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To survey trends of antipsychotic use during pregnancy and examine the associations between the use of quetiapine or any antipsychotic and adverse obstetric and neonatal outcomes. Birth register study of 36,083 women who gave birth at Kuopio University Hospital, Finland, between 2002 and 2016. Obstetric and neonatal outcomes between women using quetiapine (N = 152) or any antipsychotic (N = 227) were compared to controls (N = 35,133). Altogether 246 (0.7%) women used antipsychotic medications during pregnancy and 153 (62,2%) of these women used quetiapine. Antipsychotic usage increased from 0.4% to 1.0% during the 15-year follow-up. Women using antipsychotics were more likely to smoke, drink alcohol, use illicit drugs, use other psychotropic medications, and have higher pre-pregnancy body mass index. Quetiapine use was associated with higher risk of increased postpartum bleeding in vaginal delivery (aOR 1.65; 95%CI 1.13–2.42), prolonged neonatal hospitalization (≥5 days) (aOR 1.54; 95%CI 1.10–2.15), and higher placental to birth weight ratio (PBW ratio) (aB 0.009; 95%CI 0.002–0.016). Use of any antipsychotic was associated with a higher risk of gestational diabetes mellitus (aOR 1.64; 95%CI 1.19–2.27), increased postpartum bleeding in vaginal delivery (aOR 1.50; 95%CI 1.09–2.07), prolonged neonatal hospitalization (≥5 days) (aOR 2.07; 95%CI 1.57–2.73), and higher PBW ratio (aB 0.007; 95%CI 0.001–0.012). The use of antipsychotic medications increased among Finnish pregnant women from 2002 to 2016. Pregnant women using antipsychotics appear to have a higher risk for some adverse pregnancy and birth outcomes and may benefit from more frequent maternity care follow-ups.

Background: Several recent studies have investigated the association between maternal diet during pregnancy and asthma in children. However, whether a specific dietary pattern during pregnancy protects children from asthma remains unclear. This study investigated the association between a healthy diet, dietary inflammation potential during pregnancy, and the risk for wheezing and atopic eczema in children. Methods: This study included 1330 mother-child pairs who attended the Kuopio Birth Cohort (KuBiCo) study and had dietary information during the last trimester and information on children’s health in the first year of life. The Alternative Healthy Eating Index for Pregnancy (AHEI-P) and Dietary Inflammatory Index (DII) indicate a healthy diet and dietary inflammation potential during pregnancy. The AHEI-P and DII were compared with reported wheezing and doctor-diagnosed atopic eczema in children during the first year of life. Results: Neither the AHEI-P nor the DII was associated with wheezing or atopic eczema in children when analyzed by continuous variables or tertiles. The odds ratio for AHEI-P and wheezing was 0.99 (0.98–1.01); for AHEI-P and atopic eczema was 1.01 (0.99–1.02); for DII and wheezing was 1.02 (0.95–1.09), and for DII and atopic eczema was 0.97 (0.91–1.04). Conclusion: In this cohort study, a maternal healthy or anti-inflammatory diet during pregnancy was not associated with wheezing or atopic eczema in the first year of life. Interventions in the overall dietary pattern during pregnancy might not effectively prevent atopic diseases in children.

Purpose To study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol. Methods Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test. Results During the stimulation protocol, leptin concentrations elevated (P P = 0.03), while estradiol levels increased (P P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased. Conclusion No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

Aim: Fundamentally, aggressive care is considered to be avoided for the patients at the end of life. However, this is not always adhered in real-world practice. We attempted to determine whether, and if so how, the aggressive care is made for patients with ovarian cancer during the last month prior death. Methods: Enrolled were a total of 104 patients with ovarian cancer (including fallopian tube or primary peritoneal cancer), who were treated in Kuopio University Hospital in Finland during 2009-2014. The aggressive care was defined according to the standards outlined by the National Quality Forum; shortly, chemotherapy, emergency-room/intensive-care visit/admission, hospital admission, and death in hospital. Results: Two thirds of patients (67%) had received at least one form of aggressive care during the last month of their lives. Especially, admission in hospital in the last 30 days of life was the most common form of aggressive cancer care. Younger patients ( = 0.004). Those women that underwent end-of-life discussions earlier than one month prior to death had significantly less aggressive care than those women that had discussions during the last month (48% vs. 90%, p = 0.001). Conclusions: Ovarian cancer patients received commonly at least one form of aggressive care at the end of their lives. More efforts should be taken to improve the quality of palliative and end-of-life care.

Background/aim Examine features of blood and lymphatic vessels in ovarian tumors and their significance to prognosis of ovarian cancer. Patients and methods A total of 139 women with epithelial ovarian tumors were included: 86 malignant, 17 borderline and 36 benign. Density, percentage, mean size and number of blood microvessels in tumors were measured by immunohistochemistry with antibodies against CD34 and CD105. Lymphatic vessel density was assayed using the D2-40 antibody against podoplanin. Results Angiogenesis was most profuse in malignant tumors. Small size of lymph vessels predicted 26% shorter 5-year survival of ovarian cancer patients. Further, high percentage of lymphatic vessels in tumors was associated with lymph node metastasis, and high density with cancer recurrence. Lower number of microvessels, as assessed by CD34 staining, predicted shorter progression-free survival. Additionally, the large size of microvessels assessed by CD34 and the high number of vessels assessed by CD105 were related to residual tumor >1 cm at primary surgery and also, large vessel size was associated with stage III, as assessed by CD105 staining. Conclusion CD34 and CD105 define different characteristics of microvessels. Parameters of lymph vessels may predict the prognosis of ovarian cancer.

The partners' role in determining the alcohol consumption behavior of pregnant women is not well studied. We measured alcohol use before and during pregnancy in pregnant women and their partners to evaluate the correlation in their levels of consumption.We evaluated the self-reported alcohol use of 14,822 women and their partners during 21,472 singleton pregnancies delivered in Kuopio University Hospital, Finland during the period 2009-2018. The information was gathered during pregnancy and at the time of childbirth and recorded in two databases that were merged to yield a single cohort. Missing data were accounted for by multiple imputation using the predictive mean matching method.In 86% of the pregnancies, women reported alcohol use before pregnancy, whereas in 4.5% of the pregnancies women reported alcohol use during pregnancy. In contrast, no decrease was detected in their partners' alcohol use before or during pregnancy. In 26% of the pregnancies, the woman reported stopping alcohol use only after recognizing that she was pregnant. Before pregnancy, there were strong correlations between the pregnant women and their partners in the total Alcohol Use Disorders Identification Test score (rThe self-reported alcohol consumption of pregnant women and their partners was positively correlated both before and during pregnancy, though the correlation declined substantially during pregnancy. Evaluating the alcohol consumption of both parents before pregnancy could assist in identifying women at risk of prenatal alcohol exposure. Supporting a reduction in partners' alcohol use could help to reduce pregnant women's alcohol consumption and prevent its associated harms.

To evaluate the causes behind the association between hypothyroidism and the risk of preeclampsia.Checking of individual hospital and birth records from 149 levothyroxine users among 2,508 women in the preeclampsia case-control study (2002-2016).There were significant association between levothyroxine medication and preeclampsia (OR 1.48, 95Levothyroxine use during pregnancy was associated with 1.5-times higher risk for preeclampsia, but it is also linked to the other comorbid risk factors.

Purpose High-maternal caffeine intake during pregnancy may be harmful for perinatal outcomes and future child health, but the level of fetal cumulative exposure has been difficult to measure thus far. Here, we present maternal dietary caffeine intake during the last trimester and its correlation to caffeine content in newborn hair after birth. Methods Maternal third trimester diets and dietary caffeine intake were prospectively collected in Kuopio Birth Cohort (KuBiCo) using a 160-item food frequency questionnaire (n = 2840). Newborn hair was collected within 48 h after birth and analyzed by high-resolution mass spectrometry (HRMS) for caffeine (n = 316). Correlation between dietary caffeine intake and neonatal hair caffeine content was evaluated from 203 mother–child pairs. Results Mean dietary caffeine intake was 167 mg/days (95% CI 162–172 mg/days), of which coffee comprised 81%. Caffeine in the maternal diet and caffeine content in newborn hair correlated significantly (r = 0.50; p Conclusion Caffeine exposure, estimated from newborn hair samples, reflects maternal third trimester dietary caffeine intake and introduces a new method to assess fetal cumulative caffeine exposure. Further studies to evaluate the effects of caffeine exposure on both perinatal and postnatal outcomes are warranted, since over 40% of pregnant women consume caffeine more than the current suggested recommendations (European Food Safety Association, EFSA recommendations).

Background: Do different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol? Does the IVF stimulation induce metabolic changes, which might impact maternal health? Methods: Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs) three days before each visit. In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test, in which the blood samples were taken at five time points at every three visits. They also filled visual analog scales to exhibit satiety and appetite. Twenty-eight of the subjects had only fasting blood samples. Results: During the stimulation protocol, leptin concentrations elevated (P Conclusions: No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, no harmful metabolic effects occurred, which might have a disproportionate impact on maternal health. Trial registration: Not applicable. This study is a clinical study without intervention.

Publisher Copyright: © 2021 The Author(s) We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.

Objective This study aimed to compare outcomes of mini-invasive surgical treatment of endometriosis, especially conventional laparoscopy with robotic-assisted laparoscopy, and to evaluate the quality of life. Methods One hundred three consecutive patients with endometriosis who had surgery from 2014 to 2017 owing to an indication of pain were enrolled in this retrospective study. The majority (n = 77, 75%) of patients underwent conventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. The quality of life was postoperatively assessed with a questionnaire. Results The rates of parametrectomy (76% vs. 45%,) and rectovaginal resection (28% vs. 4%) were significantly higher in robotic-assisted laparoscopy than in laparoscopy. Additionally, the rate of bowel operations (50% vs. 17%), especially the shaving technique, was higher in robotic-assisted laparoscopy surgery than in laparoscopy (39% vs. 8%). There was no difference in the rate of postoperative complications between laparoscopy and robotic-assisted laparoscopy. Most (91%) of the patients who answered the questionnaire felt that surgical treatment had relieved their pain. In the laparoscopic and robotic-assisted groups, 88% of respondents felt that their quality of life had improved after surgery. Conclusions This study suggests that robotic-assisted laparoscopy is a feasible method to resect deep infiltrating endometriosis, especially in the rectosigmoid area.

Publisher Copyright: © 2022 Academy of Nutrition and Dietetics Background: Depression and diet quality appear to be associated in the general population. Nevertheless, little is known about their relationship among pregnant females. Objective: The aims of this study were first, to investigate longitudinally whether or not diet quality is associated with depressive symptoms during pregnancy; second, to examine whether or not variation in diet quality during pregnancy predicts variation in depressive symptoms; and third, to explore how individual dietary components are associated with depressive symptoms. Design: A longitudinal secondary analysis of the Kuopio Birth Cohort Study in eastern Finland was conducted. Data were collected from pregnant females during the first and third trimesters of pregnancy. Participants/setting: The participants were 1,362 pregnant females who entered the study between 2012 and 2017. Main outcome measures: Depressive symptoms, as measured with the Edinburgh Postnatal Depressive Scale during the first and third trimesters of pregnancy were used as continuous variables. Statistical analyses performed: The main analyses consisted of linear mixed model analyses adjusted for potential confounders to longitudinally assess the association between diet quality as measured by the Healthy Eating Index-2015, calculated using data from a food frequency questionnaire completed during the first trimester and third trimester, and depressive symptoms during the study period. An exploratory set of linear mixed models was also used to longitudinally assess the associations between selected individual food frequency questionnaire food groups and depressive symptoms. Results: Descriptive analyses revealed that 12.3% of the participants had clinically relevant levels of depressive symptoms (ie, Edinburgh Postnatal Depressive Scale score ≥10) during either the first or third trimester. Longitudinal modeling suggested that depressive symptoms in pregnant females tend to remain stable throughout pregnancy. Females with a poorer quality diet already displayed higher levels of depressive symptoms during the first trimester of pregnancy (β = –.038 ± .016; P = 0.022). Variation in diet quality did not predict variation in depressive symptoms over the course of pregnancy (β = –9.741 × 10–5 ± .001; P = 0.869). Conclusions: Females entering pregnancy with a poorer quality diet also displayed higher levels of depressive symptoms compared with females with a higher quality diet at the beginning of pregnancy, and this association remained constant throughout pregnancy. Further research is needed to assess the direction and the potential causality of the observed associations between diet quality and depressive symptoms.

Aim To evaluate the association between lactate concentrations in fetal blood samples and the different advanced labour stages. Methods Eighteen-month prospective population-based clinical study of 187 singleton pregnant women in labour who were monitored by fetal blood sampling (FBS) because of non-reassuring intrapartum CTG results at Kuopio University Hospital, Finland. Peripheral lactate concentration and pH were analysed at different stages of labour and in umbilical arterial samples immediately after delivery. Results FBS samples (N = 350) were obtained from 5.4 % of all women in labour during the study period, and 48 % had spontaneous delivery, 27 % had vacuum-assisted vaginal delivery, and 25 % had nonelective Caesarean delivery. FBS lactate levels increased 4–11% with every 1–2 cm of cervical dilation and 18 % from early labour to fully dilated cervix. In 42 women with at least two FBSs, lactate levels increased significantly from the early I stage of labour and up to a fully dilated cervix. Lactate values were significantly higher in umbilical arterial samples compared to FBSs. Sensitivity of the highest FBS lactate values for the detection of birth asphyxia were considerably low varying between 42.9–57.1%. Conclusion FBS lactate levels were related to the stage of labour during vaginal delivery attempt. Wide range of lactate levels during labour complicates its use as a predictor of birth asphyxia.

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012?2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications.

Background This study was made to figure out, does low and high estradiol levels during in vitro fertilization (IVF) cycles have a different effect on carotid artery distensibility (Cdis), carotid artery diameter (Cdia), blood pressure and metabolic factors? Can the stimulation protocol be considered safe to women’s vasculature? Methods We studied 28 women having a long agonist protocol IVF-treatment in Kuopio University Hospital during the years 2011–2016. Patients were examined at three time points: in the beginning of their own period (low estradiol), during the gonadotrophin releasing hormone (GnRH) analogue downregulation (low estradiol) and during the follicle stimulating hormone (FSH) stimulation (high estradiol). Women served as their own controls and their menstrual phase (2- to 5-day period after the beginning of menstruation with low estrogen) was used as the reference. Cdis and Cdia were assessed using ultrasound. Blood pressure, weight, estradiol levels and lipids were monitored. Results Cdis, Cdia, systolic and diastolic blood pressures peaked during the GnRH-analogue treatment with the lowest estradiol levels. Cdis, Cdia and systolic blood pressures declined by 11% (P = 0.002), 3,8% (P < 0.001) and 2,5% (P = 0.026) during the FSH-stimulation when the estradiol levels were high. Cdis correlated significantly (P < 0.05) with systolic blood pressure, diastolic blood pressure and triglycerides in high estrogenic environment and with diastolic blood pressure (P < 0.05) when estrogen profiles were low. Conclusions Carotid artery stiffens during the high estradiol levels compared to low levels and this was not explained by the higher diameter of the carotid artery, hyperlipidemia or blood pressure profiles. All the changes in Cdis and Cdia are variations of normal, and if there is no history of cardiovascular problems, it can be considered, that the stimulation protocol is not hazardous to vasculature.

AIM We aimed to determine whether maternal hemoglobin levels or anemia during pregnancy are associated with the development of asthma among offspring. METHODS Data were retrieved from the birth register database of Kuopio University Hospital between 1989 and 2007 (n = 38 381). Hemoglobin levels were measured during three trimesters of pregnancy and anemia was defined according to the World Health Organization criteria. The prevalence of asthma was determined from the register of reimbursement for medication for asthma at the Finnish Social Security Institution. Cox proportional hazard regression analysis was performed to evaluate the possible associations between prenatal factors and development of asthma ever. RESULTS A total of 8198 (21.4%) women had anemia at some stage of pregnancy. Mild maternal anemia during the first trimester was associated with an increased risk of asthma among male offspring (adjusted hazard ratio, 1.46; 95% confidence interval, 1.11-1.94) compared with those with normal maternal hemoglobin levels. This finding remained significant also after applying the Bonferroni correction. CONCLUSION Male offspring with maternal anemia during the first trimester of pregnancy had significantly more asthma ever than the offspring of women with normal hemoglobin levels during pregnancy. These findings were not strong but suggest possible sex-specific effects of maternal health on prenatal programming and future risk of asthma.

Background and objective The farm environment, especially contact with farm animals in early childhood, may prevent allergic sensitization during adulthood. However, prospective associations between exposure to the farm environment and polysensitization have not been studied. Polysensitization is a risk factor for asthma and asthma-related morbidity. Objective: To investigate whether exposure to a farming environment in early childhood, especially exposure to animals, is associated with sensitization to specific allergens and polysensitization at the age of 31. Methods In a prospective birth cohort study, 5509 individuals born in northern Finland in 1966 underwent skin prick testing against birch, timothy, cat, and house dust mite at the age of 31. Prenatal exposure to the farming environment was documented at birth, whereas information on childhood exposure to pets was only collected retrospectively at the age of 31. Data were analyzed using logistic regression. Results Being born to a family with farm animals was associated with a reduced risk of sensitization to birch, timothy, and cat (adjusted odds ratio [aOR], 0.55 [95%CI, 0.43-0.70]; aOR, 0.62 [95%CI, 0.48-0.79]; aOR, 0.60 [95%CI, 0.47-0.75]) and polysensitization at the age of 31 (aOR, 0.62 [95%CI, 0.48-0.80]). The number of animal species present during childhood was dose-dependently associated with a reduced risk of sensitization to birch, timothy, and cat, as well as of polysensitization. No association was found with sensitization to house dust mite. Conclusions Growing up on a farm and contact with higher numbers of animal species in childhood are associated with less frequent sensitization to birch, timothy, and cat allergens and polysensitization in adulthood, but not with sensitization to house dust mite.

Objective Peripartum depression (PPD) pertaining to depression in pregnancy and postpartum is one of the most common complications around childbirth with enduring adverse effects on mother and child health. Although psychiatric symptoms may improve or worsen over time, relatively little is known about the course of PPD symptoms and possible fluctuations. Methods We applied a person-centered approach to examine PPD symptom patterns across pregnancy and childbirth. 824 women were assessed at three time points: first trimester (T1), third trimester (T2), and again at eight weeks (T3) postpartum. We assessed PPD symptoms, maternal mental health history, and childbirth variables. Results Growth mixture modeling (GMM) analysis revealed four discrete PPD symptom trajectory classes including chronic PPD (1.1%), delayed (10.2%), recovered (7.2%), and resilient (81.5%). Delivery complications were associated with chronic PPD but also with the recovered PPD trajectory class. History of mental health disorders was associated with chronic PPD and the delayed PPD class. Conclusion The findings underscore that significant changes in a woman's depression level can occur across pregnancy and childbirth. While a minority of women experience chronic PDD, for others depression symptoms appear to significantly alleviate over time, suggesting a form of recovery. Our findings support a personalized medicine approach based on the woman's symptom trajectory. Future research is warranted to identify the mechanisms underlying modifications in PPD symptoms severity and those implicated in recovery.

Background Antiangiogenic therapy, although part of standard treatment in ovarian cancer, has variable efficacy. Furthermore, little is known about the prognostic biomarkers and factors influencing angiogenesis in cancer tissue. We evaluated the expression of angiopoietin-2 and two endothelial tyrosine kinase receptors, Tie-1 and Tie-2, and assessed their value in the prediction of survival in patients with malignant epithelial ovarian cancer. We also compared the expression of these factors between primary high grade serous tumors and their distant metastasis. Materials and methods We evaluated 86 women with primary epithelial ovarian cancer. Matched distal omental metastasis were investigated in 18.6% cases (N = 16). The expression levels of angiogenic factors were evaluated by immunohistochemistry in 306 specimens and by qRT-PCR in 111 samples. Results A high epithelial expression level of Tie-2 is a significant prognostic factor in primary high grade serous ovarian cancer. It predicted significantly shorter overall survival both in univariate (p Conclusions The angiogenic factor, angiopoietin-2, and its receptor Tie-2 seem to be significant prognostic factors in primary epithelial ovarian cancer. Their expression levels are also increased in metastatic lesions in comparison with primary tumors.

Article, Background To evaluate the association between maternal and paternal smoking during pregnancy, and asthma among offspring. Methods We conducted a hospital-based birth retrospective observational birth cohort study in a University-based Obstetrics and Gynecology Department, Kuopio University Hospital, Finland. 39 306 women, delivering between 1989 and 2006, were linked to the national register for asthma reimbursement for their offspring (2641 asthmatics). Pregnancy factors were recorded during pregnancy. Results The risk of asthma was significantly elevated if both parents smoked (aOR 3.7; 95 % Cl 3.2-4.4) and it remained high in only paternal smoking families (aOR 2.9; 95 % Cl 2.5-3.3) as well as only maternal smoking families (aOR 1.7; 95 % Cl 1.2-2.2). Paternal cessation of smoking during pregnancy seemed to reduce the risk of asthma regardless of maternal smoking (aOR 0.3-0.4). Conclusions Parental smoking, and especially paternal smoking, was significantly associated with the risk of asthma in offspring and paternal cessation of smoking during pregnancy was associated with a decreased risk of childhood asthma regardless of maternal smoking. The results indicate that both parents should be encouraged to quit smoking during pregnancy, since it is a relatively easy and cheap way to reduce the risk of asthma in offspring., published version, peerReviewed

Highlights • The effects of maternal smoking on the term placental proteome was studied. • Maternal smoking significantly affected 18% of protein spots. • Maternal smoking affects systems controlling the development and function of placenta. • The observed placental changes may contribute to the lowered birth weights., Detrimental effects of maternal smoking on the term placental proteome and steroid-metabolizing activities, and maternal hormone levels, were studied by using seven non-smoker and seven smoker placentae. Smoking significantly affected 18% of protein spots. The functional networks affected were i) cell morphology, cellular assembly and organization, cellular compromise (15 hits) and ii) DNA replication, recombination, and repair, energy production, nucleic acid metabolism (6 hits). Smoking significantly up-regulated such proteins as, SERPINA1, EFHD1 and KRT8; and down-regulated SERPINB2, FGA and HBB. Although maternal plasma steroids were not significantly altered, the catalytic activity of CYP1A1 was increased whereas CYP19A1 activity was reduced by smoking. Furthermore, transcript expression of CYP1A1 and CYP4B1 were induced while HSD17B2, NFKB and TGFB1 were repressed by smoking. The observed smoking induced wide-spread changes on placental proteome and transcript levels may contribute to the lowered birth weights of the new-born child and placenta.

Background: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. Methods: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omits; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. Discussion: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.

The purpose was to study the prevalence of environmental intolerance (EI) and its different manifestations, including behavioral changes and disability. Fertile-aged women (n = 680) of the Kuopio Birth Cohort Study were asked about annoyance to 12 environmental factors, symptoms and behavioral changes. We asked how much the intolerance had disrupted their work, household responsibilities or social life. We chose intolerance attributed to chemicals, indoor molds, and electromagnetic fields to represent typical intolerance entities. Of the respondents, 46% reported annoyance to chemicals, molds, or electromagnetic fields. Thirty-three percent reported symptoms relating to at least one of these three EIs, 18% reported symptoms that included central nervous system symptoms, and 15% reported behavioral changes. Indicating disability, 8.4% reported their experience relating to any of the three EIs as at least "somewhat difficult", 2.2% "very difficult" or "extremely difficult", and 0.9% "extremely difficult". Of the latter 2.2%, all attributed their intolerance to indoor molds, and two thirds also to chemicals. As the number of difficulties increased, the number of organ systems, behavioral changes and overlaps of the three EIs also grew. EI is a heterogeneous phenomenon and its prevalence depends on its definition. The manifestations of EI form a continuum, ranging from annoyance to severe disability.

We aimed to determine whether maternal hemoglobin levels or anemia during pregnancy are associated with the development of asthma among offspring.Data were retrieved from the birth register database of Kuopio University Hospital between 1989 and 2007 (n = 38 381). Hemoglobin levels were measured during three trimesters of pregnancy and anemia was defined according to the World Health Organization criteria. The prevalence of asthma was determined from the register of reimbursement for medication for asthma at the Finnish Social Security Institution. Cox proportional hazard regression analysis was performed to evaluate the possible associations between prenatal factors and development of asthma ever.A total of 8198 (21.4%) women had anemia at some stage of pregnancy. Mild maternal anemia during the first trimester was associated with an increased risk of asthma among male offspring (adjusted hazard ratio, 1.46; 95% confidence interval, 1.11-1.94) compared with those with normal maternal hemoglobin levels. This finding remained significant also after applying the Bonferroni correction.Male offspring with maternal anemia during the first trimester of pregnancy had significantly more asthma ever than the offspring of women with normal hemoglobin levels during pregnancy. These findings were not strong but suggest possible sex-specific effects of maternal health on prenatal programming and future risk of asthma.

Objective To evaluate the prevalence of various etiologies of epilepsies and epilepsy syndromes and to estimate cognitive function in cases of childhood-onset epilepsy. Methods A population-based retrospective registry study. We identified all medically treated children with epilepsy born in 1989–2007 in Finland's Kuopio University Hospital catchment area, combining data from the birth registry and the national registry of special-reimbursement medicines. We reevaluated the epilepsy diagnoses and syndromes and gathered data on etiologies and cognitive impairment. Results We identified 289 children with epilepsy. The annual incidence rate of epilepsies and epilepsy syndromes was 38 in 100,000, and the misdiagnosis rate was 3%. A specific etiology was identified in 65% of the cases, with a structural etiology accounting for 29% and a genetic or presumed genetic etiology for 32%. Most patients with unknown-etiology epilepsy had focal epilepsy and were of normal intelligence. Intellectual disability was detected in 35% of cases, and only 17% in this group had an unknown etiology for the epilepsy. Electroclinical syndromes (mainly West syndrome) were recognized in 35% of the patients. Significance Epilepsy is a complex disease that encompasses many etiologies and rare syndromes. The etiology and specific epilepsy syndrome are important determinants of the outcome and key factors in treatment selection. Etiological diagnosis can be achieved for the majority of children and syndromic diagnosis for only a third., published version, peerReviewed

Introduction Many complications of pregnancy and delivery are associated with umbilical cord length. It is important to examine the variation in length, in order to identify normal and abnormal conditions. Moreover, the factors influencing cord growth and development are not precisely known. Objective The main objectives were to provide updated reference charts for umbilical cord length in singleton pregnancies and to evaluate potential factors affecting cord length. Methods Birth register data of 47,284 singleton pregnant women delivering in Kuopio University Hospital, Finland was collected prospectively. Gender-specific centile charts for cord length from 22 to 44 gestational weeks were obtained using generalized additive models for location, scale, and shape (GAMLSS). Gestational, fetal, and maternal factors were studied for their potential influence on cord length with single variable analysis and stepwise multiple linear regression analysis. Results Cord length increased according to gestational age, while the growth decelerated post-term. Birth weight, placental weight, pregravid maternal body mass index, parity, and maternal age correlated to cord length. Gestational diabetes and previous miscarriages were associated with longer cords, while female gender and placental abruption were associated with shorter cords. Discussion and conclusions Girls had shorter cords throughout gestation although there was substantial variation in length in both genders. Cord length associated significantly with birth weight, placental weight, and gestational age. Significantly shorter cords were found in women with placental abruption. This important finding requires further investigation.

Objective To identify risk factors for true umbilical cord knot and to evaluate its association with fetal death, premature birth, low birth weight, small-for-gestational-age (SGA) infants, low Apgar score at 1 and 5 minutes, fetal venous pH of 7.15 or lower, and need for neonatal intensive care in singleton pregnancies. Methods The total population of women who delivered at Kuopio University Hospital, Kuopio, Finland, between January 2000 and August 2012 was reviewed. Risk factors for umbilical cord knot and its association with adverse pregnancy outcome were evaluated separately among women with and without true cord knot via logistic regression analysis. Results Overall, 340 (1.2%) of 27 537 singleton pregnancies were affected by umbilical cord knot, with increased incidence associated with advanced maternal age, multiparity, previous spontaneous abortion, polyhydramnios, and diabetes mellitus. Umbilical cord knot was associated with a 1.58-, 8.08-, 3.90-, 3.17-, 1.67-, and 2.00-fold increased risk of neonatal intensive care, fetal death, premature birth, SGA infants, and low Apgar score at 1 and 5 minutes, respectively. Conclusion True umbilical cord knot is relatively common and is associated with increased incidence of SGA infants, premature birth, need for neonatal intensive care, and fetal death.

Aim To estimate the transmission of maternal vaginal microbiota to neonates during term delivery, focusing on Lactobacillus flora in relation to various obstetric clinical factors. Methods Fifty consecutive pregnant healthy women with singleton term pregnancies and their newborn infants. Vertical transmission of Lactobacillus flora to the newborn during delivery was evaluated in 45 mother–newborn pairs. Results Lactobacillus-dominant mixed flora was detected in 90% (N = 45) of vaginal samples, but only in 28% (N = 14) of neonatal cultures (transmission rate 31%). All neonates with Lactobacillus-dominant mixed flora had findings similar to those in maternal cultures. Cocci-dominant flora was the most common finding in neonates. Administration of antibiotics to the mother during the intrapartum period before birth and duration of rupture of membranes (ROM), regardless of maternal antibiotic treatment, were associated significantly with a decreased transmission rate of Lactobacillus-dominant mixed flora to neonates. Conclusion Maternal intrapartum antibiotics and prolonged expectant management after ROM were associated with decreased transmission rate of vaginal Lactobacillus flora to the neonate during birth. As early colonization of Lactobacillus flora may have a preventive role in the development of allergic diseases later, the significance of intrapartum prophylactic antibiotics needs to be highlighted in forthcoming studies, especially as regards immunological development of the offspring.

To cite this article: Mustonen K, Keski-Nisula L, Vaarala O, Pfefferle PI, Renz H, Riedler J, Dalphin J-C, Buechele G, Lauener R, Braun-Fahrlander C, von Mutius E, Pekkanen J and the PASTURE Study Group. Few associations between high-sensitivity C-reactive protein and environmental factors in 4.5-year-old children. Pediatr Allergy Immunol 2012: 00. ABSTRACT: Background: Low-grade inflammation in early childhood might protect from allergic diseases later in life. Our aim was to examine the effects of different environmental factors on low-grade inflammation measured with serum high-sensitivity C-reactive protein (hsCRP) at the age of 4.5 years. Methods: The high-sensitivity CRP values (n = 653) and serum-specific IgE concentrations were measured from 4.5-year-old children in rural areas in five European countries (Austria, Finland, France, Germany, and Switzerland). Children belonged to the prospective multi-center PASTURE birth cohort. Data on early and current farming environment and domestic animal exposure were collected by questionnaires. Results: Females as well as obese or very obese children at age of 4.5 years had higher hsCRP values than males (aOR 1.84 95% CI 1.27-2.66) and healthy weight children (aOR 4.47 95% CI 1.94-10.31), respectively. Levels were lowest in the summer. Few associations were detected between hsCRP values and farm environmental factors or atopic sensitization. However, there was evidence of children with low levels of hsCRP (below the detection limit) who had increased prevalence of sensitization to inhaled and seasonal allergens. Among non-sensitized children, spending time in stables was associated with reduced hsCRP (15 min-10 h aOR 0.40 95% CI 0.16-0.96 and

Summary Background The effect of labour and different labour-related factors on the cord blood (CB) cell cytokine production is still relatively unknown. Objective To study the relationships between the production of IL-5, IL-10 and IFN-γ in CB samples and maternal, early neonatal and birth-related factors. Methods Whole-blood samples were collected after birth (n=423) and they were stimulated for 24 and 48 h with a combination of phorbol ester and ionomycin. Production of IL-5, IL-10 and IFN-γ was determined using ELISA. Maternal, early neonatal and birth-related variables were recorded prospectively during pregnancy, and during and after delivery. Results After multivariable adjustment for confounders, the strongest predictor of IL-5, IL-10 and IFN-γ production in CB cell samples was the season of birth. Children born in the spring had significantly lower cytokine responses compared with those born in the fall. IL-5 production was inversely associated with female gender of the child and maternal smoking. If corrections for white blood cell (WBC) counts were not performed, IL-5 production was also significantly associated with the mode of delivery. Respectively, the production of IL-10 and IFN-γ was inversely associated with prostaglandin induction before birth. Conclusion Environmental exposure to pollen and ultraviolet irradiation during gestation may have an effect on the cytokine profile of the offspring in CB because children born in the spring or winter showed the lowest IL-5, IL-10 and IFN-γ responses. The production of IL-10 and IFN-γ was also inversely associated with prostaglandin labour induction before birth. Other labour-related factors were not significantly associated with production of IL-5, IL-10 and IFN-γ after WBC count correction. Cite this as: L. Keski-Nisula, M. H. J. Lappalainen, K. Mustonen, M.-R. Hirvonen, P. I. Pfefferle, H. Renz, J. Pekkanen and M. Roponen, Clinical & Experimental Allergy, 2010 (40) 1658–1668.

Problem The aim of this study was to investigate maternal pre-eclampsia (PE), placental abruption (PA) and atopy among offspring. Method of study Obstetric data was recorded from 378 women who were included into the Caesarean delivery birth cohort during 1990–1992. When their children were 15–17 years old skin prick tests (SPTs) and inhalant allergen-specific (IAS) immunoglobulin E (IgE) were determined among offspring. Results Adolescents whose mothers had either PE or PA at the time of delivery had more atopy and especially more severe atopy as measured by the incidence of SPTs positive for ≥5 allergens (RR: 4.28, 95% CI: 1.54–11.92; P

Background Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life. Objective We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring. Methods Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990–1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests. Results Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56–13.0]; OR, 2.53 [95% CI, 1.19–5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44–22.03]; OR, 3.37 [95% CI, 1.46–7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring. Conclusion The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children

The purpose of this study was to explore the maternal risk profile and obstetric outcome in pregnancies affected by placenta previa. Retrospective case-control study involved all women (93 [0.37%] women with diagnosed placenta previa and 24,857 unaffected controls) who gave birth to singleton infants at Kuopio University Hospital between the years 1989 and 2000. Grand multiparity, infertility problems, and advanced maternal age were independent risk factors of placenta previa, with adjusted relative risks of 5.8, 3.7, and 2.4, respectively. Most women with placenta previa (88.2%) underwent cesarean delivery before term. They also more often had velamentous umbilical cord insertion (7.5%) and higher placental-to-birthweight ratios than the controls. Placenta previa was associated with risks of preterm delivery, low birthweight infants, and need for neonatal intensive care, at odds ratios of 27.7, 7.4, and 3.4, respectively. In conclusion, placenta previa is an infrequent pregnancy complication associated with multiparity, advanced maternal age, infertility problems, elevated placental ratio, and velamentous umbilical cord insertion.

Objective: To study whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) affects individual susceptibility to the development of placental abruption during pregnancy. Methods: One hundred and sixteen pregnant women with placental abruption and 113 healthy controls were genotyped for Glu298Asp polymorphism in the eNOS gene. Chi-square analysis was used to assess the differences in genotype and allele frequencies between the two groups. Results: A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 66.8% in the abruption group and 68.1% in the control group (OR 0.94, 95% CI: 0.64–1.39; p = 0.76). The genotype distribution of the eNOS polymorphism was also found to be statistically similar (p = 0.72). Conclusions: The observed genotype data in subjects from eastern Finland suggest that the Glu298Asp polymorphism of the eNOS gene does not contribute to placental abruption in this population.

Background Sex hormones may be associated with the risk of onset of asthma. Objective To study the association between maternal sex hormone concentrations during early pregnancy and the risk of asthma among offspring. Methods A case-control study of 129 asthmatic children and 125 control children 5 to 6 years of age. Maternal sera in early pregnancy were obtained from the Finnish Maternal Cohort serum bank. Results The means of serum progesterone and estradiol and free estradiol in mothers of asthmatic and control children were 81.0 and 82.8 nmol/L ( P = .60), 7.87 nmol/L and 7.65 nmol/L ( P = .99), and 149.5 pmol/L and 148.0 pmol/L ( P = .95), respectively. There were also no differences in the mean concentrations of maternal sex hormones according to the presence of allergic rhinitis or atopic eczema among the children. Conclusions The current results do not support an association between maternal sex hormone concentrations during early pregnancy and onset of allergic disease in early childhood.

The presence of inflammation in decidual and myometrial samples as defined by histopathologic examination and the association between the myometrial inflammation and different maternal infectious morbidity and labor-related clinical variables were evaluated in 648 consecutive women who underwent cesarean section at various gestational periods. Altogether, 1,205 histologic (559 decidual and 646 myometrial) samples were studied. In normal pregnancies, myometrial inflammatory lesions were detected rarely before parturition, indicating their abnormality in these cases. After ruptured fetal membranes with advanced cervical dilatation and in patients with clinical chorioamnionitis, myometrial samples commonly were infiltrated by leukocytes, up to moderate and marked densities. Moderate to marked myometrial inflammation showed no diagnostic value in high-risk term parturients for the prediction of postoperative endometritis. Our study is the first to show the frequency of myometrial inflammation in nonselected consecutive pregnant women and, thus, is important for better understanding the myometrial inflammatory response during human parturition.