Birth weight and prematurity are important obstetric outcomes linked to lifelong health. We studied a large birth cohort to look for evidence of epigenetic involvement in birth outcomes.DNMT1 (rs2162560), DNMT3A (rs734693), DNMT3B (rs2424913) and DNMT3L (rs7354779). We measured methylation of LINE1 and the imprinted genes, PEG3, SNRPN, and IGF2, in cord blood.We investigated the association between birth weight, length, placental weight and duration of gestation and four candidate variants in 1,236 mothers and 1,073 newborns; The minor DNMT3L allele in the baby was associated with higher birth weight , birth length , placental weight, , and reduced risk of being in the lowest birth weight decile (p = 0.018) or requiring neonatal care (p = 0.039). The DNMT3B minor allele in the mother was associated with an increased risk of prematurity (p = 0.001). Placental size was related to PEG3 (p<0.001) and IGF2 (p<0.001) methylation. Birth weight was related to LINE1 and IGF2 methylation but only at p = 0.052. The risk of requiring neonatal treatment was related to LINE1 (p = 0.010) and SNRPN (p = 0.001) methylation. PEG3 methylation was influenced by baby DNMT3A genotype (p = 0.012) and LINE1 by baby 3B genotype (p = 0.044). Maternal DNMT3L genotype was related to IGF2 methylation in the cord blood but this effect was only seen in carriers of the minor frequency allele (p = 0.050).The results here suggest that epigenetic processes are linked birth outcome and health in early life. Our emerging understanding of the role of epigenetics in health and biological function across the lifecourse suggests that these early epigenetic events could have longer term implications. Factors such as birth weight and placental weight are important indicators of the health of the newborn but they have also been linked to health and biological function in later life The nature of these associations and the causal links between them are not well understood. It has been proposed that nutritional and other environmental influences in pregnancy may programme both birth weight and health in later life We set out to look for evidence of epigenetic involvement in birth outcomes in a large birth cohort. The role of epigenetics in human complex traits is difficult to study as the epigenome of readily accessible tissues such as blood may not reflect the epigenome within the tissues of interest. Perhaps paradoxically, evidence for the involvement of epigenetic processes may be obtained from genetic association studies. DNA methylation is probably the most commonly studied epigenetic phenomenon. We investigated the association between birth weight, length, placental weight and duration of gestation and four candidate polymorphisms in genes involved in DNA methylation in mothers and newborns. Polymorphisms were measured in the four DNA methyltransferases: DNMT1 (MIM126375); DNMT3A (MIM602769); DNMT3B (MIM602900); DNMT3L (MIM606588) in order to provide additional information on specific epigenetic process.Recent work suggests that many imprinted genes maintain their allele specific methylation signal in a wide range of adult somatic tissues, independent of the absolute levels of expression The study was approved by Grampian Research Ethics Committee and all women in the study gave informed written consent to take part. Women who met the inclusion criteria were recruited consecutively. Women who were diabetic, carrying multiple pregnancies, who conceived as a result of fertility treatment, or in whom clinical data was not available, were excluded. Information on each pregnancy was abstracted from Aberdeen Maternity and Neonatal Databank and the data anonymised. Low birth weight was defined as the lowest decile for the standardised birth weight score; this is the birth weight z score adjusted for gestational age, sex and parity DNMT1 MIM126375 19p13.3-p13.2; rs2162560; DNMT3A MIM 602769; 2p23; rs734693; DNMT3B MIM602900; 20q11.2; rs2424913; DNMT3L MIM606588; 21q22.3; rs7354779) were selected for study on the basis of links to a phenotype. The DNMT3B variant has been linked to cancer Women provided a blood and buccal sample whilst attending for ultrasound scan in Aberdeen Maternity Hospital and a sample of cord blood was collected at delivery. The concentration of DNA was determined by TaqMan RNaseP detection assay  before genotyping. Genotypes were detected by allelic discrimination assay using TaqMan® MGB probes labelled with 6-FAM™ and VIC® on a 7500 Fast real-time PCR system  We studied methylation in three imprinted genes and one retrotransposon in genomic DNA extracted from cord blood. Methylation was measured by pyrosequencing using a PyroMark MD system  after bisulphite conversion of DNA using Epitect Bisulfite kits . Long interspersed nuclear element 1  is a class II retroposon which can be transcribed into RNA, reverse transcribed into cDNA, and then reintegrated as cDNAs into the genome at a new location. The genome retrotransposon content varies between individuals but there are over 500,000 LINE-1 copies in the human genome with around 80–100 active elements Statistical analysis was carried out using STATA/SE version 12 . Comparison of genotype frequencies in mothers and offspring was tested by a Pearson Chi-square test. Genotypes were also tested for deviation from Hardy-Weinberg equilibrium. Regression analysis was carried out for each variant on the basis of an intermediate heterozygote effect (homozygote minor frequency>heterozygote>homozygote common). Multiple linear regression was used for continuous dependent variables  and logistic regression for categorical outcomes , with adjustment for appropriate covariates (specified in the results section). Regression results are presented with 95% confidence intervals and p values.The mean characteristics of the mothers studied were; age at delivery 30.5 (SD 5.4) years; height 164 (SD 7) cm; gestational age at delivery 39 (SD 2) weeks; weight at booking 69 (SD 15) kg. The birth weight was 3475 (SD 531) g; placental weight 645 (SD 143) g; crown heel length 50 (SD 2) cm; gestation length 39 (SD 2) wks. Births before 37 weeks gestation made up 4.3  % of pregnancies and babies requiring neonatal care 15.3  %. The lowest birth weight decile, by definition, made up 10% of cases. The number of non-Caucasian mothers was small (n = 38). 15  % of the mothers were smokers.The distribution of genotypes was not significantly different between mothers and babies Table 1 The imprinted genes PEG3 and IGF2 were significantly related to placental size; 6.9  g/% change in methylation for PEG3 and −4.2  g/% change in methylation for IGF2 Table 3.The risk of requiring neonatal care after birth was significantly related to gestational age at delivery and baby sex Table 4.For those outcomes significantly related to birth outcomes the unadjusted means are shown by baby DNMT3L allele in There were also no significant relationships between maternal or baby DNMT1, 3A and 3B genotype and birth length or placental weight. However, mother and baby DNMT3B genotype was related to the length of gestation Table 2.All significant associations remained significant after adjustment for smoking. Removal of the non-Caucasian pregnancies made no significant difference to any of the population genotype frequencies and all the significant DNMT3L associations remained significant after exclusion of non-Caucasian mothers from the analysis. The effect of DNMT3A genotype on birth weight and DNMT3B on length of gestation were the least significant before the exclusion and just below significance following the reduction in numbers; though the stronger DNMT3B effect on risk of prematurity remained highly significant (p = 0.002) after exclusion of the non-Caucasian pregnancies.Simple Bonferonni correction results in borderline significance for the DNMT3L effects but we believe that this adjustment is too conservative. It does not take account of the fact that the genotype was linked to multiple birth outcomes . Nor does it take into account the additional biological plausibility conferred by the observation of an intermediate heterozygote effect for all but one of these outcomes.There were also significant relationships between DNMT genotype and level of methylation in cord blood DNA even after exclusion of non-Caucasians. In the full additive model the baby genotype for DNMT3A was related to PEG3 methylation  and the baby 3B genotype to LINE1 methylation . The maternal DNMT3L genotype was also related to IGF2 methylation in the cord blood but this effect was only seen in carriers of the minor frequency allele compared to non-carriers .Babies carrying the DNMT3L minor allele were heavier at birth. They were also longer and their placentas were heavier. These associations remained significant after adjustment for gestational age and sex. Compared to babies homozygous for the common allele, those homozygous for the minor frequency allele were a third as likely to be in the lowest decile for birth weight and there was a clear allele dose response (homozygote minor frequency>heterozygote>homozygote common). An intermediate effect of the heterozygote is not required to establish a link between a gene variant and health outcome but such an effect provides additional assurance that the association is likely to be biologically significant. There was also an association between maternal DNMT3A genotype and birth weight but the significance level was lower than for DNMT3L and there was no corresponding effect on birth length or placental weight. The DNMT3B variant in the mother was associated with a small effect on the average length of gestation but the effect on prematurity (birth before 37 weeks gestation) was more substantial, with the minor frequency allele being associated with an approximate doubling of the risk of prematurity.The most striking effect was observed in relation to the DNMT3L variant in the baby. The fact that the association was observed for both birth weight and length suggests that the genotype is linked to body scaling rather than a specific body component such as fat mass. The genetic effect on birth weight was relatively large, with each addition of the 3L minor frequency allele accounting for an additional 54 g in birth weight. This is similar in magnitude to the influence on birth weight of environmental tobacco smoke during pregnancy The significant effects reported here were all observed in the DNMT3 family of methyltransferases. The DNMT3L variant results in an amino acid change at codon 278 but the effect of this change has yet to be elucidated. DNMT3A, 3B and 3L are central to the process of de novo methylation Imprinted genes have a central role in controlling the fetal demand for nutrients and the placental supply and IGF2 in particular is thought to be important in modulating fetal nutrient transport There was evidence that epigenetic processes were associated with general health in the offspring at the start of life, independently of the links to birth weight and placental weight. DNMT3L genotype in the baby and methylation within LINE1 and the imprinted gene SNRPN were linked to the health of the newborn  after adjustment for birth weight, sex and gestational age.In terms of later health, loss of imprinting, of IGF2 in particular, is a common characteristic of many cancer types including; breast, lung, colon, liver, ovary but it has been proposed that more subtle epigenetic changes could play a seminal role in the earliest steps in cancer initiation The pathways of causality underpinning the epidemiological observations linking early life events and birth outcome to health and biological function throughout life are not well understood. The results here suggest that epigenetic processes are linked to birth outcome and health in early life. The epigenetic links to birth outcome are consistent with some of the known epigenetic associations with later health and biological function. Our emerging understanding of the role of epigenetics in health and biological function across the lifecourse suggests that early epigenetic events could have longer term implications.


We mimicked elements of labor and delivery , and used them to induce postnatal respiration and nipple attachment in caesarian-delivered pups. We report herein new data showing that, by simulating a fetal rat's experience of being born, specific components of vaginal birth provide sufficient conditions for the odor learning that guides newborn's sucking responses. In contrast, the absence of in utero compressions was associated with poor sucking onset. Knowing how birth stimuli contribute to the first nipple attachment and constitute a context for learning to suckle is an important step toward better management of some early feeding problems. It can serve also as a foundation for understanding the challenges of facilitating sucking by babies born prematurely so that they do not experience the typical contingencies mediating onset of oral ingestion.Understanding the developmental origins of congenital capabilities such as sucking is fundamental knowledge that can contribute to improving the clinical management of early feeding and facilitate the onset of oral ingestion. We describe analyses in rats showing that sensory stimulation  The ability of a newborn baby, fresh out of the womb, to attach to the maternal nipple and begin sucking leads many to label the behavior as “innate.” Some extend this concept of innate behavior to include reflexes, denoting fixed action patterns organized as sensory-motor circuits in the brain stem or spinal cord , 2, as w The concept of “innate” behavior is controversial, to say the least , 5. CritCongenital is a more accurate and defensible term with which to denote a capability in behavior that is present at birth. In contrast to “innate” and “instinctive”, congenital is more obviously a description of status at birth than it is an explanation of its basis or origins [ origins , 11. ExpThe experimental literature, based on studies with non-human animals, contains a wealth of information pertinent to a better understanding of the onset and development of oral feeding skills. This literature includes some impressive findings concerning the onset of nipple attachment and sucking by newborn rat pups. A brief description of the postnatal onset of sucking by rat pups will help frame the forthcoming presentation and analyses: rat pups are born after a gestation period of about three weeks. They are born as litter, averaging 10 pups (mothers have 12 nipples), blind, deaf, and furless, with limited strength and coordination. For about 6 hrs prior to parturition, labor contractions can be seen rippling vertically on the mother's abdomen or indenting her sides as she stretches her body. More than 100 labor contractions can be observed during a rat's labor [We have described and quantified the labor and delivery process in rats, noting the stimulation received by the pups during labor and throughout the birth process . In the Knowledge that amniotic fluid is a sufficient stimulus to elicit the newborn's first nipple attachment led to preliminary considerations of two, mutually exclusive possibilities. One was that the key olfactory stimulus is somehow predetermined and that the newborn is correspondingly and inherently prepared  to detect and respond to the cue. The second possibility was that the perinate responds with nipple attachment and sucking to the amniotic odor stimulus because of its previous experience with amniotic fluid. Pedersen and Blass  translatThey tested this bold hypothesis by adding a novel, lemon-like substance to the amniotic fluid, and then testing whether this chemical would rescue the newborn's ability to make its first attachment to the washed nipples of a mother rat. The previously validated experimental procedure  involvedin utero, (b) immediately after birth with stroking, or (c) both in utero and with postnatal stroking. Only pups with the combined experiences attached to the washed, citral-scented nipples and not to the unwashed, normal nipples.The test procedure involved presenting the caesarean-delivered pups with an anesthetized parturient rat dam (not the subject pups' mother). If the dam's nipples were washed, pups did not attach to nipples, but when citral was on the dam, the treated newborns attached to a nipple and sucked! The new odor elicited the sucking behavior but, remarkably, “natural” odors of an unwashed dam were not effective for the citral-treated perinates. The new odor had replaced the natural stimulus. They performed an additional experiment in which pups were exposed to citral (a) what are the essential experiences for establishing the newborn's sucking responses to maternal cues? Pedersen and Blass'  study prexperience of being born creates a context for learning. That is, embedded in flow of events that constitute the birth process are forms and levels of stimulation that, together, create the contingencies for early, rapid learning in the fetus, as it becomes a newborn. We will show that this learning, though general in initial form, is expressed in the natural context of the mother's body as organized, adaptive, seemingly goal-directed behavior.We adapted elements of our previous investigations of the perinatal rats' sensory experiences in the uterine environment and of the birth process , 18–20 tWe will first review an analysis of rat maternal behavior during labor and delivery from which we derived a set of novel tools that enabled us to simulate the major components of vaginal birth. We will also review some of our evidence that fetal and neonatal rats (perinates) have sensory capabilities sufficient to experience the birth process, at least the elements that are needed for basic associative learning. Then, we will present data showing that the perinates' responses to simulations of the birth process (a) augment nipple attachment and sucking, (b) establish odor-guided responses to the mother, and (c) induce neural conditions that mediate state transitions between fetal and neonatal behavioral systems which can account for the activation and expression of the newborn's initial sucking behavior. Under laboratory conditions, Norway rats typically give birth on the 22nd day of gestation; by breeding our animals on a known day, we were able to be present with appropriate video arrangements to view and record the dams' labor and delivery . From thr2 = .73, P < .01) across the dams.From our systematic observations, we are able to describe the labor and delivery in the rat. Parturition in all 8 dams occurred within 12 hrs of E22. Duration of the delivery phase of parturition (first to last birth) ranged from 40 to 136 min, with dams delivering and average of 10.1 (±1.1) pups. Delivery duration and litter size were positively related  or by incidental effect, contractions provide a form of stimulation that serves to facilitate two neonatal achievements: pulmonary respiration and suckling. Birth stimuli, that is, the range, levels, and patterns of stimulation that comprise the birth process, might have multiple roles in the successful transition from fetal to postnatal life . Our simThe experience of labor is associated with a number of positive neonatal outcomes, including lung compliance, respiratory integrity –37, blooWe now describe an original experiment conducted in our laboratory by Abel  in whichOur regime of stimulation was a controlled, 135 min analog of Pedersen and Blass'  50-hr-loWe predicted that a perinatal sequence of experiences in association with an otherwise neutral olfactory cue would lead to rates of nipple attachment to that cue, similar to those of vaginally delivered newborn rat pups to the odor of amniotic fluid. If the outcome of the simulated birth experience was equivalent to a natural delivery, we would consider this a successful empirical demonstration of sufficiency. We will have demonstrated that the experience of a simulated birth, quantitatively comparable to a natural, vaginal birth, is sufficient to establish a conditioned response to an odor that is expressed as nipple attachment and the onset of sucking in an, otherwise, naïve newborn.. One hundred twenty-six fetal rats, derived from 24, time-mated Sprague-Dawley rat dams (Rattus norvegicus) were used as subjects. All breeding and maintenance was conducted in the Animal Behavior Laboratory at Indiana University. The first day that sperm was detected in a vaginal lavage was recorded as the day of conception , with birth expected on G22. Dams were group-housed in maternity tubs under standard vivarium conditions.Animal experimentation was conducted in accordance with the guidelines of the Indiana University Institutional Animal Care and Use Committee and the NRC Guide for the Care and Use of Laboratory Animals On G21, pregnant dams were briefly anesthetized with isoflurane . An area overlying the lumbar region was shaved and a small (3 cm) dermal incision exposed the vertebral column. To eliminate movement and sensation below the ribcage, 100% ethyl alcohol (0.1 mL) was administered via intrathecal injection between the T12 and L1 vertebrae. After confirming loss of sensation, the female was placed in a Plexiglas holding apparatus and her lower body immersed into a heated (37.5°C ± 5°C) saline bath. A midline laparotomy was performed and the dams' paired uterine horns were gently externalized into the bath.μL in 4 mL/L isotonic saline) or vehicle alone was injected into the amniotic fluid surrounding target fetuses. Beginning with the fetus in the second ovarian position, amniotic sacs of three-to-four adjacent fetuses were injected. A 30 ga hypodermic needle was inserted through the transparent uterine wall and into the amniotic sac near each fetus' snout.Immediately following either citral or saline injections, compressions of 10–15 mm Hg pressure were administered to fetuses in one uterine horn using a small latex balloon. Such pressures are within the range of pressures typically experienced by rat fetuses during labor contractions –51. Comp Upon completion of the compressions, an incision was made along the antimesometrial border of each uterine horn. Fetuses were removed individually from the uterus and delivered onto gauze pads moistened with either citral  or isotonic saline-moistened (1 mL) gauze pads . Immediately following delivery from the uterus, two cotton-tipped swabs were used to remove the birth membranes from the newborns, umbilical cords tied with surgical silk, and placentas removed. Each neonate was stroked with a soft-bristled artist's brush until respiratory activity was established (approximately 2-3 min per litter). Next, the newborns experienced temperature fluxes similar to those observed after a natural birth sequence in the laboratory . They wePhysical stimulation in the form of compression or stroking is necessary for the establishment of respiration in newborn rat pups , 20. In  Approximately 20 min prior to testing nipple attachment, a recently parturient (1-2 day postpartum) dam was anesthetized with a ketamine/xylazine mix  and placed within a 33°C test incubator in the supine position. At 120 min post-delivery, each pup was gently grasped and held for up to 120 sec with its snout in contact with a nipple of the test dam . Success Following the first attachment trial, the dam was moved to a second heated (33°C) incubator and citral-scented gauze pads  were rubbed across the ventrum, thus infusing the fur with citral odor. Note that the solution was not placed directly on nipples. The scented pads were then placed alongside the dam, further contributing to the citral odor within the incubator. The nipple attachment test was repeated. Then, to further verify the effectiveness of perinatal exposure to citral in promoting nipple attachment to a citral-scented dam, one group of compressed but citral-naïve newborns was tested first on a citral-scented dam and then on a normal dam.P < 0.05. McNemar chi-square for dependent measures was used to analyze frequency of nipple attachment. A repeated measures ANOVA was performed on respiration scores. Posthoc comparisons were made with Newman-Keuls with a cutoff of first attachment for each pup. Thus, this testing method enables rapid and reliable expression of the onset of postnatal ingestion, and the 90% attachment rate following vaginal birth can be used as standard against which we can evaluate the results of the simulated birth experiences.The nipple attachment test used in the present experiment reveals robust and reliable behavior in newborn rats. The leftmost histogram bar in in utero compressions—Caesarean delivery—membrane stripping—cooling—stroking—rewarming . As expected, however, there was a significant increase in respiration within all groups during the final hour at the warmer temperature  = 320.8, P < .01). Respiratory rates at the three, sampled time-points  were unaffected by either citral or compression , 5134, 5 Other researchers have compared the development of feeding skills of term babies and prematurely born infants. Schaal and colleagues , for ex


Asthma is a chronic inflammatory disorder of the lung airways that is associated with airway remodeling and hyperresponsiveness. One of the most critical structural changes that affect airway functionality is fibrotic tissue deposition within the airway wall. Eosinophils have been proposed in different studies to contribute to the production of several mediators and cytokines, including the profibrotic cytokines, TGF-β and IL-11. In this study, we hypothesize that cytokines prevailing in asthmatic tissue such as Th1, Th2, and Th17 cytokines, may induce eosinophils to produce pro-fibrotic cytokines.Eosinophils were isolated from peripheral blood of 6 mild asthmatics and 6 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and production of pro-fibrotic cytokines, TGF-β and IL-11, were determined using Intra-cellular cytokine detection and FACS analysis, immunohistochemistry, as well as real time PCR.The level of basal expression of eosinophil TGF-β and IL-11 was significantly upregulated in asthmatic patients compared to healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of eosinophils derived pro-fibrotic cytokines. However, stimulating eosinophils with IL-17 resulted in the enhancement of the expression TGF-β and IL-11 in asthmatic individuals.The regulation of expression of pro-fibrotic cytokines within eosinophils is Th1/Th2 independent. However, IL-17 seems to regulate eosinophl profibrotic cytokine release in asthmatic patients and hence contributing to the accumulation of fibrotic tissue in asthmatic airways.


Dentigerous cysts are the second most common odontogenic cysts after radicular cysts and are most commonly seen in association with third molars and maxillary canines. Only 5% of dentigerous cysts involve supernumerary teeth, of which mesiodens is the most frequent type. This paper presents a case of dentigerous cyst associated with a mesiodens that caused a painless swelling in the upper lip of an 18-year-old female. The patient was treated surgically by enucleation of total cyst and surgical extraction of mesiodens under local anesthesia. Dentigerous cysts are caused by expansion of dental follicles resulting from accumulation of fluid between tooth crowns and epithelial components.3Dentigerous or follicular cysts are the second most common type of odontogenic cysts, and the most common developmental cysts of the jaws.2 The cysts most often involve impacted mandibular third molars, followed by maxillary canines, mandibular premolars, and occasionally supernumerary teeth or odontomas.4This cyst most frequently occurs in patients between 10 and 30 years of ages and there is a greater incidence in males with a 1.6:1 ratio.5 Radiographically, the cyst appears as a unilocular radiolucent shadow with a well-defined sclerotic border associated with the crown of an unerupted tooth, but an infected cyst will show ill-defined borders.6The clinical examination reveals a missing tooth or teeth and occasionally a hard swelling, sometimes resulting in facial asymmetry and possible pathologic fracture. Dentigerous cysts are tentatively diagnosed on routine dental radiographs.7Only 5% of dentigerous cysts are associated with supernumerary teeth. The usual age of clinical presentation of dentigerous cyst due to supernumerary tooth is in the first four decades of life.2Supernumerary teeth are most common in the maxilla with a strong predilection for the anterior region, in which case the supernumerary tooth is termed a mesiodens.This paper presents a case of dentigerous cyst associated with a mesiodens in an 18-year- old female.An 18-year-old female patient presented to the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry at Tabriz University of Medical Sciences, Tabriz, Iran, with the chief compliant of a painless swelling in the upper jaw, which had been gradually increasing in size for the one year. At the time of her presenting, the patient had no systemic disease.The intraoral clinical examination detected a firm labial and palatal swelling in the maxillary anterior region, on the both sides of the midline.The panoramic radiograph showed a large, well-defined radiolucent lesion with sclerotic borders. The lesion extended from the right canine to the left lateral incisor region. A supernumerary tooth was visible in the left aspect of the cyst, resulting in resorption of cortical bone at this region. Divergence of the roots of the central incisors was also noted on the radiograph. The supernumerary tooth had a cone-shaped crown and a shortened root .The lesion was totally enucleated together with the supernumerary tooth under local anesthesia, and specimens were sent to the Department of Oral and Maxillofacial Pathology, with the differential diagnoses of periapical cyst, odontogenic keratocyst, and adenomatoid odontogenic tumor. The submitted specimens consisted of two fragments of soft tissue, the largest measuring approximately 21 mm ? 13 mm ? 3 mm.Histological sections of both specimens revealed cyst walls composed of loosely arranged fibrovascular connective tissue, lined by 2-4 layers of flattened non-keratinizing stratified squamous epithelium . The epiThe clinical, radiographic and histopathological features led to the final diagnosis of dentigerous cyst associated with a mesiodens.The patient was followed up for six months. The post-operative period was uneventful.8Swelling of the upper lip may result from different conditions including infections, allergic diseases, neoplasms , granulomatous diseases, and different types of cysts.2 Most reports have shown a peak incidence of dentigerous cysts in the second and third decades of life, with a slightly higher predilection for males .This gender preference might be related to a smaller jaw size and a greater tendency for prophylactic extraction of third molars in females .9Dentigerous cyst is a common oral lesion caused by fluid accumulation between the reduced enamel epithelium and the crown of an unerupted tooth.9If a follicular space on the radiograph is more than 5 mm, an odontogenic cyst can be suspected. Differential diagnoses of such radiolucency include radicular cyst, odontogenic keratocyst, and odontogenic tumors such as ameloblastoma, Pindborg tumor, odontoma, odontogenic fibroma, and cementomas.10A panoramic radiograph of a patient with dentigerous cyst reveals a unilocular radiolucency enclosing the crown of an unerupted tooth. The radiolucency usually arises in the cemento-enamel junction of the tooth.4 First named by Bolk in 1917, mesiodens is the most frequent type of supernumerary teeth and situated in the maxillary anterior incisors region. It is a rare entity with a prevalence of 0.15-1.9% in general population and a slight male predilection.11 Mesiodens may be single or multiple, erupted or impacted and is rarely seen associated with a dentigerous cyst.12 Scolozzi et al8 reported an unusual case of a large dentigerous cyst associated with an impacted mesiodens, resulting in a slow-growing swelling in the upper lip. Khan et al13 also described an upper lip swelling caused by a large dentigerous cyst associated with mesiodens. Dinkar et al14described an unusually early presentation of multiple mesiodens with associated dentigerous cyst. Large dentigerous cysts arising from unerupted mesiodens should be kept in mind in the differential diagnosis of upper lip swellings, particularly if associated with dental anomalies of the maxillary incisors such as malposition and diastema.Although dentigerous cyst is a common developmental cyst, its association with supernumerary teeth is rare and estimated to constitute 5-6% of all dentigerous cysts.15 reported the case of a dentigerous cyst associated with an impacted inverted mesiodens that developed secondary to trauma to its predecessor, a non-vital permanent maxillary central incisor. As a consequence of trauma, the central incisor?s root development was prematurely arrested and the open apex lied close to the follicle of the underlying inverted mesiodens.Sharma et al16The presence of mesiodens causes complications such as delayed eruption of permanent teeth, rotations, retention, root resorption, pulp necrosis, and diastema as well as formation of dentigerous and primordial cysts.Therefore, to prevent the development of a dentigerous cyst and to avoid unwanted effects on neighboring teeth, early diagnosis and treatment of mesiodens are crucial.


To examine associations between maternal height and child growth during 4 developmental periods: intrauterine, birth to age 2 years, age 2 years to mid-childhood (MC), and MC to adulthood.Pooled analysis of maternal height and offspring growth using 7630 mother–child pairs from 5 birth cohorts . We used conditional height measures that control for collinearity in height across periods. We estimated associations between maternal height and offspring growth using multivariate regression models adjusted for household income, child sex, birth order, and study site.Maternal height was associated with birth weight and with both height and conditional height at each age examined. The strongest associations with conditional heights were for adulthood and 2 years of age. A 1-cm increase in maternal height predicted a 0.024 (95% CI: 0.021-0.028) SD increase in offspring birth weight, a 0.037 (95% CI: 0.033-0.040) SD increase in conditional height at 2 years, a 0.025  SD increase in conditional height in adulthood. Short mothers (<150.1 cm) were more likely to have a child who was stunted at 2 years  and as an adult . There was no evidence of heterogeneity by site or sex.Maternal height influences offspring linear growth over the growing period. These influences likely include genetic and non-genetic factors, including nutrition-related intergenerational influences on growth that prevent the attainment of genetic height potential in low- and middle-income countries. Adult height is the cumulative result of the interaction between environment and genetics over the growing period. In developing countries, growth failure in the first 1000 days (conception to 2 years) of lifeSeveral studies have examined the cross-sectional association of maternal height with child size at birth and at selected postnatal ages,We analyzed data from the 5 studies that participate in the Consortium on Health Orientated Research in Transitional Societies (COHORTS).Maternal height and offspring anthropometric measurements were measured following site-specific protocols.We included in the analysis all mother–child pairs with available anthropometry data in all periods (n = 7630). One or more predictors were missing for 19% of the analytic sample. We assumed the missing predictors  to be missing at random, and generated 5 multiple imputations (MI) using imputation chain equations. Combined estimates were obtained using MI inference rules.Maternal height was the primary exposure. Child growth  and attained height  were the outcome measures.To address the challenge of collinearity of growth measures, we computed conditional height, the child-specific residual obtained from linear site-specific regression of height at each age on birth weight and all prior height measurements.We defined offspring childhood stunting at 2 years as HAZ values <−2 SD.Descriptive characteristics are presented as means (SD) for continuous variables or as percentages for categorical variables. We assessed the secular trends in adult heights across the 2 generations by subtracting maternal height from offspring adult height. We used correlation coefficients and generalized linear regression models to determine associations between maternal height and offspring growth measures. Similarly, we used generalized estimating equations models with robust error variances to estimate the prevalence ratio (PR) of offspring stunting at 2 years and adulthood using maternal height as the main predictor. Furthermore, we assessed whether the association of maternal and offspring adult shortness was mediated through childhood stunting at age 2 years. To determine this, we developed separate multivariate estimating equation models using maternal shortness or childhood stunting as predictors, followed by a model that included both predictors. We adjusted for household wealth (SES), study site, offspring sex, and birth order (categorized as firstborns and non-firstborns), based on documented associations of these variables with child growth.P < .05, we conducted pooled analyses with adjustment for sex and site. Standard regression diagnostic procedures were followed for all models. All analyses were conducted with PC-SAS 9.3 . Statistical significance was set at a 2-tailed P value of <.05.We tested for heterogeneity of associations by site and offspring sex by examining site- and sex-specific estimates and with a formal statistical test of heterogeneity. Because no differences were observed by inspection, and no heterogeneity was detected at Mean maternal age at offspring birth was 26.4 years. Maternal height varied across sites . Mean birth weight ranged from 2.8 ± 0.4 kg (India) to 3.2 ± 0.5 Kg (Brazil). Stunting prevalence at 2 years was highest in Guatemala (84%) and lowest in Brazil (12%). Offspring adults were shortest in Guatemala and the Philippines and tallest in Brazil and South Africa . OffspriP < .001; The correlations between maternal height and offspring length/height measures at various ages ranged from 0.15-0.55 . Despite marked difference in anthropometric characteristics  across the cohorts, we observed consistent associations across the 5 cohorts as well as by sex. Maternal height was positively associated with all offspring height measures. Consistent with previous studies,Maternal height was significantly associated with offspring birth weight, and with all postnatal attained and conditional height measures. The observed correlations and linear associations were consistent with studies from high-income country settings for birth size and adult height.Short maternal stature has been associated with stunting in children.As adults, offspring in our cohorts were on average taller than their mothers. These secular increases in height are probably due to improved economic, nutrition, hygiene, and other factors in recent decades in LMICs. The secular trends varied across the 5 cohorts, probably related to the timing and success of investments in maternal/child health and nutrition. Although growth is known to exhibit sexual dimorphism, we found no significant heterogeneity of associations by offspring sex across the 5 study sites.In poor settings, the height of a mother is a proxy for nutrition during her own growth and development.The strengths of this study include the use of cohort data with growth measures from birth into adulthood, large sample sizes from 5 different countries, and the use of appropriate statistical methods to account for otherwise-correlated measures of growth. The use of MI techniques ensured efficient use of the available data and improved precision around estimates. Birth length data was not available for Brazil and South Africa; we used birth weight to address this. In our data, birth weight and birth length is correlated at 0.7; hence we do not believe that this introduced bias into our analyses. Further, we repeated the analyses using either a birth length anchor or birth weight anchor for the 3 sites for which we have both measures, but the results were very similar. Additionally, data on paternal height was not available. Because of this limitation, we were not able to distinguish the intergenerational importance of paternal or mid-parental height for offspring growth.


It has been hypothesized that birth weight is not on the causal pathway to infant mortality, at least among "normal" births , and that US racial disparities (African American versus European American) may be underestimated. Here these hypotheses are tested by examining the role of birth weight on racial disparities in infant mortality.A two-component Covariate Density Defined mixture of logistic regressions model is used to decompose racial disparities, 1) into disparities due to "normal" versus "compromised" components of the birth cohort, and 2) further decompose these components into indirect effects, which are associated with birth weight, versus direct effects, which are independent of birth weight.The results indicate that a direct effect is responsible for the racial disparity in mortality among "normal" births. No indirect effect of birth weight is observed despite significant disparities in birth weight. Among "compromised" births, an indirect effect is responsible for the disparity, which is consistent with disparities in birth weight. However, there is also a direct effect among "compromised" births that reduces the racial disparity in mortality. This direct effect is responsible for the "pediatric paradox" and maybe due to differential fetal loss. Model-based adjustment for this effect indicates that racial disparities corrected for fetal loss could be as high as 3 or 4 fold. This estimate is higher than the observed racial disparities in infant mortality (2.1 for both sexes).The results support the hypothesis that birth weight is not on the causal pathway to infant mortality among "normal" births, although birth weight could play a role among "compromised" births. The overall size of the US racial disparities in infant mortality maybe considerably underestimated in the observed data possibly due to racial disparities in fetal loss. It has been argued that birth weight may not be on the "causal pathway" to infant mortality -3. The bThe three plausible directed acyclic graphs are illustrated in Figure If birth weight is not on the "causal pathway", i.e. it does not mediate the effect of race on infant mortality Figure , then thWilcox and others ,9-11 havThe objective of this paper is to quantitatively document the role that birth weight plays in racial disparities in infant mortality using the 2001 United States non-Hispanic African and European American birth cohorts controlling for sex. In particular, we statistically test the hypothesis that birth weight is on the "causal pathway" to infant mortality and decompose racial disparities in infant mortality into effects, which are independent of birth weight (direct effects of race) and effects, which are due to the racial disparities in birth weight (indirect effects of race mediated by birth weight). A secondary aim is to estimate the magnitude of the racial disparities in infant mortality while controlling for the "pediatric paradox". We do not propose that "race" is the cause of these disparities, but simply a proxy for a collection of stressors , which are the underlying causes of these differences.The data for this analysis are obtained from 2001 NCHS Birth Cohort Linked Birth/Infant Death data set. Race and ethnic origin are based on mother's reported race and ethnic origin. Approximately 6.4% and 8.7% of the non-Hispanic European and non-Hispanic African American births, respectively, are excluded from this analysis due to missing information or LMP gestational age <20 weeks or birth weight <500 grams. Summary statistics for the samples used are presented in Table nd degree polynomial of birth weight) is the parsimonious model, that fits birth weight distributions [Covariate Density Defined mixture of logistic regressions (CDDmlr), while a generally applicable statistical procedure, was specifically designed to test the Wilcox-Russell hypothesis . It decoibutions  and birtibutions ,10 remaributions ,10,12. Cibutions  and placibutions  simply ributions  given thibutions  were resibutions ,15. Giveibutions ,10, we aibutions  that theibutions ,17 that ibutions ,5 and Heibutions  hypothesθ) in the birth weight density submodel and the six parameters  in the mortality submodel of the basic CDDmlr model [The model employed here is an extension of the two-subpopulation birth weight only CDDmlr model of infant mortality . In brielr model  as linealr model ,19. The (i) the logit of minimum mortality ;(ii) the optimal standardized birth weight ; an(iii) the particular shape of the reverse-J-shaped standardized birth weight specific mortality curve  occurs when a change in the variance of birth weight is not reflected in a compensatory change in the shape of the birth weight specific mortality curve. So that the standardized birth weight specific mortality curve changes by race. Finally, the mixing proportion may contribute to the overall observed racial disparities in infant mortality. This is an additional effect of race, which was not discussed in the Wilcox-Russell hypothesis ,4,5 or ix) only CDDmlr model (i.e. CDDmlr without any exogenous covariate) of infant mortality (y) is formally defined as a product of the conditional mortality submodel f2 and the birth weight density submodel f1:The likelihood function for the basic birth weight  is given byIn the case of two truncated Gaussian subpopulations, the birth weight density submodel πs, the mixing proportion, is defined as the proportion of births belonging to the less numerous of the two subpopulations, that is, the secondary subpopulation  as opposed to the primary subpopulation . The reparameterization of πs (Eq. 3) transforms the 0 and 1 bounds on πs to minus and plus infinity, respectively. For i = s and p, i μand variance 2f with two subpopulations is given bysq is the probability that an infant with birth weight x belongs to the s subpopulation. For i = s and p,where f1 (Eq. 2) determines thatThe birth weight density submodel Overall, there are 11 parameters, five defining the birth weight distribution, and six defining the subpopulation-specific mortalities.z) on each of the 11 parameters in the basic CDDmlr model. Second, for i = s and p, standardized birth weight (x is standardized according to the respective subpopulation mean and standard deviation) is used in the corresponding logistic regression function. ThusIn this study, the basic CDDmlr model is extended in two ways. First, we have used European American births as the default and defined the African American "race" effect as an indicator variable  account for the effects of "race" on the birth weight distribution, while the 6 indicator variable terms in the mortality submodel (i.e. i = s and p) account for the racial difference in the standardized birth weight specific mortality curves.This extended model includes 22 parameters, 11 representing the characteristics of European American births, and 11 representing the differences of African compared to European American birth outcomes, that is, the "race" effect. The 5 indicator variable terms in the density submodel . The liDecomposition of the racial disparity is carried out in two steps. First, the total absolute racial disparity in infant mortality is decomposed into deaths attributable to differences in the mixing proportion and rate effects for "normal" and "compromised" births using standard Kitagawa decomposition .The subpopulation specific disparities (rate effects) are further decomposed into direct (independent of birth weight) and indirect  effects by factoring the subpopulation relative risks into direct and indirect multiplicative components. The probability of infant death for a European American birth with i subpopulation of European American births is the weighted average probability of infant death across all birth weights, that isAnd the overall infant mortality for the i subpopulation, the probability of death for an African American birth with is given byFor an African American birth with i subpopulation of African American births is the weighted average probability of infant death across all birth weights, that isAnd the overall infant mortality for the i subpopulation is given byThe overall relative risk of infant death for African American births as compared to European American births in the iF,1 is referred to as the direct factor of "race" in the i subpopulation. It is a constant, and independent of birth weight. iF,2 is referred to as the indirect factor of "race". It represents the combined effect of all birth weight related factors on the racial disparity in infant mortality of the i subpopulation. In particular, birth weight related factors include differences in the shape and the horizontal shift of the reverse-J-shaped standardized birth weight specific mortality curve, the non-linear transformation between the probability, and the logit of infant death at any standardized birth weight, as well as the difference in the truncating value of the standardized birth weight distributions between African and European American births.The qualitative characteristics of the birth weight distributions and birth weight specific infant mortality are similar for both races Table . The "noRace has substantial effects on the distribution of birth weight Table . For botThere are substantial racial differences in infant mortality as well Table . The subThe estimated racial disparity can be decomposed into a mixing proportion effect and two rate effects  by applying Kitagawa decomposition analysis  to the mA further decomposition of the subpopulation specific racial disparities into direct (independent of birth weight) and indirect  effects based on relative risks is summarised in Table reduce African American mortality! The direction of this association is surprising given that mean birth weight of "normal" African American births is significantly smaller than that of European Americans  of race and birth weight and the logistic regressions can then estimate the direct effect of race on infant mortality versus potential interaction effects of race and birth weight on infant mortality. Direct and indirect effects can be estimated using procedures similar to direct standardization [One technical difficulty in models of this kind is estimating unbiased direct and indirect effects. The qualitative analysis in Hernández-Diaz et al.  is baseddization . The resdization , which idization . Since tdization .One advantage of the decision theory approach is that the assumptions concerning the existence of counterfactuals are not necessary. However, like counterfactual methods, the same strong unmeasured covariate assumptions are required. In particular; a) no unmeasured covariates which affect the stressor (race in this case) and the racial disparities in infant mortality, b) no unmeasured confounding of race and birth weight, and c) no unmeasured confounding of birth weight and infant mortality. Assumption a is necessary to estimate total racial disparities, all three are needed to estimate "generated direct effects" .These assumptions may be less of a problem with race than with other variables such as smoking, which have more precise definitions. Race is typically considered to be socially constructed and defined as that collection of variables (some of which may be observable and some of which are currently unobservable) that are associated in some way with reported race. Given this view, all confounders of racial effects on birth weight or infant mortality, are integral parts of the definition of race. This is the assumption generally used when reporting total "racial disparities", such as those presented in Table Based on the "pediatric paradox", Wilcox has argued that racial disparities may be underestimated due to unmeasured confounding ,9-11. GaModel-based adjustment of this effect yields relative risks of 4.2 and 3.6 for African American female and male births, respectively. These are higher than the predicted total relative risks in Table nd degree polynomial, however, is a relatively flexible function, and is considered to provide an optimal fit to birth weight specific mortality in the homogeneous case [We assume that unmeasured confounding of birth weight and infant mortality (assumption c) is responsible for the reverse-J shape of the birth weight specific mortality curve ,17 and tous case .Moreover, the CDDmlr model corrects for some unmeasured confounding of birth weight and infant mortality, referred to as "normal" versus "compromised" births. It is unlikely that dividing birth cohorts into two Gaussian subpopulations will account for all of the unmeasured confounding between birth weight and infant mortality. Nevertheless, the two subpopulations display significantly different mortality patterns indicating that the CDDmlr model accounts for some otherwise unmeasured heterogeneity ,10. In pThe statistical results presented above Tables  and 5 arOn the other hand, there is a substantial indirect effect, which disadvantages African American infant mortality among "compromised" births Table . The resOverall, the findings suggest that interventions with respect to birth weight will not reduce racial disparities in mortality among "normal" births, but might reduce them among "compromised" births. Identification of the exact mechanisms and whether birth weight plays a "causal" role conditional on "compromised" birth will require additional analysis, i.e. control of potential confounding. The "compromised" subpopulation accounts for about 29-41% of the observed racial disparity for females and males respectively , the racial disparities would decrease slightly  from the currently observed level (2.1 for both sexes). Therefore, the complete elimination of racial disparities in infant mortality requires the elimination of birth weight independent (i.e. direct) effects, as well as any birth weight dependent (i.e. indirect) effects.The authors declare that they have no competing interests.TBG planned the analysis and wrote the manuscript. FF and EKO carried out the analysis and helped revise the manuscript. AGD consulted on statistical matters and also helped revise the manuscript. All authors have read and approved this manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/10/86/prepub


This second paper in the Born Too Soon supplement presents a review of the epidemiology of preterm birth, and its burden globally, including priorities for action to improve the data. Worldwide an estimated 11.1% of all livebirths in 2010 were born preterm (14.9 million babies born before 37 weeks of gestation), with preterm birth rates increasing in most countries with reliable trend data. Direct complications of preterm birth account for one million deaths each year, and preterm birth is a risk factor in over 50% of all neonatal deaths. In addition, preterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care. The economic costs of preterm birth are large in terms of immediate neonatal intensive care, ongoing long-term complex health needs, as well as lost economic productivity. Preterm birth is a syndrome with a variety of causes and underlying factors usually divided into spontaneous and provider-initiated preterm births. Consistent recording of all pregnancy outcomes, including stillbirths, and standard application of preterm definitions is important in all settings to advance both the understanding and the monitoring of trends. Context specific innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. Strengthened data systems are required to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon.Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to  Preterm birth is a major cause of death and a significant cause of long-term loss of human potential amongst survivors all around the world. Complications of preterm birth are the single largest direct cause of neonatal deaths, responsible for 35% of the world's 3.1 million deaths a year, and the second most common cause of under-5 deaths after pneumonia  for 184 countries in 2010 and a time series for 65 countries with sufficient data suggest that 14.9 million (uncertainty range: 12.3-18.1 million) babies were born preterm in 2010 [Preterm birth is defined by WHO as all births before 37 completed weeks of gestation or fewer than 259 days since the first day of a woman's last menstrual period . PretermThe international definition for stillbirth rate clearly states to use stillbirths > 1,000 g or 28 weeks gestation, improving the ability to compare rates across countries and times ,18. For In many high-and middle-income countries, the official definitions of live birth or stillbirth have changed over time. Even without an explicit lower gestational age cut-off in national definitions, the medical care given and whether or not birth and death registration occurs may depend on these perceptions of viability ,20. HencIn addition to the definition and perceived viability issue, some reports include only singleton live births, complicating comparison even further. From a public health perspective and for the purposes of policy and planning, the total number of preterm births is the measure of interest.spontaneous preterm birth (spontaneous onset of labour or following prelabour premature rupture of membranes (pPROM)) and (2) provider-initiated preterm birth , or other non-medical reasons) (Table Preterm birth is a syndrome with a variety of causes which can be classified into two broad subtypes: (1) OM)) and  providerSpontaneous preterm birth is a multi-factorial process, resulting from the interplay of factors causing the uterus to change from quiescence to active contractions and to birth before 37 completed weeks of gestation. The precursors to spontaneous preterm birth vary by gestational age , and socAnother important risk factor is uterine over distension with multiple pregnancy. Multiple pregnancies  carry nearly 10 times the risk of preterm birth compared to singleton births . NaturalInfection plays an important role in preterm birth. Urinary tract infections, malaria, bacterial vaginosis, HIV and syphilis are all associated with increased risk of preterm birth . In addiSome lifestyle factors that contribute to spontaneous preterm birth include stress and excessive physical work or long times spent standing . SmokingPreterm birth is both more common in boys, with around 55% of all preterm births occurring in males , and is The number and causes of provider-initiated preterm birth are more variable. Globally, the highest burden countries have very low levels due to lower coverage of pregnancy monitoring and low caesarean birth rates (less than 5% in most African countries). However, in a recent study in the United States, more than half of all provider-initiated pre-term births at 34 to 36 weeks gestation were carried out in absence of a strong medical indication . UnintenDifferentiating the causes of preterm birth is particularly important in countries where cesarean birth is common. Nearly 40% of preterm births in France and the United States were reported to be provider-initiated in 2000, compared to just over 20% in Scotland and the Netherlands. The levels of provider-initiated preterm births are increasing in all these countries in part due to more aggressive policies for caesarean section for poor foetal growth ,47. In tThere are many challenges to measuring preterm birth rates that have inhibited national data interpretation and multi-country assessment. In addition to the variable application of the definition, the varying methods used to measure gestational age and the differences in case ascertainment and registration complicate the interpretation of preterm birth rates across and within nations.Measurement of gestational age has changed over time. As the dominant effect of gestational age on survival and long-term impairment has become apparent over the last 30 years, perinatal epidemiology has shifted from measuring birthweight alone to focusing on gestational age. However, many studies, even of related pregnancy outcomes, continue to omit key measures of gestational age. The most accurate "gold standard" for assessment is routine early ultrasound assessment together with foetal measurements, ideally in the first trimester. Gestational assessment based on the date of last menstrual period (LMP) was previously the most widespread method used and remains the only available method in many settings. It assumes that conception occurs on the same day as ovulation (14 days after the onset of the LMP). It has low accuracy due to considerable variation in length of menstrual cycle among women, conception occurring up to several days after ovulation and the recall of the date of LMP being subject to errors . Many coAny method using ultrasound requires skilled technicians, equipment and for maximum accuracy, first-trimester antenatal clinic attendance. These are not common in low-income set tings where the majority of preterm births occur. Alternative approaches to LMP in these set tings include clinical assessment of the newborn after birth, fundal height or birthweight as a surrogate. While birthweight is closely linked with gestational age, it cannot be used interchangeably since there is a range of "normal" birthweight for a given gestational age and gender. Birthweight is likely to overestimate preterm birth rates in some settings, especially in South Asia where a high proportion of babies are small for gestational age.The recording of births and deaths and the likelihood of active medical intervention after preterm birth are affected by perceptions of viability and social and economic factors, especially in those born close to the lower gestational age cut-off used for registration. Any baby showing signs of being live at birth should be registered as a livebirth regardless of the gestation . The regOther cultural and social factors that have been reported to affect completeness of registration include provision of maternity benefits for any birth after the registration threshold, the need to pay burial costs for a registered birth but not for a miscarriage and increased hospital fees following a birth compared to a miscarriage . In low-The definition of preterm birth focuses on live-born babies only. Counting all preterm births, both live and stillborn, would be preferable to improve comparability especially given stillbirth/livebirth misclassification. An increasing proportion of all preterm infants born will be stillborn with decreasing gestational age. The pathophysiology is similar for live and stillbirths; thus, for the true public health burden, it is essential to count both preterm babies born alive and all stillbirths . Until tNew WHO estimates of global rates of preterm births indicate that of the 135 million live births worldwide in 2010, 14.9 million babies were born preterm, representing a preterm birth rate of 11.1% [The variation in the rate of preterm birth among regions and countries is substantial and yield a different picture to other conditions in that some high-income countries have very high rates. Rates are highest on average for low-income countries (11.8%), followed by lower middle-income countries 11.3%) and lowest for upper middle- and high-income countries (9.4% and 9.3%). However, relatively high preterm birth rates are seen in many individual high-income countries where they contribute substantially to neonatal mortality and morbidity. Of the 1.2 million preterm births estimated to occur in high-income regions, more than 0.5 million (42%) occur in the United States. The highest rates by Millennium Development Goal Regions  are foun% and lowThe uncertainty ranges in Figure The maps in Figure Mortality rates increase with decreasing gestational age, and babies who are both preterm and small for gestational age are at even higher risk . Babies Absolute numbers and rates of preterm birth for 65 countries in Europe, the Americas and Australasia from 1990 to 2010 for these countries suggest an increasing burden of preterm birth . PretermIn 2010, approximately 15 million babies were born preterm, and more than 1 million died due to complications in the first month of life, more from indirect effects, and millions have a lifetime of impairment. The burden of preterm birth is highest in low-income countries, particularly those in South Asia. Yet unlike many other global health issues, preterm birth is truly a global problem with a high burden being found in high-income countries as well . However, while the risk of preterm birth is high for both the poorest and the richest countries, there exists a major survival gap in some regions for babies who are preterm. In high-income settings, half of babies born at 24 weeks may survive, but in low-income settings half of babies born at 32 weeks still die due to a lack of basic care .Preterm birth rates appear to be increasing in most of the countries where data are available. Some of this increase may be accounted for by improved registration of the most preterm babies associated with increased viability and by improved gestational assessment, with change to near universal ultrasound for dating pregnancies in these settings. It may, however, represent a true increase. Possible reasons for this include increases in maternal age, access to infertility treatment, multiple pregnancies and underlying health problems in the mother, especially with increasing age of pregnancy and changes in obstetric practices with an increase in provider-initiated preterm births in moderate and late preterm infants who would not have otherwise been born preterm . In the Distinguishing spontaneous and provider-initiated preterm birth is of importance to programs aiming to reduce preterm birth. For spontaneous preterm births, the underlying causes need to be understood and addressed while in the case of provider-initiated preterm births both the underlying conditions (e.g. preeclampsia) and obstetric policies and practices require assessment and to be addressed ,67.The proportion of neonatal deaths attributed to preterm births is inversely related to neonatal mortality rates, because in countries with very high neonatal mortality, more deaths occur due to infections such as sepsis, pneumonia, diarrhea and tetanus as well as to intrapartum-related "birth asphyxia" . HoweverPreterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care Table . Most baWe have highlighted the differences in preterm birth rates among countries, but marked disparities are also present within countries. For example, in the United States in 2009, reported preterm birth rates were as high as 17.5% in black Americans, compared to just 10.9% in white Americans, with rates varying from around 11 to 12% in those 20 to 35 years of age to more than 15% in those under age 17 or over 40 . DispariThe economic costs of preterm birth are large in terms of the immediate neonatal intensive care and ongoing long-term complex health needs frequently experienced. These costs, in addition, are likely to rise as premature babies increasingly survive at earlier gestational ages in all regions. This survival also will result in the increased need for special education services and associated costs that will place an additional burden on affected families and the communities in which they live . An incrThe estimates from the Born Too Soon report represent a major step forward in terms of presenting the first-ever national preterm birth estimates . HoweverIn many low- and middle-income countries without wide-scale vital registration, no nationally representative data are available on rates of preterm birth. Substantial investment and attention are required to improve vital registration systems and to account for all birth outcomes . In the There are sufficient data to justify action now to reduce this large burden of 15 million preterm births and more than one million neonatal deaths. Innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. This also requires strengthened data systems to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon. These are reviewed further in the following papers in this supplement.pPROM: prelabour premature rupture of membranes; WHO: World Health Organization.The author's declare that they have no conflict of interest. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.HB, MK and JL drafted the paper with SC, DC, MZO, LS, ABM. All authors reviewed the final manuscript.HB and SC were funded through a grant from the Bill & Melinda Gates Foundation through the Child Health Epidemiology Reference Group. JL and MK were funded by the Bill & Melinda Gates Foundation though Save the Children's Saving Newborn Lives program.In line with the journal's open peer review policy, copies of the reviewer reports are included as additional file Click here for file


Rodent models of Huntington disease (HD) are valuable tools for investigating HD pathophysiology and evaluating new therapeutic approaches. Non-invasive characterization of HD-related phenotype changes is important for monitoring progression of pathological processes and possible effects of interventions. The first transgenic rat model for HD exhibits progressive late-onset affective, cognitive, and motor impairments, as well as neuropathological features reflecting observations from HD patients. In this report, we contribute to the anatomical phenotyping of this model by comparing high-resolution ex vivo DTI measurements obtained in aged transgenic HD rats and wild-type controls. By region of interest analysis supplemented by voxel-based statistics, we find little evidence of atrophy in basal ganglia regions, but demonstrate altered DTI measurements in the dorsal and ventral striatum, globus pallidus, entopeduncular nucleus, substantia nigra, and hippocampus. These changes are largely compatible with DTI findings in preclinical and clinical HD patients. We confirm earlier reports that HD rats express a moderate neuropathological phenotype, and provide evidence of altered DTI measures in specific HD-related brain regions, in the absence of pronounced morphometric changes. Huntington disease (HD) is a late manifesting inheritable neurodegenerative disease caused by an expanded trinucleotide repeat in the coding region of the HD gene HDCRG . The cliHD rats exhibit progressive emotional disturbance, cognitive decline, and motor deficits  has emerged as a sensitive tool for detection of altered tissue integrity at both preclinical and clinical stages of HD  measurements obtained in 18 months old transgenic HD rats and wild-type controls. By region of interest analyses supplemented with voxel-based statistics, we demonstrate significantly altered DTI measurements in specific brain regions that are associated with clinical manifestations of HD. We confirm that DTI measures are potentially useful correlates of HD-related changes in these transgenic rats.Five male transgenic HD rats carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter . Diffusion encoding was performed using a pair of half-sine gradient pulses (δ = 3.2 ms/Δ = 8.3 ms), using b = 800 s/mm2. A reduced encoding DTI methodology  and 12 reduced encoded (512 × 128 × 128) diffusion-weighted images (DWI) sensitized in each of an optimized set of 12 directions . A diffusion-weighted spin-echo pulse sequence with extended dynamic range  using the ITK-SNAP . A p < 0.05 was considered statistically significant.We first conducted a hypothesis-driven analysis, in which measurements were obtained from a set of anatomically defined grey and white matter regions thought to be affected in HD, as well as a few control regions. Bilateral regions of interest (ROIs) were manually delineated Fig.  on the bt test at each voxel, respectively. For each of the DTI parameters significance maps showing clusters of >25 voxels that are significantly different between the groups at the level of p < 0.01 . To this end, DTI maps were initially normalized to an arbitrarily chosen reference dataset, i.e. one wild-type control animal, by an affine registration. The affine transformation matrix was estimated by maximizing the mutual information between the FA maps of the reference and floating data sets , while 1 WT acquisition failed. The animals were investigated at an age of ~18 months, well beyond the age when significant behavioral and morphological changes are demonstrated in this model , while no significant differences were seen in the regions investigated , mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), between the transgenic HD and wild-type groups, using (1) a hypothesis-driven approach in which average values were compared for anatomically defined ROIs, and (2) an exploratory approach using voxel-based statistics.p = 0.012), GP (p = 0.017), EP (p = 0.030), and SN (p = 0.028), while the average MD values were significantly decreased in the GP and EP . Similarly, AD was significantly reduced in the GP and EP , while RD was reduced in the EP and SN . When applying Bonferroni correction for multiple comparisons of the ROI analysis (p < 0.0125) significant changes were still observed in the ventral striatum, GP and EP. It should, however, be noted that these corrections probably are too conservative here, since the measured parameters have complex dependencies. No changes in average diffusivity were found in the dorsal or ventral striatum. In white  and grey matter  regions, average FA and diffusivity measurements were similar between the two groups. Figure To test the hypothesis that DTI changes occur in the striatum and its main axonal projection targets  between the transgenic HD and wild-type animals across the entire brain. Statistical maps showing significantly altered FA and diffusivity values were generated on basis of the co-registered DTI images. Adopting values from two previous investigations employing similar analyses  in theory can bias diffusion sensitivity towards the fast diffusion component in the tissue. Since multiple factors, such as tissue fixation, temperature, and the employed acquisition scheme will have complex influences on DTI measures , and tentatively interpreted as modified tissue integrity, such as neuronal remodeling, astrocytosis, and loss of specific axonal connections (Rosas et al. Variations among clinical DTI studies of HD patients and preclinical studies of rodent models may thus be ascribed to a multitude of biological and methodological factors. However, regardless of the nature of the observed DTI changes, there seems to be good consistency with respect to their spatial localization.We report evidence for DTI changes in the basal ganglia and hippocampus of aged transgenic HD rats. Owing to the high isotropic voxel resolution employed we were able to identify DTI changes in specific, small basal ganglia regions that are associated with HD. In line with several earlier investigations (Winkler et al.


Hydatid cysts are rarely asymptomatic depending on their location. Complaints may be only relevant due to secondary problems. This paper presents a case report of a myocardial hydatid cyst which was totally excised under cardiopulmonary bypass operation with median sternotomy. Patient was admitted to the hospital with complaint of atypical chest pain in pungent manner together with shortness of breath. Various methods are used for diagnosis. However, echocardiography and computerized tomography with contrast are usually enough for definitive diagnosis and for deciding the strategy of operation. Curative excision must be performed. Extra care should be provided during the operation in order to prevent contamination. Postoperative appropriate antibiotherapy must be administered. Environment should be changed, and infrastructure must be improved in order to prevent further recurrences. Echinococcus granulosus” lives inside cats and dogs which are its natural hosts. Humans are infected mostly via pets. Human myocardial involvement is very rare (%0.5–2) [ Hydatid cyst is an endemic infestation disease in various regions in the world. A parasite named “(%0.5–2) . Its tot 24-year-old male patient had pungent-stinging chest pain with shortness of breath. His history revealed that he had many cats and dogs as pets in his house. His cardiovascular system examination revealed “decreased” heart sounds. Heart beats were coming from deep inside and barely heard. There were also barely heard respiratory sounds in his right lung and middle and basal segments. Other system examinations were normal. Vital signs were stable. There was no pathological finding in his electrocardiography. Teleradiography revealed enlarged mediastinum, closed right sinus, displacement of apex more superiorly and to the left side. When we looked more carefully, we noticed that extraspur at apex was not a solid mass. Instead, it was a kind of a radiolucent tissue . Transth Thorough examination of thoracoabdominal computerized tomography revealed 4.5 × 5 cm cystic mass inside heart apex, together with 2.5 cm pericardial effusion . There w We opened the cystic mass with oblique incision. We observed germinative membrane and 15 small-to-large daughter vesicles which were having different colors and shapes. We excised the cyst from myocardium together with its sticky capsule. Myocardial cavity was washed thoroughly with hypertonic saline solution. Then, we used teflon patch (felt) and sutured myocardial cavity using pledged-U-sutures. We protected the shape and appearance (geometry) of ventricle. Laboratory results revealed no reproduction at culture-antibiogram. Pathological examination confirmed the diagnosis of hydatid cyst both macroscopically and microscopically. Germinative membrane, cuticular membrane, and eosinophilic inflammation were detected . PreoperCardiac hydatid cyst produces symptoms depending on its location and surrounding structures. However, it may sometimes be completely asymptomatic or show up with only secondary complaints , 3.  Our patient had shortness of breath and stinging chest pain. However, the symptoms of our patient were not related to myocardium itself; instead it was related to secondary problems which were pericardial effusion and adherent-sticky pericardium.  Today, treatment of cardiac cyst is surgical. Although many different methods are described in order to excise the cyst, the most preferred method is to inject hypertonic saline into the cyst itself and perform cystotomy. Cystectomy is performed after aspiration of contents; cyst is removed together with its adherent tissues , 5.Other alternative methods include enucleation, especially left ventricle apical located cysts. After total excision, residual tissue may be closed with teflon patch similar to left ventricle aneurysmorhapy. Enucleation method is accepted to decrease recurrence; contour of heart is anatomically preserved after total removal of cyst , 7.There are also some published data which suggest filling of residual cavity using biological glue . Myocard In conclusion, hydatid cyst may present itself with various symptoms. People with pets should be cautious and aware of this infestation.


Objectives. We examined association between incidence rate of low birth weight in liveborn infants and maternal sociodemographic status in Tuzla Canton during 1992–1995 war in Bosnia and Herzegovina. Methods. The present study covers a 22-year period (1988–2009), including the war period (1992–1995), and we retrospectively collected data on a total of 108 316 liveborn infants and their mothers from three different socioeconomic periods: before (1988–1991), during (1992–1995), and after the war (1996–2009). Association between incidence rate of low birth weight in liveborn infants and maternal sociodemographic status were determined for each study period. Results. There were 23 194 live births in the prewar, 18 302 during the war, and 66 820 in the postwar period. Among the liveborn infants born during the war, 1373 (7.5%) had birth weight of <2500 g, which is significantly more in comparison with 851 (3.6%) liveborn infants in this birth weight group born before and 1864 (2.8%) after the war. We found the number of examinations during pregnancy was 1.8 per pregnant woman in the war period, which was low in comparison with the number of examinations before (4.6 per pregnant woman) and after (7.1 per pregnant woman) the war (P<.001 for both). Prewar perinatal mortality LBW infants of 6.2 per 1000 live births increased to 10.8 per 1000 live births during the war (P<.001), but after the war, perinatal mortality LBW infants (5.2‰) and early neonatal mortality (2.4‰) decreased. Conclusions. We found statistically significant association between low-birth-weight and maternal sociodemographic status in Tuzla Canton during 1992–1995 war in Bosnia and Herzegovina.  Birth weight, like growth, is determined by the complex interplay of genetic and environmental factors. The proportional contribution of these influences is unclear. However, birth weight varies within genetically similar populations , 2, suggMaternal risk factors for having an infant with LBW in general include young age, unmarried marital status, less education, lower income, smoking, poor nutrition, and having had a previous infant with LBW , 9. The This has led researchers to search for new causes and risk factors for LBW. Recent literature has demonstrated that maternal stress, isolation, depression, and anxiety were associated with LBW –14. SomeAs much as 16% of all live births worldwide are LBW with a range of 3, 3–38%, >90% being in low-income countries. Birth weight figures are a useful parameter for assessing the effectiveness of prenatal medical care and indirect indicators of the share of at-risk newborns in the newborn population. Perinatal outcome is the measure of the quality of perinatal care given to the mother and child before, during, and after delivery. Low birth weight is a public health problem , and comPopulation of 4.39 million of which 2.78 million lived on the territory of the present Federation of Bosnia and Herzegovina, one of the two political entities in the Republic of Bosnia and Herzegovina. Tuzla Canton (2909 km) has 13 municipalities and 510 353 inhabitants . Before the 1992–1995 war in Bosnia and Herzegovina, primary health care was provided in health centers and their outpatient facilities, secondary health care in general and regional hospitals and only partially in health care centers , while tertiary health services were provided in medical centers which were also university teaching hospitals . Perinatal care in Tuzla Canton had not been provided at the primary health care level mostly due to insufficient perinatal knowledge and clinical skills of primary care physicians and other staff, and a lack of adequate equipment and space as well. Thus, as an addition to tertiary health care, secondary health care which was easily accessible provided most of health care services to pregnant women, women giving birth, and newborns. All deficiencies of the health care system organization in Tuzla Canton became obvious during the war period. Regular examinations during pregnancy could not be performed at any level of health care, health care at birth was inadequate, and neonatal health care was almost nonexistent. Many hospital systems and the existing equipment were damaged or destroyed in war , shortagThe present study covers a 22-year period (1988–2009), including the war period (1992–1995), and it is based on the basis of the existing delivery protocols and medical histories of pregnant women treated at the Gynecology-Obstetrics Clinic in Tuzla. For measuring socioeconomic conditions of mothers we used definition that socioeconomic status (SES) is an economic and sociological combined total measure of a person's work experience and of an individual's or family's economic and social position relative to others, based on income, education, and occupation. When analyzing a family's SES, the household income earners' education and occupation are examined, as well as combined income, versus with an individual, when their own attributes are assessed [We restricted the analysis to singleton liveborn infants of mothers who were between 15 to 49 years old, had complete information on birth weight, perinatal care, and age. Data about material and economic situation were not available during the war, because the refugees were allocated in collective accommodation and they together with domestic people had limited quantities of food. Data about marital status were not valid because pregnant women are traditionally married in Bosnia and Herzegovina, but during the war a lot of families were separated women had been raped and husbands were killed.Intrauterine growth was estimated on the basis of birth weight and gestational age. Newborns were defined as low birth weight if their estimated birth weight was <2500 g at birth, irrespective of gestational age. Infants who are born with low birth weight  are divided into 2 categories: those born too early and those born too small. Standard practice in this institution is to weigh infants without diapers and with the umbilical cord shorter than 10 cm using spring scales to the nearest 100 g. We investigated the proportion of liveborn infants with low birth weight (<2500 g) by comparing the proportions of birth weight subgroups of 500–999 g, 1000–1499 g, 1500–1999 g, and 2000–2499 g in the pre-war, war, and postwar periods. Body length (cm) was measured from crown to heal in a newborn with completely extended legs and feet at the angle of 90°. The ponderal index was calculated as 100 × (birth weight (g)/birth length (cm)). Gestational age in weeks was estimated from the number of days between the first day of the last menstrual period and date of birth and from ultrasound examination if performed. If these data were not available, gestational age was assessed on the basis of external physical characteristics of the newborn . Pretermχ2 test. For 2 by 2 tables, rate ratios with 95% confidence intervals (CI) were calculated. The linear trend was calculated for the 500-g birth weight subgroup rates per 1000 liveborn infants with extended Mantel-Haenszel χ2 test for trends. STATISTICA 6.0  was used for all statistical analyses. P < .05 was considered statistically significant.Differences in categorical data between the study periods were assessed by the P < .0001). However, during the war, more infants had LBW because the IUGR, while in the two other period more infants had LBW because of the preterm delivery (PTD). During the war of 39.5% of mothers with LBW had preterm labor (<37 weeks) and in comparison to the other two periods (45.5% and 47.4%) the difference is statistically important (P < .0001 for both periods). Bigger number of mothers who gave birth with LBW on time (51.1%) and after term (9.1%), which is in comparison to period after and before war important statistic difference (P = .04), but it significantly decreased after the war (P = .0001). Between 1988 and 2009, records on 108 316 singleton births were registered via medical childbirth notification forms. A total of 4088 (3.8%) mothers had infants who had LBW. During the war, 1373 (7.5%) mothers gave a birth to children with low birth weight (had birth weight of <2500 g) which is significantly more in comparison with 851 (3.6%) mothers who gave a birth to children with LBW before ; 1.950–2.324) and 1864  after the war ; 2.630–3.036). During the war, in the group of term infant 4.5% of liveborn had LBW, which is significantly more in comparison with the two other groups before 1.8% and after the war 1.1% (fference . HoweverP < .001).The proportion of deliveries attended by health care providers was 75.9% during the war, which was significantly lower than before (99.1%) and after (99.5%) the war (P < .001 for both).The number of examinations during pregnancy was 1.8 in the war period, which was low in comparison with the number of examinations before (4.6) and after (7.1 per pregnant woman) the war : 0.061–0.099) and 33.8% after the war which was statistically significant : 0.135–0.209, resp., ). DuringP < .0001), but after the war 2.4 per 1000 total births they did not have significant difference (P < .448). Perinatal mortality rate of 10.8 per 1000 total births was significantly higher during the war than before and after the war . The early neonatal deaths, 5.8 per 1000 total births was significantly higher during the war than before the war 2.1 per 1000 total (P < .239). The proportion of liveborn infants with birth weight 2000–2499 g (50.9%) was the highest after the war. The average birth weight, birth length, and gestation age of newborns with LBW during the war was significantly lower than before and after the war (The proportion of liveborn infants with birth weight of 500–999 g during the war did not have significant difference in comparison to the other two periods ( the war . AverageP < .0001 for both).Mothers with infants who had LBW were during the war more likely to be Muslim, refugees, had less than a high school education, married, and mostly younger than 20 years. The number of mothers between 25–29 years with infants who had LBW was noted during the war was by 5% lower than their number before the war, but not very different from the number after the war . SignifiOur results suggest that the impact of socioeconomic status on birth weight is mediated through the differential utilization of prenatal care and access to medical facilities. We found that the number of newborns with LBW in Tuzla Canton significantly increased during the 1992–1995 war. During the war, Bosnia and Herzegovina did not introduce any measures  to counteract the unfavourable socio-economic situation at least partly. We believe that a low maternal sense of control was associated with LBW which occurrence increased to 7.5% compared with the prewar rate of 3.6% and 2,8% after the war. However, during the war more infants had LBW because of the IUGR, while in the two other periods more infants had LBW because of the preterm delivery (PTD). Low birth weight and preterm delivery are the most important determinants of neonatal mortality, as well as infant and childhood morbidity. LBW contributes to approximately 65% to 75% of neonatal deaths . We founThe incidence of low birth weight shows a marked geographical pattern , 27. MorThe relationship between maternal antenatal education and perinatal outcomes is well established. Our study shows that during the war, 68.9% of mothers who delivered infants with LBW began PNC in the third trimester, which is statistically significant difference in comparison to mothers before 16.6% and after the war 27.6%. If we add other negative factors related to war condition it seems that insufficient health care for pregnant women and newborns in Bosnia and Herzegovina in war circumstances, combined with poor socioeconomic conditions, constant fear, stress, and destruction of homes and families, was the main factor accounting for the increase in number of mothers who gave a birth to a children with LBW during that period.The beneficial effects of prenatal care have been documented in many observational studies over several decades –35. StudRohrer's ponderal index in newborns was used as an indicator of fetal growth status and lower ponderal index, as in our study, indicates a strong impact of maternal factors with LBW . Several limitations should be considered when assessing our results. There is limited earlier literature on the role of sense of control and pregnancy outcomes, especially IUGR. The limitations of our study were incomplete data on the parity and pathological conditions of mothers and children during pregnancy, such as pathology associated with premature childbirths and intrauterine growth retardation with consequential low birth weight and hypertrophy of infants. We were also unable to examine risk factors such as chronic and comorbid conditions, congenital malformations, obstetric complications, and infections. Limited accessibility and quality of perinatal health care during the war had detrimental effects on infants' weight. Associations between other psychosocial factors and IUGR should be explored further for better understanding of how stress and psychosocial resources have an impact on fetal growth and possibly in a prospective manner to limit potential biases.Our results suggest that the impact of socioeconomic status on birth weight is mediated through the differential utilization of prenatal care and access to medical facilities. During the war, Bosnia and Herzegovina did not introduce any measures  to counteract the unfavorable socio-economic situation at least partly. Higher number of low birth weight newborns during the war had influence on current surveillance, but long-term effects will be seen in the future. Further investigations in Tuzla Canton should be in that direction with the aim of showing the ventual consequence on population over these years.


Intrauterine growth restriction (IUGR) indicates the presence of a pathophysiological process occurring in utero that inhibits fetal growth. IUGR has been associated with increased perinatal and infant mortality. There are many maternal factors responsible for IUGR. Some studies have suggested that HIV infection could increase the risk of IUGR. Specifically, in IUGR, the baby's estimated weight is below the 10th percentile. The objective of this study was to evaluate the proportion of children born to HIV positive women who presented IUGR.We performed a retrospective study on the relevant parameters in newborns and mothers: demographic data, duration and type of combined antiretroviral treatment (cART). We analyzed anthropometric data of the newborn: weight, length, cranial circumference, and Apgar score. Statistical analysis was performed using MedCalc Software 2013.Over a period of 5 years and 8 months, 124 newborn to 97 HIV+ mothers have been monitored. The median age in mothers was 22 (95%CI: 22-23), and mean 22.8 (range: 17 to 39). The mean Apgar score in newborns was 8.54 (range: 4 to 10), and median 9. The mean birth weight in newborns was 2670 g (range: 1000 to 3900), and median 2700 g. The proportion of children with birth weight less than 10th percentile was 58.05%. The mean length was 47.5 cm (range: 40 to 57), with a proportion of children below the 10th percentile of 29.26%. Infants who presented below the 10th percentile for weight and length were 22.76%. About 11.38% of infants were below the 10th percentile for weight, length and cranial circumference. 97.5% of children received cART after birth, and 93.1% of mothers received cART during pregnancy. In the studied period the mortality rate was 5.6% in children and 7.2% in mothers.More than half (58.53%) of the infants born to HIV positive mothers were small for gestational age. 22.76% of infants were with IUGR, and 11.38% of them presented symmetrical IUGR.