Lill Trogstad

VITAMIN D SUPPLEMENTATION AND REDUCED RISK OF PREECLAMPSIA IN NULLIPAROUS WOMEN

Background: A recent study showed that nulliparous women who develop preeclampsia had low concentrations of vitamin D in serum sampled in midpregnancy. The aim of the present study was to estimate the association between intake of vitamin D during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study. Methods: Participating women answered questionnaires at gestational week 15 (general health questionnaire), at week 22 (food frequency questionnaire), and at week 30 (general health questionnaire). Pregnancy outcomes were obtained from the Medical Birth Registry. Nutrient intake was calculated from foods and dietary supplements. We estimated relative risks as odds ratios, and controlled for confounding with multiple logistic regression. Results: The odds ratio of preeclampsia for women with a total vitamin D intake of 15–20 &mgr;g/d compared with less than 5 &mgr;g/d was 0.76 (95% confidence interval = 0.60–0.95). Considering only the intake of vitamin D from supplements, we found a 27% reduction in risk of preeclampsia (OR = 0.73 [0.58–0.92]) for women taking 10–15 &mgr;g/d as compared with no supplements. No association was found between intake of vitamin D from the diet alone and the occurrence of preeclampsia. Conclusions: These findings are consistent with other reports of a protective effect of vitamin D on preeclampsia development. However, because vitamin D intake is highly correlated with the intake of long chain n-3 fatty acids in the Norwegian diet, further research is needed to disentangle the separate effects of these nutrients.

Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination

BACKGROUND During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination. METHODS We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. RESULTS There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). CONCLUSIONS Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

A Dietary Pattern Characterized by High Intake of Vegetables, Fruits, and Vegetable Oils Is Associated with Reduced Risk of Preeclampsia in Nulliparous Pregnant Norwegian Women

Several dietary substances have been hypothesized to influence the risk of preeclampsia. Our aim in this study was to estimate the association between dietary patterns during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study (MoBa). Women participating in MoBa answered questionnaires at gestational wk 15 (a general health questionnaire) and 17-22 (a FFQ). The pregnancy outcomes were obtained from the Medical Birth Registry of Norway. Exploratory factor analysis was used to assess the associations among food variables. Principal component factor analysis identified 4 primary dietary patterns that were labeled: vegetable, processed food, potato and fish, and cakes and sweets. Relative risks of preeclampsia were estimated as odds ratios (OR) and confounder control was performed with multiple logistic regression. Women with high scores on a pattern characterized by vegetables, plant foods, and vegetable oils were at decreased risk [relative risk (OR) for tertile 3 vs. tertile 1: 0.72; 95% CI: 0.62, 0.85]. Women with high scores on a pattern characterized by processed meat, salty snacks, and sweet drinks were at increased risk [OR for tertile 3 vs. tertile 1: 1.21; 95% CI: 1.03, 1.42]. These findings suggest that a dietary pattern characterized by high intake of vegetables, plant foods, and vegetable oils decreases the risk of preeclampsia, whereas a dietary pattern characterized by high consumption of processed meat, sweet drinks, and salty snacks increases the risk.

Pre-eclampsia: Risk factors and causal models

Pre-eclampsia is a disease of many risk factors and theoretical speculations. It is, for unknown reasons, more prevalent among primiparous women. Some observations show that a change of sexual partner before the next pregnancy increases the risk, but this association disappears when correction is made for time interval since the last birth. Risk factors may be pregnancy-specific, such as twinning or mole, whereas others are linked to the woman, such as obesity and diabetes. Genetic risk factors are being searched for, but as yet with relatively little success. A previous pregnancy complicated by pre-eclampsia is probably the strongest risk factor. For practical purposes, women at increased risk can be identified and should be followed closely. No effective primary preventative action is available. Prevention of the serious consequences of pre-eclampsia still relies on early detection of increases in blood pressure and proteinuria.

Recurrence risk in hyperemesis gravidarum

Objectives  To compare the risk of hyperemesis gravidarum in second pregnancies in women with and without hyperemesis in their first pregnancy, and to determine if this risk changes with changes in paternity or with the interval between deliveries.

Recreational Physical Activity and the Risk of Preeclampsia: A Prospective Cohort of Norwegian Women

Previous case-control studies suggest that recreational physical activity protects against preeclampsia. Using a prospective design, the authors estimated the risk of preeclampsia for pregnant women according to level of physical activity, taking other variables that influence risk into consideration. The data set comprised 59,573 pregnancies from the Norwegian Mother and Child Cohort Study (1999-2006). Information on physical activity and other exposures was extracted from questionnaire responses given in pregnancy weeks 14-22, whereas diagnosis of preeclampsia was retrieved from the Medical Birth Registry of Norway. Estimation and confounder control was performed with multiple logistic regression. About 24% of pregnant women reported no physical activity, and 7% reported more than 25 such activities per month. The adjusted odds ratio was 0.79 (95% confidence interval: 0.65, 0.96) for preeclampsia when comparing women who exercised 25 times or more per month with inactive women. The association appeared strongest among women whose body mass index was less than 25 kg/m(2) and was absent among women whose body mass index was higher than 30 kg/m(2). These results suggest that the preventive effect of recreational physical activity during pregnancy may be more limited than has been shown in case-control studies and may apply to nonobese women only.

Recurrence Risk of Preeclampsia in Twin and Singleton Pregnancies

The etiology of preeclampsia is unknown. The relatively high risk of recurrence of preeclampsia in subsequent pregnancies to the same mother suggests a genetic basis for the disease, but the mode of inheritance is uncertain. We compare the risk of preeclampsia in second pregnancies for mothers whose first preeclamptic pregnancy was either a singleton or a twin pregnancy. The crude and adjusted recurrence risks of preeclampsia in twin and singleton pregnancies were estimated in a population‐based register including the first and second pregnancies of 550,218 women registered in the Medical Birth Registry of Norway, 1967–1998. The recurrence risk of preeclampsia in second pregnancy for women with a singleton pregnancy with preeclampsia the first time was 14.1% (95% CI: 13.6–14.6). For women with a first time twin pregnancy the recurrence risk was lower, 6.8% (CI: 4.3–10.1), P < 0.001. Thus, the crude excess risk for recurrent preeclampsia was 7.3% (95% CI: 4.5–10.0) in women with a first time singleton as compared to women with a first time twin pregnancy. The recurrence risk of preeclampsia is lower when the first pregnancy was a twin as compared to a singleton pregnancy. This observation is consistent with a polygenic liability model.

Maternal KIR in Combination with Paternal HLA-C2 Regulate Human Birth Weight

Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are ≤5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.

Is preeclampsia an infectious disease

Background. Studies have suggested a strong paternal factor in the etiology of preeclampsia. If preeclampsia is caused by an infectious agent transmitted by the woman’s partner, seronegative women who may experience primary infection in pregnancy should be at increased risk of preeclampsia as compared to previously infected women. The aim of this study was to assess the impact of being seronegative for some viruses transmitted by close contact on the risk of developing preeclampsia.

The effect of recurrent miscarriage and infertility on the risk of pre-eclampsia.

Objective  Pre‐eclampsia, recurrent miscarriage and infertility may all partly be caused by unsuccessful placentation early in pregnancy. If so, one will expect these disorders to be associated in population studies. The aim of the present investigation was to estimate the risk of pre‐eclampsia in women with recurrent miscarriage and infertility.