Multifactorial prevention program for cardiovascular disease in primary care: hypertension status and effect on mortality.

The aim of this study was to investigate if mortality during a 13-year follow-up varied between normotensive subjects, screen-detected hypertensive subjects, and subjects with antihypertensive medication at baseline. A population-based screening and intervention program identified 2659 apparently healthy, middle-aged cardiovascular-risk persons in southwestern Finland. Screen-detected hypertension was verified by home blood pressure measurements. Lifestyle counseling was provided for all participants and preventive medications were started or intensified if needed. All-cause and cardiovascular mortality were obtained from the official statistics. Screen-detected hypertension was diagnosed in 17% of the participants, 51% were normotensive and 32% had antihypertensive medication at baseline. The screen-detected hypertensives had higher mean blood pressure and cholesterol levels than the two other groups. Altogether 289 subjects died during the follow-up, 83 (29%) from cardiovascular disease. Those with screen-detected hypertension had decreased cardiovascular mortality risk compared to the medicated hypertensives [sHR 0.40 (95% CI: 0.19 to 0.88, p = 0.023)], and comparable with that of the normotensives [sHR 0.53 (95% CI: 0.24 to 1.15)]. Newly diagnosed diabetes at baseline was a powerful predictor of cardiovascular mortality [sHR 2.71 (95% CI: 1.57 to 4.69)]. Early detection of hypertension and timely multifactorial intervention seem to be important in preventing hypertension-related mortality.

Five-to-Fifteen-Parental Perception of Developmental Profile from Age 5 to 8 Years in Children Born Very Preterm.

Children born very preterm have increased risk of developmental difficulties. We examined the parental perception of developmental profile of children born very preterm at 5 and 8 years by using the parental questionnaire Five-to-Fifteen (FTF) compared to full-term controls. We also studied the correlation between these age points. The study included 168 and 164 children born very preterm (gestational age < 32 weeks and/or birth weight ≤ 1500 g) and 151 and 131 full-term controls. The rate ratios (RR) were adjusted for sex and the father's educational level. At 5 and 8 years, children born very preterm were more likely to have higher scores (more difficulties) compared to controls in motor skills (RR = 2.3, CI 95% = 1.8-3.0 at 5 years and RR = 2.2, CI 95% = 1.7-2.9 at 8 years), executive function (1.7, 1.3-2.2 and 1.5, 1.2-2.0), perception (1.9, 1.4-2.5 and 1.9, 1.5-2.5), language (1.5, 1.1-1.9 and 2.2, 1.7-2.9), and social skills (1.4, 1.1-1.8 and 2.1, 1.6-2.7), and at 8 years in learning (1.9, 1.4-2.6) and memory (1.5, 1.2-2.0). There were moderate-to-strong correlations (r = 0.56-0.76, p < 0.001) in all domains between 5 and 8 years in children born very preterm. Our findings suggest that FTF might help to earlier identify children at the greatest risk of incurring developmental difficulties persisting to school-age.

Renal hyperfiltration revisited-Role of the individual body surface area on mortality.

BACKGROUND: Higher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. METHODS: A population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005-2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. RESULTS: The higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. CONCLUSIONS: Higher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.

Pre-pregnancy body surface area and risk for gestational diabetes mellitus.

AIMS: To evaluate the effect of the pre-pregnancy body surface area (BSA) on the risk of gestational diabetes mellitus (GDM). METHODS: The study population consisted of all primiparous women with singleton pregnancies (n = 328,892) without previously diagnosed diabetes or chronic hypertension in Finland between 2006 and 2019. The information on GDM, oral glucose tolerance test (OGTT) results, and maternal backgrounds was derived from the Finnish Medical Birth Register. The pre-pregnancy BSA was calculated by using the Mosteller formula. Logistic regression models were used to estimate the association between BSA and GDM/ OGTT separately by the body mass index groups. RESULTS: A lower BSA predicted an increased risk for GDM and pathological OGTT among the underweight (b = - 2.69, SE = 0.25, p < 0.001; b = - 2.66, SE = 0.23, p < 0.001, respectively) pregnant women, and normal weight (b = - 0.30, SE = 0.10, p = 0.002; b = - 0.67, SE = 0.09, p < 0.001, respectively) pregnant women; and pathological OGTT among the overweight (b = - 0.31, SE = 0.10, p = 0.001) pregnant women. Within the obese class II or greater, a higher BSA predicted a higher risk for GDM (b = 0.74, SE = 0.12, p < 0.001) and pathological OGTT (b = 0.79, SE = 0.13, p < 0.001). Maternal smoking predicted a significantly higher risk of GDM and pathological OGTTs in almost all body mass index groups. CONCLUSION: This study showed that in comparison with women with a higher BSA, underweight, and normal weight pregnant women with a smaller BSA may be more susceptible to GDM and have a pathological OGTT.

New insights into smoking and urinary tract infections during pregnancy using pregnancy-pair design: A population-based register study.

INTRODUCTION: Pregnancy itself predisposes to urinary tract infections (UTI). There appears to be a higher prevalence of infections and genitourinary diseases among pregnant smokers than among non-smokers. The present study is a retrospective observational register study aiming to investigate whether maternal smoking is associated with the prevalence of UTIs during pregnancy by utilizing a pregnancy-pair analysis. MATERIAL AND METHODS: Information about pregnancies and maternal smoking was obtained from the Finnish Medical Birth Register. The study sample consisted of all singleton pregnancies (n = 723 433) of women giving birth between January 2006 and December 2018 in Finland. Information on maternal smoking was collected in three categories: (1) non-smoking; (2) quit smoking during the first trimester; and (3) continued smoking throughout the pregnancy. Information about maternal UTI diagnoses during pregnancy was received from the Hospital Discharge Register and the Medical Birth Register. UTIs were categorized as lower and upper UTIs according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 diagnosis codes. Risks were calculated as odds ratios (OR) by logistic regression with 95% confidence intervals (CI) further adjusted for maternal characteristics (aOR). Finally, pregnancy-pair analyses were performed: mothers who had changed smoking status (no smoking/any smoking) between consecutive pregnancies (n = 27 246 pregnancy-pairs) were analyzed as one cluster and compared with non-smokers. RESULTS: Smokers had UTIs more often compared with the non-smokers. The association was even stronger among those who continued to smoke (aOR 1.60, 95% CI 1.51-1.70) than among those who smoked only during the first trimester (aOR 1.27, 95% CI 1.18-1.37) compared with non-smokers. In pregnancy-pair analysis, smoking was associated with upper UTIs during pregnancy (OR 1.49, 95% CI 1.05-2.12) compared with non-smokers, but after the adjustments this association was attenuated (aOR 1.27, 95% CI 0.88-1.82). No association in lower UTIs was observed in the pregnancy-pair design. CONCLUSIONS: Maternal smoking was associated with a higher prevalence of UTIs during pregnancy in the standard comparison. The observed association was fully attenuated in the pregnancy-pair analysis, in which smoking was dichotomized. This study suggests that the association between maternal smoking during pregnancy and adverse maternal health effects might be more complex than previously thought.

New theory about the pathophysiology of preeclampsia derived from the paradox of positive effects of maternal smoking.

OBJECTIVE: The aim of this study was to evaluate if maternal height affects the link between the inverse association on smoking during pregnancy and preeclampsia. STUDY DESIGN: The study population consisted of all women with singleton pregnancies (n = 803 698) in Finland during the years 2004-2018, excluding women with unknown smoking and diagnosis of prepregnancy chronic hypertension. Information on smoking and background factors were derived from the Finnish Medical Birth Register. Smoking was categorized in three classes: no, quitted in the first trimester and continued throughout the pregnancy. Information on preeclampsia was derived from the Finnish Hospital Discharge Register and the Finnish Medical Birth Register. Multiple logistic regression models were used to estimate first the association between smoking and preeclampsia, and finally whether maternal height modified the association. RESULTS: In the standard comparison, we found evidence of an association between preeclampsia and continued smoking [adjusted odds ratio = 0.74, 95% confidence interval (95% CI) = 0.67-0.81], but no association was found between quitted smoking and preeclampsia. Thus, the interaction of continued smoking and maternal height by z-scores was estimated. Among taller mothers, continued smoking was associated with a higher risk for preeclampsia than in smoking mothers with average height (ß = 0.33, SE = 0.14, P  = 0.02). CONCLUSION: Our results partly challenge the smoking-preeclampsia paradox: smoking seems not to protect tall mothers against preeclampsia. We speculate the findings through a new theory about the pathophysiology of preeclampsia. It seems that tall pregnant smokers must raise their blood pressure aggressively to ensure perfusion in the dysfunctional placenta.

Maternal smoking during pregnancy negatively affects brain volumes proportional to intracranial volume in adolescents born very preterm.

Background: Maternal smoking during pregnancy has been shown to associate with smaller frontal lobe and cerebellar volumes in brain magnetic resonance imaging (MRI) at term age in very preterm infants. The aim of this study was to examine the effect of maternal smoking during pregnancy on volumetric brain MRI findings at 13 years. We hypothesized that adverse effects of smoking during pregnancy on brain volumes are still seen during adolescence. Methods: Included adolescents were born very preterm (gestational age < 32 weeks and/or birth weight ≤ 1,500 g) between April 2004 and December 2006 at the Turku University Hospital, Finland. Information on maternal smoking status (yes or no) during pregnancy was collected from medical records and maternal questionnaires before discharge. Adolescents underwent volumetric brain MRI at 13 years of age. Image post-processing was performed with FreeSurfer. Regional volumes, cortical thickness, surface area, and curvature were computed from 33 cortical regions of interest (ROIs). Additionally, volumes were calculated for 18 subcortical regions, as well as for white matter, gray matter, and intracranial volume. We normalized quantified absolute volumes for head size by dividing volumes with corresponding intracranial volumes. false discovery rate (FDR) correction for multiple comparisons across regions was used. Results: A total of 9/44 (21%) adolescents had been exposed to maternal smoking during pregnancy. No statistically significant differences in absolute volumes were observed between the groups (p > 0.05). Regarding volumes proportional to intracranial volume, the adolescents in the exposed group exhibited smaller gray matter volumes in the inferotemporal (FDR corrected p = 0.022) and parahippocampal (p = 0.018) regions compared to the unexposed group. The surface area in the exposed group was also smaller in the parahippocampal (p = 0.046) and postcentral (p = 0.046) regions compared to the unexposed group. No statistically significant differences after correction for multiple comparisons were found for either curvature or cortical thickness between the groups. Conclusion: Maternal smoking exposure during pregnancy may have long-term effects on brain volumes up to 13 years in adolescents born very preterm. Our findings emphasize the importance of smoking-free pregnancy.

Special Issue on the Effects of Prenatal Smoking/Nicotine Exposure on the Child's Health.

Smoking increases the risk of negative pregnancy and perinatal outcomes and may have negative effects on a child's short and long-term health [...].

Design of a prospective follow-up study on early parenthood and smoking behaviour during pregnancy in Finnish primary healthcare.

Aims: The primary aim of the study is to explore different factors affecting parents' smoking behaviour, and especially how smoking may be connected with individual differences in the psychological process of becoming a parent. In the current paper, we present the study design together with basic information on the study population. Methods: The Central Satakunta Maternity and Child Health Clinic (KESALATU) Study is an ongoing prospective follow-up study in primary healthcare of the Satakunta region of southwest Finland. Families were recruited during their first maternity clinic visit between 1 September 2016 and 31 December 2019, and participation will continue until the child is 1.5 years of age. The study combines different sources and types of data: e.g. routine data obtained from primary healthcare clinic records, specific parental self-report data and data from a new exhaled carbon monoxide meter indicating maternal smoking. The data are collected using frequently repeated assessments both during pregnancy and postnatally. The methods cover the following areas of interest: family background factors (including smoking and alcohol use), self-reported parental-foetal/infant attachment and mentalization, self-reported stress, depression and quality of life. Results: 589 pregnant women and their partners were asked to participate in the study during the collection time period. The final study population consisted of 248 (42.1%) pregnant women and 160 (27.1%) partners. Conclusions: The new methods and study design have the potential to increase our understanding about the link between early parenting psychology, prenatal psychosocial risk factors and parental health behaviour.

The feasibility and outcome of a community-based primary prevention program for cardiovascular disease in the 21st century.

OBJECTIVE: There is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality. This study aimed to evaluate the effectiveness of a primary care CVD prevention program on mortality during a 13-year follow-up. DESIGN: A risk factor survey was sent, followed by a nurse-led lifestyle counselling to respondents with at least one CVD risk factor, and a general practitioner's (GP) appointment for high-risk persons. Screening and interventions were performed during 2005-2006. SETTING: A public health care centre in the town of Harjavalta, Finland. SUBJECTS: All home-dwelling 45-70-year old inhabitants without manifested CVD or diabetes. MAIN OUTCOME MEASURES: All-cause and CVD mortality. RESULTS: Altogether 74% (2121/2856) inhabitants responded to the invitation. The intervention was received by 1465 individuals (52% of the invited population): 398 risk persons had an appointment with a nurse, followed by an appointment with a GP for 1067 high-risk persons. During the follow-up, 370 persons died. Mortality among the non-respondents was twofold compared to the participants'. In subjects who received the intervention, the age- and gender-adjusted hazard ratio for all-cause mortality was 0.44 (95% CI: 0.36 to 0.54) compared to the subjects who did not receive the intervention. CONCLUSIONS: Reducing mortality is possible in a primary care setting by raising health awareness in the community with screening, by targeted lifestyle counselling and evidence-based preventive medication for persons at high risk for CVD. Subjects not willing to participate in health surveys have the worst prognosis.Key PointsPreviously, there is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality.With a stepwise screening program it is possible to scale the magnitude of CVD prevention in the community.Reducing mortality in a community is possible by screening, targeted lifestyle counselling, and by evidence-based preventive medication for high-risk persons.Subjects not willing to participate in health surveys have the worst prognosis.

Nicotine Replacement Therapy during Pregnancy and Child Health Outcomes: A Systematic Review.

Tobacco smoking in pregnancy is a worldwide public health problem. A majority of pregnant smokers need assistance to stop smoking. Most scientific societies recommend nicotine replacement therapy (NRT) during pregnancy but this recommendation remains controversial because of the known fetal toxicity of nicotine. The objective of this systematic review was to provide an overview of human studies about child health outcomes associated with NRT use during pregnancy. The electronic databases MEDLINE, the Cochrane Database, Web of Science, and ClinicalTrials.gov were searched from the inception of each database until 26 December 2020. A total of 103 articles were identified through database searching using combination of keywords. Out of 75 screened articles and after removal of duplicates, ten full-text articles were assessed for eligibility and five were included in the qualitative synthesis. NRT prescription seems to be associated with higher risk of infantile colic at 6 months as in case of smoking during pregnancy, and with risk of attention-deficit/hyperactivity disorder. No association between NRT during pregnancy and other infant health disorders or major congenital anomalies has been reported. Well-designed controlled clinical trials with sufficient follows-up are needed to provide more information on the use of NRT or other pharmacotherapies for smoking cessation during pregnancy on post-natal child health outcomes.

The Effect of Smoking during Pregnancy on Severity and Directionality of Externalizing and Internalizing Symptoms: A Genetically Informed Approach.

The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). Principal component analysis of externalizing and internalizing behavior, assessed with the Child Behavior Checklist and Teacher Report Form, was used to create symptom severity and directionality scores. The variance in severity and directionality scores was primarily a function of differences between siblings (71% and 85%, respectively) rather than differences across families (29% and 15%, respectively). The severity score that combines externalizing and internalizing symptom severity was not associated with SDP. However, a significant within-family effect of SDP on symptom directionality (b = 0.07, p = 0.04) was observed in the sibling comparison model. The positive directionality score indicates that SDP is associated with differentiation of symptoms towards externalizing rather than internalizing symptoms after controlling for familial confounds with a sibling comparison model. This supports a potentially causal relationship between SDP and externalizing behavior.

Maternal Smoking and Hospital Treatment During Pregnancy.

INTRODUCTION: Previous research suggests that young maternal age, smoking, hospitalization during a previous pregnancy, and poor self-rated health could be risk factors for prenatal hospitalization. METHODS: The objective of this retrospective observational register study was to investigate if maternal smoking during pregnancy is associated with mother's need for hospital treatment during pregnancy. The study population consists of all singleton pregnancies (n = 961 127) in 1999-2015 in Finland. Information on maternal smoking was received from the Medical Birth Register in three classes: nonsmoker, quit smoking in the first trimester, and continued smoking throughout the pregnancy. These data were linked with the Hospital Discharge Register data and analyzed according to ICD-10 chapters. RESULTS: 10.7% of women continued to smoke after the first trimester. After adjusting for confounding factors women in both smoking groups had more hospital treatment compared with nonsmokers. Especially outpatient treatment was more common among mothers who continued to smoke compared to those who quit smoking in the first trimester in several ICD-10 chapters. Compared to non-smokers, aOR for mental and behavioral disorders (F00-F99) was 2.14 (95% confidence interval 2.00-2.30) in the quit smoking group and 3.88 (3.71-4.06) in the continued smoking group. Similarly, aOR for respiratory diseases (J00-J99) was 1.26 (1.15-1.39) and 1.61 (1.52-1.71), respectively and aOR for genitourinary diseases (N00-N99) was 1.10 (1.03-1.17) and 1.29 (1.23-1.35), respectively. Some similar findings were made also in inpatient care. Some similar findings were made also in inpatient care. CONCLUSIONS: Women who smoke during pregnancy seem to require more hospital care for various reasons. These findings emphasize the importance of actions for smoking cessation during pregnancy and women should be encouraged to quit as early as possible. IMPLICATIONS: Maternal smoking during pregnancy is associated with greater rates of both outpatient and inpatient hospital care during pregnancy. Women who quit smoking had a similar risk for hospital care during pregnancy with nonsmokers in certain diagnosis chapters, which is very motivational and could be used as an informational tool in prenatal clinics to encourage smoking cessation as it is never too late to quit smoking during pregnancy.

Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking During Pregnancy: A Multi-rater Approach.

INTRODUCTION: Maternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors. AIMS AND METHODS: The Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7-16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form). RESULTS: The variability in disruptive behavior was primarily a function of within-family differences (66%-100%). Consistent with prior genetically informed approaches, the SDP-disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses. DISCUSSION: These findings suggest that familial confounding likely plays a complex role in the SDP-disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP. IMPLICATIONS: Our study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP-behavior associations.