Janet W. Rich-Edwards

Growing evidence indicates that women with a history of common pregnancy complications, including fetal growth restriction and preterm delivery (often combined as low birth weight), hypertensive disorders of pregnancy, and gestational diabetes, are at increased risk for cardiovascular disease later in life. The purpose of this paper was to review the associations of parity and these 4 pregnancy complications with cardiovascular morbidity and mortality; to review the role of cardiovascular risk factors before, during, and after pregnancy complications in explaining these associations; and to explore the implications of this emerging science for new research and policy. We systematically searched for relevant cohort and case-control studies in Medline through December 2012 and used citation searches for already published reviews to identify new studies. The findings of this review suggest consistent and often strong associations of pregnancy complications with latent and future cardiovascular disease. Many pregnancy complications appear to be preceded by subclinical vascular and metabolic dysfunction, suggesting that the complications may be useful markers of latent high-risk cardiovascular trajectories. With further replication research, these findings would support the utility of these prevalent pregnancy complications in identifying high-risk women for screening, prevention, and treatment of cardiovascular disease, the leading cause of morbidity and mortality among women.

First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy. sFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student’s T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels. PAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002). Low first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.

Background: Nutrients, hormones and growth factors in dairy foods may stimulate growth hormone (GH), insulin-like growth factor I (IGF-I), and raise the ratio of IGF-I to its binding protein, IGFBP-3. We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children.Methods: In Ulaanbaatar, we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10–11 year old schoolchildren. In a randomized cross-over study in Boston, we compared plasma hormone levels of 28 6–8 year old girls after one week of drinking 710 ml lowfat (2%) milk with their hormone levels after one week of consuming a macronutrient substitute for milk.Results: After a month of drinking whole milk, Mongolian children had higher mean plasma levels of IGF-I (p < 0.0001), IGF-I/IGFBP-3 (p < 0.0001), and 75^thpercentile of GH levels (p = 0.005). After a week of drinking lowfat milk, Boston girls had small and non-significant increases in IGF-1, IGF-1/IGFBP-3 and GH.Conclusion: Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys. The finding that milk intake may raise GH levels is novel, and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production.