Eila Suvanto

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.

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.

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 Thyroid Dysfunction During Pregnancy and Thyroid Function of Her Child in Adolescence

CONTEXT Normal maternal thyroid function is important for fetal development. No knowledge exists on how maternal thyroid function and thyroid antibodies during early pregnancy affect thyroid function of the offspring. OBJECTIVE The aim of this study was to investigate the relationship between maternal and adolescent thyroid function parameters. DESIGN, SETTING, AND PARTICIPANTS A total of 3673 mother-child pairs from the prospective, population-based Northern Finland Birth Cohort 1986 participated in the study. Maternal serum samples were drawn in early pregnancy (<20th gestational week), and childrens samples were drawn at the age of 16 years and analyzed for TSH, free T4 (fT4), and thyroid peroxidase antibodies (TPO-Abs). MAIN OUTCOME MEASURES TSH, fT4, and TPO-Ab concentrations were measured at the age of 16 years. Children of mothers with thyroid dysfunction (hypothyroidism, hyperthyroidism, or hypothyroxinemia) or TPO-Ab positivity were compared to those of euthyroid or TPO-Ab-negative mothers. The distributions are expressed as medians with 5th to 95th percentiles. RESULTS Boys of hypothyroid mothers had higher TSH concentrations than those of euthyroid mothers: 2.0 (0.9-4.0) vs 1.7 (0.8-3.3) mU/L; P = .001. Children of hyperthyroid mothers had lower TSH concentrations than those of euthyroid mothers: 1.3 (0.6-4.2) vs 1.7 (0.8-3.3) mU/L, P = .013, for boys; and 1.3 (0.5-3.5) vs 1.6 (0.7-3.4) mU/L, P = .034, for girls. There were no differences in TSH or fT4 concentrations between children of hypothyroxinemic and euthyroid mothers. TPO-Ab-positive mothers more often had TPO-Ab-positive children (prevalence, 9.0 vs 3.7% among boys, and 22.7 vs 7.5% among girls). CONCLUSIONS Maternal thyroid dysfunction and TPO-Ab positivity during pregnancy seem to modify thyroid function parameters of offspring even in adolescence. Whether this increases the thyroid disease risk of the children is still unknown.

Smoking and Early Pregnancy Thyroid Hormone and Anti-Thyroid Antibody Levels in Euthyroid Mothers of the Northern Finland Birth Cohort 1986

BACKGROUND Smokers in the general population have lower thyrotropin (TSH) and higher free triiodothyronine (fT3) and free thyroxine (fT4) concentrations, but the results in pregnant population vary from no effect to a decrease in TSH and fT4 concentrations and an increase in fT3 levels. Our objective was to further evaluate the question of whether there is an association between smoking, before and during pregnancy, with maternal thyroid function during pregnancy and with the risk for subsequent hypothyroidism. METHODS Our study population was a prospective population-based cohort (N=9362), the Northern Finland Birth Cohort 1986, with extensive data throughout gestation. The mothers underwent serum sampling in early pregnancy. The samples were assayed for TSH, fT3, fT4, thyroid-peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Abs) (n=5805). Mothers with thyroid dysfunction diagnosed before or during pregnancy were excluded, leaving 4837 euthyroid mothers. The smoking status of mothers and fathers were requested by questionnaires during pregnancy. Subsequent maternal morbidity relating to hypothyroidism 20 years after the index pregnancy was evaluated using national registers. RESULTS Euthyroid mothers who smoked before, or continued smoking during first trimester of pregnancy, had higher serum fT3 (p<0.001) and lower fT4 (p=0.023) concentrations than nonsmokers. Smoking in the second trimester was associated with higher fT3 (p<0.001) concentrations, but no difference in fT4 concentrations compared with nonsmokers. TG-Abs were less common among smoking than nonsmoking mothers (2.5% vs. 4.7%, p<0.001), but the prevalence of TPO-Ab was similar. Paternal smoking had no independent effect on maternal early pregnancy thyroid hormone or antibody concentrations. The risk of subsequent maternal hypothyroidism after follow-up of 20 years was similar among prepregnancy smokers and nonsmokers. CONCLUSIONS In euthyroid women, smoking during pregnancy was associated with higher fT3 levels and lower fT4 levels; possibly reflecting smoking-induced changes in peripheral metabolism of thyroid hormones. No differences were found in TSH concentrations between smokers and nonsmokers. Our results differ from those of the general population, which usually have shown smoking-induced thyroidal stimulation. This is possibly due to pregnancy-induced changes in thyroid function. Decreases in fT4 levels among smokers might predispose to hypothyroidism or hypothyroxinemia during pregnancy. Despite these changes in thyroid function, smoking did not increase the womans risk of subsequent hypothyroidism.

Thyroid hormones are stable even during prolonged frozen storage

Recently, Panesar and Lit published an interesting article where they evaluated the stability of serum thyroid hormones at –808C following storage for 8–11 years (1). They used 30 archived specimens which had been initially analyzed in 2001 using an ACS180 (Bayer Siemens, IL, USA) analyzer and then analyzed using different assays after being stored frozen. Also, they compared the results of the archived samples to those obtained using 10 fresh specimens. The authors have commented on our research where we studied the effects of long-term frozen storage (at –258C) on serum thyroid hormone and antibody concentrations (2). Our study population consisted of serum samples obtained from pregnant women, aged 22–30 years, collected during early pregnancy (6.7–18.0 gestational weeks) and frozen for up to 23 years. All samples (ns50 per year) were collected between March and April during office hours (8.00 a.m.–4.00 p.m.). The samples were thawed for the first time for our study, and were analyzed immediately after thawing. This sampling procedure was done to minimize the effect of biological variation in samples stored for different periods of time. Also, our sample size collected each year is sufficient to show significant differences despite biological variation in samples stored for different times. In our study, storage time had no effect on serum concentrations of thyrotropin (TSH) and free triiodothyronine (fT3), and only minimal effects on serum concentrations of free thyroxine (fT4). Although our results showed some increase in fT4 values with extended storage time (5.5% of the total

Maternal Thyroid Function During Pregnancy and the Child’s Linguistic and Sensory Development in the Northern Finland Birth Cohort 1986

Background Maternal hypothyroidism and hypothyroxinemia are associated with poor neuropsychological development in children. Previous research is lacking on whether maternal thyroid dysfunction affects sensory and linguistic development in childhood. Methods The Northern Finland Birth Cohort 1986 included all births within a year (9,362 women, 9,479 children) from the two northernmost Finnish provinces. Maternal serum samples (n = 5,791) were obtained in early pregnancy and analyzed for TSH, free T4, and thyroid peroxidase antibodies (TPO-Abs). Five thousand three hundred and ninety-one parents evaluated their child’s sensory and linguistic development at 7 years old via a questionnaire (excluding children with an intelligence quotient ≤85). The prevalence of sensory and linguistic impairments was compared between mothers with and without thyroid dysfunction. Results There were no statistically significant differences in the prevalence of sensory or linguistic impairment between children of mothers with and without thyroid dysfunction. Children of hypothyroid and hypothyroxinemic mothers had an increased prevalence of vision impairment compared with those of euthyroid mothers (10.8 and 11.7%, respectively, versus 6.5%), but the difference was not significant. All results remained similar after excluding TPO-Ab-positive mothers and premature children. Conclusion We did not find an association between maternal thyroid dysfunction during pregnancy and sensory and linguistic development impairment in childhood. A somewhat higher prevalence of vision impairment was seen in children of hypothyroid and hypothyroxinemic mothers, which merits further research.

Maternal Thyroid Antibodies Associates With Cardiometabolic Risk Factors in Children at the Age of 16

Context and Objective: The objective of this study was to determine the effects of maternal thyroid dysfunction or antibodies during pregnancy on the cardiometabolic risk factors in children. Design, Setting, and Participants: This prospective population‐based cohort study, Northern Finland Birth Cohort 1986, included all pregnancies within a year in the area. Maternal serum samples were collected before the 20th week of gestation and analyzed for thyrotropin, free T4, thyroid‐peroxidase antibodies (TPO‐Abs), and thyroglobulin antibodies (Tg‐Abs). Cardiometabolic risk factors in children at the age of 16 years were evaluated via blood sampling and clinical examination. Data were available for 3229 to 4176 mother‐child pairs. Main Outcome Measures: Waist circumference, blood pressure, lipids and lipoproteins, and insulin resistance were measured. Odds ratios (ORs) with 95% confidence intervals (CIs) of cardiometabolic risk factors in children with and without mothers with thyroid dysfunction or antibodies were calculated with logistic regression and adjusted for covariates. Results: Children of TPO‐Ab‐positive mothers had higher odds of metabolic syndrome (OR, 2.57; 95%, CI 1.26 to 5.25) and waist circumference indicative of metabolic syndrome (OR, 1.69; 95% CI, 1.14 to 2.50). They were also more likely to be overweight or obese (OR, 1.56; 95% CI, 1.04 to 2.34). Maternal thyroid dysfunction or Tg‐Ab positivity did not associate with cardiometabolic risk factors in children. Conclusion: Metabolic syndrome, greater waist circumference, and higher body mass index were more prevalent in children of TPO‐Ab‐positive mothers, indicating an adverse cardiovascular health profile.