The nutrition and epidemiologic transition has been associated with an increasing incidence of preterm birth in developing countries, but data from large observational studies in China have been limited. Our study was to describe the trends and factors associated with the incidence of preterm birth and infant mortality due to prematurity in Hubei Province, China.We conducted a population-based survey through the Maternal and Child Health Care Network in Hubei Province from January 2001 to December 2012. We used data from 16 monitoring sites to examine the trend and risk factors for premature birth as well as infant mortality associated with prematurity.P for trend < 0.05), while the infant mortality rate due to prematurity declined from 95.0 to 13.4 per 1,000 live births (P for trend < 0.05). Older maternal age, lower maternal education, use of assisted reproductive technology (ART), higher income, residence in urban areas, and infant male sex were independently associated with a higher incidence of preterm birth . Shorter gestation, lower birth weight, and lower income were associated with a higher mortality rate, while use of newborn emergency transport services (NETS) was associated with a lower preterm mortality rate .A total of 818,481 live births were documented, including 76,923 preterm infants  and 2,248 deaths due to prematurity . From 2001 to 2012, the incidence of preterm birth increased from 56.7 to 105.2 per 1,000 live births  contains supplementary material, which is available to authorized users. Approximately 15 million infants are born prematurely each year, which is more than one tenth of all new-born infants globally . MortaliFor preterm infants who do survive, elevated risks for cognitive disorders and chronic non-communicable diseases exist , 6. PretLarge pooled analyses using data from multiple countries showed that the incidence of preterm birth has increased in recent years, with preterm birth an important risk factor for neonatal mortality , 9. HoweEconomic development and government programs in China over the past two decades have together led to improved quantity and quality of maternal, child and newborn health care . SecularA random sampling stratified by urban and rural areas was conducted in Hubei Province, China. Sixteen counties were selected randomly by zip code from 9 urban areas and 13 rural areas as the monitoring sites, including 6 urban areas and 10 rural areas.The annual number of live infant births at each of the monitoring sites was recorded by trained staff of the Maternal and Child Health Care Network in Hubei Province from January 1, 2001 to December 31, 2012.The data were collected based on an electrical “three vertical level” health care system in Hubei Province. The “three vertical levels” include community/countryside, city, and province.Upon the birth of each infant within the monitoring sites, the basic information of the mothers was collected in face-to-face interview before hospital discharge by a licensed and trained health care provider in each county. The basic information was recorded electronically through the health care system, which included maternal age, education, income, occupation, pregnancy parity, birth parity, residence, use of Newborn Emergency Transport Service, infant gender, and use of assisted reproductive technology. The gestational week was assessed by trained doctors based on early pregnancy symptoms, pregnancy tests, and B-mode ultrasound tests. The birth weight was measured by trained doctors after the infant was delivered. Electronic weighing scales were used to weigh the infants, and the accuracy of weight was to 0.01 kg.After the basic information was collected, health care providers in the city to which the counties belong reviewed and verified the total number of live births, preterm births, and preterm mortality. If the preterm infant was lost to follow-up within the first year after the infant’s birth due to migration, the migrated infant was identified by the connected health care system of the monitoring sites in other provinces of China.Finally, the data on annual births within each city was reported to the Hubei Provincial Maternity and Child Care Hospital (HBPMCCH). Validation studies on the underreport rate were conducted by randomly selecting one of the monitoring sites.HBPMCCH doctors independently collected and verified the data collected from the county health providers, and compared the data to reported data in the health care system. The underreported rate of live births decreased from 4.5 %  in 2001 to 0.54 %  in 2012. Written informed consent was obtained from at least one parent, and the study was approved by the Ethics Committee of Hubei Maternal and Child Health Hospital.Live birth refers to the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of the pregnancy . PretermP < 0.05 indicating significant difference. To identify factors significantly associated with incidence of preterm birth and mortality, we initially included all covariates into the model and used logistic regression with backward stepwise selection. Candidate variables in the logistic model included year (continuous), maternal age (<35 y vs. ≥ 35 y), education (>9 years vs. ≤ 9 years), occupation , birth weight (<2.5 kg vs. ≥ 2.5 kg), pregnancy parity (1 vs. ≥ 2), birth parity (1 vs. ≥ 2), assisted reproductive technology (yes vs. no), income (<500 USD/month vs. ≥ 500 USD/month), residence , Newborn Emergency Transport Service (yes vs. no), infant gender , and gestational week (<34 week vs. ≥ 34 week). The maternal age, gestational week, and birth weight were dichotomized based on the literature. Education, pregnancy parity, birth parity, and income were dichotomized, with the largest number of participants as the reference group. For the variables with missing values, a missing indicator was used. The data was analyzed using the Statistical Package for the Social Sciences (SPSS) version 11.5.To compare the difference of proportions between groups, a Chi-Square test was used with A total of 818,481 live births were documented in the 16 survey areas in Hubei Province between 2001 and 2012. The incidence of preterm birth increased from 56.7 per 1,000 live births in 2001 to 105.2 per 1,000 live births in 2012, while the incidence of preterm mortality decreased from 95.1 per 1,000 live births in 2001 to 13.4 per 1,000 live births in 2012  in 2011 , while tPreterm birth occurs for a variety of reasons. Early induction of labor or cesarean birth, either for medical or non-medical reasons are causes of some of the preterm births. Most preterm births occur spontaneously . MultiplOur study showed that the incidence and mortality of preterm birth differed in urban and rural areas. The regions in Hubei Province were divided into urban and rural areas according to the local economic development and population density of these areas. From 2001 to 2012, the incidence of preterm birth in urban areas was about 1.5 times that of rural areas, while the incidence of preterm mortality decreased faster in urban areas than in rural areas. The results of this study showed that premature incidence and mortality were associated with social-economic development of the area. Our results were similar to a study in North Carolina which found incidence of preterm birth was more pronounced in urban residents . EconomiIn our study, except for in 2012, preterm mortality in urban areas was lower than rural areas. Although a great achievement has been made in reducing preterm mortality in Hubei Province, it is still relatively high in poor areas. Our study found that preterm mortality risk is lower for residents in urban areas. In fact, most preterm deaths and disabilities attributable to childbirth are avoidable, as there are medical solutions to prevent or manage preterm-related complications that cause preterm death. Thus, the establishment and improvement of the three-level health care network for women and children in China has proven to be effective and essential for immediate access to high-quality maternal health care both in rural and urban areas , 23.From 2001 to 2012, premature incidence and mortality for males were higher than females, consistent with previous studies. Several mechanisms have been proposed to explain why pregnancies carrying male fetuses could have a higher risk of preterm birth. First, heavier body weight of the male fetus increases the probability of using preterm labor . Second,Our study identified several factors that were associated with incidence and mortality of preterm birth. Unhealthy habits and lack of health knowledge are factors associated with preterm infant deaths . It is eOur study found that higher preterm mortality risk is associated with lower per capita GDP. In poor areas, most of the preterm infants died at home immediately after leaving the delivery hospital. Some preterm infants born in low-income regions die within their first few days of life. In poor regions, even for those born in a clinic or hospital, primary neonatal care is often lacking . The risWith rapid socio-economic development, as well as improvements in obstetrics and neonatal rescue technology, the neonatal transport network was set up to decrease preterm child mortality. Our study found that lower preterm mortality risk was associated with improved newborn emergency transport services. Essential newborn car includes thermal care, breastfeeding support, and infection prevention and management and, if needed, neonatal resuscitation. Extra care for small babies, such as Kangaroo Mother Care program , was estimated to save approximately 450,000 babies each year . Care foThere were several potential limitations in our study. First, we did not differentiate iatrogenic and spontaneous preterm birth. The higher rate of preterm birth over time might be due to the advanced technologies, such as induction of labour and cesarean section. It has been shown that in the United States, the increase of cesarean birth is in part responsible for the overall increase in the preterm birth rate from 1990 to 2007 and the decline in perinatal mortality . Second,In summary, an increase in the incidence of preterm birth and a decrease in the mortality rate of preterm birth were observed in Hubei Province from 2001 to 2012. Our results showed that delivery at an advanced maternal age, use of ART, and the lack of NETS were associated with increased incidence and mortality of preterm birth. Our results provide important information for areas of improvements in reducing incidence and mortality of premature birth.


It is important to identify the possible risk factors for the occurrence of large for gestational age (LGA) in newborns and to determine the effect of birth weight and metabolic parameters on subsequent growth. We aimed to determine the effects of maternal weight, weight gain during pregnancy, maternal hemoglobin A1c (HbA1c), C-peptide and insulin as well as cord C-peptide and insulin levels on birth weight and postnatal growth during the first two years of life.Healthy, non-diabetic mothers and term singleton newborns were included in this prospective case-control cohort study. Fasting maternal glucose, HbA1c, C-peptide and insulin levels were studied. Cord blood was analyzed for C-peptide and insulin. At birth, newborns were divided into two groups according to birth size: LGA and appropriate for GA (AGA). Infants were followed at six-month intervals for two years and their length and weight were recorded. Forty LGA and 43 AGA infants were included in the study. Birth weight standard deviation score (SDS) was positively correlated with maternal body mass index (BMI) before delivery  and with weight gain during pregnancy . In multivariate analyses, the strongest association with macrosomia was a maternal C-peptide level >3.85 ng/mL (OR=20). Although the LGA group showed decreased growth by the 6-month of follow-up, the differences between the LGA and AGA groups in weight and length SDS persisted over the 2 years of follow-up. The control of maternal BMI and prevention of overt weight gain during pregnancy may prevent excessive birth weight. The effect of the in utero metabolic environment on the weight and length SDS of infants born LGA persists until at least two years of age. Fetal overgrowth or macrosomia can be influenced by maternal diabetes, maternal obesity and excessive maternal weight gain during pregnancy ,2,3. AdvStudies have shown that, as is the case for infants of women diagnosed with GDM, macrosomia is also common in infants born to non-diabetic obese women ,2,3,5. MThe purpose of this study was to determine some of the fetomaternal variables that may potentially influence birth weight and postnatal growth during the first two years of life.This was a prospective case-control cohort study. Our sample included healthy, non-diabetic mothers who gave consent to participate in the study together with their term singleton newborns. The newborns were in stable cardiopulmonary state in the delivery room.A physical examination was conducted on every mother prior to delivery, at which time, blood pressure and maternal weight and height were measured. BMI was calculated as kg/m2. Pre-pregnancy BMI values were obtained from files and were classified based on the following World Health Organization (WHO) categories: obesity BMI ≥30 kg/m2; overweight 25-29.9 kg/m2; normal or underweight <25 kg/m2 . BMI priAt birth, anthropometric measurements  were obtained within 24 h of delivery. Birth weight was determined using a calibrated electronic scale with an accuracy of 2 g. In infants, length was measured with the infant in the supine position with a movable footboard . Newborns were divided into two groups according to birth size. Specifically, birth weights above the 90th percentile or 2 standard deviation score (SDS) above the mean for gestational age were classified as LGA and birth weights between the 10th and 90th percentiles were classified as appropriate-for-gestational age (AGA) (Lubchenco growth charts) . SymmetrExclusion criteria were any medical or obstetric condition likely to affect birth weight such as endocrine disorders, a history of pre-pregnancy diabetes or any other chronic diseases , multiple pregnancy, drug intake that interferes with glucose metabolism in the mother, gestational age ≤37 weeks, presence of congenital malformations and newborns resuscitated in the delivery room.Written informed consent was obtained from the participants and the study was approved by the local ethics committee of Zeynep Kamil Maternity and Children’s Diseases Training and Research Hospital.Statistical analyses were performed using SPSS version 17 . T-tests were used to analyze continuous variables. Categorical variables were converted to percentages and analyzed using the χ2 test. Pearson correlations were calculated to examine the relationships between maternal and infant measures. Logistical regression analysis was conducted to identify variables that were predictive of an infant being born ≥4000 g (dependent variable). The variables included in the regression were as follows: maternal age, gestational BMI, maternal height, infant gender, maternal hyperglycemia, hyperinsulinemia, a previous history of a macrosomic newborn and the current presence of hypertension or GDM. Determination of the best model was based on the Nagelkerke R2 value. A p-value<0.05 was considered statistically significant.A total of 83 newborns were included in this study: 40 LGA and 43 AGA infants. Median maternal age was 28 years. Average pre-pregnancy BMI was 26±0.6 kg/m2. Obesity was present in 19 mothers (22.9%). The 19 obese mothers delivered 8 LGA and 11 AGA babies, whereas non-obese mothers delivered 32 LGA and 32 AGA babies. GDM was present in 12 mothers, including 7 of the 19 obese mothers (37%) and 5 of 64 (8%) non-obese mothers. GDM mothers delivered 4 LGA and 8 AGA babies. Ninety percent of the LGA babies were born to non-GDM mothers. Insulin levels could be measured in 80 of 83 pregnancies. Monitoring of growth was conducted for two years in 17 of the 40 LGA newborns (42.5%) and 17 of the 43 AGA newborns (39.5%).There were more asymmetric newborns in the LGA group (PI>3.1), with 40% and 9.3% in the LGA and AGA groups, respectively (p=0.004). The average maternal age was significantly lower in the LGA group (p=0.005). The neonatal and maternal characteristics as well as the glucometabolic parameters of the AGA and LGA groups in this study are presented in Birth weight SDS was positively correlated with maternal BMI before delivery  and weight gain during pregnancy  but not with pre-pregnancy BMI . Maternal HbA1c  and cord insulin concentrations  were also found to be related to birth weight in each cohort. Post-pregnancy weights were positively correlated with C-peptide levels .Subgroup analyses revealed that in the AGA group, there were no correlations between birth weight and HbA1c levels  or glucose levels at 6 h of life . However, in the LGA group, birth weight was positively correlated with maternal glucose  and HbA1c . Furthermore, cord C-peptide was positively correlated with maternal insulin  and C-peptide  and negatively correlated with neonatal glucose levels at 6 h of life . Maternal systolic blood pressure was significantly correlated with maternal C-peptide , pre-pregnancy BMI  and post-pregnancy BMI (p=0.02).Multivariate analyses showed that the presence of GDM increased macrosomia risk with an OR of 2.7. The strongest association with macrosomia was a maternal C-peptide level >3.85 ng/mL (OR= 20) .The differences in weight and length SDS between AGA and LGA newborns persisted throughout infancy . AnalyseThe LGA group experienced a decrease in growth by 6 months of age. Birth weight SDS correlated with weight SDS at 24 months  but not at 6 or 12 months . Birth length SDS correlated with length SDS at 12 months  but not at 6 or 24 months   and 2.In our study, birth weight correlated with higher maternal HbA1c, maternal BMI before delivery and excessive gestational weight gain. The variable with the strongest association with higher birth weight was maternal a C-peptide level >3.85 ng/mL. Furthermore, LGA newborns presented higher length and weight SDS throughout infancy than AGA newborns.The prevalence of childhood obesity has shown a dramatic increase in many populations over the last decades . This phCatalano et al  reportedBesides the mother’s weight status, her metabolic parameters also influence neonatal anthropometric outcome. In previous studies on a cohort of >20 000 newborns, 9.6% were reported to be macrosomic. The frequency of macrosomic babies was higher for mothers with higher maternal HbA1c and higher serum glucose concentrations  and highInformation about the metabolic outcomes of LGA newborns in their first years of life is limited. The EDEN Mother-Child Cohort Study Group examined the effects of fetal insulin and IGF-1 on postnatal growth. The results showed that an association existed between cord C-peptide and birth weight, but that after adjusting for IGF-1, this association disappeared. The authors suggested a role for IGF-1 on the casual path between C-peptide and birth weight . In thisSome limitations of our study should be noted. First, the study had a poor follow-up rate. In addition, we did not study maternal lipid profiles, including triglyceride, very low density lipoprotein cholesterol or IGF-1 concentrations, which may affect IR during pregnancy and the weight of the infants at birth. Because we were not able to repeat the blood tests at follow-up visits, we cannot interpret the long-term metabolic implications of birth weight.In conclusion, the results of this study indicate that control of maternal BMI and prevention of overt weight gain during pregnancy may prevent excessive birth weight and also that the effect of the in utero metabolic environment on the weight and length SDS of infants born LGA is sustained until two years of age. Thus, fetomaternal influences should be considered as factors in the development of childhood obesity. These conclusions are in line with reports stating that negative metabolic outcomes may subsequently increase the chance of adulthood obesity up to 70% . Pre-pre


Chronic kidney disease (CKD) and systemic inflammation are risk factors for sepsis. While often viewed as a marker of chronic kidney disease, Cystatin C (Cyst-C) may also reflect systemic inflammation. We sought to determine the association between elevated baseline Cyst-C and long-term rates of community-acquired sepsis, and to determine if this relationship is influenced by traditional markers of CKD  and inflammation (high sensitivity C-reactive protein [hsCRP]).We studied 30,239 adults ≥45 years old from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was elevated Cyst-C (>1.12 mg/dL) measured at study baseline. The primary outcome was the first sepsis hospitalization during a 10-year observation period. Using Cox regression, we evaluated the association between elevated Cyst-C and first sepsis event, adjusted for sociodemographics, health behaviors, chronic medical conditions, eGFR, ACR and hsCRP.2, ACR ≥ 30 mg/g and hsCRP > 3.0 mg/dL only partially attenuated the association between Cyst-C > 1.12 mg/dL and rates of sepsis .Among participants, 1,532 experienced a sepsis event. Median Cyst-C levels were: sepsis 1.08 (IQR 0.91-1.33) mg/dL (43.8% >1.12 mg/dL), non-sepsis 0.94 (IQR 0.82-1.10) mg/dL (23.4% >1.12 mg/dL). Cyst-C > 1.12 mg/dL was independently associated with increased rates of sepsis, adjusted for participant demographics, health behaviors and chronic medical conditions . The addition of eGFR < 60 mg/min/1.73 mElevated Cyst-C is associated with increased long-term rates of community-acquired sepsis, independent of abnormal eGFR, ACR or hsCRP. Cyst-C may play a role in long-term sepsis risk prediction and prevention. Sepsis is the syndrome of microbial infection complicated by systemic inflammatory response. Sepsis is a major public health problem in the United States (US), encompassing 750,000 hospitalizations, 570,000 Emergency Department visits and 200,000 deaths annually -3. The aCystatin C (Cyst-C) is a low molecular weight protein that is produced by all nucleated cells and removed from the bloodstream by glomerular filtration . Cyst-C In this study, we sought to determine the association between Cyst-C measured at baseline and future risk of community-acquired sepsis.We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national population-based longitudinal cohort. This study was approved by the Institutional Review Board of the University of Alabama at Birmingham. Written consent for participation was obtained by the parent REGARDS study.REGARDS is one of the largest ongoing national cohorts of community-dwelling adults in the US . CreatedThe REGARDS study recruited participants during 2003–2007. The study obtained baseline data for each participant using both phone interview and in-person evaluations. Baseline information included medical history, functional status, health behaviors, physical characteristics , physiologic measures , and an inventory of medications. Additional data included diet, family history of diseases, psychosocial factors and prior residences. The study also collected blood and urine specimens from each participant.Every 6 months, REGARDS contacted study participants by telephone to identify the date, location and attributed reason for all hospitalizations during the follow-up period. Study personnel then retrieved medical records for specific health events. If the participant died, the study team reviewed death certificates and medical records and interviewed proxies to ascertain the circumstances of the death.The primary outcome was a participant’s first hospitalization for a sepsis event. Using a strategy developed by Angus et al., we identified hospital admissions and emergency department visits attributed to a serious infection . TrainedConsistent with international consensus definitions, we defined sepsis events as hospitalization for infection plus two or more systemic inflammatory response syndrome (SIRS) criteria. These include heart rate >90 beats/minute, fever (temperature >38.3°C or <36°C), tachypnea (>20 breaths/min) or carbon dioxide partial pressure (PCO2) <32 mmHg, and leukocytosis  [g and 4°C. The samples were either analyzed  immediately or stored at −80°C.Study personnel collected blood and urine samples from all REGARDS participants at subjects’ homes following a 10–12 hour fast. Samples were centrifuged to separate serum or plasma within 2 hours of collection and shipped overnight on ice packs to the laboratories at the University of Vermont. On arrival, study personnel centrifuged the samples at 30,000 Serum Cyst-C and hsCRP were assessed using particle-enhanced immunonephelometry . In contrast with conventional CRP assays, the high-sensitivity CRP technique is able to detect levels as low as 0.04 mg/L. Serum creatinine was determined by colorimetric reflectance spectrophotometry . Urinary albumin was measured via nephelometry . Urinary creatinine was measured with a rate blanked Jaffé procedure . While not standardized to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) standard, Cyst-C assay values were consistently 11% lower than the international benchmark.REGARDS determined participant characteristics during the initial interview and in-home visit. Participant demographics included age, race, sex, income, educational attainment, and geographic location. Race was defined as white or black/African American. Income was divided into four categories . Education categories included less than high school, high school graduate, some college, college or higher. Geographic region included the stroke “buckle” , “stroke belt”  and non-belt.Health behaviors included tobacco and alcohol use. Smoking status included current, past and never. We defined alcohol use as moderate (1 drink per day for women or 2 drinks per day for men) and heavy alcohol use (>1 drink per day for women and >2 drinks per day for men), per the National Institute on Alcohol Abuse and Alcoholism classification .2 or waist circumference >102 cm for males or >88 cm for females.Chronic medical conditions included cancer, coronary artery disease, diabetes, dyslipidemia, hypertension, myocardial infarction, obesity and stroke. Participants self-reported history of cancer, myocardial infarction or stroke. Coronary artery disease included a history of myocardial infarction or coronary intervention. Diabetes was defined as a fasting glucose ≥126 mg/L (or a glucose ≥200 mg/L for those not fasting) or the use of insulin or oral hypoglycemic agents. Dyslipidemia consisted of low-density lipoprotein cholesterol >130 mg/dL, or use of lipid lowering medications. Hypertension included a systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the reported use of antihypertensive agents. Obesity included a body mass index of ≥30 kg/mREGARDS did not collect information on pulmonary conditions such as asthma and chronic obstructive pulmonary disease. Therefore, we defined participant use of pulmonary medications as a surrogate for chronic lung disease. Obtained from each participant’s medication inventory, pulmonary medications included beta-2 adrenergic agonists, leukotriene inhibitors, inhaled corticosteroids, combination inhalers, and other pulmonary medications such as ipratropium, cromolyn, aminophylline and theophylline.2 as abnormal [We defined elevated Cyst-C as serum levels above the fourth quartile for the cohort (>1.12 mg/dL). We converted serum creatinine to eGFR using the CKD-EPI equation, defining eGFR levels <60 ml/min/1.73 mabnormal . We simiabnormal .We compared demographic, health behavior and clinical characteristics between participants with elevated and normal Cyst-C utilizing Pearson chi-square or t-tests. We defined person-time at risk as the time (days) from first in-person examination to the first episode of sepsis, the last follow-up interview, death or December 31, 2012, whichever came first. We censored all participants who died prior to the first sepsis event.In evaluating the independent association of elevated Cyst-C with first sepsis events, we first fit a series of Cox regression models adjusting for participant demographics, health behaviors and chronic medical conditions. Because Cyst-C has been proposed as a marker of CKD, incorporation of markers of CKD to the model would be expected to attenuate the association between Cyst-C and first sepsis event. Similarly, because Cyst-C is associated with systemic inflammation, incorporation of hsCRP to the model would be expected to also reduce the magnitude of the association between Cyst-C and sepsis. Therefore, we sequentially added abnormal eGFR and ACR, elevated hsCRP, and all three variables to the multivariable model, evaluating the changes in the hazard ratio for the association between Cyst-C and first sepsis event. Due to a substantial number of missing values for several variables , we performed the multivariable modeling with multiple imputation using chained equations (Stata “MI” suite), pooling regression coefficient estimates for each model across 10 imputations using Rubin’s rules ,35.We verified the proportional hazards assumption using scaled Schoenfeld residuals as well as examining interactions with log-transformed study time. We examined multiplicative interactions between abnormal Cyst-C, eGFR, ACR and hsCRP  in the final model. We verified the absence of collinearities by examining variance inflation factors.To test the robustness of the results, we conducted a series of sensitivity analyses. We fit a model using Cyst-C quartiles. In the primary analysis we defined eGFR, ACR and hsCRP using cutoffs commonly used in clinical practice; we repeated the analysis with eGFR, ACR and hsCRP dichotomized to their 75th percentile values. Lastly, we fit models with Cyst-C, eGFR, ACR and hsCRP as continuous variables normalized by their respective standard deviations.We conducted all analyses using Stata 12.1 .Among the 30,239 REGARDS subjects, we included 29,696 participants with available follow-up information. From February 5, 2003 through December 31, 2012 there were 3,442 hospitalizations for a serious infection, encompassing 1,856 sepsis events among 1,532 individual participants. Median follow-up time for each participant was 6.6 years (interquartile range 5.1-8.1). Sepsis-free survival was lower among those with elevated Cyst-C than those with normal Cyst-C (16.0 vs. 5.9 per 1000 person-years).  mg/dL for sepsis and 0.94 IQR 0.82-1.10) mg/dL for non-sepsis individuals (p < 0.001); 43.8% of sepsis and 23.4% of non-sepsis individuals exhibited elevated Cyst-C >1.12 mg/dL. The Pearson correlations between Cyst-C and eGFR, ACR and hsCRP were −0.63, 0.35 and 0.15, respectively. Individuals with elevated Cyst-C were more likely to be older, male and of white race . Elevated Cyst-C similarly remained independently associated with sepsis after adjustment for hsCRP >3.0 mg/dL . Elevated Cyst-C also remained independently associated with sepsis after adjustment for eGFR < 60 mg/min/1.73 m2, ACR ≥30 mg/g and hsCRP >3.0 mg/dL .Following multiple imputation, in unadjusted analysis, elevated Cyst-C (>1.12 mg/dL) was independently associated with increased rates of sepsis   were not statistically significant. Based upon an examination of variance inflation factors, there was no evidence of collinearity between Cyst-C and eGFR, ACR or hsCRP.2), ACR (≥16.1 mg/g) and hsCRP (>5.0 mg/dL), and continuous forms of Cyst-C, eGFR, ACR and hsCRP normalized by their standard deviation (Table In sensitivity analyses, we repeated the effort using quartiles of Cyst-C, the 75th percentile of eGFR (<73.1 ml/min/1.73 mon Table . These mCKD and systemic inflammation are recognized risk factors for sepsis -11. WhilRecent attention has focused on the utility of serum Cyst-C as a marker of renal disease, with studies indicating its superiority to serum creatinine for detecting progression to end-stage renal disease and mortality . HoweverSelect studies have evaluated elevated Cyst-C as a proximal risk factor for sepsis. In a study of 444 intensive care unit patients, Nejat, et al. found that elevated urinary Cyst-C was associated with five-fold increased adjusted odds of sepsis . In a stThe utility of these findings is in aiding the prediction of long-term sepsis risk. Sepsis is usually conceptualized as an acute event, with current clinical and scientific efforts focused on its early detection and management . HoweverOnly Cyst-C measurements taken at baseline enrollment in the REGARDS study were available for analysis. We were unable to examine Cyst-C proximal to sepsis hospitalization or repeat Cyst-C measurements. A portion of subjects did not have Cyst-C measurements; we tried to overcome this limitation through the use of multiple imputation. While Cyst-C levels were not standardized to the IFCC standard, the application of a linear adjustment would not have affected the observed inferences.REGARDS was designed to study stroke, not sepsis. REGARDS is not a surveillance study, and thus we may not have identified all sepsis events. However, misclassification of sepsis events should be similar between Cyst-C levels, and thus the analysis should present underestimates of the true association. Early death may act as a competing risk, preventing an individual from experiencing sepsis events. Those with elevated Cyst-C exhibited higher rates of death than those with normal Cyst-C; thus, we would expect an even stronger association with sepsis risk if we were to fully account for the competing risk of death.By design, the REGARDS cohort includes only African Americans and whites, and thus these results may not generalize to other ethnic groups. We examined the presence of comorbid conditions but not their severity. The REGARDS cohort contains individuals over 45 years old only; sepsis rates and the observed associations may have differed for younger individuals. We identified individuals who presented to the hospital with sepsis, but did not include those who acquired sepsis during their hospitalization.While we adjusted for a range of potential confounders, the observed associations may have been influenced by other variables such as vaccination or access to healthcare. As with all observational studies, residual confounding is always a concern. However, our risk adjustment strategy accounted for a comprehensive range of variables that were systematically identified for each participant at the beginning of the REGARDS study. We could not account for changes in these patterns over time.In this study elevated serum Cyst-C measured at baseline was independently associated with future risk of sepsis. This association persisted event after adjustment for markers of kidney disease and systemic inflammation. Cyst-C may play a potential role in sepsis risk prediction and reduction.


Calyceal diverticula are congenital, nonsecretory abnormalities in which the transitional cell-lined cavity communicates with the renal collecting system. Here we present the case of a calyceal diverticular abscess during pregnancy. A 40-year-old primiparous woman developed the abscess at 23 weeks of gestation, with right flank pain and a 37.8°C fever. A transabdominal ultrasound revealed a 12 × 10 cm cystic mass in the right kidney. She was initially diagnosed with a simple renal cyst infection, and intravenous antibiotics were initiated. Percutaneous drainage was started at 26 weeks of gestation. When urine excretion from the cyst was confirmed by dye test using indigotindisulfonate sodium, the patient was diagnosed with a calyceal diverticular abscess. She gave birth to a 2,870 g healthy male at 38 weeks of gestation. Percutaneous drainage with low-dose antimicrobial therapy could thus allow for the continued pregnancy of women with a calyceal diverticular abscess until full term. Calyceal diverticula are congenital, nonsecretory abnormalities in which the transitional cell-lined cavity within the renal parenchyma communicates with the collecting system through a narrow infundibulum . Its preOnly one report to date has addressed pregnancy complicated by a calyceal diverticular abscess , and manThe patient was a 40-year-old Japanese woman in her first pregnancy, who conceived by intracytoplasmic sperm injection. A renal cyst of 4 cm in diameter had been found at 36 years of age, but there was otherwise no past history of urinary tract infection or other remarkable family history.9/L), elevated serum C-reactive protein , and low white blood cell (WBC) count in the urine (5–9/HPF), she was diagnosed with a simple renal cyst infection. The patient was admitted and given an intravenous injection of ampicillin/sulbactam . Her pain and fever resolved the second day after admission, and inflammation gradually decreased .The patient was referred to our hospital at 8 6/7 weeks of gestation and started prenatal care in our outpatient clinic. At 23 5/7 weeks of gestation, she presented with a 37.8°C fever and pain in her right flank. Physical examination found right costovertebral angle tenderness, and transabdominal ultrasonography (USG) revealed a 12 × 10 cm cystic mass in the lower pole of the right kidney . BecauseThe patient underwent magnetic resonance imaging (MRI) at 24 6/7 weeks of gestation to investigate the cyst in detail. The MRI revealed a large cystic mass arising from the lower pole of the right kidney, as shown in the transabdominal USG, that was compatible with the primary diagnosis of a simple renal cyst .Although the infection resolved with antibiotic therapy, the size of the cyst was unchanged. We decided to puncture the cyst to reduce the risk of recurrent infection or rupture, as the uterus in late pregnancy would be more enlarged and compress the urinary tract. At 26 4/7 weeks of gestation, percutaneous puncture was performed under ultrasound guidance to drain 800 mL of culture-negative, pus-like fluid, and the cyst was deflated. Drainage continued at 600–800 mL/day from a nephrostomy catheter left in the cyst. A dye test was performed by systemic intravenous injection of indigotindisulfonate sodium (Indigo Carmine) to examine communication between the cyst and the renal collecting system. We found dyed urine excretion from the cyst, which confirmed the cyst as the calyceal diverticulum. The patient was discharged on day 10 after nephrostomy and was started on oral cefaclor (0.25 g/day) prophylactically. Serial examinations showed no recurrence of the calyceal diverticular abscess until delivery.The patient gave birth at 38 4/7 weeks of gestation to a 2,870 g healthy male, with Apgar scores of 8 (at 1 minute) and 9 (at 5 minutes), by vacuum extraction because of arrested descent in the second stage of labor. Her postpartum period was uneventful. Anterograde pyelography on day 4 after delivery revealed communication between the cyst and the collecting system, and the cyst was clinically confirmed to be a calyceal diverticulum . The patThe present report described the successful pregnancy of a patient with a calyceal diverticular abscess. We could not initially give a precise diagnosis because imaging tools were restricted to USG and MRI, which have no adverse effects on the fetus.Identifying communication between the cyst and the renal collecting system is essential in distinguishing a calyceal diverticulum from a simple cyst. However, radiographic examinations with contrast agents are contraindicated during pregnancy due to fetal side effects. In this case report, intravenous indigotindisulfonate sodium injection was used as a proxy for the radiographic dye test because it is relatively safe for the fetus (FDA risk category of B). This agent helped detect urine secretion from the cyst, indicating communication between the cyst and the collecting system.Asymptomatic calyceal diverticula generally do not need treatment. However, enlarged calyceal diverticula with infection or pain often require intervention such as surgical resection , 5. As tAlthough we initiated antimicrobial therapy before drainage, infected renal cysts and/or large renal abscesses  are often refractory to antibiotics , 7. We cTransient fever due to temporary bacteremia during percutaneous drainage is a common complication, while gastrointestinal tract injury, significant bleeding, pneumothorax, and urinary tract injury are rare but more critical , 9. ConcThe relationship of pregnancy to the onset of calyceal diverticular abscesses is unclear. Primary onset of the abscess in the present case was at late pregnancy (at 24 weeks of gestation), which was similar to that of a previously reported case (at 28 weeks of gestation) [In summary, we could successfully manage the pregnancy complicated by the calyceal diverticular abscess with antimicrobial therapy and percutaneous drainage, and the dye test using indigotindisulfonate sodium was helpful for making the diagnosis without radiographic examinations using contrast agents.


Reproductive synchrony tends to be widespread in diverse species of plants and animals, especially at higher latitudes. However, for long‐lived mammals, birth dates for different individuals can vary by weeks within a population. A mother's birth timing can reveal useful information about her reproductive abilities and have important implications for the characteristics and survival of her offspring. Despite this, our current knowledge of factors associated with variation in birth dates is modest. We used long‐term data for known‐age Weddell seals in Antarctica and a Bayesian hierarchical modeling approach to study how birth dates varied with fixed and temporally varying features of mothers, whether sex allocation varied with birth timing, and annual variation in birth dates. Based on birth dates for 4465 pups born to 1117 mothers aged 4–31, we found that diverse features of mothers were associated with variation in birth dates. Maternal identity was the most important among these. Unlike most studies, which have reported that birth dates occur earlier as mothers age, we found that birth dates progressively occurred earlier in the year in the early part of a mother's reproductive life, reached a minimum at age 16, and then occurred later at later ages. Birth dates were positively related to a mother's age at primiparity and recent reproductive effort. The earliest birth dates were for pups born to prime‐age mothers who did not reproduce in the previous year but began reproduction early in life, suggesting that females in the best condition gave birth earlier than others. If so, our finding that male pups tended to be born earlier than females provides support for the Trivers–Willard sex‐allocation model. Average birth dates were quite consistent across years, except for 2 years that had notable delays and occurred during the period when massive icebergs were present and disrupted the ecosystem. In diverse species of plants and animals, reproduction is clustered temporally, especially at higher latitudes where seasonal changes in climate as well as biotic interactions are considered important drivers of synchrony Ims . Timing For long‐lived mammals in temperate zones, populations with strongly synchronized reproduction can have important levels of individual variation in birth dates  females of the same age can have different levels of reproductive experience  change over a lifetime, birth dates for individual mothers have also been reported to be repeatable in large mammals in studies conducted in the wild , in the 8–14 pupping colonies that form along perennial cracks in the sea ice caused by tidal movements and glacial pressure  as it could accommodate (1) no change in birth date with increasing maternal age (if βage.l = 0 and βage.q = 0), (2) linear changes whereby birth dates progressively occur earlier (as is most commonly reported in the literature) or later with age (if βage.q = 0), or (3) allow birth date to initially occur earlier with increasing maternal age until reaching a minimum at some prime age and to then occur later at older ages . Age at first reproduction (AgeFirst), which varies in Weddell seals and is predicted to be inversely related to female quality , with parity reported to be more strongly associated than age to birth date in that species  a pup's sex, (2) fixed and dynamic attributes of its mother, and (3) year. We include a binary covariate  that indicated if a pup was male or not (prediction: negative in accordance with Stirling ), who reBi,j,k , were treated as independent normal random variables with the mean μi,j.k a function of the explanatory variables:ηj is the random effect of maternal identity, and γk is the random effect of year. We used a single model because of the large amount of literature regarding factors related to variation in birth rates in long‐lived mammals; our ability to include a variety of features about mothers, pups, and years, which included random effects that allowed for individual and annual variation; and comments by Ver Hoef and Boveng  and year (γ) in the model were treated as independent, normal random variables with means equal to zero, and variances ση,σγ. The variances for the random effects were assigned diffuse uniform priors on the interval .Bayesian hierarchical models require distributional assumptions for coefficients in each level of the model. To penalize for any collinearity between the covariates and assist in the interpretation of the results, we investigated the use of several shrinkage priors in a Bayesian interpretation of regularization for the regression coefficients for the fixed effects . We assessed model fit using a hierarchical implementation of the classical R2 . Average age of first reproduction was 7.5 years . The data included birth dates for 902, 406, 2036, and 1121 mothers whose reproductive state in the previous year was Pre, FirstTime, Exp, or Skip, respectively. The overall proportion of pups that were male (n = 2197) was 0.49 .Birth dates were available for 4465 pups produced by 1117 different mothers. The mean number of birth dates available per mother was 4 . On average, mothers were aged 12 years . Although samples were modest prior to 1993 , data from those years were included to maximize the number of birth dates recorded per mother. Data from 2013 were not included in the analysis because logistical constraints prevented us from collecting birth dates during the first half of the birthing season. From 1993 through 2014, the average birth date was 30 October (SD = 7.1), and, on average, the annual birthing season was 36.5 days long (SD = 4.4), began on 14 October (SD = 2.9), and ended on 19 November (SD = 3.9). Based on the lower and upper quartiles for birth dates in each year, half of the births occurred in an average span of 9.5 days each year (SD = 2.9) from 24 October (SD = 2.9) through 2 November (SD = 2.9).Estimated parameters for the model of variation in birth dates were in agreement with most but not all of our predictions and provided several novel insights. In the deterministic portion of the model, results supported our predictions that birth dates would be earlier for sons than daughters and earlier for pups born to mothers in their late teens than for younger or older mothers Table , Fig. 2.Age of first reproduction was positively related to birth date as we predicted Table  and accoA mother's reproductive state in the previous year was also related to her pup's birth date but in a simpler manner than what we had predicted. Specifically, the model results indicate that birth dates were related to whether a mother had a pup or not in the previous year but not to previous reproductive experience within those two classes Table . FemalesR^marginal2 = 0.055). In contrast, the total amount of variance explained by both the stochastic (random effects) and deterministic portions of the model was markedly higher . The amount of variance associated with maternal identity (σ^mom2 = 25.21) was greater than the amounts associated with years (σ^year2=3.77) or fixed effects (σ^fix2 = 2.95) or the amount that remained unexplained by the model (σ^y = 21.56).The coefficients estimated for the deterministic portion of the model had 95% HDI's that did not include zero or only slightly overlapped zero Table . The typPredicted random effects for individual mothers ranged from −12.5 days (95% HDI: −15.1 to −9.9) to 14.9 days (95% HDI: 10.7–19.0), and predicted birth dates were 7 days earlier and 8 days later than the mean for 5% of mothers at either end of the distribution  did not depend on a female's parturition status in the previous year (Boyd Capreolus capreolus) were rather insensitive to female condition  found that late‐conceiving females were in poorer condition and produced a preponderance of daughters  in relation to El Niño – La Niña events  as well as with two dynamic traits (recent reproductive investment and age). When considered in combination across a suite of maternal traits, some individual mothers are predicted to give birth days to weeks apart. We predict that such differences in birth timing are likely to have biologically important effects for pup fates given that they typically gain ~2 kg/day during lactation (Wheatley et al. None declared.


Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth.Thirty-eight preadolescents  and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN  and lateral parietal DMN .Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups.Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing. Advances in perinatal care over the past few decades have increased the number of surviving preterm neonates. The effects of increased risk for medical conditions, learning disabilities, and psychological problems among early preterm infants lasting into adulthood have a visible impact on developed societies , 2. PretThis study aims to ascertain possible functional connectivity and anatomical connectivity alterations in children born at late preterm that could relate to neurocognitive differences.The default mode network (DMN) is a group of neuroanatomical structures acting in synchrony at-rest as indicated by resting state functional MRI (RS-fMRI) that are thought to integrate associative information and play a role in self-referential (introspective) thought activities , 14. ThePreterm birth-related effects demonstrate a posterior predilection with greater grey matter reductions in the parieto-occipital cortices and white matter injury predominantly affecting the posterior limb of the internal capsule and posterior portions of the corpus callosum –26. AnimAs part of a longitudinal international collaborative investigation of the genetic and environmental influences of prematurity on long-term neurocognitive functioning and health outcomes, 19 preadolescent pairs of twins (38 participants aged 9–13 years) were recruited from Minas Gerais, a developing region in Northeastern Brazil. The preadolescent twin pairs were recruited through an existing twin registry by newspaper advertisements. The registry is comprised of twins who had participated in prior studies investigating genetic influences on oral health , 29. SamResearch protocols were approved by local Institutional Review Boards in the United States  and Montes Claros, Brazil . Written informed consent was obtained from study participants’ parents or legal guardians.Neurocognitive measures employed in this study included the Rey-Osterrieth Complex Figure Test (CFT), the Trail-Making Test , and selected non-verbal subtests from the NEPSY-II, including Memory for Designs (Immediate and Delayed), Affect Recognition, 3D Block Construction, Geometric Puzzles and Route Finding. Neurocognitive test administration was carried out in Portuguese by a Brazilian neuropsychologist after all test instructions had been translated into Portuguese. Moreover, an experienced, American neuropsychologist (JLW) was present for much of the neurocognitive test administration to ensure consistency and adherence to testing protocols. The neurocognitive tests were scored in accordance with published procedures  and US n2, one scan acquired without diffusion weighting (b = 0 s/mm2) and 32 scans acquired with diffusion gradient direction according to the Philips Achieva 32-direction sequence.Diffusion scans were acquired at 1.5 T with the following parameters: Spin-Echo EPI, TR = 6000 ms, TE = 90 ms, slice thickness = 2 mm, matrix = 112 X 112, FOV = 22.4 cm X 22.4 cm, SENSE factor = 2, b value = 1000 s/mmhttp://brainsuite.usc.edu) including the SVReg atlas [http://fsl.fmrib.ox.ac.uk/fsl/fsl-4.1.9/fdt/fdt_probtrackx.html). This process is depicted graphically in 3).Between-group probabilistic tractography analysis was carried out in a similar manner as a previously published method . Diffusieg atlas –34. SeedResting-state BOLD was acquired on a Philips 1.5T Achieva scanner. Scan parameters were: TR = 3000 ms, TE = 50 ms, FOV = 21.1 cm X 21.1 cm, imaging matrix = 80 X 80, slice thickness = 4 mm, 30 slices acquired covering the whole brain, SENSE factor = 2, 100 volumes acquired for a total scan time of 5 minutes per run. Two scan runs were acquired: one with the child asked to keep his eyes open, and one with eyes closed. There was a brief time gap (approximately 15 seconds) between runs to allow the examiner to provide instructions to study participants to close their eyes.3).The data processing procedure closely followed that of Power et al. , shown tWe report results from a community-based cohort of low-to-moderate socioeconomic status preadolescent (ages 9–13) twin pairs born late preterm or at full term. This study is part of an international collaborative longitudinal research program to investigate genetic and environmental influences on prematurity, long-term neurocognitive functioning and general health outcomes. The preadolescents in this study were recruited from a city in Northeast Brazil . This region not only has a high incidence of natural multiple gestation pregnancies but also a high rate of late preterm birth coupled with limited healthcare resources . As a reThe neuropsychological test battery performed by all participants included the Rey-Osterrieth Complex Figure Test (CFT), the Trail Making Test (children’s version), and selected subtests of the NEPSY-II assessing visuospatial, visuo-perceptual, and memory functions: Affect Recognition, Memory for Designs, Block Construction, Geometric Puzzles, and Route Finding. No significant difference in cognitive performance was seen between preterm and term preadolescents after controlling for age  = 0.735, p > 0.5). A nominally significant difference in the direction of the preterm preadolescents outperforming the term preadolescents was detected only on Block Construction  = 4.131, p = 0.049), not surviving correction for multiple comparisons.Late preterm individuals during preadolescent childhood demonstrate increased functional connectivity when seeding from the PMC as shown in As shown in Strength of increased functional connectivity within the posterior DMN was greater for the right hemispheric seeds compared to left-sided seeding as displayed in Hyperconnectivity of the DMN in late preterm children was also demonstrated when seeding from the lateral parietal cortex  as shown in Increased streamlines were demonstrated within the right inferior longitudinal  fasciculus (ILF) and overlapping inferior fronto-occipital fasciculus (IFOF) as shown In seeding the right and left posteromedial cortex as depicted in Seeding from the right lateral parietal cortex as shown in Late preterm birth is increasingly recognized as an important influence in brain development with documented impairments in learning and neuropsychological performance . In our late premature birth (32–36 weeks) may affect the development of the DMN and how such possible alterations can affect brain organization.During the late third trimester, what mainly shapes brain development is the organization and reorganization of connections between existing neurons, as neurogenesis is considered largely complete . At the Recent progress has been made in understanding the early formation of resting state networks during late gestation. Some research posits a rich-club network of highly clustered cortical hubs within the infant brain develops by 30 weeks' gestation . The latDespite lacking significant cognitive differences between preadolescent children born late preterm versus at term in this study, there remains valuable information regarding possible anatomical and functional connectivity explanations for increased risk of developmental delay and cognitive disability with prematurity. Because of an increased risk of autism with preterm birth, preterm birth could share changes in brain connectivity with autism , 58. In Increased excitatory activity or, as suggested in our study, excess functional hyperconnectivity within posterior DMN structures may relate to disruption of normal synaptic pruning that is expected to occur postnatal development, but may be altered in a variety of conditions such as autism and obsessive-compulsive disorder , 67. In While the clinical significance of hyperconnectivity observed in this study is not definitively associated with cognitive dysfunction, the context of these findings combined with that of others in autism and prenatal injury strongly suggests that a developmental deficit in pruning of local connections may be responsible for neurocognitive deficits seen in late prematurity. This lack of pruning may occur with greater preponderance in the posterior regions as indicated by predominant hyperconnectivity within the posterior default mode network and established posterior cortical vulnerability.Probabilistic tractography differences were less pronounced in comparison to the previously described functional connectivity findings as expected in this group of late preterms without significant cognitive deficits. Nevertheless, in this study, we observe selectively increased streamlines in our probabilistic tractography analysis of later preterm versus term infants within the region of the right inferior occipito-frontal fasciculus (IFOF) and right inferior longitudinal  fasciculus (ILF). In addition, the left PMC showed increased streamlines within right parietal white matter. These increases occurred in the setting of decreased streamlines within the splenium of the corpus callosum from the left PMC and right lateral parietal cortex, thereby implying deceased interhemispheric connections.Previously, others  have notOn the other hand, earlier voxel-based morphometry studies of earlier preterms show decreased white matter volume in the longitudinal fasciculi both during infancy and early adolescence , 76. In We propose that the finding of increased right IFOF/ILF streamlines suggests compensatory increased anatomical connectivity within the right hemisphere. The conventional pathway for semantic language processing follows the inferior fronto-occipital fasciculus (IFOF) with the inferior longitudinal fasciculus (ILF) constituting an indirect pathway . Prior wAnother possible explanation for selective increased streamlines within the IFOF and ILF in late preterm infants may represent aberrant white matter development that affects brain function not assessed by conventional neuropsychological tests. Prior work in William’s syndrome has shown similar increased FA within the IFOF that is thought related to increased myelination . While tThis study included individuals who were born at late preterm versus term gestational age and examined brain development during the preadolescent period. One important aspect of this study population is the lack of early perinatal intervention in a preterm population from a poor, developing region , 29. Whipost hoc, there was a slight but statistically significant increase in the number of included scans in the eyes-open condition for the preterm group, although not for the eyes-closed condition. Accordingly, there was a slight but significant difference in the framewise displacement (FD) parameter between groups in the eyes-open condition  though not for the eyes-closed condition . As part of the functional connectivity data processing, WM and CSF values were not included as regressors in the analysis as they were not shown to significantly change the results. These minor technical limitations are not expected to significantly affect the results of this study due to the rigorous frame inclusion criteria, however future studies may benefit from these additional data analysis strategies.In analyzing this data Serial data examining patterns of development would strengthen our understanding developmental phenomena related to late preterm birth by looking at dynamic changes over time within the individual rather than at one point in time. Despite promising results from an increasing body of literature, both methods are indirect indicators of functional and anatomical connectivity, respectively. Moreover, conventional DTI is limited by its inability to distinguish tracts within axon-rich crossing-fiber regions, a limitation that may be overcome with future work employing diffusion spectrum imaging.One other key aspect of this study was the use of participant-specific anatomic parcellation to accurately identify the function of the anatomic PMC structures. Function-based parcellation may yield differing results that could add further detail to our study. In addition, the use of other methods such as graph theory or independent components analysis could be helpful to validate our findings. Moreover, future work comparing our findings with those of earlier preterm infants in a different setting would enrich our understanding of the magnitude of brain development alterations related to prematurity within the posterior DMN and other critical neuroanatomical regions.Our findings support appreciable abnormalities in brain development in infants born late preterm even in the absence of detectable differences in neuropsychological performance. Thus, the late prenatal period represents a key timeframe for the formation of mature resting state networks and disruption of these neural connections may incite increased local functional connectivity within the posterior DMN, greater anti-correlation with salience and executive networks and lead to the strengthening of additional axonal pathways within the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus that serve as compensatory alterations or pathologic sequelae that could affect emotional processing and social function not adequately assessed on routine neuropsychological testing.


Previous research has demonstrated that the season of birth may predict development of emotional and behavioral regulation during childhood or adolescence. This study examined whether the season of birth predicts effortful control  and aggression  in 18-month-old infants.Participants included 885 infants who were enrolled in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan. Seasons of birth were categorized into winter , spring , summer , and autumn . At 18 months of age, effortful control was assessed using the Early Childhood Behavior Questionnaire, and aggression was measured using the Cardiff Infant Contentiousness Scale. Structural equation modeling analysis with measurement and structural equations was conducted to test our prediction.B = 0.095, 95% CI (0.014 to 0.175), p = 0.021, β = 0.146] and summer  than in those born in winter. In addition, aggression was lower in those born in spring  than those born in winter, even after controlling for seven covariates.Effortful control was higher in infants born in spring [The findings suggest that season of birth may determine development of emotional and behavioral regulation skills during early infancy. Future research should pay more attention to the underlying mechanisms of the effects of birth season on development of emotional and behavioral regulation during infancy. Previous studies have suggested that higher effortful control and lower aggression represent greater emotional and behavioral regulation skills. Effortful control refers to the ability to voluntarily choose a course of action under conditions of conflict and to plan for the future and detect errors. This includes maintaining attention to a particular activity, transferring attention to other activities, and controlling behavior under instruction . In contIncreasingly, the literature has demonstrated that season of birth may predict development of emotional and behavioral regulation during childhood or adolescence. Chotai et al. , 9 invesAlthough informative, these studies have mainly focused on children and adolescents and need to be extended to early infants, in order to understand development of emotional and behavioral regulation skills. If the particular season of birth decreases effortful control and increases aggression during infancy, these emotional and behavioral aspects of personality may increase antisocial behavior both in childhood and later in life , 6, 7. TThis study was conducted to examine whether season of birth affects emotional and behavioral regulation skills – higher effortful control and lower aggression – during early infancy. To this end, we recruited infants at 18 months of age using a representative birth cohort in Japan.This study was conducted as part of the “Hamamatsu Birth Cohort for Mothers and Children (HBC Study).” The HBC Study has been described in detail elsewhere , 16 and We recruited all the pregnant women who were expected to give birth at the research sites and had a delivery between December 2007 and March 2011. Participants included 1,138 mothers who were first enrolled in the HBC Study and their infants aged 18 months. To keep all participants as independent observations, we excluded 19 mothers who delivered twins from the following analyses. Consequently, among 1,119 participants, 234 infants were not assessed for effortful control and aggression because they were not in contact with our research center or had canceled assessment at the age of 18 months due to poor health, a residential move, or death.n = 885) and excluded (n = 253) in the analysis: mean age of mother (31.1 vs. 29.9 years), mean age of father (33.0 vs. 31.7 years), average household income (6.17 vs. 5.60 million JPY), maternal history of depression and/or anxiety disorder (yes 12.1 vs. 11.4%), gender of child , older siblings (yes 54.6 vs. 51.4%), influenza by the age of 18 months (yes 8.5 vs. 0.0%), and food allergy by the age of 18 months (yes 8.6 vs. 0.0%).Our final sample comprised 885 infants. The following values were derived for the group of infants included  . This isAs with previous research based on the HBC Study , the 12 For covariates, we opted for the following seven variables that have been reported to be associated with effortful control and aggression in the literature , 19 and The study protocol was approved by Hamamatsu University School of Medicine and the University Hospital Ethics Committee .B  and standardized partial regression coefficients β .First, we calculated the number and proportion of season (and month) of birth and examined descriptive statistics for subscales of effortful control and aggression by season (and month) of birth among early infants. Second, we conducted a series of structural equation modeling analyses with measurement and structural equations to test the effects of season of birth on effortful control and aggression in 18-month-old infants  = 0.431, p = 0.934], indicating that season of birth among the participating infants were equally distributed.Table B = 0.095, 95% CI (0.014 to 0.175), p = 0.021, β = 0.146] and negatively associated with aggression . This suggests that early infants who were born in spring had higher effortful control and lower aggression than those born in winter. In addition, those born in summer were positively associated with effortful control , indicating that early infants who were born in summer had higher effortful control than those born in winter.The adjustment model revealed that, even after controlling for covariates Table , being bB = 0.122, 95% CI (0.003 to 0.242), p = 0.045, β = 0.126], April , May , August , and September  had higher effortful control than those born in January. In addition, early infants who were born in April , May , and September  had lower aggression than those born in January.As seen in Table We investigated whether season of birth affects emotional and behavioral regulation skills – higher effortful control and lower aggression – in 18-month-old infants using a Japanese birth cohort. The study demonstrated that effortful control was better for those born in spring (in particular April and May) and summer (in particular August) than in those born in winter. Furthermore, the propensity for aggression was lower in those born in spring (in particular April and May) than in those born in winter. These findings were observed even after considering maternal and paternal age, annual household income, maternal history of depression and/or anxiety disorders, infantile gender, and older siblings, thus suggesting that spring and summer births are associated with increased emotional and behavioral regulation skills during early infancy. The current findings corroborate previous studies indicating that winter births are associated with impulsivity-related traits including higher novelty seeking behavior , 11 and Although the coefficients were statistically significant, the magnitude of the effects of birth season on effortful control and aggression in 18-month-old infants seemed to be weak regardless of inclusion or exclusion of covariates because of generally low standardized partial regression coefficients that range from −1 to 1. These findings can be interpreted in three ways. One explanation is that season of birth has limited influences on development of emotional and behavioral regulation skills at 18 months after births. Therefore, because our results may be due to chance, caution is needed in interpreting the role of season of birth in emotional and behavioral regulation skills in early infants.The second explanation is that the findings may stem from the effect of season of measurement, rather than season of birth. Births in spring and summer represent measurements in autumn and winter taking place at 18 months after birth, respectively. In addition, our research site is located in the Northern Hemisphere (34°42′N 137°43′′E), and warmer months with an average temperature above 15°C are usually recorded from May to October, as seen in Table The third explanation, which we consider most likely, is that season of birth may be associated with emotional and behavioral regulation during infancy via other factors that we did not investigate in this study. Such factors that connect season of birth with effortful control and aggression during infancy include maternal postpartum depressive symptoms and parenting style. It has been suggested that childbirth in winter is a risk factor for maternal postpartum depressive symptoms . MaternaAlthough we found that early infants who were born during warmer seasons had higher effortful control and lower aggression, the exact biological mechanisms are still unknown. If season of birth predicts higher effortful control and lower aggression, this may stem from seasonal variation of serotonin (5-HT) activity, as suggested by previous research . PreviouThere are some limitations to this study that should be addressed. First, the generalizability of our findings based on the HBC Study may be restricted because the sample size was modest. Nevertheless, power analyses indicated that the number of participants in the four seasonal subgroups showed sufficient power (>80%) to detect significant effects α = 0.05). Second, this study did not clarify the direction of causality between the variables because we did not evaluate changes over time in effortful control and aggression. Consequently, the findings that season of birth predicts effortful control and aggression in 18-month-old infants should be carefully interpreted. Effortful control and higher levels of aggression are expected to emerge from 1 to 3 years of age  a general population sample in Japan, (b) a prospective study design from the second trimester of pregnancy to 18 months after birth, and (c) face-to-face interviews to measure effortful control and aggression. These strengths endorse the fact that our results are highly valid.In conclusion, 18-month-old infants who were born in spring and summer had higher levels of emotional and behavioral regulation skills, e.g., greater effortful control and less aggression, compared with those born in winter. Further research should focus on the underlying mechanisms of the effects of birth season on development of emotional and behavioral regulation during infancy.RA performed the statistical analysis and wrote the first draft of the manuscript. KT contributed to all aspects of this study, including the design, data collection and analysis, and drafting. NT provided administrative support and critical comments on the study design, data collection, and drafting. TH, YK, RN, CN, AO, YS, ST, and NM contributed to the preparation of the protocol, data collection, and interpretation of the results. All authors approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


As making preparations for birth and health facility delivery are behaviours linked to positive maternal and newborn health outcomes, we aimed to describe what birth preparations were made, where women delivered, and why.Outcomes were tabulated using data derived from a repeated sample (continuous) quantitative household survey of women aged 13–49 who had given birth in the past year. Insights into why behaviours took place emerged from analysis of in-depth interviews (12) and birth narratives (36) with recently delivered mothers and male partners.Five hundred-twenty three women participated in the survey from April 2012–November 2013. Ninety-five percent (496/523) of women made any birth preparations for their last pregnancy. Commonly prepared birth items were cotton gauze (93 %), a plastic cover to deliver on (84 %), gloves (72 %), clean clothes (70 %), and money (42 %). Qualitative data suggest that preparation of items used directly during delivery was perceived as necessary to facilitate good care and prevent disease transmission. Sixty-eight percent of women gave birth at a health facility, 30 % at home, and 2 % on the way to a health facility. Qualitative data suggested that health facility delivery was viewed positively and that women were inclined to go to a health facility because of a perception of: increased education about delivery and birth preparedness; previous health facility delivery; and better availability and accessibility of facilities in recent years. Perceived barriers: were a lack of money; absent health facility staff or poor provider attitudes; women perceiving that they were unable to go to a health facility or arrange transport on their own; or a lack of support of pregnant women from their partners.The majority of women made at least some birth preparations and gave birth in a health facility. Functional items needed for birth seem to be given precedence over practices like saving money. As such, maintaining education about the importance of these practices, with an emphasis on emergency preparedness, would be valuable. Alongside education delivered as part of focussed antenatal care, community-based interventions that aim to increase engagement of men in birth preparedness, and support agency among women, are recommended. Facility delivery with a skilled attendant in a centre providing emergency obstetric care is the primary strategy to reduce maternal and newborn mortality –5. TanzaSeveral studies have indicated that birth preparedness is associated with uptake of health facility delivery –11. RecoAlthough the intended connection between birth preparedness and health facility delivery is clear, the two are not often reported together , 16. In Results were derived from a continuous quantitative household survey conducted April 2012–November 2013, and qualitative in-depth interviews and birth narratives conducted in 2013.The study setting has been described in more detail elsewhere . TandahiQuantitative data were collected as part of a continuous cross-sectional modular household survey  . BrieflyQualitative data were collected from 12 semi-structured in-depth interviews with mothers who had recently given birth, and 23 birth narratives with recently delivered mothers and 13 men whose partners had recently given birth. No participants refused to partake. Birth narratives were considerably more open than in-depth interviews, leaving opportunities for participants to share their narrative around their or their partner’s experiences in pregnancy and childbirth. However, interviewers probed as necessary to ascertain greater detail or explanation. All in-depth interviews and birth narratives were carried out in Swahili. Participants were selected to be as diverse as possible .svy command to account for the clustered survey design, and statistical evidence of association between birth preparedness and place of delivery was determined using a weighted Pearson’s chi-squared test.Stata 13 was used to generate descriptive statistics for survey respondents with regard to age, marital status, religion, and birth preparation and place of delivery outcomes. Percentages were generated using the Qualitative data were coded line-by-line using NVivo 10 software to generate themes around participant rationale for making birth preparations (or not), or delivering in a health facility (or not). All qualitative in-depth interviews and birth narratives were analysed through constant comparison, and interview or narrative guides were adjusted to probe further into emerging themes or to further explore divergent cases. Data were collected and analysed until theoretical saturation had been reached. Emergent themes are reflected in the results through representative quotations.Five hundred and twenty-three women aged 13–49 who had given birth in the previous 12 months at the time of the survey (April 2012–November 2013) participated in the continuous survey  of women reported making birth preparations for the last live birth that they had in the 12 months prior to the survey. When asked to list what they had prepared, women reported some items more commonly than others Qualitative data provided some insight as to why some items were prepared more commonly than others. All participants made at least some birth preparations. As reflected in Table “You know nowadays there a lot of diseases, so if we use the same equipment there is a possibility of disease transmission.” An additional motivator for women was that they felt that these items were important to help in the prevention of infectious disease transmission. Having your own plastic sheet to deliver on, gloves, and a clean razor were seen to be of particular importance for this reason. Many referred to “homa kubwa” (the “big fever”), referring to HIV, and suggested that there are more diseases “nowadays” that women need to be protected against than in the past. As such, preparation of birth items was seen as essential to prevent the transmission of infections such as HIV.“[Without encouragement from the EQUIP volunteers] I could not have prepared myself because during the previous pregnancies you find all those things in the hospital. I couldn’t have known what to prepare—probably I would have carried a piece of khanga [cloth], thinking that all the services are available at the hospital.” Irrespective of parity, it was commonly stated that the education around birth preparedness that was given by EQUIP volunteers to mothers and fathers in their homes was useful in helping women to know exactly what to prepare. Women who had previously given birth indicated that for their past births, many of the functional items used in delivery such as gloves, a razor to cut the cord, a plastic sheet for laying on the bed, and others, were typically found in the hospital. Now, the expectation was for women to bring these items with them to the health facility.“It is possible there is a person whom you depend on, and [he] is poor. He doesn’t have money, like your parents [who are also poor], and the one who made you pregnant has rejected you, and if the parent has little capacity, that equipment [for birth] won’t be available.” Data from birth narratives and in-depth interviews suggested that men were typically charged with the responsibility of purchasing birth items, or conversely, giving money to their partners for them to buy the items. As such, men played a key role in ensuring birth preparations were made. It was perceived that, where birth preparations were not made, it was failure of the male partner, either because he was no longer in the pregnant woman’s life, or because he had failed to purchase the items due to financial constraints or lack of will. Making birth preparations was seen to be a particularly difficult undertaking for single pregnant women.“I planned to buy those things when I got money, but I felt labour pain without finishing doing delivery preparations, so I went to the hospital and got all the needed things there.” “I won’t prepare, rather, I will save money. I will just buy things at the hospital in case there are things that I will be asked to buy. I already know all things are sold there.” Finally, although EQUIP volunteers and health facility staff stressed the importance of starting to prepare early in a pregnancy, some participants held the view that items could be purchased at the health facility if preparations were not complete by the time of delivery. Furthermore, some had been told to replace prepared items while being at the facility, so they perceived early preparation to be futile.p-value <0.001).Table “I received education for my second child. Now they don’t allow anyone to deliver at home. Most of us now go to the hospital for delivery.” increased education of mothers and fathers about maternal and newborn health, both received at health facilities during antenatal care, but also from village volunteers like those from EQUIP;“They said that this is the fifth pregnancy, once the person reaches the fifth pregnancy they should go to the hospital.” special efforts being made to sensitise women who are young or primiparous or have had five or more children about the necessity of them delivering in a hospital due to their increased risk of complications;“[For the first pregnancy] the baby was too big, so they enlarged her birth canal [gave her an episiotomy]—that couldn’t be done at home … [Because] I saw that the first pregnancy had developed complications…I told [my wife] to prepare herself to go to the hospital.” women having previously experienced complications and therefore understanding the importance of health facility delivery;“I have seen great success in my first pregnancy; I didn’t face any problems…they followed up and I did listen to them…I have seen its importance.” women generally having positive experiences at the health facility and choosing to return for future births;“But if you deliver at home [then] at the time you go to facility, they refuse to attend you, other staff may even refuse to give you a card.” the prohibition of homebirths in some villages often through the use of fines for mothers or for traditional birth attendants who may be assisting them—established by village leaders or by volunteers like those in EQUIP as part of their strategies—or the refusal of services by local health facility staff ;“But if“[Health facilities] were few, and we used to go for long distances and there was no reliable transport. People used to carry pregnant women on a bicycle or in a basket and take them to hospital, but now if labour pains start they take them faster using motorbikes.” an increased number of facilities and more reliable modes of transportation, namely motorbikes.Health facility delivery was viewed very positively. The key perceived benefit of health facility delivery was that safety for the mother and the newborn were ensured. The most commonly cited reasons as to why health facility delivery had increased included:“I was alone…My husband was not around and my children were at school, it was around two…on the way back from school, my child went to tell his father in order to find transport…When my husband arrived with transport I had already delivered.” “I was alone…I didn’t intend to [give birth at home], I didn’t know [I was in labour] and I stayed for a long time…My husband left enough money—when he travelled he left me one hundred thousand shillings [~64 USD].” Women who had home births said that they had made birth preparations with the intention to deliver in a health facility. They commonly reported that the home birth occurred because they were alone in the house with her partner working or travelling elsewhere. One consequence of being alone was that a woman may have failed to get transport to a health facility, as men typically took on the responsibility of arranging and paying for transport. Interestingly, such was the case even if these women had been left money by their partners, suggesting a potential need for female agency in the absence of others—husbands or other family members—who would make the decision to seek care. Participants did not refer to emergency preparedness for the situation when a woman might be alone and starting labour.“The labour pain started and we sent her there [to the dispensary], but there was no one to attend her … The problem is, there are only two staff, and if they [leave], this facility remains with no one.” “The nurse just throws the patient on the bed, until the one who has come to look after the patient follows the nurse and asks her to go and look at her patient but she doesn’t and she says, ‘I feel sleepy, I am going to sleep’. So she goes to call the traditional birth attendant in the village to help with the birth [instead].” If her partner was present and a woman still gave birth at home, it was typically due to no health facility staff being present, which was particularly true among women accessing dispensaries. Poor provider attitudes were also seen to discourage women from attending the health facility.“There are changes because nowadays there is the use of services professionally, and mothers are educated and they go to deliver at the health facility. Nowadays to give birth at home is an emergency.” “Others might have no money. Another problem is she might have no one to take her to the health facility. Some are single mothers. Some…women are rejected, while others do not have relatives to help them.” Otherwise, childbirth at home was reported to be an accident or something that occurred in an urgent and unexpected situation. Less commonly, respondents discussed a lack of knowledge on the mother’s behalf, or financial struggles that would prevent a woman from being able to get to a health facility at all. As for both the long-term preparation of money and items needed for delivery, and the short-term arrangement of transportation, the need for a present male in order to make decisions was key, and as such, the absence of a male partner—either a temporary absence, or if a woman was no longer with her partner at all—was also regularly noted as a reason that may cause women to deliver from home.As seen in other studies from Tanzania, birth preparedness was carried out among the vast majority of pregnant women , 25. QuaGiven the link between birth preparedness and health facility delivery, there is an added value of having community-based volunteers who are in a position to reiterate messaging around both within a family context, and to follow-up to ensure birth preparations were being made. However, there has been a failure to take up some aspects of birth preparedness as suggested in Tanzanian policy, including the identification of a blood donor, which was not stated by any respondents. There also appears to be a need to underline the importance of making preparations from early in pregnancy, and emergency preparedness around getting to a health facility in the event of unexpected or early labour. The attitude expressed by some that the functional items to be used during birth could simply be bought at the health facility might also lead to a delay in preparedness. If an insufficient amount of money has been saved, those items might not be purchased at all, which, as participants suggested, might inhibit care-seeking during delivery. The perceived refusal of services to women who were not prepared for birth should be addressed through supportive supervision and provider education.It has been well documented that in Sub-Saharan Africa, as in other settings, males strongly influence payment for birth items, transportation to health facilities, and decision-making around care-seeking practices , 38–44. The household survey was carried out throughout the entire district of Tandahimba, but qualitative data were only collected from one division. The question around birth preparedness was open, with women encouraged to state anything they had prepared rather than being asked to respond to a structured list. Given that almost 70 % of births occurred at a facility, this method may have resulted in an underestimate of identification of a facility, saving money, and arrangement of transport, which other studies have reported to occur more frequently , 25. FinThis study highlighted that the majority of women make at least some birth preparations and give birth in health facilities. Women seemed to place importance on functional items needed for delivery rather than on arranging transport or identifying a health facility, and did not always appreciate the importance of making birth preparations early. As such, there is a need to emphasise emergency preparedness in education to women and their partners during antenatal care. Furthermore, to address some barriers to making preparations or delivering in a health facility, it would also be beneficial to continue to encourage increased male engagement in pregnancy and childbirth as well as greater female agency around both. Community-based interventions may be well poised to work toward these aims.EQUIP, Expanded Quality Management Using Information Power


Behaviour is guided by perceptions and traditions. As such, understanding culture and religion is important in order to understand healthcare behaviour. Religious perceptions shape a person's understanding of the world and are maintained through texts and tradition. One such important religious text in relation to sexual and reproductive health is the Nativity story. This account of the conception and birth of Jesus is well known in the Christian cultural sphere and beyond, and it has for generations shaped perceptions of childbirth.This paper attempts a re-reading of the Nativity story using a hermeneutic approach.This reveals a dual understanding of the Nativity, not just as an account of immaculate transcendence and a rosy Christmas tale, but as a source of identification for pregnant women and mothers and a call to action for improved maternal and child healthcare. Ideas shape our minds and our minds shape our behaviour . ConceptReligion plays a vital part in bringing sense and meaning to reality . All humHermeneutics can be described as the interpretation of text; it is a research methodology that departs from what is currently known. There are many schools and adaptations of hermeneutics, but basically hermeneutics set up rules for interpretation. By various means hermeneutic methods strive to create a deeper understanding and gain new insights by moving from the whole to the details and back to the whole, with input of experience and contextual interpretations along the way ( the way  11). Th. ThHerme the way  (11).The Nativity story is many times perceived as something of a religious success story, an account of an immaculate birth, with angels singing and the whole of creation celebrating the birth of its saviour . The accThe hermeneutic approach now directs us to go from the whole, as described in the previous paragraph, to look more closely at the details . This isThe rest of the pregnancy seems to have been without complications and the next part of the Nativity story describes the delivery. It is preceded by a long and arduous journey, from Nazareth to Bethlehem (Luke 2:4–5), a trip of about 120 kilometres. Lack of rest and hard physical exertion are known risk factors for preterm birth. This might also be the reason for the poor birth preparations made by the two parents, resulting in Mary having to give birth in a stable (Luke 2:7). There is furthermore no account of any assistance at the birth, except maybe from Joseph. The delivery can hardly be considered to have been hygienic as the newborn was placed in a feeding trough for animals (Luke 2:7). Whether Mary initiated breastfeeding within one hour or not, as is the standard recommendation today, is not mentioned in the text, but it seems that skin-to-skin care was not practised. The gospel mentions explicitly that the newborn was ‘wrapped in cloths’ (Luke 2:12), indicating that this was the preferred method of the day. The account of Jesus’ birth thus contains many examples of unfavourable birth conditions, as outlined in When we now continue in the hermeneutic circle we find that the Nativity story is far from a success story . It is fHowever, let us take another turn in the analysis and look at the parts in the light of today's global maternal and child health situation . MillionThe picture that emerges after a second round in the hermeneutic circle is a rather blunt and straightforward description of the vulnerable situation of pregnancy and childbirth still experienced by many women today. Far from being a rosy account with heavenly hosts and adoring shepherds, the Nativity story depicts a number of problems addressed in the continuum of care. It thus becomes a source of identification rather than a testimony of immaculate transcendence. Maybe it is there the strength of the story lies, in the tension between reality and divinity? Mary has become an almost divine figure, worshipped by millions the world over, while at the same time being subject to many of the same conditions still faced by so many women today.Religious texts shape our perceptions of the world, not only in relation to the divine, but also by making sense of reality through establishing standards and norms for behaviour . We have