Near-infrared spectroscopy in the fetus and neonate

Near-infrared spectroscopy allows for real-time, noninvasive measurement of cerebral hemodynamics and oxygenation at the bed-side. This article describes animal and clinical research using near-infrared spectroscopy to study cerebral hemodynamic function in the fetus, neonate, and child.     

Timing of injury in the fetus and neonate

PURPOSE OF REVIEW: The aim of this article is to assess evidence for the timing of brain injury associated with clinical encephalopathy in the fetus and newborn. RECENT FINDINGS: Older studies found strong epidemiological links between antenatal factors, including exposure to infection, and acute encephalopathy and later cerebral palsy. In contrast, recent cohort studies using early magnetic resonance imaging and spectroscopy, near-infrared spectroscopy and electroencephalogram monitoring suggest that the majority of brain injury in infants with evidence of encephalopathy occurs in the immediate perinatal period and conversely that it is relatively uncommon for chronic, antepartum injury to present with symptoms at birth. A key experimental study showed that mild infection can lead to long-lasting sensitization of the brain to subsequent mild hypoxia-ischemia. This provides a plausible mechanistic link between some antenatal complications and acute perinatal injury. Consistent with this, randomized controlled trials have demonstrated that therapeutic hypothermia can significantly improve outcome of neonatal encephalopathy at term. Electroencephalogram monitoring seems to be the most promising modality to identify infants who may benefit from potential neuroprotective treatments, but more research is needed to refine its use. SUMMARY: There is now strong evidence that brain injury commonly occurs in the immediate perinatal period, and so may be potentially treatable.     

Clinical evaluation of the fetus and neonate

Summary The relation between intra-partum cardiotocography (CTG), cord blood acid-base status, Apgar score and neonatal morbidity was studied in 1228 consecutively live-born babies and in a subgroup of 200 babies (148 babies with a 1 min Apgar score≤8 and 52 randomly selected babies with a 1 min Apgar score≥9). The scores for the individual components of the 1 min Apgar score were strongly associated with each other, whereas the scores for the individual components of the 5 min Apgar score were less strongly associated. At 1 min the scores for muscle tone, reflex irritability and respiration but not the scores for heart rate and skin colour were associated with arterial and venous cord blood pH (low scores being associated with low pH). Out of the individual components of the Apgar score, heart rate and reflex irritability at 1 min were the best discriminators between “healthy or relatively healthy” and “severely ill” babies. Intrapartum CTG, total Apgar score and cord blood acid-base status were only weakly related. Venous cord blood pH was the best predictor of the 1 min Apgar score. Intra-partum CTG (silent pattern), 5 min Apgar score and venous cord blood pH were the best predictors of severe neonatal morbidity.     

Innate immune cell recruitment in the fetus and neonate

Recruitment of innate immune cells from the vasculature into infected tissue is a key event in primary host defense against invading pathogens. This highly regulated process requires a functional interplay of specialized adhesion molecules and involves a series of steps leading from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration. In the developing fetus, innate immune functions are ontogenetically regulated and show increasing maturation throughout gestation. Developmental differences in the innate immune response leave the neonate and especially the premature newborn at high risk of severe infections. Understanding the ontogeny of immune functions in the fetus and newborn is therefore essential for the prevention and treatment of neonatal infections. In this review, an overview will be given of the developmental aspects of innate immune cell recruitment including a discussion of controversial findings and open questions.     

The development of circadian rhythms in the fetus and neonate

The circadian time-keeping system is the neural system that allows predictive adaptation of individuals to the reproducible 24-hour day/night alternations of our planet. A biological clock, the suprachiasmatic nucleus, receives environmental information and imposes a circadian pattern to physiological functions. Since the suprachiasmatic nucleus develops early in gestation and circadian rhythms are present in the fetus and newborn, the circadian system seems to be functional in fetal life and can receive circadian inputs through the mother. The neonate moves to an environment in which the main time giving signal is the light:dark cycle. Teleologically, a term newborn should be fit to face this challenge. But this may be quite different for a preterm infant that trades the circadian environment to which it was previously exposed for the timeless environment of the Neonatal Intensive Care Nursery. Scientists and physicians should seek new experimental and clinical approaches to answer the challenging questions of perinatal chronomedicine.     

Impact of maternal pheochromocytoma on the fetus and neonate

Pheochromocytoma during pregnancy is rare but potentially harmful to the mother and fetus. Fetal risks are mainly determined by the vasoconstrictive effects of maternal catecholamine on uteroplacental circulation, because the fetus is protected from the direct effects of high catecholamine levels at the placental interface. Uteroplacental insufficiency may lead to spontaneous abortion, fetal growth restriction, premature delivery, and fetal hypoxia, followed by fetal distress and/or birth asphyxia. Adrenalectomy is recommended during the second trimester. When a diagnosis is made during the late second or third trimester, appropriate medical treatment until term and planned delivery with concurrent or delayed adrenalectomy can result in good fetal outcomes. Moreover, when adrenalectomy is planned after delivery, there is concern regarding the potential of antihypertensive drugs to be transferred to breast milk. It is generally known that early detection and proper treatment of pheochromocytoma during pregnancy decrease maternal and fetal mortality. However, in recent case series, antenatal maternal pheochromocytoma diagnosis did not significantly decrease the risk of fetal and neonatal mortality and morbidity, contrary to the maternal death and complication rates. Although intrauterine ischemia and hypoxia due to uteroplacental insufficiency can affect the long-term outcomes of neonates, no systematic studies have been performed.     

Surgical advances in the fetus and neonate: esophageal atresia

This article focuses on selected topics in the diagnosis and management of patients with esophageal atresia (EA) with or without tracheoesophageal fistula. The current status of prenatal diagnosis and recent advances in surgical techniques, including thoracoscopic repair for short-gap EA and tension-induced esophageal growth for long-gap EA, are reviewed. Although no consensus exists among pediatric surgeons regarding the role of these procedures in the treatment of EA, one can reasonably expect that, as they evolve, their application will become more widespread in this challenging patient population.     

Cerebral infarctions in the fetus and neonate: maternal-placental-fetal considerations

Historical data, clinical examination findings, and laboratory information must be integrated along a variable timeline that includes antepartum, intrapartum, and postnatal time periods when cerebral infarction can occur, in the context of the neonates genetic endowment. Genetic susceptibility or prenatal acquired vulnerabilities regarding stroke syndromes may set in motion a cascade of molecular pathways that ultimately cause or exacerbate brain injury when the vulnerable child experiences adverse medical conditions. The clinician must consider maternal, placental, and fetal conditions on which a stroke syndrome may be superimposed, with or without additional brain injury from other pathogenic mechanisms. Evaluation of fetal and neonatal cerebral infarction requires knowledge of mechanisms of brain injury that cross medical disciplines and may involve consultation with maternal/fetal specialists, placental and pediatric pathologists, neonatologists, geneticists, and other pediatric subspecialties. Comprehensive evaluations of survivors of cerebral infarction are needed to better understand structural and functional plasticity of the developing brain after a cerebrovascular event in the fetal and neonatal periods.     

Neurobehavioral continuity from fetus to neonate

Neurobehavior represents development of the central nervous system (CNS). Fetuses and newborns exhibit a large number of endogenously generated motor patterns, among which general movements are often investigated pre- and post-natally. Spontaneous activity is probably a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli while testing reflexes. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects particularly on brain growth and function. Unfavorable intrauterine environment can affect adversely brain growth. All endogenously generated movement patterns from un-stimulated CNS might be observed as early as from the seven to eight weeks' gestation, with a rich repertoire of movements within the next two or three weeks, continuing for five to six months postnatally. It is still uncertain whether a new scoring system for prenatal neurological assessment will be adequate for the distinction between normal and abnormal fetuses in low-risk pregnancies. The continuity of behavioral patterns from prenatal to postnatal life might answer these intriguing questions.     

Diagnostic laboratory technologies for the fetus and neonate with isoimmunization

Maternal-fetal blood group incompatibility is common but less commonly results in hemolytic disease of the fetus and newborn (HDFN). HDFN is associated with greater peak bilirubin, at an earlier age, and for longer duration than other causes of hyperbilirubinemia. It poses a substantial risk for kernicterus and accounts for the majority of exchange transfusions for hyperbilirubinemia. Advances in diagnosis and management are described, from identification of the alloimmunized pregnancy by maternal ABO and Rh typing, antibody screen (indirect Coombs test), identification and titration; laboratory evaluation of the maternal-fetal unit with a critical maternal antibody titer to prompt fetal antigen status determination; assessment of fetomaternal hemorrhage by conventional Kleihauer-Betke testing or by flow cytometric methodology; to antenatal management of isoimmunization and fetal status assessments using the systems of Liley, Queenan, and serial Doppler fetal middle cerebral artery peak velocity measurements. The utility of laboratory diagnostics in the approach to hemolysis in the neonate, including hematology, chemistry, and peripheral blood smear review, is reviewed. The goal of management, to deliver a healthy infant at or near term, is attained for the majority of cases using current modalities; future directions include noninvasive genotyping of fetal blood from maternal serum to fully eliminate RhD alloimmunization and HDFN; and development of prophylaxis and intervention strategies for non-RhD alloimmunizations for which immune globulin is currently unavailable.     

Two-dimensional and Doppler echocardiographic evaluation of heart disease in the neonate and fetus

Two-dimensional and Doppler echocardiography has had a major impact on the diagnostic and therapeutic management of the newborn infant and fetus with a cardiovascular disorder. This article illustrates the use of the ultrasound techniques in the diagnosis of heart disease in the acyanotic newborn infant with a left-to-right shunt or ventricular outflow obstruction and the cyanotic infant with increased or decreased pulmonary vascularity. In addition, echocardiography has proven invaluable in the in utero diagnosis of cardiovascular abnormalities (structural or rhythm disturbances). This article also reviews the indications for and technical aspects of the fetal echocardiographic examination.     

Temporal response of plasma erythropoietin to hemorrhage in the ovine fetus

OBJECTIVE: In previous studies of ovine fetuses, plasma erythropoietin (EPO) concentration increased 10- to 20-fold at 24 hours after hemorrhage and returned toward normal at 48 hours. The present study in fetal sheep was designed to determine in detail the time course of the hemorrhage-induced changes in plasma EPO levels and explore the relationships among EPO concentration, blood oxygen tension, and hematocrit. METHODS: Chronically catheterized, late gestation ovine fetuses (n = 12) were hemorrhaged such that 40% of their blood volume was lost over 2 hours. Plasma EPO concentration, arterial blood gases, pH, and hematocrit were determined at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, and 36 hours after initiating the hemorrhage. Plasma EPO concentration was determined by radioimmunoassay. Statistical analyses included analysis of variance and least squares regression. RESULTS: Mean plasma EPO concentration increased significantly (2.3 +/- 0.5/+/- standard error of the mean/times basal values) at 4 hours after initiating the hemorrhage, reached a maximum (33.8 +/- 12.9 times basal values) at 10-16 hours, and decreased to 50% of maximal values at 24 hours after hemorrhage. Hematocrit decreased rapidly during the 12 hours after hemorrhage (P < .0001), whereas arterial blood oxygen tension remained unchanged. The logarithm of EPO concentration was correlated with hematocrit (r = -0.74, P < .0001) but not with arterial blood oxygen tension. CONCLUSIONS: Blood EPO concentration began to increase at approximately 3-4 hours after the onset of hemorrhage. Further, EPO concentrations at 24 hours after hemorrhage represented only 50% of the maximal EPO response. The correlation between EPO and hematocrit suggests that blood oxygen content rather than oxygen tension is the more important stimulant for augmented EPO production after fetal hemorrhage.     

Bupivacaine paracervical block. Effects on the fetus and neonate.

To evaluate effects on the fetus and neonate, 53 paracervical blocks were administered to 38 low-risk parturients using a controlled superficial injection of 0.25% bupivacaine. Continuous fetal heart rate monitoring revealed no instance of bradycardia or late deceleration pattern. Apgar scores, cord arterial and venous pH values, and neurobehavioral evaluations of the neonates were similar to those observed in other low-risk patients. The effectiveness of pain relief of the blocks was less than expected or reported by other authors. Although we observed no harmful effects on the fetus or neonate from the superficial paracervical injection of bupivacaine, we did not find this combination of drug and technique to give dependable, effective pain relief in labor.