Howard Smith, MD

  • Associate Professor
  • Anesthesiology, Internal Medicine, and Physical
  • Rehabilitation and Medicine
  • Department of Anesthesiology
  • Albany Medical College
  • Albany, New York

Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full-term children at 18 months corrected age antibiotics for acne how long should i take it buy floxin canada. Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm antibiotic resistance examples purchase floxin 200mg amex. Pain sensitivity and temperament in extremely low-birth-weight premature toddlers and preterm and full-term controls natural antibiotics for acne infection discount floxin 400 mg free shipping. Early pain experience antibiotics for sinus chest infection purchase floxin 400 mg fast delivery, child and family factors antibiotics for dogs for uti buy floxin without a prescription, as precursors of somatization: a prospective study of extremely premature and fullterm children antibiotic resistance discussion questions purchase discount floxin. Interactions of inflammatory pain and morphine treatment in infant rats: long-term behavioral effects. Neonates need to be comfortable and as free of pain as possible to grow and develop normally. Valid, reliable, and regular pain assessments are a major prerequisite for attaining this goal. Physiologic indicators of pain include increased heart rate, respiratory rate, and blood pressure, as well as decreased heart rate variability and oxygen saturations. Pain assessment in neonates is difficult in neurologically compromised, chemically paralyzed, or nonresponsive infants. Many methods for measuring the intensity of acute pain in neonates have been validated, but other aspects of painful experiences. Very few methods have been validated for the assessment of postoperative pain or chronic pain. A challenge facing clinicians is to develop and validate objective measures of prolonged pain in preterm and term neonates (Table 17-1). Are twitches, startles, and body movements pain indicators in extremely low birth weight infants? Assessment of persistent pain or distress and adequacy of analgesia in preterm ventilated infants. Validity of behavioral and physiologic parameters for acute pain assessment of term newborn infants. Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates. Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome. Opioids for neonates receiving mechanical ventilation: a systematic review and meta-analysis. Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial. What are the clinical effects of continuous morphine or fentanyl infusions in ventilated preterm neonates? Randomized placebo-controlled clinical trials have compared the efficacy and safety of intravenous fentanyl or morphine in ventilated preterm neonates. In infants treated with fentanyl, two trials reported lower behavioral stress scores at 16, 24, 48, and 72 hours; a third trial showed reduced pain scores compared with the placebo group. Infants receiving fentanyl had statistically lower heart rate values than the placebo group but required more ventilatory support. Morphine infusions did not improve short-term pulmonary outcomes among ventilated preterm neonates, whereas additional morphine doses were associated with worse respiratory outcomes among preterm neonates with respiratory distress syndrome. Comparison of continuous infusion of fentanyl to bolus dosing in neonates after surgery. Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease. Opioids for neonates receiving mechanical ventilation: a systematic review and metaanalysis. Opiates have numerous side effects, including respiratory depression, nausea, vomiting, urinary retention, decreased gut motility, and histamine release causing hypotension or bronchospasm. In addition, morphine is associated with greater effects on gut motility, and very high doses may cause biliary spasm or even seizures. Chest wall rigidity or laryngospasm occur more commonly with fentanyl, with the rapid administration of intravenous doses. Fentanyl produces less sedation than morphine but has been associated with greater opioid tolerance because of its shorter duration of action. Recommended use of morphine in neonates, infants and children based on a literature review: Part 2-clinical use. Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: a randomized trial. Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Respiratory muscle rigidity in a preterm infant after use of fentanyl during Caesarean section. Many of these signs were included in scoring systems designed to quantify opioid withdrawal in neonates born from heroin-addicted mothers. Prospective study on the occurrence of withdrawal in critically ill children who receive fentanyl by continuous infusion. The Neonatal Narcotic Withdrawal Index: a device for the improvement of care in the abstinence syndrome. Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: a literature review. Withdrawal symptoms in critically ill children after long-term administration of sedatives and/or analgesics: a first evaluation. Preventing or delaying the onset of opioid tolerance may allow the rapid weaning of opioids, thus reducing the costs and complications of prolonged opioid weaning. Although listed here, the safety and efficacy of these approaches have not been tested in neonates. The reversal of fentanyl-induced tolerance by administration of "small-dose" ketamine. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. In addition to supportive therapy and the slow weaning of opioids, some pharmacologic agents with a relatively long half-life can be used to manage opioid withdrawal. The use of drugs such as paregoric, camphorated tincture of opium, phenobarbital, and chlorpromazine are not recommended for opioid withdrawal because of major side effects and lack of standardization. Therapeutic goals are to decrease the severity of withdrawal signs to a tolerable degree, enable regular cycles of sleeping and feeding, and decrease the agitation caused by medical interventions or nursing care. Buprenorphine was as potent as high-dose methadone for adult opioid addiction, and its clinical use in opioid-addicted mothers induced significantly less opioid withdrawal in their infants compared with methadone-treated mothers. Because the alpha2adrenergic receptors activate the same inhibitory Gi-proteins, clonidine has been used to treat opioid withdrawal in neonates. Methadone as treatment for iatrogenic narcotic dependency in pediatric intensive care unit patients. Buprenorphine in pregnant opioid-dependent women: first results of a prospective study. Comparison of clinician ratings to self reports of withdrawal during clonidine detoxification of opiate addicts. Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care patients. Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Procedural pain can be minimized with an appropriate awareness program involving nursing and respiratory therapy staff members; physicians; and, most important, parents. The most common sources of minor procedural pain are heel sticks and tracheal suctioning. Heel sticks can be treated with 25% sucrose, and tracheal suctioning can be treated with facilitated tucking. Remifentanyl, for example, is a good choice for short-term procedures such as intubation, whereas more prolonged pain should be treated with a longer-acting opiate such as morphine or fentanyl. Anxiolytics such as midazolam can be used as adjuncts, but they do not treat pain. Oral sucrose and "facilitated tucking" for repeated pain relief in preterms: a randomized controlled trial. The efficacy of facilitated tucking for relieving procedural pain of endotracheal suctioning in very low birthweight infants. Remifentanil for sedation and analgesia in a preterm neonate with respiratory distress syndrome. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Prilocaine is metabolized to ortho-toluidine, which can oxidize hemoglobin to methemoglobin in neonates. Methaemoglobinaemia secondary to topical lignocaine/prilocaine in a circumcised neonate. Nonpharmacologic interventions are useful for minor pain and as adjunct therapy for severe pain. Sucrose solutions block the nociceptive transmission in the ascending pathways that transmit noxious stimuli to the brain, while activating the descending inhibitory pathways that modulate pain. Additionally, animal studies show that the gustatory receptors stimulated by sucrose lead to an activation of the endogenous opioid systems in the newborn brainstem, with reduced pain transmission to the thalamocortical circuits. These mechanisms are unlikely to lead to increased beta-endorphin levels in peripheral plasma, as noted in preterm newborns. Additional evidence for this mechanism is demonstrated by the fact that naloxone blocks the analgesic effects of sucrose. Until further evidence becomes available, the consensus opinion remains that sucrose induces effective analgesia for acute pain resulting from skin-breaking procedures in term and preterm newborns. Recently, however, safety of the long-term repeated use of sucrose solutions has been called into question, and protocols should be developed to limit sucrose dosing. Analgesic effects of sweet-tasting solutions for infants: current state of equipoise. The goals of perioperative analgesic approaches are the relief of pain, the maintenance of physiologic stability, and the prevention of adverse events such as hypoventilation or shallow respiration owing to diaphragmatic splinting, paralytic ileus, protein catabolism, and pulmonary hypertension. The management of postoperative pain should ideally start before the operative procedure, with consideration given to the size and alignment of the surgical incision; the choice of anesthetic agents; infiltration of the surgical site with lidocaine or bupivacaine; and, if possible, the placement of an epidural catheter before or after surgery. Use of analgesics may improve postoperative outcomes with fewer adverse events, shorter duration of mechanical ventilation, rapid return of gastrointestinal function, and reduced incidence of postoperative apnea and other complications. Opiates are the mainstay of therapy; however, because of their known side effects, including respiratory depression, other drugs such as ketorolac and acetaminophen are being studied. Other options include epidural or caudal anesthesia with bupivacaine, or bupivacaine mixed with fentanyl infusions continued into the postoperative period. The use of nurse-controlled analgesia using a patient-controlled analgesia pump is also under investigation. Are the doses of morphine and fentanyl for postoperative analgesia in neonates similar to the doses used for older children? Neonates may receive lower morphine infusion rates than older children after surgery, starting as low as 0. Neonates with cyanotic congenital heart defects also require lower morphine infusion rates than neonates undergoing noncardiac surgery. Depending on the dose and other patient characteristics, fentanyl and sufentanil provide variable degrees of suppression of autonomic and hormonal/metabolic responses to major surgery in neonates, although fentanyl may increase the risk of postoperative hypothermia. Critically ill neonates, whose vascular tone depends on sympathetic outflow, may become hypotensive after bolus doses of fentanyl or morphine. Randomized controlled trials show no differences in the postoperative analgesia produced by bolus doses versus continuous infusions of morphine; however, apnea or other complications were greater in the bolus-dosing groups. Intravenous boluses of opioids should be given slowly (over 15 to 30 minutes) to postoperative neonates. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. The majority of preterm neonates are capable of glucuronidating morphine, but birth weight and gestational and postnatal age influence the hepatic capacity for glucuronidation. Term and preterm neonates and older infants produce relatively greater proportions of morphine-3-glucuronide, which acts as an opioid antagonist and has a prolonged half-life. Older children and adults produce morphine-6-glucuronide, which is a potent analgesic, with 20 times the analgesic potency of morphine itself. Morphine-6-glucuronide was not detected in the plasma of any neonate, which may explain why neonates require relatively high plasma concentrations of unchanged morphine for effective analgesia. Experience of remifentanil in extremely low-birth-weight babies undergoing laparotomy. A meta-analysis performed from the reported pharmacokinetics parameters showed an increased volume of distribution for morphine, estimated to be 2. In contrast, the half-life and plasma clearance rates for morphine are clearly related to age, secondary to maturational changes in hepatic and renal function. The prolonged half-life explains why effective analgesia can be maintained, following a loading dose, with very low infusion rates of morphine (5-15 g/kg/h). Doses must be further decreased for neonates with impaired hepatic or renal functions, and a pharmacist should be consulted for these patients. Fentanyl undergoes first-pass metabolism in the liver and the elimination half-life is predictably prolonged in the presence of increased abdominal pressure, which may limit hepatic blood flow.

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If Skyla cannot be removed antibiotic 30s ribosomal subunit cheap floxin 200mg on line, follow the pregnancy closely [see Warnings and Precautions (5 suggested antibiotics for sinus infection cheap floxin 400mg otc. Studies report no adverse effects on fetal and infant development associated with long-term use of contraceptive doses of oral progestins in a pregnant woman antibiotics mechanism of action buy floxin with mastercard. However antibiotics in pregnancy buy floxin 400 mg low cost, there have been reported cases of masculinization of the external genitalia of the female fetus following exposure to progestins at doses greater than those currently used for oral contraception antimicrobial nail polish proven floxin 400 mg. There are no reports of adverse effects in breastfed infants with maternal use of progestin-only contraceptives antibiotic 5312 purchase floxin online now. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. The white T-body has a loop at one end of the vertical stem and two horizontal arms at the other end. The reservoir is covered by a semi-opaque silicone membrane, composed of polydimethylsiloxane and colloidal silica. The polyethylene of the T-body is compounded with barium sulfate, which makes it radiopaque. A monofilament brown polyethylene removal thread is attached to a loop at the end of the vertical stem of the T-body. The polyethylene of the removal thread contains iron oxide as a colorant (see Figure 10). The components of Skyla, including its packaging, are not manufactured using natural rubber latex. The inserter (Figure 11), which is used for insertion of Skyla into the uterine cavity, consists of a symmetric two-sided body and slider that are integrated with flange, lock, pre-bent insertion tube and plunger. The vertical stem of Skyla is loaded in the insertion tube at the tip of the inserter. In clinical trials with Skyla, ovulation was assessed based on serum progesterone values >2. Evidence of ovulation by these criteria was seen in 34 out of 35 women in the first year, in 26 out of 27 women in the second year, and in all 26 women in the third year. The in vivo release rate is approximately 14 mcg/day after 24 days and is reduced to approximately 10 mcg/day after 60 days and then declines progressively to approximately 6 mcg/day after 1 year and 5 mcg/day after 3 years. The most important metabolic pathways are the reduction of the 4-3-oxo group and hydroxylations at positions 2, 1 and 16, followed by conjugation. Significant amounts of conjugated and unconjugated 3, 5- are also present in serum, along with much smaller amounts of 3, 5tetrahydrolevonorgestrel and 16-hydroxylevonorgestrel. Specific Populations Pediatric: Safety and efficacy of Skyla have been established in women of reproductive age. Geriatric: Skyla has not been studied in women over age 65 and is not approved for use in this population. Race: A three-year phase 3 study in the Asian-Pacific region (93% Asian women, the majority of whom were Chinese, 7% other ethnicities) using Skyla was performed. This slightly higher exposure might be explained by the lower body weight of Asian women. Hepatic Impairment: No studies were conducted to evaluate the effect of hepatic disease on the disposition of Skyla. Renal Impairment: No formal studies were conducted to evaluate the effect of renal disease on the disposition of Skyla. Drug-Drug Interactions No drug-drug interaction studies were conducted with Skyla [see Drug Interactions (7)]. Skyla-treated women provided 15,763 evaluable 28-day cycle equivalents in the first year and 39,368 evaluable cycles over the three year treatment period. The cumulative 3-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan-Meier method was 0. About 77% of women who desired pregnancy after study discontinuation and provided follow-up information, conceived within 12 months after removal of Skyla. Risk of Ectopic Pregnancy: Inform the patient about the risks of ectopic pregnancy, including the loss of fertility. Teach her to recognize and report to her healthcare provider promptly any symptoms of ectopic pregnancy. Inform the patient about the risks of intrauterine pregnancy while using Skyla, including the risks of leaving Skyla in place and the risks of removing Skyla or probing of the uterus. Instruct her to contact a healthcare provider immediately if she develops severe pain or fever shortly after Skyla is inserted. Teach patients to recognize and report to their healthcare provider promptly any symptoms of pelvic infection. These symptoms include development of menstrual disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever. Inform her that there is no contraceptive protection if Skyla is displaced (for example, expelled or perforated the uterus). If perforation occurs, Skyla will have to be located and removed; surgery may be required. Instruct the patient to contact her healthcare provider if she cannot feel the threads. Advise the patient to contact her healthcare provider if she experiences these symptoms. If her symptoms continue or are severe she should report them to her healthcare provider. Read this Patient Information carefully before you decide if Skyla is right for you. You should also learn about other birth control methods to choose the one that is best for you. The threads are the only part of Skyla you can feel when Skyla is in your uterus; however, unlike a tampon string, the threads do not extend outside your body. Your healthcare provider can place a new Skyla during the same office visit if you choose to continue using Skyla. Skyla is intended for use up to 3 years but you can stop using Skyla at any time by asking your healthcare provider to remove it. You could become pregnant as soon as Skyla is removed, so you should use another method of birth control if you do not want to become pregnant. Talk to your healthcare provider about the best birth control methods for you, because your new method may need to be started 7 days before Skyla is removed to prevent pregnancy. What if I change my mind about birth control and want to become pregnant in less than 3 years? About 3 out of 4 women who want to become pregnant will become pregnant sometime in the first year after Skyla is removed. Skyla may work in several ways including thickening cervical mucus, inhibiting sperm movement, reducing sperm survival, and thinning the lining of your uterus. The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. Your healthcare provider will then clean your vagina and cervix with an antiseptic solution and slide a slim plastic tube containing Skyla into your uterus. Your healthcare provider will then remove the plastic tube, and leave Skyla in your uterus. If your symptoms do not pass within 30 minutes after placement, Skyla may not have been placed correctly. Yes, you should check that Skyla is in proper position by feeling the removal threads. You can check by reaching up to the top of your vagina with clean fingers to feel the removal threads. If you feel more than just the threads or if you cannot feel the threads, Skyla may not be in the right position and may not prevent pregnancy. Use non-hormonal back-up birth control (such as condoms and spermicide) and ask your healthcare provider to check that Skyla is still in the right place. Call your healthcare provider if you have any questions or concerns (see "When should I call my healthcare provider? Otherwise, you should return to your healthcare provider for a follow-up visit 4 to 6 weeks after Skyla is placed to make sure that Skyla is in the right position. There are also risks if you get pregnant while using Skyla and the pregnancy is in the uterus. Because of this, your healthcare provider may try to remove Skyla, even though removing it may cause a miscarriage. If Skyla cannot be removed, talk with your healthcare provider about the benefits and risks of continuing the pregnancy. Call your healthcare provider right away if you get flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge, or fluid leaking from your vagina. It is not known if Skyla can cause long-term effects on the fetus if it stays in place during a pregnancy. For the first 3 to 6 months, your period may become irregular and the number of bleeding days may increase. After you have used Skyla for a while, the number of bleeding and spotting days is likely to lessen. You may use Skyla when you are breastfeeding if more than 6 weeks have passed since you had your baby. If you are breastfeeding, Skyla is not likely to affect the quality or amount of your breast milk or the health of your nursing baby. The risk of Skyla becoming attached to (embedded) or going through the wall of the uterus is increased if Skyla is inserted while you are breastfeeding. If this occurs, or if you or your partner experience pain during sex, talk with your healthcare provider. There are risks if you become pregnant while using Skyla (see "What if I become pregnant while using Skyla? Life-threatening infection can occur within the first few days after Skyla is placed. Call your healthcare provider immediately if you develop severe pain or fever shortly after Skyla is placed. The risk of perforation is increased if Skyla is inserted while you are breastfeeding. If these symptoms do not stop 30 minutes after placement, Skyla may not have been placed correctly. Your healthcare provider will examine you to see if Skyla needs to be removed or replaced. If you think that Skyla has come out, use a backup birth control method like condoms and spermicide and call your healthcare provider. If you do not have a period for 6 weeks during Skyla use, call your healthcare provider. Call your healthcare provider if the bleeding remains heavier than usual or increases after it has been light for a while. Tell your healthcare provider if you have any side effect that bothers you or does not go away. If Skyla is accidentally removed and you had vaginal intercourse within the preceding week, you may be at risk of pregnancy, and you should talk to a healthcare provider. You can ask your healthcare provider for information about Skyla that is written for healthcare providers. Provide a short abstract (not to exceed 150 words), a 1-sentence summary of the conclusions, and a brief biographical sketch of first author or of both authors if only 2 authors. Articles in this section should provide insightful analysis and commentary about new and reemerging infectious diseases and related issues. Perspectives may also address factors known to influence the emergence of diseases, including microbial adaptation and change, human demographics and behavior, technology and industry, economic development and land use, international travel and commerce, and the breakdown of public health measures. Synopses Articles should not exceed 3,500 words in the main body of the text or include more than 40 references. Provide a short abstract (not to exceed 150 words), a 1-line summary of the conclusions, and a brief biographical sketch of first author or of both authors if only 2 authors. This section comprises concise reviews of infectious diseases or closely related topics. Preference is given to reviews of new and emerging diseases; however, timely updates of other diseases or topics are also welcome. If detailed methods are included, a separate section on experimental procedures should immediately follow the body of the text. Research Articles should not exceed 3,500 words in the main body of the text or include more than 40 references. Explain the value of the research in public health terms and place the findings in a larger perspective. Articles describing mathematical, economic, or statistical studies have some additional restrictions because readers of Emerging Infectious Diseases may not necessarily have extensive training in these areas.

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Epinephrine should be injected promptly (eg antimicrobial medications list buy floxin with paypal, goal of <4 minutes) for anaphylaxis infection eye buy 400 mg floxin amex, which is likely (although not exclusively) occurring if the patient has 2 or swollen lips/tongue/uvula); (2) respiratory compromise (dyspnea infection under toenail purchase generic floxin online, wheeze infection virale buy floxin 400mg on line, bronchospasm antibiotics in animals buy floxin toronto, stridor virus hiv order floxin 400 mg with mastercard, or hypoxemia); (3) low blood pressure; or (4) gastrointestinal tract involvement (eg, persistent crampy abdominal pain or vomiting). If a patient is known to have had a previous severe allergic reaction to the biologic product/serum, onset of skin, cardiovascular, or respiratory symptoms alone may warrant treatment with epinephrine. Use of readily available commercial epinephrine autoinjectors (available in 2 dosages by weight) and epinephrine is administered intramuscularly every 5 to 15 minutes, as necessary, to control symptoms and maintain blood pressure. If agent causing anaphylactic reaction was given by injection, epinephrine can be injected into the same site to slow absorption. Maintenance of the airway and administration of oxygen should be instituted promptly. Severe or potentially life-threatening systemic anaphylaxis involving severe bronchospasm, laryngeal edema, other airway compromise, shock, and cardiovascular collapse necessitates additional therapy. Administration of epinephrine intravenously can lead to lethal arrhythmia; cardiac monitoring is recommended. A slow, continuous, low-dose infusion is preferable to repeated bolus administration, because the dose can be titrated to the desired effect, and accidental administration of large boluses of epinephrine can be avoided. Corticosteroids should be used in all cases of anaphylaxis except cases that are mild and have responded promptly to initial therapy (see Table 1. However, no data support the usefulness of corticosteroids alone in treating anaphylaxis, and therefore they should not be administered in lieu of treatment with epinephrine and should be considered as adjunctive therapy. All patients showing signs and symptoms of systemic anaphylaxis, regardless of severity, should be observed for several hours in an appropriate facility, even after remission of immediate symptoms. Anaphylactic reactions can be uniphasic, biphasic, or protracted of observation has not been established, a reasonable period of observation would be 4 hours for a mild episode and as long as 24 hours for a severe episode. More aggressive therapy with epinephrine may override receptor blockade in some patients. Although studies have shown decreased immune responses to several vaccines given to neonates with very low birth weight (less than 1500 g) and neonates of very early gestational age (less than 29 weeks of gestation), most preterm infants, vaccine-induced immunity to prevent disease. Vaccine dosages given to term infants should not be reduced or divided when given to preterm or low birth weight infants. Preterm and low birth weight infants tolerate most childhood vaccines as well as do term infants. However, these postimmunization cardiorespiratory events do not appear to have a detrimental effect on the clinical course of immunized infants. Medically stable preterm infants who remain in the hospital at 2 months of chronologic age should be given all inactivated vaccines recommended at that age (see Recommended Immunization Schedule for Persons Aged 0 Through 18 Years [redbook. A medically stable infant bolic disease; or acute renal, cardiovascular, neurologic, or respiratory tract illness and who demonstrates a clinical course of sustained recovery and a pattern of steady growth. All or low birth weight infants, except for oral rotavirus vaccine, which should be deferred until the infant is being discharged from the hospital (see Rotavirus, p 684) to prevent the potential nosocomial spread of this live vaccine virus. The same volume of vaccine used for term infants is appropriate for medically stable preterm infants. The number of injections of other vaccines at 2 months of age can be minimized by using combination vaccines. When because of limited injection sites, the vaccines recommended at 2 months of age can be administered at different times. Because recommended parenteral vaccines are inactivated, any interval between doses of individual vaccines is acceptable. However, to avoid superimposing local reactions, 2-week intervals may be reasonable. The choice of needle lengths used for intramuscular vaccine administration is determined by available muscle mass of the preterm or low birth weight infant (see Table 1. Revalidation of the Score for Neonatal Acute Physiology in the Vermont Oxford Network. Only monovalent hepatitis B vaccine should be used for preterm or term infants younger than 6 weeks. Administration of a total of 4 doses of hepatitis B vaccine is permitted when a combination vaccine containing hepatitis B vaccine is administered after the birth dose. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine should be administered to all pregnant women (optimally between weeks 27 and 36 of gestation to yield high antibody levels in the infant) during every pregnancy. Tdap should be administered immediately postpartum for women who never have received a previous dose of Tdap. Health care personnel caring for pregnant women and infants and household contacts and child care providers of all infants who have not previously received Tdap should be targeted for vaccination. A single dose of Tdap is recommended for all nonpregnant adolescents as well as nonpregnant adults of any age (see Pertussis, p 608). Preterm infants born before 29 weeks, 0 days of gestation, infants born with certain congenital heart defects, and certain infants with chronic lung disease of prematurity may monoclonal antibody) during respiratory syncytial virus season (see Respiratory Syncytial Virus, p 667). Palivizumab use does not interfere with the immune response to routine childhood immunizations. Although no evidence indicates that vaccines currently in use have detrimental effects on the fetus, the traditional approach to use of vaccines during pregnancy has been that pregnant women should receive a vaccine only when the vaccine is unlikely to cause 1 See adult immunization schedule available at Increased recognition of the severof selected vaccines to the pregnant woman as well as to her newborn infant through either reducing exposure to the vaccine-preventable disease and/or providing protection 1 tion of selected vaccines during pregnancy. Two vaccines now are recommended for routine administration during pregnancy toxoids (for children 7 years or older and adults) (Td) vaccine may be indicated in some circumstances. For women who have been immunized with Pregnant women who are unimmunized or only partially immunized against tetanus should complete the primary series, using Tdap for only 1 of the doses. If a Td booster is indicated for wound management during pregnancy, Tdap should be given if the woman has not already received Tdap during the current pregnancy (see Pertussis, p 608). In resource-limited countries with a high incidence of neonatal tetanus, Td vaccine routinely is administered during pregnancy without evidence of adverse effects and with striking decreases in the occurrence of neonatal tetanus. Studies indicate that women who are pregnant and have no other underlying medical conditions are at reduce preterm birth and low birth weight and also protects infants younger than 6 months who cannot be immunized actively and in whom antiviral prophylaxis and treatment options are limited. Although only a theoretical risk to the fetus exists with a live-virus vaccine administered to the pregnant 1 2 Because measles, mumps, rubella, and varicella vaccines are contraindicated for pregnant women, efforts should be made to immunize women without evidence of immunity against these illnesses before they become pregnant or in the immediate postpartum period. Although of theoretical concern, no case of embryopathy caused by live rubella vaccine has been reported. However, a rare theoretical risk of embryopathy from inadvertent rubella vaccine administration cannot be excluded. Because pregnant women might be at higher risk dose should be high enough to achieve estimated protective levels of measles antibody titers (see Measles, p 535). The manufacturer, in collaboration with the Centers for Disease Control fetal outcomes of women who inadvertently were given varicella vaccine during the 3 months before or at any time during pregnancy. Through March 2012, more than 850 women (more than 170 of whom were known to be seronegative before vaccination) were enrolled prospectively in the Pregnancy Registry and had known pregnancy outcomes. More than 550 received varicella vaccine within 30 days prior to their last cella syndrome and no increased risk of other birth defects after exposure to varicella vaccine were detected. However, the registry data cannot rule out a maximal theoretical risk for congenital varicella syndrome lower than 4% among susceptible women with a risk of 1% documented after infection with wild-type varicella-zoster virus. The registry was discontinued for new enrollments in October 2013, because statistically more robust data on the risk of congenital varicella syndrome would likely not accrue given the diminishing seronegative population (because of implementation of universal vaccination) and diminished inadvertent immunization during pregnancy (because of completion of vaccination at a younger age). A pregnant woman in the household is not a contraindication for varicella immunization of a child or other household member. Transmission of vaccine virus from an immunocompetent vaccine recipient to a susceptible person has been reported only rarely, and only when a vaccine-associated rash develops in the vaccine recipient (see Varicella-Zoster Infections, p 846). Breastfeeding is not a contraindication for immunization of varicella-susceptible women after pregnancy. Varicellaevidence of immunity who have been exposed to natural varicella infection (see been evaluated. It should not be administered to pregnant women, and pregnancy should be avoided for 1 month following a dose. Pregnant women and nursing mothers should avoid or postpone travel to an area where there is risk of yellow fever. Vaccinia virus vaccine is a live-virus vaccine and should be given severe disease in pregnant than nonpregnant women, the risks to the mother and fetus from experiencing the disease may substantially outweigh the risks of immunization. Immunized household contacts should avoid contact with pregnant women until the vaccination site is healed. No information is available on the safety of any of the typhoid vaccines in pregnancy; it therefore is prudent on theoretical grounds to avoid vaccinating pregnant women. Pneumococcal and meningococcal vaccines can be given to a pregnant woman at high risk of serious or complicated illness from infection with Streptococcus pneumoniae or Neisseria meningitidis. Meningococcal conjugate vaccine can be given to a pregnant woman when there is increased risk of disease, such as during epidemics or before travel to an area with hyperendemic infection. Infection with hepatitis A or hepatitis B can result in severe disease in a pregnant woman and, in the case of hepatitis B, chronic infection in the newborn infant. Hepatitis A or hepatitis B immunizations, if indicated, can be given to pregnant women. Initiation of the vaccine series should be delayed until after completion of the pregnancy. If a woman is determined to be pregnant after initiating the immunization series, the remainder of the 3-dose regimen should be delayed until after completion of the pregnancy. If a vaccine dose has been administered during pregnancy, no intervention is needed. Rabies vaccine should be given to pregnant women after exposure to rabies under the same circumstances as nonpregnant women. No association between rabies immunization and adverse fetal outcomes has been reported. If the risk of exposure to rabies is substantial, preexposure prophylaxis also may be indicated. Anthrax vaccine is inactivated and has no theoretical risk to the fetus, but the vaccine has not been evaluated for safety in pregnant women, so it should be avoided unless in a postevent situation with a high risk of exposure (see Anthrax, p 234). Women should be immunized before conception, if possible, but Japanese encephalitis virus vaccine is unavoidable and the risk of disease outweighs the theoretical risk of adverse events in the pregnant woman and fetus (see Arboviruses, p 240). Immunocompromised people vary in their degree of immunosuppression and susceptibility to infection and, therefore, represent a can be grouped into primary and secondary disorders. Primary disorders of the immune system generally are inherited, usually as single-gene disorders; can involve any part of the immune defenses, including B-lymphocyte (humoral) immunity, T-lymphocyte (cell)-mediated immunity, complement and phagocytic function, and innate immunity; and share the common feature of increased susceptibility to infection. The following include general principles and 1 Centers for Diseases Control and Prevention. The only vaccine that should be given if the is some residual antibody production. All live vaccinesd,e Effectiveness of any inactivated vaccine depends on degree of immune suppression. Vaccines are indicated if not highly immunosuppressed, but doses should be repeated after chemotherapy ends. In addition to standard vaccines, consider Hib vaccine if not administered during infancy. For patients in whom initiation of immunosuppressive medication is planned, vaccinations should be administered prior to immunosuppression when feasision and should not be given within 2 weeks before initiation. Inactivated vaccines should Certain vaccines may be administered to children while they are modestly immunosuppressed, especially when the state is likely to be lengthy or lifelong. In general, people who are severely immunocompromised or in whom immune function is uncertain should not receive live vaccines, either viral or bacterial, because of the risk of disease caused by the vaccine strains. Inactivated vaccines and Immune immune response to inactivated vaccines generally is not affected by circulating antibody. Safety is not a concern, nor is risk of graft rejection or exacerbation of immune-mediated are very unlikely to respond (although also unlikely to be harmed), such as those receiving intensive chemotherapy and those who have received anti-B-lymphocyte antibody therapy within 6 months. Immune responses of immunocompromised children to inactivated vac1 compromised host. Patients with (ie, of early classic pathway, alternate pathand live vaccines on the annual immunization schedule; none is contraindicated. Patients with innate immune defects that result in defects of cytokine generation/response or cellular activation (eg, defects of interferon-gamma/interleukin-12 axis) should receive all inactivated vaccines on the annual immunization schedule. Additional vaccines not given universally are indicated for children with certain conditions. If chemotherapy is ongoing or other immunosuppressive therapy is escalated, cella) to guide management. Immunocompromised patients should avoid contact with people who develop skin lesions after receipt of varicella or zoster vaccines until lesions clear. Inactivated vaccine administration can be deferred temporarily until corticosteroids are discontinued if the hiatus is expected to be brief and adherence to return appointment is likely. Inactivated vaccines (or live vaccines, when recommended as follows) should not be avoided because of concern for exac- Guidance for Administration of Live-Virus Vaccines to Recipients of Corticosteroids Topical therapy, local injections, or aerosol use of corticosteroids. Application of low-potency topical corticosteroids to localized areas on the skin; administration by aerosolization; application on conjunctiva; or intraarticular, bursal, or tendon injections of corticosteroids usually do not result in immunosuppression that would contraindicate administration of live-virus vaccines. Children who are receiving only maintenance physiologic doses of corticosteroids can receive live-virus vaccines. Low or moderate doses of systemic corticosteroids given daily or on alternate days. High doses of systemic corticosteroids given daily or on alternate days for fewer than 14 days.

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However, because of the enormous influence they have had on my career, I would like to acknowledge four individuals by name: Bill Speck (my lifelong friend-no one has ever cared more about resident and student education), John Driscoll (the master clinician who first excited me about neonatology and who remains my role model for the warm, compassionate physician), Bill Fox (my coeditor for Fetal and Neonatal Physiology, who demonstrated to me the importance and fun in doing clinical research and who periodically reminds me how to stay focused on the important things in life), and Mark Ditmar (my coeditor of Pediatric Secrets, whose combination of humor, knowledge, and compassion has allowed me to achieve a balance in medicine and who has shown me how "academic" and wonderful the practice of general pediatrics can be). Finally, I would like to thank my developmental editor at Elsevier, Kimberly Hodges, for helping with the organization and development of this book, and my friend and senior editor at Elsevier, Linda Belfus, for hooking me on the Secrets series and allowing me to put my love of education into print. As part of this meeting, we initiated the "Legends of Neonatology" awards, which I have the honor of presenting each year. In preparing for that evening, I have had the chance to venture back into the history of neonatology, relearning the origins of much of what we do today and examining the careers of some of the greatest figures in modern neonatal medicine, whose contributions have saved and enhanced the lives of countless infants. The impact of these individuals on my perspective on medicine has been immeasurable, and learning about their lives and the challenges that many of them had to overcome to achieve at the highest levels of our specialty has often left me in awe in ways that I would never have anticipated. To date, we have honored the following: Maria DelivoriaPapadopoulos, Mary Ellen Avery, Mildred Stahlman, Lu-Ann Papile, Avroy Fanaroff, Marshall Klaus, Jerrold Lucey, Robert Bartlett, William Norwood, George Gregory, John Clements, Forrest Bird, Stanley Dudrick, Abraham Rudolph, and William Oh. Each and every one of these figures faced incredible obstacles along their paths but believed in themselves and believed that their work would profoundly improve outcomes for children. Their courage and the quality of their work have been a model that I will always deeply admire and forever aspire to match. I would be remiss, however, if I did not also thank several other people for their inspiration as role models. My current partner, Reese Clark, is the ultimate clinical scientist-thoughtful, insightful, knowledgeable, and scrupulously honest. Anyone who reads a paper with his name on it can rest assured that no one has ever provided data and its interpretation in a more ethically precise and clear manner. Lastly, my coeditor of this book, Richard Polin, is without question the consummate clinician, educator, and investigator. They summarize the concepts, principles, and most salient details of fetal and neonatal medicine. About 10% of neonates will need some degree of resuscitative support at the time of birth. Cold stress can adversely affect the resuscitation of a newborn infant in the delivery room. With the elimination of silver nitrate eye prophylaxis at the time of delivery (causing a chemical conjunctivitis), the presence of any red eye, or a discharge from the eye of a neonate, must be evaluated and treated immediately. Without pulse oximeter screening, congenital heart disease may be missed during the immediate newborn period in about 50% of neonates with the condition. The average caloric content of breast milk is 20 calories per ounce but can range from 8 to 30 calories per ounce, primarily depending on the fat content. For the first 6 months of life, breast milk alone provides adequate nutrition for virtually any term neonate. Vaginal bleeding in newborn female infants is not uncommon and usually occurs because of withdrawal of maternal hormones that are present during pregnancy. In the first 3 to 4 months of life, a newborn infant should gain about one ounce per day on average. By 4 to 5 months of age, a healthy term infant should weigh double his or her birth weight. Sonographic assessments of fetal weight are associated with a significant (approximately 10% to 20%) margin of error. Absence of end-diastolic flow in the umbilical artery is indicative of increased placental resistance, whereas reversal of flow is suggestive of worsening fetal status and impending demise. The biophysical profile is an antenatal test that uses five parameters-fetal movement, fetal breathing, fetal tone, amniotic fluid volume, and fetal heart rate monitoring-to assess fetal wellbeing; depending on the gestational age, a score of 6 out of 10 warrants additional surveillance or consideration of delivery. Weekly intramuscular progesterone has been shown to reduce the risk of prematurity in mothers with a history of previous spontaneous (not medically indicated) premature birth. Screening with endovaginal ultrasound for a short cervix and treating those with a cervical length of <2 cm with daily vaginal progesterone is an option for all pregnant women to reduce the rate of premature birth. Doppler flow studies of the fetal umbilical artery have been shown to be of value to determine risk of impending fetal death in growth-restricted fetuses. Including parents as part of the care team and in the provision of skin-to-skin care (Kangaroo Mother Care) reduces infant pain and stress and improves the medical outcome. Negative or positive environmental influences can have an impact on normal development of the senses. The four modes of heat loss in the neonate are conduction, convection, evaporation, and radiation. A subgaleal hemorrhage presents as a balottable mass on the head of a newborn, and unlike a cephalohematoma or a caput succadeneum, it can be life threatening. Failure of a term infant to pass meconium within the first 48 hours after birth should prompt an evaluation for intestinal obstruction. The absence of a murmur in the neonatal period does not rule out congenital heart disease. Maintaining patency of the ductus arteriosus is important in severe right and left heart obstructive lesions. The most common cyanotic congenital heart lesion in the newborn period is d-transposition of the great vessels. Tetralogy of Fallot is the most common cyanotic lesion presenting outside of the newborn period. Erythema toxicum is no alien to the nursery; it is present in 50% of term newborns. It is much less prevalent in premature infants and occurs in only approximately 5%. The standard recommendation for milia, sebaceous gland hyperplasia, transient neonatal pustular melanosis, erythema toxicum, and sucking blisters is to reassure the family that the condition will resolve over time. If a dermatitis involves the axillae or groin, it is more likely to be seborrheic dermatitis. Both atopic dermatitis and seborrheic dermatitis involve scalp and posterior auricular areas, although seborrheic dermatitis has large, yellowish scale; when severe, it characteristically extends down to the forehead and eyebrow areas. The spots represent dermal hematopoiesis and are a sign of serious systemic disease-often a congenital infection. Infantile hemangiomas are common vascular tumors that arise during the neonatal period. They are often not visible at birth but are noticed within the first weeks of life. Hemangiomas occur more frequently in female children, with a female-to-male incidence of 2 to 5:1. The chronological age at which hemangiomas are noted to begin proliferation in preterm infants is the same as for fullterm infants. The most common cause of hypercalcemia during the neonatal period is excessive administration of calcium. The most common cause of hypermagnesemia during the newborn period is excessive maternal administration of magnesium. Treatment for congenital hypothyroidism should begin as soon as possible after birth to prevent neurologic impairment. The in utero effects of hypothyroidism are variable and may have adverse consequences, even with early postnatal treatment. The most common cause of congenital adrenal hyperplasia and sexual ambiguity at birth in female infants is 21-hydroxylase deficiency. A neonate requires approximately 4 to 8 mg/kg/min of glucose for maintenance of blood glucose levels. The most common cause of severe recurrent hypoglycemia in neonates is hyperinsulinemia. Most premature infants lose weight after birth as the result of catabolism secondary to low caloric intake and a physiologic decrease in the extracellular water volume that is independent of caloric intake. Insensible water loss decreases with increasing gestational and postnatal age, exposure to antenatal steroids, and increasing ambient humidity. There is minimal evidence documenting the value of sodium bicarbonate infusions to correct acidemia due to lactic acidosis. In fact, data in animals, children, and adults suggest that correction of lactic acidosis with sodium bicarbonate infusions may be detrimental. Cystic kidney disease in the neonate may present with a wide spectrum of clinical abnormalities, including hypertension, respiratory distress, oliguria, myocardial dysfunction, and prematurity. Hypertension in the neonatal period is most likely secondary to renovascular etiology. Significant bilious emesis in a newborn infant should be evaluated with an upper gastrointestinal tract series to assess for malrotation and midgut volvulus. In an infant with constipation who does not pass meconium in the first 48 hours of life, Hirschsprung disease should be considered. Patchy alternations in skin pigmentation in females suggest the possibility of genetic mosaicism or X-linked disorders that result from differential lyonization. Many genetic problems occur de novo, or new, to the child and suggest a low risk of recurrence for future pregnancies. However, such genetic problems can be passed on to the children of the affected child with the de novo mutation. Although the risk of Down syndrome is highest with mothers older than age 35 years, the majority of cases occur with women younger than age 35 because they have the majority of pregnancies. A chromosome microarray study has replaced a karyotype as the first line genetic test for newborns with major congenital anomalies, dysmorphic features, or both and can also be used prenatally. Genomic tests including chromosome microarray and whole exome sequencing are useful to identify genetic etiologies for rare familial conditions as well as conditions with no family history that are due to de novo mutations. Once sepsis is suspected in a neonate, antimicrobial treatment should begin promptly after cultures have been obtained, even when there are no obvious risk factors for sepsis. When meningitis is caused by enteric organisms, cefotaxime is preferred and is often paired with an aminoglycoside. Risk factors for systemic candidiasis in neonates include extreme prematurity, indwelling central lines, histamine blockers, and long-term use of broad spectrum antibiotics. In infants born prematurely, gestational age at delivery is an important determinant of neurodevelopmental outcome. Therapeutic hypothermia has been shown to reduce the risk of neurodevelopmental disability following hypoxic-ischemic encephalopathy. Most neonatal seizures are symptomatic of acute illness and very rarely due to primary infantile epilepsy. Frequent causes of neonatal seizures include stroke and hypoxic-ischemic encephalopathy followed by infection and metabolic disruptions. This should not be confused with "axial" or "truncal" hypotonia, which describes hypotonia primarily affecting the core trunk muscles. However, any eye misalignment that persists beyond the third month of life should be referred to an ophthalmologist. Any midline dimple (especially a deep or assymetric pit), subcutaneous mass, hemangioma, nevus, tuft of hair, or areas of hypopigmentation or hyperpigmentation might indicate occult spinal dysraphism and a tethered cord. The presence of two or more midline skin lesions is the strongest predictor of spinal dysraphism. An ultrasound of the spine is indicated whenever occult spinal sysraphism is suspected. The most important orthopedic radiograph for a newborn child suspected of having a genetic skeletal dysplasia is the lateral cervical spine. One of the most common is agenesis or hypoplasia of the upper cervical spine elements. Ultrasound of the hip is the study of choice for suspected developmental dislocation of the hip in neonates and infants younger than 4 months of age. In children of this age, the ossific nucleus of the femoral head is completely cartilaginous and therefore will not be seen on x-ray. The initial treatment for clubfoot is weekly manipulation and casting using the Ponseti method. With this technique, approximately 80% to 90% of idiopathic clubfeet will be successfully treated. Those feet that cannot be corrected with this method will require surgical correction. Pain thresholds increase progressively during late gestation and in the postnatal period. In addition to supportive therapy and the slow weaning of opioids, some pharmacologic agents. We do not recommend the use of drugs such as paregoric, camphorated tincture of opium, phenobarbital, or chlorpromazine for opioid withdrawal, because of major side effects and lack of standardization. Therapeutic goals are to decrease the severity of withdrawal signs to a tolerable degree, to enable regular cycles of sleeping and feeding, and to decrease the agitation caused by medical interventions or nursing care. Procedural pain can be minimized with an appropriate awareness program involving nursing, respiratory therapy, physicians, and most importantly, parents. Pain resulting from heel sticks can be lessened with 25% sucrose, and discomfort from tracheal suctioning can be treated with facilitated tucking. Remifentanyl, for example, is a good choice for short-term procedures such as intubation, whereas more prolonged pain should be treated with a longer acting opiate, such as morphine or fentanyl. Anxietolytics such as midazolam can be used as adjuncts, but they do not treat pain. Circumcision should be performed with sucrose and local anesthetic nerve block before the procedure and acetaminophen after the procedure. Most neonates who require support in the delivery room will respond to stimulation, opening of the airway, and gentle ventilation with a bag and mask. Although the use of fetal heart rate monitoring has become a standard practice, its prognostic value remains unclear at the present time. In all instances, however, the resuscitator must weigh the advantages of bag-and-mask therapy with the risks.

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