Gestation In Women Research Articles

Utility of follow-up cervical length screening in low-risk women with a cervical length of 26 to 29 mm

In women with a previous preterm birth, a protocol for serial cervical length screening has been studied and recommended for the identification and treatment of a short cervix. Cervical length screening along with vaginal progesterone has been suggested for low-risk women with singleton pregnancies to treat a short cervix and reduce preterm birth. However, specific protocols for single vs serial ultrasound measuring cervical length in this population are not established. Cost-effectiveness of universal cervical length screening depends on the cost of screening; follow-up of borderline measurements can contribute to increased costs with uncertain benefit. This study aimed to determine the utility of follow-up cervical length screening in otherwise low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm through the assessment of the rate of short cervix (≤25 mm) on follow-up ultrasound and subsequent delivery outcomes. This was a 2-year retrospective cohort study at a single urban institution of women with singleton pregnancies with no previous spontaneous preterm birth and an initial transvaginal ultrasound cervical length measurement of 26 to 29 mm identified during universal cervical length screening at time of anatomy ultrasound (18 0/7 to 22 6/7 weeks' gestation). The primary outcome was the rate of short cervix (defined as ≤25 mm on transvaginal ultrasound) on follow-up ultrasound at <24 weeks' gestation. Secondary outcomes included the rate of spontaneous preterm birth (<37 and <34 weeks' gestation). During the study period, there were 2801 women with singleton pregnancies at 18 0/7 to 22 6/7 weeks' gestation with transvaginal ultrasound cervical length screening at time of anatomy scan. Among those women, 201 had a cervical length of 26 of 29 mm, and 184 (7%) had no previous spontaneous preterm birth and were included in the study. Furthermore, 144 women (78%) had a follow-up cervical length completed before 24 weeks' gestation. The mean follow-up interval was 1.5±0.6 weeks. Overall, the percentage of short cervix (≤25 mm) on follow-up was 15% (n=21). Baseline characteristics were similar, but the initial cervical length measurement was shorter in women who subsequently developed a short cervix (26.7±0.8 vs 27.8±1.0; P<.01). Delivery outcomes were available for 126 patients. The rate of spontaneous preterm birth at <37 weeks' gestation in women with an initial cervical length 26 to 29 mm and subsequent short cervix was significantly higher than the rate of spontaneous preterm birth in a historical cohort of low risk women with an initial cervical length >25 mm (16% vs 3%; P=.03). The rate of spontaneous preterm birth at <34 weeks' gestation in women with a subsequent short cervix was 11% (2 of 19). Here, approximately 15% of low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm will experience cervical shortening of ≤25 mm before 24 weeks' gestation. Compared to women with singleton pregnancies without a history of preterm birth, the rate of spontaneous preterm birth (16%) in women with an initial cervical length of 26 to 29 mm and a subsequent cervical shortening of ≤25 mm is significantly higher. A total of 111 follow-up ultrasounds measuring cervical length would be required to prevent 1 early preterm birth at <34 weeks' gestation.

The Feasibility of Cervical Elastography in Predicting Preterm Delivery in Singleton Pregnancy with Short Cervix Following Progesterone Treatment.

Previous studies demonstrated an association between cervical strain and risk of spontaneous preterm delivery (sPTD). The present study aimed to assess the efficacy of elastography in predicting sPTD at <32 weeks of gestation in women with singleton pregnancies receiving progesterone for short cervix (≤2.5 cm) diagnosed between 16 and 28 weeks of gestation Among 115 participants eligible for analysis, nine had sPTD at <32 weeks. Preprogesterone (PP0) mean internal os strain (IOS), elasticity contrast index (ECI), hardness ratio (HR), one-week postprogesterone (PP1) IOS, mean external os strain (EOS), ECI, and HR were significantly different between groups. Higher PP0 IOS, PP1 IOS, and PP1 EOS were associated with a 2.92, 4.39 and 3.65-fold increase in the risk of sPTD at <32 weeks, respectively (adjusted for cervical length (CL) at diagnosis; p = 0.04, 0.012 and 0.026, respectively). A combination of CL at diagnosis, PP0 IOS and PP1 EOS showed a significantly higher area under the receiver operating characteristic curve (0.858) than that of CL alone (p = 0.041). In women with singleton pregnancies receiving progesterone for short cervix, cervical elastography performed before and one week after progesterone treatment may be useful in predicting sPTD at <32 weeks of gestation.

Pregnant women who develop preeclampsia have lower abundance of the butyrate-producer Coprococcus in their gut microbiota.

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and dysfunction of several organs, that is associated with maternal and fetal complications. The human gut microbiota is related to health and disease including hypertension. Alterations in gut microbiota composition can change the short-chain fatty acid profile released by the bacteria and contribute to hypertension and metabolic syndrome. It is unclear if the composition of the gut microbiota is altered in women who develop late-onset preeclampsia. In this study, we investigated the composition of the gut microbiota at 28weeks gestation in women who developed late-onset (>34weeks gestation) preeclampsia (DPE) by 16S rRNA gene amplicon sequencing of fecal samples obtained from 213 pregnant women in the SPRING cohort (Study of Probiotics IN Gestational diabetes). Quantitative real-time PCR was used to assess the density of butyrate-producing genes. Gut microbiota composition was compared between women with and without DPE. The abundance of the butyrate-producing Coprococcus genus significantly decreased in DPE. Abundance of Coprococcus is significantly and positively correlated with the abundance of genes encoding the terminal step in bacterial butyrate formation (but and buk). Women with DPE also had significantly reduced levels of serum butyrate prior to the development of symptoms than controls. This study suggests that a reduction in the abundance of butyrate-producing bacteria, and Coprococcus spp. in particular, may contribute to an increased risk of developing preeclampsia in pregnant women.

Markers of branched-chain amino acid catabolism are not affected by exercise training in pregnant women with obesity

Despite the role of branched-chain amino acids (BCAAs) in physiological processes such as nutrient signaling and protein synthesis, there is ongoing debate about the link between circulating BCAAs and insulin resistance (IR) in various populations. In healthy women, IR mildly increases during pregnancy, whereas both BCAAs and markers of BCAA catabolism decrease, indicating that fetal growth is being prioritized. Exercise reduces IR in nonpregnant adults, but less is known about the effect of exercise during pregnancy in women with obesity on IR and BCAA breakdown. The aim of this study was to determine the effect of a moderate-intensity exercise intervention during pregnancy on maternal circulating BCAAs and markers of BCAA catabolism [short-chain acylcarnitines (ACs)], and their associations with IR. Healthy obese [n = 80, means ± SD; body mass index (BMI): 36.9 ± 5.7 kg/m2] pregnant women were randomized into an exercise (n = 40, aerobic/resistance 3×/wk, ∼13th gestation week until birth) or a nonexercise control (n = 40) group. Blood was collected at 12.2 ± 0.5 and 36.0 ± 0.4 gestation weeks and analyzed for BCAA-derived acylcarnitine concentrations as markers of BCAA breakdown toward oxidative pathways, and glucose and insulin concentrations [updated homeostatic model assessment of IR (HOMA2-IR)]. After adjusting for HOMA2-IR, there were no interaction effects of group by time. In addition, there was a main positive effect of time on HOMA2-IR (12 wk: 2.3 ± 0.2, 36 wk: 3.0 ± 0.2, P = 0.003). A moderate-intensity exercise intervention during pregnancy in women with obesity was not associated with changes in BCAA-derived ACs versus standard of care. The decrease in BCAA-derived ACs throughout gestation could not be explained by IR.NEW & NOTEWORTHY This research showed an increase in insulin resistance (IR) and decrease in branched-chain amino acid catabolism throughout gestation in women with obesity, and addition of a moderate exercise intervention (known to attenuate IR in nonpregnant populations) did not alter these shifts. Findings provide support for metabolic safety of exercise during pregnancy.

Mid-Trimester Cervical Length Screening: Effect of Poorly Developed Lower Uterine Segment on Pregnancy Outcome.

To identify whether a poorly developed lower uterine segment (PDLUS) observed during cervical length (CL) screening affects the duration of gestation in women with no prior spontaneous preterm birth (sPTB). A retrospective cohort study of women with a singleton gestation and no prior sPTB, who underwent transvaginal CL screening at our institution. We excluded women with progesterone exposure, major anomalies, and women delivering elsewhere. Women with PDLUS were compared to those with a measured (normal) CL ≥25 mm. birth gestational age (GA). sPTB <35 and 37 weeks, hospital evaluation for preterm labor without delivery, delivery indication, and mode. A Cox proportional-hazards survival model considered time from CL scan to delivery. We powered the study to detect a one-half week difference in birth GA. We included 270 women with PDLUS and 985 women with normal CL. Mean birth GA was 38.9 ± 2.0 weeks with PDLUS versus 38.7 ± 2.4 weeks with normal CL (p=.10). Women with PDLUS were less likely to experience sPTB <37 weeks (1.1% vs 3.6%; p=0.04). There was no difference in sPTB <35 weeks (0.8% vs 1.7%; p=.25). Hospital evaluation for preterm labor (17% vs 19%; p=.54), delivery indication, and mode were not different. The hazard ratio for earlier birth in women with PDLUS was 0.67 (95% CI 0.46, 0.98; p=.04). We observed no difference in mean GA at birth; however, PDLUS was protective against sPTB <37 weeks and was associated with a lower hazard ratio for earlier birth.

Maternal serum pregnancy-associated plasma protein-A concentration at 11–14 weeks of gestation of women with common congenital anatomic uterine abnormalities

Maternal serum pregnancy-associated plasma protein-A concentration at 11–14 weeks of gestation of women with common congenital anatomic uterine abnormalities

Dietary Fiber Intake Alters Gut Microbiota Composition but Does Not Improve Gut Wall Barrier Function in Women with Future Hypertensive Disorders of Pregnancy.

Pregnancy alters the inflammatory state, metabolic hormones, and gut microbiota composition. It is unclear if the lower abundance of dietary fiber-fermenting, short-chain fatty acid-producing bacteria observed in hypertension also occurs in hypertensive disorders of pregnancy (HDP). This study investigated the relationship between dietary fiber intake and the gut microbiota profile at 28 weeks gestation in women who developed HDP in late pregnancy (n = 22) or remained normotensive (n = 152) from the Study of PRobiotics IN Gestational diabetes (SPRING). Dietary fiber intake was classified as above or below the median of 18.2 g/day. Gut microbiota composition was examined using 16S rRNA gene amplicon sequencing. The gut permeability marker zonulin was measured in a subset of 46 samples. In women with future HPD, higher dietary fiber intake was specifically associated with increased abundance of Veillonella, lower abundance of Adlercreutzia, Anaerotruncus and Uncl. Mogibacteriaceae and higher zonulin levels than normotensive women. Fiber intake and zonulin levels were negatively correlated in women with normotensive pregnancies but not in pregnancies with future HDP. In women with normotensive pregnancies, dietary fiber intake may improve gut barrier function. In contrast, in women who develop HDP, gut wall barrier function is impaired and not related to dietary fiber intake.

Expert consensus: Indication criteria and screening strategy for preeclampsia using the serum sFlt-1/PlGF ratio at 18–36 weeks of gestation in women at imminent/basal risk of preeclampsia under insurance coverage

Expert consensus: Indication criteria and screening strategy for preeclampsia using the serum sFlt-1/PlGF ratio at 18–36 weeks of gestation in women at imminent/basal risk of preeclampsia under insurance coverage

Gestational Women’s Perceptions About the Harms of Cigarette and E-Cigarette Use During Pregnancy

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers' communication about these products during pregnancy. A convenience sample of gestational women (n = 218; ages 18-45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy. Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p < .05) or increased blood pressure (p < .05) for a child than currently pregnant participants. Participants reported healthcare providers asked about (p < .05), advised them not to use (p < .001), and talked to them about health effects of smoking combustible cigarettes while pregnant (p < .001) significantly more than e-cigarettes. Healthcare providers working with pregnant women should perform the 5As behavioral intervention method to provide pregnant women with tobacco cessation care. They should also discuss the absolute harm nicotine exposure (via cigarettes or e-cigarettes) can have on fetal health and development.

Differential expression of serum proteins before 20 weeks gestation in women with hypertensive disorders of pregnancy: A potential role for SH3BGRL3

IntroductionThe objective of this study was to explore serum levels of differentially abundant proteins between women with hypertensive disorders of pregnancy (HDP) and women with normal-term pregnancy, and to explore the contribution of SH3BGRL3 to the pathogenesis of HDP. MethodsAt 6–20 weeks gestation 48 pregnant women who later developed HDP (HDP group) and 48 women with normal-term pregnancy (normal group) were recruited based on maternal age and gestational age at a 1:1 ratio. Total serum protein was extracted, denatured, deoxidized, and subjected to enzymolysis. The sample was labeled with Tandem Mass Tags and analyzed via mass spectroscopy to identify differentially abundant proteins. The role of SH3BGRL3 in trophoblast invasion, proliferation and apoptosis was examined using the HTR-8/SVneo cell line and primary isolates of extravillous trophoblast (EVT) cells. ResultsIn the proteomic profiling analysis, there were 19 proteins that showed significant differential abundance (P < 0.05). Among them, 13 proteins were more abundant and 6 proteins were less abundant in the serum from the HDP group compared with the normal group. The function of one of the more abundant proteins, SH3BGRL3, in trophoblast cell invasion, proliferation and apoptosis was investigated. Treatment of the EVT cells or the HTR-8/SVneo cell line with anti-SH3BGRL3 inhibited proliferation, but stimulated both apoptosis and invasion. MMP2 and p-ERK levels were also decreased in EVT after anti-SH3BGRL3 treatment. DiscussionThe SH3BGRL3 protein can regulate various aspects of trophoblast biology, and may be useful in the clinical diagnosis of HDP.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

Problems of prescribing nonsteroidal anti-inflammatory drugs for reproductive-aged women with ankylosing spondylitis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for ankylosing spondylitis (AS); their action is associated with blockade of the enzyme cyclooxygenase 2 and with a mediated decrease in the synthesis of prostaglandins (PGs). However, PGs play an important role in regulating the functions of the female reproductive system. The paper presents an update on the participation of PG in folliculogenesis, ovulation, implantation, and development of the embryo, and labor activity. Based on experimental and clinical findings, the authors discuss whether due to inhibition of the synthesis of PGs, NSAIDs are able to cause ovulation failure, including luteinized unovulated follicle syndrome and spontaneous abortions. Further investigation is justified to determine the most optimal NSAID therapy regimens when planning pregnancy and during gestation in women with AS.

Prenatal Androgenization Alters the Development of GnRH Neuron and Preoptic Area RNA Transcripts in Female Mice.

Polycystic ovary syndrome (PCOS) is the most common form of infertility in women. The causes of PCOS are not yet understood and both genetics and early-life exposure have been considered as candidates. With regard to the latter, circulating androgens are elevated in mid-late gestation in women with PCOS, potentially exposing offspring to elevated androgens in utero; daughters of women with PCOS are at increased risk for developing this disorder. Consistent with these clinical observations, prenatal androgenization (PNA) of several species recapitulates many phenotypes observed in PCOS. There is increasing evidence that symptoms associated with PCOS, including elevated luteinizing hormone (LH) (and presumably gonadotropin-releasing hormone [GnRH]) pulse frequency emerge during the pubertal transition. We utilized translating ribosome affinity purification coupled with ribonucleic acid (RNA) sequencing to examine GnRH neuron messenger RNAs from prepubertal (3 weeks) and adult female control and PNA mice. Prominent in GnRH neurons were transcripts associated with protein synthesis and cellular energetics, in particular oxidative phosphorylation. The GnRH neuron transcript profile was affected more by the transition from prepuberty to adulthood than by PNA treatment; however, PNA did change the developmental trajectory of GnRH neurons. This included families of transcripts related to both protein synthesis and oxidative phosphorylation, which were more prevalent in adults than in prepubertal mice but were blunted in PNA adults. These findings suggest that prenatal androgen exposure can program alterations in the translatome of GnRH neurons, providing a mechanism independent of changes in the genetic code for altered expression.

Prediction of Gestation in Women with Subchorial Hematoma

Prediction of Gestation in Women with Subchorial Hematoma

Early prediction of placenta accreta spectrum in women with prior cesarean delivery using transvaginal ultrasound at 11 to 14 weeks

There is a growing body of evidence that sonographic signs of placenta accreta spectrum can be observed in the first trimester of pregnancy. The most significant marker is placental location next to or in the scar niche in women with a prior cesarean delivery. This study aimed to assess the performance of transvaginal ultrasound in the early prediction of placenta accreta spectrum in women with a prior cesarean delivery. This was a retrospective cohort of women with a history of cesarean delivery who had transvaginal ultrasound at 11 to 14 weeks' gestation between September 2016 and May 2018. Ultrasound reports were reviewed and graded for suspicion of placenta accreta spectrum as follows: Grade 0 (no suspicion) if the placenta is not next to the scar; Grade 1 (intermediate suspicion) if the placenta is next or on the scar; Grade 2 (high suspicion) if the placenta was inside the scar niche. In addition, all images were reviewed and graded by trained specialists blinded to the outcome. The primary outcome was a histologic diagnosis of placenta accreta spectrum. Sensitivity, specificity, positive predictive value, and negative predictive value of first-trimester transvaginal ultrasound to detect placenta accreta spectrum were assessed. In this study, 467 patients were included, and 8 (1.7%) had placenta accreta spectrum at delivery. Using the original report, 442 patients (94.6%) were Grade 0, 20 (4.3%) Grade 1, and 5 (1.1%) Grade 2. The revised grading had 456 patients (97.6%) with Grade 0, 5 (1.1%) with Grade 1, and 6 (1.3%) with Grade 2. Patients with Grade 2 yielded a sensitivity of 62.5% (95% confidence interval, 24.5-91.5), specificity of 100% (95% confidence interval, 99.2-100.0), positive predictive value of 100% (95% confidence interval, 97.0-100.0), and negative predictive value of 99.4% (95% confidence interval, 98.4-99.7). Any sonographic suspicion of placenta accreta spectrum (Grade 1 or Grade 2) had a sensitivity of 75% (95% confidence interval, 34.9-96.8), specificity of 95.9% (95% confidence interval, 93.6-97.5), positive predictive value of 24% (95% confidence interval, 14.8-36.4), and negative predictive value of 99.6% (95% confidence interval, 98.5-99.9). The blinded image review yielded a better specificity (99.1% vs 95.9%; P=.001) and a positive predictive value (63.6% vs 24%; P=.02) with similar sensitivity (87.5% vs 75%; P=.52) and negative predictive value (99.8% vs 99.6%; P=.55). Transvaginal ultrasound between 11 and 14 weeks' gestation in women a with prior cesarean delivery can identify at least 3 of 4 cases of placenta accreta spectrum. A finding of placental implantation within the scar niche has high positive predictive value for placenta accreta spectrum. Prospective studies are needed to assess routine screening for placenta accreta spectrum at 11 to 14 weeks' gestation in women with a prior cesarean delivery.

Objectively Measured Physical Activity During The First Trimester And Glucose Tolerance At 24-28 Weeks Gestation

Physical activity (PA) during pregnancy may improve glucose tolerance and reduce the risks of adverse outcomes associated with pregnancy hyperglycemia (e.g., pregnancy and delivery complications, delivering a large infant, and developing diabetes later in life), yet the evidence to date has primarily relied on self-reported PA via questionnaire. PURPOSE: To examine whether objectively measured PA during the first trimester of pregnancy is associated with glucose tolerance at 24-28 weeks’ gestation. METHODS: Study participants (n=261) were a subsample of the GestationaL Weight Gain and Optimal Wellness (GLOW) trial conducted at Kaiser Permanente Northern California in 2014-2016 to test whether a lifestyle intervention prevents excess gestational weight gain in women with overweight/obesity, as compared to usual medical care. Participants wore an ActiGraph wGT3X-BT for 7 days on the non-dominant wrist during the first trimester. Valid measurements were defined as having ≥ 600 minutes of wear time [by the algorithm of Choi et al. (MSSE, 2012)] on 4 days, including 1 weekend day. Wrist-specific two-regression algorithms [Hibbing et al. (MSSE, 2018)] were used to estimate daily minutes of moderate to vigorous intensity PA (MVPA), light PA (LPA), and sedentary behavior (SB). Minutes per day of MVPA, LPA, and SB were then combined into weighted (i.e., weekend day vs. weekday) averages. Plasma glucose values from a random, 50-g 1-hour glucose challenge test (GCT) performed at 24-28 weeks’ gestation were obtained from the Kaiser Permanente Northern California electronic health records. Associations of MVPA, LPA and SB (i.e., log transformed) with glucose were estimated by linear regression and adjusted for age, race-ethnicity, BMI category, and GLOW trial randomization (i.e., intervention vs. usual care). RESULTS: The cohort had a median 38 (IQR= 37) minutes per day of MVPA, 248 (81) minutes per day of LPA, and 389 (97) minutes per day of SB. The median plasma glucose value on the GCT was 112 mg/dl (35). None of the PA variables were statistically significantly associated with plasma glucose (p > .05 for MVPA, LPA, and SB). CONCLUSION: Objectively measured PA, assessed over 7 days during the first trimester of pregnancy, does not appear to impact glucose tolerance at 24-28 weeks gestation in women with overweight/obesity.

Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial

In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.

First trimester inflammatory mediators in women with chronic hypertension.

Chronic hypertension complicates 1%-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia. The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia. In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 or TNF-α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 or TNF-α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587). Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia.

Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix: study protocol for a two-by-two factorial randomised clinical trial

IntroductionWomen with twin pregnancies and a short cervix are at increased risk for preterm birth (PTB). Given the burden of prematurity and its attendant risks, the quest for effective interventions...

Timing of Delivery in Intrahepatic Cholestasis of Pregnancy With Total Bile Acids 40–99 µmol/L: A Decision Analysis [39N

INTRODUCTION: Our study models the trade-off between preterm neonatal morbidity and stillbirth for women with intrahepatic cholestasis of pregnancy (ICP) with total bile acids (TBA) between 40 and 99 µmol/L in order to determine the optimal gestational age for delivery. METHODS: A decision analytic model was created to compare the outcomes of delivery at 33 through 40 weeks gestation in women with TBA between 40 and 99 µmol/L. Baseline morbidity and mortality risks were derived from the literature and adjusted where appropriate for peak TBA and administration of antenatal steroids. We assumed a population of 10,000 women with ICP and calculated total quality-adjusted life years (QALYs) for each strategy, taking into account both maternal and neonatal perspectives. Univariate sensitivity analysis was performed for all variables to test the robustness of the model. RESULTS: In women with TBA between 40 and 99 µmol/L, delivery at 39 weeks maximized QALYs, resulting in 700.6 more QALYs but 5.3 more stillbirths than delivery at 36 weeks. Sensitivity analysis demonstrated that delivery at 38 weeks became optimal when the relative risk of stillbirth given TBA between 40 and 99 µmol/L rose from a baseline of 1.00 to 4.91. Monte Carlo analysis demonstrated that when variation was incorporated into the model, delivery at 39 weeks was optimal 38% of the time and delivery at 38 weeks 25% of the time. CONCLUSION: In women with ICP with TBA between 40 and 99 µmol/L, delivery between 38 and 39 weeks may be optimal.