Limited data exist collating most of the associated factors for strabismus in one analysis. The aim of this study was to assess the prevalence of strabismus and to analyse associated factors in former preterm and full-term infants.In this cross-sectional study, 239 former preterm infants with gestational age (GA) ≤ 32 weeks and 264 former full-term born infants with GA ≥ 37 weeks underwent detailed ophthalmologic examination in the age of 4–10 years and perinatal data assessment for risk factor analysis. Ophthalmologic examinations included cover testing, best corrected visual acuity, cycloplegic objective refraction, slit lamp as well as fundus examinations. For association analysis with strabismus, the following data was collected and included in multivariable analysis: sex, age at examination, anisometropia, myopic and hyperopic refractive error (≥ 3 dioptres), astigmatism, birth weight percentile, gestational age, retinopathy of prematurity occurrence, maternal age at childbirth, mother smoking, breastfeeding < 3 months, artificial ventilation, intraventricular bleeding, and other perinatal adverse events.p = 0.001), hyperopic refractive error  and astigmatism .Overall, 4/264 (2%) full-term infants, 15/125 (12%) preterm-infants with GA 29–32 weeks without ROP, 13/59 (22%) preterm infants with GA ≤ 28 weeks without ROP and 14/55 (26%) with GA ≤ 32 weeks with retinopathy of prematurity were affected by strabismus. In the multivariable regression model strabismus was associated with GA (OR = 0.84 per week; This investigation highlights that low gestational age and refraction of the eye are independent risk factors for strabismus, while the other factors show less independent influence. In very preterm infants with low gestational age (GA) and low birth weight the prevalence of strabismus has been reported to be up to 42% –8. FurthAs main risk factors for strabismus low GA and reduced birth weight have been repeatedly discussed in the literature , 14–18. The objective of this investigation was to assess the prevalence of strabismus in a large cohort of former preterm infants compared to full-term infants aged between 4 and 10 years. Additionally, the aim was to analyse most of the reported risk factors in one model to explore and identify independent risk factors. We will report on strabismus in general and stratify our analysis on esotropia and exotropia.The prospective controlled Wiesbaden Prematurity Study (WPS) was performed in former preterm and full-term infants born during the years of 2004 to 2010 in the Helios Dr. Horst Schmidt Klinik (tertiary centre of maximum care with level IV neonatology) in Wiesbaden, Germany between July 2014 and March 2015. The research was performed in accordance with the Declaration of Helsinki, and was approved by the Ethic Committee of the Physician Chamber Hessen. Written informed consent was obtained from all parents or legal guardians prior to examination.Inclusion criteria were (1) GA ≤ 32 weeks or ≥ 37 weeks, and (2) actual age between 4 and 10 years. The exclusion criteria were the presence of severe congenital anomalies since birth. Severe congenital anomalies were defined as infants with congenital chromosomal disorders or/and congenital heart diseases, or/and neural tube defects. Preterm and full-term infants were identified by our hospital database. Parents of all preterm infants and parents of randomly selected full-term infants received a phone call invitation to participate in our investigation.For the enrolled children, history data were assessed from each child’s recorded file. Occurrences of perinatal and postnatal complications, such as intraventricular bleeding were assessed. Furthermore, occurrence of periventricular leukomalacia, necrotizing enterocolitis and sepsis were documented and summarized as perinatal adverse events. In addition, artificial ventilation and oxygen demand were analysed. Gestational age and birth weight were recorded and percentile of birth weight was calculated. According to German guidelines, postnatal ROP screening was initiated at 6 weeks after birth with regular follow-up until full retinal vascularization or until ROP activity regression after expected date of birth was achieved. Diode laser photocoagulation was performed if treatment for ROP was necessary .For the period after hospital discharge all parents received the standard recommendation of close ophthalmic follow-up at a local eye care provider  in accordance to the current guidelines for premature infants . No routAll examinations were performed using a standardized protocol for paediatric eye examinations. Testing of best-corrected visual acuity was performed with Lea symbols until school enrolment and after that, with Landolt rings in all subjects. In cases of visual acuity below 20/200, depending on infant’s age Lea symbols or Landolt rings were used at a distance of 1 m. Values were converted for the analysis into the logarithm of the minimum angle of resolution (logMAR) .Cyclopentolate (0.5%) eye drops were administered 3 times at 10-min intervals, after which cycloplegic refraction and keratometry were analysed with Nikon Nidek ARK-1 s keratometer . The spherical equivalent (refractive error) was calculated by adding the spherical value and half of the cylindrical value. Anisometropia was defined as a difference between the patients’ eyes of ≥ 1.5 dioptres of spherical equivalent.Orthoptic examination for strabismus included the cover-uncover test and alternate cover test, Hirschberg-Test and examination of fixation behaviour, as well as presence or absence of nystagmus after having corrected refractive errors. If a child presented with heterotropia, an alternating prism cover test was added to measure the squint angle in dioptres. Strabismus was defined as constant or intermittent heterotropia of any dimension at distance and/or near fixation after having corrected refractive error. Classification of strabismus was categorized depending on deviation from primary position . Binocular function was tested by Lang-test. In addition, all parents were interviewed using a standardized protocol to request information concerning medical history of the child and parents, including ocular and general morbidities, as well as parental-specific information . Additionally, a detailed ophthalmologic examination including measurements of slit lamp examination and funduscopy, assessment of ocular movements, as well as digital fundus photography was implemented. For history of ROP and ophthalmic measurements data of the right eye was included .p-value < 0.20 in the univariate analysis. The 95% confidence interval and odds-ratio are given. A sensitivity analysis was performed taking into account maximum ROP stage of both eyes. Collinearity was assessed calculating pairwise Spearman correlation coefficients. This is an explorative analysis, a p-value < 0.05 was considered as statistically significant. Calculations were performed using IBM SPSS 20.0 .Continuous variables were expressed as the mean ± standard deviation (SD) or as the median when appropriate. Categorical variables were expressed as proportions. The chi-square test was used to analyse the association between categorical variables. Normal distribution was tested with the Kolmogorov-Smirnov test. Mann-Whitney U test was used to compare independent continuous parameters between two groups and the Kruskal-Wallis test between several different groups. Two statistical models were used for risk factor analysis. First, separate univariate logistic regression analysis was performed with presence of strabismus (esotropia/exotropia) as dependent variable and documented potential risk factors for strabismus as independent variables, namely sex, gestational age (weeks), birth weight percentile, age at examination, hyperopic and myopic refractive error ), anisometropia , astigmatism (continuous), presence of ROP, maternal age at childbirth, mother smoking before birth, breastfeeding < 3 months, artificial ventilation, intraventricular bleeding, and other perinatal adverse events . Second, we performed a multivariable logistic regression analysis to identify independently associated factors including all of the above-described factors that were associated with a Overall, 376 parents of former preterm infants and 397 randomly from the local registry of births selected parents of former full-term infants were contacted via phone and invited to take part in this study. Of these, 239 children born prematurely and 264 children born at full-term accepted to attend the clinical examination. In accordance, response rate was 63.6% for former preterm and 66.5% for former full-term born infants Fig. . Of thosp < 0.001).The distribution and parameters of visual acuity, spherical equivalent, astigmatism, and anisometropia for the different groups are displayed in Table p < 0.001). Strabismus was detected in 26/419 (6.2%) patients with a birth weight exceeding 1000 g, in 13/55 (24%) patients with a birth weight of 750 g to 1000 g and in 7/29 (24%) patients with a birth weight below 750 g (p < 0.001). Infants with esotropia had infantile strabismus, which was also true for infants with exotropia. All infants with manifest strabismus had no binocular function.Ophthalmic parameters such as strabismus and type of strabismus differed between the four groups table . In group < 0.001). Strabismus was found in 4/7 (57%) subjects with postnatal laser treatment due to ROP.Regarding stages of ROP, strabismus was observed in 7/31 (23%) children with stage 1 ROP, in 2/13 (15%) with stage 2 ROP, in 4/10 (40%) with stage 3 ROP, and in 1/1 (100%) children with stage 4 ROP (p = 0.004) (table Pathologic nystagmus was detected in one child (1%) with GA between 29 to 32 weeks without ROP, in one child (2%) with GA ≤ 28 weeks without ROP and three children (6%) with GA ≤ 32 weeks with postnatal ROP occurrence , higher astigmatism, high anisometropia (≥ 1.5D), postnatal ROP occurrence, breastfeeding for less than 3 months, artificial ventilation and intraventricular bleeding , hyperopic refractive error  , and astigmatism  , high anisometropia (≥1.5D), higher astigmatism, postnatal ROP occurrence, artificial ventilation, intraventricular bleeding Table . No assop = 0.009) and higher refractive error    Table .In univariate analysis exotropia was associated with low gestational age, low birth weight and high astigmatism, while the other factors were not associated Table . MultivaThe sensitivity analysis taking into account maximum ROP stage of both eyes revealed comparable results for strabismus and its associated factors.Our results demonstrate that prevalence of strabismus is significantly increased in children born prematurely compared to children of the same age born at full-term. In the multivariable analysis an association of strabismus with low gestational age, higher refractive error  and astigmatism was observed, while prior reported risk factors could not be confirmed.The highlight of this study is the assessment and the analysis of a broad range of prior reported risk factors for strabismus using a multivariable analysis to determine independently associated factors.In numerous studies multiple risk factors for strabismus were detected , 14–24. Few studies investigated the impact of low GA and low birth weight on strabismus development and reported different results , 14–18. Hyperopic refractive error  was found as an independent risk factor for strabismus and esotropia in our multivariable analysis. Similarly, in the Sydney Childhood Eye Study an association between increased hyperopia and strabismus was detected with a spherical equivalent of + 2.46 D in infants with strabismus compared to + 1.23 D in children without strabismus . MoreoveRobaei et al.  reportedOverall, our results revealed a relatively low strabismus proportion for premature infants of up to 26% compared to other trials. The prevalence of strabismus in children varies between studies due to different inclusion criteria, different study designs and divergent characteristics of subjects. Strabismus proportions of up to 42% are reported in long-term studies in premature infants –8, whileWith respect to type of strabismus, namely esotropia and exotropia, a study by O’Connor et al. , reportePathologic nystagmus was noticed in 5/239 (2.1%) preterm infants. These results are in accordance with previous reports, demonstrating nystagmus prevalence ranging from 2% to 10% in first decade of life in premature infants. The absence of nystagmus in the full-term children is similarly to previous trials , 34. TheThe strengths of this investigation were the prospective controlled study design with a high number of participates and the large control group of full-term children. Another important factor was the availability of pre-, peri- and postnatal medical information from all children, which allowed a very detailed examination as well as an adjustment for different possible confounding factors. The strict standardization reduced the probability of examiner-dependent variances. Limitations of the study are the single-centre and hospital-based study design, which reduces the representativeness of our study. Our data is restricted to children who had survived preterm birth, although neonatal intensive care has increased this chance in the recent year. Although, the participation rate was relatively high (> 60%), there is a chance that particular those infants with poor health outcomes did not reattend to take part in our study and may therefore be underrepresented, a common phenomenon in studies with former preterm infants. Accordingly, our results cannot be transferred to the general population. A lack of masked observers may also affect our results. In addition, a restriction of our visual acuity assessment is the fact that converted logMAR values are not as valid as visual acuity values obtained by actually using a logMAR chart. This has to be considered when interpreting our data. Furthermore, as only seven children of the former preterm infants received laser treatment, this treatment was not analysed separately, but were grouped to all infants with ROP.In conclusion, our study highlights that the main determinants for strabismus are low gestational age, hyperopic refractive error, and astigmatimsus. Furthermore, we can provide as one of few studies data about risk factors for esotropia and exotropia: esotropia was independently associated with low gestational age and hyperopic refractive error, while exotropia was linked to gestational age and higher astigmatism.


Babies are increasingly being exposed to antibiotics intrapartum in the bid to reduce neonatal and maternal deaths. Intrapartum antibiotic exposure, including even those considered safe in pregnancy, have been associated with childhood obesity and compromised immunity. Data on the extent of antibiotic use, safety and its impact on birth outcomes and neonatal health in Sub-Saharan Africa is very limited. This study sought to ascertain the extent of antibiotic use in pregnancy and its effects on birth outcomes in a rural hospital in Ghana.The study was a retrospective randomized study of mothers who delivered babies in a rural hospital between 2011 and 2015 in Ghana. A total of 412 mother/baby records out of 2100 pre-selected met the inclusion criteria of the study. Indicators of neonatal health used were birthweight, Apgar score, incidence of birth defects.Sixty five percent of pregnant women were administered antibiotics at some stage during pregnancy. Beta Lactam antibiotics accounted for more than 67% of all antibiotics prescribed. There was a statistically significant association between antibiotic exposure and pregnancy factors such as stage of pregnancy, parity and mode of delivery but not with socio-economic status of the mother. Intrapartum antibiotic exposure did not significantly affect the birthweight, incidence of congenital birth defect and mean Apgar scores. After adjusting for method of delivery, however, perinatal antibiotic use (24 h to delivery) was associated with lower mean Apgar scores. Birth weight was affected significantly by maternal socio-economic factors such as age and marital status.Sixty five percent of women attending the antenatal clinic received antibiotics. Intrapartum antibiotics did not affect early markers of neonatal health such as birthweight, congenital birth defect and mean Apgar scores. However, antibiotic use less than 24 h to delivery was associated with a decrease in mean APGAR score. There has been a sturdy increase in global antibiotic prescription and consumption . SeveralPregnancy presents with significant risk of complications which may lead to morbidity and mortality for mother-baby pairs. Globally, more than 50% of neonatal deaths occur in Sub-Saharan Africa because of infections and limited health resources , 4. To mThere have been several attempts to promote rational antibiotic use partly because of the risk of drug resistance, increased cost of healthcare, as well as the risk of teratogenicity in the developing foetus , 7. HoweNeonatal Health and Birth outcome is highly dependent on maternal health, nutrition and socio-economic factors. The use and choice of antibiotic during pregnancy depends primarily on maternal factors such as health, nutrition, mode of delivery and socio-economic factors. These maternal factors influence the indicators used to estimate birth outcomes and neonatal health such as birth weight, APGAR scores, and incidences of birth defects. To able to understand the full extent and effects of intrapartum antibiotics on mother and babies, there is a need to elucidate the complex interplay between maternal health, mode of delivery and socio-economic status and neonatal health.A key point in the millennium development goals is reducing maternal and neonatal mortality. To date there is little clinical data on the trends of antibiotic use during pregnancy and its effects on neonatal health from sub-Saharan Africa. Using Birth weight, APGAR scores, and incidences of birth defects as indicators of birth outcomes and early neonatal health and survival, this study examines the use of antibiotics during pregnancy, its effects on birth and neonatal health and as well as the effects of other maternal factors on antibiotic use in a rural health facility in Ghana.Seventh-Day Adventist Hospital, Dominase is a 45 bed capacity hospital located in Dominase about 19 km off the Kumasi–Cape coast highway. The hospital has an obstetrics and gynaecology unit which runs an antenatal clinic with a resident gynaecologist, pharmacist and several midwives and nurses. To limit the impact of un-prescribed and undocumented antibiotic usage, the area chosen was predominately rural with no existent pharmacy. Furthermore, the National Health Insurance Scheme of Ghana runs a “capitation policy” where patients choose a particular primary health care facility for their needs without paying out of pocket. Patients who visit any other facility aside the allocated facility have to pay to access healthcare. This discouraged the tendency for mothers from seeking health services from other facilities as well as reduce self –medication. This is of particular importance because antibiotics can be obtained without prescription in Ghana.The design was a retrospective descriptive study. The primary source of data was prescriptions generated and recorded in patient medical records filed in the hospital between January 2011 and December 2015.Folder numbers of all live babies born in the hospital between January, 2011 and September, 2015 were retrieved from the registration book at the maternity unit. Five hundred folder numbers were selected for each of the 5 years from the registration book using systematic sample, making a total of 2500 folders. The contents of 2100 folders were available for the study. Each folder of mother-baby pairs was subsequently screened using the inclusion and exclusion criteria. A total of 412 mother-baby pairs met the selection criteria.The mother should have attended at least three ANC at the hospital after confirmation of pregnancy either by ultrasonography or Human Chorionic Gonadotrophic (HCG) detection method.Should have delivered a live singleton baby at the facility.The Inclusion criteria included;Twin gestationsDeliveries of referral cases from other hospitalsThe exclusion criteria included;p-value less than 0.05 was considered statistically significant.Data obtained from the medical records were transferred unto a data capture form, the secondary data was later collated, scrutinized and analysed using IBM Statistical package for Social Sciences (SPSS) version 21. Pearson Chi-square test was used to analyze categorical variables. Relative risk and Odds ratio were used as a measure of the degree of association between an event (outcome) and comparable groups. Students T- test and One way analysis of variance (one-way Anova) were used to analyze the difference in mean values between a set of comparable groups or values. Bonferroni was used as the post hoc test after one- way Anova. A The study assumed that antibiotic prescribed was synonymous with exposure which is not always the case. Because of the rural nature of the setting the hospital dispensary dispenses most of the medications prescribed at the same facility. This reduces the inconvenience of patients moving to city centers for their prescribed medicines. The dose prescribed, the duration of therapy and the frequency of administration were not taken into consideration.The design of the study could not totally account for possible out-of- hospital antibiotic use. The choice of a rural community with few chemical shop outlets and no pharmacy was expected to reduce this potential confounder.The National Health Insurance Scheme runs a “capitation policy” where a patient chooses one primary health care facility for their needs. The policy also reduces patients moving from one hospital to another because if a patient visits another hospital they have to pay hospital charges. This reduces attrition and tendency for self- medication.The biodata recorded were mothers’ age at birth, gravida, marital status, occupational status and religious affiliation. Mothers’ age at birth ranged from 13 to 44 years with a mean age of 26.3 ± 6.40 years. Most of the pregnant women were between 20 and 30 years, married and average number of gravida of 3.07 ± 2.03. (Table n = 271) attending ANC clinic in the hospital were treated with an antibiotic at a point during pregnancy. There was no association between the socio-economic status of a woman, i.e., marital status, occupation, age etc. with the odds of being treated with antibiotics. However antibiotic use was associated multiple gravida and Cesarean section. The odds ratio for antibiotic exposure during Caesarean were 13.8 times higher  than that for women who delivered vaginally.About two out of three women  between antibiotic exposure with advance in stage of pregnancy   Table .Table 3Ep = 0.414, F = 1.59)). However when mothers were treated with antibiotics in less than 24 h to parturition, there was a statistically significant decrease in mean Apgar than those not treated with antibiotics i.e.  after adjusting for the effects of the mode of delivery.There was no statistically significant relationship between antibiotic prescription during pregnancy and mean Apgar scores . Younger mothers, unmarried women and mothers with less gravida had significantly higher mean Apgar scores compared with older (p = 0.046), married (p = 0.018) and higher gravida (p = 0.034) mothers respectively . There was no statistically significant association between marital status (p = 0.94), mothers age at birth (p = 0.361), occupation (p = 0.630), parity (p = 0.94) and religion (p = 0.49) and birth defects. Females had relatively higher odds ratio of incidence of birth defects than males. i.e. 2.2% vs 1.0% .Six birth defects were seen in the study representing 1.5% of all deliveries i.e. Cleft lip, mega cephalous, cleft palate and webbed feet. Intrapartum antibiotic exposure irrespective of trimester of exposure was not associated with any significant risk of birth defect  [Babies exposed to intrapartum antibiotics had mean weights slightly lower than those unexposed. A study by Vidal et al., 2013)  reported, (2013) –20. This13  repor, (2013) , 21, 22., (2013) . Older mA total six birth defects  were recorded in this study. This figure was similar to other prevalence birth defects reported other authors .65% of pregnant women received antibiotics at some stage during pregnancy. Antibiotic use did not affect mean birth weight, APGAR score or incidence of birth defects. However, antibiotic use less than 24 h to delivery was associated with a decrease in mean APGAR score.


Preterm and small for gestational age (SGA) births have been associated with adverse outcomes during the first stages of life. We evaluated the morbidity and mortality associated with preterm and SGA births during the first year of life in a rural area of Southern Mozambique.This is a retrospective cohort study using previously collected data from children born at the Manhiça District Hospital in two different periods (2003–2005 and 2010–2012). Newborns were classified as being preterm and/or SGA or as babies not fulfilling any of the previous conditions (term non-SGA). All children were followed up for a year for morbidity and mortality outcomes.A total of 5574 live babies were included in the analysis. The prevalence of preterm delivery was 6.2% (345/5574); the prevalence of SGA was 14.0% (776/5542) and 2.2% (114/5542) of the children presented both conditions. During the neonatal period, preterm delivery and SGA were associated with 13  and 5 times  higher mortality compared to term non SGA babies. Risk of hospitalization was only increased when both conditions were present . Mortality is also increased during the entire first year, although at a lower rate.Neonatal and infant mortality rates are remarkably high among preterm and SGA babies in southern Mozambique. These increased rates are concentrated within the neonatal period. Prompt identification of these conditions is needed to implement interventions aimed at increasing survival of these high-risk newborns. Preterm birth is the world’s leading cause of death in children under five years. It has Both preterm birth and SGA are intrinsically associated with low birth weight and are not mutually exclusive. On the one hand, preterm birth is associated with multiple maternal and/or foetal conditions, including maternal and neonatal infections, vascular disease, uterine overdistension, pre-eclampsia/eclampsia or intrauterine growth restriction (IUGR). On the Despite the relative high prevalence and adverse outcomes associated with preterm births and SGA in low-income settings, very few studies have assessed their impact on neonatal and infant mortality and morbidity in sub Saharan Africa. Only one longitudinal study conducted in Malawi showed that preterm birth was associated with a greater risk of death as well as growth and development disabilities. UnderstThe study was conducted at the Centro de Investigacão em Saúde da Manhiça (CISM) in the District of Manhiça, a malaria endemic semi-rural area in Southern Mozambique. The CISM is adjacent to the Manhiça District Hospital (MDH) and runs a demographic surveillance system (DSS) covering 90000 inhabitants in 2010 in what constitutes the study area. A passive case detection system is also running at the HDM that covers all paediatric outpatient visits and admissions. More than 80% of the deliveries in the district are institutional. The preThis is a retrospective cohort study of collected data from children born at the MDH in two different time periods; period 1: from August 2003 to April 2005 and period 2: form March 2010 to March 2012. During these periods, gestational age was routinely captured for all births taking place at the MDH, due to the coexistence of research studies which required the assessment of gestational age. Infants were classified as being preterm and/or SGA, or as babies not fulfilling any of the previous conditions . All babies were followed up for a year for morbidity and mortality outcomes using the hospital passive case detection system and the DSS. Inclusion criteria for this analysis included living in the study area, being a live birth, being institutionally delivered, and having the gestational age and weight assessed at birth.Gestational age was evaluated using two different methods based on postnatal examination of the newborn, namely, the Dubowitz test . Preterm birth was defined as that occurring before the completion of 37 weeks of pregnancy. Low birth weight was defined as less than 2500 grams at birth. Small-fional age.Only live born babies (single and multiple deliveries) were included in this analysis. Incidence of outpatient visits or hospitalizations and mortality rates were calculated using time at risk from date of birth until date at one year of age, death or withdrawal. Mortality rates are expressed per 1000 children years at risk (CYAR). Association between risk factors and occurrence of any of the conditions at delivery was evaluated using univariate and multivariable logistic regression models. Hazard Ratio (HR) of mortality among different cohorts was evaluated using Cox Regression Models adjusted for child sex, HIV status of the mother, number of previous pregnancies, maternal age, period and socio economic status (SES). Incidence rate ratio (IRR) of outpatient clinic visits or hospitalizations was assessed using negative binomial regression due to the possibility of several episodes during the study period. Variables for the multivariate analysis in the logistic, Cox, and negative binomial regression models were selected using the forward-stepwise approach with a p-value lower than 0.1 (obtained through likelihood ratio test). Multivariable models were estimated by a complete case analysis with missing values removed. P values lower than 0.05 were considered statistically significant.SES was calculated using Principal Component Analysis (PCA) following the methodology described elsewhere. The famAll data were captured in handwritten CRFs and then double entered by data clerks into the OpenClinica software. Data analysis was performed using Stata 13 . Microsoft Excel (Microsoft Office Package 13) was used for building graphs and tables.This study is a retrospective analysis of previously collected information. Many participants were part of two research studies, whose protocols and informed consents were reviewed and approved by the National Ethics Board in Mozambique and the Ethics Committee from the Hospital Clinic of Barcelona (Spain),19,20. TA total of 5574 live babies with available data on gestational age were included in the analysis (3189 in period 1 and 2385 in period 2). Around 51.4% (2853/5554) of the babies were male and 29.0% (656/2265) were born to HIV infected mothers. Among all children included 26.6% (1397/5256) were born to primigravidae, and 23.2%  in our sample was 10.3% (572/5570), that of very low birth weight (<1500 g) was 0.5% (29/5570), and the proportion of preterm delivery was 6.2% (345/5574). The prevalence of SGA was 14.0% (776/5542); among the SGA, 11.9% (662/5542) were at term SGA, while 2.1% (114/5542) of them fulfilled both definitions of preterm and SGA simultaneously. Nearly 4% [3.7% (205/5542)] of the infants were preterm but not SGA. Baseline characteristics of the study participants are depicted in Tables 3 show the results of the univariate and multivariable logistic regression analysis after adjusting for potential confounders.Being multigravidae and older age were each associated with lower likelihood of SGA. If the mother had more than four previous pregnancies the odds of being SGA was 52% lower compared to the odds of primigravidae women . Female sex and maternal HIV infection were also associated with being SGA . Likewise, the same variables were associated with preterm delivery, although without statistical significance in the multivariable model. . No relevant differences on mortality rates were observed by sex of the infant.The overall neonatal mortality rate associated with preterm delivery (not SGA) was 599.3 (95% CI 224.9–1596.7) per 1000 CYAR and the infant mortality rate was 79.2 per 1000 CYAR (95% CI 35.6–176.3). Among preterm newborns regardless of the SGA status, the rates were 980.2 (95% CI 542.8–1769.9) and 136.1 (95% CI 84.6–218.9), respectively. The overall neonatal mortality rate among term SGA newborns was 289.0 (95% CI 137.8–606.1) and the infant mortality rate was 55.1 (95% CI 33.2–91.4). Among SGA newborns regardless of preterm delivery, the mortality rates were 427.5 (95% CI 242.8–752.7) and 76.6 per 1000 CYAR (95% CI 51.3–114.2) for the neonatal and first year of life period. The presence of both conditions (SGA and preterm birth) boosted both neonatal and infant mortality rates to 1299.8 (95% 541.0–3122.9) and 218.3 (95% CI: 113.6–419.5) per 1000 CYAR, respectively Table 4. Both preterm birth and SGA conditions were independently associated with a higher hazard of dying during the neonatal period and infancy. During the first 28 days, preterm-non SGA delivery was associated with 13 times higher mortality rate (per unit time) compared to term deliveries not SGA , and term SGA was associated with about 5 times higher mortality rate (per unit time) when compared to the at term-non SGA group (hazard ratio 4.5 (95% CI: 1.6–12.6). The hazard of dying in the neonatal period for both preterm and SGA was higher when coexisting with each other. Mortality rates were still increased in the postneonatal period although of less magnitude, leading to lower hazard ratios associated to preterm and SGA compared to term-non-SGA babies. The hazard of dying the first year of life for both preterm and SGA was higher when coexisting with each other.Cox regression analysis adjusted for relevant variables is presented in Table 5). Most outpatient diagnoses in SGA and preterm infants were related to respiratory infections (29.2% and 20.1% respectively) followed by skin and conjunctivitis related visits . However, no differences in the proportion of these diagnoses were observed in comparison to the at term non-SGA group.The incidence rate (IR) of outpatient clinic attendance was similar for the cohort of preterm-non SGA babies compared to that of babies born at term non-SGA, both in the neonatal and in the post-neonatal period . Likewise, there were no differences on outpatient attendances among term SGA newborns compared to those born at term non-SGA (Table 6).With regard to neonatal hospitalizations, these were more frequent only in babies with both conditions  compared to the term non-SGA group. The rate of hospitalizations was also increased during the entire first year of life in preterm (IRR: 1.7: 95% CI: 1.0–2.9) and preterm and SGA babies  , but also the evaluation of these conditions without considering the presence of the other (model 2 and 3). Prematurity was associated with almost a 13 and 4 fold-increased risk of dying during the neonatal and the postneonatal period, respectively. Small for gestational age on the other hand, was associated with a lower risk of death compared to preterm births in all models, in line with findings from other studies,24. SincOur results on mortality rates associated with preterm and SGA in the neonatal period are in line with those published in a recent pooled country analysis for low and middle income countries. It has Interestingly, the results on morbidity seem to be contradictory with the mortality findings. It seems that neither prematurity nor SGA births are associated independently with higher rates of hospitalization during the neonatal period compared to those term non-SGA. Model 1, only shows an increased risk of hospitalization when both are present , but not when they are analysed separately. Moreover, we did not observe an increased risk of outpatient attendances in the preterm or SGA cohort for any of the periods. This could be due to several reasons. First, small numbers of hospitalizations and outpatient visits in the preterm and SGA cohorts might have hindered the chances of finding this association if it does indeed exist. Second, morbidity due to mild conditions might be similar between the groups, and increased morbidity risk might only be associated with severe conditions, which might be best reflected when analysing hospitalization risk of both SGA and preterm delivery. Third, in this area of southern Mozambique many children are first taken to the traditional healer when they are sick. If the potential health problems associated with preterm and/or SGA are severe, children might not be taken to the formal health system before they die. Thus, morbidity surveillance based on outpatient or inpatient attendances might be an underestimate of the true morbidity burden associated with these conditions.These findings underscore the need to identify these conditions early enough in order to implement interventions aimed at increasing the level of care, and ultimately survival. However, with currently available strategies, there is a broad room for improvement in the field of prevention, which should focus in targeting the known risk factors, including: preconception counselling and family planning; health education programs aimed at prevention, early diagnosis and treatment of infections before and during pregnancy; increased control of conditions such as diabetes, hypertension, anaemia, before and during pregnancy; close monitoring of nutritional status and mental health of the mother, as well as implementation of best practices in assisted reproduction . AlthougThis study has several limitations. First, gestational age was measured through indirect methods based on postnatal examination of the newborn . Although both methods have been validated and are broadly used in low income countries, the accIn conclusion, these results contribute to the evidence on the increased risk of mortality and morbidity associated with preterm and small for gestational age births in rural Africa. This increased risk is much higher for preterm births than for SGA without prematurity and appears to be concentrated within the neonatal period. Routine assessment of birth weight and gestational age at birth, and identification of these conditions should prompt interventions aimed at increasing the level of care among these high-risk newborns and improve survival.


The scan-rescan %COV was lower than 10% in all cases with the highest values observed for FA and the lowest for MD. This pilot study demonstrates that it is possible to obtain reliable tissue-specific estimation of DTI indices within the LSE using a rFOV ss-EPI acquisition. The DTI acquisition and analysis protocol presented here is clinically feasible and may be used in future investigations of neurological conditions implicating the lower SC.Diffusion tensor imaging (DTI) has recently started to be adopted into clinical investigations of spinal cord (SC) diseases. However, DTI applications to the lower SC are limited due to a number of technical challenges, related mainly to the even smaller size of the SC structure at this level, its position relative to the receiver coil elements and the effects of motion during data acquisition. Developing methods to overcome these problems would offer new means to gain further insights into microstructural changes of neurological conditions involving the lower SC, and in turn could help explain symptoms such as bladder and sexual dysfunction. In this work, the feasibility of obtaining grey and white matter (GM/WM) DTI indices such as axial/radial/mean diffusivity (AD/RD/MD) and fractional anisotropy (FA) within the lumbosacral enlargement (LSE) was investigated using a reduced field-of-view (rFOV) single-shot echo-planar imaging (ss-EPI) acquisition in 14 healthy participants using a clinical 3T MR system. The scan-rescan reproducibility of the measurements was assessed by calculating the percentage coefficient of variation (%COV). Mean FA was higher in WM compared to GM (0.58 and 0.4 in WM and GM respectively), AD and MD were higher in WM compared to GM (1.66 μm Diffusion-weighted imaging (DWI) can be used to study the diffusion of water molecules in neural tissue . Among sTechnical concerns associated with SC diffusion imaging are related but not limited to the signal-to-noise ratio (SNR), radiofrequency (RF) hardware design, magnetic field inhomogeneities around the SC, cerebrospinal fluid (CSF) pulsation, partial volume effects at the boundary between grey matter (GM), white matter (WM) and CSF and the choice of the acquisition scheme . Typically, DTI is performed using single-shot echo-planar imaging (ss-EPI) ; ss-EPI DTI with rFOV has been employed successfully to study the upper SC with sufficiently high resolution to distinguish between GM and WM and to allow tissue- or tract-specific estimation of indices such as mean/axial/radial diffusivity (MD/AD/RD) and fractional anisotropy (FA) in the neurologically intact cord , 23 and In this pilot study, the feasibility of obtaining tissue-specific (i.e. GM and WM) DTI indices within the lower SC was investigated in a number of healthy volunteers using DTI with rFOV , 26 on aFourteen healthy subjects were recruited . The work was approved by the National Hospital for Neurology and Neurosurgery and the Institute of Neurology Joint Research and NRES committee London Bloomsbury (London REC2 Ethics Committee). Written informed consent was obtained from all study participants.-1, radiofrequency (RF) dual-transmit technology  and the manufacturer’s product 15-channel SENSE receive-only RF spine coil were used. A conventional T2-weighted image of the lumbar spine in the sagittal plane was first obtained using a turbo spin-echo (TSE) sequence and was used to facilitate prescription of subsequent scans perpendicular to the cord. The imaging parameters for the T2-weighted TSE were: TR = 3575 ms, TE = 100 ms, flip angle α = 90°, FOV = 300 × 180 mm2, voxel size = 0.8 × 0.8 × 3 mm3, NEX = 2, slices = 15, acquisition time 3:48 min.A 3T Philips Achieva system with maximum gradient strength 65 mT m2, voxel size = 0.5 × 0.5 × 5 mm3, NEX = 8, slices = 10, acquisition time 9:51 min.Additionally, a 3D slab-selective fast field-echo (3D-FFE) sequence with fat suppression was acquired in the axial-oblique plane . The 3D-FFE scan was performed in order to identify the exact location of the LSE, necessary to obtain quantitative measurements of DTI indices. The 3D-FFE slices were prescribed between the T11—L1 level to ensure coverage of the LSE in all cases . The fol2, interleaved with 7 b = 0 measurements; Additional parameters for the DTI acquisition were: TR ~ 4000 ms (4 heart beats), TE = 40 ms, flip angle α = 90°, slices = 10; FOV = 64 x 48 mm2, voxel size = 1 × 1 × 5 mm3, trigger delay for cardiac gating of 150ms. The total acquisition time was ~ 15 min, depending on heart rate.For estimating the DTI indices within the LSE, a ss-EPI with rFOV was used , 26 withMotion during the imaging session was minimised with the use of Velcro straps to restrain the torso and with the placement of a large foam wedge beneath the knees, as this increases the level of contact between the lower back and the flat surface of the coil.http://www.xinapse.com), as previously described [Using the 3D-FFE, the three slices (i.e. 15 mm section) covering the widest section of the lumbar cord (i.e. the LSE) were identified, by outlining the cord using the active surface model (ASM) segmentation method available with JIM 6.0 (escribed .http://www.fmrib.ox.ac.uk/fsl/), with registration transformations estimated among non-DW images, interspersed throughout the diffusion acquisition [The diffusion-weighted images were corrected for motion using slice-wise linear registration implemented in FSL (uisition . Specifiuisition .http://cmic.cs.ucl.ac.uk/camino/) and voxel-wise maps of AD, RD, MD and FA were generated. These indices measure: the amount of diffusion along/across the dominant diffusion direction (AD/RD); the mean amount of diffusion (MD); and the anisotropy of the diffusion tensor  (FA).DTI was fitted with standard routines in CAMINO .MR imaging of the lower SC mostly involves RF coil designs with receiving elements beneath a flat surface. This means that inter-subject variability in positioning the volume of interest (i.e. LSE) with respect to the RF coil surface can influence image quality and therefore the reliability of the DTI measurements, for a predefined diffusion protocol. For instance, high inter-subject variations of SNR due to variable distance between the receiving elements and the volume of interest can cause subject-dependent bias of FA . This cIn this work, the quality and reproducibility of the DTI indices were evaluated by studying the effect of altering the number of diffusion encoding directions within the same protocol in all subjects. For this purpose, the DTI model was retrospectively fitted to gradually reduced sets of measurements optimally spread over the sphere  , extractWM, SIGM, SDWM and SDGM respectively indicate the mean value of each one of the DTI indices within the WM and GM masks, and the corresponding standard deviation values. C and CNR were calculated in all subjects but without inclusion of repeated scans, which were performed as part of the reproducibility assessment.The quality of the fitted DTI indices was evaluated by visual inspection and by calculating the mean values within each tissue-type  in order to quantify the contrast (C) and the contrast-to-noise ratio (CNR) between GM and WM as previously demonstrated , using tReproducibility (%COV) as a function of the number of diffusion encoding directions was also evaluated in order to establish an adequate number of diffusion-weighted measurements needed to obtain reliable tissue-specific estimation of DTI indices for the population under investigation. DTI indices were assessed in 6 study participants who had repeated scanning, and for whom the cord/coil distance was within the lower and upper bounds previously identified in a larger population .To obtain the %COV, linear mixed null models were fitted for each measure and for each diffusion encoding scheme, with subject random effect; the %COV was then calculated using the estimated within subject standard deviations and means.To examine the variation in means of the DTI indices within each tissue-type across the number of diffusion encoding schemes, linear mixed models were fitted over the various diffusion encoding schemes with diffusion encoding scheme as fixed effect; a joint wald test was then used to test the null hypothesis of no variation across the schemes. There was no evidence of departure from model normality assumptions. These models were fitted in Stata 14.1 .p<0.05.Possible differences in DTI indices between GM and WM were assessed using paired t-tests, after checking the normality of the paired differences. Statistical significance was accepted at All the study participants tolerated the imaging session well without the need to discard any data because of motion related artifacts. The number of slices obtained in the present study was sufficiently high to ensure coverage of the LSE in all cases, although it was possible that, in some cases , the same number of slices may have covered a section beyond the minimum required, in which case the extra slices were simply discarded. An example of the high-resolution structural images acquired through the T11-L1 level in a single healthy subject and the corresponding quantitative DTI parameter maps are shown in 2ms-1 and 1.20 μm2ms-1 respectively, p<0.001), MD is higher in WM compared to GM  and RD is lower in WM compared to GM . Separate box plots displaying the distribution of the DTI indices in all study participants are shown in GM, WM and whole cord values (mean ± SD) of AD, RD, MD and FA in 14 healthy subjects are shown in The results from the reproducibility assessment (%COV) using the original acquisition protocol, with diffusion-weighting applied along 60 directions, are reported in The effect of fitting the DTI model with gradually reduced sets of measurements on the quality of the DTI parameter maps is shown in The results from fitting the DTI model with gradually reduced sets of measurements on the %COV of the DTI indices within each tissue-type is demonstrated in The results of the linear mixed models examining variation in means of the DTI indices within each tissue-type across the number of diffusion directions are shown in This study has shown that tissue-specific (i.e. GM and WM) DTI indices within the LSE can be obtained reliably using a commercially available 3T MR system and analysis software. However, in order to achieve the results presented here, several technical considerations had to be addressed such as the choice of the acquisition and readout type, the localisation of the LSE to ensure consistent measurements across all subjects and the reproducibility of measurements.EPI-based rFOV acquisition variants have recently shown promise for studying the SC –21. The Recently, rFOV ss-EPI  and largThe reproducibility of DTI measurements obtained using rFOV ss-EPI acquisitions in the lower SC has not been reported to date although studies using similar acquisitions have provided results in the upper SC , 23. TheIn this study, the effect of fitting the DTI model to gradually reduced sets of measurements was examined retrospectively by assessing any changes in the quality (C and CNR measures) and reproducibility (%COV) of the DTI indices. In terms of quality, it was shown that for CNR in particular there was a trend towards increasing values when a higher number of diffusion encoding directions was used, and this effect was more pronounced between 10–40 diffusion encoding directions, while more consistent values were obtained between 40–60 directions. This suggests that there maybe a higher benefit from using 40 or more diffusion encoding directions. In terms of reproducibility, this exploratory study has shown that, even though a surface RF coil was used, the %COV values for all the DTI indices were below 10% when the DTI model was fitted with 20 or more distributed diffusion directions; this result is in agreement with previous general recommendations , 43. TheThe results of the linear mixed models examining variation in means of the DTI indices within each tissue-type across the number of diffusion directions have shown that the MD measures are the least affected in terms of the number of diffusion directions used. This is likely due to the fact that MD represents the average diffusivity over the unit sphere, and the mathematical operation of averaging effectively acts as a low pass filter i.e. it is robust towards noise. With regard to all other DTI indices, the variation in mean values becomes less significant as the number of diffusion directions increases, and the percentage size of the largest difference for each measurement also becomes lower, suggesting that there maybe a higher benefit in such measures when more directions are used e.g. 40 or more . Of cour2ms-1), RD (0.53–0.54 μm2ms-1), AD (1.41–1.6 μm2ms-1) and WM values for FA (0.76–0.8), MD (0.91–0.97 μm2ms-1), RD (0.36–0.39 μm2ms-1), AD (1.96–2.16 μm2ms-1). From 2ms-1), higher for RD (0.63 μm2ms-1) and similar for MD (0.82 μm2ms-1); values in the LSE-WM were lower for FA (0.58), AD, (1.66 μm2ms-1), higher for RD (0.58 μm2ms-1) and similar for MD (0.94 μm2ms-1). These results are in agreement with previous studies showing a reduction in FA and AD in the lower SC (both in GM and WM) as compared to the cervical SC, whereas MD remains relatively consistent throughout the entire length of the cord [In order to better interpret the DTI indices obtained in this study, one could examine previous measurements obtained in the upper SC using similar methods to establish whether DTI indices vary naturally along the length of the cord; one could also examine previous measurements obtained in the lower SC using similar methods to investigate whether or not the results are comparable. In previous research , 24, idethe cord , 41.2ms-1) [2ms-1). One of the two studies also reported GM values for FA, which were lower than the present study  [Considering the aforementioned methodological differences between this and other rFOV DTI studies of the lower SC, it may not be possible to directly compare the DTI indices obtained here. Two studies have used similar acquisition protocols as in the present study to investigate the lower SC and have obtained WM average values for FA (~0.63–0.67), MD (~0.85–0.92 μm2ms-1) , 27. Froctively) . PossiblIn the present study, variations in the DTI indices at different spinal cord levels were not examined specifically, thus the true magnitude of such potential variations is unknown. However, assuming that the same DTI protocol is employed to study the different levels of the spinal cord each time, hence minimising any influence related to technical factors, any variations in the DTI indices along the length of the spinal cord are likely to be related to microstructural differences within each tissue-type (GM and WM). For example, previous studies in the cervical cord have suggested that there is a higher alignment of white matter fibres at this level, with a proportion of these fibres having a rather large diameter , 41, 44.in vivo. Future work will aim to translate the acquisition and analysis method presented here to clinical studies of neurological conditions affecting the lower SC.In summary, the results of this work demonstrate that it is possible to obtain reliable tissue-specific DTI measurements within the LSE using a clinical MR system at 3T S1 Appendix(DOCX)Click here for additional data file.S1 Dataset(XLSX)Click here for additional data file.S1 Fig(TIFF)Click here for additional data file.S2 FigThe plot demonstrates the distribution of the measurements obtained in this study as compared with the median, lower and upper quartile values previously determined from a total of 60 randomly selected scans.(TIFF)Click here for additional data file.


It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated  with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister. It is also an indicator of processes that influence long-term health; for example, birth weight has been inversely associated with adult mortality, especially cardiovascular mortality, and positively associated with the risk of cancer deaths2. It is well established that boys are born heavier than girls, in both singletons4 and twins7. However, there is an ongoing debate as to whether birth weight in twins is affected not only by their own sex but also by the sex of their co-twin. Dizygotic twinning rate has shown a steep increase since the 1980s in most industrialized countries, mainly due to the widespread use of in vitro fertilization and other fertility treatments9. Therefore, the study of the association between birth weight and the sex of the co-twin is of clinical and epidemiological interest.Birth weight is an indicator of foetal growth and predicts short-term survival of the newborn12, but this difference did not reach significance in other studies16. The greater birth weight of boys from OS pairs has generally been ascribed to a more successful in utero competition for nutrients of boys in the presence of a sister rather than a brother co-twin17. For girls, findings are less consistent. Girls from OS pairs were heavier at birth than those from SS pairs in Canadian twins18; similar but non-significant differences were observed in other populations19. Since androgens have shown to exert a positive effect on fetal growth20, a so-called twin testosterone transfer (TTT) hypothesis has been proposed15, by which females who develop with a male co-twin are potentially exposed to higher levels of prenatal testosterone (the most potent androgen) than females who develop with a female co-twin. This would then explain the greater birth weight in girls from OS than from SS pairs. However, other studies have reported roughly similar mean birth weight in girls from SS and OS pairs12 and, although non-significant, greater birth weight in SS twins14. Part of the discrepancy between findings might be explained by the different criteria used to select SS twins in the studies , SS dichorionic twins or only SS dizygotic twins).Some studies have shown that boys from opposite-sex (OS) pairs are significantly heavier at birth than boys from same-sex (SS) pairs22, there is evidence that boy-boy pairs have a shorter gestation than boy-girl pairs and girl-girl pairs; however, it is not clear whether gestational age differs between boy-girl pairs and girl-girl pairs16. Loos et al.12 observed that when controlling for the length of gestation, the birth weight differences between boys from SS and boys from OS pairs attenuated, suggesting that gestational age has an important role and that boys from OS pairs benefited from the slightly longer gestation. This study12 additionally showed that gestational age difference between boys and girls is smaller with greater birth weight, which confirmed the findings in singletons22.According to studies in singletons showing that mean duration of gestation is shorter in boys than in girls23, alternative measures, such as birth length and ponderal index (PI), have also been of interest. PI is a measure of relative weight (assessed as birth weight per birth length cubed) that is more appropriate for newborns than body mass index. For example, short birth length has been found to be associated with adult all-cause mortality25 and greater PI with a higher risk of breast cancer mortality26. Birth length is also greater in boys than in girls6, but only one study compared SS and OS twins showing no differences18. Using only dizygotic (SS and OS) twins from 21 cohorts in 15 countries, we conducted an individual-based analysis of pooled twin cohorts (i) to analyze the association of co-twin’s sex with birth weight, length and PI, (ii) to ascertain whether gestational age differs between the three twin pair types  and (iii) to examine whether gestational age plays a role in the association between co-twin’s sex and the three indicators of birth size.Although birth weight is the most widely used measure of birth size in epidemiological studiesAll participants were volunteers and they or their parents gave informed consent when participating in their original studies. No experimental data were asked and thus we did not ask ethical approval. Only a limited set of observational variables and anonymized data were delivered to the data management center at University of Helsinki. The pooled analysis was approved by the ethical committee of Department of Public Health, University of Helsinki, and the methods were carried out in accordance with the approved guidelines.27. Information on birth weight of both SS and OS dizygotic twins was available for 21 twin cohorts from 15 countries (OS/SS ratio range = 0.3–2.2). Birth length and gestational age were available in 12 and 13 of these cohorts, respectively. The participating twin cohorts are identified in Table 27.This study is based on the data from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), which was intended to pool data from all twin projects in the world having information on height and weight3)], we additionally excluded individuals without data on birth length, with birth length <25 or >60 cm, PI <12 or >38 kg/m3, intrapair difference in birth length >10 cm or PI >12 kg/m3, or born before 1970 leaving 33,170 individuals . These cut-off limits were defined based on the visual inspection of histograms for both birth size measures and intrapair differences in birth size.After excluding monozygotic twins , we had 70,814 dizygotic twin individuals with information on birth weight . We further calculated birth weight, length and PI standardized by gestational age. These three measures of size at birth were expressed as SD scores of the respective means/weeks of gestation  to estimate their relative value for a given gestational age. Finally, birth weight standardized by gestational age was available for 23,870 twin pairs and birth length and PI standardized by gestational age for 14,890 twin pairs.Statistical analyses were conducted using the Stata statistical software package . To compare the birth size  of individuals from OS pairs with that of individuals from SS pairs, we used linear regression models (twin type was used as the explanatory variable and birth size measures as the outcomes) adjusted for birth year and twin cohort separately by sex. The non-independence within twin pairs was taken into account by using the “cluster” option available in Stata. The association between twin pair type  and gestational age was analyzed using linear regression models  adjusted for birth year and twin cohort. To calculate the odds ratios (OR) for the risk of delivery at less than 37, 34 and 31 weeks  between the three twin pair types, we used logistic regression models adjusted for birth year and twin cohort.Finally, we compared gestational age between boys and girls separately by 7 birth weight classes of 0.5 kg  and 5 birth length classes of 5 cm . For these analyses, in addition to the exclusion of unrealistic birth size values for a given gestational age, we removed birth weight values <0.75 and ≥4.25 (n = 54) and birth length values <32.5 and ≥57.5 (n = 39) because the sample size was too small to create more categories. Linear regression models  adjusted for birth year, twin cohort and non-independence within twin pairs were used.Descriptive statistics for the three birth size measures of twin individuals in relation to the sex of their co-twin are presented in Table We then compared mean gestational age and the risk of preterm delivery between twin pair types  Table . CompareIn Table Figure The present study, based on a multinational database of 21 twin cohorts from 15 countries, showed that birth weight and length are associated with the sex of the co-twin in boys. Differences in birth size between twins from SS and OS dizygotic twin pairs were of small magnitude and partly explained by differences in gestational age between boys and girls. Our results thus support the role of gestational age in the associations between co-twin’s sex and birth size and refine previous findings by considering, in addition to birth weight, also birth length and PI.10, 64 g11 and 78 g12, even when different inclusion criteria for SS twins were used. For girls, birth weight was very similar in SS and OS twins, which is also in agreement with these studies12. Boys with a co-twin sister were 0.16 cm longer than those with a co-twin brother, but differences were not significant in girls. Similar birth length in girls from SS and OS pairs was also observed in Canadian twins18. The lack of association of PI at birth with the sex of the co-twin may be because PI is a mathematical ratio of weight-to-length and proportional reduction in both birth weight and birth length will keep the ratio fairly unaffected. The attenuation of the associations between birth weight and co-twin’s sex after controlling for gestational age in boys was also observed in the study of Belgian twins12 (a part of this sample is included in the CODATwins project as the East Flanders Prospective Twin Survey), and has been attributed to a longer gestation in the presence of a co-twin sister.Boys with a co-twin sister were, on average, 31 g heavier at birth than those with a co-twin brother. Our findings are in line with previous studies showing a difference of 57 get al.16 found longer mean gestational age in OS pairs than in SS pairs in both sexes, our findings of shortest gestations in boy-boy pairs, intermediate in boy-girl pairs and longest in girl-girl pairs  are in line with those observed in Belgian12  and Israeli11  twins. In the present study, the mean gestational ages between boy-girl and girl-girl pairs were not significantly different. Loos et al.12 reported a similar pattern for gestational age and concluded that it is the girl who governs the length of gestation, in such a way that there is a female-protective factor that prolongs gestation. However, Melamed et al.11 observed that mean gestational age and the risk of delivery before 31 and 28 weeks were significantly different between boy-girl and girl-girl pairs and they suggested that a potential “dose-dependent male-offending factor” might increase the risk of prematurity. Since in this multinational study the risk of delivery before 34 weeks was lower in girl-girl than in boy-girl pairs, this interpretation concerning a “dose-dependent male-offending factor” could also be applied to our results.Although Luke et al.11 speculated that the shortest gestational age in boy-boy pairs might be explained by the higher level of androgens in pregnancies with boys, which has been implicated in the onset of preterm labor28. Moreover, we do not know by which mechanisms, even after adjustment for gestational age, boys from OS pairs are significantly heavier and longer than boys from SS pairs. It has been suggested that, if the amount of nutrient available in boy-boy and boy-girl pregnancies are equal, boys in boy-girl pregnancies compared with those in boy-boy pregnancies will be more successful in the competition for nutrient because girls are programmed to grow slower29. However, girls from OS pairs were slightly heavier than those from SS pairs , which is in opposite direction to the hypothesis of such maternal constraint. Moreover, and in agreement with previous studies in singletons22 and twins12, we showed that, to attain a given birth weight and length, the gestation of boys is shorter than that of girls, and the gestational age differences between boys and girls are smallest for the heaviest and longest children, which is not in accordance with this hypothesis either. This suggests that boys grow at a faster pace than girls, but that girls catch-up late in gestation. Pergament et al.30 found that female embryos, compared to male embryos, are already delayed in early embryonic development. It has been speculated that some critical time windows of development may be slightly different for boys and girls, and that this phenomenon may be one of the reasons for sex differences in sensitivity to fetal programming. In order to shed new light into the mechanisms behind the association between birth size and the co-twin’s sex, an interesting starting point for future studies would be to collect measures of fetal growth by ultrasound imaging at different stages of pregnancy to elucidate when these differences emerge.Although elucidating the mechanisms behind the association between the sex of the co-twin and birth size was not an objective of the present study, our results are opposite in direction to that predicted by the TTT hypothesis, at least in boys. We showed that gestational age has a role in the association between the co-twin’s sex and birth size. Melamed 27. However, the accuracy between reported birth weights and medical records of birth weights (in singletons) reached high kappa values (~0.90)32. Zygosity was also self-reported and not verified by DNA testing in the majority of studies. It is thus possible that misclassification of a small fraction of MZ twins as SS dizygotic twins could have contributed to part of the observed small differences in birth size between twin type groups. Finally, distinction between spontaneous and iatrogenic preterm birth (e.g. by caesarean section) is lacking.The main strength of the present study is the large sample size of our multinational database of twin cohorts with information on birth weight, length and gestational age. We performed an individual-based pooled analysis to provide results for this sample including the large majority of existing twin cohorts having birth related measures. Generalization for the global population is, however, not possible because countries or regions are not equally represented and the database is heavily weighted towards European ancestry populations following westernized lifestyle. Another limitation of the data is that most of the measures were parentally reportedWe conclude from this multinational study that boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother, but birth size in girls is not associated with the co-twin’s sex. The differences in boys are modest and partly explained by a longer gestation in the presence of a co-twin sister. Boy-boy pairs have a shorter length of gestation and a higher risk of preterm delivery than boy-girl and girl-girl pairs, and the difference in gestational age between boys and girls was generally smaller with greater birth size. Although the effects are too small to be of clinical significance, these findings have theoretical significance and might help to shed light on the underlying mechanisms linking birth size and the sex of the co-twin in future research.


Pseudoaneurysms are rare complications of chronic pancreatitis and are associated with a high mortality. In this article we demonstrate a novel utilization of endoscopic ultrasound (EUS) technology to embolize a large pancreatic pseudoaneurysm when gold standard therapies had proven futile. Pancreatic pseudocysts complicate pancreatitis in approximately 40% of cases -3. PropoPancreatic pseudoaneurysms have an incidence of less than 10% and are a potentially life-threatening complication of inflammatory pancreatitis, typically complicating pseudocysts. Non-enteral bleeding in the setting of pseudocysts requires swift evaluation and treatment. Pseudoaneurysms are commonly asymptomatic and likely to be detected coincidentally with CT. Presumably enzymatic autodigestion leads to vascular wall injury, with subsequent ballooning of the vascular wall. Hemorrhage is associated with a mortality rate as high as 40% . TreatmeWe report a patient with complicated pancreatitis in whom endovascular therapy of a pseudoaneurysm proved impossible, who was successfully treated with endoscopic ultrasound directed embolization of an arterial pseudoaneurysm.A 54-year-old male with chronic calcific pancreatitis presented with an infected pseudocyst. Abdominal CT with contrast demonstrated complex collections in the pancreatic head and left upper quadrant, with a 3 cm pseudoaneurysm arising from a small branch of the superior mesenteric artery . EndoscoFollowing the third attempt, a combined procedure was performed, integrating both interventional radiology and endoscopic ultrasound services. A GF-UC140P curved linear array echoendoscope  was advanced into the gastric lumen identifying the pseudoaneurysm. Doppler was used to identify the relevant vascular anatomy. A 19-gauge Cook EchoTip needle  was used. The stylet was removed and the needle flushed with sterile normal saline. The needle was advanced through the gastric lumen into the pseudoaneurysm. Location was confirmed by aspiration of blood .Pseudoaneurysm embolization was performed under fluoroscopic visualization through the 19-gauge needle utilizing multiple 0.035” Nester Embolization Coils  of varying sizes , 4. ContPseudoaneurysms are a serious complication of chronic pancreatitis and have an incidence of hemorrhage ranging from 1.4-8.4% . The mosThis case emphasized the degree of difficulty involved in successful embolization of the pseudoaneurysm. Direct visualization under ultrasound guidance led to the success of the procedure. The US-guided transgastric introduction of the needle into the pseudoaneurysm implemented the Poiseuille equation of fluid dynamics. Intuitively, introducing a needle into a highly pulsatile arterial mass would result in hemorrhage. However, the physics of fluid dynamics dictates that a longer needle attenuates pressure change from the high flow arterial pseudoaneurysm to the stomach resulting in a reduced flow velocity.Endoscopic ultrasound provides precise pseudoaneurysm location along with collateral vessel assessment, providing a safer intervention with reduced mortality and complications. Success rates of trans-catheter embolization range from 78-100% and have less than 3% peri-procedural mortality , 6. Thou


Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth.We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery.Using individual participant data from 133,957 mother–child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW , as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups . There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation.Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW.Birks L, Casas M, Garcia AM, Alexander J, Barros H, Bergström A, Bonde JP, Burdorf A, Costet N, Danileviciute A, Eggesbø M, Fernández MF, González-Galarzo MC, Gražulevičienė R, Hanke W, Jaddoe V, Kogevinas M, Kull I, Lertxundi A, Melaki V, Andersen AM, Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785–1793; http://dx.doi.org/10.1289/EHP208 Potential endocrine-disrupting chemicals (EDCs) have been described as human-made substances that alter hormone regulation in humans or wildlife . The endWomen make up half of the workforce, and many of them are of reproductive age . During In this study we aimed to assess whether maternal occupational exposure to EDCs as classified by a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery in a population of 133,957 mother–child pairs from 13 population-based birth cohorts in 11 European countries.As part of the Environmental Health Risks in European Birth Cohorts (ENRIECO) and Developing a Child Cohort Research Strategy for Europe (CHICOS) projects, data held by existing European birth cohorts were inventoried, including data on birth and child health outcomes and maternal occupation . Among thttp://www.ilo.org/public/english/bureau/stat/isco/isco88/), and with information on birth weight or length of gestation. From the 221,837 mother–child pairs followed at birth, 133,957 pregnant women fulfilled these criteria , singleton pregnancies, women being employed during the period starting 1 month before conception until birth, women with occupations coded according to the International Standard Classification of Occupations of 1988  system, the JEM was first translated from SOC2000 to ISCO88 codes using the CAMSIS tool –based length of gestation estimate was used if it was consistent by ≤ 7 days with the ultrasound-based estimate. When these estimates were not consistent, or the LMP measurement was unavailable, the ultrasound-based estimate was preferred. If both measurements (LMP and ultrasound) were unavailable, the maternal reported length of gestation measurement was used.The study focused on the following birth outcomes: birth weight (grams), term LBW , length of gestation (days), and preterm delivery (< 37 weeks vs. ≥ 37 weeks).2).Information on covariates used in this study was collected similarly in each cohort and included sex of the newborn , parity , maternal age (continuous in years), maternal country of birth , marital status , maternal education , maternal active smoking during pregnancy , and maternal prepregnancy body mass index (BMI)  and/or 2I ≥ 25%, random-effects analysis was used. We then used meta-regressions  with the unexposed group , and second by comparing classified exposure to 1–3 EDC groups and ≥ 4 EDC groups with the unexposed group. Further, exposure classification (“possible” and “probable” combined) to each of the 10 specific EDC groups was compared with the same unexposed group . Multivariate linear regression models were used for continuous variables (birth weight and length of gestation) and multivariate logistic regression models were used for dichotomous outcomes (term LBW and preterm delivery). For all models, we performed complete case analysis, including only subjects with available information on the exposure, outcome, and covariates. All models were adjusted for the following potential confounders: parity, maternal age, maternal country of birth  birth weight for newborns was 3,541 ± 561 g. Babies in the Rhea cohort were the smallest with a mean birth weight of 3,156 ± 488 g, and babies in the MoBa cohort were the largest  . The meaOverall, 11% of women held jobs that were classified as possibly or probably exposed to EDCs . INMA NeThere was no evidence for any statistically significant association with birth weight for job titles exposed to single EDC groups or for simultaneous exposure to multiple EDC groups . The risMaternal occupations classified as exposed to BPA or BFRs during pregnancy were associated with significantly longer gestational length  . Among pn = 6,889), all associations with term LBW and length of gestation were generally consistent, except for exposure to ≥ 4 EDC groups or phthalates, where ORs remained significant but weakened. Exposure to BFRs and association with term LBW lost significance (see Table S6). Stratified analyses by sex of the newborn did not change associations . Birth weight and preterm delivery were not significantly associated with JEM-classified occupational EDC exposure.This large meta-analysis suggests that maternal employment during pregnancy in occupations classified as possibly or probably exposed to EDCs during pregnancy is associated with a significant increased risk of term LBW in newborns, and that this association is fairly consistent across European populations and across specific groups of EDCs. We also observed that occupational exposure to BPA and BFRs as classified by the JEM was associated with significantly longer length of gestation, although few mothers were occupationally exposed  and found that elevated maternal levels of benzophenone-3 in urine were associated with significant reduction in gestational length only in boys, but were not significantly associated with LBW (n = 5) worked in plastics or textile operatives. BFRs were recently classified as EDCs by researchers at an international BFR workshop after they reviewed various publications from 2003 through 2007  was key for explaining associations with term LBW. It is possible also that the significant increase in risk with increasing number of EDCs is the result of other conditions related to these occupations, such as exposure to heat, unsanitary conditions, or lifting, among others . Medicalwith LBW . More stugh 2007 . Literatugh 2007 . In our ugh 2007 .Continuous birth weight was not significantly associated with any category of maternal occupational exposure to EDCs in our analysis. Previous research regarding general population exposure to EDCs and birth weight is not consistent, with varied study designs and decreases and null associations reported . Researcn = 219) embedded in the Generation R cohort, BPA in maternal urine was associated with significantly shorter gestational times or reduced fetal growth (n = 488) embedded in the INMA cohort found a small but not significant increase in length of gestation for mothers with higher levels of BPA in urine during pregnancy  among our sample was small, so these results should be interpreted with caution.Estimated exposure to BPA or BFRs was significantly associated with extended length of gestation. Workers were classified with possible or likely exposure to BPA if they held a job title as any kind of plastics operative, whereas job titles classified as exposed to BFRs were typically textile machine operators, fire service officers, or working as plastic or rubber operatives. In a smaller study , enabling adjustment for potential confounders across the cohorts; the prospective data collection in most cohorts, avoiding recall bias , so this difference may be not be meaningful. This result also may have been influenced by missing data, as education was missing for 28% of the DNBC cohort. Further, we cannot exclude residual confounding by other factors such as other maternal occupational exposures , living near sources of ambient pollution , or maternal diet and physical activity during pregnancy  of the women in our data set.For our study, this JEM was translated from SOC2000 codes to the most relevant ISCO88 codes, and this translation was not created with EDC exposure in mind. For example, the SOC2000 job title “paramedic” was translated to the ISCO88 job title “medical assistant.” Within the JEM, paramedics were classified as exposed to PAHs because they spend much of the workday driving. This means that medical assistants in our study were classified as exposed to PAHs, which may not be accurate. With this potential for error, this could be quite magnified over a large study population resulting in broad exposure misclassification. However, we assume that such misclassification is likely to be random  with respect to our outcomes, and thus most likely led to attenuation of associations . Some stThis large-scale prospective study suggests that maternal employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with a significant increased risk of term LBW newborns in cohorts throughout Europe. This finding should be followed up by studying health outcomes throughout childhood and by focusing more specifically on occupations classified as exposed to multiple EDCs.(229 KB) PDFClick here for additional data file.(43 KB) ZIPClick here for additional data file.


This study aimed to examine the associations of birth weight with ability in school sports in adolescence and participation in leisure-time physical activity (LTPA) across adulthood and to investigate whether associations between birth weight and LTPA change with age.Study participants were British singletons born in 1946 and followed up to age 68 yr . Birth weights were extracted from birth records. Teacher reports of ability in school sports were collected at age 13 yr. LTPA was self-reported at ages 36, 43, 53, 60–64, and 68 yr and categorized at each age as participating in sports, exercise, and other vigorous LTPA at least once per month versus no participation. Associations were examined using standard and mixed-effects logistic regression models.P = 0.5 for birth weight by age interaction).Relevant data were available for 2739 study participants . When compared with the low birth weight group (≤2.50 kg), those with heavier birth weights were more likely to be rated as above average or average at school sports (vs below average); fully adjusted odds ratio = 1.78 . Across adulthood, those with heavier birth weights were more likely to participate in LTPA than those with low birth weight; fully adjusted odds ratio of LTPA across adulthood = 1.52 . This association did not vary by age (Low birth weight was associated with lower ability in school sports and with nonparticipation in LTPA across adulthood. Identifying the underlying developmental and social processes operating across life for low birth weight infants may inform the design of appropriate interventions to support participation in LTPA across life. To d of life ,30,31,33in utero experiences such as undernutrition can, in addition to limiting size at birth, alter development and increase susceptibility to chronic disease. Lower birth weight has been associated with higher risks of cardiovascular disease  National Survey of Health and Development (NSHD), a nationally representative sample of 5362 British singleton births during 1 wk in March 1946 and followed up regularly across childhood and adulthood . At age n = 3322), 43 yr (n = 3262), 53 yr (n = 3035), 60–64 yr (n = 2661), and 68 yr (n = 2453), 99.6%, 100%, 98.4%, 82.2%, and 99.1%, respectively, provided information on LTPA (3766 participants had at least one measure of LTPA). The participating samples at ages 53 and 60–64 yr have been found to be broadly representative of similar age members of the general UK population  and the Scotland A Research Ethics Committee (14/SS/1009). Study participants provided written informed consent.Birth weight, recorded to the nearest quarter of a pound, was extracted from birth records within 6 wk of delivery and subsequently converted to kg.When study participants were 13 yr old, teachers were asked to complete a questionnaire rating their ability in school sports as above average, average, or below average compared with their peers . This meAt ages 36, 43, 53, 60–64, and 68 yr, study participants reported how often they participated in LTPA during nurse interviews or using self-completed questionnaires. At age 36 yr, study participants reported the number of times they took part in 27 different sports, exercises, and other leisure activities during the previous month using questions based on the Minnesota LTPA questionnaire . At age n = 173) and cognition scores (n = 199) were imputed with values recorded at ages 11 and 15 yr.Birth order, childhood socioeconomic position, and cognitive ability were identified as potential confounders based on existing literature ,14,24. O−2) was derived from height and weight measured using standardized protocols in childhood at age 11 yr and in adulthood at age 36 yr.In addition to the previously mentioned covariates, sports ability in childhood and physical health in adulthood were hypothesized to mediate associations between birth weight and adulthood LTPA. Physical health was derived from information collected during nurse interviews at age 36 yr on weight, disability, self-reported health problems, hypertension, lung function, and incidence of hospital admissions . This inFormal tests of interactions between sex and birth weight were undertaken, and subsequent analyses were adjusted for sex after no evidence of interaction was found. Formal tests of deviation from linearity were performed and showed evidence of nonlinear associations between birth weight and sports ability and LTPA. As a result, study participants were grouped into five categories of birth weight , and the low birth weight group (≤2.50 kg) was used as the reference in analyses. For these analyses, dichotomous measures of sports ability and LTPA were derived. The two groups of above average and average ability in school sports were combined and compared with the group with below average ability. At each age in adulthood, the two groups reporting moderate and regular participation in LTPA were combined and compared with the group that reported no participation in LTPA.http://links.lww.com/MSS/A745).We examined how birth weight relates to ability in school sports using logistic regression. The association between birth weight and LTPA across adulthood was examined using mixed-effects binary logistic regression with random intercepts and slopes for age so that we could include all participants with at least one measure of LTPA while also accounting for correlations among repeated LTPA responses . In all Models of the associations of birth weight with both sports ability and LTPA were first adjusted for sex and then for birth order, socioeconomic position, and cognitive ability. An additional model was then run when examining the association between birth weight and LTPA, which included adjustment for ability in school sports and physical health in adulthood. Lastly, we reran both final models in those with data on BMI and compared estimates to models with added adjustment for BMI. Sports ability models were adjusted for childhood BMI, whereas LTPA models were adjusted for adult BMI. Analyses were conducted in STATA 14 .n = 1596), higher proportions of those with at least one measure of LTPA were female (49.6% vs 42.5%) and had fathers in occupational classes I and II (23.1% vs 20.9%), and lower proportions had low birth weight (4.7% vs 8.8%). At age 13 yr, higher proportions of girls were rated as above average or average in school sports .When compared with the low birth weight group (≤2.50 kg), those in other heavier birth weight categories were more likely to be rated as above average or average (vs below average) at school sports at age 13 yr . For exaP = 0.5 for continuous and categorical birth weight by age interactions), suggesting these associations did not differ by age at assessment of LTPA. This is consistent with the finding of similar OR of LTPA at each age in adulthood in study participants with nonmissing LTPA . A plot of the log-odds of LTPA shows the decline in likelihood of activity with age for all five birth weight groups, with the lowest birth weight group always having lower probability of LTPA . The sex-adjusted relative risk ratios (95% CI) of moderate (1–4 times per month) and regular (5 or more times per month) LTPA across adulthood (vs no participation) were 1.60 (1.24–2.12) and 2.83 (1.87–4.37), respectively, when comparing all four heavier birth weight groups with the low birth weight group. These estimates were attenuated to 1.25 (0.90–1.93) and 1.81 (1.23–2.57), respectively, after full adjustment. Additional adjustment for adulthood BMI had little influence on findings .The association between birth weight and LTPA was slightly attenuated by adjustment for early life covariates and to a lesser degree by further adjustment for ability in school sports and physical health in adulthood . The sexWe examined prospectively collected data from the longest running British birth cohort and found that low birth weight was associated with lower ability in school sports and with nonparticipation in LTPA across adulthood. More precisely, our findings showed that, when compared with low birth weight, those in heavier birth weight groups were more likely to be rated by their school teacher as above average or average rather than below average in sports at age 13 yr and were more likely to participate in LTPA between ages 36 and 68 yr. These associations were only partly attenuated after adjustment for a range of covariates.Some of the other studies that have previously investigated this association in younger more recently born cohorts support our findings ,3,18. ThWe found that associations between low birth weight and lower likelihood of LTPA were consistent across adult life, which is similar to animal studies showing offspring from undernourished mothers to be less physically active across life, including at older adult ages, when compared with normal offspring . That asThe results presented here are not consistent with null associations reported between birth weight and physical activity levels in children ,28. HoweOur findings suggest that prenatal growth may influence sports ability and participation in LTPA across life ,13. MotoPoorer levels of motor skills and coordination , less faThere was some loss to follow-up in NSHD, as expected in long-running studies. This led to only slight differences in characteristics between those included and those with missing data. A survival selection bias where those healthiest and physically active from the low birth weight group survive to an older age is possible and may have biased results toward the null. However, our modeling strategy maximizes sample size and improves precision of estimates of association as all individuals with at least one measure of LTPA are included under the missing at random assumption . Other iin utero.One limitation of this study is that information on gestational age was not available, and therefore we could not distinguish between those born small-for-gestational age and those with low birth weight due to preterm birth. However, there would have been less variation in gestational age in this study population than that in more recent born cohorts as preterm births were less likely to survive in the 1940s . As a reSelf-reported LTPA can be subject to recall and misclassification errors; therefore, a cautious interpretation of the findings is necessary. However, questionnaires/interviews help capture contextual circumstances surrounding physical activity, making them suitable for widespread gathering of data on activity types and domains such as LTPA . If therIt is important to recognize that those with low birth weight may require more support than others if they are to achieve sufficient physical activity across life to realize its health benefits ,16,39. TIn conclusion, findings from this 68-yr prospective follow-up study of the 1946 British birth cohort showed that, when compared with those with low birth weight, other study participants with heavier birth weights were less likely to be rated by their school teacher as below average at sports and were more likely to participate in LTPA across adulthood. Understanding the underlying biological, developmental, and social processes that explain the relationship between low birth weight and low sports ability and nonparticipation in LTPA may help identify appropriate characteristics of effective interventions.www.acsm-msse.org).Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (Supplementary Digital Content 1Supplementary Digital Content 2Supplementary Digital Content 3