Mika Gissler

Use of antimicrobials and risk of type 1 diabetes in a population-based mother–child cohort

Aims/hypothesisThe aim of this study was to investigate whether the use of antimicrobials is associated with the risk of childhood type 1 diabetes.Materials and methodsThe study population included all children born in Finland between 1996 and 2000 who were diagnosed with type 1 diabetes by the end of 2002. For each case (n=437), four matched controls were selected. Data on diabetes and the maternal use of antimicrobials was derived from nationwide registries.ResultsMaternal use of phenoxymethyl penicillins (odds ratio [OR]=1.70, 95% CI 1.08–2.68, p=0.022) or quinolone antimicrobials (OR=2.43, 95% CI 1.16–5.10, p=0.019) before pregnancy was associated with an increased risk of type 1 diabetes in the child, whereas the use of other specific antimicrobials was not related to the risk. The risk was also higher among mother–child pairs where macrolides were used both by the mother before pregnancy and by the child, compared with pairs where neither used macrolides (OR=1.76, 95% CI 1.05–2.94, p=0.032). Maternal use of antimicrobials during pregnancy was not associated with an increased risk. The high use of antimicrobials by the child (more than seven vs seven or less purchases) was related to greater risk (OR=1.66, 95% CI 1.24–2.24, p=0.001).Conclusions/interpretationOverall, the use of antimicrobials before pregnancy, during pregnancy or during childhood was not related to the risk of childhood type 1 diabetes. However, the use of some specific antimicrobials by the mother before pregnancy and by the child may be associated with an increased risk. Further studies are needed to confirm these associations and to elucidate the underlying mechanisms of action.

Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987–2010

Introduction: People with severe mental illness have increased risk for premature mortality and thus a shorter life expectancy. Relative death rates are used to show the excess mortality among patients with mental health disorder but cannot be used for the comparisons by country, region and time. Methods: A population-based register study including all Swedish patients in adult psychiatry admitted to hospital with a main diagnosis of schizophrenia, bipolar or unipolar mood disorder in 1987–2010 (614 035 person-years). Mortality rates adjusted for age, sex and period were calculated using direct standardization methods with the 2010 Swedish population as standard. Data on all residents aged 15 years or older were used as the comparison group. Results: Patients with severe mental health disorders had a 3-fold mortality compared to general population. All-cause mortality decreased by 9% for people with bipolar mood disorder and by 26–27% for people with schizophrenia or unipolar mood disorder, while the decline in the general population was 30%. Also mortality from diseases of the circulatory system declined less for people with severe mental disorder (−35% to − 42%) than for general population (−49%). The pattern was similar for other cardiovascular deaths excluding cerebrovascular deaths for which the rate declined among people with schizophrenia (−30%) and unipolar mood disorder (−41%), unlike for people with bipolar mood disorder (−3%). Conclusions: People with mental health disorder have still elevated mortality. The mortality declined faster for general population than for psychiatric patients. More detailed analysis is needed to reveal causes-of-death with largest possibilities for improvement.

Variations in very preterm birth rates in 30 high-income countries: are valid international comparisons possible using routine data?

Concerns about differences in registration practices across countries have limited the use of routine data for international very preterm birth (VPT) rate comparisons.

At what age does the risk for adverse maternal and infant outcomes increase? Nationwide register-based study on first births in Finland in 2005–2014

It is poorly understood if there are specific ages at which adverse outcomes during pregnancy and childbirth start to increase (threshold‐ages). The purpose of this study was to examine at which maternal ages the use of maternity care and the risks for adverse maternal and infant outcomes increase.

Lichen sclerosus and risk of cancer

Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population‐based Finnish Cancer Registry data to further study this connection.

Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium

Importance Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is a need to better understand their safety. Objective To examine the risk of congenital malformations associated with intrauterine exposure to stimulants. Design, Setting, and Participants Cohort study of the Medicaid-insured population in the United States nested in the 2000-2013 US Medicaid Analytic eXtract, with follow-up of safety signals detected in the Medicaid Analytic eXtract data using the Nordic Health registries (2003-2013) (Denmark, Finland, Iceland, Norway, and Sweden). A total of 1 813 894 publicly insured pregnancies in the United States and 2 560 069 singleton pregnancies in the 5 Nordic countries ending in live births were included. Relative risks were estimated accounting for underlying psychiatric disorders and other potential confounders. Relative risk estimates for the US and Nordic data were pooled using a fixed-effects meta-analytic approach. The study was conducted from July 1, 2015, to March 31, 2017. Exposures Methylphenidate and amphetamines dispensed during the first trimester. Main Outcomes and Measures Major congenital malformations and subgroup of cardiac malformations. Results In the US data, of the 1 813 894 pregnancies evaluated, 35.0 per 1000 infants not exposed to stimulants were diagnosed as having congenital malformations, compared with 45.9 per 1000 infants for methylphenidate and 45.4 for amphetamines. For cardiac malformations, the risks were 12.7 (95% CI, 12.6-12.9), 18.8 (95% CI, 13.8-25.6), and 15.4 (95% CI, 12.5-19.0) per 1000 infants, respectively. The adjusted relative risks for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations. No increased risks were observed for amphetamines: 1.05 (95% CI, 0.93-1.19) for any malformations and 0.96 (95% CI, 0.78-1.19) for cardiac malformations. Findings were confirmed in sensitivity analyses accounting for proxies of unmeasured confounders and increasing the specificity of the exposure and outcome definitions. Replication of the analyses for methylphenidate using the Nordic data including 2 560 069 pregnancies yielded a relative risk of 1.28 (95% CI, 0.83-1.97) for cardiac malformations, resulting in a pooled estimate of 1.28 (95% CI, 1.00-1.64). Conclusions and Relevance These findings suggest a small increase in the risk of cardiac malformations associated with intrauterine exposure to methylphenidate but not to amphetamines. This information is important when weighing the risks and benefits of alternative treatment strategies for attention-deficit/hyperactivity disorder in women of reproductive age and during early pregnancy.

Is underage abortion associated with adverse outcomes in early adulthood? A longitudinal birth cohort study up to 25 years of age

STUDY QUESTIONnIs underage abortion associated with adverse socioeconomic and health outcomes in early adulthood when compared with underage delivery?nnnSUMMARY ANSWERnUnderage abortion was not found to be associated with mental health problems in early adulthood, and socioeconomic outcomes were better among those who experienced abortion compared with those who gave birth.nnnWHAT IS KNOWN ALREADYnTeenage motherhood has been linked with numerous adverse outcomes in later life, including low educational levels and poor physical and mental health. Whether abortion at a young age predisposes to similar consequences is not clear.nnnSTUDY DESIGN, SIZE, DURATIONnThis nationwide, retrospective cohort study from Finland, included all women born in 1987 (n = 29 041) and followed until 2012.nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnWe analysed socioeconomic, psychiatric and risk-taking-related health outcomes up to 25 years of age after underage (<18 years) abortion (n = 1041, 3.6%) and after childbirth (n = 394, 1.4%). Before and after conception analyses within the study groups were performed to further examine the association between abortion and adverse health outcomes. A group with no pregnancies up to 20 years of age (n = 25 312, 88.0%) served as an external reference group.nnnMAIN RESULTS AND THE ROLE OF CHANCEnWe found no significant differences between the underage abortion and the childbirth group regarding risks of psychiatric disorders (adjusted odds ratio 0.96 [0.67-1.40]) or suffering from intentional or unintentional poisoning by medications or drugs (1.06 [0.57-1.98]). Compared with those who gave birth, girls who underwent abortion were less likely to achieve only a low educational level (0.41 [95% confidence interval 0.31-0.54]) or to be welfare-dependent (0.31 [0.22-0.45]), but more likely to suffer from injuries (1.51 [1.09-2.10]). Compared with the external control group, both pregnancy groups were disadvantaged already prior to the pregnancy. Psychiatric disorders and risk-taking-related health outcomes, including injury, were increased in the abortion group and in the childbirth group similarly on both sides of the pregnancy.nnnLIMITATIONS, REASONS FOR CAUTIONnThe retrospective nature of the study remains a limitation. The identification of study subjects in order to collect additional data was not allowed for ethical reasons. Therefore further confounding factors, such as the intentionality of the pregnancy, could not be checked.nnnWIDER IMPLICATIONS OF THE FINDINGSnPrevious studies have found that abortion is not harmful to mental health in the majority of adult women. Our study adds to the current understanding in suggesting that this is also the case concerning underage girls. Furthermore, women with a history of underage abortion had better socioeconomic outcomes compared with those who gave birth. These findings can be generalized to settings of high-quality social and health-care services, where abortion is accessible and affordable to all citizens. Social and health-care professionals who care for and counsel underage girls facing unplanned pregnancy should acknowledge this information.nnnSTUDY FUNDING/COMPETING INTERESTSnThis study was financially supported by the Finnish Cultural Foundation and the Päivikki and Sakari Sohlberg Foundation. The researchers are independent of funders and the funders had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors have no competing interests.

Risks of Adverse Perinatal Outcomes after Repeat Terminations of Pregnancy by their Methods: a Nationwide Register‐based Cohort Study in Finland 1996–2013

BACKGROUNDnRepeat terminations of pregnancy (TOPs) are associated with an increased risk of adverse outcomes in the subsequent birth. The perinatal outcomes after repeat TOPs by their methods have not yet been properly studied. This study aimed to examine perinatal outcomes in subsequent pregnancy among the women with a singleton birth and a history of TOPs.nnnMETHODSnAll the first-time mothers (nxa0=xa0419xa0879) with a singleton birth during 1996-2013 in Finland were identified from the Medical Birth Register and linked to the Abortion Register. Adjusted multivariable logistic regression analysis was used to estimate risks of adverse perinatal outcomes.nnnRESULTSnThe increased incidence of adverse perinatal outcomes was found with increasing number of surgical TOPs. After adjusting for confounders, the women with one surgical TOP had slightly increased but significant odds of 1.07 (95% CI 1.02, 1.13) for being small for gestational age compared with the women having no TOP. A significantly high risk for extremely preterm birth (OR 1.51, 95% CI 1.03, 2.23) was found among the women having had repeat surgical TOPs when compared to the women with no TOP. Non-significant risks were found for adverse perinatal outcomes after womens repeat surgical TOPs than repeat medical TOPs.nnnCONCLUSIONnInformation regarding the consequences of repeat induced TOPs will be significant in sexual health education as well as counselling women after first termination.

Neonatal outcomes after the obstetric near-miss events uterine rupture, abnormally invasive placenta and emergency peripartum hysterectomy - prospective data from the 2009-2011 Finnish NOSS study.

Neonatal outcomes after the maternal obstetric near‐miss complications of uterine rupture, abnormally invasive placenta, and emergency peripartum hysterectomy were assessed.

Maternal Smoking During Pregnancy and the Risk of Psychiatric Morbidity in Singleton Sibling Pairs

Abstract Introduction: Maternal smoking during pregnancy has been associated with an increased risk for psychiatric morbidity. We further studied this with Finnish siblings to control for genetic/familial factors. Methods: From the Finnish Medical Birth Register, sibling pairs were selected as the first two children born 1987–1995 to the same mother (n = 150 168 pairs), along with information on maternal smoking (no smoking/smoking). Information on the children’s psychiatric diagnoses related to outpatient care visits (1998–2013) and inpatient care (1987–2013), and the mothers’ psychiatric morbidity (1969–2013) was derived from the Finnish Hospital Discharge Register. The first pair analysis compared siblings of mothers who only smoked in the first pregnancy (Quitters, 4.7%) and mothers who smoked in both pregnancies (Smokers, 9.6%); the second analysis included mothers who smoked only in the second pregnancy (Starters, 3.3%) and mothers who did not smoke in either pregnancy (Nonsmokers, 77.5%). Smoking information was missing for 5.0% of pairs. Psychiatric morbidity of the siblings and mother was included in the statistical analyses. Results: The risk of psychiatric diagnoses was significantly lower for the second child of quitters (adjusted OR 0.77, 95% CI 0.72–0.83) compared to the risk among smokers. A higher risk for psychiatric diagnoses was found for the second child of starters (1.39, 1.30–1.49) compared to the risk among nonsmokers. The effect of smoking was more robust for externalizing diagnoses. Conclusions: Maternal smoking was independently associated with a higher risk for psychiatric morbidity in children, even when controlling thoroughly for genetic and familial factors. Implications: Maternal smoking during pregnancy has an independent effect on the risk of psychiatric morbidity in children, even after controlling for non-measurable genetic/familial factors by using a sibling pair design. The effect of maternal smoking was robust for externalizing diagnoses. Maternal smoking during pregnancy had an effect on diagnoses both in outpatient and inpatient care.