Norwegian Medical Birth Registry Research Articles

Folic Acid and Risk of Preterm Birth, Preeclampsia, and Fetal Growth Restriction Among Women With Epilepsy: A Prospective Cohort Study.

Background and ObjectivesWomen with epilepsy treated with antiseizure medication (ASM) have increased risk of pregnancy complications including preterm birth, fetal growth restriction, and preeclampsia. We aimed to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM.MethodsSingleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) (1999–2008) were included. Information on maternal epilepsy, ASM, folic acid supplementation, and pregnancy outcomes was obtained from the MoBa questionnaires and the Norwegian Medical Birth Registry. The main exposure, periconceptional folic acid supplementation, was defined as intake between 4 weeks before pregnancy and 12 weeks into pregnancy, retrospectively collected by recall of the mothers in weeks 17–19. The primary outcomes were preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia.ResultsThe study included 100,105 pregnancies: 99,431 without maternal epilepsy, 316 with maternal epilepsy and ASM exposure in pregnancy, and 358 with untreated maternal epilepsy. Among ASM-treated women with epilepsy, the risk of preterm birth was higher in those who did not use periconceptional folic acid (n = 64) compared with those who did (n = 245, the reference) (adjusted odds ratio [aOR] 3.3, 95% CI 1.2–9.2), while the risk of preterm birth among the reference was similar to the risk among women without epilepsy using folic acid periconceptionally (aOR 0.9, 95% CI 0.5–1.6). ASM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared with women without epilepsy with similar timing of folic acid (aOR 2.6, 95% CI 1.1–6.5), and even higher if not using folic acid (aOR 9.4, 95% CI 2.6–34.8). Folic acid was not associated with risk of preterm birth among women with epilepsy without ASM or among women without epilepsy. Folic acid was not associated with risk of preeclampsia or SGA among women with epilepsy.DiscussionIn women with epilepsy using ASM, periconceptional folic acid was associated with a lower risk of preterm birth. This finding supports the recommendation that ASM-treated women with epilepsy of childbearing potential should use folic acid supplementation on a regular basis.Classification of EvidenceThis study provides Class III evidence that for women with epilepsy using ASM, periconceptional folic acid supplementation decreases the risk of preterm birth.

Peripartum hysterectomy due to severe postpartum hemorrhage: A hospital-based study.

A peripartum hysterectomy is typically performed as a lifesaving procedure in obstetrics to manage severe postpartum hemorrhage. Severe hemorrhages that lead to peripartum hysterectomies are mainly caused by uterine atony and placenta accreta spectrum disorders. In this study, we aimed to estimate the incidence, risk factors, causes and management of severe postpartum hemorrhage resulting in peripartum hysterectomies, and to describe the complications of the hysterectomies. Eligible women had given birth at gestational week 23+0 or later and had a postpartum hemorrhage ≥1500 mL or a blood transfusion, due to postpartum hemorrhage, at Oslo University Hospital, Norway, between 2008 and 2017. Among the eligible women, this study included those who underwent a hysterectomy within the first 42 days after delivery. The Norwegian Medical Birth Registry provided the reference group. We used Poisson regression to estimate adjusted incidence rate ratios with 95% confidence intervals to identify clinical factors associated with peripartum hysterectomy. The incidence of hysterectomies with severe postpartum hemorrhage was 0.44/1000 deliveries (42/96313). Among the women with severe postpartum hemorrhage, 1.6% ended up with a hysterectomy (42/2621). Maternal age ≥40, previous cesarean section, multiple pregnancy and placenta previa were associated with a significantly higher risk of hysterectomy. Placenta accreta spectrum disorders were the most frequent cause of hemorrhage that resulted in a hysterectomy (52%, 22/42) and contributed to most of the complications following the hysterectomy (11/15 women with complications). The rate of peripartum hysterectomies at Oslo University Hospital was low, but was higher than previously reported from Norway. Risk factors included high maternal age, previous cesarean section, multiple pregnancy and placenta previa, well known risk factors for placenta accreta spectrum disorders and severe postpartum hemorrhage. Placenta accreta spectrum disorders were the largest contributor to hysterectomies and complications.

Changes in maternal risk factors and their association with changes in cesarean sections in Norway between 1999 and 2016: A descriptive population-based registry study.

BackgroundIncreases in the proportion of the population with increased likelihood of cesarean section (CS) have been postulated as a driving force behind the rise in CS rates worldwide. The aim of the study was to assess if changes in selected maternal risk factors for CS are associated with changes in CS births from 1999 to 2016 in Norway.Methods and findingsThis national population-based registry study utilizes data from 1,055,006 births registered in the Norwegian Medical Birth Registry from 1999 to 2016. The following maternal risk factors for CS were included: nulliparous/≥35 years, multiparous/≥35 years, pregestational diabetes, gestational diabetes, hypertensive disorders, previous CS, assisted reproductive technology, and multiple births. The proportion of CS births in 1999 was used to predict the number of CS births in 2016. The observed and predicted numbers of CS births were compared to determine the number of excess CS births, before and after considering the selected risk factors, for all births, and for births stratified by 0, 1, or >1 of the selected risk factors. The proportion of CS births increased from 12.9% to 16.1% (+24.8%) during the study period. The proportion of births with 1 selected risk factor increased from 21.3% to 26.3% (+23.5%), while the proportion with >1 risk factor increased from 4.5% to 8.8% (+95.6%). Stratification by the presence of selected risk factors reduced the number of excess CS births observed in 2016 compared to 1999 by 67.9%. Study limitations include lack of access to other important maternal risk factors and only comparing the first and the last year of the study period.ConclusionsIn this study, we observed that after an initial increase, proportions of CS births remained stable from 2005 to 2016. Instead, both the size of the risk population and the mean number of risk factors per birth continued to increase. We observed a possible association between the increase in size of risk population and the additional CS births observed in 2016 compared to 1999. The increase in size of risk population and the stable CS rate from 2005 and onward may indicate consistent adherence to obstetric evidence-based practice in Norway.

An 11-year nationwide registry-linkage study of opioid maintenance treatment in pregnancy in Norway

Aim: We aimed to describe opioid maintenance treatment (OMT) to pregnant women in Norway and study thebackground characteristics of the pregnant women compared to the general population of pregnant women andto a previous clinical cohort study of OMT in pregnancy.Methods: Population-based cohort study with linked data from the Norwegian Medical Birth Registry, theNorwegian Prescription Database, the Norwegian Patient Registry, and Statistics Norway. The study populationconsisted of women giving birth between 2005-2015 in Norway. We defined OMT pregnancies as pregnancieswhere the woman was dispensed OMT medications (methadone, buprenorphine, or buprenorphine/naloxone) at least once during pregnancy.Results: The study population consisted of 420,808 women with 645,440 pregnancies ending in a live birth inNorway in 2005-2015 (the general pregnant population). Of these, 261 women (0.6‰) had altogether 306OMT pregnancies. The mean number of pregnancies was 28 OMT pregnancies per year and quite stable duringthe study period. Women with OMT pregnancies were older, smoked tobacco more frequently, had lowereducation, and fewer of them had a partner, compared to the general population of pregnant women. In mostpregnancies, the women were treated with buprenorphine (n=183 (59.8%)), while in 120 (39.2%) pregnancies,the woman received methadone. From 2008, buprenorphine replaced methadone as the most frequently useddrug. In only 38 (12.4%) pregnancies, OMT treatment was initiated in pregnancy. In 201 (66%) pregnancies,the woman used OMT medications in all trimesters. For these women, the mean amount of dispensed drug was3.4 DDD/day (85 mg/day) in pregnancy for methadone and 1.9 DDD/day (15.2 mg/day) for buprenorphine.Conclusion: The number of OMT pregnancies per year has been low and stable in the period 2005-2015.Following Norwegian recommendations, there has been a shift from treatment with methadone towardsbuprenorphine. The women receiving OMT during pregnancy had more risk factors for adverse outcomes thanthe general pregnant population but were quite similar to the previous clinical cohort.

Caesarean section and the association with migraine: a retrospective register-linked HUNT population cohort study

ObjectivesTo evaluate the association between caesarean section and migraine in a population-based register-linked cohort study.SettingData from the population-based Nord-Trøndelag Health Studies (HUNT2 and HUNT3) were linked to information from the...

P0767INTRAUTERINE GROWTH RESTRICTION AND RISK OF KIDNEY DISEASE DURING THE FIRST 50 YEARS OF LIFE

Abstract Background and Aims Previous studies have shown that Low Birth Weight (LBW) and small for gestational age (SGA) are associated with increased risk of end-stage renal disease. Few population-based studies have however investigated risk of less severe kidney disease and in the present study, we investigate risk of chronic kidney disease and other kidney disease diagnoses. Method The Norwegian Patient Registry (NPR) has registered ICD diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008 (available for 2008-2016 in this study). The Norwegian Medical Birth Registry (MBR) has registered birth weight, gestational age and several other data on maternal and offspring health for all birth in Norway since 1967. Data from these registries were linked and risk of chronic kidney disease (CKD) and other groups of kidney disease were analyzed with logistic regression statistics. LBW (less than the 10th percentile), SGA (less than the 10th percentile) and preterm birth (less than 37 weeks) were analyzed as risk markers. Adjusted analyses were performed for the main analyses by including birth year, gender, maternal disease, maternal preeclampsia, maternal marital status and malformations in the newborn. Results Of the 2,663,010 included individuals, 4,495 had been diagnosed with CKD and 12,818 with acute kidney disease, glomerulonephritis, hereditary kidney disease or kidney disease due to kidney or urinary tract malformations. LBW was associated with an adjusted odds ratio (aOR) for CKD of 1.61 (1.48-1.74), SGA with an aOR of 1.51 (1.39-1.63) and preterm birth with an aOR of 1.47 (1.31-1.66). As compared to subjects with none of these risk factors (LBW, SGA or preterm birth), subjects with only one risk factor had an aOR of 1.49 (1.35-1.66), subjects with 2 risk factors had adjusted aOR of 1.72 (1.57-1.88) and subjects with 3 risk factors had aOR of 2.56(1.99-3.29). Analyses of chronic kidney disease stage 3, 4 and 5 showed similar results. There were no significant gender differences. We further analysed aOR for other groups of kidney disease and found that LBW was associated with aOR of 1.52 (1.40-1.65) for acute kidney disease, 1.26 (1.16-1.38) for glomerulonephritis, 1.55 (1.34-1.80) for hereditary kidney disease and 1.38 (1.27-1.49) for kidney disease due to kidney or urinary tract malformations; analyses for the other risk factors showed similar results. Conclusion LBW and SGA are strong risk factors for diagnosis of all stages of CKD during the first 50 years of life and the risks seem to be increased also for other groups of kidney disease. Our results underline the public health importance of LBW and SGA.

Effect of maternal country of birth on intrapartum epidural use – A population-based register study of 602 095 deliveries

ObjectiveTo assess intrapartum epidural use during vaginal delivery among immigrant women giving birth in Norway, compared with Norwegian born women, and to explore associations between epidural use and other maternal characteristics, fetal and obstetrical variables. Study designPopulation-based cohort study. Data were obtained from Norwegian Medical Birth Registry and Statistics Norway, including 602 095 deliveries in 1999-2014. Intrapartum epidural analgesia use was described in percentages. Multivariable logistic regression analysis was performed to investigate the association between maternal country of birth and intrapartum epidural use, adjusted with maternal and fetal comorbidity, age, stillbirth, birthweight, fetal presentation, delivery method and time period. ResultsThere were significant differences in epidural use between women born in different parts of the world. Among nulliparous women, increased odds for intrapartum epidural use was observed among women born in Latin America compared with Norwegian born women, even after adjustment for maternal, fetal and obstetrical factors (aOR 1.93, CI 1.79-2.09). Reduced odds for intrapartum epidural use was observed among nulliparous women born in Sub-Saharan Africa (aOR 0.83, CI 0.78-0.88), East Asia and Pacific area (aOR 0.83, CI 0.80-0.87), and women with unknown country of birth (aOR 0.79, CI 0.71-0.89) compared with Norwegian born women. Similar pattern was observed among parous women from Latin America (aOR 1.69, CI 1.54-1.87), Sub-Saharan Africa (aOR 0.62, CI 0.57-0.67), East-Asia and Pacific area (aOR 0.68, CI 0.64-0.73), unknown country of birth (aOR 0.97, CI 0.84-1.13). Maternal hypertensive disorders, high infant birthweight, stillbirth, breech presentation and operative vaginal delivery increased the odds for use of intrapartum epidural analgesia. ConclusionsWe found differences between immigrant women from different parts of the world and use of intrapartum epidural, possibly related to un-measurable issues like cultural differences, maternal expectations and knowledge of safety on pain relief during childbirth. Intrapartum epidural use was more frequent in conditions related to maternal co-morbidity and factors indicating complicated delivery.

Perinatal complications and executive dysfunction in early-onset schizophrenia

BackgroundThe present study examined the association between perinatal obstetric complications and executive dysfunction in early-onset schizophrenia (EOS), compared to healthy controls. Higher incidences of obstetric complications and more severe executive dysfunctions characterize EOS. Research shows extensive brain maturation in newborns, suggesting them to be particularly vulnerable for perinatal insults. Executive function is mainly mediated by the prefrontal cortex, an area that matures last during pregnancy. Thus, exposure to perinatal complications may influence executive dysfunction in EOS.MethodsThe participants were 19 EOS patients and 54 healthy controls. Executive function was assessed with the D-KEFS Color Word Interference Test and the Wisconsin Card Sorting Test. Information on perinatal obstetric complications and Apgar 5-min scores were obtained from the Norwegian Medical Birth Registry. Associations between perinatal conditions and executive function were studied using stepwise regression analyses.ResultsPerinatal complications, and especially shorter gestational lengths, were significantly associated with significant executive dysfunctions in EOS. Perinatal complications did not affect executive function among healthy controls. A significant relationship between lower Apgar 5-min scores and executive dysfunction was found among both EOS patients and healthy controls.ConclusionsExposure to perinatal complications, and particularly a shorter gestational length, was associated with increased executive dysfunction in EOS. Exposed healthy controls did not exhibit similar executive difficulties, suggesting that the EOS patients seemed especially vulnerable for executive deficits due to perinatal insults. The findings indicate that EOS youths learn more slowly and experience more difficulty with problem-solving, which carry important implications for clinical practice. Lower Apgar 5-min scores were associated with executive dysfunction in both groups. Low Apgar score at 5 min may therefore be an important early indicator of executive difficulties among adolescents, independent of diagnosis.

The effect of nitrogen dioxide on low birth weight in women with inflammatory bowel disease: a Norwegian pregnancy cohort study (MoBa)

Background: Adverse birth outcomes are more frequent among mothers with inflammatory bowel diseases (IBDs) than non-IBD mothers. In recent studies, air pollution, such as high concentrations of nitrogen dioxide (NO2), is reckoned as a risk factor for preterm birth in the general population. In this study, we investigated whether IBD mothers are at higher risk of preterm birth when exposed to NO2 compared to non-IBD mothers.Methods: We used information from the Norwegian Mother, Father and Child Cohort Study (MoBa). The pregnancy cohort was linked to the Norwegian Medical Birth Registry and air-pollution exposure data available from a subset of the study cohort. The relevant outcome in this study was preterm birth. A total of 16,170 non-IBD and 92 IBD mothers were included in the study.Results: The mean exposure of NO2 during the pregnancy was similar for IBD and non-IBD mothers, 13.7 (6.9) μg/m3 and 13.6 (4.2) μg/m3, respectively.IBD mothers with higher exposure of NO2 in the second and third trimester were at significant risk of preterm birth compared to non-IBD mothers [OR = 1.28 (CI 95%: 1.04–1.59) and OR = 1.23 (95% CI: 1.06–1.43), respectively]. The mean NO2 exposure was significantly higher in IBD mothers with preterm birth than in IBD mothers who delivered at term, at 19.58 (1.57) μg/m3 and 12.89 (6.37) μg/m3, respectively.Conclusions: NO2 exposure influenced the risk of preterm birth in IBD mothers. Higher risk of preterm birth in IBD was associated with higher exposure of NO2, suggesting vulnerability of preterm birth in IBD when exposed to NO2.

Maternal Thyroid Hormone Replacement Therapy Exposure and Language and Communication Skills of Offspring at 8 Years of Age

Hypothyroidism during pregnancy is associated with neurodevelopmental delays in the offspring. However, it remains unknown whether prenatal thyroid hormone replacement therapy (THRT) has benefits regarding children's language and communication skills. To quantify associations between prenatal THRT exposure and risk of language impairment diagnosis and parent-reported symptoms of language and communication skill deficits in offspring at 8 years of age. The Norwegian Mother, Father and Child Cohort Study (MoBa), a nationwide population-based cohort study, recruited pregnant women from throughout Norway between June 1999 and December 2008. MoBa was linked to several nationwide registries: the Norwegian Medical Birth Registry, Norwegian Prescription Database, and Norwegian Patient Registry. For this study, the analyzed cohort was restricted to singleton pregnancies resulting in a live-born infant, enrolled in the MoBa between 2005 and 2008. Statistical analysis was performed from January 2 to May 7, 2019. In both study samples, mother-child pairs were categorized into 3 mutually exclusive groups: THRT exposure during pregnancy, based on dispensed prescription records; unexposed to THRT during pregnancy (population comparison); and mothers initiating THRT after delivery (THRT after delivery), comprising incident postpartum THRT users. Two defined study samples were analyzed with different outcome measures. In the Norwegian Patient Registry sample, outcome was defined by a diagnosis of language and speech impairment. In the MoBa sample, children were followed up until age 8 years via parental self-completed questionnaires. Hazard ratios were calculated for language impairment diagnosis, estimated by Cox proportional hazards regression. Standardized mean score (β) was calculated for parent-reported symptoms of language and communication deficits, estimated using generalized linear models. The Norwegian Patient Registry sample included 53 862 mother-child pairs (mean [SD] age, 30.4 [4.6] years; offspring, 26 145 girls and 27 717 boys; 1204 pairs exposed to THRT [2.2%]) and the MoBa sample included 23 686 mother-child pairs (mean [SD] age, 30.8 [4.4] years; offspring, 11 536 girls and 12 150 boys; 532 pairs exposed to THRT [2.2%]). Language and speech impairment diagnosis was not significantly associated with prenatal THRT exposure compared with the unexposed group (adjusted hazard ratio, 0.75; 95% CI, 0.38-1.43) or the THRT after delivery group (adjusted hazard ratio, 0.63; 95% CI, 0.26-1.53). Language outcomes also did not significantly differ between these groups. There was no significant difference in child outcomes between children exposed to THRT in the prenatal period compared with children in the population comparison group. These results support current guidelines recommending hypothyroidism treatment during pregnancy. Future research should further examine the use of THRT after delivery or a proper disease comparison group.

Associations between maternal dietary patterns and infant birth weight, small and large for gestational age in the Norwegian Mother and Child Cohort Study

Background/ObjectivesTo assess whether quality of maternal diet affects birth weight and the risk of small for gestational age (SGA) and/or large for gestational age (LGA) babies.Subjects/MethodsThis study is based on the Norwegian Mother and Child Cohort Study (MoBa) and includes 65,904 pregnant women who answered a validated food frequency questionnaire at mid-pregnancy. Three maternal dietary patterns were extracted based on characteristics of food items in each pattern. From these we created four non-overlapping groups: “high prudent,” “high Western,” “high traditional,” and “mixed”. We obtained information about birth weight from the Norwegian Medical Birth Registry and calculated birth weight z-scores, SGA, and LGA according to an ultrasound-based, population-based, and a customized growth standards. Associations were studied by linear and multiple logistic regression.ResultsCompared to the high Western group, the high prudent group was associated with lower birth weight (βultrasoundz-scores −0.041 (95% confidence interval (CI): −0.068, −0.013)) and the high traditional group with higher birth weight (βultrasound 0.067 (95% CI: 0.040, 0.094)) for all three growth standards. The high prudent pattern was associated with increased SGA risk (SGAultrasound odds ratio (OR) 1.25 (95% CI: 1.02, 1.54)) and decreased LGA risk (LGApopulation OR 0.84 (95% CI: 0.75, 0.94)), while the high traditional group on the contrary was associated with decreased SGA (SGAcustomized OR 0.92 (95% CI: 0.84, 0.99)) and increased LGA risk (LGApopulation OR 1.12 (95% CI: 1.02, 1.24)).ConclusionsFood quality was associated with birth weight in this well-nourished Norwegian population. Food quality may affect a woman’s risk of giving birth to a SGA or LGA baby.

The effect of foetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study.

BackgroundThere is little knowledge about how factors early in life affect the development of migraine and tension-type headache. We aimed to examine whether growth restriction in utero is associated with development of migraine and frequent tension-type headache in adults.MethodsThe population-based Nord-Trøndelag Health Study (HUNT 3) contained a validated headache questionnaire, which differentiated between migraine and tension-type headache. These data were linked to information on weight and gestational age at birth from the Norwegian Medical Birth Registry. In total 4557 females and 2789 males, aged 19–41 years, were included in this registry-based study. Participants were categorized as appropriate for gestational age (AGA, 10th-90th percentile), small for gestational age (SGA, 3rd-10th percentile) or very small for gestational age (VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for migraine and tension-type headache, with exposure being growth restriction at birth.ResultsThe effect of growth restriction on migraine was modified by sex, with a significant association in males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA were at increased risk of developing migraine (OR 2.73, 95% CI 1.63–4.58, p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96–2.35, p = 0.08) compared to those born AGA. There was no significant association between growth restriction and frequent TTH (p = 0.051).ConclusionGrowth restriction was associated with increased risk of migraine in adulthood among males, but not among females. This suggests that migraine might, in part, be influenced by early life events, and that males seem to be particularly vulnerable.

Factors Associated With Increased Risk of Clubfoot: A Norwegian National Cohort Analysis.

Previous studies investigating the causes of clubfoot have shown conflicting results, potentially because of retrospective study designs or incomplete assessment of causative factors. The study aim was to examine risk factors for clubfoot in a large prospective Norwegian cohort. Exposures prior and during pregnancy were identified through the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. This was linked to the Norwegian Medical Birth Registry, which provided clubfoot diagnosis through ICD-10 code Q66.0. Logistic regression analysis investigated associations between potential risk factors and development of clubfoot. A total of 121 clubfoot cases were identified; 1.1 per 1000 births. Parental diagnosis of clubfoot [odds ratio (OR): 31.5; 95% confidence interval (CI):9.61-103.3] and cigarette smoking, both in the three months prior to pregnancy (OR:1.82; 95%CI:1.05-3.18) and the first trimester (OR:2.67; 95% CI:1.28-5.55) were associated with clubfoot. Infants with clubfoot had greater solvent exposure (OR:1.66; 95% CI:1.00-2.76). Oligohydramnios, parental age, parental education, parity, maternal anxiety or depression, alcohol use, season of birth did not have statistically significant associations. In addition to parental diagnosis of clubfoot, results confirm the previously reported association between clubfoot and smoking, and counter previous evidence supporting season of birth, parental education, and other risk factors. Further studies are needed to investigate solvent exposure as a risk factor for clubfoot. Exposure to smoke and solvents can be controlled; this study highlights the importance of public health initiatives to limit these exposures both during pregnancy and in those considering conceiving in the future.

Medication Use before, during, and after Pregnancy among Women with Eating Disorders: A Study from the Norwegian Mother and Child Cohort Study.

IntroductionLittle is known about medication use among women with eating disorders in relation to pregnancy.AimsTo explore patterns of and associations between use of psychotropic, gastrointestinal and analgesic medications and eating disorders in the period before, during and after pregnancy.MethodThis study is based on the Norwegian Mother and Child Cohort Study (MoBa). A total of 62,019 women, enrolled at approximately 17 weeks' gestation, had valid data from the Norwegian Medical Birth Registry and completed three MoBa questionnaires. The questionnaires provided diagnostic information on broadly defined anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and recurrent self-induced purging in the absence of binge eating (EDNOS-P), along with self-reported use of medication six months before, during, and 0–6 months after pregnancy.ResultsThe prevalence of eating disorder subtypes before and/or during pregnancy was: 0.09% AN (n = 54), 0.94% BN (n = 585), 0.10% EDNOS-P (n = 61) and 5.00% BED (n = 3104). The highest over-time prevalence of psychotropic use was within the AN (3.7–22.2%) and EDNOS-P (3.3–9.8%) groups. Compared to controls, BN was directly associated with incident use of psychotropics in pregnancy (adjusted RR: 2.25, 99% CI: 1.17–4.32). Having AN (adjusted RR: 5.11, 99% CI: 1.53–17.01) or EDNOS-P (adjusted RR: 6.77, 99% CI: 1.41–32.53) was directly associated with use of anxiolytics/sedatives postpartum. The estimates of use of analgesics (BED) and laxatives (all eating disorders subtypes) were high at all time periods investigated.ConclusionsUse of psychotropic, gastrointestinal, and analgesic medications is extensive among women with eating disorders in the period around pregnancy. Female patients with eating disorders should receive evidence-based counseling about the risk of medication exposure versus the risk of untreated psychiatric illness during pregnancy and postpartum.

Risk of fetal death with preeclampsia.

To estimate gestational age-specific risks of fetal death in pregnancies complicated by preeclampsia. Population-based cohort study comprising all singleton births (N=554,333) without preexisting chronic hypertension recorded in the Norwegian Medical Birth Registry from 1999 to 2008. Additional data come from a subset of preeclamptic pregnancies enrolled in the Norwegian Mother and Child Cohort Study with available medical records (n=3,037). The risk of fetal death, expressed per 1,000 fetuses exposed to preeclampsia, was calculated using a life table approach. Preeclampsia was recorded in 3.8% (n=21,020) of all pregnancies. Risk of stillbirth was 3.6 per 1,000 overall and 5.2 per 1,000 among pregnancies with preeclampsia (relative risk 1.45, 95% confidence interval [CI] 1.20-1.76). However, relative risk of stillbirth was markedly elevated with preeclampsia in early pregnancy. At 26 weeks of gestation, there were 11.6 stillbirths per 1,000 pregnancies with preeclampsia compared with 0.1 stillbirths per 1,000 pregnancies without (relative risk 86, 95% CI 46-142). Fetal risk with preeclampsia declined as pregnancy advanced, but at 34 weeks of gestation remained more than sevenfold higher than pregnancies without preeclampsia. For clinical purposes, the fetal risk of death associated with preeclampsia begins when preeclampsia becomes clinically apparent. Using a method that takes into account the clinical diagnosis of preeclampsia and the population of fetuses at risk, we find a remarkably high relative risk of fetal death among pregnancies diagnosed with preeclampsia in the preterm period. II.

Change in paternity, risk of placental abruption and confounding by birth interval: a population-based prospective cohort study in Norway, 1967–2009

ObjectivesWe examined abruption risk in relation to change in paternity, and evaluated if birth interval confounds this association.SettingPopulation-based study of singleton births in Norway between 1967 and 2009.ParticipantsWomen who had...

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Objectives To compare long-term cardiovascular mortality in mothers whose firstborn offspring had folate-related malformations with mothers whose firstborns were non-malformed, and to evaluate if women’s total reproduction modified the associations. Methods Data from the Norwegian Medical Birth Registry and Cause of Death Registry were linked to study cardiovascular mortality among women with first singleton births in 1967–2002 ( N = 1,016,654). Births were linked to their mothers, and 83.8% women continued reproducing. Cox regression analysis was used to estimate associations between folate-related malformations (neural tube defects, oral clefts, cardiac defects) in first births and cardiovascular mortality at age 40–69 years, adjusting for maternal age, education, pregnancy year, and taking account of women’s following births. Results Women with folate-related malformations in their firstborns ( N = 7319) had increased cardiovascular mortality (adjusted hazard ratio relative women with non-malformed firstborns (adjHR) = 1.6; 95% confidence interval 1.1, 2.5). Taking account of women’s total reproduction, women with malformed first births who stopped reproducing had 7 times higher cardiovascular mortality than mothers with non-malformed first births who continued (adjHR 7.0 (4.1–12.2)). In contrast, mothers with malformed firstborns who continued reproducing did not have increased cardiovascular mortality: adjHR 0.9 (0.42–1.69). Conclusions The increased cardiovascular mortality in women whose firstborns had folate-related malformations is confined to women with only one birth. Disclosures K. Klungsoyr: None. L.A. DeRoo: None. S. Hernandez-Diaz: None. N. Morken: None. R. Skjaerven: None.

Multiple births and maternal mental health from pregnancy to 5 years after birth: A longitudinal population-based cohort study

Background: There is a lack of population-based studies on multiple births and maternal mental health. Having a high-risk pregnancy by bearing two or more children is a stressful life event, and the challenges of parenting two or more children probably also lead to a high level of parental stress. There are a few results on multiple births and maternal mental health from studies on in vitro fertilization samples. The only previous cohort study on multiple birth and maternal mental health included a single measure of depressive symptoms at 9 months postpartum. We aim to estimate the relative risk for depression and anxiety after multiple birth in a population-based prospective cohort study while adjusting for factors prior and subsequent to fertilization.Methods: We used data from 87,807 pregnancies included in the Norwegian Mother and Child Cohort study. Information on multiple birth was retrieved from the Norwegian Medical Birth Registry, and maternal mental health was assessed at 17th and 30th week of gestation and 0.5, 1.5, 3, and 5 years postpartum. There were 1,842 plural births included in the study (i.e. 1,821 twin births and 21 higher order births). We predicted maternal mental health at each time point, subsequently adjusting for 1) factors prior to fertilization (e.g. maternal age and in vitro fertilization); 2) factors during pregnancy (e.g. hypertensive states); 3) factors at delivery (e.g. cesarean section); 4) child-related postnatal complications (e.g. intracranial hemorrhage); and 5) concurrent depression or anxiety after pregnancy.Results: Adjusted for antecedents of plural birth, mothers expecting a plural birth had a normal risk for anxiety (RR=1.05; 95% CI 0.92-1.20) and depression (RR=1.02; 95% CI 0.89-1.16) at 17th week of gestation. However, plural birth was associated with maternal depression at 1.5, 3, and 5 years postpartum and maternal anxiety at 3 years postpartum. The trend was for the association to increase across time, and mothers of multiplets had a significant higher risk for depression at 5 years (RR=1.77; 95% CI 1.33-2.35). Fully adjusted the RR for depression was 1.51 (95% CI 1.10-2.08). By adjusting depression for concurrent anxiety, and vice versa we found the effect of multiple pregnancy to be specific to depression and not anxiety.Conclusions: Mothers expecting multiplets have normal mental health during pregnancy. After birth there is an increasing risk for depression up to 5 years of age. Our findings indicate that more is simply more, and mothers of multiplets have need for additional support several years postpartum

Abstract 124: Role of different biomarkers for progression of the cervical dysplasia: a prospective molecular epidemiological study combining information from the nationwide registries and biobanks.

Abstract A prognostic marker predicting the progression or regression of the cervical intraepithelial neoplasia (CIN) would greatly impact cervical cancer screening. Proliferation markers like MIB 1 antibody Ki67, p16 showing HPV's oncogenic activity, and presence of the HPV DNA has been considered. However, the markers’ prognostic ability can reliably be assessed in prospective study only. We established a model by selecting a patient material in relation to pregnancy as a treatment is usually postponed and the natural development of the lesion remains undisturbed for a limited period of time. The aim of the study was to investigate whether positivity for HPV type-specific DNA, p16, Ki67 indicates progression to a more severe lesion. Material and methods: Through linkage between the Norwegian Medical Birth Registry and the Cancer Registry of Norway, all women with CIN grade I-III during pregnancy in 1996-1997 were identified. 149 women with minimum of two serial histology specimens were included into the study. From the national histology biobank, relevant formalin fixed paraffin embedded tissue blocs (altogether 400) were identified, collected and analyzed. Each case was judged from serial histology diagnoses to define progression, i.e. upward change of at least two CIN grades during the period of &amp;gt;6 month. For HPV DNA GP5+/6+ was used, followed by reverse line-blot for typing of 39 HPV types individually and pool of 6 rare HPV types. P16/Ki67 were detected immunohistochemically (Cell Marque, p16, 16P04 and Assey, Filled Disp., CONFIRM Anti-KI76 K-2, Ventana). Presence of biomarkers by dysplasia grade (normal, CINI-III) was estimated. Linear mixed models were used for the longitudinal analyses to accommodate somewhat unbalanced structure of the data. The outcome was degree of seriousness (CIN grade) in the histology-samples and the different biomarkers served as the time varying covariates. Results and Conclusion: The mean age of subjects (at 1st visit) was 29 years. Prevalence of HPV DNA, Ki-67 and p16 increased by increasing grade of CIN lesion. By our criteria, 28 (18%) women showed progression. Ki67, overexpression of p16, presence of high risk HPV and HPV16 DNA showed strong association with CIN seriousness in longitudinal analyses while positivity for low risk HPV showed negative association (albeit not statistically significant). Further studies addressing progression and time-span of CIN are urgently needed to improve screening programs. Citation Format: Mari Nygård, Ole Klungsøyr, Bjørn Hagmar. Role of different biomarkers for progression of the cervical dysplasia: a prospective molecular epidemiological study combining information from the nationwide registries and biobanks. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 124. doi:10.1158/1538-7445.AM2013-124

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study

Artificially sweetened (AS) and sugar-sweetened (SS) beverages are commonly consumed during pregnancy. A recent Danish study reported that the daily intake of an AS beverage was associated with an increased risk of preterm delivery. We examined the intake of AS and SS beverages in pregnant women to replicate the Danish study and observe whether AS intake is indeed associated with preterm delivery. This was a prospective study of 60,761 pregnant women in the Norwegian Mother and Child Cohort Study. Intakes of carbonated and noncarbonated AS and SS beverages and use of artificial sweeteners in hot drinks were assessed by a self-reported food-frequency questionnaire in midpregnancy. Preterm delivery was the primary outcome, and data were obtained from the Norwegian Medical Birth Registry. Intakes of both AS and SS beverages increased with increasing BMI and energy intake and were higher in women with less education, in daily smokers, and in single women. A high intake of AS beverages was associated with preterm delivery; the adjusted OR for those drinking >1 serving/d was 1.11 (95% CI: 1.00, 1.24). Drinking >1 serving of SS beverages per day was also associated with an increased risk of preterm delivery (adjusted OR: 1.25; 95% CI: 1.08, 1.45). The trend tests were positive for both beverage types. This study suggests that a high intake of both AS and SS beverages is associated with an increased risk of preterm delivery.