Pregnancy Outcomes in Patients With Hepatitis C Virus Infection.

OBJECTIVE: To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection. METHODS: This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal intensive care (NICU); small-for-gestational-age (SGA) birth weight; and neonatal infection, defined as sepsis or pneumonia. Models were adjusted for maternal age, body mass index, injection drug use, and maternal medical comorbidities. RESULTS: The 249 individuals in the case group were prospectively matched to 486 individuals in the control group who met eligibility criteria. There were significant differences in demographic characteristics between the groups, including race, socioeconomic markers, education, insurance status, and drug and tobacco use. The frequencies of maternal outcomes of gestational diabetes, preeclampsia, and abruption were similar between the case and control groups. Preterm birth was similar between groups, but neonates born to individuals in the case group were more likely to be admitted to the NICU (45.1% vs 19.0%, adjusted odds ratio [aOR] 2.6, 95% CI, 1.8-3.8) and to have SGA birth weights below the 5th percentile (10.6% vs 3.1%, aOR 2.9, 95% CI, 1.4-6.0). There were no increased odds of hyperbilirubinemia or neonatal infection. CONCLUSION: Despite no increased odds of preterm birth or other adverse maternal outcomes in adjusted analyses, maternal HCV infection was associated with twofold increased odds of NICU admission and nearly threefold increased odds of SGA birth weight below the 5th percentile.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Maternal and Delivery Characteristics and Self-Reported Perceived Control During Labor.

OBJECTIVE: To evaluate the association between maternal and delivery characteristics and self-reported perceived control during childbirth. METHODS: A secondary analysis of a multicenter randomized trial was conducted to compare labor induction at 39 weeks of gestation with expectant management in low-risk nulliparous people. Six to 96 hours after delivery, participants who experienced labor completed the Labor Agentry Scale, a validated self-administered questionnaire to ascertain perceived control during childbirth. Scores range from 29 to 203, with higher scores indicating a sense of greater control. Multivariable linear regression was used to determine which maternal and delivery characteristics were associated with the Labor Agentry Scale score. Eligible characteristics included age, self-reported race and ethnicity, marital status, employment status, type of insurance, previous pregnancy loss before 20 weeks of gestation, body mass index (BMI), smoking, alcohol use, mode of delivery, labor pain (0-10 points), and a composite of perinatal death or severe neonatal complications. Significant variables ( P <.05) were retained in the final multivariable model, and adjusted mean differences (95% CIs) between groups were estimated. RESULTS: Of 6,106 people enrolled in the trial, 6,038 experienced labor, of whom 5,750 (95.2%) completed the Labor Agentry Scale and were included in this analysis. Mean [95% CI] adjusted Labor Agentry Scale scores were significantly lower among those who identified as Asian (-6.4 [-10.5 to -2.3]) or Hispanic (-3.7 [-5.7 to -1.7]) compared with White, smoked compared with did not smoke (-2.8 [-5.5 to -0.1]), had BMIs of 35 or higher compared with less than 30 (-2.0 [-3.8 to -0.2]), were unemployed (-3.15 [-4.76 to -1.55]), did not have private health insurance (-2.61 [-4.47 to -0.76]), underwent operative vaginal (-5.1 [-7.7 to -2.6]) or cesarean (-14.4 [-16.1 to -12.6]) delivery compared with spontaneous vaginal delivery, and reported greater labor pain score of 8 or higher compared with less than 8 (-11.9 [-13.4 to -10.4]). Mean [95% CI] adjusted Labor Agentry Scale scores were significantly higher among people who were employed compared with unemployed (3.2 [1.6-4.8]) and had private compared with nonprivate insurance (2.6 [0.76-4.5]). CONCLUSION: In nulliparous people at low risk, unemployment, lack of private health insurance, Asian race, Hispanic ethnicity, smoking, operative delivery, and more labor pain were associated with lower perceived control during labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01990612.

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

Prenatal medication use in a prospective pregnancy cohort by pre-pregnancy obesity status.

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m2) and pattern of medication use during pregnancy in the United States is not well-studied. Higher pre-pregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19-29.9 kg/m2), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

Making the most of the first prenatal visit: The challenge of expanding prenatal genetic testing options and limited clinical encounter time.

OBJECTIVE: Advances in prenatal genetics place additional challenges as patients must receive information about a growing array of screening and testing options. This raises concerns about how to achieve a shared decision-making process that prepares patients to make an informed decision about their choices about prenatal genetic screening and testing options, calling for a reconsideration of how healthcare providers approach the first prenatal visit. METHODS: We conducted interviews with 40 pregnant women to identify components of decision-making regarding prenatal genetic screens and tests at this visit. Analysis was approached using grounded theory. RESULTS: Participants brought distinct notions of risk to the visit, including skewed perceptions of baseline risk for a fetal genetic condition and the implications of screening and testing. Participants were very concerned about financial considerations associated with these options, ranking out-of-pocket costs on par with medical considerations. Participants noted diverging priorities at the first visit from those of their healthcare provider, leading to barriers to shared decision-making regarding screening and testing during this visit. CONCLUSION: Research is needed to determine how to restructure the initiation of prenatal care in a way that best positions patients to make informed decisions about prenatal genetic screens and tests.

Hepatitis C Virus Antibody Screening in a Cohort of Pregnant Women: Identifying Seroprevalence and Risk Factors.

OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015. METHODS: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody-positive, two women at similar gestational age who were HCV antibody-negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group. RESULTS: Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1-2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case-control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2-64.0), blood transfusion (aOR 3.7, 95% CI 1.3-10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8-22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4-19.8), and smoking (aOR 2.4, 95% CI 1.2-4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%). CONCLUSION: In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959321.

Fetal Growth Patterns in Pregnancies With First-Trimester Bleeding.

OBJECTIVE: To assess the relationship between first-trimester vaginal bleeding and fetal growth patterns. METHODS: We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, a prospective cohort study of low-risk, nonobese women with healthy lifestyles. Duration of bleeding was self-reported at enrollment (10 0/7 to 13 6/7 weeks of gestation) and categorized as 0, 1, or more than 1 day. Longitudinal measures of fetal biometrics were obtained in up to six study visits, and estimated fetal weight was computed. Growth trajectories were created for biometrics and estimated fetal weight. When global tests among groups was significant (P<.05), week-specific global and pairwise differences were tested. Birth weight and risk of a small-for-gestational-age (SGA) neonate were secondary outcomes. All analyses were adjusted for maternal age, weight, height, parity, and racial-ethnic group and neonatal sex in a sensitivity analysis. RESULTS: In 2,307 eligible women, 410 (17.8%) reported first-trimester bleeding, of whom 176 bled for 1 day and 234 bled for more than 1 day. Women with more than 1 day of bleeding demonstrated decreased fetal abdominal circumference from 34 to 39 weeks of gestation compared with women without bleeding. For women with more than 1 day of bleeding, compared with women without bleeding, estimated fetal weight was 68-107 g smaller from 35 to 39 weeks of gestation. Mean birth weight at term was 88 g smaller, confirming differences in calculated fetal weight, and SGA neonates were delivered to 148 (8.5%), 9 (5.7%), and 33 (15.7%) women in the no bleeding, 1 day, and more than 1 day of bleeding groups, respectively. CONCLUSION: More than 1 day of first-trimester vaginal bleeding was associated with smaller estimated fetal weight late in pregnancy driven by smaller abdominal circumference. The magnitude of decrease in birth weight was small, albeit comparable with observed decreases associated with maternal smoking. It remains unknown whether early pregnancy bleeding is associated with short-term or long-term morbidity and whether additional intervention would be of benefit. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00912132.

Medical and Surgical Interventions Available Before a Periviable Birth.

Periviable birth contributes disproportionately to perinatal morbidity and mortality. By analyzing the most relevant outcomes after a preterm birth some information can be provided on the potential benefit of interventions. This article discusses surgical and medical interventions that may offer neonatal benefit including cerclage, amniocentesis, progesterone, antenatal corticosteroids, magnesium sulfate for neuroprotection, and tocolysis. Cervical cerclage has the greatest promise at reducing morbidity and mortality related to periviable birth even though it may not reduce the overall preterm birth rate. The use of antenatal corticosteroids, magnesium sulfate, progesterone, and tocolytics may also improve outcome. Studies specifically evaluating these interventions are needed.

Antenatal Betamethasone for Women at Risk for Late Preterm Delivery.

BACKGROUND: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities. METHODS: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery. RESULTS: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001). CONCLUSIONS: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).

Placental inflammation is not increased in inflammatory bowel disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls. METHODS: Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn's disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery. RESULTS: Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32). CONCLUSIONS: Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes.

Prevention of periviable birth: bed rest, tocolysis, progesterone, and cerclage.

The periviable period is associated with a rapid improvement in both mortality and morbidity with increasing gestational age. Therapies that can prolong gestation have the potential for markedly improving outcome compared to later in pregnancy. The therapies commonly prescribed in order to prolong gestation include bed rest, tocolysis, progesterone, and cerclage. Although these therapies are used to prevent preterm birth throughout gestation, their impact on perinatal outcome during the periviable period remains largely unknown. These therapies are discussed relative to the periviable period exploring available data and possible impact on perinatal outcome. Studies specifically evaluating therapeutic interventions during the periviable period are lacking.

Progesterone modulates integrin {alpha}2 (ITGA2) and {alpha}11 (ITGA11) in the pregnant cervix.

OBJECTIVE: Fibrillar collagen in the cervical extracellular matrix (ECM) is the predominant component providing mechanical support. Cellular integrins contribute to structural integrity by cross-linking ECM components. We investigated the expression of collagen-binding integrins in the normal rat gestation and after treatment with mifepristone to determine whether integrin modulation is involved in changes in tissue resistance. STUDY DESIGN: Cervical tissue was harvested from nonpregnant and timed pregnant Sprague-Dawley rats. Normal gestational expression was evaluated in nonpregnant and timed pregnant tissue on days 12, 16, 18, 20, 21 and 22. Progesterone inhibition was induced with 3 mg mifepristone administered on day 15. Primary rat cervical stromal (RCS) cell cultures were generated from nonpregnant rats using tissue explants. The effects of progesterone environment on RCS cells were evaluated in the presence and absence of various inhibitors. Protein expression and signaling pathways were evaluated by Western blot. RESULTS: Integrin α2 (ITGA2) expression increased over gestation, peaking at the end of gestation (analysis of variance [ANOVA] P < .01). Integrin α11 (ITGA11) expression increased through mid-gestation, peaking on day 18 and decreasing through day 22 (ANOVA P < .001). Progesterone increased the expression of ITGA11 and phosphorylated focal adhesion kinase ([pFAK] P < .002). Mifepristone blocked these effects in vitro. Mifepristone increased ITGA2 and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) in vivo and in vitro. Mifepristone-induced upregulation of ITGA2 was abrogated by inhibition of ERK1/2. CONCLUSION: Progesterone/progesterone withdrawal is involved in regulating the expression of collagen-binding integrins. These changes differ among the collagen-binding integrins. Mitogen-activated protein kinase (MAPK) signaling is involved in regulating some of these integrins.

Early onset preeclampsia and second trimester serum markers.

OBJECTIVE: To examine serum markers measured in the second trimester to identify women who subsequently develop preeclampsia. METHODS: Clinically defined preeclampsia was confirmed in 45 women who had provided a serum sample as part of Down syndrome screening. Preeclampsia was categorized as mild or severe, as well as early (<32 weeks) or late onset. Each case was matched with five controls based on gestational age and date of serum collection. Stored sera were retrieved and tested for inhibin A, soluble vascular endothelial growth factor receptor 1 (sVEGF R1), placental growth factor (PlGF), and endoglin. Results were converted to multiples of the median (MoM) and compared in case and control pregnancies. Univariate analysis was used to identify the strongest markers, which were then used in a multivariate model. RESULTS: Inhibin A, PlGF, and endoglin were consistently associated with preeclampsia, especially for early onset disease. A multivariate model using the three markers could identify 50% of the pregnancies with early onset preeclampsia with a 2% false positive rate. CONCLUSION: The levels of inhibin A, PlGF, and endoglin in the second trimester can be combined using a predictive model to provide individualized risk estimates for early onset preeclampsia.

Prostaglandin E2-regulated cervical ripening: analysis of proteoglycan expression in the rat cervix.

OBJECTIVE: Prostaglandins reduce cervical resistance by reorganizing collagen fibrils. Proteoglycans are involved in collagen fibril organization and structure. We evaluated the changes in proteoglycan composition induced by prostaglandin E(2) (PGE(2)). STUDY DESIGN: Prostaglandins were administered intravaginally to induce cervical ripening in timed pregnant Sprague-Dawley rats. Changes in proteoglycan messenger ribonucleic acid (mRNA) expression were measured using reverse transcription (RT-PCR) for core protein. Fluorophore assisted carbohydrate gel electrophoresis (FACE) was used to evaluate proteoglycan glycosaminoglycan composition along with size exclusion high-performance liquid chromatography (HPLC). RESULTS: No change in core protein mRNA expression was detected after PGE(2) treatment. Total glycosaminoglycan (GAG) decreased more than 20% after PGE(2) (P = .02). FACE demonstrated a shift in disaccharide subunit composition after PGE(2), with a decrease in 4-sulfated disaccharides (P = .02). HPLC confirmed a decrease in total GAG (P = .04). CONCLUSION: Although there was no change in core protein mRNA expression, alterations in GAG composition was detected after PGE(2). The decrease in sulfated GAG could decrease electrostatic interactions that would weaken interfibrillar interactions. These findings would be consistent with a decline in cervical resistance.

Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events.

OBJECTIVE: The purpose of this study was to assess the structural, biomechanical, and biochemical effects of mifepristone-induced progesterone withdrawal on the rat cervix to identify possible mechanisms by which mifepristone incites cervical ripening. STUDY DESIGN: After the administration of mifepristone, cervical tensile strength was determined by the cervical creep method. With polarized light microscopy and transmission electron microscopy, collagen organization and microstructure were quantified. Matrix metalloproteinase expression was assessed by Western Blot and Real-time reverse transcriptase-polymerase chain reaction. RESULTS: Mifepristone induced a decrease in cervical tensile strength at mid gestation that was associated with a decrease in collagen organization. Additionally, mifepristone led to collagen fragmentation with a significant decrease in fibril length and diameter, although fibril bundling remained unaffected. Matrix metalloproteinase-2 expression increased after the administration of mifepristone. CONCLUSION: Mifepristone-induced cervical ripening is associated with collagen degradation, and the collagenase activity of matrix metalloproteinase-2 may play a role in this process.

Nitroglycerin for relaxation to establish a fetal airway (EXIT procedure).

BACKGROUND: The ex utero intrapartum treatment (EXIT) procedure is a technique designed to establish an airway at the time of delivery in fetuses at risk of airway obstruction and requires maintenance of uterine relaxation to continue placental perfusion and prevent placental separation. We describe the use of intravenous nitroglycerin to maintain uterine relaxation during the EXIT procedure. CASE: A 17-year-old primigravida with a fetus known to have an anterior neck mass was admitted for a scheduled operative delivery at 38 weeks of gestation using a modified EXIT procedure. Anesthesia was administered with a combined spinal-epidural technique. Intravenous nitroglycerin was administered as a bolus and then as a continuous infusion to maintain uterine relaxation until evaluation of the neonatal airway was completed. CONCLUSION: Intravenous nitroglycerin is an effective agent for maintenance of uterine relaxation and placental perfusion during the EXIT procedure.