Dr. Allen Cherer | Neonatal Care & Pediatrics

Dr. Allen Cherer is a neonatal care expert with over 30 years of medical accomplishments to his name.

Tag: Pediatrics

Congenital Hypothyroidism and Newborn Screening

Congenital Hypothyroidism and Newborn Screening

Newborn screening for Congenital Hypothyroidism (CH) is a major public health achievement. Thyroid hormone is essential for the maturation of brain function and somatic growth, and its deficiency early in life can lead to mental retardation. For the fetus, maternal thyroid status is important during the first half of gestation; thereafter, the fetus’  hypothalamus-pituitary-thyroid axis is functional in the normal situation. For the hypothyroid newborn, it is well documented that provision of thyroid hormone is critical during the first weeks of life to avoid severe intellectual impairment. Notably, congenital hypothyroidism is considered one of the most common preventable causes  of mental retardation.

Studies showed that affected newborns were rarely identified during the first months of life and were often missed until 1-3 years of age. Congenital hypothyroidism  was found to be  an ideal candidate with the introduction of dried blood newborn screening by Dussault in Canada. With the development of increasingly sensitive assays to measure thyroid hormone (T4) and thyroid stimulating hormone (TSH) using a dried blood spot (DBS), newborn screening programs have developed throughout much of the world. In the 1980s, the incidence of CH in the United States was estimated to be 1:3000-1:4000. More recently, screening programs have reported an increased incidence of 1:1400-1:2800, most probably due to changes in screening strategies and the identification of milder cases.

Typically, newborn screening requires a heel stick blood specimen obtained at 48-72 hrs of life prior to an infant’s discharge from the hospital. Most current assays measure TSH alone as an indicator of thyroid function.  Results above established cutoff levels generally signify thyroid gland dysfunction and indicate further testing. Although most helpful in early identification of term newborns with anatomic or functional thyroid gland abnormalities, the screening does miss a percentage of newborns, for example those with central hypothyroidism due to hypothalamic-pituitary failure and the increasingly larger group of preterm  infants with congenital hypothyroidism who demonstrate delayed elevations in TSH. Numerous questions remain regarding the optimal timing of follow up laboratory studies and even treatment of certain types of newborn thyroid dysfunction.Nevertheless, newborn screening has proved invaluable for the great number of affected newborns.

The American Academy of Pediatrics recommends the measurement of TSH in all newborns with the goal that all infants with CH be identified by 2 weeks of age and that effective treatment with thyroid hormone replacement be started such that serum TSH levels less than 5 mIU/L be achieved within 4 weeks of diagnosis. Unfortunately, despite the significant successes following early identification and treatment of newborns with CH, obstacles persist in reaching the Academy’s goals. Screening programs continue to be plagued with the practical problems of screening all newborns, particularly those discharged home early who are lost to recall or lost to follow up altogether.  In addition, dried blood specimens are collected or processed improperly. Delays occur with recall of infants with abnormal results and with appropriate referrals for definitive treatment and management. A recent study conducted in Utah and reported at the 86th Annual Meeting of the American Thyroid Association highlights some of the problems which currently exist. After reviewing the TSH assays of 4394 children under 2 years of age, 48% of initial samples with elevated  levels (>20 mIU/L) were obtained after  the first 2 weeks of life, 15% of the initial abnormal TSH assays were not retested, and only 34% of those infants with initial elevated TSH assays achieved the goal of TSH < 5 mIU/L within 28 days of the initial assay.

The final message is that it is not enough to rely on the known efficacy of newborn screening for congenital hypothyroidism, but greater vigilance must be exercised to maximize its benefits in the lives of children.

Ehrenkranz J, Butler A, Snow G, Bach P. oral Abstract 19. The Diagnosis and Treatment of Congenital Hypothyroidism in Utah 2006-2015. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado

Noting the Extraordinary Success of Hib Vaccination

August is observed as National Immunization Awareness Month and is a time to highlight the extreme importance and value of vaccination for people of all ages. Vaccination serves as one of the best ways to protect infants, children, and adolescents from sixteen potentially harmful, and even deadly, diseases. Although it is common to think of the vaccines against measles, pertussis, and polio, an astonishingly important vaccine since the end of the 20th century has targeted the bacteria, Haemophilus influenzae type b (Hib).

Haemophilus influenzae is a small, pleomorphic, gram negative coccobacillus. Some strains of H. influenzae possess a polysaccharide capsule, and these strains are serotyped into six different types (a-f) based on their biochemically different capsules.

The H. influenzae strains with no capsule are termed nonencapsulated H. influenzae or nontypable H. influenzae (NTHi). H. influenzae type b is the most virulent, with its polysaccharide capsule being the main factor. Antibody to the capsule is the primary contributor to serum bactericidal activity, and increasing levels of antibody are associated with decreasing risk of invasive H. influenzae disease.

H. influenzae type b most commonly causes pneumonia, bacteremia, meningitis, epiglottitis, and cellulitis. Non-type b encapsulated forms present in a similar manner to type b infections, while non typable strains more commonly cause infections of the respiratory tract, such as pneumonia, otitis media, sinusitis, and conjunctivitis.

Generally, the mode of transmission is person to person by inhalation of respiratory tract droplets or by direct contact with respiratory tract secretions. Pharyngeal colonization by H. influenzae is relatively common, especially with nontypable and non-type b capsular strains.
Before effective Hib conjugate vaccines for infants older than 2 months were available in 1990, Haemophilus influenzae type b was the leading cause of invasive bacterial disease among children in the United States.

One in 200 children developed invasive Hib disease by 5 years of age; approximately 60% of these children had meningitis and 3-6% died from the disease. Of the Hib meningitis survivors, many exhibited permanent sequelae ranging from mild hearing loss to mental retardation.

Sadly, I recall as a Pediatric resident admitting to the hospital at least one infant with H. influenzae type b meningitis almost every night when on call.Remarkably, since the introduction of Hib conjugate vaccines in the United States, the incidence of invasive Hib disease has decreased a stunning 99% to fewer than 1 case/100,000 children younger than 5 years of age, and in 2012, only 30 cases of invasive type b disease were reported in children under 5 years old.

Truly, it has been an amazing accomplishment. Nevertheless, the risk for invasive Hib disease persists among unimmunized and underimmunized children, highlighting the importance of full vaccination with the 2 or 3 injection (depending on the product) series between 2 and 6 months old and a single booster dose given between 12 and 15 months of age.

Certain additional doses may be indicated over 5 years of age depending on medical conditions, such as anatomic or functional asplenia, hematopoietic stem cell transplantation, or HIV infection. The Hib vaccine is very safe. The most common side effects are usually mild and consist of fever and rednesss, swelling, or warmth at the injection site. As with all current vaccines, significant advances and improvement in public health have been witnessed. It is incumbent upon each of us to maintain that success.

Providing Care for Drug-exposed Newborns: Time for the Next Step

During the years 1999-2013, the amount of prescription opioids dispensed in the United States nearly quadrupled, and since 2000, it is estimated that opioid use during pregnancy has tripled. Notably, the tragic consequences of the extreme availability of such drugs include abuse, physical dependence, and increasingly, death through inadvertent overdose.

newborn-boy-sleepingIn addition, for the individual pregnant woman, a minimum of two lives is affected: her own and that of her unborn child. The prevalence of prenatally exposed newborns to one or more illicit drugs approximates 6%. Neonatal Abstinence Syndrome (NAS) refers to the withdrawal symptoms from physical dependence experienced by the newborn exposed during pregnancy generally to illicit drugs, prescribed drugs, or to those opioids employed in medication-assisted treatment of maternal opioid addiction.

Withdrawal symptoms can vary markedly in terms of time of onset and severity but typically manifest as tremulousness, agitation, sleeplessness, and poor feeding. NAS increased threefold from 2000-2009 and frequently requires prolonged newborn hospitalization. It has been reported that aggregate hospital charges for NAS increased from 732 million dollars to 1.5 billion dollars with approximately 80% attributed to state Medicaid programs in 2012. Clearly, NAS is a costly public health problem resulting in significant human suffering and expense.

Traditionally, infants who are known to be at risk for NAS have been monitored in the postpartum unit after birth for at least 96 hours and withdrawal symptoms scored based on the Finnegan Scale developed in the mid 1970’s. Typically, if the scores exceed certain values, the newborn is admitted to a Special Care Unit where pharmacologic treatment is frequently started. As withdrawal symptoms subside, dosing is gradually tapered and ultimately stopped. The newborn is observed off medication and monitored for recurrence of disabling withdrawal symptoms. The entire process can generally result in a prolonged Special Care Unit hospital stay of 2-10 weeks.

With the seemingly overnight explosion in the number of newborns demonstrating withdrawal symptoms in the early 2000’s, medical caregivers and hospitals were caught off-guard. On short notice, staff addiction education, medication and weaning protocols, general care policies, and hospital space allocation were required. After a number of years of concerted, collaborative work, much has been learned and achieved in improving the care of the substance-exposed infant.

Nevertheless, pharmacologic treatment continues to require prolonged hospital stays, often in costly Special Care Units. In addition, it effectively excludes full participation by the eventual sole primary caregivers, ideally the parents. It is with these disturbing issues in mind that it is refreshing to note the work and studies over the past several years to further optimize the care provided to infants with NAS and their families.

One of the earlier studies to suggest the therapeutic benefits of a different approach to caring for the drug-exposed infant was that of Abrahams et al. published in the Canadian Family Physician in 2007. During the same period of frenzy involving inpatient hospital transfers, guaranteeing interobserver scoring reliability, pharmacologic treatment protocols, and nursing care directives, the Canadian group with extensive previous experience in addiction medicine reported in a retrospective cohort study the benefits of a rooming-in policy whereby infants remained with their mothers as primary caretakers.

They noted that infants who roomed-in were less likely to require pharmacologic therapy for withdrawal and more likely to be discharged to mother’s care compared to infant’s who received standard nursery care. Subsequently, other retrospective cohort studies both in Europe and the United States demonstrated equally beneficial effects of rooming-in regarding decreased requirement for pharmacologic therapy and decreased duration of hospital stay.

Most recently, the results of a quality collaborative project from the Children’s Hospital at Dartmouth Hitchcock were described in the May, 2016 Pediatrics and demonstrated the beneficial effects of combined standardized protocols and family-centered care in the management of the drug-exposed infant. Over time, the project safely reduced the number of infants requiring pharmacologic therapy, average length of stay, and overall hospital costs.

Among others, key drivers to success were prenatal education of family caregivers including expressed expectation that they would provide meaningful rooming-in care, baby-centered NAS scoring including on demand feeding schedules, pharmacologic therapy when necessary with dosing adjustment based on overall infant condition rather than solely Finnegan score and determined by a consistent team, and an infant “snuggler” volunteer program to assist families when times required their absence.

Overall, the project demonstrated that despite many practical obstacles to providing high quality care for drug-exposed newborns and their families in the hospital setting, where there’s a will, there’s a way.

Antenatal Corticosteroid Use for Late Preterm Delivery

In 1972, Drs. Liggins and Howie published their landmark study demonstrating that antenatal corticosteroids administered to women 24-36 weeks of gestation reduced the incidence of respiratory distress syndrome and  neonatal mortality. Liggins had previously noted that lambs, treated with intrafetal  ACTH, cortisol, or dexamethasone, delivered prematurely, and sacrificed, demonstrated partially expanded  lungs.

Such alveolar stability was not typically noted until later in gestation. It suggested to Liggins that glucocorticoids might cause premature liberation of surfactant into the alveoli and served as the basis for his study. In the trial, the most significant difference in the incidence of respiratory distress syndrome among those treated vs. not treated with corticosteroids occurred in those gestations  less than 32 weeks.

Although those gestations treated between 32 and 37 weeks exhibited a decreased incidence of respiratory distress, the number did not reach statistical significance. Nevertheless, even at that time, Liggins postulated that mechanisms in addition to enhanced surfactant production and release might be responsible for the improved pulmonary function noted in more advanced gestations treated with antenatal corticosteroids.  

Interestingly, despite the findings of the initial study and similar results in multiple subsequent studies , the 1994 NIH Consensus report on the effect of corticosteroids for fetal maturation on perinatal outcomes found that only 20% of women who delivered newborns  501-1500 grams received the benefit of antenatal steroids. After a thorough review of available evidence, including  12 year neurodevelopmental follow up showing no adverse outcomes, the Consensus Panel felt  the benefits of antenatal administration of corticosteroids vastly outweigh the risks and all fetuses between 24 and 34 weeks gestation at risk of preterm delivery should be considered candidates for antenatal  treatment.

Only in those few pregnancies where corticosteroids would have an adverse effect on the mother or delivery was imminent  should steroid treatment be withheld. In addition, although Grade 1 evidence existed at the time to support the use of antenatal corticosteroids for gestations greater than 34 weeks, it was judged insufficient to recommend their use.

Since the Consensus statement, the use of antenatal corticosteroid use has become common and has resulted in considerable reduction in mortality and morbidity, as well as total health care costs. In addition, further neurodevelopmental follow up, including the original Auckland steroid trial participants, continues to demonstrate no adverse effects on psychological functioning and health-related quality of life. Other studies have demonstrated a decrease in overall respiratory disease in infants born beyond 34 weeks who had previously been exposed to antenatal corticosteroids when compared to unexposed infants born at similar gestations.

More than 300,000 pregnancies deliver in the late preterm period (34 0/7 – 36 6/7 weeks gestation) each year in the United States. Seventy per cent of Intensive Care Nursery admissions are late preterm newborns. Their increasing numbers and the broad range and severity of respiratory disorders with which they present beg for a re-evaluation of antenatal corticosteroid use in this range of gestations. This is especially appropriate with a better understanding of the multiple actions of corticosteroids as gestation approaches term.

A recent study, titled Antenatal Late Preterm Steroids (ALPS), a Randomized Trial to Reduce Neonatal Respiratory Morbidity, was published in The New England Journal of Medicine in April, 2016. The study enrolled over 2800 women with singleton pregnancies at high risk for late preterm delivery.

The participants were randomized to receive antenatal betamethasone by injection or a matching placebo. Greater than 80% of women in the trial delivered prior to 37 weeks gestation. The primary outcome was a neonatal composite of treatment in the first 72 hours (CPAP or High Flow Nasal Cannula for at least 2 hours, supplemental oxygen with fraction of inspired oxygen of at least 0.3 for at least 4 hours, mechanical ventilation, or ECMO) or stillbirth or neonatal death within 72 hours of birth.

The study found a significant decrease in neonatal respiratory complications in the group given the steroid treatment (11.6% vs. 14.4%). In addition, severe respiratory complications occurred significantly less frequently in the betamethasone group. The incidence of neonatal hypoglycemia  was increased in those treated with betamethasone (24% vs. 14.9%), but no other adverse neonatal outcomes were noted between the groups.

The study is authoritative due to its size, generalizability, and methodologic rigor. Although the issue of long term follow up cannot be specifically addressed, follow up studies of similar treatment in earlier gestations are reassuring. Late preterm births comprise a high risk group for hypoglycemia regardless of maternal antenatal steroid treatment and warrant vigilant monitoring during the newborn period.  In sum, the findings of the Antental Late Preterm Steroids study are consistent with other randomized controlled trials of antenatal corticosteroids administered at gestations less than 34 weeks.

Both the American College of Obstetrics and Gynecology with an endorsement by the American Academy of Pediatrics and the Society for Maternal-Fetal Medicine have addressed and published recommendations based on the study’s findings. Although the recommendations do not establish exclusive standards of care, the organizations approve the use of antenatal corticosteroids in certain defined late preterm pregnancies.  It is only with thoughtful application of the recommendations and further studies that the efficacy and safety of antenatal steroids in the late preterm pregnancy will be realized. It is a significant start.

Promoting Safe Sleep for Infants

Very few life events result in the anguish that comes with the death of an infant, especially one that is sudden and unexpected. Each year in the United States, approximately 3500 sudden, unexpected infant deaths (SUIDs) occur generally between the ages of 1 month and 1 year at a time when most infants sleep between 12 -18 hours/day.

They consist of three main types with Sudden Infant Death Syndrome (SIDS) being the predominant one, and deaths due to unknown causes and those due to accidental suffocation and strangulation in bed (ASSB) comprising the remainder.

The combined SUID death rate declined markedly following the 1992 American Academy of Pediatrics infant sleep recommendations and the initiation of the Back to Sleep campaign in 1994 with a primary focus on supine positioning during all infant sleep.

The combined SUID death rate decreased again slightly in 2009, and since that time has remained fairly constant. On the other hand, the ASSB, traditionally the least common of the three main causes of SUID, mortality rate remained unchanged until the late 1990s and has started a slow increase with its highest point in 2014.

Due in part to the success of the Back to Sleep campaign and to the increasing incidence of other sleep-related causes of SUID, the American Academy of Pediatrics broadened its focus since 2005 to include other factors resulting in an unsafe sleep environment and contributing to sleep-related infant deaths.

It is important to remember that the recommendations from the Safe to Sleep campaign are wholly derived from case-control studies and are based for the most part on epidemiologic studies including infants up to 1 year of age. The recommendations should therefore be applied to infants up to 1 year of age, except for those individuals in whom medical conditions warrant modification.

baby sleepingWhen it comes to safe sleep environment, remember the phrases “Back to Sleep”, “Bare is Best”, and “Room-sharing without Bed-sharing”. The basic underlying point to promote a safe sleep environment starts with every caretaker positioning every healthy infant on his or her back for every sleep.

Protective airway mechanisms prevent choking and aspiration. Only those infants with significant upper airway disorders warrant modification. Side sleeping is not recommended, and elevation while supine can be complicated by respiratory compromise if the infant’s position changes.

Preterm infants requiring prolonged hospitalization should also be maintained in the supine position during sleep when they are medically stable and long before they are ready for discharge to home.

Although the general recommendation pertains to infants up to one year of age, once an infant is capable of rolling from supine to prone and vice versa, the infant can remain in the sleep position that he or she assumes.
Since infants spend almost all of their time in a crib, bassinet, or play yard, these environments are especially important. Many infant deaths are associated with broken cribs with loose or missing parts.

Cribs should be no older than ten years and conform to the safety standards of the Consumer Product Safety Commission. Before use, the product should be checked for previous recall. Cribs require narrow slats and stable sides. Since 2011, federal safety standards prohibit the sale of drop side rail cribs. Specific mattresses designed for the crib should be firm and covered with a fitted sheet.

There should be no gaps larger than two finger breadths between the mattress and the crib. Soft materials or objects, such as pillows, comforters, or sheepskins even when covered with a sheet , should not be placed under a sleeping infant. Research shows that babies who sleep on soft surfaces which allow the baby’s head to sink into the surface are at higher risk for SIDS and suffocation.

If an infant falls asleep in a sitting device, such as a car safety seat, stroller, swing, or infant carrier, he or she should be removed from the product and moved to a crib or other appropriate firm flat surface as soon as practical.

When infant slings or cloth carriers are used, the infant’s head should be up and above the fabric, the face visible, and the nose and mouth not obstructed. The crib surface should be free of stuffed animals, pillows, toys, bumper pads, or blankets to reduce the risk of suffocation or entrapment. The crib, bassinet, or play yard should be positioned away from wall hangings, and the area should be free of blind and curtain cords which can result in strangulation.

Room-sharing without bed-sharing is recommended and is most likely to prevent accidental suffocation especially from overlaying, strangulation, and entrapment that might occur when an infant is sleeping in an adult bed. Soft mattresses, pillows, quilts, and loose bed linens provide a high risk environment for infants. Certainly, infants can be brought into the bed for feeding or comforting but should be returned to their own crib or bassinet when the parent is ready to return to sleep.

Epidemiologic studies have demonstrated increased risks for SIDS and suffocation when bed-sharing involves infants less than three months of age, other children or multiple persons, and caretakers who are excessively tired, current smokers, or are using medications or substances that impair alertness or ability to arouse. It is best to provide separate sleep areas and avoid co-bedding for twins and higher multiples in the hospital and at home.

Certain sudden, unexpected infant deaths are not preventable. Continuing research particularly related to SIDS will provide new insights into the mechanisms resulting in this tragedy. Nevertheless, vigilance in attending to those modifiable environmental risk factors is highly desirable.

IVF and Childhood Cancer Risk

Assisted Reproductive Technology  (ART) has been successfully employed to treat infertility. In vitro fertilization (IVF)  is one form of ART, and it is unclear whether it increases the risks of birth defects . Since childhood cancers, such as leukemia, occur earlier in life, it is reasonable to question if factors related to early embryonic development and intrauterine environment may play a role in their occurrence.

A recent study from Norway suggests a slightly increased risk of childhood leukemia and Hodgkin’s lymphoma among children born through the use of ART. The findings were based on a review of children born between the years 1984 and 2011 and the use of ART. The data were then paired with cancer registry data. Out of 4500 cancer patients identified, 51 were conceived via ART.  Although overall cancer risk was not found to be increased among ART children, the odds of leukemia and Hodgkin’s lymphoma were.

As pointed out by Dr. Susan Amirian, assistant professor with the Baylor College of Medicine’s Duncan Cancer Center in an accompanying editorial, although the findings suggest a possible association, the very small numbers of actual cases  (17 cases of leukemia and 3 cases of Hodgkin’s lymphoma) call for caution in interpretation of the results. It would require more studies to establish a true association. Certainly other health factors that result in infertility may play a role in the apparent association.

At this point, the study results should not deter parents from using assisted reproductive technology and only careful monitoring of children born using the techniques is warranted. Take a look at this link for more information about this study.

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