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As mothers age, the risk of adverse pregnancy outcomes may increase, but the results so far are controversial and several issues remain unknown, such as the impact of maternal weight on the effects associated with older age. In a prospective cohort of 912 Polish women with singleton pregnancies (recruited in 2015-2016), we assessed the pregnancy outcomes depending on the mother's age (18-24, 25-29, 30-34, 35-39, and ≥40 years). Women aged ≥35 years (vs. <35 years) were assessed in terms of body mass index (BMI). Multidimensional logistic regression was used to calculate the odds ratios (with 95% confidence intervals) of the pregnancy results. The risk profiles (using the Lowess method) were applied to determine the threshold risk. We found that both the youngest and the oldest group members displayed higher adjusted odds ratios of preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth <37th week (U-shaped risk). In the remaining cases, the age ≥40 years, compared to the youngest age 18-24 years, was associated with a higher adjusted risk of gestational hypertension (GH) (AOR = 5.76, p = 0.034), gestational diabetes mellitus GDM-1 (AOR = 7.06, p = 0.016), cesarean section (AOR = 6.97, p <0.001), and low birth weight LBW (AOR = 15.73, p = 0.033) as well as macrosomia >4000 g (AOR = 8.95, p = 0.048). We found that older age ≥35 years (vs. <35 years) was associated with higher adjusted odds ratios of all the pregnancy outcomes investigated. In obese women, these adverse older age related results were found to be more intense in GH study, as well as (though weaker) in birth <37th week study, small-for-gestational age birth weight (SGA), LBW, large-for-gestational age birth weight (LGA), and macrosomia. In overweight women, these adverse older age related results were found to be more intense in preterm birth study, as well as (though weaker) in SGA and LBW. In underweight women, adverse pregnancy outcomes related to older age were more intense in a study of cesarean section. At the same time, underweight was associated with reversal of some negative effects of older age (we found lower odds ratios of GDM-1 diabetes). The maternal threshold age above which the risk of GH, PE, GDM, caesarean section, and preterm birth increased was 33-34 years (lower than the threshold of 35 years assumed in the literature), and the threshold risk of IUGR, LBW, SGA, LGA, and macrosomia was 36-37 years. Main conclusions: Older maternal age was associated with a higher chance of all kinds of obstetric complications. Older women should particularly avoid obesity and overweight. more...

In the face of the obesity epidemic around the world, attention should be focused on the role of maternal obesity in the development of pregnancy. The purpose of this analysis was to evaluate the prediction of preeclampsia (PE) and isolated gestational hypertension (GH) for a number of maternal factors, in order to investigate the importance of pre-pregnancy obesity (body mass index, BMI ≥ 30 kg/m 2 ), compared to other risk factors (e.g., prior PE, pregnancy weight gain (GWG), infertility treatment, interpregnancy interval, family history, the lack of vitamin supplementation, urogenital infection, and socioeconomic factors). In total, 912 women without chronic diseases were examined in a Polish prospective cohort of women with a single pregnancy (recruited in 2015-2016). Separate analyses were performed for the women who developed GH ( n = 113) vs. 775 women who remained normotensive, as well as for those who developed PE ( n = 24) vs. 775 controls. The probability of each disease was assessed for the base prediction model (age + primiparity) and for the model extended by one (test) variable, using logistic regression. Three measures were used to assess the prediction: area under curve (AUC) of the base and extended model, integrated discrimination improvement (IDI) (the index shows the difference between the value of the mean change in the predicted probability between the group of sick and healthy women when a new factor is added to the model), and net reclassification improvement (NRI) (the index focuses on the reclassification table describing the number of women in whom an upward or downward shift in the disease probability value occurred after a new factor had been added, including results for healthy and sick women). In the GH prediction, AUC increased most strongly when we added BMI (kg/m 2 ) as a continuous variable (AUC = 0.716, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.068, p < 0.001). The addition of BMI as a continuous variable or BMI ≥ 25 kg/m 2 improved the classification for healthy and sick women the most (NRI = 0.571, p < 0.001). In the PE prediction, AUC increased most strongly when we added BMI categories (AUC = 0.726, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.050, p = 0.080). The addition of BMI categories improved the classification for healthy and sick women the most (NRI = 0.688; p = 0.001). After summing up the results of three indexes, the probability of hypertension in pregnancy was most strongly improved by BMI, including BMI ≥ 25 kg/m 2 for the GH prediction, and BMI ≥ 30 kg/m 2 for the PE prediction. Main conclusions: Pre-pregnancy BMI was the most likely factor to increase the probability of developing hypertension in pregnancy, compared to other risk factors. Hierarchies of PE and GH risk factors may suggest different (or common) mechanisms of their development. more...

Microelements involved in the oxidative balance have a significant impact on human health, but their role in pregnancy are poorly studied. We examined the relationships between first trimester levels of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu), as well as maternal characteristics and pregnancy results. The data came from a Polish prospective cohort of women in a single pregnancy without chronic diseases. A group of 563 women who had a complete set of data, including serum microelements in the 10-14th week was examined, and the following were found: 47 deliveries <37th week; 48 cases of birth weight <10th and 64 newborns >90th percentile; 13 intrauterine growth restriction (IUGR) cases; 105 gestational hypertension (GH) and 15 preeclampsia (PE) cases; and 110 gestational diabetes mellitus (GDM) cases. The microelements were quantified using mass spectrometry. The average concentrations (and ranges) of the elements were as follows: Se: 60.75 µg/L (40.91-125.54); Zn: 618.50 µg/L (394.04-3238.90); Cu: 1735.91 µg/L (883.61-3956.76); and Fe: 1018.33 µg/L (217.55-2806.24). In the multivariate logistic regression, we found that an increase in Se of 1 µg/L reduces the risk of GH by 6% (AOR = 0.94; p = 0.004), the risk of IUGR by 11% (AOR = 0.89; p = 0.013), and the risk of birth <34th week by 7% (but close to the significance) (AOR = 0.93; p = 0.061). An increase in Fe of 100 µg/L reduces the risk of PE by 27% (AOR = 0.73; p = 0.009). In the multivariable linear regression, we found negative strong associations between prepregnancy BMI, Se (β = -0.130; p = 0.002), and Fe (β = -0.164; p < 0.0001), but positive associations with Cu (β = 0.320; p < 0.000001). The relationships between Se and maternal age (β = 0.167; p < 0.0001), Se and smoking (β = -0.106; p = 0.011) and Cu, and gestational age from the 10-14th week (β = 0.142; p < 0.001) were also found. Secondary education was associated with Zn (β = 0.132; p = 0.004) and higher education was associated with Cu (β = -0.102; p = 0.023). A higher financial status was associated with Fe (β = 0.195; p = 0.005). Other relationships were statistically insignificant. Further research is needed to clarify relationships between first trimester microelements and pregnancy complications. In addition, attention should be paid to lifestyle-related and socioeconomic factors that affect microelement levels., Competing Interests: The authors declare no conflict of interest. more...

Early identification of women at risk of developing pregnancy-induced hypertension (PIH) is very important. The involvement of copper (Cu) and zinc (Zn) in the oxidative balance suggests the possibility of their association with this disease, in which oxidative stress plays a key role. However, it has not been established so far whether the microelement levels in early pregnancy may be risk markers of the disease, as prospective studies are limited in number. In our innovative single-center study, we identified from a prospective cohort of healthy women in the 10-14th week of a single pregnancy: women subsequently developing pregnancy-induced hypertension ( n = 121) and matched women remaining normotensive ( n = 363). We measured the concentrations of microelements in the serum from 10-14 week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of the disease (and 95% confidence intervals) were assessed in logistic regression. In the whole cohort, the odds ratio (OR) of PIH was 1.52 ( p = 0.174) for women in the lowest (Q1) quartile of Cu (≤1540.58 µg/L) compared with women in the highest (Q4) quartile (>1937.46 µg/L), but adjusted odds ratio (AOR) was 2.17 ( p = 0.019) after adjusted for pre-pregnancy body mass index (BMI) and gestational age at recruitment. The higher levels of Cu in the subgroup of BMI ≥ 25 kg/m 2 compared to normal BMI were found (1847.64 vs. 1673.36 µg/L; p < 0.0001). In the subgroup of women with the normal pre-pregnancy BMI, the adjusted odds ratio of PIH was AOR = 2.95 ( p = 0.040) for Q1 vs. Q4 quartile. Our results suggest that lower Cu levels in early pregnancy may be connected with higher risk of PIH, but BMI affected estimated odds ratios. Zinc levels had no effect on the risk. more...

It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10-14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) ( n = 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10-90th percentile) ( n = 192). We measured the maternal microelement concentrations in the serum from the 10-14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L; p = 0.020). Women in the lowest Q 1 quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q 2 or Q 4 ); the odds ratio of SGA was OR = 3.02 ( p = 0.019) for Q 1 vs. Q 2 quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups. more...

The aim of this study was to assess the relationship between serum iron concentrations in early healthy pregnancy and the risk of pregnancy-induced hypertension. The data comes from our prospective cohort study in which we recruited healthy women in week 10-14 of single pregnancy. We examined a study group ( n = 121) consisting of women subsequently developing pregnancy-induced hypertension and a control group ( n = 363) of matched women remaining normotensive. We measured iron concentrations in the serum collected in 10-14 gestational week, using the ICP-MS technique (mass spectrometry with inductively coupled plasma). The odds ratios of the disease (95% confidence intervals) for iron concentrations were assessed in multivariate logistic regression. We found that the mean microelement concentration was lower in the case group compared to normotensive controls ( p = 0.011). Women in the lowest quartile of iron (≤801.20 µg/L) had a 2.19-fold increase in pregnancy-induced hypertension risk compared with women in the highest quartile (>1211.75 µg/L) (odds ratio (OR) = 2.19; 95% CI: 1.24-3.88; p = 0.007). This result was sustained after adjusted for all the accepted confounders. Women in the higher Q 2 quartile (801.20-982.33 µg/L) had a 17% lower risk, compared with those in the highest quartile (OR = 0.83; 95% CI: 0.65-2.32; p = 0.519). more...

Selenium (Se) is an antioxidant nutrient whose deficiency can influence adverse outcomes of pregnancy. The aim of this study is to determine whether serum Se level in early healthy pregnancy may be a risk marker for pregnancy induced hypertension. We obtained data from our prospective study in which we recruited healthy women in weeks 10-14 of a single pregnancy. In this analysis, we examined 121 women who subsequently developed pregnancy-induced hypertension and matched 363 women who remained normotensive. We measured Se levels (using the ICP-MS technique) in the serum in weeks 10-14 of the pregnancy. The odds ratios of pregnancy-induced hypertension (95% confidence intervals) were calculated using multivariate logistic regression. We found that the mean Se level was lower in the case group compared to the control (57.51 vs. 62.89 μg/L; p = 2.6 × 10 -10 ). Excessive body mass index (BMI) and smoking influenced the estimated odds ratios. In the subgroup of women who had never smoked with normal pre-pregnancy BMI, the adjusted odds ratio (AOR) of pregnancy-induced hypertension was 15.34 (95% CI: 2.73-86.31, p = 0.002) for Se levels in the lowest quartile (≤57.68 µg/L), as compared to the highest quartile (>66.60 µg/L), after adjusting for all the accepted confounders. In the whole cohort, the prognostic value of Se by logistic regression showed that the area under curve (AUC) = 0.814. In our study, one can consider the role of Se as a risk marker of pregnancy-induced hypertension. more...