Proposed Screening for Congenital Hyperinsulinism in Newborns: Perspective from a Neonatal-Perinatal Medicine Group.

This perspective work by academic neonatal providers is written specifically for the audience of newborn care providers and neonatologists involved in neonatal hypoglycemia screening. Herein, we propose adding a screen for congenital hyperinsulinism (CHI) by measuring glucose and ketone (i.e., ß-hydroxybutyrate (BOHB)) concentrations just prior to newborn hospital discharge and as close to 48 h after birth as possible, at the same time that the mandated state Newborn Dried Blood Spot Screen is obtained. In the proposed protocol, we do not recommend specific metabolite cutoffs, as our primary objective is to simply highlight the concept of screening for CHI in newborns to newborn caregivers. The premise for our proposed screen is based on the known effect of hyperinsulinism in suppressing ketogenesis, thereby limiting ketone production. We will briefly discuss genetic CHI, other forms of neonatal hypoglycemia, and their shared mechanisms; the mechanism of insulin regulation by functional pancreatic islet cell membrane KATP channels; adverse neurodevelopmental sequelae and brain injury due to missing or delaying the CHI diagnosis; the principles of a good screening test; how current neonatal hypoglycemia screening programs do not fulfill the criteria for being effective screening tests; and our proposed algorithm for screening for CHI in newborns.

Timing of treatment for opioid use disorder among birthing people.

BACKGROUND: The number of pregnant women with opioid use disorder (OUD) has increased over time. Although effective treatment options exist, little is known about the extent to which women receive treatment during pregnancy and at what stage of pregnancy care is initiated. METHODS: Using a national private health insurance claims database, we identified women aged 13-49 who gave birth in 2006-2019 and had an OUD or nonfatal opioid overdose (NFOO) diagnosis during the year prior to or at delivery. We then identified women who received their first OUD treatment prior to or during pregnancy. In this cross-sectional study, we investigated how rates and timing of the initial OUD treatment changed over time. Furthermore, we examined factors associated with early initiation of OUD treatment among birthing people. RESULTS: Of the 7057 deliveries from 6747 women with OUD or NFOO, 63.3 % received any OUD treatment. Rates of OUD treatment increased from 42.9 % in 2006 to 69 % in 2019. Of those treated, in 2006, 54.5 % received their first treatment prior to conception and 24.2 % initiated care during the 1st trimester. In 2019, 68.9 % received their first treatment prior to conception, and 15.1 % initiated care during the 1st trimester. The percentage of women who were first treated in the 2nd trimester or later decreased from 21.2 % in 2006 to 16.1 % in 2019. Factors associated with early treatment initiation include being 25 years or older (age 25-34: aOR, 1.51, 95 % CI, 1.28-1.78; age 35-49: aOR, 1.82, 95 % CI, 1.39-2.37), living in urban areas (aOR, 1.28; 95 % CI, 1.05-1.56), having pre-existing behavioral health comorbidities such as anxiety disorders (aOR, 1.8; 95 % CI, 1.40-2.32), mood disorders (aOR, 1.63; 95 % CI, 1.02-2.61), and substance use disorder other than OUD (aOR, 2.56; 95 % CI, 2.03-3.32). CONCLUSION: Overall, rates of OUD treatment increased over time, and more women initiated OUD treatment prior to conception. Despite these improvements, over one-third of pregnant women with OUD/NFOO either received no treatment or did not initiate care until the 3rd trimester in 2019. Future research should examine barriers to OUD treatment initiation among pregnant women.

Association of Pregnancy-Specific Alcohol Policies With Infant Morbidities and Maltreatment.

Importance: Research has found associations of pregnancy-specific alcohol policies with increased low birth weight and preterm birth, but associations with other infant outcomes are unknown. Objective: To examine the associations of pregnancy-specific alcohol policies with infant morbidities and maltreatment. Design, Setting, and Participants: This retrospective cohort study used outcome data from Merative MarketScan, a national database of private insurance claims. The study cohort included individuals aged 25 to 50 years who gave birth to a singleton between 2006 and 2019 in the US, had been enrolled 1 year before and 1 year after delivery, and could be matched with an infant. Data were analyzed from August 2021 to April 2023. Exposures: Nine state-level pregnancy-specific alcohol policies obtained from the National Institute on Alcohol Abuse and Alcoholism's Alcohol Policy Information System. Main Outcomes and Measures: The primary outcomes were 1 or more infant injuries associated with maltreatment and infant morbidities associated with maternal alcohol consumption within the first year. Logistic regression, adjusting for individual-level and state-level controls, and fixed effects for state, year, state-specific time trends, and SEs clustered by state were used. Results: A total of 1 432 979 birthing person-infant pairs were included (mean [SD] age of birthing people, 32.2 [4.2] years); 30 157 infants (2.1%) had injuries associated with maltreatment, and 44 461 (3.1%) infants had morbidities associated with alcohol use during pregnancy. The policies of Reporting Requirements for Assessment/Treatment (adjusted odds ratio [aOR], 1.28; 95% CI, 1.08-1.52) and Mandatory Warning Signs (aOR, 1.18; 95% CI, 1.10-1.27) were associated with increased odds of infant injuries but not morbidities. Priority Treatment for Pregnant Women Only was associated with decreased odds of infant injuries (aOR, 0.83; 95% CI, 0.76-0.90) but not infant morbidities. Civil Commitment was associated with increased odds of infant injuries (aOR, 1.26; 95% CI, 1.08-1.48) but decreased odds of infant morbidities (aOR, 0.57; 95% CI, 0.53-0.62). Priority Treatment for Pregnant Women and Women With Children was associated with increased odds of both infant injuries (aOR, 1.12; 95% CI, 1.00-1.25) and infant morbidities (aOR, 1.08; 95% CI, 1.03-1.13). Reporting Requirements for Child Protective Services, Reporting Requirements for Data, Child Abuse/Neglect, and Limits on Criminal Prosecution were not associated with infant injuries or morbidities. Conclusions and Relevance: In this cohort study, most pregnancy-specific alcohol policies were not associated with decreased odds of infant injuries or morbidities. Policy makers should not assume that pregnancy-specific alcohol policies improve infant health.

Nutritional Status Differs by Prescription Opioid Use among Women of Reproductive Age: NHANES 1999-2018.

Prescription opioid use among pregnant women has increased in recent years. Prenatal exposure to opioids and poor nutrition can both negatively impact maternal-fetal outcomes. The objective of this study was to characterize the nutrition and health status of reproductive-age women taking prescription opioids, compared to women not taking opioids. Using NHANES 1999-2018 data, non-pregnant women aged 20-44 years were classified as taking a prescription opioid in the last 30 days (n = 404) or unexposed controls (n = 7234). Differences in anthropometric, cardiovascular, hematologic, and micronutrient status indicators between opioid-exposed and unexposed women were examined. Opioid-exposed women were older, had lower income and education, and were more likely to be non-Hispanic White, to smoke, and to have chronic health conditions compared to unexposed women. In unadjusted analyses, several nutrition and health markers were significantly different between opioid exposure groups. After controlling for covariates, women taking opioids had higher odds of Class II (OR = 1.6, 95% CI = 1.1-2.3) or III obesity (OR = 1.6, 95% CI = 1.1-2.5), and lower levels of serum folate, iron, and transferrin saturation. Reproductive-age women taking prescription opioids may be at risk for poorer nutritional and cardiometabolic health. Future research is needed to explore whether nutritional status impacts maternal-fetal outcomes for women exposed to opioids during pregnancy.

Obstetricians' prescribing practices for pain management after delivery.

Aim: To examine postpartum opioid prescribing practices. Materials & methods: Obstetricians were interviewed about opioids: choice of opioid, clinical factors considered when prescribing, thoughts/beliefs about prescribing, and typical counseling provided. Inductive thematic analyses were used to identify themes. Results: A total of 38 interviews were analyzed. Several key points emerged. The choice of opioid, dosing and number of pills prescribed varied widely. The mode of delivery is the primary consideration for prescribing opioids. All providers would prescribe opioids to breastfeeding women. Some providers offered counseling on nonopioid treatment of pain. Discussion: At two large tertiary centers in Pennsylvania, the 38 physicians interviewed wrote 38 unique opioid prescriptions. Patient counseling addressed short-term pain management, but not the chronic overuse of opioids.

We wanted to look at the way opioid pain drugs are provided to mothers after the birth of their children and see what doctors tell mothers about the pain drugs. We interviewed doctors and asked which opioid pain drug they would choose, what made them prescribe the drug, the thoughts about giving mothers the drug and what they told the mothers about the drug. We then looked at all the responses to look for patterns in how doctors gave pain drugs to mothers. Our team interviewed 38 doctors. Some key points were seen; first is that the choice of opioid pain drug, dose and number of pills prescribed was different from doctor to doctor; second is that whether the baby was delivered vaginally or by cesarean was the main factor upon which doctors based their decisions for giving opioid pain drugs. Whether a mother was taking medications that help with addiction, the doctor's assessment of the mother's pain and the doctor's thoughts on the mother's risk of opioid addiction were also considered. All doctors would give opioid pain drugs to breastfeeding mothers. Finally, some doctors talked to mothers about using other medications for pain, but not about the overuse of opioid pain drugs. At our two hospital centers in Pennsylvania, the 38 doctors gave opioid pain drugs to mothers in 38 different ways. Doctors said that opioids are necessary after cesarean, but not after vaginal birth, unless there is a problem. A mother's history and social situation inform decision making. Doctors talk to mothers about short-term pain, but not about the overuse of opioid pain drugs.

Body composition during the first 4 months in infants affected by neonatal abstinence syndrome: a pilot study.

Newborns with neonatal abstinence syndrome (NAS) display symptoms related to neurologic excitability and autonomic dysfunction that result in increased metabolic demands. These infants also exhibit feeding difficulties and/or hyperphagia. Because the effects of these symptoms and behaviors on growth are unknown, we sought to measure serial body composition measurements over the first 4 months in infants with NAS requiring pharmacologic treatment using air displacement plethysmography. Fourteen infants of singleton birth with appropriate-for-gestational-age (AGA) weight and a gestational age of ≥35 weeks and <42 weeks were evaluated. In mixed-effects models, per week, infants increased in mean fat percent by 1.1% (95% confidence interval [CI]: 0.85-1.43), fat mass by 90 g (CI: 70-100), and fat-free mass by 140 g (CI: 130-150). The subgroup of infants (N = 5) requiring multidrug therapy for symptom control had lower mean fat percent (-1.2%, CI: -5.2-2.1), fat mass (-60 g, CI: -25-13), and fat-free mass (-270 g, CI: -610-80) across time compared to infants requiring monotherapy. We are the first to report how body composition measures change over time in a small group of patients with NAS. Infants with NAS were smaller and leaner in the first several weeks compared to previously reported body composition measurements in term infants, but grew similarly to their healthy counterparts by 16 weeks. Infants with more severe NAS may be at risk for abnormalities in longer term growth.

Improving Hospital Infant Safe Sleep Compliance by Using Safety Prevention Bundle Methodology.

BACKGROUND AND OBJECTIVES: Sudden unexpected infant death often results from unsafe sleep environments and is the leading cause of postneonatal mortality in the United States. Standardization of infant sleep environment education has been revealed to impact such deaths. This standardized approach is similar to safety prevention bundles typically used to monitor and improve health outcomes, such as those related to hospital-acquired conditions (HACs). We sought to use the HAC model to measure and improve adherence to safe sleep guidelines in an entire children's hospital. METHODS: A hospital-wide safe sleep bundle was implemented on September 15, 2017. A safe sleep performance improvement team met monthly to review data and discuss ideas for improvement through the use of iterative plan-do-study-act cycles. Audits were performed monthly from March 2017 to October 2019 and monitored safe sleep parameters. Adherence was measured and reviewed through the use of statistical process control charts (p-charts). RESULTS: Overall compliance improved from 9% to 72%. Head of bed flat increased from 62% to 93%, sleep space free of extra items increased from 52% to 81%, and caregiver education completed increased from 10% to 84%. The centerline for infant in supine position remained stable at 81%. CONCLUSIONS: Using an HAC bundle safety prevention model to improve adherence to infant safe sleep guidelines is a feasible and effective method to improve the sleep environment for infants in all areas of a children's hospital.

Longitudinal Health Care Utilization of Medicaid-Insured Children with a History of Neonatal Abstinence Syndrome.

OBJECTIVE: To describe longitudinal health care utilization of Medicaid-insured children with a history of neonatal abstinence syndrome (NAS) compared with similar children without NAS. STUDY DESIGN: Retrospective, longitudinal cohort study. Data were extracted from the Medicaid Analytic eXtract files for all available states and DC from 2003-2013. Subjects were followed up to 11 years. In total, 17 229 children with NAS were identified using the International Classification of Diseases, Ninth Revision code 779.5. Children without NAS, matched on demographic and health variables, served as the comparison group. Outcomes were number of claims for inpatient, outpatient, and emergency department encounters, numbers of prescription claims, and costs associated with these services. Linked claims were identified for each subject using a unique, within-state ID. RESULTS: Children with NAS had increased claims for inpatient admissions (marginal effect [ME] 0.49; SE 0.01) and emergency department visits (ME 0.30; SE 0.04) through year 1; increased prescriptions (ME 1.45; SE 0.08, age 0) (ME 0.69; SE 0.11, age 1 year) through year 2; and increased outpatient encounters (ME 20.13; SE 0.54, age 0) (ME 3.95; SE 0.62, age 1 year) (ME 2.90; SE 1.11, age 2 years) through year 3 after adjusting for potential confounders (P < .01 for all). Beyond the third year, health care utilization was similar between those with and without NAS. CONCLUSIONS: Children with a diagnosis of NAS have greater health care utilization through the third year of life. These differences resolve by the fourth year. Our results suggest resolution of disparities may be due to shifts in developmental health management in school-age children and inability to track relevant diagnoses in a health care database.

Management of newborns exposed to mothers with confirmed or suspected COVID-19.

There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother-newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

One-Year Postpartum Mental Health Outcomes of Mothers of Infants with Neonatal Abstinence Syndrome.

INTRODUCTION: Women with substance use disorders have high incidences of psychiatric and mood disorders, which may affect their ability to cope with an infant with neonatal abstinence syndrome (NAS), particularly one with a protracted NICU course, exacerbating symptoms of mental health disorders. We examined the incidence of mental health diagnoses in the first 12 postpartum months in mothers of an NAS infant compared to mothers of an infant without NAS. METHODS: In this retrospective, cohort study, data were extracted from MarketScan® database (2005-2013). NAS newborns were identified using ICD-9 codes. Each mother of an NAS newborn was matched to a mother of a newborn without NAS on age at delivery, birth year, gestational age, NICU stay and maternal mental health diagnoses in the 9 months prior to delivery. Primary outcomes were claims for major depression, postpartum depression, anxiety, adjustment reaction, post-traumatic stress disorder, and suicidal ideation. RESULTS: 338 mother-infant pairs met all inclusion/exclusion criteria and were matched 1-to-1 with controls. 245 (73%) of the NAS infants had a NICU admission. Median length of stay for these infants was 10 days compared to 3 days for infants with no NICU admission (p < 0.001). Mothers of NAS infants were more likely to have claims for major depression (33% vs. 15%, p < 0.01), postpartum depression (7% vs. 3%, p = 0.04), and anxiety (27% vs. 13%, p < 0.01). CONCLUSION: Mothers of infants with NAS have a higher incidence of mental health diagnoses in the first 12 months postpartum compared to mothers of infants without NAS.

A Longitudinal Healthcare Use Profile of Children with a History of Neonatal Abstinence Syndrome.

OBJECTIVE: To describe healthcare use over time of children with a history of neonatal abstinence syndrome (NAS) compared with children without NAS. STUDY DESIGN: In this retrospective, longitudinal cohort study, data were obtained from MarketScan Commercial Claims and Encounters database from 2005 to 2014. Children with and without NAS based on International Classification of Diseases, Ninth Revision diagnostic codes were followed until 8 years or disenrollment (mean: 35 months). Numbers of claims for inpatient, outpatient, and emergency department encounters; prescription drugs; and costs associated with these encounters were evaluated. RESULTS: Children with NAS had a significantly greater number of claims per year from age 1 to 8 for inpatient hospitalizations (adjusted mean ratio 3.20; 95% CI 1.74-5.90), outpatient encounters (1.23; 1.08-1.41), and emergency department visits (1.46; 1.25-1.70) after we adjusted for confounders. Subsequently, adjusted mean annualized costs were nearly double for all healthcare services in children with NAS (1.86; 1.34-2.60) and >4 times as high as for inpatient hospitalizations (4.34; 2.03-9.30) compared with children without NAS. CONCLUSIONS: Children with a diagnosis of NAS have significantly greater rates of healthcare use through age 8 years compared with children without NAS. These findings suggest that children affected by NAS have medical disparities that linger well beyond early infancy.

Growth during the first year in infants affected by neonatal abstinence syndrome.

BACKGROUND: Infants with neonatal abstinence syndrome (NAS) initially experience neurologic excitability, poor feeding, and/or hyperphagia in the setting of increased metabolic demand. Because the longitudinal effects of these early symptoms and behaviors on weight trends are unknown, we sought to contrast weight gain patterns through age 1 year for infants diagnosed with NAS with matched controls. METHODS: Retrospective cohort of 70 singletons with a gestational age of ≥37 weeks and an ICD-9 or ICD-10 diagnosis of NAS made ≤7 days after birth with institutional follow-up matched to patients without NAS. Infants were matched on gestational age (±2 weeks), birth weight (±20 g), sex (exact), and insurance type (exact). Quantile regression methods were used to estimate 10th, 25th, 50th, 75th and 90th percentiles of weight over time. RESULTS: The mean gestational age for an infant with NAS was 38.8 weeks (standard deviation [SD], 1.3). The mean birth weight was 3.141 kg (SD, 0.510). NAS patients had a median of 24 weights recorded between birth and 400 days (inter-quartile range [IQR], 16-32 weights). Patients without NAS had a median of 12 weights recorded (IQR, 10-16). Growth curves were similar over the first 400 days of life. Patients with NAS had non-significantly higher and lower estimated weights for the 90th and 10th percentiles, respectively. CONCLUSION: Infants with a diagnosis of NAS grew similarly to controls during their first year. Given the frequently-encountered NAS symptoms of hyperphagia and irritability, future studies may evaluate whether early differences in caregiver feeding exist and whether they have longer-term impacts on growth.

The economic burden of neonatal abstinence syndrome in the United States.

BACKGROUND AND AIMS: While hospital charges related to neonatal abstinence syndrome (NAS) have increased recently, there are no data available regarding costs. Therefore, we sought to describe the NAS population and compare with the non-NAS population, determine the incidence of NAS in the United States and estimate the total annual costs and hospital days of NAS admissions, and estimate the incremental costs and length of stay of an NAS admission compared with a non-NAS admission. DESIGN: Retrospective, observational study. Data were obtained from the Kids' Inpatient Database (2003-12). Survey-weighting was used to obtain national counts of NAS births. The incremental burden of costs and length of stay were estimated for NAS admissions and compared to non-NAS admissions. SETTING: United States hospitals from states participating in the Kids' Inpatient Database (KID), a nationally representative sample of all-payer in-patient pediatric discharges. PARTICIPANTS: Infants with a diagnosis of NAS (27 943) were identified from the KID using ICD-9-CM codes and compared with non-NAS infants (3 783 629). MEASUREMENTS: Primary outcome measures were provider costs and length of stay for NAS and non-NAS admissions. Costs were calculated using cost-to-charge ratios and were adjusted for inflation to 2014 US dollars. FINDINGS: Between 2003 and 2012, NAS admissions increased more than fourfold, resulting in a surge in annual costs from US$61 million and 67 869 hospital days in 2003 to nearly US$316 million and 291 168 hospital days in 2012. For an infant affected by NAS, the hospital stay was nearly 3.5 times as long (16.57 hospital days compared with 4.98 for a non-NAS patient, P < 0.001) and the costs more than three times greater (US$16 893 compared to US$5610 for a non-affected infant, P < 0.001). CONCLUSION: The incidence of neonatal abstinence syndrome is increasing in the United States, and carries an enormous burden in terms of hospital days and costs. The number of US hospital admissions involving neonatal abstinence syndrome increased more than fourfold between the years 2003 and 2012. In 2012, neonatal abstinence syndrome cost nearly $316 million in the United States.

Steroids alone or as adjunctive therapy with doxycycline fail to improve oviduct damage in mice infected with Chlamydia muridarum.

In women, Chlamydia trachomatis can ascend from the cervix to the fallopian tubes, where an overly aggressive host inflammatory response can cause scarring that leads to chronic pelvic pain, infertility, or ectopic pregnancy. Although screening and treatment programs for women have resulted in decreased rates of sequelae, morbidities associated with oviduct scarring continue to occur. Since corticosteroids have anti-inflammatory and antifibrotic effects, we tested the ability of dexamethasone to inhibit inflammation and prevent oviduct scarring in mice genitally infected with Chlamydia muridarum. The administration of 1 or 2.5 mg/kg of body weight of dexamethasone on days 7 to 21 of infection resulted in reduced accumulation of inflammatory cells in the oviducts compared to that in controls. However, a concomitant increase in bacterial burden was observed, and chronic oviduct disease was not reduced. Adjunctive administration of a prolonged (21-day) or short (3-day) course of dexamethasone in combination with the antibiotic doxycycline also failed to reduce chronic oviduct pathology compared to antibiotic treatment alone. Steroids administered alone or adjunctively with antibiotics failed to prevent oviduct damage in this murine model of C. trachomatis infection.