Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA) groups than that of appropriate for gestational age (AGA) groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes. Several studies have shown that small birth size and indices in poor fetal growth are associated with the development of metabolic syndrome in adulthood, such as insulin resistance, type 2 diabetes, hypertension, dyslipidemia and coronary heart disease In spontaneous pregnancies smaller increases of thyroid stimulating hormone levels are related to higher magnesium (Mg) levels The role of Mg as a cofactor for enzymes in carbohydrate metabolism also involves insulin activity In this review, we propose that intrauterine Mg deficiency may later manifest as metabolic syndrome in adulthood, and discuss the association of Mg regulation with low birth weight and metabolic syndrome.2.Small for gestational age (SGA) babies are those who are smaller in size than normal by gestational age and are commonly defined as having a birth weight below the 10th percentile by gestational age 2.1.+/Mg2+ exchanger that functions to maintain low intracellular Mg The levels of total Ca, ionized Ca, and Mg are higher in fetal circulation than in maternal blood In mammals, the placenta is a highly developed organ which, along with nutrient exchange, has numerous other functions during the gestational period with maternal-fetal homeostasis dependant on a properly functioning placenta. Maternal Mg deficiency obviously affects the health of the fetus. However, some studies have not found a significant association between maternal trace elements and birth weight 2.2.Ca and Mg are cofactors in the synthetic activity of a number of enzymes. A variety of hormones, cytokines and growth factors produced by fetal membranes and placenta can act locally on the myometrium Mg along with Ca and NO has an immediate effect on placental vascular flow. Reduced placental vascular flow is at least, in part, responsible for placental insufficiency and SGA .A variety of hormones, cytokines and growth factors produced by fetal membranes and placenta can act on the myometrium. The ability of the uterine artery to dilate may be related to nitric oxide. Several candidate processes have been proposed to explain gestational programming, i.e. epigenetic modification of gene.  Possible relationship between low birth weight and magnesium status: from the standpoint of “fetal origin” hypothesis. Magnes. Res. 20, 63-9) IGF-1: insulin-like growth factor-1, iP: inorganic phosphorus, NO: Nitric oxide, Mg: magnesium, SGA: small for gestational age.2.3.Human platelets are often used in studying cellular cation metabolism in various diseases 2+]i) in platelets 2+]i deficiency We and other investigators have proposed that insulin action could be mediated by intracellular Mg  Intracellular Mg and small for gestational age2+]i of platelets in the cord blood of infants with SGA and with AGA 2+]i, but not plasma Mg, was lower in the SGA than in the AGA group . [Mg2+]I was significantly correlated with the birth weight (p < 0.001) and birth length (p < 0.001)  ,3.2+]i plays a promotive role in fetal growth, low [Mg2+]i may partly be responsible for SGA. In regard to fetal life, it has been postulated that nutritional and environmental factors during pregnancy, as well as hormonal factors such as insulin and IGF-1 As i and insulin resistance(B) Correlation of i, and adiponectin were correlated with QUICKI in all subjects , IGF-1, QUICKI -1 and ghrelin were higher in SGA groups . Quantitsubjects  [39]. Th< 0.0001). From th2+]i, may influence the prenatal programming of insulin resistance, and may have lifelong effects on metabolic regulation characterized by insulin resistance.In summary low  a potential role for the hypothalamic-pituitary-adrenal axis has been suggested, as the mediators of the fetal response to nutrient stress, i.e. maternal low protein diet, were profoundly suppressed (2) Thrifty phenotype hypothesisThe “thrifty phenotype hypothesis”, which postulates that fetal programming for adaptation to an adverse intrauterine environment results in lower insulin sensitivity in utero, is one of the hypotheses to explain the association between low birth weight and insulin resistance in later life 2+]i in infants with SGA can be the initial pathophysiologic events of fetal programming. A recent animal study supported our data demonstrating that the maternal Mg restriction irreversibly increases body fat and induces insulin resistance in pups by 6 months of age Decreased i may be a marker of early growth restriction, which may be of future diagnostic use as an early predictor of adult diseases. Low [Mg2+]i, which may represent the prenatal programming of insulin resistance, has lifelong effects on metabolic regulation. A biological interpretation of the association between birth size and risk of insulin-resistant diseases should emphasize the possible underlying roles of [Mg2+]i.Birth weight is only a crude index of early growth and does not indicate the success of a fetus in achieving its growth potential. [Mg


Encouraging institutional birth is an important component of reducing maternal mortality in low-resource settings. This study aims to identify and understand the determinants of persistently low institutional birth in rural Nepal, with the goal of informing future interventions to reduce high rates of maternal mortality.Postpartum women giving birth in the catchment area population of a district-level hospital in the Far-Western Development Region of Nepal were invited to complete a cross-sectional survey in 2012 about their recent birth experience. Quantitative and qualitative methods were used to determine the institutional birth rate, social and demographic predictors of institutional birth, and barriers to institutional birth.The institutional birth rate for the hospital’s catchment area population was calculated to be 0.30 . Institutional birth was more likely as age decreased (ORs in the range of 0.20–0.28) and as income increased (ORs in the range of 1.38–1.45). Institutional birth among women who owned land was less likely . Ninety percent of participants in the institutional birth group identified safety and good care as the most important factors determining location of birth, whereas 60 % of participants in the home birth group reported distance from hospital as a key determinant of location of birth. Qualitative analysis elucidated the importance of social support, financial resources, birth planning, awareness of services, perception of safety, and referral capacity in achieving an institutional birth.Age, income, and land ownership, but not patient preference, were key predictors of institutional birth. Most women believed that birth at the hospital was safer regardless of where they gave birth. Future interventions to increase rates of institutional birth should address structural barriers including differences in socioeconomic status, social support, transportation resources, and birth preparedness.The online version of this article (doi:10.1186/s12884-016-1022-9) contains supplementary material, which is available to authorized users. The maternal mortality ratio in Nepal is estimated at 281 per 100,000; approximately half of these cases are attributed to postpartum hemorrhage . DespiteIn a literature review of the determinants of birth service use in the Global South, maternal age, parity, education, household wealth, and urban residence were positively associated with service usage –9. In a Specific barriers to safe institutional birth can be understood within the framework of the Three Delays Model: first, delay in the decision to seek care, second, delay in arrival at a health facility, and third, delay in the provision of appropriate care at the healthcare facility , 14. TheData for this study was obtained from the Pre-Surgical Expansion Survey . The CHWs’ coverage area, at the time of research, included seven village clusters  around the hospital that contributed a large portion of patients to Bayalpata Hospital and defined a catchment area population of approximately 17,000 people for this study. At the time of the survey, the hospital’s ambulance service charged a distance-based fee, while the hospital provided Basic Emergency Obstetrics Care, with no capacity for cesarean sections or blood transfusion.Bayalpata Hospital is located in Achham, a rural district in the Far-Western Development Region of Nepal. It is a district-level hospital run through a private-public partnership between the Ministry of Health of Nepal and the Nepali non-profit organization Study parameters included a convenience sampling of nearly all women who gave birth in the home setting as well as an emergency obstetric care facility over a 3 month period. Taking the findings of the Nepal Safe Motherhood study into account, which found that only 2 % of the mothers make the decision regarding where to give birth themselves, the study team sought to include a subset of male family members. However, because the survey’s male sample size was too small to analyze trends, this group was ultimately excluded. Therefore the final inclusion criteria included only post-partum women in the catchment area population who had given birth in the previous 6 weeks.Power was calculated for a planned evaluation of the Pre- and Post- Surgical Expansion Survey data. Using an algorithm based on the Wald test, with power set at 0.80, statistical significance set at 0.05, and a baseline institutional birth rate of 20 %, the study was powered to detect a 150 % increase  in institutional births after the implementation of comprehensive emergency obstetric services. This power calculation required a total sample size of 200 subjects over both Pre- and Post- Surgical Expansion Surveys. For the Pre-Surgical Expansion survey, the study team stopped data collection at 3 months, when the target of 100 participants was nearly reached. All eligible women were approached for recruitment during this time period.Possible’s Director of Research was present for the majority of survey administration to ensure consistency. The CHWs and ANMs were also given weekly reminders to complete the survey forms.Bayalpata Hospital Pre-Surgical Expansion Survey data were used to examine attitudes and behaviors toward institutional birth before the establishment of the hospital’s comprehensive emergency obstetric care facility. The survey included demographic inquiries and questions to assess the decision-making process, accessibility of institutional birth, and acceptability of services. In addition, patient narratives of their birth stories and their recommendations for improving utilization of institutional services were collected. Community Health Worker Leaders (CHWLs), paid employees in Bayalpata Hospital’s Community Health Program managing the CHWs, administered the surveys to post-partum women in the catchment area population of the hospital who had given birth at home or at a village clinic in the prior 6 weeks. If more than one woman in a household was eligible for participation, all eligible women were approached for enrollment. Auxiliary Nurse Midwives (ANMs) administered surveys to post-partum women who had given birth at the hospital in the prior 6 weeks, inclusive of both uncomplicated and complicated births. An attempt was made to reach all post-partum women during the study period. Surveys were printed in Nepali and enumerators conducted the surveys in Nepali or in Achhami, the local dialect. The primary outcome was location of birth. The goals were to describe and quantify factors associated with institutional birth and home birth, and to understand which factors are significant predictors of institutional birth. The following factors were examined: age, distance from hospital, household income, land ownership, race, literacy, parity, antenatal care, birth decision-making, and father’s presence. The qualitative analysis was based on the social contextual theoretical framework , and aimAll data were collected on paper forms and input into Excel  by the staff of the Community Health Program and the Hospital Program at Bayalpata Hospital. For this study, survey data were analyzed using Stata 12.1  and JMP Pro version 10.0.0. Data collection tools were pilot tested for errors at Bayalpata Hospital prior to the survey.Each variable was examined by location of birth. For categorical variables, cell counts were examined. Each continuous variable was examined for normality of distribution. For normally distributed variables, means and standard deviations were calculated, for non-normal data, medians and inter-quartile ranges were calculated.p < 0.10) or if it altered the beta coefficient by more than 20 %. This process led to a final logistic regression model with five covariates: parity, literacy, monthly household income, land, and presence of father of baby. To examine the effect of these covariates on the outcome of location of birth, odds ratios with 95 % confidence intervals were used. To test the significance of the effects, the likelihood ratio tests were used.For the logistic regression, a manual forward-selection method was used, starting with scientifically important covariates: age, parity, literacy, income, and distance from the hospital. A covariate in the model was kept if it was significant . Because age and monthly household income have a non-linear relationship with institutional birth, squared terms were included in the final regression model. As age increased, the likelihood of institutional birth decreased. The odds ratio was higher in older age groups , whereas most women in the home birth group selected "long distance" . Overall, the most common participant recommendation for improving institutional service utilization was improving ambulance accessibility (72 %); only 37 % of the institutional birth sample arrived via an ambulance.In terms of acceptability of services, institutional birth satisfaction was at 93 % while home birth satisfaction was 32 %. All participants in the institutional birth group stated they would prefer an institutional birth in the future, while only one participant from the home birth group stated a preference for home birth in the future.The qualitative analysis examined women’s ‘birth stories’ for social contextual factors as they would relate to the proposed expansion of emergency obstetric services. Modifying factors and mediating factors were identified and fit into a conceptual model Fig. . ModifyiThe importance of family and partner support was identified in the stories of many women, as this quote exemplifies: “She wanted to deliver in the hospital but her in-laws did not listen. Her husband was not in Achham. She didn't have the courage to come to the hospital by herself so she delivered at home.” The factors of access to transportation, birth planning, and preparedness were also seen as community level factors due to the need for several community members to participate in the process of getting to an institution: “A [20–30] year old woman who was pregnant with [a] child was herding her goats during the day. She went into labor around 7 pm. The family was trying to gather people to bring her to the hospital but she had her baby an hour and half later.” A societal level modifying factor identified was the quality of services at the village clinics, which was often poor: “They wanted to go to the village clinic but no medical staff were there.” The government-provided financial incentive was another societal level modifying factor that motivated women to have an institutional birth.“[A 40–50] year old woman who had [multiple] prior deliveries in her home, just had [a] delivery in the hospital. One year ago there was a maternal death in a nearby village while a woman was delivering at home. News of this death changed her mind about having her [next] baby at home. She wanted to come to the hospital, where there was a doctor and good medical staff to keep her safe.”The birth stories also revealed social and contextual factors that would likely be affected by the proposed expansion of services. On an individual and interpersonal level, perceptions of safety and intention to present to an institution seemed important for achieving institutional birth, as this woman’s story exemplifies:Unlike this story of a woman who achieved institutional birth, there were several women who gave birth at home and mentioned that they had limited awareness of the hospital or services provided there. Referral to a higher level of care was an organizational level mediating factor. Three women were referred to an institution with comprehensive emergency obstetric care services, but delivered at home due to delays caused by referral.The results of this study are in line with prior literature, in that age, income, and land, were significantly related to institutional birth. However, age is inversely related to institutional birth, with younger women more likely to give birth in an institution. The direction of this relationship is contrary to findings in other settings . This maHigher income predicted institutional birth in our analysis. The non-linear relationship, however, reveals that the amount of income matters less in the higher range for achieving institutional birth. Land has an opposite effect on institutional birth, as ownership of more land negatively predicts institutional birth. Perhaps this is due to the specific very rural context of the study as families with more land are unlikely to be earning other sources of cash revenue. In a remote area like Achham, cash is important to secure transportation. Perhaps those with less land had easier access to that cash. Further analysis of the current data, however, shows no significant association between land and income. This issue warrants further research in a larger sample of women or with qualitative methods.Findings suggest that the most important consideration for women is safety/good care among the institutional birth group and long distance/transportation in the home birth group. The majority of all women stated that the hospital was safer place to give birth and would prefer an institutional birth in the future. These findings indicate that underutilization of institutional birth services is unlikely to be the result of patient preference, and rather due to socioeconomic vulnerability to structural barriers.Although distance from the hospital was not a significant predictor of institutional birth in the final regression model, ‘long distance or transportation’ was the most important consideration reported by the home birth group. Other studies show distance to be a significant factor that affects choice of birthplace , 19. In The mediating social and contextual factors identified in the qualitative analysis are those that will most likely be impacted by the proposed expansion of emergency obstetric services: perceptions of safety, intent to give birth in the hospital, referrals, and awareness of services. On the other hand, modifying social and contextual factors, such as social support, gender equality, financial and transportation resources, and birth preparedness, are less likely to be impacted by the expansion of services. Thus, they should be the targets of interventions conducted alongside expansion of emergency obstetric services to improve institutional birth in this region.Limitations to this study include a small sample size that was made smaller by missing values. The power calculation was for the larger study, comparing Pre- and Post- Surgical Expansion Survey data, not for the present analysis of determining factors associated with location of birth. Thus, the study may be under-powered to detect all factors associated with institutional birth. The convenience sampling strategy employed may have biased the findings. Future research with a consecutive sampling strategy should be employed to address this issue. Additionally, the institutional birth rate among this sample (42 %) was higher than the estimated rate in the hospital catchment area population (30 %). The skew towards women who had an institutional birth brings bias to the sample. The use of community health workers and nurse midwives as enumerators also increases bias in self-reported perceptions of and preferences for institutional birth. The generalizability of the findings is limited due to the data being obtained from a single hospital and its catchment area population. Finally, due to resource limitations in our setting, qualitative interviews could not be audio-recorded, perhaps leading to error in transcription and translation of participant responses. Despite these limitations, this study makes a unique contribution to the small and growing literature on determinants of institutional birth in the Global South.In exploring determinants of institutional birth in rural Nepal, we found that socioeconomic vulnerability to structural barriers are paramount in understanding who gives birth at home versus an institution and why. Contrary to data from the Nepal Demographic and Health Survey 2011, where 62 % of women who gave birth at home believed it was not necessary to give birth in a health facility , most wo


Patients with FOB present also had significantly earlier gestational age at the first US visit (15 weeks) than those who did not . For AYA, the presence of FOB at initial prenatal US visits is a predictor of improved pregnancy outcome and likely represents increased support during the pregnancy.This study examined whether the presence of the father of the baby (FOB) at the first prenatal ultrasound study (US) visit of pregnant adolescents and young adults (AYA) is a marker for improved pregnancy outcomes. Charts of 400 pregnant AYA aged 14–22 years seen at an academic maternity hospital were assessed retrospectively for support persons brought to prenatal US visits. Logistic regression analysis was used to examine the association between FOB presence and gestational age and birth weight. Of 400 charts with support person recorded, 298 charts with first US visit data, singleton birth, and complete gestational data available were analyzed. FOB was present at 30.2% of visits, while the parent of the mother was present at 34.2% of visits. With FOB present, 3.3% of infants were born preterm  compared with 10.5% of infants with FOB absent ( Even though the national teen pregnancy rate is declining , adolescInadequate prenatal care for adolescents is strongly associated with prematurity , and adoShah et al. recently looked at the effect of partner support on birth outcomes in pregnant adolescents and, using a secondary analysis of survey data, found that teens with a supportive or involved partner were less likely to have adverse outcomes such as low birth weight or pregnancy loss . Few stuUltrasound study visits are a visual confirmation of pregnancy. An ultrasound study also offers the opportunity for a support person to be with the pregnant teen. We hypothesized that the presence of the father of the baby at the first ultrasound visit would be associated with improved pregnancy outcomes, specifically birth weight and pregnancy duration. While first ultrasounds are recommended at our center to be performed at 12-13 weeks, the tendency of AYA to have later diagnosis of pregnancy and later prenatal care contributed to the choice of first ultrasound visit for this study as some women would not have a subsequent ultrasound. Extensive literature search failed to find any study aimed at finding possible correlations between the presence of the father of the baby at adolescent prenatal ultrasound study visits and pregnancy outcomes.Approval was obtained from the Institutional Review Board. A retrospective chart review was conducted at an academic maternity and women's hospital located in a Midwestern city in the United States that serves women who receive both private insurance and Medicaid. The hospital has approximately 4,500 deliveries per year. The charts of pregnant adolescents and young adults seen over a two-year and a year and half period were assessed. Inclusion criteria were support person documented (presence or absence) and age between 12 and 22 years at first ultrasound study (US) visit. Twin pregnancies were excluded.support person and relationship type;gestational age at visit;pregnancy complications;gestational age at delivery;birth weight at delivery;birth complications.Additional demographic data was not available.Data collected includedLogistic regression analysis was used to examine the association between the presence of support persons at prenatal US visits and gestational age. Statistical analysis was conducted using SAS 9.3.n = 1444); 400 had the presence or absence of support person(s) noted. Support person is not a required field in patient charts. A total of five charts were excluded because the first US visit was not available, and additional 6 charts were excluded because of twin pregnancies. A total of 298 charts had gestational age at delivery recorded, and 205 charts had birth weight recorded.Over 1400 charts were reviewed  or the father of the baby (30.2%). Other support persons included family members and friends, and 17.8% of pregnant adolescents and young adults were alone in the visit . The majp = 0.04). Adolescents and young adults with the father of the baby present also presented for first US at a significantly earlier gestational age . Fewer infants with the father of the baby present at first US were with low birth weight, but this was not a significant difference   compared with 10.5% of infants with the father of the baby absent ( = 0.22) .To our knowledge this study is one of the first to look at the association between the father of the baby at adolescent and young adult ultrasound study visits and pregnancy outcomes. Multiple studies have looked at paternal support (and support of family and peers) in adolescent and adult pregnant women; however, few have looked at the actual presence of these support people at any prenatal visit . One of This study found that the presence of the father of the baby at the adolescent and young adult prenatal US visit was associated with lower rates of preterm delivery. Studies in adult women have found that paternal support may decrease stress in pregnant women which in turn may decrease poor birth outcomes . Stress We also found that the presence of the father of the baby at the adolescent and young adult prenatal US visit was associated with earlier gestational age at the time of the first ultrasound. An early US implies that prenatal care has begun early in the pregnancy. Improved prenatal care may help to explain the improved birth outcomes. The involvement of the father of the baby might lead to earlier acceptance and acknowledgement of the pregnancy. Also, the father of the baby may be able to help in the decision-making that occurs at US visits. Pregnant adolescents and young adults are more likely to make noninformed decisions about prenatal screening . HoweverThis study does have several limitations including an absence of outcome data due to changing documentation system. Also, many charts were excluded because the presence or absence of a support person was not recorded, leading to an overall small number of charts included.Future directions would include both quantitative and qualitative studies to examine the role of fathers in pregnancy outcomes. Interviews with adolescents and young adult parents would help give insight into paternal engagement and its potential influence on maternal and infant outcomes.In conclusion, the presence of the father of the baby at the prenatal US visits of adolescents and young adults is associated with improved pregnancy outcomes. The presence of father of the baby at adolescent and young adult prenatal US visits is also associated with earlier gestation at first ultrasound and may imply better prenatal care. Interventions to encourage paternal involvement may lead to improved pregnancy outcomes for adolescents and young adults.


Small for gestational age (SGA) births have been associated with both short- and long-term adverse health outcomes. Although social risk factors for SGA births have been studied earlier, such data are limited from Northern Russia.We assessed maternal social risk factors for term SGA births based on data from the population-based Murmansk County Birth Registry (MCBR).W) or for both birth weight and birth length (SGAWL). Binary logistic regression was used to estimate the effect of independent variables on SGA males and females with adjustment for known risk factors and potential confounders. Both crude and adjusted odds ratios with 95% confidence intervals for the studied risk factors were calculated.Data on term live-born singleton infants born between 2006 and 2011 in Murmansk County were obtained from the MCBR. We applied the 10th percentile for only birth weight (SGAW and SGAWL births were 9.7 and 4.1%, respectively. After adjustment for potential confounders, the risk of term SGA births among less educated, unemployed, unmarried, smoking and underweight women was higher compared with women from the reference groups. Evidence of alcohol abuse was also associated with birth of SGAWL and SGAW boys. Maternal overweight and obesity decreased the risk of SGA.The proportions of term SGAMaternal low education, unemployment, unmarried status, smoking, evidence of alcohol abuse and underweight increased the risk of term SGA births in a Russian Arctic setting. This emphasizes the importance of both social and lifestyle factors for pregnancy outcomes. Public health efforts to reduce smoking, alcohol consumption and underweight of pregnant women may therefore promote a decrease in the prevalence of SGA births. Small for gestational age (SGA) birth is an unfavourable pregnancy outcome and contributes to both short- and long-term adverse health effects for children born SGA. To date, many risk factors of SGA births have been reported.W) or length (SGAL) or both low BW and BL (SGAWL) for GA  defines SGA birth as a birth with infant birth weight (BW) and birth length (BL) below the 10th percentile (P10) for gestational age (GA) (ICD-10 code P05.1)  for GA , 3. ThisCompared with appropriate weight for GA births, infants born SGA have higher risk of perinatal, early neonatal , as wellMaternal cigarette smoking , 14, obeW prevalence of 9.2% during 1973–2003. The proportion of SGA infants is highest among unemployed women/homemakers . Murmansk County is situated in Northwest Russia. Data collection in the MCBR began on 1 January 2006 and continued until 31 December 2011. The Registry contains socio-demographic information, data about the index pregnancy and mother's pre-pregnancy health, delivery and infant's health. A set of previously published studies describes MCBR in detail –34.W and SGAWL births’ prevalence analyses and the analyses of percentiles of BW and BL for each gestational week between 37 and 41. We excluded 1,996 records with missing data on studied independent variables or potential confounders to perform further logistic regression analyses. Our final study sample included 42,239 births. The algorithm of sampling is presented in The study population included 52,806 births. We excluded multiple births, stillborn infants and those born with a birth defect reported at birth as well as records with missing data on BW, BL, GA and missing or unknown infant sex . GA was determined on the basis of first ultrasound (US) in pregnancy. We used last menstrual period (LMP) to estimate GA in 4,001 births with missing US data. Births before 37 and after 41 weeks of gestation were also excluded from the analyses. A total of 44,235 births were included in SGAW and SGAWL births.We used SGA as a dichotomous dependent variable. The 10th percentile for BW or both BW and BL for each gestational week between 37 and 41 was applied to classify, respectively, SGA2), normal weight (BMI=18.5–24.9 kg/m2), and overweight and obese (BMI≥25.0 kg/m2). Mothers were divided into non-smokers and smokers according to their smoking status during pregnancy. Evidence of mother's alcohol abuse during pregnancy was recorded as “no” or “yes.” Place of mother's residence was dichotomized into rural and urban, with rural residence serving as the reference group.In our study, marital status, mother's age, education, BMI, smoking, evidence of alcohol abuse during pregnancy, place of residence and occupation were used as independent variables. Maternal age was divided into three groups: <18, 18–34 and ≥35 years. We selected maternal age of 18–34 years as reference group. Maternal education was categorized as none or primary (Grades 1–9), secondary (Grades 10 and 11), vocational school and higher with the last one as the reference category. By marital status, all mothers were divided into two groups: married and unmarried. Unmarried included single, cohabiting, divorced or widowed. Maternal occupation status was divided into employed/student (including pupils) and unemployed. Mothers’ BMI was categorized as underweight  with 95% confidence intervals for the studied risk factors separately for male and female infants. Analysis was done with IBM SPSS Statistics for Macintosh, Version 23.0 .Binary logistic regression was used to estimate the effect of studied variables on SGAThe MCBR registration forms do not contain personal identifiers, which means that the health information is confidential and therefore no personal consent was needed. The study received ethical approvals from the Ethical Committee of the Northern State Medical University  (Protocol 04/5-13) and the Regional Committee for Medical and Health Research Ethics in Northern Norway (2013/2300 REK nord).WL and SGAW, respectively  women had lower risk to deliver SGAW boys and girls compared with 18–34 years old mothers; hence, the association between advanced maternal age and decreased risk of SGAW males has not reached statistical significance  with SGA births  and V. Uificance .WL births of both sexes among low educated, unmarried, smoking or underweight women was higher compared with the corresponding reference groups  unemployed women. Evidence of alcohol abuse contributed to increased risk of SGAWL males. Unemployed, unmarried and underweight mothers were at higher risk to deliver SGAW boys and girls  education  was found in a multicentre cohort study  was reported for singleton boys born at 37 weeks  in 2011, which was the year the data collection in MCBR ended. Smaller settlements with high-developed medical service were not included in the list. Therefore, these settlements might be misclassified as rural areas in this study.While some studies show that maternal residence in urban areas or large cities increase the risk for SGA births , 44, othConsistent with findings from a previous study , unemploWL infants, but it still remained high; adjusted ORs in SGAWL males and females groups were 1.91 and 2.23, respectively. These ORs correspond to results of others (W births among smokers at any level of maternal education. A study from the Netherlands (WL and SGAW groups, respectively, compared with non-SGA births. The odds to have term SGAWL and SGAW boys is, respectively, 4- and 3-times higher among alcohol abusing mothers compared with those not being alcohol dependent. In contrast to our findings, the results of a meta-analysis show non-significant effect of alcohol in studies adjusted for confounders (Our findings that smoking and evidence of alcohol abuse significantly associated with SGA birth are in line with other studies , 25, 37.f others . In our founders . The samW and SGAWL was associated with maternal underweight. These findings are in line with earlier studies from other countries (2 compared with overweight women. We found that overweight and obesity decreased the risk of SGA births irrespective of SGA definition. In fact, high maternal BMI does not play a role as a protective factor; obese women have elevated risk of foetal macrosomia, which is caused by both an increase in the foetus size and changes in its body composition (In this study, higher risk of both SGAountries , 16, 37.ountries  reports position , 46. Decposition . In factposition . A studyposition  demonstrposition .The main strength of our study is the use of a birth registry including socio-demographic information, detailed data about maternal medical history and infant's health. The initial MCBR database included the entire population of mothers and newborns in Murmansk County over a period of 6 years. Individual data on maternal smoking and alcohol consumption considered as strong predictors of SGA birth , 37 wereWL and SGAW, we applied two definitions of SGA that are widely used in practice. The possibility to investigate multiple outcomes is one of the strengths of any cohort study (To investigate possible differences in associations between a set of selected social factors and SGArt study .In our study, we did not examine the contribution of medical conditions or other predictors to SGA births, which other studies have focused on , 13, 42.We used sex-specific P10 values for both BW and BL as this may improve identification of SGA infants . Data onWe found social disparities in SGA birth at the individual level in a Russian Arctic setting. Maternal low education, unemployment, unmarried status and underweight carried a significantly higher risk of term SGA births irrespective of SGA definition. Smoking and evidence of alcohol abuse are also associated with SGA birth. Therefore, early identification of women with the above risk factors and implementation of public health programmes aimed at reducing smoking, alcohol consumption and underweight before and in early pregnancy may potentially result in reduction of SGA births.


We conducted a dual choice experiment using artificial flowers under semi-natural conditions in the butterfly pavilion at Tama Zoological Park to examine the effects of the presence of a dead mantis and resident butterflies have on the flower-visiting behavior of several butterfly species. From 173 hours of recorded video, we observed 3235 visitations by 16 butterfly species. Statistical analysis showed that (1) butterflies avoided visiting flowers occupied by a dead mantis, (2) butterflies avoided resident butterflies that were larger than the visitor, and (3) butterflies showed greater avoidance of a predator when the predator was present together with the resident butterfly than when the predator was located on the opposite flower of the resident. Finally, we discuss the similarities and differences in behavioral responses of butterfly pollinators and bees.The flower-visiting behaviors of pollinator species are affected not only by flower traits but also by cues of predators and resident pollinators. There is extensive research into the effects of predator cues and resident pollinators on the flower-visiting behaviors of bee pollinators. However, there is relatively little research into their effects on butterfly pollinators pr The relationship between flowering plants and insect pollinators is one of the most important mutualisms in terrestrial ecosystems –4. The fFirst, flower-visiting insects may face predation risks from ambush predators on and near the flowers –13. BecaSecond, if most of the flower nectar and pollen is consumed by pollinators, avoiding flowers occupied by live resident pollinators might be adaptive behavior for flower-visiting pollinators. On the other hand, if the nectar and pollen are not limited resources, following and preference for resident pollinators can be advantageous by reducing the energy cost of flower-searching behavior . While mThe effects of predators, conspecific or heterospecific pollinators on the flower-visiting behavior of pollinators have been extensively explored in recent years. However, the majority of studies have been done on Hymenoptera . The effThousands of butterflies are released throughout the year in the butterfly pavilion of the insectarium at Tama Zoological Park . All adult butterflies fly freely in the pavilion. The pavilion provides several benefits for experimental studies of the flower-visiting behavior of butterflies. First, the pavilion has stable environmental conditions (e.g. temperature) with minimal impact from natural disturbances such as wind and rain. Second, a number of flower-visiting behaviors of many butterfly species can be easily observed in one location. Therefore, we can compare variations in visiting behavior between species and examine how wing size variation of butterfly species affect their behavioral responses to predators and resident butterflies. Third, most individuals in the butterfly pavilion were reared in captivity and had no (or little) experience with predators. Although a few predators (mantises and spiders) manage to enter the pavilion, they are evicted as soon as they are discovered. Therefore, the butterflies in the pavilion can be regarded as displaying an almost exclusively innate response to predators on flowers.In this study, we set up a dual choice experiment in the butterfly pavilion to explore the effects that the presence of predators and resident pollinators have on the flower-visiting behavior of butterflies. Specifically, we addressed following questions: (1) Do predator cues near an artificial flower and wing size of the visiting butterfly affect the flower-visiting behavior of butterflies? (2) Do the live resident butterfly and wing size differences between the resident and the visiting butterfly affect the flower-visiting behavior of butterflies? (3) How does the spatial relationship of predator cues and resident butterflies change the flower-visiting behavior of butterflies?2 and a maximum ceiling height of 16 m and is covered by a glass roof . The height of the board from the ground was approximately 100 cm. Artificial flowers were included in the study rather than real flowers to be able to control the flower characters . The artificial flowers were created by arranging a flower-shaped yellow nylon on sponge (9 cm in diameter) in a white plastic dish (10 cm in diameter and 2 cm deep). The sponge was soaked in 10% sugar-water. The two artificial flowers were separated from one another by a center-to-center distance of 20 cm . The artTenodera aridifolia, was set to the side of one of the two artificial flowers. The mantis was collected in the pavilion and dried at room temperature. We changed the position of the mantis every day to randomize the effect of the position. The mantis was positioned so that the head was located over the center of the artificial flower and the rear of the abdomen was facing away from the other artificial flower . One recording period was approximately 84 minutes due to the camera’s memory capacity, and recording was carried out twice a day at each experimental site. Video was recorded at 15 frames per second at a spatial resolution of 320 × 240 pixels. The camera was located approximately 120 cm away at an upward angle from the artificial flowers. After excluding data that contained any artificial disturbance by the pavilion’s keepers, 4853 minutes for the predator experiment and 5530 minutes for the no-predator experiment were used for the analysis. It was not possible to score the data blind because our study involved focal animals in the field.For the statistical analyses, we identified the species of the visiting butterflies and classified all visiting behaviors observed in the predator experiments into three categories depending on the number of resident butterflies : “predatTo examine whether the species variation in wing size affect a visiting butterfly’s behavioral response to the presence of predators or resident butterflies, we measured the forewing length of three to five individuals of each butterfly species. For the statistical analysis, we used averaged lengths of each butterfly species as a representative value . The majTo investigate the factors affecting the flower-visiting behavior of butterfly species, we adopted a generalized linear mixed model (GLMM) with the visiting choice (left or right as seen from video) and time spent on the artificial flower as response variables and species ID and setup  as the random effect. We applied a binomial distribution for the analysis of visiting choice and a Gaussian distribution for the analysis of time spent on the flower. The models were fitted by using the lmer function in the “lme4” package in R. For all statistical analyses, we used the likelihood ratio test to evaluate the significance of the explanatory variables. We excluded the visiting data of butterflies that had not flown away from the artificial flower at the time recording was terminated.To investigate how the presence of predators and the wing size of the visiting butterfly species affected the flower-visiting behavior, we analyzed the data of “predator and no resident” category . In the In total, 3235 visitations by 16 butterfly species (1087 for the predator experiment and 2148 for the no-predator experiments) were observed . For theThe presence of the dead mantis affected the visiting behavior of butterflies . ButterfThe type of resident species  and interaction between the location of and type of resident butterfly did not affect the visiting choice and time spent on the flower . On the The interaction between the presence of the predator and the presence of the resident had a significant effect on the visiting choice . However, our experimental setting could not determine whether the butterflies truly perceived the dead mantis as a predatory cue or whether they were merely avoiding any foreign object on the flower. Previous studies have suggested that Hymenoptera pollinators portray avoidance response to any object on flowers rather than avoidance of the predator per se . In addi studies ,18,21. FGonçalves-Souza et al. (2008) suggested that unpalatable or toxic butterflies might have no or little avoidance response to the predator cues. In this study, we could not test the effect of toxicity on the avoidance behavior because of the high collinearity between the wing size and the potential toxicity  reported that two terflies . In contWhen the resident butterfly was located on the opposite side to the predator, the visiting butterfly avoided the resident side and preferred the predator side . This reOur dual choice experiments focused on the local-scale response of flower-visiting butterflies to predators and resident butterflies. However, the broad-scale response of pollinators is also important for the understanding of the effect of predators and residents on the behavior of pollinators in the context of community ecology. Although the present study could not directly compare the data between the predator and no-predator experiments because the periods of the two experiments differed, the visitation rate  and the species compositions of visiting butterflies seemed to differ between the no-predator and predator experiments . These dS1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


Hydatid cyst liver rupture into the biliary tree may involve the common hepatic duct, lobar biliary branches, the small intrahepatic bile ducts or rarely the gallbladder. Rupture can be occult or frank. A frank intrabiliary rupture of hepatic hydatid cyst is a rare but serious event. The authors are reporting a case of concomitant rupture of hydatid cyst of liver into right hepatic duct and the gallbladder. A 50-year-old female patient who presented with acute cholangitis was confirmed as a case of intrabilary rupture on ultrasonography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography. Rupture of hydatid cyst of liver in right hepatic and the gallbladder was confirmed on surgery. Suture repair of cystobiliary fistula, choledochoduodenostomy with cholecystectomy was done. A myriad of complications of hydatid cyst of liver may occur. The complications may include rupture, infection, or anaphylaxis. Rupture of hydatid cyst of liver is the most common complication. Liver hydatid can rupture in any part of biliary system but the communication with the hepatic bile ducts is most common. Rupture between a hepatic hydatid cyst and the gallbladder is rare . An elevA 65-year-old female presented with abdominal pain and jaundice of 17 days duration. After 10 days she had fever with chills and high colored urine. General physical examination revealed yellowish discoloration of sclera. Systemic examination was normal. Abdominal examination revealed tenderness in right hypochondrium and epigastrium. Liver function test parameters were bilirubin of 9.57 mg/dl, AST 52 U/L, and ALP 407 U/L. Ultrasonography abdomen revealed cystic lesion in liver with internal echogenic areas in right lobe of liver anteriorly, the gallbladder distended with thickened wall  with echogenic material (membranes) within it. Common bile duct was dilated with internal debris and linear echogenic areas (membranes) present in right hepatic duct as well as in common bile duct suggestive of intrabilary rupture of hydatid cyst of liver. Upper gastrointestinal endoscopy revealed stomach containing lot of bilious fluid with erythematous papilla with tongue like projection from papilla ruptured hydatid membrane. ERCP showed swollwen papilla, dilated common bile duct, with ruptured membranes present, the right intrahepatic duct was seen communicating with cyst cavity. Wide papillotomy was done and plastic stent 10F × 10 cm was placed across papilla. MRCP revealed 4.5 cm liver cyst in segment IV and V with internal echoes and irregular hyperintensities inside seen in direct communication with right hepatic duct. Common bile duct (CBD) was dilated with internal debris seen inside. Gallbladder was distended showing irregular linear intensities inside .The patient had repeat ERCP after four weeks revealing ruptured membranes and swollen papilla. ERCP cholangiogram revealed tube in cyst cavity with ruptured membranes present inside.The patient had exploratory laparotomy with peroperative findings revealing gallbladder placed vertically with short cystic duct with neck abutting hydatid cyst of liver with thickened walls. Atretic hydatid liver cyst containing infected bile with ruptured membranes. A small fistula measuring 1 cm was seen between liver hydatid cyst and right hepatic duct. Another fistula measuring 0.5 cm was found with the gallbladder  A-C. Sut2O 13]. PromUltrasound abdomen is the most commonly employed initial investigation. In frank communicating rupture, the cyst becomes smaller, and undulating membranes may be seen within it. Extrahepatic biliary dilatation is a constant feature. Echogenic or non-echogenic material without posterior acoustic shadowing is seen in the biliary tree, suggestive of sludge and daughter cysts. Direct communication was visualized in only 20% of cases. On CT abdomen visualization of detached undulating membranes and calcification of the cyst wall can be present. A dilated CBD with low attenuation intraluminal material suggests the presence of hydatid sand and cysts in the CBD. An interrupted area of the cyst wall proximal to a dilated duct may be identified as representing the site of communication. Cyst wall discontinuity, a direct sign of rupture, is seen in only 75% of cases . CT can Presurgical use of albendazole or mebendazole in echococcoosis infestations facilitates surgery by reducing intracystic pressure and by reducing the risk of recurrence after surgery or endoscopic evacuation of a ruptured cyst into biliary tree . The locLiver hydatid require pericystectomy, the evacuation and drainage or resection. A waiting period of 2 months for spontaneous closure has been recommended in small fistula for most patients having small and occult fistulas, or fistulas closing within 2 weeks . In largHowever surgery is associated with many post operative complications including persistent post operative biliary drainage, infection of residual cavity, sinus formation, recurrence or dissemination. Persistent postoperative external bile drainage is a serious complication, occurring in 3.8% to 27.5% of cases, that often necessitates reoperation , 25.In conclusion, concomitant intrabiliary rupture in hepatic duct and gallbladder is rare to see. ERCP is useful in diagnosis. Surgery can give final diagnosis.


Recent resuscitation practice changes, such as targeted oxygen therapy, end-expiratory pressure, and rescue surfactant may influence these associations.Early studies suggest an association of abnormal carbon dioxide  with mean (SD) gestational age of 28 (3) weeks and birth weight of 1,111 (403) g were included. None of the infants with arterial blood gases had hypocarbia (<30 mmHg), 32 (43%) had normocarbia (30–55 mmHg), and 43 (57%) had hypercarbia (>55 mmHg). Seventeen of the infants with arterial blood gases (22%) had hypoxia (<50 mmHg), 50 (67%) normoxia, and 8 (11%) hyperoxia (>80 mmHg). In infants with venous blood samples, none had venous PCO2 < 40 mmHg, 41 (43%) had venous PCO2 40–60 mmHg, and 54 (57%) had venous PCO2 > 60 mmHg. Multivariable logistic regression analysis showed no association of low or high PCO2 or PO2 with death or major inpatient morbidities.One hundred seventy infants (arterial With current resuscitation and stabilization practices, hyperoxia and hypocarbia was uncommon, and hypercarbia occurred frequently. None of these findings correlate with adverse inpatient outcomes or death. Our findings are in direct contrast to published observations using historical practices. Abnormally high and low levels of carbon dioxide and oxygen in the first few hours or days after birth have been associated with inpatient mortality and morbidities in very preterm babies –3. Over Practice changes in the DR have included (i) using PEEP during positive-pressure ventilation (PPV) –12, (ii)2) and oxygen (PO2) and their correlation with inpatient morbidities and mortality.We hypothesize that improved resuscitation practices have led to less variation in blood gas values and thus a reduced contribution of these values to adverse inpatient outcomes. We describe early blood gas measurements (in the first hour after birth) in preterm neonates  receiving current DR stabilization techniques to control oxygenation and ventilation. In addition, we evaluate the association of initial partial pressures of carbon dioxide . The Neonatal Research Committee, Northern Alberta Neonatal Program, and Health Research Ethics Board, University of Alberta approved the study, and written deferred parental consent was obtained for chart abstraction after delivery. When available, the research team attended deliveries of preterm infants of <33 weeks gestational age in addition to the Resuscitation-Stabilization-Triage team . The research team was not involved in the clinical care of the infants.http://ClinicalTrials.gov Identifier: NCT01739114). Infants were excluded if there was uncertainty about their gestational age, if they had a congenital abnormality, or if parents refused to give consent.The study was limited to infants <33 weeks gestational age who were part of a randomized controlled trial of lung aeration at birth . Local protocol dictated predefined intubation criteria if chest compressions were required, heart rate remained <100 beats/min despite 60 s of PPV or prolonged PPV of >10 min. Indications to start CPAP, mask ventilation (PPV), intubation, surfactant administration, chest compressions, and epinephrine administration were decided by Resuscitation-Stabilization-Triage-team according to local protocol.All practitioners attending deliveries received training on the use of equipment and initiation of resuscitation interventions according to the current Neonatal Resuscitation Program protocol . At the All included infants had either an umbilical venous and/or arterial catheter placed based on their clinical situation. Local protocol recommends both umbilical arterial and umbilical venous catheters in infants <27 weeks of age and selective use of umbilical venous catheters in infants >27 and <33 weeks of age. Blood gases are routinely drawn within the first hour after birth to assess respiratory status. We also collected outcomes of DR resuscitation and important neonatal morbidities including intraventricular hemorrhage grade 3 and 4 according to Papile et al. , periven2 and PO2 values as follows: hypocarbia PCO2, <30 mmHg; normocarbia PCO2, 30–55 mmHg; hypercarbia PCO2, >55 mmHg; hypoxia PO2, <50 mmHg, normoxia PO2, 50–80 mmHg; and hyperoxia PO2, >80 mmHg. For venous blood gases, we arbitrarily classified a PCO2 < 40 mmHg (hypocarbia), PCO2 40–60 mmHg (normocarbia), and PCO2 > 60 mmHg (hypercarbia). For each infant, the first blood gas sample within an hour after birth was analyzed. The data are presented as mean (SD) for normally distributed continuous variables and median (interquartile range) when the distribution was skewed. Data were compared using Student’s t-test and Mann–Whitney U test for parametric and non-parametric comparisons of continuous variables, respectively, and χ2 for categorical variables. p Values are two sided, and p < 0.05 was considered statistically significant. Binomial logistic regressions (log-linear logistic regression) were performed to ascertain the adjusted and unadjusted effects of PCO2 and PO2 on intraventricular hemorrhage (grade > 3) and chronic lung disease (defined as oxygen or ventilation requirement at 36 weeks corrected age). Ordinary logistic regression was performed to evaluate the adjusted and unadjusted effects of PCO2 and PO2 on necrotizing enterocolitis (stage > 2 according to Bell). Statistical analyses were performed with Stata  and IBM SPSS Statistics version 24 (IBM Corp.). This was an observational study, and therefore, no sample size calculation before the study was performed. The study was reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines  within first hour (a mean of 47 min) after birth. The infants had mean (SD) gestational age of 28 (3) weeks and birth weight of 1,111 (403) g. Overall, there was a greater number of arterial blood gases collected from preterm infants who were <27 weeks gestation , had lower 1- and 5-min Apgar scores, and were less likely to have delayed cord clamping, compared to infants ≥27 weeks gestation  (p < 0.05). There were no differences in gender or Cesarean section rate.Demographics of study infants are presented in Table In the whole cohort, 43% had normocarbia, 57% had hypercarbia, and 3% had hyperoxia.Of 75 infants who had arterial blood gas drawn within the first hour after birth, none had hypocarbia, 32 (43%) had normocarbia, and 43 (57%) had hypercarbia. A total of 17 (22%) had hypoxia, 50 (67%) had normoxia, and 8 (11%) had hyperoxia. Details regarding DR and secondary outcomes are presented in Tables 2 and PO2 on intraventricular hemorrhage, necrotizing enterocolitis, and chronic lung disease. Adjustments were made for sex, gestational age, and birth weight separately and then for all three variables together. Ordinary logistic regression was performed to evaluate the adjusted and unadjusted effects of PCO2 and PO2 on necrotizing enterocolitis. With respect to the outcome (necrotizing enterocolitis), three categories were considered: “no,” “yes,” and “death from necrotizing enterocolitis.” Sex was excluded from the ordinary logistic regression analysis because of the very small size of male and female infants who died because of necrotizing enterocolitis . Therefore, the effects of PCO2 and PO2 on necrotizing enterocolitis were adjusted for gestational age and birth weight separately and then for both together. No statistical significance in p values and odds ratios was found for either PCO2 or PO2 , both of which are implicated in tissue injury. We were unable to demonstrate an association of abnormal blood gases with major inpatient morbidity or death.2 and PO2 values in preterm infants immediately after birth. A decade ago, Tracy et al. reported that 26% of preterm infants <34 weeks gestation had hypocarbia, 73% had normocarbia, and none had hypercarbia at NICU admission . Although there is no comprehensive study comparing arterial and venous PCOurements . In addiMeasurement and confirmation of hypoxia, hyperoxia, hypocarbia, and hypercarbia after very preterm birth is an inexact science, and prevalence may vary based on clinical practices. Current practices lead to low rates of hyperoxia or hypocarbia. Given the study limitations, no associations were found between early blood gas measurements up to 1 h of age and inpatient morbidity or death.HH was involved in data collection, analysis, and interpretation; wrote the first draft; performed revisions of the drafted article; and approved the final version of the manuscript for submission. P-YC, MO, KA, and GS were involved in the conception and design of the study; involved in data collection, analysis, and interpretation; performed critical revisions of the drafted article; and approved the final version of the manuscript for submission. SO and AS were involved in data collection, analysis, and interpretation; performed critical revisions of the drafted article; and approved the final version of the manuscript for submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To describe the effect of maternal vaccination on birth outcomes in rural Nepal, modified by timing of vaccination in pregnancy and influenza virus activity.A secondary analysis was conducted using data from two annual cohorts of a randomized controlled trial. A total of 3693 pregnant women from Sarlahi District were enrolled between April 25, 2011, and September 9, 2013. All participants were aged 15–40 years and received a trivalent inactivated influenza vaccine or placebo. The outcome measures included birth weight, pregnancy length, low birth weight (<2500 g), preterm birth, and small‐for‐gestational‐age birth.CI] 8–76). The magnitude of this increase varied by season but was greatest among pregnancies with high influenza virus circulation during the third trimester. Birth weight increased by 111 g (95% CI −51 to 273) when 75%–100% of a pregnancy's third trimester had high influenza virus circulation versus 38 g (95% CI −6 to 81) when 0%–25% of a pregnancy's third trimester had high influenza virus circulation. However, these results were nonsignificant.Data were available on birth weight for 2741 births and on pregnancy length for 3623 births. Maternal vaccination increased mean birthweight by 42 g (95% confidence interval [Seasonal maternal influenza vaccination in rural Nepal increased birth weight; the magnitude appeared larger during periods of high influenza virus circulation.NCT01034254. Maternal influenza vaccination in rural Nepal increased birth weight, particularly among pregnancies with high levels of influenza virus circulation during the third trimester. Those born small‐for‐gestational‐age (SGA)—a proxy for fetal growth restriction—experience increased risk of neonatal and infant mortality, stunted growth, and chronic disease in adulthood.Observational studies and randomized controlled trials (RCTs) exploring the effect of maternal influenza vaccination on rates of SGA and preterm delivery have reported mixed findings.The aim of the present analysis was to present further details of the effect of maternal influenza vaccination on birth weight and pregnancy length among participants enrolled in the Nepal Mothers’ Gift Trial. The effect of maternal vaccination on birth outcomes and its modification by pregnancy length at which vaccination was given and by influenza virus activity were assessed. These issues are particularly important to address in locations with year‐round influenza circulation to determine the ideal timing of maternal vaccination.2A secondary analysis was performed using the data from an RCT that examined the efficacy of influenza immunization on the incidence of respiratory illness and laboratory‐confirmed influenza infection among pregnant women and their neonates, with 6 months of postpartum follow‐up.Full details of the original methods and the results for the primary outcomes have been described elsewhere.All enrolled women were visited weekly by study staff, both during and after pregnancy (follow‐up continued to 180 days after delivery), to collect data on maternal and infant morbidities for each day in the previous week. These illness signs were all self‐reported by the women or other household members. Influenza‐like illness was defined as a fever in the presence of either a cough or sore throat, based on daily self‐reported data that was collected on a weekly basis. Nasal swabs were taken for influenza testing by polymerase chain reactionThe participants were instructed to notify study staff immediately after delivery, at which time a staff member visited the household to collect data on maternal, fetal, and neonatal status, as well as morbidities and conditions during labor and delivery.The main outcome measures were birth weight and pregnancy length at delivery, and dichotomous variables LBW, preterm delivery (<37 weeks), and SGA. Only neonatal weights taken within 72 hours of delivery were included; when weight was taken beyond 72 hours, data on pregnancy length could still be contributed. A birth weight lower than the 10th percentile of the sex‐specific and gestational‐age‐specific INTERGROWTH‐21st birth weight standardThe data were analyzed using Stata version 13 . The distribution of birth weight and pregnancy length at delivery was summarized by vaccination group. The data were also stratified by the formulation of the vaccine the mother received. The infants were categorized by creating mutually exclusive categories of delivery weight and pregnancy length as follows: term‐AGA‐not LBW, term‐AGA‐LBW, term‐SGA‐not‐LBW, term‐SGA‐LBW, preterm‐AGA‐not‐LBW, preterm‐AGA‐LBW, and preterm‐SGA Fig. .8 Infant3The flow diagrams for the two annual cohorts are shown in Figures Among the 2741 women whose newborns were weighed within 72 hours of delivery, 31 (1.1%) had at least one laboratory‐confirmed influenza episode during pregnancy whereas 2710 (98.9%) did not. Additionally, 175 (6.4%) women experienced at least one episode of influenza‐like illness during pregnancy, whereas 2566 (93.6%) did not.Table The birth weight distribution in the placebo and vaccination groups is presented in Table As previously reported,Figure With regard to secular trends, the mean birth weight increased by 5 g (95% CI 2–8) per month for the placebo group and 7 g (95% CI 4–10) per month for the vaccinated group through the course of the study.Table The vaccination effect on birth weight was stratified by exposure to high levels of influenza virus circulation in the third trimester Table . AlthougWhen stratifying by timing of vaccination in pregnancy, an increase in birth weight was seen in each category, but was only statistically significant among women vaccinated before 26 weeks  .4Maternal influenza vaccination increased birth weight among live births in the present study. The magnitude differed by season, appearing greatest among pregnancies for which the third trimester occurred at a time of high influenza virus circulation; however, the results were inconclusive. Sarlahi District in southern Nepal is a subtropical region that experiences influenza virus circulation for two‐thirds of the year and is epidemiologically similar to other parts of South Asia. Seasonal peaks of circulation appear to overlap temporally with an increased effect of vaccination on birth weight. In a low‐resource setting such as rural Nepal, vaccination delivery can be logistically difficult; therefore, alternatives to year‐round vaccination should be considered. The present study also indicated a marginal reduction in the prevalence of infants born both preterm and SGA. No clear trends were observed to link timing of vaccination during pregnancy with the effects on birth weight.Previous observational studies reported mixed results regarding the effect of maternal influenza vaccination on birth outcomes. Data collected in the USA between 2004 and 2009 showed no effect on preterm birth or SGA,Four maternal influenza vaccination trials have been conducted to date, including the Nepal Mothers’ Gift Trial.The present study examined only the effect of vaccination on birth weight and pregnancy length; however, there is evidence to suggest that influenza vaccination might positively impact fetal and neonatal health outcomes through other mechanisms. Animal studies have indicated effects of maternal influenza infection on fetal brain development,The present study could not determine what period in pregnancy would be associated with the largest effect from exposure to influenza virus. Given that the greatest fetal weight gain occurs late in pregnancy,In conclusion, maternal influenza vaccination exerted the greatest effect on birth weight among pregnant women who were exposed to high influenza virus circulation during the third trimester. A strategy of seasonal maternal influenza vaccination in resource‐limited settings could potentially increase birth weight during periods of high influenza circulation. Taking into consideration the barriers to providing year‐round vaccination, it may be possible to target key times of the year to maximize the impact on birth outcomes.NK conducted the data analysis and wrote the first draft of the manuscript. JKa, JAE, MCS, SKK, LS, JKu, LCM, and JMT contributed to the study design. JKa, SKK, LS, LCM, SCL, and JMT supervised the conduct of the study in the field. JAE and JKu determined the virology assay collection protocols. HYC assisted in study implementation and cord‐blood collection. JAE and MCS determined the antibody assay protocols. All authors contributed to the writing or revisions to the manuscript and approved the final version.JKa, MCS, LCM, HYC, and JMT have received grants from the Bill & Melinda Gates Foundation. JAE has received grants and personal fees from GlaxoSmith Kline, Pfizer, and Gilead; research support from Roche, Novavax, Chimerix, MedImmune, and Alio; and personal fees from Abbvie. MCS has received funding from Pfizer. HYC has received grants from PATH and the Thrasher Foundation, and research funding from Sanofi, GlaxoSmith Kline, and Novavax. The other authors have no conflicts of interests.Figure S1. Categorical breakdown of birth weight and pregnancy length.Click here for additional data file.Figure S2. Flow of patients through the first cohort.Click here for additional data file.Figure S3. Flow of patients through the second cohort.Click here for additional data file.Figure S4. Birth weight distribution by vaccine status and vaccine type.Click here for additional data file.Figure S5. Bimonthly mean birth weight against weekly influenza circulation, by influenza type.Click here for additional data file.Table S1. Birth weight distribution (restricted to those measured within 72 hours of birth), comparing women who had influenza or influenza‐like illness during pregnancy with those who did not.Click here for additional data file.Table S2. Effect of maternal vaccination on birth outcomes, stratified by calendar time of vaccination.Click here for additional data file.Table S3. Effect of vaccination on gestational age, stratified by third trimester exposure to high influenza circulation and timing of vaccination in pregnancy.Click here for additional data file.Appendix S1. Influenza vaccine type.Click here for additional data file.


Objectives Preterm birth is the leading pregnancy outcome associated with perinatal morbidity and mortality and remains difficult to prevent. There is evidence that some modifiable maternal health characteristics may influence the risk of preterm birth. Our aim was to investigate the relationships of self-reported maternal health behaviour and psychological characteristics in nulliparous women with spontaneous preterm birth in prenatal primary care. Methods The data of our prospective study was obtained from the nationwide DELIVER multicentre cohort study (September 2009–March 2011), which was designed to examine perinatal primary care in the Netherlands. In our study, consisting of 2768 nulliparous women, we estimated the relationships of various self-reported health behaviours  and psychological characteristics  with spontaneous preterm birth as a dichotomous outcome. Due to the clustering of clients within midwife practices, Generalized Estimating Equations was used for these analyses. Results Low health control beliefs was the sole characteristic significantly associated with spontaneous preterm birth  after being adjusted for socio-demographics, anthropometrics and the remaining health behaviour and psychological characteristics. The other characteristics were not significantly associated with spontaneous preterm birth. Conclusions for Practice Maternal low health control beliefs need to be explored further as a possible marker for women at risk for preterm birth, and as a potentially modifiable characteristic to be used in interventions which are designed to reduce the risk of spontaneous preterm birth. What is already known on this subject? Spontaneous preterm birth is associated with perinatal mortality and morbidity, but remains difficult to predict and prevent. There is some evidence that maternal health behaviour and psychological characteristics during pregnancy may be associated with spontaneous preterm birth.What this study adds? Of all the self-reported maternal health behaviour and psychological characteristics examined in this study, low health control beliefs was the sole maternal characteristic associated with having a spontaneous preterm birth in nulliparous women. Further studies should explore the role of low health control beliefs as a possible marker, or as a potentially modifiable characteristic to help reduce the risk of spontaneous preterm birth.Preterm birth occurs in about 7.6 % of all pregnancies in the Netherlands  of women are referred to secondary care as complications arise  among nulliparous women.Our study is prospective in design and uses data on health behaviour and psychological characteristics collected by the multicentre prospective cohort DELIVER study (September 2009–March 2011), by means of self-administered questionnaires completed by pregnant women in primary prenatal care. DELIVER is an acronym for Data EersteLIjns VERloskunde, which is translated as Data Primary Care Midwifery. This data was linked to the National Midwifery Registry [Landelijke Verloskunde Registratie (LVR1)] and pregnancy record data provided by midwives, for additional information on birth and pregnancy outcomes.The DELIVER study consisted of 7865 low risk pregnant women starting their pregnancy in primary care. Details on the study can be obtained elsewhere  as well as available LVR1 and pregnancy record data. As previous preterm birth is a well-established risk factor for having a preterm birth in multiparous women . Where information was incomplete or missing, this variable was complemented by self-reported information provided by women who had completed the third questionnaire as well (after birth). This variable was dichotomised into ‘full term’  and ‘preterm’ .Selected health behaviour and psychological characteristics were based on earlier studies and on plausible associations with spontaneous preterm birth. These were folic acid supplementation, alcohol consumption, smoking, daily fruit, daily fresh vegetables, daily hot meal and breakfast consumption, health control beliefs and anxious or depressed mood  and ‘heavy smoker’ (≥10 cigarettes daily). Respondents were also asked if they ate fruit daily, fresh vegetables daily and a hot meal daily, with all three questions containing response options ‘yes’ or ‘no’. The variable ‘breakfast consumption’ was obtained by an item asking women how often per week they ate breakfast; the four response options were categorized into ‘daily’ and ‘4–6 times per week’ and ‘up to 3 times per week’.Psychological characteristics: The variable health control beliefs was included, as feeling in control is often considered a component of managing stress , ‘medium’  or ‘higher’ . Respondents were asked about their country of birth as well as their parents’ country or countries of birth and the ethnicity variable was categorized as either ‘Dutch’ or ‘non-Dutch ethnicity’, based on the definition used by Statistics Netherlands , ‘normal weight’ (18.5–24.99 kg/m2), ‘overweight’ (25–29.99 kg/m2) and ‘obesity’ (30+ kg/m2).Respondents were asked to report their height in centimetres and weight in kilograms before they became pregnant. We categorized the variable ‘height’ as ‘>177 cm’, ‘164–177 cm’ and ‘<164 cm’. The variable Body Mass Index (BMI) was calculated using maternal height and weight and categorized according to the World Health Organization criteria of weight status: ‘underweight’  were treated as outcome. These analyses showed that the missing data of ‘preterm/full term birth’ was associated with higher educational level and lower maternal age, and the missing data of BMI with lower maternal education. These associations meant there was an increased likelihood that the data were of the type Missing At Random (MAR) to adjust for possible correlations within each midwife practice. First the associations of social demographics and anthropometrics (considered as confounders) with preterm birth were examined univariably using GEE logistic regression. Then the association of each health behaviour and psychological characteristic with preterm birth was examined univariably using GEE logistic regression in model 1. Each characteristic was then examined again, but with adjustment for potential confounders in stages: first socio-demographics in model 2, then socio-demographics and anthropometrics in model 3, and finally socio-demographics, anthropometrics and all other health behaviour and psychological characteristics together in model 4. The GEE analyses on the multiple imputed datasets resulted in pooled regression coefficients and 95 % intervals of regression coefficients. Odds ratios with their 95 % confidence intervals were calculated from these coefficients and were reported for each model. Sensitivity analyses were carried out to compare complete case analyses with multiple imputed data analyses and to compare spontaneous preterm with all types of preterm birth as outcome; differences and similarity in results were reported. All analyses were carried out in IBM SPSS version 22.Spontaneous preterm birth occurred in 138/2196 (6.3 %) pregnancies in our nulliparous population of complete cases, of which the median gestational age at birth was 35.1 weeks  vs ]. For all the other variables, univariable and multivariable analyses in both complete case and multiple imputed datasets, produced similar results and therefore led to the same conclusions. The sensitivity analyses examining all types of preterm birth as outcome showed similarity in all the relationships, except for low education, low maternal height, and low health control beliefs. Although there was an effect, these variables were not significantly associated with aggregated preterm birth in the univariable analyses. Low health control beliefs remained insignificant in all the models with aggregated preterm birth as outcome.We aimed to study the prevalence of spontaneous preterm births among nulliparous women starting their pregnancy in prenatal primary care, as well as the association of self-reported health behaviour and psychological characteristics with having a spontaneous preterm birth (<37 weeks of gestation at birth). The prevalence of spontaneous birth in our nulliparous population was 6.3 %, which is somewhat higher than what was found for the Dutch national nulliparous singleton population over the years 2000–2007 (6.3 % vs about 5.5 %)  (Statistics Netherlands There are advantages and disadvantages to examining spontaneous and indicated preterm births separately, as well as together. Different types of preterm birth share many similar risk factors, such as pre-eclampsia and foetal growth restriction, but the size of the effects of these risk factors differ per preterm birth type (Savitz et al. In our study, we found almost no health behaviour and psychological characteristics to be associated with spontaneous preterm birth. Low health control beliefs was the sole variable associated with spontaneous preterm birth after adjusting for potential confounding factors. Maternal low health control beliefs need to be explored further as a possible marker for women at risk for preterm birth and as a potentially modifiable characteristic to be used in interventions which are designed to reduce the risk of spontaneous preterm birth.


Background: Studies in older adults and animals have suggested contrasting relations between bone health and different vitamin A compounds. To our knowledge, the associations between maternal vitamin A status and offspring bone development have not previously been elucidated.Objective: We examined the associations between maternal serum retinol and β-carotene concentrations during late pregnancy and offspring bone mineralization assessed at birth with the use of dual-energy X-ray absorptiometry.Design: In the Southampton Women’s Survey mother-offspring birth cohort, maternal health, lifestyle, and diet were assessed prepregnancy and at 11 and 34 wk of gestation. In late pregnancy, maternal serum retinol and β-carotene concentrations were measured. Offspring total body bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured within 2 wk after birth.Results: In total, 520 and 446 mother-offspring pairs had measurements of maternal serum retinol and β-carotene, respectively. Higher maternal serum retinol in late pregnancy was associated with lower offspring total body BMC  and BA  but not BMD. Conversely, higher maternal serum β-carotene concentrations in late pregnancy were associated with greater total body BMC  and BA  but not BMD.Conclusions: Maternal serum retinol and β-carotene concentrations had differing associations with offspring bone size and growth at birth: retinol was negatively associated with these measurements, whereas β-carotene was positively associated. These findings highlight the need for further investigation of the effects of maternal retinol and carotenoid status on offspring bone development. Identifying novel strategies to improve bone health is important in addressing the high incidence of both pediatric fractures  and fragFew studies to our knowledge have related maternal vitamin A nutrition during pregnancy to offspring bone development. In the prospective Avon Longitudinal Study of Parents and Children cohort study, maternal dietary intakes of retinol and carotene, measured by a food-frequency questionnaire (FFQ)n = 12,583), were initially recruited into the study. Thereafter, there were 3158 live-born singleton births to women in the study between 1998 and 2007. A flowchart of the study population, for whom there were maternal serum retinol and β-carotene concentration data and neonatal bone measures, is presented in SWS is a prospective mother-offspring birth cohort study . NonpregSWS was conducted according to Declaration of Helsinki guidelines, and the Southampton and South West Hampshire Research Ethics Committee approved all procedures. Written informed consent was obtained from all participating women.r = 0.67) (At study entry (prepregnancy), early pregnancy (∼11 wk of gestation), and late pregnancy (34 wk of gestation), research nurses administered questionnaires on maternal demographics, lifestyle, and health. The highest level of educational attainment was recorded. Diet was assessed with the use of a validated 100-item FFQ, and anthropometric measurements were obtained , 14. Wit2 and D3 and meets the requirements of the Vitamin D External Quality Assurance Scheme. Intra- and interassay CVs were <10%.A maternal blood sample was obtained during the late-pregnancy assessment. The serum was stored at −80°C until analysis to determine maternal serum concentrations of retinol and β-carotene. The sample measurements were carried out in the laboratory of the Institute of Human Nutrition, University of Southampton, based on the existing birth cohort at the end of 2003. HPLC with multiwavelength spectrophotometric detection was used to analyze retinol and β-carotene. The HPLC equipment consisted of a Beckman Coulter System Gold 125 Solvent System and 508 Autosampler connected to a Supelcosil C18 reverse-phase column  (Sigma-Aldrich). Retinol and β-carotene were measured by absorbance at 325 and 460 nm, respectively. Standards of retinol and β-carotene were prepared daily from stock solutions stored at −80°C, and their concentrations were determined by spectrophotometry. Acceptable accuracy and precision were confirmed by the use of frozen aliquots of pooled serum. The CVs were between 5% and 10%. Maternal vitamin D status was determined from serum 25-hydroxyvitamin D concentrations. These were analyzed by radioimmunoassay (Diasorin). This assay measures 25-hydroxyvitamins DMothers registered with selected general practitioner practices were invited to participate in the SWS bone substudy. DXA scans of neonatal total body BMC, bone area (BA), and BMD were obtained within 2 wk after birth with the use of a Lunar DPX-L instrument with specific pediatric software . Daily quality assessment and weekly calibration against a water phantom were performed. Measurements were standardized with regard to the child being pacified, fed if necessary, wearing no clothing and placed on a waterproof sheet in a standard position on the scanner. The child was kept in place with the use of rice bags placed over the bottom end of the towel. The short- and long-term CVs of the DXA instruments were 0.8% and 1.4%, respectively.e-transformed to normalize the distribution before standardization could be applied. Diagnostic plots were used to check for heteroscedasticity. Unpaired t tests were used to check for sex differences in the exposure and outcome variables of the offspring. The model was adjusted a priori for offspring sex, gestational age, age at DXA scan, maternal smoking during pregnancy, late-pregnancy walking speed, late-pregnancy triceps skinfold thickness, parity, and maternal educational status because these factors have previously been associated with neonatal bone mineralization , triceps skinfold thicknesses, and parity, but in our analysis fewer women smoked during pregnancy and they had attained a higher educational status. In total, <2% of the women studied took retinol-containing supplements in late pregnancy ; 7% took β-carotene-containing supplements . The use of vitamin A supplements was comparable for women included in this analysis and other women in the SWS cohort  and BA (P = 0.010) at birth  and a weaker correlation between maternal serum retinol and late-pregnancy prudent diet score . Including maternal prudent diet score in the linear regression model did not materially change the associations between β-carotene and offspring BMC and BA. In the final analyses, maternal vitamin D status in late pregnancy was included in the models. Adjusting for vitamin D status made little difference; the pattern of associations observed between serum retinol and β-carotene concentrations and neonatal bone indexes remained the same (data not shown).There was a positive correlation between maternal serum β-carotene and late-pregnancy prudent diet score  and β-carotene (positive) and offspring neonatal total BMC, BA at birth, and birth weight. We did not observe the same associations with BMD and scBMC. The relations were independent of maternal anthropometric, lifestyle, and socioeconomic factors and a measure of dietary quality.The observed associations with BA, BMC, and birth weight would suggest that maternal serum retinol and β-carotene might influence body size rather than having an independent effect on BMD. Previous intervention studies have not consistently demonstrated that prenatal vitamin A supplementation can increase birth size. However, these studies have typically been performed in developing countries with a high prevalence of vitamin A deficiency, and many have used an interventional product containing both retinol and β-carotene . ConsideThere are few studies to our knowledge that have related maternal vitamin A status to offspring bone development. In the Avon Longitudinal Study of Parents and Children mother-offspring birth cohort study, maternal dietary retinol and β-carotene intake assessed by an FFQ at 32 wk of gestation were not significantly associated with offspring whole-body less head or lumbar spine BMC, BMD, or scBMC in children aged 9 y . HoweverAnimal studies have shown that both high and low intakes of vitamin A can be detrimental to the bone. Rats with dietary-induced hypervitaminosis A caused by increased retinyl ester intakes have a smaller humeral cross-sectional area and cortical thinning than in controls but similar cortical and trabecular volumetric BMD . This isStudies in rats have shown that treatment with retinoids increases osteoclast number and markers of bone turnover , 19 but We studied a large prospective cohort and biochemically assessed serum retinol and β-carotene concentrations and DXA measures of offspring bone indexes. However, there are limitations that should be considered in the interpretation of our findings. First, retinol and β-carotene concentrations were measured in maternal blood, which correlates only weakly with umbilical cord blood measurements , 24. HowWe have demonstrated that late-pregnancy serum retinol concentration is negatively associated with offspring bone size and mineralization at birth, whereas β-carotene is positively associated with these measurements. These findings may lend further support to dietary recommendations to limit retinol intake during pregnancy and highlight the potential for the further investigation of possible beneficial effects of carotenoids on offspring bone development.