Postpartum hemorrhage in families : A Norwegian population-based study

Bakgrunn: Postpartum blødning (PPB) er den ledende direkte årsaken til verdens mødredødelighet og forekomsten har en økende trend i utviklende land. Mål: Å studere gjentagelsesrisiko for PPB hos en kvinne, over generasjoner og mellom søsken, samt å utforske hvordan risikoen påvirkes høy fødselsvekt. Materiale og metode: Med data fra Medisinsk Fødselsregister (MFR) gjennomførte vi en populasjonsbasert studie av enlinger (1967–2017). Vi identifiserte individer som nyfødte, foreldre , besteforeldre og søsken. Vi benyttet multilevel logistisk regresjon for å beregne odds ratio (OR) med 95% konfidensintervall (KI). I tillegg beregnet vi justerte populasjonstilskrivbare fraksjoner. Resultater: Gjentagelsesrisikoen hos en kvinne var sterkest for alvorlig PPB (OR: 6.0; 5.5–6.6). Gentagelsesrisikoen over generasjoner var sterkere på morssiden enn farssiden av slekten. Gjentagelsesrisikoen mellom søsken var størst mellom helsøstre (OR 1.47; 1.41–1.52), fulgt av maternelle halvsøstre, paternelle halvsøstre og partnere av helbrødre. Tidligere PPB hos en kvinne og fødselseslsvekt ≥4000 g representerte 15 av PPB tilfellene. Maternelle, føtale og obstetriske egenskaper hadde forskjellige assosiasjoner med type-spesifikk PPB. Det var sterkest tendens til at PPB typene gjentok seg selv. Denne effekten var sterkest for dystocirelatert PPB (aOR: 6.8; 6.3–7.4). PPB grunnet retinert placenta var oftest registrert som alvorlig blødning og viste størst effekt av fosterets kjønn; guttefostre hadde lavere risiko for PPB (aOR: 0.80; 0.78–0.82). Tidligere keisersnitt var sterkt assosiert med dystocirelatert PPB (aOR: 13.2; 12.5–13.9). Konklusjon: Individuell og familiehistorikk med PPB påvirker den fødendes risiko for PPB i et dose-respons mønster og samsvarer med den forventede andelen av delte gener. Risikoen var uavhengig av risikoen assosiert med høy fødselsvekt. Vår studie indikerer at genetiske eller vedvarende miljøfaktorer bidrar til PPB. Retinert placenta var oftest assosiert med alvorlig PPB. Dystocirelatert PPB hadde høyest gjentagelsesrisiko og var sterkt assosiert med tidligere keisersnitt. Dette gjør det naturlig å sette søkelys på disse to typene i fremtidige studier som omhandler PPB og forebyggende tiltak hos kvinner med egen eller familiehistorikk med PPB.Background: Postpartum haemorrhage (PPH) is the leading cause of direct maternal morbidity in the world. The trend of PPH occurrence increase in developed countries. Aim: To explore the risk of recurrent PPH in a woman, through generations and between siblings. Secondly, to study how these risks interact with high birthweight. Material and methods: With data from the Medical Birth Registry of Norway we performed a population-based cohort study including singleton births (1967–2017). We identified individuals as newborns, parents, grandparents, and siblings. We used multilevel logistic regression to calculate the odds ratios (OR), with 95% confidence interval (CI). We also calculated adjusted population attributable fractions (aPAR). Results: The PPH recurrence risk was strongest for severe PPH (OR: 6.0; 5.5–6.6). Generational recurrence risk was stronger through the maternal than paternal line. Recurrence between siblings was highest between full sisters (OR 1.47; 1.41–1.52), followed by maternal half-sisters, paternal half-sisters and partners of full brothers. A history of PPH in a woman or birthweight ≥4000 g each accounted for 15% (aPAR) of PPH cases. Maternal, fetal, and obstetric characteristics showed differential associations with PPH types. Recurrence risk was strongest for the same type to reoccur and most pronounced for PPH due to dystocia (aOR: 6.8; 6.3–7.4). PPH due to retained placenta was most often registered as severe and showed the strongest effect of the sex of the neonate: males carried lower risk (aOR: 0.80; 0.78–0.82). Previous cesarean section showed strong association with PPH due to dystocia (aOR of 13.2; 12.5–13.9). Conclusion: Individual and family history of PPH affected women’s risk of PPH in a dose response pattern and consistent with the anticipated proportion of shared genes. This was independent of the risk associated with high birthweight. Our findings implies that genetic or sustained environmental factors contribute to PPH. Retained placenta was the type of PPH most often registered with severe PPH. Dystocia related PPH had strongest recurrence risk and was strongly associated with previous cesarean. This makes these two types of PPH self-appointed for future study on PPH-preventive measures in woman with individual or family history of PPH.Doktorgradsavhandlin

Paternal and maternal birthweight and offspring risk of macrosomia at term gestations: A nationwide population study

Background There is a paucity of data on whether parents' macrosomia (birthweight ≥4500 g) status influences the risk of macrosomia in the offspring. The role of maternal overweight in the generational effect of macrosomia is not known. Objective To estimate the risk of macrosomia by parental birthweight at term and evaluate if this risk varied with maternal body mass index (BMI, kg/m2) early in pregnancy. Methods We used data from the Medical Birth Registry of Norway on all singleton term births (37–42 gestational weeks) during 1967–2017. The primary exposure was parental macrosomia, and the outcome was macrosomia in the second generation. The secondary exposure was maternal BMI. We used binomial regression to calculate relative risk (RR) with a 95% confidence interval. We assessed potential unmeasured confounding and selection bias using a probabilistic bias analysis and performed analyses with and without imputation for variables with missing values. Results The data included 647,957 singleton parent-offspring trios born at term. The prevalence of macrosomia was 3.2% (n = 41,396) in the parental generation and 4.0% (n = 25,673) in the offspring generation. Macrosomia in parents was associated with an increased risk of macrosomia in offspring, with the RR for both parents were born macrosomic being 6.53 (95% confidence interval [CI] 5.31, 8.05), only mother macrosomic 3.37 (95% CI 3.17, 3.57) and only father macrosomic RR 2.22 (95% CI 2.12, 2.33). These risks increased by maternal BMI in early pregnancy: if both parents were born macrosomic, 17% of infants were macrosomic among mothers with normal BMI. If both parents were macrosomic and the mothers were obese, 31% of offspring were macrosomic. Macrosomia-related adverse outcomes did not differ with parental macrosomia status. Conclusions Parents' weight at birth and maternal BMI appear to be strongly associated with macrosomia in the offspring delivered at term gestations.publishedVersio

Recurrence of postpartum hemorrhage in relatives: A population-based cohort study

Introduction Studies on the family aggregation of postpartum hemorrhage (PPH) are scarce and with inconsistent results, and to what extent current birthweight influences recurrence between relatives remains to be studied. Further, family aggregation of PPH has been studied from an individual, but not from a public heath perspective. We aimed to investigate family aggregation of PPH in Norway, how birthweight influences these effects, and to estimate the proportion of PPH cases attributable to a family history of PPH and current birthweight. Material and methods Using data from the Medical Birth Registry of Norway, Statistics Norway, and Central Population Registry of Norway we identified individuals as newborns, parents, grandparents, and full and half-siblings, and studied 1 002 687 mother–offspring, 841 164 father–offspring, and 761 011 both-parents–offspring pairs. We used multilevel logistic regression to calculate odds ratios (OR) with 95% CI. Results If the birth of the mother but not of the father involved PPH, then the OR of PPH (>500 mL) in the next generation was 1.44 (95% CI 1.39–1.49). If the birth of the father but not of the mother involved PPH, then OR was 1.12 (95% CI 1.08–1.16). These effects were stronger in severe PPH. Recurrence between siblings was highest between full sisters (OR 1.47, 95% CI 1.41–1.52), followed by maternal half-sisters, paternal half-sisters, and partners of full brothers. A family history of PPH or birthweight of 4000 g or more accounted for ≤5% and 15% of the total number of PPH cases, respectively. Conclusions A history of PPH in relatives influenced the recurrence risk of PPH in a dose–response pattern consistent with the anticipated proportion of shared genes. The recurrence was highest through the maternal line.publishedVersio

Recurrence of postpartum hemorrhage, maternal and paternal contribution, and the effect of offspring birthweight and sex: a population-based cohort study

Purpose: This study examines individual aggregation of postpartum hemorrhage (PPH), paternal contribution and how offspring birthweight and sex influence recurrence of PPH. Further, we wanted to estimate the proportion of PPH cases attributable to a history of PPH or current birthweight. Methods: We studied all singleton births in Norway from 1967 to 2017 using data from Norwegian medical and administrational registries. Subsequent births in the parents were linked. Multilevel logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PPH defined as blood loss > 500 ml, blood loss > 1500 ml, or the need for blood transfusion in parous women. Main exposures were previous PPH, high birthweight, and fetal sex. We calculated adjusted population attributable fractions for previous PPH and current high birthweight. Results: Mothers with a history of PPH had three- and sixfold higher risks of PPH in their second and third deliveries, respectively (adjusted OR 2.9; 95% CI 2.9–3.0 and 6.0; 5.5–6.6). Severe PPH (> 1500 ml) had the highest risk of recurrence. The paternal contribution to recurrence of PPH in deliveries with two different mothers was weak, but significant. If the neonate was male, the risk of PPH was reduced. A history of PPH or birthweight ≥ 4000 g each accounted for 15% of the total number of PPH cases. Conclusion: A history of PPH and current birthweight exerted strong effects at both the individual and population levels. Recurrence risk was highest for severe PPH. Occurrence and recurrence were lower in male fetuses, and the paternal influence was weak.publishedVersio

A Symmetry for the Cosmological Constant

We study a symmetry, schematically Energy -> - Energy, which suppresses matter contributions to the cosmological constant. The requisite negative energy fluctuations are identified with a "ghost" copy of the Standard Model. Gravity explicitly, but weakly, violates the symmetry, and naturalness requires General Relativity to break down at short distances with testable consequences. If this breakdown is accompanied by gravitational Lorentz-violation, the decay of flat spacetime by ghost production is acceptably slow. We show that inflation works in our scenario and can lead to the initial conditions required for standard Big Bang cosmology.Comment: 18 pages, 3 figures, References correcte

Chaotic Inflationary Universe on Brane

The chaotic inflationary model of the early universe, proposed by Linde is explored in the brane world considering matter described by a minimally coupled self interacting scalar field. We obtain cosmological solutions which admit evolution of a universe either from a singularity or without a singularity. It is found that a very weakly coupled self-interacting scalar field is necessary for a quartic type potential in the brane world model compared to that necessary in general relativity. In the brane world sufficient inflation may be obtained even with an initial scalar field having value less than the Planck scale. It is found that if the universe is kinetic energy dominated to begin with, it transits to an inflationary stage subsequently.Comment: 13 pages, no fig., accepted in Physical Review

Generalizing the ADM Computation to Quantum Field Theory

The absence of recognizable, low energy quantum gravitational effects requires that some asymptotic series expansion be wonderfully accurate, but the correct expansion might involve logarithms or fractional powers of Newton's constant. That would explain why conventional perturbation theory shows uncontrollable ultraviolet divergences. We explore this possibility in the context of the mass of a charged, gravitating scalar. The classical limit of this system was solved exactly in 1960 by Arnowitt, Deser and Misner, and their solution does exhibit nonanalytic dependence on Newton's constant. We derive an exact functional integral representation for the mass of the quantum field theoretic system, and then develop an alternate expansion for it based on a correct implementation of the method of stationary phase. The new expansion entails adding an infinite class of new diagrams to each order and subtracting them from higher orders. The zeroth order term of the new expansion has the physical interpretation of a first quantized Klein-Gordon scalar which forms a bound state in the gravitational and electromagnetic potentials sourced by its own probability current. We show that such bound states exist and we obtain numerical results for their masses.Comment: 42 pages, 8 figures, 1 table, uses LaTeX2

Postpartum hemorrhage in families : A Norwegian population-based study

Bakgrunn: Postpartum blødning (PPB) er den ledende direkte årsaken til verdens mødredødelighet og forekomsten har en økende trend i utviklende land. Mål: Å studere gjentagelsesrisiko for PPB hos en kvinne, over generasjoner og mellom søsken, samt å utforske hvordan risikoen påvirkes høy fødselsvekt. Materiale og metode: Med data fra Medisinsk Fødselsregister (MFR) gjennomførte vi en populasjonsbasert studie av enlinger (1967–2017). Vi identifiserte individer som nyfødte, foreldre , besteforeldre og søsken. Vi benyttet multilevel logistisk regresjon for å beregne odds ratio (OR) med 95% konfidensintervall (KI). I tillegg beregnet vi justerte populasjonstilskrivbare fraksjoner. Resultater: Gjentagelsesrisikoen hos en kvinne var sterkest for alvorlig PPB (OR: 6.0; 5.5–6.6). Gentagelsesrisikoen over generasjoner var sterkere på morssiden enn farssiden av slekten. Gjentagelsesrisikoen mellom søsken var størst mellom helsøstre (OR 1.47; 1.41–1.52), fulgt av maternelle halvsøstre, paternelle halvsøstre og partnere av helbrødre. Tidligere PPB hos en kvinne og fødselseslsvekt ≥4000 g representerte 15 av PPB tilfellene. Maternelle, føtale og obstetriske egenskaper hadde forskjellige assosiasjoner med type-spesifikk PPB. Det var sterkest tendens til at PPB typene gjentok seg selv. Denne effekten var sterkest for dystocirelatert PPB (aOR: 6.8; 6.3–7.4). PPB grunnet retinert placenta var oftest registrert som alvorlig blødning og viste størst effekt av fosterets kjønn; guttefostre hadde lavere risiko for PPB (aOR: 0.80; 0.78–0.82). Tidligere keisersnitt var sterkt assosiert med dystocirelatert PPB (aOR: 13.2; 12.5–13.9). Konklusjon: Individuell og familiehistorikk med PPB påvirker den fødendes risiko for PPB i et dose-respons mønster og samsvarer med den forventede andelen av delte gener. Risikoen var uavhengig av risikoen assosiert med høy fødselsvekt. Vår studie indikerer at genetiske eller vedvarende miljøfaktorer bidrar til PPB. Retinert placenta var oftest assosiert med alvorlig PPB. Dystocirelatert PPB hadde høyest gjentagelsesrisiko og var sterkt assosiert med tidligere keisersnitt. Dette gjør det naturlig å sette søkelys på disse to typene i fremtidige studier som omhandler PPB og forebyggende tiltak hos kvinner med egen eller familiehistorikk med PPB

Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study

<div><p>Objectives</p><p>To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length.</p><p>Design</p><p>Population based registry study.</p><p>Setting</p><p>Medical Birth Registry of Norway 1999–2013.</p><p>Population</p><p>All singleton births (gestational age>22weeks<45 weeks) (n = 856 300).</p><p>Methods</p><p>Descriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders.</p><p>Main outcome measures</p><p>Short or long cord (<10^th or >90^th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death.</p><p>Results</p><p>Increasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman.</p><p>Conclusion</p><p>Cord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse outcomes including perinatal death. We provide population based reference ranges for umbilical cord length.</p></div

Odds ratios of adverse pregnancy outcomes in pregnancies with a short umbilical cord (<10th sex and parity specific percentile) in the population of singleton births in Norway 1999–2013.

<p>Odds ratios of adverse pregnancy outcomes in pregnancies with a short umbilical cord (<10th sex and parity specific percentile) in the population of singleton births in Norway 1999–2013.</p