Marja Vääräsmäki

Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study.

CONTEXT There are only a few large prospective studies involving evaluation of the effect of maternal thyroid dysfunction on offspring and observations are inconsistent. OBJECTIVE The objective of the study was to investigate the effects of thyroid dysfunction or antibody positivity on perinatal outcome. SETTING AND PARTICIPANTS The study included prospective population-based Northern Finland Birth Cohort 1986 including 9247 singleton pregnancies. First-trimester maternal serum samples were analyzed for thyroid hormones [TSH, free T(4) (fT4)] and antibodies [thyroid-peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab)]. Mothers were classified by their hormone and antibody status into percentile categories based on laboratory data and compared accordingly. MAIN OUTCOMES Outcomes were perinatal mortality, preterm delivery, absolute and gestational age-adjusted birth weight, and absolute and relative placental weight. RESULTS The offspring of TPO-Ab- and TG-Ab-positive mothers had higher perinatal mortality, which was not affected by thyroid hormone status. Unadjusted and adjusted (for maternal age and parity) risk for increased perinatal mortality was an odds ratio of 3.1 (95% confidence interval 1.4-7.1) and 3.2 (1.4-7.1) in TPO-Ab- and 2.6 (1.1-6.2) and 2.5 (1.1-5.9) in TG-Ab-positive mothers. TPO-Ab-positive mothers had more large-for-gestational age infants (2.4 vs. 0.8%, P = 0.017), as did mothers with low TSH and high fT4 concentrations vs. reference group (6.6 vs. 2.5%, P = 0.045). Significantly higher placental weights were observed among mothers with low TSH and high fT4 or high TSH and low fT4 levels as well as among TPO-Ab-positive mothers. CONCLUSIONS First-trimester antibody positivity is a risk factor for perinatal death but not thyroid hormone status as such. Thyroid dysfunction early in pregnancy seems to affect fetal and placental growth.

Elevated Blood Pressure in Pregnancy and Subsequent Chronic Disease Risk

Background— Preeclampsia, a new-onset hypertensive disorder of pregnancy, is associated with lifetime cardiovascular disease risk, but less is known about risk after other pregnancy-related hypertension. Methods and Results— The Northern Finland Birth Cohort 1966 included all expected births from 1 year (N=12 055 women). Blood pressure measurements and other prospective data were determined from prenatal care records and questionnaires for 10 314 women. Subsequent diagnoses were ascertained from Finnish registries (average follow-up, 39.4 years). Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) estimate risks in hypertensive women compared with normotensive women. Hypertension during pregnancy was associated with increased risk of subsequent cardiovascular disease and arterial hypertension. Women with chronic hypertension and superimposed preeclampsia/eclampsia had high risk for future diseases. Gestational hypertension was associated with increased risk of ischemic heart disease (HR, 1.44 [95% CI, 1.24–1.68]), myocardial infarcts (HR, 1.75 [95% CI, 1.40–2.19]), myocardial infarct death (HR, 3.00 [95% CI, 1.98–4.55]), heart failure (HR, 1.78 [95% CI, 1.43–2.21]), ischemic stroke (HR, 1.59 [95% CI, 1.24–2.04]), kidney disease (HR, 1.91 [95% CI, 1.18–3.09]), and diabetes mellitus (HR, 1.52 [95% CI, 1.21–1.89]). Isolated systolic hypertension was associated with increased risk of myocardial infarct death (HR, 2.15 [95% CI, 1.35–3.41]), heart failure (HR, 1.43 [95% CI, 1.13–1.82]), and diabetes mellitus (HR, 1.42 [95% CI, 1.13–1.78]), whereas isolated diastolic hypertension was associated with increased risk of ischemic heart disease (HR, 1.26 [95% CI, 1.05–1.50]). Results were similar in nonsmoking women aged <35 years with normal weight and no diabetes mellitus during pregnancy. Conclusions— Elevated blood pressure during pregnancy, regardless of type and even without known risk factors, signals high risk of later cardiovascular disease, chronic kidney disease, and diabetes mellitus. Clinical monitoring, risk factor evaluation, and early intervention could benefit women with hypertension in pregnancy.

Risks of Overweight and Abdominal Obesity at Age 16 Years Associated With Prenatal Exposures to Maternal Prepregnancy Overweight and Gestational Diabetes Mellitus

OBJECTIVE The associations of prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus (GDM) with offspring overweight are controversial. Research estimating risk for offspring overweight due to these exposures, separately and concomitantly, is limited. RESEARCH DESIGN AND METHODS Prevalence of overweight and abdominal obesity at age 16 years and odds ratios (ORs) for prenatal exposures to maternal prepregnancy overweight and GDM were estimated in participants of the prospective longitudinal Northern Finland Birth Cohort of 1986 (N = 4,168). RESULTS The prevalence and estimates of risk for overweight and abdominal obesity were highest in those exposed to both maternal prepregnancy overweight and GDM (overweight prevalence 40% [OR 4.05], abdominal obesity prevalence 25.7% [3.82]). Even in offspring of mothers with a normal oral glucose tolerance test during pregnancy, maternal prepregnancy overweight is associated with increased risk for these outcomes (overweight prevalence 27.9% [2.56], abdominal obesity prevalence 19.5% [2.60]). In offspring of women with prepregnancy normal weight, the prevalence or risks of the outcomes were not increased by prenatal exposure to GDM. These estimates of risk were adjusted for parental prepregnancy smoking, paternal overweight, and offspring sex and size at birth. CONCLUSIONS Maternal prepregnancy overweight is an independent risk factor for offspring overweight and abdominal obesity at age 16 years. The risks are highest in offspring with concomitant prenatal exposure to maternal prepregnancy overweight and GDM, whereas the risks associated with GDM are only small.

A comparison of intrapartum automated fetal electrocardiography and conventional cardiotocography—a randomised controlled study

Objective  To examine whether intrapartum monitoring by means of automatic ST analysis (STAN) of fetal electrocardiography could reduce the rate of neonatal acidemia and the rate of operative intervention during labour, compared with monitoring by means of cardiotocography (CTG).

Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life

CONTEXT Knowledge is scarce concerning the significance of thyroid dysfunction/antibodies during pregnancy in regard to pregnancy complications/later maternal morbidity. OBJECTIVE The aim of this study was to evaluate the association between maternal thyroid dysfunction/antibodies during pregnancy and pregnancy complications or later maternal hypertension, diabetes, and thyroid disease. DESIGN AND SETTING We studied a prospective population-based cohort, Northern Finland Birth Cohort 1986 (NFBC 1986), with follow-up of 20 yr. Medication and hospital discharge records were used to assess maternal morbidity to hypertension, diabetes, and thyroid diseases. PARTICIPANTS The study consisted of mothers of NFBC 1986 with early pregnancy serum samples for thyroid function and antibody analyses (n = 5805). Mothers were grouped and compared according to these test results. MAIN OUTCOME MEASURES We focused on preeclampsia and gestational diabetes during index pregnancy, later maternal hypertension, diabetes, and thyroid disease morbidity and total mortality. RESULTS Thyroid dysfunction and antibodies were not associated with pregnancy complications. Overt hypothyroidism was associated with subsequent maternal thyroid disease [hazard ratio (HR) (95% confidence interval), 17.7 (7.8-40.6)] and diabetes [6.0 (2.2-16.4)]. Subclinical hypothyroidism [3.3 (1.6-6.9)], TPO-Ab-positivity [4.2 (2.3-7.4)], and TG-Ab-positivity [3.3 (1.9-6.0)] were also associated with later thyroid disease. No association was found between thyroid dysfunction/antibodies and hypertension or overall mortality. CONCLUSIONS Thyroid dysfunction and antibodies during pregnancy seem to predict later thyroid disease. Overt hypothyroidism poses risk of diabetes.

Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study

Please cite this paper as: Ijäs H, Vääräsmäki M, Morin‐Papunen L, Keravuo R, Ebeling T, Saarela T, Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG 2011;118:880–885.

Adolescent manifestations of metabolic syndrome among children born to women with gestational diabetes in a general-population birth cohort.

The association between maternal gestational diabetes (GDM) and manifestations of metabolic syndrome among Caucasian adolescents was studied with data from the population-based Northern Finland 1986 Birth Cohort. This is a longitudinal cohort study from early pregnancy until offspring age 16 years and includes data from a risk group-based GDM screen of pregnant mothers by an oral glucose tolerance test. Metabolic outcomes were compared between the offspring of women with GDM (OGDM; n = 95) and reference group offspring (n = 3,909). The prevalence of overweight was significantly higher in the OGDM group (18.8 vs. 8.4%; P < 0.001) than in the reference group. The median body mass index (20.8 vs. 20.2 kg/m(2), 95% confidence interval (CI) for the percentage difference adjusted for sex: 3.5%, 9.5%), waist circumference (73.3 vs. 71.5 cm, 95% CI: 3.2%, 7.5%), and fasting insulin (10.20 vs. 9.30 milliunits/L, 95% CI: 5.9%, 26.0%) were higher, and homeostatic model assessment-insulin sensitivity (74.7 vs. 82.3, 95% CI: -20.6%, -5.4%) was lower in the OGDM group. These differences were similar after an additional adjustment for birth weight and gestational age. The differences in waist circumference, insulin, and homeostatic model assessment-insulin sensitivity were attenuated but remained statistically significant after additional adjustment for body mass index at 16 years. These findings highlight the importance of prevention strategies among children born to women with GDM.

Early Pregnancy Reference Intervals of Thyroid Hormone Concentrations in a Thyroid Antibody-Negative Pregnant Population

BACKGROUND Thyroid dysfunction and antibodies are increasingly recognized as risk factors during pregnancy. Thyroid function changes during pregnancy and there is a need for gestational age-specific reference intervals for thyroid hormones. The aim of this study was to calculate gestational age-specific thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) reference intervals in an iodine-sufficient thyroid antibody-negative population. METHODS The study population consisted of a large, prospective population-based cohort, the Northern Finland Birth Cohort 1986 (singleton births, n = 9362), with extensive data throughout gestation. The subjects underwent serum sampling in early pregnancy. Samples were assayed for TSH, fT4, fT3, thyroid-peroxidase, and thyroglobulin antibodies (n = 5805). All mothers with thyroid antibodies or previous thyroid diseases were excluded when calculating gestational age-specific percentile categories for TSH, fT4, and fT3. Also, associations between body mass index (BMI) and thyroid hormones were established. RESULTS The upper reference limit for TSH was 2.5 multiples of median (2.7-3.5 mU/L, depending on gestational week). The lower reference limit was as low as 0.07 mU/L. Reference intervals for fT4 rose during early pregnancy and decreased thereafter, ranging between 11-22 pmol/L. Reference intervals for fT3 were uniform throughout gestation, ranging between 3.4 and 7.0 pmol/L. BMI was associated positively with early pregnancy TSH and fT3 concentrations and negatively with fT4 concentrations. CONCLUSIONS These gestational age-specific reference intervals for thyroid hormones provide a framework for clinical decision making. Overweight and obesity are increasing problems among fertile women and they are associated with possibility of thyroid dysfunction during pregnancy.

Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study.

Please cite this paper as: Laitinen J, Jääskeläinen A, Hartikainen A, Sovio U, Vääräsmäki M, Pouta A, Kaakinen M, Järvelin M. Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study. BJOG 2012;119:716–723.

Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study

Please cite this paper as: Laitinen J, Jääskeläinen A, Hartikainen A, Sovio U, Vääräsmäki M, Pouta A, Kaakinen M, Järvelin M. Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study. BJOG 2012;119:716–723.