Browsing by Subject "gestational age"

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  • ALBINO Study Group; Maiwald, C.A.; Annink, K.V.; Rüdiger, M.; Benders, M.J.N.L.; Van Bel, F.; Allegaert, K.; Naulaers, G.; Bassler, D.; Klebermaß-Schrehof, K.; Vento, M.; Guimarães, H.; Stiris, T.; Cattarossi, L.; Metsäranta, M.; Vanhatalo, S.; Mazela, J.; Metsvaht, T.; Jacobs, Y. (2019)
    Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653,, May 22, 2017. © 2019 The Author(s).
  • Kajantie, Eero; Osmond, Clive; Eriksson, Johan G. (2017)
    BACKGROUND: Women with hypertensive disorders in pregnancy are at an increased risk of cardiovascular disease and type 2 diabetes later in life. Offspring born from these hypertensive pregnancies have increased levels of cardiovascular risk factors; whether they are at an increased risk of type 2 diabetes is not known. OBJECTIVE: The objective of the investigation was to study the risk of type 2 diabetes in the adult offspring exposed to maternal preeclampsia or gestational hypertension in utero. STUDY DESIGN: We studied 5335 members of the Helsinki Birth Cohort Study, who were born between 1934 and 1944 and who lived in Finland in 1995 when the National Medication Purchase Register was initiated. We ascertained gestational hypertension and preeclampsia according to modern criteria by using maternal and birth records. We defined type 2 diabetes through purchases of antidiabetic medication recorded in the comprehensive National Medication Purchase Register, excluding the 31 subjects who had purchased only insulin. We used Cox regression to assess hazard ratios for type 2 diabetes. RESULTS: A total of 590 men (21.6%) and 433 women (16.9%) had purchased medication for diabetes. The hazard ratio for type 2 diabetes for offspring exposed to any maternal hypertension in pregnancy was 1.13 (95% confidence interval, 1.00-1.29; n = 1780). For maternal gestational hypertension, it was 1.15 (95% confidence interval, 1.00-1.33; n = 1336) and for preeclampsia 0.98 (95% confidence interval, 0.71-1.34; n = 231). For type 2 diabetes with first medication purchase before 62 years, the corresponding hazard ratios were 1.25 (95% confidence interval, 1.04-1.51); 1.28 (95% confidence interval, 1.05-1.58), and 1.18 (95% confidence interval, 0.75-1.84). The hazard ratios were similar when adjusted for birthweight SD score for gestation, length of gestation, maternal body mass index in late pregnancy, height, age, and parity and for childhood or adult socioeconomic position. An increased risk of type 2 diabetes was also associated with low birthweight SD score, independent of the association with gestational hypertension. CONCLUSION: Offspring exposed to maternal gestational hypertension in utero have an increased risk of type 2 diabetes in late adult life. This finding underlines the role of the whole spectrum of hypertensive disorders of pregnancy as risk factors of offspring disease throughout life. It also reinforces previous suggestions that adult health care providers should incorporate birth histories when evaluating an individual's risk to develop type 2 diabetes.
  • Kazmi, Nabila; Sharp, Gemma C.; Reese, Sarah E.; Vehmeijer, Florianne O.; Lahti, Jari; Page, Christian M.; Zhang, Weiming; Rifas-Shiman, Sheryl L.; Rezwan, Faisal I.; Simpkin, Andrew J.; Burrows, Kimberley; Richardson, Tom G.; Ferreira, Diana L. Santos; Fraser, Abigail; Harmon, Quaker E.; Zhao, Shanshan; Jaddoe, Vincent W. V.; Czamara, Darina; Binder, Elisabeth B.; Magnus, Maria C.; Haberg, Siri E.; Nystad, Wenche; Nohr, Ellen A.; Starling, Anne P.; Kechris, Katerina J.; Yang, Ivana V.; DeMeo, Dawn L.; Litonjua, Augusto A.; Baccarelli, Andrea; Oken, Emily; Holloway, John W.; Karmaus, Wilfried; Arshad, Syed H.; Dabelea, Dana; Sorensen, Thorkild I. A.; Laivuori, Hannele; Räikkönen, Katri; Felix, Janine F.; London, Stephanie J.; Hivert, Marie-France; Gaunt, Tom R.; Lawlor, Debbie A.; Relton, Caroline L. (2019)
    Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R-2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.
  • Morlando, Maddalena; Schwickert, Alexander; Stefanovic, Vedran; Mhallem Gziri, Mina; Pateisky, Petra; Chalubinski, Kinga M.; Nonnenmacher, Andreas; Morel, Olivier; Braun, Thorsten; Bertholdt, Charline; van Beekhuizen, Heleen J.; Collins, Sally; International Society for Placenta accreta spectrum (IS-PAS) (2021)
    Introduction Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS). Material and methods Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery. Results In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4-7.7). Emergency delivery due to vaginal bleeding was more frequent with false-positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34(+1) to 36(+0) weeks and 19% at >36(+0) weeks. Conclusions Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36(+0) weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.
  • Strang-Karlsson, Sonja; Alenius, Suvi; Näsänen-Gilmore, Pieta; Nurhonen, Markku; Haaramo, Peija; Evensen, Kari Anne I.; Vääräsmäki, Marja; Gissler, Mika; Hovi, Petteri; Kajantie, Eero (2021)
    Objective Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. Methods In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or >= 2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3-27.0). Results Among individuals born extremely preterm (23-27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25-1.24) when compared with the full-term reference group (39-41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28-31 weeks); 0.95 (0.68-1.31), moderately preterm (32-33 weeks); 0.96 (0.73-1.27), late preterm (34-36 weeks); 1.01 (0.91-1.11), early term (37-38 weeks); 0.98 (0.93-1.03), and post term (42 weeks); 0.98 (0.89-1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. Conclusion We found no evidence for a higher risk of migraine among individuals born preterm.
  • Vehkanen, Minja (Helsingin yliopisto, 2022)
    Keskosuus tarkoittaa syntymää ennen raskausviikkoa 37+0, ja pikkukeskosiksi kutsutaan ennen raskausviikkoa 32+0 syntyneitä. Tämän tutkimuksen tarkoitus on vertailla keskenään ennen raskausviikkoa 32+0 syntyneitä kaksosia ja yksösiä keskenään. Tutkimuksessa on eroteltu A- kaksoset, B- kaksoset ja yksöset. Muuttujiksi on valittu yleisempiä keskosten sairastavuuksia ja vertailtu näiden esiintyvyyttä kaksosten ja yksösten välillä raskausviikkokohtaisesti. Myös kuolleisuutta vertailtiin keskosten välillä. Kyseessä on retrospektiivinen tutkimus, jossa käytettiin aineistona THL:n Pienten keskosten rekisteriä Suomessa vuosilta 2006-2017. Tiedot kirjattiin Excel -taulukoihin ja luvut muutettiin prosenttiosuuksiksi tarkastelun helpottamiseksi. Tulokset vaihtelivat muuttujien ja raskausviikkojen välillä. Kokonaisuudessaan selvää trendiä ei ollut näkyvissä kummankaan ryhmän selvästi suuremman sairastavuuden puolesta. Raskausviikoilla 25 syntyneiden kuolleisuudessa 7 vrk:n ikään mennessä oli merkitsevä ero yksösten ja kaksosten välillä. Yksösistä oli kuollut 10,4 %, kun taas A-kaksosista oli kuollut 22,2 % (p=0,04) ja B-kaksosista 27,8 % (p=0,003). Korionamnioniitti ja paineluelvytys olivat kaikilla raskausviikoilla yksösillä yleisempiä kuin kaksosilla. Syntymäpainot odotetusti kasvoivat raskausviikkojen edetessä, mutta raskausviikkoa 42+0 vastaavassa iässä paino oli suurempi niillä, jotka olivat syntyneet hyvin varhaisilla raskausviikoilla (rv 23-26). Joissain tutkimuksissa ennenaikaisesti syntyneet kaksoset pärjäävät paremmin kuin vastaavassa raskaudenkestossa syntyneet yksöset, mutta tämän tutkimuksen perusteella selvää eroa ei todettu. Tärkeä havainto oli se, että painonkehitys on kaikissa ryhmissä parempaa hyvin varhaisilla raskausviikoilla syntyneillä. Tämän tiedon johdosta myös muilla raskausviikoilla syntyneiden ravitsemukseen on syytä kiinnittää entistä tehokkaammin huomiota. Korionisiteettitietoja ei ollut vielä THL:sta saatavilla, mutta jatkotutkimuksia joissa ne on huomioitu, tarvitaan.
  • Suarez, Anna; Lahti, Jari; Czamara, Darina; Lahti-Pulkkinen, Marius; Knight, Anna K.; Girchenko, Polina; Hämäläinen, Esa; Kajantie, Eero; Lipsanen, Jari; Laivuori, Hannele; Villa, Pia M.; Reynolds, Rebecca M.; Smith, Alicia K.; Binder, Elisabeth B.; Räikkönen, Katri (2018)
    Objective: Maternal antenatal depression may compromise the fetal developmental milieu and contribute to individual differences in aging and disease trajectories in later life. We evaluated the association between maternal antenatal depression and a novel biomarker of aging at birth, namely epigenetic gestational age (GA) based on fetal cord blood methylation data. We also examined whether this biomarker prospectively predicts and mediates maternal effects on early childhood psychiatric problems. Method: A total of 694 mothers from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) Study provided information on history of depression diagnosed before pregnancy; 581 completed the Center for Epidemiological Studies Depression Scale throughout pregnancy, and 407 completed the Child Behavior Checklist at child's age 3.7 years (SD = 0.75 year). DNA methylation (DNAm) GA of fetal cord blood DNA was based on the methylation profile of 148 selected cytosine linked to guanine by phosphate (CpG) sites. Epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA. Results: Maternal history of depression diagnosed before pregnancy (mean difference = -0.25 SD units, 95% CI = -0.46 to -0.03) and greater antenatal depressive symptoms (-0.08 SD unit per I-SD unit increase, 95% CI = -0.16 to -0.004) were associated with child's lower epigenetic GA. Child's lower epigenetic GA, in turn, prospectively predicted total and internalizing problems and partially mediated the effects of maternal antenatal depression on internalizing problems in boys. Conclusion: Maternal antenatal depression is associated with lower epigenetic GA in offspring. This lower epigenetic GA seems to be associated with a developmental disadvantage for boys, who, in early childhood, show greater psychiatric problems.