US term stillbirth rates and the 39-week rule: a cause for concern?

BACKGROUND: More than a decade ago an obstetric directive called "the 39-week rule" sought to limit "elective" delivery, via labor induction or cesarean delivery, before 39 weeks 0 days of gestation. In 2010 the 39-week rule became a formal quality measure in the United States. The progressive adherence to the 39-week rule throughout the United States has caused a well-documented, progressive reduction in the proportion of term deliveries occurring during the early-term period. Because of the known association between increasing gestational age during the term period and increasing cumulative risk of stillbirth, however, there have been published concerns that the 39-week rule-by increasing the gestational age of delivery for a substantial number of pregnancies-might increase the rate of term stillbirth within the United States. Although adherence to the 39-week rule is assumed to be beneficial, its actual impact on the US rate of term stillbirth in the years since 2010 is unknown. OBJECTIVE: To determine whether the adoption of the 39-week rule was associated with an increased rate of term stillbirth in the United States. STUDY DESIGN: Sequential ecological study, based on state data, of US term deliveries that occurred during a 7-year period bounded by 2007 and 2013. The patterns of the timing of both term childbirth and term stillbirth were determined for each state and for the United States as a whole. RESULTS: A total of 46 usable datasets were obtained (45 states and the District of Columbia). During the 7-year period, there was a continuous reduction in all geographic entities in the proportion of term deliveries that occurred before 39 weeks of gestation. The overall rate of term stillbirth, when we compared 2007-2009 with 2011-2013, increased significantly (1.103/1000 vs 1.177/1000, RR 1.067, 95% confidence interval 1.038-1.096). Furthermore, during the 7-year period, the increase in the rate of US term stillbirth appeared to be continuous (estimated slope: 0.0186/1000/year, 95% confidence interval 0.002-0.035). Assuming 3.5 million term US births per year, and given 6 yearly "intervals" with this rate increase, it is possible that more than 335 additional term stillbirths occurred in the United States in 2013 as compared with 2007. In addition, during the 7-year period, there was a progressive shift in the timing of delivery from the 40th week to the 39th week. Absent this confounding factor, the magnitude of association between the adoption of the 39-week rule and the increase in rate of term stillbirth might have been greater. CONCLUSIONS: Between 2007 and 2013 in the United States, the adoption of the 39-week rule caused a progressive reduction in the proportion of term births occurring before the 39th week of gestation. During the same interval the United States experienced a significant increase in its rate of term stillbirth. This study raises the possibility that the 39-week rule may be causing unintended harm. Additional studies of the actual impact of the adoption of the 39-week rule on major childbirth outcomes are urgently needed. Pressures to enforce the 39-week rule should be reconsidered pending the findings of such studies.

What is the optimal gestational age for women with gestational diabetes type A1 to deliver?

OBJECTIVE: Type A1 gestational diabetes mellitus (A1GDM), also known as diet-controlled gestational diabetes, is associated with an increase in adverse perinatal outcomes such as macrosomia and Erb palsy. However, it remains unclear when to deliver these women because optimal timing of delivery requires balancing neonatal morbidities from early term delivery against the risk of intrauterine fetal demise (IUFD). We sought to determine the optimal gestational age (GA) for women with A1GDM to deliver. STUDY DESIGN: A decision-analytic model was built to compare the outcomes of delivery at 37-41 weeks in a theoretical cohort of 100,000 women with A1GDM. Strategies involving expectant management until a later GA accounted for probabilities of spontaneous delivery, indicated delivery, and IUFD during each week. GA-associated risks of neonatal complications included cerebral palsy, infant death, and Erb palsy. Probabilities were derived from the literature, and total quality-adjusted life years were calculated. Sensitivity analyses were used to investigate the robustness of the baseline assumptions. RESULTS: Our model showed that induction at 38 weeks maximized quality-adjusted life years. Within our cohort, delivery at 38 weeks would prevent 48 stillbirths but lead to 12 more infant deaths compared to 39 weeks. Sensitivity analysis revealed that 38 weeks remains the optimal timing of delivery until IUFD rates fall <0.3-fold of our baseline assumption, at which point expectant management until 39 weeks is optimal. CONCLUSION: By weighing the risks of IUFD against infant deaths and neonatal morbidities from early term delivery, we determined that the ideal GA for women with A1GDM to deliver is 38 weeks.

Induction of labor compared to expectant management in low-risk women and associated perinatal outcomes.

OBJECTIVE: We sought to examine the association of labor induction and perinatal outcomes. STUDY DESIGN: This was a retrospective cohort study of low-risk nulliparous women with term, live births. Women who had induction at a given gestational age (eg, 39 weeks) were compared to delivery at a later gestation (eg, 40, 41, or 42 weeks). RESULTS: Compared to delivery at a later gestational age, those induced at 39 weeks had a lower risk of cesarean (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.88-0.91) and labor dystocia (aOR, 0.88; 95% CI, 0.84-0.94). Their neonates had lowered risk of having 5-minute Apgar <7 (aOR, 0.81; 95% CI, 0.72-0.92), meconium aspiration syndrome (aOR, 0.30; 95% CI, 0.19-0.48), and admission to neonatal intensive care unit (aOR, 0.87; 95% CI, 0.78-0.97). Similar findings were seen for women who were induced at 40 weeks compared to delivery later. CONCLUSION: Induction of labor in low-risk women at term is not associated with increased risk of cesarean delivery compared to delivery later.

The risk of stillbirth and infant death stratified by gestational age in women with gestational diabetes.

OBJECTIVE: We sought to compare the different mortality risks between delivery and expectant management in women with gestational diabetes mellitus (GDM). STUDY DESIGN: This is a retrospective cohort study that included singleton pregnancies of women diagnosed with GDM delivering at 36-42 weeks' gestational age in California from 1997 through 2006. A composite mortality rate was developed to estimate the risk of expectant management at each gestational age incorporating the stillbirth risk during the week of continuing pregnancy plus the infant mortality risk at the gestational age 1 week hence. RESULTS: In women with GDM, the risk of expectant management is lower than the risk of delivery at 36 weeks (17.4 vs 19.3/10,000), but at 39 weeks, the risk of expectant management exceeds that of delivery (relative risk, 1.8; 95% confidence interval, 1.2-2.6). CONCLUSION: In women with GDM, infant mortality rates at 39 weeks are lower than the overall mortality risk of expectant management for 1 week; absolute risks of stillbirth and infant death are low.

Enhancing Value-Based Care With a Walk-in Clinic: A Primary Care Provider Intervention to Decrease Low Acuity Emergency Department Overutilization.

Background Emergency department overutilization is a known contributor to the high per-capita healthcare cost in the United States. There is a knowledge gap regarding the substitution effect of walk-in clinic availability in primary care provider (PCP) offices and emergency department utilization (EDU). This study evaluates associations between PCP availability and EDU and analyzes the potential cost savings for health systems. Methods A retrospective cohort analysis compared low acuity EDU rates in established patients at a family medicine residency's PCP office before and after walk-in clinic implementation. The practice had 12 providers, 12 residents, and a patient panel of approximately 7,000-8,000. Inclusion criteria were met if patients were: (1) established with the PCP office, (2) had a low acuity emergency department (ED) visit (emergency index score level 4 or 5) OR had a walk-in clinic visit at the family practice. ED visits were tracked from January 2018 to January 2020 and encounters were compared numbers to pre and post-implementation of a walk-in clinic. Cost savings for comparable management was estimated with average price differences for low acuity encounters in the ED versus clinic. Results Over the two-year timeframe, there were 10,962 total visits to the ED by family practice patients, 4,250 of these visits were low acuity. Despite gross monthly increases of EDU from 2018-2020, after implementation of a walk-in clinic in 2019, rates of total EDU decreased by 1.5% and low acuity utilization rates also decreased. The average annual patient census nearly doubled from 5,763 to 8,042. T-tests confirmed statistical significance with p-values <0.05. Average low acuity ED visits ($437) cost 4.9 times more than comparable PCP office visits ($91). Managing 2,387 patients in the walk-in clinic resulted in an estimated annual cost savings of $825,902. Conclusion Extended walk-in availability in primary care offices provides non-ED capacity for low acuity management and might mitigate low acuity ED utilization while providing more cost-effective care. This study supports similarly described pre-hospital diversions in reducing ED over-utilization by increasing access to care. Higher levels of evidence are needed to establish causality.

Fourier transform infrared microspectroscopy identifies symmetric PO(2)(-) modifications as a marker of the putative stem cell region of human intestinal crypts.

Complex biomolecules absorb in the mid-infrared (lambda = 2-20 microm), giving vibrational spectra associated with structure and function. We used Fourier transform infrared (FTIR) microspectroscopy to "fingerprint" locations along the length of human small and large intestinal crypts. Paraffin-embedded slices of normal human gut were sectioned (10 microm thick) and mounted to facilitate infrared (IR) spectral analyses. IR spectra were collected using globar (15 microm x 15 microm aperture) FTIR microspectroscopy in reflection mode, synchrotron (

The active management of risk in multiparous pregnancy at term: association between a higher preventive labor induction rate and improved birth outcomes.

OBJECTIVE: To determine whether exposure of multiparous women to a high rate of preventive labor induction was associated with a significantly lower cesarean delivery rate. STUDY DESIGN: Retrospective cohort study involving 123 multiparous women, who were exposed to the frequent use of preventive labor induction, and 304 multiparous women, who received standard management. Rates of cesarean delivery and other adverse birth outcomes were compared in the 2 groups. Logistic regression controlled for confounding covariates. RESULTS: The exposed group had a lower cesarean delivery rate (adjusted odds ratio, 0.09; 0.8% vs 9.9%; P = .02) and a higher uncomplicated vaginal delivery rate (odds ratio, 0.53; 78.9% vs 66.4%; P = .01). Exposure was not associated with higher rates of other adverse birth outcomes. CONCLUSION: Exposure of multiparous women to a high rate of preventive labor induction was significantly associated with improved birth outcomes, including a very low cesarean delivery rate. A prospective randomized trial is needed to determine causality.

Active management of risk in nulliparous pregnancy at term: association between a higher preventive labor induction rate and improved birth outcomes.

OBJECTIVE: The objective of the study was to determine whether exposure of nulliparous women to a high rate of preventive labor induction was associated with improvement in birth health. STUDY DESIGN: A risk-scoring system was used to guide the frequent use of preventive labor induction in 100 nulliparous women. The birth outcomes of this group were compared with those of 352 nulliparous women who received usual care. Cesarean delivery was the primary study outcome. The Adverse Outcome Index and the rate of uncomplicated vaginal delivery were used to measure overall birth health. RESULTS: The exposed group experienced a higher labor induction rate (48% vs 23.6%; P < .001), a lower cesarean rate (9% vs 25.8%; adjusted odds ratio, 0.36; P = .02), and better composite birth outcomes. CONCLUSION: Exposure of nulliparous women to a high preventive induction rate was significantly associated with improvement in birth health. Prospective randomized trials are needed to further explore the utility of risk-guided preventive labor induction.

"One end has nothing to do with the other:" patient attitudes regarding help seeking intention for depression in gynecologic and obstetric settings.

Many women rely on their obstetrician/gynecologist (OB/GYN) as their primary contact with the health care delivery system. There have been few studies exploring patient views on getting help for depression from these providers. The purpose of this study is to assess help seeking intention for depression and identify beliefs which moderate this intention. Telephone interviews of women following a routine gynecologic visit or in the immediate postpartum period (regarding prenatal care) were used to assess intention to seek help from their providers in a case of depression. For women who lacked this intention, related beliefs were elicited with the open ended question "why not?" Among the 225 women in the study more than half receiving gynecologic care (59%) and nearly a third of women who received prenatal care (29%; p < 0.001) stated they would not seek help from their OB/GYN for depression. Report that a prenatal provider had mentioned depression was associated with help seeking intention for depression but was not independent of confounding variables. Beliefs among women who lacked help seeking intention clustered into two attitude themes: 1) an OB/GYN is the wrong doctor for depression care and 2) OB/GYN is not a good setting for depression care. Many women have attitudes which reduce their intention to seek help for depression from their OB/GYN. Interventions aiming to increase delivery of depression care in these settings should consider these beliefs in their design.

First- vs second-trimester ultrasound: the effect on pregnancy dating and perinatal outcomes.

OBJECTIVE: The objective of the study was to examine the effect of first-trimester obstetric ultrasound (OBUS) on the measurement of the effect of complications ascribed to postterm pregnancies. STUDY DESIGN: We conducted a retrospective cohort study of all term, singleton pregnancies delivered at our institution who had an OBUS at a gestation of 24 weeks or less. Those women who underwent an OBUS at a gestation of 12 weeks or less (OBUS12) were compared with those who had an OBUS at 13-24 weeks of gestation (OBUS13-24). The primary outcome measures were the rates of postterm pregnancies greater than 41 or 42 weeks' gestation. Secondary outcomes were the differences between the postterm and term gestations in maternal and neonatal outcomes. RESULTS: In the OBUS12 group, the rate of postterm pregnancy 42 weeks or longer was lower (2.7%) as compared with the OBUS13-24 group (3.7%, P = .022). With regard to reaching 41 weeks of gestation, the OBUS12 group was again lower (18.2%) as compared with the OBUS13-24 group (22.1%, P < .001). There were also fewer postterm inductions at 42 weeks or longer in the OBUS12 group (1.8%) as compared with the OBUS13-24 group (2.6%, P = .017). When comparing perinatal outcomes between those women who reached 41 weeks of gestation and those prior to 41 weeks of gestation, the OBUS12 group demonstrated greater differences between these 2 groups. CONCLUSION: Our findings suggest that earlier obstetric ultrasound, which leads to better pregnancy dating, reduces the rate of estimated postterm pregnancies. This may, in turn, reduce unnecessary intervention and lead to better identification of postterm pregnancies at greater risk of complications.

The impact of the active management of risk in pregnancy at term on birth outcomes: a randomized clinical trial.

OBJECTIVE: The purpose of this study was to compare birth outcomes that result from the active management of risk in pregnancy at term (AMOR-IPAT) to those outcomes that result from standard management. STUDY DESIGN: This was a randomized clinical trial with 270 women of mixed parity. AMOR-IPAT used preventive labor induction to ensure delivery before the end of an estimated optimal time of delivery. Rates of 4 adverse obstetric events and 2 composite measures were used to evaluate birth outcomes. RESULTS: The AMOR-IPAT-exposed group had a similar cesarean delivery rate (10.3% vs 14.9%; P = .25), but a lower neonatal intensive care unit admission rate (1.5% vs 6.7%; P = .03), a higher uncomplicated vaginal birth rate (73.5% vs 62.8%; P = .046), and a lower mean Adverse Outcome Index score (1.4 vs 8.6; P = .03). CONCLUSION: AMOR-IPAT exposure improved the pattern of birth outcomes. Larger randomized clinical trials are needed to explore further the impact of AMOR-IPAT on birth outcomes and to determine the best methods of preventive labor induction.

Perinatal outcomes in low-risk term pregnancies: do they differ by week of gestation?

OBJECTIVE: The objective of the study was to examine whether the risk of perinatal complications increases with increasing gestational age among term pregnancies. STUDY DESIGN: This is a retrospective cohort study of low-risk women with term, singleton births in 2003 in the United States. Gestational age was subgrouped into 37, 38, 39, 40, and 41 completed weeks. Statistical comparison was performed using chi(2) test and multivariable logistic regression models, with 39 weeks' gestation as the referent. RESULTS: There were 2,527,766 women meeting study criteria. Compared with 39 weeks, delivery at 37 or 38 weeks had lower risk of febrile morbidity but slightly higher risk of cesarean delivery. Delivery at 40 or 41 weeks was also associated with higher overall maternal morbidity. For neonates, delivery at 40 or 41 weeks had higher risk of birthweight greater than 4500 g, neonatal injury (40 weeks: adjusted odds ratio [aOR] 1.11 [95% confidence interval (CI), 1.05-1.18]; 41 weeks: aOR 1.27 [95% CI, 1.17-1.37]) and meconium aspiration (40 weeks: aOR 1.55 [95% CI, 1.43-1.69]; 41 weeks: aOR 2.12 [95% CI, 1.91-2.35]). Delivery at 37 or 38 weeks had higher risk of hyaline membrane disease (37 weeks: aOR 3.12 [95% CI, 2.90-3.38]); 38 weeks: aOR 1.30 [95% CI, 1.19-1.43]) but lower risk of meconium aspiration. CONCLUSION: The risk of cesarean delivery and neonatal morbidity in low-risk women increases at 40 weeks and beyond, whereas the odds of serious neonatal pulmonary disease were highest at 37 weeks. Recognition of such variation in term outcomes should lead providers to avoid iatrogenic morbidity and consider interventions to prevent complications of late-term pregnancy.

The oxidised histone octamer does not form a H3 disulphide bond.

A H3 dimer band is produced when purified native histone octamers are run on an SDS-PAGE gel in a beta-mercaptoethanol-free environment. To investigate this, native histone octamer crystals, derived from chicken erythrocytes, and of structure (H2A-H2B)-(H4-H3)-(H3'-H4')-(H2B'-H2A'), were grown in 2 M KCl, 1.35 M potassium phosphates and 250-350 microM of the oxidising agent S-nitrosoglutathione, pH 6.9. X-ray diffraction data were acquired to 2.10 A resolution, yielding a structure with an Rwork value of 18.6% and an Rfree of 22.5%. The space group is P6(5), the asymmetric unit of which contains one complete octamer. Compared to the 1.90 A resolution, unoxidised native histone octamer structure, the crystals show a reduction of 2.5% in the c-axis of the unit cell, and free-energy calculations reveal that the H3-H3' dimer interface in the latter has become thermodynamically stable, in contrast to the former. Although the inter-sulphur distance of the two H3 cysteines in the oxidised native histone octamer has reduced to 6 A from the 7 A of the unoxidised form, analysis of the hydrogen bonds that constitute the (H4-H3)-(H3'-H4') tetramer indicates that the formation of a disulphide bond in the H3-H3' dimer interface is incompatible with stable tetramer formation. The biochemical and biophysical evidence, taken as a whole, is indicative of crystals that have a stable H3-H3' dimer interface, possibly extending to the interface within an isolated H3-H3' dimer, observed in SDS-PAGE gels.

A preventive approach to obstetric care in a rural hospital: association between higher rates of preventive labor induction and lower rates of cesarean delivery.

PURPOSE: Annual cesarean delivery rates in North America are increasing. Despite the morbidity associated with cesarean delivery, a safe preventive strategy to reduce the use of this procedure has not been forthcoming. During the 1990s, clinicians in a rural hospital developed a method of care involving prostaglandin-assisted preventive labor induction. An inverse relationship was noted between yearly hospital rates of labor induction and cesarean delivery. The purpose of our study was to compare cesarean delivery rates between practitioners who often used preventive induction and practitioners who did not, while controlling for patient mix and differences in practice style. METHODS: Between 1993 and 1997, different hospital practitioners used risk-guided prostaglandin-assisted preventive labor induction with differing intensity. We used a retrospective cohort design, based on the practitioner providing prenatal care, to compare birth outcomes in women exposed to this alternative method of care with those in women not exposed. Multiple logistic regression analysis controlled for patient characteristics and clustering by practitioner. RESULTS: The exposed group (n = 794), as compared with the nonexposed group (n = 1,075), had a higher labor induction rate (31.4% vs 20.4%, P <.001), a greater use of prostaglandin E2 (23.3% vs 15.7%, P <.001), and a lower cesarean delivery rate (5.3% vs 11.8%, P <.001). Adjustment for cluster effects, patient characteristics, and the use of epidural analgesia did not eliminate the significant association between exposure to this preventive method of care and a lower cesarean delivery rate. Rates of other adverse birth outcomes were either unchanged or reduced in the exposed group. CONCLUSIONS: A preventive approach to reducing cesarean deliveries may be possible. This study found that practitioners who often used risk-guided, prostaglandin-assisted labor induction had a lower cesarean delivery rate without increases in rates of other adverse birth outcomes. Randomized controlled trials of this method of care are warranted.

The association between the regular use of early-term labor induction and improved birth outcomes: new evidence from an Italian hospital.

BACKGROUND: Associations have been recently reported between the frequent use of early-term preventive labor induction and improvements in multiple parameters of birth health. We sought to replicate these findings in an Italian hospital. METHODS: The outcomes of 120 consecutively delivered women who were exposed to the alternative method of care were compared to the outcomes of 159 women who received standard management. The primary and secondary outcomes were group cesarean delivery rate and group adverse outcome index score. RESULTS: Exposed women had a higher induction rate, a lower cesarean delivery rate (1.7% vs. 43.4%), and a lower group AOI Score (0.2 vs.5.8). CONCLUSIONS: Exposure to high levels of early term preventive labor induction was associated with a lower group cesarean delivery rate and improvement in several other major birth outcomes. An adequately powered randomized controlled trial is needed to further explore this alternative method of care.

Induction of labor and cesarean delivery by gestational age.

OBJECTIVE: Studies of cesarean delivery (CD) rates among women undergoing induction of labor (IOL) often compare such women to women experiencing spontaneous labor at similar gestational ages. We sought to examine the association between IOL at various gestational ages and CD, accounting for the effect of increased gestational age among the comparison group who were managed expectantly. STUDY DESIGN: We conducted a retrospective cohort study of all term, singleton, cephalic presentation pregnancies delivered at our institution over 15 years excluding cesarean deliveries before labor. For each gestational age of induction, we created a comparison group of women who were undelivered at that gestational age, and who experienced labor at some future gestational age. RESULTS: In women undergoing IOL at 38 weeks gestation, the CD rate was 11.9% as compared to 13.3% (P = .42) of women beyond 38 weeks gestation. The CD rate for induction of labor compared to ongoing pregnancy was 14.3% versus 15.0% (P = .62) at 39 weeks, 20.4% versus 19.0% (P = .41) at 40 weeks, and 24.3% versus 26.0% (P = .39) at 41 weeks. When controlling for potential confounding, there was a higher rate of CD among women with expectant management beyond 38 weeks (adjusted odds ratio [AOR] 1.80; 95% CI 1.29-2.53), 39 weeks (1.39; 95% CI 1.08-1.80), and 40 weeks (AOR 1.27; 95% CI 1.00-1.62). CONCLUSION: Our findings suggest that IOL may not increase a woman's risk of CD when compared to expectant management. While this question has been addressed prospectively at 41 weeks gestation, it requires further examination at earlier gestations and among various subgroups.

High-resolution structure of the native histone octamer.

Crystals of native histone octamers (H2A-H2B)-(H4-H3)-(H3'-H4')-(H2B'-H2A') from chick erythrocytes in 2 M KCl, 1.35 M potassium phosphate pH 6.9 diffract X-rays to 1.90 A resolution, yielding a structure with an R(work) value of 18.7% and an Rfree of 22.2%. The crystal space group is P6(5), the asymmetric unit of which contains one complete octamer. This high-resolution model of the histone-core octamer allows further insight into intermolecular interactions, including water molecules, that dock the histone dimers to the tetramer in the nucleosome-core particle and have relevance to nucleosome remodelling. The three key areas analysed are the H2A'-H3-H4 molecular cluster (also H2A-H3'-H4'), the H4-H2B' interaction (also H4'-H2B) and the H2A'-H4 beta-sheet interaction (also H2A-H4'). The latter of these three regions is important to nucleosome remodelling by RNA polymerase II, as it is shown to be a likely core-histone binding site, and its disruption creates an instability in the nucleosome-core particle. A majority of the water molecules in the high-resolution octamer have positions that correlate to similar positions in the high-resolution nucleosome-core particle structure, suggesting that the high-resolution octamer model can be used for comparative studies with the high-resolution nucleosome-core particle.