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.

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.

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.

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.

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.

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.

Neuropsychological deficits in young adults born small-for-gestational age (SGA) at term.

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 <10th centile) born at term, and 81 term non-SGA controls (birth weight ≥10th centile). The SGA group obtained significantly (p < .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below -1.5 SD on 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.

Association between low blood glucose increase during glucose tolerance tests in pregnancy and impaired fetal growth.

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.

Small for gestational age and intrauterine growth restriction decreases cognitive function in young adults.

OBJECTIVE: To examine the effect on adult cognitive function of being born small for gestational age (SGA), and to evaluate whether cognitive function is related to intrauterine growth restriction (IUGR). STUDY DESIGN: Fifty-nine SGA subjects (birth weight <10th percentile) and 81 controls (birth weight ≥10th percentile) born at term underwent cognitive assessment with the Wechsler Adult Intelligence Scale-Third Edition at age 19-20 years. Repeated ultrasound measures of fetal growth were available for weeks 25, 33, and 37 in a subgroup of 29 SGA subjects and 75 control subjects, and these were data used to dichotomize the 29 SGA subjects into those with IUGR and those without IUGR. IUGR was defined as growth deviating more than -2 SD from the mean value of the control group. The effect of maternal smoking during pregnancy was considered as well. Group differences were analyzed using a general linear model, controlling for sex and socioeconomic status. RESULTS: The SGA group had lower full IQ scores than the control group (mean difference, -6.3; 95% CI, -2.8 to -9.7; P = .001), including lower scores on 6 of the Wechsler Adult Intelligence Scale-Third Edition subtests. In the SGA subgroup with repeated ultrasound measures, 6 of 29 subjects (21%) had IUGR, and these subjects also had a lower IQ compared with controls (mean difference, -14.0; 95% CI: -4.8 to -23.3; P = .003). Maternal smoking during pregnancy was related to lower IQ in the control group but not in the SGA group, independent of IUGR or non-IUGR status. CONCLUSION: IQ scores were lower in young adults born SGA compared with controls. Our analysis suggest that this outcome is related to IUGR.

Folic acid supplementation in early pregnancy and asthma in children aged 6 years.

OBJECTIVE: The objective of the study was to assess whether folic acid intake during the first trimester of pregnancy is related to asthma in the offspring by the age of 6 years. STUDY DESIGN: This was a prospective cohort study of 1499 women who were followed up from the first trimester of pregnancy. Their children were followed up until they were 6 years old. RESULTS: Fifty-one percent of the women used folic acid in the month before conception and 88% in the third month of pregnancy. The adjusted odds ratio for asthma per 100 µm increase in the average daily intake of folic acid was 0.98 (95% confidence interval, 0.93-1.04). For categories of daily folate intake, there was no evidence of associations with childhood asthma or evidence of any dose response relation for any time period (all P(trend) > .05). CONCLUSION: Our results do not support any association of folic acid supplementation in pregnancy and asthma risk in offspring by age 6 years.

Being born small for gestational age reduces white matter integrity in adulthood: a prospective cohort study.

BACKGROUND: Being born small for gestational age (SGA) (birth weight <10th percentile) is connected to decreased white matter (WM) integrity in newborns and increased prevalence of psychiatric symptoms in adulthood. The aims of this study were to investigate whether being born SGA at term affects WM integrity in young adulthood and to explore possible relationships between fractional anisotropy (FA) and pre- and perinatal factors and cognitive and psychiatric outcomes in adulthood in SGA and controls. METHODS: Diffusion tensor imaging and tract-based spatial statistics were conducted to test for voxelwise differences in FA in SGAs (n = 46) and controls (n = 57) at 18-22 y. RESULTS: As compared with controls SGAs had reduced FA in ventral association tracts and internal/external capsules. In the SGAs, no relationship was found between FA and intrauterine head growth in the third trimester, although total intelligence quotient was negatively correlated to FA. In controls, a positive correlation was found between FA and brain growth in the third trimester and maternal smoking. No relationship was found between FA and psychiatric measures in SGAs or controls. CONCLUSION: These results demonstrate that being born SGA leads to reduced WM integrity in adulthood, and suggest that different factors modulate the development of WM in SGA and control groups.

Maternal recall of breastfeeding duration twenty years after delivery.

BACKGROUND: Studies on the health benefits from breastfeeding often rely on maternal recall of breastfeeding. Although short-term maternal recall has been found to be quite accurate, less is known about long-term accuracy. The objective of this study was to assess the accuracy of long-term maternal recall of breastfeeding duration. METHODS: In a prospective study of pregnancy and birth outcome, detailed information on breastfeeding during the child's first year of life was collected from a cohort of Norwegian women who gave birth in 1986-88. Among 374 of the participants, data on breastfeeding initiation and duration were compared to recalled data obtained from mailed questionnaires some 20 years later. Intraclass correlation coefficient (ICC), Bland-Altman plot, and Kappa statistics were used to assess the agreement between the two sources of data. Logistic regression was used to assess predictors of misreporting breastfeeding duration by more than one month. RESULTS: Recorded and recalled breastfeeding duration were strongly correlated (ICC=0.82, p < 0.001). Nearly two thirds of women recalled their breastfeeding to within one month. Recall data showed a modest median overestimation of about 2 weeks. There were no apparent systematic discrepancies between the two sources of information, but recall error was predicted by the age when infants were introduced to another kind of milk. Across categories of breastfeeding, the overall weighted Kappa statistic showed an almost perfect agreement (κ = 0.85, 95% confidence interval [CI] 0.82 - 0.88). CONCLUSION: Breastfeeding duration was recalled quite accurately 20 years after mothers gave birth in a population where breastfeeding is common and its duration long.

"No doubt this childhood disease on Vestmannö can be prevented"--neonatal tetanus on the Westman Islands.

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 60­70% 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.

Screening and treatment of latent tuberculosis in a cohort of asylum seekers in Norway.

AIMS: Asylum seekers are screened for tuberculosis at entry to Norway. We aimed to assess follow-up of screening results at different healthcare levels in relation to demographics, screening results and organizational factors, and how this influenced treatment of latent tuberculosis. METHODS: All asylum seekers >or=18 years with a Mantoux test >or=6 mm or positive x-ray findings who arrived at the National Reception Centre from January 2005 to June 2006, were included. Data were collected from public health authorities in the municipality where the asylum seekers had moved, and from internists in case they had been referred to a specialist. Specialists are responsible for treating latent tuberculosis. Individual subjects were matched with the National Tuberculosis Register to which everybody who had started treatment for latent tuberculosis was reported. RESULTS: Of 4,643 asylum seekers, 2,237 fulfilled the inclusion criteria. By May 2008, 30 persons had started treatment for latent TB, a median of 17 months (range 3-36) after arrival. A Mantoux test >or=15 mm on arrival was significantly associated with treatment. Demographic factors influenced follow-up in primary healthcare while screening results did not. Referral to specialist was related to screening results. Several specialists were reluctant to diagnose and treat latent tuberculosis and to treat persons without a permanent visa in particular. CONCLUSIONS: Just 1% of the study group received treatment for latent tuberculosis and with a long time delay. The reason for this may be organizational factors affecting follow-up and referral and specialists not following current guidelines.

The role of entry screening in case finding of tuberculosis among asylum seekers in Norway.

BACKGROUND: Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers.We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis. METHODS: All asylum seekers who arrived at the National Reception Centre between January 2005--June 2006 with an abnormal chest X-ray or a Mantoux test ≥ 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008.Cases reported within two months after arrival were defined as being detected by screening. RESULTS: Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux ≥ 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB. CONCLUSION: In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB.