Season, dietary factors, and physical activity modify 25-hydroxyvitamin D concentration during pregnancy

Peer reviewe

Most women living with HIV can deliver vaginally — national data from Finland 1993–2013

Abstract Introduction: Vaginal delivery has been recommended for more than ten years for women living with HIV (WLWH) with good virological control. However, in Europe most WLWH still deliver by cesarean section (CS). Our aim was to assess the rate of vaginal delivery and the indications for CS in WLWH over 20 years in a setting of low overall CS rate. Materials and methods: This was a retrospective study of all WLWH delivering in Finland 1993–2013. We identified the women by combining national health registers and extracted data from patient files. Results: The study comprised 212 women with 290 deliveries. Over 35% of the women delivered several children during the study years. During 2000–2013, with consistent viral load monitoring, 80.0% showed HIV viral loads <50 copies/mL in the last measurement preceding the delivery. Altogether 74.5% of all WLWH delivered vaginally and the rate of both elective CS and emergency CS was 12.8% each. For most CSs (63.5%) the indication was obstetrical, for 28.4% it was avoiding HIV transmission and for 0.7% it was mother’s request. In hospitals with less than ten HIV-related deliveries during the study period, the rate of elective CS was higher than in more experienced hospitals (22.7% versus 10.6% [p = 0.024]). No perinatal HIV transmissions occurred. Conclusions: Most WLWH can achieve good virological control and deliver vaginally. This will help them to maintain their future child bearing potential and reduce CS-related morbidity.Members of the FINHIVPREG study team: Inka Aho, Helsinki University Hospital, Helsinki; Sanna Uusitalo, University of Oulu, Oulu; Taru Finnilä, Turku University Hospital, Turku; Hanna Viskari, Tampere University Hospital, Tampere; Pirjo Alho, Kanta-Häme Hospital District, Hämeenlinna; Sari Hämäläinen, Kuopio University Hospital, Kuopio; Tuomas Nieminen, Satakunta Central Hospital, Pori; Elina Kärnä, Seinäjoki Central Hospital, Seinäjoki; Ville Lehtinen, Päijät-Häme Central Hospital, Lahti; Maija Rummukainen, Central Finland Health Care District, Jyväskylä; Antti Väänänen, Lapland Central Hospital, Rovaniemi; Jukka Heikkinen, North Carelia Central Hospital, Joensuu; Risto Pietikäinen, Kymenlaakso Central Hospital, Kotka; Pekka Suomalainen, South Carelia Central Hospital, Lappeenranta; Sakari Vuorinen, Mikkeli Central Hospital, Mikkeli)

Associations between maternal prenatal C-reactive protein and risk factors for psychosis in adolescent offspring:findings from the Northern Finland Birth Cohort 1986

Abstract Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis

Fatigue and health-related quality of life depend on the disability status and clinical course in RRMS

Abstract Background: Fatigue is a prominent and disabling symptom of multiple sclerosis (MS), impairing quality of life. The disease course of relapsing remitting MS (RRMS) is individual. Objectives: We aimed to study the effects of demographic and clinical characteristics, as well as lifestyle risk factors on experienced fatigue and health-related quality of life (HRQoL) among RRMS patients, comparing benign and severe disease types. Methods: Altogether 198 Finnish RRMS patients were recruited for this real-life cross-sectional study. Self-reported questionnaires were used to evaluate fatigue and HRQoL by using Fatigue Scale for Motor and Cognitive Functions and 15D health-related quality of life questionnaires. Patients were categorized into subgroups based on the current disability status measured by the Expanded Disability Status Scale (EDSS) cut-off value of 4.5, and by retrospective clinical course divided into benign and aggressive RRMS. Results: All in all, 73% of the RRMS patients suffered from fatigue. Lower HRQoL had a strong correlation with more prominent fatigue (r = -0.719). Higher EDSS was associated with more prominent fatigue and lower HRQoL in the whole RRMS cohort. Older age at the disease onset was associated with more prominent fatigue and decreased HRQoL in the groups of aggressive RRMS and EDSS > 4.5. In the groups of EDSS ≤ 4.5 and benign RRMS, a higher number of used disease-modifying treatments (DMTs) was associated with more pronounced fatigue and reduced HRQoL. In addition, higher BMI was associated with lower HRQoL in patients with benign RRMS. Side effects (45 %) and lack of efficacy (26 %) were the most common reasons for discontinuing a DMT. Cessation due to side effects was the only reason that was significantly associated with more prominent fatigue and lower HRQoL. Use of nicotine products, gender, or disease duration were not associated with fatigue or HRQoL. Conclusions: Individuals with severe RRMS and higher EDSS scores are more prone to experience fatigue and lower HRQoL. In addition, fatigue and lower HRQoL are more commonly observed among RRMS patients with older age at disease onset and in those with multiple DMT switches

Maternal first trimester metabolic profile in pregnancies with transposition of the great arteries

Abstract Background: Higher maternal body mass index (BMI) and abnormal glucose metabolism during early pregnancy are associated with congenital heart defects in the offspring, but the exact mechanisms are unknown. Methods: We evaluated the association between maternal first trimester metabolic profile and transposition of the great arteries (TGA) in the offspring in a matched case–control study with 100 TGA mothers and 200 controls born in Finland during 2004–2014. Cases and controls were matched by birth year, child sex, and maternal age and BMI. Serum samples collected between 10- and 14-weeks of gestation were analyzed for 73 metabolic measures. Conditional logistic regression was used to assess the risk for TGA in the offspring, and a subgroup analysis among mothers with high BMI was conducted. Results: Higher concentrations of four subtypes of extremely large very-low-density lipoprotein (VLDL) particles and one of large VLDL particles were observed in TGA mothers. This finding did not reach statistical significance after multiple testing correction. The pooled odds ratio (OR) of the all metabolic variables was slightly higher in TGA mothers in the subgroup with maternal BMI over 25 (OR 1.25) and significantly higher in the subgroup with maternal BMI over 30 (OR 1.95) compared to the original population (OR 1.18). Conclusions: Our findings indicate that an abnormal maternal early pregnancy metabolic profile might be associated with TGA in the offspring, especially in obese mothers. A trend indicating altered VLDL subtype composition in TGA pregnancies warrants further research

Epstein–Barr virus and multiple sclerosis risk in the Finnish Maternity Cohort

Abstract Objective: To determine whether maternal Epstein–Barr virus (EBV) IgG antibody levels are associated with risk of multiple sclerosis (MS) in the offspring. Methods: We conducted a prospective nested case–control study in the Finnish Maternity Cohort (FMC) with serum samples from >800,000 women collected during pregnancy since 1983. Cases of MS among offspring born between 1983 and 1991 were identified via hospital and prescription registries; 176 cases were matched to up to 3 controls (n = 326) on region and dates of birth, sample collection, and mother‘s birth. We used conditional logistic regression to estimate relative risks (RRs) and adjusted models for sex of the child, gestational age at sample collection, and maternal serum 25‐hydroxyvitamin D and cotinine levels. Similar analyses were conducted among 1,049 women with MS and 1,867 matched controls in the FMC. Results: Maternal viral capsid antigen IgG levels during pregnancy were associated with an increased MS risk among offspring (RRtop vs bottom quintile = 2.44, 95% confidence interval [CI] = 1.20–5.00, p trend = 0.004); no associations were found between maternal EBV nuclear antigen 1 (EBNA‐1), diffuse early antigen, or cytomegalovirus IgG levels and offspring MS risk. Among women in the FMC, those in the highest versus lowest quintile of EBNA‐1 IgG levels had a 3‐fold higher risk of MS (RR = 3.21, 95% CI = 2.37–4.35, p trend <1.11e‐16). These associations were not confounded or modified by 25‐hydroxyvitamin D. Interpretation: Offspring of mothers with high viral capsid antigen IgG during pregnancy appear to have an increased risk of MS. The increase in MS risk among women with elevated prediagnostic EBNA‐1 IgG levels is consistent with previous results

Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity

Abstract Aims: We studied whether androgen excess and low sex hormone-binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post-prandial hyperglycaemia, gestational diabetes (GDM), and its severity. Materias and Methods: This nationwide case–control study included 1045 women with GDM and 963 non-diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early-onset GDM (<20 gestational weeks) and the need for anti-diabetic medication. Results: After adjustments for gestational weeks at sampling, pre-pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%–7.3%) lower SHBG levels, 3.1% (95% CI 0.1%–6.2%) higher T levels, and 4.6% (95% CI 1.9%–7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post-prandial glucose concentrations. Women with early-onset GDM had 6.7% (95% CI 0.7%–12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%–14.8%) lower SHBG levels than other women with GDM. Conclusions: Lower SHBG levels were associated especially with early-onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post-prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post-prandial insulin secretion

Association of antiparietal cell and anti-intrinsic factor antibodies with risk of gastric cancer

Abstract Importance: Autoimmune gastritis is an alternative cause of gastric carcinogenesis. This cause may be gaining importance with declining prevalence of chronic Helicobacter pylori infection. Objectives: To determine the association of prediagnostic autoantibodies to gastric mucosa with gastric cancer (GC) risk. Design, Setting, and Participants: This cohort study used nested GC case-control analyses within separate Finnish cohorts of women of reproductive age (Finnish Maternity Cohort [FMC]; born 1938‐1989) and older men (Alpha-Tocopherol, Beta-Carotene Cancer Prevention [ATBC] Study; born 1916‐1939). There were 529 and 457 matched pairs from the FMC and ATBC Study, respectively, with mean participant ages of 30.5 and 57.5 years and medians of 17 and 11 years from baseline to cancer diagnosis. Data analyses were performed between August 2019 and November 2020. Exposures: Antiparietal cell antibodies (APCAs), anti-intrinsic factor antibodies, and anti–H pylori antibodies were measured in baseline serum using immunoassays. Main Outcomes and Measures: Autoantibody associations were estimated by odds ratios (ORs) and 95% CIs. Results: Of the 529 control participants in the FMC and 457 control participants in the ATBC Study, 53 (10%) women and 35 (7.7%) men were APCA seropositive, respectively, whereas 146 (28%) women and 329 (72%) men were H pylori seropositive. In the FMC, APCA seropositivity was statistically significantly associated with GC risk among H pylori-seronegative women (OR, 5.52; 95% CI, 3.16‐9.64) but not H pylori-seropositive women (OR, 1.29; 95% CI, 0.64‐2.60; P for interaction = .002). The APCA association with H pylori seronegativity was strongest for tumors in the fundus and corpus (OR, 24.84; 95% CI, 8.49‐72.72). In the ATBC Study, APCA seropositivity was not associated with GC among either H pylori–seronegative men (OR, 0.99; 95% CI, 0.32‐3.04) or H pylori–seropositive men (OR, 1.06; 95% CI, 0.60‐1.88). In both cohorts, anti-intrinsic factor antibody seroprevalence was less than 2% among cases as well as controls and not statistically associated with GC risk. Conclusions and relevance: Results of this cohort study demonstrate that autoantibody positivity may reflect subclinical autoimmune gastritis in younger women. The findings among young females and corpus subsite align with increasing cancer incidence trends for these groups. Stronger autoimmune associations in H pylori-seronegative individuals support a model of autoimmune gastritis replacing H pylori as the driving factor

Long‐term follow‐up of human papillomavirus type replacement among young pregnant Finnish females before and after a community‐randomised HPV vaccination trial with moderate coverage

Abstract Large scale human papillomavirus (HPV) vaccination against the most oncogenic high‐risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population‐based serological survey of unvaccinated young women over 12 years. The women were under 23‐years‐old, residents from 33 communities which participated in a community‐randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre‐CRT and post‐CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk‐taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population‐based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender‐neutral vaccination (PR16/18A = 0.8, 95% CI 0.7‐0.9). HPV6/11 and HPV73 were decreased after gender‐neutral vaccination (PR6/11A = 0.8, 95% CI 0.7‐0.9, PR73A = 0.7, 95% CI 0.6‐0.9, respectively) and girls‐only vaccination (PR6/11B = 0.8, 95% CI 0.7‐0.9, PR73B = 0.9, 95% CI 0.8‐1.0). HPV68 alone was increased but only after girls‐only vaccination (PR68B = 1.3, 95% CI 1.0‐1.7, PRcore68B = 2.8, 95% CI 1.2‐6.3). A large‐scale, long‐term follow‐up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls‐only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638)