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BackgroundThe age at onset of the association between poverty and poor health is not understood. Our hypothesis was that individuals from highest household income (HI), compared to those with lowest HI, will have increased fetal size in the second and third trimester and birth.Methods.Second and third trimester fetal ultrasound measurements and birth measurements were obtained from eight cohorts. Results were analysed in cross-sectional two-stage individual patient data (IPD) analyses and also a longitudinal one-stage IPD analysis.ResultsThe eight cohorts included 21 714 individuals. In the two-stage (cross-sectional) IPD analysis, individuals from the highest HI category compared with those from the lowest HI category had larger head size at birth (mean difference 0.22 z score (0.07, 0.36)), in the third trimester (0.25 (0.16, 0.33)) and second trimester (0.11 (0.02, 0.19)). Weight was higher at birth in the highest HI category. In the one-stage (longitudinal) IPD analysis which included data from six cohorts (n=11 062), head size was larger (mean difference 0.13 (0.03, 0.23)) for individuals in the highest HI compared with lowest category, and this difference became greater between the second trimester and birth. Similarly, in the one-stage IPD, weight was heavier in second highest HI category compared with the lowest (mean difference 0.10 (0 .00, 0.20)) and the difference widened as pregnancy progressed. Length was not linked to HI category in the longitudinal model.ConclusionsThe association between HI, an index of poverty, and fetal size is already present in the second trimester.

In this narrative review, we outline recent evidence relating longitudinal ultrasound (US) measurements to offspring outcomes in the perinatal period and in childhood, with an emphasis on the methodological approaches for describing fetal growth. The utility of longitudinal ultrasonography (US) to measure fetal growth and determine fetal trajectories is valued in both clinical and research environments. Evidence shows that repeated measures of US throughout pregnancy are useful for distinguishing between a growth-restricted and constitutionally small fetus, the former burdened by adverse clinical outcomes. Fetal growth restriction and small for gestational age are not interchangeable terms, although both can exist in the same individual. The application of longitudinal US may have predictive value when determining longer-term health and disease outcomes in offspring born growth-restricted. However, it is important to remember that associations between fetal growth restriction and increased risk for non-communicable diseases are likely modified by postnatal growth.

Background Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. Method and findings Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986–88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels 75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 μmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS. Conclusions This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD. Copyright: © 2019 Balasuriya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986-1988). Size at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks' gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval (CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R(2) increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth.

IntroductionThe maternal mortality ratio is decreasing globally, although it remains high in Malawi. Unsafe abortion is a major cause and treatment of complications after abortion is a big burden on the health system. Even though manual vacuum aspiration (MVA) is the recommended surgical treatment of incomplete abortions in the first trimester, many hospitals in Malawi continue to use sharp curettage. It is known to have more complications and is more expensive in the long run. The purpose of this study was to determine the effectiveness of a structured MVA training programme in the treatment of incomplete abortions in Malawi.MethodsA quasi-experimental before-and-after study design was employed in an MVA training programme for health personnel at three hospitals in Southern Malawi. A total of 53 health personnel at the Queen Elizabeth Central Hospital and the district hospitals of Chikwawa and Chiradzulu (intervention hospitals) were trained in the use of MVA. Kamuzu Central Hospital in Lilongwe and the Thyolo District Hospital served as control institutions. Medical files for all women treated for an incomplete abortion at the study hospitals were reviewed before and after the intervention. Information on demographic and obstetric data and the type of treatment was collected.ResultsThere was a significant increase in the use of MVA from 7.8% (95% CI 5.8 to 10.3) to 29.1% (95% CI 25.9 to 32.5) 1 year after the intervention. In comparison, we found a mere 3% increase in the control hospitals.ConclusionsBy providing a refresher training programme to health personnel who treat women with incomplete abortions, it was possible to increase the use of MVA as recommended in the Malawi national guidelines.

Background Prenatal exposure to persistent organic pollutants (POPs), may influence offspring weight gain. More prospective epidemiological studies are needed to compliment the growing body of evidence from animal studies. Methods Serum from 412 pregnant Norwegian and Swedish women participating in a Scandinavian prospective cohort study were collected in 1986–88, and analyses of two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were conducted. We used linear and logistic regression models with 95% confidence intervals (CIs) to evaluate the associations between maternal serum POP concentrations at 17–20 weeks of gestation and child overweight/obesity (body mass index (BMI) ≥ 85th percentile) at 5-year follow-up. Results were further stratified by country after testing for effect modification. We also assessed potential non-monotonic dose-response (NMDR) relationships. Results In adjusted linear models, we observed increased BMI-for-age-and-sex z-score (β = 0.18, 95% CI: 0.01–0.35), and increased triceps skinfold z-score (β = 0.15, 95% CI: 0.02–0.27) in children at 5-year follow-up per ln-unit increase in maternal serum perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for child overweight/obesity (BMI ≥ 85th percentile) for each ln-unit increase in maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11–3.74), with stronger odds among Norwegian children (OR: 2.96, 95% CI: 1.42–6.15). We found similar associations between maternal serum perfluorooctanoate (PFOA) concentrations and child overweight/obesity. We found indications of NMDR relationships between PFOS and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish children. Conclusion We found positive associations between maternal serum PFAS concentrations and child overweight/obesity at 5-year follow-up, particularly among Norwegian participants. We observed some evidence for NMDR relationships among Swedish participants. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Malawi has a high maternal mortality rate, of which unsafe abortion is a major cause. About 140,000 induced abortions are estimated every year, despite there being a restrictive abortion law in place. This leads to complications, such as incomplete abortions, which need to be treated to avoid further harm. Although manual vacuum aspiration (MVA) is a safe and cheap method of evacuating the uterus, the most commonly used method in Malawi is curettage. Medical treatment is used sparingly in the country, and the Ministry of Health has been trying to increase the use of MVA. The aim of this study was to investigate the treatment of incomplete abortions in three public hospitals in Southern Malawi during a three-year period. All medical files from the female/gynecological wards from 2013 to 2015 were reviewed. In total, information on obstetric history, demographics, and treatment were collected from 7270 women who had been treated for incomplete abortions. The overall use of MVA at the three hospitals during the study period was 11.4% (95% CI, 10.7–12.1). However, there was a major increase in MVA application at one District Hospital. Why there was only one successful hospital in this study is unclear, but may be due to more training and dedicated leadership at this particular hospital. Either way, the use of MVA in the treatment of incomplete abortions continues to be low in Malawi, despite recommendations from the World Health Organization (WHO) and the Malawi Ministry of Health. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Background/objectives: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose–response relationship across number of cigarettes and whether this differs by sex remains unclear. Subject/methods: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. Results: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother–child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02–1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. Conclusions: A linear dose–response relationship of maternal smoking was observed in the range of 1–15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

This is the peer reviewed version of the following article: Jacobsen, G.W., Ræder, H., Stien, M., Munthe, L.A. & Skogen, V. (2018). Springboard to an academic career—A national medical student research program. PLoS ONE, 13:e0195527(4), 1-8. https://doi.org/10.1371/journal.pone.0195527, which has been published in final form at https://doi.org/10.1371/journal.pone.0195527. Over the last decades there has been a decline in the recruitment of medical students into academia in all medical fields. Concurrently, medical research has increasingly included other disciplines in multidisciplinary convergence, introducing an unmet recruitment gap and requirement for medical researchers. To counteract the trend and recruit students to academic medicine, a national intercalated Medical Student Research Program (MSRP) was established in Norway in 2002. A preliminary evaluation in 2009 suggested that the MSRP had resulted in recruitment, but could not conclude on a lasting effect beyond graduation in a study that did not include any controls. These results led us to hypothesize that the MSRP could increase the number of PhD degrees and attract medical students towards academic medicine. Adopting a case cohort design, we here report that the intercalated MSRP had a significant impact of the throughput of physician-scientists to PhD, by increasing the rate of PhD completion 10-fold (p

To assess whether folic acid intake during the first trimester of pregnancy is related to pregnancy outcomes preeclampsia, low birth weight or preterm birth.Prospective cohort study of 3647 women who were followed from the first trimester of pregnancy. Detailed information on quantity of folic acid intake before and during the first three months of pregnancy was recorded. Pregnancy outcome data were abstracted from obstetric records.Lean mothers who used folic acid supplementation the month before pregnancy had a 40% reduced risk of developing preeclampsia. The adjusted odds ratio (OR) with 95% confidence intervals (95%CI) for preeclampsia in lean mothers (BMI25) who used folic acid supplements the month before pregnancy was 0.6 (95% CI 0.4-1.0). Obese mothers who used folic acid supplementation in the first trimester had an increased, but not statistically significant risk for preterm birth (adjusted OR 1.9 with 95% CI 0.9-4.0). There were no significant associations between folic acid supplementation and low birth weight.Our study supports a possible protective effect of folate intake in early pregnancy on preeclampsia in lean mothers. There was no support for any beneficial effect of folic acid use on preterm birth or low birth weight, and we found no evidence of any harmful effects of folate use for the outcomes included in our study.

To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years.Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years.Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, P.05). Although there were no differences between the SGA non-fetal growth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, P.05) and 9 years (96.2 compared with 107.5, P.05) compared with those in the control group. There were some brain volume differences at 15 years between SGA children and those in the control group, but after adjustment for total intracranial volume, age at examination, and sex, there were only significant differences between the SGA fetal growth restriction and control groups for thalamic (17.4 compared with 18.6 cm, P.01) and cerebellar white matter volumes (21.5 compared with 24.3 cm, P.01).Small-for-gestational-age children had lower intelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth.II.

available from 2018-02-01 Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight

© The Author(s) (2016). This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. DOI: 10.1038/pr.2016.187 Background: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. Methods: This case–cohort study included 424 mother– child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. Results: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. Conclusions: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption.

Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis. Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements. There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18 SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked. Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy. The study was supported by the European Cooperation in Science and Technology, who provided funds for publication. KMG is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Programme (FP7/2007-2013), projects Early Nutrition and ODIN under grant agreement numbers 289346 and 613977.

Objective To evaluate how different levels of increase in maternal blood glucose from a fasting state to 2 h after an oral glucose challenge in late pregnancy are associated with fetal growth, with special emphasis on those with a low increase. Design Prospective cohort study. Subjects We followed 855 women, of whom 70% had an increased risk for carrying lighter babies. Study design and methods Ultrasound was used to estimate fetal growth in gestational weeks 25, 33 and 37. In week 37 the women had a 75-g oral glucose tolerance test, and fasting and 2-h capillary glucose values were recorded with the difference between these two called delta (∆) glucose. Three groups were constructed from the ∆ glucose distribution: Low below the 10th centile; Medium between the 10th and 90th centiles; and High above the 90th centile. Missing data were imputed. Linear and Poisson regression models were applied. Outcome measures Estimated fetal weight, percent deviation from expected fetal weight and anthropometric measures at birth. Results The Low group carried the lightest fetuses and the High group the heaviest. The fetal growth in the Low group deviated increasingly more in a negative direction from week 25 to 37 than in the other groups. Conclusion In a high-risk population, a positive relation between ∆ glucose and fetal growth was found. The Low group demonstrated impaired growth. More attention should be paid to pregnant women with an insufficient increase in glucose after a glucose challenge. Future studies should challenge our findings in high-risk and low-risk populations.

Reduced IQ, learning difficulties and poor school performance have been reported in small-for-gestational-age (SGA) subjects. However, few studies include a comprehensive neuropsychological assessment. Our aim was to study neuropsychological functioning in young adults born SGA at term. A comprehensive neuropsychological test battery was administered to 58 SGA subjects (birth weight p< .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below −1.5SDon the memory domain (odds ratio = 13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group obtained lower scores on most neuropsychological tests, with significant differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the Wechsler Memory Scale mental control and the auditory immediate memory scale, the Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI) motor coordination subtest. Young adults born SGA score more poorly on neuropsychological tests compared with non-SGA controls. Differences were modest, with more significant differences in the memory domain. (JINS, 2014,20, 1–11)

Background: The developing fetus is particularly vulnerable to the effects of endocrine disrupting chemicals (EDCs). Molecular fingerprints of EDCs can be identified via microRNA (miRNA) expression profiles and may be etiologically implicated in the developmental origin of disease (DOHaD). Methods/design: This pilot study includes pregnant women at high risk (smoking at conception), and low risk (non-smoking at conception) for SGA birth (birthweight

A potential link between intimate partner violence (IPV) and cardiovascular disease (CVD) has been suggested, yet evidence is scarce. We assessed cardiovascular risk and incident prescription of cardiovascular medication by lifetime experiences of physical and/or sexual IPV and psychological IPV alone in women.A population-based cohort study of women aged 30-60 years was performed using cross-sectional data and clinical measurements from the Oslo Health Study (2000-2001) linked with prospective prescription records from the Norwegian Prescription Database (January 1, 2004 to December 31, 2009). We used age-standardized chi-square analyses to compare clinical characteristics by IPV cross-sectionally, and Cox proportional hazards regression to examine cardiovascular drug prescription prospectively.Our study included 5593 women without cardiovascular disease or drug use at baseline. Altogether 751 (13.4%) women disclosed IPV experiences: 415 (7.4%) physical and/or sexual IPV and 336 (6.0 %) psychological IPV alone. Cross-sectional analyses showed that women who reported physical and/or sexual IPV and psychological IPV alone were more often smokers compared with women who reported no IPV. Physical and/or sexual violence was associated with abdominal obesity, low high-density lipoprotein cholesterol, and elevated triglycerides. The prospective analysis showed that women who reported physical and/or sexual IPV were more likely to receive antihypertensive medication: incidence rate ratios adjusted for age were 1.27 (95% confidence interval 1.02-1.58) and 1.36 (CI 1.09-1.70) after additional adjustment for education and systolic and diastolic blood pressure, respectively. No significant differences were found for cardiovascular drugs overall or lipid modifying drugs.Our findings indicate that clinicians should assess the cardiovascular risk of women with a history of physical and/or sexual IPV, and consider including CVD prevention measures as part of their follow-up.

Context and objectives Peak bone mass (PBM) is regarded as the most important determinant of osteoporosis. Growing evidence suggests a role of intrauterine programming in skeletal development. We examined PBM and trabecular bone score (TBS) in adults born preterm with very low birth weight (VLBW) or small for gestational age (SGA) at term compared with term-born controls. Design, setting, participants, and outcomes This follow-up cohort study included 186 men and women (25 to 28 years); 52 preterm VLBW (≤1500 g), 59 term-born SGA ( 10th percentile). Main outcome was bone mineral density (BMD) by dual x-ray absorptiometry. Secondary outcomes were bone mineral content (BMC), TBS, and serum bone markers. Results VLBW adults had lower BMC and BMD vs controls, also when adjusted for height, weight, and potential confounders, with the following BMD Z-score differences: femoral neck, 0.6 standard deviation (SD) (P = 0.003); total hip, 0.4 SD (P = 0.01); whole body, 0.5 SD (P = 0.007); and lumbar spine, 0.3 SD (P = 0.213). The SGA group displayed lower spine BMC and whole-body BMD Z-scores, but not after adjustment. Adjusted odds ratios for osteopenia/osteoporosis were 2.4 and 2.0 in VLBW and SGA adults, respectively. TBS did not differ between groups, but it was lower in men than in women. Serum Dickkopf-1 was higher in VLBW subjects vs controls; however, it was not significant after adjustment for multiple comparisons. Conclusions Both low-birth-weight groups displayed lower PBM and higher frequency of osteopenia/osteoporosis, implying increased future fracture risk. The most pronounced bone deficit was seen in VLBW adults.

Human in utero growth restriction (IUGR) is associated with an increased risk for perinatal mortality and morbidity among newborns and infants. To pursue this challenge, a Request For Proposals (RFP) was issued in 1983 by The U.S. Epidemiology and Biometry Research Program at the National Institute of Child Health and Human Development (NICHD). A consortium was set up at the universities and university hospitals in Trondheim, Bergen (Norway) and Uppsala (Sweden) and was funded by the NICHD to conduct the Scandinavian Successive Small-for-Gestational Age (SGA) pregnancy and birth outcome study. The study design included a comprehensive biobank with maternal and cord serum samples, placental tissue, and a multitude of data collected from interviews, questionnaires, and clinical examinations. The SGA cohort study involved 6,354 Caucasian pregnant women in the three study sites who expected their second or third child from 1986-88. The study women were screened in early second trimester and mothers who had an increased risk to deliver a smaller than expected newborn were followed in detail through the second half of pregnancy and at birth. Selected children were screened several times through their first and up to five years of age. Moreover, a highly selected subgroup in Trondheim has been followed at 14, 19, and 26 years’ age. Almost thirty years later, we have searched the body of scientific publications that originated from this cohort study in an attempt to assess if and to what extent the main aims and objectives were achieved and to summarize the overall outcomes. The SGA cohort has resulted in close to 100 published papers in peer reviewed journals and some 40 graduate and undergraduate degrees. Risk factors of SGA, like maternal smoking, low prepregnancy weight and education attainment, and a previous SGA birth outcome were confirmed. Conversely, no totally new and unknown risk factors were identified. Serial ultrasound measures have enabled a distinction between SGA with restricted and normal intrauterine growth, and has further indicated that being born SGA is mainly a problem in combination with IUGR. Further, the consequences of IUGR are more pronounced at adolescence and young adulthood than at five years of age. An increased understanding of the pathogenesis of different categories of growth restriction is essential to recognize and diagnose IUGR properly, and to reduce the perinatal mortality and morbidity from SGA. Moreover, SGA is a significant predictor at follow-up of the child. An up to date biobank has ensured the quality of data and biological samples, and has been crucial for the outcome of the entire SGA study. It continues to be a valuable resource in future research. Copyright (c) 2016 Eli Kjøbli, Ragnhild Bach, Haakon Skogseth, Geir W. Jacobsen. This work is licensed under a Creative Commons Attribution 4.0 International License.

Original version at 10.1371/journal.pone.0166127 Copyright: © 2016 Lauritzen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Perfluoroalkyl substances (PFASs) and organochlorines (OCs) are ubiquitous and persistent in the environment and proposed endocrine disrupting chemicals (EDCs). They can be transferred across the placenta during pregnancy, and studies suggest that the prenatal period may be particularly sensitive for influences on fetal growth and development. Several studies have investigated socio-demographic and pregnancy related factors associated with maternal serum PFAS and OC levels, but few studies have been conducted in time periods with increasing emissions of PFASs and recent emissions of OCs. Methods Serum from 424 pregnant women participating in the NICHD Scandinavian Successive Small-for-gestational Age (SGA) births study was collected in 1986–1988, and analyses of two PFASs and six OCs were conducted. Associations between EDCs and geographic, time dependent, socio-demographic and pregnancy related variables were evaluated by using multivariable linear regression models. Results Previous breastfeeding duration, time since last breastfeeding period, sampling date and country of residence were important factors associated with serum levels of PFOS and PFOA. Smoking status and pre-pregnancy BMI were negatively associated with PFOS, and maternal height was borderline negatively associated with PFOS and PFOA. Glomerular filtration rate (GFR) was negatively associated with PFOS in a sub-sample. Maternal serum levels of OCs were positively associated with maternal age, and negatively associated with previous breastfeeding duration and sampling date. Smoking had a consistently negative association with PCB 118 in a dose-dependent manner. Education level, pre-pregnancy BMI and alcohol consumption varied in importance according to the compound under study. Conclusions Several maternal factors, including potentially modifiable factors, markers of pregnancy physiology and factors also related to perinatal outcomes were associated with EDC levels. Results from this study are relevant to populations with still high PFAS and OC levels, i.e. developing countries. Moreover, we can use this knowledge about associated factors on emerging EDCs with similar properties.

Background Small birth size may be associated with increased risk of cardiovascular diseases (CVD), whereas large birth size may predict increased risk of obesity and some cancers. The net effect of birth size on long-term mortality has only been assessed in individual studies, with conflicting results. Methods The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines for conducting and reporting meta-analysis of observational studies were followed. We retrieved 22 studies that assessed the association between birthweight and adult mortality from all causes, CVD or cancer. The studies were systematically reviewed and those reporting hazard ratios (HRs) and 95% confidence intervals (95% CIs) per kilogram (kg) increase in birthweight were included in generic inverse variance meta-analyses. Results For all-cause mortality, 36 834 deaths were included and the results showed a 6% lower risk (adjusted HR = 0.94, 95% CI: 0.92-0.97) per kg higher birthweight for men and women combined. For cardiovascular mortality, the corresponding inverse association was stronger (HR = 0.88, 95% CI: 0.85-0.91). For cancer mortality, HR per kg higher birthweight was 1.13 (95% CI: 1.07-1.19) for men and 1.04 (95% CI: 0.98-1.10) for women (P(interaction) = 0.03). Residual confounding could not be eliminated, but is unlikely to account for the main findings. Conclusion These results show an inverse but moderate association of birthweight with adult mortality from all-causes and a stronger inverse association with cardiovascular mortality. For men, higher birthweight was strongly associated with increased risk of cancer deaths. The findings suggest that birthweight can be a useful indicator of processes that influence long-term health

At the beginning of the 1800 s neonatal tetanus was a major health hazard on the Westman Islands, an archipelago immediately south of Iceland. Up to 60–70% of newborn babies died in the course of the first two weeks of life, and Danish health authorities were almost helpless in the face of this mysterious disease. In 1847 the young Danish doctor Peter Anton Schleisner (1818-1900) was sent to the islands to investigate the conditions there. He established a maternity hospital, gave advice on hygiene and encouraged breast-feeding and a number of changes in diet. Since there was no known treatment, Schleisner's only option was to resort to preventive measures. He dressed the umbilical stump with balsamum copaivae and tried well-established methods such as opium tincture with saffron and mercurial ointment if there was any sign of infection. By the time he returned to Denmark after nine months, mortality had been halved. Neonatal mortality on the Westman Islands remained at the same low level throughout the rest of the 19th century. According to popular belief this was due to the naflaolian (navel oil) which Schleisner introduced. Nevertheless, it can be partly attributed to generally improved living standards, a relatively higher number of mothers in better social circumstances, a greater urban influence, changed lifestyle and hygienic measures. Schleisner's efforts are considered to have had major significance when conditions are compared with those on the Scottish island of St Kilda where the situation was the same and improved only just before the turn of the century.

Aims: To investigate psychotropic drug use among women ever exposed to intimate partner violence (IPV) in relation to mental distress and sociodemographic, lifestyle and somatic health characteristics, and to assess whether drug use differed for physical and/or sexual violence compared with psychological abuse alone. Methods: Cross-sectional data from women aged 30—60 years were drawn from self-reported questionnaires in the Oslo Health study 2000—2001. Women reporting hypnotic, anxiolytic and/or antidepressant drug use in the previous four weeks were defined as users. Differences in psychotropic drug use by IPV exposure were examined by logistic regression analyses. Results: In total, 880 (14%) of 6,471 included women reported ever experiencing IPV; 494 (8%) reported physical and/or sexual IPV, and 386 (6%) reported psychological IPV alone. Physical and/or sexual IPV was significantly associated with use of all psychotropic drugs: hypnotics (odds ratio (OR) 2.28; 95% confidence interval (95% CI), 1.73—3.00); anxiolytics (OR 3.29; 95% CI, 2.43—4.44); and antidepressants (OR 2.72; 95% CI, 1.97—3.76). The associations remained significant for anxiolytics (OR 1.67; 95% CI, 1.14—2.45) and antidepressants (OR 1.50; 95% CI, 1.02—2.19) after adjusting for mental distress, sociodemographic, lifestyle and somatic health characteristics. Psychological IPV alone was associated with use of anxiolytics (OR 1.81; 95% CI, 1.20—2.75) and antidepressants (OR 2.38; 95% CI, 1.64—3.45). After adjustments the association persisted for use of antidepressants only (OR 1.64; 95% CI, 1.05—2.55). Conclusions: Women exposed to IPV were more likely to report use of psychotropic drugs, even after adjusting for mental distress. The study indicates that exposure to IPV; including psychological abuse should be evaluated as a possible source of distress when psychotropic drug treatment is considered.

Summary Hutcheon JA, Egeland GM, Morin L, Meltzer SJ, Jacobsen G, Platt RW. The predictive ability of conditional fetal growth percentiles. Paediatric and Perinatal Epidemiology 2010; 24: 131–139. Conditional fetal growth percentiles are percentiles that are calculated taking into account (conditional on) an infant's weight earlier in pregnancy. Although they have been proposed in the statistical literature as a more methodologically appropriate method of measuring fetal growth, their ability to predict adverse perinatal outcomes due to fetal growth restriction is unknown. Using a large, unselected clinical ultrasound database at the Royal Victoria Hospital in Montreal, Canada, we calculated conditional growth percentiles for infants' weight at birth, given their weight at the time of a routine 32- or 33-week ultrasound. The risk of adverse perinatal outcome (perinatal mortality, low Apgar, acidaemia, or seizures/organ failure due to asphyxia) among small-for-gestational-age infants (SGA) as established by conditional growth percentiles was calculated as well as the risk among infants classified as SGA by conventional weight-for-gestational-age percentiles. Regardless of the threshold used to define SGA (fifth, 10th, 15th, 20th), conditional percentiles did not appear to improve the identification of adverse perinatal outcomes compared with conventional weight-for-gestational-age charts. Further work is needed to confirm our results as well as to explore potential reasons for the lack of benefits from using a measure of growth instead of size to identify fetal growth restriction.

Breastfeeding depends on endocrine changes during pregnancy. The association between gestational hormones and lactation has been sparsely investigated. Previously, androgens were used for lactation inhibition. We investigated a possible association between second trimester maternal androgen levels and breastfeeding.Prospective observational study.University hospital setting. POPULATION. Women from a random sample of pregnancies (n = 63) and from a group with an increased risk for giving birth to a small-for-gestational age newborn (n = 118) were included. All participants had singleton pregnancies and one or two previous births.Maternal androgen levels were measured in gestational week 25. The association with reported breastfeeding was explored by univariate and multivariate linear regression analyses. Analyses were adjusted for factors known to be associated with breastfeeding.Breastfeeding at six weeks, three months, and six months postpartum.In the random group, breastfeeding at three and six months was negatively associated with maternal testosterone, androstendione, and free testosterone index levels. After correction for maternal age, education and smoking, breastfeeding at both three and six months was negatively associated with the free testosterone index. In the group of women with an increased risk for giving birth to a small-for-gestational age newborn, breastfeeding at six weeks and three months was associated negatively with maternal dehydroepiandrosterone and this association persisted after correction for maternal age, education, and smoking.Maternal androgen levels in mid-pregnancy are negatively associated with breastfeeding.

To evaluate the diagnostic usefulness of temporal artery biopsy in the diagnosis of giant cell arteritis, the clinical records of 98 patients who underwent this procedure between 1984 and 1992 were reviewed. The biopsies were positive for giant cell arteritis in 13 (13%) cases. In addition, 9 patients with negative biopsy were considered to have giant cell arteritis based on clinical examination, while 76 patients had other diagnoses. About 90% of the patients with giant cell arteritis were women. Evaluating the clinical features and laboratory findings, a history of headache, a combination of headache and the erythrocyte sedimentation rate > 40 mm/h and a combination of headache and temporal tenderness were significantly more common among patients with positive diagnosis than among the other patients.

We investigated, in new hearing aid candidates, whether or not the use of coping strategies and the life situation, in terms of activity limitation, participation restriction and psychological well-being, were associated with the outcome of audiological counselling, i.e. the patients’ acceptance or rejection of a hearing aid (HA). The study included 173 consecutive adult patients (104 men and 69 women) with a need for audiological rehabilitation including HA-fitting. Use of communication strategies (Communication Strategies Scale, CSS), experience of activity limitation and participation restriction (Hearing Disability and Handicap Scale, HDHS), and general psychological well-being (Psychological General Well-being scale, PGWB) were assessed by self-report inventories. The hospital records, reviewed 1.5 years after the first consultation, showed that 39 patients (25 men and 14 women, 23%) had not accepted a hearing aid. In crude and adjusted logistic regression analyses a low report (high scores) of malad...

We explored whether or not perceived health, subjective well-being, everyday life consequences of hearing loss, and/or use of communication strategies in experienced hearing aid users were associated with the outcome of renewed counselling, i.e. a prescription of a new hearing aid(s) (HA(s))or keeping the existing HA(s). The study included 170 subjects (84 men and 86 women) who had previously undergone HA fitting and audiological rehabilitation and at study entry had indications for a renewed rehabilitation and HA prescription. Self-report inventories assessed general health, well-being, activity limitation, participation restriction, and use of communication strategies. The outcome was studied by logistic regression. Review of medical records 18 months after the renewed counselling showed that 147 (86.5%) subjects had been fitted with new hearing aids. Gender, duration of hearing loss and previous use of one versus two aids influenced the outcome under study. Reported high degree of activity limitation a...

The relationship between the reported use of coping strategies and experience of everyday life prior to audiological rehabilitation and the number of rehabilitation consultations needed, were studied in a group of adults. The study took place at St. Olav's University Hospital, Norway and included 132 adult patients (77 men and 55 women) with no previous audiological rehabilitation or experience with hearing aid (HA) use. Hearing impairment was assessed by pure tone audiometry, while use of communication specific coping strategies and daily life situations were obtained using self-report inventories. The latter concerned activity limitation, participation restriction, and psychological well-being. The patients’ hospital records were reviewed approximately 18 months after their first consultation. In total, 41 patients (31%) needed no more than the required minimum number of three consultations to complete rehabilitation including HA fitting, while 91 patients needed more than this. Logistic regression was ...

Objective. To compare the profiles of people visiting only a general practitioner (GP), those visiting only a practitioner of complementary and alternative medicine (CAM), and those visiting both (GP&CAM). Design. A comparative total population health survey in central Norway (HUNT 2). Subjects. A total of 54 448 persons 20 years of age and over who answered questions about their use of health services during the previous 12 months. Variables. Sociodemographic characteristics, self-perceived health, subjective health complaints, and a variety of common diseases. Results. Some 34 854 (64.0%) of those who answered the health service use question had visited only a GP, 837 (1.5%) only a CAM practitioner, and 4563 (8.4%) both during the last 12 months. The likelihood of being a CAM-only user as compared to a GP-only user was significantly increased (p < 0.005) if the participant was male; aged between 30 and 69; and without cardiovascular disease. The likelihood of being a GP&CAM user compared with a GP-only user was significantly increased (p < 0.005) for those who were female; aged between 30-59; had a higher education level; were non-smokers; had lower perceived global health; had a limiting chronic complaint; had experienced a health complaint during the last 12 months; had musculoskeletal disease; had a psychiatric complaint; and had hay fever. Conclusion. There were few CAM-only users and they differ from GP-only users by being male, aged 30-69, and without cardiovascular disease. Users of both GP&CAM were less healthy with more complaints and poorer self-reported health than GP- and CAM-only users. © 2007 Taylor & Francis.

The consequences of hearing loss in terms of perceived activity limitation and participation restriction were studied in a general population of 343 adults with hearing impairment using the Hearing Disability and Handicap Scale. Coping was measured by the Sense of Humour Questionnaire and the Communication Strategies Scale and combined with objective and subjective audiological variables and demographic factors (age, gender and education). In stepwise linear modelling, several variables contributed significantly to the outcome (adjusted R2=53.3% for activity limitation and 47.2% for participation restriction). Audiological factors explained most of the variance in activity limitation (R2=37.1%), while coping factors were the main predictors for participation restriction (R2=35.2%). Maladaptive behaviour in the Communication Strategies Scale was the strongest predictor and explained 13.7% and 32.4% of the variance in activity limitation and participation restriction, respectively. More frequent use of maladaptive behaviour was related to larger limitation and restriction. This study adds to the understanding of factors that negatively influence daily life in terms of activity limitation and participation restriction. This may in turn have consequences for aural rehabilitation efforts.

We first aimed to describe demographic and audiological characteristics of adults referred to a university hospital for hearing aid (HA) fitting and rehabilitation. Our second aim was to employ an inventory that assesses life consequences of hearing impairment (HI) in terms of perceived activity limitation and participation restriction for the first time in a Norwegian adult outpatient population. A third aim was to study life consequences by audiological and demographic characteristics.During one year consecutive patients (n = 343) were requested to answer the Hearing Disability and Handicap Scale (HDHS) assessing activity limitation and participation restriction in relation to an audiological examination and medical consultation. The mean threshold of hearing (MTH) was ascertained by pure tone thresholds at 0.5 - 1 - 2 - 4 kHz in the better ear.Activity limitation and participation restriction were both higher for HA experienced than HA naïve subjects ( p0.01). In a multivariable model, the explained adjusted variance of activity limitation (R2) was 43.4% with MTH, perceived duration, and severity of hearing problems as predictor variables. Correspondingly, the explained adjusted variance of participation restriction was 28.4% for a model with MTH, age, gender and perceived severity of hearing problems as predictors.As a standard supplement to audiometric tests, HDHS may be successfully applied as a clinical tool among similar hearing impaired outpatients in order to assess activity limitation and participation restriction as part of audiological rehabilitation.

To study psychological well-being (health-related quality of life) in a population of adults 20 years and over with hearing impairment (HI) and its relation to audiological factors, consequences of the HI, sense of humour, and use of communication strategies.Consecutive adults (n = 343) at the outpatient Unit of Audiology of a Norwegian university hospital answered the Psychological General Well-being inventory (PGWB), Hearing Disability and Handicap Scale (HDHS), Sense of Humour Questionnaire-6 (SHQ-6), and Communication Strategies Scale (CSS) in relation to an audiological examination and medical consultation.Mean PGWB index for the whole sample was 81.4 (SD 14.3) and females reported a significantly lower psychological well-being. In multiple linear regression analyses well-being was negatively associated with high levels of activity limitation and participation restriction. PGWB index was positively associated with high sense of humour, but was neither explained by audiological factors nor use of communication strategies.Psychological well-being was associated with the outcome of a standard HI assessment of activity limitation and participation restriction, but not with degree of HI and use of communication strategies.

Aim. To investigate whether maternal caffeine consumption is associated with increased maternal homocysteine (Hcy) levels in uncomplicated pregnancies.Methods. Ninety-two pregnant women were randomly selected, and maternal serum levels of folate, vitamin B12, and Hcy at gestational weeks 17 and 33 were measured. Caffeine consumption was estimated from dietary records collected at the same gestational ages.Results. In women who smoked, Hcy levels were associated with caffeine consumption both in gestational weeks 17 and 33 and with folate at week 33. Consumption of one cup of coffee was associated with an increase in maternal Hcy of 0.26 mmol/l at week 17 and 0.69 mmol/l at week 33, indicating that one extra cup (150 ml) of coffee per day may increase Hcy by 5–10% in pregnant smokers. In non-smokers, caffeine consumption was not associated with Hcy levels.Conclusions. In uncomplicated pregnancies, maternal caffeine consumption early in the second and in the third trimester is associated with increased mate...

Objective. To explore the hypothesis that maternal androgen levels are elevated before the onset of preeclampsia.Methods. Acase-control study in three university hospitals inNorway and Sweden included 29 women with mild preeclampsia and 142 controls. Maternal levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone and sex hormone binding globulin (SHBG) were measured, and the free testosterone index (FTI) was calculated in weeks 17 and 33 of gestation.Results. Androstenedione, testosterone and FTI were elevated in gestationalweeks 17 and 33 in women who eventually developed preeclampsia, while DHEAS was elevated at week 17 only. At week 17 elevated testosterone and FTI were seen in women bearing both male and female fetuses. At week 33 elevated levels of androstenedione, testosterone and FTI was seen in women with male fetuses only. Comparing the lower tertile with the upper tertile of FTI at week 17 of gestation gave an odds ratio (OR) for preeclampsia of 3.7 [95% confidence inter...

Background. The objective of the present study was to investigate the hypothesis that maternal androgen levels associate with nausea and vomiting in otherwise uncomplicated pregnancies. Methods. One hundred and twenty-nine women with uncomplicated pregnancies, reported nausea and vomiting in weeks 17, 25, 33, 37, and when admitted for delivery. Maternal levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin (SHBG) were measured and the free testosterone index calculated in weeks 17 and 33 of pregnancy. Results. Maternal levels of androstenedione and DHEAS associated positively with nausea and vomiting in week 17. In week 33, testosterone and DHEAS associated positively with nausea and vomiting, as well as androstenedione. A calculated emesis score associated positively with increasing average levels of both androstenedione and testosterone during pregnancy, as well as the free testosterone index. Conclusions. Nausea and vomiting associate with inc...

Summary It has been hypothesised that oestrogen exposure in utero influences the risk for breast cancer in adult life. Although several studies report associations between breast cancer and maternal factors associated with birthweight of the offspring – a marker for antenatal oestriol exposure – little is known about the relations between maternal oestrogen levels and these factors per se. We therefore analysed the association between oestriol levels in 188 women in the 17th, 25th, 33rd and 37th weeks of pregnancy, and maternal age, prepregnancy weight, height and pregnancy weight gain. Both maternal prepregnancy body mass index and maternal height were, after controlling for infant birthweight, independently and inversely associated with oestriol levels (P = 0.0021 and P = 0.0006 respectively). We found no association between maternal age or pregnancy weight gain and pregnancy oestriol levels. These findings suggest that the previously reported associations between maternal age and maternal pregnancy weight gain and the offspring’s risk of breast cancer are due to factors other than antenatal exposure to oestriol.

To describe lower urinary tract symptoms, prostate volume and peak urinary flow rate, and investigate the relationships among urological variables in a community sample of Norwegian men.A cross-sectional study of 611 men, aged 55-70 years, who underwent a clinical urological examination including uroflowmetry, residual urine measurement, and transrectal ultrasonography of the prostate. All the men completed a questionnaire which included the International Prostate Symptom Score (IPSS).Severe symptoms were reported by 5%, while 23.6% reported moderate symptoms, and the overall median IPSS was 4 (q1 = 25th percentile, 1; q3 = 75th percentile, 9). The median peak flow rate was 15 ml/s (q1 = 11; q2 = 22) while median prostate volume was 30 cm(3) (q1 = 23; q3 = 38), with little variation evident across the narrow age range of 55-70 years. A positive modest correlation (r = 0.176) was found between IPSS and prostate volume, and a negative correlation between IPSS and peak flow rate (r = -0.278). There was a modest correlation between body mass index (BMI) and prostate size, but no significant correlation between BMI and IPSS.In this population-based study, moderate lower urinary tract symptoms were reported by 24% and severe symptoms by 5% of community men. The distribution of lower urinary tract symptoms, prostate volume and peak urinary flow rate in Norwegian men is comparable to that described in similar studies conducted in Spain, Holland and USA.