Anna-Karin Wikström

The risk of maternal ischaemic heart disease after gestational hypertensive disease

Objective  The aim of this study was to investigate whether the risk of developing ischaemic heart disease (IHD) later in life increases with severity and recurrence of gestational hypertensive disease.

Placental Growth Factor and Soluble FMS- Like Tyrosine Kinase-1 in Early-Onset and Late-Onset Preeclampsia

OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic proteins placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1 (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia. METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1, PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early control group of women at 24–32 weeks of gestation, in a late control group of women at 36–42 weeks of gestation, and in cases of women with early-onset (before 32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia. RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had a three times higher median plasma sFlt1 level than late controls (P<.001). Women with early-onset preeclampsia had a 21 times lower median plasma PlGF level than early controls (P<.001). Women with late-onset preeclampsia had a five times lower median plasma PlGF level than late controls (P=.01). The median level of VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women. CONCLUSION: Both early- and late-onset preeclampsia are associated with altered plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early-onset rather than in late-onset disease. LEVEL OF EVIDENCE: II

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.

High birth weight and obesity—a vicious circle across generations

OBJECTIVES:Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers’ birth weight for gestational age and adult body mass index (BMI) and these factors’ joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean).DESIGN:A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973–2006.RESULTS:Compared with mothers with appropriate birth weight for gestational age (AGA; −1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0–29.9; odds ratio (OR), 1.50; 95% CI 1.39–1.61), obesity class I (BMI 30.0–34.9; OR 1.77; 95% CI 1.59–1.98), obesity class II (BMI 35.0–39.9; OR 2.77; 95% CI 2.37–3.24) and obesity class III (BMI ⩾40.0; OR 2.04; 95% CI 1.49–2.80). In each stratum of mothers birth weight for gestational age, risk of having an LGA offspring increased with mothers BMI. The risk of an LGA offspring was highest among women with a high (⩾30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (⩽24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI ⩾35.0 compared with the OR among SGA mothers with normal BMI (ORs=4.61 and 0.35, respectively).CONCLUSIONS:Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.

Maternal Body Mass Index, Height, and Risks of Preeclampsia

BACKGROUND There is an association between maternal body mass index (BMI) and preeclampsia, but if BMI has an effect on preeclampsia of all severities is debated. If there is an association between maternal height and preeclampsia of all severities is unknown. METHODS In this population-based cohort study including 503,179 nulliparous women, we estimated risks of preeclampsia of different severity in short (<164 cm) and tall (≥172 cm) women, using women of average height (164-171 cm) as reference, and in underweight (BMI: ≤18.4kg/m(2)), overweight (BMI: 25.0-29.9 kg/m(2)), obese class I (BMI: 30.0-34.9kg/m(2)) and obese class II-III (BMI: ≥35.0 kg/m(2)) women, using women with normal weight (BMI: 18.5-24.9kg/m(2)) as reference. Severity of preeclampsia was classified as early (<32 weeks), moderately early (32-36 weeks), and late (≥37 weeks) preeclampsia, or severe preeclampsia and mild to moderate preeclampsia, as defined by diagnostic codes. RESULTS Short women had increased risks of all types of preeclampsia, but especially of early disease (adjusted odds ratio (OR) 1.3; 95% confidence interval (CI) 1.2-1.5). The risks of all preeclampsia types increased with BMI, but seemed higher for milder than more severe types of preeclampsia. Obesity class II-III was associated with a four-fold increased risk of mild to moderate preeclampsia (adjusted OR 4.0; 95% CI 3.7-4.4). CONCLUSION A short maternal stature and a high BMI increase risks of preeclampsia of all severities. The associations seem especially strong between short stature and severe types of preeclampsia, and high BMI and mild types of preeclampsia.

Maternal use of Swedish snuff (snus) and risk of stillbirth.

Background: Swedish snuff has been discussed internationally as a safer alternative to tobacco smoking. International cigarette manufacturers are promoting new snuff products, and the use of Swedish snuff is increasing, especially among women of childbearing age. The effect of Swedish snuff on pregnancy complications is unknown. Methods: In this population-based cohort study, we estimated the risk of stillbirth in snuff users (n = 7629), light smokers (1–9 cigarettes/day; n = 41,488), and heavy smokers (≥10 cigarettes/day; n = 17,014), using nontobacco users (n = 504,531) as reference. Results: Compared with nontobacco users, snuff users had an increased risk of stillbirth (adjusted odds ratio = 1.6 [95% confidence interval = 1.1–2.3]); the risk was higher for preterm (<37 weeks) stillbirth (2.1 [1.3–3.4]). For light smokers, the adjusted odds ratio of stillbirth was 1.4 (1.2–1.7) and the corresponding risk for heavy smokers was 2.4 (2.0–3.0). When we excluded women with preeclampsia or antenatal bleeding and infants who were small for gestational age, the smoking-related risks of stillbirth was markedly attenuated; the elevated risk for snuff users remained the same level. Conclusions: Use of Swedish snuff during pregnancy was associated with a higher risk of stillbirth. The mechanism behind this increased risk seems to differ from the underlying mechanism in smokers. Swedish snuff does not appear to be a safe alternative to cigarette smoking during pregnancy.

Hyperemesis gravidarum and risks of placental dysfunction disorders: a population‐based cohort study

To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12 weeks) or second (12–21 weeks) trimester are associated with placental dysfunction disorders.

Angiopoietin-1/Angiopoietin-2 Ratio for Prediction of Preeclampsia

BACKGROUND A number of different biophysical and biochemical markers have been proposed as predictors of preeclampsia. Factors involved in the angiogenic balance are suggested as candidate markers. The purpose of this prospective, longitudinal cohort study was to determine whether a ratio between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) can be used to predict preeclampsia in a low-risk population. METHODS A cohort of healthy pregnant women (n = 469) were enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. By using commercially available enzyme-linked immunosorbent assay kits Ang-1 and Ang-2 were analyzed. RESULTS The median Ang-1/Ang-2 ratio increased during pregnancy in all women, but the ratios were significantly lower at gestational weeks 25 and 28 in women who later developed preeclampsia than in normal pregnant women (1.49 compared to 2.19 and 2.12 compared to 3.54, P < 0.05 and P < 0.05). CONCLUSION Our data indicate that in a low-risk population of women the Ang-1/Ang-2 ratio in plasma constitutes a possible biomarker for prediction of later onset of preeclampsia.

Previous preeclampsia and risks of adverse outcomes in subsequent nonpreeclamptic pregnancies

OBJECTIVE We hypothesized that preeclampsia partly shares pathophysiology with stillbirth, placental abruption, spontaneous preterm birth, and giving birth to a small-for-gestational-age infant, and that women who develop preeclampsia in the first pregnancy may have increased risks of the other outcomes in the second pregnancy, even in the absence of preeclampsia. STUDY DESIGN In a nationwide Swedish cohort (n = 354,676) we estimated risks of adverse outcomes in the second pregnancy related to preterm (< 37 weeks) and term (≥ 37 weeks) preeclampsia in the first pregnancy, using women without preeclampsia in the first pregnancy as reference. RESULTS Women with prior preterm preeclampsia had, in second pregnancy, more than doubled risks of stillbirth, placental abruption, and preterm births, and an even greater risk of giving birth to a small-for-gestational-age infant. CONCLUSION Women with previous preterm preeclampsia have increased risks of adverse pregnancy outcomes in a second pregnancy despite the absence of preeclampsia.

Thyroid Testing and Management of Hypothyroidism During Pregnancy: A Population-based Study

CONTEXT There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. OBJECTIVE In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. DESIGN AND PARTICIPANTS In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. RESULTS All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. CONCLUSIONS The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.