The objectives of this study were to determine rates of prenatal care utilization in Winnipeg, Manitoba, Canada from 1991 to 2000; to compare two indices of prenatal care utilization in identifying the proportion of the population receiving inadequate prenatal care; to determine the association between inadequate prenatal care and adverse pregnancy outcomes , using each of the indices; and, to assess whether or not, and to what extent, gestational age modifies this association.We conducted a population-based study of women having a hospital-based singleton live birth from 1991 to 2000 . Data sources consisted of a linked mother-baby database and a physician claims file maintained by Manitoba Health. Rates of inadequate prenatal care were calculated using two indices, the R-GINDEX and the APNCU. Logistic regression analysis was used to determine the association between inadequate prenatal care and adverse pregnancy outcomes. Stratified analysis was then used to determine whether the association between inadequate prenatal care and LBW or SGA differed by gestational age.Rates of inadequate/no prenatal care ranged from 8.3% using APNCU to 8.9% using R-GINDEX. The association between inadequate prenatal care and preterm birth and LBW varied depending on the index used, with adjusted odds ratios (AOR) ranging from 1.0 to 1.3. In contrast, both indices revealed the same strength of association of inadequate prenatal care with SGA (AOR 1.4). Both indices demonstrated heterogeneity (non-uniformity) across gestational age strata, indicating the presence of effect modification by gestational age.Selection of a prenatal care utilization index requires careful consideration of its methodological underpinnings and limitations. The two indices compared in this study revealed different patterns of utilization of prenatal care, and should not be used interchangeably. Use of these indices to study the association between utilization of prenatal care and pregnancy outcomes affected by the duration of pregnancy should be approached cautiously. Prenatal care (PNC) is a frequently used health service that has the potential to reduce the incidence of perinatal morbidity and mortality by treating medical conditions, identifying and reducing potential risks, and helping women to address behavioral factors that contribute to poor outcomes. PrenataSeveral studies using the PNC utilization indices have demonstrated an association between inadequate PNC and preterm birth or low birth weight (LBW) -16. HoweSeveral studies in the United States have reported on rates of inadequate PNC, while other studies have compared two or more of the indices in monitoring utilization of PNC ,6,8,20. • To determine rates of PNC utilization in Winnipeg, Manitoba from 1991 to 2000;• To compare the two most commonly used indices of PNC utilization in identifying the proportion of the population receiving inadequate PNC;• To determine the association between inadequate PNC and preterm birth, low birth weight (LBW), and small-for-gestational age (SGA), using each of these indices; and• To assess whether or not, and to what extent, gestational age modifies the association between inadequate PNC and LBW or SGA.We conducted a population-based cohort study of women having a hospital-based singleton live birth in Winnipeg, Manitoba over a ten-year period, from 1991 to 2000. Winnipeg is the capital city of the province of Manitoba, and had a population of 618,477 residents in 1996 . Data soThere were 83,101 births to women residing in the city of Winnipeg from 1991 to 2000. After eliminating cases with missing or out-of-range gestational age (< 18 weeks or > 45 weeks), missing parity, maternal age less than 12 years, stillbirths or multiple births, and birth weight <400 grams but gestation >22 weeks, the final sample consisted of 80,989 births. Several mothers (37.6%) gave birth to more than one child during the ten years, and all these births were included in the analyses.We combined two sources of data in order to estimate the number and timing of prenatal visits. We first recorded the gestational age at first visit and the total number of prenatal visits from the linked mother-baby database. These data were abstracted from the prenatal record as part of the hospital discharge abstract data system. However, several limitations of these data have been documented, including a high percent of missing information and an underestimate of timing of the first prenatal visit and total number of visits . We therth month of pregnancy or receiving less than 50% of expected visits based on the schedule of PNC visits recommended by ACOG [1. The Adequacy of Prenatal Care Utilization (APNCU) index, proposed by Kotelchuck, is comp by ACOG ,26. Inte2. The revised GINDEX (R-GINDEX), proposed by Alexander and Kotelchuck , has sixAlgorithms for calculating both of these indices have been published ,8. Once th percentile for gestational age) were determined using a population-based Canadian reference [Differences in rates of inadequate/no PNC by maternal age and parity were calculated. SGA births (birth weight less than 10eference . LogistiA stratified analysis was conducted to determine whether the association between inadequate/no PNC and LBW or SGA differed by gestational age. The Breslow-Day test of homogeneity was used to test the null hypothesis that the effect measure was uniform across strata .Table The proportion of preterm births and LBW by category of PNC varied among the two indices Table , with hiTable The stratified analyses of the association between inadequate/no PNC and SGA and LBW are reported in Tables The proportion of cases assigned to PNC utilization categories varied using the two different indices. This finding is similar to the conclusions of Alexander and Kotelchuck  and KogaThe rates of inadequate and no PNC utilization among women in Winnipeg are lower than those reported in the United States, likely as a result of universal health care for residents of Manitoba. About 1.5 to 2.0% of pregnant women in the United States do not receive any PNC , compareThe association between inadequate/no prenatal care and LBW varied using the two indices, with AOR ranging from 1.1 using the R-GINDEX to 1.3 using the APNCU. Caution needs to be used in interpreting these results because our analyses also confirmed the presence of effect modification by gestational age for both indices, with the association between inadequate/no care and LBW becoming stronger as gestational age increased. Koroukian and Rimm state, "Although adjusting the number of prenatal visits for gestational length is clearly important to assess the adequacy of prenatal care utilization, we must be mindful of the bias introduced by its use in an Index, because the gestational length is itself a birth outcome that is so strongly correlated with birth weight". AlexandOf the three adverse pregnancy outcomes selected for this study, SGA may be the preferable outcome to study because by definition it adjusts for gestational age. However, our findings still showed some degree of effect modification by gestational age when studying the association between inadequate/no PNC and SGA, so the results should be interpreted with caution. After controlling for maternal age, parity, and within-mother dependency, women receiving inadequate/no PNC were up to 40% more likely to have a SGA birth compared to women receiving other categories of care. This result is consistent with the findings of a New Zealand study that less frequent attendance at PNC was associated with SGA . The reaAs with most research, this study has limitations. First, administrative data are prone to a certain degree of coding errors and incomplete data, which may be random or contain systematic biases. The number and timing of PNC visits was estimated from hospital discharge abstracts and physician claims files, and the accuracy of our estimates may be affected by several factors, such as missing PNC records or receipt of PNC from non-physician providers. We were unable to differentiate missing data from no care using this approach. As well, inaccurate ascertainment of gestational age may affect assignment to a PNC utilization category or determination of a preterm or SGA birth. We compared the rate of adverse birth outcomes among women with inadequate/no PNC to the remainder of the population. However, Kotelchuck suggests there is a U-shaped relationship between PNC and birth outcomes, in which women with both fewer and greater number of visits than expected are at higher risks of having poorer birth outcomes , so perhThe rates of no PNC and inadequate PNC are lower for women giving birth in Winnipeg, Canada, compared to rates reported for women in the U.S. The two indices compared in this study revealed different utilization patterns and resulted in varying degrees of association of inadequate PNC with adverse pregnancy outcomes. Selection of a PNC utilization index for research or program evaluation requires careful consideration of the methodological underpinnings and limitations of the chosen index . AlthougThe authors declare that they have no competing interests.MIH conceived of the study and supervised all aspects of its implementation. All authors contributed to conceptualizing ideas and designing the study, provided input regarding analysis of the data, interpreted findings, and reviewed drafts of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Low birth weight remains a major reason behind childhood malnutrition. The NFHS findings show no dent in this problem.This study was undertaken to explore change in birth weights in a period from 1989 to 2007 and any associations thereof.All birth records of a private rural hospital spanning two decades (1989-2007) were analyzed for birth weight, age of mother, gender, birth order of the baby, proportion of pre-term babies and low birth weight babies.No change was observed in the average birth weights (average 2.71 kg) over the period. Although the birth weight shows some expected variance with the age of mother, it was found to have no relation with the baby’s birth order and gender. The low birth weight proportion is about 24% and shows little difference before and after the series midpoint of year 1998.The birth weights have hardly changed in this population in the two decades. Birth weight is a major determinant of child’s health and nutrition. In India, birth weight has remained low, with the NFHS reported proportion of low birth weight (LBW) babies about 23% for rural and 19% for urban population. However,A study from urban population of Bhilai reports LBW proportion of 23% which is rather high for urban population.. A studySystematic studies with standardized methods are rare in Indian literature. In this situation, secondary data from hospitals and gram panchayat birth records can be highly rewarding, though the issue of standardization of weighing scales and methodology in recording of birth weights are bound to remain a concern. Also the large proportion of home births create huge gaps in birth weight information, mainly as they are likely to be from disadvantaged communities and hence from the lower end of the birth weight distribution. We took up this study with an impression that the proportion of low birth weight babies must be declining over the two decades at least in hospital data. The secondary data available to us from this rural hospital should provide some insights.This retrospective study is an analysis of the childbirth records of a private nursing home in Dindori block of district Nashik (Maharashtra) from 1989 to 2007. This block of Nashik district has a mixed population of tribal and non-tribal communities. The block has both prospering grape growing villages as well as tribal communities migrating in search of seasonal labour after one paddy crop in monsoon. The block has two rural hospitals, 10 primary health centers (PHC) and 66 health sub-centers. The block has 95 doctors (private and public sector) distributed in clusters. in the two decades and had both tribal and non-tribal families. The case records were available in year wise bound books. Incomplete case records were deleted. Factors such as weight, mother’s education, and hemoglobin were not mentioned on the birth record because they were recorded on the ANC  record sheet, which was not available for this retrospective study. The baby weighing machines reportedly changed three times in the study period, but the same type and brand was used . There was no conscious attempt for standardization or validation of the scale; hence instrument error cannot be eliminated. The observer remained nearly the same for most births except in the last five years when one more doctor joined the hospital. The spot location of the scale has also remained unchanged for the two decades-in the delivery room, ensuring the same eye level from the delivery table. The practice of weighing the baby after wrapping in old cotton sari-cloth adds about 25 g to the bare baby weight, (we found that two such clothes together weighed 50 g).The data covers period from 1989 to 2007 -19 calendar years. The number of births recorded in the first four years in the hospital has been clubbed since the numbers were small as the hospital was new in the locality and home births were the norm. The work picked up from 1993 onwards, with a maximum of 202 births in 2003. The expected annual number of deliveries in the block  is 6600+ at a birth rate 25. Other deliveries took place at other hospitals including the PHCs and Rural Hospitals and at homes. The data (2586 births) represents about 2% of the childbirth cases in the block over the period of 19 years.The average BW is generally influenced by, among other things, proportion of pre-term babies. The data shows a variable proportion of pre-term deliveries (3% in 2002 to 15% in 1995) with an average level of 6% . Total nThe regression equation is2 is poor. It indicates even the third degree curve is also not a good fit. . Since this fit is not ‘good’ and all the regression coefficients are not significant, it supports the claim that birth weight has all most remained the same although there are some unexplained outliers. We conclude that the average birth weight has remained nearly stagnant over the study period. There is no gender difference in the average birth weight. The t-test for testing equality of means shows that the difference in mean birth weight for male  and female babies  is not significant .Value of RThe overall proportion of low birth weight (<2.5 kg) babies in the period (2498 cases including pre-term babies) was 24%, with some unexplained spikes in the year 1995 and 1996.P value >0.05).The year 1998 is midpoint of the series. Incidentally an ultrasound machine was introduced in service in 1998 to improve ANC diagnosis. When tested for BW difference in the series before and after 1998; there was slight difference in proportion of low birth weight (LBW) babies before and after 1998 (25% and 24%) which was statistically not significant . The correlation coefficient between age of a mother and birth weight of baby was weak (0.159), though statistically significant.The data on age of mother were available for 1947 cases. Only 2% of the mothers were below 18 years of age. The mention of age on the case paper is approximate and may not be very factual, as often happens in rural areas and more so when a woman arrives for childbirth in labor pains. The mean BW for this data is 2.71 kg. The average BW does not change across different age groups of mother . BW is aBirth weight is a major determinant of childhood malnutrition and mortality. Low birth weight (LBW) is a hard-core factor in chronic malnutrition in India as seen from NFHS3 data. While post-natal efforts for improving child’s weight are important, improving the BW itself is still a major issue. NFHS data shows–4 that bThis study, with its limitations of possible instrument error, offers a cross-section of rural birth weights over the last twenty years in a single block of Maharashtra. Notably, the data shows that the LBW proportion and mean birth weights have changed little over the years. The NFHS surveys show that LBW percentage among weighed children showed very small decline through the decade viz 24.7 (1992-1993), 23.9 (1998-1999) and 23.3 (2005-2006). The present study is therefore consistent with the NFHS data.This study shows some expected positive correlation of BW with age of mother. This reinforces the general importance of preventing early marriages and childbirths. The NFHS3 findings of 2003-2004 in WHO Growth standards, may be bDid the ANC make a difference to the BW? This is a difficult question to answer from our data. This is because we have no access to records of ANC visits. We also do not know how many of these women were registered for ANC with PHCs. Many unregistered cases need to be admitted for delivery in this hospital. We assume that the data is homogenous for hemoglobin (Hb) since many rural women have a starting level Hb under 8 g and rural women’s weights do not vary highly. The proportion of low body mass index (BMI) for rural women in Maharashtra in NFHS3 is as high as 43%.(Birth weights have not changed much in the study period in this rural block despite the changing economy of the region. We need to act on the proximate social-familial and gender factors for improving birth weights.


Recent studies have reported developmental toxicity among rodents dosed with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA).in utero exposures) and gestational age, birth weight, and birth size in humans.We examined the relationship between concentrations of PFOS and PFOA in cord serum (surrogates for n = 293) were analyzed for PFOS and PFOA by online solid-phase extraction, coupled with reversed-phase high-performance liquid chromatography–isotope dilution tandem mass spectrometry. Maternal characteristics and anthropometric measures were obtained from medical charts.We conducted a hospital-based cross-sectional epidemiologic study of singleton deliveries in Baltimore, Maryland. Cord serum samples , and head circumference . No associations were observed between either PFOS or PFOA concentrations and newborn length or gestational age. All associations were independent of cord serum lipid concentrations.After adjusting for potential confounders, both PFOS and PFOA were negatively associated with birth weight , ponderal index (per ln-unit: β = −0.074 g/cmDespite relatively low cord serum concentrations, we observed small negative associations between both PFOS and PFOA concentrations and birth weight and size. Future studies should attempt to replicate these findings in other populations. Polyfluoroalkyl compounds (PFCs) comprise a class of man-made, fluorinated organic compounds that have been used in a variety of consumer and industrial applications. Although these have been produced for many years, only recently have reports surfaced suggesting widespread exposure in wildlife and humans . Two of Both PFOS and PFOA have shown the potential for developmental toxicity in animal studies. PFOS has been shown, in rats and mice, to induce developmental and reproductive effects, such as reduced birth weight, decreased gestational length, structural defects, developmental delays, and increased neonatal mortality . Recent PFOS and PFOA have also been shown to cause reductions in serum cholesterol and/or triglycerides in several animal species . ConversIn a previous report, we documented factors associated with cord serum concentrations of PFOS and PFOA in a population of newborn deliveries known as the Baltimore THREE study . In thisWe conducted a cross-sectional study  of newborn deliveries at the Johns Hopkins Hospital in Baltimore, Maryland. This study received approval from the Johns Hopkins Medicine Institutional Review Board and received a waiver from the Health Insurance Portability and Accountability Act. The study required the collection only of specimens that otherwise would have been discarded and information from medical records that were available to hospital personnel. There was no requirement for informed consent due to the anonymization of all samples and data. Members of a community advisory committee, who were selected for their specific knowledge, expertise, and focus on important child health concerns in Maryland, had the opportunity to learn about and comment on this study before it was conducted. Between 26 November 2004 and 16 March 2005, all singleton, live birth deliveries occurring in the labor and delivery suite at the hospital were eligible for participation in the study. We excluded women who gave birth to multiple children or women who delivered a single child but had an initial twin gestation with fetal loss at ≥ 20 weeks. Newborns with major congenital anomalies likely to affect fetal growth were excluded as well.n = 5) or an initial twin gestation (n = 1), leaving a total of 293 study participants. We conducted a brief survey of hospital personnel to understand the major reasons for missed specimen collection. The most common explanations included complications during delivery, premature birth and/or small size of the infant resulting in small quantity of available cord blood, and logistical factors such as understaffing. The babies who were not included had somewhat lower gestational ages and birth weights. In addition, factors associated with insufficient blood volumes collected were preterm birth, low birth weight, being first born, and younger age of mother.Over the course of the study period, 609 live births occurred at the Johns Hopkins Hospital, of which 597 were singleton births. We obtained cord blood specimens from 341 of these, of which 42 had insufficient volume for laboratory analyses and were excluded from this study. Additionally, six births were excluded due to known major congenital anomalies , and a random 10% sample was verified by two others . Additional information was obtained from forms filled out by the nursing staff at the time of delivery. Age, race, education, and parity were based on self-report. Body mass index (BMI) was calculated from reported prepregnancy weight and height. Gestational age was based on the best obstetric estimate. Infant sex was abstracted from the mother’s medical record and confirmed with the infant record. Information on maternal health conditions was abstracted from the medical record. Maternal smoking status at birth was defined using a combination of the maternal medical record and cord serum cotinine concentrations. Cotinine concentrations > 10 ng/mL were categorized as exposure to maternal active smoking. If the clinical record indicated that the mother reported smoking at any time during pregnancy, she was considered an active smoker regardless of the cotinine concentration in cord serum.birth-weight/length3 × 100). We examined the relationships among gestational age, birth weight, length, and head circumference to identify outlying values, which were verified using the infant and maternal record. All congenital conditions on the birth record were recorded and reviewed by a clinician blinded to exposure status to determine which subjects had major malformations and should be excluded from this study. Because only singleton births were eligible for this study, we retrospectively excluded one birth, which, unknown to us at the time of sample collection, was from a twin gestation with demise of the other twin at 20 weeks.Infant anthropometric measures were abstracted from the infant medical record. Birth weight in grams obtained from the maternal record was confirmed with the infant record. Head circumference and length in centimeters were abstracted from the infant record. Ponderal index was calculated as the ratio of birth weight in grams to length in centimeters cubed, multiplied by 100  and 13C2-PFOA provided by Dupont Co. . The limit of detection (LOD), calculated as 3S0, where S0 is the standard deviation as the concentration approaches zero (m/z transition used for the quantification of PFOS (499/99) had an interference. Therefore, PFOS concentrations were calculated using another transition (499/130), normally used to confirm the presence of PFOS. The standard accuracies (93–118%) were obtained at three spike levels  ] . Qualityr PFOS)] . Under tConcentrations of cotinine in serum were determined using a method described by Serum lipid concentration analyses were conducted using commercially available test kits from Roche Diagnostics Corp.  for the quantitative determination of total triglycerides (product no. 011002803-0600) and total cholesterol (product no. 011573303-0600). Final determinations were made on a Hitachi 912 Chemistry Analyzer .R2. Concentrations below the LOD for PFOS, PFOA, and cotinine were set to the LOD divided by the square root of two for all analyses , height, parity, infant sex, diabetes, and hypertension. Diabetes was defined to include subjects with preexisting or gestational diabetes, assuming that both conditions would result in increased fetal weight for age. Similarly, hypertension was defined to include subjects with preeclampsia, pregnancy-induced hypertension, and chronic hypertension, which were expected to result in decreased weight for age. For consistency, the same set of covariates was included in the primary regression model for each end point other than gestational age, except for delivery mode [vaginal versus caesarian section (C-section)], which was included as a predictor of head circumference. We also explored the possibility of an interaction between delivery mode and cord PFOS or PFOA concentrations on head circumference. Based on the empirical evidence, a quadratic term for maternal age was included in regressions of gestational age, birth weight, head circumference, and ponderal index, but not for length. A quadratic term for gestational age was included in regressions of head circumference only. All other terms were included in the models as linear or categorical (indicator) variables. We considered maternal education level as a measure of socioeconomic status, but it was not included in the final models because it did not materially change the coefficient estimates. We also conducted regressions before and after controlling for total lipids, total cholesterol, and triglycerides to examine the possible role of serum lipids as a mediator of any relationships between PFOS or PFOA concentrations and birth weight and size.A small number (< 4%) of participants were missing data on prepregnancy weight, height, and/or net weight gain during pregnancy, which are important predictors of birth weight and size. We imputed the missing data with the median value of height, weight, and/or weight gain. As a sensitivity analysis, we examined the impact of imputing BMI or weight gain with extreme values and found no material effect on the regression coefficients for PFOS or PFOA.Regression diagnostics were conducted for all models, including examination of fit, heteroskedasticity, and influence. Statistical analyses were performed using STATA version 8.0 .p < 0.01).PFOA was detected in 100% of cord blood serum samples, and PFOS was detected in > 99% of samples. The median PFOA concentration was 1.6 ng/mL  and the median PFOS concentration was 5 ng/mL . Concentrations of PFOS and PFOA in cord serum were highly correlated  in median PFOS concentrations were observed by race, smoking status, and hypertension, and differences in median PFOA concentrations were observed by BMI category, parity, and infant sex. The distribution of fetal growth indices are shown in p < 0.05). Further adjustment for additional covariates resulted in an attenuation of this association. In the fully adjusted model, a ln-unit increase in cord concentration was associated with a decrease in mean birth weight of 69 g .We examined the relationships between PFOS and PFOA concentrations with serum total cholesterol, triglycerides, and total lipids and found no evidence of an association between chemical exposure and any of these biomarkers. Consequently, adjusting for these measures had no impact on the associations observed between PFOS or PFOA and the end points under study . Among C-sections, there was a nonsignificant positive association between both PFOS and PFOA and head circumference. To further explore this issue, we evaluated whether this statistical interaction was also present for birth weight and ponderal index (data not shown). For birth weight, some evidence of an interaction in the same direction was observed with PFOA (p < 0.05) and PFOS (p = 0.08). No evidence of an interaction was observed for ponderal index.As expected, delivery mode was associated with head circumference, with babies born by C-section having larger head circumferences, on average, compared with vaginal deliveries, after adjusting for potential confounders. Because of the potential for increased measurement error due to head molding in vaginal deliveries, we included an interaction term between PFOS and PFOA with delivery mode, which was statistically significant  for PFOS and birth weight in rats of 0.39 mg/kg/day, equivalent to a rat fetal serum concentration of about 34,000 ng/mL. 10s for several postnatal developmental end points for PFOA in rats, ranging from 22 to 44 mg/kg/day, equivalent to rat fetal serum concentrations from 29,000 to 59,000 ng/mL. Thus, the serum concentrations of these compounds associated with developmental effects in rats are several orders of magnitude higher than the concentrations observed here.The toxicology literature provides evidence of developmental effects among animals dosed with PFOS and PFOA, albeit at substantially higher levels than observed here . For exaOnly limited epidemiologic data on PFCs and developmental outcomes exist. In one recent occupational epidemiologic study of perfluorooctanesulfonyl fluoride manufacturing workers, investigators examined the relationship between occupational PFOS exposure and self-reported medical conditions . Among fHypolipidemic effects have been among the sensitive changes observed in animals in response to PFOS and PFOA exposure . In occuThere are some potential limitations to this cross-sectional study, described below, which should lead to cautious interpretation of the results. We used a precise analytical method for the detection of subparts per billion PFC concentrations in human serum . In thisGiven the relatively low serum concentrations, future studies should examine possible noncausal mechanisms that may be responsible for the associations reported here. PFOS and PFOA have an affinity for protein-binding and have been shown to accumulate in protein-rich compartments in biological systems . Becausehttp://www.ehponline.org/docs/2007/10334/suppl.pdf)], suggesting that the degree of residual confounding is likely to be small. Although we adjusted for the major known determinants of birth size and weight, it remains possible that other unmeasured factors, such as diet, may be confounding the relationships observed in this study. The maternal diet would be expected to be related to weight and size of the fetus, and it remains possible that the consumption of contaminated food or water, including the use of fast-food containers, is a pathway of exposure to PFOS and/or PFOA. To confound the relationships observed, undernutrition would have to be associated with greater PFOS or PFOA exposure. In this and in a previous publication, we reported slightly higher concentrations of both chemicals in underweight and obese mothers compared with normal weight mothers, although not all differences were statistically significant (The use of medical records as the principal source for data on potential confounders is likely to result in some degree of misclassification. However, we observed the expected relationships between key predictors and birth outcomes [see Supplemental Material (online at nificant .Finally, our study population represented a group of individuals with more risk factors for adverse birth outcomes than the United States as a whole. Compared with national estimates, the subjects in our population were more likely to be black, teenagers, unmarried, and cigarette smokers . This isIn summary, we observed a small negative association between PFOS and PFOA concentrations in cord blood and birth weight, ponderal index, and head circumference. Although lipid metabolism alterations have been among the more sensitive effects observed in animal and human data, the associations observed here were independent of cord serum lipid levels. We suggest cautious interpretation of this study until the findings can be replicated in other populations.


A 4-year-old boy presented with history of left anterolateral neck swelling since birth. He was clinically diagnosed to have a branchial cleft cyst. A CT scan revealed findings suggestive of a thymic remnant cyst. The lesion was excised and the diagnosis was confirmed by histopathology. A thymic remnant cyst (TRC) is a rare lesion. The diagnosis cannot be established solely on the basis of the clinical findings. The main differential diagnosis is a second branchial cleft cyst and imaging is necessary for diagnosis. It not only permits a firm diagnosis to be made but also depicts the exact anatomical location, the relationship of the cyst to the contents of the carotid sheath, and the extent of the lesion.A 4-year-old boy presented with an asymptomatic, left-sided neck swelling that had been present since birth. He underwent a CT scan of the neck, which revealed a 6.7 × 4.3 × 3.3-cm, well-defined, thin-walled, cystic lesion on the left side, with CT attenuation values of 5–10 HU and subtle peripheral rim enhancement. The lesion was deep to the left sternocleidomastoid muscle and parallel to it. It extended cranially up to the level of the left pyriform sinus  and caudThe thymus develops from the third pharyngeal pouch. During development, it traverses the neck to its final position in the anterosuperior mediastinum. Thymic remnants are therefore likely to be found in the neck, often presenting as neck masses.3One type of thymic remnant is the TRC, a remnant of one of the paired tracts of embryological thymic descent. TRCs are rare lesions and are also referred to as thymopharyngeal cysts because they presumably follow the course of resorbed thymopharyngeal ducts.–6About two-thirds of the TRCs occur in the first decade of life and the remaining in the second and the third decades. The majority of these cysts are located on the left side of the neck.Although they can present anywhere in the neck from the angle of the mandible to the sternum, most TRCs are present in the lower neck as slowly enlarging masses. They are usually oriented along the long axis of the sternocleidomastoid muscle. They may be completely isolated from the normal thymic tissue or may be attached to the thymus by a fibrous band.On imaging, a TRC usually appears as a solitary, off-midline  cyst, situated low in the anterior neck, either adjacent to the lower part of the pyriform sinus or just caudal to the thyroid gland. On USG, TRC appear as an anechoic neck mass with thin, distinct walls, extending up through the thoracic inlet behind the thyroid. A CT scaThe differential diagnosis of TRC includes conditions such as thyroglossal cyst, malformation of the lymphatic system, cystic neuroblastoma, external laryngocele, vallecular cyst, and lymphadenopathy. The mostTo summarize, we conclude that although the TRC is a rare lesion, it must be considered in the differential diagnosis of neck masses. CT scan is helpful in delineating the exact anatomical location, the relationship to the contents of the carotid sheath, and the extent of this uncommon neck mass.


Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. They represent the most common malignant brain tumors . DespiteEvidence of an association between adult-onset glioma and date of birth suggests an etiologic role for a seasonally variable environmental exposure occurring prenatally around the time of birth. The period between an environmental exposure and the appearance of cancer may be lengthy, as illustrated by the development of vaginal cancer in daughters years after their mothers used diethylstilbestrol (DES) during pregnancy . SimilarThe origins of many childhood and adult malignancies are believed to be determined during a finite perinatal window. During this period the brain and immune systems are less developed, undergoing greater cell growth and differentiation, and possibly more susceptible to DNA and epigenetic changes underlying cancer development in the near or distant future ,8–13. In2.2.1.Articles were identified by systematically searching the Medline/PubMed database from inception to January 2010 using the key words: brain tumors and season of birth. Furthermore, we manually examined the bibliography of the papers that were identified electronically. We also searched for unpublished studies, PhD dissertations, internal reports, and conference proceedings/abstracts. Finally, to make our search inclusive of those studies in which season of birth was a secondary factor we checked the tables of every article known to us that examined risk factors for brain tumors. A similar process was used to identify papers on risk factors related to season of birth.2.2.Studies were included only if the target population, outcome and exposures of interest were clearly defined and results were based on valid statistical methodology with evaluation of errors and discussion of study bias. Studies in which participants were chosen at convenience were not considered in this review. In the case of a cohort appearing in the literature multiple times only the most recent version was included since it provided the largest number of cases and the longest follow-up. Priority was given to papers that presented original data rather than reviews or meta-analyses.3.Several recent studies have explored season of birth as a risk factor for adult glioma, but results have been mixed . Three i4.The underlying rationale for the occurrence of a glioma decades after a seasonal exposure remains elusive. No specific etiologic agent to date has been identified to support such a long induction period for this cancer. Several hypothetical arguments have been offered in explanation of a season of birth effect for adult gliomas, if such an association exists. Thus far, the major evidence in support of a seasonal effect involves farming, allergies/immunity, viruses, and vitamin D. Other possible factors related to seasonal birth are diet, birth weight, and handedness.4.1.Farming, by virtue of its seasonal nature, conveys increased risk at certain times of the year of exposure to pesticides and other agricultural chemicals. Insecticides and herbicides constitute the bulk of farm chemical exposures: two key routes of exposure are dermal and respiratory , bypassiIndoor exposures to these agents frequently occur ,30. PareIn tandem with living on a farm, infants have unique vulnerabilities that may lead to higher levels of exposures in the same environment than adults . For exaAt birth, children are less able to detoxify chemicals and other inorganic substances commonly used on farms ,34, and While farmers live longer than the population-at-large , and die4.2.The perinatal period represents a time of heightened sensitivity to environmental allergens ,52. WithEfforts to reduce allergen exposure immediately after birth often only delay the onset of allergic conditions, rather than preventing it, suggesting that immunologic memory may predate birth . While gIn a number of studies, season of birth has been associated with the development of allergic conditions later in life, such as asthma –65, atopFactors known to influence the development of asthma include race ,81, low i.e., reverse causality) [Asthma, allergies, and other atopic diseases have been inversely associated with adult glioma risk in several epidemiologic studies and meta-analyses –93, althusality) . Inflammusality) ,101.Being raised on a farm –114 or iLittle is known about specific determinants of asthma and atopy in the farm setting. Any relationship with glioma risk is probably complex and must be interpreted in light of differences in farming practices and the protective ability of farming environments, especially with respect to microbial exposures ,103,114.Differences in the definition of atopy, a lack of objective measures of atopy, residual confounding, and bias  are important to consider when interpreting the above studies ,121. FurInterestingly, increased risk for glioma has been observed in patients with AIDS-related immuno-suppression –124, but4.3.Environmental exposures to viruses, microbes and other pathogens generally tend to occur more often in particular seasons ,126,127.Toxoplasma gondii infection has been associated with a greater prevalence of astrocytomas [Epidemiologic evidence in support of a viral or pathogenic etiology for adult brain tumors remains controversial and the windows of interest of these studies have been outside the perinatal period. In adults, ocytomas , while docytomas , and chiocytomas ,136. On ocytomas , influenocytomas ,139, meaocytomas , generalocytomas ,141, andocytomas . Similarocytomas ,142.A seasonal infectious etiology for disease is complicated by many factors . The sam4.4.Vitamin D is a fat-soluble prohormone which operates via a nuclear receptor . MaternaAntiproliferative and proapoptotic activity of vitamin D3 has been noted in model glioma cell lines and a primary culture, as well as tumor tissue experiments . FurtherChildren who live in polluted, inner city environments and who are deprived of regular sunlight exposure have been shown to suffer a higher prevalence of rickets (due to vitamin D deficiency) than children in rural areas . Seasona4.5.in utero when the fetus is plastic and adaptively imprints to its environment. In utero adaptation may lead to lifelong changes in the body’s metabolism, hormone regulation, and the number of cells present in key organs [The “developmental plasticity hypothesis” refers to the critical developmental period y organs ,157,158.y organs ,160, andy organs . Foods hy organs –165. They organs .Vitamin C, which is mostly found in seasonal fruits and vegetables, can react with and then inhibit nitrite formation of nitrosamines . An 18-f4.6.Birth weight has been reported to vary by season of birth –170. Hig4.7.in utero [Handedness is believed to be determined in utero , possiblin utero –183, andin utero ,185, varin utero , epilepsin utero , and brein utero –190. Expin utero . Testostin utero –194.in utero to the estrogen-like compound DES show a higher prevalence for left handedness [in utero levels of androgeizing hormones [Results from several studies hint that non-genetic factors may play an important role in the determination of handedness. Women exposed ndedness ,196. Simhormones . Of notehormones , and sexhormones ,200. Michormones , furtherhormones –207.Handedness has been shown to follow a gender-invariant seasonal pattern, with more left-handers than right-handers born between March and July ,178. BeiThe putative connection between handedness, season of birth, and glioma risk remains difficult to interpret. For example, glioma risk is greater for males than females , yet the5.Season of birth in its own right cannot be deemed a cause for glioma. Rather, it is a surrogate marker for underlying risk factors that may offer subtle clues about the possible perinatal etiology of adult gliomas.There is probably no specific etiologic agent acting in isolation that completely explains a season of birth association with adult glioma risk. If an association exists the effect probably represents the interplay between various environmental, genetic, lifestyle, and socioeconomic factors, operating on mother and child within a precise window of vulnerability. The mechanism of action may involve epigenetic processes or DNA changes with the capacity to modulate or influence oncogenic outcomes in the distant future. A patient’s innate and adaptive immune response and a host of hormonal and metabolic factors, likely play important and closely interrelated roles in understanding the complex biologic and etiologic mechanisms in the season of birth effect for adult gliomas.In the studies conducted to date, risk estimates and p-values for the association between season of birth and glioma risk have been nominal to borderline in strength. However, a weak association does not necessarily imply the absence of causality, nor is a strong association necessary or sufficient for causality ,214. TheOn the present evidence, it is not possible to definitively answer the question of how season of birth influences glioma risk, or to favor any specific hypothesis. Many questions remain and future research will benefit from focused studies aimed at specific exposures and subpopulations, allowing for more detailed analyses by histologic subtypes.


Sir,Low birth weight (LBW) has been defined by the World Health Organization (WHO) as weight at birth of less than 2500 g. LBW at bWe undertook a retrospective analysis of LBW data available at the Sri Narayani Hospital and Research Centre, a 100 bed hospital situated outside Vellore city limits. The women who attended the ante-natal clinic or came for delivery were from the rural and peri-urban population of Vellore district of Tamil Nadu, India. We also investigated the association between LBW, random blood glucose level (RBS), hemoglobin (Hb) levels, maternal age and complications during delivery of the patients. Generally, information from rural areas of India is sparse in published literature.Information on all pregnant women who came for pre-natal check-ups and who delivered a child at the obstetrics and gynecology facility in the hospital during the period January 2005 to October 2008 were included in the analysis. Relevant information was acquired from the medical charts. Hemoglobin level was estimated by the cyanmethemoglobin method. The weights of the newborns were recorded using an appropriate balance . All babies were weighed within one hour of birth by a trained nursing personnel. The blood glucose levels were measured by GOD-POD method in a fully automated biochemistry analyzer .Statistical analysis was done by comparison of proportions using the Chi-square test in the Epi Info ver.6.03 programme.Among 1024 subjects studied, a total of 121 (11.81%) newborn babies were less than 2,500 g. There were 304 mothers from peri-urban areas and 720 mothers from rural areas. Among the mothers who had newborn babies with LBW, 36 (11.84%) belonged to peri-urban population and 85 (11.08%) belonged to rural population. There was no statistically significant difference. The widespread problem is a reflection of the lower socio-economic status of rural and peri-urban women affecting their nutritional status. Similar findings have been reported from some parts of India.(The range of age of mothers who delivered normal weight babies was 17–32, median-20, and for those who delivered LBW babies was 21–30, median-22. No obvious difference in maternal age was found. In our series, we did not find any newborn in the category of extremely low birth weight infants, as defined in the literature. The randBirthweight remains an important factor affecting infant andchild mortality. Babies of low birth weight are also prone to perinatal morbidity. The results of this study suggest that for reducing the problem of LBW in rural India, the public health strategy needs to focus attention on better maternal nutrition and education. Indian intervention programs encourage wider birth interval, avoidance of teenage marriages and early pregnancies. The public health measures have been most effective only in the state of Kerala; other parts of the country have to play catch-up.


Bronchiolitis is a distressing, potentially life-threatening respiratory condition that affects infants. We evaluated the incidence and risk factors of hospitalization for broncholitis in preterm infants  born between 2000 and 2006, and the use and impact of Palivizumab, a monoclonal antibody that in randomized clinical trials has been shown to lessen the severity of RSV-related bronchiolitis.Retrospective cohort study that linked data from four health administrative databases in the Lazio region : the birth register, the hospital discharge register, and two ad-hoc databases that record the doses of Palivizumab administered at two local health units.Among 2407 preterm infants, 137 had at least one hospitalization for bronchiolitis in the first 18 months of life, an overall incidence rate of 4.70 per 100 person-years (95%CI: 3.98-5.56); similar incidence rates were observed by calendar year. A multiple Poisson model showed that the following characteristics were associated with higher incidence: younger age of the infant, the period between October-April, male gender, low Apgar score at birth, low birth weight, and low maternal educational level. At least one dose of Palivizumab was administered to 324 (13.5%) children; a dramatic increase from 2000 (2.8%) to 2006 (19.1%) (p < 0.01) was observed. Other factors independently associated with more frequent Palivizumab use were older maternal age, Italian-born mothers, female gender, low Apgar score, low birth weight, shorter gestational age, a diagnosis of broncho-dysplasia, and the month of birth. It is of note that none of the 34 children with congenital heart disease were prescribed Palivizumab. Performing several multiple Poisson models that also considered Palivizumab use as covariate, although the point estimates were in agreement with previous clinical trial results, we did not find in most of them a significant reduction for immunized children to be hospitalized for bronchiolitis.In Italy the incidence of hospitalization for bronchiolitis, and its associated risk factors, are similar to that found in other countries. Although Palivizumab use is associated with the most important characteristics of severe prematurity, other aspects of its non-use in children with congenital heart disease, the age and the birth country of the mother suggest the need for public health measures that can reduce these health disparities. Finally, the estimated effectiveness of Palivizumab in routine practice, although not significant, confirms the results of previous clinical trials, but its impact on modifying the temporal trend in this population is still negligible. Bronchiolitis is an acute respiratory illness that particularly affects infants and young children characterized by coryza and sometimes low-grade fever that progress over a few days to cough, tachypnoea, hyperinflation, chest retraction, and widespread crackles, wheezes, or both .The incidence of bronchiolitis has a seasonal trend with a peak during the winter months in temperate climates, during the cool rainy season in tropical and subtropical areas, and during the cool dry season in South America and South Africa . A studyHospital admission rates for bronchiolitis in the US and Europe are reported to be around 3% for children less than 1 year of age . IndepenIt has been estimated that the respiratory syncytial virus (RSV) is the etiologic agent in more than 70% of the cases (80%-90% during the winter)  and of maternal characteristics . Incidence rates were also calculated stratifying for age of the infants  and calendar month. Crude and adjusted incidence rate ratios (IRR) of bronchiolitis hospitalizations for the previously described characteristics were estimated using univariate and multiple Poisson models.Descriptive frequency tables of the previously described characteristics and use of Palivizumab were provided. To evaluate the association of some characteristics with Palivizumab use we calculated the Chi-squared test. To evaluate the independent association of these characteristics with the administration of Palivizumab, a multiple logistic analysis was performed.To evaluate the impact of the administration of Palivizumab on the risk of being hospitalized, we performed additional Poisson models that estimated IRRs for immunized compared to non-immunized infants using two different approaches of selecting specific at risk time periods among those who received prophylaxis. The first approach evaluated the effectiveness of the immunization in its entirety considering as the at-risk-time the period since the date of the first dose of Palivizumab administered to the first hospitalization for bronchiolitis, or the date the subject turned 18 months of age, or the first of January 2007, whichever comes first ; the management of these data for public health purposes does not require a patient's informed consent nor it does require any authorization regarding privacy laws.During the period 2000-2006, 67,292 children were born to mothers living in the two LHUs of Rome; the median gestational age was 39 (mean = 38.9) weeks. Among them, 2407 (3.6%) were born at <36 weeks of gestation; the median gestational age among preterm infants was 34 (mean = 33) weeks and 201 (8.3% of preterm infants) were born at <29 weeks.Table Table Overall, 324 (13.5%) children received at least one dose of Palivizumab. There were 1291 doses administered with a median of 4 doses received per child. Doses were administered exclusively between October and April, with the mode of administration in December . Table Among the 324 preterm children who received at least one dose of Palivizumab, 8 2.5%) were hospitalized with bronchiolitis in the first 12 months of life. Among them, 6 were hospitalized in the 30-day period just after each administration of Palivizumab. The incidence rate was 5.72  per 100 PY, slightly lower than that observed in non-immunized children . The incidence rate in the 30 days immediately after each administration of Palivizumab was 9.55  per 100 PY. Table % were hoWe evaluated the incidence and the risk factors of hospitalization for bronchiolitis in preterm children in and around Rome, Italy. Overall, the incidence of hospitalization was 4.70 per 100-PY in the first 18 months of age and this estimate is in agreement with that reported in other studies ,16,23,24During the 2000-2006 study period we observed a significantly increasing trend of the percentage of pre-term children who received at least one dose of Palivizumab. After adjusting for other covariates, year of birth was still strongly associated with the administration of Palivizumab; other factors independently associated were low birth weight, shorter gestation, low Apgar score, reported diagnosis of bronchodysplasia, female gender, birth country and maternal age. While the first four factors were expected to be associated with Palivizumab prophylaxis, there is no clear explanation for the latter three. In particular, it was expected that male children, being at higher risk of hospitalization, were more likely to have received prophylaxis with Palivizumab than females and not vice versa. One possible explanation could be related to unknown, uncontrolled confounders for which the effect was indirectly expressed through gender . RegardiWe evaluated if there was a risk reduction of hospitalization for bronchiolitis in infants who received at least one dose of Palivizumab with two different analyses trying to identify both the effectiveness of each single dose and of the scheduled immunization program offered. In both cases we did not find, using different multiple models and different selected populations, a signficant risk reduction, but in one model  was reported in the hospital discharge form; this most likely occurred because no diagnostic exams had been performed to identify the underlying infectious agent. This did not permit us to perform specific analyses of RSV-associated bronchiolitis. However, many studies reported that between 70% and 90% of hospitalizations for bronchiolitis in infants are RSV-associated (2). Finally, preterm infants have a high risk of death and we cannot exclude that for some of them we could have overestimated the person-time at risk of broncholitis if they died before 18 months of age. However, since we excluded those who died during their first hospital admission the impact of this issue on our results should be limited.In conclusion, this is the first report since the introduction of Palivizumab to evaluate the incidence and risk factors associated with hospitalizations for bronchiolitis in preterm infants in Italy. We highlighted that in Italy the incidence of hospitalization for bronchiolitis and the risk factors associated with it are similar to those found in other countries. Although the use of Palivizumab is associated with the most important characteristics of severe prematurity, its non-use in children with congenital heart disease contrasts with international guidelines; furthermore, its association with maternal age and the country of birth suggests the need for public health measures that can reduce health disparities.The authors declare that they have no competing interests.PP conceived the study design, supervised all the phases of the study, planned and performed the statistical analysis, drafted and revised the manuscript. JM contributed to the design of the study, performed the record linkages among the health information systems, performed the statistical analyses, drafted and revised the manuscript. NB and EM conceived of the initial idea of the study, collected all the data regarding Palivizumab administration in their own LHU, revised the manuscript. DDL conceived of the initial idea of the study, participated in the design of the design, revised the manuscript and contributed especially to the intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Although neuroanatomical and cognitive sequelae of low birthweight and preterm birth have been investigated, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population. Our aim was to address these issues in a sample of young people receiving additional learning support.One hundred and thirty-seven participants aged 13–22 years, receiving additional learning support, were recruited via their schools or colleges and underwent structural magnetic resonance imaging (MRI). Obstetric records, available in 98 cases, included birthweight and gestational data in 90 and 95 cases, respectively. Both qualitative and quantitative voxel-based analyses of MRI data were conducted.n = 72) demonstrated significantly greater scores for several anomalies, including thinning of the corpus callosum, loss of white matter and abnormalities of shape of the lateral ventricles.A history of low birthweight and preterm birth was present in 13.3% and 13.7% of cases, respectively. Low birthweight and preterm birth were associated with specific qualitative anomalies, including enlargement of subarachnoid cisterns and thinning of the corpus callosum. Low birthweight was associated with reduced grey matter density (GMD) in the superior temporal gyrus (STG) bilaterally, left inferior temporal gyrus and left insula. Prematurity of birth was associated with reduced GMD in the STG bilaterally, right inferior frontal gyrus and left cerebellar hemisphere. Comparison of subjects with no history of low birthweight or preterm birth with a previously defined control sample of cognitively unimpaired adolescents (Although a two-fold increased prevalence of a history of low birthweight and preterm birth exists within the special educational needs population, other aetiological factors must be considered for the overwhelming majority of cases. Neuroanatomical findings within this sample include qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. These findings suggest a neurodevelopmental mechanism for the cognitive difficulties associated with these obstetric risk factors. Intellectual disability is a lifelong disability that is associated with considerable cost to society and often considerable limitations to the quality of life of affected individuals. A widely employed definition of intellectual disability is that of the American Association on Mental Retardation (AAMR), which requires three criteria to be met: 1) the presence of sub-average intellectual functioning, comprising an intelligence quotient (IQ) of less than 70; 2) the presence of impaired adaptive functioning, comprising deficits within domains such as academic or occupational functioning, social skills and activities of daily living; and 3) an onset prior to the age of 18 years [ the pres the pres an onsetLow birthweight (less than 2500 g) and preterm birth (less than 37 weeks' gestation) are relatively common within developed countries, affecting approximately 7% (see ) and 6% Low birthweight and preterm birth are also known to be associated with a range of qualitative and quantitative abnormalities of brain structure. Low birthweight is associated with ventricular dilatation, white matter loss and thinning of the corpus callosum ,11 and cOur understanding of the neuroanatomical and cognitive sequelae of these conditions is largely derived from longitudinal cohort studies, investigating brain structure and cognitive impairments within groups of subjects identified, either at the time of birth or during subsequent recruitment from clinical samples, as being born preterm and/or with a low birthweight. To the best of our knowledge, no study has as yet examined these issues within a cohort of cognitively impaired individuals, recruited as such via the educational system. Consequently, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population.This study addresses these issues within a clinically well cohort of young people receiving additional learning support at school, recruited as part of a longitudinal study investigating the prevalence and evolution of psychopathology within adolescents with special educational needs because of an apparent intellectual disability in comparison to a control group of normally developing young people . StructuOne hundred and thirty-seven young people aged 13–22 years receiving additional learning support at their school or college of education were included in this study. The recruitment of these participants has been described elsewhere : in brieAdditional written informed consent was sought from all participants and their mothers in order to examine their obstetric records, held centrally by the Information and Statistics Division of the National Health Service of Scotland. Where consent was provided and records were available, data concerning birthweight and gestational age were extracted. Low birthweight was defined as a birthweight of less than 2500 g and preterm birth was defined as a gestational age of less than 37 weeks.2 = 1.122, degrees of freedom (df) = 1, p = 0.289), age  or IQ .All participants were scanned on the same 1.5 T GE MRI scanner  with a 3D inversion-recovery prepared T1-weighted coronal gradient echo sequence, yielding 128 contiguous 1.7 mm coronal slices of 256 × 192 voxels . All scans were visually inspected blind to clinical and obstetric data prior to inclusion within the analysis. Scans from an additional 19 participants were excluded from this study: in eighteen cases this was due to insufficient image quality for voxel-based morphometric (VBM) analysis, primarily because of magnetic interference from dental braces and movement artefact, and in one case this was due to massive porencephaly observed in the scan which was incompatible with VBM analysis. The 137 included subjects did not differ from the 19 excluded subjects in terms of gender (χAll MRI scans were assessed by a neuroradiologist (RJG) experienced in paediatric neuroradiology who was blind to clinical and obstetric details, according to a standardised checklist of qualitative anomalies of brain structure . The chea priori tissue maps created specifically for this cohort [Image processing was performed using the Statistical Parametric Mapping package , running in Matlab version 6.5.1 . VBM analysis was performed using an adaptation of the optimised methodology proposed by Good et al , wherebys cohort ,32. The s cohort .U test.Qualitative anomaly scores from subjects with and without a history of low birthweight and prematurity were compared using the two-tailed Mann-Whitney VBM correlation analyses were conducted to examine the linear associations between grey matter density (GMD) and the degree of obstetric adversity . Owing to the non-linear nature of the effects of these parameters  obstetric data was transformed from absolute values to figures representing the degree of adversity, as follows: (i) the 'degree of low birthweight' was taken as zero where the birthweight was greater than or equal to 2500 g, or as the difference from 2500 g where the birthweight was below this level; and (ii) the 'degree of prematurity' was taken as zero where the gestational age was 37 weeks or more, or as the difference from 37 weeks where the gestational age was less than this.T-contrast results were generated as statistical parametric maps with a threshold set at an uncorrected significance level of T = 3.2. Voxelwise correction for multiple comparisons was performed using Gaussian random fields theory within SPM99 [p < 0.05 (corrected for multiple comparisons) were considered significant, and coordinates of significant voxels were converted from Montreal Neurological Institute (MNI) space to Talairach and Tournoux [All analyses were performed using a multiple regression model in SPM99, and were adjusted for age, gender and normalised total brain volume by including them as covariates. in SPM99 . MaximumTournoux  space usTournoux . Where s2 = 0.006, df = 1, p = 0.939), age  or IQ .A total of 137 scans from 85 male and 52 female participants, with mean age 15.9  and mean IQ 73.0  were included in this study. Obstetric data was available for 98 participants: these participants did not differ from those in whom obstetric data was unavailable in term of gender , with a mean birthweight of 1730 g  as compared with a mean of 3399 g  among those participants with normal birthweight.Gestational age data was available for 95 subjects, of whom 13 were recorded as being born prematurely , with a mean gestational age of 33.2 weeks  as compared with a mean gestational age of 40.4 weeks  among the remaining participants.U = 294.0, Z = -3.119, p = 0.002). Prematurity was associated with significantly higher scores for white matter high intensity of myelination delay , arachnoid cysts , enlarged subarachnoid cisterns  and thinning of the corpus callosum . No significant associations were detected between these obstetric parameters and the total qualitative abnormality score.Low birthweight was associated with significantly higher scores for enlarged subarachnoid cisterns (pcorrected = 0.009), left STG (pcorrected = 0.031), left inferior temporal gyrus  and left insula (pcorrected = 0.049); see Figure Significant negative correlations between GMD and the degree of low birthweight were detected in the right superior temporal gyrus , right inferior frontal gyrus (pcorrected = 0.009), right STG (pcorrected = 0.026) and the posterior lobe of the left cerebellar hemisphere (pcorrected = 0.036); see Figure Significant negative correlations between GMD and the degree of prematurity were detected in the left STG , the left STG  and the left insula , but not the left ITG . No significant correlations were found to exist between birthweight and GMD data for subjects with birthweight of at least 2500 g.In the case of participants with low birthweight, extracted GMD data from the loci of all significant VBM results demonstrated significant correlations with birthweight for the right STG , the right IFG , the right STG  and the left cerebellar hemisphere . No significant correlations were found to exist between gestational age and GMD data for subjects with gestational age of at least 37 weeks, although the associations between gestational age and extracted GMD from the right STG and right IFG demonstrated trends towards significance  and , respectively.In the case of participants with preterm birth, extracted GMD data from the loci of all significant VBM results demonstrated significant correlations with gestational age for the left STG  as described in our previous report [It is therefore clear that in this sample recruited from the educational system both low birthweight and preterm birth are associated with an excess of demonstrable structural brain anomalies. The question of the extent to which these obstetric adversities could account for the differences demonstrated between the group with special educational needs as a whole and the controls is obviously raised and this was addressed by comparing (i) a group of 73 participants, comprising the 137 participants investigated within this study, with the exclusion of those with a history of low birthweight or preterm birth and those for whom no birthweight or gestational age data was available; and (ii) the same control group , loss of white matter , abnormal shape of the lateral ventricles  and blunting of the lateral angles of the frontal horns of the lateral ventricles ; (two-tailed Mann-Whitney U test applied to the data).The group of subjects with no history of low birthweight or preterm birth had significantly higher scores than controls for thinning of the corpus callosum , only 12 (13.3%) and 13 (13.7%) cases, respectively, had a history of low birthweight and preterm birth. Although this represents an approximately two-fold increase as compared with previously reported prevalences of these conditions within developed world populations as a whole, of 7% (see ) and 6% The association between these obstetric adversities and increased rates of occurrence of corpus callosal thinning and arachnoid cysts is consistent with previous qualitative MRI analyses demonstrating similar findings ,14. Low Our quantitative analyses demonstrated a pattern of abnormalities of brain structure, predominantly within temporal lobe areas, associated with low birthweight and preterm birth. Children born preterm or with low birthweight are at risk of significant cognitive impairment into childhood ,39. GiveWe also identified a correlation between gestational age and GMD within the left cerebellar hemisphere of individuals born preterm. Previous volumetric studies reported reduced cerebellar volume in adolescents born very preterm ,19, withTo our knowledge, this is the first study to investigate the prevalence and neuroanatomical correlates of a history of low birthweight and preterm birth in a clinically well sample of individuals within the special educational needs system. In contrast with previous studies, this sample was not selected in order to identify individuals with a history of obstetric adversities, but instead was recruited via an educational route  and retrospective review of these obstetric parameters was subsequently conducted. This sampling approach lends an important strength to this study, in that the sample of cases is free from sources of bias associated with the use of selected clinic samples, is representative of a large population of individuals within our educational system and lends new insight into previously unaddressed issues affecting this population.A recent US Institute of Medicine report estimated that preterm birth in the US cost society US$26.6 billion in 2005, with US$1.1 billion representing the cost of provision of special educational services, and stated the need for outcome studies extending into adolescence . Our finThe author(s) declare that they have no competing interests.MDS designed the protocol for qualitative analysis, analysed the study data and wrote the first draft of the manuscript. TWJM oversaw the quantitative image analysis methodology. RJG undertook the qualitative assessments of MRI data. AMM supervised the extraction, by JEDS, of data from obstetric records, and assisted in refining statistical analyses. DGCO participated in the recruitment and clinical interviews of participants. SML supervised imaging aspects of the study. ECJ conducted clinical interviews of participants, critically revised the manuscript, obtained programme grant funding for and had overall responsibility for the project and provided overall leadership. All authors participated in meetings to review findings and revise the manuscript.The pre-publication history for this paper can be accessed here:


Infants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results.Data for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy.No difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy.The findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes. On September 11, 2001, the United States suffered terrorist attacks against the World Trade Center and the Pentagon. The psychological stress resulting from these events affected not only those individuals who witnessed or experienced them directly, but people across the nation as well . StudiesBiological studies of stress hormones suggest that maternal stress may be associated with the timing of parturition -14. Highet al. (2007), were limited by relatively small (fewer than 300 participants) sample sizes [In New York and California, reproductive health effects, such as reductions in birth sex ratios (an indirect measure of pregnancy loss), have been associated with acute maternal stress after the events of September 11 ,16. Howele sizes -20. Pregle sizes ,23. Thusle sizes ,25.Mixed results regarding the events of September 11 and several birth outcomes may be reconciled, in part, by larger population-based analyses. The Department of Defense (DoD) Birth and Infant Health Registry includes births from all 50 states, the District of Columbia, and more than 20 foreign countries . As suchThe population for this study included up to 164,743 infants born to active-duty military families included in the DoD Birth and Infant Health Registry. Specifically, the cohort of infants "exposed" to the stress of September 11 during pregnancy was compared with a referent population composed of all infants born to US military families whose gestations were exactly comparable in timing from 2000 and 2002. Approximately 19% of infants in the database were born to women serving in the military; others were born to families in which the father was serving in the military .The primary data source for this study was the DoD Birth and Infant Health Registry . Since 1Demographic and military personnel data include maternal age , maternal military status (civilian or active duty), infant's military sponsor's education level , race/ethnicity , service branch , pay grade (enlisted or officer), and occupation .Infant sex was evaluated from birth records. Male:female sex ratio was calculated among infants born to women who experienced the stress of September 11 during their first trimester of pregnancy (0–13 weeks EGA), and compared with the referent population.International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM)[Major birth defects were evaluated using the definitions from the National Birth Defects Prevention Network , which iICD-9-CM) 4- and 5ICD-9-CM). Health Preterm birth was assessed using EGA, defined by ICD-9-CM codes for weeks of gestation, 765.0x-765.2x. Due to ICD-9-CM limitations, an infant's EGA at birth was assigned using the maximum end of each range. Infants born with less than 37 completed weeks of gestation were considered preterm. If more than one 5-digit code existed for a single infant, as might occur if EGA was revised over time, the most recent code assigned was used. Additionally, multiple births were excluded from this analysis, since multiple gestations would confound the evaluation of preterm delivery.Growth deficiencies in utero were examined using ICD-9-CM codes for slow fetal growth and fetal malnutrition (764.x), often clinically referred to as "small-for-gestational age" (SGA). These codes may be in the birth record, while codes for growth deficiencies in infancy may appear on records from birth through the first year of life. Growth deficiencies in infancy were examined using ICD-9-CM codes indicating lack of normal physiological development in childhood (783.4x). Code 783.42  was not included as a growth deficiency in infancy, since this code is not expected to be applied during the first year of life.The terrorist attacks of September 11, 2001 were considered a universal acute stressor. For analyses of male:female infant sex ratio and birth defects, exposed infants were defined as those born to women in their first trimester of pregnancy on September 11. The first trimester of pregnancy was considered 13 weeks after the onset of pregnancy, and was selected because this is the period of greatest vulnerability to teratogens or fetal compromise , and forThe referent group of infants for analyses of sex ratio and birth defects included those conceived exactly 1 year prior and 1 year after the exposed group. Specifically, the referent group included all infants with EGA zero between June 12, 2000 and September 11, 2000, and those with EGA zero between June 12, 2002 and September 11, 2002.The selection of a referent group that included conceptions 1 year prior and 1 year after the exposure of interest was intended to control for both seasonal variations and annual temporal trends in the outcomes of interest. It is possible, however, that infants conceived in 2002 would still be "exposed" to the stress of September 11, 2001 due to long-lasting sequelae from the attacks. Therefore, alternative analyses limited the referent group to only those infants conceived 1 year prior to the exposed group.To examine the outcomes of preterm birth and growth deficiencies in utero and in infancy, the exposed group of infants was expanded to include all those born to women who were pregnant, but less than full term, on September 11, 2001. Thus, the exposure group for these outcomes includes infants in utero, from 0–36 weeks EGA, on September 11, 2001. Full term may be clinically defined as pregnancy later than 37 completed weeks (252 days) EGA. Thus, the exposed group of infants in these analyses had EGA zero from January 2, 2001 to September 11, 2001, and were born after September 11, 2001.Consistent with the definitions above, the referent group of infants for analyses of preterm birth and growth problems included those conceived exactly 1 year before and 1 year after the exposed group. Specifically, the referent group had EGA zero from January 2, 2000 to September 11, 2000, and were born after September 11, 2000; or had EGA zero from January 2, 2002 to September 11, 2002, and were born after September 11, 2002. As above, alternative analyses limited the referent group to only those infants conceived 1 year prior to the exposed group.Univariate analyses, including chi-square tests, were conducted to determine significant associations between infant health outcomes and maternal exposure to the stressors of September 11 during pregnancy. Multivariable logistic regression analyses were completed, adjusting models for maternal age and other demographic variables. Regression diagnostics were applied. Presence of multicollinearity was assessed using the variance inflation factor, with a value greater than 4 suggesting presence of this condition. No variables in the models used met the threshold for multicollinearity. Adjusted odds of health outcomes of infants born to active-duty military families exposed in utero to the acute stress of September 11 were compared with infants born to active-duty military families in the referent population. Data management and statistical analyses were performed using SAS software version 9.1.3 .Male:female infant sex ratio and birth defects were evaluated based on exposure to the stressors of September 11, 2001 in first-trimester pregnancy, with referent groups in the first trimester of pregnancy in years 2000 and 2002. Of 61,088 infants born to military families in this timeframe, 49%  were female and 51%  were male. No differences in the male:female sex ratios of infants were observed among the 2000, 2001, and 2002 infant cohorts , with respect to most parental demographic variables. Infants born to women of advanced maternal age (≥ 35 years) had a significantly higher prevalence of birth defects  compared with infants born to younger women. No significant association was found between infants in utero, from 0–13 weeks EGA, on September 11, 2001, and birth defects, relative to infants in the referent population .Infants with at least 1 major birth defect, defined by ICD-9-CM coding in the first year of life, accounted for 4.9%  of the study population. Table Preterm birth, growth deficiencies in utero, and growth deficiencies in infancy, were evaluated based on exposure from 0 to 36 weeks EGA, on September 11, 2001, with referent groups in the same time interval in 2000 and 2002. There were 164,743 infants who met these criteria and were included in these analyses.Approximately 7% of infants in this population were born preterm. Of these 11,453 infants, 3,761 were in utero on September 11, 2001. Table The logistic regression models for growth deficiencies in utero and growth deficiencies in infancy adjusted for the same covariates as the previous models Table . There wIn alternative models, infants in utero from 0 to 13 weeks EGA, on September 11, 2000, were considered the referent group for the analysis of birth defects and sex ratio. Infants in utero, from 0 to 36 weeks EGA, on September 11, 2000, were considered the referent group for analyses of preterm birth, growth deficiencies in utero, and growth deficiencies in infancy. No statistically significant associations were observed between maternal exposure to September 11 and birth defects, preterm birth, and growth deficiencies in utero or in infancy. Detailed results from the alternative analyses are not shown.In this study, we analyzed specific health outcomes of infants in utero during the terrorist attacks of September 11, 2001, and compared them with infants in utero in the preceding and following years (2000 and 2002). We found no significant associations between exposure to this putative maternal stressor and adverse outcomes. Specifically, infants born to exposed women had the same sex ratio, prevalence of birth defects, prevalence of preterm births, and prevalence of growth deficiencies as infants born to the referent population. These findings were consistent when alternative referent populations were considered.Using the terrorist attacks of September 11, 2001 as a crude measure of acute maternal stress, we hypothesized that birth defects and the male:female sex ratio might be different among infants exposed to such acute maternal stress in the first trimester of pregnancy. Prior studies suggest that sex ratios may differ after maternal exposure to September 11, 2001 ,16. ExpoWe further hypothesized that the prevalence of preterm births and growth deficiencies in utero and growth deficiencies in infancy might be different among infants exposed to the maternal stress of September 11, 2001 at any time during pregnancy. Exposure at any time in the gestational period, up to full-term EGA, was considered when evaluating these outcomes because such exposures could plausibly affect preterm birth, fetal growth, or infant growth . Again, Although our findings may be applicable to the general population, the possibility exists that military families experienced the stress of September 11, 2001 in unique ways. One study has suggested that military members experienced healthy psychological responses in the months after the terrorist attacks . The autThe effects of acute maternal stress on pregnancy outcomes are complex. Most prior studies following natural disasters, such as earthquakes and nationally stressful events , suggest that maternal stress plays a role in birth outcome ,41. SimiDefining acute maternal stress based on the date of September 11, 2001 makes several assumptions about the event, since the stress was experienced differently by many individuals. This study cannot account for self-reported perception or response to the stressful event on an individual basis, and could contribute to the lack of significant findings in this study. Nonetheless, the objective measure of a catastrophic event limits biases related to recall and response. Other limitations of our analyses may relate to use of health care databases to define EGA and ICD-9-CM-code outcomes. Although validated on several measures, health care databases contain a margin of error that can influence results. Any misclassification bias resulting from the use of these databases was likely to be nondifferential. Finally, military databases, while providing extensive demographic information, are vulnerable to some unique limitations. In particular, births to both married and unmarried military women are identified in the DoD Birth and Infant Health Registry, but only births to married military men are identified since partners of unmarried men are not military beneficiaries. Also, distinguishing births to dual-military parents was not possible, since only one parent can be identified as the military sponsor of a beneficiary child in the databases. Defining the exposed and referent groups from the same population, however, should have mitigated any challenges related to such idiosyncrasies.Despite these limitations, the analyses contain valuable information. The DoD Birth and Infant Health Registry is well positioned to study birth defects, preterm births, and growth problems in utero or in infancy because the database contains all available medical diagnoses during the first year of life. This information is especially important for birth defects diagnoses that may present weeks or months after delivery. In addition, the large sample size of geographically diverse infants makes the detection of rare events possible.In summary, findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes. Future analyses, such as those planned using prospective data from the Millennium Cohort , remain CRH: corticotropin-releasing hormone; DoD: The Department of Defense; ICD-9-CM: International Classification of Diseases 9th Revision, Clinical Modification; EGA: estimated gestational age: SGA: small for gestational age.The authors declare that they have no competing interests.SME, MAKR, CJS, ASC, CAM and TCS were responsible for the design, planning, analysis, writing, and revising of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


We report a rare case of non-communicating large orbital cyst with microphthalmos which was surgically separated from the globe and excised. Histopathology reported it to be a teratoma. Congenital cystic teratoma should be a part of the differential diagnosis in an infant presenting with a clinical picture of microphthalmos with orbital cyst, in view of the different management required. A congenital orbital teratoma is an extremely rare benign tumor2 which cA seven-month-old female child presented with history of mass lesion in the left lower lid since birth which was progressively increasing in size. Examination revealed a swelling in the lateral two-third of left lower lid, bluish in color and measuring 3 × 3 cm. The swelling was soft, fluctuant, with ill-defined borders and the surface had engorged blood vessels. It was nontender and did not increase in size on crying. The lower tarsal conjunctiva was everted and mechanical ectropion was visible . The rigThe specimen consisted of a flattened cyst like structure measuring 2.5 cm in diameter. It had congested outer surface and smooth inner surface. There were large areas containing multiple cysts. Microscopic examination revealed tissue derived from all three germ layers. The wall of the cyst was lined focally by tall columnar epithelium . There wPostoperative evaluation revealed a microphthalmic eye with no light fixation. The ocular movements were present with some limitation in abduction only. Microcornea was opaque with no view of anterior segment details. Patient's parents were explained about the poor visual prognosis and the need for ocular prosthesis. One year postoperatively there was no recurrence.The clinical presentation of primary congenital orbital teratoma is spectacular. Extreme proptosis at birth, coupled with a developmentally intact globe and an orbital mass having a variegated appearance and consistency, is essentially diagnostic of primary orbital teratoma. ClinicalHistopathologically, teratomas are benign growths of mature and immature tissues characterized by aggregations of well-differentiated tissue of diverse germ cell origin. The predIn conclusion, though congenital orbital teratoma is characteristically associated with a developmentally normal globe, rarely the globe could be microphthalmic. Orbital teratoma must be considered in the differential diagnosis of a child presenting with an orbital mass and a small or unrecognizable eye. In such cases prompt surgical excision is the treatment of choice.


EHP 116:1071–1076; Akre et al.][.Hypospadias is a male birth defect in which the opening of the urethra is located on the underside of the penis instead of the tip. Although the defect is common and increasing in prevalence , the causes of most cases are unknown. Some studies suggest that reduced levels of the placental hormone human chorionic gonadotropin (hCG) may play a role; others suggest associations between hypospadias and conditions such as low birth weight, preterm birth, and preeclampsia that could be caused by malfunction of the placenta and subsequent abnormalities in hormone regulation and nutrition provided to the fetus . A new study now presents additional evidence that hypospadias has its origins in malfunction of the placenta Data on 292 cases of hypospadias and 427 controls were collected as part of a joint Danish–Swedish study of both hypospadias and cryptorchidism (undescended testes). In Sweden, hypospadias cases were recruited at a pediatric surgery clinic, and data were collected via self-administered questionnaires. In Denmark, cases were from the Danish National Birth Cohort, a population-based cohort of women and children. Mothers were interviewed while pregnant and twice after delivery. Matched controls were born within at least 6 months of each case and within the same county, and were randomly selected from national birth and population registries.The investigators found several conditions independently associated with increased hypospadias risk, most of which they say could be explained by impaired production of hormones by the placenta. Mothers without first-trimester nausea were twice as likely to bear sons with hypospadias, as were mothers who had a prepregnancy body mass index of 30 or greater. These findings support the theory that placental insufficiency contributes to hypospadias. Nausea is believed to be caused by an early surge of pregnancy hormones, and the absence of first-trimester nausea is associated with low hCG levels. A previous study showed that obese women have lower levels of a family of proteins called plasminogen activator inhibitors, some of which are derived from the placenta.The team also determined that a maternal diet lacking both fish and meat was associated with more than a fourfold increased risk of hypospadias in baby boys. This finding complements a 2000 study by other authors that showed a strong positive association between maternal vegetarian diet and hypospadias in offspring. The authors of the current study conclude that exclusion of animal proteins could increase the risk of a transient deficiency of some nutrient that’s essential for formation of the organs or the placenta. Another explanation is that some protein sources in vegetarians’ diets (such as soybeans) contain compounds with hormonal effects that may affect the development of the urogenital organs in humans.