Hydatic disease has always been the most common in countries where large amount of sheep and cattle is raised, but increased travel and immigration have made this condition a serious worldwide public problem. Cyst hydatid may affect all parts of the human body like the heart, the bone marrow, the eye, the brain, the kidney, and the spermatic cord. Humans can become infested by accidentally ingesting the eggs that are passed in the feces from definitive hosts . Even in endemic countries, the primitive pleural hydatid cyst is exceptional, and it is very difficult to distinguish from other pleural and parietal cystic masses especially that in majority of cases the immunologic tests are negative. We report two cases of pleural hydatid cyst discovered in two young patients, with a nonspecific clinical presentation. The interest of this paper is to raise the primordial role of imaging in the positive diagnosis of primary pleural hydatid cyst. Hydatidosis is a parasitic disease caused by the development in humans of the larval form of Echinococcus Granulosus, a small dog tapeworm. Pleural localization is extremely rare even in endemic countries and represents only 1.3% of thoracic locations [We report two observations of primary pleural hydatid cyst by insisting on the fundamental place of different imaging techniques in diagnosis.Miss A. L., a 17-year-old girl, with no pathological history and no notion of contact with dogs, reported since 3 months right thoracic pain, stage III of mMRC dyspnea, chest tightness, and some episodes of hemoptysis of low abundance evolving in a context of apyrexia, and conservation of the general state. The clinical examination revealed a right fluid effusion syndrome. The posteroanterior chest roentgenogram showed a homogeneous right basal opacity that effaced the diaphragmatic cupola and merged with mediastinum; its upper limit is convex .Thoracic ultrasonography revealed an intrapleural cyst with a duplication of its wall suggesting a proliferative membrane without associated pleurisy .∗ 93 ∗ 93 mm, with a discreet slope with the adjacent parenchyma; its wall was thickened and enhanced after injection of contrast product. The lung parenchyma was without anomaly with the exception of passive atelectasis adjacent to the cyst, confirming the diagnosis of a right pleural cyst type II of Gharbi classification , hence the primitive character of pleural hydatidosis in our observation. During surgery, the presence of a cystic formation in the parietal pleural was noted. The delicate dissection had objectified thickened visceral pleura. The cystectomy was successfully performed without rupture and the piece was sent to the parasitology laboratory with evidence of proliferative membrane  and alive scolex in the intracystic fluid  .Mr. SF, a 26-year-old man, without any notable pathological history, have a notion of contact with dogs in childhood, asymptomatic on the respiratory plane. The posteroanterior chest roentgenogram was performed for him as a preemployment checkup. It objectified a homogeneous oval opacity, well limited, left hilar, and having the internal edge in intimate contact with the left edge of the heart .In this context, a chest CT scan revealed a left anterolateral mediastinal mass with a total parietal calcification measuring 70 mm in height and 55 mm in lateral diameter .∗ 53mm. Its tonality was hypointense on T1 and hyperintense on T2  showed a mediastinal cyst next to the anterolateral wall of the left cardiac ventricle, in close contact with the pericardium but with a cleavage plane and no mass effect on the cardiac cavities, measuring 72mm se on T2 .The blood count was normal and the ELISA and Indirect Agglutination serologies were negative. In a second stage, the research for other localizations of the hydatid cyst was negative , hence the primitive character of pleural hydatidosis in this second observation. In operation, the heart was of normal volume with no intrapericardial mass. At the opening of the left pleura, the exploration found a solid mass contiguous to the mediastinal pleura and in contact with the left phrenic nerve. The careful dissection and excision of the mass were successfully performed without complications.The hydatid cyst is a parasitic disease that is still endemic in several parts of the world, especially around the Mediterranean rim. The lung constitutes the second hydatid localization 20 to 40%) after the liver (75%). The primary pleural localization is exceptional, representing only 1.3% of thoracic locations [0 to 40% Once a human has been infested with the taenia eggs, gastric and enteric digestion facilitates the release of larvae, which penetrate the intestinal wall until they reach a small vessel system. Passing through the bloodstream, they arrive at the organ where they can settle and transform into small cysts that increase in size by 2 to 3 cm per year. The usual locations are the liver and lungs; intrathoracic but extrapulmonary locations like the pleura, diaphragm, mediastinum, pericardium, and chest wall are uncommon. Pleural hydatid cysts can develop chiefly as a result of liver or lung cyst rupture into the pleural space with complications of pneumothorax, pleural effusion, or empyema . The pleThe clinical symptomatology is poor and nonspecific; it can simulate any pleural-pulmonary disease . The diagnosis can be made in the acute phase in front of a symptomatology of sudden onset of thoracic pain and dyspnea, following the rupture of the cyst. In other cases, this new location may remain asymptomatic for a long time and the diagnosis can be done tardily. Exceptionally, there may exist some signs of mediastinal compression depending on the location. The discovery can also be fortuitous on a chest roentgenogram , 7. As rImaging is a fundamental element for positive diagnosis. The chest roentgenogram shows a homogeneous pleural opacity, well-defined with water tonality. Rarely, it shows peripheral calcifications that it orientates the diagnosis. In some cases, radiography may guide the diagnosis at an early stage by showing characteristic iconography, such as the presence of cystic formation having a calcified wall, which is rare but represents a strong diagnostic presumption; the chest roentgenogram in our second patient was very characteristic and diagnosis was very probable; the other investigations had an objective to determine the exact localization of the cyst . Ultrasound is a second-line examination; it is very efficient with a diagnostic specificity estimated at 96%. It can make the diagnosis and make the extension assessment and the surveillance, as the case of our first patient ; it can Biologically, hypereosinophilia is generally absent in cases of intrathoracic hydatid disease. Immunological tests such as IgG ELISA, indirect hemagglutination, and Western Blot may be helpful, but their sensitivity is only about 60%. A combination of two or more biological tests and radiological imaging should be used for accurate diagnosis [In the absence of rupture, the puncture of the cyst is formally contraindicated, which explains why cytological or pathological diagnosis is usually performed only after its surgical excision .The positive diagnosis is difficult to establish due to the rarity of the condition and the lack of clinical, radiological, and biological specificity. Indeed, several other causes of cystic lesions can be evoked: bronchogenic cyst, enteric cyst, pleuropericardial cyst, thymic cyst, and lymphangioma. The diagnosis of certitude is almost always operative by visualizing the hydatid membrane and/or daughter's vesicles or after pathological study of the operative piece in case of infected or thickened cyst . The mobAs a general rule, when the presurgical diagnosis of hydatid cyst is suspected, surgeon should take care of four things in order to achieve complete resection and to avoid recurrence of disease from pleural hydatid cysts:(i) Three days before emergency resection if necessary and 1 week before elective surgery albendazole treatment should start to increase the blood and tissue concentration of the medicine in case of the risk of contamination(ii) Plan the appropriate surgical approach to prevent cystic rupture or spillage when doing the thoracotomy.(iii) Inactivate daughter cysts and scolices prior to removal by injecting 20% hypertonic saline solutions into the cyst.(iv) To give the anticoloidal agent into the cyst, it is necessary to empty some of the cyst content; otherwise, it will leak out of the injection site during surgery. Distention may be reduced by aspiration, and this will ease the manipulation and surgical dissection.(v) Do not spill cyst contents during surgery to avoid anaphylactoid reaction, recurrence, and multiple hydatidosis.(vi) Completely remove of the cyst including the innermost germinative layer, which can produce scolices, with en-bloc excision whenever possible; sometimes, to avoid recurrence, it is necessary to resect the affected surrounding tissues completely.Postoperatively, it may be necessary to place patients on an anthelmintic medical regimen (Albendazol) with appropriate follow-up reevaluations .The primary pleural localization of the hydatid cyst is very rare or even exceptional. Its discovery is often fortuitous. More rarely, primary pleural hydatid cyst is symptomatic with a discreet and nonspecific clinical presentation. Imaging especially in section, plays a fundamental role; it makes it possible to guide the diagnosis, to specify the topography and the relations with the neighboring organs, and to look for other localizations.The feature of our observations, compared to literature, is the similarity to the young age, the discreet clinical presentation, the absence of hypereosinophilia, the negative hydatid serology, and especially the diagnostic orientation thanks to imaging.


Despite positive changes in most maternal risk factors in Brazil, previous studies did not show reductions in preterm birth and low birthweight. We analysed trends and inequalities in these outcomes over a 33-year period in a Brazilian city.Four population-based birth cohort studies were carried out in the city of Pelotas in 1982, 1993, 2004 and 2015, with samples ranging from 4231 to 5914 liveborn children. Low birthweight (LBW) was defined as <2500 g, and preterm birth as less than 37 weeks of gestation. Information was collected on family income, maternal skin colour and other risk factors for low birthweight. Multivariable linear regression was used to estimate the contribution of risk factors to time trends in birthweight.Preterm births increased from 5.8% (1982) to 13.8% (2015), and LBW prevalence increased from 9.0% to 10.1%, being higher for boys and for children born to mothers with low income and brown or black skin colour. Mean birthweight remained stable, around 3200 g, but increased from 3058 to 3146 g in the poorest quintile and decreased from 3307 to 3227 g in the richest quintile. After adjustment for risk factors for LBW, mean birthweight was estimated to have declined by 160 g over 1982–2015 (reductions of 103 g in the poorest and 213 g in the richest quintiles).Data from four birth cohorts show that preterm births increased markedly. Mean birthweights remained stable over a 33-year period. Increased prevalence of preterm and early term births, associated with high levels of obstetric interventions, has offset the expected improvements due to reduction in risk factors for low birthweight. Preterm birth and low birthweight are major risks factor for neonatal, infant and under-five mortality. Globally, 16% of all children are born with low birthweight ,LBW may result from preterm delivery, intrauterine growth restriction or a combination of both. A systematic review found that each of these conditions contributes to approximately half of all LBW babies.Fetal or intrauterine growth restriction  was estimated to affect 19.3% of all babies born in low- and middle-income countries in 2012.In 2008, we reported on trends in birthweight and preterm births in three population-based birth cohorts in the city of Pelotas in 1982, 1993 and 2004.Over the course of the years of 1982, 1993, 2004 and 2015, all hospital births in the city of Pelotas were identified through daily visits to all maternity wards, and mothers who lived in the urban area were invited to join the studies. Those who accepted were interviewed by the study team using a structured questionnaire, and anthropometric data were obtained from the women and their newborns. Methodological details of each cohort  are provided elsewhere.Newborns were weighed within 24 h of birth, using paediatric scales with a precision of 10 g, in each participating hospital. LBW was defined as a birthweight below 2 500 g.The method of assessment of gestational age changed over time. In 1982 and 1993 it was based on the date of the last menstrual period (LMP) provided by the mother, and unknown and unreliable cases were excluded. These represented 21.0% and 10.2% of all newborns, respectively. In 2004 and 2015, we adopted the best obstetric estimate based primarily on first- or second-trimester ultrasound when available. When ultrasound was not available, the estimate was based on the LMP. For the 2004 and 2015 cohorts, we also present estimates based solely on the LMP for comparability with the earlier cohorts.Mothers were interviewed during the hospital stay and provided information on monthly family income, calculated from the sum of incomes of family members, and divided into quintiles. As noted in a previous publication,2), smoking during pregnancy , parity , preceding birth interval , antenatal care  and marital status . In the multivariable analyses, income was measured in minimum wages at the time of each cohort, and coded as <=1.0, 1.1–3.0, 3.1–6.0, 6.1–10.0 and >10. Details on the instruments used to collect these variables are available in other articles in this issue.For the multivariable analyses, information was also collected on known risk factors for birthweight which were measured in the four cohorts, including maternal age , schooling , height , pre-pregnancy body mass index  and concentration index (CIX) were calculated to assess absolute and relative inequalities. The SII can be interpreted as the difference, in percentage points, between prevalence at the top and at the bottom of the income scale; it ranges from -100% to 100% points. The concentration index is a measure similar to the Gini coefficient; a value of zero indicates perfect equality, whereas negative values indicate higher prevalence of the outcome among the poor.All analyses were restricted to live, singleton newborns.Ethical approval for studies was not required in Brazil until 1996. The 2004 and 2015 studies were each approved by the Ethics Committee of the School of Medicine and School of Physical Education, Federal University of Pelotas, and written consent was obtained from the mothers.The numbers of liveborn singletons in the four cohorts were 5816, 5168, 4147 and 4164. Birthweight information was missing for 5 (0.09%), 17 (0.33%), 1 (0.02%) and 13 (0.31%) children, respectively.For consistency, we reanalysed the data from the four cohorts using only the date of the LMP to assess gestational age, instead of also using ultrasound results in the two more recent cohorts. The resulting prevalences of preterm birth were 5.8%, 11.2%, 16.2% and 17.7% in 1982, 1993, 2004 and 2015, respectively. The corresponding prevalences of early term births were 21.9%, 19.7%, 27.6% and 33.0%.P for trend = 0.80). Mean birthweight also remained stable at around 3.2 kg (P for trend = 0.47)The distribution of birthweights was remarkably similar in the four cohorts, as was the case for the mean and standard deviation values. The proportion of newborns with low birthweight remained stable at around 8% to 9% throughout the period  1.3] in 1982, -4.5 (SE 1.4) in 1993, -7.6 (SE 1.6) in 2004 and -4.7 (SE 1.6) in 2015. The concentration indices for relative inequalities were equal to -16.3 (SE 2.5) in 1982, -8.9 (SE 2.5) in 1993, -13.3 (SE 3.0) in 2004 and -9.5 (SE 3.0) in 2015. Both indices show that inequalities remained unchanged during the study period.P for trend 0.004) and decreased by 57 g (P = 0.049) in the fourth and by 80 g (P < 0.001) in the richest quintile. The mean difference between the richest and poorest quintile fell from 249 g in 1982 to 81 g in 2015. Regarding maternal skin colour, mean birthweight remained stable for children born to white mothers, but increased by about 60 g (P = 0.01) for those born to black and brown-skinned women.Similar analyses for mean birthweight are shown in Because there were important changes in the distribution of risk and protective factors associated with birthweight , we usedOur results show that preterm and early term births increased markedly over a 33-year period in the Brazilian city of Pelotas. For gestational age, changes over time are affected by differences in the methods of assessment of gestational age, and the high proportion of missing cases in 1982 and 1993 when only the date of the last menstrual period was used. Missing data were more common among less educated and poorer mothers, and thus the prevalence of preterm births was likely underestimated in the early cohorts. With increased use of ultrasound during pregnancy, our methods of gestational age assessment changed in the 2004 and 2015 cohorts. In the latter, 84.4% of all newborns had ultrasound results during the first or second trimester recorded in their mother’s antenatal cards, and the prevalence of preterm birth for these gestations was 13.8%. During the postpartum interview, 90.7% of the mothers provided information on the date of the last menstrual period, and the prevalence of preterm birth was 18.9%. Even if prevalence for gestations with missing data was twice as high for gestations with existing information as those with data, the corrected prevalence would be 7.0% in 1982 and 12.4% in 1993, which are lower values than for the more recent cohorts. The rise in preterm births was even more marked when we analysed the four cohorts using LMP data. Therefore, in spite of different methods being used in each study, there is strong evidence of an increase in preterm deliveries in Pelotas.The increased preterm prevalence had been described in our earlier publication,One important finding of our study is that—for the whole population—mean birthweight and LBW prevalence remained stable. The only other Brazilian study spanning several decades was carried out in the southeastern city of Ribeirão Preto and showed an increase in LBW from 7.2% to 10.7% from 1978–79 to 1994.Our results are compatible with other Brazilian studies. Prevalence of low birthweight in Latin America is estimated at 9%, with 7% in Argentina and 8% in Uruguay, countries that are closest to Pelotas.,Brazilian studies on LBW suggest that the main risk factors include low family income, low education, black or brown skin colour, young maternal age, short stature, low pre-pregnancy weight, primiparity, short birth intervals, lack of prenatal care and maternal smoking during pregnancy.The findings from this regression analysis support the hypothesis that obstetric interventions, which increased over time and are particularly frequent among high-income women, may explain why birthweights failed to increase in accordance with the reduction in the prevalence of risk factors. A simple comparison of birthweights in vaginal and cesarean deliveries is not useful, because the latter include a mixture of procedures with medical indications (associated with lower birthweights due to morbidity) and those without medical indications (which would primarily affect women of high socioeconomic position whose newborns should present higher birthweights). We do not have comparable data on reasons for caesarean sections in the four cohorts, and in addition there are indications that obstetricians may often report medical indications for purely elective procedures; for these reasons, it was not possible to separate these two categories of caesarean sections and assess their specific associations with birthweights.Time trends in low birthweight prevalence according to income groups were not as clear-cut as for mean birthweight, which suggests that the main impact of caesarean sections has been on babies born weighing 2500 g or more. This is consistent with the marked increase in the prevalence of early term deliveries at 37–38 weeks, from 22.3% in 1982 to 37.1% in 2015, which must have had a negative impact on mean birthweight. The hypothesis is also supported by the actual decline in mean birthweight among children born to wealthy women , accompaDuring the 33-year period covered by our cohorts, there have been substantial improvements in maternal and child health in Brazil as a whole,At the population level, mean birthweight remained stable from 1982 to 2015, as did low birthweight.Preterm birth prevalence increased markedly, despite changes in methods of ascertainment over time.The stability in mean birthweight resulted from a combination of increases among children born to women in the poorest quintiles and declines in the richest quintiles.The prevalences of most risk factors for low birthweight were markedly reduced over time; after adjustment for these factors, it is estimated that mean birthweight declined by 160 g from 1982 to 2015.The most likely explanation for these results is the extremely high prevalence of caesarean section, particularly among rich women, with a resulting increase in preterm and early term deliveries due to schedule deliveries.The four cohorts received funding from the following agencies: Wellcome Trust, International Development Research Centre, World Health Organization, Overseas Development Administration of the United Kingdom, European Union, Brazilian National Support Program for Centres of Excellence (PRONEX), Brazilian National Council for Scientific and Technological Development (CNPq), Science and Technology Department (DECIT) of the Brazilian Ministry of Health, Research Support Foundation of the State of Rio Grande do Sul (FAPERGS), Brazilian Pastorate of the Child, and Brazilian Association for Collective Health (ABRASCO).1 Ana M B Menezes,1 Andrea Dâmaso Bertoldi,1 Diego G Bassani,2 Fernando C Wehrmeister,1 Helen Gonçalves,1 Iná S Santos,1 Joseph Murray,1 Luciana Tovo-Rodrigues,1 Maria Cecilia F Assunção,1 Marlos Rodrigues Domingues1 and Pedro R C Hallal1Aluisio J D Barros,1Federal University of Pelotas, Brazil and 2University of Toronto, Canada.Conflict of interest: None declared.


Clostridium tetani that thrives in an anaerobic environment  is defined as “a neonate with the normal ability to suck and cry during the first 2 days of life, and between 3 and 28 days of age cannot suck normally and becomes stiff or has spasms” . In the immunization and clean delivery and cord care practices (and to much extent surveillance as well)  , 8, 10. as well) –13. Mainas well) . Traditias well) –17. The as well) , 16. In as well) .Neonatal tetanus is historically neglected as a health problem in developing countries . This isTo date, 14 countries have yet to achieve elimination goal in 2020 and where maternal and neonatal tetanus remains a big challenge mainly due to wars, conflicts, and politically vulnerable environment. These include Afghanistan, Angola, Central African Republic, Chad, Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, Sudan, South Sudan, and Yemen  28). In. In28). immunization. Tetanus toxoid vaccine is available as a monovalent tetanus toxoid, a bivalent toxoid combined with diphtheria or reduced diphtheria toxoid content, or a trivalent vaccine combined with diphtheria and whole cell or acellular pertussis (DTP vaccine). Other vaccine combinations with hepatitis B, Hemophilus influenzae type b, and polio also exists  are employed in areas deemed to be high risk for neonatal tetanus where the first approach may not be effective. In SIAs, opportunities for vaccination are provided beyond the conventional antenatal settings such as school-based programs, markets, and community-based settings. Worldwide, the additional application of SIAs has been helpful in making significant progress in many countries between 1999 and 2013 (The elimination initiative for maternal and neonatal tetanus uses two immunization approaches. The first approach most commonly used is the and 2013 , 32, 33.and 2013 . The autThe second elimination strategy for maternal and neonatal tetanus is improving birth hygiene or practicing clean deliveries. The importance of clean practices during delivery has been emphasized for centuries from times of Ancient Greeks and from texts of Avicenna . One of High neonatal mortality rates are observed in developing countries due to neonatal umbilical cord infections. Preventions of these infections involve practicing “six cleans” along with increased coverage of tetanus toxoid immunization. However, in regions of the world where vaccination and immunization are now viewed with suspicion , 26, proWHO has been endorsing supply of clean birth kits that are disposable in resource-poor settings for many decades , 40. ThiAvailability of skilled birth attendants such as doctors, nurses, and trained midwives who have access to clean services in health care facilities are crucial in reducing neonatal deaths. While availability of skilled attendants is accepted as benchmark in many countries, this alone is not enough to bring down neonatal mortality in a short period of time in less developed countries . Again, Maternal and neonatal tetanus cannot be eradicated because of the ubiquitous nature of the bacterium in the environment, and therefore continuous efforts are needed to invest in vaccination programs for its elimination. However, in some lower- to middle-income countries of the world, these elimination programs through vaccination are likely to face multiple serious challenges on a similar pattern as in the case of other vaccine-preventable diseases , 23, 49.In many countries, maternal and neonatal tetanus were eliminated through clean delivery practices even before vaccines were introduced; e.g., clean cord care practices through skilled delivery assistance have been shown to be an effective intervention in reducing neonatal mortality by 50–70% . A studyClean birth kits to ensure clean practices have shown to be a promising strategy in reducing maternal and neonatal morbidity and mortality , 53, 54.The main limitation in literature regarding clean delivery practices through clean birth kits has been the lack of good quality data assessing the effect of these kits on neonatal outcomes. Since it would not be ethical to randomize expectant mothers to receive or not receive birth kits during the time of delivery, there are very few randomized trials highlighting the effectiveness of these kits. A clustered randomized trial carried out in rural Pakistan examined the effects of training traditional birth attendants with the supply of clean birth kits; however, the specific contribution of kit usage in reducing mortality could not be estimated . EvidencBased on pooled estimates from epidemiological studies and extensive review by Blencowe et al. , facilitEven though clean birth kits have shown to have the potential to improve quality of care at birth, some questions still remain. One important issue to understand is whether mothers using the kits act as a disincentive for giving birth in the hospitals. Further information can be gained through new surveys and analyses of existing research datasets in developing countries. Another important public health priority is regarding the question of cost and health system impact of adding more contents in birth kits such as disinfectants like chlorhexidine or labor-inducing medications such as misoprostol for highly trained delivery attendants. Here, “Implementation Science Research” will be needed for these add-ons for additional contents. For these add-ons, extreme caution should be practiced; e.g., labor-inducing medications should not be available to untrained delivery attendants. Then, there is also a question of facility-based kits in low-resource settings that could be much more extensive with the inclusion of a blood pressure device and a suction device with other essential drugs. Implementation research will again be required to examine advantages in their efficiency over alternative approaches.coverage of immunization and quality of antenatal care. This, however, requires a very proactive approach to invest in human resources of developing countries such as health care workers who have deep roots with their communities and who are well equipped with essential supplies for basic, safe, and clean delivery practices.Because of the increasing provision of vaccines, under-five mortality has been declining. However, in order to further accelerate progress toward Sustainable Development Goals in developing regions of the world, a major focus must be placed on increasing conflict or humanitarian emergencies or in settings where facility-based clean deliveries are not always possible. For countries that are already planning to promote clean birth kits or adding new contents, it will be crucial to collect data on their experiences, e.g., implementation techniques, impact, as well as costs involved.Clean birth kits have already been made available in many developing countries; however, as pointed out in Blencowe's policy brief , robust SR carried out the literature review and wrote the first draft of the manuscript. BA provided critical revisions of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Neurodevelopmental disability (NDD) is increasingly acknowledged as one of the important causes of disease burden in low income countries. None the less, there is a dearth of data on the burden of NDD and its determinants in these settings. We aimed to establish the prevalence and factors associated with NDD among infants in Eastern Uganda.We assessed 487 infants aged 9–12 months within Iganga-Mayuge Health Demographic Surveillance Site in Eastern Uganda using the Malawi Developmental Assessment Tool. The tool has four domains: gross motor, fine motor, language and social domains. An infant failed a domain if she/he failed more than two parameters of the expected at his/her age.We interviewed mothers on factors that could influence the infants’ neurodevelopmental outcomes. Data were analysed using STATA version 14. We used odds ratios and 95% confidence intervals to assess statistical significance of associations.Of the 487 infants, 62(12.7%) had an NDD in at least one of the domains. The most affected was social behaviour where 52(10.7%) infants had an NDD. Severe impairment was seen among 9(1.8%) infants with NDD in either three or four domains.Factors associated with NDD at multivariate logistic regression included: parity of more than three children ; failure to cry at birth  and post-neonatal complications . Low birth weight, immediate and exclusive breast feeding were not significantly associated with NDD.We found a high NDD burden among infants particularly in the social behaviour domain. To optimise the socio-neural development of infants, programs are needed to educate and work with families on how to engage and stimulate infants. Existing immunisation clinics and community health worker strategies provide an excellent opportunity for stemming this burden. Globally, for the past decade there have been significant strides to curb neonatal and infant mortality, albeit with an increased risk of neurodevelopmental disabilities (NDD) –3. More According to the bio-ecological systems theory of early child development, biological and environmental risk factors have a complex interaction that may result in NDD . The envBiological risk factors on the other hand, comprise of insults to the unborn baby, including poor health status and nutritional deficiencies during the prenatal period, child birth, infancy and early childhood .There is consistent evidence showing that newborn babies suffering from conditions such as sepsis/infections, asphyxia (defined as failure to cry at birth at community level), premature birth, low birth weight and pathological jaundice have a higher likelihood of NDD , 13–15. In Uganda, more than a quarter of births occur at home or with the aid of unskilled traditional birth attendants who are not considered effective to reduce the burden of ill-health but pose a higher risk of intrapartum complications and resultant NDD , 18. TheThe Uganda national policy framework on early child development gives guidance for access to quality services for all children from conception to eight years. These services include education, nutrition, child protection, health care, family and community support and empowerment. Despite the existence of this policy framework, implementation of some essential interventions is still inadequate . For insTo inform policies and programming for appropriate responses and actions in the country and areas with similar settings, this study aimed at assessing the prevalence of NDD and associated factors among infants aged nine to twelve months of age in a health demographic site in Eastern Uganda. This study focused on health care factors that can potentially influence neurodevelopmental outcomes during pregnancy, child birth, neonatal and the post-neonatal period. In addition, we also assessed the demographic and socio-economic factors of the parents.Basoga, the third largest ethnic tribe in Uganda. Generally, in this context, there is preference for large families, and child rearing is mostly the responsibility of the mother. However, due to the many responsibilities of women, children are usually left to play with fellow children, and parents are rarely involved in active stimulation of their children. There is also an extended family system with controlling parenting practices by multiple family members, like the rest of the country [We conducted a cross-sectional study in December 2017 in the Iganga/Mayuge Health Demographic Surveillance Site (HDSS) in Eastern Uganda. The HDSS has 65 villages with a population of about 86,000 people who are mostly (80%) rural and practice subsistence farming. Most of the people in the study area are  country . The tot country . The neo country .We used data of the surveillance round done between March and May 2017. Five hundred seventeen infants born between January and March 2017 (who were expected to be nine to twelve months in December 2017) were identified. Information captured from the surveillance round data included: the villages, household heads, and mothers’ names, names of the babies and dates of birth. Household identification numbers were also recorded and used to help in physical identification of the homesteads during data collection.kappa of more than 0.75.We carried out neurodevelopmental assessments using the Malawi Developmental Assessment Tool (MDAT) in December 2017. The MDAT tool has four developmental domains: Gross motor, Fine motor, Language and Social behaviour. The tool was created and validated to assess neurodevelopmental outcomes of children in rural African setting from birth to six years. The validation tests of the MDAT tool indicated high sensitivity and specificity to identify NDDs of 97 and 82% respectively . SimilarIn our study, the assessment involved getting a parental report, observation with a checklist, and direct administration to the child. Table In addition to assessment using the MDAT tool, the infants were evaluated on other neurodevelopmental parameters such as sight, hearing and whether the infant had had any convulsions. We placed a dangling object in front of an infant to assess whether he/she could track and reach out. Similarly, observations were made on whether the child could turn towards the direction of a rattling noise. In case of a history of convulsions, we ruled out any associated fevers to enable differentiation of febrile convulsions from convulsions due to neural impairment. We also measured the head circumference of infants using a tape measure, and took their body weights using Seca scales.The mothers were interviewed on socioeconomic and demographic characteristics, and health care practices which could potentially affect the neurodevelopment of the infant such as antenatal care (ANC) attendance, vaccination with tetanus toxoid, uptake of sulfadoxine pyrimethamine to prevent malaria, and ferrous sulphate and folic acid tablets. We also included delivery care practices  at birth of the child, and birth outcome), and postnatal practices . In addition, we asked for a history of post-neonatal complications defined as any danger sign  after the neonatal period.Data from the MDAT and on risk factors as assessed in the interviews with the mothers were processed  using EPIDATA version 3.2 and exported to STATA version 14 for analysis.p-value = 0.2 in the univariate analysis, together with factors known a priori to be predictors of NDD  were included in multivariable analysis. The model was refined by backward elimination using the change in log likelihood ratio of successive models with a significance level of 0.05. Variables were tested for collinearity by examining correlation coefficients, and if found to be related one was dropped.Descriptive statistics were generated on socio-demographic characteristics, care practices of the mothers during pregnancy, delivery and postnatal period, and on weight and head circumference of the infants. We generated Z-scores for weight for age and head circumference for age using Zanthro techniques . Z-scoreWe assessed 487 babies out of the targeted 517 in Iganga/Mayuge HDSS. Thirty infants could not be accessed: 7 were out of the age range, 3 had died and 20 had either shifted, or were not at home on three repeated visits. Out of the 487 babies assessed 144 (29.6%) were aged nine months, 116 (23.8%) were 10 months, 126 (25.9%) were 11 months, and 101 (20.7) were 12 months. The mean weight of infants at time of data collection was 8.5 kg . The weight for age Z-scores had a normal distribution, with 5.0% below − 2.0 Z score. Similarly, the head circumference had a normal distribution of the Z scores, with a mean of 45.4 cm, SD = 1.4 cm (range: 39.0–50.3 cm). There were no significant sex differences among the infants: 250 (51.3%) were male.We found 62 (12.7%) infants with neurodevelopmental disability in at least one of the domains. The most affected domain was the social behaviour where 52 (10.7%) infants had a NDD followed by the language domain with 20 (4.1%) affected children. Severe impairment, defined as NDD in at least three or all the four domains, was seen in 9 (1.85%) infants. Eleven (2.3%) babies, had NDD in two domains. Gross motor and Fine motor were equally affected at 1.8% (9/487). Five babies (1.03%) were reported to have had non-febrile convulsions. None of the babies had visual or auditory disabilities.At bivariate analysis, socio-demographic factors independently associated with NDD included: parity of the mother of more than three children  , infant failing to cry at birth  and post-neonatal complications  (Table p = 0.190)  was 5% (21/417), and NDD distribution among them was not different from those who had normal weight (0) Table . Most  were significantly associated with NDD. While post-neonatal complications and failure of the infant to cry at birth may be considered biological factors, there could also be an environmental component related with challenges in the health systems readiness to offer quality services due to various delays in care seeking. On the other hand, the mother’s parity of more than three children is more of an environmental factor, related with social and economic demands on the family, which limit adequate child care and nurturing.p = 0.036). This is in line with what was reported among Ethiopian infants in whom a third of the disabilities occurred after the neonatal period in infancy. Similar to a Nepalese study, [Infants with post-neonatal complications had a higher likelihood of developing neural disability  assessed yet some disabilities may manifest later and minor disabilities may eventually change with time, especially, if addressed . In addiThe study has revealed a high NDD prevalence especially in the social domain. The key factors associated with NDD are: failure to cry at birth, post-neonatal complications and mother’s parity of more than three children. Failure of a baby to cry at birth is a proxy for challenges in the quality of perinatal service provision and efforts should be made to address this as a priority area in order to minimize the risk of disability.The post-neonatal complications suggest limited access as well as low quality service provision in the postnatal period. In resource limited settings, having a high number of children poses challenges in parent-child interaction. This calls for integration of innovative strategies in existing VHT/CHW programmes, and in ANC and immunization clinics to improve awareness of parents on opportunities for effective stimulation, child encouragement and regulation during daily nurturing to enable optimal neurodevelopment.


Although infant mortality because of birth defect has increased in both developed and developing countries, had not got attention like other health issues at national, regional, or local levels. Documenting the risk factors that influence the occurrence of birth defects and its seasonality will help to inform the community and to develop preventive strategies for the country.Factors associated with higher likelihood of a major structural birth defects included maternal age; neonates born from women living in urban; and in Dega; history of fever during pregnancy; intake of herbal medicine; and drinking alcohol. Counselling for pregnancy preparation and folic acid supplementation was found protective for the likelihood of birth defect. Birth defects also are known as, congenital anomalies, congenital disorder or congenital malformations , 2 are dEvery year an estimated 7.9 million children—6 percent of total births worldwide—are born with a serious birth defect of genetic or partially genetic origin. Data presented in a global report on birth defects show that at least 3.3 million children under 5 years of age die from birth defects each year and an estimated 3.2 million of those who survive may be disabled for life. This disability can have a severe human and economic toll on those affected children, their families, communities and health-care systems [Although birth defects are a global problem, their impact is severe in middle- and low-income countries where more than 94% of the births with serious birth defects and 95% of the deaths of these children occur . FurtherResearches on birth defects and associated risk factors were not conducted adequately in Ethiopia and had not got attention like other health issues at national, regional, or local levels.Documenting the risk factors that influence the occurrence of birth defects and its seasonality will help to inform the community and to develop preventive strategies for the country. Studying the seasonality of congenital anomalies can also help trace risk factors for birth defect.The main objective of the study was to assess determinants and seasonality of major structural birth defects among newborns delivered at primary and referral hospital of East and West Gojjam zone, Northwest Ethiopia 2017–2018.Institutional based unmatched case–control study design was conducted at selected primary and referral hospital of East and West Gojjam zone from September 2017 to October 2018.All newborns in selected hospitals who was born from September 2017 to October 2018 and who fulfill the case and control definition criteria for this particular study.Inclusion criteria Newborns with major structural birth defect and the next three newborns (delivered after the case) without defect and whose mothers are voluntary, was included in the study.Exclusion criteria Newborns whose mothers could not be interviewed because they were very sick, emotionally upset, and mute or die post-delivery was excluded from the study.The sample size was calculated using the Fleiss with continuity correction factor formula with a case–control ratio of 1:3; assuming the proportion of controls exposed was 50%, the minimum odds ratio to be detected is 2.0, power of 80% and a significance level of 95%. The computed sample size was 398, (100 cases and 298 controls).Independent variables Socio demographic characteristics of mothers and fathers, obstetrical history of mother and newborn, maternal illness and medication use of the mother during pregnancy and, environmental exposures of mothers during pregnancy.Dependent variable Patient control status of major structural birth defect.Socio demographic characteristics of mothers and fathers; obstetrical history of mother and newborn; history of maternal illness, medication use, environmental exposures during pregnancy was assessed using structured interviewer administered questionnaire. Patient control status of the fetus/newborn was assessed by detail observation and physical examination.p value of < 0.05 in the bivariate analysis was included in the multivariate analysis. p values of < 0.05 was considered statistically significant.Data was entered via Epi data and analyzed using STATA version 14. Bivariate and multivariate analyses was employed, and factors which had a A total of 398 newborns, male 219 (55%) and female 179 (45%), with gestational age (using ultrasound) of 16–43 weeks was included in this study. All 398 mothers whose newborns were included, were aged between 18 and 42 years with a mean age of 27.51 years and 388 (97.5%) were married .During the study period, 100 new born were found with major structural birth defects in a proportion as depicted on Fig. Socio-demographic characteristics of mothers and fathers; the obstetrical history of the mother and newborn; the history of maternal illness, medication use, environmental exposures during pregnancy were analyzed in bivariate and multivariate logistic regression. We identified risk and protective factors for the occurrence of the major structural birth defects as depicted by Table Factors associated with higher likelihood of a major structural birth defects included maternal age ; neonates born from women living in urban ; history of fever during pregnancy ; intake of herbal medicine; and drinking alcohol   and folic acid supplementation  was found protective for the likelihood of birth defect (Table Many studies have been conducted to determine the association of various risk factors with the incidence of birth defects. For example, in Kenya, Tanzania and Iran the number of malformed babies appeared to increase with increasing maternal age especially from 35 years and above . The samIn rural areas of Gabon structural birth defects were rare or absent as compared to the number recorded in urban areas . In thisThis may be due to diet diversification habits and non-fat diet in rural areas of Ethiopia as has been shown its effect in an animal model study  and a grStudies conducted in a variety of settings around the world have observed a significant association between maternal fever and birth defects consistent with our findings , 14, 15.As reported from northern Ghana the use of herbal medicines by pregnant women poses a potential danger to the fetus and development of 70% birth defects of unknown etiology . In our The 2011 Ethiopia Demographic and Health Survey found that 45% of women and 53% of men reported drinking alcohol at some point in their lives . The assIn our study Maternal history of alcohol intake during pregnancy was found to be significantly associated with birth defect. Women who took alcohol during their pregnancy were around thirteen times more likely to have newborns with birth defect as compared to those women who didn’t take alcohol during their pregnancy.Both moderate and high levels of alcohol intake during early pregnancy may result in alterations in growth and morphogenesis of the fetus. Microcephaly, short palpebral fissures, epicanthal folds, maxillary hypoplasia, short nose, thin upper lip, abnormal palmar creases, joint anomalies, and congenital heart disease are also present in most infants .Counselling has a positive effect on a range of health outcomes like prevention of birth defects . PhysiciSimilar to above report counselling for pregnancy preparation in our study was found protective for the incidence of birth defect. Women who didn’t get counselling for pregnancy preparation were about five times more likely to have neonates with the birth defect as compared to women who got counselling for pregnancy preparation.Nearly one-half of pregnancies are unintended so preconception care should be considered an integral part of primary care for women of reproductive age. Provide counselling regarding common issues in preconception care like family planning, screening and treatment for infectious diseases, updating appropriate immunizations, and reviewing medications for teratogenic effects can prevent poor birth outcomes including birth defect .Researches in different setup showed that women who took folic acid were less likely to have babies with birth defects as compared to those who did not take folic acid during and before early pregnancy , 28–34.Intake of folic acid supplementation can reduces nearly 75% of the rate of neural tube defects . It is rIn our study women who didn’t get folic acid supplementation at or before pregnancy were about seven times more likely to have neonates with birth defect as compared to those women who had been supplemented with folic acid during and before pregnancy which is consistent with other studies that have shown folic acid supplementation is protective against birth defects –41.Folate acts as a cofactor for enzymes involved in DNA and RNA biosynthesis. Interruption of DNA biosynthesis or methylation reactions could prevent the proper closure of the neural tube. Such inhibition could be caused by simple deficiency of either folic acid or vitamin B12 .In this study, there is no statistically significant association between season of birth and the absence or presence of birth defects. But the data should be collected and analyzed based on the season of conception rather than the season of birth or termination. This was the main limitation of the study.


Child low and high birth weight are important public health problems. Many studies have looked at factors of low and high birth weight using mean regression. This study aimed at using quantile regression to find out determinants of low and high birth weight.Spatial quantile regression models at 0.05 and 0.95 percentiles of birth weight were fitted to 13,087 children birth weight in kilograms using Malawi demographic health survey data of 2010 study. Full Bayesian method by integrated nested Laplace approximations (INLA) was used to estimate the model. Second order random walk priors were assigned for mother age and antenatal visits for pregnancy while Gaussian markov random field prior was used for district of the child.2), birth order 2–3, mother secondary education and height (≥150 cm) negate low birth weight while weight 45–70 kg promote low birth weight. Birth order category 6+, mother height (≥150 cm) and poor wealth quintile, promote high birth weight, while richer and richest wealth quintiles and education categories: primary, secondary, and higher, and mother overweight (BMI > 25 kg/m2) reduce high birth weight. Antenatal visits for pregnancy reduce both low and high birth weight.Residual spatial patterns reveal areas in the southern region promoting high birth weight while areas in the central and northern region promote low birth weight. Most fixed effects findings are consistent with the literature. Richest family, normal mother body mass index (BMI), mother over weight (BMI > 25 kg/mStrategies to reduce low and high birth weight should simultaneously address mother education, weight gain during pregnancy and poverty while targeting areas increasing low and high birth weight. High birth weight (HBW) defined as new born weight greater than 4.5 kg is an emerging public health issue in developing countries . It is gA number of factors influence high birth weight. HBW is associated with gestational diabetes. Birth order, a previous HBW infant, male fetus, maternal and paternal birth weight, ethnicity, gestational hypertension, preeclampsia, and increased interval between pregnancies are also known to be associated with HBW . NeverthOn the other hand, LBW is primarily caused by uterine growth retardation or preterm delivery or both. Smoking, low maternal education, young and advanced maternal age, single marital status, less weight gain during pregnancy, hypertension, genitourinary tract infection in pregnancy, first births and fewer prenatal consultations are other factors of LBW –19. FurtIn addition, most studies that have looked at factors of LBW and HBW have used mean regression instead of quantile regression , 23. In The purpose of this research article was to investigate factors of low and high birth weight using the quantile regression so as to have an understanding of effects of covariates on the extreme distribution of the response. The modeling frame work also modeled metrical covariates non parametrically so as to capture their subtle influences. In addition, there was incorporation of spatial random effects so as to take into account the effect of unobserved area level covariates. Incorporation of spatial effects avoided the underestimation of model parameters’ standard errors which if not incorporated could result in erroneous rejection of null hypothesis about significance of the covariates.The article content is presented as follows: first, methods in terms of study population, area, data and statistical analysis are presented. Results, discussion and conclusion follow there after.The study looked at children in Malawi less than 5 years and used secondary data  data). The data was accessed from the demographic health survey (DHS) website after being given permission. According to , the MalStata version 12  was used to extract and generate new variables in the data. Variables found in previous studies on child birth weight were used in this study. Child birth weight in kilograms was the dependent variable in the extracted data set and the independent variables were mother smoking status, mother age, mother education, mother height, mother weight, mother BMI, number of antenatal visits for pregnancy, birth order, wealth index and district of the child. Birth order, mother smoking status, mother education, wealth index, mother height, mother weight, mother BMI and district of the child were categorical variables. The inclusion of mother BMI, weight and height instead of either BMI or the two, weight and height was based on previous research  who inclFirst bivariate quantile regression was performed in R using quantreg package to select potential independent variables for the multiple variable regression. Independent variables that were significant at 20% significance level were taken as candidate variables for multiple variable regression. The 20% significance level was used in selecting independent variables for multiple variable regression, to allow more potential independent variables to be selected. Cross tabulation between factor independent variables and categorized birth weight  was performed to have percentage distribution of low and high birth weight per factor variable levels.yi be the dependent variable and Xi =  be the vector of p independent variables. The quintile regression of yi on Xi is defined asp(yi < q(τ| Xi)) = τ ϵ  is the quantile level and γτ = (γ1(τ), γ2(τ), …, γp(τ)) is the vector of p covariates effects. The value of τ considered in this study was 0.05 and 0.95 where 0.05 corresponds to low birth weight (birth weight = 2.5 kg), and 0.95 corresponds to high birth weight (birth weight = 4.5 kg). If τ = 0.5, then we have the usual linear regression, that is, mean regression. Model (1) assumes that the predictor is linear and in the presence of non linear and spatial predictors (1) becomes:fj for j = 1, 2, 3, …, p represent the effect of non linear independent variables including the spatial effect. The vector of coefficients γτ determine the parametric relationship between the response and the categorical covariates. The two unknown parameters γτ, fj(τ) are normally estimated via minimization problemρτ is the loss function for the given τ and λ0 is the intial smooth paramer for function fj(τ) and λj is j smooth parameter, Multiple variable quantile regression models were then fitted in R using INLA package. Quantile regression models the conditional quantiles on the covariates instead of the mean. Let fτ(.) were assigned functions from Gaussian markov random field (GMRF) family, that is, if fτ(.) has mean μ and precision matrix δQ, it is assumed to have the density of the formQ is the semi-definite matrix of constants with rank n − m(m ≥ 0) which also determines the kind of the particular GMRF. For the metrical covariates, we selected the second order random walk (RW2) priors  ∝ constant. In this case we assumed prior ignorance for the fixed effects and had let the data speak for itself in estimation of parameters.The fixed effects were assigned diffuse priors i.e. [Inference of joint posterior distribution of model parameters was by integrated nested laplace approximations (INLA). Other methods like markov chain monte carlo (MCMC) could be used to infer about posterior distribution but INLA approach is faster for the quantile regression than MCMC according to . Model i2 = 24.93, p < 0.001) . An indirect relationship exists between low or high birth weight and mother education . The same relationship is observed between low or high birth weight and wealth quintile . In this case, the percentage of low or high birth weight babies decreases with increase in education and household wealth. Looking at the regions  compared to districts in the central  and southern region .Since the bivariate analysis was similar to that of  the resu2, birth order 4–5 , mother secondary education , mother height ≥ 150 cm , and variable with negative association is weight 45–70 kg . For the 95% percentile model, birth order category 6 +  and mother height ≥ 150 cm  have a positive association with birth weight, that is, they promote high birth weight, while poor wealth index , richer wealth index , richest wealth index  and education categories: primary , secondary , higher , mother BMI > 25 kg/m2) are negatively related with birth weight on higher values of birth weight.Table Figure Figure This study employs the use of spatial quantile regression to explore the relationship of birth weight with its covariates at different quantiles of birth weight while taking into account residual spatial effects. Investigating covariate effect at different response quartiles is important as relationship may be different at different levels of the response. Not only relationships may be different at different quantiles of the response but also the significance of these relationships. For example in this study, birth order category 4–5 is significant at 5% percentile and is insignificant at 95% percentile. Quantile regression also allows one to model percentiles of interests of the data, for example, extreme values of the data, as it is the case in this study where the interest was to investigate factors affecting high and low birth weight.2), birth order category 2–3, mother secondary education, and height (≥150 cm) with positive association and variables with negative association (promoting low birth weight) is weight 45-70 kg. For the 95% percentile model, birth order category 6+ and mother height (≥150 cm) and poor wealth quintile have a positive association with birth weight, that is, they promote high birth weight, while richer wealth index, richest wealth quintile and education categories: primary, secondary, and higher, mother overweight (BMI > 25 kg/m2) have a negative association with birth weight. Poor wealth quantile promoting high birth weight may seem unexpected but sometimes it has been found like this, for example [Fixed effects factors found as significant predictors of lower values of birth weight is wealth category of richest family, smoking status, mother normal BMI, mother over weight (BMI > 25 kg/m example  found a  example  where bi height ≥50 cm wit example , though The nonlinear effect of mother age on birth weight is almost the same on lower and high values of birth. With prenatal visits, there is a positive association with low values of birth weight for the fewer number of antenatal visits and a negative correlation with increased number of antenatal visits. For high birth weight, the effect of antenatal visits start in flattening out mode and then ends with strong reducing effect. This finding is consistent with  where anThe residual spatial patterns observed in low and high child birth weight are likely due to unmeasured factors not represented in the models, and it is a matter of suggestion to find them. According to , the areThe study did not go without weaknesses. Since the study was cross sectional in design, no causal inference can be made between the outcome and the independent variables. In addition, since the study used secondary data, there was limitation in the inclusion of some variables, that is, variables not in the data but known to be associated with outcome. For instance, pregnancy history which is known to influence birth weight according to  could noThe study supports non linear modeling of some covariates like mother age and antenatal visits that show non-linear effect. Nonetheless there is no support of incorporating location as a spatial effect as there was no significant spatial variation of child birth weight. Nonetheless, the spatial patterns shown reveal the effect of unmeasured variables with some spatial dependence or may be epidemiological processes that are responsible for this spatial dependence, and the maps created can be used for prioritizing the areas with high risk. Strategies to minimize low/high birth weight must include education for mothers, weight gain during pregnancy in this study approximated by mother weight, and poverty reduction especially in areas shown to increase low/high birth weight.Additional file 1. Child birth weight data.


An early developmental lack of the optic vesicle can result in congenital anophthalmia, defined as a complete absence of the eye, which can be distinguished from congenital microphthalmos, where ocular rudiments are present. Here, a rare pediatric case of congenital clinical anophthalmos with orbital cyst in the left orbit is reported. The patient was a 14-month-old girl with no other congenital defects who underwent surgical and prothetic management in St. Joseph's Hospital Kinshasa, Democratic Republic of the Congo (DRC). Surgery was carried out under general anesthesia. The cyst was punctured and its wall fully excised. Near the orbital apex pigmented elements representing iris, ciliary body, and choroidal or retinal remnants were found. The specimens were fixed in formalin for histological examination. Surgical cyst removal including socket deepening for an artificial eye was performed. Postoperative wound healing was uneventful and a satisfactory cosmetic outcome was achieved in all follow-up examinations. Histological examination revealed rudimentary ocular structures similar to degenerated lens tissue with a typical, PAS-positive capsule. Additionally, pigmented epithelial structures, which seem to be of ciliary body, iris, and choroidal or retinal-type epithelium origin, could be detected, prompting the final diagnosis, microphthalmia with dominant cyst formation. During development, ocular abnormalities of the eye include a wide range of malformations, depending on the embryonic age at onset of the disease . One of In industrial countries malformations like congenital anophthalmos and microphthalmos are usually treated as soon as possible in the first few weeks after birth to avoid serious aesthetic problems in the future provoked by an underdeveloped bony orbit as the result of the missing eyeball in utero. Different surgical implantation techniques like self-inflating orbita expanders  or sockeIn contrast, in developing countries and especially in rural areas where patients do not have access to standard medical care systems, the aesthetic aspect of congenital anophthalmos is of secondary importance. As a consequence, untreated cases of congenital anophthalmos are more common, which under given circumstances will not be present in industrialized nations.Here we present the case of a clinical anophthalmos with an extensive orbital cyst in a 14-month-old African patient, who was finally treated during a foreign medical aid program.In the year 2000 the Rostock University Medical Center funded an ophthalmologic medical aid program in Kinshasa, Democratic Republic of the Congo. Over time, this funding developed to a close cooperation between Rostock and Kinshasa mainly focused on treatment of children with congenital cataract. Elective surgery outside this field was performed 1-2 times a year during visits of the Rostock team. At the last visit in Kinshasa in spring 2016, a Congolese mother of a 14-month-old female requested medical attendance for her daughter, who had a large orbital cyst with clinical anophthalmos in the left orbita since birth A. The moVisual inspection of the cyst disclosed a tissue mass, which protruded out of the left orbit. The tissue mass was nonpulsatile and irreducible. First examination by using a small pen light demonstrated transillumination, which indicated an expectation that it was filled with liquid B. The cyThe procedure was carried out under general anesthesia and well tolerated by the patient. In a first step the cyst was punctured and 1.5 ml of liquid was drained A. After Undefined tissue structures were excised D. The cyThe patient recovered well from the surgical intervention and sutures were removed 14 days after surgery. Six months after surgery the child was doing well and the examination of the orbit showed no complications . Two months later, an acrylic prefabricated artificial eye was placed in the socket I but theThe surgical specimens were submitted in formalin and transferred to the Institute of Pathology, Rostock University Medical Center.Macroscopic inspection disclosed several membranous tissue specimens with diameters up to 1.5 cm. One of these specimens contained a small, partly calcified nodule, measuring 2 mm.Histologic sections showed the wall of a pseudocyst, consisting of fibrous tissue . The calcified nodule was reminiscent of a degenerated lens with a typical, PAS-positive capsule C. AdjaceBased on the histological findings a pathological diagnosis of a microphthalmia with dominant cyst formation was made.Here, we present a case of a 14-month-old girl with microphthalmos with a prolapsing, lid spreading cyst from the left orbit. Transillumination and B-scan ultrasonography strongly supported this diagnosis. Final confirmation was made after excision by histological examination and based on existing rudimental ocular structures. As far as the family history is determined this child is the only one in this family with such an ophthalmological defect. None of the other family members have had a similar eye problem before. No other nonophthalmic deficits or malfunctions were obvious and the physical and mental development of this child was within normal limits for her age. After cyst removal through surgical intervention and dispensing of a prosthesis, a satisfactory cosmetic result was achieved.The failure of fetal fissure closure during ocular development in embryogenesis can result in orbital and ocular malformations including congenital cystic eye  and microphthalmos with cyst (“colobomatous cyst”) –11. BothFor reasons that are not entirely clear the congenital cystic eye develops as a result of partial or complete arrest in the invagination of the primary optic vesicle between the 2 mm and 7 mm stages of fetal development. In contrast, microphthalmos with cyst develops as a result of disturbances during later stages (7 mm to 14 mm), when the optic vesicle has already merged with the surface ectoderm and intraocular elements such as the lens or other ocular structures such as the cornea can be present , 18, 19.A distinguishing feature between these two malformations is the existence of a small eye or rudimentary ocular tissues in the microphthalmos with cyst that sometimes are difficult to visualize. Clinically, it may also appear as an eye with invisible cyst, as an obvious cyst with a small malformed eye or as a huge cyst, which can displace the eye and fills out the whole orbit . In thisCysts in both malformations are benign structures and can occur unilaterally as well as bilaterally. It is also possible that both forms of cystic eyes can occur in the same patient, but in the majority of children with a congenital cystic eye the fellow eye is normal , 13, 16.In some cases, most often in bilateral presentations, additional systemic/nonocular defects such as clef lip or basal encephalocele, agenesis of the corpus callosum, midbrain deformity, microcephalus, and saddle nose have been observed. To establish the correct diagnosis of these malfunctions, recognition of the clinical features, imaging techniques, and histopathologic findings are necessary. Histological examinations can differentiate between congenital anophthalmos and microphthalmos and are important for gaining information regarding insights of the pathogenesis , and to help determine the prevalence of each entity.Imaging diagnostic tools like ultrasonography, CT scan, or MRI not only are useful in the diagnosis of this rare entity, but also can be helpful in the identification of other associated brain abnormalities. In general, imaging should be performed preoperatively, because meningocele and optic nerve sheath cysts should be ruled out , 14. UnfThere is no standardized protocol for managing a congenital cystic eye . A volumSurgical intervention of congenital clinical anophthalmos with orbital cyst is desirable to increase patient's acceptance in society, with or without adaptation of an artificial eye. By performing histological examinations it is possible to differentiate between congenital anophthalmos and microphthalmos. This is important for gaining information regarding insights of the pathogenesis and to learn about prevalence rates of each entity.


Studies have suggested that the variability is linked to the Atlantic multidecadal variability; a spatially persistent pattern of warm/cold sea surface temperatures in the North Atlantic. In the last few years, several promising century-long reanalysis datasets have been made available, opening up for further studies into the dynamics inducing the observed low-frequency rainfall variability in Sahel. We find that although three of the 20th century ECMWF reanalyses show clear multidecadal rainfall variability with extended wet and dry periods, the timing of the multidecadal variability in two of these reanalyses is found to exhibit almost anti-phase features for a large part of the 20th century when compared to observations. The best representation of the multidecadal rainfall variability is found in the ECMWF reanalysis that, unlike the other reanalyses (including NOAA’s 20th century), do not assimilate any observations and may well be a critical reason for this mismatch, as discussed herein. This reanalysis, namely ERA-20CM, is thus recommended for future studies on the dynamics driving the multidecadal rainfall variability in Sahel and its linkages to the low-frequency North Atlantic oceanic temperatures.Summer rainfall in the Sahel region has exhibited strong multidecadal variability during the 20 Previous observational data show that Sahel rainfall has exhibited clear, extended dry and wet periods during the 20th century in conjunction with strong inter-annual variability, with severe consequences for the people living in the region as a result5. The long persistent drought in 1970s and 1980s and later rainfall recovery drew attention to the regime shift in Sahel and emphasized the need for more research into the causes of the decadal climate change6. However, identifying the exact driving dynamics behind the low-frequency variability of the Sahel rainfall is challenging. Statistical analysis has indicated that the multidecadal variability in Sahel is associated with periods of warm/cold sea surface temperatures (SSTs) in the North Atlantic, referred to as the Atlantic Multidecadal Variability (AMV)9, a phenomenon that has been linked to climate variability in several regions globally10. At the same time, the understanding of the dynamics driving the observed multidecadal climate variability in Sahel and the possible dynamical link to the AMV has long been hindered by the lack of century-long, dynamically consistent datasets. Studies suggest that the warm/cold phases of the AMV warms/cools the Sahara region which in turn strengthen/weaken the Saharan Heat Low, an important feature of the West African Monsoon13. Comparisons of the extended wet and dry periods using reanalysis with shorter time-spans indicate that this in turn strengthens the meridional circulation, the low-level westerlies and the African Easterly Jet, increases the moisture flux convergence in the Sahel and intensifies the West African Monsoon leading to increased rainfall in the region14. As these studies are performed using shorter time-series with often un-filtered data it is however still difficult to separate influence from high- and low-frequency variability.Multidecadal variability is a global phenomenon of climate variabilityth century both using coupled and un-coupled models 15. These datasets are currently being used for e.g. studies on dynamical processes and evaluation of models in many different regions and fields globally17. Due to their long time-coverage it also opens up the opportunity to study low frequency rainfall variability in Sahel. In addition, the complete dynamical framework in reanalysis would certainly broaden and deepen our understanding on the multidecadal variability. But it is, first and foremost, dependent on whether these reanalyses can capture the realistic multidecadal variability of Sahelian rainfall as seen in observations. Furthermore, as some of these reanalyses are driven by the observed Sea Surface Temperature (SST), one can expect the similar variability would appear in the forced atmosphere and climate.In the last few years several new reanalysis datasets have been released which span the entire 20th century reanalyses  and the National Oceanic and Atmospheric Administration (NOAA) and the Cooperative Institute for Research in Environmental Sciences (CIRES) 20th century reanalysis version 2 (20CRv2). The results are compared to the rainfall as described by the observational Climate Research Unit (CRU) TS3.24.01 dataset18 in order to quantify how well they represent the multidecadal rainfall variability in Sahel. The datasets represent different methods of producing reanalyses data, and through evaluation and inter-comparison different possible causes for discrepancies are discussed.In this study, we examine the representation of the multidecadal rainfall variability in Sahel using four recently released reanalysis datasets; the un-coupled, coupled and AMIP-style European Centre for Medium-Range Weather Forecasts’ (ECMWF) 20th century. The ERA-20C and CERA-20C datasets do not realistically reproduce the Multidecadal Sahel rainfall variability, and our results indicate that the assimilation process might play an important role in the clear mismatch of this multidecadal feature. The 20CRv2 dataset exhibits a lower multidecadal variability compared to the ECMWF datasets, making it less suitable for analysis than other available 20th century reanalyses.The best representation of the Sahelian rainfall is obtained by the ERA-20CM dataset which, surprisingly, in spite of not assimilating any observations, recreate the multidecadal rainfall variability well throughout the 2019. ERA-20C is a single member reanalysis that is forced by sea surface temperatures and sea ice concentrations from the HadISST dataset version 2.1.0.0 control member. The reanalysis assimilates surface pressure and marine wind observations from the International Surface Pressure Databank (ISPD)20 version 3.2.6 and the International Comprehensive Ocean-Atmosphere Data Set (ICOADS)21 version 2.5.1.The three ECMWF reanalyses are produced using an Integrated Forecast System (IFS) with the horizontal resolution of T159 . The spread of the ensemble reflects the uncertainties of the SST/SIC observations, and decreases throughout the 2023. Ocean-atmosphere feedback is created through coupling of the IFS for the atmosphere, waves and land to the ocean model Nucleus for European Modelling of the Ocean (NEMO), and the air-sea interface is relaxed with a Newtonian relaxation scheme towards SSTs from the HadISST2.1. In production, the reanalysis period (1900–2010) was divided into 14 streams, and the IFS is started with initial conditions from ERA-20C and NEMO from the 10-member ensemble ORA-20C. The ORA-20C members are initialized with different initial conditions, representing probable ocean states for the year 190024.The CERA-20C is a coupled reanalysis dataset consisting of 10 ensemble members, which uses the coupled CERA system to assimilate surface pressure and marine winds25 is a 56-member ensemble that assimilates surface pressure and sea level pressure observations from ISPD version 2 using an Ensemble Kalman Filter. It is forced by SST and SIC from HadISST1 and only the ensemble mean is presented in this article.NOAA/CIRES 20CRv226, we define a Sahelian Rainfall Index (SRI) averaged over the domain  for July, August and September (JAS) mean to analyse the variability from 1901 to 2015. The SRI is detrended and low-pass filtered to extract the multidecadal variability. As shown in previous studies7, the SRI exhibits clear multidecadal variability with dry conditions in the 1900–1920s and 1970–2000s, and wet conditions in the 1920–1960s and 2000 onwards , with the AMV leading the SRI , for the period 1940–1991 the correlation increases to RLF = −0.84 , thereby indicating that for the several decades in the middle of the 20th century the reanalysis is in the opposite phase of the multidecadal variability to the observed ones. For instance, the decades of relatively high Sahelian rainfall seen in observations in the 1940–1960s correspond to a dry regime in the ERA-20C. Among these reanalyses, the ERA-20CM ensemble mean has a high and statistically significant positive correlation to the observation with RLF = 0.77. The correlations for the ten individual members range from RLF = 0.37–0.89 with the highest correlation for ensemble member 3. The 20CRv2 reanalysis is weakly correlated to the observations on the multidecadal scale with RLF = 0.29. Moreover, it appears that although the 20CRv2 reanalysis does contain a variability with a 60–80 years period, the dominating period within this reanalysis’ Sahel rainfall is ~20 years long  while the CERA-20C and ERA-20CM have lower levels of bias with 40.3 mm/month and 28.2 mm/month respectively.Figure th century (the deviation seen for the last decade is a result of the low-pass filtering).ERA-20CM ensemble member 3 is, as previously mentioned, the dataset with the single highest correlation to the observations on the multidecadal scale. In Fig. th century reanalyses shows that these datasets do exhibit a clear multidecadal rainfall variability in the Sahel region over the past century. However, the dry and wet regimes do not match the observations well and some reanalyses even exhibit an anti-phase relationship. For the absolute rainfall amount, most reanalyses such as ERA20C, CERA-20C and ERA-20CM show a large dry bias. The dry bias feature in ECMWF reanalyses has been reported in previous studies, which show a total column water vapour dry bias in the ERA-20C and ERA-20CM reanalyses30. The total column water vapour is resulted from the cloud physics and convection parameterizations, and may therefore be the major reason for the dry bias seen in these reanalyses, not least since they all use the same atmospheric model.The above analysis on the 2032. A comparison of the JAS surface temperature over the western Sahara has shown a consistent cold bias in the ERA-20C compared to the observational dataset CRU TS 3.24 by −0.97 K  compared to 1901–1975 (pre-satellite era). Although this is somewhat expected, it demonstrates the importance of satellite observations introduced later into HadISST2 dataset in improving the SST forcing, as discussed by Hersbach et al.22.The overall improvement seen in CERA-20C compared to ERA-20C evidently indicates that the implementation of a coupled ocean-atmosphere has had a positive effect on the hydrological representation over the Sahel region, even though it does not capture the multidecadal rainfall variability correctly. The dry bias is reduced and the high-frequency variability has a higher correlation to the observations compared to the ERA-20C. As discussed in Laloyaux th century. Similar anomalies are visible in the CERA20C reanalysis, indicating that the coupling did not improve the timing of the multidecadal variability. Figure th century. The ERA-20CM e0 does not exhibit the same pronounced dry regime in the 1960s which is seen in both the ERA-20C and CERA-20C reanalyses and its multidecadal variability correspond well to the observations, which suggests that the mismatch of the variability pattern could be related to the assimilations. The dry extended regime in ERA20C corresponds to a weakened latitudinal pressure gradient ranging from the 1940s to the end of the 1970s which is not present in the HadSLP2 observational datasets33 . This is consistent with our knowledge of the dependence on the land-ocean temperature gradient as well as SST-fields for the monsoon rainfall in Sahel, and underlines the importance of realistic representation of the SSTs. The CERA-20C, which also consists of 10 ensemble members, exhibits an inter-ensemble variance of 8.7 mm/month, i.e. the variance is 48% lower than for ERA-20CM. The ocean model is initialized with different initial ocean states for each ensemble member, but the air-sea interactions are relaxed towards the same HadISST2.1 realization which could have contributed to the reduced variance in CERA-20C.The ERA-20CM ensemble members exhibit a large variability throughout the 20Compared to the ECMWF-reanalyses, the NOAA/CIRES 20CRv2 dataset exhibits a wet bias of 31.4 mm/month and has a dominating period of ~20 years rather than the 60–80 year period seen in the European reanalyses. The correlation is also lower than ERA-20CM on low-frequency  timescales and lower than CERA-20C on high-frequency timescales . This makes the dataset less suitable for analysis of the multidecadal Sahel rainfall variability compared to other available century-long reanalysis datasets.Multidecadal rainfall variability in the Sahel region still require further research in order to fully understand the governing forcing and dynamical processes. This requires century-long, dynamically consistent datasets in order to better understand the mechanism of the low-frequency variability. We conclude that the high, statistically significant correlation between the ERA-20CM reanalysis and the observational CRU dataset together with the lower dry bias makes this dataset most suitable for low-frequency climate analysis in the Sahel region. As demonstrated herein, the ensemble mean reproduces the multidecadal variability well, but ensemble member 3 has the single highest correlation and is therefore recommended if one attempts to look into the physics inducing the low-frequency Sahel rainfall variability in more detail.18 dataset, consisting of monthly mean values for the years 1901–2015. The dataset is constructed using land-based in-situ observations from meteorological stations across the globe, which are interpolated into a grid with 0.5° latitude/longitude resolution. The availability of in-situ observations varies in both time and space, and grid cells lacking station data are supplied with their 1961–1990 climatological mean. Approximately 60–80% of the grid cells in Africa have station data for most of the 20th century, with lower coverage at the beginning of the century and for the last decades. The CRU dataset was chosen due to its high spatial resolution and long time series, which is crucial for multidecadal analysis. A comparison to other available century-long observational datasets 36 and the University of Delaware) also showed a high consistency with CRU 37 were analyzed for the period 1901–2014.Monthly mean sea surface temperatures from the Hadley Centre’s sea surface temperature dataset (HadSST2)38. The low-pass filtering is performed using a 4th order Butterworth low-pass filter with a 20-year cur-off frequency, while the high-pass filtering is performed using a high-pass filter of the same order with a 10-year cut-off frequency.The Sahel rainfall was averaged over the area 10–18°N and 20°W-30°E and over the months July-September to create the Sahel Rainfall Index (SRI) which represents the summer monsoon rainfall in the region. JAS rainfall dominates the annual cycle and represents 73–79% of the mean annual rainfall in both observations and all reanalyses used in this study. To facilitate comparison between the land-only observational dataset and the reanalyses, whose values also cover the ocean, only values over land are used and the ocean is masked out. The AMV index is created in a similar way, by averaging SSTs over the area 0–60°N and 7.5–75°W and calculated as annual mean values. The resulting time series are linearly detrended using a least-square fit and filtered using a Butterworth filter39 for the period 1901–2010, except for the correlation between the CRU SRI and the AMV which is calculated for 1901–2014. The significance of the correlation is calculated taking the effective degree of freedom into account using the Modified Chelton method as described by Pyper and Peterman (1998)40. The bias of the reanalysis is calculated on low-pass filtered time series, using Eq. 41, and all analysis is performed using Matlab and Climate Data Operators (CDO).The correlation is calculated using a Pearson correlation coefficientSupplementary Material


To review the clinical features of brachial synovial cyst.A case of bilateral brachial synovial cysts is described in a child suffering from systemic juvenile idiopathic arthritis during a relapse. Magnetic resonance imaging and ultrasonography were conducted to further evaluate the nature of the cysts. The case is compared with known cases in a literature review.Review of the literature showed that brachial synovial cysts occur most commonly in systemic juvenile idiopathic arthritis. It is considered that uncontrolled systemic inflammation and recurrent disease activity might be the cause of synovial cysts.Brachial synovial cyst is a rare manifestation of juvenile idiopathic arthritis. Uncontrolled systemic inflammation inducing chronic damage to joint structure may be the primary cause of synovial cyst formation. Popliteal synovial cyst is a common occurrence in children with JIA, but cyst formation in other locations, such as brachial synovial cysts are rare.2A 7‐year‐old boy diagnosed with sJIA 4 years prior to admission, responded to a regimen of prednisone and methotrexate. The dosages of the medications were tapered gradually as symptoms of disease decreased. On follow‐up, he was asymptomatic with normal laboratory tests for 2 years without any therapy.He returned to our hospital on the date of admission with a fever, truncal rash and swollen left ankle. Of note, neither of his shoulder joints had any tenderness or limitation of function at that time. Elevated inflammation markers as well as ferritinemia were found but laboratory tests for infectious pathogens were negative. Other rheumatic diseases were also excluded and therefore it was concluded that this patient had recurrence of his sJIA. He was treated with parenteral methylprednisolone and tocilizumab in accordance with the treatment algorithm for recurrent sJIA. A few weeks later, he developed swelling of his right upper arm, and then the left arm, without redness or pain. At this point, the patient had been treated with three doses of tocilizumab along with prednisone and methotrexate. Ultrasonography (US) displayed cystic mass with internal septation in both arms Figure . When co3We then performed a comprehensive review of the literature regarding “brachial synovial cyst” or “bicipital synovial cyst” published in English language journals Table . Literat4The exact etiology of brachial synovial cyst has been a source of controversy. In adults, joint degeneration and complete tear of the rotator cuff with increased fluid production are thought to be the two distinct causes for the formation of synovial cyst.For children, JIA is the only reported association with brachial synovial cyst formation. The reason for the cyst formation is not clear. Pathological findings reveal that the cyst wall is surrounded by granulation and fibrous tissue with abundant inflammatory cell infiltrates, which indicate active inflammation in those patients.The reason why brachial synovial cyst happens more often in sJIA but not other types of juvenile arthritis is unknown. When treating sJIA, clinicians tend to pay more attention to control of the systemic inflammation than local joint symptoms. Further, clinicians tend to conduct relatively less joint examination than the other types of JIA, such as poly‐JIA or oligo‐JIA during follow‐up. This treatment bias may lead to a false conclusion that local joint symptoms have disappeared when systemic inflammation is under control. For those patient with recurrent sJIA, chronic damage to the joint synovium as well as surrounding structure may be ongoing, even though systemic inflammation is not obvious at that time.5Brachial synovial cyst occurs more often in sJIA than any other type of juvenile arthritis. Uncontrolled systemic inflammation and recurrent disease activity maybe the primary cause of synovial cysts. Subclinical synovitis should be monitored closely by ultrasonography, especially in sJIA patients.None.