Cohort Profile : The Finnish Gestational Diabetes (FinnGeDi) Study

Peer reviewe

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P &lt; 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.</p

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P &lt; 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.</p

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.</p

Care and outcome of Finnish diabetic pregnancy

Abstract The aim of this study was to evaluate the treatment, course and outcome of pregnancy in Finland using two cohorts of diabetic women. The clinical cohort consisted of data from all 210 women with Type 1 diabetes and their 296 pregnancies managed between 1986 and 1995 in the two northernmost provinces of Finland. The register-based study population included all 1442 mothers with a singleton birth who had insulin treatment during pregnancy in 1991-1995 according to the Medical Birth Register. Of these mothers, 954 (66%) had pre-existing diabetes. Insulin-treated diabetes complicated 4.5/1000 births in Finland in 1991-1995, the prevalence of Type 1 diabetes being 2.9/1000 in the whole country and 3.3/1000 in Northern Finland. In the 1990's the care of these women shifted from tertiary level only to include the secondary level hospitals as well, and was more often carried out on an out-patient basis. This care policy in association with the self-monitoring of blood glucose levels contributed to an obvious improvement in glycaemic control during pregnancy. Despite that, the high proportion (73%) of women entering pregnancy with unsatisfactory glycaemic control did not decrease during the study period. Retinopathy complicated 134 (45.3%) diabetic pregnancies, while clinical nephropathy was found in 23 (7.8%) cases. Although retinopathy was more often aggravated during the first pregnancy, the occurrence of retinopathy or its severe form was not increased at the beginning of consecutive pregnancies. Of the mothers, 50 (16.9%) had pre-eclampsia during pregnancy, and in 28% of these cases it was classified as superimposed. It was found more often among primiparous than multiparous (25.6% vs. 11.0%, respectively), and its occurrence rose with the severity of diabetes. In both cohorts, the rates of preterm deliveries, Caesarean sections and large for gestational age (LGA) infants were significantly (p &lt; 0.001) higher in Type 1 diabetic pregnancies than in the background population. The rates of congenital anomalies (CA) were 540-629/10000 in two study populations, both being 2-3-fold as compared to the background population. Cardiac malformations were most common, with anomalies in the genitourinary tract and the musculoskeletal organs being next in frequency. Sixty-three percent of malformed infants were boys. Though pregnancy itself was not found to worsen the prognosis of diabetes, at least in the short term, pregnancy in diabetic women still remains a high risk state with an increased rate of prematurity, operative deliveries, CAs and peri- and neonatal mortality. In order to decrease the mortality rate in diabetic births, attention should be directed at both the prevention of CA and at identifying the foetuses at risk for intrauterine death. The postneonatal mortality rate is also high, reflecting a shift in the deaths from the early neonatal period to a later age. Therefore, a combined mortality, including induced abortions, stillborns and infant deaths, would give a more realistic idea of the outcomes in diabetic pregnancies

Raskaus ja synnytys keisarileikkauksen jälkeen

Abstract One out of seven of all parturients and one out of five primigravid women deliver by caesarean section. Of four women having undergone caesarean section, three will give birth vaginally, provided that the indication for surgery has been temporary by nature. Spontaneous beginning of labor and a previous vaginal delivery improve the chances of succesful of vaginal delivery. Rupture of the uterus in subsequent pregnancies is the most feared sequel to a caesarean section, with an occurrence of 0.2 to 1.5%. Delivery by caesarean is indicated in case of previous rupture of the uterus, hysterotomy through vertical incision, and more than two previous caesarean sections.Tiivistelmä Suomessa kaikista synnyttäjistä joka seitsemäs ja ensisynnyttäjistä joka viides synnyttää nykyään keisarileikkauksella. Siksi myös keisarileikkauksen jälkeinen synnytys on synnytysyksiköiden arkipäivää. Kolme neljästä aiemmin keisarileikatusta naisesta synnyttää alakautta, kun leikkausindikaatio on ollut luonteeltaan satunnainen. Synnytyksen spontaani käynnistyminen ja aiempi alatiesynnytys parantavat alatiesynnytyksen onnistumisedellytyksiä. Kohdun repeäminen seuraavissa raskauksissa on keisarileikkauksen pelätyin jälkiseuraus, jonka esiintyvyys on 0,2 — 1,5 %. Synnytyksen hoito keisarileikkauksella on aiheellinen, jos synnyttäjällä on aikaisempi kohturepeämä, pystysuoraan tehty kohtuavaus ja enemmän kuin kaksi aiempaa keisarileikkausta. Muissa tapauksissa synnytystapa voidaan valita tapauskohtaisesti, odottavan naisen kanssa keskustellen. Synnytyksen käynnistyksessä suositaan mekaanisia menetelmiä ja oksitosiinia. Hyvä potilasneuvonta ja riskien tunnistaminen on olennaista, kun keisarileikkauksen jälkeistä synnytystä suunnitellaan ja hoidetaan

Paracetamol preceding very preterm birth:is it safe?

Abstract Introduction: The use of paracetamol for pain relief in pregnancy is common. However, the influence of paracetamol on the perinatal adaptation of high-risk infants has not been studied. These data are important for safety, since another inhibitor of prostaglandin synthesis is harmful to infants born very preterm and increases serious morbidity. We studied whether the use of paracetamol had an adverse influence on neonatal adaptation and the outcomes of infants during the first hospitalization. Material and Methods: We studied the patient records of high-risk mothers and their infants born before 32 weeks of gestation for multiple variables over a period of 84 months in Oulu University Hospital, a regional tertiary care hospital caring for high-risk deliveries and providing neonatal intensive care. In a matched cohort setting, the exposition was defined as paracetamol use &lt;24 h before childbirth. The controls had consumed no paracetamol up to 1 week before delivery. Infants with major anomalies were excluded. The primary outcome was defined as the need for early interventional treatments for the preterm infants. Outcomes during the first hospitalization were also studied. Results: Altogether, 170 fetuses from 149 mothers were exposed to paracetamol during the study period. The control population, delivering during the same period, consisted of 118 non-exposed fetuses from 104 mothers. Among them, the mothers were pairwise matched according to their medications, amniotic fluid leakage time, clinical infections, and delivery mode. After matching, 72 mothers/group remained, resulting in 88 paracetamol-exposed infants and 85 controls. No perinatal adverse reactions were detected. There were no differences in either circulatory support during the first postnatal day or in the risk for major diseases during the first hospitalization. Paracetamol-exposed infants needed fewer acute delivery room therapies (51.1% vs 65.9%, mean difference −14.89; 95% confidence interval −0.29 to −0.003). Maternal total paracetamol dose in the 1 week before delivery correlated positively with Apgar scores. Conclusions: Antenatal paracetamol given within 24 h before birth had no adverse effects on extremely or very preterm infants. The long-term safety of paracetamol and the potential acute benefits for preterm infants during perinatal transition remain to be proven in larger, prospective settings

The increased trend of medical treatment for thyroid diseases during pregnancy:a 13-year national study

Abstract Objective: Thyroid dysfunction affects up to 5–7% of all pregnancies. The rates of thyroid hormone use in nonpregnant population have substantially increased in recent years. The aim of this study was to assess possible changes in the use of levothyroxine substitution and antithyroid drugs over time in pregnant women. Methods: The study data consisted of all singleton pregnancies (N = 736,873) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The Prescription Register and Special Refund Entitlement Register provided information on levothyroxine and antithyroid drug purchases. The annual rates of levothyroxine and antithyroid drug prescription redemptions were explored to estimate changes in exposure rates to thyroid medication from 2004 to 2016. Joinpoint regression analyses were performed to explore interannual variability in levothyroxine and antithyroid drug treatment. Results: There was more than a five-fold increase in levothyroxine use during the study period; in 2004, 1.1% of pregnant women had levothyroxine treatment, and by 2016, the prevalence increased to 6.2%. In addition, we observed a slight increase in antithyroid medication during pregnancy, but antithyroid drug use during pregnancy overall was very rare. In 2004, 0.05% of pregnant women used antithyroid drugs, and by 2016, this percentage had increased to 0.14%. Conclusions: Our study shows that the rate of levothyroxine use in pregnancy has markedly increased. This suggests that tracing and screening relevant patients and awareness of thyroid disorders on pregnancy and their significance for the pregnancy outcome have increased and the threshold to treat thyroid disorders has declined

Indications for intensive care unit treatment among neonates born to mothers with thyroid disease:a population-based cohort study

Abstract Introduction: Thyroid diseases in pregnancy are relatively common and are associated with adverse pregnancy and perinatal outcomes, increasing a neonate’s risk of admission to the neonatal intensive care unit (NICU). The aim of this study was to evaluate the indications for increased risk of NICU admission among the neonates of hypothyroid and hyperthyroid mothers. Material and methods: The study data consisted of all singleton deliveries (n = 734 773) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The odds of NICU admission (with 95% confidence intervals) were compared between the neonates of hypothyroid or hyperthyroid mothers and of mothers without any thyroid diseases by specified neonatal characteristics and morbidities using logistic regression analysis. The studied neonatal characteristics were preterm birth (&lt;37+0 gestational weeks), low birthweight (&lt;2500 g), the rate of small- and large-for-gestational age infants, and eight disease-specific neonatal outcomes: asphyxia, respiratory distress syndrome, meconium aspiration syndrome, pneumothorax, cardiovascular problems, infections, jaundice and hypoglycemia. Results: The most common indications for NICU care were principally the same in the neonates of the mothers with and without thyroid disease: respiratory distress syndrome, infections, preterm birth, low birthweight and neonatal hypoglycemia. The preterm neonates, neonates with low birthweight, and large-for-gestational-age infants had increased odds of NICU admission if their mother had hypothyroidism. Also neonates with cardiovascular problems, jaundice or hypoglycemia associated with maternal diabetes had increased odds of NICU admissions if their mother had hypothyroidism. Further, the preterm neonates, large-for-gestational-age infants, and term infants with jaundice had increased odds of NICU admission if their mother had hyperthyroidism. Conclusions: The most common indications for NICU care were similar for the neonates of the mothers with and without thyroid disease. However, the neonates of the mothers with thyroid diseases were more likely to need NICU care. The neonates of the mothers with thyroid diseases had higher odds of NICU treatment in cases of preterm birth, large for gestational age, and hypoglycemia