Browsing by Subject "GESTATIONAL-AGE"

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  • Wehkalampi, Karoliina; Muurinen, Mari; Wirta, Sara Bruce; Hannula-Jouppi, Katariina; Hovi, Petteri; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Andersson, Sture; Kere, Juha; Kajantie, Eero (2013)
  • Jääskeläinen, Tiina; Heinonen, Seppo; Hämäläinen, Esa; Pulkki, Kari; Romppanen, Jarkko; Laivuori, Hannele (2018)
    Objectives: To study first and second/third trimester levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in FINNPEC case-control cohort. The participants were further divided into subgroups based on parity and onset of the disease. Recommended cut-off values in aid of pre-eclampsia (PE) prediction and diagnosis were also tested. Methods: First trimester serum samples were available from 221 women who later developed PE and 239 women who did not develop PE. Second/third trimester serum samples were available from 175 PE and 55 non-PE women. sFl1-1 and PlGF were measured electro-chemiluminescence immunoassays and sEng by ELISA. Results: In all timepoints PlGF, endoglin and the sFlt-1/PlGF ratio were increased in the PE group compared to the non-PE group. The serum concentrations of sFlt-1 were increased only a second/third trimester in PE women. Higher concentrations of s-Flt1, endoglin and higher sFlt/PlGF ratio were found a the third trimester in primiparous women compared to multiparous women. Primiparous PE women also had lower concentrations of PlGF a the third trimester. The proportion of women exceeding all cut-offs of the sFlt-1/PlGF ratio (>= 33, >= 38, >= 85 and >= 110) was greater in the PE group, but there were also pre-eclamptic women who met rule-out cut-off or did no meet rule-in cut-off. Conclusions: Primiparous pregnancies have more anti-angiogenic profile during second/third trimester compared with multiparous pregnancies. Our findings also suggest that certain maternal characteristics, e.g. BMI, smoking and pre-existing diseases, should be taken into account when different sFlt-1/PlGF ratio cut-offs are utilized.
  • Jelenkovic, Aline; Mikkonen, Janne; Martikainen, Pekka; Latvala, Antti; Yokoyama, Yoshie; Sund, Reijo; Vuoksimaa, Eero; Rebato, Esther; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Stazi, Maria A.; Fagnani, Corrado; Brescianini, Sonia; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Krueger, Robert F.; Mcgue, Matt; Pahlen, Shandell; Nelson, Tracy L.; Whitfield, Keith E.; Brandt, Ingunn; Nilsen, Thomas S.; Harris, Jennifer R.; Cutler, Tessa L.; Hopper, John L.; Tarnoki, Adam D.; Tarnoki, David L.; Sorensen, Thorkild I. A.; Kaprio, Jaakko; Silventoinen, Karri (2018)
    Background There is evidence that birth weight is positively associated with education, but it remains unclear whether this association is explained by familial environmental factors, genetic factors or the intrauterine environment. We analysed the association between birth weight and educational years within twin pairs, which controls for genetic factors and the environment shared between co-twins. Methods The data were derived from nine twin cohorts in eight countries including 6116 complete twin pairs. The association between birth weight and educational attainment was analysed both between individuals and within pairs using linear regression analyses. Results In between-individual analyses, birth weight was not associated with educational years. Within-pairs analyses revealed positive but modest associations for some sex, zygosity and birth year groups. The greatest association was found in dizygotic (DZ) men (0.65 educational years/kg birth weight, p=0.006); smaller effects of 0.3 educational years/kg birth weight were found within monozygotic (MZ) twins of both sexes and opposite-sex DZ twins. The magnitude of the associations differed by birth year in MZ women and opposite-sex DZ twins, showing a positive association in the 1915-1959 birth cohort but no association in the 1960-1984 birth cohort. Conclusion Although associations are weak and somewhat inconsistent, our results suggest that intrauterine environment may play a role when explaining the association between birth weight and educational attainment.
  • Mardones, Francisco; Arnaiz, Pilar; Pacheco, Paz; Dominguez, Angelica; Villarroel, Luis; Eriksson, Johan G.; Barja, Salesa; Farias, Marcelo; Castillo, Oscar (2014)
  • Gomez, Marta; Moles, Laura; Espinosa-Martos, Irene; Bustos, Gerardo; de Vos, Willem M.; Fernandez, Leonides; Rodriguez, Juan M.; Fuentes, Susana; Jimenez, Esther (2017)
    An abnormal colonization pattern of the preterm gut may affect immune maturation and exert a long-term influence on the intestinal bacterial composition and host health. However, follow-up studies assessing the evolution of the fecal microbiota of infants that were born preterm are very scarce. In this work, the bacterial compositions of fecal samples, obtained from sixteen 2-year-old infants were evaluated using a phylogenetic microarray; subsequently, the results were compared with those obtained in a previous study from samples of meconium and feces collected from the same infants while they stayed in the neonatal intensive care unit (NICU). In parallel, the concentration of a wide range of cytokines, chemokines, growth factors and immunoglobulins were determined in meconium and fecal samples. Globally, a higher bacterial diversity and a lower interindividual variability were observed in 2-year-olds' feces, when compared to the samples obtained during their first days of life. Hospital-associated fecal bacteria, that were dominant during the NICU stay, seemed to be replaced, two years later, by genera, which are usually predominant in the healthy adult microbiome. The immune profile of the meconium and fecal samples differed, depending on the sampling time, showing different immune maturation statuses of the gut.
  • Bonamy, Anna-Karin Edstedt; Mohlkert, Lilly-Ann; Hallberg, Jenny; Liuba, Petru; Fellman, Vineta; Domellof, Magnus; Norman, Mikael (2017)
    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
  • Hjort, Line; Moller, Sofie Lykke; Minja, Daniel; Msemo, Omari; Nielsen, Birgitte Bruun; Christensen, Dirk Lund; Theander, Thor; Nielsen, Karsten; Larsen, Lise Grupe; Grunnet, Louise Groth; Groop, Leif; Prasad, Rashmi; Lusingu, John; Schmiegelow, Christentze; Bygbjerg, Ib C. (2019)
    Purpose Low-income and middle-income countries such as Tanzania experience a high prevalence of noncommunicable diseases (NCDs), including anaemia. Studying if and how anaemia affects growth, placenta development, epigenetic patterns and newborns' risk of NCDs may provide approaches to prevent NCDs. Participants The FOETALforNCD (FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life) Study is a population-based preconception, pregnancy and birth cohort study (n= 1415, n= 538, n= 427, respectively), conducted in a rural region of North-East Tanzania. All participants were recruited prior to conception or early in pregnancy and followed throughout pregnancy as well as at birth. Data collection included: maternal blood, screening for NCDs and malaria, ultrasound in each trimester, neonatal anthropometry at birth and at 1 month of age, cord blood, placental and cord biopsies for stereology and epigenetic analyses. Findings to date At preconception, the average age, body mass index and blood pressure of the women were 28 years, 23 kg/m(2) and 117/75 mm Hg, respectively. In total, 458 (36.7%) women had anaemia (haemoglobin Hb <12 g/dL) and 34 (3.6%) women were HIV-positive at preconception. During pregnancy 359 (66.7%) women had anaemia of which 85 (15.8%) women had moderate-tosevere anaemia (Hb = 9 g/dL) and 33 (6.1%) women had severe anaemia (Hb = 8 g/dL). In total, 185 (34.4%) women were diagnosed with malaria during pregnancy. Future plans The project will provide new knowledge on how health, even before conception, might modify the risk of developing NCDs and how to promote better health during pregnancy. The present project ended data collection 1 month after giving birth, but follow-up is continuing through regular monitoring of growth and development and health events according to the National Road Map Strategic Plan in Tanzania. This data will link fetal adverse event to childhood development, and depending on further grant allocation, through a life course follow-up.
  • Stevenson, N. J.; Oberdorfer, L.; Koolen, N.; O'Toole, J. M.; Werther, T.; Klebermass-Schrehof, K.; Vanhatalo, S. (2017)
    Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95% CI: 0.932-0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.
  • Sammallahti, Sara; Lahti, Marius; Pyhala, Riikka; Lahti, Jari; Pesonen, Anu-Katriina; Heinonen, Kati; Hovi, Petteri; Eriksson, Johan G.; Strang-Karlsson, Sonja; Jarvenpaa, Anna-Liisa; Andersson, Sture; Kajantie, Eero; Räikkönen, Katri (2015)
    Objectives Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) ( Study Design As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction. Results Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations. Conclusions Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.
  • Hovi, Petteri; Kajantie, Eero; Soininen, Pasi; Kangas, Antti J.; Järvenpää, Anna-Liisa; Andersson, Sture; Eriksson, Johan G.; Ala-Korpela, Mika; Wehkalampi, Karoliina (2013)
  • Martino, David; Loke, Yuk Jin; Gordon, Lavinia; Ollikainen, Miina; Cruickshank, Mark N.; Saffery, Richard; Craig, Jeffrey M. (2013)
  • Haataja, Ritva; Karjalainen, Minna K.; Luukkonen, Aino; Teramo, Kari; Puttonen, Hilkka; Ojaniemi, Marja; Varilo, Teppo; Chaudhari, Bimal P.; Plunkett, Jevon; Murray, Jeffrey C.; McCarroll, Steven A.; Peltonen, Leena; Muglia, Louis J.; Palotie, Aarno; Hallman, Mikko (2011)
  • Sentenac, Mariane; Benhammou, Valerie; Aden, Ulrika; Ancel, Pierre-Yves; Bakker, Leonhard A.; Bakoy, Hannah; Barros, Henrique; Baumann, Nicole; Bilsteen, Josephine Funck; Boerch, Klaus; Croci, Ileana; Cuttini, Marina; Draper, Elizabeth; Halvorsen, Thomas; Johnson, Samantha; Kallen, Karin; Land, Tuuli; Lebeer, Jo; Lehtonen, Liisa; Maier, Rolf F.; Marlow, Neil; Morgan, Andrei; Ni, Yanyan; Räikkönen, Katri; Rtimi, Anass; Sarrechia, Iemke; Varendi, Heili; Vollsaeter, Maria; Wolke, Dieter; Ylijoki, Milla; Zeitlin, Jennifer (2021)
    Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at = 37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (= 27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.
  • Robinson, Rachel; Lahti-Pulkkinen, Marius; Schnitzlein, Daniel; Voit, Falk; Girchenko, Polina; Wolke, Dieter; Lemola, Sakari; Kajantie, Eero; Heinonen, Kati; Räikkönen, Katri (2020)
    Preterm birth research is poised to explore the mental health of adults born very preterm(VP;1970) included VP/VLBW individuals with controls born at term(≥37+0 weeks) or with normal birth weight(NBW; ≥2500g). Thirteen studies were included. Studies consistently showed an increased risk for psychotropic medication use for VP/VLBW adults in comparison to NBW/term controls, but whether VP/VLBW adults have an increased risk for mental health disorders or symptoms appearing in adulthood remains uncertain. The quality of the evidence was moderate (65.8%) to high (34.2%). Further research in larger samples is needed.
  • Risnes, Kari; Bilsteen, Josephine Funck; Brown, Paul; Pulakka, Anna; Andersen, Anne-Marie Nybo; Opdahl, Signe; Kajantie, Eero; Sandin, Sven (2021)
    IMPORTANCE Adverse long-term outcomes in individuals born before full gestation are not confined to individuals born at extreme gestational ages. Little is known regarding mortality patterns among individuals born in the weeks close to ideal gestation, and the exact causes are not well understood; both of these are crucial for public health, with the potential for modification of risk. OBJECTIVE To examine the risk of all-cause and noncommunicable diseases (NCD) deaths among young adults born preterm and early term. DESIGN, SETTING, AND PARTICIPANTS This multinational population-based cohort study used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland for individuals born between 1967 and 2002. Individuals identified at birth who had not died or emigrated were followed up for mortality from age 15 years to 2017. Analyses were performed from June 2019 to May 2020. EXPOSURES Categories of gestational age (ie, moderate preterm birth and earlier [23-33 weeks], late preterm [34-36 weeks], early term [37-38 weeks], full term [39-41 weeks] and post term [42-44 weeks]). MAIN OUTCOMES AND MEASURES All-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD). RESULTS A total of 6 263 286 individuals were followed up for mortality from age 15 years. Overall, 339 403 (5.4%) were born preterm, and 3 049 100 (48.7%) were women. Compared with full-term birth, the adjusted hazard ratios (aHRs) for all-cause mortality were 1.44 (95% CI, 1.34-1.55) for moderate preterm birth and earlier; 1.23 (95% CI, 1.18-1.29) for late preterm birth; and 1.12 (95% CI, 1.09-1.15) for early-term birth. The association between gestational age and all-cause mortality were stronger in women than in men (P for interaction = .03). Preterm birth was associated with 2-fold increased risks of death from CVD (aHR, 1.89; 95% CI, 1.45-2.47), diabetes (aHR, 1.98; 95% CI, 1.44-2.73), and chronic lung disease (aHR, 2.28; 95% CI, 1.36-3.82). The main associations were replicated across countries and could not be explained by familial or individual confounding factors. CONCLUSIONS AND RELEVANCE The findings of this study strengthen the evidence of increased risk of death from NCDs in young adults born preterm. Importantly, the increased death risk was found across gestational ages up to the ideal term date and includes the much larger group with early-term birth. Excess mortality associated with shorter gestational age was most pronounced for CVDs, chronic lung disease, and diabetes.
  • Holmberg, Ville; Onkamo, Paivi; Lahtela, Laura Elisa; Lahermo, Paivi; Bedu-Addo, George; Mockenhaupt, Frank P.; Meri, Seppo (2012)
  • Pyhala, Riikka; Wolford, Elina; Kautiainen, Hannu; Andersson, Sture; Bartmann, Peter; Baumann, Nicole; Brubakk, Ann-Mari; Evensen, Kari Anne I.; Hovi, Petteri; Kajantie, Eero; Lahti, Marius; Van Lieshout, Ryan J.; Saigal, Saroj; Schmidt, Louis A.; Indredavik, Marit S.; Wolke, Dieter; Nat, Rer H. C.; Räikkönen, Katri (2017)
    CONTEXT: Preterm birth increases the risk for mental disorders in adulthood, yet findings on abstract self-reported or subclinical mental health problems are mixed. OBJECTIVE: To study self-reported mental health problems among adults born preterm at very low birth weight (VLBW; DATA SOURCES: Adults Born Preterm International Collaboration. STUDY SELECTION: Studies that compared self-reported mental health problems using the Achenbach Young Adult Self Report or Adult Self Report between adults born preterm at VLBW (n = 747) and at term (n = 1512). DATA EXTRACTION: We obtained individual participant data from 6 study cohorts and compared preterm and control groups by mixed random coefficient linear and Tobit regression. RESULTS: Adults born preterm reported more internalizing (pooled beta =.06; 95% confidence interval.01 to.11) and avoidant personality problems (.11;.05 to.17), and less externalizing (-.10;-. 15 to-. 06), rule breaking (-.10;-. 15 to-. 05), intrusive behavior (-.14;-. 19 to-.09), and antisocial personality problems (-.09;-. 14 to-.04) than controls. Group differences did not systematically vary by sex, intrauterine growth pattern, neurosensory impairments, or study cohort. LIMITATIONS: Exclusively self-reported data are not confirmed by alternative data sources. CONCLUSIONS: Self-reports of adults born preterm at VLBW reveal a heightened risk for internalizing problems and socially avoidant personality traits together with a lowered risk for externalizing problem types. Our findings support the view that preterm birth constitutes an early vulnerability factor with long-term consequences on the individual into adulthood.
  • Magnusson, Åsa; Laivuori, Hannele; Loft, Anne; Oldereid, Nan B.; Pinborg, Anja; Petzold, Max; Romundstad, Liv Bente; Söderström-Anttila, Viveca; Bergh, Christina (2021)
    Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences. Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes. Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes. Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded. Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I ( was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR ( was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed. Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes. Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies.
  • Bezold, Katherine Y.; Karjalainen, Minna K.; Hallman, Mikko; Teramo, Kari; Muglia, Louis J. (2013)
  • Mohlkert, Lilly-Ann; Hallberg, Jenny; Broberg, Olof; Rydberg, Annika; Halvorsen, Cecilia Pegelow; Liuba, Petru; Fellman, Vineta; Domellof, Magnus; Sjoberg, Gunnar; Norman, Mikael (2018)
    Background-Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results-In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions-Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.