The author subsequently visited the 12 hospitals that replied affirmatively and welcomed collaboration, to assess the completeness and quality of the records and the feasibility of tracing people born in the hospital many decades earlier. CSI (Church of South India) Holdsworth Memorial Hospital (HMH) in the city of Mysore, southern India, had preserved its obstetric records in hard copy from 1934 to the present. The records were in good condition and were remarkably complete for birth measurements . Furthermore, the relative isolation of Mysore has ensured stability of the population, and a tracing exercise showed that it was possible to locate people born in HMH as far back as 1934 and match them accurately to their birth records.Between 1993 and 2001, in a collaborative study with the Medical Research Council Environmental Epidemiology Unit (now Lifecourse Epidemiology Unit), University of Southampton, UK, the birth records at HMH were used to trace people born in the hospital between 1934 and 1966. A house-to-house survey, of an 8-square-mile section of the city surrounding HMH, located individuals who said they had been born in the hospital. They were matched to birth records using an algorithm; 3427 men and women born during 1934–66 were matched in this way and 1069 were recruited to the study see.n = 1069, 1993–2003) examined associations of size at birth with adult cardiometabolic disorders  and lung function.n = 518) were invited to participate in follow-up studies that examined:The first study , 2–3 years after the initial study,n = 383, 2003–04;whether smaller size at birth was associated with higher incident diabetes and CHD, 10 years after the initial study,and a small intergenerational study between 1997 and 2003 examined associations between the birth size of members of the cohort and cardiometabolic risk factors of their children; this study included 506 adult offspring of cohort members.Holdsworth Memorial Hospital (HMH) is a mission hospital, now governed by the Church of South India. It was built as a maternity hospital in 1905 in a poor, crowded area of the city. At that time it was one of only two major maternity units in the city. Since 1934, birthweight, length and head circumference have been recorded routinely for all babies born in the hospital. Until the 1960s these measurements were made by one of three midwives, using an agreed protocol, although the details of how the measurements were made have been lost. The birth records also contain the parents’ names, occupations, address, religion or caste and the mother’s obstetric history. Some of the mothers attended the antenatal clinic, and their records (approximately 40%) include their weight during pregnancy, whereas others came to the hospital for the first time only when they were in labour. In the latter case, maternal weight was generally missing, but approximately 55% of mothers had pelvic diameters measured on admission in labour.A total 24 824 singleton babies were born alive in HMH between 1934 and 1966. The house-to-house survey in 1993–2001 identified 6059 people who said they had been born as singletons in the hospital between 1934 and 1966, and of these 3427 were successfully matched to their birth records. The main difficulties in matching were that most adults were unaware of their date of birth and knew their age only vaguely, and that the birth records did not contain the infant’s name because Indian babies are usually named several weeks after birth. Cohort members were therefore matched to their birth record through their parents’ names, addresses and occupations, the number, sex and order of older siblings and the mother’s obstetric history. All of these details had to match exactly. Of the 3427, 1069 participated in the first study between 1993 and 2003 and constitute the Mysore Birth Records Cohort.As a part of the current ongoing study we are recruiting men and women from the original 3427 matched to their birth records but who were not approached for the first study in 1993–2003. These will potentially boost the cohort numbers in future.In 1996–97, 435 of the original cohort members, who had investigations between 1993 and 1995, were assessed for cardiac dimensions and arterial compliance.In 2003–04, 383 of the original cohort members who had investigations between 1993 and 1995 participated in a follow-up study for incident diabetes and CHD..There was no contact with the cohort between 2005 and 2011. The surviving members of this cohort are now being retraced and asked to participate in a follow-up study  to measure cognitive function, cardiometabolic disorders and mental disorders in late life.n = 1069) took part in the initial study. Compared with the remainder of the original births, the 3427 individuals who were traced were 48 g heavier , 0.25 cm longer  and had a 0.092-cm larger head circumference  at birth. Compared with the 3427, the 1069 men and women who were studied were slightly lighter and shorter, but had similar head size .The 3427 cohort members who were re-traced and matched to their birth records in 1993–2001 were only a small percentage (14%) of all the births in HMH during 1934–66, and of these approximately 30% (p = 0.06) and 0.62cm ] than those lost to follow-up. Looking at adult characteristics, they were of higher socioeconomic status [Kuppuswamy score +2.14 ]. However, the groups were similar in age, gender mix, height, body mass index, educational attainment and prevalence of diabetes and clinical coronary heart disease in the earlier study.When we attempted to re-trace a sub-sample of 518 in 2003–04  56 (11%) had died, 25 (5%) had moved away from Mysore and we were unable to obtain any information about them and 53 (10%) did not wish to take part in a follow-up study. This made a loss to follow-up rate of 26%. The 383 men and women who were successfully re-studied were heavier and longer at birth compared with the remainder of the 517  or [muralidoc@gmail.com], or Prof. Caroline Fall at MRC Lifecourse Epidemiology Unit, Southampton in the UK at [chdf@mrc.soton.ac.uk].Profile in a nutshellBetween 1993 and 2001, 3427 men and women born as singletons during 1934–1966 at Holdsworth Memorial Hospital, Mysore, southern India, were traced by a house-to-house survey of the area of the city surrounding the hospital, and matched to their birth records. A total of 1069 of these participated in a study (1993–2003) to examine the relationship between size at birth and adult cardiometabolic disorders and lung function. They constitute the Mysore Birth Records Cohort.The studies with this cohort were among the first in a low- and middle-income country to test developmental origins of health and disease (DOHaD) concepts with predicted associations between small size at birth and adult coronary heart disease, insulin resistance and low lung function.This is one of few birth cohorts in a low- and middle-income country in which a substantial proportion of surviving members are aged over 60 years, and is a unique resource for lifecourse epidemiology studies in old age.Surviving members of this cohort are now being asked to participate in a cross-sectional study to measure cognitive function, cardiometabolic disorders and mental disorders in late life.Researchers wishing to access the data from this cohort should contact Dr SC Karat, Dr Murali Krishna or Prof. Caroline Fall.This work was funded by the: Medical Research Council, Parthenon Trust, Wessex Medical Trust, Wellcome Trust, Wellcome DBT India Alliance and Department for International Development, UK.Conflict of interest:None of the authors report any conflict of interest.


Late preterm births have enormously increased in the last decades and there is mounting evidence showing that infants born late preterm are less healthy than infants born at term  and theyMore recently, an increased neuromorbidity has been documented and long-term neurodevelopmental impairments  have been reported in this population ,4. The nTherefore, late preterm infants have a risk to develop brain lesions which is lower than more premature babies but higher than term newborns and they can be affected by brain lesions common to both preterm and term infants . HoweverConsidering that most of the brain lesions are clinically subtle or silent during the neonatal period, a cranial ultrasound screening may play a role in: 1. detecting babies at risk of impaired neurodevelopment later in childhood and who may benefit from early intervention programs; 2. identifying the most significant perinatal risk factors associated with brain abnormalities in such a large low-risk population in order to target the potential need for cranial ultrasound at birth. Based on these assumptions we performed a cranial ultrasound screening project on late preterm infants. Our preliminary data (unpublished data) suggest that lower gestational age, within the late preterm period, and early neonatal morbidities, can provide an indication at birth to undergo a cranial ultrasound scan as they are associated with a higher risk to develop brain abnormalities. Late preterm infants represent a vulnerable population and investigation and follow-up program should be modulated according to the prenatal, perinatal and postnatal characteristics.Follow-up studies are needed to correlate neonatal ultrasound findings with long-term neurobehavioral outcomes in late preterm infants.


Major birth defects are an important public health issue because they are the leading cause of infant mortality. The most common birth defects are congenital heart defects, neural tube defects, and Down syndrome. Birth defects surveillance guides policy development and provides data for prevalence estimates, epidemiologic research, planning, and prevention. Several factors influence birth defects surveillance in the United States of America (USA). These include case ascertainment methods, pregnancy outcomes, and nomenclature used for coding birth defects. In 2015, the nomenclature used by most birth defects surveillance programs in USA will change from ICD-9-CM to ICD-10-CM. This change will have implications on birth defects surveillance, prevalence estimates, and tracking birth defects trends. Birth defects are an important public health issue because they are the leading cause of infant mortality in the United States of America (USA) causing one in every five infant deaths . In USA,The most common birth defects are congenital heart defects , 6, 7, nBirth defects surveillance provides data for prevalence estimates, epidemiologic research, planning, and prevention and it guides policy development . HoweverThis paper reviews the challenges of birth defects surveillance in USA and explores the implications of the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) in the year 2015 and its potential impact on birth defects surveillance.Public health surveillance is the systematic and continuous collection, management, analysis, and interpretation of data which is disseminated in a timely manner to individuals working in public health . InteresFollowing the thalidomide tragedy, the Metropolitan Atlanta Congenital Defects Program (MACDP), the first population-based birth defects surveillance program in USA, was established by Centers for Disease Control and Prevention (CDC) in 1967 to conduct birth defects surveillance . The BirThe National Birth Defects Prevention Network (NBDPN), a volunteer-based organization which works in collaboration with CDC, was established in 1997. NBDPN's goals are to maintain a national network of state- and population-based birth defects surveillance programs and to be involved in birth defects research and prevention. The NBDPN has done a tremendous job of improving the uniformity of birth defects surveillance in USA and also provides technical assistance to states whenever needed. In 2004, NBDPN published guidelines for conducting birth defects surveillance .In 2013, there were 43 population-based birth defects surveillance programs in USA and 41 of these programs reported data on select birth defects to NBDPN , 18. ThiGlobal birth defects surveillance and research are conducted by the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), a voluntary nonprofit organization affiliated with World Health Organization (WHO) that was established in 1974 . USA hasPhysical examination of infants provides the best assessment of birth defects; however, this is very expensive and most birth defects surveillance programs cannot afford this resource intensive method. Conversely, birth defects are underreported in birth certificates; therefore this method of surveillance does not capture all cases of birth defects in a given population . ConsequBirth defects data can be obtained from multiple sources which provide the necessary information for each case. Birth and pediatric hospitals can be used to obtain a majority of the cases. However, other data sources, such as laboratories and outpatient clinics, may provide birth defects data. Case ascertainment methods used by birth defects programs include active, passive, and active-passive (hybrid).Active case ascertainment is the preferred method for birth defects surveillance because program staff go out to find birth defects cases from hospitals, clinics, and other health care facilities . This meIn passive case ascertainment, the birth defects surveillance program receives reports of cases of infants with birth defects from different data sources such as hospitals, clinics, and other sources. These sources may be voluntary or are mandated by law . The comSome birth defects surveillance programs use active-passive case ascertainment, a hybrid approach, whereby birth defects cases are reported to them by hospitals and other reporting facilities just as in passive surveillance. However, program staff uses various methods to ascertain the cases from these sources . For exaIn 2013, 43 population-based birth defects surveillance programs reported data to NBDPN; of these, 17 (40%), 13 (30%), and 13 (30%) used active case finding, passive case finding, and passive case finding with active case ascertainment, respectively .Data from the three case ascertainment methods may be comparable; however, birth defects surveillance programs that use passive case ascertainment need to incorporate various measures to ensure that the birth defects reports they receive are an accurate representation of birth defects in their targeted population . This maResearchers linked data for select birth defects from two independent birth defects surveillance programs in Florida that used active and passive case ascertainment methods, respectively . The geoAnother study used 2006–2010 nationwide Down syndrome data reported to NBDPN by 41 population-based birth defects surveillance programs . The prePopulation-based birth defects surveillance programs include live births only, live births and stillbirths only, and live births, stillbirths, and elective terminations  in their birth defects case definition. The pregnancy outcome included by a birth defects surveillance program depends on the purpose, resources available, and access to the pregnancy outcome information . Birth dEthen and Canfield compared birth defects prevalence rates for elective terminations of any gestation and elective terminations of at least 20-week gestation or 500-gram birth weight . They reIt is imperative that prevalence estimates that use data from live births only are interpreted cautiously because the above studies clearly demonstrate that including all pregnancy outcomes provides the most accurate birth defects prevalence estimates. In addition, elective terminations should include cases of any gestation and not be limited to those equal to or greater than 20-week gestation. Moreover, there is need for a general consensus on whether elective terminations will include all cases irrespective of gestation age and birth weight or include elective termination of at least 20-week gestation and birth weight of 500 grams , 26. ThiMedical advances have made it possible for prenatal screening and detection of birth defects during pregnancy. Most prenatal procedures occur in outpatient settings and active surveillance would be the best method for prenatally diagnosed birth defects because of the followup needed with the outpatient clinics to abstract cases of birth defects. Birth defects surveillance programs that use passive surveillance and rely on hospitals and other reporting facilities would be faced with the challenge of receiving reports of prenatally diagnosed birth defects. Cragan and Gilboa conducted a study using data from outpatient prenatal diagnostic clinics to estimate birth defects prevalence . They noThe International Classification of Diseases (ICD) is the standard method for coding morbidity and mortality data to monitor disease incidence, prevalence, and other health conditions . ICD-10 In 1990, WHO published ICD-10 in a continued effort for detailed descriptions of diseases and health conditions in the ever changing medical field, with new diseases and health conditions being added frequently. Most countries around the world use this coding scheme for both morbidity and mortality . HoweverNBDPN has already translated ICD-9-CM birth defects codes to ICD-10-CM . HoweverSome shortcomings of ICD-10-CM include a lack of distinction between birth defects among premature and mature infants such as patent ductus arteriosus. In addition, polydactyly, although not a major birth defect, does not have a code to indicate the position of the extra digit .Researchers used Alberta Congenital Anomalies Surveillance System (ACASS) data to compare an adaptation of the ICD-10-Royal College of Paediatrics and Child Health (ICD-10-RCPCH) coding with ICD-9-British Paediatric Association (ICD-9-BPA) . ACASS tMoczygemba and Fenton conducted a pilot study to evaluate the use of ICD-10-CM for diabetes, heart disease, and pneumonia . The resThe full impact of the implementation of ICD-10-CM will be best evaluated after all the healthcare facilities transition to the new system. However, birth defects surveillance should be aware of some of the anticipated issues and address them accordingly. In addition, WHO will release the ICD-11 in 2017, two years after the proposed implementation of ICD-10-CM in USA. It is questionable whether USA will be ready to implement the ICD-11 soon after its release in order to allow comparison of morbidity and mortality data with the rest of the world.ICD-9-CM is the coding scheme that has been used in USA for over 30 years to code diagnoses and procedures during a hospital encounter. It is also used for research, hospitalization rates, and estimation of healthcare costs. ICD-9-CM is based on 1978 WHO's ICD-9 and was modified to meet statistical needs in USA and implemented in 1979 . The ICDOver half of the 43 USA population-based birth defects surveillance programs that report data to NBDPN use ICD-9-CM to code birth defects . This ha 741.085 spina bifida, meningocele, cervicothoracic, with hydrocephalus, 741.086 spina bifida, meningocele thoracolumbar, with hydrocephalus, 741.087 spina bifida, meningocele, lumbosacral, with hydrocephalus .The British Paediatric Association (BPA) modified the ICD-9 in 1979 to be used for pediatric and neonatal cases. The codes range from 740.000 to 759.999 in order to be similar to ICD-9 codes. The first four digits match the ICD-9; however, the fifth digit is specific to children. In 1983, the staff of CDC's Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, modified the BPA coding system and created a 6-digit code for the birth defects classification system to provide more details of a birth defect . In addiThe CDC/BPA coding scheme while being very detailed has some shortcomings. These include being complicated to use; comprehensive coding instructions for some birth defects are not provided; it is over 30 years old and the birth defects field has evolved in this time period making some codes outdated, and individuals using the coding scheme need to be familiar with medical terminology, human anatomy, and birth defects .Like the ICD-10-CM coding system, the 6-digit CDC-modified BPA system allows a more robust system that provides greater specificity of birth defects, laterality of the defect, whether a defect is possible or probable or diagnosed only prenatally, and related conditions. For example, omphalocele is coded as 756.700 and gastroschisis is coded as 756.710. In addition, the CDC/BPA coding scheme is even more detailed than the ICD-10-CM for some birth defects such as spina bifida without anencephalus in which CDC/BPA has 21 codes compared to 10 and 2 codes for ICD-10-CM and ICD-9-CM, respectively.Birth defects surveillance in USA faces some challenges and a more standardized surveillance method used by all birth defects programs is needed. Cancer surveillance and the behavioral risk factor surveillance system (BRFSS) core questions have standardized surveillance procedures. Furthermore, the aforementioned surveillance systems are federally funded in all 50 states, District of Columbia (DC), and USA territories. Yet, only one-third of state-based birth defects surveillance programs receive federal funding . With reBRFSS and birth defects surveillance are inherently very different; however, some guidelines from BRFSS such as having core, rotating, optional, and state-added modules or questions may be applicable to birth defects surveillance. Categorization of birth defects reported to NBDPN, for instance, core and optional, may be very useful especially after October 2015 once the ICD-10-CM is implemented. NBDPN recently revised the birth defects list which will be implemented soon by birth defects surveillance programs. The revised birth defects list has now categorized birth defects as core, recommended, and extended . The revision of the birth defects list will potentially increase reporting of all core birth defects to NBDPN by most birth defects surveillance programs. Currently, NBDPN has a list of 45 birth defects  that areBirth defects surveillance programs in USA use various case ascertainment methods (passive versus active surveillance), include various pregnancy outcomes , and use different nomenclature (ICD-9-CM and CDC/BPA) in their surveillance efforts. The change in nomenclature from ICD-9-CM to the more comprehensive ICD-10-CM in 2015 will have an impact on birth defects surveillance, especially the comparison of data in the two coding systems. Individual state's birth defects surveillance legislation and resources available greatly determine the scope of birth defects surveillance efforts of state programs. However, the effects of this nomenclature change can only be fully assessed once the implementation of ICD-10-CM has occurred.


Birth weight is a crucial determinant of the development potential of the newborn. Abnormal newborn weights are associated with negative effects on the health and survival of the baby and the mother. Therefore, this study was designed to determine the prevalence of abnormal birth weight and related factors in Northern region, Ghana.The study was a facility-based cross-sectional survey in five hospitals in Northern region, Ghana. These hospitals were selected based on the different socio-economic backgrounds of their clients. The data on birth weight and other factors were derived from hospital records.p < 0.001), female gender (p < 0.001) and location  (p < 0.001) were significantly associated with decreased risk of macrosomic births. On the other hand, female infant sex (p < 0.001), residential status  (p < 0.001) and parity (0–1) (p < 0.001) were significantly associated with increased risk of low birth weigh.It was observed that low birth weight is still highly prevalent (29.6 %), while macrosomia (10.5 %) is also increasingly becoming important. There were marginal differences in low birth weight observed across public hospitals but marked difference in low birth weight was observed in Cienfuegos Suglo Specialist Hospital  as compared to the public hospitals. The private hospital also had the highest prevalence of macrosomia (20.1 %). Parity (0–1) (Our findings show that under nutrition (low birth weight) and over nutrition (macrosomia) coexist among infants at birth in Northern region reflecting the double burden of malnutrition phenomenon, which is currently being experienced by developing and transition counties. Both low birth weight and macrosomia are risk factors, which could contribute considerably to the current and future burden of diseases. This may overstretch the already fragile health system in Ghana. Therefore, it is prudent to recommend that policies aiming at reducing diet related diseases should focus on addressing malnutrition during pregnancy and early life. Weight at birth can be classified into three categories, that is normal (birth weight ≥2.5 kg < 4.0 kg), too light (low birth weight (birth weight < 2.5 kg) or too heavy (macrosomia) (birth weight ≥ 4.0 kg). The last two conditions have adverse consequences on the life of the infant. Studies have shown that apart from short-term consequences such as high infant mortality and childhood growth failure among survivors, abnormal birth weight has a long-term risk in the form of high prevalence of adult coronary heart disease and type 2 diabetes . AccordiLow birth weight is caused by either a short gestation period <37 weeks) or retarded intrauterine growth (or a combination of both)  weeks or, 9. AccoPre-term birth, maternal age (<20 years and >35 years), stress during pregnancy, maternal under nutrition before pregnancy and first parity may lead to low birth weight . Other eOn the other hand, macrosomia prevalence in the developed countries is between 5 % and 20 % but an increase of 15 %-25 % has been reported in the past decades, which is solely driven by an ascendance of maternal obesity and diabetes . HoweverHigh pre-pregnancy weight or BMI, mother’s age (20-34years) and height, excessive gestational weight gain, gestational and pre-gestational diabetes mellitus, post-term pregnancy and male sex are found to be associated with macrosomia –19.Ghana, like many other developing countries, is experiencing the double burden of malnutrition phenomenon where maternal under nutrition coexists with maternal over-nutrition , 21. ThiAbnormal birth weight (low birth weight and macrosomia) may contribute to the current and future burden of chronic diseases. Complications during delivery as a result of macrosomia can lead to additional hazards to the mother and newborn in resource scarce settings as compared to resource rich settings because of the restricted availability of emergency obstetric and other essential care . TherefoThe aim of this study was to determine the prevalence of abnormal birth weight (low birth weight and macrosomia) and related factors such as socio-economic status and demographic characteristics of mothers in the Northern region of Ghana.The study examined the delivery records of the year 2013 in five hospitals in Northern Ghana where there has been steady economic growth in the past decade amidst extreme poverty, to determine the prevalence of abnormal birth weight. Findings from the study will provide useful information to policy makers for the design of appropriate public health interventions. The region is among the poorest regions in the country. The main occupation of the people in the region is agriculture and related activities. The region has 26 districts, with 24 of them being predominantly rural [According to UNICEF  about 62Prior to the selection of health facilities for the study, ten key informants  who know and understand issues related to facility-based deliveries were identified and contacted. The discussion with these key informants was to get their inputs into the design and to seek their advice on the selection of the facilities. Their knowledge on the number of facility-based deliveries, availability and completeness of delivery records informed their recommendation. Based on this advice, five hospitals were purposively selected including one of the oldest private facilities in Tamale with the highest number of deliveries, Cienfuegos Suglo Specialist Hospital.The five facilities were located in three districts, which accounted for about half of all the facility-based deliveries in 2013 in the region .Standard of measurement across the hospitals was checked by placing a standard weight in the scale used to measure the newborn weight in all the hospitals; there was no significant difference observed in the five hospitals selected for this study.p-value of less than 0.05 at 95 % confident level was considered as statistically significant.A multinomial logistic regression model was used to determine the associations between maternal factors and abnormal birth weight. This model was used because the dependent variable in this study was nominal  and the Hausman test performed showed no evidence of violation of the independent of irrelevant alternative (IIA) condition. A Consistency and plausibility checks were done after the data entry to ensure that errors were reduced. Overall, 0.01 % of the data on birth weight, 0.05 % of the data on parity, 0.03 % of the data on maternal age were missing. Only 1100 (33 %) of the infants had their gestational age recorded and for that matter it was not used in the multinomial logistic regression analysis. No attempt was made to input missing data because there was no information about whetehr these data were missing at random .Ethical approval for the research was obtained from the Navrongo Health Research Centre’s Ethical Review Board and Heidelberg University. Written permission was obtained from the health Hospitals to use the health records. However, because this study was done at the population level whereby data were extracted from medical records with no individual identifications, individual informed consent was not obtained.The hospitals in this study offer various services to clients with varied socio-economic backgrounds. For instance, Cienfuegos Suglo Specialist Hospital  provides specialized obstetric and gynecology services to urban and high-income class in the Tamale Metropolis.. The clients of Tamale Teaching Hospital have mixed socio-economic backgrounds but are mostly from the high and middle-income classes who are largely urban dwellers. The hospital also gets clients from the lower income class who mostly come from the rural areas of the Metropolis and through referrals. Tamale Central Hospital also gets their clients predominantly from the middle-income class who are mostly urban dwellers but a significant proportion also comes from low-income class.Tamale West Hospital provides Obstetric and Gynecology services to mostly the urban poor, some middle-income class and women from rural Tamale and surrounding districts while Savelugu District Hospital provides Obstetric and Gynecology services to mostly farming communities and a small proportion of middle-income class and urban dwellers in the District capital. Table The data was analyzed for 3318 deliveries in 5 hospitals. The mean age of the mothers was 27 ± 6 years. The mean birth weight observed among the infants was 2.9 ± 0.73 kg. Prevalence of low birth weight was 29.6 % while the prevalence of macrosomia was 10.94 %  was 48 % higher as compared to those born in the Tamale Teaching Hospital  whereas in Tamale Central Hospital (clients are mostly from middle income class) the risk of being born macrosomic versus normal was 58 % lower relative to Tamale Teaching Hospital when age, location and parity of the mother as well as sex of the infant were held constant  was 60 % higher compared to Tamale Teaching Hospital Table .More to the point, the risk of being born macrosomic for a first/second born as against normal was 52 % lower compared to a third/fourth born. Likewise, the risk of being born macrosomic as against normal for infants born by a rural mother was 45 % lower compared to an infant born by an urban mother. The risk of being born macrosomic as against normal for female infants was also 37 % lower compared to male infants . The findings of the study show that prevalence of low birth weight in Northern Ghana is high as compare to the national prevalence  and abouOne of the factors that could explain this observation is that more of the regions’ population is engaged in subsistence farming which is mainly rain fed but due to regular drought and erratic rainfall patterns their harvest is not always sufficient to take them throughout the year. Quaye  reportedThe high prevalence of LBW observed in the present study could also be due to poor access to health services such as antenatal services due to socio economic barriers which are found to be strongly related to access to adequate prenatal services , 31. AboThough it must be said that the government of Ghana has already put measures in place to improve access to pre-natal services by making antenatal care services free for all pregnant women across the nation, the success of these programs is limited due to socio-economic barriers. Other evidence adduced by Betegeka & co.  shows thThe low prevalence of low birth weight in the private hospital was expected because it is obvious that the mothers who deliver in the private clinics are from high-income class of the society and have a better socio-economic status as compared to those who deliver in the public hospitals. Better socio-economic status is found to have a positive impact on delivery outcome. It is reported that improved maternal education, income and occupation have strong positive association with birth weight .High prevalence of macrosomia was also observed in the present study but this appeared not to be very different from prevalence reported by studies in other developing countries, which used a similar cut-off point as this study especially in Africa. For example, a prevalence of 7.5 %, 8.4 % and 14.9 % was reported in Nigeria, Uganda and Algeria respectively  and in CThe study also confirmed established risk factors of macrosomia. For example, parity 2–3 was associated with increased risk of macrosomic births, which is consistent with the findings of the study conducted by Koyanagi & co. . They shThe study had some limitations because of irregularities of data in the delivery register. For example in every hospital the delivery records were under the responsibility of the nurse in charge of the maternity ward. They were kept in a variety of places and could only be located if the in-charge was present. There were difficulties in locating the maternity register in some facilities. This was because the active maternity register books were kept on the desk in the nursing station and the old one (previous years) kept by the maternity ward in-charge. Tamale Central Hospital could not provide delivery records for April, May, June, and July while at the Tamale West Hospital, January, February and March delivery records could not be found.There was wide variation in the level and type of information provided in the maternity records. Some facilities recorded gestational age while others did not. The availability of data varied, ranging from 99.9 % for birth weight to 33 % for gestational age at delivery. As a result of the absense of gestational age at delivery in the delivery register in some of the hospitals gestational age, which is noted as a confounder of birth weight was excluded in the analysis.Our findings show that under nutrition (LBW) and over nutrition (macrosomia) coexist among infants at birth in the Northern region of Ghana reflecting the double burden of malnutrition phenomenon, which is currently being experienced by developing and transition counties. Given the paradox with increased risk of obesity at both ends of the birth weight spectrum and the potential health risks of low birth weight and macrosomia coupled with the ‘obesogenic’ environment that is being created by the steady urbanization in developing countries, there is a need for a paradigm shift in the fight against diet related diseases by focusing on preconception and maternal nutrition during pregnancy in a comprehensive and inclusive manner.Our findings also provided empirical support for the link that existed between infant sex, maternal age, parity and differences in socio-economic classes and birth weight.


Uterine artery pseudoaneurysms are dangerous and can lead to severe hemorrhage. We report an uncommon cause of a giant pseudoaneurysm in a missed miscarriage in a woman with a cesarean scar pregnancy.The patient was a 25-year-old Chinese woman with a missed miscarriage in a cesarean scar pregnancy. Curettage was performed under ultrasound monitoring. A uterine artery pseudoaneurysm measuring 71 × 44 × 39 mm was detected the next day by Doppler ultrasonography. While waiting for admittance to an advanced institution to undergo embolization treatment, the pseudoaneurysm ruptured spontaneously. The subsequent severe hemorrhage necessitated hysterectomy.A delay in diagnosis of uterine artery pseudoaneurysms may result from a long period between the curettage and follow-up examination. Ultrasound and Doppler ultrasonography should be performed repeatedly at short intervals to rule out them, especially in cesarean scar pregnancies. For a giant uterine artery pseudoaneurysm, interventional embolization might be the first treatment choice. If time allows, intra-operative ligation of the feeding vessels should be attempted before any decision to perform a hysterectomy is made. However, hysterectomy remains a possibility when severe bleeding occurs. Uterine artery pseudoaneurysms are rare complications that can arise after repeated curettage, abortions, cesarean sections, uncomplicated vaginal deliveries or reproductive tract infections. They are dangerous and can lead to severe hemorrhage. The interval from pelvic surgery to the onset of symptoms is typically 1 week to 3 months . This deA literature search found three case reports of cesarean scar pregnancies complicated with a uterine artery pseudoaneurysm -7. Here,The 25-year-old Chinese female patient had been amenorrheic for 2 months and was referred to the hospital because of painless vaginal bleeding that had lasted for 15 days. Four years ago she had a missed miscarriage at 9 weeks of gestation, which was managed by surgical curettage. Two years prior to presentation she had delivered a baby by elective cesarean. Twenty days before presenting at the hospital she had been diagnosed as 40 days pregnant based on elevated urinary levels of beta human chorionic gonadotropin (β-hCG).The study was approved by the Institutional Review Board at the First Affiliated Hospital, College of medicine, Zhejiang University. The procedures were conducted according to the principles of the Helsinki Declaration. On presentation the vaginal bleeding was scanty and her serum β-hCG level was 1200 mIU/mL. Transvaginal ultrasonography showed that the uterus measured 106 × 64 × 60 mm. There was an echo-free area above the inner cervical os, measuring 43 × 23 mm, without any blood flow signal, yolk sac or embryo present. A mixed echo mass measuring 29 × 15 mm was detected in the uterine cavity but no blood flow signal could be found in it. The patient was diagnosed as having had a missed miscarriage in the cesarean scar region of the uterus and curettage was performed with ultrasound monitoring. During the procedure, massive bleeding (~600 mL) occurred but this was stopped with an intravenous injection of oxytocin and uterine massage. Chorionic tissue was aspirated and proven as such by histopathology. When the curettage was finished, the uterine cavity was revealed as a clear thin line by ultrasound and was considered normal. Vaginal packing was performed subsequently.At 18 hours after curettage, the serum β-hCG level was 1164 mIU/mL. A cystic lesion with an uneven wall in the lower part of the uterus measuring 71 × 44 × 39 mm was detected with gray-scale ultrasonography (Figure The patient was examined by interventional radiologists; however, they lacked experience in treating such a giant lesion and thought that repeated treatment might be required. A persistently high serum β-hCG concentration suggested that there were retained chorionic villi present within the pseudoaneurysm. Thus, recanalization of the pseudoaneurysm by rapid recruitment of collateral vessels might occur even after arterial embolization. Repeated uterine curettage immediately after embolization, or methotrexate therapy, might decrease the likelihood of recanalization. Therefore, the patient sought admittance to an advanced institution for embolization treatment. However, while waiting to be admitted, massive bleeding occurred suddenly at day 10 and emergency surgery was performed.During the operation, a 60 × 70 × 50 mm pseudoaneurysm was located in the cesarean scar position Figure . IdeallyUterine artery pseudoaneurysms are very dangerous and should be diagnosed as soon as possible. Potential causes include vascular injury following abortion, curettage, and pelvic surgery. Traumatic injury to the vessel wall causes wall incompetence and hemorrhage leading to a pseudoaneurysm. In this case, both two-dimensional and Doppler ultrasound scans were useful in detecting the pseudoaneurysm.In two-dimensional ultrasonographic images, a pseudoaneurysm manifests as a hypoechoic mass and is thereby not easily differentiated from a hematoma or a true aneurysm. Color Doppler ultrasonography was helpful in this case as it demonstrated turbulent arterial flow with a to-and-fro pattern, connected to a parent artery by a narrow neck in the pseudoaneurysm. Blood flow into the mass during systole and away from the mass during diastole can be explained by the pressure gradient between a distended high-pressure pseudoaneurysm and the low pressure in the artery during diastole . A true In this case, the pseudoaneurysm was located in the cesarean scar. The wall of the pseudoaneurysm was very thin and at high risk of rupture, it should have been treated as rapidly as possible. In such cases, endovascular treatment is often the first-line therapy. Embolization can be achieved with coils, stents and injectable liquids ,10, and If time allows, and if embolization is not an option, intra-operative ligation of the pseudoaneurysm feeding vessels should be attempted prior to resorting to hysterectomy, especially in patients with low parity . LigatioAnother possible treatment method was direct injection of thrombin into the pseudoaneurysm , but no A delay in diagnosis of uterine artery pseudoaneurysms may be caused by a long period between the curettage and follow-up examination. Ultrasound and Doppler ultrasonography are recommended to be performed repeatedly at short intervals to rule out them, especially in cesarean scar pregnancies. For a giant uterine artery pseudoaneurysm, interventional embolization might be the first treatment option when the diagnosis is made. Alternatively, if time allows, intra-operative ligation of the feeding vessels should be performed prior to any decision to resort to hysterectomy. However, hysterectomy remains a possibility when severe bleeding occurs.Written informed consent was obtained from the patient for publication of this Case Report and the accompanying images. A copy of the written consent is available for review by the Editor of this journal.The authors declare that they have no competing interests.YM carried out the ultrasonography, participated in treatment of the patient and wrote the manuscript. YX assisted with the ultrasonography and followed up the treatment of the patient. YH participated in the design of the study and helped to draft the manuscript. TJ conceived of the study and participated in the diagnosis and in drafting the report. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/14/89/prepub


In this study, we first suggest a simple approach to characterize configuration of gas-aqueous liquid two–phase flow based on discrete solid-liquid contact electrification, which is a newly defined concept as a sequential process of solid-liquid contact and successive detachment of the contact liquid from the solid surface. This approach exhibits several advantages such as simple operation, precise measurement, and cost-effectiveness. By using electric potential that is spontaneously generated by discrete solid–liquid contact electrification, the configurations of the gas-aqueous liquid two-phase flow such as size of a gas slug and flow rate are precisely characterized. According to the experimental and numerical analyses on parameters that affect electric potential, gas slugs have been verified to behave similarly to point electric charges when the measuring point of the electric potential is far enough from the gas slug. In addition, the configuration of the gas-aqueous liquid two-phase microfluidic system with multiple gas slugs is also characterized by using the presented approach. For a proof-of-concept demonstration of using the proposed approach in a self-triggered sensor, a gas slug detector with a counter system is developed to show its practicality and applicability. A two-phase microfluidic system that requires two immiscible fluid phases inside a microfluidic channel has been rapidly developed in various science and engineering fields because of its own benefits, such as decreased sample/reagent consumption, reduced diffusion times, enhanced throughput, and fast response time12346783101112131415To characterize configuration of gas-aqueous liquid two-phase flow  several techniques have been previously developed1317181920171920discrete solid–liquid contact electrification process resulting in generation of electric field and potential. In a gas-aqueous liquid two-phase flow inside a microfluidic channel, the presence of a gas slug plays a role in detaching liquid from the channel substrate, and thus, a discrete solid-liquid contact electrification process arises. As a result, electric potential is spontaneously generated by the net charge on the gas–solid contact surface in the microfluidic channel based on the same mechanism of the spontaneous charging of an aqueous droplet that detaches from the inner surface of the pipette tipOur group recently reported the spontaneous electrical charging of aqueous droplets through conventional pipetting, which was mainly attributed to solid–liquid contact electrification2223In the current work, a simple approach to characterize configuration of gas-aqueous liquid two–phase flow inside a microfluidic channel is first suggested and demonstrated. Given that the net electric charge is spontaneously generated on the microfluidic channel substrate as a gas slug passes through the channel, measuring the spontaneously generated electric potential caused by the electric charge on the substrate with the gas slug can be a simple indirect approach for characterizing the flow configuration. To measure the generated electric potential, we simply have to place the microfluidic chip on an additional electrode surface that is connected to an electrometer. Experimental and numerical investigations on the parameters that affect the amount of electric potential are systematically performed, and consequently, the gas slug inside the microfluidic channel is verified to behave similar to that of a point electric charge source when the measuring point of the electric potential is far enough from the gas slug. The average flow velocity inside the microfluidic channel is also demonstrated to be measured precisely by the proposed approach. In addition, the configuration of the gas-aqueous liquid two–phase microfluidic system with multiple gas slugs is characterized by using the presented strategy. Furthermore, for a proof-of-concept demonstration of the use of this strategy in a self-triggered sensor, a gas slug detector with a counter system is developed. It exhibits the practicality and applicability of the proposed approach. Given that this pioneering approach enables easy characterization of two-phase flow configuration by simply introducing an additional electrode to the conventional microfluidic chip, it exhibits several advantages including simple operation, precise measurement, self-triggering, and cost-effectiveness.ζ) of the solid surface with respect to the contact liquid. Numerous polymers have negative ζ relative to an aqueous liquid in nearly all experimental conditions, which results in a negative electric charge accumulation on the solid surface and a positive electric charge accumulation on the liquid side, as shown in Stage 0 of Given the experimental setup, we simply need to generate the gas-aqueous liquid two-phase flow inside the microfluidic channel, and then read the developed electric potential through the connected electrometer. The detailed procedure is as follows. Filling the microfluidic channel with aqueous liquid spontaneously generates an electric double layer (EDL) that consists of electric charge pairs. In this case, generating the electric charge pairs and the EDL is strongly affected by the zeta potential (VOC), which is a minimum plateau value of the measured electric potential that reflects the total net electric charge on the solid surface; and 2) traveling time (Tt), which represents the flow time of the gas slug head from one end of the electrode to the other end; it implies the time-dependent behavior of the gas slug movement above the electrode. This electric potential behavior is similar to the result of the simplified numerical analysis of the moving gas slug inside the microfluidic channel with the ad hoc negative surface charge. ( charge. VOC when changing the contact area between the gas slug and the solid surface (A), where A ≈ L (length of a gas slug) × w (width of a gas slug), as shown in VOC is determined to be nearly linearly proportional to A, regardless of w. This relationship between A and VOC is confirmed by the numerical analysis, although the magnitude of the electric potential is rather different. Since the aim of the numerical analysis is indirect verification of the fundamental mechanism of the present approach, our concern is the tendency of the generated electric potential, rather than the magnitude itself. The difference of the magnitude may arise from following reasons: 1) inaccurate surface charge density in the numerical analysis, 2) transformation of 3-dimensional empirical phenomenon into simplified 2-dimensional numerical domain . The result of numerical analysis enables us to suppose that the gas slug in our experiment is sufficiently small to be regarded as a point electric charge source rather than as a planar surface charge source. The electric potential developed at a distance t from the point electric charge source on the solid substrate to the external electrode, that is, the substrate thickness, in this case, can be expressed as follows:Considering that the fundamental mechanism of the present characterization approach is a surface-related phenomenon, we investigate the behavior of σ is the surface charge density on the solid surface generated by discrete solid–liquid contact electrification. In Equation A increases the total electric charge (σA) and thus strengthens the electric field at the electrode, which results in higher t on VOC is also experimentally and numerically investigated by varying substrate thickness. As shown in VOC. However, it could be easily noticed that the slope of the electric potential becomes flatten as t becomes thinner. It indirectly shows that the gas slug behaves like a point electric charge source only when the measuring point of the electric potential is far enough  from the gas slug. The detail result of numerical analysis about the thickness of the substrate to assume the gas slug as a point electric charge source is in the w) as well as t are important factors which determine the size of the system, we perform the experiment to investigate the dependency of w on VOC. As a result, it is checked that there is a critical width of the microfluidic channel which is a maximum width where the point electric charge source assumption in this study is valid. The detailed information about it is in the Supporting Information. In our system, it is verified that the critical width seems to exist within w range of 1500 ~ 2000 μm and thus, it indirectly shows that the point electric charge source assumption is valid with smaller w than the critical width , which is illustrated in Tt. To demonstrate this procedure, the experiments with flow velocity (vset), which varies from 0.3 to 1.3 cm/s , are performed as shown in vimg and velp, respectively. Among three variables, vimg is the most accurate and is analogous to the real movement of the gas slug because it directly presents the actual situation within the microfluidic channel. As shown in vset and vimg, which indicates that the real flow velocity within the PDMS microfluidic channel differs from the flow velocity calculated using the flow rate set on the syringe pump. A number of studies have recently reported that inaccurate estimates of the average flow velocity within PDMS microfluidic channels have several causes, such as syringe pump-induced fluctuation, deformation of a flexible PDMS microfluidic channel and tubing system, and solvent-induced PDMS swelling behavior2526vset and vimg, that is, vset > vimg. By contrast, no significant difference is observed between velp and vimg. The experimental result implies that the average flow velocity that has been analyzed using the proposed approach based on discrete solid-liquid contact electrification (velp) is more analogous to the real movement of the gas slug within the PDMS microfluidic channel (vimg) than the flow velocity set on the syringe pump (vset). Consequently, the average flow velocity within the PDMS microfluidic channel can be conveniently and accurately evaluated with the presented approach.Utilizing the electric potential behavior generated by the moving gas slug inside the microfluidic channel, the average flow velocity can also be measured. The time-dependent parameter . This characterization of the configuration of two-phase flow with multiple gas slugs demonstrates that the present novel approach based on discrete solid–liquid contact electrification cannot only characterize a single gas slug, but also multiple gas slugs and even liquid plugs inside a microfluidic channel.To verify the electric potential behavior during the movement of multiple gas slugs, experiments using two and three gas slugs are performed. In VOC from the gas slug is well above the noise level, the presence of a gas slug is easy to be detected from the electric potential behavior. To achieve real-time detection of a gas slug, an additional detecting part, which consists of a computer and an embedded system with an external electric power, is directly connected to the sensing part, which consists of a microfluidic channel and an external electrode as shown in The present approach for characterizing two-phase flow configuration based on discrete solid–liquid contact electrification can be applied practically to the development of self-triggered sensors for sensing the gas slug within a continuous aqueous liquid flow inside the microfluidic channel through the generation of a voltage output  during the movement of a gas slug. Several recent studies have reported on the use of solid–liquid contact electrification as an energy harvesting method and self-powered or triggered sensors that use the generated electric output282930As the first demonstration, this study exploits a discrete solid-liquid contact electrification phenomenon to characterize configuration of gas-aqueous liquid two-phase flow inside a microfluidic channel. In this study, the connection between the spontaneously developed electric potential and the configuration of the two-phase flow allows simple indirect measurement of the size and moving velocity of the gas slug which have of paramount importance in various gas-aqueous liquid processing systems. Since the electric potential is generated by the net electric charge on the substrate, the necessary condition for measurement is contact between the gas slug and the solid substrate with concomitant generation of the net electric charge. In other words, it could not be applied on the two-phase systems including gas bubble passage (not gas slug phase), which does not contact with the substrate at all. Although this becomes major shortcoming of the proposed approach, this electric charge based approach has possibility to be utilized on the above system with the generally accepted concept that the gas/liquid interface also carries electric charges. Then, the applicability of the present approach could be strongly broaden to the wetting system with gas bubble passage. The further study about it is needed to clarify the applicability of the present method. Along with it, for applying the present approach to the bulk-system, there is also a need to perform comprehensive study about critical bulk factors such as width and thickness, as mentioned above.VOC. Given that the fundamental mechanism of the present approach is based on generation of the net electrical charges on the solid substrate caused by discrete solid-liquid contact electrification, another crucial factor determining VOCis the amount of generated net electrical charges  microfluidic chip for generating gas-liquid two-phase flow was fabricated using the standard soft-lithography technique. Briefly, a 150-μm-thick SU-8 2150 photoresist was spin-coated on a 4-inch silicon wafer. The SU-8 layer was selectively exposed to the UV light and then developed to obtain a master. The PDMS pre-polymer was mixed with a curing agent in a 10:1 weight ratio and degassed. After pouring the PDMS mixture over the fabricated master, it was cured at 65 °C for 4 hours, and then it was peeled off from the master. Along with, a metal electrode for measuring the electric potential was selectively deposited onto a conventional glass slide and the PDMS is directly spin-coated with the controlled thickness with an adequate rotational speed of the spin coater. The PDMS microfluidic chip including an open channel is set on the PDMS coated glass slide.The aqueous liquid with gas slugs of desired volumes was introduced through tubing by using the syringe pumps (KDScientific KDS230). The inlet and outlet of the PDMS microfluidic chip were both electrically grounded to minimize the noise from the unexpected charge in fluid. The metal deposited on the glass slide was electrically connected with the electrometer (Keithley 6517A) for measuring the generated electric potential. The electrometer was synchronized with a CCD camera (Viewworks VH-310C). Both electric potential and image of the microfluidic channel were recorded on a computer in real time.How to cite this article: Choi, D. et al. A Simple Approach to Characterize Gas-Aqueous Liquid Two-phase Flow Configuration Based on Discrete Solid-Liquid Contact Electrification. Sci. Rep.5, 15172; doi: 10.1038/srep15172 (2015).


Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm-SGA, despite evidence of varying risk of child mortality and poor developmental outcomes.We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression.rd trimester, short maternal stature, being firstborn, and male sex . Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth . In addition, receiving ANC services in the 1st trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk .Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm-AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa.ACTRN12610000636055, registered on 3rd August 2010.Australian New Zealand Clinical Trials Registry (ANZCTR) –  It is estimated that of the 135 million babies born in 2010 in LMICs, 21.9 % were term-SGA, 8.1 % were preterm-appropriate for gestational age (AGA) and 2.1 % were preterm-SGA [Globally, more than 20 million infants (15.5 % of live births) each year are born low birthweight (LBW) or <2500 g , 4. SmalPreterm and SGA births are both well documented to increase the risk of morbidity and mortality, and newborns who are both preterm and SGA have the highest risk , 7. A muDespite a significant body of literature that mortality, morbidity, growth and development outcomes vary for preterm and SGA births, few studies have identified risk factors for combinations of preterm and SGA births . In this2 and allowed for enrollment of both health facility and home births.This study consist of women and singleton infants enrolled in a randomized double-blind, placebo- controlled neonatal vitamin A supplementation trial conducted in Tanzania between August 2010 and March 2013. Trial recruitment and data collection procedures have been presented elsewhere . BrieflyNewborns were eligible for randomization if they were able to feed orally, were born within the past 72 h, were not previously enrolled in other clinical trials, the family intended to stay in the study area for at least six months post-delivery, and the parents provided written informed consent to participate. A total of 32,843 mothers and their newborns were screened for inclusion in the parent trial. A total of 844 (2.6 %) were excluded for the following reasons: 237 (0.7 %) were not age eligible (>72 h since birth), 38 (0.1 %) were not able to feed orally and 569 (1.7 %) did not plan to reside in the study area for the next six months after delivery. A total of 31,999 newborns were randomized in the trial of which 11,895 resided in Dar es Salaam and 20,104 in Morogoro. There were 30,891 singleton births, and 1,108 were of multiple gestation.Trained study staff administered a baseline questionnaire to mothers in order to collect information on demographic, socioeconomic, and environmental factors as well as date of mother’s last menstrual period (LMP). We assessed LMP twice, during pregnancy surveillance and at the time of Vitamin A dosing. All infants had their birthweight measured at the time of dosing  by study staff using calibrated scales with digital screens. Scale calibration with standard weights and weight standardization for all study staff was completed regularly for quality assurance.rd percentile for gestational age and sex using INTERGROWTH standards.We restricted this analysis to 19,269 (62.4 %) singleton infants who had complete data on birth weight and gestational age. Gestational age was calculated from maternal last normal menstrual period (LMP) report and preterm birth was defined as delivery at <37 completed weeks of gestation. SGA was defined as birth weight <10th percentile for gestational age and sex using INTERGROWTH standards . We combst, 2nd, 3rd trimester), maternal height , parity , and infant sex. Home versus facility births were only examined in univariate analyses due to issues of causality (preterm births may lead to home births). Wealth index quintile was defined by a principal component analysis of household assets and characteristics  stratified by Dar es Salaam and Morogoro residence. A priori we decided to examine potential effect modification of all predictors by location . Effect modification was assessed through use of interaction terms with statistical significance determined by the log-rank test. If statistically significant effect modification by site was determined in the univariate model, the interaction term was automatically included in the multivariate model. Missing data were retained using the missing indicator method. All p-values were 2–sided with a p < 0.05 considered statistically significant. Statistical analyses were performed using SAS v 9.4 .We then examined demographic, socioeconomic, and environmental risk factors of term-SGA, preterm-AGA, and preterm-SGA as compared to reference term-AGA using log-binomial regression models to obtain risk ratio estimates. Variables assessed in univariate and multivariate analyses included location , maternal age , maternal and paternal education , wealth quintile, trimester of first ANC visit  and most mothers attended their first ANC visit during the second trimester (58.9 %). A total of 1,707 (8.9 %) births took place in the home and there was no difference in mean birthweight for home (mean: 3085 ± 460 g) versus facility births (mean: 3083 ± 476 g) (p = 0.87). Baseline characteristics of singleton mothers unable to recall their LMP and who were excluded from the analysis, were similar to singleton mothers who were able to recall their LMP , with no formal paternal and maternal schooling showing slight protective associations in unadjusted analysis (p < 0.05). There was significant interaction between wealth quintile and study site in the crude analysis. Poverty  was a significant risk factor for term-SGA in Dar es Salaam  but was slightly protective in Morogoro  . Risk factors for preterm-AGA in unadjusted analysis included: younger maternal age, small stature, firstborns, and low maternal and paternal education (p < 0.05). We also found that decreased wealth was a significant risk factor for preterm-AGA in both Dar es Salaam and Morogoro , but the magnitude of association was significantly greater for Morogoro newborns . In the unadjusted analysis risk factors for preterm-SGA included: both maternal age less than 25 years and older than 30 years as compared to the 25–30 year reference, being firstborn, and decreased maternal height (p < 0.05).In Table p = 0.002), late ANC first visit in 3rd trimester as compared to 2nd trimester (p = 0.025), decreased maternal stature under 160 cm (p < 0.001), being firstborn (p < 0.001), and male sex (p = 0.007). Significant protective factors for term-SGA included maternal secondary education (p = 0.018) and no formal paternal schooling (p = 0.028). For preterm-AGA, significant risk factors included: maternal age <25 years, decreased maternal stature (p < 0.001), and being firstborn (p = 0.003). In addition, attending ANC for the first time in the first trimester as compared to second trimester (p = 0.009) and paternal secondary education were associated with significantly reduced risk of preterm-AGA. Decreased wealth was a significant risk factor for preterm-AGA in Morogoro (p < 0.001) and the results indicated a similar, but smaller in magnitude and not statistically significant trend in Dar es Salaam (p = 0.076) . For preterm-SGA, significant independent risk factors included maternal age >30 years, firstborns, and decreased maternal height (p = 0.042). Figure In the multivariate analysis, we identified several important risk factors for term-SGA, preterm-AGA, and preterm-SGA as compared to the term-AGA reference Table . Signifird percentile are presented in n = 2). Young maternal age, late ANC, short maternal stature, starting ANC in 3rd trimester, and firstborns remained significant risk factors for term-SGA (<3rd percentile) and were of similar magnitude (rd percentile). As for preterm (<34 weeks) –SGA, young maternal age and decreased wealth in Morogoro region remained significant predictors  or Dr. Honorati Masanja (hmasanja@ihi.or.tz) for data requests.


Dear EditorFlavivirus contains important human pathogens, including dengue (DENV), yellow fever (YFV), West Nile (WNV), Japanese encephalitis (JEV), and tick-borne encephalitis (TBEV) viruses, which cause a number of serious human diseases throughout the world , and 7 non-structural proteins   in the space group Flaviviradae family, whose structures have already been solved. To gain further structural insight, we generated a structure-based phylogenetic tree for these homologous helicases , DENV-4, DENV-2, YFV, JEV, Kunjin virus (KUNV), and Hepatitis C virus (HCV) from the ses Fig. D, using ses Fig. . Structu2+ or Mg2+) ; Erin Weber and Lanfeng Wang for discussion and advice. This work was supported by the National Basic Research Program (973 Program) (Nos. 2015CB859800 and 2014CB542800) and the National Natural Science Foundation of China (Grant No. 31528006).Haitao Yang and Hongliang Tian conceived and designed the experiments. Hongliang Tian, Xiaoyun Yang, Wei Xie, Heng Chi and Zhongyu Mu performed the experiments. Haitao Yang, Xiaoyun Ji, Cheng Chen, Chen Wu and Zefang Wang analyzed the data. Haitao Yang, Hongliang Tian, Xiaoyun Ji and Kailin Yang wrote the paper. Hongliang Tian, Xiaoyun Ji, Xiaoyun Yang, Wei Xie, Kailin Yang, Cheng Chen, Chen Wu, Heng Chi, Zhongyu Mu, Zefang Wang, and Haitao Yang declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by the any of the authors.Supplementary material 1 (PDF 1224 kb)Below is the link to the electronic supplementary material.


To analyze trends in LBW (low birth weight) rate using birth registry data and identify factors associated with LBW in São Luís comparing two birth cohorts separated by a 12-year interval.2,426 births were included in 1997/98 and 5,040 in 2010. The dependent variable was LBW . Multiple logistic regression was performed to determine the association of independent variables with LBW. Data were also obtained from SINASC  to analyze stillbirth and LBW rates trends from 1996 to 2010, using 3-year moving averages.LBW, intrauterine growth restriction (IUGR) and preterm birth rates did not differ between the two cohorts. Despite this, birth registry data showed increasing LBW rate up to 2001, coinciding with decreasing stillbirth rate. Both stillbirth and LBW rates decreased thereafter. A significant reduction was observed in the percentage of teenage mothers, mothers with up to 4 years of education, family income up to one minimum wage and mothers who did not attend prenatal care. There was an increase in maternal age ≥35 years and schooling ≥12 years. The variables associated with LBW in 1997/98 were young maternal age (<18 years), maternal smoking during pregnancy and primiparity. Variables that remained in the adjusted model in 2010 were female gender, income <3 minimum wages, lack of prenatal care, maternal smoking during pregnancy and primiparity.Although LBW rate did not differ between the two cohorts, this apparent stability masked an increase up to 2001 and a decrease thereafter. The rise in LBW rate paralleled reduction in the stillbirth rate, suggesting improvement in obstetrical and newborn care. Maternal, socioeconomic and demographic factors associated with LBW differed between the two cohorts, except for smoking during pregnancy and parity that were significantly associated with LBW in both cohorts. Considered to be the major factor affecting perinatal, neonatal and postnatal health, low birth weight (LBW) is defined as a birth weight of less than 2,500 g .LBW is due either to preterm birth, most common in developed countries, to intrauterine growth restriction (IUGR), more frequent in developing countries or to a combination of both. Factors associated with LBW are low maternal weight and height, multiple births, low calorie intake, hypertension during pregnancy, maternal smoking, genetic syndromes, hard maternal physical work, maternal exposure to toxic substances, and inadequate prenatal care use ,3.LBW rates differ in various regions of the world, being higher in less developed countries, since they are associated with unfavorable socioeconomic conditions. LBW rate is estimated to be 15% for developing countries and 7% for developed countries ,5. LBW rIncreasing LBW rates began to be observed in developed countries in the 1980 decade . The incIn Brazil, LBW rate increased significantly in its state capital cities from 8.5% in 1996 to 9.1% in 2010. Part of this increase in LBW rate may be explained by a simultaneous increase in the multiple birth rate and in the number of newborns (NB) weighing 500 to 999 g and by a reduction in the stillbirth rate [Studies monitoring LBW trends as well as changes in its risk factors over time are important in order to determine whether such factors are changing, thus allowing identification of targets for public health interventions.Increasing LBW rate was also observed in Brazilian birth cohorts performed in Ribeirão Preto and Pelotas. In Ribeirão Preto, part of the increase in LBW rate was attributed to shortened gestational age due to elective cesarean sections . In PeloIn São Luís, Brazil, a second birth cohort was performed in 2010, and comparison with data from a previous birth cohort (undertaken in 1997/98) has shown that LBW rates remained stable, in contrast to the ascending rates that have been described earlier in the other two Brazilian cohorts performed in Pelotas . Since dThus, the objectives of the present study were to determine the temporal trend in LBW rate by analyzing historical series of birth registry data from the System of Information about Liveborns (SINASC in the Portuguese acronym) and to verify if risk factors for LBW and their prevalences differed between the two cohorts in the city of São Luís, Northeastern Brazil, comparing two birth cohorts separated by a 12-year interval. To avoid confounding by multiplicity, only singleton live births were included.Data was abstracted from two birth cohorts performed in the municipality of São Luís, the capital of Maranhão state, located in Northeastern Brazil, with a population of 1,014,837 inhabitants in 2010. São Luís has a human development index (HDI) of 0.768, the first in the state of Maranhão and the 249th in Brazil .The first cohort included 2,831 hospital births from March 1997 to February 1998 and its methods have been published previously . The secData from the two birth cohorts are population based. Hospital births comprised 96.3% of all births in 1997/98  and 98% The sample was stratified by maternity hospital with sharing proportional to the number of births at each facility. In each maternity hospital sampling was systematic and all live births and stillbirths were listed in order of occurrence. The sampling interval was seven in 1997/98 and three in 2010. A random number from 1 to 7 in 1997/98, and from 1 to 3 in 2010 was drawn to determine the starting point for each study unit. Thus one out of seven births in 1997/98 and one out of three births in 2010 were randomly selected for interview. Losses due to refusal or early discharge from hospital occurred in 5.8% of cases in 1997/98 and in 4.6% in 2010.In the present study only data from mothers residing in São Luís, liveborns and singletons were used. In 1997/98, after exclusion of births from non-residents (n = 290), stillbirths (n = 48), multiples (n = 50) and missing information on study variables (n = 17), 2426 cases remained for analysis. In 2010, after exclusion of stillbirths (70), multiple births (99), newborns weighing <500 g (n = 3), and missing information on study variables (n = 24), data from 5,040 births remained for analysis.Considering an 8.7% LBW rate for São Luís based on birth registry data, a 95% confidence level, and 1% absolute precision the necessary sample size would be 2,624 newborns.The interviews were held within the first 24 hours after delivery by means of a standardized questionnaire including socioeconomic, demographic and life style questions; sexual and reproductive health; characteristics of current pregnancy and prenatal care; characteristics of delivery and birth. The newborns, wearing no clothing, were weighed on a baby scale with 5-gram graduations, shortly after delivery. The dependent variable was birth weight categorized as LBW  and without LBW .The independent variables were: newborn’s sex, maternal age , marital status , maternal schooling in years of study , parity , maternal smoking during pregnancy (yes or no), monthly family income in minimum wages , occupation of family head , preterm birth , type of delivery , and category of delivery care (public or private). Prenatal care utilization was classified as: none, inadequate, adequate, or missing data on gestational age and prenatal care. The adequacy of prenatal care use was measured using an index created on the basis of the minimum number of visits recommended by the Brazilian Health Ministry, and time of initiation. The index was adjusted for gestational age, because mothers of preterm babies tend to have fewer prenatal visits . The catThe classification of IUGR by Kramer et al.  is basedst of the respective years.In 1997 the monthly minimum wage was R$ 120.00, which corresponded to U$ 110.80 and in 2010 it was R$ 510.00, which corresponded to U$ 291.54 considering the value of the dollar on July 31th day of the month was imputed for all cases in which the day of the last menstrual period was unknown. Birth weights located above the 99th percentile of the British reference [Gestational age (GA) was based on the date of the last menstrual period as reported by the mother. The 15eference , consideeference .Birth registry data from SINASC (Portuguese acronym for the System of Information on Livebirths) for São Luís, from 1996 to 2010, were used to analyze trends in stillbirth and LBW rates, using 3-year moving averages. Births weighing <500 g, missing data on birth weight and multiples were excluded. The stillbirth rate was calculated as the ratio of the number of fetal deaths by the total number of births multiplied by 1,000.p < 0.20 were considered as candidates for the final model, but only those presenting p < 0.10 were retained. Data were analyzed using Stata 11.0.The chi-square test was used to compare proportions between the two birth cohorts. Univariable analysis was performed using simple logistic regression to estimate non-adjusted odds ratios (OR) and their 95% confidence intervals (95%CI). Multivariable analysis was performed using multiple logistic regression. The independent variables that showed Since LBW is due to preterm birth and IUGR, these variables were not selected for the multivariable model since they are mediators and they would tend to mask associations between maternal, socioeconomic and demographic factors with LBW.Sensitivity analysis was conducted to examine the effect of imputation of gestational age on the findings reported. Selected data on maternal socioeconomic, demographic variables and birth weight from the two birth cohorts were compared with birth registry data by the chi-square test to assess how representative the cohorts are of the city births.The project was approved by the Research Ethics Committee of the University Hospital, Federal University of Maranhão (protocol no.350/08 4771/2008-30) and all mothers gave written informed consent to participate before being interviewed.p = 0.847). However, observation of the historical series based on birth registry data from SINASC from 1996 to 2010 revealed variation between years, with an abrupt fall in 1997 and a later elevation from 1998 to 2001, when the rate peaked at 9.4%. The rate decreased thereafter up to 2009/2010  than in 2010 (51.0%) (Table p < 0.001). A significant improvement was observed in maternal schooling, with a 224.5% increase in the percentage of mothers with ≥12 years of study and a 380% reduction in the percentage of mothers with 0 to 4 years of study (p < 0.001). The proportion of mothers who were not living with a companion and of married mothers was reduced, while the percentage of mothers living in consensual union increased significantly (p < 0.001). There was a reduction in the percentage of families that lived on less than one minimum wage and of those living with >3 wages and an increase in the intermediate category (1-3 minimum wages) (p < 0.001). The results were worse regarding occupation of the family head, with a reduction of skilled manual workers and an increase in unskilled manual workers. Prenatal care use improved significantly, with an increase in the percentage of mothers who received adequate prenatal care and a reduction from 8.2% to 1.9% of those who received no prenatal care (p < 0.001). Cesarean section rate increased from 34.7% to 47.9% (p < 0.001). There was an increase in deliveries attended by private health care providers (p < 0.001)  was significantly reduced from 29.4% in 1997/98 to 18.7% in 2010. Conversely, there was a significant 80.9% increase in the percentage of mothers aged ≥35 years  and primiparity (OR = 1.66). The variables that remained in the adjusted model for the 2010 cohort were female sex (OR = 1.29), maternal age ≥35 years (OR = 1.55), family income from 1 to 3 minimum wages (OR = 1.38), lack of prenatal care (OR = 2.79), maternal smoking during pregnancy (OR = 2.51), and primiparity (OR = 1.57) . Although there were differences with respect to maternal schooling, missing data were too high in birth registry data for a meaningful comparison .A significant improvement in access to prenatal care and in maternal schooling was observed, as well as a reduction in the percentage of teenage mothers, a fall in the stillbirth rate and an increase in deliveries held at private facilities. However, LBW rate was not significantly different comparing data from the two birth cohorts at the two time points.In contrast, analysis of birth registry data from SINASC revealed that the stability in the LBW rate observed between the two cohorts actually masked an abrupt fall in 1997 and an increase from 1998 to 2001, with a later reduction up to 2010.It is worth noting that LBW rate increased whereas stillbirth rates decreased from 1996 to 2001. From 2001 onwards, LBW and stillbirth rates tended to fall simultaneously. According to data from the two birth cohorts, stillbirth rate decreased from 18.9 in 1997/98 to 13.4 per thousand in 2010. These changes suggest improving obstetric and neonatal care including careful fetal surveillance and prompt obstetric intervention where indicated . From 19There was a significant reduction in the percentage of mothers who did not receive prenatal care in the 12-year interval. The absence of prenatal care was considered to be a risk factor for LBW only in 2010. With increasing access to prenatal care, there was a probable increase in the contrast between the better off and more vulnerable groups who showed the worst outcomes. According to some studies ,20,23,24Extremes of maternal age were associated with LBW, with differences between cohorts. In 1997/98 an association was observed with maternal age of more than 18 years, whereas in 2010 age ≥35 years was associated with higher LBW rate. The association between more advanced age in 2010 was not detected in 1997/98, possibly due to the increased proportion of women who, more recently, have been engaged in conquering their space on the job market and having financial stability, a fact that delays maternity plans. However, a fall in fertility occurs with advancing age, a fact that often leads women to seek ovarian stimulation and assisted reproductive technology, which represent two major risk factors for twinning and LBW .Maternity at more advanced ages seem to be a more serious public health problem than teenage pregnancy. The prognosis of pregnancy in women older than 35 years is worse than that for teenage mothers. Pregnancy during the age range of highest risk can be prevented with public policies supporting women who hold jobs outside home.An improvement in socioeconomic level was observed based on maternal schooling, the reduction of families who live on less than one minimum wage, and the increased proportion of families with an income of 1-3 minimum wages. Conversely, proportion of non-skilled manual workers rose and the percentage of families earning more than 3 minimum wages was reduced, what suggests worsening in life conditions. A possible explanation for this apparent contradiction is the increase in the monthly minimum wage, which went from U$ 110.80 to U$ 291.54 during this period. Thus, the fall in the proportion of persons earning more than 3 minimum wages did not represent a worse mean family income but reflected the increased purchasing power of the minimum wage during this period.Among the socioeconomic variables analyzed, only income of less than 3 minimum wages was associated with LBW in 2010, while the remaining variables showed no statistical significance. In a study conducted in the city of São Paulo, the authors pointed out the low magnitude of the difference detected between the various social strata with respect to LBW . AnotherMarital status was significantly associated with LBW only in univariable analysis in the 2010 cohort, with a loss of significance after adjustment. Following changes in the way of life and in thinking of today’s society, there was a reduction of prejudice regarding single mothers. Single mothers possibly started to count on greater social support, with a reduction of stress. From this perspective, the studies are inconclusive regarding the relation between marital status and LBW [More girls started to be born in 2010, but the percentage of boys continued to be higher. Newborn’s sex was not associated with LBW in the 1997/98 cohort, but in 2010 female sex was associated with 1.26 increased risk of LBW. Other studies have also shown association between newborn’s sex and LBW, demonstrating that females have a higher risk of being born weighing less than 2,500 g ,28.There was no change in the proportion of mothers who smoked during pregnancy. Maternal smoking was associated with LBW in both cohorts, in agreement with other reports ,26.Primiparity was associated with LBW in both cohorts studied, in accordance with a synopsis based on scientific evidence about LBW .The two highest ORs for LBW in 2010 are for no prenatal care and for smoking. It is very important to continue improving access to prenatal care and promoting smoking cessation to reduce LBW rate.Despite the significant increase in cesarean section rate, type of delivery was not associated with LBW in the adjusted analysis. This association was only observed in univariable analysis in 1997/98. After adjustment for confounding variables, type of delivery was not considered to be a risk factor for LBW in any of the cohorts studied, in contrast to other studies ,12. PrevThe strengths of the present study are that data were abstracted from two population based cohort studies conducted on large samples, with low percentage of losses. Validated measurements were used. Under-registration of birth weights in registry data from SINASC, especially in 1997, represents a limitation. Another limitation is that there was slightly overrepresentation of male births in the 1997/98 cohort and underrepresentation of low schooling and married mothers and those born by a cesarean section. However, there are some concerns regarding quality of registry data, especially in the earlier period . Lack ofIn addition there was a high percentage of missing results regarding gestational age. However, this limitation was partially remedied by imputation of gestational age. Furthermore, results regarding preterm birth and intrauterine growth restriction rates did not change using unimputed gestational age data.Despite improved living conditions regarding maternal schooling, prenatal care use, and childbirth care, no change was observed in birth weight distribution comparing the two birth cohorts. However, this apparent stability masked an increase in LBW rate from1996 to 2001. The increase and the fall in LBW paralleled reduction in stillbirths, a fact that suggests improving obstetrical and neonatal care. Maternal, socioeconomic and demographic factors associated with LBW differed significantly between the two cohorts, except for smoking during pregnancy and parity that were significantly associated with LBW in both cohorts.LBW: Low birth weight; OR: Odds ratio; IUGR: Intrauterine growth restriction; NB: Newborn; SINASC: Portuguese acronym for the Information System on liveborns.The authors declare that they have no competing interests.HJFV and AAMdS contributed to the conception of the project, the analysis and interpretation of the data and the writing of the paper and analyzed the article for final approval of the version to be published. HB, MZG, FLF, VMFS, RFLB and MAB contributed to the analysis and interpretation of the data and the writing of the paper and performed a relevant critical review of the manuscript intellectual content and analyzed the article for final approval of the version to be published.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/14/155/prepubTable S2. Comparison of socioeconomic, demographic characteristics and birth weight between birth registry and birth cohort data, São Luís, 2010.Comparison of socioeconomic, demographic characteristics and birth weight between birth registry and birth cohort data, São Luís, 1997. Click here for file