[Postpartum hemorrhage in singleton births in Iceland 2013 - 2018, incidence proportion and risk factors].

INTRODUCTION: Many countries have reported an increased incidence proportion of postpartum hemorrhage (PPH). The proportion might also have increased at the National University Hospital of Iceland, based on the registration of the ICD-10 code O72. This study aimed to assess the incidence proportion and risk factors for ≥1000 ml PPH in singleton births in Iceland 2013-2018. METHODS: This population-based cohort study included data from the Icelandic Birth register on 21.110 singleton births in 2013-2018. Incidence proportion of PPH was assessed based on three definitions: PPH >500 ml, PPH ≥1000 ml, and O72. Binomial regression was used to assess both the change in the proportion of ≥1000 ml PPH over time, stratified by maternal BMI, and risk factors for ≥1000 ml PPH. RESULTS: There was an inconsistency in the proportion of PPH when defined by blood loss >500 ml and O72. In obese women, PPH ≥1000 ml was more than twice as likely in those delivering in 2018 compared with 2013 (OR 2.23; CI 1.35-3.81). The strongest risk factors were emergency cesarean (OR 2.68; CI 2.22-3.22) and instrumental delivery (OR 2.18; CI 1.80-2.64), but macrosomia, primiparity and BMI ≥30 were also independent risk factors. CONCLUSION: The incidence proportion of ≥1000 ml PPH has increased among obese women. The detrimental health effects of obesity and the increased prevalence of interventions among these women could explain these results. It is necessary to use registered blood loss in milliliters in the Icelandic Birth Register because of the under-registration of the diagnostic code O72.

Twin birth rates and obstetric interventions in Iceland: A nationwide study from 1997 to 2018.

OBJECTIVE: Twin pregnancies are associated with increased antepartum and intrapartum risks. Limited multiple embryo transfers are associated with decreased twin birth rates. We aimed to study the effect of 2009 Icelandic regulations on twin birth rates and examine obstetric intervention rates for twin births during the study period. METHODS: The study included all births (N = 94 028) in Iceland during 1997-2018. Twin birth rates and obstetric intervention rates were compared over birth year periods using modified Poisson regression adjusted for confounders. RESULTS: An observed decrease in the twin birth rate trend was most notable from 2006 until 2009. Twin birth decreased in 2009-2013 (prevalence ratio [PR] 0.74, 95% confidence interval [CI] 0.64-0.86) and in 2014-2018 (PR 0.74, 95% CI 0.64-0.86) compared with 1997-2002. This decrease was only evident for women aged 30+ years in stratified analysis. Induction of labor rates increased from 26% in 1997-2002 to 44% in 2014-2018 (adjusted rate ratio [ARR] 2.10, 95% CI 1.72-2.57) whereas elective cesarean section (ARR 0.80, 95% CI 0.59-1.07) and urgent cesarean section (ARR 0.79, 95% CI 0.63-1.00) rates appeared to decline. CONCLUSION: Twin births decreased during the study period. International guidelines published before the Icelandic regulations may have affected twin birth rates in Iceland. Induction of labor rates for twins increased while cesarean section rates decreased.

Trends in labor induction indications: A 20-year population-based study.

INTRODUCTION: Use of labor induction has increased rapidly in most middle- and high-income countries over the past decade. The reasons for the stark rise in labor induction are largely unknown. We aimed to assess the extent to which the rising rate of labor induction is explained by changes in rates of underlying indications over time. MATERIAL AND METHODS: The study was based on nationwide data from the Icelandic Medical Birth Register on 85 620 singleton births from 1997 to 2018. The rate of labor induction and indications for induction was calculated for all singleton births in 1997-2018. Change over time was expressed as relative risk (RR), using Poisson regression with 95% confidence intervals (CI) adjusted for maternal characteristics and indications for labor induction. RESULTS: The crude rate of labor induction rose from 12.5% in 1997-2001 to 23.9% in 2014-2018 (crude RR = 1.91, 95% CI 1.81-2.01). While adjusting for maternal characteristics had little impact, adjusting additionally for labor induction indications lowered the RR to 1.43 (95% CI 1.35-1.51). Induction was increasingly indicated from 1997-2001 to 2014-2018 by gestational diabetes (2.4%-16.5%), hypertensive disorders (7.0%-11.1%), prolonged pregnancy (16.2%-23.7%), concerns for maternal wellbeing (3.2%-6.9%) and maternal age (0.5%-1.2%). No indication was registered for 9.2% of inductions in 2014-2018 compared with 16.3% in 1997-2001. CONCLUSIONS: Our results show that the increase in labor induction over the study period is largely explained by an increase in various underlying conditions indicating labor induction. However, indications for 9.2% of labor inductions remain unexplained and warrant further investigation.

[Reducing rate of macrosomia in Iceland in relation to changes in the labor induction rate].

AIM: Diabetes and prolonged pregnancy are risk factors of macrosomia. The aim was to explore the relationship between the increased rate of labor induction and macrosomia in Iceland. Changes in the incidence proportion of macrosomia was estimated by gestational age. Further, the association between labor induction and macrosomia was estimated in reference to expectant management. MATERIAL AND METHODS: Data from the Iceland birth registry on 92,424 singleton births from 1997 to 2018 was used in this cohort study. Macrosomia was defined as birth weight more than 4.5 kg. The incidence proportion during three periods, 1997-2004, 2005-2011, 2012-2018, was calculated and stratified by gestational age. The relative risk reduction of macrosomia over time was calculated with log-binomial regression, using the first period as reference. The risk and relative risk of macrosomia compared with expectant management was estimated and adjusted for diabetes. RESULTS: The total number of macrosomic infants was 5110 and of those only 313 had a mother with diabetes. The incidence proportion of macrosomia was 6.5% during the period 1997-2004, but 4.6% during 2012-2018. A relative risk reduction of macrosomia over time was seen for deliveries after estimated due date. Labor induction decreased the risk of macrosomia, but the association persisted after adjustment for diabetes. CONCLUSION: The rate of macrosomia decreased in Iceland during the last two decades, but only a small proportion of macrosomic infants had a mother with diabetes. Labor induction decreased the risk of macrosomia, an association which seemed independent of diabetes.

Cesarean birth, obstetric emergencies, and adverse neonatal outcomes in Iceland during a period of increasing labor induction.

BACKGROUND: The rate of labor induction has risen steeply throughout the world. This project aimed to estimate changes in the rates of adverse maternal and neonatal outcomes in Iceland between 1997 and 2018, and to assess whether the changes can be explained by an increased rate of labor induction. METHODS: Singleton live births, occurring between 1997 and 2018, that did not start by prelabor cesarean, were identified from the Icelandic Medical Birth Register (n = 85 971). Rates of intrapartum cesarean birth (CB), obstetric emergencies, and neonatal outcomes were calculated, and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated with log-binomial regression (reference: 1997-2001). Adjustments were made for: (a) maternal characteristics, and (b) labor induction and gestational age. RESULTS: The rate of labor induction increased from 13.6% in the period 1997-2001 to 28.1% in the period 2014-2018. The rate of intrapartum CB decreased between the periods of 1997-2001 and 2014-2018 for both primiparous (aRR 0.76, 95% CI: 0.69 to 0.84) and multiparous women (aRR 0.55, 95% CI: 0.49 to 0.63). The rate of obstetric emergencies and adverse neonatal outcomes also decreased between these time periods. Adjusting for labor induction did not attenuate these associations. CONCLUSIONS: The rates of adverse maternal outcomes and adverse neonatal outcomes decreased over the study period. However, there was no evidence that this decrease could be explained by the increased rate of labor induction.

Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood.

BACKGROUND: Preeclampsia is associated with low birth weight, both because of increased risks of preterm and of small-for-gestational-age (SGA) births. Low birth weight is associated with accelerated childhood height gain and cardiovascular diseases later in life. The aim was to investigate if prenatal exposure to preeclampsia is associated with accelerated childhood height gain, also after adjustments for SGA-status and gestational age at birth. METHODS: In a cohort of children prenatally exposed to preeclampsia (n = 865) or unexposed (n = 22,898) we estimated height gain between birth and five years of age. The mean difference in height gain between exposed and unexposed children was calculated and adjustments were done with linear regression models. RESULTS: Children exposed to preeclampsia were on average born shorter than unexposed. Exposed children grew on average two cm more than unexposed from birth to five years of age. After adjustments for maternal characteristics including socioeconomic factors, height, body mass index (BMI) and diabetes, as well as for parents smoking habits, infant's breastfeeding and childhood obesity, the difference was 1.6 cm (95% CI 1.3-1.9 cm). Further adjustment for SGA birth only slightly attenuated this estimate, but adjustment for gestational age at birth decreased the estimate to 0.5 cm (95% CI 0.1-0.7 cm). CONCLUSION: Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood. The association seemed independent on SGA-status, but partly related to shorter gestational age at birth.

Prehypertension in Pregnancy and Risks of Small for Gestational Age Infant and Stillbirth.

It is not fully known whether maternal prehypertension is associated with increased risk of adverse fetal outcomes, and it is debated whether increases in blood pressure during pregnancy influence adverse fetal outcomes. We performed a population-based cohort study in nonhypertensive women with term (≥37 weeks) singleton births (n=157 446). Using normotensive (diastolic blood pressure [DBP] <80 mm Hg) women as reference, we calculated adjusted odds ratios with 95% confidence intervals between prehypertension (DBP 80-89 mm Hg) at 36 gestational weeks (late pregnancy) and risks of a small-for-gestational-age (SGA) birth or stillbirth. We further estimated whether an increase in DBP from early to late pregnancy affected these risks. We found that 11% of the study population had prehypertension in late pregnancy. Prehypertension was associated with increased risks of both SGA birth and stillbirth; adjusted odds ratios (95% confidence intervals) were 1.69 (1.51-1.90) and 1.70 (1.16-2.49), respectively. Risks of SGA birth in term pregnancy increased by 2.0% (95% confidence intervals 1.5-2.8) per each mm Hg rise in DBP from early to late pregnancy, whereas risk of stillbirth was not affected by rise in DBP during pregnancy. We conclude that prehypertension in late pregnancy is associated with increased risks of SGA birth and stillbirth. Risk of SGA birth was also affected by rise in DBT during pregnancy. Our findings provide new insight to the relationship between maternal blood pressure and fetal well-being and suggest that impaired maternal perfusion of the placenta contribute to SGA birth and stillbirth.

Risk of placental dysfunction disorders after prior miscarriages: a population-based study.

OBJECTIVE: The objective of the investigation was to study the association between prior miscarriages and the risks of placental dysfunction disorders, including preeclampsia, stillbirth, birth of a small for gestational age (SGA) infant, placental abruption, and spontaneous preterm birth. STUDY DESIGN: In a population-based cohort study including 619,587 primiparous women, we estimated risks of placental dysfunction disorders for women with 1 (n = 68,185), 2 (n = 11,410) and 3 or more (n = 3823) self-reported prior miscarriages. Risks were calculated as odds ratios by unconditional logistic regression analysis and adjustments were made for maternal age, early pregnancy body mass index, height, smoking habits, country of birth, years of formal education, in vitro fertilization, chronic hypertension, pregestational diabetes, hypothyroidism, systemic lupus erythematosis, fetal sex, and year of childbirth. RESULTS: Compared with women with no prior miscarriage, women with 1 prior miscarriage had almost no increased risks. Women with 2 prior miscarriages had increased risks of spontaneous preterm birth, preterm (<37 weeks) SGA infant, and placental abruption. The rates of all disorders were higher for women with 3 or more prior miscarriages compared with women without prior miscarriages: preeclampsia, 5.83% vs 4.27%; stillbirth, 0.69% vs 0.33%, SGA infant, 5.09% vs 3.22%, placental abruption, 0.81% vs 0.41%; and spontaneous preterm birth, 6.45% vs 4.40%. The adjusted odds ratios for preterm (<37 weeks) disorders in women with 3 prior miscarriages were approximately 2. CONCLUSION: History of 2 or more miscarriages is associated with an increased risk of placental dysfunction disorders and should be regarded as a risk factor in antenatal care.

The paternal role in pre-eclampsia and giving birth to a small for gestational age infant; a population-based cohort study.

OBJECTIVE: To estimate the effect of partner change on risks of pre-eclampsia and giving birth to a small for gestational age infant. DESIGN: Prospective population study. SETTING: Sweden. PARTICIPANTS: Women with their first and second successive singleton births in Sweden between 1990 and 2006 without pregestational diabetes and/or hypertension (n=446 459). OUTCOME MEASURES: Preterm (<37 weeks) and term (≥37 weeks) pre-eclampsia, and giving birth to a small for gestational age (SGA) infant. Risks were adjusted for interpregnancy interval, maternal age, body mass index, height and smoking habits in second pregnancy, years of involuntary childlessness before second pregnancy, mother's country of birth, years of formal education and year of birth. Further, when we calculated risks of SGA we restricted the study population to women with non-pre-eclamptic pregnancies. RESULTS: In women who had a preterm pre-eclampsia in first pregnancy, partner change was associated with a strong protective effect for preterm pre-eclampsia recurrence (OR 0.24; 95% CI 0.07 to 0.88). Similarly, partner change was also associated with a protective effect of recurrence of SGA birth (OR 0.75; 95% CI 0.67 to 0.84). In contrast, among women without SGA in first birth, partner change was associated with an increased risk of SGA in second pregnancy. Risks of term pre-eclampsia were not affected by partner change. CONCLUSIONS: There is a paternal effect on risks of preterm pre-eclampsia and giving birth to an SGA infant.

[Shortened hospital stay for elective cesarean section after initiation of a fast-track program and midwifery home-care]. / Stytt sjúkrahúslega við valkeisaraskurði eftir upptöku flýtibatameðferðar og heimaþjónustu.

OBJECTIVE: To audit whether hospital stay shortened without increasing readmissions after implementation of fast-track methodology for elective cesarean section and characterize what influences length of stay. METHODS: A fast-track program was initiated in November 2008, with a one year clinical audit and satisfaction survey. Discharge criteria were predefined and midwife home visits included if discharge was within 48 hours. Hospital stay by parity for women with elective section for singleton pregnancy between 1.11. 2008 - 31.10. 2009 (n=213, fast-track 182) was compared to 2003 (n=199) and 2007 (n=183). Readmissions and outpatient visits 2007 and 2008-9 were counted. Reasons for longer stay were recorded in fast-track, and body mass index. RESULT: Median hospital stay decreased significantly from 81 to 52 hours between 2007 and 2008-9. Readmissions were four in each period and outpatient visit rates similar. In 2008-9, 66% of all women were discharged within 48 hours. Women in the fast-track program were satisfied with early discharge. Hospital stay for parous women was shorter in 2007 compared to 2003, but unchanged for nulliparas. Parity had a minimal influence on length of stay in 2008-9, although nulliparous women ≤ 25 years were more likely to stay >48 hours. Body mass index did not correlate with length of stay. Pain was rarely the reason for a longer stay in the fast-track program and 90% were satisfied with pain-medication after discharge. CONCLUSION: Most healthy women can be discharged early after singleton birth by elective cesarean, without increasing readmissions.

Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide.

BACKGROUND: The natriuretic hormone peptide (NHP)(99-126), a C-terminal peptide of pro-atrial natriuretic factor (proANF), induces bronchodilatory effects in people with asthma. Recently, another plasmid-encoded C-terminal peptide, pNHP(73-102), was shown to induce a long-lasting bronchoprotective effect in a mouse model of allergic asthma. OBJECTIVE: This study was carried out to determine the role of lung epithelial cells in the bronchoprotective and anti-inflammatory activity of these peptides. METHODS: Human type II alveolar epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells were transfected with pNHP(73-102) to test the effect of this peptide on activation of these cells. After transfection, cells were analyzed for changes in Ca(++) and nitric oxide (NO) levels. Also, activation of NFkappaB and the extracellularly regulated kinase (ERK) 1, 2 signaling pathway was examined by luciferase reporter assay and phosphorylation studies respectively. RESULTS: Analysis of intracellular Ca(++) levels in pNHP(73-102) -transfected A549 or NHBE showed that the peptide increases release. This Ca(++) release was accompanied by an increase in the production of NO. Also, overexpression of pNHP(73-102), but not pVAX control, in phorbol myristate acetate-activated A549 cells resulted in a significant decrease in expression of a cotransfected nuclear factorkappaB (NFkappaB)-luciferase reporter. Similarly, pNHP(73-102) decreased TNF-alpha-induced NFkappaB activation in NHBE cells. Furthermore, NHP(73-102) but not atrial natriuretic peptide decreased phosphorylation of Erk-1, 2 in A549 cells. CONCLUSIONS: Overexpression of pNHP(73-102) in epithelial cells causes increased production of intracellular Ca(++) and NO, with a concomitant decrease in activation of NFkappaB and ERK1, 2. These results suggest a bronchodilatory and anti-inflammatory activity of this peptide.