Prevalence and nature of prior developmental and medical concerns in toddlers who screen positive for autism in primary care.

LAY ABSTRACT: The American Academy of Pediatrics recommends that all children be screened for autism at their 18- and 24-month well-child visit. For children who screen positive for autism, it is unknown whether this usually represents the first time a developmental concern has been raised or if other developmental concerns typically precede a positive autism screen. Such knowledge could help guide providers in how to appropriately convey feedback regarding autism screening. This study found that, for close to 80% of children with a positive autism screen, caregivers or providers had a prior autism, language, motor, or other developmental concern documented in the electronic health record. Many also had other prior concerns frequently linked to autism, such as sleep and gastrointestinal problems, and received physical or speech therapy. On average, prior to screening children who received a positive Modified-Checklist for Autism in Toddlers had two documented concerns by at 1 year of age and three concerns by 2 years of age. These findings imply that screening for autism as a part of routine pediatric care likely takes place in the context of larger conversations regarding existing developmental concerns, allowing for a less stigmatizing discussion of autism. Framing the presence of prior concerns in the setting of a positive screen in this context may create a reaffirming space for existing caregiver concerns and a lessened emotional burden on caregivers.

Predictive Value of Early Autism Detection Models Based on Electronic Health Record Data Collected Before Age 1 Year.

Importance: Autism detection early in childhood is critical to ensure that autistic children and their families have access to early behavioral support. Early correlates of autism documented in electronic health records (EHRs) during routine care could allow passive, predictive model-based monitoring to improve the accuracy of early detection. Objective: To quantify the predictive value of early autism detection models based on EHR data collected before age 1 year. Design, Setting, and Participants: This retrospective diagnostic study used EHR data from children seen within the Duke University Health System before age 30 days between January 2006 and December 2020. These data were used to train and evaluate L2-regularized Cox proportional hazards models predicting later autism diagnosis based on data collected from birth up to the time of prediction (ages 30-360 days). Statistical analyses were performed between August 1, 2020, and April 1, 2022. Main Outcomes and Measures: Prediction performance was quantified in terms of sensitivity, specificity, and positive predictive value (PPV) at clinically relevant model operating thresholds. Results: Data from 45 080 children, including 924 (1.5%) meeting autism criteria, were included in this study. Model-based autism detection at age 30 days achieved 45.5% sensitivity and 23.0% PPV at 90.0% specificity. Detection by age 360 days achieved 59.8% sensitivity and 17.6% PPV at 81.5% specificity and 38.8% sensitivity and 31.0% PPV at 94.3% specificity. Conclusions and Relevance: In this diagnostic study of an autism screening test, EHR-based autism detection achieved clinically meaningful accuracy by age 30 days, improving by age 1 year. This automated approach could be integrated with caregiver surveys to improve the accuracy of early autism screening.

Human Chorionic Gonadotropin-A Review of the Literature.

Importance: The measurement of human chorionic gonadotropin (hCG) levels in different body fluids is a commonly utilized tool in obstetrics and gynecology, as well as other fields. It is often one of the first steps in the medical workup of female patients, and the results and interpretation of this test can have significant downstream ramifications. It is essential to understand the uses and limitations of hCG as a testing and therapeutic measure to appropriately evaluate, counsel, and treat patients. Objective: The purpose of this article is to review the current literature on hCG, including its origins, structure, pharmacokinetics, metabolism, and utility in testing and medical treatment. Evidence Acquisition: Original research articles, review articles, and guidelines on hCG use were reviewed. Conclusions and Relevance: While the primary function of hCG is to maintain early pregnancy, testing for hCG demonstrates that this molecule is implicated in a multitude of different processes where results of testing may lead to incorrect conclusions regarding pregnancy status. This could affect patients in a myriad of settings and have profound emotional and financial consequences. In addition, hCG testing may be revealing of alternative pathology, such as malignancy. It is imperative to understand the nuances of the physiology of hCG and testing methods to effectively use and interpret this test for appropriate patient management.

The risk for recurrent preterm birth after prior preterm birth complicated by major fetal anomaly.

Major fetal anomalies (MFA) are a known risk factor for preterm birth (PTB), though the etiology of this is not well-studied, making counseling of these patients difficult. Thus, we sought to describe the rate of recurrent PTB in a second-observed pregnancy among persons with a history of PTB of an infant with a MFA in a first observed pregnancy, and to assess the difference in delivery timing between the first- and second-observed pregnancy. This was a retrospective cohort study of patients with a first-observed pregnancy complicated by MFA and a second-observed pregnancy in single healthcare system between 2013 and 2017. The primary outcome was recurrent PTB (PTB in second-observed pregnancy) and secondary outcomes were recurrent spontaneous PTB (SPTB), delivery gestational age (GA) in second-observed pregnancy, and difference in delivery GA between the first- and second-observed pregnancy. Recurrent PTB in the setting of prior PTB complicated by an MFA is common (∼1/4 patients), though median delivery timing for individuals who delivered preterm in the first-observed pregnancy was 6 weeks later in the second-observed pregnancy. These data suggest that PTB in the setting of MFA is a comparable risk factor to PTB in the absence of MFA.

Functional characterization of a subtilisin-like serine protease from Vibrio cholerae.

Vibrio cholerae, the causative agent of the human diarrheal disease cholera, exports numerous enzymes that facilitate its adaptation to both intestinal and aquatic niches. These secreted enzymes can mediate nutrient acquisition, biofilm assembly, and V. cholerae interactions with its host. We recently identified a V. cholerae-secreted serine protease, IvaP, that is active in V. cholerae-infected rabbits and human choleric stool. IvaP alters the activity of several host and pathogen enzymes in the gut and, along with other secreted V. cholerae proteases, decreases binding of intelectin, an intestinal carbohydrate-binding protein, to V. cholerae in vivo IvaP bears homology to subtilisin-like enzymes, a large family of serine proteases primarily comprised of secreted endopeptidases. Following secretion, IvaP is cleaved at least three times to yield a truncated enzyme with serine hydrolase activity, yet little is known about the mechanism of extracellular maturation. Here, we show that IvaP maturation requires a series of sequential N- and C-terminal cleavage events congruent with the enzyme's mosaic protein domain structure. Using a catalytically inactive reporter protein, we determined that IvaP can be partially processed in trans, but intramolecular proteolysis is most likely required to generate the mature enzyme. Unlike many other subtilisin-like enzymes, the IvaP cleavage pattern is consistent with stepwise processing of the N-terminal propeptide, which could temporarily inhibit, and be cleaved by, the purified enzyme. Furthermore, IvaP was able to cleave purified intelectin, which inhibited intelectin binding to V. cholerae These results suggest that IvaP plays a role in modulating intelectin-V. cholerae interactions.

Delivery mode and breastfeeding outcomes among new mothers in Nicaragua.

Breastfeeding has been shown to benefit infants and mothers. Women who have caesarean deliveries (C-sections) are expected to be less likely to initiate and continue breastfeeding than those who have vaginal deliveries. Given the high rate of C-sections in Nicaragua, the importance of breastfeeding, and the centrality of culture in choices about breastfeeding, this study sought to examine if mode of delivery relates with breastfeeding initiation and exclusivity in Nicaragua. Two hundred fifty mothers were surveyed about birth experiences and breastfeeding behaviour in 3 public clinics in León, Nicaragua, between June and August 2015. Logistic regression analyses were performed to examine the association of mode of delivery with initiation of breastfeeding within 1 hr of birth (early initiation) and exclusive breastfeeding for 6 months post-partum. The rate of early initiation was 68.8% and that of exclusively breastfeeding for 6 months was 12.7%. Mode of delivery was not significantly associated with early initiation (p = .383) or exclusive breastfeeding (p = .518). Early initiation was negatively associated with prelacteal feeding, AOR = 0.30, 95% CI [0.16, 0.58]; p = .001. Mothers who had perceived their infants as large at birth were significantly less likely to exclusively breastfeed for 6 months, AOR (95%CI) = 0.25 (0.06-0.97); p = 0.046. Mode of delivery was not significantly associated with optimal breastfeeding initiation and exclusivity among mothers in Nicaragua. The 2 risk factors identified for delayed initiation of breastfeeding and lack of exclusive breastfeeding were prelacteal feeding and maternal perception of a large infant at birth, respectively.

Determinants of perceived insufficient milk among new mothers in León, Nicaragua.

Breastfeeding has been shown to improve maternal and child health. In Nicaragua, the primary risk of death and disability-adjusted life years among children under 5 years of age is suboptimal breastfeeding. Although the Nicaraguan Ministry of Health promotes exclusive breastfeeding from within the first half hour through the first 6 months of life, less than a third of children in the country under 6 months of age are exclusively breastfed. As part of a larger, mixed-methods study, 21 semi-structured, in-depth interviews were conducted with new mothers recruited from three primary health centers between June and August 2015 in order to identify the social, cultural, and structural factors that contribute to infant feeding practices and the discrepancy between recommendations and practices among mothers who delivered at an urban public hospital in León, Nicaragua. Audio recordings were transcribed verbatim, and interview transcripts were coded and analyzed by a three-member team using a grounded theory approach. Findings highlight a widespread perception of insufficient milk among mothers that influenced early cessation of exclusive breastfeeding and other infant feeding practices. This perception stemmed from anxiety about meeting infant nutritional needs and infant satiety, anxiety about maternal nutrition, advice from and role modeling of family members about mixed feeding, and perceived infant feeding norms. Results suggest that support modeled after the 10 steps of the Baby-friendly Hospital Initiative as well as strengthened policy-level support are needed. Community interventions that address cultural and structural barriers to improve breastfeeding practices may also help to increase breastfeeding rates.