Journal articles on the topic 'Newborn infants Effect of drugs on Case studies'

BackgroundCaffeine has been extensively used in the treatment of apnoea in premature infants,1 its disposition varies with postnatal age2 and can differ markedly between premature and term neonates.MethodsThe Preterm population within the Simcyp Simulator V18R1 population library was used to replicate clinical studies to predict caffeine exposure after single3 and multiple4 intravenous administration to preterm neonates of gestational weeks 28.5 and 29 (28–33) respectively, ranging in postnatal age of 3–30 days and 0–3 days respectively. Predictive performance of the Physiologically Based Pharmacokinetic Model (PBPK) was evaluated by comparing the simulated to the clinical results. A population simulation was performed for the single dose study as only pharmacokinetic parameters were available. However, for multiple doses study, where individual plasma concentration-time profile data were available, simulations were performed for each individual.ResultsPBPK model predictions for caffeine in preterm neonates were in good agreement with the clinical observations. In the case of single dose administration, the ratios of predicted vs observed mean Volume of distribution (Vss), peak plasma concentration (Cmax), Clearance (CL) and Half-life (t1/2) were 1, 1.2, 1 and 1.1, respectively. Individual predicted concentration-time profiles following multiple dose administration were in close agreement with the observed data for all 16 subjects, overall 95% of individual observed data points were within the 5th and 95th percentile of predicted plasma concentration-time profile.ConclusionsThe predictive performance of preterm PBPK models for caffeine was found to be appropriate. A similar PBPK approach can be utilized in the clinics for the accurate prediction of pharmacokinetic parameters and plasma concentrations and for dosage adjustment to attain specific plasma concentrations of drugs in premature population.ReferencesGiacoia, et al. Effects of formula feeding on oral absorption of caffeine in premature infants. Dev Pharmacol Ther 1989; 12:205–210.Johnson, et al. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet 2006; 45(9):931–56.Aranda, et al. Population Pharmacokinetic profile of caffeine in the premature newborn infant with apnea; The Journal of Pediatrics 1979; 94(4.):663–668.Lee, et al. Caffeine in apnoeic asian neonates: a sparse data analysis. Br J Clin Pharmacol 2002; 54:31–37.Disclosure(s)Nothing to disclose

BACKGROUND: Benzodiazepines are being used in neonatal intensive care units for sedation and control of seizures. However, anecdotal reports suggest that their use in infants may be associated with serious adverse effects (AEs). OBJECTIVE: To determine the incidence of AEs from benzodiazepine use in preterm and full-term infants. METHODS: Retrospective chart review of 63 infants who received benzodiazepines as a sedative or anticonvulsant over a 16-month period. RESULTS: Mean ± SD gestational age of the infants was 33.1 ± 6.2 weeks, and birth weight was 2.3 ± 1.2 kg. Median (range) postnatal age at commencement of drug administration was 19 (5–54) days. Forty-one infants received lorazepam, 8 received midazolam, and 14 received both. Ten (16%) of the infants had 14 documented adverse events: seizures (n = 6), hypotension (n = 5), and respiratory depression (n = 3). Using a validated adverse drug reaction probability scale, a probable association with benzodiazepine use was demonstrated in 12 of the AEs. Due to the retrospective nature of the data, a score for definite association was not attainable. Anticonvulsant administration was required for 4 of 6 infants and, in all cases of respiratory depression, ventilatory support was initiated or increased. Two cases of significant hypotension were treated with inotropes. There was no statistically significant correlation between AEs and benzodiazepine dose or concomitant use of inotropes or analgesics (morphine), although most infants had underlying medical conditions or received multiple drugs that may have predisposed them to experience AEs. CONCLUSIONS: Administration of benzodiazepines was frequently associated with AEs in full-term and preterm infants. It is possible that underlying illnesses and concomitant drug use predisposed these effects. Until the benefit-to-risk ratio is determined by further studies, judicious use of benzodiazepines is recommended in this vulnerable population.

AbstractThe Prenatal Alcohol and Sudden Infant Death Syndrome and Stillbirth Network, known as the “Safe Passage Study,” enrolled approximately 12,000 pregnant women from the United States and South Africa and followed the development of their babies through pregnancy and the infant’s first year of life to investigate the role of prenatal alcohol exposure in the risk for sudden infant death syndrome (SIDS) and adverse pregnancy outcomes, such as stillbirth and fetal alcohol spectrum disorders.Auditory system tests were included in the physiologic test battery used to study the effects of prenatal alcohol exposure on neurophysiology and neurodevelopment, as well as potential causal relationships between neurodevelopmental disorders and SIDS and/or stillbirth. The purpose of this manuscript is to describe normative results when using the auditory test battery applied.The test battery included the auditory brainstem response (ABR) and transient-evoked otoacoustic emissions (TEOAEs). Data were collected on individual ears of newborns and 1-month-old infants.From a cohort of 6,070 with auditory system exams, a normative subsample of 325 infants were selected who were not exposed prenatally to alcohol, cigarette smoke, or drugs nor were they preterm or low birthweight. The subsample is small relative to the overall study because of strict criteria for no exposure to substances known to be associated with SIDS or stillbirth and the exclusion of preterm and low birthweight infants. Expectant mothers were recruited from general maternity at two comprehensive clinical sites, in the northern plains in the United States and in Cape Town, South Africa. These populations were selected for study because both were known to be at high-risk for SIDS and stillbirth.ABR and TEOAE recordings were stored electronically. Peak latency and amplitude analysis of ABRs were determined by study personnel, and results were evaluated for differences by age, sex, test site, race, and ear (left versus right).TEOAE findings were consistent with existing literature including the increase in signal-to-noise (SNR) over the first month of life. The SNR increase is due to an increase in amplitude of the emission. TEOAE amplitude asymmetry favoring the right ear was found, whereas SNR asymmetry was not, perhaps because of the small sample size. A nonsignificant trend toward larger responses in female babies was found; a result that is generally statistically significant in studies with larger samples. Latencies were found to be shorter in ABRs elicited in the right ear with amplitudes that were slightly bigger on average. An expected decrease in wave V latency was observed from birth to 1-month of age, but the finding was of borderline significance (p = 0.058).One month is a short time to judge development of the auditory system; however, the ABR and TEOAE findings were consistent with current literature. We conclude that the auditory system data acquired for the Safe Passage Study, as reflected in the data obtained from this cohort of “unexposed” infants, is consistent with published reports of these auditory system measures in the general population.

Osteopathic manipulative treatment (OMT) is used in both inpatient and outpatient settings. Evidence suggests that OMT can reduce both patients’ recovery time and the financial cost of their acute medical treatment and rehabilitation. Multiple studies from neonatal intensive care units (NICUs) are presented in this article that demonstrate infants treated with OMT recover faster, are discharged earlier, and have lower healthcare costs than their non-OMT-treated counterparts. Data clearly show that adjunctive OMT facilitates feeding coordination in newborns, such as latching, suckling, swallowing, and breathing, and increases long-term weight gain and maintenance, which reduces hospital length of stay (LOS). Osteopathic techniques, such as soft tissue manipulation, balanced ligamentous tension, myofascial release, and osteopathic cranial manipulation (OCM), can reduce regurgitation, vomiting, milky bilious, or bloody discharge and decrease the need for constipation treatment. OMT can also be effective in reducing the complications of pneumonia in premature babies. Studies show the use of OCM and lymphatic pump technique (LPT) reduces the occurrence of both aspiration and environmentally acquired pneumonia, resulting in significantly lower morbidity and mortality in infants. Based on published findings, it is determined that OMT is clinically effective, cost efficient, a less invasive alternative to surgery, and a less toxic choice to pharmacologic drugs. Therefore, routine incorporation of OMT in the NICU can be of great benefit in infants with multiple disorders. Future OMT research should aim to initiate clinical trial designs that include randomized controlled trials with larger cohorts of infants admitted to the NICU. Furthermore, a streamlined and concerted effort to elucidate the underlying molecular mechanisms associated with the beneficial effects of OMT will aid in understanding the significant value of incorporating OMT into optimal patient care.

The central nervous system injuries are a common neonatal pathology, hypoxia being one of the main causes of cerebral dysfunction. The purpose of this study was studying the incidence of hypoxic cerebral disorders in premature infants with an extremely low body weight and a very low birth weight and revealing the risk factors that adversely affected the disease outcome. The subject of the study was preterm infants whose gestational age did not exceed 31 weeks. The main criterion for inclusion into the study was the presence of hypoxic-ischemic and hypoxic-hemorrhagic brain damage. To reveal the perinatal risk factors, the somatic health of mothers, and pregnancy and childbirth peculiarities were studied. The structure of children’s pathology and intensive care techniques were analyzed. Cerebral disorders were verified in 42 out of 176 patients (23.5 %). 2–3rd-degree intraventricular hemorrhage was diagnosed in 34 newborns (80.9 %), severe ischemia in 8 children (19.1 %). To determine the structure of the disease outcome, all children were divided into deceased and survivors. A fatal outcome was observed in 14 cases (33.3 %). The mothers of deceased children were more likely to have obstetric and concomitant extragenital pathologies. Analysis of pediatric pathology showed that the hemodynamically significant functioning arterial duct and severe asphyxia in childbirth were much more frequent in deceased children. Intensive therapy of deceased children included «hard» parameters of artificial ventilation and high doses of cardiotonic drugs. Thus the presented risk factors can be considered as predictors of an unfavorable outcome in children with this pathology.

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Preterm infants who are also intrauterine growth restricted (IUGR) experience more frequent and earlier hemodynamic consequences of patent ductus arteriosus (PDA). This may be related to altered levels of prostaglandins or altered number or sensitivity of their receptors in IGUR infants. Few studies have examined the efficacy of pharmacologic therapy (non-steroidal anti-inflammatory drugs [NSAIDs]: indomethacin, ibuprofen, or acetaminophen) for PDA closure among preterm infants based on their degree of IUGR with differing results. Objectives Primary: To determine if the degree of IUGR [defined by birth weight (BW) z-score] affects the efficacy of pharmacologic PDA closure and rate of surgical PDA ligation in preterm infants. Secondary: To compare the side effects of NSAIDs and neonatal outcomes based on the severity of IUGR. Design/Methods This retrospective cohort study included infants of < 30 weeks’ GA, admitted to a tertiary neonatal intensive care unit (NICU) between 2010 and 2018, with hemodynamically significant PDA and treated with NSAIDs. Infants with major congenital anomalies, those who received prophylactic Indomethacin and those who died in the first 48 hours were excluded. Birth weight (BW) z-scores were calculated using Olsen nomograms and classified into 3 categories: z-score > −0.5 (normal), z-score −0.5 to −2.0 (mild to moderate growth restriction), z-score <−2 (severe IUGR). We compared responses to NSAID treatment and PDA ligation. Multivariate logistic regression analysis was done to examine the association of BW z-score and response to pharmacological therapy and subsequent surgical PDA ligation. Results Of the 1511 eligible infants, 769 (51%) had a diagnosis of PDA. Of 517 included infants, 323 (62.5%) had BW z-score >− 0.5, while 154 (29.8%) had z-scores − 0.5 to −2.0 and 40 (7.7%) had z-score < −2. Table 1 shows their demographic characteristics. Efficacy of first course of NSAIDs was not different among these birth weight groups (Table 2). There was no difference in the side effects and neonatal morbidities amongst the three groups (Table 2). Multivariate logistic regression analysis after controlling for GA, gender, antenatal steroids, C-section, and SNAP II showed that the odds of PDA ligation was significantly higher among infants with BW z-score < −2 (aOR 2.68, 95% CI 1.13- 6.36) but not among infants with z-score −0.5 to−2.0 (aOR 1.41, 95% CI 0.84, 2.39) as compared to z-score >-0.5. Conclusion Preterm severe IUGR infants with z-score < −2 have an associated increased risk of PDA ligation following pharmacologic treatment as compared to normally grown infants.

Abstract This study focuses on the role of a clinical pharmacist in the optimisation of pharmacotherapy in the case of patients during pregnancy and its importance within the hospital sector in Slovakia. Retrospective evaluation of pharmacotherapy in pregnant patients with a focus on teratogenicity and appropriate drug selection was used. The hospital data were collected during 24 months from 22 female patients. The main observed outcome was health condition of the newborn, and it was expressed as healthy newborn, illness of the newborn, any congenital defect or malformation, spontaneous abortion, or unspecified information about the newborn. Based on a foetal risk assessment of used therapeutic agents from the Summary of Product Characteristics (SmPC), basal foetal and neonatal risk assessment (Briggs et al., 2017), and recommendations and related human past reports and supporting evidence studies, drugs were divided into two groups: confirmed foetal risk drugs and negative (nonconfirmed) foetal risk drugs. A total of 36.3% of the patients used two drugs. Patients most frequently used drugs during the first trimester (81.8%). During pregnancy, the most used drugs were for the nervous system (25.5%), anti-infective agents (23.6%), and respiratory therapeutic agents (14.5%). Of the 22 patients, 16 (73%) had healthy newborns, despite the use of therapeutic agents with different foetal-risk variations. In the group of therapeutic agents with confirmed risk, in some, negative effect on the newborn's health was clinically manifested. Spontaneous abortion was present after using norethisterone acetate and valproic acid; birth defect (unspecified) was present after usage of interferon β-1a and methylprednisolone sodium succinate. An illness (heart murmur) was present after the use of monohydrate sodium salt of metamizole. Another illness (Wilm's tumour) was present after the use of budesonide. Unspecified information about the newborn was observed in four cases after the use of prednisone, allopurinol, nadroparin, and fluvastatin.

Fetal arrhythmia develops in 0.1–5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.

AbstractHuman chorionic gonadotropin (HCG) is used parenterally for treatment of threatened abortions and repeated spontaneous abortion in pregnant women. No controlled epidemiological studies of preterm birth and low birthweight newborns in pregnant women with HCG treatment have been published while the results of animal investigations were controversial. The data of 97 pregnant women with HCG treatment in the second and third months of pregnancy due to threatened abortion and/or previous spontaneous abortion(s) was compared with the data of other 38,054 pregnant women in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. There was no difference in mean gestational age at delivery and birth weight, in addition the rate of preterm birth and low birthweight newborns. Parenteral HCG treatment in the early pregnancy due to threatened abortion did not associate with a higher risk for preterm births or low birthweight newborns. However, a higher occurrence of gestational diabetes was found in pregnant women with HCG treatment and there was a slight male excess among newborn infants (p=0.06).

Many neonates are referred to neonatal intensive care units (NICUs) for specialized care far from their parents' residence. This distance can add to the stress of the parents and reduce the contact of the parents with their newborn. Small studies have found that back transporting these neonates to hospitals closer to their homes is safe and cost-effective. Despite these findings, the reluctance of many insurers to pay for back transports prevents or delays many back transports. Insurers may not consider the findings of the previous studies to be conclusive, given that the comparisons were between small numbers of neonates back transported and neonates who remained in tertiary care, and the potential for differences in severity of illness between the groups is significant. In this study the effect on hospital charges of back transports was examined by comparing the charges for care in community hospitals with what these charges would have been in a tertiary care center. The advantage of this method is that it avoids case-mix differences between the groups and thus minimizes the potential for small-sample bias. Data were collected for all back transports from a NICU to non-tertiary care centers (n = 90) for a 9-month period. We were able to obtain the itemized bills for the care at community hospitals for 42 of these patients. Each bill was recalculated using the charges for the NICU to determine potential for savings. The average charges for recovery care were about $6200 lower at the community hospital than they would have been at the NICU. When the charges for the back transport are subtracted (mean = $1603), the average net savings are $4,600. These savings are even larger ($6163) for neonates who stayed at the community hospital for more than 7 days.

Background. The drugs that are often given to children with GERD are stomach acidsuppressants, namely the H2 receptor antagonist and proton pump inhibitor (PPI) classof drugs, but the effectiveness of the two drugs is still controversial. Objective. Toevaluate the use of PPIs and H2 RA in children with GERD through evidence-basedcase studies. Methods. Systematic search for literature using the search instrumentPUBMED, Cochrane, Google Scholar, Pediatrica Indonesiana, and Sari Pediatri.Searches included systematic review articles, randomized controlled clinical trials andcohort studies. Abstract only studies, non-clinical evaluation results, and case reportswere excluded. Results. The study was obtained from three RCT studies comparingthe effectiveness of omeprazole and ranitidine in the treatment of GERD, all of whichhave differences. Azizollahi et al demonstrated that after 2 weeks of standard doses ofomeprazole or ranitidine there was a comparable significant improvement. Ummarinoet al demonstrated that omeprazole was significantly better than high-dose ranitidine.Cucchiara et al (1993) showed that high doses of ranitidine were as good as omeprazole.Another study by Pfefferkorn et al showed no significant effect on the addition ofomeprazole therapy combined with ranitidine in preventing the incidence of NAB. Astudy by Boccia et al comparing omeprazole, ranitidine, and non-therapy, found verylow relapse rates. Conclusion. Evidence regarding the use of ranitidine versusomeprazole in infants and children is lacking. Based on one study specifically in theinfant age group, omeprazole and ranitidine were of comparable effectiveness. A higherdose of ranitidine may have a better effect. In terms of complete symptom relief,omeprazole is likely to be superior to ranitidine.

Abstract Primary Subject area Clinical Pharmacology and Toxicology Background The most common vascular anomaly (VA) requiring medical treatment are infantile hemangiomas, but many other vascular anomalies affecting children are treated with local, systemic drugs or sclerosing agents. Rational drug prescribing implies assessment of whether a drug’s benefits outweigh the risk of adverse effects for treatment of a specific vascular anomaly. This process relies on the quality of the literature on efficacy and safety for drug treatment of vascular anomalies. Objectives To evaluate the level of evidence surrounding drug use in vascular anomalies. Design/Methods A list of drugs used in vascular anomalies was created with existing guidelines. For each drug, the article displaying the highest level of evidence was determined, using Oxford criteria. Levels of evidence were compared between efficacy and safety data, routes of administration, pharmacological categories, and a subset of specific vascular anomalies. The influence of research quality on study results was explored by comparing the percentage of clinical efficacy between high- and low-quality studies. Results We identified 71 different drugs for treating vascular anomalies. The median level of evidence was low, with a predominance of retrospective cohort studies and case reports. The level of evidence was higher for efficacy than safety data and for common diseases like infantile hemangiomas. The level of evidence was lower for systemic vs. local drugs. Clinical efficacy was more frequently reported in low quality studies (retrospective cohort studies and case reports) than in high quality studies (randomized clinical trial and meta-analysis). Conclusion Quality of research on drugs used for treating vascular anomalies in infants is poor and challenges rational drug use. Indeed, knowledge of drug treatment in VA relies mainly on research of poor methodological quality. Despite the use of drugs carrying a significant risk of adverse effects, drug safety is also poorly reported. This is alarming because some treatments, like antineoplastic agents and immunosuppressants, display an unsafe adverse effect profile. A publication bias towards positive results probably leads to overestimation of drug efficacy in vascular anomalies. An independent international pharmacovigilance system for drug use in vascular anomalies is proposed to improve efficacy and safety reporting and promote quality drug prescribing.

Introduction: Overweight/obesity (OWOB) causes low-grade systemic inflammation which induces hepcidin and a reduces fractional iron absorption (FIA) even when iron stores are low. Pregnancy increases iron needs because of the expansion of maternal blood volume and fetal needs. It is unclear whether and/or to what extent OWOB during pregnancy influences FIA, iron supply of the fetus and risk of iron deficiency in mother and newborn. In this study, we (1) determined the impact of maternal OWOB on FIA in pregnancy and on the transfer of iron to the fetus and newborn iron status; (2) confirmed the relationship between BMI, hepcidin, serum ferritin (SF) and inflammatory markers. Methods: In this prospective experimental multi-center case-control study (normal-weight (NW) n=40; OWOB n=37) we administered labeled [57Fe]- or [58Fe]-FeSO4 to women during the 2nd and 3rd trimester of pregnancy. We measured FIA by determining erythrocyte incorporation of iron stable isotopes 14 days after administration. From pregnancy week (PW) 12 until PW 36, iron-, inflammation and hepcidin were monitored. Iron transfer to the fetus was determined isotopically as the concentration of circulating iron in the infant aged three days. We assessed iron status in infants born to NW (n=29) and OWOB (n=31) at age three days, three months and six months. Results: Subject characteristics in PW 12 for the NW/OWOB were: mean (±SD) age: 29±6/ 30±6 years, median (IQR) pre-pregnancy BMI: 21.6 (20.3-23.7)/ 31.6 (28.4-35.9) kg/m2 (p<0.001), mean (±SD) hemoglobin: 12.3±1.1/ 12.4±0.9 g/dL, median (IQR) SF: 27.7 (17.3-48.2)/ 30.6 (16.6-64.4) µg/L and median (IQR) interleukin-6: 1.41 (1.03-1.95)/ 2.37 (1.91-3.85) pg/ml (p<0.001). Independent sample t-test showed no difference in FIA between NW and OWOB in the 2nd trimester with median FIA (IQR) 12.3 (7.2-20.6) and 10.1 (6.9-17.2) % (p=0.788). Despite the OWOB had ≈30% lower body iron stores (BIS) and comparable hepcidin concentrations to the NW in the 3rd trimester, FIA was significantly higher in the NW compared to the OWOB with median FIA (IQR) 22.3 (10.6-33.8) and 12.7 (10.4-18.1) % (p=0.042). In the NW, FIA was upregulated by 80% in the 3rd trimester compared to the 2nd trimester, whereas in the OWOB FIA, it was only upregulated by 25%. Linear mixed effect model analysis (LMM) showed a significant group-effects on weight, IL-6 and CRP throughout pregnancy (all p<0.05), but surprisingly no group-effect on hepcidin. In multiple regression analysis, the main predictor of hepcidin throughout pregnancy was BIS, not inflammation. Iron transfer to the newborn was non-significantly higher in the NW compared to the OWOB with mean (±SD) circulating iron in the newborn at age three days 136.6 ± 42.7 and 126.3 ± 32.4 mg. LMM on infant BIS and on infant serum transferrin receptor (sTfR) over the first six months showed significant group (p=0.024, p=0.046) and time-effects (both p<0.001) with lower BIS and higher sTfR in infants born to OWOB. Median (IQR) BIS at age six months were 7.7 (6.3-8.8) and 6.6 (4.6-9.2) mg/kg bodyweight in infants born to NW and OWOB. Conclusion: In normal pregnancy, FIA increases over time to support increased iron needs of mother and fetus. Our data show a dramatically reduced increase in FIA in OWOB pregnant women in the 3rd trimester, despite low BIS and low hepcidin, and this results in less iron transfer to the fetus. Future molecular studies are needed to clarify the mechanism of reduced FIA and fetal iron transfer in OWOB. To our knowledge, this is the first study assessing the impact of maternal OWOB on infant iron status at multiple time points over the first six months. Our findings strongly argue for careful monitoring of iron status in OWOB pregnancy and for defining a more effective iron supplementation regimen for this population group. Prevalence of anemia in pregnancy and infancy is high, especially in low and middle income countries and is often associated with severe health consequences. If iron status of OWOB pregnant women and their infants could be improved by optimizing iron supplementation guidelines for OWOB, this could have major benefits. Disclosures No relevant conflicts of interest to declare.

Introduction: Congenital heart disease is a form of heart abnormality that has been acquired since the newborn. The clinical course of this disorder varies from mild to severe. In mild forms, there are often no symptoms, and no abnormalities are found on clinical examination. Whereas in severe CHD, symptoms have been visible since birth and require immediate action. Generally, the management of congenital heart disease includes non-surgical management and surgical management. Non-surgical management includes medical management and interventional cardiology. Medical management is generally secondary as a result of complications from heart disease itself or due to other accompanying disorders. In this case, the goal of medical therapy is to relieve symptoms and signs in addition to preparing for surgery. The duration and method of administration of drugs depend on the type of disease at hand. Discussion: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to the coronavirus disease 2019 (COVID-19) pandemic, was initially reported in Wuhan, China in December, 2019. The rapid rise in the number of cases worldwide led to hospitals struggling to cope with the sudden influx of patients. This has had a ripple effect on other parts of health care as manpower and supplies needed to be reallocated. Within cardiology, this has led to outpatient appointments and elective surgeries being reduced and/or postponed. COVID-19 appears to have a complicated relationship with cardiovascular system, as studies have suggested cardiovascular diseases increase disease severity and mortality rates in those who are infected. However, the virus has also been shown to cause cardiovascular complications such as acute myocardial injury, heart failure, and arrhythmia. Conclusion: Coronavirus may also cause myocardial injury via the cytokine storm that occurs in response to a possible large immune response during the infection. Cardiac involvement such as right ventricular failure and congestion can either be a result of respiratory distress or direct cardiac injury caused by the virus, as suggested by the raised cardiac troponin I in critical patients compared to non-critical patients.

Background: The most common cause of persistent hypoglycemia in infancy is hyperinsulinemic hypoglycemia. When conservative measures fail, providers often use medications to treat persistent hypoglycemia. Diazoxide is first-line therapy for neonatal hypoglycemia and works by inhibiting insulin secretion. Diazoxide is associated with fluid retention, and less commonly with respiratory decompensation and pulmonary hypertension. Case reports documenting these severe adverse events exist in the literature, although the overall incidence, risk factors, and timing for these effects in a newborn are not clearly defined. Methods: We performed a retrospective chart review of all infants admitted to the neonatal intensive care unit (NICU) at Regional One Health from 1 January 2013 until 15 August 2019, who received diazoxide as a treatment for persistent hypoglycemia secondary to hyperinsulinism. Patients were stratified as either having no adverse event or having an adverse outcome to the medication. A severe adverse outcome was defined as any known major side effect of the medication, which a patient developed within 2 weeks of medication initiation that led to medication discontinuation. Results: From our pharmacy database, we identified a total of 15 babies who received diazoxide for persistent hypoglycemia. Of these patients, eight (53%) were classified as having a complication requiring discontinuation of the medication. Six out of eight patients required intubation with mechanical ventilation and five out of eight patients developed pulmonary hypertension. All patients returned to their baseline respiratory support after drug discontinuation. Conclusions: A total of 53% of our study population had an adverse outcome to diazoxide. Previous studies suggest 5% of patients may have respiratory decompensation and require ventilatory support while on diazoxide; however, 40% of our patients deteriorated and then required mechanical ventilation. Based on our data, respiratory deterioration may be more likely to occur when diazoxide is used in preterm infants, those with lower birth weight and intrauterine growth restriction. Plain language summary The dangers in diazoxide Newborns could experience a transient period of low blood glucose levels soon after birth. However, some may progress to persistent low blood glucose levels that cannot be controlled with adequate glucose infusion and may require other ways of treatment. Diazoxide is the first-line drug approved by the US Food and Drug Administration (FDA) for this condition. However, certain cases have reported the development of respiratory deterioration, including increased blood pressure in lung circulation after its use. This prompted a black box warning in 2015 by the FDA. The incidence of neonatal low blood glucose levels seems to have increased and so has the use of this drug. Our study identifies 15 newborns who received diazoxide at Regional One Health neonatal intensive care unit in the past 6 years and reports a significantly higher rate of adverse events in our population leading to drug discontinuation in almost 53% of our cases.

Abstract Purpose of review The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents. Recent findings Dolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution. Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Given the importance of cognitive and metabolic co-morbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Pharmacogenetics seems to be a promising tool. Safety during pregnancy is also another important issue to further clarify. Summary INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a higher antiviral potency compared to other classes of ARV. Clinicians and patients need however to be aware of some red flags when starting with and monitoring patients on INSTIs. All INSTIs can lead to mild increases in creatinine levels, usually without clinical significance, but caution is needed in patients with low eGFR (<30ml/min), when using other nephrotoxic drugs, such as as tenofovir disoproxil. Neuro-psychiatric (NP) effects are to be monitored with INSTIs, especially with DTG (though reports are at times contradictory); clinicians might want to avoid DTG for patients with history of severe NP symptoms, until clarity is provided. Weight gain was reported with all INSTIs, especially with DTG, with possible differential effects according to sex and ethnicity (female and non-white patients being at increased risk). This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase. Discrepancies between clinical trials – with low rates of adverse events – and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure. Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG. Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster. We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions. Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class.

Recent studies have documented that an increasing number of women of childbearing age are using licit and illicit substances. Although statistical data are insufficient, there are indications that approximately 1 in 10 infants may have been exposed to illicit drugs in utero. The Office of Applied Studies 1992 National Household Survey1 revealed that 6.8% of women of childbearing age admitted to having used an illicit drug in the month before questioning. Recent state surveys have shown that between 8% and 12% of women delivering in their hospitals had used illegal drugs at some time during the pregnancy, including just before delivery.2-5 These studies support information from a study in Pinellas County, FL, which demonstrated that illicit substance use during pregnancy occurs in all racial and socioeconomic lines.6,7 In addition to the use of illegal drugs, the use of alcohol or nonprescribed drugs shortly before delivery is also identified as a problem.8 These incidence data parallel the increasing number of infants being admitted to special-care nurseries for complications caused by intrauterine exposure to alcohol and other drugs. Drug-exposed infants also often go unrecognized and are discharged from the newborn nursery at increased risk for a complex of medical and social problems, including abuse and neglect. This statement addresses illicit substance use in pregnancy and its medical, educational, social, mental health, and legal consequences for children and families. The Academy recently has developed a separate statement to address the issue of infants exposed to alcohol in utero.9 The Problem All illicit drugs reach the fetal circulation by crossing the placenta and can cause direct toxic effects on the fetus, as well as fetal and maternal dependency.10

Recent studies have documented that an increasing number of women of childbearing age are abusing licit and illicit substances. Although statistical data are insufficient, there are indications that approximately 1 in 10 infants may be exposed to illicit drugs during pregnancy. The National Institute on Drug Abuse 1988 National Household Survey1 revealed that 8.8% of women of childbearing age admitted to having used an illicit drug in the month before questioning. A recent survey of 36 private and public hospitals2 showed that approximately 11% of women delivering in these hospitals had used illegal drugs at some time during their pregnancies. A preliminary study in Pinellas County, Florida, demonstrated that cocaine and marijuana use during pregnancy were almost equally distributed across racial and socioeconomic lines.3 These incidence data parallel the increasing number of infants being admitted to special-care nurseries for complications caused by their intrauterine exposure to alcohol and other drugs. It is also important to consider that drug-exposed infants often go unrecognized and are discharged from the newborn nursery to homes where they are at increased risk for a complex of medical and social problems including abuse and neglect. This statement addresses illicit substance use in pregnancy and its medical, social, mental health, and legal consequences for children and families. The Academy is developing a separate statement to address the issue of infants exposed to alcohol in utero. THE PROBLEM All illicit drugs reach the fetal circulation by crossing the placenta and can cause direct toxic effects on the fetus, as well as fetal and maternal dependency.

<b><i>Aim:</i></b> Pain management is important for newborns’ immediate and long-term well-being. While intranasal analgesia and sedation have been well studied in children, their use could be extended to term and preterm infants. This systematic review aims to assess the use of intranasal medications for procedural analgesia or sedation in the neonatal intensive care unit. <b><i>Methods:</i></b> MEDLINE via Ovid, Scopus, Embase, and Cochrane Library were searched independently by two reviewers for clinical studies on sedation or analgesia given intranasally. <b><i>Results:</i></b> Seven studies, with 401 patients, were included. The studies described various molecules (midazolam, fentanyl, ketamine, or dexmedetomidine) for different procedures such as intubation in the delivery room, screening for retinopathy, or magnetic resonance imaging. All studies reported significant reduction in pain and sedation markers (based on clinical scales, skin conductance, and clinical variables such as heart rate and crying time). Adverse effects were uncommon and mostly consisted in desaturation, apnoea, hypotension, or paradoxical reactions. <b><i>Discussion and Conclusion:</i></b> The intranasal route seems a potential alternative for procedural pain management and sedation in neonates, especially when intravenous access is not available. However, data about safety remain limited. Reported sides effects could be attributed to molecules used rather than the intranasal route. Optimal drugs and doses still need to be characterized. Further studies are needed to ensure safety before promoting a widespread use of intranasal medications in neonatology.

Cannabis is one of the most widely used illicit drugs during pregnancy and lactation. With the recent legalization of cannabis in many countries, health professionals are increasingly exposed to pregnant and breastfeeding women who are consuming cannabis on a regular basis as a solution for depression, anxiety, nausea, and pain. Cannabis consumption during pregnancy can induce negative birth outcomes such as reduced birth weight and increased risk of prematurity and admission to the neonatal intensive care unit. Yet, limited information is available regarding the pharmacokinetics of cannabis in the fetus and newborn exposed during pregnancy and lactation. Indeed, the official recommendations regarding the use of cannabis during these two critical development periods lack robust pharmacokinetics data and make it difficult for health professionals to guide their patients. Many clinical studies are currently evaluating the effects of cannabis on the brain development and base their groups mostly on questionnaires. These studies should be associated with pharmacokinetics studies to assess correlations between the infant brain development and the exposure to cannabis during pregnancy and breastfeeding. Our project aims to review the available data on the pharmacokinetics of cannabinoids in adults, neonates, and animals. If the available literature is abundant in adult humans and animals, there is still a lack of published data on the exposure of pregnant and lactating women and neonates. However, some of the published information causes concerns on the exposure and the potential effects of cannabis on fetuses and neonates. The safety of cannabis use for non-medical purpose during pregnancy and breastfeeding needs to be further characterized with proper pharmacokinetic studies in humans feasible in regions where cannabis has been legalized. Given the available data, significant transfer occurs to the fetus and the breastfed newborn with a theoretical risk of accumulation of products known to be biologically active.

Background: Drug-induced immune hemolytic anemia is a serious adverse reaction that may result from drug administration, especially in cases of glucose-6-phospate dehydrogenase (G6PD) deficiency. Objective: To report a case of acute hemolytic anemia in a 30-year-old Saudi male after receiving Semaglutide injection. Case Report: A 30-year-old Saudi male with G6PD deficiency presented to the Emergency Department of Aseer Central Hospital, Abha City, Saudi Arabia with acute onset of yellow discoloration of the eyes, palpitation, mild backache, fatigue, and dark urine. The symptoms started one day after receiving the second dose of Semaglutide injection. He looked pale and the sclera were slightly icteric. Laboratory investigations showed high serum levels of liver enzymes and the total bilirubin. The RBCs count as well as the hemoglobin and the hematocrit were low, while reticulocyte count was high. The diagnosis was acute hemolytic anemia, most probably triggered by a recent Semaglutide injection. Following the discontinuation of Semaglutide, his clinical condition improved. Conclusions: G6PD deficiency should be considered in all clinical settings, and the hemolytic conditions that can possibly be precipitated by drugs not well known to cause hemolysis. Screening of newborn infants to early detect G6PD deficiency early is highly recommended, especially in those with positive family history of G6PD. Key Words: Semaglutide, Hemolytic anemia, G6PD deficiency, Case report.

Abstract Background Congenital syphilis (CS) depends on the placental transmission of Treponema pallidum (TP) spirochetes from an infected mother to fetus during pregnancy. It shows a wide clinical variability with cutaneous and visceral manifestations, including stillbirths, neonatal death, and asymptomatic cases. Preterm infants with CS may have more severe features of disease than the term ones, due to the combined pathogenic effect of both CS and prematurity. Case presentation We report on a female preterm (32+6 weeks of gestation) newborn showing most of the typical CS manifestations, in addition to gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth restriction. The mother resulted positive at the syphilis screening test of the first trimester of pregnancy, but she did not undergo any treatment. At birth, our newborn was VDRL positive (antibody titer four times higher compared to the mother), and she was treated with intravenous benzathine benzylpenicillin G for 10 days (50,000 IU/Kg three times per day). Poor tolerance to enteral nutrition (abdominal distension, increased biliary type gastric secretions) was observed. A barium enema X-Ray identified a colon stenosis within the descending tract. However, the poor general conditions due to a concurrent fungal sepsis did not allow to perform any surgical procedure, and a conservative approach with total parenteral nutrition was started. The following evolution was marked by difficulties in enteral feeding including refusal of food and vomiting, to which also contributed the neurological abnormalities related to a perinatal asphyxia, and the affective deprivation for the physical absence of the mother during hospitalization. At 5 months of age, after the introduction of an amino acid-based formula (Neocate LCP Nutricia ®), an improvement of enteral feeding was observed, with no further and significantly decreased episodes of abdominal distension and vomiting respectively, and regular stool emission. A psychological support offered to the family allowed a more stable bond between the mother and her baby, thus providing a significant additional benefit to food tolerance and growth. She was discharged at 5 months of age, and included in a multidisciplinary follow-up. She at present shows global growth delay, and normal development apart from mildly increased tone of lower limbs. Conclusions Our report highlights less common clinical CS manifestations like gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth delay. Moreover, it underlines how prematurity may worsen the clinical evolution of such congenital infection, due to the additional pathogenic effect of possible associated diseases and/or conditions like sepsis, hypoxic/ischemic injury, or use of drugs. CS may be observed also in high-income countries, with high rates of antenatal screening and availability of prenatal treatment. A multidisciplinary network must be guaranteed to the affected subjects, to ensure adequate care and improve the quality of life for patients and their families.

Abstract Background Most extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA) < 28 completed weeks) require supplemental oxygen and experience frequent intermittent hypoxemic and hyperoxemic episodes. Hypoxemic episodes and exposure to inadequately high concentrations of oxygen are associated with an increased risk of retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC), neurodevelopmental impairment (NDI), and death beyond 36 weeks PMA. Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the hemoglobin oxygen saturation (SpO2) target range, number and duration of hypo- and hyperoxemic episodes and caregivers’ workload. Effects on clinically important outcomes in ELGANs such as ROP, BPD, NEC, NDI and mortality have not yet been studied. Methods An outcome-assessor-blinded, randomized controlled, parallel-group trial was designed and powered to study the effect of FiO2-C (in addition to routine manual control (RMC) of FiO2), compared to RMC only, on death and severe complications related to hypoxemia and/or hyperoxemia. 2340 ELGANS with a GA of 23 + 0/7 to 27 + 6/7 weeks will be recruited in approximately 75 European tertiary care neonatal centers. Study participants are randomly assigned to RMC (control-group) or FiO2-C in addition to RMC (intervention-group). Central randomization is stratified for center, gender and PMA at birth (< 26 weeks and ≥ 26 weeks). FiO2-C is provided by commercially available and CE-marked ventilators with an FiO2-C algorithm intended for use in newborn infants. The primary outcome variable (composite of death, severe ROP, BPD or NEC) is assessed at 36 weeks PMA (or, in case of ROP, until complete vascularization of the retina, respectively). The co-primary outcome variable (composite outcome of death, language/cognitive delay, motor impairment, severe visual impairment or hearing impairment) is assessed at 24 months corrected age. Discussion Short-term studies on FiO2-C showed improved time ELGANs spent within their assigned SpO2 target range, but effects of FiO2-C on clinical outcomes are yet unknown and will be addressed in the FiO2-C trial. This will ensure an appropriate assessment of safety and efficacy before FiO2-C may be implemented as standard therapy. Trial registration The study is registered at www.ClinicalTrials.gov: NCT03168516, May 30, 2017.

Caring for preterm and low birthweight babies, collectively termed ‘small babies,’ has long been the predicament of perinatal and neonatal medicine experts throughout the world. Its occurrence is, by and large, associated with maternal morbidities, which consequently contribute to neonatal mortality and morbidity, both in the short and long term. For this reason, its prevention and optimal management remain a challenge and the subject of much deliberation, research, policy and even, legislation. Traditionally kept in incubators for long periods, small premature babies grow in this environment; not much different from ‘poultry hatcheries’ where the environment is artificially controlled, and nurturing is programmed. The shortage of incubators in an overcrowded Colombian neonatal intensive care unit (NICU) turned out to be a blessing-in-disguise for Dr. Edgar Rey Sanabria,1 who recognized that such an environment only led to more unwanted complications and even death. Taking the cue from the kangaroo and other marsupials, he transferred the caring of stable small babies from incubators to their mothers’ chests and valiantly sent them home earlier than the standard recommendation, with the mothers’ breastmilk and warmth to nurture and care for them. This innovation which took place in the 1970s, took 15 years for the scientific community to take notice after the first scientific evidence was published in the literature.2 This landmark study and all those that followed, consistently showed the impact of kangaroo mother care (KMC) on neonatal mortality, growth, neurodevelopment, and overall wellness of the mother-baby dyad in the company of a supportive family, decreased postpartum anxiety and depression, improved breastfeeding exclusivity and duration, decreased NICU sepsis rates3,4 with no increase in community-acquired infections.2 Amidst the shortage of NICU nursing personnel, the other significant ‘side-effect’ of the KMC intervention is the improved allocation of NICU nursing and auxiliary personnel to high-risk neonates with the integration of the mother in the overall care of the small baby, a prelude to the concept of family-centered/ integrated NICU care currently being recommended.5 KMC in the Philippines started in 1999 at the Dr. Jose Fabella Memorial Hospital, after two of its personnel received training in Colombia (Fundacion Canguro). Its standard implementation as a hospital policy of care for small babies soon followed the first local in-house publication of data6 showing its favorable impact on mortality and overall outcomes on its population of preterm small babies. Involvement of the community of Manila through the city health government improved follow-up and ambulatory KMC implementation.7 By 2005, the nidus of a comprehensive KMC program implementation was realized and technically ready for replication in other health facilities caring for preterm and small babies. Such endeavor, however, was not possible at the time. The KMC Foundation Philippines, registered in 2008, helped pave the way for KMC acceleration in the country. This followed the issuance of the DOH Administrative Order 2009-0025 in Dec 2009 on the essential newborn care (ENC) protocol, which included initiation of KMC for small babies at birth, for better thermoregulation and maternal-infant bonding. The KMC Foundation offered the complete program concept to regional DOH facilities and helped establish regional KMC Centers of Excellence nationwide. Between 2012 and 2014, the foundation gained the support and collaboration of development partners in the Philippines, i.e., the World Health Organization, UNICEF, Save The Children/USAID, and most importantly, the Family Health Office of the Department of Health. ENC, basic newborn resuscitation, and KMC integration into the Care for Small Babies (CSB) package of interventions, henceforth, was cascaded to all DOH facilities.8 Capacity-building efforts have led to the establishment of 27 CSB centers for training and excellence and 195 program-implementing facilities nationwide by the end of 2018. The first draft of the DOH Policy on CSB, entitled “National Policy on the Quality of Care for Small Babies: Accelerating the Reduction of Newborn Deaths” was composed in 2015. Included in this policy, are 1) capacity development of health care providers 2) provision of a KMC unit within the NICU complex or Pediatrics ward and 3) networking with the community through the service delivery network and collaboration with local government units. The initial draft fueled the constitution of a PhilHealth Z-benefit package for the care of preterm and small babies which was launched in 2016 and initiated by 2017 in the established CSB Centers of Excellence. The draft policy has been revised in a workshop in 2019. While so much has happened on the ground level towards the acceleration and efficient implementation of the CSB package of interventions, the DOH policy that should reinforce its standard practice in all of 1,871 PhilHealth-accredited facilities nationwide, remains in the shadows, awaiting an official stamp of approval. This focused Acta Medica Philippina special issue on KMC highlights the research evidence generated by various institutions currently implementing the standard program in the Philippines. It is hoped that this publication will help substantiate and facilitate the approval of the pending DOH policy on care for small babies. Socorro De Leon-Mendoza, MD, FPPS, FPSNbM President, Kangaroo Mother Care Foundation Philippines, Inc. Immediate Past President, Federation of Asia and Oceania Perinatal Societies REFERENCES Rey SE, Martínez HG. Rational management of the premature child. Fetal Medicine Course. Bogotá: National University; 1983. p. 137-15. Charpak N, Ruiz-Peláez JG, Charpak Y. Rey-Martinez Kangaroo Mother Program: an alternative way of caring for low birth weight infants? One year mortality in a two cohort study. Pediatrics. 1994 Dec; 94(6 Pt 1):804-10. PMID: 7970993. Conde-Agudelo A, Díaz-Rossello JL. Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database Syst Rev. 2016 Aug 23; 2016(8):CD002771. doi: 10.1002/14651858.CD002771.pub4. PMID: 27552521. Charpak N, Tessier R, Ruiz JG, Hernandez JT, Uriza F, Villegas J, et al. Twenty-year follow-up of kangaroo mother care versus traditional care. Pediatrics. 2017 Jan; 139(1):e20162063. doi: 10.1542/peds.2016-2063. Epub 2016 Dec 12. PMID: 27965377. USAID. Every Preemie: Nurturing Care for Small and Sick Newborns. Evidence Review and Country Case Studies. Eds. New K, Durairaj A, Robb-McCord J, Khadka N. Aug 2019. pp54-62 [Internet]. 2021 [cited October 2021]. Available from: https://www.everypreemie.org/wp-content/uploads/2019/09/Nurturing-Care-Evidence-Review-and-Case-Studies-13Aug2019.pdf De Leon-Mendoza S. Impact of kangaroo mother care (KMC) on the survivability of the moderately-low birth weight neonate. Dr. Jose Fabella Memorial Hospital Medical J. 2001; 2:1 Bergh AM, de Graft-Johnson J, Khadka N, Om’Iniabohs A, Udani R, Pratomo H, et al. The three waves in implementation of facility-based kangaroo mother care: a multi-country case study from Asia. BMC Int Health Hum Rights. 2016 Jan 27; 16:4. doi: 10.1186/s12914-016-0080-4. PMID: 26818943. Calibo AP, De Leon Mendoza S, Silvestre MA, Murray JCS, Li Z, Mannava P, et al. Scaling up kangaroo mother care in the Philippines using policy, regulatory and systems reform to drive changes in birth practices. BMJ Glob Health. 2021 Aug; 6(8):e006492. doi: 10.1136/bmjgh-2021-006492. PMID: 34417273.

Photo by Hédi Benyounes on Unsplash ABSTRACT The current incarceration facilities for the growing number of women are depriving expecting mothers of adequate care crucial for the child’s mental and physical development. Programs need to be established to counteract this. INTRODUCTION Currently, Diana Sanchez was eight months pregnant when she was arrested for identity theft and put in a prison cell in Denver. At five a.m., two weeks after being incarcerated, she announced to a deputy outside her cell that she was going into labor. Footage from a camera in her cell shows her pacing anxiously or writhing in her bed for the five hours preceding the arrival of her son. She banged on the door and begged for help. All she received was an absorbent pad. She gave birth alone in her prison cell on July 31, 2015, around 10:45 am. At 11:00 am, a prison nurse walked in to cut the umbilical cord and take Sanchez’s newborn baby without offering postnatal care. Sanchez was later sent to a hospital, and her baby was separated from her until she was put on probation. In 2018, on behalf of her three-year-old son, Sanchez sued Denver Health and Denver Sheriff Department and won a $480,000 settlement.[1] Though many more men are incarcerated than women, the rate of growth of female incarceration has exceeded that of male incarceration for decades. One study estimated that 231,000 women are currently incarcerated in the US,[2] 80 percent of whom are mothers, and 150,000 pregnant.[3] Another recent study of 1,396 incarcerated pregnant women found that 92 percent had live births, 6.5 percent had stillbirths or miscarriages, and 4 percent terminated the pregnancy. The authors found that there is no system of reporting pregnancy outcomes in US prisons. There is a noteworthy ethical lapse in mental, emotional, and medical care that threatens the well-being of pregnant women in prison. According to Carolyn Sufrin, “Pregnant incarcerated people are one of the most marginalized and forgotten groups in our country… and women who don't get counted don't count.” [4] Poor documentation, visibility, and transparency contribute to the systemic abuse of incarcerated women. Studies document women giving birth alone in cells and shackles in solitary confinement. Their complaints regarding contractions, bleeding, and other pains of labor are often ignored.[5] l. Prenatal Care in American Prisons Diana Sanchez was not offered any prenatal care after she was incarcerated. And neither she nor her son received appropriate postnatal care.[6] Sanchez was on medication for opioid withdrawal while pregnant, which could have been detrimental to her baby’s health.[7] There is an unacceptable absence of pre- and postnatal care in most US prisons. A lack of regulation makes the availability of perinatal care unpredictable and unreliable. Several studies confirmed that there is not a standard for prenatal care for women incarcerated during pregnancy. [8] Knowledge of the appropriate mental and physical care pregnant women require, addiction support, and support for maternal-infant bonding all exists outside the prison system and ought to be used as a benchmark. At the very least, pregnant women, birthing women, and new mothers should not be placed in solitary confinement or shackled.[9] In the prenatal arena, depriving an individual of adequate healthcare is not appropriate and could be cruel and unusual. Only 18 percent of funding in prisons goes to health care for the prisoners. That is roughly $5.7 thousand per prisoner, according to an NIH study done in 2015.[10] There should be an adequate amount of funding for the health needs of incarcerated pregnant women. By depriving pregnant women of healthcare, the prisons are depriving the fetus of adequate care. ll. Respect for Autonomy During Incarceration Women maintain healthcare autonomy even when incarcerated. The purpose of a prison sentence is retribution for crimes and rehabilitation to prevent reoffending.[11] The separation of a mother and newborn causes significant developmental and psychological harm to the child and the parent. Parent-child separation does not serve the purpose of retribution or rehabilitation and is authorized only due to prisons’ limited space and resources that make it difficult to accommodate children, as well as a state interest in children’s best interests or the custody rights of the other parent. When it is possible to keep a family together, prisons should make every effort to do so for the health of the mother-child relationship. Incarcerated people may become a burden to family or society due to prison medical neglect. For example, diabetes and hypertension, which can occur during pregnancy, can worsen without treatment. The inability to access the care they would otherwise want and need endangers women and poses a burden to the healthcare system after incarceration, Depersonalizing individuals convicted of crimes must be placed in the context of historical eugenics practices. State-sanctioned sterilization and efforts to prevent women from reproducing were widespread during the early 20th century.[12] Cases of coerced and nonconsensual sterilization of incarcerated women and men evidence the history of eugenics.[13]Abortions are offered to some incarcerated women.[14] However, many incarcerated women are denied the right to see healthcare providers to thoroughly discuss abortion or other options.[15] Although the abortions are consensual, the quality of consent is questionable. lll. Prison Nursery Programs, “I need something to live for…” Indiana Women’s Prison (IWP), a max security female prison, has a program called Wee Ones that enables women convicted of nonviolent crimes to spend 30 months bonding with their newborn child. It is one of eight programs in the country that allows pregnant mothers to spend the last few months of their sentence with their children. It is a voluntary program that allows pregnant offenders a private room in a housing unit. It offers parent education, resources that are accessible after release, and career education. The program application process and the rules to which women must adhere to remain in the program are stringent. The programs generally have a zero-tolerance policy. Even simply sleeping in the same bed as the child or arguing with other mothers can result in termination from the program. Kara, a pregnant woman incarcerated for drug possession, had a history of abuse in her family and tended to act out in anger against her peers in the program. She was learning how to have healthy reactions to anger when handling her child, but her temper ultimately led to her removal from the program. Her son was placed in foster care, and Kara returned to the regular cells. In an interview before her transfer, she told the camera that Charlie gave her a purpose. With tears in her eyes, she said, “Charlie was my way of life here [...] I need something to live for [,] and I screwed up.”[16] Pregnancy in prison can be a way to improve quality of life for some women. Studies demonstrate that nursery programs improve mental health of the incarcerated women.[17] The secure attachment of the infant to its primary caregiver promotes healthy development in the child and a bonded relationship with the mother.[18] The close bond between mother and child in prisons has been shown to decrease recidivism and to reduce the burden on the foster care system.[19] Women who do not qualify for these programs, or are incarcerated in prisons without them, are separated from their newborn babies and their other children. The disconnect can lead to the child rejecting the incarcerated mother once she is released.[20] Programs like Wee Ones honor women’s autonomy while they are incarcerated. During interviews, the women expressed that although raising a child in that environment is difficult, it was better than not being with their children. While rocking a baby in her lap, one inmate expressed her frustrations with Wee Ones but then paused to express gratitude and said, “After all, it’s prison. And prison ain’t supposed to be nice.”[21] The ethical issue of autonomy reflects a more difficult dilemma in the prison landscape. lV. Counter Arguments: Do the Nursery Programs Work for the Children and the Women Typically, newborns are taken from their incarcerated mothers within two to three days of birth and sent to live with a relative or placed in foster care. Many women are never reunited with their babies. There is much debate over whether the programs are beneficial to the children. One ethical issue is whether children, as innocents, are being punished either by being in the prison system or by being separated from their mothers. Skeptics, like James Dwyer, have argued against keeping innocent babies in the custody of incarcerated mothers asserting that there is little evidence demonstrating that the programs rehabilitate the women.[22] Dwyer commented on the “reckless” hopefulness the programs provide: "It might, in fact, be the babies distract them from rehabilitation they should be doing instead. […] They're so focused on childcare and have this euphoria — they think they'll be just fine when they get out of prison and they're not. We just don't know."[23] One study showed that 58 percent of incarcerated women are arrested again after release, 38 percent are reconvicted, and 30 percent return to prison within three years.[24] Dwyer uses this data to argue that the programs are not worthwhile. However, the data is not limited to the special population that had the prison nursery experience. The data applies to all incarcerated women limiting its applicability. More importantly, there is compelling evidence to support prison nursery programs.[25] The programs do decrease recidivism[26] and prison misconduct,[27] and they allow women to create stronger bonds with their children.[28] Bev Little argues that allowing mothers to bond with their babies only delays the inevitable separation and will cause trauma and have other ill effects on the baby. [29] But others feel that stronger maternal-fetal attachment is best for both parties. There is evidence that the bond, once formed, is long-lasting. Later in life, there is less drug addiction among children who stayed in the nursery rather than being separated from their mothers.[30] Another counterargument is that the policies in prison nurseries are not as useful for motherhood outside of the facility; thus, an issue with recidivism occurs because the women are less prepared for motherhood upon release from prison. Prison nursery programs establish methods and procedures for successful motherhood that are unique to operation within correctional environments. Yet, fortunately, parenting classes offered by prisons and jails emphasize sacrifice, self-restraint, and dedicated attention to the baby. These classes aptly apply to motherhood outside of prison.[31] One incarcerated mother experiencing addiction, Kima, was described as ambivalent toward her pregnancy. “It’s something about knowing but not knowing that makes me not accountable or makes me think I’m not accountable,” Kima shared.[32] After the nurse confirmed her pregnancy, she acknowledged fear and knew she would be held accountable to the baby. The occurrence of pregnancy ambivalence is common.[33] A study of a population of prisoners from Rhode Island found that 41 percent of the women expressed ambivalent attitudes about pregnancy. 70 of the women from a population in San Francisco expressed ambivalent or negative attitudes towards pregnancy.[34] But the ambivalence of some women toward pregnancy is not a reason to prevent women who feel differently from reaping the full benefits of programs that support them during pregnancy. Another counterargument is that prison is becoming a comfort that women might seek if they are homeless or housing insecure. For example, Evelyn was released from a San Francisco jail after being arrested for using cocaine. She was 26 weeks pregnant and had a four-year-old son in the custody of her aunt. Following her release, she was homeless and using drugs in the streets. She felt that her only hope of keeping her baby safe was to go back to jail. Like Kima, she had been in and out of jail from a young age. She grew accustomed to and dependent on the care provided there. While incarceration can provide a home and a nursery, there is no ethical reason to argue for making prison less comfortable by separating babies and children from incarcerated women. Instead, these facts suggest we are not doing enough for women outside prisons either. CONCLUSION Many experts stress the dearth of research and information on these women and their babies. There is no empirical data to show how big the problem is, but there is evidence that programs providing nursery care for the children of incarcerated women have many benefits. Because the research is not largescale enough, many pregnant women in the prison system are ignored. Many women give birth in unacceptable conditions, and their children are taken from them the moment the umbilical cord is cut. While the US incarcerates too many women, a movement to expand prison nurseries could help new mothers bond with their children. Strong educational programs could aid in lowering the rates of recidivism by providing therapeutic resources for mothers.[35] There is a growing problem of mass incarceration in the US as many women are placed in correctional facilities. Most of these women are convicted of possession or use of illegal substances.[36] Many women come from disadvantaged backgrounds, poverty, and have experienced addiction. Depriving an expectant mother of adequate care is cruel and irresponsible both to the mother and her innocent child. The criminal justice system is harming children both mentally and physically. Reform of the system is needed to provide the basic care those children need. Programs like IWP’s Wee Ones are necessary for physical, psychological, and social development. A program that offers a place for mothers to raise their babies in the community of other mothers would incentivize and facilitate healthy parental habits. Further programs for mothers who are released from prison would give them valuable resources to keep them from returning and encourage healthy relationships between the mother and the baby. - [1] Li, D. K. Video allegedly shows woman giving birth in Denver jail cell alone, with no assistance. Denver: NBC News, 2019. [2] Kajstura, Aleks. “Women's Mass Incarceration: The Whole Pie 2019.” Prison Policy Initiative, 29 Oct. 2019, https://www.prisonpolicy.org/reports/pie2019women.html. (“Including those in prisons, jails, and other correctional facilities.”) [3] Swavola, E, K Riley and R Subramanian. "Overlooked: Women and Jails in an Era of Reform." Vera Institute of Justice August 2016. [4] Sufrin, C. Pregnant Behind Bars: What We Do and Don't Know About Pregnancy and Incarceration Allison Chang. 21 March 2019. Transcript. [5] Sufrin, C., 2019. (Suffrin expressed that she had seen such practices firsthand working as an OB/GYN for incarcerated women.) [6] Padilla, M. “Woman Gave Birth in Denver Jail Cell Alone, Lawsuit Says,” New York Times, Sep. 1, 2019. [7] Li, D. “Video allegedly shows woman giving birth in Denver jail cell alone, with no assistance,” NBC U.S. News, Apr. 29. 2019. [8] Knittel, A. and C. Sufrin. "Maternal Health Equity and Justice for Pregnant Women Who Experience Incarceration." JAMA Network Open 3.8 (2020). A study in Ontario, Canada, coincided with a study done in Australia. [9] Sufrin, C., et al. "Pregnancy Outcomes in US Prisons, 2016–2017." p. 803-804. [10] Sridhar, S., R. Cornish and S. Fazel. "The Costs of Healthcare in Prison and Custody: Systematic Review of Current Estimates and Proposed Guidelines for Future Reporting." Frontiers in Psychiatry 9.716 (2018). [11] Kifer, M., Hemmens, C., Stohr, M. K. “The Goals of Corrections: Perspectives from the Line” Criminal Justice Review. 1 May 2003 [12] Perry, D. M. "Our Long, Troubling History of Sterilizing the Incarcerated." The Marshall Project: Sterilization of Women in Prison 26 July 2017. [13] Rachel Roth & Sara L. Ainsworth, If They Hand You a Paper, You Sign It: A Call to End the Sterilization of Women in Prison, 26 Hastings WOMEN's L.J. 7 (2015); See Skinner v. Oklahoma ex rel. Williamson, 316 U.S. 535 (1942) (procreation considered a fundamental right; fact pattern of male sterilization in prison based on type of crime.) [14] Sufrin, C., M. D. Creinin, J. C. Chang. “Incarcerated Women and Abortion Provision: A Survey of Correctional Health Providers.” Perspectives on Sexual and Reproductive Health. p. 6-11. 23 March 2009. [15] Kasdan, D. “Abortion Access for Incarcerated Women: Are Correctional Health Practices in Conflict with Constitutional Standards?” Guttmacher Institute. 26 March 2009. [16] Born Behind Bars. Season 1, Episode 5, “They Can Take Your Baby Away,” produced by Luke Ellis, Francis Gasparini, & Jen Wise, aired on 15 Nov. 2017 A&E Networks [17] Bick, J., & Dozier, M. (2008). Helping Foster Parents Change: The Role of Parental State of Mind. In H. Steele & M. Steele (Eds.), Clinical applications of the Adult Attachment Interview (pp. 452–470). New York: Guilford Press. [18]Sroufe, L. A., B. Egeland, E. A. Carlson, W. A. Collins. (2005). The Development of the Person: The Minnesota Study of Risk and Adaptation from Birth to Adulthood. New York: Guilford Press. [19] Goshin, L. S., & Byrne, M. W. “Converging Streams of Opportunity for Prison Nursery Programs in the United States.” Journal of Offender Rehabilitation. 15 Apr 2009. [20] Babies Behind Bars. Dirs. W. Serrill and S. O'Brien. 2015. Another IWP pregnant woman is Taylor. At the time of the show, she was pregnant and expecting twins. In interviews throughout the episode, she expressed how her pregnancies in prison had put her in a better mood and felt beneficial to her. She had tried to sign up for the nursery program for her previous pregnancy, but her sentence was too long to get it. Her child was sent to live with a caregiver, and when Taylor was on probation, Taylor’s daughter didn’t want to be around Taylor. Taylor was so distraught that she messed up and went back, this time, pregnant with twins. After she was reincarcerated, she was able to be accepted into Wee Ones. She expressed to the camera man that the program might help her feel more like a mother so that when she gets out, she will have someone to care for. Taylor, Kara, and many other women depend on their children or their pregnancy for a purpose while behind bars. They relied on their babies to be a boon for them. [21] Babies Behind Bars. Dirs. W. Serrill and S. O'Brien. 2015. [22] Corley, C. "Programs Help Incarcerated Moms Bond with Their Babies in Prison." Criminal Justice Collaborative (2018). [23] Corley, C. "Programs Help Incarcerated Moms Bond with Their Babies in Prison." Criminal Justice Collaborative (2018). [24] Owen, B. & Crow, J. “Recidivism among Female Prisoners: Secondary Analysis of the 1994 BJS Recidivism Data Set” Department of Criminology California State University (2006) p. 28 [25] Prison Nursery Programs: Literature Review and Fact Sheet for CT. Diamond Research Consulting, 2012, www.cga.ct.gov/2013/JUDdata/tmy/2013HB-06642-R000401-Sarah Diamond - Director, Diamond Research Consulting-TMY.PDF. [26] New York Department of Correction Services (NYDOCS). (1993). Profile of Participants: The Bedford and Taconic Nursery Program in 1992. Albany, NY. Department of Correction Services.Rowland, M., & Watts, A. (2007). Washington State’s effort to the generational impact on crime. Corrections Today. Retrieved September 12, 2007, from http://www. aca.org/publications/pdf/Rowland_Watts_Aug07.pdf. [27] Carlson, J. R. (2001). Prison nursery 2000: A five-year review of the prison nursery at the Nebraska Correctional Center for Women. Journal of Offender Rehabilitation, 33, 75–97. [28] Carlson, J.R. [29] Little, B. "What Happens When a Woman Gives Birth Behind Bars?" A+E Networks, 29 October 2019. <https://www.aetv.com/real-crime/what-happens-when-a-woman-gives-birth-in-jail-or-prison>. [30] Margolies, J. K., & Kraft-Stolar, T. When “Free” Means Losing Your Mother: The Collision of Child Welfare and the Incarceration of Women in New York State 1, 9 (Correctional Association of N.Y. Women in Prison Project 2006) [31] Sufrin, C. Jailcare: Finding the Safety Net for Women Behind Bars. Berkeley: University of California Press, 2017. [32] Sufrin, C. Jailcare: p. 155. [33] Peart, M. S. & Knittel, A. K. “Contraception need and available services among incarcerated women in the United States: a systematic review.” Contraception and Reproductive Medicine. 17 March 2020 [34] LaRochelle, F., C. Castro, J. Goldenson, J. P. Tulsky, D.L. Cohan, P. D. Blumenthal, et al. “Contraceptive use and barriers to access among newly arrested women.” J Correct Health Care. (2012) p. 111–119. [35] Goshin, L., & Byrne, M. (2009). “Converging streams of opportunity for prison nursery programs in the United States.” Journal of Offender Rehabilitation. 2009. p.271–295. [36] Elizabeth Swavola, Kristine Riley, Ram Subramanian. Overlooked: Women and Jails in an Era of Reform. New York: Vera Institute of Justice, 2016.

Ozone is a powerful oxidant, surpassed, in this regard, only by fluorine. Its doubtless strong reactivity has contributed to establish the dogma that ozone is always toxic and its medical application must be proscribed. However, ozone therapy has been used for therapeutic purposes since the beginning of the last century and its use is increasingly demanded nowadays. For proper enlightenment and guidance of the person interested in the use of ozone for medical purposes, scientific documentation on the safety/toxicity profile of this acclaimed procedure becomes necessary. Taking into account that the National Health Regulatory Agencies require of documentation with scientific trials for sanitary registration of drugs and therapy procedures, different toxicological tests were performed in Cuba using experimental animals, following the guidelines from the Cuban Regulatory Agency, Food Drug Administration, International Standards Organization and the Health World Organization aimed at proving the safety of ozone therapy administration. In this lecture, the teratogenic study of ozone by rectal insufflation (RI) is presented. Female Wistar rats (200-250 g) were divided into 3 experimental groups: 1- control (n=15), without any treatment; 2- treated with 1 mL of ozone (n=17) at a concentration of 34 ?g/mL (150 ?g/kg); 3- treated with 4 mL of ozone (n=17) at a concentration of 90 ?g/mL (1600 ?g/kg). Ozone was administered by RI during 10 sessions, from the 6th to the 15th day of gestation. The pregnancy was confirmed by the presence of spermatozoa in the vaginal exudates. It was considered that the animals with positive exudates were in the 0 day of gestation. In the 19th day of gestation, animals were euthanized by an ether overdose and the fetuses were obtained by cesarean. The number of corpus luteum, implantations, alive and dead fetuses, reabsorptions, as well as the weight and the length cranium-caudal of each fetus were registered. Alive fetuses were examined to find any external malformations. No toxic effect was observed in the pregnant rats subjected to the ozone treatment by RI. Mother weight gain did not show significant differences among the groups, neither the other indicators (number of corpus luteum, implantations, alive and dead fetus, reabsorptions). In respect to the fetus morphology, no external, skeletal or visceral malformations were observed. The weight and the length cranium-causal did not show significant differences among the groups. It is concluded that no teratogenic nor embriotoxic effects were found after the ozone application by rectal insufflation at the doses studied. With respect to the application of ozone therapy in Obstetrics, an update of the papers published about this topic was presented. They referred the use of ozone therapy in: pregnant womens with hypertension, genital or no genital infections during pregnancy, threatened abortion, intrauterine fetal hypoxia, among others. For example, the effect of ozone therapy by rectal insufflation on fetoplacental blood flow in hypertensive pregnant women, with 24 weeks of gestation, indicated a better fetoplacental blood flow, achieving a greater oxygenation in the group treated with ozone plus antihypertensive treatment (methyldopa) in comparison with a control group treated only with the conventional treatment. Also, a reduction of methyldopa in 23.7 % of the initial doses was found in the ozone group as opposed to an increase of 40.8% in the control group. Another study about ozone therapy as the main component of the complex treatment of threatened abortion, using ozonated saline solution in the first (group I) or second semester (group II) showed a decrease in the molecular products of lipid peroxidation and a simultaneous increase in the antioxidant activity. Also, with ozone therapy the pregnancy was preserved and prolonged to the physiological terms of labor in 86% of patients inside group I and in 85% of patients inside group II. However, in the control group (conventional treatment) I and II, it was possible to preserve the pregnancy in 65 and 60% of cases, respectively. In the ozone group, 80% of newborn babies received 7-10 points (maximum value) according to Apgar's score, however, only 58.3% in the control group. In Gynecology, an interesting paper was reviewed about distal fallopian tube recanalization using ozone treatment. In the ozone group, the ozone was introduced in the uterine cavity and in the case of the control group, anti-inflammatory drugs and antibiotics was used. The overall recanalization rate was significantly higher in the ozone group (93%) as compared to the control group (79%) 6-months after intervention (p < 0.01). The re-adhesion rate in the ozone group was significantly lower than the control group (p < 0.01). The pregnancy rate after 12 months of intervention was significantly higher in the ozone group (59%) compared to the control group (43%) (p < 0.05). These results were highly encouraging and hold promise for treating distal tubal obstruction in infertile females. For inflammatory diseases in female genital organs, intravaginal ozone has been used. Ozone restores the body's own defense abilities by the normalization of vaginal mucosa local immunity, prevents the generalization of inflammatory processes, facilitates uterus healing, reduces the treatment time with no complications or side effects. In Cuba we have a vast experience in the use of ozonated sunflower oil in the treatment of vulvovaginitis, human papillomavirus, acuminate condyloma, genitalis herpes virus with very good results. In summary, we can state that preclinical and clinical studies presented here about the application of ozone therapy in Obstetrics and Gynecology, in the different ways of ozone applications, do not demonstrate any adverse effect or complication. However, more controlled clinical trials are necessary to perform in order to prove the inocuity of ozone therapy, mainly in Obstetrics, where threre are still questions to be clarified.