Pre-term and post-term births are major determinants of neonatal mortality, including short- and long-term morbidity. In developing countries, where pre-term and post-term births are disproportionately common, the magnitude and underlying causes are not well understood, and evidence is required to design appropriate interventions. This study measured the incidence and identified risk factors of pre-term birth and post-term births in Ethiopia. In addition, it examined the effects of pre-term and post-term birth on neonatal mortality.This study is a portion of prospective cohort study conducted on 1152 live births born between April and July 2014 in seven hospitals in Tigray region, Northern Ethiopia. Neonatal mortality and birth outcomes were considered as dependent variables. Data were collected using a structured questionnaire and weekly neonatal follow up directed at midwives. Data were described using frequency, percentage, ratio of relative risk (RRR), and 95 % confidence interval (CI). We used multinomial and binary logistic regression to identify independent predictors of birth outcome and neonatal mortality respectively.The prevalence of pre-term and post term births was 8.1 % and 6.0 % respectively. Underweight maternal body mass index , medium reported income , length of neonate , and multiple births  were associated with pre-term birth. Predictors for post-term birth were overweight maternal body mass index , high reported income mothers , as well as unmarried, widowed and divorced marital status . With regards to binary logistic regression, pre-term birth  was an independent predictor for neonatal mortality, but this was not true for post-term births .Socioeconomic and proximate factors are important predictors for pre-term and post-term births. Empowering women in terms of income status and controlling body mass index within the normal range are recommended. In addition, early detection and close antenatal follow-ups for mothers, who are at risk before and during pregnancy, are necessary to prevent both pre-term and post-term births. Labour outcomes are the essence of successful prenatal programs and the launching of successful post-natal health. Pre-term and post-term births are defined as live births occurring at less than 37 weeks and at 42 or more weeks, respectively, and are associated with both short- and long-term childhood mortality and morbidities –5. In reThe aetiology of pre-term birth is multi-factorial and it is affected by social, psychological, biological and genetic factors. Its prevalence and risk factors depends on geographic and demographic features of the population studied. Hence, the results of studies from one area might not be applicable to another , 9, 10. The morbidities associated with pre-term births often extends to later life resulting in physical, psychological, and economic costs , 14. WhiEvidence on the effect of post-term birth on neonatal mortality is not consistent. Some studies reported that post-term birth is associated with neonatal death , while no association was observed in another study . Post-teTo our knowledge, in Ethiopia, there is no a systematic evidence respecting the burden and predictors of pre-term, post-term birth and their associations with neonatal mortality. Evidence of the levels of pre-term and post-term births is important to design evidence based health care interventions to reduce the unacceptable prevalence of neonatal and childhood mortality in developing countries. Therefore, the present study aimed to identify the predictors of pre-term birth and post-term birth as well as the relationship of pre-term and post-term birth to neonatal mortality in Northern Ethiopia.This report reflects findings from a portion of a large prospective observational study undertaken in one of the nine administrative regions of Ethiopia to investigate pregnancy outcomes and neonatal survival. The current study is a cross-sectional survey and analysis of prospective data on 1162 neonates delivered at selected hospitals between April and July 2014 in Tigray, Ethiopia.This study was part of a study conducted in seven randomly selected public hospitals in Tigray Region, located in northern Ethiopia. The Ethiopian healthcare system has a decentralized four-tier system of primary, district, zonal, and specialized hospitals. The primary care includes rural health posts nested into health centers serving populations of approximately 25,000. District hospitals form the tiers expected to serve catchments of 250,000. Zonal hospitals and specialized hospital serve 500,000 and 5,000,000 people, respectively. In Tigray Region, one of the nine administrative regions and two administrative cities in Ethiopia, there are 15 public hospitals categorized as zonal (6), one specialized hospitals (1), and the district and primary health care (8). All hospitals provide comprehensive maternal and newborn services including delivery service free of charge. Seven hospitals were selected by simple random sampling from across the region using lottery method .Data were collected using a pre-tested structured questionnaire and checklist partially based on the World Health Organization’s verbal autopsy for neonatal deaths . Data onMothers with neonates born at the selected facilities between April and July 2014 were eligible for the study. Mothers referred from other health facilities or coming directly from their homes and admitted to one of the seven participating hospitals within six hour of birth were also included. Mothers who came from other neighbouring regions of Ethiopia, who were not able to speak, who had a psychiatric diagnosis, and/or who had no companion were excluded from the study.We used previous literature and Mosley and Chen’s conceptual framework  with somThis study had two outcome variables that were analyzed independently. The first outcome variable was neonatal mortality, which is death of a live birth baby within 28 days of birth, categorized into binary outcomes for death or survival. The second outcome variable was birth outcome, which is the onset of the labour determined by gestational age of the live birth. This variable was categorized according to World Health Organization’s definitions of pre-term, term births, and post-term births . Pre-terGestational age was estimated based on the last menstrual period. If mothers were not able to recall their last menstrural period, gestational age was estimated using ultrasound methods.The independent variables were broadly categorized as distal factors, such as socio-economic and demographic factors ; proximal factors ; and immediate variables .Maternal complications, which were categorizes into ‘Yes’ or ‘No’ responses on assessment, included presence or absence of obstetric haemorrhage, puerperal sepsis, pyrexia, prolonged labour eclampsia and pre-eclampsia, mal-presentation and mal-positioning, premature rupture of membrane, cord prolapse, obstructed labour, cephalo-pelvic disproportion, emergency Caesarean section, and/or retained placenta. In addition, body mass index (BMI) was one of the maternal factors captured and categorized using the standardized categories of underweight (<18.5), normal (18.5–25), and overweight (>25.0). Neonatal factors considered included birth weight , sex, and weight for gestational age.Birth outcomes were analyzed by categorizing into three outcomes variables  and post-term) considered at the nominal level. Neonatal mortality was fit in a separate model categorized as death (coded “1”) or survival (coded “0”). Potential predictors for pre-term and post-term births were analyzed on the same model based on the assumption of multinomial logistic regression. The predictors were categorized as 1) immediate factors; 2) proximate factors ; and 3) distal factors . The independent variables considered for neonatal mortality were pre-term and post-term births.P-values of less than 0.05 were retained in the multiple regression models. Variables considered in the final model by using the hierarchical method of multiple regression reflected immediate factors (Model 1) followed by proximal factors (Model 2) and, finally, distal factors being added (Model 3) as predictors of pre-term and post-term births. Multinomial and binary logistic regression was used to estimate the relative risk ratios (RRR) and relative risk (RR) as well as corresponding 95 % confidence interval (CI) for the predictors of birth outcomes and neonatal mortality at P < 0.05. During model building, cofounders were checked by looking for 15 % change in the regression coefficient. Interaction between predictor variables was tested at a significance level P < 0.05 by including an interaction term in the multivariate model. Multicollinearity among independent predictors was tested using Variance Inflation Factor. Data was entered, cleaned, and analyzed using STATA™ Version 11.0 Statistical Package.A bivariate logistic regression was performed, and variables with likelihood ratio test n = 1152). We excluded 10 mothers from the study due to inconsistency and/or inaccuracy of their questionnaires. During follow-up, most mothers  were followed by phone calls, with 112 mothers met by health extension workers, with 44 discontinuing due to neonatal death prior to discharge, and 60 lost to follow up.In this study, we found a high response rate of 99.14 %  of the mothers were between 25–35 year. Regarding education, 275 (23.9 %) of the study participants were unable to read and write . Of all mothers, 327 (32.2 %) were in the low monthly income category . In this study, we found a prevalence of 93 8.1 %) and 69 (6 %) pre-term and post-term births, respectively. Our participants showed high rates of pre-term and post-term births of 21 (22.5 %) and 18 (27 %) in Adwa and Adigrat hospitals respectively. Mothers in the medium and high income categories had lower risk of pre-term and higher risk of post-term births with relative risk ratio  respectively. Mothers, who were unmarried, widowed, and divorced [81 (7 %)], were at higher risk of post-term births  ], showed higher risk of pre-term delivery  over term births. In relation to maternal BMI, 119 (10.6 %) were in the underweight and 96 (8.6 %) overweight categories; however, overweight mothers were found to be at greater risk for a post-term birth   of neonate, length of neonate, monthly income, and marital status were independently associated with pre-term and post-term births relative to term births.The risk for pre-term births relative to term births in a multiple birth scenario  was 2.86 times greater relative to singleton births ; however, post-term birth was not associated with multiple births given the other factors in the model are held constant. Body length of neonates was also associated with pre-term infants, but not with post-term. Neonates, who were 46–56 cm and ≥56 cm at birth, were found to be 88 %  and 99.95 %  at lower risk of pre-term birth relative to term births. Post-term birth was not associated with length of the neonate. Relative to term births, overweight status was significantly associated with post-term births at a 3.88 times higher relative risk . Underweight maternal status relative to normal weight status showed a decrease in relative risk by a factor of 0.47 of delivering pre-term births relative to term births when other factors are held constant . Marital status was also associated with post-term births. Neonates from mothers who were either widowed, divorced, separated, or unmarried relative to married mothers were 2.43 times at higher relative risk for post-term birth than term births , but pre-term births were not significantly associated on the final models. Regarding income status, mothers in the medium income category were 74 % less relative risk to experience a pre-term birth than mothers in the low income category . Mothers in the high income category were 2.17 times more at relative risk for delivering a post-term birth relative with mothers in the low income category   were pre-term and only one was post-term birth. On bivariate analysis, pre-natal birth , history of abortion, history of stillbirth, low birth weight, and being a primiparae were associated with high risk of neonatal mortality . However, post-term births were not found to be associated with neonatal mortality  , were at higher risks of post-term births, which is inconsistent with previous studies. This might be because unmarried women could be more vulnerable to stressful life, heavy and risky activities, inappropriate weight gain and associated chronic disease; consequently, this may result in post term births. Hence, our study result may give insight for future research in determining the association of marital status with post-term birth.Our study found that, in our population, 38.23 % of neonatal deaths occurred because of pre-term births. Similarly, previous reports showed that 35 % of all neonatal mortality and 28 % of early neonatal mortality were related to pre-term births , 38. It After adjusting for potential confounders, pre-term births were associated with neonatal mortality but post-term births was not associated with neonatal mortality, which is congruent with previous studies , 5.The strength of this study is the use of a prospective cohort study which shows good validity and reliability of data. We were able to consider a large sample size which is good to detect effect on the predictors.One limitation of this study is that reliance on the gestational age determined using last menstrual period is known to overestimate or underestimate pre-term and post-term births compared to ultrasound , 39. AnoOverall, this study reported that the prevalence of pre-term and post-term births to be 8 % and 6 % respectively. Low reported income, underweight, multiple birth, and short body length of the neonate were found to be associated with pre-term births, while high reported income, overweight, and being a single mother were associated with post-term births. The study also reports that pre-term births significantly increase the risk of neonatal deaths.Considering that the global incidences of pre-term birth and its association with neonatal mortality, the World Health Organization recommends a 50 % reduction in pre-term births in developing countries like Ethiopia . TherefoThis study suggested that focusing on pre-term births rather than on post-term births is necessary to reduce neonatal mortality. Tigray Region Health Bureau, Ethiopia Ministry of Health, Ethiopian policy makers, program planners and other stakeholders who are engaged on improving neonatal health, including pre-term and post-term births, should be made aware of the predictors in order to reduce neonatal mortality and adverse birth outcomes.


Blood volume and haemoglobin (Hb) levels are increased by delayed umbilical cord clamping, which has been reported to improve clinical outcomes of preterm infants. The objective was to determine whether Hb level at birth was associated with short term outcomes in preterm infants born at ≤32 weeks gestation.Data were collected retrospectively from electronic records: Standardised Electronic Neonatal Database, Electronic Patient Record, Pathology (WinPath), and Blood Bank Electronic Database. The study was conducted in a tertiary perinatal centre with around 5,500 deliveries and a neonatal unit admission of 750 infants per year. All inborn preterm infants of 23 to 32 weeks gestational age (GA) admitted to the neonatal unit from January 2006 to September 2012 were included.The primary outcomes were intra-ventricular haemorrhage, necrotising entero-colitis, broncho-pulmonary dysplasia, retinopathy of prematurity, and death before discharge. The secondary outcomes were receiving blood transfusion and length of intensive care and neonatal unit days. The association between Hb level (g/dL) at birth and outcomes was analysed by multiple logistic regression adjusting for GA and birth weight (BWt).Overall, 920 infants were eligible; 28 were excluded because of missing data and 2 for lethal congenital malformation. The mean (SD) GA was 28.3 (2.7) weeks, BWt was 1,140 (414) g, and Hb level at birth was 15.8 (2.6) g/dL.P <0.001) in univariate analyses. Once GA and BWt were adjusted for, only death before discharge remained statistically significant; the OR of death for infants with Hb level at birth <12 g/dL compared with those with Hb level at birth of ≥18 g/dL was 4.1 . Hb level at birth was also significantly associated with blood transfusion received (P <0.01) but not with duration of intensive care or neonatal unit days.Hb level at birth was significantly associated with all primary outcomes studied  contains supplementary material, which is available to authorized users. Short-term outcomes of a preterm infant are influenced by the gestational age (GA), birth weight (BWt), sex, antenatal factors, and condition of the infant at birth and during the first few hours of life . InterveHct and haemoglobin (Hb) level could be improved by delaying clamping and/or by milking of the umbilical cord in term  and pretCurrently, there is a paucity of evidence regarding the relationship between Hb level at birth and morbidity and mortality of preterm infants irrespective of the mode of delivery and time of umbilical cord clamping. The objectives of our study were to evaluate the relationship between Hb level at birth and primary outcomes of IVH, NEC, broncho-pulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and death before discharge as well as secondary outcomes of receiving red blood cell transfusions, length of intensive care stay, and total neonatal unit days in preterm infants born at ≤32 weeks gestation.The study was conducted in a tertiary referral obstetric and neonatal unit in London, UK, with an average neonatal unit admission of 750 infants per year. All inborn preterm infants of 23 to 32 weeks GA admitted to the neonatal unit between January 2006 and September 2012 were included. Infants with a life-limiting major congenital abnormality  were excluded. Data were collected retrospectively from electronic records: Standardised Electronic Neonatal Database, Electronic Patient Record, Pathology (WinPath), and Blood Bank Electronic Database. Two researchers collected data independently (AK and DPS) and the data were verified by two senior researchers (JB and NA). Patient demographics , antenatal details , mode of delivery , Hb level (g/dL) at birth, admission temperature, blood transfusion details, and short-term outcomes  were collected.Ante-partum haemorrhage was defined as any per-vaginal bleed in the antenatal period, and chorioamnionitis was defined as presence of maternal fever (>38°C), maternal tachycardia (>100 bpm), foetal tachycardia (>160 bpm), foul smelling vaginal discharge, and preterm prolonged (>18 hours) rupture of membranes . Maternat-tests and χ2 tests were performed, respectively. Hb level at birth was categorised into five groups . The association between the Hb level at birth and primary outcomes as well as blood transfusion received was analysed by multiple logistic regression. For infants who survived to discharge, the association between Hb level at birth and length of intensive care and neonatal unit days was analysed by linear regression. As BWt is highly correlated with GA, standardised BWt z-scores were calculated using the 2010 UK-WHO growth chart [P value of <0.05 was considered statistically significant.Informed parent consent was not required as this was a retrospective study using anonymised routinely collected patient data. As required by the UK research ethics principles, the study protocol was reviewed by the hospital research and development committee and permission was granted to conduct the study (R&D Reference no. PA 1207). Data was analysed using statistical software STATA 12.0 . For continuous and for categorical variables P <0.01; Figure Overall, 920 infants were eligible for the study; 28 infants were excluded because of missing Hb level at birth n = 13) and outcome data (n = 15). Two infants were excluded because of major congenital abnormalities: one Trisomy 13 and one Trisomy 18. In total, 890 infants were included in the analysis with a mean  GA of 28.3 (2.7) weeks and BWt of 1,140 (414) g. The mean (SD) admission temperature was 36.6 (0.7)°C. The mean (SD) Hb level at birth was 15.8 (2.6) g/dL and Hct 46.5 (7.6)%. The Hb level at birth was positively associated with GA up until 30 weeks of gestation and BWt up until 1,500 g (3 and outP <0.01). After adjusting for GA and BWt, this association reduced but remained statistically significant  even after adjusting for GA and BWt. For the 787 infants who survived to discharge, the median (IQR) duration of intensive care and total neonatal unit days were 5 (2 to 22) and 42 (27 to 66) days, respectively. Hb level at birth was inversely associated with both intensive care days (P <0.01) and total neonatal unit days  as well as total neonatal unit (P = 0.17) days were not significant.Hb level at birth was significantly associated with the secondary outcomes of receiving a blood transfusion and duration of intensive care and neonatal unit stay Table . OverallWe have shown that lower Hb level at birth was significantly associated with the primary outcome of death before discharge in preterm infants born at ≤32 weeks of gestation independent of GA and BWt. This result is consistent with that observed by Hosono et al. , who demWe have shown that lower Hb level at birth was significantly associated with IVH but this was not significant when GA and BWt were adjusted for. The incidence of IVH (26.2%) was comparable to that reported in previous studies ,22. SimiLower Hb level at birth was associated with risk of NEC, ROP, and BPD, although this association was not significant when adjusted for GA and BWt in the present study. Increased Hb level at birth by delaying umbilical cord clamping has been demonstrated to reduce the risk of NEC but not ROP or BPD . The incOverall, 58.2% of infants in our study received a blood transfusion during their hospital stay, which is comparable that in other studies . Rabe etOne of the limitations of this study was that the actual timing of umbilical cord clamping was not available. However, during the study period, the standard practice was early cord clamping. We also did not collect details of antenatal steroids received by mothers in this study, which is likely to have an impact on the short-term outcomes and mortality of infants studied ; howeverTo our knowledge, this is the first study reporting a low Hb level at birth as an independent risk factor for mortality and probability of receiving blood transfusion in preterm infants born at ≤32 weeks gestation, irrespective of mode of delivery and time of umbilical cord clamping. Hence, more thought should be given to delayed cord clamping in preterm infants to improve the Hb level at birth, which in turn could reduce mortality and short-term complications of prematurity. The neonatal mortality prediction scores need to be investigated by incorporating Hb level at birth to see whether this increases the robustness of prediction of short-term outcomes and mortality in preterm infants. Further studies are required to investigate the association between Hb level at birth and long-term neurodevelopmental outcomes.


Results: Median FMI (preterm) increased from 0.4 kg/m2 at 30 weeks to 2.5, 4.3, and 4.8 kg/m2 compared to 1.7, 4.7, and 6 kg/m2 in term infants at 40, 52, and 64 weeks, respectively. Median FFMI (preterm) increased from 8.5 kg/m2 (30 weeks) to 11.4 kg/m2 (45 weeks) and remained constant thereafter, whereas term FFMI remained constant at 11 kg/m2 throughout the tested time points. Conclusion: The study provides a large dataset of length normalized BC indices. Followed longitudinally, term and preterm infants differ considerably during early infancy in the pattern of change in FMI and FFMI for age.Objective: Postnatal tissue accretion in preterm infants differs from those in utero, affecting body composition (BC) and lifelong morbidity. Length normalized BC data allows infants with different body lengths to be compared and followed longitudinally. This study aims to analyze BC of preterm and term infants during the first six months of life. Methods: The BC data, measured using dual energy X-ray absorptiometry, of 389 preterm and 132 term infants from four longitudinal studies were combined. Fat-mass/length Body composition measurements, particularly longitudinal measurements of lean and fat mass can be used to study the effects of nutrition on growth and developmental programming during the “critical period” of early infant development ,2,3. OptTotal weight gain, the most commonly used clinical tool for guiding nutritional management in preterms, fails to differentiate between proportionate gain in fat mass and lean mass. Fat-free mass (FFM) and fat mass (FM) considered separately are true estimates of nutritional status of the individual infant when compared to a reference. The use of body weight (BW) for normalization  fails to account for independent tissue accretion rates because %FM depends on the amount of FFM and vice versa. This approach is, therefore, not useful in the longitudinal assessment of body composition in neonates who undergo skeletal and muscle growth along with fat accretion. The %FM value underestimates true fat accretion in the presence of increasing FFM and overestimates the fat gain if there is poor tissue growth . To overAs body composition measurements are yet to become a part of bedside practice, reference data for newborns and infants are scarce. It was therefore the aim of this study to develop growth charts for length normalized body composition indices for preterm and term infants from birth until six months corrected age.Data were combined from 4 longitudinal studies involving a total of 521 infants, 22 to 42 weeks of gestation, from a predominantly Northern European descent population. Infants with major congenital, chromosomal, or metabolic anomalies and multiple births other than twins were excluded. Infants with severe chronic lung disease, sepsis, and NEC were also excluded. Infants were fed using the same feeding protocol in both units. During the study measurements, they were on full enteral feeds (150 to 170 mL/kg/day) with fortified breast milk or formula  for preterm and breast milk or formula  for term infants. Body composition measurements were taken after the infants had reached full enteral feeds and were clinically stable and growing at term corrected gestation and two further occasions up to a corrected age of 6 months. Post-feed measurements were obtained in a quiet, warm room during sleep, with the infants swaddled in cotton blankets without additional clothing. The details of the included studies are summarized in All studies were approved by local University Ethical Committee and the German studies were approved by the State Authority for Radiation Exposure and Control. Informed consent was obtained from parents prior to performing the measurement. Ethics Approval codes for Study 1 SNF# 3200-43586, study 2 is REB#: UV 07/01, study 3 is REB#: UV 26/98, study 4 is REB#: UV 70/03. Study 4 was registered with clinicaltrials.gov as NCT00196482.Weight was measured to the nearest 10 g by using a standard beam balance. Body length and head circumference (HC) were measured in triplicate to the nearest 0.5 and 0.1 cm, respectively. Body length was measured using a measuring board . HC was measured using a standard tape.2), bone mineral content (g), fat mass (g), lean mass (g), and percentage body fat (%). Fat free mass (FFM) is the sum of bone mineral content and lean mass.Body composition was measured using a whole body scanner  in single-beam mode. The X-ray tube was pulsed between high and low voltage (140 or 70 kV) at a rate of 50 Hz to produce dual-energy X-ray beams. A detector mounted above the infant measured the transmitted intensity on a pixel-by-pixel basis. External calibration was performed with a step phantom with known equivalent amounts of fat and lean tissue. Daily quality control scans were done using a manufacturer-supplied anthropometric spine phantom. For ethical reasons, duplicate measurements were not performed. All scans were performed on an infant platform with the infant in supine position by a whole-body scan procedure. The platform filtered the low-energy beam to improve system linearity in the small subjects and reduced the radiation dose. The scan time was approximately 5 min. The scans were analyzed using modified infant whole-body software . The device had been previously calibrated for neonatal body composition using chemical analysis in a sophisticated piglet model [i is the infant, t is the measurement, and Y is any longitudinal variable with missing data. The fixed effect represents the regression model for the population, while the random effect indicates that for each infant. The individual regression curves are allowed to deviate from the population regression curve with an intercept n sets of estimate n is the number of infants. With the estimate of coefficients, we can obtain the predictive model (2):To control for variation at the right tail due to missing values by dropout imputation was applied to replace missing data with plausible values predicted from regression models based on the observed data. The regression model used for our data is a linear mixed-effect model, given by (1)t distribution family and cubic splines as a smoothing technique. An automated iterative optimization process was used to find the degrees of freedom and fit the model by maximizing penalized likelihood [We used Generalized Additive Models for Location, Scale and Shape (GAMLSS) to estimate age-dependent percentile curves for all parameters. GAMLSS was one of the methods evaluated for developing the WHO child growth standards . GAMLSS kelihood .Among 521 infants recruited, 132 were terms, and 389 were preterms. Each observation was regarded as an independent data point for construction of the growth curves. We had a total of 858 measurements including 571 data points from preterm and 287 from term infants. The percentage of infants who had two, three, and four repeated observations were 17%, 21%, and 3% respectively. To compensate for the lower percentage of infants who had multiple measurements, we imputed our data as described in the Materials and Methods section. For term infants, we used imputation so that they had at least three measurements and, for preterm infants, at least four measurements. A mixed effect model was used to create the individual models so that the prediction was based on a subject-specific level. Thus, the infants who had only one measurement could not be predicted because of the limited information. After imputation, 1383 observations in preterm and 399 in term infants were used for the final data analysis. Median body weight and length of preterm infants remained consistently lower than term infants at the same postmenstrual age (PMA) . The heaLength in preterm infants increased by 0.84 cm/week and in term infants by 0.76 cm/week, but preterm infants remained shorter than did terms. Preterm HC increased by 0.52 cm/week, slightly higher than 0.41 cm/week in terms. Median length of preterm infants at 28, 38, 50, 60, and 70 weeks PMA was 36 cm, 46 cm, 56 cm, 63 cm, and 69 cm, respectively. Term infants had a median length of 49cm, 59 cm, and 66 cm at 38, 50, and 60 weeks PMA. The median centile for the head circumference in term infants increased from 34 cm at 38 weeks to 39 cm (50 weeks) and 42 cm (60 weeks). The corresponding centile in preterm infants was 25 cm, 33 cm, 39 cm, 43 cm, and 46 cm at 28, 38, 50, 60, and 70 weeks PMA, respectively.From birth to 50 weeks PMA, preterm infants acquired FM faster than term infants, beyond which the gain in FM was less than that for term infants a. Until 2) to 50 weeks PMA and then remained constant around 15 kg/m2 up to six months corrected age (2 and achieved up to 16 kg/m2 by early infancy. The BMI in preterm infants increased linearly with %FM (r2 = 0.55), FM (r2 = 0.58), FFM (r2 = 0.65), and bone mineral content (r2 = 0.57). In term infants, BMI increased linearly with %FM (r2 = 0.65), FM (r2 = 0.72), FFM (r2 = 0.63), and bone mineral content (r2 = 0.72).The median BMI of preterm infants increased from birth . A rapid increase in FMI and FFMI was noted in preterm infants from birth until TE, the latter being faster. FMI of both term and preterm infants increased with age until around 50 weeks, the rate of increase in preterms being much higher than terms. Subsequently, both groups slowed down indicated by the flattening of the curves  [r2 = 0.47) and %FM (r2 = 0.34) [r2 = 0.7) with %FM and FM than the BMI of preterm infants (r2 = 0.5). Compared with terms, the correlation between BMI and bone mineral content is also poor. However, there is a good correlation (r2 = 0.72) between BMI and FFM irrespective of gestational age at birth. This is likely, because neonates gain both FM and FFM simultaneously as they grow, and there is a substantial difference in the proportion of these compartments at different PMAs. BMI alone is insufficient in assessing the gain of FM and bone growth in preterm infants, whereas FMI and FFMI may be informative.Weight for age is considered to be a poor tool to assess growth when weight gain is disproportionate with linear growth . We have = 0.43)  and the  = 0.34) . We founFrom birth to TE, preterm infants gain FFM faster than FM. When considered in relation to overall weight gain, %FM increases, while %FFM decreases reciprocally. The faster gain in FFM relative to linear growth is evident from a steeper curve of FFMI compared to FMI over time. Two studies have published BMI curves in preterm infants, but there is no previous data on the change in FMI/FFMI with age in preterms. The initial rapid increase of FFMI supports the importance of aggressive nutrition to prevent protein and energy deficit. The more immature the infant is at birth, the higher is the protein: energy (PE) ratio needed to meet the goal of adequate weight gain relative to fat . ProvidiAt TE, preterm infants in our study were noted to have higher absolute FM than terms, but a lower length, HC, and FFM. A meta-analysis of eight studies that used recognized techniques of body composition measurements concluded that preterm infants at TE had greater %FM but significantly less FM than term infants at birth, in the methodology subgroup analysis of studies done with DEXA there was no difference in FM between the two groups . RoggeroThe preterm cohort in our study did not achieve the same in utero length and FFM at TE as term infants at birth, although they were a relatively healthy population on a standard diet, and the unit policy for nutrition was to avoid postnatal growth retardation. We used an up-to-date feeding regimen and assessment of growth and evaluation of nutrition was an integral part of daily rounds. In this respect, our data constitute normative distribution data. The observed differences between the growth of preterm and term infants may reflect a reduced longitudinal growth potential as a reaction to the switch from intra- to extra-uterine environment, as the optimal dietary regime for longitudinal growth has not yet been determined. This hypothesis is supported by the recent observation that unstandardized breast milk composition  and inapIn comparing the body composition centiles of our term cohort to reference data published from an Ethiopian cohort of healthy term infants, we noted a similar pattern of change in the first half of infancy, but our FMI centiles were higher . This diOur study had several limitations. Measuring body composition in the clinical setting is expensive, skill-based, and requires sophisticated equipment. Radiation exposure with DEXA makes it unsuitable for repeated measurements. The data points were not equally distributed over the observation period. The density of data points used in our study to plot the growth curves is higher in the first 3 months. Beyond 60 weeks, especially in term infants, less data points are available, so the interpretation is guarded. We tried to compensate for the low number of infants with multiple measurements by using imputation in our analysis. The current study was not designed to investigate the association between body composition in the first six months and later morbidity or neurodevelopmental outcome. Measurement of length in infants is challenging due to the need for extension of limbs. We did not include variables such as maternal BMI and postnatal factors that might affect growth in early infancy. Our data analysis does not differentiate grown infants from growth-restricted infants appropriately. Thus, it would be difficult to derive whether the growth trajectory in each sub-population is different. The longitudinal change in body composition, especially %FM, can be different in AGA and SGA preterm infants . It may Standardization of growth rates in preterm infants is needed. One multicenter, prospective study on 26- to 37-week-old infants concluded that human growth across different ethnic groups is similar and generalizable despite socioeconomic constraints . The autWe propose the use of FMI and FFMI centiles to standardize the evaluation of nutritional status in preterm infants. Measuring fat and lean mass in individual infants cannot give a true assessment of the nutritional status unless the linear growth is accounted for. FMI and FFMI are independent indices that allow longitudinal assessment of the change in fat and lean mass separately and thus help in the optimization of nutritional interventions. Knowledge of the expected changes in body composition of healthy preterm infants in early infancy can help us set more realistic goals for growth. Our study provides normative reference data for well preterm infants compared with term infants in the first six months of life. Future studies are needed to establish the value of longitudinal changes in body composition in predicting metabolic risk and neurodevelopmental outcome. It will also be interesting to investigate how nutritional management can be tailored to attain the desired changes in body composition.


This current study has been conducted to clarify the relationship between the mother's post-traumatic reaction triggered by premature birth and the mother-infant interactions. In this article, the precocious maternal feelings are described.A multicenter prospective study was performed in three French hospitals. 100 dyads with 100 very premature infants and their mothers were recruited. Mothers completed, at two different times self-questionnaires of depression/anxiety, trauma and social support. The quality of interactions in the dyads was evaluated.Thirty-nine percent of the mothers obtained a score at HADS suggesting a high risk of depression at the first visit and approximately one-third at visit two. Seventy-five percent of the mothers were at risk of suffering from an anxiety disorder at visit one and half remained so at visit two. A “depressed” score at visits one and two correlated with a hospitalization for a threatened premature labor. We noted a high risk of trauma for 35% of the mothers and high interactional synchrony was observed for approximately two-thirds of the dyads. The mothers' psychological reactions such as depression and anxiety or postnatal depression correlate strongly with the presence of an initial trauma. At visit one and visit two, a high score of satisfaction concerning social support correlates negatively with presence of a trauma. A maternal risk of trauma is more frequent with a C-section delivery.Mothers' psychological reactions such as depression and anxiety correlate greatly with the presence of an initial trauma. The maternal traumatic reaction linked to premature birth does not correlate with the term at birth, but rather with the weight of the baby. Social support perceived by the mother is correlated with the absence of maternal trauma before returning home, and also seems to inhibit from depressive symptoms from the time of the infant's premature birth. In January 2008, in an article titled, “Preterm: What Can be Done?”In this article we want to discuss very preterm births or births occurring before 32 Gestational Weeks (GW). An infant, who is born very preterm, worries neonatologists as to his/her viability and his/her pathologies for the short-term outlook. Premature births are considered to be responsible for 75% of perinatal mortality, and more than 75% of the long-term perinatal morbidity Our intervention in the maternity and neonatal wards sensitized us to the immediate parental reaction of the premature birth. Among these reactions, most often the parents are what they call “stressed”, which is the origin of trauma. The unexpected confrontation with a baby is far from what the parents had anticipated; the shock experienced during a rapid chain of events taking place, an experience of emptiness when the baby is placed in the intensive care unit, the feeling of powerlessness when facing the real risk of the infant's death, the invasive treatments, etc. The parents worry about the viability and future of their premature infant. Their parental reactions and more specifically those of the mother facing the premature birth could have repercussions on the development of the infant, due to complex and atypical interactions.These observations have driven us to elaborate on a hypothesis that distinguishes itself separate to the lesion model commonly applied to premature infants, and shifts the psychopathological approach to the post-traumatic reaction of the mother following the premature birth; it repositions the question of behavioral disorders of the child in the mother-infant interactions. In a second phase, we think that a premature birth can bring about post-traumatic symptoms as described in the post-traumatic stress state, and most notably in the mother. Therefore, this reaction could have effects on the mother-infant interactions.We have conducted this current study to clarify the relationship between the mother's post-traumatic reaction triggered by the premature birth and the mother-infant interactions. In this article, our research aims to describe precocious maternal feelings when the mother has to face the premature birth of her infant.This present study is part of the larger research program that was a multicenter prospective study performed in 3 French hospitals  between January 2008 and January 2011. The follow-up period was 18 months for each participant. The entire research program covers 5 visits: the first visit, in the maternity service following the birth of the child, and the second visit, in the neonatology service, right before the discharge. The three following visits with the same design took place at 6, 12 and 18 months, within the framework of the systematic tracking of premature babies within the early medico-social actions' center (CAMSP). The study described in this article analyses the results of the first two visits of the research program.All the preterm infants who were admitted to one of the NICU of the 3 investigation centres  from January 2008 to January 2010 and who matched our principal inclusion criteria  were considered for inclusion in the study. Exclusion criteria were for the mothers with an evident psychiatric illness, drug or alcohol abuse, aged <18 years, and language barriers; for the newborn: unfavourable vital prognosis evaluated with the Perinatal Risk Inventory The 3 maternities and NICU are levels 3B  or 3C . These definitions are based on the American Academy of Paediatrics report on NICU levels of care Given the observational nature of the study, which is not governed by French biomedical law, it could not be approved by the Committee for the Protection of Persons. Given the guidelines of publishers focused on the ethics of the investigations published, CHU de Reims has established an IRB since 2007. This study has been approved globally for all the centers  and all the participating patients. It received the approval of the local Institutional Review Board: IRB of Reims University Hospital. The study was conducted in compliance with good clinical practice, as indicated in the Declaration of Helsinki. Written consent was obtained from all the patients after providing specific information on the study. After a premature birth below 32 gestational weeks, NICU pediatricians contacted our research team and one of the practicians/author in charge of the clinical part of the research, met the mother and her baby to introduce the research program. Therefore, some of the authors have been in contact with participants as expected in a clinical research. Patients were free to refuse to take part in the study or to withdraw from it at any stage on simple request, without any alteration to the care provided to them. Data collection was made anonymous.Sociodemographic variables recorded during the study were age, marital status, level of education and profession.For the mothers, clinical data were: number of childbirths, number of pregnancies, medical history of the pregnancy , obstetric history , delivery conditions , multiple pregnancy (number of babies), anesthesia type , personal histories .For the infants, clinical data were: date of birth, term of birth, weight, size, cranial perimeter, Apgar score at five and ten minutes, necessity or not of a neonatal resuscitation, method of feeding .For the dyads, clinical data was the presence or absence of specific care .The design of this study's two visits is described in mPPQ  For the mothers, the evaluation of the mother's trauma was done by using In order to compensate for the biases identified, we also evaluated the maternal co morbidity using:HADS The EPDS The The Social Support Questionnaire (SSQ) of SarasonPerinatal Risk Inventory (PRI)For the infants, we identified some who were at risk of significant developmental abnormalities by using the In the dyad, Censullo's DMC  instrument The quantitative variables are the average, the standard deviation, and the minimal and maximal values. The qualitative variables are the number of observations and the associated frequency. The search for a link between the quantitative and qualitative variables was accomplished by using the Mann-Whitney/Wilcoxon or Kruskal-Wallis test. We did Spearman's correlation analysis between two quantitative variables. For all statistical tests, a p value<0.05 was considered statistically significant. Analyses were performed using the SAS software .We included 100 dyads (100 babies and their mothers). The average age of the mothers is just under 30 years old  and work (69%). Most of the mothers (88.8%) have been hospitalized for a risk of premature labor. The majority of them (58.2%) have obstetrical antecedents . It is generally a first (48%) or a second pregnancy (32%), with a small majority of births by C-section (54%) and a rather homogeneous distribution of the method of feeding . The average term is from 29 weeks of amenorrhea and 6 days  and did not correlate with the babies' birth term (p = 0.64) or birth weight (p = 0.55) at visit two.Our first results show that 39% of the mothers obtained a score at HADS suggesting a high risk of depression at the first visit and approximately one-third at the second visit . HADS anxiety sub-score reveals that 75% of the mothers were at risk of suffering from an anxiety disorder at visit one and half (50%) were still at risk at visit two We noted a high risk of trauma in 35% of the mothers and a high interactional synchrony score was observed for approximately two-thirds (66%) of the dyads.Access to services to a psychologist or a psychomotor therapist was offered to 30.1% of the mothers and their babies.In The mothers' psychological reactions at visit one and two such as a high risk of depression and/or anxiety disorder or postnatal depression at visit two correlated strongly with the high probability of initial trauma (p<0.0001).At visit one (p = 0.03) and visit two (p = 0.04) a high score of satisfaction concerning social support correlates negatively with a high score on the PPQ scale (which indicates a mother's trauma). A high score obtained on the PPQ is significantly (p = 0.0092) more frequent with a C-section delivery  and the majority of the mothers with a high risk of trauma (PPQ's high score) belong to the dyads having specific psychological care with psychologists or psychomotor therapists (p = 0.0026).The babies' health characteristics correlate with the presence of an initial trauma: state of health of the newborn (PRI score to V2) (p = 0.04), his or her's evolution of state of health (p = 0.04) and his or her birth weight (p = 0.03).We looked for correlations between the quality of interactions in the dyads  and the characteristics collected on Visit 1 as: pregnancy conditions , delivery conditions , babies' clinical characteristics , and the infant's measures (PRI score), and also the mothers' measures  for evaluating states of mind of the mothers; but we did not find any significant correlation.As clinicians, it's essential to underline the complexity of the subject. Prematurity, depending on the term at birth, takes many different forms. Many innate and acquired factors, outside of the gestation period itself, intervene in clinical prematurity. It would be simplistic and inexact to consider clinical prematurity as a well-defined entity. Also, for facilitating the reading, in this discussion, we will use the terminology of depressed or anxious for mothers with high scores on specific self questionnaires (HADS and EPDS), allowing them enough substantial to assess anxious and depressive symptomatology, especially by using the cutoff mentioned in the method paragraph.The general characteristics  of our population were comparable with other studies also addressing the maternal reactions after a premature birth We didn't find any significant correlations between maternal distress and dysfunctional interactions, whereas our hypothesis was that a maternal traumatic reaction would be correlated with difficulties in parent-child interactions, especially as the general sense of this hypothesis has been partially confirmed by some studies Nonetheless, the findings of this study about precocious, maternal and emotional reactions are interesting and consistent with previous studies which suggest that the premature birth of an infant has repercussions on maternal emotional responses A large majority of mothers (75%) present a post-natal symptomatology of anxiousness in the early post-natal period following the premature birth of their child and before their child goes home. The results are in concordance with a New Zealand study Traumatism, measured by the PPQ scale after the birth and before the return home, is objective among 35% of the mothers. Our results confirm those of previous studies According to our results and the results of another recent study Our results show a correlation between the somatic state of health of the baby quantified by the Perinatal Risk Inventory (PRI), and the maternal trauma (measured by the PPQ). During the premature infant's hospitalization in the NICU, the parents are worried and are constantly listening to the information being relayed to them several times a day by the professionals in regards to the state of their infant's health. Daniel Sibertin-Blanc Social support perceived by the mother, both in the number of people recognized to support the mother and the quality of this support is essential and is significantly correlated with the absence of maternal trauma before returning home, and also seems to protect from depressive symptoms from the time of the infant's premature birth.One of the most interesting results on the clinical level of our research involves the support given to mothers in neonatal units. The identified mothers as having psychological distress in the aftermath of the premature birth through the study's questionnaires  are those who have benefited from support. They benefit from care by a psychologist or psychomotor therapist during the hospitalization of their infant in the NICU, without the results of their self-questionnaires being known by professionals.By not using structural interviews for the mothers' assessments at the time of the inclusion to respond categorically to the mother exclusion criteria, and also to diagnostic depression symptoms in the two visits, is a main limitation of our study. However, structured assessments might have been too intense, even too emotionally difficult for the mothers having just experienced the premature birth of their infant, and have to continue to live with this supposed traumatic event. About the representation of our population, the location restrictions (explained in the “Sample and Procedure” paragraph), could appear as a limitation to our study, because our population most probably live in big cities or nearby. Concerning our data collection, we didn't have any data concerning mother anxiety and or depressive symptoms before the infant's birth, so this remains a limitation for us to discuss our results. Also it would have been pertinent to investigate the mother's smoking habits, so as to correlate to the infant's characteristics. At least, as for any study, a control group would have permitted the results to be more consistent.The mother is the central figure of anxiety related to premature birth. She experiences and expresses her feelings about it (not necessarily), and it is up to the clinical staff to hear what she is feeling. In our study, we observed that professionals have been sensitive to the expression of maternal suffering, and have proposed specific support. This kind of intervention is now well described in literature (38), so we believe that being able to express suffering is a good prognosis in the evolution of trauma for the mother.


Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth  and low birth weight (<2500 g) with childhood asthma outcomes.P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain . Preterm birth was positively associated with an increased risk of preschool wheezing  and school-age asthma  independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing  and school-age asthma .Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth. Respiratory diseases have at least part of their origins in early life. It has been hypothesized that adverse exposures in fetal and early postnatal life might influence lung growth and development, which could lead to persistently smaller airways and impaired lung function. These developmental adaptations might predispose the subject to asthma and chronic obstructive pulmonary disease in childhood and adulthood.Most children with low birth weight show catch-up growth in infancy.Therefore we conducted a meta-analysis of individual data from 147,252 children up to the age of 10 years participating in 31 European cohort studies to assess the strength, consistency, and independence of the associations of gestational age, birth weight, and infant weight gain with the risk of preschool wheezing and school-age asthma. We specifically explored the combined effects of gestational age, birth weight, and infant growth.www.chicosproject.eu, www.birthcohortsenrieco.net, www.ga2len.org, and www.birthcohorts.net assessed until May 29, 2012). We invited the 52 potentially eligible cohorts, of which 41 responded to our invitation. From those, 31 cohorts agreed to participate, leading to 147,252 children with information on at least 1 early growth characteristic and respiratory outcome (see the flow chart shown in www.jacionline.org). All original cohort studies were approved by their local institutional review boards and provided written informed consent for using their data. Anonymized data sets were stored on a single central secured data server with access for the main analysts  only.European population-based birth and mother-child cohorts participated if they included children born between 1989 and 2011, had information available on at least gestational age and weight at birth and preschool wheezing (1-4 years) or school-age asthma (5-10 years), and were willing and able to exchange original data. We identified 52 European cohorts selected from the existing collaborations on childhood health or asthma-related outcomes (www.jacionline.org) and used as continuous and categorical variables. Infant weight gain in the first year was defined as the difference between weight at 1 year  and weight at birth divided by the exact number of months between those 2 measurements. We created gestational age–adjusted birth weight standard deviation scores (SDS) based on a North-European reference chart.www.jacionline.org.Information about birth weight, gestational age at birth, and weight in the first year of life per cohort was obtained by using measurements, medical registries, or parental questionnaires .www.jacionline.org). We considered breast-feeding status , lower respiratory tract infections , and eczema  in the first 2 years of life as potential intermediates (description of available intermediates per cohort is shown in www.jacionline.org).We included covariates based on known associations with childhood asthma from previous studies.First, we performed a 1-stage random-effect meta-analysis on an individual participant's data to examine the separate and combined associations of gestational age, birth weight, and infant weight gain with preschool wheezing and school-age asthma. For this analysis, individual participants' data from all cohorts were included in 1 multilevel analysis and were analyzed, simultaneously taking into account clustering of participants within studies.Q and I2 values, which varied per analysis.Second, we performed a 2-stage random-effect meta-analysis to examine the associations of gestational age at birth, birth weight, and infant weight gain and dichotomized preterm birth and low birth weight with the risks of preschool wheezing and school-age asthma. For this analysis, which was used for the clinically relevant associations of preterm birth and low birth weight, we first used logistic regression models to calculate effect estimates per cohort and then used calculated pooled odds ratios (pORs) from the per-cohort effect estimates.The cohort-specific information about the main exposures and outcomes are shown in A and B). Almost all children born before a gestational age of 40.0 weeks had an increased risk of preschool wheezing and school-age asthma. Birth weight SDS were not consistently associated with childhood asthma outcomes (C and D). Results for birth weight in grams without taking gestational age into account are shown in www.jacionline.org, showing an inverse association. We observed a positive association of infant weight gain with preschool wheezing and school-age asthma. Compared with children with a weight gain of between 500 and 600 g/mo (largest group), children with a mean infant weight gain of between 900 and 1000 g/mo had the highest risk of preschool wheezing  and school-age asthma . The overall results for the linear associations of gestational age at birth, birth weight, and infant weight gain from the 1-stage meta-analysis of individual participants' data were similar to those from the 2-stage meta-analysis of individual participants' data (results are shown in www.jacionline.org). The results from the confounder model were not materially different from those from the crude model. Also, additionally adjusting the confounder model for potential intermediates  did not materially change the effect estimates (results are shown in www.jacionline.org). Also, we observed similar effect estimates for preschool wheezing and school-age asthma after excluding cohorts one by one, indicating no disturbing effect of any particular population (data not shown). After exclusion of the Danish National Birth Cohort, the largest cohort in our meta-analysis (COPSAC) and a high-risk asthma and atopy cohort, we also did not observe major changes in effect estimates (data not shown).In the 1-stage meta-analysis of individual participants' data, we observed consistent inverse associations of gestational age at birth with the risk of preschool wheezing and school-age asthma. Compared with term-born children, children born before 28 weeks of gestation had the highest risk of preschool wheezing  and school-age asthma , between gestational age and infant weight gain , and between birth weight and infant weight gain . We performed stratified analyses and an overall test for interaction. In each analysis the largest group was used as the reference group. For the combined effect analysis of gestational age at birth and birth weight SDS, we observed a higher risk of preschool wheezing among children born at an earlier age with higher birth weight SDS, but the overall interaction term with birth weight SDS was not significant (A). Similarly, we observed a tendency toward a higher risk of school-age asthma in children born at an earlier gestational age with higher birth weight SDS . The highest risks for school-age asthma were observed for children born before 32 weeks of gestation with a moderately high birth weight SDS  and with a high birth weight SDS  compared with children born at term with a normal birth weight SDS. The P value for interaction between gestational age at birth and infant weight gain for the associations with preschool wheezing and school-age asthma were 0.05 and 0.23, respectively (C and D). We observed the highest risk of preschool wheezing and school-age asthma among children born before 32 weeks of gestation with an infant weight gain of more than 700 g compared with children born at term with a normal weight gain . The interactions between birth weight SDSs and infant weight gain for the associations with preschool wheezing and school-age wheezing were not significant (E and F). As a sensitivity analysis, we performed our analysis in Northwest European cohorts only and observed similar results (results are shown in www.jacionline.org). The results of complete case analyses were similar (data not shown). Also, we observed similar effect estimates for preschool wheezing and school-age asthma after excluding cohorts that used parental reports of birth weight or non–ISAAC-based questions on wheezing. With this exclusion, only the youngest and lowest weight-for-gestational-age groups tended to show stronger effects (see www.jacionline.org). This indicates that differences in data collection did not lead to systematic differences in effect estimates.Next, we explored the combined effects of gestational age at birth, birth weight SDS, and infant weight gain. The significant correlations were between gestational age and birth weight . These associations were independent of birth weight. The population-attributable risk of preterm birth was 1.96% for preschool wheezing and 2.14% for school-age asthma. Compared with children with a normal birth weight, those with a low birth weight (<2500 g) had an increased risk of preschool wheezing  and school-age asthma . These associations were stronger without adjustment for gestational age at birth (results are shown in Results from the 2-stage meta-analysis focused on the associations of preterm birth and low birth weight with childhood asthma outcomes are shown in Results from this large-scale meta-analysis of individual participants' data suggested that younger gestational age at birth and higher infant weight gain were associated with increased risks of preschool wheezing and school-age asthma. The associations of low birth weight with childhood asthma outcomes were largely explained by gestational age at birth. The highest risk for childhood asthma outcomes was observed among children born before a gestational age of 32 weeks with high infant weight gain.Adverse exposures in fetal and early postnatal life can lead to developmental lung adaptations, such as persistently smaller airways and impaired lung function. These developmental adaptations might predispose the patients to obstructive pulmonary diseases in childhood and adulthood.Jaakkola et alCombining childhood asthma outcomes from different age periods is not easy. Asthma is a difficult clinical diagnosis and cannot easily be diagnosed in children younger than 5 years. Many studies used asthma-related outcomes, such as wheezing and shortness of breath, as main outcomes in children. Wheezing seems to be the strongest risk factor for childhood asthma.Mechanisms underlying the associations of factors in early life with asthma outcomes in later childhood might include smaller airways and lungs.We performed a large meta-analysis of individual participants' data from many birth cohorts throughout Europe. We did not rely on published data, which limits any potential publication bias. The large number of participants enabled us to assess small effects and to adjust for various potential confounders. We presented results from random-effects models, which allow heterogeneity in the true effect estimates between different populations and take between-study variation into account. Another strength is that information on exposures in early life was collected from records and did not depend on long-term participant recall. Misclassification of gestational age is always possible because of the large number of pregnant women who did not know their exact gestational duration.Children born at a younger gestational age at birth or higher infant weight gain have increased risks of childhood asthma.Younger gestational age at birth and higher weight gain in infancy were associated with childhood asthma outcomes. The association of lower birth weight with childhood asthma outcomes was largely explained by gestational age at birth. Further studies are needed to evaluate the effects of early-life characteristics on specific asthma-related outcomes, such as lung function, airway size, and airway inflammation.


Globally, about 15 million neonates are born preterm and about 85% of global preterm birth occurs in Asia and Africa regions. We aimed to estimate the incidence and risk factors for preterm birth in a rural Bangladeshi cohort.Between June 2007 and September 2009, community health workers prospectively collected data from 32,126 mother-live-born baby pairs on household socio-demographic status, pregnancy history, antenatal care seeking and newborn gestational age determined by recall of date of last menstrual period.Among all live births, 22.3% were delivered prior to 37 weeks of gestation (i.e. preterm); of which 12.3% were born at 35–36 weeks of gestation (late preterm), 7.1% were born at 32–34 weeks (moderate preterm), and 2.9% were born at 28–31 weeks of gestation (very preterm). Overall, the majority of preterm births (55.1%) were late preterm. Risk of preterm birth was lower among women with primary or higher level of education , women who sought antenatal care at least once during the index pregnancy , and women who had completed all birth preparedness steps . In contrast, risk of preterm birth was higher among women with a history of child death , who had mid-upper arm circumference (MUAC) ≤250 mm, indicative of under nutrition , who reported an antenatal complication , and who received iron-folic acid supplementation for 2–6 months during the index pregnancy .In resource poor settings with high burden of preterm birth, alike Bangladesh, preterm birth risk could be reduced by close monitoring and/or frequent follow-up of women with history of child death and antenatal complications, by encouraging women to seek antenatal care from qualified providers, to adopt birth preparedness planning and to maintain good nutritional status. Additional research is needed to further explore the associations of antenatal iron supplementation and maternal nutritional status on preterm birth. Recent global estimates suggest that more than 1 in 10 or an estimated 15 million babies born in 2010 were preterm, of which more than 1 million died as a result of preterm birth and related complications. PretermIdentification of at-risk women and their risk factors for preterm birth is important for targeting of services and initiation of risk-specific interventions and/or preventive measures. Study of risk factors might also provide important insights leading to new discoveries for prevention and management of preterm births. We describe the burden and associated risks factors of preterm birth in a cohort of rural Bangladeshi women.We analyzed prospectively collected data from a large community-based cluster-randomized trial conducted in Sylhet district of Bangladesh. Data for our study were primarily collected to evaluate the impact of two regimens of umbilical cord cleansing - single-day vs. 7-day - with 4.0% chlorhexidine solution on all-cause neonatal mortality and incidence of cord infections,12.upazila) of Sylhet district  in north-eastern Bangladesh with an estimated total population of 546,000 people. The study area was divided into 133 working units (clusters) each served by a female community health worker (CHW). CHWs implemented the interventions and collected data from respondent women and their babies.The study was implemented during June 2007- September 2009 in 22 unions  in 3 rural sub-districts , messages on birth and newborn care preparedness (BNCP), and advice on essential newborn care  and on neonatal danger sign recognition and care-seeking,13. At eAll reported live births within the study area for which data was available on the first day of the last menstrual period (LMP) were included in this study. Reported stillbirths and abortion  were excluded. Pregnancies terminated before 28 weeks of gestation were defined as miscarriage/abortion. A stillbirth was defined as an infant born without any signs of life  at 28 weeks of gestation or later.Socio-demographic and economic information  and previous pregnancy history were collected by CHWs using a structured instrument in face-to-face interviews during the enrolment visit. Relevant data on antenatal care seeking, compliance with BNCP, consumption of supplied iron tablets, TT immunization dosage and antenatal complications  were also collected from all women during BNCP visits or the first postpartum visit. Compliance with BNCP was categorized as “fully compliant” , “partially compliant” (1–5 steps), or “non-compliant” (0 steps). CHWs measured the mid upper arm circumference (MUAC) of the enrolled mothers during enrollment visits. Data on antenatal complications (except fever) were self-reported by respondent women. CHWs measured axillary temperature from women who reported having fever during the interview.The primary outcome was preterm birth as defined by the World Health Organization as: “Any birth before 37 completed weeks of gestation or fewer than 259 days since the first day of the women’s LMP”. GestatiCHWs received 6 weeks of classroom-based and hands-on supervised training. These training sessions followed a structured curriculum including skills development for behavior change communication, provision of BNCP and essential newborn care, clinical assessment of neonates, and identification and management of sick newborns using an algorithm adapted from Integrated Management of Childhood Illness. Quality of data collected by CHWs was ensured through direct supervision by respective Field Supervisors. Supervisory visits and standardization exercise sessions were organized routinely to ensure quality of data collected. Every reported neonatal death was confirmed by a repeat visit to the household by a supervisory staff. A sample (5%) of newborns who survived the neonatal period was revisited for quality assurance of vital status reporting by CHWs.CHWs submitted data forms to their supervisor, who checked the forms for completeness and consistency. Data entry system was custom-designed with built in range and consistency checks. Field verifications were conducted to resolve identified inconsistencies and incompleteness if required.Births at ≥37 weeks were classified as term births. Preterm births were sub-categorized as: 1) Very preterm (28 – 31 weeks of gestation), 2) Moderate preterm (32–34 weeks of gestation) and 3) Late Preterm (35–36 weeks of gestation). We estimated the incidence of preterm birth by dividing all live preterm births, whether singleton, twin or higher order multiples, by all live births in the population; 95% confidence intervals (CI) were calculated for the estimated proportion of preterm birth incidence.a priori, the potential risk factors for preterm birth into three groups: 1) Proximal factors: antenatal care seeking and antenatal complications during the index pregnancy; 2) Intermediate factors: previous pregnancy history; 3) Distal factors: socio-demographic characteristics. We constructed a wealth index score and progressively adding previous pregnancy/birth information [Model2] and thereafter distal/socio-demographic factors) [Model3]. The association (risk ratio) between potential risk factors and preterm birth was modeled using binomial regression with a log link function; generalized estimating equations with exchangeable correlation structure were used to adjust standard errors to account for clustering[Covariates showing moderate strength of association . The study was registered at ClinicalTrials.gov (NCT00434408).A total of 37,630 pregnancy outcomes, including 35,908 live births Figure .The majority 61.7%) of respondents was in the 20–29 year age group and most of them (95.5%) were Muslim (Table .7% of reThe index pregnancy was fourth or higher order for 42.4% of respondent women (Table Most women 57.3%) sought antenatal care at least once, 79.5% reported receiving any dose of tetanus toxoid (TT) immunization, and 89.9% consumed iron-folic acid (IFA) during the index pregnancy .Bivariate association of each of these proximal factors with preterm birth risk is presented in Table Risk estimates from bivariate analyses for proximal factors, specifically for any antenatal visit, any antenatal complication, birth preparedness steps, and any dose of TT immunization, were not changed significantly after adding all proximal factors into the multivariate Model-1 Table . Associath on the top-10 country list for high preterm birth rates in 2010[We have presented the incidence of and risk factors for preterm birth using prospectively collected data from a large cohort of 32,126 pregnant women in a rural population of Bangladesh who delivered a live-born infant. Among live-born babies, more than one-fifth was preterm 22.3%) and the majority of preterm births (55.1%) were late preterm. If we could support these pregnancies to continue an additional 1–2 weeks, that could lead to a substantial decrease in the preterm birth toll and burden of disease due to preterm. A small of number of behavioral , clinical  and health system interventions  have been shown to reduce the preterm birth rate[.3% and t in 2010,24) and  in 2010.Maternal factors increasing the risk of preterm birth in our population included socioeconomically poorer status, poor nutritional status (lower MUAC), antenatal iron consumption, history of a previous child death, multiple pregnancies and having any antenatal complication. Factors which were protective for preterm birth included practicing all 6 BNCP steps, first child, education at primary level (grade 5) or above, TT immunization, and female sex of the baby. Study results from Ahmedabad, India reportedMaternal nutritional status before and during pregnancy may contribute to the risk for preterm birth. In the Our finding on consumption of IFA during pregnancy as a risk factor for preterm birth differs from conventional knowledge and previous study reports. Traditionally, gestational anemia has been prevented with the provision of daily iron supplementation throughout pregnancy. ResultsHowever, many studies also fail to show beneficial effects of antenatal iron supplementation on pregnancy outcomes. Cochrane review and meta-analyses-37 conclEducation is the dimension of socioeconomic status that most strongly and consistently predicts health status,44. A loStudies from several developing countries have found that “no ANC visit” is a significant risk factor for preterm birth, ranging from 1.3 times to 7 times higher than for women having any ANC visit,46,49,50The main strengths of this study are that we analyzed prospectively collected, population-based data from a large sample  of live births. In addition, since we collected data through visiting study women at home, the common concerns about selection bias in hospital-based studies from developing countries were avoided.A limitation of our study was reliance on LMP to determine gestational age. Some of the common criticisms of this method are possible inaccurate recall of LMP, including heaping on certain dates, and reliance of the calculations on a “normal” menstrual cycle of 28 days with ovulation on day 14-55. HoweSince preterm birth is the leading cause of neonatal deaths globally, and theIn addition to demonstrating high burden of preterm births in a rural area in Bangladesh, our study has identified several risk factors for preterm birth, and thus can inform resource planning and design of community-based interventions to reduce mortality from preterm birth. Recognizing that the majority of preterm births are late or moderate preterm , even small reductions in the rates of these categories of preterm birth would mean sizable decreases in the number of overall preterm deliveries. From a program planning perspective, it is important to take risk factors for preterm birth into account, since addressing women at higher risk could help reduce late and moderate preterm births. Focusing on factors shown to reduce risk for preterm births  also can help community-based programs to reduce the preterm birth toll at population level. Our finding that preterm birth was associated with IFA consumption during pregnancy reveals one critical area for future studies. Better understanding of the relationship between maternal nutritional status and risk of preterm birth is needed. Overall, given the range of variability of preterm birth risks among ethnic and socioeconomic groups, similar studies should be conducted to generate more population-based evidence on burden and risk factors of preterm birth in developing countries.ANC: Antenatal care; BMI: Body mass index; BNCP: Birth and newborn care preparedness; CDK: Clean delivery kit; CHW: Community Health Worker; IFA: Iron-folic acid; LMP: Last menstrual period; MUAC: Mid-upper arm circumference; ProjAHNMo: Project for Advancing Health of Newborns and Mothers; TT: Tetanus toxoid.The authors declare that they have no competing interests.RS, AHB and LCM were primarily responsible for conceptualizing and designing this study. LCM, AHB, SEA and GLD were responsible for protocol development and study design of the main study . AHB and SEA were the principal investigators of the ProjAHNMo Chlorhexidine study. RS, IM, SMR, GLD, LCM were co-investigators of the main study. RS conducted data analyses and drafted the manuscript. RRT, JAA, DM and NB contributed in literature review, interpretation of results and manuscript editing. DM and NB assisted in data management and analyses. All authors provided critical intellectual input in editing and revising the manuscript and approved the manuscript for submission.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/112/prepubReported antenatal complications and risk of preterm birth.Click here for file


We hypothesized that deterministic tractography is practical and sensitive to changes in the complex nigrostriatal and nigropallidal pathway (NSP) in Parkinson’s disease (PD). Using diffusion tensor imaging (DTI) tractography, we investigated the NSP to evaluate differences between PD patients and controls, and examined their clinico-radiologic correlation. Structural and DTI brain scans were obtained in 40 subjects . We isolated the NSP using a user-friendly DTI toolkit based on deterministic brute-force tractography. DTI parameters of fractional anisotropy (FA), mean, axial, and radial diffusivity, and streamline count of the NSP were measured. Average FA (p < 0.01) and streamline count (p < 0.001) were significantly lower in the PD compared to control group. Mean diffusivity and radial diffusivity were significantly higher in the PD group (p < 0.05). Average streamline count correlated with the United Parkinson’s Disease Rating Scale motor score (p < 0.05). Point-to-point FA profiles of the tract demonstrated peak divergence between PD and control towards the tract midpoint rather than the distal grey matter. Our findings demonstrated a clinically and radiologically practical application of DTI tractography to the NSP in PD, without requiring complex imaging sequences for anatomical localization or segmentation software. The hallmark of Idiopathic Parkinson’s disease (PD) is severe loss of dopaminergic projection neurons of the substantia nigra (SN)2in vivo using computer algorithms, improving anatomical specificityOptimizing imaging methods to facilitate PD diagnosis and tracking disease progression has been a challenge. Diffusion tensor imaging (DTI) has emerged as a promising surrogate marker for PDWe hypothesize that the NSP is dysregulated in PD and examining it with tractography, to obtain more data points as opposed to sampling the SN alone, could quantify neurodegeneration in PD with greater sensitivity. The potential of deterministic tractography as an alternative to probabilistic tractography also needs to be further explored given its advantages for clinical applicability. We utilized a user-friendly DTI toolkit based on deterministic brute-force tractography to evaluate for differences in the NSP pathway between PD patients and healthy individuals, and examined their clinico-radiologic correlation.The characteristics of subjects and averaged NSP tract parameters are depicted in Average streamline count correlated with the UPDRS . Point-to-point FA profiles of the NSP tract demonstrated peak divergence between PD and control groups towards the tract midpoint rather than the distal grey matter . UnivariWe demonstrated a feasible application of deterministic DTI tractography to investigate the NSP pathway in PD. The tool allowed for easy localization of the SN and GP, and visualization and manipulation of the NSP tract complex. Our excellent inter-rater reliability values attest to reproducible and accurate seed-point positioning. Significant differences between PD and control in the diffusion parameters were obtained despite limited ability of deterministic tractography to resolve branching and crossing fibers. The NSP complex of PD patients had significantly lower FA than in healthy controls, and higher MD, AD and RD values, consistent with reduced fiber integrity from chronic white matter degeneration4There was greater variation in point-to-point FA profiles towards the middle of the NSP tract compared to distal points in SN and lentiform nucleus. The findings in the lentiform nucleus are consistent with most DTI studies using manual ROI and voxel-based morphometry, which have found no difference in FA in the GP and putamen4Previous tractography studies in PD that included the NSP tracts used the FMRIB software library (FSL) for image processing, segmentation of subcortical structures, and probabilistic tractography9et al.12Our results are strongly consistent with the observations by Zhang Limitations of our study include a small sample size that was insufficient to run multiple regression models accounting for age and gender, although our PD and control groups are age- and gender-matched. Additionally, diffusion tractography cannot distinguish the functional directionality of fibre tracts, and the tracts isolated may include both anterograde nigrostriatal-nigropallidal pathways and retrograde pallidonigral/thalamonigral pathways. The degree to which the latter is affected in PD is unclear, as its effect on the DTI results.Subjects were scanned under dopaminergic medication. While this reduced movement artefact, which causes severe and significant inaccuracies to DTI measurements, the influence of dopaminergic medications on DTI results is poorly understood and requires further investigation.In summary, we demonstrated a clinically and radiologically practical application of deterministic tractography to DTI data to evaluate the NSP pathway in PD, and detected decreased NSP connectivity in PD without requiring complex imaging sequences for anatomical localization or segmentation software. Our findings provide impetus to better model diffusion parameters for small fibre tractography in further larger, prospective longitudinal MR study in PD.2; TE/TR = 86/8200 ms; 1.875 × 1.875 × 2 mm3 voxel size). Structural sequences were reviewed to exclude pathology in the regions of interest.Institutional ethics approval and written subject consent from subjects were obtained. The methods were carried out in accordance with the approved guidelines and regulations, and all experimental protocols were approved by Singhealth ethics committee. Forty subjects  had structural brain MRI and DTI scans on a 3Tesla MR scanner3 resolution in MATLAB  using SPM8 , based on published protocol1416Deterministic brute-force tractography was performed using Diffusion Toolkit  on DTI images after upsampling with trilinear interpolation to 1 mmMost of the tracts isolated extended beyond the SN and GP ROIs into the brainstem and cerebral cortex probably due to limitations in the resolution of the DTI data, causing the algorithm to incorporate other tracts close to its ends as part of itself. Since our primary interest was the connectivity of the SN to the GP and putamen and to avoid dilution of any effects by extraneous, pathologically-uninvolved tracts, the tracts isolated were segmented by identifying the tract midpointStatistical analysis was performed using SPSS (Version 20.0) and R (Version 3.0.0). Intraclass correlation coefficient (ICC) values comparing the tract parameters obtained by the two raters were calculated using a two-way mixed model with absolute agreement and a confidence interval of 95%. The gender in PD and control groups was compared with Chi-square test, and the age with Student’s t-test. Averaged DTI parameters and streamline count of the NSP complex in PD and control groups were compared using Student's t-test, and correlated with UPDRS motor score using Pearson's correlation. The midpoint of the tract profiles was selected for univariate logistic regression analysis since it had were no missing values across subjects and was probably less susceptible to contamination by intersecting fibres. As there was no significant asymmetry in the DTI variables or in the motor symptoms between left and right, the values of the left and the right tracts were averaged.How to cite this article: Tan, W.-Q. et al. Deterministic Tractography of the Nigrostriatal-Nigropallidal Pathway in Parkinson's Disease. Sci. Rep.5, 17283; doi: 10.1038/srep17283 (2015).