The association between parental age differences and perinatal outcomes.

STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome. LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes. WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Postpartum pharmacologic thromboprophylaxis and complications in a US cohort.

BACKGROUND: Venous thromboembolism accounts for approximately 9% of pregnancy-related deaths in the United States. National guidelines recommend postpartum risk stratification and pharmacologic prophylaxis in at-risk individuals. Knowledge on modern rates of postpartum pharmacologic thromboprophylaxis and its associated risks is limited. OBJECTIVE: This study aimed to describe the rate of, and factors associated with, initiation of postpartum pharmacologic prophylaxis for venous thromboembolism, and to assess associated adverse outcomes. STUDY DESIGN: This was a secondary analysis of a multicenter cohort of individuals delivering on randomly selected days at 17 US hospitals (2019-2020). Medical records were reviewed by trained and certified personnel. Those with an antepartum diagnosis of venous thromboembolism, receiving antepartum anticoagulation, or known SARS-CoV-2 infection were excluded. The primary outcome was use of postpartum pharmacologic thromboprophylaxis. Secondary outcomes included bleeding complications, surgical site infection, hospital readmission, and venous thromboembolism through 6 weeks postpartum. The rate of thromboprophylaxis administration was assessed by mode of delivery, institution, and continuance to the outpatient setting. Multivariable regression models were developed using k-fold cross-validation with stepwise backward elimination to evaluate factors associated with thromboprophylaxis administration. Univariable and multivariable logistic models with propensity score covariate adjustment were performed to assess the association between thromboprophylaxis administration and adverse outcomes. RESULTS: Of 21,114 individuals in the analytical cohort, 11.9% (95% confidence interval, 11.4%-12.3%) received postpartum pharmacologic thromboprophylaxis; the frequency of receipt was 29.8% (95% confidence interval, 28.7%-30.9%) following cesarean and 3.5% (95% confidence interval, 3.2%-3.8%) following vaginal delivery. Institutional rates of prophylaxis varied from 0.21% to 34.8%. Most individuals (83.3%) received thromboprophylaxis only as inpatients. In adjusted analysis, cesarean delivery (adjusted odds ratio, 19.17; 95% confidence interval, 16.70-22.00), hysterectomy (adjusted odds ratio, 15.70; 95% confidence interval, 4.35-56.65), and obesity (adjusted odds ratio, 3.45; 95% confidence interval, 3.02-3.95) were the strongest factors associated with thromboprophylaxis administration. Thromboprophylaxis administration was not associated with surgical site infection (0.9% vs 0.6%; odds ratio, 1.48; 95% confidence interval, 0.80-2.74), bleeding complications (0.2% vs 0.1%; odds ratio, 2.60; 95% confidence interval, 0.99-6.80), or postpartum readmission (0.9% vs 0.3%; adjusted odds ratio, 1.38; 95% confidence interval, 0.68-2.81). The overall rate of venous thromboembolism was 0.06% (95% confidence interval, 0.03%-0.10%) and was higher in those receiving prophylaxis (0.2%) compared with those not receiving prophylaxis (0.04%). CONCLUSION: Approximately 1 in 10 patients received postpartum pharmacologic thromboprophylaxis in this US cohort. Rates of prophylaxis varied widely by institution. Cesarean delivery, hysterectomy, and obesity were predominant factors associated with postpartum thromboprophylaxis administration.

Validation of Three Models for Prediction of Blood Transfusion during Cesarean Delivery Admission.

OBJECTIVE: Prediction of blood transfusion during delivery admission allows for clinical preparedness and risk mitigation. Although prediction models have been developed and adopted into practice, their external validation is limited. We aimed to evaluate the performance of three blood transfusion prediction models in a U.S. cohort of individuals undergoing cesarean delivery. STUDY DESIGN: This was a secondary analysis of a multicenter randomized trial of tranexamic acid for prevention of hemorrhage at time of cesarean delivery. Three models were considered: a categorical risk tool (California Maternal Quality Care Collaborative [CMQCC]) and two regression models (Ahmadzia et al and Albright et al). The primary outcome was intrapartum or postpartum red blood cell transfusion. The CMQCC algorithm was applied to the cohort with frequency of risk category (low, medium, high) and associated transfusion rates reported. For the regression models, the area under the receiver-operating curve (AUC) was calculated and a calibration curve plotted to evaluate each model's capacity to predict receipt of transfusion. The regression model outputs were statistically compared. RESULTS: Of 10,785 analyzed individuals, 3.9% received a red blood cell transfusion during delivery admission. The CMQCC risk tool categorized 1,970 (18.3%) individuals as low risk, 5,259 (48.8%) as medium risk, and 3,556 (33.0%) as high risk with corresponding transfusion rates of 2.1% (95% confidence interval [CI]: 1.5-2.9%), 2.2% (95% CI: 1.8-2.6%), and 7.5% (95% CI: 6.6-8.4%), respectively. The AUC for prediction of blood transfusion using the Ahmadzia and Albright models was 0.78 (95% CI: 0.76-0.81) and 0.79 (95% CI: 0.77-0.82), respectively (p = 0.38 for difference). Calibration curves demonstrated overall agreement between the predicted probability and observed likelihood of blood transfusion. CONCLUSION: Three models were externally validated for prediction of blood transfusion during cesarean delivery admission in this U.S. COHORT: Overall, performance was moderate; model selection should be based on ease of application until a specific model with superior predictive ability is developed. KEY POINTS: · A total of 3.9% of individuals received a blood transfusion during cesarean delivery admission.. · Three models used in clinical practice are externally valid for blood transfusion prediction.. · Institutional model selection should be based on ease of application until further research identifies the optimal approach..

Thrombotic Markers in Pregnant Patients with and without SARS-CoV-2 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities and increased risk for venous and arterial thrombi. This study aimed to evaluate D-dimer levels and lupus anticoagulant (LAC) positivity in pregnant individuals with and without Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: This was a prospective cohort study of pregnant individuals delivering at a single academic institution from April 2020 to March 2022. Individuals with a positive SARS-CoV-2 result during pregnancy were compared with a convenience sample of those without a positive SARS-CoV-2 result. For individuals with SARS-CoV-2 infection, severity was assessed based on the National Institutes of Health classification system. The primary outcome was D-dimer level measured during delivery admission. The secondary outcomes were LAC positivity and thromboembolic events. Outcomes were compared between individuals with and without a positive SARS-CoV-2 result, and further by disease severity. RESULTS: Of 98 participants, 77 (78.6%) were SARS-CoV-2 positive during pregnancy. Among individuals with SARS-CoV-2 infection, severity was asymptomatic in 20 (26.0%), mild in 13 (16.9%), moderate in 4 (5.2%), severe in 38 (49.4%), and critical in 2 (2.6%). The D-dimer concentration at delivery did not significantly differ between those with a SARS-CoV-2 positive result compared with those without (mean 2.03 µg/mL [95% confidence interval {CI} 1.72-2.40] vs. 2.37 µg/mL [95% CI 1.65-3.40]; p = 0.43). Three individuals (4%) with SARS-CoV-2 infection and none (0%) without infection were LAC positive (p = 0.59). There were no clinically apparent thromboses in either group. D-dimer concentrations and LAC positive results did not differ by COVID-19 severity. CONCLUSION: Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection; however, high rates of LAC positivity were detected. KEY POINTS: · Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection.. · Higher than expected rates of LAC positivity were detected.. · There were no clinically apparent thromboses..

Incidence and Clinical Characteristics of and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Pregnant Individuals in the United States.

BACKGROUND: Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population. METHODS: We prospectively followed a cohort of pregnant individuals during August 2020-March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription-polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)-like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. RESULTS: Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7-14.3) person-weeks for any infection, 5.7 per 1000 (1.7-9.7) for symptomatic infections, and 3.5 per 1000 (0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6-16) days. CONCLUSIONS: Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community.

Challenges in Interpreting Obstetrics and Gynecology Literature.

The field of obstetrics and gynecology is constantly replenished with the newest research findings. In an era of rapidly available study publications, there are a number of challenges to interpreting the obstetrics and gynecology literature. Common pitfalls include the over reliance on the dichotomized P-value, lack of transparency, bias in study reporting, limitations of resources, absence of standardized practices and outcomes in study design, and the rare concerns for data integrity. We review these predominant challenges and their potential solutions, in interpreting the obstetrics and gynecology literature.

Adjunct Therapy at Time of Examination-Indicated Cervical Cerclage in Singleton Pregnancies: A Systematic Review and Meta-analysis.

OBJECTIVE: Physical examination-indicated cerclage for cervical insufficiency prolongs gestation, but evidence on the addition of adjuncts to further prolong latency is limited. The aim of this systematic review and meta-analysis was to compare gestational latency between those who did and did not receive adjunct antibiotic or tocolytic therapy at the time of examination-indicated cerclage. STUDY DESIGN: Electronic databases (1966-2020) were searched for randomized controlled trials (RCTs) and cohort studies comparing adjunct antibiotic or tocolytic use versus nonuse at time of examination-indicated cerclage, defined as placement for cervical dilation ≥1 cm, in a current singleton pregnancy. Studies including individuals with intra-amniotic infection, cerclage in place, nonviable gestation, or ruptured membranes were excluded. The primary outcome was latency from cerclage placement to delivery. Secondary outcomes included preterm birth, preterm premature rupture of membranes, birth weight, and neonatal survival. Risk of bias was assessed using standardized tools. Heterogeneity was assessed using χ 2 and I 2 tests. Results were pooled and analyzed using a random-effects model. This study is registered with The International Prospective Register of Systematic Reviews (PROSPERO) with registration no.: CRD42021216370. RESULTS: Of 923 unique records, 163 were reviewed in full. Three met inclusion criteria: one RCT and two retrospective cohorts. The included RCT (n = 50) and one cohort (n = 142) compared outcomes with and without adjunct use of antibiotic and tocolytic, while the second cohort (n = 150) compared outcomes with and without adjunct tocolytic, with a subpopulation also receiving antibiotics. The RCT was nested within one of the cohorts, and therefore only one of these two studies was utilized for any given outcome to eliminate counting individuals twice. Risk of bias was "critical" for one cohort study, "moderate" for the other cohort study, and "some concerns" for the RCT. Gestational latency could not be pooled and meta-analyzed. Adjunct tocolytic-antibiotic therapy was not associated with a decrease in risk of preterm delivery <28 weeks (relative risk [RR] = 0.90, 95% confidence interval [CI]: 0.65-1.26; χ 2 = 0.0, I 2 = 0.0%) or neonatal survival to discharge (RR = 1.11, 95% CI: 0.91-1.35; χ 2 = 0.05, I 2 = 0.0%). CONCLUSION: There is not enough evidence to robustly evaluate the use of adjunct tocolytics or antibiotics at time of examination-indicated cerclage to prolong latency. KEY POINTS: · Limited data on adjunct antibiotic tocolytics at cerclage.. · Widely variable practices at time of cerclage identified.. · Role of adjunct therapies at time of examination-indicated cerclage remains unclear..

Impact of the p-Value Threshold on Interpretation of Trial Outcomes in Obstetrics and Gynecology.

OBJECTIVE: Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. STUDY DESIGN: A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. RESULTS: Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n = 49) would maintain significant (p < 0.005), while 45.6% (n = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. CONCLUSION: Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. KEY POINTS: · New p-value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature.. · Highly variable methodological quality was identified.. · Reduced use of binary interpretations of significance is necessary..

Acidemia Can Occur Despite Category I Tracing.

OBJECTIVE: Electronic fetal monitoring (EFM) is intended to assess fetal well-being during labor. Our objective was to test the hypothesis that findings of a category I tracing at any time in the 60 minutes prior to delivery would rule out neonatal acidemia. STUDY DESIGN: This was a planned secondary analysis of a single-center prospective cohort study of 8,580 singleton pregnancies undergoing labor with nonanomalous infants at term. Monitoring was reviewed by obstetric research nurses at 10-minute intervals in the 60 minutes prior to delivery. The primary outcome was acidemia, defined as an umbilical cord arterial pH of 7.10 or less. RESULTS: Of the 4,274 patients included, 42 (0.98%) infants had acidemia at birth. Of the 42 infants with acidemia, 13 (31%) had category I tracings in the 30 minutes prior to delivery. Three (7%) infants had neonatal acidemia despite category I tracing for >40 minutes in the 60 minutes prior to delivery. CONCLUSION: Even in the presence of category I tracing in the 60 minutes prior to delivery, neonatal acidemia can still occur. Periods of category I should be interpreted within the clinical context of a priori risk for acidemia, knowing that it does not completely rule out acidemia.

Delayed Introduction of Parenteral Phosphorus Is Associated with Hypercalcemia in Extremely Preterm Infants.

BACKGROUND: Early parenteral nutrition (PN) provides essential macro- and micronutrients for extremely low birth weight (ELBW) infants <1000 g. Frequent cases of hypercalcemia [whole blood ionized calcium (iCa) > 1.45 mmol/L] in the first week of life while receiving PN solutions at our large quaternary center prompted investigation and 2 plan-do-study-act (PDSA) cycles to reduce rates of hypercalcemia. OBJECTIVE: We compared 2 cohorts of ELBW infants separated by PDSA cycles to evaluate and reduce the incidence of abnormal iCa concentration. METHODS: Data were recorded for 150 premature infants with mean birth weight of 726 ± 164 g, 48% male, and mean gestational age of 26 ± 2.1 wk. This process included an internal practice analysis and PDSA cycles monitored prospectively over 3 y. From December 2011 to September 2012, 66 infants received 0-1.2 mmol parenteral phosphorus supplementation/(kg ⋅ d) beginning at 72 h of life. In the second protocol, 84 infants born September 2012 to July 2013 received earlier phosphorus supplementation within 24 h of life. The peak whole blood iCa and serum phosphorus concentrations in the first week of life were monitored. RESULTS: Early introduction of phosphorus was significantly associated with a decreased mean peak iCa (1.64 ± 0.27 mmol/L to 1.50 ± 0.23 mmol/L, P = 0.001), and the incidence of severe hypercalcemia (iCa > 1.60 mmol/L) decreased from 50.0% to 21.4% (P = 0.002) in the first week of life. There was no difference in mortality, bronchopulmonary dysplasia, renal calcifications, seizures within 7 d of birth, brain calcifications, or intracranial hemorrhage between cohorts. CONCLUSION: Early introduction of phosphorus in PN solutions is associated with reduced incidence of whole blood iCa abnormalities in the first week of life and should be considered for ELBW infants. Ongoing evaluation of optimal mineral provision to this population after birth should be performed.

Coronavirus Disease 2019 (COVID-19) and Venous Thromboembolism During Pregnancy and Postpartum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk for macro- and micro-thrombi. Consensus guidelines recommend use of thromboprophylaxis in nonobstetric patients with SARS-CoV-2 infection admitted to the hospital. National-level studies evaluating venous thromboembolism (VTE) among pregnant and postpartum individuals with and without SARS-CoV-2 infection have not been completed. We performed a retrospective cohort study of individuals aged 18 years or older delivering at more than 20 weeks of gestation with data in the MarketScan Commercial Insurance Database from 2016 through 2020. Of 811,008 deliveries, SARS-CoV-2 infection during pregnancy or through 6 weeks postpartum was associated with increased risk for VTE compared with no infection (1.0% vs 0.5%, adjusted hazard ratio 2.62, 95% CI 1.60-4.29). Findings support further consideration of thromboprophylaxis in the obstetric population with SARS-CoV-2 infection.

Validation of a Vaginal Birth After Cesarean Delivery Prediction Model Without Race and Ethnicity in Individuals With Two Prior Cesarean Deliveries.

Previous models for prediction of vaginal birth after cesarean (VBAC) relied on race and ethnicity, raising concern for bias. In response, the Maternal-Fetal Medicine Units Network (MFMU) created a new prediction model without race and ethnicity for individuals with one prior cesarean delivery. We performed a secondary analysis of the MFMU Cesarean Registry database to evaluate whether the MFMU VBAC prediction model without race and ethnicity could accurately predict VBAC for individuals with two prior cesarean deliveries. Overall, 353 individuals were included and 252 (71%) had VBAC. An area under the curve for the receiver operating curve of 0.74 (95% CI, 0.69-0.80) was reported for the predicted probabilities for VBAC, indicating that the model can be used for prediction of VBAC in this population.

Impact of Prostate Cancer-related Genitourinary Radiation Injury on Mental Health Diagnosis and Treatment: Assessment of 55,425 Men.

OBJECTIVE: To investigate the association of low-grade radiation injury (LGRI) and high-grade radiation injury (HGRI) following prostate cancer treatment with mental health diagnoses and therapy. METHODS: A retrospective study of men diagnosed with prostate cancer who were treated with radiotherapy. Men were followed to assess for LGRI or HGRI using IBM MarketScan. Cohorts included: no injury (no-RI), LGRI, HGRI, and controls. Mental health diagnoses and related treatment (medication/therapy) were identified using ICD-10 codes, CPT codes, and national drug codes. A multivariable Cox proportional hazards model from time of radiation to first instance of mental health diagnosis was modeled against injury group, age, and comorbidities. RESULTS: Between 2011 and 2020 we identified 55,425 men who received radiotherapy for prostate cancer. 22,879 (41.3%) experienced a LGRI while 4128 (7.4%) experienced a HGRI. Prior to radiation therapy, mental health diagnoses were equally distributed across cohorts (P > .05). Every marker of mental health showed a step-wise increase in incidence from no-RI to LGRI to HGRI except for alcohol abuse. Use of mental health medications and therapy visits were slightly more likely in the LGRI and HGRI groups prior to radiation, however, this difference was greatly increased postradiation therapy. LGRI (HR 1.38; P < .001) and HGRI (HR 2.1; P < .001) were independently associated with an increased likelihood of mental health diagnoses. CONCLUSION: LGRI and HGRI following prostate cancer radiotherapy are associated with increased risk of mental health diagnosis, medication use, and therapy need compared to men who do not develop injuries. The most common mental health diagnoses were depression and anxiety.

Association between acquiring SARS-CoV-2 during pregnancy and post-acute sequelae of SARS-CoV-2 infection: RECOVER electronic health record cohort analysis.

Background: Little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) after acquiring SARS-CoV-2 infection during pregnancy. We aimed to evaluate the association between acquiring SARS-CoV-2 during pregnancy compared with acquiring SARS-CoV-2 outside of pregnancy and the development of PASC. Methods: This retrospective cohort study from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centred Clinical Research Network (PCORnet) used electronic health record (EHR) data from 19 U.S. health systems. Females aged 18-49 years with lab-confirmed SARS-CoV-2 infection from March 2020 through June 2022 were included. Validated algorithms were used to identify pregnancies with a delivery at >20 weeks' gestation. The primary outcome was PASC, as previously defined by computable phenotype in the adult non-pregnant PCORnet EHR dataset, identified 30-180 days post-SARS-CoV-2 infection. Secondary outcomes were the 24 component diagnoses contributing to the PASC phenotype definition. Univariable comparisons were made for baseline characteristics between individuals with SARS-CoV-2 infection acquired during pregnancy compared with outside of pregnancy. Using inverse probability of treatment weighting to adjust for baseline differences, the association between SARS-CoV-2 infection acquired during pregnancy and the selected outcomes was modelled. The incident risk is reported as the adjusted hazard ratio (aHR) with 95% confidence intervals. Findings: In total, 83,915 females with SARS-CoV-2 infection acquired outside of pregnancy and 5397 females with SARS-CoV-2 infection acquired during pregnancy were included in analysis. Non-pregnant females with SARS-CoV-2 infection were more likely to be older and have comorbid health conditions. SARS-CoV-2 infection acquired in pregnancy as compared with acquired outside of pregnancy was associated with a lower incidence of PASC (25.5% vs 33.9%; aHR 0.85, 95% CI 0.80-0.91). SARS-CoV-2 infection acquired in pregnant females was associated with increased risk for some PASC component diagnoses including abnormal heartbeat (aHR 1.67, 95% CI 1.43-1.94), abdominal pain (aHR 1.34, 95% CI 1.16-1.55), and thromboembolism (aHR 1.88, 95% CI 1.17-3.04), but decreased risk for other diagnoses including malaise (aHR 0.35, 95% CI 0.27-0.47), pharyngitis (aHR 0.36, 95% CI 0.26-0.48) and cognitive problems (aHR 0.39, 95% CI 0.27-0.56). Interpretation: SARS-CoV-2 infection acquired during pregnancy was associated with lower risk of development of PASC at 30-180 days after incident SARS-CoV-2 infection in this nationally representative sample. These findings may be used to counsel pregnant and pregnant capable individuals, and direct future prospective study. Funding: National Institutes of Health (NIH) Other Transaction Agreement (OTA) OT2HL16184.

Trends in Attempted and Successful Trial of Labor After Cesarean Delivery in the United States From 2010 to 2020.

The vaginal birth after cesarean (VBAC) delivery rate was last reported as 13.8% in 2019. However, contemporary trends in attempted and successful trial of labor after cesarean (TOLAC) delivery among individuals with prior cesarean delivery have not been evaluated. We performed a repeated cross-sectional analysis of singleton, cephalic, term deliveries in individuals with a history of one or two cesarean deliveries in the National Vital Statistics System from 2010 to 2020. Temporal trends in attempted and successful TOLAC, as well as VBAC, were characterized using joinpoint regression. Overall, 4,277,800 deliveries were included. Attempted TOLAC increased from 15.3% in 2010 to 21.7% in 2020, with an annual percent increase (relative) of 4.25% (95% CI 2.9-5.6%). Successful TOLAC increased from 69.8% to 74.7%, with an annual percent change (relative) of 0.91% (95% CI 0.7-1.2%). The VBAC rate similarly increased such that, by 2020, it was 16.2%.

Hypertensive disorders of pregnancy pre- and postaspirin guideline publication in individuals with pregestational diabetes mellitus.

BACKGROUND: The US Preventive Services Taskforce published guidelines in 2014 recommending that low-dose aspirin be initiated between 12 and 28 weeks of gestation among high-risk patients for preeclampsia prophylaxis. Moreover, low-dose aspirin is recommended by some clinicians for the prevention of preterm birth. OBJECTIVE: This study aimed to evaluate whether there is an association between the US Preventive Services Taskforce aspirin guideline hypertensive disorders of pregnancy and the rates of hypertensive disorders of pregnancy and preterm birth in individuals with pregestational diabetes mellitus. STUDY DESIGN: This was a repeated cross-sectional analysis of individuals with pregestational diabetes mellitus and at least 1 singleton delivery at >20 weeks of gestation with records available in the National Vital Statistics System between 2010 and 2018. The primary outcome was hypertensive disorders of pregnancy, and the secondary outcome was preterm birth. Demographics and clinical characteristics among individuals in the pre-US Preventive Services Taskforce guideline cohort (2010-2013) were compared with that of individuals in the post-US Preventive Services Taskforce guideline cohort (2015-2018). Multivariable regression estimated the odds ratios and 95% confidence intervals for the association between guideline publication and the selected endpoints. Effect modification was assessed for access to prenatal care using the Kotelchuck Index (<80% vs ≥80%). Furthermore, a sensitivity analysis limited to nulliparas was performed. RESULTS: Overall, 224,065 individuals were included. Individuals in the post-US Preventive Services Taskforce guideline cohort were more likely to be older, be obese, and have a history of preterm birth. In unadjusted and adjusted modeling, delivery in the post-US Preventive Services Taskforce guideline cohort was associated with hypertensive disorders of pregnancy (adjusted odds ratio, 1.25; 95% confidence interval, 1.22-1.28) and preterm birth (adjusted odds ratio, 1.10; 95% confidence interval, 1.08-1.12). The adjusted odds ratios for hypertensive disorders of pregnancy and preterm birth were more pronounced among those with less than adequate access to care. The findings were similar in the sensitivity analysis of only nulliparas. CONCLUSION: Delivery after US Preventive Services Taskforce aspirin guideline publication was associated with higher rates of hypertensive disorders of pregnancy and preterm birth in a population of individuals with diabetes mellitus. It is unknown whether patient or practitioner factors, or other changes in obstetrical care, contributed to these findings.

Physician cesarean delivery rates and severe perinatal morbidity among low-risk nulliparas.

OBJECTIVE: To estimate the individual physician cesarean delivery rate associated with serious perinatal morbidity. STUDY DESIGN: Study of nulliparous, term, singleton, vertex deliveries with maternal-neonatal dyad data (2015-2017) in the MarketScan Research Database. An individual cesarean delivery rate was calculated for all delivering physicians. The primary maternal outcome included transfusion of ≥4 units of blood, intensive care unit (ICU) admission, venous thromboembolism, or hysterectomy. The primary neonatal outcome included hypoxic ischemic encephalopathy, seizure, cardiopulmonary resuscitation or ventilator use (within 24 h), or ICU admission. Multivariable modeling of the association between physician cesarean delivery rate and each outcome was performed. RESULTS: Among 77,058 maternal-neonatal dyads, the maternal composite occurred in 1.3% of deliveries and neonatal composite in 3.6% of deliveries. The likelihood of the maternal (aOR 1.03 for each 3% increase in physician cesarean delivery rate, 95% CI 1.021-1.043) and neonatal (aOR 1.02 for each 3% increase, 95% CI 1.014-1.027) composite outcome increased linearly with increasing physician cesarean delivery rate. CONCLUSIONS: Severe perinatal morbidity was associated with increasing individual physician cesarean delivery rates.

Association Between Periviable Delivery and New Onset of or Exacerbation of Existing Mental Health Disorders.

OBJECTIVE: To evaluate whether there is an association between periviable delivery and new onset of or exacerbation of existing mental health disorders within 12 months postpartum. METHODS: We conducted a retrospective cohort study of individuals with liveborn singleton neonates delivered at 22 or more weeks of gestation from 2008 to 2017 in the MarketScan Commercial Research Database. The exposure was periviable delivery , defined as delivery from 22 0/7 through 25 6/7 weeks of gestation. The primary outcome was a mental health morbidity composite of one or more of the following: emergency department encounter associated with depression, anxiety, psychosis, posttraumatic stress disorder, adjustment disorder, self-harm, or suicide; new psychotropic medication prescription; new behavioral therapy visit; and inpatient psychiatry admission in the 12 months postdelivery. Secondary outcomes included components of the primary composite. Those with and without periviable delivery were compared using multivariable logistic regression adjusted for clinically relevant covariates, with results reported as adjusted incident rate ratios (aIRRs). Effect modification by history of mental health diagnoses was assessed. Incidence of the primary outcome by 90-day intervals postdelivery was assessed. RESULTS: Of 2,300,244 included deliveries, 16,275 (0.7%) were periviable. Individuals with periviable delivery were more likely to have a chronic health condition, to have undergone cesarean delivery, and to have experienced severe maternal morbidity. Periviable delivery was associated with a modestly increased risk of the primary composite outcome, occurring in 13.8% of individuals with periviable delivery and 11.0% of individuals without periviable delivery (aIRR 1.18, 95% CI 1.12-1.24). The highest-risk period for the composite primary outcome was the first 90 days in those with periviable delivery compared with those without periviable delivery (51.6% vs 42.4%; incident rate ratio 1.56, 95% CI 1.47-1.66). CONCLUSION: Periviable delivery was associated with a modestly increased risk of mental health morbidity in the 12 months postpartum.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy.

Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Trends in Hypertensive Disorders of Pregnancy in the United States From 1989 to 2020.

Hypertensive disorders of pregnancy affect up to 8% of pregnancies, but updated national trends are lacking. We performed a repeated cross-sectional analysis of individuals with singleton pregnancies who delivered at greater than 20 weeks of gestation, with data in the U.S. National Vital Statistics System from 1989 to 2020. Temporal trends in hypertensive disorders of pregnancy, chronic hypertension, and eclampsia were characterized using joinpoint regression. Overall, 122,329,914 deliveries were included. Hypertensive disorders of pregnancy increased from 2.79% in 1989 to 8.22% in 2020, representing an average annual percentage change (AAPC) of 3.6% (95% CI 3.0-4.1%). Chronic hypertension increased (AAPC 4.1%, 95% CI 3.3-4.9%), whereas eclampsia decreased (AAPC -2.5%, 95% CI -4.0% to -1.0%). Hypertensive disorders of pregnancy are associated with significant morbidity and mortality; the rising incidence is concerning.