Background Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Given its large public health burden, there is a need to identify modifiable factors that can be targeted for preeclampsia prevention. In this study, we examined whether a Mediterranean‐style diet is protective for preeclampsia in a large cohort of racially and ethnically diverse, urban, low‐income women. Methods and Results We used data from the Boston Birth Cohort. Maternal sociodemographic and dietary data were obtained via interview and food frequency questionnaire within 24 to 72 hours postpartum, respectively. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records. We derived a Mediterranean‐style diet score from the food frequency questionnaire and performed logistic regression to examine the association of the Mediterranean‐style diet score with preeclampsia. Of 8507 women in the sample, 848 developed preeclampsia. 47% were Black, 28% were Hispanic, and the remaining were White/Other. After multivariable adjustment, greatest adherence with MSD was associated with lower preeclampsia odds (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% CI, 0.64–0.96). A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76–0.96). Conclusions Self‐report of higher adherence to a Mediterranean‐style diet is associated with lower preeclampsia odds, and benefit of this diet is present among Black women as well.

BACKGROUND: No studies have examined whether the cord blood metabolome—a reflection of in utero metabolism—influences blood pressure (BP) in children. OBJECTIVES: To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in children. METHODS: In the Boston Birth Cohort, we measured metabolites in cord blood plasma, and SBP and DBP at clinic visits between 3 and 18 years. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression. RESULTS: Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (interquartile range, 6.7–11.7) years, and the median number of BP observations per child was 7 (interquartile range, 4–11). After false discovery rate correction, 3 metabolites were associated with SBP, 96 with DBP, and 24 with elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all 3 outcomes, and 22 metabolites were associated with both DBP and elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and elevated BP included nucleotides (eg, xanthosine, hypoxanthine, xanthine) and acylcarnitines (eg, C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways. CONCLUSIONS: In our urban and predominantly racial/ethnic minority cohort, we provide evidence that metabolomic alterations in utero, in particular, acylcarnitine- and purine-metabolism metabolites, may be involved in the early life origins of hypertension.

OBJECTIVE To investigate the association of plasma insulin levels and their trajectories from birth to childhood with the timing of menarche. RESEARCH DESIGN AND METHODS This prospective study included 458 girls recruited at birth between 1998 and 2011 and followed prospectively at the Boston Medical Center. Plasma nonfasting insulin concentrations were measured at two time points: at birth (cord blood) and in childhood (age 0.5–5 years). Age at menarche was obtained from a pubertal developmental questionnaire or abstracted from electronic medical records. RESULTS Three hundred six (67%) of the girls had reached menarche. The median (range) age at menarche was 12.4 (9–15) years. Elevated plasma insulin concentrations at birth (n = 391) and in childhood (n = 335) were each associated with an earlier mean age at menarche: approximately 2 months earlier per doubling of insulin concentration (mean shift, −1.95 months, 95% CI, −0.33 to −3.53, and −2.07 months, 95% CI, −0.48 to −3.65, respectively). Girls with overweight or obesity in addition to elevated insulin attained menarche about 11–17 months earlier, on average, than those with normal weight and low insulin. Considering longitudinal trajectories (n = 268), having high insulin levels both at birth and in childhood was associated with a roughly 6 months earlier mean age at menarche (mean shift, −6.25 months, 95% CI, −0.38 to −11.88), compared with having consistently low insulin levels at both time points. CONCLUSIONS Our data showed that elevated insulin concentrations in early life, especially in conjunction with overweight or obesity, contribute to the earlier onset of menarche, suggesting the need for early screening and intervention.

Background: Although insulin resistance is closely related to hypertension, the debate continues as to whether insulin resistance is a cause or a consequence of hypertension. This study investigated the associations of cord blood insulin concentration with blood pressure (BP) and hypertension in childhood and adolescence. Methods: This study included 951 children enrolled from 1998 to 2012 and followed from birth onwards at the Boston Medical Center, Boston, MA. Cord blood insulin concentration was measured using a sandwich immunoassay. Hypertension in childhood and adolescence was defined based on the 2017 American Academy of Pediatrics Clinical Practice Guidelines. Results: The median (interquartile range) for cord blood insulin concentration was 12.1 (7.2–19.0) µIU/mL. The age range of BP measurements was 3 to 18 years (median, 10.6 years). Cord blood insulin concentration was positively associated with systolic and diastolic BP as well as the risk of hypertension at age 3 to 18 years. Compared with the lowest tertile of cord blood insulin concentration, the top tertile insulin concentration was associated with a 5.18 (95% CI, 1.97–8.39) percentile increase in systolic BP, 4.29 (95% CI, 1.74–6.84) percentile increase in diastolic BP, and 1.62-fold (95% CI, 1.27–2.08) higher risk of hypertension. The association between insulin and hypertension was stronger among children born preterm ( P for interaction=0.048). Furthermore, preterm birth and childhood overweight or obesity enhanced the associations. Conclusions: Our results suggest that elevated insulin concentration at birth plays a critical role in the early life origins of hypertension and support the hypothesis implicating insulin resistance in the etiology of hypertension.

Rationale & Objective: Pregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods: This study included 576 mothers of multiple ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and cystatin-C were measured 1-3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. Results: During an average of 8.2±2.9 years of follow-up, 33 of 576 mothers developed one or more CVD. Although no associations were found between creatinine and risk of CVD, each doubling of cystatin-C was associated with a hazard ratio (HR) of 4.6 (95% CI=1.5 - 14.0) for CVD. A significant synergistic effect was observed between elevated cystatin-C (≥75th percentile) and preeclampsia (P for interaction =0.049). Compared to those without preeclampsia and with normal cystatin-C level (<75th percentile), mothers with preeclampsia and elevated cystatin-C had the highest risk of CVD (HR=4.2, 95%CI=1.6-11.2), while mothers with preeclampsia only or with elevated cystatin-C only had no significantly increased CVD risk. Similar synergistic effects for CVD were observed between cystatin-C and preterm delivery. Conclusions: In this sample of US, traditionally underrepresented multi-ethnic high-risk mothers, maternal plasma cystatin-C and pregnancy complications synergistically increased risk of CVD later in life. These findings warrant further investigation.

OBJECTIVE To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This prospective cohort study enrolled 1,409 women at 24–72 h after delivery of a singleton baby and followed them prospectively at the Boston Medical Center. The lipidome was profiled by liquid chromatography-tandem mass spectrometry. Diagnoses of GDM and incident T2D were extracted from medical records and verified using plasma glucose levels. RESULTS Mean (SD) age of study women at baseline was 28.5 (6.6) years. A total of 219 (16.4%) women developed incident diabetes over a median follow-up of 11.8 (interquartile range 8.2–14.8) years. We identified 33 postpartum lipid species associated with GDM, including 16 inverse associations (primarily cholesterol esters and phosphatidylcholine plasmalogens), and 17 positive associations (primarily diacyglycerols and triacyglycerols). Of these, four were associated with risk of incident T2D and mediated ∼12% of the progression from GDM to T2D. The identified lipid species modestly improved the predictive performance for incident T2D above classical risk factors when the entire follow-up period was considered. CONCLUSIONS GDM was associated with a wide range of lipid metabolic alterations at early postpartum, among which some lipid species were also associated with incident T2D and mediated the progression from GDM to T2D. The improvements attained by including lipid species in the prediction of T2D provides new insights regarding the early detection and prevention of progression to T2D.

Background: Risk factors for high blood pressure (BP) in children start in utero . Cord blood metabolites reflect exposures of the developing fetus to the in utero environment. No studies have examined whether cord blood metabolites are associated with BP in children. Objectives: To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in childhood and adolescence. Methods: We used data from the Boston Birth Cohort. Metabolites were measured in cord blood plasma samples collected at birth. SBP and DBP were measured at clinic visits between 3 to 18 years. We calculated BP percentiles per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression. We used the False Discovery Rate (FDR) method to adjust for multiple comparisons. Results: Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (IQR: 6.7-11.7) years, and the median number of BP observations per child was 7 (IQR: 4-11). After FDR adjustment, 3, 94, and 22 metabolites were respectively associated with SBP, DBP, and risk of elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all three outcomes, and 22 metabolites were associated with both DBP and risk of elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and risk of elevated BP included nucleotides (e.g., xanthosine, hypoxanthine, xanthine) and acylcarnitines (e.g., C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways. Conclusions: In this predominantly urban, low-income, minority cohort, cord blood metabolites were prospectively associated with BP and risk of elevated BP from childhood to adolescence. Acylcarnitines and purine metabolism may be involved in the early life origins of hypertension. Cord metabolites may explain the intergenerational effects of in utero environments on BP in childhood and adolescence.

No abstract