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Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case-control study of change in maternal plasma soluble Flt-1 ( sFlt-1), soluble endoglin ( sEng) and placenta growth factor ( PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Thorp J, Camargo C, McGee P, Harper M, Klebanoff M, Sorokin Y, Varner M, Wapner R, Caritis S, Iams J, Carpenter M, Peaceman A, Mercer B, Sciscione A, Rouse D, Ramin S, Anderson G. Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women. BJOG 2012;119:1617-1623. Objective To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. Design A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Setting Fourteen academic health centres in the USA. Population Women with prior spontaneous preterm birth. Methods In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. Main outcome measures Recurrent preterm birth at <37 and <32 weeks of gestation. Results The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (−0.18, P < 0.01). Conclusions In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth. [ABSTRACT FROM AUTHOR]

Objective: To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16-20 weeks in women with twin gestations who received 17-α hydroxyprogesterone caproate (17OHPC) or placebo.Methods: This is a secondary analysis of a randomised, double-blind, placebo-controlled trial of twin gestations exposed to 17OHPC or placebo. Baseline transvaginal ultrasound evaluation of cervical length was performed prior to treatment assignment at 16-20 weeks. Cervical length measurements were categorised according to the 10th, 25th, 50th and 75th percentiles in the women studied. The effect of 17OHPC administration in women with a short (25th percentile) and long (75th percentile) cervix was evaluated.Results: Of 661 twin gestations studied, 221 (33.4%) women enrolled at 11 centers underwent cervical length measurement. The 10th, 25th, 50th, 75th percentiles for cervical length at 16-20 weeks were 32, 36, 40 and 44 mm, respectively. The risk of preterm birth <35 weeks was increased in women with a cervical length <25th percentile (55.8 vs. 36.9%, p=0.02). However, a cervical length >75th percentile at this gestational age interval was not protective for preterm birth (36.5 vs. 42.9%, p=0.42). Administration of 17OHPC did not reduce preterm birth before 35 weeks among those with either a short or a long cervix (64.3 vs. 45.8%, p=0.18 and 38.1 vs. 35.5%, p=0.85, respectively).Conclusion: Women with twin gestations and a cervical length below the 25th percentile at 16-20 weeks had higher rates of preterm birth. In this subgroup of women, 17 OHPC did not prevent preterm birth before 35 weeks gestation. A cervical length above the 75th percentile at 16-20 weeks did not significantly reduce the risk of preterm birth in this high risk population. [ABSTRACT FROM AUTHOR]

Doing so can lead to serious--even fatal--complications. To protect mother and fetus alike, manage these patients just as aggressively as your nonpregnant asthmatics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to determine if second-trimester amniotic fluid thrombin-antithrombin (TAT) complexes concentration correlates with subsequent preterm birth. STUDY DESIGN: A cohort of 550 women with singleton nonanomalous pregnancies undergoing second-trimester genetic amniocentesis was followed up to delivery and analyzed as a nested case-control study. Cases of preterm birth (n = 52) were compared with 104 term control subjects. Amniotic fluid collected at amniocentesis was tested for TAT. RESULTS: TAT concentrations were significantly higher in women who delivered preterm (median 115.9 ug/L) than in those who did not (median 62.2 ug/L; P < .001). This difference persisted when 31 spontaneous preterm births and 21 indicated preterm births were analyzed separately. The odds ratios for preterm birth in the highest TAT quartile relative to the lowest quartile was 4.98 (95% confidence interval, 1.17-22.01; P = .007). CONCLUSION: We found a difference in the pattern of intraamniotic thrombin generation between women destined to deliver at term and those who deliver preterm, regardless of the type of preterm birth. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to report the frequency of fetal growth restriction (FGR) based on indication for late preterm birth (LPTB). STUDY DESIGN: Singleton live born pregnancies that were delivered from 34-36 weeks 6 days of gestation over a 1-year period at a tertiary care medical center were studied. Indications for delivery were categorized as spontaneous (spontaneous preterm birth or premature rupture of membranes), medically indicated, or elective. A customized birthweight percentile was calculated for each pregnancy; the rate of FGR was compared based on indication for LPTB. RESULTS: There were 482 LPTBs that met all criteria. Customized birthweight percentiles (median; interquartile range) were different among groups (spontaneous, 45.5%; 20.8-73.5%; medically indicated, 26.9%; 4.1-63.6%; elective, 45.9%; 22.2-78.3%; P = .001). The rate of FGR was also different among groups (spontaneous, 13%; medically indicated, 32%; elective, 21%; P = .001). CONCLUSION: With the use of customized birthweight standards, we found that FGR complicated approximately one-third of all cases of medically indicated LPTB. [ABSTRACT FROM AUTHOR]

Objective: The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17alpha-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed.Study Design: This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter randomized trial of 17OHPC to prevent recurrent preterm delivery.Results: Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio.Conclusion: 17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit. [ABSTRACT FROM AUTHOR]

Background: Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery.Methods: We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle.Results: Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.Conclusions: Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants., Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p  < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p  < 0.05 in the replication cohort., Results: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p  < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis ( p  = 4.1 × 10 -4 ) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p  = 0.039)., Conclusion: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants., Key Points: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death., Study Design: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes ( n  = 11) and demographic and clinical factors ( n  = 10) evident by the time of discharge among surviving infants ( n  = 1889) and the primary outcome of death or moderate/severe CP at age 2 ( n  = 73) was estimated, and a prediction model was created., Results: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants., Conclusion: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae., Key Points: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The fetal consequences of intrapartum fetal tachycardia with maternal fever or clinical chorioamnionitis are not well studied. We evaluated the association between perinatal morbidity and fetal tachycardia in the setting of intrapartum fever., Study Design: Secondary analysis of a multicenter randomized control trial that enrolled 5,341 healthy laboring nulliparous women ≥36 weeks' gestation. Women with intrapartum fever ≥ 38.0°C (including those meeting criteria for clinical chorioamnionitis) after randomization were included in this analysis. Isolated fetal tachycardia was defined as fetal heart rate (FHR) ≥160 beats per minute for at least 10 minutes in the absence of other FHR abnormalities. FHR abnormalities other than tachycardia were excluded from the analysis. The primary outcome was a perinatal composite (5-minute Apgar's score ≤3, intubation, chest compressions, or mortality). Secondary outcomes included low arterial cord pH (pH < 7.20), base deficit ≥12, and cesarean delivery., Results: A total of 986 (18.5%) of women in the trial developed intrapartum fever, and 728 (13.7%) met criteria to be analyzed; of these, 728 women 336 (46.2%) had maternal-fetal medicine (MFM) reviewer-defined fetal tachycardia, and 349 of the 550 (63.5%) women during the final hour of labor had validated software (PeriCALM) defined fetal tachycardia. After adjusting for confounders, isolated fetal tachycardia was not associated with a significant difference in the composite perinatal outcome (adjusted odds ratio [aOR] = 3.15 [0.82-12.03]) compared with absence of tachycardia. Fetal tachycardia was associated with higher odds of arterial cord pH <7.2, aOR = 1.48 (1.01-2.17) and of infants with a base deficit ≥ 12, aOR = 2.42 (1.02-5.77), but no significant difference in the odds of cesarean delivery, aOR = 1.33 (0.97-1.82)., Conclusion: Fetal tachycardia in the setting of intrapartum fever or chorioamnionitis is associated with significantly increased fetal acidemia defined as a pH <7.2 and base excess ≥12 but not with a composite perinatal morbidity., Key Points: · The perinatal outcomes associated with fetal tachycardia in the setting of maternal fever are undefined.. · Fetal tachycardia was not significantly associated with perinatal morbidity although the sample size was limited.. · Fetal tachycardia was associated with an arterial cord pH <7.2 and base deficit of 12 or greater.., Competing Interests: None declared., (Thieme. All rights reserved.)

A social contract exists between medicine and society. In fulfilling the social contract to our patients and society, physicians have an obligation to provide the evidence-based care that patients want and need. What do the data regarding knowledge, judgment, and skills required to practice obstetrics and gynecology show? Obstetrics and gynecology job task analyses assess the importance of knowledge, judgment, and skills through surveys asking practicing physicians about the criticality and frequency of a variety of task statements to create an importance score. Excerpts from a 2018 practice analysis survey clearly indicate that reproductive health care and abortion are important components of the knowledge, judgment, and skills to practice obstetrics and gynecology in the United States. These standards help to assure the knowledge, judgment, and skills of current and future generations of ob-gyns, so their patients and the public can be provided the comprehensive reproductive health care they want and need. It is sometimes important to restate principles and standards that have become ingrained in thoughts and practices that guide physicians and serve to protect our patients. This concept is important now, as our country, health care professionals, and patients examine the future of reproductive health care, including abortion., Competing Interests: Financial Disclosure Susan M. Ramin reports that she is the Associate Executive Director and full-time employee of the ABOG and a non-voting member of the ABOG Board of Directors. She is also a volunteer member and the Secretary-Treasurer of the American Board of Medical Specialties (ABMS) Board of Directors for which she receives a yearly honorarium. George A. Macones serves a volunteer member of the ABOG Board of Directors and is the President of the Board of Directors. The non-employee directors of ABOG receive a yearly honorarium for their time and effort to serve as directors. George D. Wendel disclosed that he is the Executive Director and full-time employee of the ABOG and Secretary and non-voting member of the ABOG Board of Directors. He is also a Member of the American Board of Medical Specialties (ABMS) Board of Directors representing the ABOG and an ex-officio member of the Accreditation Council for Graduate Medical Education (ACGME) Review Committee for Obstetrics and Gynecology. The other authors did not report any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)