Medically-indicated Preterm Birth Research Articles

Pregnancy and neonatal outcomes among women with early-onset colorectal cancer: a nationwide case–control study

Early-onset colorectal cancer has risen worldwide, leaving more women with colorectal cancer at reproductive ages. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among women with early-onset colorectal cancer. We conducted a nationwide, matched case-control study of maternal/pregnancy outcomes including pre-eclampsia and Cesarean delivery (C-section) as well as neonatal outcomes including preterm birth among 207 births in women with early-onset colorectal cancer (ages 18-49) and 1019 births in women without colorectal cancer in Sweden (1992-2019). Early-onset colorectal cancer cases were identified through the Cancer Register, and outcome data were retrieved through linkage to Medical Birth Register and National Patient Register. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between Jan 1, 1992, and Dec 31, 2019, women with early-onset colorectal cancer who gave birth had increased odds of pre-eclampsia (7.2% vs 3.2%; OR=2.52, 95%CI=1.25-5.08), any C-section (24.6% vs 19.4%; OR=1.43, 95%CI=1.00-2.06), particularly emergency C-section (17.4% vs 10.5%; OR=1.79, 95%CI=1.17-2.75), after adjustment for maternal education level, country of birth, body mass index and smoking in early pregnancy, and comorbidities. Maternal history of early-onset colorectal cancer was also associated with offspring preterm birth (12.1% vs 5.2%; OR=2.31, 95%CI=1.34-3.99), delineated as spontaneous (OR=1.06, 95%CI=0.47-2.39) or medically-indicated preterm birth (OR=4.48, 95%CI=2.05-9.79). There was no increased risk of congenital malformation or small for gestational age birth. In this population-based study, maternal history of early-onset colorectal cancer was associated with risk of both adverse pregnancy (pre-eclampsia, C-section) and neonatal outcomes (preterm birth). US National Institutes of Health, Swedish Society of Medicine, Swedish Cancer Foundation.

An increased proportion of progesterone receptor A in peripheral B cells from women who ultimately underwent spontaneous preterm birth

The enormous challenge in unraveling the etiology of preterm birth (PTB) is to understand the complex interactions between gestational hormones, the immune system and reproductive tissues. PTB can be divided into spontaneous PTB (sPTB) and medically-indicated PTB, e.g. due to preeclampsia (PE) or HELLP syndrome. Progesterone (P4), important for establishment and maintenance of pregnancy, exerts anti-inflammatory effects. The impact of P4 on B cells and its support of maintaining maternal-fetal tolerance is widely unexplored. Therefore, we aimed to determine whether B cells express the progesterone receptor (PR) and to dissect a possible role of PR+ B cells in PTB.We found enhanced IL-6, IL-21 and TNF-α concentrations in maternal plasma in patients with sPTB and PE/HELLP compared to term delivery (TD), accompanied by enhanced PR-A expression by CD19+ B cells. In a second phase of the study, we recruited patients with imminent PTB (iPTB) and controls. Samples were collected at hospital admission and to a later time point, then divided into iPTB patients who delivered preterm and patients whose PTB was prevented. Within the group of iPTB patients, we observed very clear differences: enhanced levels of pro-inflammatory cytokines and increased percentages of PR-A+CD19+ B cells were found in iPTB patients that delivered preterm compared to patients who did not deliver preterm.We conclude that PTB is associated with the activation of an inflammatory pathway leading to the induction of PR-A by B cells. This might further trigger inflammation, result in the break of maternal-fetal tolerance and induce delivery.

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters.

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature.

522 The legacy of racial inequality and risk of modern-day preterm birth (PTB)

Previous studies have shown an association between geographic racial prejudice and disparities in infant mortality. We sought to evaluate if women living in areas with historically high rates of racial inequities would be at greater risk of PTB. Retrospective cohort of women with non-anomalous singleton or twin gestations from a large University-based healthcare system, 2014-2020. Women at high risk for spontaneous ± medically-indicated PTB were matched 1:2 with randomly chosen low-risk controls. We considered 3 historic county-level census data parameters: % enslaved Black pop. in 1860, % pop. in 1860 that was "free" Black, and % of farms Black-owned in 1925. Each census parameter was broken into quartiles (Q); Q1=assigned 1 point (lowest inequity) and Q4=4 points (highest inequity). The # of total points across the 3 census parameters for each county were added to generate the “historic racial inequity score” (min. possible score=3, max=12). Each woman was then assigned a historic racial inequity score based on her county of residence during pregnancy. The primary outcome was PTB <37 wks; secondary outcomes were PTB <34 and <28 wks. Data were analyzed with chi-square, t-test, & logistic regression. 39,695 women met inclusion criteria; 8.6% had PTB <37, 2.7% <34, and 0.9% <28 wks. Population characteristics are in Table 1. The mean inequity score was 8.22 ± 1.45; the mean score was higher for those with PTB <37 (8.28 ± 1.49), <34 (8.40 ± 1.40), and <28 (8.46 ± 1.44) wks vs. term birth (8.21 ± 1.44), all p<0.001. In adjusted analysis, each one-point increase in the inequity score was associated with increased aOR of PTB at each GA cutoff. The aOR of PTB was highest at the earliest gestational ages (Figure 1). Regression results were similar when considering all women, Black women only, and non-Black women only. Women living in counties with historically high racial inequities, as reported 95-160 yrs ago, had a higher aOR of PTB <37, <34, and <28 wks, regardless of race. Historic racial inequities may have persistent effects on PTB for women of all races.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Subclinical and clinical chorioamnionitis, fetal vasculitis, and risk for preterm birth: A cohort study

ObjectiveTo evaluate the association between subclinical and clinical chorioamnionitis and risk of preterm birth (PTB). MethodsDemographic and clinical characteristics were abstracted from medical records and placental examinations performed (N = 1371 pregnancies including spontaneous and medically-indicated PTBs). Pregnancies were classified as having clinical chorioamnionitis (with or without histologic chorioamnionitis), subclinical chorioamnionitis (histologic, but not clinical, chorioamnionitis), or no chorioamnionitis; pregnancies with histologic chorioamnionitis were further evaluated for fetal vasculitis. Relative risks for PTB, early and late PTB, and PTB ± premature rupture of membranes (PROM) were adjusted for maternal characteristics. ResultsClinical (4.3%) and subclinical (24.5%) chorioamnionitis were not associated with PTB overall. In pregnancies without clinical or subclinical chorioamnionitis, the risk of PTB with PROM and early PTB was 2.2% and 8.6%, respectively. In comparison, clinical chorioamnionitis was associated with an increased risk of PTB with PROM (aRR: 3.42 (95%CI: 1.07, 10.98), whereas subclinical chorioamnionitis was associated with increased risk of PTB with PROM (aRR: 3.92 (95% CI: 2.15, 7.12)) and early PTB (aRR: 1.77 (95% CI: 1.18, 2.64)). Histologic chorioamnionitis with fetal vasculitis was associated with increased risk of PTB with PROM (aRR: 7.44 (95% CI: 3.68, 15.05)) and early PTB (aRR: 2.94 (95% CI: 1.78, 4.87)), whereas histologic chorioamnionitis without fetal vasculitis was associated with increased risk of PTB with PROM only (aRR: 2.64, 95% CI: 1.27, 5.50). ConclusionsSubclinical chorioamnionitis and histologic chorioamnionitis with fetal vasculitis were associated with early PTB and PTB with PROM but not with PTB overall, likely due to inclusion of indicated PTBs.

The Effect of Hypertensive Disorders in Pregnancy on Preterm Birth Rates Among African-American Women [4L

INTRODUCTION: To investigate the role gestational and chronic hypertension (HTN) play in rates of preterm birth (PTB) among African-American women. METHODS: The study population was drawn from singleton, non-anomalous live births delivered between 20 and 44 weeks' among African-American Women from 2007-2011 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development. Poisson logistic regression was used to calculate the risk of PTB by gestational age and type of PTB among women with a diagnosis of chronic or gestational HTN. Relative risks (RR) and 95% confidence intervals (CI) were calculated for PTB, adjusting for maternal age; payment for delivery; level of education; body mass index; pre-gestational diabetes mellitus; smoking; location of mother's birth; urban or rural residence; previous PTB; and inter-pregnancy interval less than 6 months. RESULTS: 61,561 African-American women were included; 2,276 had chronic HTN and 5,861 had gestational HTN. Women with chronic HTN progressing to preeclampsia were at 43-fold higher risk of a medically-indicated PTB less than 32 weeks compared with women without chronic HTN. When comparing women with the diagnosis of chronic HTN progressing to preeclampsia versus those with gestational HTN progressing to preeclampsia, those with chronic HTN had higher risks of spontaneous and medically-indicated PTB, especially less than 32 weeks (aRR 2.5 and 3.4, respectively). CONCLUSION: Among African-American women, chronic HTN progressing to preeclampsia increased the risk for spontaneous and medically-indicated PTB, especially less than 32 weeks. Further inquiry into the pathophysiology of hypertensive disorders and evaluation of inequality should accompany research on PTB.

337: Use of a second trimester serum-based proteomic risk classifier for prediction of spontaneous and medically-indicated preterm birth

337: Use of a second trimester serum-based proteomic risk classifier for prediction of spontaneous and medically-indicated preterm birth

The risk of neonatal respiratory morbidity according to the etiology of late preterm delivery.

The risk of neonatal respiratory morbidity between indicated deliveries vs. spontaneous deliveries has not been consistent in previous studies, in spite of the traditional belief that chronic intrauterine stress might have protective effect on fetal lung maturation. We hypothesized that the heterogeneous etiology of indicated preterm delivery may obscure the relationship between the etiologies of preterm birth and neonatal respiratory morbidity. To address this issue, we divided the indicated preterm birth (PTB) into medically-indicated (without fetal compromise) PTB and maternal/fetal-indicated PTB, and compared the neonatal respiratory morbidity according to the etiology of late PTB. Neonatal respiratory morbidities were examined in neonates who were delivered between 34+0 and 36+6 weeks of gestation according to the etiology of PTB: 1) medically-indicated PTB (but without fetal compromise), 2) maternal/fetal-indicated PTB, or 3) spontaneous PTB such as preterm labor or preterm premature rupture of membranes. A total of 710 late preterm neonates were included in the study population, including 31 cases of medically-indicated PTB, 202 cases of maternal/fetal-indicated PTB, and 477 cases of spontaneous PTB. The rate of composite respiratory morbidity in cases of medically-indicated PTB is higher than both maternal/fetal-indicated PTB and spontaneous PTB (19% in medically-indicated PTB, 6% in maternal/fetal-indicated PTB, and 7% in spontaneous PTB). This difference between medically-indicated PTB and maternal/fetal-indicated PTB remained significant after adjustment for confounding variables. The medically-indicated PTB is associated with highest risk of neonatal respiratory morbidity in late PTB.

Comparison of the incidence and clinical presentation of preterm birth less than 34 weeks gestation at University hospitals in Dublin, Ireland and Denver, Colorado, USA

Objective: To determine the incidence and clinical presentations of preterm birth (PTB) <34 weeks gestation at the National Maternity Hospital (NMH), Dublin, Ireland and the University of Colorado Hospital (UCH), Denver, Colorado, between January 2007 to June 2008. Study Design: Retrospective cohort study using data from perinatal databases. Pregnancies complicated by anomalies, multiple gestations, and fetal demise were excluded. PTB was categorized as resulting from preterm labor (PTL), premature rupture of the membranes (PROM), and medically indicated preterm birth (MIPTB). Data were analyzed using univariate analyses, χ2, and Fisher exact test. Results: There were 12 739 births at NMH and 4 029 at UCH with a total of 407 PTBs <34 weeks at NMH (1.7%) and UCH (4.8%), respectively (P<.0001). Spontaneous preterm labor, PPROM, and MIPTB occurred 4, 2, and 3 times more frequently at UCH versus NMH. Chorioamnionitis was 3-fold higher at UCH (13.2% vs. 3.2% at NMH, p=0.001). Conclusion: Although the rate of PTB <34 weeks was significantly higher at UCH, the distribution of indications was remarkably similar. The incidence of chorioamnionitis was significantly higher at UCH. Further investigation of the similarities and differences between these populations is imperative in the effort to understand PTB and reduce its incidence worldwide.

Étude des circonstances de naissance prématurée avant 35SA dans le sillon alpin : étude PREMALP

In a regional study of preterm infants born before 35weeks of gestation, the aim was to propose a new classification of preterm births into three groups, and to describe the pregnancy complications and fetal disorders in each group. In two areas covered by a perinatal network, all preterm births, live births and stillbirths, which occurred between 22 and 34 completed weeks were recorded over a 21-month period. Each case was classified either in the medically-indicated preterm birth (I) group, or in the accepted spontaneous preterm birth (ASp) group or in the non-accepted spontaneous preterm birth (NASp) group. One thousand and sixty cases of preterm births were included; among them, 981 were live births or ended with per partum infant death. Forty-nine percent of these births were medically indicated, 32 % were ASp and 19 % were NASp. The distribution of pregnancy complications and fetal disorders differed between preterm birth groups: ischemic placental diseases were present in 38,2 % of medically-indicated births; preterm premature rupture of membranes occurred twice more often in I and ASp preterm births than in NASp preterm births. This classification is based on the medical decision; it allows to compare medical practices in given obstetrical situations. It appears to be reproducible and easy to use.

Appropriate antenatal corticosteroid use in women at risk for preterm birth before 34 weeks of gestation

To determine the utilisation of antenatal corticosteroid administration in women presenting at risk of preterm birth (PTB) in a centre where tocolytics are not prescribed. A prospective cohort study. Tertiary referral centre, Dublin, Ireland. Four hundred and fourteen consecutive women presenting at risk of PTB. Clinical details were collated prospectively on all booked patients who presented at risk of PTB (i.e. at <34 weeks of gestation) during 2008. Rate of administration of antenatal corticosteroids in PTB. Of 8985 deliveries, 414 women (5%) presented at <34 weeks of gestation with a clinical potential for PTB, of whom 277 (67%) received antenatal corticosteroids. Amongst women delivering at <34 weeks of gestation, 93% (80/86) received any corticosteroids and 76% (65/86) received a complete course. The ratio of women given a complete course of corticosteroids to the number who actually delivered before 34 weeks of gestation was 4:1 overall. Analysis by indication for PTB revealed this ratio to be 15:1 in suspected preterm labour (PTL), 8:1 in antepartum haemorrhage (APH), and 2:1 in both preterm prelabour rupture of membranes (PPROM) and medically indicated PTB (MIPTB). Seven of ten multiparae (70%) who delivered prematurely during the study period following PTL had a history of previous PTL before 34 weeks of gestation. The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at <34 weeks of gestation was high in categories such as PTL and substantial APH, whereas selection in PPROM and MIPTB approached 100%. There should be a low threshold for single course therapy for women with prior PTL before 34 weeks of gestation.

Obesity in older mothers, gestational weight gain, and risk estimates for preterm phenotypes

Objective To assess whether advanced maternal age modifies the relationship between maternal pregravid weight status, gestational weight gain patterns, and the occurrence of spontaneous preterm birth (SPB) and medically indicated preterm birth (MIPB). Methods Retrospective cohort analysis of vital statistics data from the state of Florida for the period 2004 through 2007 comprising 311,422 singleton pregnancies (two age groups: 20–24 years old or younger women and ≥35 years or older women). Mothers were classified into five clusters based on their pre-pregnancy body mass index (BMI) values: non-obese (less than 30), class I obese (30.0 ≤ BMI ≤ 34.9), class II obese (35.0 ≤ BMI ≤ 39.9), class III obese (40 ≤ BMI ≤ 49.9), and super-obese (BMI ≥ 50.0). Results MIPB occurred more frequently among older than younger women [11.8% vs. 6.4%, respectively ( p < 0.0001)) whereas SPB occurred more frequently among younger women [11.3% vs. 10.5%, respectively ( p < 0.0001)). Maternal obesity increased the risk for MIPB but not for SPB. Regardless of BMI status, the risk of MIPB was elevated among older mothers, particularly among those with suboptimal (<0.23 kg/week) and supraoptimal (>0.68 kg/week) gestational weight gain. A dose–response relationship with increasing gestational weight gain was evident ( p < 0.01); the greatest risk for MIPB occurred among older mothers with weekly gestational weight gain in excess of 0.79 kg (OR = 7.76, 95% CI = 5.73–10.5). Conclusion The occurrence of medically indicated preterm birth is positively associated with increased maternal pregravid body weight, older maternal age and extremes of gestational weight gain. Targeted pre- and inter-conception weight management efforts should be particularly encouraged in older mothers.

Prepregnancy body size, gestational weight gain, and risk of preterm birth in African-American women.

Studies of the association of prepregnancy body mass index (BMI) and preterm birth have been inconclusive, and no studies have examined the effect of central adiposity on risk. There is also uncertainty about optimal gestational weight gain among Black women. Using self-reported prospective data from the Black Women's Health Study, we investigated the relation of preterm birth to prepregnancy BMI (kg/m), waist circumference, and gestational weight gain among 7840 singletons born to black women, ages 21-44, during 1995-2003. We compared mothers of 1114 infants born 3 or more weeks early (597 spontaneous preterm births and 517 medically-indicated preterm births) with mothers of 6726 term infants. We used generalized estimating equation models to derive multivariable odds ratios (ORs) and 95% confidence intervals (CIs). Relative to normal weight women (BMI: 18.5-24.9), underweight women (BMI: <18.5) were at increased risk of both preterm birth subtypes; obese women (BMI > or = 30.0) were at increased risk of medically-indicated preterm birth and very early spontaneous preterm birth (<32 weeks' gestation). Waist circumference, a measure of central adiposity, was positively associated with medically-indicated preterm birth. Among obese women, average gestational weight gain in the second and third trimesters of <0.4 or >0.6 lbs/wk was associated with an increased risk of both preterm birth subtypes. Our data suggest that underweight increases risk of both preterm birth subtypes, while obesity increases risk of medically-indicated preterm birth and only a subgroup of spontaneous preterm births (<32 weeks' gestation). Central adiposity was an independent risk factor for medically-indicated preterm birth only. Among obese women, gestational weight gain within the range recommended by the 2009 Institute of Medicine report (0.4-0.6 lbs/week in the second and third trimesters) was associated with the lowest risk of preterm birth.

Classification and heterogeneity of preterm birth

Three main conditions explain preterm birth: medically indicated (iatrogenic) preterm birth (25%; 18.7–35.2%), preterm premature rupture of membranes (PPROM) (25%; 7.1–51.2%) and spontaneous (idiopathic) preterm birth (50%; 23.2–64.1%). The majority of multiple pregnancies (10% of all preterm births) are delivered preterm (50% for medical reasons). Although medical indications relate more to feto-maternal conditions, PPROM to infections and idiopathic preterm birth to lifestyle, these risk factors are identified in any category, emphasising that preterm birth has a multifactorial origin. Still, several incidences of preterm birth are not completely explained with a plausible cause for PPROM or spontaneous preterm labour suggesting that other causes have yet to be identified. In addition, preterm birth is associated with unrecognised severe congenital anomalies. Variability within the main categories may be explained by the studied population, ethnic group, social class and preventive interventions towards reducing spontaneous preterm birth where the proportion of medically-indicated preterm birth is increased. Despite being retrospective a classification according to gestational age at birth is important for neonatal prognosis. Preterm birth is stratified into mild preterm (32–36 weeks), very preterm (28–31 weeks) and extremely preterm (<28 weeks) with increasing neonatal mortality and morbidity. Recent studies suggested that infection was mostly responsible for extreme preterm birth, while stress and lifestyle accounted for mild preterm birth, and a mixture of both conditions contributed to very preterm birth.