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Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy (1H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated 1H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury.

OBJECTIVES: Unscheduled admission to the PICU is a stressful experience for families. During the admission process, families communicate with 4 types of clinicians (resident, nurse practitioner, fellow, and attending physician). All clinicians must manage family stress while communicating concise, accurate information. The manner and variability in how different clinicians communicate with families at the time of PICU admission is not yet known. METHODS: We performed a prospective observational study to evaluate communication patterns of various clinician types, including the length of communication encounters and the number of provider interruptions at the time of admission to the PICU during a 3-month period. All nonscheduled admissions to the PICU were eligible for enrollment. The admission intake was audio recorded and directly observed. RESULTS: We observed 45 different family–clinician interactions for a total of 19 unique family encounters (48% of eligible admissions). Residents and nurse practitioners spent the most time communicating with families (14.3 and 19 minutes, respectively) compared with fellows (7.3 minutes) and attending physicians (6.6 minutes). Residents were frequently interrupted by pages and phone calls (64% of interactions) and spoke at a higher reading level than all other clinician types (P = .03; 95% confidence interval 74.6–83.9). Qualitatively, residents had more challenges coping with distractions, acknowledging parental emotions, and aligning with parental goals compared with other clinician types. CONCLUSIONS: Resident trainees spend significantly more time with families and, during this time, are burdened with frequent interruptions. In this stressful communication environment, residents encounter more barriers to communication and may require additional communication skills to manage relaying complex information while simultaneously responding to parental emotions.

Introduction: Transition of medical care from pediatrics to adult can be challenging and difficult. Until the 1970s, only half of patients diagnosed with sickle cell disease (SCD) reached adulthood. As a result of patients living longer, there is a growing need to understand factors that influence readiness to transition. This descriptive study examined age-specific SCD knowledge, self-management skills of patients, and education goals in a convenience sample of patients and their parents. Method: One hundred eighty-three transition surveys were distributed during scheduled hematology clinic visits. Surveys were analyzed with descriptive statistics to determine differences of knowledge between age groups, self-care skills, vocational supports, and educational goals. The parent group consists of children aged 0 to 4 years (32), 5 to 8 years (52), 9 to 11 years (12); the child group consists of children aged 9 to 11 years (24) and 12 to 15 years (31); and adolescent and young adult (AYA) group consists of children aged 16 to 21 years (32). Results: Indeed, 50% of parents of the 0 to 4 years age group and 33% of 5 to 8 years age group knew their child’s baseline hemoglobin. Only 38% of patients aged 16 to 21 years knew their baseline hemoglobin. However, 79% of patients aged 9 to 11 years, 74% of patient aged 12 to 15 years, and 78% of AYAs could name their hematology provider. Only 66% of patients aged 16 to 21 years knew what symptoms required medical attention. Discussion: Most patients and parents had adequate basic knowledge regarding SCD. AYAs lack the disease knowledge necessary to transition care away from parents to become more independent. An assessment for transition readiness should be ongoing to include disease-specific knowledge and self-management skills.

Background: Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada. Methods: In this retrospective cohort study, fetuses and infants z score using the neighborhood summary score or Canadian Chan index and separated into quartiles. Insurance type and self-reported race and ethnicity were obtained from medical charts. We evaluated associations among SEQ, insurance type, race and ethnicity, rural residence, and distance of residence with PND of HLHS and TGA (aggregate and individually) using bivariate analysis with adjusted associations for confounding variables and cluster analysis for centers. Results: Data on 1862 subjects (HLHS: n=1171, 92% PND; TGA: n=691, 58% PND) were submitted by 21 centers (19 in the United States). In the United States, lower SEQ was associated with lower PND in HLHS and TGA, with the strongest association in the lower SEQ of pregnancies with fetal TGA (quartile 1, 0.78 [95% CI, 0.64–0.85], quartile 2, 0.77 [95% CI, 0.64–0.93], quartile 3, 0.83 [95% CI, 0.69–1.00], quartile 4, reference). Hispanic ethnicity (relative risk, 0.85 [95% CI, 0.72–0.99]) and rural residence (relative risk, 0.78 [95% CI, 0.64–0.95]) were also associated with lower PND in TGA. Lower SEQ was associated with later PND overall; in the United States, rural residence and public insurance were also associated with later PND. Conclusions: We demonstrate that lower SEQ, Hispanic ethnicity, and rural residence are associated with decreased PND for TGA, with lower SEQ also being associated with decreased PND for HLHS. Future work to increase PND should be considered in these specific populations.

BACKGROUND Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH

ObjectivesTo investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age.MethodsWe collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats.ResultsAmong 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05).ConclusionSignificant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.

Context: When comparing success rates between treatments, it is more appropriate to structure analyses in terms of equivalence rather than traditional analyses that assess differences. Unfortunately, no studies of elective single blastocyst transfer (eSBT) have been conducted in this manner. Aims: The objective of this study was to assess clinical equivalence of in vitro fertilization success rates among patients undergoing eSBT. Settings and Design: A historical prospective study was conducted at a private fertility center. Methods: Medical records were reviewed to identify patients eligible for eSBT. Equivalency of success rates, defined as no more than a 10% difference based on 95% confidence intervals (CIs), was compared between eSBT (n = 125) and eDBT (n = 213) groups. Results: Using traditional analysis techniques, no differences in pregnancy or live-birth rates were seen (eSBT: 84.6% vs. eDBT: 84.5%, P = 0.99; eSBT: 65.3% vs. eDBT: 72.3%, P = 0.23). The 95% CI around the difference in pregnancy rates ranged from -7.9 to 8.1, suggesting clinically equivalent pregnancy rates. Clinical equivalence was not established for live-births (95% CI = −18.5–4.5). Conclusions: Findings suggest comparable pregnancy rates can be achieved in a clinical setting when utilizing eSBT in good-prognosis patients. Although live-birth rate equivalence was not demonstrated, it is thought the additional complications associated with multiple gestations outweigh the potentially higher live-birth rate. The present study highlights the importance of utilizing equivalence analyses when making statements regarding the similarity of two treatments in reproductive health, rather than relying on superiority analyses alone.

The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, “good prognosis” patients predominantly with secondary infertility who are less than 35 years of age. Using de-identified clinic records, 414 women

Increased childhood adversity may be affect adult fertility, however, the mechanism through which this occurs is unclear. Menstrual cycle abnormalities are predictive of fertility difficulties, and stress influences menstrual cycle characteristics. Here, we assess whether adverse childhood experiences (ACEs) are associated with fertility difficulties and menstrual cycle dysregulation, offering a plausible mechanism for the link between lifetime stress and fertility.From April 2012 to February 2014, 742 pregnant and non-pregnant women aged 18-45 years residing in southeastern Louisiana provided information on childhood adversity and reproductive history. Associations between ACEs and fertility difficulties and menstrual cycle patterns were evaluated.As the number of ACEs increased, risk of fertility difficulties and amenorrhea increased (RR = 1.09, 95% CI 1.05-1.13 and RR = 1.07, 95% CI 1.04-1.10, respectively), while fecundability decreased [fecundability ratio (FR) = 0.97, 95% CI 0.95-1.00]. Compared to women with no adversity, women in the high adversity group were more likely to experience both infertility and amenorrhea (RR = 2.75, 95% CI 1.45-5.21 and RR = 2.54, 95% CI 1.52-4.25, respectively), and reduced fecundability (FR = 0.75, 95% CI 0.56-1.00). Although similar patterns were seen for menstrual cycle irregularity, associations were diminished. Associations did not materially change following adjustment for age, body mass index, race, education, smoking and income. Results are constrained by the self-report nature of the study and the limited generalizability of the study population.To our knowledge, this is the first study to present evidence of a link between childhood stressors, menstrual cycle disruption and fertility difficulties. The effect of childhood stress on fertility may be mediated through altered functioning of the HPA axis, acting to suppress fertility in response to less than optimal reproductive circumstances.

High impact experiences following a natural disaster have been shown to influence later psychopathology. Individual-level factors such as age may also contribute to a disaster's impact on mental health, though it is unclear whether young age confers a protective effect or represents a period of increased risk as compared to adulthood.The present study evaluated the influence of adolescent age and hurricane experiences on mental health in the years following multiple hurricanes in the New Orleans region.794 women, currently aged 18-45, participating in a cohort study of lifetime adversity and reproductive health completed a survey about hurricane experience and current mental health. Joint associations between disaster experience and age at the time of disaster on depression and post-traumatic stress disorder (PTSD) were evaluated.Compared to women who were adults at the time of the disaster, being in early adolescence resulted in reduced depression and PTSD up to 9-years post-disaster, controlling for hurricane experiences, time since disaster, and income. A similar effect was not observed among older adolescents. Increased endorsement of feeling one's life was in danger and experiencing illness or injury resulted in increased odds of depression, while danger was associated with increased odds of PTSD.Younger age at the time of a natural disaster may confer a protective effect on mental health outcomes post-disaster, even when disaster experiences are considered, potentially representing the importance of parental support and cognitive development on disaster effects.

Objective To examine the relationship between generation 1 (grandmaternal) cardiometabolic risk factors and generation 3 (grandchild's) birthweight and gestational age. Study Design Mother-daughter pairs in the Bogalusa Heart Study (1973-present) were linked to their children's birth certificates; women were also interviewed about their reproductive histories, creating a 3-generation linkage including 177 generation 1 (grandmothers), 210 generation 2 (mothers), and 424 generation 3 (children). Prepregnancy cardiometabolic risk factors (body mass index [BMI], lipids, glucose) or generation 1 (mean age 16.2 years) and 2 (mean age 11.1 years) were examined as predictors of generation 3 birthweight and gestational age using linear and logistic regression with adjustment for age, race, parity, and other confounders. Results Generation 2 higher BMI was associated with higher birthweight (28 g per 1 unit, 95% CI 12-44) and gestational age (0.08 weeks, 95% CI 0.02-0.14) in generation 3, and generation 1 higher BMI was associated with higher birthweight (52 g, 95% CI 34-70) in the generation 2. Generation 1's higher glucose levels were associated with higher birthweight in generation 3 (adjusted beta 111 g, 95% CI 33-189), and triglycerides (adjusted beta −21, 95% CI −43-0) and low-density lipoprotein (adjusted beta −24, 95% CI −48-0) were associated with lower birthweight. Conclusions These results suggest the possibility of multigenerational developmental programming of birth outcomes, although mechanisms (whether biological or environmental) are undetermined.

Objective To examine associations of gravidity and parity with all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in postmenopausal women. Design Prospective cohort study. Setting Rancho Bernardo, a southern California community. Patient(s) One thousand two hundred ninety-four postmenopausal women ages 50–96 who attended a 1984–87 research clinic visit at which reproductive and medical histories were obtained and who were followed through 2007. Intervention(s) None. Main Outcome Measure(s) All-cause, CVD, CHD, and non-CHD CVD mortality, determined by nosologist-coded death certificates. Result(s) Average baseline age was 70.6 ± 9.2. Numbers of pregnancies ranged from 0 to 13 (median = 2); births ranged from 0 to 11 (median = 2). During a median of 19.3 years of follow-up, 707 women (54.6%) died, with 46.5% attributed to CVD, 20.5% to CHD, and 26.0% to non-CHD CVD. Trend analyses showed inverse associations of gravidity with CVD mortality and non-CHD CVD mortality. Women with four or more pregnancies were less likely than nulligravidas to have fatal CVD (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.40–0.99) and non-CHD CVD (HR = 0.48, 95% CI=0.26–0.91) independent of age, years postmenopause, obesity, and HDL. Associations increased after the first decade of follow-up. Parity and gravidity were not associated with overall or CHD mortality. Conclusion(s) High gravidity was associated with reduced CVD and non-CHD CVD mortality in postmenopausal women. Protective associations could reflect biological mechanisms that occur with repeated pregnancy or greater social support related to family size among multiparous women.

The objective of this study was to assess the association between apolipoprotein E (apoE) genotype and preterm birth (PTB) and small for gestational age (SGA). ApoE phenotyping was performed on 680 women linked to 1065 births. Allele frequencies were compared and PTB and SGA risk was estimated using log-binomial regression. The ɛ2 allele was more common in SGA births (P