Evidence suggests that the highest proportion of Aboriginal people from NSW who never identify are aged 15–24 years and the propensity to identify decreases as remoteness increases . InteresThe datasets used in this study, and commonly in public health research, are not collected for research purposes and are prone to errors in data entry and linkage. There is also reason to believe that linkage errors may be more common among Aboriginal people than Non-Aboriginal people due to their names, date of birth and address information being less consistently reported across routinely collected datasets than for other Australians . ConsequFor all of our populations, we had a constant baseline population based on the recorded Aboriginal status on the birth data. That is, no women who were recorded as Aboriginal in the birth data, were subsequently reported as non-Aboriginal in any of the enhanced populations. This assumption was made as we were looking to ‘enhance’ the known under-reporting in the birth data, and also have a constant baseline on which to build the enhanced populations.Since mothers recorded as Aboriginal through the ERA only made up 5% and 10% of study population 2 and 3 respectively, the demographics of women from study population 1, 2 and 3 differed little from each other. A third of study population 4 consisted of mothers eligible through the ERA and consequently this influenced the demographics of this population. Of particular note was the rate of smoking during pregnancy among women from study population 4 at 44%, almost 6% lower than that in study population 1. To a lesser extent, rates of perinatal outcomes also differed depending on the study population used, results that are consistent with the literature [The way in which indigenous peoples are recorded on health data and how these populations are quantified has important implications for reporting of health statistics around the world . EnhanceIt is widely acknowledged that Aboriginality is under-recorded in routinely collected datasets across Australia and enhanced reporting using linked data attempts to adjust for this. Although valuable efforts have been made, it is impossible to determine the extent to which Aboriginality is under-reported or how close any algorithm gets to the truth because there is simply no gold standard for comparison. This poses many difficulties for establishing the prevalence of health outcomes among Aboriginal people, the magnitude of the ‘gap’ between Aboriginal and non-Aboriginal Australians and tracking changes over time. Our work supports this but, more interestingly, provides evidence that estimates of within-group relative risks are reliable regardless of the assumptions made for establishing the study population through the enhanced reporting of indigenous peoples. Under-recoding of Indigenous status is not unique to Australia and these findings may have broader implications for countries that experience similar issues such as New Zealand, Canada and the United States of America.This study has obtained ethics approval from the Aboriginal Health & Medical Research Council of New South Wales (HREC Reference number: 1326/17).


To assess the extent to which maternal histories of newborn danger signs independently or combined with birth weight and/or gestational age (GA) can capture and/or predict postsecond day (age>48 hours) neonatal death.Data from a cluster-randomised trial conducted in rural Bangladesh were split into development and validation sets. The prompted recall of danger signs and birth weight measurements were collected within 48 hours postchildbirth. Maternally recalled danger signs included cyanosis (any part of the infant’s body was blue at birth), non-cephalic presentation (part other than head came out first at birth), lethargy (weak or no arm/leg movement and/or cry at birth), trouble suckling . Last menstrual period was collected at maternal enrolment early in pregnancy. Singleton newborns surviving 2 days past childbirth were eligible for analysis. Prognostic multivariable models were developed and internally validated.Recalling ≥1 sign of lethargy, cyanosis, non-cephalic presentation or trouble suckling identified postsecond day neonatal death with 65.3% sensitivity, 60.8% specificity, 2.1% positive predictive value (PPV) and 99.3% negative predictive value (NPV) in the development set. Requiring either lethargy or weight <2.5 kg identified 89.1% of deaths  while lethargy or preterm birth (<37 weeks) captured 81.0% of deaths . A simplified model  predicted death with good discrimination  0.80, 95% CI 0.73 to 0.87). A further simplified model  predicted death with moderate discrimination .Maternally recalled danger signs, coupled to either birth weight or GA, can predict and capture postsecond day neonatal death with high discrimination and sensitivity. Neonatal mortality declines in low-income countries have slowed significantly.Current approaches to identifying illness in communities heavily rely on infrequent visits by overburdened community health workers; first contact with a trained provider may be long after the period of greatest danger has passed.Reaching and assessing newborns in the first week of life can be challenging, but is also likely to have the greatest survival benefit.Neonatal danger signs ascertained through prompted maternal recall shortly after childbirth, if coupled with either birth weight or gestational age (GA), can predict and capture neonatal death with good discrimination and high sensitivity, respectively.Given the severe resource limitations experienced in many communities, neonatal illness screening and referral may potentially be improved on the basis of a limited set of predictors which include maternal recall of the newborn’s condition at birth, birth weight and GA.Moreover, these findings provide support for systematically capturing GA and birth weight in low-income and middle-income countries.Despite dramatic reductions in under-five mortality in recent years, progress has largely benefitted infants surviving past the neonatal period, with a marked plateau in neonatal mortality declines.Increasing rates of facility-based births have not resulted in marked improvements in neonatal survival outcomes likely because poor quality of care persists and the onset of complications begins after discharge from the facility.At the community level, home-based neonatal care programmes have been used to identify and treat neonatal illnesses.We sought to assess, through a secondary analysis of a large, prospective dataset from a cluster-randomised trial conducted in Gaibandha and Rangpur, northern Bangladesh, whether the prompted maternal recall of neonatal danger signs  defined in local terms, could be predictive of postsecond day neonatal death and whether predictive capacity was improved by combining these risk factors with birth weight and gestational age (GA). For this purpose, the aims of this study were to characterise the association between these danger signs and postsecond day neonatal mortality; to describe the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at which combinations of these danger signs with GA and birth weight captured mortality and to develop and internally validate prognostic multivariable models using birth weight, GA and maternally reported danger signs as predictors.This is a secondary analysis of the JiVitA-3 cluster-randomised trial dataset, of which the protocol and methods are published elsewhere.The outcome of interest, postsecond day neonatal death (age>48 hours), was ascertained for all infants through a 1-month vital status visit, with details captured in an extensive verbal autopsy performed within 30–45 days after an infant death was reported. Few (n=5) infants were lost to follow-up prior to the final 1-month visit, and for this analysis were presumed to have survived. No actions were performed to blind the assessment of the outcome.An assessment of the infant was performed at home as soon as possible after birth where measurements  were collected by a trained anthropometrist and a simple interview regarding the condition of the infant at birth and newborn care practices was performed.Baseline maternal characteristics were collected at the time pregnant women were enrolled into the parent trial. Information included age at pregnancy identification , gravidity, pregnancy history , anthropometry , tobacco exposure  and education. A living standards index capturing socioeconomic status was calculated from reported household assets and household construction materials by principal components analysis.No actions were performed to blind the assessment of any predictors of the outcome. The parent trial’s allocation of multiple micronutrient or iron-folic acid supplementation was double-masked. However, the parent trial intervention was not a predictor in this analysis.No sample size calculations were performed; all available data from the parent trial dataset were used in this analysis. Analyses were performed and models were developed and validated using participants with data available for all predictors .χ2 tests for categorical variables and t-tests for continuous variables. The variables used to model associations were handled as categorical. Associations between risk factors and outcomes were calculated using the development set only. The sensitivity, specificity, PPV and NPV of individual risk factors and combinations of risk factors to classify/predict neonatal death was calculated for infants in the development and validation sets, separately.Maternal and infant baseline characteristics were compared between the development and validation sets. Groups were compared using For multivariable prediction models, birth weight was modelled as a continuous variable through a linear spline with knot at 1.5 kg, GA was modelled as a continuous variable and all other predictors were modelled as categorical. Birth weight was analysed in kilograms as opposed to grams in order to improve the interpretability of model parameters. Three multivariable models were fitted on the development set. Model coefficients (β) and odds ratio (OR) estimates were calculated using multivariable logistic regression models.The rationale for developing prediction models for this study was to assess the predictive performance of maternally reported danger signs in relation to birth weight and/or GA. Therefore, models whose variables were selected before modelling were based on demographic factors, common risk factors for adverse pregnancy outcomes observed in the literature (including birth weight and GA) and purposively, the maternally reported danger signs of interest. The first model (Model 1) was based on an expanded set of risk factors for neonatal death: birth weight, GA, lethargy, cyanosis, non-cephalic presentation, trouble suckling, infant sex, maternal age at positive urine test, primigravidae, maternal body mass index (BMI), maternal betel nut chewing, maternal tobacco chewing, husband smoking, maternal education and living standards index (above median). The second model (Model 2) focused on a limited set of risk factors for neonatal distress and death: lethargy, cyanosis, non-cephalic presentation, suckling, GA and birth weight.The variables for the third model (Model 3) were selected during modelling. This further simplified model (Model 3) is based on a limited set of risk factors that may be approximated when birth weight cannot be measured: GA, lethargy, non-cephalic presentation and suckling. Cyanosis was excluded from Model 3 because its parameter estimate was not statistically significant in multivariable analyses . A subgroup analysis was also performed to assess if prior infant loss, prior stillbirth, prior miscarriage or prior abortion/menstrual regulation improved model discrimination among women reporting a previous pregnancy. The predictors in these models are specified in the 10.1136/bmjgh-2019-001983.supp1Supplementary dataModel fit  was assessed with a Hosmer-Lemeshow goodness of fit test, where observations were divided by predicted probability into ten quantiles unless otherwise specified. The degrees of freedom for the Hosmer-Lemeshow test were adjusted for tests on the validation sample. Discrimination was assessed through the area under the receiver-operator characteristic curve (AUC) with asymptotic normal CIs calculated using the DeLong method for estimating standard errors (SEs).All statistical tests were two-sided. All analyses were performed using Stata 15 .Once identified as pregnant from a population-based surveillance, oral consent to participate in the parent trial was obtained from pregnant women before a witness. The parent trial was approved by the Institutional Review Board at the Johns Hopkins Bloomberg School of Public Health  under registration number IRB00000570 and the Bangladesh Medical Research Council . The parent trial is registered at clinicaltrials.gov (Identifier: NCT00860470). This reporting of this analysis followed the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines .25 26Patients and/or the general public were not involved in the design, execution or drafting of this secondary analysis.2, living standards index, experience of an prior infant death (among multigravidae), location of delivery, GA at birth, birth weight, cyanosis, non-cephalic presentation, lethargy and trouble suckling , measured predictors  and neonatal death was assessed for the development set. Each of the maternally reported danger signs was associated with mortality in bivariate analyses . HoweverThe sensitivity, specificity, PPV and NPV of neonatal death were calculated for each risk factor and combinations of risk factors . The PPVThree multivariable prediction models were developed; model fit and discrimination were compared across development and validation sets. All models fit the data across development and validation sets (Hosmer-Lemeshow p>0.05). Model 1 (expanded set of risk factors) predicted neonatal death with good discrimination in the development set  and the validation set  . Model 2This analysis provides evidence on the ability of maternally recalled danger signs , birth weight and GA to predict postsecond day neonatal mortality. It is important to note that for maternally recalled danger signs mothers were neither trained nor standardised in the detection or reporting of these signs, but that these findings are based on over 19 000 such reports captured in a typical rural setting in Bangladesh.Predictive models of likely adverse pregnancy outcomes or increased propensity for neonatal distress, prior to the onset of clinical symptoms, have been highly sought after for decades. Scores which discriminate healthy neonates from those at higher risk of early newborn illness, susceptibility to infection or failure to thrive have been attempted—often with variable performance, depending on the skill of the observer and the context of use. The Apgar score is among the most-used metrics for newborn assessments, with demonstrated predictive reliability in clinical settings, captured by trained clinical staff at 1 and 5 min postnatally.These challenges underscore the importance of seeking a minimum set of maternally observable danger signs which can reliably distinguish neonates at high risk of mortality. While efforts are made to improve the coverage of institutional delivery and postnatal care in the first week of life, these findings suggest that maternally reportable indicators are both assessable and could reduce preventable neonatal mortality in these settings in the interim. Specifically, our findings help to identify a minimum set of key danger signs worthy of triggering referral that can be highlighted in a late-in pregnancy antenatal care visit or that can be used to counsel recently delivered women and/or their family members, given infrequent CHW postnatal visits. For deliveries that occur in the home, caretakers are generally advised to seek immediate, qualified care from a CHW or health centre if they recognise danger signs. However, given the challenges associated with spontaneous warning sign recognition, caretakers recall may need to be prompted. A recent study in this population demonstrated that a mobile health package of short message service and home visits was a cost-effective addition to census enumeration and pregnancy surveillance. Such a package could potentially be leveraged to prompt recall of these danger signs.Concerns about maternal capacity to recognise a newborn in danger, nonetheless, exist. Maternal recall of lethargy, non-cephalic presentation or robust suckling have been shown in this data to be reliable, despite likely variability in maternal interpretation of their own child’s condition. Coupling these perceived conditions to information about GA or birth weight could provide a powerful risk index to trigger a CHW home visit or immediate care seeking by the family. Although the PPV of individual and combined danger signs (ranging from 1% to 10%) may be clinically relevant given the low absolute risk of mortality in this population, the PPV of these signs may seem too low to capture deaths in the context of a standalone, one-time screening test. However, we do not see this as problematic. A programmatic approach that aims for high sensitivity, ensuring that no babies at risk of dying are missed while helping overburdened health workers target their resources and time, can be acceptable despite the loss of specificity, but only if it is followed by a more specific screening test or examination on referral. Any infants in the community that are falsely classified at risk of death due to both a loss of sensitivity and low absolute risk of mortality could therefore be introduced into the continuum of care; intervened on in ways that may yield benefits beyond immediate survival . This approach may be acceptable because the NPV exceeds 98%, suggesting that most infants that screen negative will survive the neonatal period.Maternal histories of danger signs can be used to support a highly sensitive first test in a two-stage sequential screening process if birth weight and/or GA measurements are available. Because countries with the highest burden of birth weight tend to also lack reliable birth weight data,For facilities with the resources to ascertain valid birth weight and GA measurements, a model that also includes lethargy, cyanosis, non-cephalic presentation and trouble suckling will be able to discriminate infants as well as a model with other risk factors for neonatal mortality among primigravidae and multigravidae. As the quality of care in lower-level facilities increases with time and infants are triaged on the basis of more sophisticated risk assessment tools, the predictors we present may potentially be used for purposes other than immediate intervention. For example, these predictors may be used to flag infants for additional monitoring before discharge. If discharged, community health workers may be instructed to selectively follow-up with infants born preterm, with low birth weight or presenting as lethargic on delivery.The strengths of this analysis include a large sample size and complete follow-up for infant outcomes in a rigorous research environment, ensuring high-quality data capture. The risk of recall bias and misclassification was reduced because the analytic sample was restricted to infants assessed either on the date of delivery or the day after. Assessments were performed before infant deaths and the predictors selected for analysis were expressly chosen due to their easy observability. There is a risk of recall bias for poor suckling because it was collected either at a 1-month postpartum assessment or during a verbal autopsy. Other predictors for neonatal illness that could be ascertained through maternal report such as temperature, fast breathing and severe chest indrawing,Although the risk of recurrence of adverse birth outcomes has been previously reported for stillbirth,A higher proportion of infants that died during the neonatal period were not assessed on the day of their birth or the day after (within age ≤48 hours) compared with those infants that survived the neonatal period. Although we attempted to mitigate this survivorship bias by restricting any inferences drawn to those infants that survived past 48 hours following childbirth, the postsecond day mortality rate in the development set was 19 deaths per 1000 live births before exclusions and 13 deaths per 1000 live births after exclusions. We speculate that this bias attenuated model coefficient estimates because neonatal deaths were differentially depleted from the study population.Nevertheless, the most important limitation of this analysis is that it attempts to use predictors that are probably most useful at the point of delivery  to predict mortality during the period of time at which they may be less relevant, past 48 hours postbirth. Non-cephalic presentation, for example, is strongly associated with birth asphyxia and stillbirth.Furthermore, the use of split sample validation as opposed to cross-validation or temporal validation as the method for internal validation, Hosmer-Lemeshow tests for the calibration of a model with a binary outcome, the relatively few events per predictor, and the absence of imputation methods for predictors are major weaknesses for the model’s internal validity. However, the purpose of developing prediction models was to assess how well maternally observed danger signs, in addition to birth weight and/or GA, discriminates infants. Given these results, we would recommend that these data be used to inform the future development of prediction models that prospectively capture and assess how maternally reported danger signs may improve discrimination among all neonates (including outcomes occurring within 48 hours of childbirth). Moreover, the generalisability and programmatic applications of these predictors and models will ultimately depend on their validation in other populations.Maternal histories of lethargy, non-cephalic presentation and trouble suckling in their newborn shortly after birth were, in this rural Bangladeshi setting, reasonably predictive of postsecond day neonatal death, but only if coupled to a measurement of birth weight and GA. These findings may be used to support efforts to triage and focus care to high-risk newborns, to advocate for the systematic capture of birth weight and GA at birth to improve prediction and ultimately, to reduce preventable neonatal mortality in resource-constrained settings. As Bangladesh and neighbouring countries struggle to cover existing workforce gaps, strategies which enable resource prioritisation and target care to those at greatest risk may be useful in accelerating reductions in neonatal mortality.


Whether the associations are due to the preterm birth insult We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ , preparation-vigilance measures and measures of error processing . There was a negligible within-sibling association between preterm birth with executive control measures of inhibition  or verbal working memory .Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms  is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult  Of the sibling pairs, 45% (n = 47) were same-sex siblings. In total, 55% of the preterm-born siblings were older than their term-born sibling. A 48-h ADHD medication-free period was required prior to assessments. Written informed consent was obtained following procedures approved by the National Research Ethics Service Committee London – Bromley (13/LO/0068).The present analysis only uses siblings discordant for preterm birth. Therefore, the final sample in this analysis consisted of 208 participants: 104 preterm-born participants (GA ranged from 23 weeks to 36) and their 104 term-born siblings (GA ranged from 37 to 42 weeks). On average, the siblings in a pair were discordant by 5.97  assessment with cognitive tests and clinical interviews. As part of the EEG assessment, participants completed a cued continuous performance test (CPT) with flankers (CPT-OX) , the national standard development record given to parents. Preterm birth was considered as <37 gestational weeks and term birth was considered ⩾37 weeks.The vocabulary and block design subtests of the Wechsler Abbreviated Scale of Intelligence (WASI)   were calculated for each condition.Participants performed a four-choice RT task with a baseline condition  with four empty circles  first appearing for 8000 ms, after which one of them (the target) was coloured in , with a 500 Hz sampling rate, impedances kept under 10 kΩ, and FCz as the recording reference electrode. The electrooculograms were recorded from electrodes above and below the left eye and at the outer canthi. The EEG data were analysed using a Brain Vision Analyzer (2.0) . After down-sampling the data to 256 Hz, the EEG data were re-referenced to the average (turning FCz into an active electrode) and filtered offline with digital band-pass  Butterworth filters. Ocular artefacts were identified and removed from the data using Independent Component Analysis ; lower IQ, as well as decreased CNV amplitude and decreased Go-P3 amplitude on the CPT-OX task, decreased N2 amplitude and decreased Pe and ERN on the flanker task, increased MRT and RTV in the baseline condition of fast task, and decreased CNV amplitude and P3 amplitude on the fast-incentive condition of fast task, independent of familial factors  or NoGo-P3 amplitude  on the CPT-OX, compared to their term-born siblings; these within-sibling associations were therefore largely attenuated compared to the unrelated comparisons  and NoGo-P3 amplitude , compared to the unrelated control group; the results remained similar when IQ was additionally adjusted .Within-sibling comparisons showed that those who were born preterm were more likely to have increased parent-rated total ADHD symptoms [and on both inattentiveness .et al., et al., per se.In this sibling-comparison study of adolescents, we find evidence for significant associations of preterm birth with increased ADHD symptoms, including both inattentiveness and hyperactivity-impulsivity sub-scales, and with specific cognitive-neurophysiological impairments, including IQ, preparation-vigilance processes  and error and conflict processing , which are independent of familial factors shared by siblings, indicating that preterm birth is likely in the causal pathway leading to these identified impairments. In contrast, the association of preterm birth with executive control measures of working memory (DSB) and inhibition (NoGo-P3) was not independent of familial factors, indicating that these previously obtained associations  and attenuated response inhibition (NoGo-P3) when controlling for unmeasured familial confounding factors. This suggests that familial factors shared by siblings, which include factors correlated with preterm birth , may account for these deviations with preterm birth previously observed in preterm individuals when compared to unrelated controls. The finding that working memory is not on the causal pathway from preterm birth is in line with results from a study which demonstrated that a combined measure of short-term auditory memory and verbal working memory (combining DSF and DSB) were not on the causal pathway between birth weight and ADHD symptoms in adolescents (Morgan et al., et al., The present study is, to our knowledge, the first study investigating the effects of preterm birth on cognitive-neurophysiological measures in adolescents in a quasi-experimental sibling design, which is essential for drawing stronger causal inferences. However, as is the case for all such non-randomised quasi-experimental studies, we cannot rule out all confounding factors (D'Onofrio In conclusion, our findings provide novel insight into the potential causal pathways to cognitive-neurophysiological impairments and increased ADHD symptoms in adolescents born preterm. By distinguishing impairments that are consistent with a causal inference of preterm birth from those that are instead linked to background characteristics of families with a preterm-born child, these results suggest that interventions need to target both preterm-birth specific and family-level risk factors to minimise impairments in those at risk. If replicated, clinical implications include raising the awareness about the increased risk of cognitive and brain impairments in preterm-born children; and understanding the increased risk of IQ and cognitive/brain impairments are likely causally related to preterm birth itself, whereas executive function impairments are via different causal mechanisms associated with families at risk.


Background: Low birth weight (LBW) is linked with fetal and neonatal mortality and morbidity; also it can slow down growth and cognitive development. Several factors contribute to pregnancy outcomes, including LBW deliveries, maternal nutrition, and additional dietary intake. Our study was aimed to identify the frequency and factors associated with LBW mothers in Karachi, Pakistan. Methods: A cross-sectional survey was carried out at the Obstetrics and Gynaecological Department of Hamdard Hospital, Karachi. A total of 195 healthy pregnant females were enrolled. All the relevant data were collected from March 1st, 2019 to August 31st, 2019 with the help of a structured questionnaire designed specifically for the study where mothers were also asked about consumption of iron, vitamin, and extra meals since they became pregnant. Written, informed consent was taken from all of the participants before data collection. Data analysis was performed using a statistical package for the social sciences (SPSS) version 20.0. A Chi-square test was used for checking associations between the studied maternal factors and the weight of the children. 2 or more, 102 (52.3%) of them had hemoglobin (Hb) between 10 and 11 mg/dL. The study results further showed that maternal Hb (p=0.02), vitamin C intake (p=0.037), iron intake (p=0.01), and consumption of extra meals during pregnancy (p=0.021) were significantly associated with a LBW of the children. Mothers whose Hb <10 mg/dL, no intake of vitamin C, or iron, and extra meals during pregnancy were more likely to have a child with LBW than others.Results: There was a total of 195 pregnant females selected for the study. The frequency of LBW infants was found to be 57 (29.2%) in these women. The mean age of the females was 29.29 ± 5.22 years, 142 (72.8%) of them had a body mass index (BMI) of 25.0 kg/mConclusion: It can be concluded that maternal nutritional and dietary factors are very important during fetal development, and they have a significant relationship with the birth weight.  According to the World Health Organization (WHO), low birth weight (LBW) is defined as the first weight after birth which is less than 2500 g (5.5 pounds), resulting from preterm birth (birth before 37 completed weeks) or due to intrauterine growth restriction or from both -2. BirthAs we know, the nutritional needs during pregnancy are higher than usual days of life, and proper balance with extra nutrients can help both mother and fetus in protecting long-term health outcomes. Many physiological modifications in mother, as well as the growth of fetus, increase the metabolic demand, and inadequate maternal nutritional status showed adverse pregnancy outcomes, poor infant survival, and impaired intellectual development in the coming life -12. PrevA cross-sectional survey was carried out at the Obstetrics and Gynecological Department of Hamdard University Hospital, Karachi, among 195 healthy pregnant females. A nonprobability convenient sampling technique was used in this study. The ethical approval was taken from the institutional review board of the hospital. Taking the percentage frequency of the study outcome as 50% for the most liberal estimate, with a 95% confidence level and 7.5% precision, the minimum calculated sample size was 171 pregnant females. Healthy pregnant females with either singleton or multiple pregnancies with at least three antenatal checkups were included while females giving birth at gestational age less than 34 weeks or above 41 weeks and 6 days, or with a complicated pregnancy were excluded from the study. Written, informed consent was taken from all of the participants before data collection. No incentive, monetary or otherwise, was offered to the study participants. All the relevant data were collected from March 1st, 2019 to August 31st, 2019 with the help of a structured questionnaire designed specifically for the study. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0. For descriptive analysis, means and standard deviations were calculated for continuous variables while frequencies and percentages were generated for categorical variables. Inferential analysis was performed using the chi-square test to check associations between the maternal factors and the weight of the children whereas the significance level was kept at 0.05 .  There was a total of 195 pregnant females selected for the study. The frequency of LBW infants was found to be 57(29.2%) in these women. The mean age of the females was 29.29 ± 5.22 years, 142(72.8%) of them had a body mass index (BMI) of 25.0 kg/m2 or more, 102(52.3%) of them had Hb between 10 and 11 mg/dL, 172(88.2%) of them used to take each of vitamin C and iron during pregnancy, 136(69.7%) of them consumed extra meals during pregnancy while only 5(2.6%) of them were tobacco smokers/chewers (Table The study results further showed that most of the neonates 20(45.5%) with weight less than 2.5 kg were having the maternal Hb of less than 10 mg/dL, whereas 39(79.6%) of neonates were related to the mothers with Hb of >11 mg/dL, with a significant association (p=0.02). It was also revealed that vitamin C intake (p=0.037), iron intake (p=0.01), and consumption of extra meals during pregnancy (p=0.021) were significantly associated with a LBW of the children, where mothers whose Hb <10 mg/dL, no intake of vitamin C, or iron, and extra meals during pregnancy were more likely to have a child with LBW than others , where almost all deaths account for LBW cases . There aThe frequency of LBW infants was 29.2% in this study, which is very alarming because this is the future cause of neonatal death. In this study, we observe that BMI, Hb levels, vitamin C, iron intake, and extra meal intake were the factors associated with LBW deliveries. Hence, the maternal factors mentioned above should be considered important while striving to achieve a good birth weight of infants before and during pregnancy. If we make efforts to prevent or reduce LBW by takings steps and improving maternal nutritional and dietary intake, we will be able to reduce neonatal death. Policy makers may also consider the need for time for quality healthcare, nutrition education, and lifestyle changes in LBW high-risk mothers.


We aimed to identify common features of upright vaginal breech births with good outcomes to refine a physiological approach to teaching breech birth.We performed a structured analysis of 42 videos of successful upright breech births , facilitated by obstetricians (n = 34) and midwives (n = 8) in nine different countries. Precise timings and relevant clinical details were recorded on an Excel spreadsheet. Each video was analyzed twice by at least two members of the research team. Time‐to‐event intervals, frequencies of interventions, and descriptive statistics were calculated using SPSS.A completely spontaneous  birth occurred in 14/42 (33%) cases. The median time between the birth of the fetal pelvis and the head in all births was 1:52 . Lack of spontaneous rotation to a sacro‐anterior position by the time the fetus had emerged to the nipple line was strongly associated with fetal arm entrapment. The following maneuvers were used: shoulder press to flex the aftercoming head in midpelvis or outlet (n = 24), sweeping down arm/s (n = 12), buttock lift to assist shoulder press (n = 6), modified Mauriceau (n = 6), rotational maneuvers to release an entrapped arm (n = 6), elevate and rotate fetal head to assist engagement (n = 2), and conversion into supine maternal position (n = 2).Most upright breech births occur within 3 minutes of the birth of the fetal pelvis. Upright breech birth attendants use variations of traditional maneuvers. We introduce a physiological breech algorithm as an initial timekeeping framework for teaching, research, and practice. Of these, 37/42 (88%) videos were contained in our personal teaching collections, used with consent, anonymized, and in semi‐public circulation on the Breech Birth Network Vimeo teaching platform accessible to trained health care professionals via password. They were donated for use in research in teaching either by practitioners, who obtained local consent, or by women themselves, who intended them to contribute to understanding and increased safety of vaginal breech birth. Others were publicly available online on other platforms .Although we were not provided with specific outcome data, we were informed that all births had good outcomes. We included all birth videos of upright breech births that we were able to locate during the study period (May 2017‐July 2019), had permission to use, and showed the birth continuously from pelvis to head. We attended fewer than half of the births ourselves . The videos originated in Germany (22), USA (6), UK (4), Brazil (3), Belgium (3), New Zealand (1), Israel (1), Ecuador (1), and Spain (1). Because the videos were already completely anonymized and in circulation, this study qualified as an analysis of pre‐existing data, not subject to review by a Research Ethics Committee.Our research team included a Lead Obstetrician in a hospital in which vaginal breech births account for >6% of the total birth rate because of late‐term transfers of care (AR); a Consultant Breech Specialist Midwife in a large teaching hospital (SW); and a Research Assistant (AH) who was trained in physiological breech birth methods and video analysis. Each video was initially analyzed by AR, SW, or AH and was checked for accuracy by SW or AR. A data collection tool was created using Microsoft Excel spreadsheet software. This database comprised more than 80 items, including the time intervals between the birth of the fetal pelvis, umbilicus, arms, and head, as well as any interventions performed during the birth. After an initial analysis, the team met to discuss and modify the data collection tool. A second analysis of each video and accuracy check was completed. Time‐to‐event intervals, frequencies, and descriptive statistics were calculated using IBM SPSS Statistics software (Version 23). Fisher exact test was used to determine association between variations in fetal mechanisms and performance of maneuvers.In this study, a spontaneous birth is defined as one resulting from labor mechanisms and maternal effort alone, in which no direct manipulation of the fetus occurred.33.1In our sample, the median length of time between the birth of the fetal pelvis and the head was 1:52  Table .3.2Birth of the fetal pelvis with the sacrum transverseSacro‐anterior rotation of the fetal pelvis with descentExtended legs born simultaneously by hip extensionFull body recoil flexion: From an extended position, the fetus flexes his/her hips/legs, adducts his/her arms, and flexes his/her head, recoiling to the previous fetal positionFlexed arms born across the body with the shoulders in the transverse diameterHead born by further flexion and maternal effortIn the videos, we were able to observe the following mechanisms, each of which occurred in over half of the sample:In our sample, the fetal sacrum most often emerged in a transverse position , followed by oblique 15/42; 36%). In no cases did the sacrum emerge in a direct sacro‐anterior or sacro‐posterior position. After emergence of the fetal pelvis, in 28/42 (67%) cases the fetus began to rotate in a sacro‐anterior direction with further descent. At the time of the birth of the umbilicus, only 7/42 (17%) cases had rotated completely into a direct sacro‐anterior position. By the time the fetus had emerged to the nipple line, 27/42 (64%) had rotated completely spontaneously to sacro‐anterior, and only 3/42 (7%) remained sacro‐transverse .Among the cases where spontaneous rotation to sacro‐anterior had completed by the nipple line, in only 4/27 (15%) were maneuvers performed to release one or both of the arms, compared with 10/15 (75%) of cases where it had not. In all three cases of no rotation after birth of the pelvis (persistent sacro‐transverse), rotational maneuvers were performed to release entrapped fetal arms. Lack of spontaneous rotation to sacro‐anterior position by the nipple line was associated with use of manual maneuvers to release fetal arms (P = 1).The fetal back began on the maternal right in 23/42 (55%) cases and on the maternal left in 19/42 (45%) cases. Maneuvers were used at a similar frequency for both positions  cases overall, including 10/34 (29%) cases attended by obstetricians and 4/8 (50%) cases attended by midwives Table . IndirecWe were able to record the timings of birth of both legs in 35/42 (83%) cases Table . In our Both fetal arms were also born at approximately the same time in completely spontaneous births Table . The medIn all remaining  cases where sweeping release of the sacral arm was successful, further rotational maneuvers were required to release the pubic arm. In these cases, the total time required to release both arms was 30, 40, 65, and 66 seconds. In one case, release of the pubic arm through rotation was performed before attempting to sweep down the sacral arm; in this case, the birth was complete within 33 seconds of initiating the rotational maneuver. When rotational maneuvers were used, they were used to release the pubic arm in all 6/6 (100%) cases.Full fetal body rotational maneuvers were performed using “flat hands”  or “shoulder girdle grip” . Rotations were performed by rotating the fetal body either 180° through sacro‐anterior  and 90° back, as described by Louwen (3/6),Among the 24 instances (57%) shoulder press was used, the median time required to perform the maneuver and deliver the fetal head was 9 seconds . Either a “fingers below the clavicle”  or the “thumbs below the clavicle with fingers wrapped around the shoulder girdle”  methods were used.Mothers were asked to turn into a supine position on two occasions , one before delivery of the arms and one before the delivery of the head. The births were completed 50 and 20 seconds after initiating the position change, respectively.3.4Our findings have been translated into an algorithm by Shawn Walker Figure  containi4In historical obstetric practice, vaginal breech births have been managed with the woman in a supine position. However, as “standard” practice has declined in preference for delivery by cesarean birth, many centers that have re‐implemented vaginal breech births are discovering the benefits of upright maternal positioning.(p.17)In general, intervention to expedite breech birth is required if there is evidence of poor fetal condition or if there is a delay of more than 5 minutes from delivery of the buttocks to the head, or of more than 3 minutes from the umbilicus to the head. Our close analysis of 42 upright breech births suggests that spontaneous breech births occur very quickly once the buttocks have descended past the ischial spines and onto the perineum. The data suggest that delay of 90 seconds or more at any point after “rumping” indicates a completely spontaneous birth is unlikely. In this sample, even most assisted births were completed within 3 minutes of the birth of the fetal pelvis. The 2017 Royal College of Obstetricians and Gynaecologists (RCOG) guideline suggests:any point during emergence indicates a completely spontaneous birth is unlikely and consideration should be given to assisting the birth. Encouraging maternal movement and effort before performing hands‐on interventions will help to spontaneously resolve minor delays, or to confirm the need for manual assistance.We suggest that for upright breech births, a delay of 90 seconds or more occurring at Video analysis has been used by other research teams in related studies around the time of birth. Zhang et alThe mechanisms of vaginal breech birth have been described by others.This is the first paper to report timings and variations in fetal mechanisms during the final moments of upright breech births with this level of detail, which cannot be captured in even the most comprehensive contemporaneous notes. Previous studies of breech births in upright maternal positions have reported higher rates of completely spontaneous births than we have. Bogner et alOur work suggests that the strategy of instructing the woman to breathe through her urge to push while “waiting for the next contraction” should be reconsidered. When the fetus is delivered to the shoulders, the fetal head should be in the maternal pelvis or needs urgent assistance to engage. Because the uterine myometrium is no longer stretched, the positive feedback cycle that stimulates physiological labor progressExperienced practitioners have suggested that when women birth in an upright, forward‐facing position, such as kneeling, it is easier to observe for signs that the delivery will be more difficult.Whereas the fetal pelvis will usually emerge with the sacrum pointing in a transverse or anterior oblique direction, lack of rotation to a direct sacro‐anterior position by the time the fetus has emerged to the nipple line (when the scapulae would be apparent in a supine birth) was associated with the performance of rotational maneuvers to release an extended fetal arm. Physiological breech birth strategies involve purposeful noninterference if the birth is progressing normally,When confronted with a delay of fetal arms in the midpelvis, clinicians in this sample tended to attempt the release of the sacral arm first. This is possibly because of its proximity to the clinician in upright births, or a belief that reaching the arm will be easier with more space under the sacrum. We have begun to teach novices to attempt release of the pubic arm first, based on our observations and experience in practice. Further research should systematically explore whether releasing the pubic arm first is a more efficient and successful strategy for “restoring the mechanism.”We observed that clinicians expedited the birth of the fetal legs in 7/42 cases. Each time this was done by lifting the perineum or maternal buttocks, and in each case, subsequent interventions were performed to deliver the arms and/or head. After reviewing the videos, we suggest that if encouragement of maternal movement and effort is insufficient to release extended legs, gentle pressure on the popliteal fosse may release the legs more easily and may cause less disturbance for the woman.In 5/42 (12%) cases, clinicians used a finger in the fetal mouth to flex the head. This strategy is often discouraged in the performance of the Mauriceau‐Smellie‐Veit/Mauriceau‐Cronk maneuver to avoid the theoretical risk of jaw dislocation or distocclusion, in which the lower jaw becomes positioned in a distal or posterior position in relation to the upper.4.1Because we used videos to which we had historical access for teaching/research purposes but without linking personal demographics, we did not correlate our observations with parity or detailed fetal outcomes. According to those who provided them, all fetal outcomes were positive, even among the videos which contained complications. We did not exclude any videos we had permission to use. Very complicated births may have provided comparative insight into what is “normal for breech,” but their inclusion is unlikely to have affected our conclusions about what happens in the majority of spontaneous upright breech births. Additionally, our findings relate to upright breech births only, and not to breech births in other maternal positions. We advocate a larger, prospective study, including births in supine maternal positions, detailed outcome data, and careful ethical arrangements around informed consent.The parameter for which we have the least evidence is the interval between “rumping” and the birth of the head. This is because most video footage in our sample begins after this point. At this point, cord occlusion is more likely4.2The Physiological Breech Algorithm designed by Walker accounts for expected timings in a normally progressing breech birth, as well as time required to perform maneuvers in cases of obstruction. We suggest this can be used to guide further research and key clinical documentation points such as the time of “rumping” ; birth of the fetal pelvis; birth of the umbilicus; and encouragement of maternal movement and effort to confirm obstruction before initiating “hands‐on” interventions. Future studies concerning the safety of vaginal breech birth should clarify whether this algorithm is used to guide timekeeping and intervention strategy, or if not, which alternative parameters have been used. Click here for additional data file.


It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health.While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise.The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning.Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected.52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes.This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.The online version contains supplementary material available at 10.1186/s12887-021-02505-6. The probability of survival in preterm infants, especially in extreme premature babies born before 28 weeks of gestation has extended over the last few years due to great advances in both obstetric and neonatology procedures. Whilst in 1990 only a few babies born before 25 weeks of gestation had a chance of survival [Next to improving prenatal care, ventilation strategies and the introduction of advanced techniques in neonatal acute management, optimising nutrition led to dropping mortality and morbidity rates in these very vulnerable infants.Preterm infants have increased nutritional needs and studies show that meeting those increased demands in calories, proteins, minerals and vitamins from the very beginning is not only important for the children’s survival but essentially contributes to the infants’ overall development and long-term health .There have been international accepted guidelines regarding the optimal early parenteral and enteral nutrition in extremely preterm infants during their hospitalisation since the mid-90s. Special preterm formulas as well as human milk fortifiers are available and of high-quality for feeding preterm infants from birth until their hospital discharge. As of 2010 there are also post-discharge formulas available in Austria which are developed to meet the premature infant’s nutritional needs and help with catch-up growth after hospital discharge.A recent commentary shows the significance of adequate parenteral and enteral nutrition as well as appropriate growth in this period and the need of further investigations .A special group of preterm infants are late preterm infants. Almost 70% of all premature born infants are “late preterms” with a gestational age of 34/0–36/6 weeks. Because of their birth weight being usually above 2000 g, they are often regarded to as “almost term”. Often these preterm infants do not receive fortifiers or special preterm formula. In fact, these children are at higher risk to develop obesity in later life . DespiteIn 2012 the Austrian Society for Paediatric and Adolescent Medicine (ÖGKJ) has modified the current guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)  and deveWhilst there are many studies on preterm nutrition regarding breast- and/or formula-feeding, the weaning period in preterm infants has attracted very little attention yet, despite the fact that solid foods will provide the main amount of macro-, und micronutrients from the time on when breastmilk or formula cannot longer meet a child’s nutritional needs.Within the last few years the emphasis on infant nutrition, including complementary feeding has shifted from only prevention of malnutrition and promoting appropriate growth toward a well-balanced diet, facilitating long-term health benefits while preventing the risk of chronic disease. Studies show, that rapid weight gain during infancy puts children at higher risk of suffering from cardiovascular disease in adulthood , also unWhile there are some guidelines and recommendations regarding the timing of weaning particularly for term infants, by now , evidencPrevious studies on this subject suggest that preterm infants are introduced to complementary food significantly earlier than the recommended 17 weeks corrected age and also show that different factors like the mothers educational level or the infant’s gestational age at birth had an impact on the weaning behaviour , 14.The aim of this study was to assess the current feeding practices amongst caregivers of preterm infants born in the Landeskrankenhaus Salzburg (Austria), including determining those factors that may influence the introduction of solids.Ethical consent has been obtained from the responsible local research Ethical Committee.100 premature infants born at Salzburg university medical hospital reached a corrected age of 17 weeks in a 4-month study-period, ranged from 24 0/7 weeks to 36 5/7 weeks gestational age.All parents who agreed to participate in the study provided informed consent.Eligibility criteria included prematurity and at least one of the parents had to be fluent in either German or English.Exclusion criteria included surgical problems that interfered with normal nutritional behaviour , genetic syndromes, metabolic diseases and mothers who suffered from an untreated psychiatric illness as well as children who were placed in foster care. In addition, an extremely prolonged necessity for gavage feeding or the recurrent need of a feeding tube around the time of inquiry was an exclusion criterion.To prevent biasing the study by raising extraordinary awareness to complementary feeding and its guidelines, all families were contacted as early as 16 weeks corrected age to minimise recall bias regarding the time of weaning and which food groups they were first introduced to, carers were contacted at the latest of 18 weeks corrected age.Detailed structured interviews were administered either via telephone or in person in the outpatient clinic.Collected data included sociodemographic data like information on the infant’s family situation, particularly information concerning the mothers, like maternal age, special diet and potential diseases before and during gestation, previous pregnancies and births, as well as educational status and family income [Table 6, supplemental file Questionnaire Perinatal data contained gestational age, birth weight, birth height and head circumference at birth, along with gender, whether it was a singleton or multiple pregnancy, birth mode, 1,5, and 10-min APGAR  and relevant medical problems and interventions during or immediately after birth [Table 6, supplemental file Questionnaire Information regarding the infant’s feeding practices from birth were obtained, including detailed information on milk-feeding practices. It was documented whether the infants have been breastfed or formula-fed right after birth, if they still were breast-fed at the time the survey was conducted and if so, if they were still fully or partially breastfed along with solids and/or formula. Duration of exclusively vs. partially breastfeeding was documented both from birth and term.Since all our participants were born preterm, information on fortifying breastmilk or feeding special preterm formula regarding the duration and type of supplementation also have been obtained.It was documented whether the infants were already started on solids or not, and if so the corrected age as well as the uncorrected age of the complementary food introduction was noted in weeks. All mothers provided us with information about when they introduced specific food groups to their children, which were again recorded in weeks from birth and term.Foods or food groups of interest included vegetables, potatoes, meats, cereal, cereal-milk purees, fruits, eggs, fish, water, tea and sweetened beverages.Information was collected on how often children were introduced to new foods within 1 week and whether they received a special diet (for example vegetarian).Mothers also provided information about personal reasons on why they started weaning their infants and whether they specifically sought information on this topic like talking to their paediatrician, reading on-topic books, brochures etc. [Table 7, supplemental file Questionnaire Weight, height and head circumference at birth and at the time of the interview were collected, as well as those of previous outpatient-clinic visits.All measurement-data has either been gathered from medical reports of our department during in- and outpatient visits, or measured by paediatricians and were provided to us by the infant’s mothers.Weight and height data until a gestational age of 50 weeks were scaled based on the gender-specific Fenton Preterm Growth Charts .“weight for age, birth to 6 months” and “height for age, birth to 6 months” using the infant’s corrected age.Measurements taken as of 51 weeks gestational age were scaled based on the gender-specific WHO growth charts All weight measurements, whether obtained in the clinic or those taken by family paediatricians were taken on calibrated baby-scales. All height measurements were taken by measuring the infant in a supine position from the top of the head to heel, with the infant’s leg being stretched out on a flat surface.p-values < 0.05 were considered as statistically significant. All statistical analyses in this report were performed by use of NCSS , Mathematica 7 , STATISTICA 13 .Data consistency was checked and data were screened for outliers and normality by using quantile plots. Crosstabulation tables with Fisher’s Exact test or Pearson’s test were used to analyze crosstabulations. Two-sided Student t-tests with and without the assumption of variance homogeneity were used to compare expectation values among different groups and 95% confidence intervals were used estimate the effects. Kaplan-Meier analyses were done and survival curves were tested using Cox-F and Gehan’s and Wilcoxon test. All reported tests were two-sided, and An overall of 68 infants were successfully recruited into the study. Flow chart of search strategy and selection process is shown in Fig. early weaning group in the following. The remaining 48% of infants who received solids at the earliest of 17 weeks corrected age will be referred to as the appropriate weaning group.52% of the study group were started on complementary feeding before the recommended 17 weeks corrected age. The 95% confidence interval ranges from 34 to 64%. This group will be referred to as Infants were recruited from a cross-section of socio-economic groups. All but four infants were of Caucasian ethnic origin.In Table In the following passage, you can find the maternal and family characteristics. The mean age of mothers in the study was 31.54 years that did not differ significantly in the two groups.p < 0,01). Mothers who experienced more pregnancies overall started introducing solids earlier than those with less pregnancies .Infants born into families with more children were introduced to solids significantly earlier than those with fewer siblings , preeclampsia or hypertonia showed no significant differences between the two groups.p < 0,01).Another factor significantly associated with earlier complementary food introduction was lower household income, infants of families who lived on less than 30.000€/year received solids significantly earlier .In addition, measurements at 17 weeks corrected age showed no significant differences in the two groups except for weight percentile, which was again significantly higher in the early weaning group. Although the infant’s gender did not have any effect on the timing of complementary food introduction, there were significantly more twins in the early weaning group . 70% in the appropriate weaning group still received breastmilk at 17 weeks corrected age, as opposed to 40% in the early weaning group. Almost 50% of the infants in the appropriate weaning group were still exclusively breastfed at the time of the inquiry.60% of all infants in the early weaning group completely stopped breastfeeding before 17 weeks corrected age, compared to 30% in the appropriate weaning group, which was significant .70% of all infants exclusively received formula; almost 40% were fed special preterm-formula. In the early weaning group, 90% of the infants were formula-fed, in the appropriate weaning group it was only 50%, which was highly significant  of the preterm infants in this cohort were introduced to complementary food before 17 weeks corrected age as recommended by the ÖGKJ . The prePrevious research has identified predictors of early weaning in preterm infants including male sex, gestational age, younger maternal age, maternal smoking, lower level of maternal education, higher maternal pre-pregnancy BMI and formula-feeding .Results of this study support the finding that formula-feeding increases the odds for an early introduction of complementary feeding. Also symptomatically for that are mothers with non-insulin dependent gestational diabetes. All these mothers in our study started weaning their infants before the corrected age of 17 weeks. Mothers suffering from gestational diabetes usually tend to come into lactation more slowly and to have less breastmilk than healthy mothers do, which often leads to early formula feeding. Just as the number of pregnancies, the number of children living in the same household as well as twins being a predictor we think this may be explained by the mother’s lack of time, possible due to lack of supportive help. Furthermore, having more children to take care of might leave mothers too stressed to keep up breastfeeding for a prolonged period of time, so they start formula-feeding only a few weeks postpartum which leads them to be prone to earlier solid food introduction. Typically, formula fed infants with higher weight percentile at 17 weeks corrected age are weaned early. Additionally, a lower household income is also associated with earlier weaning. It might be speculated that a lower household income is associated with a lower level of maternal education and “normal” family food is cheaper than buying formula. A direct correlation of a lower level of maternal education is not found. As well younger maternal age, higher maternal pre-pregnancy BMI, male sex and gestational age are also not correlated in our study. This may be due to the small sample size. Information on smoking habits was not obtained.In adherence to data from term and preterm infants  the presduring their weaning period and further on. In comparison, mothers who decided on combined milk feeding during the infant’s first weeks of life tended to completely stop breastfeeding very soon after starting formula-feeding and those mothers were also found to start feeding solids early.An additional key aspect of this study was to identify the types of food given to preterm infants mainly during the first few weeks of complementary feeding. Again, this study can only provide data on those aspects from the early weaning group.There is international consensus that from time complementary foods is started, relatively fast – within 2 to 3 weeks complex food containing high energy density, proteins and minerals like iron and zinc should be introduced . It is aPrevious research found international discrepancies on weaning foods, particularly on the first solid foods given. While almost 85% of British preterm infants received baby rice as their first complementary food and 6% received fruit or vegetables , in ItalWhen asked about if and where they obtained information on introducing complementary feeding to their infant, about half of mothers reported talking with their family paediatrician about introducing solids, most of them during one of their infant routine check-ups, some called or made an extra appointment. Many mothers felt insecure about how and when to wean their premature born infant, even if they already had older children, which is why they set high value on the family paediatrician’s recommendations.As already mentioned above, this study identified detailed information on caregiver’s reasons for weaning their preterm infant early. More than one third of mothers reported their infant showed increased interest in food during family meal times and they felt breastmilk respectively formula did not satisfy their infant any longer. It is possible that mothers over interpreted those signs of dissatisfaction as infants at this age naturally start putting their hands and toys into their mouths and showing more and more interest to their environment which represents only a developmental step without necessarily expressing readiness for complementary feeding. It is stated in other studies that one important factor, before weaning children, is that they have a good head control in terms of an adequate neurological muscular development and can sit in an upright position . AnotherNearly 10% of mothers felt pressured by their family and close friends to start introducing solids, which can be explained by unawareness of prematurity as well as absent knowledge and understanding of current recommendations and corrected age. About 6% of mothers reported introducing complementary feeding because their infants were 4 months uncorrected age, which supports the assumption that the term “corrected age” is not something all caregivers fully understand. If the data are considered from birth, preterm infants in the present study were weaned with 19.37 weeks ±2.31 weeks chronological age. If that was the case, mothers would very well follow the current guidelines on weaning their infants and missing compliance would not be as big a problem as previous studies suggest .To our knowledge, this study is the first to explore complementary feeding practices in Austria and there is no similar national data on preterm infants. The classification “preterm” includes a very heterogeneous group with a wide range of gestational age and birth weight; however, most of the infants will be developmentally challenged to some extent, for example poor sucking reflex, reduced respiratory capacities.One major strength of this study is its prospective design. Because the questionnaires were conducted at exactly 17 weeks corrected age with a maximal variances of 1 week before or after, recall bias regarding the time of solid food introduction, types of food or reasons for starting complementary feeding is nearly impossible.There are studies about different factors that affect the introduction of complementary foods in preterms e.g. earlier weaning in formula-fed infants . HoweverThere are a few limitations to the present study. The preterm cohort studied in Salzburg was self-selected and is not representative of the preterm population in general. The rather small study cohort is due to a very limited time frame for recruiting families and because we only recruited infants from Salzburg. Therefore, only assumptions can be made regarding the weaning practices for the rest of Austria. Mean maternal age in this study was 31.54 y ± 5.43, that is slightly older than the mean maternal age of 30.5y in Austria (data obtained from the 2015 report of Austrian Institute for Family Studies). Regarding the types of complementary food given there is only data from the 52% of preterm infants who received solids before 17 weeks corrected age, which was the time of our questionnaire being obtained, as we interviewed the families only once. Naturally, from the infants who had not yet received any solids at 17 weeks, any information on complementary feeding could not be obtained. Also reasons for introducing complementary feeding as well as sources of information on this topic could only be provided by families who had already started weaning their infants.The results of this study clearly highlight the need for practical guidelines for introducing complementary food to preterm infants. Those guidelines ideally will be based on the specific requirements of this heterogeneous group of infants, contributing to improved long-term health outcomes in an increasing number of premature born infants. For now, it is important to provide individual advice for parents, based on the infant’s gestational age at birth, nutritional requirements, medical problems and developmental status.It would be reasonable for mothers of preterm infants to receive information on this topic during their NICU stay or during one of their outpatient follow-up visits. Furthermore, it would be beneficial to make sure caregivers fully understand the difference between chronological and corrected age. This could not just lead to a reduced incidence of early weaning but also might help mothers to explain their decision to delay introducing solids, hopefully reducing them feeling pressured by others.Family paediatricians should be informed about current research and also be reminded that late preterm infants are still to be considered as premature born infants rather than almost term born infants, and therefore require special attention to some extent. This point is of particular importance if there are already term born infants in the family.Additional file 1.Additional file 2.


Parabens are a group of esters of para-hydroxybenzoic acid utilized as antimicrobial preservatives in many personal care products. Epidemiological studies regarding the adverse effects of parabens on fetuses are limited. The aim of this study was to determine the association between placental paraben exposure and birth outcomes. We assessed paraben concentrations in placental tissue, which potentially gives a better understanding of fetal exposure than the maternal urinary concentrations which are the current golden standard.ONAGE birth cohort. The placental concentrations of four parabens (methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)) were determined by ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Generalized linear regression models were used to determine the association between paraben exposure levels and birth outcomes.Placental tissue was collected immediately after birth from 142 mother-child pairs from the ENVIRp = 0.04) after adjustment for a priori selected covariates. The sum of parabens was negatively associated with head circumference  and borderline associated with birth length . In newborn girls the placental concentration of EtP was negatively associated with head circumference  and borderline significantly associated with birth weight and birth length. Lastly, placental EtP and ∑parabens were negatively associated with placental weight in newborn girls but not in newborn boys .The geometric means of placental MeP, EtP, PrP, and BuP were 1.84, 2.16, 1.68 and 0.05 ng/g tissue, respectively. The sum of parabens  was negatively associated with birth weight in newborn girls (− 166 g, 95% CI: − 322, − 8.6, The negative association between maternal paraben exposure and birth outcomes warrants further research and follow-up over time to determine long term effects of gestational exposure to parabens. Endocrine disrupting chemicals (EDCs) interfere with the endocrine system, resulting in adverse health effects . It has  in utero period is an extremely sensitive time window for environmental exposures as the fetus develops rapidly and perturbations inferred during this period could have lifelong effects on human health [Environmental exposure to chemicals that perturb the endocrine balance and inflammatory status are particularly harmful during pregnancy, a time in which an adequate hormonal and oxidative balance, is of utmost importance –5. Parabn health . Recentln health , a decren health , and a dn health , 13. HowFetal growth is dependent on genetic, placental, and maternal factors. The fetus is thought to have an inherent growth potential that, under normal circumstances, results in a healthy newborn of appropriate size. The maternal-placental-fetal units act in harmony to provide the needs of the fetus while supporting the physiologic changes of the mother. Low birth weight infants have a 10–20 fold increased risk of dying in the perinatal period  and are Up to now, no reports on placental exposure to parabens and birth outcomes have been reported. Placental concentrations might reflect fetal exposure better than maternal urinary concentrations, as the placenta consists of fetal material and is in close physical contact with the fetus. As such, it could give a clearer picture of fetal exposure.ONAGE birth cohort to participate in the current study. These mother-newborn pairs arrived at the hospital East –Limburg for delivery between December 2014 and December 2016. Technicalities of the cohort are described elsewhere in detail [non-smokers those who never smoked, current-smokers those who continue smoking during pregnancy and past-smokers those who quit smoking before pregnancy. Educational status was likewise categorized into three levels: low-level without a diploma or only a primary school diploma, middle-level with a high school diploma and high-level with a college or university diploma. Lastly, the maternal body mass index (BMI), gestational weight gain, method of delivery and data on health complications were provided by the medical records from the hospital archives.We selected 142 participants from the ongoing ENVIRBirth weight, length, and head circumference were obtained at birth from hospital maternity records. The date of conception was estimated on the basis of the first day of the mother’s last menstrual period combined with the first ultrasonographic examination, to accurately calculate gestational age of the newborn. Placental weight was determined after birth and prior to taking placental biopsies for molecular and (bio) chemical analyses. For this, after the umbilical cord was removed, placentas were placed on a HR2393 scale  and weight was assessed without any handling of the placenta to 1 g precision.Placentas were frozen at − 40 °C within 10 min after birth and stored until homogenization. After thawing, the chorio-amniotic membrane was removed before further processing. Approximately half of the placenta (fixed orientation) was homogenized using a Knife mill Grindomix GM 200  during two 20 s pulses at 10.000 rpm, in order to minimize site-variation within the placenta. Homogenized samples were frozen at − 20 °C until analysis.2O and MeOH, subsequently filtered across a 0.20 μm PVDF filter  prior to UPLC-MS/MS analysis.The levels of MeP, EtP, PrP and BuP were assessed using a previously published sensitive method . In brieUPLC-MS/MS analysis was performed on an Acquity UPLC  system in combination with a triple quadrupole XevoTQ-S mass spectrophotometer. The limits of detection (LOD) were defined as the mean concentration in the blank plus 3 times the standard deviation of the blank. LODs were 0.1 (MeP), 0.2 (EtP), 0.1 (PrP) and 0.2 (BuP) ng/g respectively. Quality control was performed using spiked matrices at three different concentration levels. For samples below the LOD, the value was substituted as LOD/2, apart for BuP, as none of the samples were detected above the LOD, the exposure to BuP was dropped from further analyses.The sum of parabens was calculated as the combined exposure level to MeP, EtP and PrP for each individual.n = 1) the final dataset contained 141 mother-newborn pairs for analysis. We additionally stratified our study population by sex and corrected the model for the same confounders as above apart for sex. We calculated the interaction term for sex in the association between paraben exposure and birth outcomes, to better understand the role sex potentially plays in this association between exposure and outcome. The presence of a significant interaction indicates that the effect of the exposure variables on the measured birth outcomes is different for both sexes.All statistical analyses were performed using SAS  software. Multivariate linear regression models were used to examine the relationship between placental paraben concentrations and birth outcomes. We constructed a directed acyclic graph Fig.  to guideDetailed information on the study population is shown in Table p = 0.48 for EtP and p = 0.38 for ∑parabens.Table p = 0.11 and p = 0.08). When stratifying the data by sex of the newborn the negative association between exposure and placental weight became significant in girls, with p = 0.02 for EtP exposure and p = 0.03 for ∑paraben exposure. The results for boys alone were not significant.Table Table p = 0.01) and showed a negative trend for birthweight (p = 0.06) and birth length (p = 0.08), whereas placental sum of paraben exposure was significantly and inversely associated both with head circumference (p = 0.008) and with birth weight (p = 0.04) and showed a negative trend for birth length (p = 0.08).After stratifying by sex, the observed associations appear to be driven by the girls, as they have stronger associations than the total population combined, whereas results in boys alone are not significant. In girls, placental EtP exposure was significantly inversely associated with head circumference  exposure and birth weight, birth length and head circumference in newborns from the ENVIRght Fig.  remains Our manuscript is the first to describe placental exposure levels of parabens. To the best of our knowledge, previous studies on the relation between maternal exposure during pregnancy and birth outcomes in the newborn have been based on urinary concentrations. Maternal urinary concentrations might not reflect fetal responses well, as the fetus is more sensitive to the effects of EDC exposure than adults . FurtherCurrent literature on maternal paraben exposure during pregnancy in association with birth parameters is inconsistent. In a Taiwanese population of 199 mother-newborn pairs, maternal urinary MeP levels were negatively associated with birth weight, birth length, and head circumference, although only in female newborns . A largeThe biological mechanisms involved in the observed association between placental paraben levels and birth parameters is unclear. Although it is known that parabens have weak estrogenic activity in vitro , it is uLastly, maternal urinary EtP was negatively associated with interleukin-1β in mothers from the LIFECODES cohort , indicatp-values, just around or below the standard 0.05 cut-off point of significance, we believe our data are not chance findings based on their associated estimated effect sizes, i.e. sum of placental paraben exposure in newborn girls is associated with a considerable difference in birthweight of 166 g . Furthermore, the investigated variables indicating newborns’ size, including birthweight, birth length and head circumference, show consistent findings between these antropometeric outcomes at birth and paraben exposure. Because we tested an a priori hypothesis involving interrelated outcomes  as well as exposure (sum of parabens). Therefore, the newborn birth outcomes or exposure indicators did not provide a completely independent opportunity for a type I error. Hence, we did not perform an approach on multiple comparisons as this considers independence between the different statistical analysis.Although our reported findings have relatively large Our estimates of in utero paraben exposure and birth outcomes in girls have a public health relevance. Indeed increasing the placental paraben exposure from the 25th to the 75th percentile resulted in an 112 g reduction in birth weight. This is a relevant reduction compared with other exposures, as exposure to second-hand smoke (SHS) in non-smoking women reduced the mean BW of their infants by 53 g, and even with 92 g in actively smoking mothers exposed to SHS compared to active smoking mothers not exposed to SHS . In addiIn conclusion, our study showed a significant inverse association between placental ethyl paraben exposure and birth weight, birth length and head circumference, both before and after adjustment for selected covariates. We also observed a negative association between the sum of placental paraben exposure and birth weight and birth length, only after adjustment for selected covariates. A trend for a negative association with placental weight was furthermore observed both for EtP and sum of paraben exposure. Further studies are necessary to identify the underlying molecular mechanisms behind these associations.