Anxiety and depression in pregnant women who have experienced a previous perinatal loss: a case-cohort study from Scandinavia.

BACKGROUND: Perinatal loss can have long-lasting adverse effects on a woman's psychosocial health, including during subsequent pregnancies. However, maternal mental health status after perinatal loss during subsequent pregnancy is understudied with very little data available for Scandinavian populations. AIMS: The primary aim of the study was to explore the association between previous perinatal loss and anxiety/depression symptoms of expectant mothers during the subsequent pregnancy. The secondary aim of this study was to explore possible determinants of maternal mental health during the subsequent pregnancy, independent of previous perinatal loss. METHOD: This case-cohort study is based on primary data from Scandinavian Successive Small-for-Gestational Age Births Study (SGA Study) in Norway and Sweden. The total case-cohort sample in the current study includes 1458 women. Cases include 401 women who had reported a previous perinatal loss (spontaneous abortion, stillbirth, or neonatal death) and who responded to two mental health assessment instruments, the State-Trait Anxiety Inventory (STAI), and the Centre for Epidemiological Studies Depression (CES-D) scale. Multiple linear regression models were used to assess the association between previous perinatal loss and maternal mental health in subsequent pregnancy. RESULTS: Scandinavian pregnant women with previous perinatal loss reported higher symptoms for both anxiety and depression during their subsequent pregnancy compared to mothers in the same cohort reported no previous perinatal loss. Multiple linear regression analyses showed a positive association between previous perinatal loss and per unit increase in both total anxiety score (ß: 1.22, 95% CI: 0.49-1.95) and total depression score (ß: 0.90, 95% CI: 0.06-1.74). We identified several factors associated with maternal mental health during pregnancy independent of perinatal loss, including unintended pregnancy despite 97% of our population being married/cohabitating. CONCLUSION: Women who have experienced previous perinatal loss face a significantly higher risk of anxiety and depression symptoms in their subsequent pregnancy.

In utero exposure to endocrine disrupting chemicals, micro-RNA profiles, and fetal growth: a pilot study protocol.

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<10th percentile for gestational age). We have randomly selected 12 mothers (3 high-risk SGA birth, 3 low-risk SGA birth, 3 high-risk non-SGA birth, 3 low-risk non-SGA birth), with EDC measurements from gestational week 17. All offspring are female. We aim to test the stability of our samples (maternal serum, cord blood, placenta tissue), observe the differential expression of miRNA profiles over time (gestational weeks 17, 25, 33, 37, birth), and study the consistency between maternal EDC measures and miRNA expression profiles across our repeated measures. Expected impact of the study for Public Health: Results from this pilot study will inform the development of a larger cohort wide analysis, and will impact the current state of knowledge in the fields of public health, epigenetics, and the DOHaD.

Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up.

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 <30 and >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.

Short interpregnancy interval and poor fetal growth: Evaluating the role of pregnancy intention.

BACKGROUND: Previous studies have demonstrated that short interpregnancy interval (the interval between delivery and estimated last menstrual period of a subsequent pregnancy) is associated with small for gestational age birth. It is controversial if this association is causal, as few studies have accounted for likely confounding factors such as unintended pregnancy. We examined the association between interpregnancy interval and infant birthweight, adjusting for pregnancy intention and other socio-economic and obstetrical risk factors. METHODS: We used data from the Scandinavian Successive Small-for-Gestational-Age births study (1986-1988). Birthweight was expressed as a gestational age-standardised z-score. RESULTS: Among 1406 women, a trend towards lower birthweight z-score with short interpregnancy interval was not statistically significant (unadjusted difference in birthweight z-score of -0.25, 95% confidence interval (CI) -0.55, 0.05). After adjusting for pregnancy intention, detailed measures of socio-economic status, and other covariates, the estimated magnitude of effect between interpregnancy interval and birthweight z-score was further attenuated (adjusted difference in birthweight z-score of -0.13, 95% CI -0.46, 0.20). CONCLUSIONS: In this cohort study with detailed information on pregnancy intention and socio-economic status, short interpregnancy interval was not associated with lower birthweight. These findings suggest that previously observed associations between short interpregnancy interval and lower birthweight may reflect confounding by socio-economic and/or other unmeasured confounders.

Springboard to an academic career-A national medical student research program.

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<0.001). Moreover, almost twice as many MSRP physicians reported an academic aspiration (49% vs 22%, p<0.001). Results suggested that an MSRP-like approach could efficiently address the unmet recruitment gap and strengthen the medical disciplines in medical research.

Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysis.

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.

The Use of Manual Vacuum Aspiration in the Treatment of Incomplete Abortions: A Descriptive Study from Three Public Hospitals in Malawi.

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.

Prenatal exposure to persistent organic pollutants and child overweight/obesity at 5-year follow-up: a prospective cohort study.

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 (ß = 0.18, 95% CI: 0.01-0.35), and increased triceps skinfold z-score (ß = 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.

Peak Bone Mass and Bone Microarchitecture in Adults Born With Low Birth Weight Preterm or at Term: A Cohort Study.

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), and 75 controls (>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.

A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study.

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.

Factors Associated with Maternal Serum Levels of Perfluoroalkyl Substances and Organochlorines: A Descriptive Study of Parous Women in Norway and Sweden.

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.

Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth?

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 (ß = 0.24 (95% confidence interval (CI): 0.18, 0.31), ß = 0.16 (95% CI: 0.09, 0.23), ß = 0.08 (95% CI: 0.01, 0.16), and ß = 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.

Folic acid supplementation in early pregnancy and the risk of preeclampsia, small for gestational age offspring and preterm delivery.

OBJECTIVE: To assess whether folic acid intake during the first trimester of pregnancy is related to pregnancy outcomes preeclampsia, low birth weight or preterm birth. STUDY DESIGN: 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. RESULTS: 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 (BMI<25) 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. CONCLUSION: 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.

Decrease in use of manual vacuum aspiration in postabortion care in Malawi: a cross-sectional study from three public hospitals, 2008-2012.

OBJECTIVES: To investigate the use of manual vacuum aspiration in postabortion care in Malawi between 2008-2012. METHODS: A retrospective cross-sectional study was done at the referral hospital Queen Elisabeth Central Hospital, and the two district hospitals of Chiradzulu and Mangochi. The data were collected simultaneously at the three sites from Feb-March 2013. All records available for women admitted to the gynaecological ward from 2008-2012 were reviewed. Women who had undergone surgical uterine evacuation after incomplete abortion were included and the use of manual vacuum aspiration versus sharp curettage was analysed. RESULTS: Altogether, 5121 women were included. One third (34.2%) of first trimester abortions were treated with manual vacuum aspiration, while all others were treated with sharp curettage. There were significant differences between the hospitals and between years. Overall there was an increase in the use of manual vacuum aspiration from 2008 (19.7%) to 2009 (31.0%), with a rapid decline after 2010 (28.5%) ending at only 4.9% in 2012. Conversely there was an increase in use of sharp curettage in all hospitals from 2010 to 2012. CONCLUSION: Use of manual vacuum aspiration as part of the postabortion care in Malawi is rather low, and decreased from 2010 to 2012, while the use of sharp curettage became more frequent. This is in contrast with current international guidelines.