Low birth weight is one of the global agendas that have an impact on the short and long-term health status. A cross-sectional study from March 1 to April 1, 2018 was conducted. 381 mother–newborn pairs were participated. This study aimed to assess the prevalence and associated factors of low birth weight in the Northwest part of Ethiopia.The prevalence of low birth weight was 14.9% (95% CI 11.7–18.9). Being preterm , absence of ante-natal care follow-up , malaria attack during pregnancy , anemia during pregnancy , and lack of iron supplementation  were predisposing factors to low birth weight. On the other hand, infants born from employed mothers  were less likely to born with below normal birth weight. The prevalence of low birth was high as compared to WHO estimation. Low birth weight (LBW) is one of the reliable indicators and monitoring parameters of maternal and child health programs . AccordiBeing below normal birth weight is the greater risk for different severe and life-threatening health complications. Notably, hypothermia, hypoglycemia, birth asphyxia, anemia, impaired nutrition, and respiratory problems are the major complications of LBW .It is possible to prevent LBW prior to its occurrence. Accordingly, WHO sets a 30% reduction of LBW by 2025 through providing affordable, accessible, and appropriate healthcare services . Accessi]. The social and economic [Despite different healthcare services, LBW is continuing to be one of the important public health problems worldwide. Correspondingly, 15% to 20% of all births worldwide were LBW in 2014 , Nigeria11economic , maternaeconomic , 13.There was no study found in the current study area related to LBW. Even if there are studies in other parts of the country, it cannot be represent the current study area due to the difference in demographic, socio-cultural, and other health coverage status.Therefore, we aimed to assess the prevalence of low birth weight and its associated factors in the Northwest part of Ethiopia.An institution based cross-sectional study was employed from March 1 to April 1, 2018, at two hospitals in the delivery clinics of Northwest part of Ethiopia. These hospitals are Assosa and Pawi general hospitals, where the majority of the population of the region gets healthcare services. Based on the current Ethiopian government classification, these hospitals are found in the Benishangul-Gumuz Region, which is located 632 km far from Addis Ababa. Based on the 2007 Census conducted by the Central Statistical Agency of Ethiopia , the BenAll mother–neonate pairs were the study population.2(0.174) (0.826)/(0.04)2 = 346.The sample size is calculated using single population formulaConsidering 10% non-response rate, the total sample size is 346 + 35 = 381.Participants were selected using proportional allocation; 241 samples from Assosa, and 140 from Pawi Hospital from the total of 710 mother–infant pairs. A systematic random sampling technique was conducted. Each participant was selected using (k ≈ 2) after providing a number to pregnant mothers attending delivery room from day one to the end of data collection. In situations, where a respondent did not agree or not met the inclusion criteria, the next random position would be considered.Below normal birth weight: neonates whose birth weight less than 2500 g.Data was collected using a structured and pre-tested questionnaire, measurement, and chart review. The questionnaire was adapted from the Ethiopian demographic and health survey  and otheTwo diploma midwives and nurses who were working outside the study area collected the data. The weight of the newborn was measured after 30 min of delivery using a balanced weight scale. Maternal height was measured against a wall height scale to the nearest centimeter. Maternal weight was measured by beam balance to the nearest kilogram. Participants’ medical charts were reviewed to take some important variables like maternal hemoglobin level.Firstly, data were checked for completeness and inconsistencies. The collected data was entered into Epi-data version 4.2.0.0. and then exported to STATA version 14.0 for analysis. The socio-demographic distributions of the participants were described using descriptive statistics. Binary logistic regression analysis was applied. The multivariable logistic regression analysis was done for variables with a P-value less than 0.25 in the bivariable analysis. Those variables with P-value ≤ 0.05 were claimed as significantly associated factors of LBW.Ethical clearance was obtained from the School of Nursing on behalf of the University of Gondar Institutional Ethical Review Committee. Written permission was taken to both Assosa and Pawi General Hospitals’ manager. Then, each respective manager wrote permission letter to the focal persons. Name or identification number of study participants was not recorded. Participant data was used only for the study purpose.Three hundred seventy-five mother–neonate pairs have participated with a response rate of 98.4%. Mean age of mothers in this study was 27.19 ± 5.13 years. Of these, 72.53% mothers were between the ages of 20–35 years. About 45.6% of mothers were housewives. Regarding the residence, 33.33% were rural dwellers. The majority (41.87%) of mothers were diploma and above. The majority (30.13%) were Amhara ethnic group  , mother who did not get iron tablet during pregnancy , malaria attack during pregnancy , and anemia during pregnancy  are identified associated factors with LBW. Regarding neonatal-related factors, being preterm  was associated with LBW . The finding of the current study was comparable with a study conducted in Tigray Ethiopia (14.6%) , Gondar On the other hand, it was higher than other Ethiopian settings, like Axum (9.9%)  and JimmThe current finding also higher than the finding from other African settings, like Nigeria , the UniBelow normal birth weight is associated with the infant, maternal and obstetric related or environment and behavioral factors. Gestational age, malaria attack during pregnancy, anemia during pregnancy, the absence of ANC follow-up, and absence of iron intake during pregnancy were associated with LBW.Regarding gestational age, preterm neonates were 4.2 times more likely to be LBW than term neonates. This finding was in agreement with a study done in Bale Ethiopia . This miThe absence of ANC follow-up during pregnancy was another variable. Women had not ANC follow-up were 3.5 times more likely to give LBW baby than women who had ANC follow-up. The possible reason might be due to, in those who had no ANC follow-up, unable to detect early major health problems, pregnancy danger sign, and cultural malpractices that can affect the birth outcome of the neonate . The othThose mothers had history of malaria attack during pregnancy were 4.3 times more likely to deliver LBW baby than mothers had no history of malaria attack during pregnancy. This result is consistent with a study done in Gondar Ethiopia  and sub-This study found anemia was one of the risk factors of LBW. Anemic mothers had 2.7 times more likely of getting a LBW baby than non-anemic mothers. This finding is in agreement with a study done in Sudan . This isMothers who did not take iron during pregnancy were 4.1 times more likely of getting LBW baby than who took iron. A study in India  was agreThis study found that the prevalence of LBW was still high compared with WHO goal by 2025 which is a 3% reduction every year from 2012 to 2025. Being preterm, lack of ANC follow-up, malaria attack during pregnancy, lack of iron supplementation, and employed mothers were associated factors of LBW.This study shares the limitation of cross-sectional study design and therefore, it does not show the seasonal variation of LBW.


To check the efficacy of decompression technique in children with dentigerous cysts.1 According to Kramer, a cyst is defined as a pathological cavity having fluid, semi-fluid, or gaseous contents, which is not created by the accumulation of pus. A cyst which is lined by epithelium is known as a true cyst and that which is not lined by epithelium known as a pseudocyst.2 The dictionary meaning of dentigerous is “structures resembling teeth”.3 A dentigerous cyst is found enveloping the crown of an unerupted, embedded, or submerged tooth by the expansion of its follicle till the neck of the tooth.1 It is not unusual for a dentigerous cyst to mimic a radicular cyst, especially when the cyst is associated with a pulpectomized or carious primary tooth and its unerupted permanent successor. This article presents two cases of infected dentigerous cysts. The first case was of a female patient associated with tooth 45; and another case was of a male patient associated with tooth 35. The infected dentigerous cyst in both the cases was treated with the most conservative option available, i.e., decompression technique.Most commonly occurring odontogenic cysts in the oral cavity are radicular cysts and dentigerous cysts.In this article, two cases of infected dentigerous cysts are discussed, in which one case deals with the female patient associated with tooth 45 and the other case deals with the male patient associated with tooth 35. The infected dentigerous cysts in both the cases were treated conservatively, i.e., with the decompression technique.The present case report states that the decompression technique may be the most conservative method available for managing dentigerous cysts in children.et al. Infected Dentigerous Cyst and its Conservative Management: A Report of Two Cases. Int J Clin Pediatr Dent 2019;12(1):68–72.Patil AS, Jathar PN,  Medical history was non-contributory. Extra-orally facial asymmetry was noted on the left side of the jaw with swelling extending anterio-posteriorly from the angle of the mouth to the lower border of the mandible . The swe6 A plastic stent made up of a needle cap was used to keep the cystic cavity in contact with the oral cavity and to open it for irrigation. The stent was stabilized using a ligature wire (26 gauge) and the patient was recalled after one week. A slight reduction in swelling and tenderness was noticed after 1 week. After 3 weeks recall, clinical and radiographic examination (orthopantomograph (OPG)), a gradual reduction in swelling and tenderness was observed  was planned. The procedure to be done was explained to the parents and the patient and their consent was obtained. The FNAC sample was sent to the Department of Oral Pathology and extraction of 75 was planned. Extraction of the involved primary tooth was carried out under local anesthesia (LIGNOX 2%), followed by aspiration of the cystic fluid and further irrigation with povidone iodine 5% (Indiamart). The socket was curated and the sample along with the extracted tooth was sent for confirmatory diagnosis. To prevent the loss of the impacted permanent premolar, the decompression technique was chosen as the treatment of choice. The cystic cavity was opened through the alveolar socket of 75, which helped to relieve the intra-cystic pressure of the cystic cavity further decreasing its size.observed . At the observed . The panobserved .A 11-year-old-female patient reported to the Outward Patient Department of Pediatric and Preventive Dentistry , with the chief complaint of pain and swelling in the lower right back region of the jaw since 20 days. Medical history was non-contributory. Extraorally facial asymmetry was noted on the lower right side of the jaw, extending antero-posteriorly from the angle of the mouth to the lower border of the mandible. Palpatory findings revealed the swelling was woody hard and tender on palpation. Intraorally expansion of the buccal cortical plate was seen extending from the region mesial to tooth 44 to the region distal to tooth 46. The overlying mucosa was hard in consistency and tender on palpation. Also, the involved primary tooth, i.e., 85, was grossly carious. There were no abnormalities associated with the soft tissues . OPG exa2 Dentigerous cyst on radiographic examination shows unilocular, radiolucent lesion characterized by well-defined sclerotic margins associated with the crown of an unerupted tooth. The dentigerous cyst can be classified into two types based on its origin, i.e., originated from reduced enamel epithelium (REE), they occur in 2nd and 3rd decades, and predominantly involves mandibular 3rd molars. Based on the presence or absence of inflammation into inflammatory and non-inflammatory, diagnosed in 1st and early 2nd decade , with mandible is more commonly involved than maxilla in the ratio of 10:1.7Dentigerous cyst is also known as “follicular cyst”. An odontogenic cyst of developmental origin. Most of the times it was an accidental finding when radiographs are taken to investigate the adjacent tooth that was either infected, carious, or mal-aligned. The dentigerous cyst seems to enclose impacted, embedded, or submerged tooth by the expansion of its follicle. The normal follicular space is approximately 3–4 mm, whereas a dentigerous cyst can be suspected when the space is more than 5 mm.8 The prevalence of dentigerous cyst development within the jaw close to the region of the second primary molars has been connected to the observations that the second primary molars are associated with greater caries susceptibility. The close relationship between a second primary mandibular molar and the follicle of the successor has been associated with a facilitated spread of infection in comparison with other primary teeth.8Dental caries are considered as one of the most common etiological factors for periapical inflammation involving primary molars. There are many schools of thoughts for the development of inflammatory dentigerous cyst like, (1) accumulation of fluid  between the reduced enamel epithelium and the enamel organ due to the spread of infection to the dental follicle leading to the development of a dentigerous cyst. (2) It is seen that seldom the crown of a permanent tooth might erupt into a radicular cyst of a primary precursor leading to the development of a dentigerous cyst. Shear in 1994 stated that most jaw cysts occur in the first decade of life.8The cystic potential of radicular lesions particularly in primary dentition as a result of native irritation could induce adverse effects on the successor tooth follicle . These conditions are very common in primary molars. Thus, a close follow up protocol should be implemented bearing in mind that the pathological changes associated with an endodontically treated deciduous tooth may remain symptom-free. The materials used for dental treatment in deciduous teeth will trigger the expansion of cysts.9 The differential diagnosis of the dentigerous cyst includes ameloblastoma, odontogenic keratocyst, odontogenic fibroma, odontogenic myxoma, cementomas, and Pindborg tumor. Early identification and removal is necessary as they may rarely have the potential to develop into odontogenic tumors like ameloblastoma and malignancy like squamous cell carcinoma and mucoepidermoid carcinoma.10Pathophysiology for inflammatory dentigerous cysts is obstruction of venous outflow, due to the pressure exerted by a potentially erupting tooth on the impacted follicle, which induces rapid transudation of serum through capillary walls. The increased hydrostatic pressure of this pooling fluid separates the follicle from the crown with or without reduced enamel epithelium.8 A cyst is sometimes related to the roots of a non-vital tooth and therefore the crown of an unerupted permanent successor with a sclerotic border. The histopathological image of cyst evaluated in these case reports showed inflammation with reduced enamel epithelial tissues. Hence, this case was diagnosed as inflammatory dentigerous cyst.8 According to the location of radiolucency around the crown of an unerupted tooth, there are three main varieties of dentigerous cyst and they are central, lateral, and circumferential types.11 Enucleation is the preferred treatment modality when there is no likelihood of damaging adjacent anatomical structures. On the other side, marsupialization will maintain disorder in its cavity, promote eruption of a tooth and conjointly minimize the danger of harm to special anatomical structures. Especially for young patients, the treatment modality should be as conservative as possible in order to decrease possible problems to the adjacent developing structures.10The radiographic view of inflammatory dentigerous cyst shows spherical or ovoid, well-demarcated unilocular radiolucency at the border of the lower jaw.10The conservative treatment modality is extremely important in cases of huge lesions and once the permanent teeth concerned have eruptive potential. The marsupialization or Partsch's technique involves removing a window from the lesion and suturing the encircling mucoperiosteum to the margins of the cyst wall. The ensuing cavity is filled with gauze, which is removed after seven to ten days.10 This modality was called as the decompression technique. The procedure aims to reduce the size of the cyst. Opening the cyst lumen eliminates its osmotic pressure and bone apposition gradually occurs at the site, which was previously occupied by the epithelial covering of the cyst. The insertion of a device in cystic lumen is done in order to maintain patent communication between the interior of the cyst and the oral cavity. This procedure characterizes the decompression and differs from marsupialization because this technique involves the biopsy of large fragments of tissues.13Thomas modified Partsch's method; in his modification, a small opening is made in the defect and a soft metal or polyethylene tube for drainage is inserted and fixed at the site by attaching it to an adjacent tooth.13 Thus, to conclude, the decompression technique can be considered as a conservative treatment of choice since the preservation of the permanent successor was desirable.Periapical radiolucency associated with primary teeth is often misdiagnosed either as an infected radicular cyst of a preceding tooth or a dentigerous cyst of the successor. It is very common for a dentigerous cyst to mimic an infected radicular cyst, especially when associated with a carious primary tooth as well as its unerupted permanent successor. Also, a carious primary tooth may have the potential to involve in the development of inflammatory dentigerous cysts and thus proper diagnosis is important to plan a proper treatment protocol. Decompression is the most conservative technique which results in significant reduction of the cyst size.This technique can be employed in situations when the underlying permanent tooth needs to be retained. Some other advantages of this technique are minimal bone loss with faster wound healing. Thus, to summarize, this technique is the most conservative with minimal limitations compared to other techniques.


Information is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases.Between 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn’s Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumab-exposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort . Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort , but not compared to the diseased unexposed cohort . No significant increased risks were noted with adalimumab exposure for any other study outcomes.Adalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn’s Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure. Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been available for the treatment of various chronic inflammatory diseases for over 20 years. Many of these diseases are prevalent in women of child-bearing age. For this reason, evaluation of the safety of anti-TNF-α therapies used in pregnancy is needed. This includes information on drug-specific risks of major birth defects, pregnancy loss, preterm delivery, and pre-and postnatal growth deficiency. In addition, due to the immunosuppressive action of TNF inhibitors, it is also relevant to examine risks for serious or opportunistic infections and malignancies in infants who have had prenatal exposure to an anti-TNF-α medication.Adalimumab is an anti-TNF-α medication first approved in the U.S. in 2002 for the treatment of rheumatoid arthritis and subsequently indicated for psoriatic arthritis, ankylosing spondylitis, Crohn's Disease (adult and pediatric), ulcerative colitis, plaque psoriasis, hidradenitis suppurativa (adult and adolescent), non-infectious uveitis (adult and pediatric), and juvenile idiopathic arthritis. Adalimumab is a fully humanized monoclonal antibody with a high molecular weight and is expected to require active transport in order to cross the human placenta. For this reason, it is thought that potential exposure of the embryo via placental transfer is limited earlier in pregnancy, while transfer to the fetus later in pregnancy has been documented .There are limited data regarding the fetal safety of adalimumab when used in human pregnancy. Two published studies are notable. One study conducted in nine countries compared birth outcomes in 495 women exposed to any anti-TNF-α therapy in the first trimester to outcomes in 1,532 women without chronic inflammatory diseases who had consulted with a European or Australian Teratology Information Service between 1998 and 2013. The investigators found a 2.2-fold increased risk  for all major birth defects combined, and an increased risk of preterm birth and low birth weight in the exposed compared to unexposed. However, there was no specific pattern of major birth defects noted in exposed infants nor any differential risk for major birth defects in the subset of 177 women in the sample who were exposed to adalimumab [A second study combined data from Danish and Swedish population health registers for 1,272,424 pregnancies ending in live birth between 2004–2012. The risk of major birth defects overall was compared between 683 women treated with any anti-TNF-α medication for chronic inflammatory disease and 21,549 women with chronic inflammatory disease not treated with any anti-TNF-α therapy. The adjusted odds ratio (OR) for major birth defects was 1.32 (95% CI 0.83 to 1.82) for exposed vs. disease-matched unexposed. There was no evidence of a specific pattern of major birth defects with exposure to any anti-TNF-α medication. The adjusted OR for major birth defects in the subset of 161 adalimumab-exposed pregnancies compared to women with chronic inflammatory disease and no anti-TNF-α treatment was 1.22 (95% CI 0.58 to 2.27) [Taken together, these studies suggest that the underlying maternal inflammatory diseases may play a role in birth outcomes in women treated with anti-TNF-α medication in pregnancy. However, to our knowledge no study to date has comprehensively examined the range of pregnancy outcomes among pregnancies specifically exposed to adalimumab compared to disease-matched and healthy women without the same chronic inflammatory diseases. The purpose of this study was to evaluate the birth prevalence and patterns of major and minor structural birth defects, spontaneous abortion, preterm birth, pre- and postnatal growth deficiency, and risks for serious or opportunistic infections or malignancies in infants born to mothers treated with adalimumab during part or all of pregnancy.MotherToBaby pregnancy studies conducted by the Organization of Teratology Information Specialists (OTIS) are prospective pregnancy cohort studies involving study participants across the U.S. and Canada. The methods of MotherToBaby OTIS cohort studies have been described previously –6.In brief, MotherToBaby services, located in academic institutions or hospitals throughout the U.S. and Canada, provide counseling to women and their health care providers who contact the services with questions about the risks of exposures in pregnancy. Pregnant women who meet the criteria for a study are referred to the OTIS Research Center at the University of California San Diego where they are screened, consented to participate and where all subsequent data collection takes place. Additional methods of recruitment are also employed, including physician referrals and direct-to-consumer marketing through social media and the MotherToBaby website. In all cases, the pregnant woman is the individual who provides consent to participate in the study and she is the primary source of medication exposure data.MotherToBaby/OTIS pregnancy studies select topics for research in part based on input from patients and the public. This includes assessment of public and patient interest based on the frequency of queries received by MotherToBaby/OTIS services about a specific medication, the specific concerns raised, and whether or not there is a lack of adequate human pregnancy data for a given exposure. Women who enroll in MotherToBaby/OTIS pregnancy studies are asked to refer others who may have interest in the study. Participants in MotherToBaby/OTIS pregnancy studies are formally surveyed about their experience and satisfaction with the study procedures, and asked about reasons for decline to participate or withdrawals. These factors are considered in designing or amending the study procedures. Finally, mothers receive feedback on the results of the study-related physical examinations for their infants, and all participants are provided overall study results.A Pregnancy Registry study for adalimumab was initiated in January, 2004, and enrollment continued until August, 2016. Women with a diagnosis of rheumatoid arthritis or Crohn’s Disease and prenatal exposure to adalimumab were prospectively recruited into an exposed cohort. Women with the same diagnoses but no treatment with adalimumab at any time in pregnancy were recruited into a disease comparison cohort. An additional cohort of healthy comparison women without rheumatic or inflammatory bowel diseases was also recruited and followed in the same manner.Women met the inclusion criteria for all three cohorts if they enrolled in the study prior to 20 weeks’ gestation, did not have prenatal diagnosis prior to enrollment with this pregnancy of a fetus with a major structural birth defect, and had not enrolled in the study with a previous pregnancy. Inclusion criteria for the adalimumab-exposed group required receipt of any dose of adalimumab at any time in pregnancy from the date of conception (DOC) to the end of the first trimester defined as 11 weeks after the estimated date of conception, with or without continued use of the medication through the remainder of gestation. Women met the inclusion criteria for the disease comparison group if they had a diagnosis of rheumatoid arthritis or Crohn’s Disease, but were not treated with adalimumab at any time in pregnancy, although they could have been treated with another anti-TNF agent such as etanercept. Women enrolled in the healthy cohort did not have a rheumatic disease or an inflammatory bowel disease, no treatment with a monoclonal antibody medication in pregnancy and no exposure to a known human teratogen in pregnancy at the time of enrollment. Women in this cohort were primarily recruited from MotherToBaby services from callers who initiated contact with the service about non-teratogenic exposures, e.g., cosmetic products, an antibiotic or over-the-counter cold preparation.Women in both the exposed and unexposed cohorts completed up to three telephone interviews during pregnancy and one interview at the completion of pregnancy. These were administered by trained study staff in English or Spanish. The first interview obtained information on demographic, pregnancy and family medical history, tobacco, alcohol and caffeine consumption, and recreational drug use, as well as infections, fever, and prenatal tests. Data regarding products, dosages, dates and indications for exposure were collected on all medications , vitamins/minerals, herbal products, and vaccines used/administered from the first day of the last menstrual period (LMP) through the date of the interview. Subsequent maternal interviews elicited information on additional exposures or events since the last interview. The Slone Epidemiology Center’s Drug Dictionary was used to code exposures .In the exposed and disease comparison cohorts, women also responded to questionnaires at enrollment and in the third trimester interview about disease activity or symptom control. For women with rheumatoid arthritis, patient-reported measures consisted of the Health Assessment Questionnaire with Disability Index (HAQ-DI) , a measuOutcomes were collected by maternal interview and by medical records obtained from the obstetrician, rheumatologist or gastroenterologist, pediatrician, and delivery hospital as well as pathology reports if relevant. Data were collected on outcome status of each pregnancy , gestational age at outcome, mode of delivery, sex and number of infants, birth weight, length, and head circumference and the presence or absence of major birth defects detected up through the first year of life. Maternal report of major birth defects was confirmed by medical record review.th centile for sex and gestational age in live born infants using standard U.S. growth charts for full and preterm infants [Major structural defects were reviewed by a birth defects specialist who was a co-investigator for this study (KLJ) and final classification was made using the U.S. Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects Program coding system . Spontan infants –13.Minor structural defects were evaluated through a study-specific physical examination of live born infants conducted by one of a team of pediatric specialists in dysmorphology/genetics. Examinations were performed most commonly in the participant’s home, and the examiners were blinded to the mother’s/infant’s exposure status at the time of the evaluation. A study-specific checklist of minor structural defects  was usedth centile for weight, length and head circumference for sex and chronological age at about one year using standard U.S. growth charts. Serious or opportunistic infections were defined as infections requiring hospitalization or those from a specific checklist  for the outcome of major structural birth defects. The unit of analysis for major structural birth defects was the pregnancy, i.e., a singleton or multiple pregnancy that ended in one or more malformed infants was considered one major birth defect outcome. For minor structural birth defects, the analysis was restricted to infants for whom the study-related physical examination was completed. The prevalence of any three or more minor structural birth defects was compared between the adalimumab-exposed infants and the unexposed infants. In addition, among the adalimumab-exposed, clusters of any two or more infants with the exact same three or more minor structural defects were identified and the prevalence of those patterns was compared to the same specific clusters in the unexposed.Secondary comparisons for all outcomes were performed between the group of women exposed to adalimumab and the healthy cohort.Exact methods were used to calculate crude relative risks (RRs) and their 95% CIs for the pregnancy outcomes of major birth defects overall, minor structural defects, small for gestational age infants, and infants with serious or opportunistic infections or malignancies. Adjusted RRs and their 95% CIs were estimated when numbers permitted using logistic regression with the adjusted odds ratios (ORs) used as an approximation of the adjusted RRs.For spontaneous abortion, Kaplan Meier estimates were used to estimate the probability of spontaneous abortion accounting for left truncation due to varying gestational timing of enrollment, and data were censored at 20 weeks’ gestation . Cox proControl for confounding was conducted where numbers permitted. A minimum of 30 events for a binary outcome was considered the threshold for conducting adjusted analyses. A minimum of 20 events was required for Cox regression as it does not contain an intercept. All relevant covariates for each specific outcome including maternal age , race, ethnicity, socioeconomic status , year of enrollment , referral source, country of residence, tobacco or alcohol use in pregnancy, pre-pregnancy body mass index , use of vitamin supplements, pregnancy history, infection, fever, psychiatric conditions, use of corticosteroids , use of other immunosuppressant medications, exposure to known human teratogens , and comorbid autoimmune diseases were considered as possible confounders. A criterion of ≥10% change in the estimate of the OR or the HR for the outcome under consideration with the addition of each covariate in a model containing exposure to adalimumab (yes/no) was used to select potential confounders for each outcome. If one confounder was identified, direct adjustment was performed. If two or more confounders were identified for a particular outcome, a propensity score approach was used. In this approach, the selected confounders for each analysis were used to build the propensity score model, and the propensity score for each woman was then used as a single adjustment factor in the regression models , 16. ProDisease severity/symptom control measures were used to evaluate comparability of the adalimumab-exposed and disease-matched comparison women on disease status. However, it was not possible to collect these measures at baseline . Therefore, in the final adjusted analyses disease severity measures were not considered as confounders as they could have been influenced by treatment.Missing values were excluded from each analysis . HoweverFor the primary outcome of major birth defects, sensitivity analyses were conducted in five ways: 1) logistic regression with adjustment for the logit of a propensity score comprised of all considered confounders, 2) inverse probability weighting with the propensity score comprised of only the selected confounders, 3) inverse probability weighting with the propensity score comprised of all considered confounders, 4) restricting the analysis to women who enrolled prior to any prenatal diagnostic test for major birth defects, and 5) excluding women from the disease-matched unexposed group who had exposure to another anti-TNF-α medication in pregnancy.All analyses were conducted using R open-source statistical software or StatXact (2011).This study was approved by the University of California, San Diego’s institutional review board . The study was conducted according to the current regulations of the International Conference on Harmonization guidelines and the principles of the Declaration of Helsinki. Informed consent was obtained from participants.Between 2004 and 2016, 602 pregnant women enrolled in the study; 257 were exposed to adalimumab in pregnancy, 120 were disease-matched unexposed, and 225 were healthy comparison pregnancies. A total of 42/602 of enrolled women (7.0%) were lost-to-follow-up primarily due to inability to obtain birth outcome information from the participant despite repeated attempts to contact up to one year after the estimated date of delivery. Although all women in the adalimumab-exposed cohort were exposed for some period of time in the first trimester, 65% of the sample used the medication in all three trimesters . The disWomen in the adalimumab-exposed cohort compared to the disease comparison group were more likely to enroll earlier in gestation, to have been referred by their health care provider or the study sponsor. Women in the adalimumab-exposed cohort were less likely to have had a previous child with a birth defect, and reported fewer weeks of treatment with systemic corticosteroids . Women iA total of 25/602 (4.1%) of pregnancies resulted in live born twins. There were no stillbirths reported in any cohort; one elective termination was reported in the adalimumab-exposed group . Among pAmong all pregnancies excluding those lost-to-follow-up, there were 25/247 (10.1%) first-trimester adalimumab-exposed pregnancies that resulted in at least one fetus/infant classified as having a major birth defect. In the diseased unexposed group, 9/111 (8.1%) resulted in at least one fetus/infant with a major birth defect . In the healthy unexposed group, 12/202 (5.9%) resulted in at least one fetus/infant with a major birth defect . In the Crohn’s Disease stratum, the unadjusted RR for major birth defects among live births in adalimumab-exposed compared to disease comparison pregnancies was 1.12 (95% CI 0.38 to 4.45) .th fingers. One of these four children also had multiple major structural birth defects including asymmetry of the brain ventricles, bicuspid aortic valve, and congenital chordee. Neither of the same two clusters were identified in the comparison groups . A total of 416/543 (76.6%) of live born infants (including twins) received the study-specific dsymorphology examination. Reasons for non-participation in the physical examination were difficulty in scheduling the home visit or inability to contact the mother to schedule the visit. There were no significant differences between groups in the incidence of infants with three or more minor anomalies. Two sets of two infants in the adalimumab-exposed group had the same three minor structural defects. One set of two children each had an unruly hair pattern, bilateral epicanthal folds (folds of skin on inner corner of eye), and short palpebral fissures . The other two infants with a cluster of the same three minor defects each had a prominent nasal bridge, a sacral dimple, and bilateral incurving of the 5n groups .The adjusted HR for spontaneous abortion in the adalimumab-exposed cohort compared to the diseased unexposed cohort was 2.22 (95% CI 0.67 to 7.29). The adjusted HR was somewhat higher in comparison to the healthy cohort, but with wide confidence intervals . The adjusted HR for preterm birth was 0.82 (95% CI 0.66 to 7.20) in adalimumab-exposed pregnancies compared to the diseased unexposed group. However, in comparison to the healthy group, the adjusted HR for preterm delivery was elevated  .th centile at birth or at approximately one year of age on weight, length and head circumference did not differ significantly in any between-group comparisons  of live born infants. There were no significant differences between the adalimumab-exposed group compared to the diseased unexposed group  or to the healthy comparison group . Unadjusted RRs were similar when restricting the comparisons to those in the adalimumab-exposed group to those with third-trimester use of the drug (data not shown). No malignancies were reported in any infant up to one year of age .In this prospective U.S. and Canada-wide cohort study, in comparing adalimumab-exposed to disease-matched pregnancies, the overall risk for major structural birth defects was not increased among live births . Furthermore, among the major structural birth defects identified in the adalimumab-exposed group, there was no evidence of a consistent pattern. There was evidence of an approximate doubling of risk for preterm delivery in adalimumab-exposed but only in comparison to the healthy unexposed women.Previous publications on the risk of major structural birth defects following adalimumab exposure in pregnancy have been largely limited to small case series which are difficult to interpret. While Weber-Schoendorfer et al 2015) noted a borderline two-fold elevated risk for any major structural birth defect with any anti-TNF-α exposure, the authors did not find a differentially elevated risk or a specific pattern of defects in the subset of 177 women exposed to adalimumab. Furthermore, in that study, the comparison group was not matched on disease and therefore could not address the contribution of the maternal underlying condition 015 noted.The birth prevalence of major birth defects in live births ranged from 6.1% in the healthy comparison cohort to 10.0% in the adalimumab-exposed cohort, which is higher than the 3–5% general population rates typically reported. It is possible that erring on the side of caution in careful abstraction of medical records over the first year of life, as is typical in pregnancy registries, led to identification of more defects. In support of this, the birth prevalence of major defects in another similar sized pregnancy registry for an asthma biologic, omalizumab, was 8.1% in the exposed and 8.9% in the comparison group . In addiThe overall prevalence of three or more of any minor anomalies in the subset of infants who received the dysmorphology examination was reduced in the adalimumab-exposed cohort compared to the healthy cohort. However, two clusters of two infants with the same three minor defects were identified among the adalimumab-exposed who had three or more minor anomalies, one of which had associated major structural birth defects. The minor defects evaluated in the study examination in and of themselves have no clinical or cosmetic importance and could be familial. The purpose of this level of evaluation was to identify potential patterns of major and minor defects that may represent a teratogenic effect. While no child with either of these clusters was identified in the comparison groups, the finding of these minor anomalies in the adalimumab-exposed group could be due to chance.In the current study, we also did not find significantly increased risks for spontaneous abortion, preterm delivery, pre- or postnatal growth restriction, serious or opportunistic infections, or malignancies when comparing adalimumab-exposed to disease comparison pregnancies/infants.Similarly, there were no differences in comparisons for these same outcomes between the adalimumab-exposed group and the healthy cohort, except for an approximate doubling of risk for preterm delivery . This isolated finding is consistent with several previous studies in women with rheumatoid arthritis or Crohn’s Disease, suggesting that the diseases themselves contribute to the risk of early delivery.Using a Norwegian register, Wallenius et al (2013) noted an increased risk of preterm delivery among first pregnancies in 1,496 women with rheumatoid arthritis compared to 625,642 deliveries from the general population  . SimilarAn analysis of Danish Birth Cohort data found that among 644 women with Inflammatory Bowel Disease (including 266 with Crohn’s Disease), there was an approximate two-fold risk for preterm delivery compared to 83,795 with no bowel disease . SimilarWe found no evidence of an increased risk for small for gestational age infants with adalimumab exposure or among women with the underlying diseases we studied. Although women enrolled in the study were of higher socioeconomic status and predominately white, rates of small for gestational age infants on birth weight were within the range of the expected population rate of 10% in all cohorts. In contrast, Norgaard et al (2010) noted a modest increased risk of small for gestational age on birth weight  among infants born to women with rheumatoid arthritis, but the overall incidence of smaller birth weight in this population-based sample was low (3.8% to 5.9%) .Although we found no significant increases in spontaneous abortion in any comparison, the point estimates for the HRs were well above 1 with very wide confidence intervals. However, as women enrolled on average at the end of the first trimester, we were not able to evaluate spontaneous abortion in the early weeks of gestation when the risk is highest. Further study of this outcome is needed.It is generally thought that little anti-TNF medication crosses the placenta in the first trimester. However, there is direct and indirect evidence of placental transfer of anti-TNF-α medications in the third trimester via measurable cord blood levels even weeks after maternal discontinuation of treatment . One casWe did not measure cord blood or infant levels of adalimumab or infant immune function in this study. However, we did examine anytime exposure and exposure near the time of delivery to adalimumab with respect to risk of serious or opportunistic infections in the first year of life, and did not find support for this theoretical concern. This finding is consistent with a U.S. claims database analysis for anti-TNF-α medications in general and adalimumab specifically . In thatThere are several limitations to this study. First, the sample sizes of pregnancy registries, including this one, are typically insufficient to rule out elevated risks for most specific individual major birth defects. However, specific patterns of major structural birth defects are characteristic of known human teratogens. Therefore, it is reassuring that no such pattern was identified in this study. Secondly, we relied on volunteers, most of whom were white and of higher socioeconomic status, which could introduce bias and affect generalizability of the study results. However, pregnant women were enrolled in all three cohorts before the known outcome of pregnancy and similar data collection was completed for the comparison groups thereby supporting internal validity. We did not follow infants beyond one year of age and therefore were unable to assess longer term risk for malignancies or obtain data on child neurodevelopment. As with all studies of prenatal exposures, data on longer term outcomes including neurodevelopment would be valuable.In summary, in this study, we found no evidence of an increased risk of major structural birth defects as well as a wide range of other pregnancy outcomes attributable to prenatal exposure to adalimumab. In addition, for women being treated for rheumatoid arthritis or Crohn’s Disease, this study confirms previous findings regarding elevated risks for preterm delivery that are associated with the maternal disease.S1 Fig(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


The surgical indication and treatment of sacral meningeal cyst have not been well established and current methods are usually accompanied by complications and recurrence. The aim of this study is to discuss the treatment of symptomatic sacral meningeal cyst, by investigating the surgical results of our surgically treated patients, and minimize the complications and recurrence.We retrospectively reviewed all patients with symptomatic sacral meningeal cysts who were surgically treated by a single surgeon in the same institution from 2002 to 2017. All patients underwent the same operation by incising the cyst wall and obstructing the communicating hole with muscle graft, while the cyst wall was left untreated instead of resected or imbricated. The obstruction was verified by doing a Valsalva-like maneuver. The preoperative symptoms and signs, and the outcomes at most recent follow-up were rated and compared by Neurological Scoring System.p < 0.01).A total of 18 patients  were followed up for an average of 51.7 months. All patients had communicating holes linking the cysts and the dural sacs. The average preoperative neurological score was 19.7 ± 2.2, and it was improved to 23.2 ± 2.8 at the most recent follow-up (The sacral meningeal cyst originated from the communication with the dural sac. Surgical treatment of symptomatic sacral meningeal cysts can yield a long-term resolution of the appropriately selected patient’s symptoms. Obstructing the communicating hole with muscle graft is an effective and simple method to obliterate the cyst. The incised cyst wall can be left untreated instead of resected or imbricated. The cyst located within the sacral spinal canal, known as the sacral meningeal cyst, was well documented in the literature. It was first described by Tarlov in 1938 as an incidental finding at autopsy , 3.Several authors have reported varying outcomes with surgical treatment of the sacral meningeal cysts –7. NeverBetween 2002 and 2017, 18 patients  ranging in age from 20 to 70 years  with symptomatic sacral meningeal cysts were treated surgically by the senior author (H.T.). The diagnoses of the sacral meningeal cyst were confirmed by MRI in all patients. The medical reports and images were reviewed, as well as the numbers, sizes and locations of the cysts. All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of Second Affiliated Hospital of Xi’an Jiaotong University (No. XJTU1AF2018LSK-78) and informed consents were obtained from all individual participants included in the study.Only those patients who met following criteria received surgery: 1) clinically, the patient had neurological signs and symptoms, including S1 radicular symptoms , or sacral plexus disorder . 2) MRI confirmed the existence of the cyst. 3) excluding other causes, such as lumbar disc herniation or spinal stenosis.The preoperative symptoms and signs, and the outcomes at most recent follow-up were rated by the Neurological Scoring System, which was designed for clinical evaluation of patients with spinal lesions . This scUnder general or epidural anesthesia, the patient was put in a prone position. After incision of the skin and fascia, subperiosteal dissection of the paravertebral muscle was done with extreme care not to intrude into the sacral canal through the thinned sacral roof, which had been eroded by the cyst. Sacral laminectomy was done meticulously to preserve the integrity of the cysts. The cyst was then fenestrated at its thinnest site using a scalpel to drain off the fluid, and its inner surface was carefully examined. After fenestration of the cyst wall, as long a longitudinal incision as possible was made on the cyst wall to get the widest exposure for convenient inspection of the interior and closure of the communicating hole.For the purpose of obstructing the communicating hole to prevent the recurrence of the cyst and postoperative cerebrospinal fluid (CSF) leakage, an appropriate block of muscle was used to plug the hole and was fixed by purse-string suture using 4/0 sutures Fig. . The musAfter the communicating hole being blocked, the incised cyst wall was left untreated instead of resected or imbricated. The residual space was filled with gelfoam and/or fibrin glue, or a local pedicled sacrospinalis muscle flap for temporary equalization of the pressure between the cavity and dural sac. Then a closed non-pressure drainage was inserted into the cavity and the wound was closed.After surgery, the drainage was removed when the amount of drain decreased to less than 100 ml, which was usually 24–72 h after surgery. However, an excessive amount of drain indicated failure to block the communicating hole, which might lead to recurrence in the future.p < 0.05.The neurological scores were given as mean value and standard deviation. Statistical analysis was conducted using SPSS software for Windows . Neurological scores before the operation and at most recent follow-up were compared by Wilcoxon signed rank test. The significance level was set at After bony decompression, semitransparent and highly tensioned cysts were exposed Fig. , bearingAdditional file 1: Video S1. Cerebrospinal fluid through communicating hole. A video shows that the cerebrospinal fluid flow through the communicating hole before the obstruction, the flow can be triggered by a Valsalva-like maneuver (pressuring the patient’s abdomen).Of the 18 patients, fifteen patients presented with sacral meningeal cysts which contained nerve root fibers, three patients had sacral meningeal cysts without nerve root fibers in the cyst. The characteristics of the cysts were shown in Table p < 0.01). During the postoperative recovery, local pain and radicular symptoms were most likely to improve or disappear after surgery, and residual lumbosacral pain was the most common postoperative complaint. For each item of the Neurological Scoring System, the improvement of pain  and sensory function  was statistically significant, while motor, gait and sphincter function improved slightly, although not statistically significant (p > 0.05) . All the preoperative symptoms and neurological sores before surgery and at the most recent follow-up are listed in Table Three patients had a recurrence of the cyst, as confirmed by MRI. The recurrence, in one of them (case 16) manifested as persistent perianal pain in addition to deterioration of the lumbosacral pain at 6 months postoperatively, despite the improvement in bowel and bladder function. There was no significant improvement of clinical symptoms in another case (case 17) with recurrence. Another recurrence happened at 1 year after surgery (case 12), and all symptoms were resolved after the second operation. The patient had 4 cysts before the first surgery, three of them were operated while the other one was too small to be treated. During the second surgery, the three operated cysts were found to be the same as that after the first operation with muscularized obstruction in the communicating holes, and significant expansion of the previously untreated cyst was also found. After treating this cyst with the same method, the patient had relief of all symptoms up to the most recent follow-up (158 months).Two patients had epidermis erosion at the distal end of the incision, which healed after repeated dressing changes and physiotherapy. There was no postoperative neurological deterioration or CSF leakage.In 1964, Holt and Yates  found thIn the current series, communicating holes were found in all the patients. During the surgery, CSF flow through the communicating holes was found, which can be triggered by increasing the abdominal pressure using a Valsalva-like maneuver. This fact further supports following hypothesis: the CSF flows into the congenital pouch (cyst) via the communicating hole when the abdominal pressure is increased or with the pulsation of artery, but the ball-valve mechanism does not allow the CSF to flow back to the thecal sac as the communicating hole is one-way open to it, and consequently the cyst is gradually distended , 15.Since not all of the sacral meningeal cysts are symptomatic, it is important to identify the cysts which are responsible for the clinical complaints, which is pivotal to successful treatment. Voyadzis  suggesteThe clinical features and complaints caused by sacral meningeal cysts vary from simple lumbosacral pain to a spectrum of symptoms including local pain, bowel/bladder/sex dysfunction and S1 radicular symptoms. There exists controversy regarding the efficacy of surgery in the management of sciatica. Tanaka  believedIt is our opinion that whether or not to have the patient treated surgically depends on whether there are neurological symptoms related to the cyst. S1 radicular symptoms, perineal/perianal pain and bowel/bladder/sex dysfunction are all caused by compression of the sacral plexus, on condition that tumor, disc herniation and the like have been ruled out and the patient fails to respond to conservative treatment, then an operation intended for sacral cyst is justified. When there were multiple cysts in one patient, although some smaller cysts were not directly related to the symptoms, we tended to treat every cyst because these smaller cysts had a large chance to expand and cause symptoms in the future due to their inherent pathophysiology (e.g. case 12).Various strategies have been proposed to manage patients with sacral cysts, but up to now, there has not been a universally accepted one. The widely accepted strategies fall into three categories: 1. Approaches to equalize the CSF pressure between the cyst and the thecal sac , 19, 20.Among these popular methods, no effective blockage of the communicating hole was done , 7, 16. Moreover, it is unnecessary to eliminate the cyst wall altogether since it has no excretory function. To obviate the risk of damaging the nerves, during the operation we did not give any try to remove the cyst wall forcibly but left it undisturbed. The overall satisfying outcome and relatively less recurrence and complications exhibited the safety and efficacy of our strategy.Adjuvant procedures were applied to enhance the obstruction. After the obstruction with muscle graft, the residual space was filled with gelfoam and/or fibrin glue, or a muscle flap. Such materials were not expected to fill the cavity effectively or consistently but served as temporary compression to equalize the pressure between the cavity and the dural sac. This temporary equalization might help to prevent laceration of the muscle graft and provide a stable condition for fixation of the obstruction, thus preventing recurrence. However, the confirmation of such an assumption demands histological evidence and further study. In addition, a closed non-pressure drainage was inserted into the cavity to drain the hemorrhage in the surgical site. Furthermore, if CSF leakage happened, although not seen in the current series, the leakage could be identified immediately in the drainage and managed in time. Altogether, we would like to suggest the current strategy for potential consideration by surgeons confronting a sacral meningeal cyst case.Limitations of our study included its retrospective nature and relatively small sample size. Additionally, the subsequent changes in the muscle graft and surrounding tissues were not investigated. A prospective study with a large cohort is in need in the future, as well as histological research in the surgical site.The sacral meningeal cyst originated from a communication with the dural sac. Surgical treatment of symptomatic sacral meningeal cysts can yield a long-term resolution of the appropriately selected patient’s symptoms. Obstructing the communicating hole with a block of muscle graft is an effective and simple method to obliterate the cyst. The incised cyst wall can be left untreated instead of resected or imbricated.


To evaluate the impact of the introduction of secondary civil registration centres on birth registrations within 60 days of birth, in Burkina Faso.The faith-based organization Sant’Egidio supported the inauguration of secondary birth registration centres within seven health centres in Réo from July 2015 and four health centres in Godyr from February 2015, at which delivery and vaccination services were available. We calculated the number of timely registrations per 1000 population before and after the launch of the intervention in both the intervention and control municipalities. We used a logistic regression model to evaluate the probability of non-registration as a function of the health centre services used and various demographic and health characteristics, obtained through health registers data and interviews.Compared with the previous 12 months, the number of timely birth registrations in Réo and Godyr rose from 502 to 2094 (317.1%) and from 267 to 793 (197.0%) during the first 12 months of the intervention. In the two control municipalities, the numbers were unchanged. Infants whose mothers attended health centres for delivery, but did not return for vaccinations, had the lowest proportions of birth registration . Infants of mothers who were not interviewed were more likely to not having a timely birth registration .Introduction of secondary registration centres within health centres increased timely birth registrations. The mayor is permitted to establish secondary civil registration centres in villages and health centres, but these are rare. Births and deaths can be registered for free within 60 days of their occurrence. Event registration after this period is only possible in principal registration centres after a judicial procedure and payment of a fine of about 4 United States dollars., To promote civil registration, Sant’Egidio, an international faith-based organization, launched the Birth Registration for All Versus Oblivion (BRAVO) programme in 2008. The programme is currently active in Burkina Faso, Malawi and Mozambique.To further promote the timely civil registration of births, the Sant’Egidio birth registration programme cooperated with the local authorities to set up secondary civil registration centres in health centres at which deliveries and vaccinations take place. Here, we present the results of a 2-year impact evaluation of this intervention, by estimating the number of timely birth registrations and, by considering several possible factors that may facilitate or hamper registrations.The Centre-Ouest region of Burkina Faso was selected for the location of the intervention for its below-average proportion of registered births. In 2010 the proportion of children younger than 5 years whose birth had been registered was 62.4% .We also obtained data on the numbers of births registered within 60 days from two comparable control municipalities (Yako and Gomponsom) located in the Nord region, where registration is only available in principal registration centres. This allowed us to assess any potential external variables that may influence birth registration trends, for example, the time of year or the occurrence of political and administrative changes.With the assistance of the ministries of Justice and Territorial Administration, the Sant’Egidio birth registration programme provided a 3-day training course for all registrars. The course included training on civil registration and procedures, the importance of raising awareness of civil registration, and on interviewing consenting mothers and recording their personal data. At health centres, registrars approached mothers and informed of the availability of the registration office and invited the mothers to be interviewed. However, some mothers left the health centres without meeting registrars, due to closed register or short visit. During the interviews, registrars recorded on paper whether a mother was a French speaker.The numbers of timely birth registrations at principal and secondary registration centres were collected during January 2014–April 2017 for the study municipalities of Réo and Godyr, and for the period January 2014–June 2016 for the control municipalities of Yako and Gomponsom. Delivery and vaccination data from the health centres hosting secondary registration centres were acquired for the study municipalities for the approximate 2-year period until April 2017. We digitalized and integrated paper-based data from the civil and health registers and from the interviews. We eliminated obvious recording errors, such as improbable birth dates, by manually linking records at the individual level with deliveries and vaccinations retrieved from health registers; we did not use any software to correct for missing or false data. In the event of data discrepancies, we considered civil registers to be the most accurate source. We considered all children recorded in the civil or health registers to be eligible for the impact evaluation, except for 779 records in Réo and 1026 in Godyr . Data from the control municipalities sometimes included incomplete registrations, referred to as “birth declarations with no birth record.” In these cases, birth certificates were given to the parents and the corresponding pages of the registers were left blank; an attached note reported the birth declaration. Both birth records and birth declarations were included in the comparisons between study and control municipalities.To determine the impact of our intervention, we compared the numbers of timely birth registrations before and after the introduction of the secondary registration centres. To compare municipalities with different population sizes we calculated the number of timely birth registrations per 1000 population (no. registered births × 1000/population). To consider seasonality, we analysed data from the 12 months leading to the start of the intervention and the first 12 months of the intervention.We estimated the populations of Réo and Godyr in 2015, the middle year of the study, by applying the annual growth rates for Burkina Faso to the 2006 census data,To calculate the proportion of birth registration we first divided the number of timely birth registrations by the number of newborns. To estimate the crude number of newborns, we calculated the expected number of births applying the birth rate of 4.12 births per 1000 inhabitants at regional level, according to 2010 Demographic and Health Surveys,t-test and the Pearson 2χ-test. We used a logistic regression model to study the association between the probability of a birth not being registered within 60 days and demographic and health characteristics of the mother and child. The binary outcome variable was birth registration . As predictors, we included which health centre services had been used , mother’s characteristics , birth characteristics (sex and month of birth) and the distance between the health centre and usual residence. We used the Wald 2χ-test and the likelihood-ratio test to assess the partial effect of predictors and the goodness of fit.We anonymized all data before conducting statistical analyses. We performed comparisons between timely registered births in the study and control municipalities, as appropriate, with the two-sample We only included parity, weight of mother  and any problems at delivery in the models for Godyr. Such data were either unreliable (in the case of parity) or had only been partially recorded in the registers of the Réo health centres . Parity information was obtained either during the interview with the mother or extracted from the register for delivery. Whether any delivery problems were experienced was considered as a binary variable: either no problems (0), or a preterm birth, resuscitated child or perinatal death (1).P-values of less than 0.05 were considered statistically significant. Statistical analyses were performed using SAS software 9.3 .Comité d’ethique pour la recherche en santé of Burkina Faso and our institutional review boards all approved our study procedures.The Of the 7512 deliveries and vaccinations recorded in the health registers of Réo, 779 (10.4%) were not eligible for the impact evaluation; of the 4354 recorded in the health registers of Godyr, 1026 (23.6%) did not meet the eligibility criteria . During Comparisons between the first 12 months of the intervention and the previous 12 months in Réo and Godyr indicate an increase in the number of timely registrations from 502 to 2094 in Réo (317.1%) and from 267 to 793 in Godyr (197.0%). After the introduction of secondary registration centres, birth registrations in Réo (from July 2015) and Godyr (from February 2015) followed similar seasonal trends ; both weComparing the trends in timely birth registration showed that before the intervention, the numbers of birth registrations per 1000 population were lower in Réo than in the control municipality Yako; however, these increased in Réo after opening secondary registration centres . The levP < 0.0001) and 7.3 ± 11.3 days (P < 0.0001), respectively.Before the intervention, the mean period between birth and registration was 19.5 ± 15.3 days in Réo and 25.3 ± 18.5 days in Godyr. During the intervention, this period was significantly reduced to 10.8 ± 14.4 days (P = 0.339), and from 23.2 ± 55.7 days to 21.3 ± 18.3 days in Gomponsom (P = 0.745). Over the same interval, the mean period between birth and registration did not change significantly in control municipalities: from 27.3 ± 18.6 days to 24.8 ± 16.0 days in Yako  and 31.5% in Godyr (250/793) were registered on the day of delivery or the day of vaccination.During the first year of the intervention, 68.4% (1665/2433) of newborns in Réo and 87.5% (725/829) in Godyr were delivered and vaccinated in a health centre; among these infants, the percentages of timely civil registrations were 88.5% (1473/1665) and 98.3% (713/725), respectively. Considering newborns who received vaccinations only, the births of 93.4% (212/227) in Réo and 82.9% (34/41) in Godyr were formally registered within 60 days. Of newborns delivered in health centres, but who did not receive vaccinations, the births of 69.0% (294/426) in Réo and 70.2% (40/57) in Godyr were formally registered . No signWe developed two basic logistic models for Réo and Godyr to test for the probability of a birth being registered within 60 days during the intervention . In both2χ statistic was not statistically significant (P = 0.261).For Godyr, we developed an expanded logistic model by incorporating the health conditions of the mother and child, which might have affected birth registration. None of these covariates had a statistically significant association with timely registration . To vali,–,,Compared with the number of birth registrations during the year before the start of our intervention, we observed an increase in timely registrations of more than threefold in Réo and an almost twofold increase in Godyr; no major changes were observed in the control municipalities. This increase could be explained by the provision of registration offices in health centres habitually used by families, staffed by dedicated personnel. Several reported factors for registration Of all the services provided by health centres, birth registration proportions were lowest among mothers who attended for delivery, but did not return for vaccination. This lower performance might be due to poor access to health centres after birth, early infant mortality or high mobility. Poor access does not seem likely, however, given the high vaccination rates in the area.We noted that mothers who attended a health centre and were not interviewed by registrars demonstrated the lowest probability of registering their children. We also observed monthly fluctuations in registration trends, which could not be fully explained by adverse climate conditions. Further possible reasons must be investigated .,–,Our study has several limitations. First, we recorded all deliveries and/or vaccinated children at health centres; this covered the large majority of newborns, but not the whole infant population of the area. Our municipal birth rates implied from the number of eligible infants  are lower than the national birth rates provided by the United Nations Population Division (4.1%),,We argue that a widespread registration system based in health centres already used by mothers for delivery and vaccination, with dedicated registry personnel, could considerably improve the proportion of births which are formally registered. The strengthening of civil status services during our intervention reinforced the administrative structure of the study municipalities, guaranteeing registration continuity during the political upheavals between 2014 and 2016. In contrast, control municipalities experienced operating problems due to political and administrative hardships, as shown by the high numbers of birth certificates with no birth records. Unlike studies that suggest the use of health personnel to register births,We believe that our system of introducing secondary registration centres also lends itself to meeting the challenge of recording deaths, laying the foundations for reliable civil registration systems.


Low birth weight (LBW) is one of the most important factors affecting child morbidity and mortality worldwide. Antenatal care (ANC) is an opportunity for reaching pregnant women with a number of interventions that may be vital to their health and well-being of their infants. However, data on the link between ANC quality and LBW remain limited especially in developing countries. Therefore, this study was aimed at investigating the effect of ANC service quality on birth weight among pregnant women attending ANC at public health facilities of Bahir Dar City Administration, Bahir Dar, Ethiopia using provision of essential services by providers as proxy for quality of care.Nine hundred seventy pregnant women with gestational age ≤ 16 weeks who came for their first ANC visit and selected by systematic sampling were enrolled and followed until delivery. Longitudinal data was collected during consultation with ANC providers using structured observation checklist. Women who gave birth at home and those who deliver a premature or still birth baby were excluded as data on birth weight could not be obtained for home deliveries and as the birth weight of the baby might be affected due to prematurity and still birth. Completed data were obtained from 718 women . The overall ANC service was considered as acceptable quality if women received ≥75th percentile of the essential ANC services. Generalized Estimating Equation was carried out to identify predictors of birth weight by controlling the cluster effect among women who received ANC services in the same facility.P-value< 0.001. Maternal nutritional advice, iron-folic acid supplementation, tetanus toxoid vaccination, maternal educational status, parity and age were determinants for birth weight.The prevalence of low birth weight (< 2500 g) was 7.8%  with 1.4% versus 10.5% among those who received acceptable and not acceptable quality ANC services respectively, The study showed that access to quality ANC services led to good birth weight outcome. Strengthening adherence of providers to essential components of antenatal care through regular monitoring and need based capacity building is very important for reducing the risk of low birth weight. A child’s birth weight or size at birth is an important indicator of the child’s vulnerability to the risk of childhood illnesses and the child’s chances of survival. Low birth weight (LBW) contributes to 60% to 80% of all neonatal deaths. Though this is the fact, based on the 2016 Ethiopian demographic and Health survey report, the prevalence of LBW in Ethiopia is 13.4%. It is also worth noting the prevalence might be higher as only 14% of children in Ethiopia are weighed at birth. However, data on the link between ANC quality and LBW remain limited especially in low income countries like Ethiopia.Pregnant women with gestational age ≤ 16 weeks who came for their first ANC visit and selected by systematic random sampling were enrolled and followed until delivery. Longitudinal data were collected during consultation with ANC providers to assess the quality of ANC services during their four focused ANC visits using structured observation checklist. The overall ANC service was considered as acceptable quality if women received ≥75th percentile of the essential ANC services.Among 970 enrolled pregnant women, completed data for this study was obtained from 718 women .The prevalence of low birth weight (< 2500 g) for the current study was 7.8%  with 1.4% versus 10.5% among those who received acceptable and not acceptable quality ANC services respectively. This indicates quality ANC service has a better birth weight outcome, that implied a woman’s contact with her ANC provider should be more than a simple visit.The World Health Organization (WHO) has defined low birth weight (LBW) as the weight of live born infants of < 2500 g regardless of gestational age or any other factor that might have an influence on it. A child’s birth weight or size at birth is an important indicator of the child’s vulnerability to the risk of childhood illnesses and the child’s chances of survival. The global prevalence of LBW is in the range between 15 and 20%, which accounts to about 20 million infants born; approximately one third of neonatal deaths are attributable to LBW [The prevalence of LBW in Ethiopia and Amhara region in particular was 11 and 11.2% respectively. It is also worth noting these rates might be higher as only 5% of children in Ethiopia are weighed at birth .Antenatal care (ANC) is an opportunity for reaching pregnant women with a number of interventions that may be vital to their health and well-being of their infants . Its putThe assessment of prenatal care uptake and quality are essential steps toward improving accessibility and birth outcomes. Some elements of the ANC package  have been shown to be cost-effective in a Sub-Saharan African context , 7.Even though the prevalence of LBW is higher in low and middle income countries, most of the research on the link between antenatal care and birth weight has been conducted in high income nations  and manyA facility based prospective follow up study was conducted from October 2015 to August 2016 in Bahir Dar City Administration, Amhara National Regional State, which is located in the North West part of Ethiopia. According to the Amhara National Regional State Bureau of Finance and Economic Development report, the projected population by 2015/16 was 297,775 , of these 156,515 (52.6%) were females and there were 10,035 eligible pregnant women in the same year [The study was conducted on seven public health facilities, one hospital and six health centers. All selected first visit pregnant women with gestational age ≤ 16weekss and attending ANC service during data collection period that were voluntary to participate verbal informed consent were included in the study. Women who gave birth at home were excluded as data on birth weight could not be obtained. In addition, those who gave a premature or still-birth baby; those who had any medical complication while pregnant  were excluded as the birth weight of the baby might be affected due to the underlying conditions.The current study is part of a large follow up study with multiple objectives. The detail of the sample size calculation assumptions to address all objectives is described in the other part of the study published on Plos ONE . For theA structured observation check list to measure ANC quality was developed based on focused antenatal care protocol and used to observe the routine ANC practice for each visit. The weight of naked neonates was measured in kilograms to the nearest 100 g by using standard beam balance in the delivery room immediately after birth (preferably within 1 hour) by trained diploma midwives. Seven female diploma Midwives and two Bachelor of Science female Midwives were recruited as data collectors and supervisors respectively. Both data collectors and supervisors were not working in health facilities under the study. Training was given on the data collection instrument and how to approach and observe the ANC service provision. Pretest of the instrument, close supervision and daily checkup of the filled questionnaire for completeness were also done to maintain the data quality.Birth weight in kilograms; which was measured within 1 hour after birth.Quality of ANC service was the main exposure variable.Quality of ANC service was measured based on the interventions that the mother received during antenatal care: laboratory tests done like blood and urine tests, physical examinations like weight, height, blood pressure, providing TT vaccination, iron - folic acid supplementation, deworming, nutritional advice, information on immunization and breast feeding.If the essential ANC service was given it was coded as 1 otherwise 0 and a composite index for the overall ANC service quality was calculated. Percentile was computed to categorize the quality of the services a woman received. If she scored ≥75th percentile, of essential ANC services, ANC service was considered acceptable quality otherwise not .p-value < 0.2 was considered to retain variables for the multivariable Generalized Estimating Equation linear regression analysis and P-value < 0.05 was considered to identify statistically significant predictors for birth weight.Data were coded and entered into EPI data version3.1 and exported to SPSS version 20 for analysis. Descriptive statistics were used to describe the data. Generalized Estimating Equation linear regression analysis with robust estimator and exchangeable working correlation matrix was carried out to control the cluster effect of women who received ANC services within the same facility and to identify the predictor variables for birth weight of neonates. A Among 718 women who gave birth at health facilities, those with age ≤ 19 years (teen age pregnancy) and those with age ≥ 35 years (elderly pregnancy) were 4.9 and 4.0% respectively. The mean (±standard deviation) age at birth was 25.32 ± 4.21 years. Above 90 %, (94.2%) of women were urban residents and more than half of them (52.9%) were house wives. Above 90 %, (90.9%) of study participants were Orthodox Christian and almost all women (98.8%) were currently married. With regard to their educational status, 11.4% of women had no formal education while 63.3% of women had joined secondary school and above  were primi-para; while more than one out of two 378 (52.6%) of women were multi-para and 14 (1.9%) of them were grand multi para.Above 95 %, 701(97.6%) of pregnant women received two doses of tetanus toxoid vaccine but the rest 17 2.4%) missed one dose. About two third (57.1%) of the pregnant women were counselled about BPCRP at least once in their four ANC visits. The information provision on maternal nutrition, breast feeding and immunization was also heterogeneous , 327 (45.5%), 77 (10.7%) and 10 (1.4%) of pregnant women were supplemented with 120, 90, 60 and 30 tablets of iron- folic acid respectively. In addition, 509 (70.9%) and 564 (78.6%) of pregnant women received anti-heliments for deworming and were advised to use insecticide treated bed net for prevention of malaria respectively (Table The mean (± SD) birth weight of neonates was 3113.0 (±474.9) gram with the minimum and maximum birth weights of 1800 and 4400 g respectively. The mean birth weight of neonates among women who received acceptable and unacceptable quality of ANC service was 3232 (± 0.478) and 3062 (± 0.476) grams. Of the total pregnant women who deliver at health facilities, 56  gave a low birth weight baby, 648  gave a baby with normal birth weight (2500-4000 g) and 14  gave birth overweight babies (> 4000 g).In a bivariate Generalized Estimating Equation linear regression analysis, there was a positive association between birth weight of neonates with the maternal nutritional advice during ANC, Iron –folic acid supplementation, deworming with anti-heliments, doses of tetanus toxoid vaccination of the mother, Venereal Disease Research Laboratory (VDRL) test of the mother, hematocrit test of the mother at first ANC visit, hematocrit test of the mother at fourth ANC visit, advice on Insecticide Treated Bed Net (ITN) use and most of the socio-demographic factors such as residence, maternal age, educational status, occupation and parity. Therefore, all these variables were fitted to the multivariable GEE linear regression analysis.In multivariable Generalized Estimating Equation linear regression analysis, maternal nutritional advice during ANC, Iron supplementation, tetanus toxoid vaccination, educational status and parity remained to have statistically significant association with birth weight. In addition, deworming with anti-heliments, advice on ITN use, having VDRL test, having hemoglobin test at fourth ANC visits and living in urban areas showed an increase in birth weight but the association was not statistically significant.When the frequency of maternal nutritional advice during ANC visits was increased by one, the birth weight of a neonate was increased by 147 g . When the number of iron tablet supplementation to pregnant women during ANC visits decreased from 90 or more tablets to less than 90 tablets, the birth weight of their neonates decreased by 358 g . When the dose of tetanus toxoid vaccine given to pregnant women during ANC visits increased from one to two doses till delivery, the birth weight of their neonates increased by 609 g . When the educational status of women increased by one unit, the birth weight also increased by 79 g . When the parity of women increased by one the birth weight of their neonates decreased by 174 g   by 2030 also aimed to reduce neonatal mortality to at least as low as 12 per 1000 live births. Though LBW contributes to 60%to 80% of all neonatal deaths , in ColoThe possible reason might be due to the difference in the characteristics of study participants as all the participants in this study were enrolled if they started their ANC in their first trimester and were also followed till their four antenatal visits and most (94%) were from urban and peri- urban populations that might increase the tendency to get the essential components of antenatal care like maternal nutritional advice, Iron-folic acid supplementation and other services during subsequent ANC visits that might contribute positively for birth weight. The difference in the study period might also have its own effect for the difference in the findings as many interventions like the community based newborn care packages for improving maternal and newborn health are being implemented by different countries including Ethiopia. In addition, except the current study and the study in Ghana all other studies collect information about birth weight based on mother’s recall or birth registration records that might affect accuracy of their result.This study revealed that the frequency of nutritional advice given to pregnant women during their ANC visits have statistically significant effect on increasing the birth weight of their babies. In contrary to this finding a meta-analysis done from thirty-three studies evidenced nutrition education and counselling significantly improved mean birth weight but was not significantly associated with the risk of low birth weight . The difIn low-income countries, 25% of low birth weight was attributable to maternal anemia during pregnancy . In spitThis finding is also supported with a Meta-analysis done from ten randomized control trials indicating 2 % increase in birth weight for every two-fold increase in folate intake. Other studies conducted in Spain and Atlanta also revealed duration longer than 4 months of iron supplementation gave significant protective odds ratio for low birth weight and women with low folate intake ≤240 mg/d) had > 3 times greater risk for low birth weight infant than women with folate intake > 240 μg/d respectively –23. The 0 mg/d haIn this study majority (97.6%) of pregnant women were given two doses of tetanus toxoid vaccinations compared to the Ethiopian Demographic and Health Survey report in 2016 revealed that only half of the pregnant women who gave birth 5 years prior to the survey took two doses  . The curThis study also found that there was an increase in birth weight as educational status of pregnant women increased from no education or primary education to secondary education and above. This is also supported by studies conducted in Bangladesh and Beirut , 27. In Prospective follow up of pregnant women through observation while they get the ANC service; collecting information about birth weight of the neonate at the moment of birth and applying a generalized estimating equation analysis to control the cluster effect of women who received the ANC service in the same health facility could be taken as the strength of the study but excluding women who gave birth at home due to missing of birth weight data and Hawthorn effect could be the limitation as those women might have different characteristics.The study found that near to one in ten neonates were born with low birth weight. Access to quality antenatal care increases the birth weight of new born babies. Essential components of antenatal care  and socio- demographic variables like maternal educational status and parity were determinants for birth weight. Strengthening adherence of providers to essential components of antenatal care like nutritional advice, iron- folic acid supplementation and tetanus toxoid vaccination for every pregnant woman through regular monitoring and provision of feedback and need based capacity building is very important for reducing the risk of low birth weight.