Olof Stephansson

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Design Population based cohort study using data from the national health registers. Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants More than 1.6 million infants born after gestational week 33. Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Women's fear of childbirth and preference for cesarean section – a cross-sectional study at various stages of pregnancy in Sweden

Objective. To investigate Swedish womens level of antenatal fear of childbirth at various gestational ages, and factors associated with intense fear and with preference for cesarean section. Design. A cross‐sectional study. Setting. All antenatal clinics in four geographical areas. Sample. Thousand six hundred and thirty‐five pregnant women at various gestational ages recruited during September–October 2006. Method. A questionnaire completed at the antenatal clinic. The women reported their appraisal of the approaching delivery according to the Wijma Delivery Expectancy/Experience Questionnaire (W‐DEQ). Main outcome measures. The level of fear of childbirth and preferred mode of delivery. Results. Mean W‐DEQ score was 62.8. The prevalence of intense fear of childbirth (W‐DEQ score ≥85) was 15.8% and very intense fear (tocophobia) (W‐DEQ score ≥100) 5.7%. Nulliparous women had a higher mean score than parous women, but more parous women reported an intense fear. Preference for cesarean section was associated with fear of childbirth (OR 11.79, 6.1–22.59 for nulliparous and OR 8.32, 4.36–15.85 for parous women) and for parous women also with a previous cesarean section (OR 18.54, 9.55–35.97), or an instrumental vaginal delivery (OR 2.34, 1.02–5.34). The level of fear of childbirth was not associated with the gestational age. Conclusions. When a woman requests a cesarean section, both primary fear of birth and traumatic childbirth experiences need to be considered and dealt with. The W‐DEQ can be used at any time during pregnancy in order to identify pregnant women who suffer from intense fear of childbirth.

Outcomes of Pregnancy after Bariatric Surgery

BACKGROUND Maternal obesity is associated with increased risks of gestational diabetes, large-for-gestational-age infants, preterm birth, congenital malformations, and stillbirth. The risks of these outcomes among women who have undergone bariatric surgery are unclear. METHODS We identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented. For each pregnancy after bariatric surgery, up to five control pregnancies were matched for the mothers presurgery body-mass index (BMI; we used early-pregnancy BMI in the controls), age, parity, smoking history, educational level, and delivery year. We assessed the risks of gestational diabetes, large-for-gestational-age and small-for-gestational-age infants, preterm birth, stillbirth, neonatal death, and major congenital malformations. RESULTS Pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25; 95% confidence interval [CI], 0.13 to 0.47; P<0.001) and large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33; 95% CI, 0.24 to 0.44; P<0.001). In contrast, they were associated with a higher risk of small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20; 95% CI, 1.64 to 2.95; P<0.001) and shorter gestation (273.0 vs. 277.5 days; mean difference -4.5 days; 95% CI, -2.9 to -6.0; P<0.001), although the risk of preterm birth was not significantly different (10.0% vs. 7.5%; odds ratio, 1.28; 95% CI, 0.92 to 1.78; P=0.15). The risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39; 95% CI, 0.98 to 5.85; P=0.06). There was no significant between-group difference in the frequency of congenital malformations. CONCLUSIONS Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality. (Funded by the Swedish Research Council and others.).

Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome

BACKGROUND Endometriosis, a common gynaecological disease, is characterized by local and systemic inflammation, which may cause infertility and consequently, increased utilization of assisted reproduction technology (ART). We aimed to estimate the risk for preterm birth, small-for-gestational-age (SGA) birth, stillbirth, Caesarean section, pre-eclampsia and antepartal haemorrhage among women with a previous diagnosis of endometriosis compared with women with no previous diagnosis of endometriosis. METHODS In a nationwide Swedish study including 1,442,675 singleton births we assessed the association between adverse pregnancy outcome, ART and a previous diagnosis of endometriosis. Information was obtained by linkage of data between 1992 and 2006 in the Medical Birth Register with the Patient Register between 1964 and 2006. RESULTS There were 13,090 singleton births among 8922 women diagnosed with endometriosis. Compared with women without endometriosis, women with endometriosis had higher risks of preterm birth [adjusted odds ratio 1.33, 95% confidence interval (CI), 1.23-1.44]. Among women with endometriosis 11.9% conceived after ART compared with 1.4% of women without endometriosis. The risk of preterm birth associated with endometriosis among women with ART was 1.24 (95% CI, 0.99-1.57), and among women without ART 1.37 (95% CI, 1.25-1.50). Women with endometriosis had higher risks of antepartal bleeding/placental complications, pre-eclampsia and Caesarean section. There was no association between endometriosis and risk of SGA-birth or stillbirth. CONCLUSIONS Endometriosis appears to be a risk factor for preterm birth, irrespective of ART. Women with endometriosis may be more likely to be delivered by Caesarean section and to suffer from antepartal haemorrhage/placental complications and pre-eclampsia.

Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study

Objective To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome, taking into account maternal characteristics and assisted reproductive technology. Design Population based cohort study. Setting Singleton births registered in the Swedish medical birth register between 1995 and 2007. Participants By linkage with the Swedish patient register, 3787 births among women with a diagnosis of polycystic ovary syndrome and 1 191 336 births among women without such a diagnosis. Main outcome measures Risk of adverse pregnancy outcomes (gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score (<7 at five minutes), meconium aspiration, large for gestational age, macrosomia, small for gestational age), adjusted for maternal characteristics (body mass index, age), socioeconomic factors (educational level, and cohabitating with infant’s father), and assisted reproductive technology. Results Women with polycystic ovary syndrome were more often obese and more commonly used assisted reproductive technology than women without such a diagnosis (60.6% v 34.8% and 13.7% v 1.5%). Polycystic ovary syndrome was strongly associated with pre-eclampsia (adjusted odds ratio 1.45, 95% confidence interval 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90) and the risk of gestational diabetes was more than doubled (2.32, 1.88 to 2.88). Infants born to mothers with polycystic ovary syndrome were more prone to be large for gestational age (1.39, 1.19 to 1.62) and were at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and having a low Apgar score (<7) at five minutes (1.41, 1.09 to 1.83). Conclusions Women with polycystic ovary syndrome are at increased risk of adverse pregnancy and birth outcomes that cannot be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition.

Tobacco Use During Pregnancy and Preeclampsia Risk: Effects of Cigarette Smoking and Snuff

Preeclampsia is a leading cause of maternal and infant mortality and morbidity worldwide. Both Swedish snuff and cigarette smoke include nicotine, but combustion products accompany only smoking. The aims of this study were to compare the effects of Swedish snuff and cigarette smoking on preeclampsia risk and to estimate whether changes in tobacco habits during pregnancy affect the risk of developing term preeclampsia. We used information from the Swedish Birth Register on all singleton births in Sweden during the years 1999–2006 (n=612 712). Compared with nontobacco users, women who used snuff in early pregnancy had an adjusted odds ratio (OR) for preeclampsia of 1.11 (95% CI: 0.97 to 1.28). The corresponding ORs for light and heavy smokers were 0.66 (95% CI: 0.61 to 0.71) and 0.51 (95% CI: 0.44 to 0.58), respectively, with ORs lower for term than preterm preeclampsia. Compared with nontobacco users, women who smoked in early pregnancy but had quit smoking before late pregnancy (weeks 30 to 32) had an adjusted OR for term preeclampsia of 0.94 (95% CI: 0.83 to 1.08). The corresponding OR for women who did not use tobacco in early pregnancy but had started to smoke before late pregnancy was 0.65 (95% CI: 0.50 to 0.85). We conclude that tobacco combustion products rather than nicotine are the probable protective ingredients against preeclampsia in cigarette smoke. Because change of smoking habits during pregnancy influence risk, we further conclude that it is the smoking habits in the middle or late rather than in the beginning of pregnancy that seem to affect the risk of preeclampsia.

Pregnancy Outcome and Risk of Celiac Disease in Offspring: A Nationwide Case-Control Study

BACKGROUND & AIMS Studies on pregnancy characteristics and mode of delivery and risk of later celiac disease in offspring are inconsistent. In recent decades rates of cesarean delivery and preterm birth survival have increased while at the same time the prevalence of celiac disease has doubled. METHODS In this population-based case-control study we examined the risk of celiac disease in individuals exposed to cesarean delivery and adverse fetal events (ie, low Apgar score, small for gestational age, low birth weight, preterm birth, and neonatal infections). Prospectively recorded pregnancy data were obtained from the Swedish Medical Birth Register between 1973 and 2008. Study participants consisted of 11,749 offspring with biopsy-verified celiac disease identified through histopathology reports from Swedens 28 pathology departments, and 53,887 age- and sex-matched controls from the general population. RESULTS We found a positive association between elective cesarean delivery and later celiac disease (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.04-1.26), but no increased risk of celiac disease after emergency (adjusted OR, 1.02; 95% CI, 0.92-1.13) or any cesarean delivery (adjusted OR, 1.06; 95% CI, 0.99-1.13). Infants born small for gestational age were at a 21% increased risk of celiac disease (95% CI, 1.09-1.35), whereas other pregnancy exposures did not increase the risk of future celiac disease. CONCLUSIONS The positive association with elective, but not emergency, cesarean delivery is consistent with the hypothesis that the bacterial flora of the newborn plays a role in the development of celiac disease.

Drug use during pregnancy in Sweden - assessed by the Prescribed Drug Register and the Medical Birth Register.

Purpose: The purpose of this research is to study drug use during pregnancy in Sweden and agreement between use according to antenatal medical records and dispensed drugs from a pharmacy database. Patients and methods: From the Swedish Medical Birth Register (MBR), we established a population-based cohort of 102,995 women who gave birth in 2007. Using the unique personal registration number, information on dispensed drugs from the Prescribed Drug Register (PDR) was obtained prior to, during, and after the pregnancies and compared with MBR information on drug use from standardized antenatal medical records. Results: According to the PDR, 57.6% of the 102,995 women filled a prescription with at least one drug during pregnancy and 50.9% during the lactating period (until 3 months after delivery). The most dispensed drugs during pregnancy were B-lactam antibacterials and penicillins. Agreement between drugs recorded in antenatal medical records and dispensed drugs was highest for drugs used for chronic conditions. The agreement was particularly high for thyroid therapy (85.3%), anti-intestinal inflammatory drugs (80.3%), antiepileptics (69.2%), immunosuppressants (67.4%), and insulin (63.8%). Agreement for drugs used for occasional use was generally lower, ranging between 42.5% for antihistamines and 0.8% for gynecological anti-infectives. Conclusions: A large proportion of women filled a prescription during pregnancy or the lactating period. Agreement between drug use in medical antenatal records and register information from a national pharmacy database was high for drugs used for chronic conditions but low for occasional use. For occasionally used drugs, medical record and register-based data may provide incomplete exposure information because of nonreporting or noncompliance.

Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study.

Abstract.  Nørgaard M, Larsson H, Pedersen L, Granath F, Askling J, Kieler H, Ekbom A, Sørensen HT, Stephansson O (Aarhus University Hospital, Denmark, Karolinska Institutet; Karolinska University Hospital, Solna; and Karolinska Institutet, Solna; Stockholm, Sweden). Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study. J Intern Med 2010; 268: 329–337.

Perinatal outcomes after bariatric surgery: nationwide population based matched cohort study

Objective To compare perinatal outcomes in births of women with versus without a history of bariatric surgery. Design Population based matched cohort study. Setting Swedish national health service. Participants 1 742 702 singleton births identified in the Swedish medical birth register between 1992 and 2009. For each birth to a mother with a history of bariatric surgery (n=2562), up to five control births were matched by maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, educational level, and year of delivery. Secondary control cohorts, including women eligible for bariatric surgery (body mass index ≥35 or ≥40), were matched for the same factors except body mass index. History of maternal bariatric surgery was ascertained through the Swedish national patient register from 1980 to 2009. Main outcome measures Preterm birth (<37 weeks), small for gestational age birth, large for gestational age birth, stillbirth (≥28 weeks), and neonatal death (0-27 days). Results Post-surgery births were more often preterm than in matched controls (9.7% (243/2511) v 6.1% (750/12 379); odds ratio 1.7, 95% confidence interval 1.4 to 2.0; P<0.001). Body mass index seemed to be an effect modifier (P=0.01), and the increased risk of preterm birth was only observed in women with a body mass index <35. A history of bariatric surgery was associated with increased risks of both spontaneous (5.2% (130/2511) v 3.6% (441/12 379); odds ratio 1.5, 1.2 to 1.9; P<0.001) and medically indicated preterm birth (4.5% (113/2511) v 2.5% (309/12 379); odds ratio 1.8, 1.4 to 2.3; P<0.001). A history of bariatric surgery was also associated with an increased risk of a small for gestational age birth (5.2% (131/2507) v 3.0% (369/12 338); odds ratio 2.0, 1.5 to 2.5; P<0.001) and lower risk of a large for gestational age birth (4.2% (105/2507) v 7.3% (895/12 338); odds ratio 0.6, 0.4 to 0.7; P<0.001). No differences were detected for stillbirth or neonatal death. The increased risks for preterm and small for gestational age birth, as well as the decreased risk for large for gestational age birth, remained when post-surgery births were compared with births of women eligible for bariatric surgery. Conclusion Women with a history of bariatric surgery were at increased risk of preterm and small for gestational age births and should be regarded as a risk group during pregnancy.