Nirupama Laroia | University of Rochester (original) (raw)

Papers by Nirupama Laroia

Pediatric Research, Apr 1, 1999

Pediatric Research, Apr 1, 1996

Neurology, 2001

Article abstract-Background: Preclinical studies suggest that glutamate antagonists help ameliora... more Article abstract-Background: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. Methods: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. Results: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. Conclusion: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Pediatric Research, Apr 1, 1996

Journal of Neonatology, Mar 1, 2000

Pediatric Research, Apr 1, 1997

Cochrane Database of Systematic Reviews, Apr 22, 2003

Neurology, Aug 22, 2000

To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and ... more To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and to compare the outcome of neonates with ESz with those who were at risk but did not have ESz recorded. Methods: The EEG and outcome data were reviewed from 68 infants who met at-risk criteria for neonatal seizures and underwent prolonged continuous EEG monitoring. Forty infants had ESz. The control group contained 28 infants monitored for at least 18 hours and found not to have ESz. Outcomes for both groups were evaluated using hospital and follow-up clinic records and a standardized telephone interview. Results: The etiology of ESz included asphyxia (n ϭ 23), stroke (n ϭ 7), and other (n ϭ 10, intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis; hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to 30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one without died from causes related to neurologic instability. The occurrence of ESz was correlated with microcephaly (p ϭ 0.04), severe cerebral palsy (CP) (p ϭ 0.03), and failure to thrive (p ϭ 0.03). In the subgroup of infants with asphyxia, those with ESz were more likely to die of neurologic causes (p ϭ 0.02) and have microcephaly (p ϭ 0.05) or severe CP (p ϭ 0.04). Additionally, those with the greatest number of ESz were more likely to have these severe outcomes. Conclusion: The authors' data indicate an association between the amount of electrographic seizure activity and subsequent mortality and morbidity in at-risk infants in general and in infants with perinatal asphyxia. Only with more effective treatment of neonatal electrographic seizures can their potential contribution to poor neurodevelopmental outcome, independent of degree of insult, be ascertained.

Journal of pediatric neurology, Jul 30, 2015

Felbamate, a non-selective anticonvulsant thought to act via blocking the N-methyl-D-aspartate re... more Felbamate, a non-selective anticonvulsant thought to act via blocking the N-methyl-D-aspartate receptor, has been shown in animal studies not only to block seizures, but also to be neuroprotective. Excessive discharge of the excitatory pathways, involving primarily the glutamate receptor system, is important in the cascade of neuronal injury in hypoxic ischemic encephalopathy (HIE). Because of renewed interest in adjunctive therapy in addition to hypothermia to minimize hypoxic ischemic injury in neonates, we report the absorption and time to peak level of felbamate preliminary to testing its neuroprotective effects in this population. A single dose of either 45 mg/kg or 200 mg/kg of felbamate was given via nasogastric tube to four infants with severe HIE. We measured serum felbamate levels at 2, 4, 8, 12 and 24 hours after administration of the drug. Oral absorption of felbamate is slow. Peak levels of 40-64 µg/mL were achieved at 12 to 24 hours in the two infants who received 200 mg/kg dose. In conclusion, oral felbamate is unsuitable for infants with HIE as oral doses are unlikely to reach adequate neuroprotective levels in a timely fashion.

The Cochrane library, Apr 18, 2007

BackgroundStudies have shown improved survival of newborn infants maintained in the thermoneutral... more BackgroundStudies have shown improved survival of newborn infants maintained in the thermoneutral range. Incubators with a double plexiglass wall for additional insulation may help to provide an improved thermoneutral environment for very low birth weight infants.ObjectivesTo assess the effects of double walled incubator versus a single wall incubator on insensible water loss, rate of oxygen consumption, episodes of hypothermia, time to regain birth weight, duration of hospitalization and infant mortality in premature infants.Search methodsThe standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 to 2006), EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants in all published languages, and CINAHL (1982 to 2006). The electronic search was updated in July 2009.Selection criteriaOnly studies using random or quasi‐random methods of allocation were considered for this review. Eligible studies assessed at least one of the outcome variables identified as important to this topic.Data collection and analysisIndependent data extraction and quality assessment of included trials was conducted by the review authors. Data were analyzed using generic inverse variance methodology and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta‐analysis was undertaken using a fixed effect model.Main resultsThree studies met the criteria. Four other studies were excluded, as they did not compare double versus single wall incubators. Double wall incubators have the advantage of decreasing heat loss, decreasing heat production and decreasing radiant heat loss when compared to single wall incubators. There is also the advantage of reduced oxygen consumption. A minimal increase in conductive heat loss was noted when compared to single wall incubators. All of these effects are small and do not support the proposition that double wall incubators have a beneficial effect on long‐term outcomes including mortality or the duration of hospitalization.Authors' conclusionsAlthough it appears that caring for extremely small infants in double wall incubators may theoretically result in shorter hospitalization and may have metabolic advantages, this review was unable to find any data in the literature to support or refute this hypothesis. The studies do not provide any evidence that the small decrease in heat loss improves clinical outcome. Therefore, the available data is insufficient to directly guide clinical practice.

Developmental Brain Research, May 1, 1997

Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore, NMDA receptor block... more Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore, NMDA receptor blockade with dextromethorphan Ž. DM , a non-competitive channel blocker, was hypothesized to ameliorate injury even when given after the hypoxic insult. Rats were exposed to 8% oxygen for 3 h on postnatal day 7. Within 20 min of exposure, animals received 30 mgrkg i.p. DM or normal saline. Littermates maintained in room air for 3 h also received DM or saline. At 14 days of age, 7 days after exposure, cortical thickness and hippocampal area were measured. At 70-90 days of age, approximately two months after exposure, in a separate group of rats, seizure Ž. threshold using pentylenetetrazol PTZ and passive avoidance learning and retention were determined. There were no gross changes in cellular morphology and no evidence for cellular necrosis in any of the exposure groups. However, cortical thickness was decreased in animals exposed to hypoxia. DM administration prevented this decrease. Hippocampal area was unaffected. Seizure susceptibility in adulthood was increased in animals exposed to hypoxia in the neonatal period. DM prevented the decrease in seizure threshold. There was no difference in passive avoidance learning or retention as a function of neonatal exposure condition. Mild to moderate hypoxia, previously thought not to produce any histologic changes, causes significant short-term loss of cortical thickness and long-term decrease in seizure threshold. DM appears to ameliorate these effects even when given after the hypoxic insult. These results implicate the glutamate receptor system in the pathophysiology of hypoxia damage and suggest that treatment with a glutamate receptor blocker when neonatal asphyxia is suspected would help ameliorate the consequences of such an insult. q Elsevier Science B.V. All rights reserved.

PubMed, Sep 1, 2009

Background: Complete, congenital arhinia is a rare condition characterized by total absence of th... more Background: Complete, congenital arhinia is a rare condition characterized by total absence of the nose and generally associated with other facial anomalies, including absence of the underlying nasal structures and frontal sinuses. There have been 2 case reports of prenatal diagnosis of arhinia in the second and early third trimesters. To our knowledge, however, this is the first case of total arhinia suspected prenatally with an associated normal chromosomal microarray. Case: A 20-year-old primigravida presented for her first obstetric ultrasound evaluation at 27 weeks' gestation. Ultrasound was limited by maternal habitus but revealed a flattened midface with an abnormal profile. Repeat ultrasound at 38 weeks showed a flattened midface without a distinguishable fetal nose. The diagnosis of complete arhinia was confirmed at delivery. Chromosomal analysis revealed a 46,XX karyotype, with normal 500K SNP microarray. Conclusion: This report reviews both the diagnosis of arhinia and the associated neonatal care and outcome. Arhinia should be considered when the fetal profile appears to have a flattened midface and a prominent upper lip. Diagnosis may be aided by third or fourth ultrasound imaging. Due to neonatal airway issues, delivery with pediatric support available is recommended if the condition is suspected prenatally.

The Journal of reproductive medicine, 2009

BACKGROUND Complete, congenital arhinia is a rare condition characterized by total absence of the... more BACKGROUND Complete, congenital arhinia is a rare condition characterized by total absence of the nose and generally associated with other facial anomalies, including absence of the underlying nasal structures and frontal sinuses. There have been 2 case reports of prenatal diagnosis of arhinia in the second and early third trimesters. To our knowledge, however, this is the first case of total arhinia suspected prenatally with an associated normal chromosomal microarray. CASE A 20-year-old primigravida presented for her first obstetric ultrasound evaluation at 27 weeks' gestation. Ultrasound was limited by maternal habitus but revealed a flattened midface with an abnormal profile. Repeat ultrasound at 38 weeks showed a flattened midface without a distinguishable fetal nose. The diagnosis of complete arhinia was confirmed at delivery. Chromosomal analysis revealed a 46,XX karyotype, with normal 500K SNP microarray. CONCLUSION This report reviews both the diagnosis of arhinia and t...

The Journal of Pediatrics

Pediatrics, 2017

Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spe... more Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion). Infants ≥34 weeks' gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice. A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38...

Pediatric Research, Apr 1, 1999

Pediatric Research, Apr 1, 1996

Neurology, 2001

Article abstract-Background: Preclinical studies suggest that glutamate antagonists help ameliora... more Article abstract-Background: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. Methods: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. Results: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. Conclusion: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Pediatric Research, Apr 1, 1996

Journal of Neonatology, Mar 1, 2000

Pediatric Research, Apr 1, 1997

Cochrane Database of Systematic Reviews, Apr 22, 2003

Neurology, Aug 22, 2000

To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and ... more To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and to compare the outcome of neonates with ESz with those who were at risk but did not have ESz recorded. Methods: The EEG and outcome data were reviewed from 68 infants who met at-risk criteria for neonatal seizures and underwent prolonged continuous EEG monitoring. Forty infants had ESz. The control group contained 28 infants monitored for at least 18 hours and found not to have ESz. Outcomes for both groups were evaluated using hospital and follow-up clinic records and a standardized telephone interview. Results: The etiology of ESz included asphyxia (n ϭ 23), stroke (n ϭ 7), and other (n ϭ 10, intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis; hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to 30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one without died from causes related to neurologic instability. The occurrence of ESz was correlated with microcephaly (p ϭ 0.04), severe cerebral palsy (CP) (p ϭ 0.03), and failure to thrive (p ϭ 0.03). In the subgroup of infants with asphyxia, those with ESz were more likely to die of neurologic causes (p ϭ 0.02) and have microcephaly (p ϭ 0.05) or severe CP (p ϭ 0.04). Additionally, those with the greatest number of ESz were more likely to have these severe outcomes. Conclusion: The authors' data indicate an association between the amount of electrographic seizure activity and subsequent mortality and morbidity in at-risk infants in general and in infants with perinatal asphyxia. Only with more effective treatment of neonatal electrographic seizures can their potential contribution to poor neurodevelopmental outcome, independent of degree of insult, be ascertained.

Journal of pediatric neurology, Jul 30, 2015

Felbamate, a non-selective anticonvulsant thought to act via blocking the N-methyl-D-aspartate re... more Felbamate, a non-selective anticonvulsant thought to act via blocking the N-methyl-D-aspartate receptor, has been shown in animal studies not only to block seizures, but also to be neuroprotective. Excessive discharge of the excitatory pathways, involving primarily the glutamate receptor system, is important in the cascade of neuronal injury in hypoxic ischemic encephalopathy (HIE). Because of renewed interest in adjunctive therapy in addition to hypothermia to minimize hypoxic ischemic injury in neonates, we report the absorption and time to peak level of felbamate preliminary to testing its neuroprotective effects in this population. A single dose of either 45 mg/kg or 200 mg/kg of felbamate was given via nasogastric tube to four infants with severe HIE. We measured serum felbamate levels at 2, 4, 8, 12 and 24 hours after administration of the drug. Oral absorption of felbamate is slow. Peak levels of 40-64 µg/mL were achieved at 12 to 24 hours in the two infants who received 200 mg/kg dose. In conclusion, oral felbamate is unsuitable for infants with HIE as oral doses are unlikely to reach adequate neuroprotective levels in a timely fashion.

The Cochrane library, Apr 18, 2007

BackgroundStudies have shown improved survival of newborn infants maintained in the thermoneutral... more BackgroundStudies have shown improved survival of newborn infants maintained in the thermoneutral range. Incubators with a double plexiglass wall for additional insulation may help to provide an improved thermoneutral environment for very low birth weight infants.ObjectivesTo assess the effects of double walled incubator versus a single wall incubator on insensible water loss, rate of oxygen consumption, episodes of hypothermia, time to regain birth weight, duration of hospitalization and infant mortality in premature infants.Search methodsThe standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 to 2006), EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants in all published languages, and CINAHL (1982 to 2006). The electronic search was updated in July 2009.Selection criteriaOnly studies using random or quasi‐random methods of allocation were considered for this review. Eligible studies assessed at least one of the outcome variables identified as important to this topic.Data collection and analysisIndependent data extraction and quality assessment of included trials was conducted by the review authors. Data were analyzed using generic inverse variance methodology and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta‐analysis was undertaken using a fixed effect model.Main resultsThree studies met the criteria. Four other studies were excluded, as they did not compare double versus single wall incubators. Double wall incubators have the advantage of decreasing heat loss, decreasing heat production and decreasing radiant heat loss when compared to single wall incubators. There is also the advantage of reduced oxygen consumption. A minimal increase in conductive heat loss was noted when compared to single wall incubators. All of these effects are small and do not support the proposition that double wall incubators have a beneficial effect on long‐term outcomes including mortality or the duration of hospitalization.Authors' conclusionsAlthough it appears that caring for extremely small infants in double wall incubators may theoretically result in shorter hospitalization and may have metabolic advantages, this review was unable to find any data in the literature to support or refute this hypothesis. The studies do not provide any evidence that the small decrease in heat loss improves clinical outcome. Therefore, the available data is insufficient to directly guide clinical practice.

Developmental Brain Research, May 1, 1997

Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore, NMDA receptor block... more Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore, NMDA receptor blockade with dextromethorphan Ž. DM , a non-competitive channel blocker, was hypothesized to ameliorate injury even when given after the hypoxic insult. Rats were exposed to 8% oxygen for 3 h on postnatal day 7. Within 20 min of exposure, animals received 30 mgrkg i.p. DM or normal saline. Littermates maintained in room air for 3 h also received DM or saline. At 14 days of age, 7 days after exposure, cortical thickness and hippocampal area were measured. At 70-90 days of age, approximately two months after exposure, in a separate group of rats, seizure Ž. threshold using pentylenetetrazol PTZ and passive avoidance learning and retention were determined. There were no gross changes in cellular morphology and no evidence for cellular necrosis in any of the exposure groups. However, cortical thickness was decreased in animals exposed to hypoxia. DM administration prevented this decrease. Hippocampal area was unaffected. Seizure susceptibility in adulthood was increased in animals exposed to hypoxia in the neonatal period. DM prevented the decrease in seizure threshold. There was no difference in passive avoidance learning or retention as a function of neonatal exposure condition. Mild to moderate hypoxia, previously thought not to produce any histologic changes, causes significant short-term loss of cortical thickness and long-term decrease in seizure threshold. DM appears to ameliorate these effects even when given after the hypoxic insult. These results implicate the glutamate receptor system in the pathophysiology of hypoxia damage and suggest that treatment with a glutamate receptor blocker when neonatal asphyxia is suspected would help ameliorate the consequences of such an insult. q Elsevier Science B.V. All rights reserved.

PubMed, Sep 1, 2009

Background: Complete, congenital arhinia is a rare condition characterized by total absence of th... more Background: Complete, congenital arhinia is a rare condition characterized by total absence of the nose and generally associated with other facial anomalies, including absence of the underlying nasal structures and frontal sinuses. There have been 2 case reports of prenatal diagnosis of arhinia in the second and early third trimesters. To our knowledge, however, this is the first case of total arhinia suspected prenatally with an associated normal chromosomal microarray. Case: A 20-year-old primigravida presented for her first obstetric ultrasound evaluation at 27 weeks' gestation. Ultrasound was limited by maternal habitus but revealed a flattened midface with an abnormal profile. Repeat ultrasound at 38 weeks showed a flattened midface without a distinguishable fetal nose. The diagnosis of complete arhinia was confirmed at delivery. Chromosomal analysis revealed a 46,XX karyotype, with normal 500K SNP microarray. Conclusion: This report reviews both the diagnosis of arhinia and the associated neonatal care and outcome. Arhinia should be considered when the fetal profile appears to have a flattened midface and a prominent upper lip. Diagnosis may be aided by third or fourth ultrasound imaging. Due to neonatal airway issues, delivery with pediatric support available is recommended if the condition is suspected prenatally.

The Journal of reproductive medicine, 2009

BACKGROUND Complete, congenital arhinia is a rare condition characterized by total absence of the... more BACKGROUND Complete, congenital arhinia is a rare condition characterized by total absence of the nose and generally associated with other facial anomalies, including absence of the underlying nasal structures and frontal sinuses. There have been 2 case reports of prenatal diagnosis of arhinia in the second and early third trimesters. To our knowledge, however, this is the first case of total arhinia suspected prenatally with an associated normal chromosomal microarray. CASE A 20-year-old primigravida presented for her first obstetric ultrasound evaluation at 27 weeks' gestation. Ultrasound was limited by maternal habitus but revealed a flattened midface with an abnormal profile. Repeat ultrasound at 38 weeks showed a flattened midface without a distinguishable fetal nose. The diagnosis of complete arhinia was confirmed at delivery. Chromosomal analysis revealed a 46,XX karyotype, with normal 500K SNP microarray. CONCLUSION This report reviews both the diagnosis of arhinia and t...

The Journal of Pediatrics

Pediatrics, 2017

Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spe... more Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion). Infants ≥34 weeks' gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice. A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38...