Age of onset for increased dose-adjusted serum concentrations of antidepressants and association with sex and genotype: An observational study of 34,777 individuals.

PURPOSE: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype. METHODS: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs). RESULTS: A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive. CONCLUSION: The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.

Pre-pregnancy obesity among immigrant and non-immigrant women in Norway: Prevalence, trends, and subgroup variations.

INTRODUCTION: This study assessed prevalence and time trends of pre-pregnancy obesity in immigrant and non-immigrant women in Norway and explored the impact of immigrants' length of residence on pre-pregnancy obesity prevalence. MATERIAL AND METHODS: Observational data from the Medical Birth Registry of Norway and Statistics Norway for the years 2016-2021 were analyzed. Immigrants were categorized by their country of birth and further grouped into seven super regions defined by the Global Burden of Disease study. Pre-pregnancy obesity was defined as a body mass index ≥30.0 kg/m2, with exceptions for certain Asian subgroups (≥27.5 kg/m2). Statistical analysis involved linear regressions for trend analyses and log-binomial regressions for prevalence ratios (PRs). RESULTS: Among 275 609 pregnancies, 29.6% (N = 81 715) were to immigrant women. Overall, 13.6% were classified with pre-pregnancy obesity: 11.7% among immigrants and 14.4% among non-immigrants. Obesity prevalence increased in both immigrants and non-immigrants during the study period, with an average yearly increase of 0.62% (95% confidence interval [CI]: 0.55, 0.70). Obesity prevalence was especially high in women from Pakistan, Chile, Somalia, Congo, Nigeria, Ghana, Sri Lanka, and India (20.3%-26.9%). Immigrant women from "Sub-Saharan Africa" showed a strong association between longer residence length and higher obesity prevalence (≥11 years (23.1%) vs. <1 year (7.2%); adjusted PR = 2.40; 95% CI: 1.65-3.48), particularly in women from Kenya, Eritrea, and Congo. CONCLUSIONS: Prevalence of maternal pre-pregnancy obesity increased in both immigrant and non-immigrant women from 2016 to 2021. Several immigrant subgroups displayed a considerably elevated obesity prevalence, placing them at high risk for adverse obesity-related pregnancy outcomes. Particular attention should be directed towards women from "Sub-Saharan Africa", as their obesity prevalence more than doubled with longer residence.

Associations between non-registered ultrasound examination in pregnancy and adverse perinatal outcomes in immigrant and non-immigrant women: a Norwegian population-based study 1999-2016.

BACKGROUND: Prenatal ultrasound examinations are important to detect placental dysfunction. Several ultrasound-detected abnormalities can be managed during pregnancy or childbirth, thus improve health outcomes. Maternal birth country is known to influence the risk of placental dysfunction, but little is known about the possible mechanisms of this relation. AIMS: (a) To estimate the proportion of non-registered prenatal ultrasound examinations; (b) to examine associations between non-registered ultrasound examinations and adverse perinatal outcomes, by migrant-related factors, in women giving birth in Norway. METHODS: Individually linked data from the Medical Birth Registry of Norway and Statistics Norway, 1999-2016, comprising 999,760 singleton pregnancies to immigrants (n=196,220) and non-immigrants (n=803,540). Crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using logistic regression with robust standard error estimations, adjusted for year of childbirth, maternal age, parity, maternal smoking, educational level and Norwegian health region at birth. RESULTS: Compared with non-immigrants, immigrant women had a higher proportion of non-registered ultrasound examinations (2.3% vs. 4.3%; aOR 2.0 (95% CI 1.9, 2.0)). Compared with women with ultrasound examination, the aOR for perinatal mortality for women with non-registered ultrasound was 2.27 (95% CI 1.85, 2.79) for immigrants and 3.61 (3.21, 4.07) for non-immigrants. Non-registered ultrasound examination was also associated with placental abruption (aOR 1.32 (1.08, 1.63)) for non-immigrant women, but it was not associated with preeclampsia. Compared with non-immigrants, immigrant women have a higher proportion of non-registered data on prenatal ultrasound examinations. Both immigrants and non-immigrants with non-registered ultrasound examinations have an increased aOR of perinatal mortality. Non-immigrant women also had an increased aOR for placental abruption.

Loneliness increases the risk of type 2 diabetes: a 20 year follow-up - results from the HUNT study.

AIMS/HYPOTHESIS: Type 2 diabetes is one of the leading causes of death globally and its incidence has increased dramatically over the last two decades. Recent research suggests that loneliness is a possible risk factor for type 2 diabetes. This 20 year follow-up study examined whether loneliness is associated with an increased risk of type 2 diabetes. As both loneliness and type 2 diabetes have been linked to depression and sleep problems, we also investigated whether any association between loneliness and type 2 diabetes is mediated by symptoms of depression and insomnia. METHODS: We used data from the Trøndelag Health Study (HUNT study), a large longitudinal health study based on a population from central Norway (n=24,024). Self-reports of loneliness (HUNT2 survey, 1995-1997) and data on HbA1c levels (HUNT4 survey, 2017-2019) were analysed to evaluate the associations between loneliness and incidence of type 2 diabetes. Associations were reported as ORs with 95% CIs, adjusted for sex, age and education. We further investigated the role of depression and insomnia as potential mediating factors. RESULTS: During the 20 year follow-up period, 4.9% of the study participants developed type 2 diabetes. Various degrees of feeling lonely were reported by 12.6% of the participants. Individuals who felt most lonely had a twofold higher risk of developing type 2 diabetes relative to those who did not feel lonely (adjusted OR 2.19 [95% CI 1.16, 4.15]). The effect of loneliness on type 2 diabetes was weakly mediated by one subtype of insomnia but not by symptoms of depression. CONCLUSIONS/INTERPRETATION: This study suggests that loneliness may be one factor that increases the risk of type 2 diabetes; however, there is no strong support that the effect of loneliness on type 2 diabetes is mediated by depression or insomnia. We recommend that loneliness should be included in clinical guidelines on consultations and interventions related to type 2 diabetes.

Sexual dysfunction in women with type 1 diabetes in Norway: A cross-sectional study on the prevalence and associations with physical and psychosocial complications.

AIM: To estimate the prevalence of sexual dysfunction in women with type 1 diabetes (T1D) compared with women without diabetes and to analyse associations between sexual dysfunction and the presence of chronic physical diabetes complications, diabetes distress and depression in women with T1D. METHODS: This cross-sectional study was conducted in Norway, and 171 women with T1D and 60 controls completed the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). Diabetes distress was assessed with the Problem Areas in Diabetes (PAID) scale. Data on diabetes complications were retrieved from medical records. We performed logistic regression to estimate differences in the prevalence of sexual dysfunction (defined as FSFI ≤26.55) between women with T1D and women without diabetes and to examine associations of sexual dysfunction with chronic diabetes complications, diabetes distress and depression in women with T1D. RESULTS: The prevalence of sexual dysfunction was higher in women with T1D (50.3%) compared with the controls (35.0%; unadjusted odds ratio [OR] 1.89 [95% confidence interval (CI) 1.06-3.37]; adjusted OR 1.93 [1.05-3.56]). In women with T1D, sexual dysfunction was associated with both diabetes distress (adjusted OR 1.03 [1.01-1.05]) and depression (adjusted OR 1.28 [1.12-1.46]), but there were no clear associations with chronic diabetes complications (adjusted OR 1.46 [0.67-3.19]). CONCLUSIONS: This study suggests that sexual dysfunction is more prevalent in women with T1D compared with women without diabetes. The study findings emphasize the importance of including sexual health in relation to diabetes distress and psychological aspects in diabetes care and future research.

Gestational diabetes mellitus by maternal country of birth and length of residence in immigrant women in Norway.

AIMS: Immigrant women are at higher risk for gestational diabetes mellitus (GDM) than non-immigrant women. This study described the prevalence of GDM in immigrant women by maternal country of birth and examined the associations between immigrants' length of residence in Norway and GDM. METHODS: This Norwegian national population-based study included 192,892 pregnancies to immigrant and 1,116,954 pregnancies to non-immigrant women giving birth during the period 1990-2013. Associations were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models, adjusted for year of delivery, maternal age, marital status, health region, parity, education and income. RESULTS: The prevalence and adjusted OR [CI] for GDM were substantially higher in immigrant women from Bangladesh (7.4%, OR 8.38 [5.41, 12.97]), Sri Lanka (6.3%, OR 7.60 [6.71, 8.60]), Pakistan (4.3%, OR 5.47 [4.90, 6.11]), India (4.4%, OR 5.18 [4.30, 6.24]) and Morocco (4.3%, OR 4.35 [3.63, 5.20]) compared to non-immigrants (prevalence 0.8%). Overall, GDM prevalence increased from 1.3% (OR 1.25 [1.14, 1.36]) to 3.3% (OR 2.55 [2.39, 2.71]) after 9 years of residence in immigrants compared to non-immigrant women. This association was particularly strong for women from South Asia. CONCLUSIONS: Gestational diabetes mellitus prevalence varied substantially between countries of maternal birth and was particularly high in immigrants from Asian countries. GDM appeared to increase with longer length of residence in certain immigrant groups.

Placental abruption in immigrant women in Norway: A population-based study.

INTRODUCTION: Placental abruption is a serious complication in pregnancy. Its incidence varies across countries, but the information of how placental abruption varies in immigrant populations is limited. The aims of this study were to estimate the incidence of placental abruption in immigrant women compared with non-immigrants by maternal country and region of birth, reason for immigration, and length of residence. MATERIAL AND METHODS: We conducted a nationwide population-based study using data from the Medical Birth Registry of Norway and Statistics Norway (1990-2016). The study sample included 1 558 174 pregnancies, in which immigrant women accounted for 245 887 pregnancies and 1 312 287 pregnancies were to non-immigrants. Crude and adjusted odds ratios with 95% CI for placental abruption in immigrant women compared with non-immigrants were estimated by logistic regression with robust standard error estimations (accounting for within-mother clustering). Adjustment variables included year of birth, maternal age, parity, multiple pregnancies, chronic hypertension, and level of education. RESULTS: The incidence of placental abruption decreased during the study period for both immigrants (from 0.68% to 0.44%) and non-immigrants (from 0.80% to 0.34%). Immigrant women from sub-Saharan Africa had an adjusted odds ratio of 1.35 (95% CI 1.15-1.58) compared with non-immigrants for placental abruption, whereas immigrant women from Ethiopia had an adjusted odds ratio of 2.39 (95% CI 1.67-3.41). We found a small variation in placental abruption incidence by other countries or regions of birth, length of residence, and reason for immigration. CONCLUSIONS: Immigrant women from sub-Saharan Africa, especially Ethiopia, have increased odds for placental abruption when giving birth in Norway. Reason for immigration and length of residence had little impact on the incidence of placental abruption.

Associations of overweight, obesity and osteoporosis with ankle fractures.

BACKGROUND: Studies exploring risk factors for ankle fractures in adults are scarce, and with diverging conclusions. This study aims to investigate whether overweight, obesity and osteoporosis may be identified as risk factors for ankle fractures and ankle fracture subgroups according to the Danis-Weber (D-W) classification. METHODS: 108 patients ≥40 years with fracture of the lateral malleolus were included. Controls were 199 persons without a previous fracture history. Bone mineral density of the hips and spine was measured by dual-energy x-ray absorptiometry, and history of previous fracture, comorbidities, medication, physical activity, smoking habits, body mass index and nutritional factors were registered. RESULTS: Higher body mass index with increments of 5 gave an adjusted odds ratio (OR) of 1.30 (95% confidence interval (CI) 1.03-1.64) for ankle fracture, and an adjusted OR of 1.96 (CI 0.99-4.41) for sustaining a D-W type B or C fracture compared to type A. Compared to patients with normal bone mineral density, the odds of ankle fracture in patients with osteoporosis was 1.53, but the 95% CI was wide (0.79-2.98). Patients with osteoporosis had reduced odds of sustaining a D-W fracture type B or C compared to type A (OR 0.18, CI 0.03-0.83). CONCLUSIONS: Overweight increased the odds of ankle fractures and the odds of sustaining an ankle fracture with possible syndesmosis disruption and instability (D-W fracture type B or C) compared to the stable and more distal fibula fracture (D-W type A). Osteoporosis did not significantly increase the odds of ankle fractures, thus suffering an ankle fracture does not automatically warrant further osteoporosis assessment.

Paternal country of origin and adverse neonatal outcomes in births to foreign-born women in Norway: A population-based cohort study.

BACKGROUND: Migration is a risk factor for adverse neonatal outcomes. The various impacts of maternal origin have been reported previously. The aim of this study was to investigate associations between paternal origin and adverse neonatal outcomes in births to migrant and Norwegian-born women in Norway. METHODS AND FINDINGS: This nationwide population-based study included births to migrant (n = 240,759, mean age 29.6 years [±5.3 SD]) and Norwegian-born women (n = 1,232,327, mean age 29.0 years [±5.1 SD]) giving birth in Norway in 1990-2016. The main exposure was paternal origin (Norwegian-born, foreign-born, or unregistered). Neonatal outcomes were very preterm birth (22+0-31+6 gestational weeks), moderately preterm birth (32+0-36+6 gestational weeks), small for gestational age (SGA), low Apgar score (<7 at 5 minutes), and stillbirth. Associations were investigated in migrant and Norwegian-born women separately using multiple logistic regression and reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs), adjusted for year of birth, parity, maternal and paternal age, marital status, maternal education, and mother's gross income. In births to migrant women, a foreign-born father was associated with increased odds of very preterm birth (1.1% versus 0.9%, aOR 1.20; CI 1.08-1.33, p = 0.001), SGA (13.4% versus 9.5%, aOR 1.48; CI 1.43-1.53, p < 0.001), low Apgar score (1.7% versus 1.5%, aOR 1.14; CI 1.05-1.23, p = 0.001), and stillbirth (0.5% versus 0.3%, aOR 1.26; CI 1.08-1.48, p = 0.004) compared with a Norwegian-born father. In Norwegian-born women, a foreign-born father was associated with increased odds of SGA (9.3% versus 8.1%, aOR 1.13; CI 1.09-1.16, p < 0.001) and decreased odds of moderately preterm birth (4.3% versus 4.4%, aOR 0.95; CI 0.91-0.99, p = 0.015) when compared with a Norwegian-born father. In migrant women, unregistered paternal origin was associated with increased odds of very preterm birth (2.2% versus 0.9%, aOR 2.29; CI 1.97-2.66, p < 0.001), moderately preterm birth (5.6% versus 4.7%, aOR 1.15; CI 1.06-1.25, p = 0.001), SGA (13.0% versus 9.5%, aOR 1.50; CI 1.42-1.58, p < 0.001), low Apgar score (3.4% versus 1.5%, aOR 2.23; CI 1.99-2.50, p < 0.001), and stillbirth (1.5% versus 0.3%, aOR 4.87; CI 3.98-5.96, p < 0.001) compared with a Norwegian-born father. In Norwegian-born women, unregistered paternal origin was associated with increased odds of very preterm birth (4.6% versus 1.0%, aOR 4.39; CI 4.05-4.76, p < 0.001), moderately preterm birth (7.8% versus 4.4%, aOR 1.62; CI 1.53-1.71, p < 0.001), SGA (11.4% versus 8.1%, aOR 1.30; CI 1.24-1.36, p < 0.001), low Apgar score (4.6% versus 1.3%, aOR 3.51; CI 3.26-3.78, p < 0.001), and stillbirth (3.2% versus 0.4%, aOR 9.00; CI 8.15-9.93, p < 0.001) compared with births with a Norwegian-born father. The main limitations of this study were the restricted access to paternal demographics and inability to account for all lifestyle factors. CONCLUSION: We found that a foreign-born father was associated with adverse neonatal outcomes among births to migrant women, but to a lesser degree among births to nonmigrant women, when compared with a Norwegian-born father. Unregistered paternal origin was associated with higher odds of adverse neonatal outcomes in births to both migrant and nonmigrant women when compared with Norwegian-born fathers. Increased attention to paternal origin may help identify women in maternity care at risk for adverse neonatal outcomes.

Country of first birth and neonatal outcomes in migrant and Norwegian-born parous women in Norway: a population-based study.

BACKGROUND: This study compares subsequent birth outcomes in migrant women who had already had a child before arriving in Norway with those in migrant women whose first birth occurred in Norway. The aim of this study was to investigate the associations between country of first birth and adverse neonatal outcomes (very preterm birth, moderately preterm birth, post-term birth, small for gestational age, large for gestational age, low Apgar score, stillbirth and neonatal death) in parous migrant and Norwegian-born women. METHODS: National population-based study including second and subsequent singleton births in Norway from 1990 to 2016. Data were retrieved from the Medical Birth Registry of Norway and Statistics Norway. Neonatal outcomes were compared between births to: 1) migrant women with a first birth before immigration to Norway (n = 30,062) versus those with a first birth after immigration (n = 66,006), and 2) Norwegian-born women with a first birth outside Norway (n = 6205) versus those with a first birth in Norway (n = 514,799). Associations were estimated as crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using multiple logistic regression. RESULTS: Migrant women with a first birth before immigrating to Norway had increased odds of adverse outcomes in subsequent births relative to those with a first birth after immigration: very preterm birth (22-31 gestational weeks; aOR = 1.27; CI 1.09-1.48), moderately preterm birth (32-36 gestational weeks; aOR = 1.10; CI 1.02-1.18), post-term birth (≥42 gestational weeks; aOR = 1.19; CI 1.11-1.27), low Apgar score (< 7 at 5 min; aOR = 1.27; CI 1.16-1.39) and stillbirth (aOR = 1.29; CI 1.05-1.58). Similar results were found in the sample of births to Norwegian-born women. CONCLUSIONS: The increased odds of adverse neonatal outcomes for migrant and Norwegian-born women who had their first births outside Norway should serve as a reminder of the importance of taking a careful obstetric history in these parous women to ensure appropriate care for their subsequent pregnancies and births in Norway.