Subtypes Of Preterm Delivery Research Articles

Increased Risk of Preterm Delivery Subtypes and Hypertensive Disorders of Pregnancy in First Deliveries of Patients With Systemic Vasculitis.

The goal of this study was to investigate the risk of preterm birth subtypes and hypertensive disorders of pregnancy in patients with systemic vasculitis using large, statewide databases. Births to nulliparous patients with prevalent systemic vasculitides (Takayasu arteritis [TAK], Behçet disease [BD], antineutrophil cytoplasmic antibody-associated vasculitis [AAV], and Kawasaki disease [KD]) were identified using International Classification of Diseases, Ninth Revision codes in linked administrative data and birth records from the California Department of Health Care Access and Information and California Vital Statistics from 1991 to 2012. Hypertensive disorders of pregnancy and preterm delivery (PTD) subtypes were identified. Multivariable-adjusted Poisson models estimated risk ratios (RRs) of these outcomes compared with the general birthing population without history of rheumatic disease. A total of 96 births to nulliparous patients with systemic vasculitis were identified (TAK, 14; AAV, 31; BD, 26; KD, 15) and compared with 4,191,900 births of the nulliparous general population. Adjusted RRs for all PTD types were elevated in patients with vasculitis (RR 3.21, 95% confidence interval [CI] 2.15-4.79), as were the RRs of all PTD subtypes including preterm premature rupture of membranes (RR 4.30, 95% CI 2.05-9.01) and spontaneous PTD (RR 4.99, 95% CI 3.01-8.28). Of the spontaneous PTDs among patients with vasculitis, 16.7% were early PTDs (20-31 weeks), with the remaining 83.3% occurring between 32 to 36 weeks. Patients with vasculitis also had an elevated risk of hypertensive disorders of pregnancy (RR 2.96, 95% CI 1.72-5.10). Among first-time births, we found that patients with systemic vasculitis have an elevated risk of PTD subtypes as well as hypertensive disorders of pregnancy.

Postpartum plasma metabolomic profile among women with preeclampsia and preterm delivery: implications for long-term health

BackgroundPreeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population.MethodsThis study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.ResultsA total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10−4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.ConclusionIn this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women’s future cardiometabolic health.

Candidate Gene and MicroRNA Expression in Fetal Membranes and Preterm Delivery Risk.

We investigated candidate gene and microRNA (miRNA) expression in amnion and chorion in relation to risk of preterm delivery (PTD). Amnion and chorion were separated from placenta and collected at delivery from participants who delivered at term (N = 10) and from participants who delivered preterm following spontaneous labor (sPTL-PTD; N = 10), premature rupture of membranes (PPROM-PTD; N = 10), and preeclampsia (PE-PTD; N = 10). Expression of genes (metalloproteinase [MMP] 2, MMP-9, and tissue inhibitors of MMP-1) and miRNAs (miR-199a*, -202*, -210, -214, -223, and -338) was profiled using quantitative real-time polymerase chain reaction approaches. Adjusted multinomial logistic regression models were used to calculate relative risk ratios (RRR), 95% confidence intervals, and P values. Among controls, the expression of miR-199a*, -202*, and -214 was lower in the amnion compared with their expression in the chorion, whereas the expression of miR-210 was higher in the amnion compared with its expression in the chorion (all P values < .05). In the amnion, MMP-9 expression was associated with PTD risk (overall P value = .0092), and MMP-9 expression was positively associated with the risk of PPROM-PTD (RRR: 31.10) and inversely associated with the risk of PE-PTD (RRR:6.55e-6), although individual associations were not statistically significant. In addition, in the amnion, the expression of miR-210 (RRR: 0.45; overall P value = .0039) was inversely associated with the risk of PE-PTD, and miR-223 was inversely associated with all subtypes of PTD (overall P value = .0400). The amnion and chorion differ in their miRNA expression. The expression of MMP-9, miR-210, and -223 in the amnion is associated with PTD risk.

Maternal bereavement and the risk of preterm delivery: the importance of gestational age and of the precursor of preterm birth

Maternal stress during pregnancy may increase the risk of preterm delivery (PD), but the associations between stress and subtypes of PD are not clear. We investigated maternal loss of a close relative and risks of very and moderately PD (<32 and 32-36 weeks, respectively) and spontaneous and medically indicated PD. We studied 4 940 764 live singleton births in Denmark (1978-2008) and Sweden (1973-2006). We retrieved information on death of women's family members (children, partner, siblings, parents), birth outcomes and maternal characteristics from nationwide registries. Overall, the death of a close family member the year before pregnancy or in the first 36 weeks of pregnancy was associated with a 7% increased risk of PD [95% confidence interval (CI) 1.04-1.10]. The highest hazard ratios (HR) for PD were found for death of an older child [HR (95% CI) 1.20 (1.10-1.31)] and for death of a partner [HR (95% CI) 1.31 (1.03-1.66)]. These losses were associated with higher risks of very preterm [HR (95% CI) 1.61 (1.29-2.01) and 2.07 (1.15-3.74), respectively] than of moderately preterm [HR (95% CI) 1.14 (1.03-1.26) and 1.22 (0.94-1.58), respectively] delivery. There were no substantial differences in the association between death of a child or partner and the risk of spontaneous v. medically indicated PD. Death of a close family member the year before or during pregnancy was associated with an increased risk of PD, especially very PD. Possible mechanisms include both spontaneous and medically indicated preterm birth.

Preterm subtypes by immigrants' length of residence in Norway: a population-based study.

BackgroundThe reduction of the preterm delivery (PTD) rate is a maternal and child health target. Elevated rates have been found among several immigrant groups, but few studies have distinguished between PTD according to the mode of birth start. In addition, migrants’ birth outcomes have further been shown to be affected by the time in residence; however, the association to PTD subtypes has not previously been assessed. In this study we examined if the risk of spontaneous and non-spontaneous, or iatrogenic, PTD among immigrants in Norway varied according to the length of residence and the country of birth, and compared with the risks among the majority population.MethodsWe linked population-based birth and immigration data for 40 709 singletons born to immigrant women from Iraq, Pakistan, the Philippines, Somalia, Sri Lanka and Vietnam and 868 832 singletons born to non-immigrant women from 1990–2009. Associations between the length of residence and subtypes of PTD were estimated as relative risks (RRs) with 95% confidence intervals (CIs) from multivariable models.ResultsIn total, 48 191 preterm births occurred. Both spontaneous and non-spontaneous PTD rates were higher among immigrants (4.8% and 2.0%) than among non-immigrants (3.6% and 1.6%). Only non-spontaneous PTD was associated with longer lengths of residence (p trend <0.001). Recent immigrants (<5 years of residence) and non-immigrants had a similar risk of non-spontaneous PTD, whereas immigrants with lengths of residence of 5–9 years, 10–14 years and ≥15 years had adjusted RRs of 1.18 [95% CI 1.03,1.35], 1.43 [95% CI 1.20,1.71] and 1.66 [95% CI 1.41,1.96]. The association was reduced after further adjustments for maternal and infant morbidity. Conversely, the risk of spontaneous PTD among immigrants was not mitigated by length of residence, but varied with country of birth according to the duration of pregnancy in term births.ConclusionsNon-spontaneous PTD increased with the length of residence whereas spontaneous PTD remained elevated regardless of the length of residence. Policies to improve birth outcomes in ethnically mixed populations should address the modifiable causes of PTD rather than aiming to reduce absolute PTD rates.

Maternal Obesity and Risk of Preterm Delivery

Cnattingius, Sven*; Villamor, Eduardo†; Johansson, Stefan*; Bonamy, Anna-Karin Edstedt*; Persson, Martina‡; Wikström, Anna-Karin*§; Granath, Fredrik* Author Information

Inflammation biomarkers in vaginal fluid and preterm delivery.

Which inflammation biomarkers detected in the vaginal fluid are most informative for identifying preterm delivery (PTD) risk? Elevated interleukin (IL)-6 at mid-trimester was associated with increased odds of spontaneous PTD at <35 weeks and with PTD plus histologic chorioamnionitis (HCA), and had the greatest sensitivity for detecting these two PTD subtypes. Maternal and/or fetal inflammation play a role in some preterm deliveries, therefore inflammation biomarkers might help to identify women at greater risk. We examined 1115 women from the Pregnancy Outcomes and Community Health Study, a cohort study conducted from September 1998 through June 2004, for whom data were available on mid-pregnancy inflammatory biomarkers. At enrollment at 16-27 weeks gestation, vaginal fluid samples were collected from a swab and 15 eluted biomarkers were measured using the Meso Scale Discovery multiplex electrochemiluminescence platform. Associations of biomarkers with PTD were examined, according to clinical circumstance, week at delivery and presence/absence of HCA. Weighted logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) adjusted for race. Sensitivity and specificity were compared between individual and multiple biomarkers, identified by a bootstrapping method. Elevated IL-6 (>75th percentile) displayed the strongest association with spontaneous PTD <35 weeks (OR 2.3; CI 1.3-4.0) and PTD with HCA (OR 2.8; CI 1.4-6.0). The sensitivity of IL-6 to detect spontaneous PTD <35 weeks or PTD with HCA was 0.43 and 0.51, respectively, while specificity was 0.74 and 0.75, respectively. IL-6 plus IL1β, IL-6r, tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor increased specificity (range 0.84-0.88), but decreased sensitivity (range 0.28-0.34) to detect both PTD subtypes. Results were similar when a combination of IL-6 and bacterial vaginosis (BV) was explored. Thus, the use of multiple biomarkers did not detect PTD subtypes with a greater sensitivity than IL-6 alone, and IL-6 is a specific but non-sensitive marker for the detection of spontaneous PTD. Our ability to find small effect size associations between PTD and inflammation biomarkers (OR <2.0) might have been limited by the modest number of less common PTD subtypes in our population (e.g. spontaneous delivery <35 weeks, PTD accompanied by HCA) and by relatively higher variability for some cytokines, for example tumor necrosis factor-α, IL-12p70, IL-10 and granulocyte-macrophage colony-stimulating factor, that are less stable and commonly undetectable or detectable at low levels in human vaginal secretions. Larger studies are needed to further explore a role of inflammation biomarkers in combination with other risk factors, including specific BV-associated organisms, for the prediction of PTD subtypes. This work was supported by the National Institute of Child Health and Human Development, National Institute of Nursing, March of Dimes Foundation, Thrasher Research Foundation and Centers for Disease Control and Prevention. The authors have no conflicts of interest.

Maternal Obesity and Risk of Preterm Delivery

Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Among 1,599,551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67,059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI≥30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.

Evidence of placental haemorrhage and preterm delivery

To evaluate evidence of placental haemorrhage (PH) obtained through maternal interviews, patient charts and placental pathology examinations as potential indicators of a 'bleeding pathway' to preterm delivery (PTD). Prospective cohort. Fifty-two clinics in five communities in Michigan, USA (1998-2004). A subset (n = 996) of cohort participants with complete placental pathology data. First-trimester bleeding and placental abruption were ascertained by mid-trimester interviews and chart review, respectively. Disc-impacting blood clot was defined as a gross placental examination finding of a blood clot impacting adjacent tissue. Microscopic haemorrhage was defined as 'high' (top quintile) scores on an aggregate measure of placental pathology findings suggestive of atypical maternal vessel haemorrhage. These four PH indicators were compared with one another and with risk of PTD assessed by logistic regression analyses. Preterm delivery and PTD subtypes (i.e. <35 weeks, 35-36 weeks; spontaneous, medically indicated) compared with term deliveries. Placental abruption cases had 2.3-fold to 5.5-fold increased odds of the other three PH indicators. Disc-impacting blood clots and microscopic haemorrhage were associated with one another (odds ratio [OR] = 4.6), but not with first-trimester bleeding. In a multivariable model that included all four PH indicators and confounders, risk of PTD < 35 weeks was elevated with first-trimester bleeding (OR = 1.9 [1.0, 3.4]), placental abruption (OR = 5.2 [1.7, 16.2]), disc-impacting blood clots (OR = 2.3 [1.0, 5.0]) and microscopic haemorrhage (OR = 2.4 [1.4, 4.2]). Multiple clinical and subclinical PH indicators are associated with PTD, particularly early PTD.

A case–control study of preterm delivery risk factors according to clinical subtypes and severity

To examine risk factors of preterm delivery (PTD) among Thai women. Our case-control study included 467 term controls and 467 PTD cases. PTD was studied in aggregate and in subgroups (i.e. spontaneous preterm labor and delivery [SPTD], preterm premature rupture of membrane [PPROM], medically indicated preterm delivery [MIPTD], moderate preterm delivery [32-36 weeks], and very preterm delivery [<32 weeks]). We used multivariable logistic regression procedures to estimate odds ratio (OR) and 95% confidence intervals (CI) of potential PTD risk factors. Advanced maternal age (>or=35 years) was associated with a 2.27-fold increased PTD risk overall (95%CI: 1.40, 3.68); and with a 3.79-fold increased risk of MIPTD (95%CI: 1.89, 7.59). Young maternal age (<20 years) was associated with a 2.07-fold increased risk of SPTD (95%CI: 1.19, 3.61). Prior history of PTD was associated with a 3.64-fold increased PTD risk overall (95%CI: 1.87, 7.09), and with a 5.69-fold increased risk of MIPTD (95%CI: 2.44, 13.24). No prenatal care was associated with all PTD subtypes. Lean women (body mass index < 18.5 kg/m(2)), compared with normal weight women (18.5-24.9 kg/m(2)), had a 1.70-fold increased risk of PTD (95%CI: 1.21, 2.39). Risk of SPTD (OR = 2.16, 95%CI: 1.44, 3.24) and very PTD (OR = 2.45, 95%CI: 1.35, 4.45) were also elevated in lean women. Maternal age, pre-pregnancy body mass index, prior history of PTD and no utilization of prenatal care were covariates identified in this study as risk factors for PTD. Our findings also suggest heterogeneity in risk factors for clinical subtypes of PTD.

The Association between Prepregnancy Maternal Body Mass Index and Preterm Delivery

We investigated the association between prepregnancy maternal body mass index (BMI) and preterm delivery (PTD). The study included 44,421 American women presenting for care in Saint Louis, Missouri between 1990 and 2006. Only singleton gestations were included. The authors examined the associations between categories of BMI with PTD <37 and <34 weeks, respectively. A stratified analysis by subtypes of PTD was also performed. The subtypes of PTD evaluated included spontaneous PTD without preterm premature rupture of membranes (PPROM), PPROM, and indicated PTD. Univariate and multivariable analyses were used to estimate the association between maternal BMI categories and PTD <37 weeks, PTD <34 weeks, and subtypes of PTD. Among women meeting the inclusion criteria, PTD <37 occurred in 4783 (10.8%) and PTD <34 weeks in 1132 (2.5%). Being underweight was associated with increased risks of PTD <37 weeks (adjusted odd ratio [OR] = 1.3, 95% confidence interval [CI]: 1.2, 1.5). Being obese was associated with decreased risks of spontaneous PTD without PPROM <37 weeks (adjusted OR = 0.8, 95% CI: 0.7, 0.9) and increased risk of PPROM <37 weeks (adjusted OR = 1.3, 95% CI: 1.1, 1.6) and PPROM <34 weeks (adjusted OR = 1.4, 95% CI: 1.0, 2.0). Prepregnancy obesity increases the risk of PPROM and decreases risk of spontaneous PTD without PPROM.

Maternal Catecholamine Levels in Midpregnancy and Risk of Preterm Delivery

Associations between stress hormones and preterm delivery have not been fully explored. In this study, pregnant women enrolled from 52 clinics in 5 Michigan communities (1998-2004) provided urine samples for 3 days (waking and bedtime) during midpregnancy. Urinary catecholamine levels (epinephrine, norepinephrine, and dopamine) were measured in a subcohort (247 preterm and 760 term deliveries), and a 3-day median value was calculated. Polytomous logistic regression models assessed relations between catecholamine quartiles (of the median) and a 4-level outcome variable (i.e., term (referent) and 3 preterm delivery subtypes: spontaneous; premature rupture of membranes; and medically indicated). Final models incorporated other relevant covariates (e.g., creatinine, demographic, behavior). The risk of spontaneous preterm delivery was increased in the highest versus lowest quartile of norepinephrine and dopamine: norepinephrine, waking (adjusted odds ratio (AOR) = 3.7, 95% confidence interval (CI): 1.8, 7.9) and bedtime (AOR = 2.5, 95% CI: 1.3, 4.9); dopamine, waking (AOR = 2.6, 95% CI: 1.4, 5.1) and bedtime (AOR = 2.3, 95% CI: 1.2, 4.6). Adjusted odds ratios were further strengthened after removing women whose placentas showed evidence of acute infection or vascular pathology. High catecholamine levels in maternal urine may be indicative of excess stressors and/or predisposition to elevated sympathetic activation that contributes to increased risk of spontaneous preterm delivery.

Hostility and anomie: Links to preterm delivery subtypes and ambulatory blood pressure at mid-pregnancy

Underlying maternal vascular disease has been implicated as one of several pathways contributing to preterm delivery (PTD) and psychosocial factors such as hostility, anomie, effortful coping, and mastery may be associated with PTD by affecting maternal vascular health. Using data from the Pregnancy Outcomes and Community Health (POUCH) study, we included 2018 non-Hispanic White and 743 African American women from 52 clinics in five Michigan, USA communities. Women were interviewed at 15–27 weeks' gestation and followed to delivery. We found that relations between psychosocial factors and PTD subtypes (i.e. medically indicated, premature rupture of membranes, spontaneous labor) varied by race/ethnicity and socio-economic position (Medicaid insurance status). Among African American women not insured by Medicaid, anomie levels in mid-pregnancy were positively associated with medically indicated PTD after adjusting for maternal age and education. Among all women not insured by Medicaid, hostility levels were positively associated with spontaneous PTD after adjusting for maternal race/ethnicity, age, and education. Failure to detect links between psychosocial factors and PTD risk in poorer women may be due to their excess risk in multiple PTD pathways and/or a more complex web of contributing risk factors.In a subset of 395 women monitored for blood pressure, anomie scores were positively associated with systolic blood pressure and heart rate and hostility scores were positively associated with systolic and diastolic blood pressure, heart rate and mean arterial pressure in models that included time, awake/asleep, race/ethnicity, and age as covariates. Further adjustment for body mass index and smoking attenuated the anomie-vascular relations but had little effect on the hostility-vascular relations. Overall this study of pregnant women provides some physiologic evidence to support findings linking levels of anomie and hostility with risk of PTD.

Defining preterm delivery - the epidemiology of clinical presentation

It is possible that preterm delivery is not a single entity but a cluster of conditions with different aetiologies that ultimately result in the delivery of an infant before 37 completed weeks of gestation. Whereas some researchers have reported aetiological heterogeneity, others have found no differences between subtypes or have disputed the desirability and utility of classifying preterm birth into subtypes. This study explores the relationship of maternal risk factors to type of preterm delivery in a cohort of over 7000 black and white women delivering singleton infants at the University of California, San Francisco's Moffitt Hospital between 1980 and 1990. Although the magnitude of the effect of individual risk factors differed between preterm delivery subtypes, the set of risk factors significantly associated with both categories of spontaneous preterm delivery was identical, while that associated with medically indicated preterm births was different. This study indicates that whereas the distinction between spontaneous preterm deliveries and those that are medically indicated seems valid, distinguishing between types of spontaneous preterm births may not lead to useful aetiological inferences.