The purpose of this prospective, population-based cohort study was to evaluate the roles of polycystic ovary syndrome (PCOS), obesity, weight gain, and hyperandrogenemia in the development of ...hypertensive disorders of pregnancy (HDP) through fertile age both in PCOS and in non-PCOS women. The study population-NFBC1966 (Northern Finland Birth Cohort 1966)-allowed a long-term follow-up of women from age 14 until 46 years who developed HDP (n=408) or did not (n=3373). HDP diagnosis was confirmed by combining hospital discharge records, data from Finnish Medical Birth Registers, and the questionnaire data at age 46. Women with self-reported PCOS (srPCOS; n=279), defined by both oligo-amenorrhea and hirsutism at age 31 or with PCOS diagnosis by age 46, were compared with women without reported PCOS (n=1577). Women with srPCOS had an increased HDP risk (odds ratio, 1.56 95% CI, 1.03-2.37), but the association disappeared after adjustment for body mass index. In women with srPCOS and HDP, body mass index increased from age 14 to 46 significantly more than in srPCOS women without HDP (median interquartile range, 9.82 6.23-14.6 and 7.21 4.16-10.5 kg/m
, respectively;
<0.001). Also, in non-PCOS women, the increase was higher in women with (7.54 5.32-11.62 kg/m
;
<0.001) than without HDP (6.33 3.90-9.33 kg/m
;
<0.001). Increase in waist circumference between ages 31 and 46 years was associated with HDP but not with PCOS. Hyperandrogenemia at 31 or 46 years did not associate with HDP (1.44 0.98-2.11). In conclusion, obesity, especially abdominal obesity, and weight gain from adolescence to age 46, but not srPCOS or hyperandrogenemia, were associated with an increased risk of HDP.
Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized ...that changes in offspring DNA methylation (DNAm) underline these associations.
To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). We performed lookup analyses for identified cytosine-guanine dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression.
Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β SE -0.013 2.1 × 10-3, P value corrected for false discovery rate PFDR = 5.1 × 10-3) and cg02988288 (β SE-0.013 2.3 × 10-3, PFDR = 0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm.
Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent lookup analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.
Incidence of gestational diabetes (GDM) has increased rapidly. It poses significant risks for both mother and fetus affecting also negatively their longer-term metabolic heath. We asked whether early ...pregnancy maternal hemoglobin (Hb) levels, indicative for tissue oxygenation, would affect mother's metabolic health and fetal outcome. We assessed in FinnGeDi, a Finnish multicenter case-control study for GDM (n = 1828), association of maternal 1st trimester Hb levels with metabolic parameters and perinatal outcome. Our data show that mothers with GDM had higher Hb levels compared to controls (mean difference 1.746 g/L). Hb levels associated positively with pre-pregnancy body mass index (BMI), fasting glucose levels and glucose levels in a glucose tolerance test and systolic and diastolic blood pressure (bp) levels. When assessed in quartiles the highest Hb quartile had more chronic and gestational hypertension and the most adverse outcome of the metabolic parameters, dose-dependency seen in bp, BMI and glucose levels. In a multivariable regression analysis Hb levels remained an independently associated parameter for GDM after adjusting for key covariates (OR 1.019, 95% CI 1.007; 1.031). In conclusion, higher maternal Hb levels within the normal variation are an independent risk factor for GDM in this population but have little effect on perinatal outcome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
Thyroid dysfunction and antibodies during pregnancy seem to predict later maternal morbidity to thyroid diseases.
Data concerning the effects of freezing, thawing, and storage on serum thyroid-stimulating hormone (TSH) and thyroid hormones free thyroxine (fT4) and free triiodothyronine (fT3) are scarce (1-3), ...and we can find no data on their effects on thyroid autoantibodies thyroid-peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). Higher thyroid autoantibody concentrations were likely to be the result of storage time, because preanalytic conditions (sampling, tubes, transportation, sample processing, freezing, thawing, or storage conditions) did not differ in our study.
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.
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.
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.
Adolescents and adults born as small preterm infants show more pronounced risk factors of cardiovascular disease. Whether similar risks apply across all degrees of preterm birth is poorly known.
We ...studied the association between preterm birth and cardiovascular risk factors in 6642 16-year-old adolescents of the population-based Northern Finland Birth Cohort 1986. Of these, 79 (1.2%) were born at <34 gestational weeks (early preterm), 238 (3.6%) at 34 to 36 weeks (late preterm), and 6325 at term (controls).
Girls born early preterm had 6.7 mm Hg (95% confidence interval: 3.1-10.2) higher systolic blood pressure (BP) and 3.5 mm Hg (1.1-5.8) higher diastolic BP, but no difference in serum lipid levels compared with control girls. Boys showed no differences in BP, but boys born early preterm had 6.7% (0.2%-13.7%) higher total cholesterol, 11.7% (2.1%-22.3%) higher low-density lipoprotein cholesterol, and 12.3% (3.1%-22.4%) higher apolipoprotein B concentrations. The differences were similar (BP) or stronger (lipids) when adjusted for maternal smoking, birth weight SD score, parental education, pubertal stage, BMI, and lifestyle. There were similar associations with length of gestation as a continuous variable. Accordingly, mean differences between late preterm and controls were in the same direction but weaker, although most were not statistically significant.
Preterm birth was associated with elevated BP in adolescent girls and an atherogenic lipid profile in boys. Because these associations were strongest among those born early preterm, our findings are consistent with a dose-response relationship between shorter length of gestation and cardiovascular risk factors.
Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be ...partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
OBJECTIVE Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is ...hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. RESEARCH DESIGN AND METHODS To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). We performed lookup analyses for identified cytosine-guanine dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression. RESULTS Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β SE −0.013 2.1 × 10−3, P value corrected for false discovery rate PFDR = 5.1 × 10−3) and cg02988288 (β SE−0.013 2.3 × 10−3, PFDR = 0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm. CONCLUSIONS Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent lookup analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.
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