Neonatal Reflexes Research Articles

Severe but reversible neonatal neurological dysfunction associated with in utero exposure to Sibelium (flunarizine dihydrochloride

Sibelium is a Ca ++ channel blocker used as a prophylactic treatment of migraine. No published data exist on the effect of Sibelium on the human fetus during pregnancy or newborn infant following delivery. We report two female siblings who were exposed to Sibelium during fetal life. Both were born with severe neurological depression requiring mechanical ventilation for 5 and 7 days. The findings consisted of hypotonia, hypoventilation/apnea, absent spontaneous movements, absent neonatal reflexes, contractures and skin edema. All the neurological abnormalities reversed by 5 to 7 days. The use of Sibelium during pregnancy can be associated with significant and severe, but reversible, neurological manifestations. The long term effect on neurological development remains concerning but unknown.

Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals

Electrocortical arousal (ECA) as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 ± 3.4 wk were tested at 36.8 ± 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P < 0.05), swallow sequences were associated with arousals and sleep state changes, and arousals were associated with incomplete peristalsis, response delays to lower esophageal sphincter relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked arousals, and arousals were associated with response delays to peristaltic reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct when accompanied by arousals. Aerodigestive homeostasis is defended by multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes are delayed, cortical hypervigilance (ECAs) occurs.

GSTM1 Modifies the Effect of Maternal Exposure to Environmental Tobacco Smoke on Neonatal Primitive Reflexes

The aim of this study was to examine whether infant metabolic gene polymorphisms modify the effect of maternal environmental tobacco smoke (ETS) on neonatal neurobehavior. We conducted a birth cohort study of 87 nonsmoking women who delivered single births of normal birth weight. We enrolled the women before delivery, interviewed them using a structured questionnaire, and collected umbilical cord blood. Umbilical cord cotinine, a blood indicator of prenatal ETS exposure, was analyzed. The Neonatal Neurobehavioral Examination-Chinese Version (NNE-C) was administrated within 5 days after delivery to examine neonatal neurobehavior. Four infant metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1, and GSTM1, were identified. Maternal ETS exposure during pregnancy was not related to neonatal neurobehavior when infant genetic polymorphisms were not considered. However, maternal ETS exposure did cause adverse effects in neonates with the absent type of GSTM1. Adverse effects were seen on the total NNE-C (β = -2.55; p = .02) and on primitive reflexes (β = -1.70; p = .004), especially in grasp reflexes (β = -.36; p = .011) and tonic neck reflexes (β = -.36; p = .049). In addition, there was a significant interaction between maternal ETS exposure and infant GSTM1 genotype on neonate grasp reflexes (p for interaction = .019). These data indicate that weaker responses in neonatal primitive reflexes in infants with the absent type GSTM1 were related to maternal ETS exposure during pregnancy.

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

Maternal voluntary drinking in C57BL/6J mice: Advancing a model for fetal alcohol spectrum disorders

Fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of behavioural abnormalities and cognitive deficits, yet little is known about the biological mechanisms involved in FASD pathology. Maternal voluntary ethanol consumption in mice may be a useful model for establishing the biological basis of moderate ethanol exposure phenotypes, which make up the majority of FASD cases. We have employed a two-bottle choice paradigm of maternal ethanol consumption throughout gestation and the early postnatal period in C57BL/6J mice. We assessed the efficacy of this model to produce a range of FASD-relevant phenotypes and evaluated gene expression changes in the adult offspring. Results showed stable maternal consumption and lack of maternal care differences between ethanol-consuming and water-only dams. Ethanol-exposed offspring showed delays in neonatal reflex and coordination development. Further, ethanol-exposed adolescent mice showed decreased activity in a novel environment that appeared to be the result of novelty-induced anxiety, and acquisition learning deficits. Evaluation of the neurotransmitter-associated genes Gabra6, Glra1, and Grin2c revealed significant down-regulation of Glra1 and Grin2c in the brains of ethanol-exposed young adult males. These results suggest that this model is able to produce a range of behavioural phenotypes consistent with prenatal ethanol exposure and may be used to evaluate resulting long-term genetic changes. Given the range of genetic resources available for inbred mouse strains, the model described here may prove to be a useful tool in evaluating the molecular basis of FASD.

559 Effect of Intrapartum Oxytocin Administration on Primitive Neonatal Reflex

Background and aims: The effect of the infusion of synthetic oxytocin (OT) on newborn behaviour has received little attention although there is a growing body of evidence that suggests it can affect the behaviour of non human mammals both early and in the long term. The impact of exogenous OT on primitive neonatal reflex has not been thoroughly investigated. The objective of the study is to evaluate the effect of OT used during induced labour on primitive neonatal reflex. Methods: Observational descriptive study approved by Local Ethical Committee. 22 women with their first term pregnancies were studied. All had singleton, healthy pregnancies and epidural analgesia was used. Newborns were vaginal delivered and immediately placed in skin-to-skin contact (SSC) with the mother. Patients were excluded if no immediately SSC was applied (n=7), caesarean section was made after study inclusion (n=3) or newborn was admitted in NICU (n=1). 11 patients fulfilled inclusion criteria. 16 primitive neonatal reflexes in Biological Nurturing position were recorded during 20 minutes and evaluated by a blind observer. Patients were asked to sign a letter of consent. Newborn's reflexes were recorded at 34±13.4h of life. Results: Mean GA and birthweight was 39±1.3w and 3339.7±252.2g respectively. Mean OT dose was 1749.8±1971.5 mUI. Mean neonatal reflexes observed were 85.2±8.8%. A negative correlation was found between the amount of OT infused during labour and the amount of neonatal reflexes observed (r= -0.78; p< 0.01). Conclusions: Total dose of oxytocin infused during labour may affect primitive neonatal reflexes.

Delayed Acquisition of Neonatal Reflexes in Newborn Primates Receiving A Thimerosal-Containing Hepatitis B Vaccine: Influence of Gestational Age and Birth Weight

This study examined whether acquisition of neonatal reflexes in newborn rhesus macaques was influenced by receipt of a single neonatal dose of hepatitis B vaccine containing the preservative thimerosal (Th). Hepatitis B vaccine containing a weight-adjusted Th dose was administered to male macaques within 24 h of birth (n = 13). Unexposed animals received saline placebo (n = 4) or no injection (n = 3). Infants were tested daily for acquisition of nine survival, motor, and sensorimotor reflexes. In exposed animals there was a significant delay in the acquisition of root, snout, and suck reflexes, compared with unexposed animals. No neonatal responses were significantly delayed in unexposed animals. Gestational age (GA) and birth weight (BW) were not significantly correlated. Cox regression models were used to evaluate main effects and interactions of exposure with BW and GA as independent predictors and time-invariant covariates. Significant main effects remained for exposure on root and suck when controlling for GA and BW, such that exposed animals were relatively delayed in time-to-criterion. Interaction models indicated there were various interactions between exposure, GA, and BW and that inclusion of the relevant interaction terms significantly improved model fit. This, in turn, indicated that lower BW and/or lower GA exacerbated the adverse effects following vaccine exposure. This primate model provides a possible means of assessing adverse neurodevelopmental outcomes from neonatal Th-containing hepatitis B vaccine exposure, particularly in infants of lower GA or BW. The mechanisms underlying these effects and the requirements for Th requires further study.

The logistic score: A criterion for hypothermia after perinatal asphyxia?

Objective. To identify during the first hour of life the asphyxiated term neonates who further develop moderate or severe neonatal encephalopathy.Methods. In 75 asphyxiated term infants, we measured postnatal arterial base deficit (BD30), assigned an early neurological score (ENS) according to their level of consciousness, respiration pattern and neonatal reflexes at 30 min of life and calculated the logistic score (LS) = (0.33 × BD30) – ENS. The receiver operating characteristics (ROC) methodology was applied to analyze the ability of the LS to correctly classify patients into two groups: normal or mild encephalopathy (60 patients) versus moderate or severe encephalopathy (15 patients).Results. The area under the ROC curve of the LS for moderate or severe encephalopathy (± standard error) was 94.4 ± 3.6%. At the threshold value of 1.2, the LS provided 87.5% sensitivity and 73.7% positive predictive value (PPV). The PPV of LS reaches 100% for a value >3.2, but this threshold allowed only 53.3% sensitivity.Conclusions. The LS is predictive of the neonatal neurological evolution after birth asphyxia and may help to select the high risk patients who are potential candidates for hypothermia therapy.

Teaching Neuro Images : MRI in maple syrup urine disease

A baby girl, born normally to consanguineous parents, presented on the fifth postnatal day with poor feeding, lethargy, and seizures. Examination on the 10th day showed hypotonia and poor neonatal reflexes. Tandem mass spectroscopy showed elevated …

A 3-day-old boy with a right preauricular swelling

A 3-day-old boy was admitted for right preauricular swelling. Examination showed a toxic looking neonate with poor neonatal reflexes. There was erythema and swelling of 4 × 3 cm at the level of the right cheek. Laboratory investigation pointed to a bacterial infection. With parenteral antibiotics, the lesion resolved completely.

INTRACRANIAL HEMORRHAGE DUE TO VITAMIN K DEFICIENCY IN INFANTS: A CLINICAL STUDY

The hospital records of 30 infants with a diagnosis of intracranial hemorrhage (ICH) due to late onset of vitamin K deficiency, seen during a 5-year period (2001–2005) were retrospectively evaluated. Signs and symptoms of the patients were convulsions (80%), poor sucking (50%), irritability (40%), vomiting (47%), acute diarrhea (33%), and fever (40%). On physical examination there were bulging or full fontanel in 19 patients (63%), collapsed fontanel in one (3%), diminished or absent neonatal reflexes in 11 (37%), pallor in 14 (47%), and cyanosis in one (3%) patient. Gastrointestinal disorder, skin hemorrhagic findings, and epistaxis each were noted in two (7%) patients. All the infants had prolonged prothrombin time (PT) and seven had prolonged activated partial thromboplastin time (APTT), both of which were corrected by the administration of vitamin K. All the infants had ICH, with the most common being intraparenchymal hemorrhage, followed by multiple type ICH (27%). Neurosurgical intervention was performed in five patients (17%). The overall case fatality rate was 33%. In conclusion, we would like to stress that ICH due to vitamin K deficiency in infants is still an important health problem in Turkey resulting in high mortality rate.

WITHDRAWN: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight

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162. THE EFFECT OF MATERNAL FOLIC ACID SUPPLEMENTATION THROUGHOUT PREGNANCY ON NEURODEVELOPMENT, MOTOR FUNCTION AND BEHAVIOUR OF PROGENY IN THE RAT

Background: Maternal folic acid supplementation (mFAS) during early pregnancy is recommended to reduce the incidence of neural tube defects and has recently been associated with improved neurodevelopment in children. However, the effect on neurodevelopment of mFAS from before conception and throughout pregnancy is unknown. We examined the effect of mFAS throughout the gestational period on postnatal growth, neurodevelopment and early adult motor function and behaviour in rat offspring. Methods: Female Wistar Rats were fed either a control (folic acid 2mg/kg, n=6) or moderate mFAS diet (folic acid 6mg/kg, n=6) from two weeks before mating with Lewis males, until birth of progeny. Male and female progeny (Control=36, mFAS=36) were weighed on postnatal day (PD) 3, 7, 14, 21, 40 and 90, and underwent various tests between PD4 and 14: righting reflex, palm-grasp reflex, negative geotaxis, forelimb hanging, ascent test and eye opening. Locomotor/ exploratory behaviour, motor coordination and anxiety were assessed using an open field test (PD52), rotarod (PD55) and elevated plus maze (PD58) (Control=24, mFAS=24). Results: mFAS did not alter maternal weight gain, litter-size at birth or progeny growth between PD3-90. mFAS tended to increase righting reflex time (p=0.057) and impair ascent ability (p=0.085). Negative geotaxis time was reduced at PD7 but not later (Diet x Age p=0.051). mFAS increased the proportion of progeny with eyes open at PD14 (p=0.008) and tended to increase forelimb hanging time(p=0.097). mFAS did not alter motor learning/function (rotarod), but increased ambulatory and exploratory behaviour (open field test; p=0.027). Conclusions: mFAS delays some early aspects of neurodevelopment including neonatal postural reflex maturation and proprioceptive/vestibular function, but accelerates others such as eye opening. However, the open field test indicated that mFAS improved the offspring's locomotion and exploratory behaviours in adulthood. Further studies will differentiate the neurodevelopmental effects of mFAS around conception from gestation-long mFAS.

A new neonatal primitive reflex: “The elbowing”. First experiences obtained on 543 Hungarian human newborns and infants

Between March 2007 and March 2008, authors studied the characteristics of a newly described neonatal primitive reflex, named "elbowing", on 481 mature, mostly healthy human newborns, and 62 premature ones. 1329 examinations were done at birth and later on at different ages, during the first 6 months. The reflex proved to be positive to around 70-80% on the first days of life, and with decreasing prevalence, remained positive to around 25-30% between 4-6 months. There were no significant differences between mature and premature newborns. Further studies are needed especially on pediatric patients with different neonatal pathology, and following newborns with unusual screening (early negative and/or late positive) results is essential.

Pesticides and child neurodevelopment

This review summarizes the recent research on pesticide exposure and child neurobehavioral development with a focus on in-utero exposure to organochlorine and organophosphate pesticides. Recent studies on in-utero exposure to the organochlorine pesticide dichlorodiphenyltrichloroethane and its breakdown product, dichlorodiphenyldichloroethene, indicate that exposure is associated with poorer infant (6 months and older) and child neurodevelopment. Yet, the studies differ on the domain of development that is affected. Research on organophosphate pesticide exposure and neurodevelopment is limited but suggests some negative association of exposure and neurodevelopment at certain ages. Two reports agree that increased levels of organophosphate exposure in utero result in greater numbers of abnormal reflexes in neonates and studies in older infants and young children also point to a negative association with development. In young children (2-3 years) two separate studies observed an increase in maternally reported pervasive developmental disorder with increased levels of organophosphate exposure. Given that the literature suggests a link between organochlorine and in-utero pesticide exposure and impaired child neurodevelopment, clinicians should educate parents about prevention of exposure, especially in populations living in agricultural areas or where household use is common.

S1815 Defining the Sensory-Motor Disconnect in Basal and Adaptive Esophageal Reflexes in Human Neonates with Laryngoscopic Abnormalities

S1815 Defining the Sensory-Motor Disconnect in Basal and Adaptive Esophageal Reflexes in Human Neonates with Laryngoscopic Abnormalities

Optimal positions for the release of primitive neonatal reflexes stimulating breastfeeding

Background Despite widespread skills-teaching, 37% of UK mothers initiating breastfeeding stop by six weeks suggesting a need to reappraise current support strategies. Rooting, sucking and swallowing have been studied extensively but little is known about the role other primitive neonatal reflexes (PNRs) might play to support breastfeeding. Aims To describe and compare PNRs observed during feeding, investigating whether certain feeding behaviours and positions, collectively termed Biological Nurturing, (BN) are associated with the release of those reflexes pivotal in establishing successful feeding. Method 40 breastfed healthy term mother/baby pairs were recruited using quota sampling to stratify term gestational age. Feeding sessions were videotaped in the first postnatal month, either in hospital or at home. Findings 20 PNRs were validated and classified into 4 types (endogenous, motor, rhythmic and anti-gravity) and 2 functional clusters (finding/latching, milk transfer) either stimulating or hindering feeding. Significantly more PNRs were observed as stimulants in semi-reclined postures (BN) than when mothers were upright or side-lying ( p = < 0.0005). Discussion This study is the first to describe a range of semi-reclined maternal postures interacting with neonatal positions, releasing maternal instinctual behaviours and PNRs stimulating breastfeeding. Traditionally the human neonate has been considered a dorsal feeder with pressure needed along the baby's back. Compelling visual data here illustrate that the newborn is an abdominal feeder and, like some other animals, displays anti-gravity reflexes aiding latch. Findings suggest that breastfeeding initiation is innate for both mother and baby, not learned, thus challenging the routine skills-teaching currently central to breastfeeding support.

Isolated Absence of the Moro Reflex in a Baby With CHARGE Syndrome Could Reflect Vestibular Abnormalities

We describe a term baby girl with (CHARGE syndrome coloboma, heart anomaly, choanal atresia, retardation, and genital and ear anomalies association) who had persistent complete absence of the Moro reflex but preservation of other primary neonatal reflexes. A computed tomography scan revealed bilateral absence of the semicircular canals and hypoplastic vestibules. We suggest that isolated absence of the Moro reflex may reflect underlying abnormalities of the vestibular system and may, therefore, not necessarily be associated with a generalized disturbance of the central nervous system as is usually the case. This suggestion has implications for the diagnostic and prognostic relevance of an isolated absent Moro reflex.

Mechanisms of pathogenesis in the Sudden Infant Death Syndrome

The likely processes of the Sudden Infant Death Syndrome (SIDS) were identified many years ago (apnea, failed arousal, failed autoresuscitation, etc.). The neurophysiological basis of these processes and the neurophysiological reasons some infants die of SIDS and others do not are, however, only emerging now. We reviewed recent studies that have shed light on the way in which epidemiological risk factors, genetics, neurotransmitter receptor defects and neonatal cardiorespiratory reflex responses interact to lead to sudden death during sleep in a small number of normal appearing infants. As a result of this review and analysis, we hypothesize that the neurophysiological basis of SIDS resides in a persistence of fetal reflex responses into the neonatal period, amplification of inhibitory cardiorespiratory reflex responses and reduced excitatory cardiorespiratory reflex responses. The hypothesis we developed explores the ways in which multiple subtle abnormalities interact to lead to sudden death and emphasizes the difficulty of ante-mortem identification of infants at risk for SIDS, although identification of infants at risk remains an essential goal of SIDS research.

Growth and developmental outcomes of three high‐risk infant rhesus macaques (Macaca mulatta)

Infants classified as "high risk" are born with a greater chance of developing medical complications at birth, and may have cognitive and other developmental complications later in life. Very few reports exist regarding the survival and outcome of such infants in primate colonies. Here we present early growth and developmental data on three high-risk infant rhesus macaques (one female and two males) that were born either with intrauterine growth restriction (IUGR; born below the 1st birth weight percentile for gestational age) or extremely prematurely (at gestational days 128 and 140; mean full-term gestation=164 days). We compared the outcome of these infants with that of healthy controls born at term and found no gross developmental delays in these infants with respect to growth, neonatal reflex and motor skill development, early cognitive development, or social behavior. Neurological and cognitive assessments were compared in terms of both postnatal and gestational age. The survival of these infants was dependent on a 24-hr staffed nursery and a fluid protocol that catered to each high-risk infant's individual needs. When such measures are implemented, infants such as these have a good chance of survival and can serve as excellent models for high-risk human babies and their subsequent development.