Maternal risk of hypertension 7-15 years after pregnancy: clues from the placenta.

OBJECTIVE: To assess whether pre-eclampsia (PE)-related placental/extraplacental membrane findings are linked to moderately elevated blood pressure (BP) in pregnancy and later-life hypertension. DESIGN: Prospective cohort. SETTING: 52 prenatal clinics, 5 Michigan communities. SAMPLE: The POUCH Study recruited women at 16-27 weeks' gestation (1998-2004) and studied a sub-cohort in depth. This sample (n = 490) includes sub-cohort women with detailed placental assessments and cardiovascular health evaluations 7-15 years later in the POUCHmoms follow-up study. METHODS: PE-related placental/extraplacental membrane findings (i.e. mural hyperplasia, unaltered/abnormal vessels or atherosis in decidua; infarcts) were evaluated in relation to pregnancy BP and odds of Stage 2 hypertension at follow up using weighted polytomous regression. Follow-up hypertension odds also were compared in three pregnancy BP groups: normotensives (referent) and moderately elevated BP with or without PE-related placental/extraplacental membrane findings. MAIN OUTCOME MEASURES: Stage 2 hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg, or using antihypertensive medications) at follow up. RESULTS: After excluding women with pregnancy hypertension (i.e. chronic, PE, gestational), mural hyperplasia and unaltered/abnormal decidual vessels were each associated with Stage 2 hypertension at follow up: adjusted odds ratio (aOR) = 2.7, 95% CI 1.1-6.6, and aOR = 1.7 (95% CI 0.8-3.4), respectively. Women with moderately elevated BP in pregnancy and evidence of mural hyperplasia or unaltered/abnormal decidual vessels had greater odds of Stage 2 hypertension at follow up: aOR = 4.5 (95% CI 1.6-12.5 and aOR = 2.6, 95% CI 1.1-5.9, respectively. CONCLUSIONS: PE-related placental/extraplacental membrane findings help risk-stratify women with moderately elevated BP in pregnancy for later development of hypertension. TWEETABLE ABSTRACT: Placental findings associated with mother's risk of later-life hypertension.

Preterm birth with placental evidence of malperfusion is associated with cardiovascular risk factors after pregnancy: a prospective cohort study.

OBJECTIVE: Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. DESIGN: Pregnancy cohort study. SETTING: Pittsburgh, PA, USA. POPULATION: Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. METHODS: Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME MEASURES: Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. RESULTS: Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). CONCLUSION: PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. TWEETABLE ABSTRACT: Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk.

Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; <37 weeks' gestation) and small for gestational age (SGA; birthweight <10th percentile) delivery. DESIGN: Prospective, longitudinal. SETTING: Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011). POPULATION: 768 nulliparous women at baseline who reported ≥1 live birth by the Y25 exam. METHODS: We used Poisson regression to determine associations of exposures with PTB/SGA. MAIN OUTCOME MEASURES: PTB and/or SGA births. RESULTS: Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 ± 1 versus 142 ± 1 mmHg, P < 0.04). After adjustment, no exercise test variables were associated with PTB/SGA, though the association with HRR and submaximal SBP approached significance in the subset of women who completed the exercise test <5 years before the index birth. CONCLUSIONS: Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy. TWEETABLE ABSTRACT: Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA.

Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study.

OBJECTIVE: Hypertensive disorders in pregnancy signal an increased risk of cardiovascular disease for women. However, future hypertension risk among pregnant women with moderately elevated blood pressure (BP) is unknown. We examined associations among moderately elevated BP or hypertensive disorders during pregnancy and later prehypertension or hypertension. DESIGN: Longitudinal cohort study. SETTING: Five communities in Michigan, USA. SAMPLE: Data are from pregnant women enrolled in the Pregnancy Outcomes and Community Health Study. We included 667 women with gestational BP measurements who participated in the POUCHmoms Study follow-up 7-15 years later. METHODS: Moderately elevated BP was defined as two measures of systolic BP ≥ 120 mmHg or diastolic BP ≥80 mmHg among women without a hypertensive disorder. Weighted multinomial logistic regression models estimated odds of prehypertension or hypertension at follow-up, adjusted for maternal confounders and time to follow-up. MAIN OUTCOME MEASURES: Prehypertension or hypertension. RESULTS: Women meeting the moderately elevated BP criteria (64%) had significantly higher odds of hypertension at follow-up (adjusted odds ratio 2.6; 95% confidence interval 1.2-5.5). These increased odds were observed for moderately elevated BP first identified before or after 20 weeks of gestation, and for elevated systolic BP alone or combined with elevated diastolic BP. CONCLUSIONS: Moderately elevated BP in pregnancy may be a risk factor for future hypertension. Pregnancy offers an opportunity to identify women at risk for hypertension who may not have been identified otherwise. TWEETABLE ABSTRACT: Moderately elevated blood pressure in pregnancy may be associated with hypertension later in life.

First trimester coffee and tea intake and risk of gestational diabetes mellitus: a study within a national birth cohort.

OBJECTIVE: Coffee and tea consumption is associated with a decreased type 2 diabetes risk in non-pregnant adults. We examined the relation between first trimester coffee and tea consumption and gestational diabetes mellitus (GDM) risk. DESIGN: Population-based cohort study. SETTING: Denmark 1996-2002. POPULATION: Non-diabetic women with singleton pregnancies in the Danish National Birth Cohort (n = 71,239). METHODS: Estimated adjusted relative risks (RR) and 95% confidence intervals (95%CI) for the association between first trimester coffee and tea or estimated total caffeine and GDM. MAIN OUTCOME MEASURES: GDM ascertained from the National Hospital Discharge Register or maternal interview. RESULTS: Coffee or tea intake was reported in 81.2% (n = 57,882) and 1.3% (n = 912) of pregnancies were complicated by GDM. Among non-consumers, 1.5% of pregnancies were complicated by GDM. Among coffee drinkers, GDM was highest among women who drank ≥8 cups/day (1.8%) with no significant difference across intake levels (P = 0.10). Among tea drinkers, there was no difference in GDM across intake levels (1.2%; P = 0.98). After adjustment for age, socio-occupational status, parity, pre-pregnancy body mass index, smoking, and cola, there was suggestion of a protective, but non-significant association with increasing coffee (RR ≥8 versus 0 cups/day = 0.89 [95%CI 0.64-1.25]) and tea (RR ≥8 versus 0 cups/day = 0.77 [95%CI 0.55-1.08]). Results were similar by smoking status, except a non-significant 1.45-fold increased risk with ≥8 coffee cups/day for non-smokers. There was a non-significant reduced GDM risk with increasing total caffeine. CONCLUSIONS: Our results suggest that moderate first trimester coffee and tea intake were not associated with GDM increased risk and possibly may have a protective effect.

Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth.

OBJECTIVE: To evaluate the association of early pregnancy concentrations of thrombin-antithrombin III complex with subsequent spontaneous preterm birth. METHODS: In a nested case-control study, thrombin-antithrombin III complex was measured in plasma before 20 weeks of gestation (mean 9.9 weeks) among women without chronic conditions, preeclampsia, or growth restriction. C-reactive protein and non-high-density lipoprotein cholesterol were also measured. Women with spontaneous preterm birth before 34 weeks of gestation (n=29) and 34 weeks to 36 weeks of gestation (n=72) were compared with women with term births occurring at or after 37 weeks (n=219). Polychotomous logistic regression was used to relate elevated thrombin-antithrombin III complex (greater than 5.5 ng/mL), dyslipidemia (non-high-density lipoprotein cholesterol greater than the 90th percentile), and inflammation (C-reactive protein at or above 8 micrograms/mL) to risk of spontaneous preterm birth subtypes. RESULTS: Women with spontaneous preterm birth compared with term births had elevated thrombin-antithrombin III complex (P=.02), and they were more likely to have a thrombin-antithrombin III complex greater than 5.5 ng/mL (P<.01). Women with thrombin-antithrombin III complex in the highest compared with lowest quartile had a 4.6-fold (95% confidence interval 1.3-15.8) increased risk for spontaneous preterm birth before 34 weeks of gestation, adjusted for body mass index, race, inflammation, dyslipidemia, and gestational age at sampling. There was a dose-response trend between thrombin-antithrombin III complex and spontaneous preterm birth before 34 weeks (P<.01) and 34 to 36 weeks (P=.03). CONCLUSION: There is evidence of early pregnancy systemic fibrinolysis among women with spontaneous preterm birth before 34 weeks of gestation independent of inflammation and dyslipidemia, perhaps secondary to microvascular injury. LEVEL OF EVIDENCE: II.

Placental pathology measures: Can they be rapidly and reliably integrated into large-scale perinatal studies?

INTRODUCTION: Normal placental function is critical to optimize fetal growth and development, but few perinatal studies incorporate placental measures. Our objectives were to link clinical placental pathology records to birth records, and validate an automated abstraction strategy. METHODS: Of the 47,329 deliveries at our hospital from 2008 to 2012, we retrieved electronic copies of pathology reports (n = 21,585, 45.4%). Pathology data were extracted with Extensible Markup Language (XML) script using Java and structured query language (SQL) transformed the text information into variables that were linked to delivery data. A subgroup of records was selected for a validation study that compared automated to manual abstraction (n = 144). RESULTS: Linked birth-placental records included 93% of all preterm (<37 weeks, n = 5108) and 37.1% of term births (n = 14,019). Over 90% of deliveries complicated by preeclampsia, chronic hypertension, or gestational diabetes included pathology data. The validation study indicated excellent agreement, sensitivity and specificity between the two abstraction strategies. DISCUSSION: We demonstrate a reliable approach to electronically integrate placental pathology and delivery data. These linked data provide a platform to identify risk factors and sequelae associated with placental lesions.