Predicting neonatal respiratory morbidity by lamellar body count and gestational age.

AIMS: To develop a predictive model for assessing the risk of developing neonatal respiratory morbidity using lamellar body counts (LBCs) and gestational age (GA) to provide a more patient-specific assessment. METHODS: Retrospective cohort study of patients' ≥32 weeks' gestation who received amniocentesis with LBC analysis over a 9-year period. Respiratory morbidity was defined as respiratory distress syndrome, transient tachypnea of the newborn or oxygen requirement for >24 h. Logistic regression analyses were used to predict the absolute risk and odds of respiratory morbidity as a function of GA and lamellar body count. RESULTS: Two hundred and sixty-seven mother-infant pairs included in the analysis with 32 cases (12.0%) of respiratory morbidity. When compared to those without respiratory morbidity, neonates with respiratory morbidity had amniocentesis performed at an earlier median GA, had lower mean birthweight and had lower median LBC (P<0.01). The GA specific absolute risks and odds ratios for the presence of respiratory morbidity were calculated. The predicted absolute risks of neonatal respiratory morbidity ranged from 38% at 32 weeks to 6% at 40 weeks when LBC were 35,000/µL. CONCLUSION: GA specific predicted risk of neonatal respiratory morbidity using LBC provides a statistical model, which can aid clinicians in individually counseling patients regarding the absolute risk of their neonate developing respiratory morbidity.

Idiopathic Polyhydramnios: Severity and Perinatal Morbidity.

Objective To estimate the association between the severity of idiopathic polyhydramnios and adverse outcomes. Study Design Retrospective cohort study of deliveries at one hospital from 2000 to 2012 with an amniotic fluid index (AFI) measurement ≥24 + 0 weeks' gestation. Pregnancies complicated by diabetes, multiples, or fetal anomalies were excluded. Exposure was the degree of polyhydramnios: normal (AFI 5-24 cm), mild (≥ 24-30 cm), and moderate-severe (> 30 cm). Primary outcomes were perinatal mortality, neonatal intensive care unit (NICU) admission, and postpartum hemorrhage. Results There were 10,536 pregnancies: 10,188 with a normal AFI, 274 mild (78.74%), and 74 moderate-severe polyhydramnios (21.26%). Adverse outcomes were increased with idiopathic polyhydramnios: NICU admission (adjusted odds ratio [AOR] 3.71, 95% confidence interval [CI] 2.77-4.99), postpartum hemorrhage (AOR 15.81, 95% CI 7.82-31.96), macrosomia (AOR 3.41, 95% CI 2.61-4.47), low 5-minute Apgar score (AOR 2.60, 95% CI 1.57-4.30), and cesarean (AOR 2.16, 95% CI 1.74-2.69). There were increasing odds of macrosomia (mild: AOR 3.19, 95% CI 2.36-4.32; moderate-severe: AOR 4.44, 95% CI 2.53-7.79) and low 5-minute Apgar score (mild: AOR 2.24, 95% CI 1.23-4.08; moderate-severe: AOR 3.93, 95% CI 1.62-9.55) with increasing severity of polyhydramnios. Conclusion Idiopathic polyhydramnios is independently associated with increased risks of morbidity. There appears to be a dose-response relationship for neonatal macrosomia and low 5-minute Apgar score risks.

A single center's experience with noninvasive prenatal testing.

PURPOSE: Massively parallel sequencing to detect fetal aneuploidy has high sensitivity and specificity for the detection of trisomies 21, 18, and 13 in high-risk populations. The purpose of our study was to review our institution's experience with the use of noninvasive prenatal testing for aneuploidy screening. METHODS: This was a descriptive study of patients who had undergone noninvasive prenatal testing between January and September 2012 at the UNC Prenatal Diagnosis unit. RESULTS: Two hundred and eight women had undergone noninvasive prenatal testing during the study period. The majority of patients were white (62.9%) and of advanced maternal age (71.2%). The fetal fraction was below the threshold in three obese patients (1.4%). An abnormal noninvasive prenatal test (aneuploidy detected or "unclassified" result) was reported in 6.3% (13/208) of the patients. Noninvasive prenatal testing had a combined sensitivity of 87.5% and specificity of 99.5% for detection of trisomies 21, 18, and 13. There were "unclassified" results in 11.1% (5/45) of the patients. Over the study period, the number of patients requesting noninvasive prenatal testing increased monthly. The rate of amniocenteses significantly declined (8.1% before vs. 5.3% after noninvasive prenatal testing, P < 0.01). CONCLUSION: An increase in uptake of noninvasive prenatal testing and a significant decline in amniocentesis procedures were observed. The rates of "unclassified," false-positive, and false-negative results were higher than anticipated based on published preclinical trials.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Factors influencing visualization of the intracranial translucency during first-trimester screening for aneuploidy.

OBJECTIVE: Neural tube defects occur in 1/2000 live births. Imaging of the intracranial translucency (IT) during first-trimester screening has been proposed as an early screen for open neural tube defects (ONTD). This study evaluates visualization of the IT and factors influencing its visualization during first-trimester ultrasound screening for aneuploidy. METHODS: Ultrasound images for patients undergoing first-trimester screening for aneuploidy from January 1, 2009, through July 31, 2009, were reviewed for IT visualization, defined as an intracranial translucency parallel to the nuchal translucency. Second-trimester ultrasounds and delivery records were reviewed for the presence of fetal ONTD. RESULTS: The IT was visualized in 74.8% of 759 gestations studied at a mean gestational age of 12 weeks, 5 days. Among gestations where the IT was visualized, we found a larger crown-rump length, lower maternal weight, and more fetuses in the supine position (p < 0.0001). Predictive models for visualization of the IT were formulated based on these factors. CONCLUSION: The IT can be visualized in the majority of patients in the standard midsagittal plane used for measurement of the nuchal translucency. Visualization is significantly associated with crown-rump length, gestational age, maternal weight, and fetal position. Visualization of the IT is feasible.

Maternal antimullerian hormone levels do not predict fetal aneuploidy.

PURPOSE: To determine if diminished ovarian reserve (measured by maternal antimullerian hormone (AMH) levels), is associated with fetal aneuploidy (determined by prenatal karyotype). METHODS: This case-control study included 213 women with singleton pregnancies who underwent both serum aneuploidy screening and invasive prenatal diagnosis. 18 patients carrying an aneuploid fetus served as cases and the remaining 195 women with a euploid fetus were controls. Serum AMH was measured using two assays: AMHbc (Beckman-Coulter) and AMHdsl (Diagnostic Systems Laboratories). Karyotypes were determined by chorionic villus sampling or amniocentesis. RESULTS: AMHbc levels did not differ between women with an aneuploid fetus and women with a euploid fetus (p = 0.46) and did not predict aneuploidy (ROC Area = 0.57). Additionally, AMHbc values declined significantly with advancing gestational age. CONCLUSIONS: Maternal AMH does not appear to be a marker of fetal aneuploidy in ongoing pregnancies. Contrary to previous reports, we found a significant decline in maternal AMH levels with advancing gestational age.

Risk Factors for Postcesarean Maternal Infection in a Trial of Extended-Spectrum Antibiotic Prophylaxis.

OBJECTIVE: To identify maternal clinical risk factors for postcesarean maternal infection in a randomized clinical trial of preincision extended-spectrum antibiotic prophylaxis. METHODS: We conducted a planned secondary analysis of a randomized clinical trial. Patients were 24 weeks of gestation or greater and delivered by cesarean after a minimum of 4 hours of ruptured membranes or labor. All participants received standard preincision prophylaxis and were randomized to receive azithromycin or placebo. The primary outcome for this analysis is maternal infection: a composite outcome of endometritis, wound infection (superficial or deep), or other infections occurring up to 6 weeks postpartum. Maternal clinical characteristics associated with maternal infection, after controlling for azithromycin assignment, were identified. These maternal factors were included in a multivariable logistic regression model for maternal infection. RESULTS: Of 2,013 patients, 1,019 were randomized to azithromycin. Overall, 177 (8.8%) had postcesarean maternal infection. In the final adjusted model, compared with the reference groups, women of black race-ethnicity, with a nontransverse uterine incision, with duration of membrane rupture greater than 6 hours, and surgery duration greater than 49 minutes, were associated higher odds of maternal infection (all with adjusted odds ratios [ORs] of approximately 2); azithromycin was associated with lower odds of maternal infection (adjusted OR 0.4, 95% confidence interval 0.3-0.6). CONCLUSION: Despite preincision azithromycin-based extended-spectrum antibiotic prophylaxis, postcesarean maternal infection remains a significant source of morbidity. Recognition of risk factors may help guide innovative prevention strategies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT012235546.