In this population study of adiponectin levels in cord blood of pregnancies with preeclampsia and pregnancies without preeclampsia, we found that in preterm pregnancies, the preeclampsia group had higher levels of adiponectin, and in pregnancies with delivery after spontaneous contractions, adiponectin levels were also higher in the preeclampsia group.
Previously, one study has reported no association of adiponectin with preeclampsia after adjustment for birth weight, gestational age and gender of the offspring [13
]. That study included only 22 pregnancies with preeclampsia, and differences in adiponectin levels could not be reliably studied. In another Norwegian study, there was no difference in cord blood levels of adiponectin in the offspring of preeclamptic pregnancies and pregnancies without preeclampsia, after adjustment for length of gestation [26
]. That study was hospital-based, and the comparison groups were rather small (30 preeclampsia and 62 control pregnancies).
In our study, concentrations of adiponectin in cord blood were comparable to those of another study [27
], but slightly higher than reported by others [13
]. At low temperatures (~ −80°C), adiponectin concentrations are believed to be stable (Linco Research, Inc.). The samples were stored for a few hours at 4°C before deep freezing. To explore the stability of adiponectin, we conducted a pilot study and applied the same method of measurement in 10 fresh cord blood samples. Concentrations of adiponectin in fresh cord blood were similar to those obtained using the stored blood of the study. There was no difference in the handling of samples between the groups.
In a previous study, cord blood adiponectin was lower in pregnancies of mothers who smoked compared to non-smokers [29
]. This observation could be of relevance for our findings, because maternal smoking is negatively associated with risk of preeclampsia [30
]. We had information about smoking at the beginning of pregnancy, but there was no association of smoking with cord blood adiponectin in our data, in either normotensive or preeclamptic pregnancies.
Fetal adiponectin is believed to increase with increasing length of pregnancy [13
], and our findings concur with this. Given the consistently shorter length of gestation of preeclamptic pregnancies, it was appropriate to adjust for gestational age in the initial analyses. However, adiponectin concentrations did not differ between the groups, also after adjustment, and differences were only observed in the subgroup analyses, with higher cord adiponectin in preterm preeclampsia, and in preeclampsia with delivery after spontaneous contractions. Therefore, the higher levels of adiponectin in cord blood that we report in preeclamptic pregnancies with spontaneous delivery, and in preterm preeclampsia, should be interpreted with caution.
The study was based on preeclampsia cases and selected controls that occurred within a cohort of nearly 13,000 pregnant women. Controls were selected to minimize bias both in selection and cord blood measurements, and cord blood adiponectin was measured with standardized methods, where the technicians were blinded to the preeclampsia status of the blood samples.
There was not sufficient cord blood to analyze adiponectin from all participants of the original study. Among controls, there were no differences in perinatal data between the group with missing blood and those with available cord blood. However, in the preeclampsia group, those with missing cord blood tended to have lower gestational age and lower birth size compared to pregnancies with available cord blood. Thus, more severe cases of preeclampsia appear to have missing blood. This suggests that the differences that we report in this paper may be underestimates of the true differences. Also, the number of samples was low from normotensive pregnancies with low gestational age and from preeclampsia pregnancies with high gestational age. Therefore, the study does not have statistical power to detect differences between offspring with high or low gestational age.
Adiponectin is widely expressed both in the fetus and placenta and in various isoforms that were not measured in this study. In a recent study the most biological active isoform of adiponectin was found to represent the greatest part of total adiponectin in cord blood [26
]. However, we do not know if this is the case in offspring of mothers with preeclampsia or in prematurely born offspring, and it would be of interest to study different isoforms of adiponectin in cord blood. In general, adiponectin will promote energy expenditure, and in cases of placental dysfunction, such as in preeclampsia, nutritional supply to the fetus may be compromised. It has been suggested that high levels of cord blood adiponectin is associated with greater central adiposity in children, and therefore, adiponectin could play a role in optimizing energy supply to the fetus as well as energy expenditure in infancy [18
]. The higher levels of cord adiponectin that we found in pregnancies with preterm preeclampsia could be consistent with the hypothesis that upregulation of adiponectin may represent an adaptive response to relative scarcity of nutritional and energy input, maybe caused by placental dysfunction/placentation problems. Since we only have data on the result of such scarcity (preeclampsia in the mother, lower birth weight and gestational age in the offspring) we do not have data to show this directly and this suggestion is still speculative.
In adults, low adiponectin levels are associated with endothelial dysfunction related to atherosclerosis and angiogenesis, and low levels have been associated with increased risk of vascular disease, diabetes, prostate cancer and breast cancer [31
]. Women who have experienced preeclampsia, either in one of their own pregnancies, or as offspring, appear to be at reduced risk of breast cancer later in life [34
] whereas men whose mothers had preeclampsia may be at reduced risk of prostate cancer [37
]. It has also been shown that offspring of preeclamptic pregnancies may have higher blood pressure already in puberty compared to other children [38
]. It has therefore been suggested that adiponectin and preeclampsia share associations with several diseases that may occur subsequent to pregnancy. By comparing adiponectin levels through the life course in offspring of preeclamptic and normotensive pregnancies, associations with adult diseases may be further elucidated.
In this study we found that in preterm pregnancies and in pregnancies with delivery after spontaneous contractions, cord blood levels of adiponectin were higher in pregnancies with preeclampsia than in pregnancies without preeclampsia.