Evaluation of three-year neurodevelopmental outcomes in infants prenatally exposed to substance use.

INTRODUCTION: Prenatal exposure to substance use is associated with long-term deficits in the neurodevelopment of children. The objective was to investigate the association between cognitive, motor, and language neurodevelopment at three years of age in infants prenatally exposed to substance use. MATERIAL AND METHODS: A prospective matched case-control study was conducted. Biomarkers of fetal exposure were measured in meconium samples. The Bayley Scales of Infant and Toddler Development (BSID-III) were used to calculate neurodevelopment scores. RESULTS: 32 non-exposed and 32 exposed infants were evaluated, of which 16 were exposed to cannabis, 8 to ethanol, 2 to cocaine and 6 to more than one substance. Normal BSID-III scores ≥85 in all domains, were detected in 23 exposed infants to any substance and 29 infants non-exposed. Neurodevelopmental delay was detected in the language domain, specifically in male infants exposed to cannabis. Two infants exposed to cannabis had a severe developmental delay (score<70). Infants exposed to any substance obtained significantly lower total scores than control infants in all domains. Infants exposed to cannabis obtained significantly lower composite scores in the cognitive and motor domains. Infants exposed to more than one substance had lower scores in motor skills. By gender, only males exposed obtained significantly lower composite scores than non-exposed males in the cognitive domain. CONCLUSIONS: The most common and severe neurodevelopmental delay at 36 months was detected in the domain of language in male infants prenatally exposed to cannabis. Neurodevelopmental disorders detected can enable an early intervention and plan therapeutic strategies.

Características clínicas y factores de riesgo asociados a la exposición prenatal a drogas de abuso / Clinical features and risk factors associated with prenatal exposure to drugs of abuse

Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso.Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales.Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante.Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]).Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas. (AU)

Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management.Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit.Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed.Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)).Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Clinical features and risk factors associated with prenatal exposure to drugs of abuse.

INTRODUCTION: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. OBJECTIVES: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. METHODS: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. RESULTS: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). CONCLUSIONS: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Role of Neonatal Biomarkers of Exposure to Psychoactive Substances to Identify Maternal Socio-Demographic Determinants.

BACKGROUND: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices. METHODS: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed. RESULTS: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, p < 0.05). Cocaine (50.0% vs. 96.9%, p < 0.05) and polydrug users (37.5% vs. 96.9%, p < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, p < 0.05). Single-mother families (14.3% vs. 2.5%, p < 0.05) and mothers with primary level education (75.5% vs. 55.1%, p < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12-5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51-21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37-8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03-16.43). CONCLUSIONS: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates.

[Clinical features and risk factors associated with prenatal exposure to drugs of abuse]. / Características clínicas y factores de riesgo asociados a la exposición prenatal a drogas de abuso.

INTRODUCTION: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. OBJECTIVES: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. METHODS: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. RESULTS: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). CONCLUSIONS: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Efficacy of gabapentin for the prevention of postherpetic neuralgia in patients with acute herpes zoster: A double blind, randomized controlled trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear. OBJECTIVE: To assess the efficacy of a 5-week course of gabapentin on acute herpetic pain and on the prevention of PHN at 12 weeks in patients with acute HZ. METHODS: This was a randomized, double blind, placebo-controlled trial conducted in 17 primary care health centers in Mallorca, Spain. All patients were older than 50 years, presented with HZ within 72 h of rash onset, and had moderate-severe pain (≥4 on a 10-point visual analogue scale [VAS]). Ninety-eight patients were randomized to receive gabapentin or placebo. All patients received valaciclovir for 7 days and analgesia if needed. The treatment period was 5 weeks, followed by 7 weeks of follow-up. Gabapentin was initiated at 300 mg/day and gradually titrated to a maximum of 1800 mg/day. The main outcome measure was pain at 12 weeks. RESULTS: Seventy-five patients completed the study, 33 in the gabapentin group and 42 in the control group. A total of 18.2% of patients in the gabapentin group and 9.5% in the control group reported pain at 12 weeks (p = 0.144). Four patients in the gabapentin group (12.1%), but no patients in the placebo group, reported pain of 4 or more on a 10-point VAS. Patients taking gabapentin reported worse health-related quality of life and poorer sleep quality. Three patients discontinued the trial due to adverse effects from gabapentin. CONCLUSION: Addition of gabapentin to the usual treatment of HZ within 72 h of rash onset provided no significant relief from acute herpetic pain or prevention of PHN. TRIAL REGISTRATION: ISRCTN Registry identifier: ISRCTN79871784.

Quantification of Methamphetamine «Shabu¼ in Biological Matrices to Detect Prenatal Exposure: A Case Report and a Literature Review.

BACKGROUND: Methamphetamine misuse represents an increasing global public health problem. Its consumption during pregnancy becomes a relevant issue, since it has clinical consequences for the child's health and the pregnant woman. Despite this, there are only few data in the literature that include analytical results in the matrices used to detect prenatal exposure. OBJECTIVES: 1) Present a case report of prenatal methamphetamine exposure with toxicological analytical confirmation in biological matrices; and 2) Perform a compilation of prenatal methamphetamine exposure studies and case reports which include toxicological analytical results. METHODS: Prenatal methamphetamine exposure was confirmed using a traditional "screen with reflex" approach. Methamphetamine and amphetamine were quantified in urine, meconium and hair samples of the neonate and mother by gas chromatography-mass spectrometry. Also, a detailed revision of the existent literature that provides information on the analytical toxicology results has been included. RESULTS: In the neonatal biological matrices test results of methamphetamine/amphetamine were: urine 2,966.43/1,638.71 ng/mL, meconium 1,450/<0.1 ng/g and hair 36.54/9.66 ng/mg. In the maternal biological matrices, test results were: urine 13,393.89/3,074.95 ng/mL and hair 11.29/3.37 ng/mg (0-3 cm), 4.68/2.58 (3-6 cm), 6.43/3.13 ng/mg (6-9 cm) and 4.72/2.49 ng/mg (9-12 cm). These results confirm a recent and continued regular substance use throughout pregnancy including delivery. CONCLUSION: The data provided will be useful for clinical purposes to improve the diagnostic and follow- up of acute and chronic intoxications. Additionally, results will be used to support interpretations in the field of forensic and legal medicine.

Neonatal swallowing assessment using fiberoptic endoscopic evaluation of swallowing (FEES).

OBJECTIVES: Swallowing disorders which lead to aspiration are common in premature infants with a postmenstrual age (PMA) of >36 weeks. Aspiration is often silent and the unique symptom is desaturation during feeding. The aim of this study was 1) to determine the number of prematures with desaturations during feeding due to aspiration, using Fiberoptic Endoscopic Evaluation of Swallowing (FEES); 2) to relate clinical factors and FEES findings to aspiration; and 3) to describe type and efficacy of suggested treatments. METHODS: A retrospective review of 62 ex-premature babies with a median PMA of 40 weeks which underwent FEES due to persistent feeding desaturations. Aspiration was related to other FEES findings and to clinical and demographic data. The efficacy of the treatment was evaluated during the FEES and by comparing recorded desaturations during feeding 7 days before and after FEES. RESULTS: A total of 44 (71%) infants were diagnosed with aspiration and/or penetration. No relation was found to demographic or clinical data. The accumulation of saliva and residues post-swallowing were related to aspiration (P < 0.01). In 77.3% of the infants, use of a thickener seemed to reduce aspiration during FEES and was suggested as a treatment. 13.6% of infants received anti-reflux treatment after FEES and 9.1% required gastrostomy. CONCLUSIONS: Aspiration is very frequent in premature infants who present desaturations during feeding and FEES is a useful method for diagnosing and suggesting treatments.

Efficacy of gabapentin for prevention of postherpetic neuralgia: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition. METHODS/DESIGN: Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited. The aim is to recruit 134 patients from the practices of general physicians. Participants will be randomized to receive gabapentin to a maximum of 1800 mg/day for 5 weeks or placebo. Both arms will receive 1000-mg caplets of valacyclovir three times daily for 7 days (initiated within 72 h of the onset of symptoms) and analgesics as needed. The primary outcome measure is the percentage of patients with a VAS pain score of 0 at 12 weeks from rash onset. The secondary outcomes measures are changes in quality of life (measured by the SF-12 questionnaire), sleep disturbance (measured by the Medical Outcomes Study Sleep Scale), and percentage of patients with neuropathic pain (measured by the Douleur Neuropathique in 4 Questions). DISCUSSION: Gabapentin is an anticonvulsant type of analgesic that could prevent the onset of PHN by its antihypersensitivity action in dorsal horn neurons. TRIAL REGISTRATION: ISRCTN Registry identifier: ISRCTN79871784 . Registered on 2 May 2013.