Tag: research

DiGeorge Syndrome: An Overview

On April 30, 2019

In Child Health Care, Newborns, Research

Primarily observed in children under the age of two, DiGeorge Syndrome is a rare neonatal chromosomal disorder affecting bodily development. The condition, which is also called 22q11.2 deletion syndrome, is caused by a defect in chromosome 22 and has a varying range of symptoms impacting both physical and mental growth. In some cases, it can be passed genetically from an affected parent to a child.

Due to the condition’s long list of symptoms — many of which are caused by a myriad of other conditions — DiGeorge Syndrome can be difficult to diagnose and treat, which means you will need to seek out an accurate and prompt evaluation from a trusted healthcare professional. Starting out, however, here is a quick overview of the condition to potentially point you in the right direction.

Knowing the signs

As mentioned before, symptoms of DiGeorge Syndrome can be vast, and therefore the condition can be hard to pinpoint at first. That said, there are several broad symptoms that have become listed as common warning signs; these include, but are certainly not limited to:

Cyanosis (a bluish tint to the skin caused by a lack of oxygen).
Learning difficulties, including those typically associated with Attention Deficit Disorder (ADD)

Skeletal abnormalities

Seizures and other epileptic symptoms

Feeding problems and failure to gain weight

Other, less externally evident symptoms may include autoimmune disorders, heart murmurs, frequent infections, and issues with the palate. In any scenario, the easiest and most established way to diagnose the condition is genetic testing, which can

Treating DiGeorge Syndrome

Unfortunately, there is currently no known cure for DiGeorge Syndrome — though certain symptoms may be individually treatable; this can fluctuate based on the urgency of the symptoms in question. For example, symptoms associated with certain immune-based disorders should ideally be addressed sooner than later to increase the chances of effective treatment. Other condition-based byproducts, like learning disabilities and anxiety, can be mitigated through proper intervention aimed at fostering intellectual growth and emotional stability.

These efforts may not treat the underlying root of the issue, but they can help on other fronts, such as improving the child’s overall quality of life.

Prevention can also be key in stopping the condition; if you feel you may have a family history of DiGeorge Syndrome, consult a specialist prior to any future pregnancies.

Fine-tuning the Elimination of Perinatal Hepatitis B Infection

By Dr. Allen Cherer

On February 13, 2018

In Neonatal Care

Hepatitis B virus (HBV) infection is a serious illness in the newborn and young infant. The virus, first discovered in the mid-1960s, is transmitted through percutaneous (i.e., puncture through skin) or mucosal (i.e., direct contact with mucous membranes) exposure to infectious blood or body fluids. The virus is highly infectious, can be transmitted in the absence of visible blood, and remains viable on environmental surfaces for at least seven days. Once the virus enters the body, it is transported to the liver where it replicates. Although one generally thinks of the acute illness as a self-limited one in the adult with characteristic signs and symptoms, HBV infection in the infant is almost exclusively asymptomatic and hence, unrecognized. The devastating aspect of the infection is that the infant and young child frequently fail to clear the virus, and the illness becomes chronic. As many as 80-90% of infected infants progress to chronic infection, and chronically infected persons as adults are at increased risk of cirrhosis, hepatocellular carcinoma, and liver failure with approximately 25% dying from these serious complications.

Before 1982, an estimated 200,000-300,000 persons in the U.S. alone were infected with HBV annually, including approximately 20,000 infants. No effective pre-exposure prophylaxis existed, and only post-exposure prophylaxis in the form of hepatitis B immune globulin (HBIG) was available. However, the first hepatitis B vaccine was approved in the United States in 1981 and proved to be a real game changer. The availability of the vaccine set the stage for remarkable progress in the elimination of HBV infection among all age groups. With the advent of an effective vaccine, incurable hepatitis B infection had become preventable. The vaccine saves lives!

It is in this setting of disease prevention through widespread vaccination that an evolving strategy to eliminate perinatal hepatitis B infection was initiated over 30 years ago. Early epidemiological studies had demonstrated that a major contributor to perinatal HBV infection is mother-to-child transmission (MTCT) at the time of delivery. In utero infection is felt to account for less than 2% of infections. The risk of transmitting the virus was estimated to be 20-80% depending on the activity of the maternal infection. Initial attempts in the early 1980s to limit vertical HBV transmission were risk-based and aimed at identifying those pregnant women considered infectious by virtue of the serum marker, HBsAg. With reliable identification of mothers and expeditious treatment of their newborns with hepatitis B vaccine and HBIG, HBV infection could be prevented. However, it became clear within several years that such screening was inadequate with as many as 35-65% of HBsAg-positive women being missed. Consequently in 1988, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention recommended universal testing of all women early in each pregnancy such that at risk babies would receive appropriate post-exposure HBV prophylaxis. Throughout the 1990s, efforts were intensified to eliminate all HBV-related illness through widespread vaccination of children, adolescents, and at-risk adults. Studies showed that receipt of the 3-dose hepatitis B vaccine series produced a protective antibody response in approximately 98% of healthy infants. During 1990-2004, the incidence of acute hepatitis B in the U.S. declined by 75%. The greatest decline (94%) occurred among children and adolescents, most likely due to increasing hepatitis B vaccine coverage. As of 2004, over 92% of children less than 3 years of age had been fully vaccinated with the complete series.

Coupled with the remarkable success of the hepatitis B elimination strategy is the knowledge that the task is not complete. As a response to the persistence of perinatal HBV infection and aware that errors in testing as well as in communication of results may occur, ACIP has recommended a change in the administration of the initial hepatitis B vaccine dose over time. Initially, the first dose could be administered to an infant born to a HBsAg-negative mother any time from birth to 2 months of age. Subsequently the initial dose became the “birth dose” with the recommendation that it be given prior to discharge, and in 2017, the initial dose was to be administered within 24 hrs of birth. The previous permissive language that allowed the dose to be delayed “on a case-by –case basis and only in rare circumstances” was omitted. Based on the fact that the vaccine alone is 75% effective in preventing MTCT, these changes reflect reality and provide basic protection. Then too, the emerging concept that maternal viral load (HBV DNA) plays a significant role in risk of MTCT now plays a prominent role in management. Testing pregnant HBsAg-positive women for HBV DNA is now recommended to guide the use of antiviral therapy during the third trimester for the purpose of preventing perinatal HBV transmission.

Fighting the P-Hack

By Dr. Allen Cherer

On October 20, 2017

In Research

It’s been said that statistics can be used to prove just about anything. Take, for example, one study that I recently read about, which examined the link between vegetarianism among pregnant women and an increased risk of drug and alcohol abuse among their children. The study examined over 5,000 women and their children, and finding that if their mothers ate little to no meat while pregnant, then the children were more likely to drink, smoke, and do drugs at 15. It’s an interesting study, but at the same time, it’s one that could be part of a phenomenon that’s tragically common in the field of science, and is often used to push an agenda at the cost of objectivity. I’m talking, of course, about “p-hacking”.

In this phenomenon, “p” is the value used to determine statistical significance. Ultimately, a difference between two groups is only meaningful if it’s statistically significant. Let’s say a “p” value is less than .001: this means that there’s a less than 0.1% chance that an observed finding is due to chance, and more than a 99% chance that it represents a real difference. This means that a statistically significant result is almost certainly real. However, large datasets may involve countless variables. If mining a dataset of 10,000 possible variables, for example, 10 statistically significant results should be treated as coincidence.

Ultimately, p-hacking is a constant possibility when analyzing large datasets, so that treating every statistically significant result as real is dangerous. Luckily, there are plenty of statistical tests to give a greater insight into whether or not a result is real. The basic one is reproducibility. If other data sets produce the same results, then you might just be onto something. But until that happens, there’s no reason to believe that results are real. Plenty of times, however, mining large datasets is used to find a point and push an agenda. In the case of this study, eating meat. Yet until that study is duplicated, you need to treat it with a grain of salt.

Noting the Extraordinary Success of Hib Vaccination

By Dr. Allen Cherer

On September 9, 2016

In Neonatal Care, Research

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

By Dr. Allen Cherer

On September 6, 2016

In Child Health Care, Neonatal Care, Newborns, Research

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.

In 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

By Dr. Allen Cherer

On July 15, 2016

In Child Health Care, Neonatal Care, Research

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

By Dr. Allen Cherer

On June 12, 2016

In Child Health Care

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.

When 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.

Newborn Screening and Severe Combined Immune Deficiency

By Dr. Allen Cherer

On May 15, 2016

In Child Health Care, Neonatal Care

April (April 22-29) has been designated as National Primary Immunodeficiency Awareness Month and provides an opportunity to better understand the more than 250 rare, genetic disorders in which the body’s normal immune system is absent or functions improperly. Since an important function of the immune system is to protect against infection, patients with primary immune deficiency have an increased susceptibility to infection.

Severe Combined Immune Deficiency (SCID), popularized in the 1976 movie “The Boy in the Plastic Bubble”, is generally considered to be the most serious of the primary immunodeficiencies. There are at least 13 different genetic defects that can cause the disease; all of which are present at birth, involve missing T lymphocytes which are important in identifying and attacking perceived “invaders”, and affect the function of B lymphocytes which produce antibodies against infection.

The absence of T lymphocytes and antibody immunity results in severe infections, diarrhea, and failure to thrive. Regardless of the genetics, patients invariably succumb to an early death due to overwhelming infection. New approaches to diagnosis and management have changed what at one time was a dismal prognosis.

Treatment options have come a long way over the past 4 decades and include enzyme replacement, bone marrow transplant, and gene therapy. Paramount to this change is early diagnosis before the infant has had a chance to develop any serious infections.

The most effective therapy to date is immune reconstitution via stem cell transplant which has been shown to be highly successful (94%) if performed by 3.5 months of age. Hence, timing is crucial in terms of diagnosis and treatment.

Typically, infants with SCID appear totally normal at birth and have no family history of immunodeficiency. In the past, patients were primarily identified either by previous family history, physical manifestations, or after onset of life-threatening infection. Early identification of SCID has been achieved through the use of the 7-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.

Absent or low TREC levels can indicate insufficient T lymphocyte production characteristic of SCID, as well as low T lymphocyte, non-SCID conditions as seen in DiGeorge Syndrome, Trisomy 21, CHARGE Syndrome, and ataxia telangiectasia. On May 21, 2010, The U.S. Department of Health and Human Services (HHS) recommended that every state include the assay as part of the newborn screen.

In the landmark study based on retrospective data on more than 3 million infants from 11 newborn screening programs using the TREC methodology conducted by Jennifer Puck, MD and colleagues and published August 20, 2014 in The Journal of the American Medical Association, the value of early detection and treatment of SCID was confirmed.

In addition, the study found an incidence rate almost twice as great (1 in 58,000 births) as had been previously estimated. Since the point of newborn screening is to identify conditions for which early treatment is life-saving, the study was a crucial step in the adoption of universal screening.

As of April 1, 2016, all, except for 11, states have adopted routine newborn screening programs for SCID. A 2016 study published in the Journal of Pediatrics by Ding and others provided an eloquent cost-benefit analysis of newborn screening in the treatment of Severe Combined Immune Deficiency.

Based on data obtained from 86,000 infants in Washington state, the study showed that newborn screening for SCID is clearly cost-effective. Hopefully, the study provides additional support in economic terms for the adoption of universal screening programs in all 50 states.

Reflections on Cesarean Section Rates

By Dr. Allen Cherer

On May 9, 2016

In Child Health Care, Neonatal Care

Cesarean section delivery is among the most common surgical procedures. It is estimated that in 2012 alone, over 22 million cesarean deliveries were performed worldwide. Data from the National Vital Statistics show that the total cesarean section rate in the U.S. in 1996 was approximately 21%.

Since that time, there has been a rapid increase in the rate, such that in 2011, close to 1 in 3 mothers delivered by cesarean. Although the rate has leveled since then, there remains no evidence that such a significant increase has been accompanied by a concomitant decrease in maternal or neonatal mortality.

Although cesarean delivery can be life-saving for the fetus, the mother, or both in certain cases, the concern exists that cesarean delivery is overused. Hence, the matter is a global health issue. Since one of the main driving forces for the increased total cesarean rate has been a marked shift to repeat cesarean delivery following a previous primary cesarean section, a concerted effort over the past several years has been to examine closely the factors related to the safe management of the nulliparous pregnancy.

As early as 1985, the World Health Organization (WHO) stated there was no justification for any region to have a cesarean delivery rate greater than 10-15 /100 live births. Nevertheless, the rates continued to increase worldwide with no scientific evidence indicative of substantial maternal or perinatal benefit.

In fact, a number of studies have associated higher rates of cesarean deliveries with negative consequences, including increased maternal and neonatal morbidity and mortality as well as increased consumption of limited health resources by procedures without medical indications.

In March 2014, a consensus report was issued by the American College of Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine on the safe prevention of the primary cesarean section. Among other points, it addressed management guidelines for the most frequent indications for primary cesarean deliveries, namely, labor dystocia, abnormal or indeterminate fetal heart rate tracing, fetal malpresentation, multiple gestation, and suspected macrosomia.

The report encouraged obstetricians to allow more time to progress through a vaginal delivery without intervention, recommended improved and standardized fetal heart rate interpretation and management, and advocated access to non-medical interventionsduring labor, such as continuous labor and delivery support.

A study by researchers at Harvard Medical School and the Stanford University School of Medicine published December 2015 in The Journal of the American Medical Association suggested that based on analyses of cesarean section rates and maternal and neonatal outcomes among 194 WHO member countries the ideal rate of childbirth by cesarean section approximates 19% of all births as opposed tothe previously considered optimal rate of 10-15%. Although the finding is higher than the former target, it remains significantly lower than the current rate in U.S. hospitals.

In its April 2015 position statement on cesarean delivery, the WHO moved away from any target rate. Rather, it emphasized that every effort should be made to ensure cesarean sections are provided to the women in need and only be performed when medically necessary.

It is gratifying that the concept of “target rate” is no longer tied to the delivery of quality medical care. Primarily due to the lack of a consistent classification system to monitor and compare different obstetric profiles, meaningful data relative to cesarean section rates is missing.

It is only when such systems as the Robson Ten Group Classification System are widely adopted by institutions that valid “risk-adjusted”cesarean section rates can potentially be developed and comparisons be made between institutions, regions, and countries.

Physical Trauma and Pregnancy

By Dr. Allen Cherer

On February 20, 2016

In Neonatal Care

Trauma is an important cause of maternal and fetal morbidity and mortality, and blunt abdominal trauma is a particular concern. Approximately 8% of pregnant women sustain some form of traumatic injury. Automobile accidents and falls account for most of the injuries.

Studies of pregnant women involved in automobile accidents have demonstrated increased rates of premature rupture of membranes, placental abruption, preterm birth, and stillbirth. A recent study examines pregnancies complicated by traumatic injuries and outcomes in relation to place of triage.

According to the retrospective study published in the Journal of the American College of Surgeons, pregnant women who sustained traumatic injuries and were triaged to trauma centers experienced improved pregnancy outcomes compared to women cared for in non-trauma hospitals. For the study, the researchers linked two databases, the Washington State Birth Events Records Database and the Comprehensive Hospital Abstract Recording System.

The method allowed them to assess the maternal and neonatal outcomes of all injured, pregnant women (3429 patients) who were hospitalized in Washington State between the years 1995 and 2012. The findings showed that after adjusting for a number of confounding factors, including injury severity score, pregnant women who were cared for in trauma facilities had better outcomes with significantly decreased odds of preterm labor, preterm birth, and low birth weight infants.

Since trauma centers are specialized medical facilities which have optimal processes and resources in place to monitor and treat injured patients, the study suggests that many injured, pregnant women may in fact be under-triaged and treated in non-trauma hospitals where their care may not be optimal.

According to the coauthors, John Distelhorst, DO, MPH and Vijay Krishnamoorthy, MD, the findings may lead to further analyses of state trauma systems and the triage of specific patient populations to improve quality of care and patient outcomes. To read more about this, please visit this site.