Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Risk of Severe Maternal Morbidity in Birthing People With Opioid Use Disorder.

INTRODUCTION: We examined severe maternal morbidity (SMM) among birthing people with opioid use disorder (OUD) and evaluated the extent to which differences in SMM exist by race and ethnicity. METHODS: We performed a retrospective cohort study using hospital discharge data for all Massachusetts births between 2016 and 2020. SMM rates for all SMM indicators, except transfusions, were computed for those diagnosed with and without OUD. Multivariable logistic regression was used to examine the association between OUD and SMM after adjusting for patient and hospital characteristics, including race and ethnicity. RESULTS: Among 324,012 childbirths, the SMM rate was 148 (95% confidence interval [CI]. 115-189) per 10,000 childbirths among birthing people with OUD compared with 88 (95% CI, 85-91) for those without. In adjusted models, both OUD and race/ethnicity were significantly associated with SMM. Birthing people with OUD had 2.12 (95% CI, 1.64-2.75) times the odds of experiencing an SMM event compared with those without. Non-Hispanic Black and Hispanic birthing people were at 1.85 (95% CI, 1.65-2.07) and 1.26 (95% CI, 1.13-1.41) higher odds of experiencing SMM compared with non-Hispanic White birthing people. Among birthing people with OUD, the odds of SMM were not significantly different between birthing people of color and non-Hispanic White individuals. CONCLUSIONS: Birthing people with OUD are at an elevated risk of SMM, underscoring the need for improved access to OUD treatment and increased support. Perinatal quality improvement collaboratives should measure SMM in bundles aimed at improving outcomes for birthing people with OUD.

Assessing the clinical utility of toxicology testing in the peripartum period.

BACKGROUND: Toxicology testing is frequently used as a means of gathering objective data about substance use in pregnancy, but little is known about the clinical utility of testing in the peripartum setting. OBJECTIVE: This study aimed to characterize the utility of obtaining maternal-neonatal dyad toxicology testing at the time of delivery. STUDY DESIGN: We performed a retrospective chart review of all deliveries in a single healthcare system in Massachusetts between 2016 and 2020, and identified deliveries with either maternal or neonatal toxicology testing at delivery. An unexpected result was defined as a positive test for a nonprescribed substance that was not known on the basis of clinical history, self-report, or previous toxicology testing within a week of delivery, excluding results for cannabis. We evaluated the characteristics of maternal-infant dyads with unexpected positive results, unexpected positive results by rationale for testing, changes in clinical management after an unexpected positive test, and maternal outcomes in the year after delivery using descriptive statistics. RESULTS: Of the 2036 maternal-infant dyads with toxicology tests performed during the study period, there were 80 (3.9%) with an unexpected positive result. Diagnosis of substance use disorder with active use in the last 2 years was the clinical rationale for testing that yielded the greatest number of unexpected positive results (10.7% of total tests ordered for this rationale). Inadequate prenatal care (5.8%), maternal use of medication for opioid use disorder (3.8%), maternal medical indications such as hypertension or placental abruption (2.3%), history of substance use disorder in remission (1.7%), or maternal cannabis use (1.6%) yielded lower rates of unexpected results compared with a recent substance use disorder (within the last 2 years). Solely on the basis of findings from unexpected test results, 42% of dyads were referred to child protective services, 30% of dyads had no documentation of maternal counseling during delivery hospitalization, and 31% did not receive breastfeeding counseling after an unexpected test; 22.8% had monitoring for neonatal opioid withdrawal syndrome. Postpartum, 26 (32.5%) were referred to substance use disorder treatment, 31 (38.8%) attended a postpartum mental health visit, and only 26 (32.5%) attended a postpartum visit. Fifteen individuals (18.8%) were readmitted in the year after delivery, all for substance-related medical complications. CONCLUSION: Unexpected positive toxicology results at delivery were uncommon, particularly when tests were sent for frequently used clinical rationales for testing, suggesting a need to revisit guidelines surrounding appropriateness of indications for toxicology testing. The poor maternal outcomes in this cohort highlight a missed opportunity for maternal connection to counseling and treatment in the peripartum period.

Limited Utility of Toxicology Testing at Delivery for Perinatal Cannabis Use.

OBJECTIVES: To describe the characteristics of individuals undergoing toxicology testing at delivery for a sole indication of cannabis use and to evaluate the rate of unexpected positive toxicology testing results among this cohort. METHODS: This retrospective cohort study included dyads with a maternal history of cannabis use who underwent peripartum toxicology testing between 2016 and 2020 at 5 birthing hospitals in Massachusetts. We collected information on maternal demographic characteristics and toxicology test results and reviewed records of dyads with unexpected positive results to identify additional social risk factors and clinical outcomes. RESULTS: Of 60 608 live births reviewed, 1924 dyads underwent toxicology testing, including 614 (31.9%) for a sole indication of cannabis use. Significantly greater percentages of patients in the cannabis cohort were <25 years old (32.4% vs 6.1% of the birthing population, P <.001), non-Hispanic Black (32.4% vs 8.1%, P < .001), Hispanic or Latino (30.5% vs 15.5%), American Indian/Alaskan (0.7% vs 0.1%), and publicly insured (39.9% vs 15.6%, P <.001). Eight of the 614 dyads (1.3%) had an unexpected positive toxicology test result, including 2 (0.3%) unexpectedly positive for opioids. Seven dyads (1.1%) had false positive test results for unexpected substances. Only 1 test result changed clinical management; a urine test positive for opioids prompted monitoring (but not medication) for neonatal opioid withdrawal syndrome. CONCLUSIONS: Toxicology testing of patients for a sole indication of cannabis use, without other risk factors, may be of limited utility in elucidating other substance use and may exacerbate existing disparities in perinatal outcomes.

Disparities in Maternal-Infant Drug Testing, Social Work Assessment, and Custody at 5 Hospitals.

OBJECTIVE: To evaluate for disparities in peripartum toxicology testing among maternal-infant dyads across a hospital network and subsequent child protective services (CPS) involvement. METHODS: Retrospective chart review of 59,425 deliveries at 5 hospitals in Massachusetts between 2016 and 2020. We evaluated associations between maternal characteristics, toxicology testing, and child welfare involvement with disproportionality risk ratios and hierarchical logistical regression. RESULTS: Toxicology testing was performed on 1959 (3.3%) dyads. Younger individuals and individuals of color were more likely to be tested for cannabis use or maternal medical complications compared to white non-Hispanic individuals. Among those without a substance use disorder, age <25 (adjusted odds ratio [aOR] 2.81; 95% confidence interval [CI], 2.43-3.26), race and ethnicity (non-Hispanic Black (aOR 1.80; 95% CI, 1.52-2.13), Hispanic (aOR 1.23; 95% CI, 1.05-1.45), mixed race/other (aOR 1.40; 95% CI, 1.04, 1.87), unavailable race (aOR 1.92; 95% CI, 1.32-2.79), and public insurance (Medicaid [aOR 2.61; 95% CI, 2.27-3.00], Medicare [aOR 13.76; 95% CI, 9.99-18.91]) had increased odds of toxicology testing compared to older, white non-Hispanic, and privately insured individuals. The disproportionality ratios in testing were greater than 1.0 for individuals under 25 years old (3.8), Hispanic individuals (1.6), non-Hispanic Black individuals (1.8), individuals of other race (1.2), unavailable race (1.8), and individuals with public insurance (Medicaid 2.6; Medicare 10.6). Among dyads tested, race and ethnicity was not associated with CPS involvement. CONCLUSIONS: Peripartum toxicology testing is disproportionately performed on non-white, younger, and poorer individuals and their infants, with cannabis use and medical complications prompting testing more often for patients of color than for white non-Hispanic individuals.

Fentanyl in the labor epidural impacts the results of intrapartum and postpartum maternal and neonatal toxicology tests.

BACKGROUND: A positive urine fentanyl toxicology test may have considerable consequences for peripartum individuals, yet the extent to which fentanyl administration in a labor epidural may lead to such a positive test is poorly characterized. OBJECTIVE: This study aimed to quantify the extent to which neuraxial fentanyl in labor neuraxial analgesia can lead to a positive peripartum maternal or neonatal urine toxicology test. STUDY DESIGN: We performed a prospective cohort study of pregnant participants planning a vaginal delivery with neuraxial analgesia. Participants with a history of substance use disorder, hypertension, or renal or liver disease were excluded. A urine sample was collected before initiation of neuraxial analgesia, each time the bladder was emptied during labor, and up to 4 times postpartum. Neonatal urine was collected once. Urine fentanyl testing was performed using 2 common toxicology testing methods, namely immunoassay and liquid chromatography with tandem mass spectrometric detection. RESULTS: A total of 33 maternal-infant dyads yielded a total of 178 urine specimens. All maternal specimens were negative for fentanyl using liquid chromatography with tandem mass spectrometric analysis and immunoassay before initiation of neuraxial analgesia. Intrapartum, 26 of 30 (76.7%) participants had positive liquid chromatography with tandem mass spectrometry results for fentanyl or its metabolites, and 12 of 30 (40%) participants had positive immunoassay results. Postpartum, 19 of 21 (90.5%) participants had positive liquid chromatograph with tandem mass spectrometric results, and 13 of 21 (61.9%) had a positive immunoassay result. Of the 13 neonatal specimens collected, 10 (76.9%) were positive on liquid chromatography with tandem mass spectrometry analysis, the last of which remained positive 29 hours and 50 minutes after delivery. CONCLUSION: Neuraxial fentanyl for labor analgesia may lead to positive maternal and neonatal toxicology tests at various times after epidural initiation and cessation and at different rates depending on the testing method used. Caution should be used in interpreting toxicology test results of individuals who received neuraxial analgesia to avoid false assumptions about nonprescribed use.

Report of Prolonged Neonatal Hypoglycemia in Three Infants of Mothers With Variants in HNF1A.

Background/Objective: Genetic variants in hepatic nuclear factor 1α (HNF1A) cause maturity-onset diabetes of the young (MODY). We sought to examine whether HNF1A MODY variants also cause neonatal hypoglycemia. Case Report: We present 3 infants with variants in HNF1A shared with their mothers. The infants experienced neonatal hypoglycemia, 2 extending beyond 1 year and the third resolving by 28 days, and all were large for gestational age (birth weights of >99th percentile). In 2 cases, genetic testing for neonatal hypoglycemia revealed pathogenic variants in HNF1A; 1 mother was previously diagnosed with HNF1A MODY, and the other's genetic testing and ultimate MODY diagnosis were prompted by her child's hypoglycemia workup. In the third case, the infant's persistent hypoglycemia prompted genetic testing, revealing an HNF1A variant of uncertain significance, which was then identified in the mother. Discussion: Genetic variants causing HNF1A MODY have not been definitively linked to neonatal hypoglycemia or fetal overgrowth in utero. MODY caused by HNF1A is clinically similar to that caused by HNF4A, for which a causal relationship with neonatal hypoglycemia is more certain. Case reports have previously implicated variants in HNF1A in congenital hyperinsulinism; however, these cases have generally not been in families with MODY. The cases presented here suggest that HNF1A variants causing MODY may also cause neonatal hypoglycemia. Conclusion: Although confounding factors make the assessment of neonatal hypoglycemia challenging, these cases offer potential support for single genetic variants in HNF1A causing both MODY and neonatal hypoglycemia, with associated fetal overgrowth in utero.

Impact of a Hybrid Model of Prenatal Care on the Diagnosis of Fetal Growth Restriction.

OBJECTIVE: Fetal growth restriction (FGR) is associated with poor neonatal outcomes and stillbirth, and screening via fundal height or ultrasound is routinely performed. During the novel coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid model of prenatal care which decreased the frequency of in-person visits and incorporated telemedicine visits. We sought to determine if prenatal FGR diagnoses decreased with this hybrid model compared with routine prenatal care. STUDY DESIGN: This was a retrospective cohort study of singleton nonanomalous neonates with birth weights <10th percentile at term. The "routine care" group was consisted of those who born between April and July 2019 with in-person prenatal care, and the "hybrid care" group was consisted of those who born between April and July 2020 with both in-person and telemedicine prenatal cares at a collaborative academic practice. The primary outcome was the rate of diagnosis of small for gestational age (SGA) as defined as infant birth weight <10th percentile without a prenatal diagnosis of FGR. The secondary outcome was timing of diagnosis of FGR. RESULTS: Overall, 1,345 and 1,296 women gave birth in the routine and hybrid groups, respectively. The number of in-person prenatal care visits decreased from 15,024 in the routine period to 7,727 in the hybrid period; 3,265 telemedicine visits occurred during the hybrid period. The total number of prenatal patients remained relatively stable at 3,993 and 3,753 between periods. Third trimester ultrasounds decreased from 2,929 to 2,014 between periods. Birth weights <10 percentile occurred in 115 (8.6%) births during the routine period and 79 (6.1%) births during the hybrid period. Of 115, 44 (38.3%) cases were prenatally diagnosed with FGR in the routine versus 28 of 79 (35.4%) in the hybrid group (p = 0.76). Median gestational age at diagnosis did not vary between groups (36 vs. 37 weeks, p = 0.44). CONCLUSION: A hybrid prenatal care model did not alter the detection of FGR. Future efforts should further explore the benefits of incorporating telemedicine into prenatal care. KEY POINTS: · Telemedicine visits can provide comprehensive prenatal care.. · FGR was diagnosed equally with hybrid versus routine prenatal care.. · FGR diagnosis was not delayed with hybrid care..

Informed consent is poorly documented when obtaining toxicology testing at delivery in a Massachusetts cohort.

BACKGROUND: Positive toxicology testing at delivery can have enormous consequences for birthing persons and their families, including charges of child abuse or neglect and potential loss of custody for the birthing parent. Therefore state and national guidelines stipulate that, clinicians must obtain consent before toxicology testing at delivery. OBJECTIVE: This study aimed (1) to determine clinician documentation of patient consent for peripartum toxicology testing and (2) to characterize the extent to which patient and hospital characteristics were associated with documented consent. STUDY DESIGN: This was a retrospective cohort of individuals who underwent toxicology testing within 96 hours of delivery between April 2016 and April 2020 at 5 affiliated hospitals across Massachusetts. Medical records were reviewed for documentation of clinician intent to obtain maternal toxicology, testing indication, verbal consent to testing, and child protective services involvement. Hierarchical multivariable logistic regression was used to examine the association between patient and hospital characteristics and documentation of verbal consent. RESULTS: Among 60,718 deliveries, 1562 maternal toxicology tests were obtained. Verbal consent for testing was documented in 466 cases (29.8%). Documented consent was lacking across most demographic groups. Consent was no more likely to be documented when a report was filed with child protective services and less likely in cases where the birthing parent lost custody before discharge (P=.003). In our multivariable model, consent was least likely to be documented when a maternal complication (abruption, hypertension, preterm labor, preterm premature rupture of membranes, or intrauterine fetal demise) was the indication for testing (adjusted odds ratio, 0.46; 95% confidence interval, 0.28-0.76). Verbal consent was twice as likely to be documented in delivery hospitals with established consent policies (adjusted odds ratio, 2.10; 95% confidence interval, 1.01-4.37). CONCLUSION: Consent for toxicology testing at delivery seemed to be infrequently obtained on the basis of clinician documentation. Provider education and hospital policies for obtaining informed consent are needed to protect the rights of birthing individuals.

Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors.

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.

Acceptability of virtual prenatal care: thinking beyond the pandemic.

OBJECTIVE: Obstetrical providers have had to rapidly rethink how to provide comprehensive prenatal care during the SARS-CoV-2 pandemic. At our institution, we implemented a risk-stratified approach to incorporating telemedicine into our prenatal care. The objective of this study was to determine acceptability of virtual prenatal care and preferences for future pregnancies among our patient population. STUDY DESIGN: We sought feedback from a convenience sample of patients regarding the acceptability of virtual prenatal care and desires for future pregnancies. RESULTS: We found that virtual prenatal care is acceptable to patients, and the majority would like to incorporate it into future post-pandemic pregnancy care, although preferences differ by race. CONCLUSION: Virtual prenatal care should continue to be employed in post-pandemic obstetric practice. Obstetrical providers must determine how to incorporate this practice in a risk-stratified and equitable fashion.

Sequencing Cell-free Fetal DNA in Pregnant Women With GCK-MODY.

CONTEXT: Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available. OBJECTIVE: This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA. METHODS: This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT). RESULTS: In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type-linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case. CONCLUSION: We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.

Relationship between carbohydrate intake and oral glucose tolerance test results among pregnant women.

AIMS: Evaluate the relationship between self-reported carbohydrate intake and oral glucose tolerance test (OGTT) results in pregnancy. METHODS: We measured carbohydrate intake using 24-hour dietary recall and performed a 2-hour 75-gram OGTT in 95 pregnant women with risk factors for gestational diabetes (GDM) at a median of 26 weeks' gestation. We tested for associations between carbohydrate intake in the 24 hours preceding the OGTT and 60-minute OGTT glucose, glucose at other timepoints, and glucose area under the curve (AUC) using linear regression, with adjustment for potential confounders. RESULTS: We observed an inverse linear relationship between carbohydrate intake (median 237 grams [interquartile range: 196, 303]) and 60-minute OGTT glucose. For every 50 gram reduction in carbohydrate intake, there was an 8.9 mg/dl increase in 60-minute OGTT glucose (P < 0.01) in an adjusted model. Lower carbohydrate intake was also associated with higher 30-minute (adjusted ß = -6.5 mg/dl, P < 0.01) and 120-minute OGTT glucose (adjusted ß = -8.1 mg/dl, P = 0.01) and AUC (adjusted ß = -767, P < 0.01). CONCLUSIONS: Carbohydrate intake in the day preceding an OGTT in pregnancy is associated with post-load glucose values, with lower carbohydrate intake predicting higher glucose levels and higher carbohydrate intake predicting lower glucose levels. Carbohydrate restriction or excess before an OGTT may affect GDM diagnosis.

Longitudinal Changes in the Relationship Between Hemoglobin A1c and Glucose Tolerance Across Pregnancy and Postpartum.

OBJECTIVE: To characterize the relationship between hemoglobin A1c (HbA1c) levels and glucose tolerance across pregnancy and postpartum. DESIGN AND PARTICIPANTS: In a longitudinal study of pregnant women with gestational diabetes risk factors (N = 102), we performed oral glucose tolerance testing (OGTT) and HbA1c measurements at 10-15 weeks of gestation, 24-30 weeks of gestation (N = 73), and 6-24 weeks postpartum (N = 42). Complete blood counts were obtained from clinical records. We calculated HbA1c-estimated average glucose levels and compared them with mean OGTT glucose levels (average of fasting, 1- and 2-hour glucose levels). Linear mixed effects models were used to test for longitudinal changes in measurements. RESULTS: Mean OGTT glucose increased between 10-15 and 24-30 weeks of gestation (ß = 8.1 mg/dL, P = .001), while HbA1c decreased during the same time period (ß = -0.13%, P < .001). At 10-15 weeks of gestation and postpartum the discrepancy between mean OGTT glucose and HbA1c-estimated average glucose was minimal (mean [standard deviation]: 1.2 [20.5] mg/dL and 0.16 [18.1] mg/dL). At 24-30 weeks of gestation, the discrepancy widened (13.2 [17.9] mg/dL, ß = 12.7 mg/dL, P < .001, compared to 10-15 weeks of gestation, with mean OGTT glucose being higher than HbA1c-estimated average glucose). Lower hemoglobin at 24-30 weeks of gestation was associated with a greater discrepancy (ß = 6.4 mg/dL per 1 g/dL lower hemoglobin, P = .03 in an age- and gestational age-adjusted linear regression model). CONCLUSIONS: HbA1c accurately reflects glycemia in the 1st trimester, but underestimates glucose intolerance in the late 2nd trimester. Lower hemoglobin level is associated with greater underestimation. Accounting for gestational age and maternal hemoglobin may improve the clinical interpretation of HbA1c levels during pregnancy.

High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes.

OBJECTIVE: To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. STUDY DESIGN: This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th-95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. RESULTS: A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant

Low Fetal Fraction and Birth Weight in Women with Negative First-Trimester Cell-Free DNA Screening.

OBJECTIVE: To determine the association between low fetal fraction and birth weight among women with a negative cell-free DNA (cfDNA) result for common aneuploidies in the first trimester. STUDY DESIGN: This is a retrospective cohort of women who delivered a singleton between July 2016 and June 2018 at a single institution and had normal cfDNA testing in the first trimester. The primary variable of interest was "low fetal fraction," which was defined as fetal fractions less than 5th percentile among all fetal fractions in the cohort (fetal fraction < 5.34%). The primary outcomes were birth weight ≤ 5th and ≤ 10th percentiles. Multivariable logistic regressions assessed for the association between low fetal fraction and birth weight. RESULTS: A total of 7,478 women delivered a singleton at ≥24 weeks' gestation, of which 2,387 (32%) underwent genetic screening through cfDNA; the majority were in the first trimester (n = 2,052 [86%]). 2,035 met the inclusion criteria. Birth weight ≤ 5th percentile was significantly higher in the low fetal fraction group (6.9 vs. 3.2%; p = 0.04). A low fetal fraction was associated with higher odds of an infant with a low birth weight: adjusted odds ratio (aOR) of 2.32 (95% CI 1.15-4.67) for birth weight ≤ 10th percentile (p = 0.02) and aOR of 3.73 (95% CI 1.40-9.03) for birth weight ≤ 5th percentile (p = 0.004). CONCLUSION: Low fetal fractions of ≤ 5th percentile were associated with an increased risk of birth weights ≤ 5th and ≤ 10th percentiles in women with negative cfDNA screening in the first trimester. Future work is needed to further investigate this relationship and to determine the potential clinical implications, such as third-trimester screening for growth restriction in women with low fetal fractions and negative cfDNA screening results.

Management of the Cardiovascular Complications of Substance Use Disorders During Pregnancy.

PURPOSE OF REVIEW: Substance use disorder in pregnancy and subsequent cardiovascular complications are on the rise in the USA. The care of pregnant women with substance use disorder is complex, and requires a thorough understanding of mechanisms of action, pathophysiology, and cardiovascular response during pregnancy. The goal of this review is to provide information about the most common drugs of abuse in pregnancy and to recommend management guidelines. RECENT FINDINGS: Pregnant women with substance use disorder are at increased risk of significant cardiovascular complications, both as a direct effect of acute intoxication as well as the secondary risk from infection and cardiotoxicity associated with chronic use. This risk must be considered in the antepartum management, delivery, and postpartum periods. Understanding the increased cardiovascular risk of pregnant women with substance use disorder, as well as specific drug interactions, anesthesia considerations, best practices, and management considerations, is important for all clinicians caring for this population.

Preconception Counseling for Women With Cardiac Disease.

OPINION STATEMENT: All providers who care for reproductive-aged women with cardiac disease should assess these patients' desires and plans for pregnancy at every encounter. For those considering pregnancy, preconception counseling, often performed by a maternal-fetal medicine specialist, can help patients understand the potential implications of pregnancy on their health and estimate the risks of an adverse cardiac event prior to conceiving. There are cardiac conditions, such as pulmonary hypertension and aortic stenosis, in which pregnancy may be contraindicated given the high morbidity and mortality; there are tools available to help quantify a patient's risk. Furthermore, some cardiac lesions may be inherited, which may warrant parental testing or a discussion of strategies to reduce the risk of an affected child, such as the use of assisted reproductive technologies. Preconception counseling is also important to identify other maternal risk factors, such as obesity, hypertension, and tobacco use, which are associated with adverse pregnancy outcomes and develop a strategy to mitigate their potential risks, ideally before pregnancy. For women on medications for their heart disease or other comorbidities, a thorough review of these medications can potentially avoid an exposure to a teratogen during conception and pregnancy. Once pregnant, a patient's obstetrical provider and cardiologist should work together to outline a plan to monitor a patient's cardiac status as the normal physiologic changes of pregnancy, such as increased blood volume and cardiac output, may challenge a patient's functional status and increase the risk for an adverse outcome. Labor and delivery planning are essential to ensure patients with cardiac disease deliver at the appropriate hospital, equipped with the staff and resources to care for women with complex conditions. In summary, preconception counseling aims to stratify a patient's risk in pregnancy, inform patients of possible complications, and discuss strategies to best ensure a healthy mother and baby during pregnancy, labor, and delivery.