In low- and middle-income countries (LMICs), pesticides are widely used in agricultural and residential settings. Little is known about how pesticides affect child growth.To systematically review and synthesise the evidence on the associations between pesticide exposure and adverse birth outcomes and/or impaired postnatal growth in children up to 5 years of age in LMICs.We searched 10 databases from inception through November 2021. We included cohort and cross-sectional studies investigating associations between self-reported or measured prenatal or postnatal pesticide exposure and child growth . Two researchers screened studies, extracted data, and assessed certainty using GRADE. The protocol was preregistered with PROSPERO (CRD42021292919).Of 939 records retrieved, 31 studies met inclusion criteria . All studies assessed prenatal exposure. Twenty-four studies reported on birth weight. Four found positive associations with organochlorines (0.01–0.25 standardised mean difference (SMD)) and two found negative associations (–0.009 SMD to –55 g). Negative associations with organophosphates  and pyrethroids  were also documented. Two (out of 15) studies reporting on birth length found positive associations with organochlorines (0.21–0.25 SMD) and one found negative associations (–0.25 to –0.32 SMD). Organophosphate exposure was negatively associated with birth length . Organophosphate exposure was also associated with higher risk/prevalence of low birth weight (2 out of nine studies) and preterm birth (2 out of six studies). Certainty of the evidence was “very low” for all outcomes.The limited literature from LMICs shows inconclusive associations between prenatal pesticide exposure, child growth, and birth outcomes. Studies with accurate quantitative data on exposure to commonly used pesticides in LMICs using consistent methodologies in comparable populations are needed to better understand how pesticides influence child growth. In someChildren are especially vulnerable to the harmful effects of pesticides due to their increased exposure relative to their body weight, behavioural factors , and the fact that their brains and organs are still developing . Human aStudies conducted in high-income countries (primarily the United States) have consistently shown that prenatal exposure to organochlorines is associated with adverse birth outcomes, including preterm birth, small-for-gestational age, smaller head circumference, and shorter femur length . In contThough more limited, evidence on postnatal exposure suggests that postnatal pesticide exposure can also be harmful for child growth. Another recent systematic review assessing prenatal and postnatal pesticide exposure and obesity in children included eight studies of postnatal pesticide exposure (five in high-income countries and three in LMICs) . This sywhat is the effect of pesticide exposure on child growth in children <5 years of age living in LMICs? With this objective in mind, we systematically reviewed and synthesised the evidence on the associations between pesticide exposure and adverse birth outcomes and/or impaired postnatal growth in children up to 5 years of age in LMICs. Given the limited evidence from LMICs, we kept the review broad: considering any active ingredients or mixtures of active ingredients and a wide range of child growth outcomes at birth and postnatally.In contrast to this large body of evidence in high-income countries, less is known about the relationship between prenatal and postnatal pesticide exposure and child growth in LMICs. Therefore, the research question we aimed to answer was: 22.1Population: children <5 years of age in LMICs.Exposure: self-reported or measured prenatal (at any time during pregnancy) or postnatal exposure to pesticides.Comparator: a less exposed reference population .Outcomes: any anthropometric measures of child linear or ponderal growth, and/or any of six birth outcomes .This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines . It was We searched 10 electronic databases from inception to November 2021, with no language restriction: PubMed, Cochrane Library, Embase, Scopus, LILACS, Web of Science, CAB abstracts, Global Health (CABI), Global Index Medicus, and SciELO. The selection of databases was informed by databases searched in prior systematic reviews on pesticide exposure and child neurodevelopment  and throPeer-reviewed articles were included if they met the following criteria: (1) conducted in a LMIC (based on The World Bank categorisation at the time the study was conducted); (2) assessed children <5 years of age; (3) evaluated self-reported or measured prenatal (at any time during pregnancy) or postnatal exposure to pesticides; (4) measured at least one anthropometric measure of child linear or ponderal growth, and/or one of six birth outcomes see . We inclTwo reviewers (LB and LMJ) independently screened all titles and abstracts for inclusion using Covidence (n.d). Disagreements were resolved through discussion, and input from a third reviewer (AR) as needed. Full texts of eligible studies were reviewed for inclusion and data extraction. One reviewer (LB) extracted information on: (1) publication details , (2) study meta-data  of data collection, duration of study, inclusion and exclusion criteria, funding source); (3) participant characteristics ; (4) pesticide exposure ; (5) outcomes; and (6) methodological quality . Data extraction was reviewed by two additional reviewers (AR and LMJ). Any disagreements regarding the extracted data were resolved through discussion between the three reviewers . When information was unclear or unavailable, we did not attempt to contact the authors of the original study.2.2The primary outcomes were any anthropometric measures of child linear or ponderal growth measured at any time point up to 5 years of age: length/height-for-age Z-score, weight-for-age Z-score, weight-for-length/height Z-score, BMI Z-score, and stunting, underweight, wasting, and overweight as defined by individual articles. The secondary outcomes were six birth outcomes: birth weight, birth length, low birth weight, preterm birth, small-for-gestational age, and large-for-gestational age as defined by individual articles.2.3Characteristics of the studies included in the review were summarised narratively by exposure characteristics , types of outcomes assessed, and study characteristics . Data were summarised narratively using two groupings: outcomes assessed and pesticides assessed. First, we grouped studies by the frequency of outcomes they assessed. Then, by outcome, we grouped studies by the frequency of pesticide types they assessed: organochlorines, organophosphates, pyrethroids, carbamates, and chlorophenols (non-specific biomarkers of organochlorines). Where both unadjusted and adjusted estimates were reported, we summarised evidence on adjusted estimates. For continuous outcomes, we reported mean differences (MD) and standardised mean differences (SMD). For binary outcomes, we reported odds ratios (ORs), relative risks (RR), and proportions in exposed and unexposed groups. We were unable to extract all necessary information to convert and standardise effect estimates across articles. We therefore reported effect estimates as reported by individual articles. Meta-analysis was not conducted due to the heterogeneity of studies: <2 eligible studies were conducted on the same population, assessed the same pesticides, assessed exposure over the same period, and included the same outcomes.2.4Two reviewers (LB and LMJ) independently assessed the study risk of bias and quality of the evidence for outcomes reported in ≥ 4 studies using the GRADE approach . The GRA33.1A total of 939 records were identified: 929 from the search strategy and 10 from other sources . After r3.2Five out of the 31 studies assessed multiple pesticide types . The mosFour of the eight studies assessing self-reported exposure did not specify the types of pesticides used . One stuThe most frequently analysed outcome was birth weight  , followeSmall-for-gestational age was reported in three studies , which d3.3Risk of bias was “not serious” for most studies  . Risk of3.4Of the 24 articles reporting on birth weight, 12 assessed associations with organochlorines , nine wiOf the 12 studies that assessed associations between organochlorines and birth weight, nine found significant associations. Four studies found significant positive associations with DDT, DDE, and DDD ranging from 0.008 to 0.25 SMD . One stuOf the nine studies that assessed associations between organophosphates and birth weight, one found a significant negative association of 170 ± 60 g with higher concentrations of 4-nitrophenol (a metabolite of parathion and methyl parathion) comparing quartile 3 to quartile 1, but no significant associations with 3,5,6-trichloro-2-pyridinol  or 2-isopropyl-4-methyl-6-hydroxypyrimidine  . None ofTwo of the studies that assessed associations between pyrethroids and birth weight found significant negative associations ranging from 96.76 to 233.3 g  and two 3.5Of the 15 articles reporting on birth length, seven assessed associations with organochlorines , five wiOf the seven studies that assessed the associations between organochlorines and birth length, one study found a significant positive association of 0.21 SMD with higher levels of p,p′-DDT . AnotherFour of the five studies that assessed prenatal organophosphate exposure found no significant associations with birth length . One stu3.6Of the nine articles reporting on low birth weight, two assessed associations with organochlorines , five wiNone of the studies that assessed the associations between organochlorines or pyrethroids and low birth weight found significant associations . Of the 3.7Of the six studies reporting on preterm birth, one assessed associations with organochlorines , four wiThe study assessing associations between organochlorines and preterm birth found significantly higher prenatal levels of total DDT in women with preterm births (715 ± 952 ng/g) than in women with normal births (687 ± 1393 ng/g), but lower prenatal levels of total HCH in women with preterm births (174 ± 210 ng/g) than in women with normal births (207 ± 337 ng/g) . One of 3.8Of the three studies that assessed associations with small-for-gestational age, one found that higher prenatal concentrations of 4-nitrophenol were associated with 4-times higher risk of a small-for-gestational age birth, whereas higher prenatal concentrations of TCPY and 3-PBA were associated with 0.12–0.75 times significantly lower risk of a small-for-gestational age birth, respectively . The sec3.9Of the four studies that reported outcomes later in infancy, two studies found that prenatal exposure to organochlorines was not associated with child height or weight at 8–9 or 12–14 weeks of age , or with3.10Of the 31 studies included in this review, six conducted subgroup analyses: five by child gender  and one 3.11Of the 31 articles included in this review, 23 assessed exposure at a single time point: 16 at delivery/birth , five du3.12The certainty of the evidence was “very low” for all outcomes reported in ≥4 studies  due to downgrades for inconsistency, indirectness, and imprecision .4In this systematic review, we sought to assess the effect of pesticide exposure on birth outcomes and/or postnatal growth in children <5 years of age living in LMICs. Although we searched 10 databases and allowed for broad definitions of the exposures and outcomes, our search strategy identified only 653 unique records, highlighting the limited literature on the topic in both high-income countries and LMICs. We included 31 studies from LMICs assessing the associations between prenatal pesticide exposure and child growth outcomes at birth or up to age 5 years. We found no consistent associations between prenatal pesticide exposure and birth weight and birth length for all pesticide classes, including associations for subgroups by child sex. Prenatal exposure to organochlorines appeared to be associated with birth weight, but the direction of this association remained unclear with studies demonstrating both positive and negative associations. Prenatal exposure to pyrethroids may be associated with lower birth weight. Similarly, findings with respect to birth length were not consistent, with positive, negative, and null associations observed in the literature. In addition, we found no consistent evidence of an association between prenatal pesticide exposure and low birth weight and preterm birth. Associations with growth outcomes later in infancy  were also inconclusive given the limited number of studies. The certainty of the evidence was “very low” for all outcomes.Our findings extend existing evidence on the associations between pesticide exposure and child growth in two key ways. First, to the best of our knowledge, this is the first systematic review to focus only on LMICs. Previous systematic reviews have included both high-income countries and LMICs without comparing and contrasting findings across these two groups . This diConsiderable evidence shows that several mechanisms underlie the associations between pesticide exposure and child growth, including endocrine, hormonal, thyroid, and placental disruption in pregnancy , thyroidGiven these plausible biological and physiological mechanisms through which pesticide exposure during pregnancy can influence child growth, the lack of consistent associations in LMICs is likely due to two important limitations of the current literature. One major limitation is the incomplete toxicology picture. Most studies included in this review assessed a few active ingredients and some did not assess specific pesticides but used residential location or occupation as a proxy for pesticide exposure. A recent study identified 239 active pesticide ingredients approved for use in China , the couThe second major limitation of the existing literature is that most studies assessed pesticides at a single time point during the third trimester of pregnancy or at delivery/birth. Moreover, studies of or ganophosphates, pyrethroids, and carbamates mostly assessed biomarkers with short half-lives. Thus, most of the included studies did not capture chronic exposure levels. Chronic low-level exposure to pesticides has been linked to numerous neurologic functioning, neuro development, and growth problems in animals and adults . HoweverRelatedly, one limitation of our methodology was the inclusion of cross-sectional studies, which do not capture chronic exposure to pesticides with short half-lives and are subject to reverse causation . However, of the 20 cross-sectional studies we included, only one assessed exposure to organophosphates using biomarkers with short half-lives . The remAlthough included studies were limited to a single prenatal assessment, their findings do suggest that the effects of prenatal exposure to pesticides may manifest later in life. Specifically, one study found that prenatal exposure to organophosphates was associated with poor child linear and ponderal growth at two years of age , and anoDespite the strengths of our methodology, including a pre-registered protocol, a search strategy developed in consultation with a research librarian, the lack of language restrictions, and the inclusion of 10 databases, some limitations of the current literature are worth noting. First, we identified only three studies (out of 653 unique records) conducted in sub-Saharan Africa, none of which met our inclusion criteria. Two of these studies were conducted in South Africa; one assessed prenatal pesticide exposure in the context of insecticide-treated bednets for malaria prevention , whereasLastly, none of the studies included in this review examined the causal impact of pesticide exposure on child growth. More conclusive studies identifying causal impacts are needed. One approach could be to conduct randomised controlled feeding trials of organic foods. Three small studies in the United States (sample sizes ranging from 9 to 40 children) have shown that substituting conventional foods with organic foods significantly reduced pesticide biomarkers in children . Another5This systematic review of pesticide exposure and child growth among children <5 years of age living in LMICs identified 31 articles examining the associations between prenatal pesticide exposure and child growth outcomes at birth and later in infancy. The existing literature suggests no consistent associations between prenatal pesticide exposure and birth weight, birth length, low birth weight, and preterm birth. Many included studies were at serious risk of bias, and the quality of the evidence was “very low” for all outcomes. More studies with accurate quantitative data on commonly used pesticides and their metabolites are needed to better understand if, and how, pesticides influence child growth in LMICs. Ideally, these studies should capture chronic exposure to complex mixtures using consistent methodologies in comparable populations of pregnant women and children. Given the limited resources in LMICs to accurately measure pesticides in various biological matrices following gold-standard methods, capacity and infrastructure strengthening are needed to ensure the feasibility of toxicological cohort studies in LMICs. Precautionary guidelines may be needed given the potentially harmful effects of pesticide exposure on child growth.Appendix A. Supplementary data


Birth weight has emerged as the pointer of infant wellbeing and the fundamental focus of infant health policy. Low birth weight predisposes newborns to loads of health disarray like underweight, stunting, hypoglycemia, hypothermia, mental retardation, physical, and neurodevelopment problems which results in high rates of morbidity and mortality. This study aimed to assess the prevalence and associated factors of low birth weights in term newborns.  This study designed to assess the prevalence and associated factors of low birth weight among term newborns in Dilla town, Southern Ethiopia.  Institutional based cross-sectional study design was used on 472 term newborns. The study setting includes three health centers  within Dilla town and Dilla University referral hospital from September 1, 2018, to January 30, 2019. The study subjects were mothers with term newborns delivered in the above institutions and those delivered at home and received care within the first 24 hours after delivery in the above health care settings.  A total of 161 (34.1%) of the term newborns were low birth weight. Divorced mothers, rural residents, maternal age <20 years old, unwanted and unintended pregnancy, no ANC follow-up, no dietary counsel, no foliate supplementation, and cigarette smoking have shown an association with low birth weight of neonates.  Even though the method of sampling used in this study has its confines, the prevalence of low birth weight in this study was higher than the estimate in Ethiopia. Therefore, it is recommended that special attention should be given to pregnant mothers to get adequate rest, additional diet, and antenatal services available and accessible to all pregnant women. Low birth weight (LBW) is defined as having a birth weight of less than 2.5 kilograms irrespective of the gestational age of the neonate according to World Health Organization (WHO) . The chaUsually, a baby born with less than 2.5 kilograms needs extra hospital care, and there are a regular alarm and uncertainty over future health outcomes . In someThe prevalence of LBW in Ethiopia was 17.3%  which isA study was done in Olkalou district hospital, Kenya, on factors associated with low birth weight among neonates reported that the proportion of LBW was 12.3% . MoreoveThe study was conducted in Dilla town  from September 1, 2018, to January 30, 2019. Dilla is the capital city of Gedeo zone, SNNPR, Ethiopia; Dilla is 359 km and 100 km away from Addis Ababa and Hawassa, respectively. The town has 8 woredas and bordered by Sidama in the north, Oromiya in the south, east, and west. It is also bounded by the rivers Legedara north and east, Michelle in south and Waleme in the west. The town has a Woinadega type of weather condition with a total of 954,120 populations and has one referral hospital, three health centers owned by the government, and other private clinics.An institution-based cross-sectional study was conducted.Term newborn mother pair who delivered in the three health centers, one referral hospital, and those delivered at home but received care in the above health institutions within 24 hours of delivery during the study period were considered.N) is less than 10,000, we made a correction formula and multiply by 4 to maximize the sample size. Then, the sample was proportionally allocated to government health facilities in Dilla town based on the number of previous childbirth attendance. Finally, all eligible postpartum mothers to term newborn pairs were consecutively recruited until subsamples for the facilities and the total sample for the study were achieved.A sample size of 472 was calculated with the following assumptions: 8.1% expected proportion of low birth outcome took from similar Ethiopian study , 95% conTerm newborn with mother who delivered in the three health centers, one referral hospital, and those delivered at home but received care in the above health institutions within 24 hours of delivery.Twins and neonates delivered from mothers who had known chronic or pregnancy-induced pathologies were excluded from the study.Data were collected by trained midwives using structured interviewer-administered questionnaires from mothers. The weights of newborns were measured using the digital Seca balance scale (Germany) to the nearest 1 g. The scale was adjusted to the zero levels before weighing each newborn. Measurement was taken immediately after birth for those delivered in the health institutions, however, for those delivered at home took within the first 24 hours. The investigator supervised the data collectors randomly while interviewing the mothers and weighing newborn babies.To guarantee the validity of the information gathered, midwives who are well experienced in delivery care were recruited and training was given on techniques of data collection before the actual data collection. The questionnaire was pretested on subjects with the same socio-demographic characteristics in another similar health institution before being applied to the study population, and the necessary modifications were made before the main study. The investigators reviewed and checked the data each day after data collection for its completeness and accuracy.Ethical clearance was obtained from the Institutional Review Committee of Dilla University, College of Medicine and Health Sciences. Official letter of cooperation will be distributed to each of the data collection sites. Before the questionnaire, the aims and objectives of the study were clearly explained to the participants. Verbal informed consent was obtained from each study participant before data collection. Confidentiality of the data was maintained by excluding their identifiers. All participants were involved in this study only with their willingness.p values of up to 0.20 in the bivariate logistic regression analysis were identified and fitted to the multiple logistic regression analysis to identify the independent effects of each variable to the outcome variable. The odds ratio with 95% confidence intervals (CI) was calculated to distinguish the occurrence and strength of associations, and statistical significance was affirmed if p < 0.05.The entire data collected using a structured questionnaire were validated, edited, coded, and entered into SPSS version 23. Followed by checking for any inconsistencies, descriptive analysis was performed. Descriptive statistics, such as frequencies, and percentages were used to describe the maternal socio-demographic and obstetric history, sex, and weight of the neonates. A chi-square test was used to find the potential association of dependent and independent variables. Bivariate logistic regression analysis was done to decide whether there is an association between low birth weight and different factors to select nominee variables for multivariate logistic regression. Variables with Socio-demographic characteristics: in this study, a total of 472 singleton deliveries from the three health centers and one referral hospital were included giving a response rate of 100%. The socio-demographic characteristics of mothers studied revealed that 143 (30.3%) were 20-30 years, 120 (25.4%) were between 31 and 40 years of age, 108 (22.9%) were less than 20 years of age, while the remaining 101 (21.4%) were above 40 years of age. The predominant religion of the study population was found to be Protestant 244 (51.7), followed by Orthodox 98 (20.8%), and Muslim 75 (15.9%), while the rest were neither Christians nor Muslims. The predominant ethnic group was 288 (61%) Gedeo followed by Gurage 73 (15.5%). Analysis of educational levels of mothers showed that the majority 257 (54.4%) had elementary education, 111 (23.5%) had no formal education, while the rest 104 (22%) had secondary school and above levels of educational. Concerning monthly family income among the study population, 242 (51.3%) earned less than 2001 ETB, followed by 119 (25.2%) who earned between 2001 and 4000 ETB, while the rest 111 (23.5%) earned greater than 4000 ETB. The mothers' response to their occupational status revealed that 107 (22.7%) were farmers, 105 (22.2%) were government employees, 99 (21%) were merchants, 84 (17.8%) were daily workers, while the remaining 77 (16.3%) were housewives. Among the mothers studied, majority 221 (46.8%) were married, 130 (27.5%) were unmarried, and the rest 121 (25.6%) were divorced. The majority of the respondents, 369 (78.2%), were urban, and 103 (21.8%) were rural residents .Two hundred twenty-three (47.2%) of mothers were primiparous, 128 (27.1%) of mothers gave 2–4 births, and the rest gave 5 and more births. Concerning pregnancy type among the study population, 173 (36.7%) were wanted but unintended, followed by 168 (35.6%) who were unwanted and unintended, and the rest 131 (27.8%) were wanted and intended. The majority, 235 (49.8%), of the mothers gave birth to the current newborn with less than two years (<24 months) after previous childbirth. The majority, 225 (47.7%), had no antenatal care (ANC) follow-up, 124 (26.3%) had complete follow-up, and the rest of 123 (26.1%) had 1-3 ANC follow-up during recent pregnancy. 307 (65%) mothers drank alcohol during pregnancy, and the rest 165 (35%) had not drunk alcohol during pregnancy. 337 (71.4%) mothers had no cigarette smoking habits during recent pregnancy, whereas 135 (28.6%) had a cigarette smoking experience. 369 (78.2%) mothers affirmed for getting dietary advice during ANC follow-up. The majority of the respondents, 345 (73.1%), took iron-folic acid. Analysis of sex of neonates showed that slightly more than half, 240 (50.8%), were female, while the rest 232 (49.2%) were male .In this study, 34.1% of term neonates were found to be LBW. The bivariate logistic regression analysis showed that maternal age, residency, educational status, occupation, marital status, birth interval, pregnancy type, ANC follow-up, dietary counsel, foliate supplementation, alcohol drinking, and cigarette smoking were associated with a low birth weight of neonates. After adjustments for possible effects of confounding variables, ANC follow-up, residency, dietary counsel, foliate supplementation, cigarette smoking, pregnancy type, marital status, and maternal age were significantly and assertively associated with low birth weight.No ANC follow-up during pregnancy showed a significant association with low birth weight. In epidemiological explanation, this showed us that mothers who had no ANC follow-up were 6.83 times more likely to give low birth weight term neonates as compared to those mothers who had complete ANC follow-up during pregnancy with . Being a rural resident was strongly associated with low birth weight. Those mothers who were rural residents were 6.78 times more likely to give term low birth weight neonates as compared to their counterparts with . The likelihood of delivering low birth weight neonates among mothers who did not get dietary counsel was 6.21 times  more compared with mothers who got dietary counsel. Those mothers who did not take folate supplementation during pregnancy were 5.48 times  as likely to give term low birth weight neonate as those mothers who took foliate. Furthermore, cigarette smoking during pregnancy was a significant factor associated with low birth weight neonates. Mothers who smoke a cigarette during pregnancy were 4.35 times more likely to give term low birth weight neonate as compared with those mothers who did not smoke with . Unwanted and unintended pregnancy was strongly associated with low birth weight. Those mothers who got pregnant unwanted and unintendedly were 3 times more likely to give term low birth weight neonates compared to mothers who got pregnant in a wanted and intendedly with . Being divorced and age <20 years old mothers were another significant factor associated with low birth weight. Divorced as well as age <20 years old mothers were 3.12 and 4 times more likely to give term low birth weight neonates as compared to married and age ≥40 years old mothers, respectively, for being divorced  and age <20 years old  .The prevalence of LBW in this study was 34.1%, relatively higher than the estimate of LBW from the Ethiopian Demographic Health Survey (EDHS) 2011 (28%) . AnotherIn this study, the risk of delivering LBW term newborn was found to be significantly higher in those mothers who were residing in rural areas than those residing in urban areas. This may be related to the lifestyles of rural dwellers such as poor balanced diet habits and drinking local alcohol, which is commonly practiced by young women of rural areas. Another possible explanation for the difference might be the study settings, such as access to the health facility and acquiring maternal care education through media is more common in urban than rural. Maternal age was an important determinant of the low birth weight of term neonates in this study. Mothers who had less than 20 years at the time of delivery gave a higher proportion of LBW babies as compared to mothers whose age were greater than or equal to 40 years old. This result is similar to the study conducted in Adwa , systemaThe pregnancy type was also another associated factor for the term LBW. Those mothers whose pregnancies were unwanted and unintended gave more low birth weight neonate as compared to those mothers whose pregnancies were wanted as well as intended. This finding is in line with studies carried out on low birth weight and associated factors in Axum and Laelay Maichew districts , Adwa geFurthermore, in this study, we observed that those mothers who had not ANC follow-up and dietary counsel were more likely to give term LBW neonates as compared to mothers who had complete ANC follow-up and dietary counsel, respectively. The current findings are supported by findings from 2006 to 2011 NDHS , Axum anLastly, smoking was another maternal factor significantly associated with the term LBW. Mothers who had a habit of smoking during pregnancy were more likely to give LBW neonates as compared with nonsmoker mothers. There was a dissimilar result done by Cogswell et al. .The magnitude of low birth weight in Dilla town was too high. ANC follow-up, residency, dietary counsel, foliate supplementation, cigarette smoking, pregnancy type, marital status, and maternal age showed significant association with LBW neonates. Thus, it is recommended that special attention should be given to pregnant mothers to get adequate rest and additional diet, and making antenatal services available and accessible timely to all pregnant women is recommended to minimize the prevalence of low birth weight.


Pregnancy may represent a time of exceptional vulnerability to intimate partner violence because of changes in women’s conditions. Despite the fact that intimate partner violence during pregnancy confers considerable risk to the health of the woman and her fetus, data regarding to association of stillbirth and intimate partner violence is lacking in Tigray region. The objective of this study is to assess intimate partner violence during pregnancy and its association with still birth among postpartum mothers in hospitals in Tigray Region of Ethiopia.Cross-sectional study design was used to assess 648 women about intimate partner violence during pregnancy and its association with still birth. Simple random sampling technique was employed to select health facilities and systematic sampling was used to select the study participants. Data was entered by using Epi info version 3.5.1 and analyzed using SPSS version 20. Logistic regression analysis was done to assess the association between exposure to intimate partner violence during pregnancy and stillbirth while adjusting for possible confounders.The prevalence of still birth was 3.6%in this study population. There was a statistically significant association between exposure to intimate partner violence during pregnancy and still birth. Pregnant women who were exposed to intimate partner violence during pregnancy were three times more likely to have still birth 3.3(95% CI: 1.1–9.7) as compared to those who were not exposed. Another important factor associated with stillbirth was low birthweight 16.7.The prevalence of still birth in this study was high. Women who subjected to intimate partner violence during pregnancy had greater risk of having stillbirth baby. Intimate partner Violence (IPV) is defined as a psychological, sexual and physical harm by a current or former partner . IntimatA multi-country study by the World Health Organization shows that 15 to 71% of women experience physical and/or sexual in their lifetime . DomestiThe prevalence of IPV among pregnant mothers ranged from 13.5% in Uganda to 2% in Australia . Study fIn Ethiopia, IPV during pregnancy was found to range from 4%  to 8%  , 10. StuAccording to Ethiopia’s demographic health Survey data in 2016, perinatal mortality rate was 33 per 1000 pregnancies [According to 2014 new born action plan global multi partner movement to end preventable still birth, the target was set to reduce the magnitude of stillbirth to less than 12 per 1000 births[ comprise 251,650 of the population. According to 2015 Tigray regional health bureau annual report, there are a total of one specialized referral hospital, 15 general hospitals, 22 primary hospitals, 204 health centers and 712 health posts and three private hospitals. There are 51 doctors with specialty training in obstetrics and gynecology, 87 general practitioners, 3092 nurses and 792 midwives in the region. The study was conducted from November 2017–June 2018. Institutional based cross-sectional study was used.The study population was all women who gave birth in hospitals within the Tigray region. Women who are unable to hear were excluded from the study.There are 41 hospitals  which provide delivery service in the study area. Health facilities were stratified in to private and public hospitals. For the purposes of this study, one private hospital and eight public hospitals were selected by simple random sampling technique. Participants from each selected health facilities were sampled by systematically. Every 3rd postpartum women were included until the required sample size was reached. Consecutive participant was included if the selected participant was not eligible. Average client load for each hospital was assessed using the patient flow three months’ prior to data collection period and proportional allocation to each hospital was made based on their respective quarterly client flow.To calculate the sample size, we used available data that indicates 25.8% prevalence of IPV during pregnancy in Ethiopia  and 95% Data on socio-demographic characteristics of participants  and obstetrics characteristic  were collected through interviews and chart view.Data was collected using a structured questionnaire that was administered to post-partum women by trained staff. Staff involved in administering the questionnaires included nine midwives (diploma level training) who were supervised four Midwives (bachelor level training). Training was given to both data collectors and supervisors about the aim of the study, procedures, how to approach the study participants and data collection techniques.Stillbirth: is typically defined as fetal death at or after 28 weeks of pregnancy. It results in a baby born without signs of life.Maternal exposure to IPV was determined through the question: “when you were pregnant with this child, did your current partner or boyfriend do any of the following things to you? The lists of potential offences were as follows: Physical violence: slapped, pushed or shoved, hit with fist or something else that could hurt her, trauma to the abdomen, choked or burnt on purpose, used or threatened to use knife, gun or weapon. Emotional violence: insult, humiliation, intimidation on purpose, verbal threats. Sexual violence: Forced into sexual intercourse when you did not want, had sexual intercourse when you did not want to because you were afraid of what partner might do, forced to do something sexual that you found degrading or humiliating. Questionnaire was prepared first in English and then translated into Tigrigna and back translated to English by language expert to ensure the accuracy of the information.Data on still birth was collected from the medical charts and direct interviews via questionnaires. Outcomes of interest for this analysis pertained directly to neonatal outcomes and were obtained through chart review within 72 h of delivery. Birth weight (g) and gestational age (weeks) were taken directly from the chart. Low birth weight was assigned if the neonate weighed < 2500 g, and preterm birth was considered if the neonate was born at < 37 completed weeks of gestation and > 28 weeks. Gestational age was computed (dated) from either first trimester ultrasound or reliable last menstrual period.An ethical approval for the study was obtained from Mekelle University College of health science health research ethics review committee. Permission letter was obtained from regional health office and was presented to selected hospitals. Written consent was taken from each participant before the starting of data collection and for those women who are under age, written consent was obtained from their parent. Since IPV is sensitive issue the interviews were conducted in a private room. Confidentiality was maintained throughout the study. In addition, participants were told that they have the right not to participate and/or could withdraw from the study at any point.Double data entry was done by using Epi info version 3.5.1 and exported to SPSS version 20 software package for analysis. Experience of any physical, sexual or emotional violence was considered if a woman reported being exposed to at least one of the acts of violence exerted by her partner while she was a pregnant for current neonate.To estimate the association between maternal exposure to intimate partner violence and risk of still birth, logistic regression analyses were performed and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Multivariable logistic regression analysis was performed where intimate partner violence plus other covariates that could influence still birth such as age, educational level, occupation during pregnancy and alcohol intake etc. The degree of association between independent and dependent variables were assessed using odds ratio with 95% confidence interval.N = 610; 94.28%) were married. Out of the participants, nearly half were housewives   of them were urban residents. The mean age of the respondents was 27 ± 6 years. Majority of respondents 53081.9%), were between ages 20–35 years old although a few were younger. Most participants were married  delivered via cesarean section. Similarly, a quarter of the women (25%) experienced premature rupture of membrane, 66 (10.2%) experienced hypertension and 35 (5.4%) had antepartum hemorrhage (APH). Among these participants, 611(94.4%) had at least one antenatal care (ANC) follow up during their last pregnancy. In this study population, 42 (6.5%) of the women admitted that their index pregnancy was unwanted. Data on pregnancy outcome shows that 70 (10.8%) women delivered before reaching term and 120 (18.5) babies were low birth weight. The magnitude of still birth in this study was 23 (3.6%)  women admitted that they ingested alcohol during pregnancy sometimes and 10(1.6%) ingested chat (a stimulant leaf) while they were pregnant with the index neonate. Three (0.5%) women smoked while pregnant.Around 47 (7.3%) women experienced intimate partner violence during their index pregnancy in which 22 of them were subjected to physical violence, 39 of them experienced sexual violence and the remaining 8 women were subjected to psychological violence.In our study, women who were subjected to intimate partner violence during pregnancy are 3.3 times  more likely to have stillborn baby than who did not experience IPV during pregnancy.Low birth weight was also significantly associated with still birth. Babies with low birth weight have 16.7 times  risk of still birth as compared with babies’ weight greater than or equal to 2.5 kg. Having unwanted pregnancy and preterm birth were significant associated with still birth in bivariate analysis but is has no association in multivariate analysis Table .Table 3This study which assessed the association between IPV during pregnancy and stillbirth provided new and important information that has been missing from research in low income countries like Ethiopia. The magnitude of intimate partner violence during pregnancy is concerning and can have important implications on neonatal outcome. This study revealed that the magnitude of intimate partner violence during their index pregnancy was 7.3%. This is lower than study done in Tanzania (30%), Vietnam (32.5%) and Ethiopia hosanna (23%) , 17. TheIn this study the prevalence of still birth was found to be 3.6%. Our finding is similar with the findings from Tanzania  and Zimb, 20. ThiThis study found that IPV has significant association with still birth. This finding is in line with a research done in Columbia, South Carolina and California which indicated that women who experienced IPV during pregnancy have increased risk of still birth , 22. IPVIn this study still birth has association with low birth weight. Babies delivered with low birth weight increased the risk of still birth by sixteen times. This finding is supported by research done in north Tanzania and peri-urban District in Ghana; being low birth weight increase the risk of still birth by more than nine times , 23. FetSince IPV during pregnancy is sensitive and self-reported, there is a risk of under reporting. Given that this is a cross-sectional rather than a prospective study, it is not possible to establish the temporal relation between IPV and stillbirth.This study shows that still birth is high in this population and intimate partner violence during pregnancy has significant association with pregnancy outcome, namely still birth. It is important that healthcare providers involved in maternal care as well as the federal ministry of health prioritize formulating a protocol for screening intimate partner violence during pregnancy to reduce still birth.


LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm (p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g (p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring >850K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the  Fetal exposure to tobacco smoke throughout pregnancy is prevalent and a preventable risk for child morbidity and mortality ,2. DespiBirth weight is an informative indicator of pregnancy outcome and neonatal health. Both low and high birth weight categories have been linked to adverse health outcomes later in life ,13,14,15A plausible mechanism through which exposure to adverse intrauterine conditions may negatively impact long term health is through modulation of deoxyribonucleic acid (DNA) methylation. It has been suggested that the effects of maternal factors during pregnancy on birth weight are exerted through differential methylation of DNA in offspring . A meta-DNAm has a vital role in repressing gene expression by blocking promoters at which activating transcription factors could bind, thereby controlling cell differentiation and embryonic development . Sutter Although previous studies ,27 have To the best of our knowledge, no study has explored whether the mediation of DNAm after carbon monoxide exposure in early pregnancy would affect birth weight, direct and indirectly. This study aims to investigate CpG methylation in cord blood samples with self-reported maternal smoking during pregnancy and with exhaled carbon monoxide (eCO) as a biochemical marker for current cigarette exposure. To reduce the number of CpG sites to be tested we focused on DNA methylation sites related to smoking as reported by Joubert et al.  based onThis investigation focuses on a subsample of infants from the randomised controlled trial (RCT), the Breathing for Life Trial (BLT) . BLT is At enrolment, between 12 and 23 weeks gestation, information was collected about sociodemographic characteristics and lifestyle factors, such as self-reported maternal smoking, maternal age, ethnicity, level of education, parity, health status, height, weight, and exhaled carbon monoxide (eCO) . Postcodes were collected at baseline and used for socioeconomic status within state or territory based on the Socioeconomic Index for Areas (SEIFA) percentiles . For thoAfter delivery, trained staff blinded to the intervention group extracted information from medical records on gestational age at birth, birth weight, birth length, type of delivery, maternal and neonatal complications.Cord blood samples from BLT participants were collected at John Hunter Hospital  immediately after birth by needle puncture of the umbilical vein after the umbilical cord was detached from the infant. Samples were transferred into EDTA tubes to be processed within six hours.+, CD193+, CD16−), Neutrophils , B cells , Natural Killer (NK) cells , lymphocytes TCD4 cells +, CD4+, CD25+, CD127+), lymphocytes TCD8 cells  and Monocytes . After 30 min of incubation, red blood cells were lysed using BD FACS™ Lysing Solution and washed. Samples were stored at 4 °C until acquisition of LSRFortessa X-20 flow cytometer . Samples were analysed using FlowJo software .Cord blood cells were stained in whole blood and subsets were predefined based on specific surface markers as follow: Eosinophils  where bisulphite conversion and subsequent methylation quantification was conducted using the Illumina Methylation EPIC array platform according to the manufacturer’s instructions.Epigenome-wide DNAm was assessed using the Illumina Infinium MethylationEPIC BeadChip , which interrogates >850,000 CpGs associated with over 24,000 genes. A standard protocol was used to process arrays . To contThe Pregnancy and Childhood Epigenetics (PACE) consortium , in ordehttp://cran.r-project.org/web/packages/ttScreening/ (accessed on 1 February 2021)) [Analyses were conducted using SAS™ software, Version 9.4 of the SAS System for Windows, and Stata software . In the IoW birth cohort, potential associations of DNAm sites with birth weight were screened using the ttScreening R package ) . This mep < 0.05/), to account for multiple testing in EWAS results.Chi-squared tests were performed to compare the distribution of demographic and obstetric descriptors among women with smoking and no smoking exposure during pregnancy. Models used confounders including maternal age, parity, and infant sex. To adjust for possible confounding in DNAm that might occur from cell composition in whole blood , we alsop > 0.05, (2) standardized root mean square residual < 0.08, (3) adjusted goodness of fit > 0.95, and (4) root mean square error of approximation < 0.05. All analyses were performed using the Statistical Analysis System .Path analysis or structural equation modelling (SEM) ,39 were p < 0.001) , and 83 self-reported not to have smoked during pregnancy (mean age 30 ± 4.8). Using an eCO level of 6 ppm as recommended by Gomez et al.  as the r< 0.001) .p = 0.18). Using the eCO (>6 ppm) to discriminate between smokers and non-smokers, the average difference in birth weight was 429 g (p = 0.005). Infant sex differences were identified, such as higher birth weight among males. In female newborns, the average birth weight was 459 g lower in the eCO ≤ 6 ppm subgroup compared to >6 ppm , 81.8% of the mothers reported smoking (Sensitivity), whereas among those with lower eCO levels 97.6% stated no smoking . The average methylation at this site is 39%. For ease of interpretation and estimation, the effect of DNAm on birth weight on the path diagram is represented as the percentage methylation value (β × 100). For each 1% increase in methylation at this site, the birth weight increased by 44.8 g (p < 0.001). In other words, a 1% reduction of methylation of cg0226440 by eCO also resulted in a reduction of birth weight by 44.8 g.To further test whether this CpG site mediates the effect of smoking on birth weight, we conducted structural equation analyses . Essential confounders were infant sex and the proportion of B cells, CD4 cells, and eosinophils in cord blood. Methylation at cg02264407 in the h weight , controlh weight . CD4+ T LMO7 gene was significantly linked with exhaled CO measurements. Interestingly, none of the CpGs was associated with self-reported smoking. Finally, path analyses showed a direct effect of CO-exposure and an indirect effect of CO-exposure on birth weight via the CpG site cg02264407 on the LMO7 gene. These results add to the developing literature demonstrating that maternal smoking during pregnancy can influence epigenetic modifications in early fetal/infant development [We measured variation in cord blood DNAm in 94 infants born to mothers with asthma. Using secondary analysis, an analysis focusing on 520 smoking related CpGs sites was used to identify that CpGs also associated with birth weight. We discovered 30 CpGs. Then, in the BLT cohort, we tested whether self-reported smoking status during pregnancy, and/or CO exhalation as a biomarker of current cigarette exposure, are statistically significantly associated with any of these 30 DNAm sites. We found nine CpGs sites (on nine genes), after Bonferroni correction, to be significantly associated with birth weight. Focusing on the effects of maternal smoking, the methylation of cg02264407 on the elopment ,41,42, pAssessing an epigenetic role in disease pathogenesis is of interest when investigating physical development in early childhood ,43, in pLMO7, in turn affecting birth weight. Differential methylation of this gene related to maternal smoking was also observed in other EWAS in cord blood [LMO7 is a multifunctional protein that can be found in several sites, mostly in the nucleus, plasm membrane, and at epithelial adherence junctions. Besides, it is broadly expressed in skeletal muscle and heart, with increased levels of expression in the lung [LMO7, gene ontology annotations reported connections between the LMO7 gene and the biological process of regulation of cell adhesion (GO:0030155) and regulation of signalling (GO:0023051). A Reactome pathway [p < 0.05) and neddylation (p < 0.05). Albeit the latter hypothesis is controversial [LMO7 gene in mice resulted in an increased postnatal lethality due to a dramatic growth abnormality [LMO7 in human development has yet to be studied.Our results are consistent with the hypothesis that tobacco smoke exposure in utero exerts direct biological influence on the developing infant through altering methylation of specific CpGs, in particular at rd blood  and anotrd blood ; howeverthe lung ,60,61. I pathway  analysisoversial , deletioormality . Moreoveormality . Despite+ cells.The small sample size of 94 pregnant mothers and their offspring is a limitation. Hence, we tried to focus on a limited number of DNAm sites that were detected in prior studies related to gestational smoking. Nevertheless, it is likely that other CpGs related to maternal smoking and offspring birth weight were not detected due to the reduced statistical power. In the present work, a potential limitation was that eCO measurements were not performed throughout pregnancy. The eCO measurement depended on the randomisation to the control or the intervention arm, which dictated a different regime of study visits. Consequently, we used only the baseline eCO measurement for both arms, it being unfeasible to use the data from attendance at other visits. A previous study indicated that differential methylation at some CpGs related to maternal smoking seems to require a sustained exposure to observe the effects on DNAm at birth . DespiteStrengths of our study include more objective measurement of CO as a marker of maternal smoking. Nevertheless, to avoid false-negative CO assessments, future studies should increase the density of CO measurement, since CO has a short half-life of five-six hours resulting in lower or non-detectable CO-levels in some participants. A second strength is the use of cord blood samples to assess DNAm as a likely mediator of adverse effects of in utero exposure to tobacco smoking on offspring birth weight without confounding from any post-birth exposures. Thirdly, even though we could only include participants for whom cord blood samples were available, the mode of delivery was not limited to vaginal birth. Thus, it is unlikely that only relatively healthier infants were included, excluding the possibility of underestimating the effects of smoking exposure during pregnancy. Fourthly, we compared associations of smoking related CpG sites with active tobacco use information collected through a self-administered questionnaire and eCO. The usual practice of analysing multiple exposures concurrently can lead to errors in explanation, as it is possible that the multicollinearity of exposures biases their assessment.LMO7 gene. In turn, a reduction of the methylation of cg02264407 was associated with lower birth weight. Our results are consistent with previous findings and demonstrate a potential epigenetic mediating effect with the consequence of in utero tobacco smoke exposure affecting fetal growth, showing a specific pathway via reducing the methylation of LMO7. Additional investigations to confirm these findings are recommended due to limited sample size. Finally, emerging approaches such as diet intervention hold the potential to prevent indirect adverse effect of maternal smoking on birth weight in vulnerable populations.This is the first study to show that measurement of eCO between the 12th and 22nd week of pregnancy had inverse association with cord blood methylation of cg02264407 on the


The northern part of the province of Khyber Pakhtunkhwa in Pakistan experienced armed conflict since September 2007 till the autumn of 2011. Conflict involved widespread insurgency activity and military intervention including in 2009 internally displacing the 2.5 million people of the valley of Swat to live in camps, with relatives, or in rented accommodation across the region for approximately 4 months. It was during this period the current study was conducted to determine whether Post-Traumatic Stress Disorder in pregnant women was independently associated with Low Birth Weight (LBW) in an area affected by conflict and militancy.p-value of < 0.25 on uni-variate analysis were entered.A case control study was conducted in tertiary care hospitals of district Peshawar, Khyber Pakhtunkhwa. Two hundred twenty-five cases (neonates with birth weight <  2.5 kg) and 225 controls (neonates with birth weight of > 2.5 kg) were enrolled within 24 h of delivery. Post-Traumatic Stress Disorder was assessed through the MINI Neuropsychiatric Interview 5.0, a validated questionnaire along with the birth weight of the newborn. Maternal anthropometry, anemia and other sociodemographic details were also obtained during data collection. Data was analyzed using statistical package (STATA version 14). Logistic regression analysis of the association between LBW and all variables collected with a A total of 450 newborn and mother pairs participated in the study with 225 cases and 225 controls. On univariate analysis factors significantly associated with LBW include: less than 5 years of paternal schooling and PTSD. On logistic regression, PTSD was independently associated with low birth weight in the presence of other factors like maternal/paternal schooling, gravida, history of preterm, BMI of the mother and maternal anemia.PTSD was found to be independently associated with LBW. In light of the current findings and other similar literature, intervention programs should be considered for pregnant women exposed to traumatic events. There is a gradual rise in natural and man-made disasters in the past few decades, with a global estimates of the Internally Displaced Persons (IDPs) resulting from these conflicts since 1990 to 2009 exceeding 23 million. Alarmingly around half of these numbers have occurred in the Eastern Mediterranean Region (EMR) of the World Health Organization (WHO) which includes Pakistan . PTSD ocLBW baby is defined by the international statistical classification of diseases as a live newborn with a birth weight less than 2500 g regardless of gestational age . LBW maiThe northern part  of Pakistan was a nexus of conflict and militancy between the Taliban and the security forces since July, 2008, resulting in a large scale displacement of the local population. Around 2 million had been registered to be displaced from the region. Only 20% of the displaced were living in 23 camps established by the Pakistan government, the rest were with relatives, rented accommodation, within family homes, in schools, mosques and other community buildings . Most ofThis case control study was conducted in three tertiary care hospitals of district Peshawar . These are tertiary level referral hospitals for the entire province and it was forecasted that most of the displaced people will avail services in these facilities. The total duration of the study was 4 months, from April 20th to July 3rd, 2009. The study population were single live newborns of 24 or more weeks of gestation and their mothers delivered at or admitted within 24 h of birth at the hospital maternity wards of the three tertiary care hospitals of Peshawar. Newborn with recognizable congenital anomalies, twin pregnancy, born to mothers whom labor was induced for medical complications or with maternal history of cervical incompetence were excluded. Mothers with known mental health problems or any other serious medical condition were excluded from the study. Cases were newborn mother pairs with the newborn weighing less than 2.5 kg delivered or admitted within 24 h of birth in the above mentioned hospital maternity wards. Similarly, controls were newborn mother pairs with the newborn weighing more than or equal to 2.5 kg delivered or admitted within 24 h of birth. Cases and controls were enrolled on 1:1 ratio. The controls were selected from the same maternity ward at the same time of the inclusion of the case by random sampling among the women with normal birth weight i.e. 2.5 kg or more.To determine the study objective of finding the association between the LBW and the exposure to PTSD, the sample size was estimated based on the following assumptions: an alpha of 0.01, power of 90%, and assuming a prevalence of PTSD in the population at 10%, ratio of cases vs controls of 1:1, and an odds ratio of 3 as a measure of clinical significance. Using OpenEpi version 3.01  a sampleFor the diagnosis of current PTSD the MINI Neuropsychiatric Interview 5.0, a validated questionnaire that uses DSM-IV criteria was administered . StudiesBirth weight of the newborn was measured by weighing the infant with minimum clothing on and recording the weight to the nearest 0.1 kg, by the trained medical officers. The standard cut-off for LBW in newborns was used i.e. 2.5 kg or less .Women’s height and weight measurements were recorded from the clinical records. Body Mass Index (BMI) calculations were later done during analysis. BMI was calculated using the standard as weight in kilogram divided by height in meter square classified according to WHO criteria as underweight (< 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (> 30) . LikewisData was also collected regarding the gender of the newborn, maternal age, maternal and paternal schooling, household income, rural/urban residence, Gravida, inter-pregnancy interval, and previous history of preterm births. Maternal age was participant reported at the time of interview. Maternal and paternal schooling were also recorded and was assessed through formal years of schooling and later categorized as less than 5 years and more than 5 years for analysis as the overall rates of literacy was very low in the study participants. Similarly, household income was categorized as less than or more than Rs. 10,000/month for analysis. Gravidity was defined as the total number of pregnancies including live births, still births and abortions and categorized as primigravida (first pregnancy), 2–3 Gravida (2–3 pregnancies) and 4 or more Gravida (≥4 pregnancies). Inter-pregnancy interval was defined as duration between conception for index pregnancy and the preceding delivery, abortion or stillbirth and was also self-reported by the mother.p-value of < 0.25 on uni-variate analysis were entered in the logistic regression model.The data collection was regularly supervised and monitored by the Principal Investigator (PI). The filled questionnaires by the data collection team were checked by the PI (HR) daily at the end of the day for their completeness. Data were coded and entered into the SPSS version 23 and analyzed using statistical package (STATA version 14). Descriptive analysis included frequencies and percentages for all the variables. For uni-variate analysis of the association between LBW and all other factors Chi square test (Fisher’s two-sided exact test was used if numbers in the cells < 5) was used. Associations were considered significant at 5%. Logistic regression analysis of the association between LBW and all those variables with a The study was approved by the ethical committee of Health Services Academy, Islamabad. Informed written consent obtained from study participants following explanation of the study aims and objectives. In case of illiterate women, the information was verbally explained to them in the local language and consent taken thereafter. The right to withdraw from the study was reinforced to all the participants throughout the study conduct. All information obtained in the study was kept confidential with access to personal information available only to the study lead (HR). Cases of severe distress and other health concerns requiring immediate treatment were referred to the concern department accordingly.p = 0.017) and PTSD (p <  0.001). All other factors were not found to be statistically significant and were; sex of the newborn child, maternal age, maternal schooling, monthly family income, rural/urban residence, Gravida, inter-pregnancy interval, previous history of preterm birth, maternal BMI and maternal anemia.A total of 450 newborn and mother pairs participated in the study with 225 cases (LBW mother pairs) and 225 controls . Table Table p value of < 0.25 in the uni-variate regression model were included in the analysis. These include maternal education, paternal education, Gravida status, inter-pregnancy interval, history of preterm birth and PTSD. The logistic regression model  is a valid and reliable diagnostic tool with high inter-rater and test–retest reliabilities and is considered as a gold standard for psychiatric disorders . The maiTo conclude PTSD was found to be independently associated with LBW in the displaced population following the conflict in the Malakand division of Pakistan. LBW is a major public health problem as most of the children face short and long-term consequences , therefo


Low birth weight is a global public health problem having various severe and life-threatening health effects. The World Health Organization is working to reduce the prevalence of low birth weight to 30% by the year 2025. Pinpointing the determinants of low birth weight at different scenarios is crucial to reduce the rate of low birth weight in low-income countries which consist of 96.5% of global low birth weight newborns. Thus, the aim of this study was to assess determinants of low birth weight in Sidama Zone public hospitals of South Ethiopia. An institution-based case-control study was conducted from March 1 to May 5, 2019, in Sidama Zone public hospitals. Data were collected from 354 mother-neonate samples with 118 of them having newborns with birth weight < 2500 g (cases) and 236 of them having birth weight ≥ 2500 g (controls) using a pretested, interviewer-administered structured questionnaire and medical record review. The odds of being rural dweller women was 3.51 times higher among cases (low birth weight babies) than among controls  as compared to being urban dweller women ). The likelihood of initiating antenatal care late was 3.22 times more among cases than among controls when compared with timely initiation of antenatal care ). The probability of having pregnancy-induced hypertension was 4.49 times higher among mothers of the cases than among mothers of the controls as compared to not having pregnancy-induced hypertension ). The odds of not taking iron and folic acid during pregnancy was 3.92 times higher among mothers of the cases than mothers of the controls when compared with taking iron and folic acid ). The likelihood of having Mid-Upper Arm Circumference (MUAC) < 23 cm was 4.27 times higher among mothers of the cases than among mothers of the controls as compared to having MUAC ≥ 23 cm ). The probability of having inadequate dietary diversity was 3.75 times higher among cases than among controls as compared to having adequate dietary diversity ). Interventions targeting the aversion of low birth weight should focus on promotion of iron-folic acid supplementation and dietary diversification through timely initiation of antenatal care. A newborn's weight at birth is a vital indicator of maternal nutritional status and fetal health . GloballWith regard to its consequence, about 2.5 million and 23,091 newborns die every year due to LBW across the world and in Ethiopia, respectively . It alsoExisting evidences from different parts of the world showed that the causes of low birth weight have been broadly grouped into individual-related, provider-related, and health service-related factors , 23–28.The WHO has set a policy to reduce the prevalence of LBW by 30% at the end of 2025 . PromotiDespite several studies being conducted in a different part of Ethiopia, the majority were reported from small settings and urban populations, which may underestimate the effect of possible risk factors from the rural population. This study is relatively a comprehensive study which covers more than 30 districts to determine predictors of LBW among newborns in public hospitals of Sidama Zone, South Ethiopia, where recent studies investigating the problem were not common. Thus, the study would give an input to programmatic interventions and policy considerations in the region and by extension to Ethiopia.An institution-based case-control study was conducted in Sidama Zone public hospitals from March 1 to May 5, 2019. Sidama Zone is one of 18 zones of the Southern Nations, Nationalities, and Peoples' Region (SNNPR) of Ethiopia. It is located 272 km to the south east of Addis Ababa, the capital city of Ethiopia. The zone has a total area of 6981.8 square kilometers and is administratively divided into 31 districts and 6 town administrations. According to the 2018 estimate, the zone has a total population of 4,294,730 , and the expected number of deliveries was 148,598. Currently, 15 hospitals, 126 health centers, 531 health posts, and 107 private and 7 NGO clinics are providing health service for the population. According to the zonal health department report, the proportion of women who delivered in the health facilities in Sidama Zone in the year 2018/2019 was 71.6%. All mothers with their newborns delivered at public hospitals in Sidama Zone were considered source populations for cases and controls. Cases were newborns with birth weight < 2500 g, and controls were newborns with birth weight ≥ 2500 g.Sample size was estimated using OpenEpi software with the consideration of the proportion of rural women among controls (24.8%) and the odds ratio of 2.1  and withFive hospitals were selected out of 15 public hospitals by using the simple random sampling lottery method. The required sample was allocated proportionally to each hospital based on the number of LBW deliveries reported from each hospital in the year preceding the survey. Cases were selected consecutively, and two controls were also included consecutively for each case. Women with twin deliveries and who were seriously ill during the data collection were excluded from the study.Data were collected by 10 female diploma holder midwives who speak the local languages fluently. Five male midwives with a bachelor degree were recruited as supervisors. Data collectors interviewed mothers using an interviewer-administered structured questionnaire. The serum hemoglobin level of mothers was extracted from their medical records since the hemoglobin level test is routinely done for all mothers who come for delivery services. The questionnaire was adapted by reviewing different related literatures , 29–41.Weights of the newborns were measured by using a digital Seca balance scale (Germany) to the nearest 1 g. The scale was adjusted to the zero level before weighing each newborn. Height of the mothers was measured using a height board while the mother was in standing position. Each height was taken to the nearest 0.01 m. MUAC of the mother was measured with a nonstretchable standard tape to the nearest 0.1 cm. Minimum Dietary Diversity for Women (MDD-W) was measured by the ten questions developed by FAO and FANTA as a proxy indicator to reflect the micronutrient adequacy of women's diets. Those women who replied “yes” for each food item interviewed were taken as “consumed,” and those who replied “no” did not consume anything in the previous 24 hours .Detailed training was given to both data collectors and supervisors in the context of the study and measurement of weight of the newborns and height and MUAC of the mothers. The questionnaire was prepared in English and translated to Amharic then retranslated back to English. A pretest was conducted on 5% of the total sample size one week before the actual data collection. The data collection was supervised, and the collected data were checked for completeness and consistency on a daily basis.p value ≤ 0.25 were entered into multivariable logistic regression. The multivariable logistic regression model was built using the backward likelihood ratio method in the final model. Model fitness was assessed by using the Hosmer and Lemeshow goodness-of-fit test. Finally, the determinants of LBW were reported by an adjusted odds ratio (AOR) with 95% confidence interval (CI).The collected data was checked for completeness and then coded, checked, and entered into EpiData version 4.2.1. After completing the entry in EpiData software, the data was exported to SPSS version 20 for cleaning and analysis. Data transformation was done where appropriate. Crosstabulations were made to check for the fulfillment of chi-squared assumptions. Descriptive analysis was conducted and presented using frequency tables and summarized using the mean and standard deviation. To determine the wealth index of participants, a principal component analysis was carried out after checking the fulfillment of assumptions. Women's household wealth was ranked into five groups (quintiles) as poor, second, medium, fourth, and highest from the lowest to the highest quintiles. Bivariate logistic regression was carried out, and variables with One hundred eighteen cases (birth weight < 2500) and 236 controls (birth weight ≥ 2500) participated in the study. The mean birth weight was 2089 g (SD ± 260 g) and 3181 g (SD ± 358 g) for the cases and controls, respectively. More than half of the cases (61 (51.7%)) and controls (140 (59.3%)) were males. Majority of mothers of the cases (107 (90.7%)) and controls (215 (91.1%)) were married; most of the mothers of the study participants among cases (81 (68.6%)) and controls (176 (74.6%)) were between the age of 20 and 34 years. Similarly, 107 (90.7%) mothers of cases and 148 (62.7%) mothers of controls were taking inadequate minimum dietary diversity .Fifty-one (43.2%) mothers of cases and 82 (34.7%) mothers of controls were Prim-Para. Similarly, 23 (34.3%) mothers of cases and 44 (28.6%) mothers of controls had a history of low birth weight, and also 18 (26.9%) mothers of cases and 31 (20.1%) controls had a history of stillbirth. With regard to their pregnancy intention, 50 (42.4%) mothers of cases and 98 (41.5%) mothers of controls had unintended pregnancy. Thirty-four (28.8%) mothers of cases and 54 (22.9%) mothers of controls were having preterm deliveries .p value < 0.25 in the bivariate analysis were included in multivariable logistic regression. The odds of being rural dweller women was 3.51 times higher among cases (low birth weight babies) than among controls  as compared to being urban dweller women ). The likelihood of initiating antenatal care late was 3.22 times more among cases than among controls when compared with timely initiation of antenatal care ). The probability of having pregnancy-induced hypertension was 4.49 times higher among mothers of the cases than among mothers of the controls as compared to not having pregnancy-induced hypertension ). The odds of not taking iron and folic acid during pregnancy was 3.92 times higher among mothers of the cases than among mothers of the controls when compared with taking iron and folic acid ). The likelihood of having Mid-Upper Arm Circumference (MUAC) < 23 cm was 4.27 times higher among mothers of the cases than among mothers of the controls as compared to having MUAC ≥ 23 cm ). The probability of having inadequate dietary diversity was 3.75 times higher among cases than among controls as compared to having adequate dietary diversity ) ) .The odds of being rural dweller women was higher among cases (low birth weight babies) than among controls  as compared to being urban dweller women. The low accessibility of health facility and maternal health service utilization in a rural area might increase the likelihood of having LBW infants. This finding was consistent with studies conducted in Ethiopia and Zimbabwe , 32, 33.The likelihood of initiating antenatal care late was more among cases than among controls when compared with timely initiation of antenatal care. This finding is in line with studies conducted in Algeria, Nepal, and Ethiopia , 34–36. This study indicated that the maternal history of pregnancy-induced hypertension was found to be an independent factor contributing to low birth weight where the probability of having pregnancy-induced hypertension was higher among mothers of the cases than among mothers of the controls as compared to not having pregnancy-induced hypertension. This finding is in line with studies conducted in Ethiopia, Malaysia, Nepal, and Gambia , 37, 38.The odds of not taking iron and folic acid during pregnancy was higher among mothers of the cases than among mothers of the controls when compared with taking iron and folic acid. This finding is comparable with studies conducted in different parts of Ethiopia , 32, 35.The likelihood of having Mid-Upper Arm Circumference (MUAC) < 23 cm was higher among mothers of the cases than among mothers of the controls as compared to having MUAC ≥ 23 cm. This might be explained by the mistaken perception of women that frequent and much diet consumption during pregnancy could lead to excessive fetal growth which they perceive would be beyond tolerance of the birth canal and pose difficulty during childbirth , 39. DueEven though the findings on the factors associated with LBW in this study were consistent with the majority of pocket studies in the country, it was not supported by a recent systematic review in Ethiopia . This miThe present study has few limitations to consider. The self-reported nature of the determinants based only on the mothers' memory might have a recall bias, and there may also be an intra- or interobserver bias that might have led to misclassification of cases and controls. The data was collected from mothers who gave birth at the health facility limiting its generalizability to all women in the zone as those who gave birth at home have been left out.The finding of this study showed that time of antenatal care initiation, the residence of participants, maternal malnutrition measured by Mid-Upper Arm Circumference and inadequate dietary diversity during pregnancy, not getting iron and folic acid supplementation, and having pregnancy-induced hypertension were found to be independent determinants of birth weight among newborn babies. So concerned health authorities and health professionals should strengthen the existing promotion on timely initiation of antenatal care and stick to iron and folic acid supplementation recommendations during the antenatal care. Nutrition education and capacity building should be strengthened during the prenatal care in the local setup and by extension to the country as a whole.


Early diagnosis of asymptomatic carotid artery stenosis (ACAS) is important to prevent the incidence of cerebrovascular events. This study aimed to investigate the circulating expression of microRNA-92a (miR-92a) in ACAS patients and evaluate its diagnostic value for ACAS and predictive value for cerebrovascular events.Circulating expression of miR-92a was measured using quantitative real-time PCR. Chi-square test was used to analyze the association of miR-92a with ACAS patients’ clinical characteristics. A receiver operating characteristic (ROC) was used to evaluate the diagnostic value of miR-92a, and the Kaplan-Meier method and Cox regression analysis were used to assess the predictive value of miR-92a for cerebrovascular events.P <  0.001), and associated with patients’ degree of carotid stenosis (P = 0.013). The elevated miR-92a expression could distinguish ACAS patients from healthy individual, and was an independent predictive factor for the occurrence of cerebrovascular events (P = 0.015).Serum expression of miR-92a was higher in ACAS patients than that in the healthy controls (The data from this study indicated that circulating increased miR-92a may serve as a noninvasive diagnostic biomarker for ACAS and a potential risk factor for the future onset of cerebrovascular events. Stroke, a major cerebrovascular event, is a severe healthcare burden worldwide. According to the statistics, stroke ranks the second leading cause of global deaths, inferior to ischemic heart disease . CarotidEmerging studies have reported the important role of microRNAs (miRNAs) in various human diseases . miRNAs MiR-17-92 cluster plays a crucial role in the physiological and pathological processes of CAS . SeveralThis study was approved by the Ethics Committee of Binzhou Medical University Hospital, and the written consent was obtained from each participant before blood sampling. A total of 122 ACAS patients were enrolled in this study from Binzhou Medical University Hospital between 2011 and 2013 following the inclusion criteria: (1) more than 18 years old; (2) the stenotic degree of ipsilateral internal carotid artery more than 50%; (3) no history of TIA or stroke; (4) no malignancies. A color Doppler ultrasound was used to diagnose CAS with a high-resolution duplex ultrasound system and a probe at scanner frequency of 7–10 MHz. The ultrasonography examination was performed by two experienced radiologists and the degree of stenosis was calculated. Besides, 62 healthy volunteers were recruited in this study as normal controls, who had no history of metabolic diseases, malignancies, cardiovascular diseases, cerebrovascular diseases, or inflammatory diseases. Venous blood was collected from the participants and used to isolate serum samples using centrifugation. The demographic and clinicopathological characteristics of the patients were recorded for further analysis.All the patients were recruited in a 5-year follow-up survey. The occurrence of ipsilateral cerebrovascular events, including stroke, TIA, or sudden death, was defined as the primary endpoint. The patients who died from other unrelated incidents were excluded from the analysis. The diagnosis of stroke was determined by the combination of clinical symptom and brain imaging examination, including Doppler ultrasound, MRI, CT, and angiography . The TIATotal RNA in the collected serum was extracted using TRIzol reagent  following the manufacturer’s instruction. The concentration and purity of RNA were determined by a NanoDrop 2000 . The pure RNA was used for reverse transcription to synthesize cDNA using a PrimeScript RT reagent kit  according to the protocols of the manufacturer.−ΔΔCt method and normalized to U6. The primers used were as follows: miR-92a forward, 5′-TATTGCACTTGTCCCGGCCTGT-3′ and reverse, 5′- CTTTCTACACAGGTTGGGATCG-3′; and U6 forward, 5′-CTCGCTTCGGCAGCACA-3′ and reverse, 5′-AACGCTTCACGAATTTGCGT-3′.The expression of miR-92a in serum samples was estimated using qRT-PCR, which was carried out using a SYBR green I Master Mix kit  and the 7500 Real-Time PCR System . U6 was used as an internal control in the reactions. The relative expression value of miR-92a was calculated by using the 2t test. Chi-square test was used to estimate the relationship between miR-92a and patients’ clinical data. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of circulating miR-92a, and the area under the curve (AUC) was calculated to examine the diagnostic accuracy. The value of miR-92a on predicting cerebrovascular diseases was analyzed using the Kaplan-Meier method and Cox regression analysis. A P value of less than 0.05 was considered statistically significant.The data obtained in this study were expressed as mean ± standard deviation (SD) and analyzed using SPSS 21.0 software  and GraphPad Prism 7.0 software . Differences between groups were analyzed using student’s P > 0.05). However, the levels of fasting blood glucose (P <  0.001), total cholesterol  and low-density lipoprotein  were significantly higher in ACAS group than that in the control group, and more cases with hypertension were identified in ACAS group (P <  0.001).The demographic and clinicopathological characteristics of the control groups and ACAS patients group were summarized in Table P < 0.001, Fig. According to qRT-PCR, the expression of miR-92a in serum samples was significantly higher in patients with ACAS than that in the healthy volunteers, and the difference reached statistical difference P < 0.00, Fig. 1.P = 0.040), TC (P = 0.046) were significantly high in high miR-92a expression group than that in low miR-92a expression group, and more patients with hypertension (P = 0.035) and high degree of carotid stenosis (P = 0.013) were observed in high miR-92a group. The results indicated that the increased miR-92a expression was associated with fasting blood glucose, TC, hypertension, and degree of carotid stenosis. No significant relationship was detected between miR-92a and age, gender, BMI, LDL-C, or HDL-C .The demographic and clinicopathological characteristics of ACAS patients were recorded and summarized in Table According to the serum levels of miR-92a in ACAS patients, this study further evaluated the diagnostic significance of miR-92a for ACAS by constructing a ROC curve  and larger degree of carotid stenosis . The subsequent multivariate analysis data revealed that ACAS patients with higher miR-92a  or larger degree of carotid stenosis  had high risk for the occurrence of cerebrovascular events.According to the 5-year follow-up survey, cerebrovascular events occurred in 28 patients, including 20 TIA and 8 strokes. Among 28 patients who suffered from cerebrovascular events, 8 cases were observed in the low miR-92a expression group, while 20 cases were in the high miR-92a expression group. No death nor contralateral ischemic events occurred. By a Kaplan-Meier analysis, the patients with high miR-92a expression experienced more cerebrovascular events compared with those with low miR-92a expression (log-rank This study aimed to evaluate the diagnostic performance of miR-92a for ACAS and its predictive value for cerebrovascular events in patients with ACAS by analyzing miR-92a expression levels. According to qRT-PCR, circulating miR-92a expression was elevated in ACAS patients compared with healthy individuals. The serum increased miR-92a expression levels were associated with the degree of carotid stenosis and some vascular risk factors in ACAS patients. According to the deregulated expression pattern, the diagnostic value of miR-92a was evaluated, and the ROC data demonstrated the relatively high diagnostic accuracy of serum miR-92a for ACAS patients. Furthermore, the occurrence of cerebrovascular disease was recorded by a 5-year follow-up survey, and we found that ACAS patients with high miR-92a experienced more cerebrovascular events, suggesting that miR-92a might serve as a risk factor for the occurrence of cerebrovascular event.CAS is a progressive pathological condition, which is generally considered as a result of atherosclerosis and plaque rupture . The preMiR-92a has been determined as one of the vascular-related microRNAs , and canSerum miRNAs are generally considered a group of good diagnostic tools for various pathological conditions and diseases . The dysIn conclusion, elevated miR-92a expression was detected in ACAS patients, which is associated with carotid stenosis and serves as a candidate diagnostic biomarker for ACAS. MiR-92a has the potential as a predictor for the onset of cerebrovascular events in ACAS patients. Although our results provide a novel insight into the value of miR-92a in ACAS diagnosis and future cerebrovascular events prediction, further investigations with a larger study population are needed to confirm the role of miR-92a.